Evaluation activities of daily living in patient`s rehabili

Transcription

1
New ORs - Central Medical Building - Clinical Center University of Sarajevo
Novi operacioni blok - Klinički Centar Univerziteta u Sarajevu
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New ICU - Central Medical Building - Clinical Center University of Sarajevo
Nova Intenzivna njega - Klinički Centar Univerziteta u Sarajevu
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New Central Medical Building - Clinical Center University of Sarajevo
Novi Centralni Medicinski Blok - Klinički Centar Univerziteta u Sarajevu
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Contents
Medical Journal (2014) Vol. 20, No. 1
Original article
Incidence of anticardiolipin antibodies evaluated by elisa method on hytec 288 ................................................................................ 7
Marina Delić-Šarac, Jasenko Karamehić, Đemo Subašić, Nejra Džananović, Suvada Švrakić, Aida Šaban, Ognjen Riđić
Appearance of N-metastases in presence of peritumoral lymphovascular infiltration at lung cancer ................................... 13
Kemal Grbić, Safet Guska, Alma Alihodžić-Pašalić, Alen Pilav, Ferid Krupić
The usefulness of penile compression-release index for diagnosing bladder outlet obstruction ............................................... 18
in patients with benign prostatic enlargement
Damir Aganović, Alden Prcić, Munira Hasanbegović, Osman Hadžiosmanović, Hajrudin Spahović
Evaluation activities of daily living in patient’s rehabilitation with osteoporosis ............................................................................... 24
Edina Tanović, Aldijana Kadić, Haris Tanović, Dževad Vrabac
Testicular volume in healthy prepubertal boys ................................................................................................................................................... 27
Zlatan Zvizdić, Denisa Zvizdić, Sandra Vegar Zubović, Amra Džananović, Faris Fočo
Correlation of gastroesophageal reflux disease and Helicobacter pylori infection ........................................................................... 30
Nenad Vanis, Amila Mehmedović, Rusmir Mesihović, Amir Redžepović, Aida Saray
A prospective comparison of preperitoneal with prefascial herniorrhaphy for the treatment of inguinal hernias .................... 33
Ismar Rašić, Goran Akšamija, Adi Mulabdić, Adis Kandić
Assessment of initial diagnostic procedures in isolated thoracic injuries .............................................................................................. 38
Alma Alihodžić-Pašalić, Safet Guska, Ademir Hadžismailović, Alen Pilav, Kemal Grbić
Medicamentous abortion induction in the second trimester in pathological pregnancies ........................................................... 42
Naima Imširija, Zulfo Godinjak, Lejla Imširija, Edin Idrizbegović, Fatima Gavrankapetanović, Admir Rama, Muhamed Ardat
Professional article
Endoscopic retrograde cholangiopancreatography: our experience .............................................................................................................. 46
Kenan Nahodović, Rusmir Mesihović, Nenad Vanis, Amra Puhalović, Srdjan Gornjaković, Amila Mehmedović, Alma Nahodović
People with disabilities and their free access to hospital facilities in the compound of Clinical Center
University of Sarajevo: special focus on Central Medical Building ............................................................................................................ 50
Mirza Dilić, Mustafa Hiroš, Mirela Imširija, Naima Imširija-Galijašević
Case report
Intraluminal lipoma as a cause of intestinal obstruction ............................................................................................................................... 60
Amir Hadžibeganović, Adnan Kulo, Lana Sarajlić, Dijela Kulo, Abdulah Efendić
Entrapment syndrome of the left renal vein ........................................................................................................................................................ 63
Zoran Roljić, Božina Radević, Dušan Janičić, Slavko Grbić, Milan Žigić, Jevrosima Roljić,
Vladimir Keča, Severin Dunović, Novak Milović
Instructions to authors ................................................................................................................................................................................................... 66
Uputstva autorima .......................................................................................................................................................................................................... 68
Original article
Medical Journal (2014) Vol. 20, No. 1, 7-12
Incidence of anticardiolipin antibodies evaluated by
elisa method on hytec 288
Incidenca antikardiolipin antitijela evaluiranih elisa
hytec 288 metodom
Marina Delić-Šarac1*, Jasenko Karamehić1, Đemo Subašić1, Nejra Džananović1,
Suvada Švrakić2, Aida Šaban3, Ognjen Riđić4
Department for Clinical Immunology, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; 2 Department for Quality Improvement and Safety of Health Services, Clinical Center University of Sarajevo Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; 3 Stomatology
Department, Primary Health Care Center Travnik, 72270 Travnik, Bosnia and Herzegovina; 4 Health Faculty, University of Zenica, Crkvice 57, 72000 Zenica,
Bosnia and Herzegovina.
1
*Corresponding author
ABSTRACT
SAŽETAK
Antiphospholipid antibody syndrome (commonly called antiphospholipid syndrome or APS) is an autoimmune disease present mostly
in young women. Antibodies that are found in the blood of these patients are called anti-phospholipid autoantibodies (commonly called
aPL). Phospholipid antibodies and lupus anticoagulants are found with
increased frequency in patients with systemic rheumatic diseases, especially lupus erythematosus. The term antiphospholipid syndrome
(APS) is used to describe the triad of thrombosis, recurrent fetal
loss and thrombocytopenia accompanied by phospholipid antibodies
or a lupus anticoagulant. The aCL (anticardiolipin antibodies) assay
is only one of the methods used to detect aPL, and the test should
be administered with the LA and anti-B2GPI assays.The aCL assay is
reasonably sensitive, but not at all specific; therefore, clinicians should
treat the clinical state and not an incidentally found antibody. There
is an association between antibody titer and risk of thrombosis and
this is not a ground for ignoring or not reporting weakly positive
results. False-positive results that are difficult to interpret are particularly likely to occur when there are other causes of thrombosis,
such as atherosclerosis in the elderly; therefore, screening widely
should not be encouraged.
Antifosfolipidni sindrom je autoimuno oboljenje koje se javlja
uglavnom kod mlađih žena. U serumu pacijenata se nalaze specifična
antitijela koja se nazivaju antifosfolipidna antitijela (često se nazivaju
aPL). Antifosfolipidna antitijela i lupus antikoagulans se nalaze kod
pacijenata sa autoimunim oboljenjima i posebno lupus eritematodesom. Kao najčešći simptomi antifosfolipidnog sindroma javljaju
se učestale tromboze, ponavljani pobačaji i trombocitopenija koji
su udruženi sa pojavom antifosfolipidnih antitijela i lupus antikoagulansa u serumu pacijenata. Najčešće se za detekciju ovih antitijela
koristi aCL (antikardiolipinska antitijela) esej, a to je esej za detekciju antikardiolipinskih antitijela, kojeg treba uvijek raditi uporedo sa detekcijom lupus antikoagulansa i beta 2 glikoproteina. Test
kojim se radi detekcija antikardiolipinskih antitijela ima značajnu
senzitivnost, ali ne i specifičnost, pa je značajno da kliničari tretiraju simptome kod pacijenta, a ne slučajno detektovana antitijela.
Postoji povezanost između titra antitijela i rizika od razvoja tromboze, što ne isključuje praćenje slabo pozitivnih rezultata. Lažno
pozitivne rezultate je iz tog razloga jako teško pratiti i interpretirati, posebno ukoliko postoji i tromboza kod starijih pacijenata sa
aterosklerozom; zato i nije preporučnjiv široki screening pacijenata.
Key words: antiphospholipid antibody syndrome, thrombosis, miscarriages, phospholipid antibodies, lupus anticoagulants
Ključne riječi: antifosfolipidni sindrom, tromboza, ponavljani
pobačaji, antifosfolipidna antitijela, lupus antikoagulans.
INTRODUCTION
Antiphospholipid antibody syndrome (commonly called antiphospholipid syndrome or APS) is an autoimmune disease present
mostly in young women. Antibodies that are found in the blood of
these patients are called anti-phospholipid autoantibodies (commonly called aPL). These autoantibodies interfere with coagulation,
leading to thrombosis. Patients can also experience the following
symptoms:
• neurological symptoms,
• chronic headaches, migraines, dementia and seizures,
• livedo reticularis on their wrists and knees,
• cardiovascular disease and
• thrombocytopenia
There are also some infrequent signs and symptoms, which may
include:
• Movement disorder, chorea,
• Cognitive problems,
8
M. Delić Šarac et al.
• Sudden hearing loss,
• Mental health problems, depression or psychosis
The damage caused by this clotting can vary depending on the
site of the clot. Repeated small clots in the heart can cause heart
valve thickening or damage, with the risk of releasing clots into the
blood, which can ultimately lead to an arterial embolism. aPL may
also be associated with heart attacks in young people without any
known cardiac risk factors. Blood clots in the arteries can lead
to heart attacks and strokes or pulmonary embolism. Blood clots
from aPL can occur anywhere in the circulation and can affect any
organ in the body. Clots forming in the veins most frequently occur
in the lower legs (1,2,3,4).
Patients with the antiphospholipid syndrome can have a specific
of antibodies. These antibodies include: VDRL/RPR (a syphilis test
that can be falsely positive in these patients), lupus anticoagulant,
prolonged PTT and cardiolipin antibody. As mentioned above, the
anticardiolipin antibody has also been found in patients with the
immune disease called systemic lupus erythematosus (5,6,7).
The cause of antiphospholipid syndrome is not completely
known. Antiphospholipid antibodies reduce the levels of annexin
V, a protein that binds phospholipids and has potent clot-blocking
(anticoagulant) activity.The reduction of annexin V levels is thought
to be a possible mechanism underlying the increased tendency of
blood to clot and the propensity to pregnancy loss, characteristic of the antiphospholipid syndrome. Antiphospholipid antibodies,
such as anticardiolipin, have also been associated with decreased
levels of prostacyclin that prevents the clumping of platelets. The
treatment of patients with anticardiolipin syndrome has substantially evolved, since they were discovered to be clinically important
in the mid-1980s. Each manifestation of the antiphospholipid syndrome, and each individual patient with the condition, is treated
uniquely. Because many of the features of illness with anticardiolipin syndrome are associated with an abnormal grouping of normal platelets, the treatment is often directed toward preventing
clotting. Patients with this disorder have an abnormal tendency to
thrombosis. Aanticoagulation treatment such as heparin and warfarin are used. Aspirin has an effect on platelets by inhibiting their
aggregation and has also been used in low doses. Cortisone-related
medications, such as prednisone, have been used to suppress the
immune activity and inflammation in patients with certain features
of the condition. For patients with systemic lupus erythematosus
who also have antiphospholipid syndrome, hydroxychloroquine
was shown to be effective in thrombosis (8,9,10).
Other reported treatments include; the use of intravenous
gamma globulin for selected patients with histories of premature
miscarriage and those with thrombocytopenia during pregnancy.
However, recent research studies, suggest that intravenous gamma
globulin may be no more effective than combination of aspirin and
heparin treatment.
The plasma membranes of mammalian cells are formed from
phospholipids. Phosphatidylserine is found on the cytoplasmic surface and phosphatidylcholine on the external surface. They both
participate in several important cellular functions including: exchanging metabolites across membranes, transferring molecular
signals and serving as a platform for the assembly of protein-lipid
complexes. During platelet-mediated blood coagulation, phosphatidylserine is translocated from the inner platelet membrane and
provides a surface for the assembly of the prothrombinase enzyme
complex that catalyzes the formation of thrombin. Complexes of
negatively charged phospholipids and endogenous plasma proteins
provide epitopes recognized by natural autoantibodies. Plasma
from normal individuals contains low concentrations of natural IgG
autoantibodies of moderate affinity. Pathologic levels of autoantibodies reflect loss of tolerance and increased production of antibodies. These autoantibodies are called phospholipid or cardiolipin
antibodies, when they are detected by immunoassays that employ
anionic phospholipids, as substrates (11,12,13).
The most commonly used phospholipid substrate is cardiolipin.
The autoantibodies react with epitopes of protein’s molecules that
associate noncovalently with reagent phospholipids. The best characterized phospholipid-binding protein is beta 2 glycoprotein 1 and
most immunoassays for phospholipid antibodies employ a composite substrate consisting of cardiolipin plus beta 2 glycoprotein 1(beta
2 GP1). Beta 2 GP1 is a 326 amino acid polypeptide that contains
5 homologous domains, each of them consisting of approximately
60 amino acids. Most phospholipid antibodies bind to an epitope
associated with domain 1 near the N-terminus. Autoantibodies can
also be detected by the use of functional, phospholipid-dependent
coagulation assays. Phospholipid antibodies detected by functional
assays are often called lupus anticoagulants, because they produce
prolongation of phospholipid-dependent clotting in vitro. Not all
phospholipid antibodies possess lupus anticoagulant activity. Only
those phospholipid antibodies that are capable of cross-linking beta
2 GP1 molecules can interact efficiently with phospholipid surfaces
in functional coagulation assays. It is hypothesized that complexes
formed in vivo between bivalent, natural autoantibodies and beta 2
GP1 bind to translocated, anionic phospholipid on activated platelets at sites of endothelial injury.This binding is believed to promote
further platelet activation that may lead to thrombosis. Phospholipid
antibodies occur in patients with a variety of clinical signs and symptoms such as: thrombosis (arterial or venous), pregnancy morbidity
(i.e. unexplained fetal death, premature birth, severe preeclampsia,
or placental insufficiency), unexplained cutaneous circulation disturbances (e.g. livido reticularis or pyoderma gangrenosum) thrombocytopenia or hemolytic anemia and nonbacterial thrombotic
endocarditis. Phospholipid antibodies and lupus anticoagulants are
found with increased frequency in patients with systemic rheumatic
diseases, especially lupus erythematosus. The term antiphospholipid
syndrome (APS) is used to describe the triad of thrombosis, recurrent fetal loss and thrombocytopenia accompanied by phospholipid
antibodies or a lupus anticoagulant (14,15).
APS is diagnosed when, at least one requirement, from both clinical
and laboratory criteria is met.
Clinical criteria include the following:
• Vascular thrombotic episodes in any tissue or organ and
• Pregnancy loss (≥1 unexplained loss of a normal fetus
beyond the 10th gestational week, ≥1 premature birth
before the 34th gestational week due to eclampsia or placental insufficiency or ≥3 spontaneous abortions before
the 10th gestational week)
Incidence of anticardiolipin antibodies evaluated by elisa method on hytec 288
Laboratory criteria include the following:
• Lupus anticoagulant (LA) present in serum,
• Anticardiolipin (aCL) antibody of immunoglobulin G (IgG)
and/or immunoglobulin M (IgM) isotype present in serum
(>40 GPL or MPL units or above the 99th percentile) and
• Anti–beta2 glycoprotein-I (b2-GPI) antibody of IgG and/or
IgM isotype (i.e. in titer above the 99th percentile) in serum
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Picture 1 HYTEC 288 instrument for ELISA assays
Although not included in the diagnostic criteria, other clinical
symptoms, such as: livedo reticularis, nephropathy, thrombocytopenia, cardiac valvular disease and neurological symptoms are commonly associated comorbidities (16).
MATERIALS AND METHODS
We analyzed serums of patients that were sent to department
of Immunology at Clinical Center University of Sarajevo (CCUS), in
period from 17.05.2013. to 30.11. 2013. These patients sera were
analyzed on Hytec 288. Hytec 288 is an automated immunoassay instrument for the performance of Allergy and Autoimmune antibody
testing, and for ELISA commercial or developed assays. It is specifically designed for increased productivity and enhanced efficiency.
The HYTEC 288 is compatible with many interface protocols and
provides quality control management. It also complies with FDA’s
Quality System Regulation, current International ISO Standards,
NCCLS guidelines and CE-mark guidelines (17,18,19).
For each patient, we analyzed separately anticardiolipin antibodies (i.e. IgG and IgM and beta 2 glycoprotein IgG and IgM). The results of anti cardiolipin assay can be used as aid in diagnosis of autoimmune diseases associated with elevated levels of anti-cardiolipin
antibodies, including anti-phospholipid syndrome. Levels of these
auto antibodies represent one indicator in a multi-facorial diagnostic regime. Anti cardiolipin and anti phosphatidyl serine antibodies,
along with others, such as Lupus Anticoagulant, belong to the family
of anti-phospholipid antibodies. Anticardiolipin antibodies are circulating serum antibodies often associated with recurrent arterial
and venous thromboembolism, recurrent fetal loss and thrombocytopenia. These symptoms are often present in cases of Systemic
Lupus Erithematodes (SLE) and in many other conditions, both of
an autoimmune and non-autoimmune nature. Some studies show
that over 50% of SLE patients have one or more classes of anti
cardiolipin antibodies. The presence of these antibodies serves as
a marker for the risk of a thromboembolic event. Those SLE patients exhibiting high levels of these auto antibodies are four times
more likely to experience such an event than those not expressing
the auto antibodies. Anti cardiolipin auto antibodies can be of any
combination of the IgM, IgA and IgG classes. IgG antibodies are the
most prevalent class of auto antibody and the class with the greatest clinical correlation. Samples found to have IgG levels in the “high
“ anti-cardiolipin band are the most likely to display overt clinical
symptoms. However, IgA and IgM auto antibodies are often found,
either alone or in association with the IgG class. Measurement of
all three classes is therefore recommended. Anti-cardiolipin are the
most commonly measured anti-phospholipid antibodies. It is known
that some patients with infectious diseases and other autoimmune
disorders show some antibody activity against cardiolipin (20).
Patients samples were collected in tubes with gel, and centrifuged on 3000 x15 minutes. After that process we collected sera of
the patients and prepared them for automatized ELISA assay. The
Autostat II assay for detection of auto antibodies is a solid phase
immunosorbent assay (ELISA), in which the analyte is indicated by
a color reaction of an enzyme and substrate. The Autostat II wells
are coated with purified antigen. On adding diluted serum to the
wells the antibodies present bind to the antigen. After incubating at
room temperature and washing away unbound material, horseradish peroxidase conjugated anti-IgG antibody is added, which binds
to the immobilized antibodies. Following further incubation and
washing, tetra methyl benzidine substrate (TMB) is added te each
well.The presence of the antigen antibody conjugate complex turns
the substrate to a dark blue color. Addition of the stop solution
turns the color to yellow. The color intensity is proportional to
the amount of autoantibodies present in the original serum sample.
Reference values of antiphospholipid antibodies were:
•
<10.0 GPL (negative),
•
10.0-14.9 GPL (borderline),
•
15.0-39.9 GPL (weakly positive),
•
40.0-79.9 GPL (positive),
•
or =80.0 GPL (strongly positive).
GPL refers to IgG Phospholipid Units. One GPL unit is 1 microgram of IgG antibody. Reference values apply to all ages.
RESULTS
We examined 158 serum samples of patients in the period from
30.01.2012. to 03.05.2012 at the Institute for Clinical Immunology
- Clinical Center University of Sarajevo. We analyzed 124 serum
samples of female and 34 male patients. The serum sample distribution was 78 percent of female and 22 percent of male patients.
Table1 Number of analyzed female and male samples
10
we analyzed the patients in this way, we have seen that the total
positive were 24 and 134 negative samples.
Table 3 Review of positive and negative samples
Figure 1 Percentage share of female and male patients
Of the total number of samples analyzed we had following
proportion of positive samples proportioned between female and
male patients: 71% (18 patients) of female patients and 29% of positive samples of male patients (6 patients).
Figure 4 The percentage share of positive antiphospholipid antibodies specific to the inclusion criteria for antiphospholipid
syndrome
Figure 2 The percentage share of positive samples of female
and male patients
When we analyzed separatel ACA IgG, ACA IgM, B2G IgG and B2G
IgM antibodies we noticed the following:
Table 2 Positive samples
Next, we analyzed which of the antibodies were most frequently positive in these samples, so we received the following results.
Among all the specific positive samples in female patients ACAM
was usually present, followed by B2GG and B2GM.
Table 4 Positive separate antibodies in female patients samples
We had the most positive samples in class ACA IgM, followed
by ACA IgG, B2G IgG and IgM B2G. The high proportion of positive ACA IgM can be attributed to the fact that the ACA IgM was
elevated in non-specific inflammatory changes of different etiology.
Figure 5 Percentage of positive separate antibodies in female
patients samples
We also measured ACAM and B2GM in male patients’ samples.
Figure 3 Percentage share of single positive
antiphospholipid antibodies
According to the criteria for the diagnosis of antiphospholipid
syndrome, it is necessary that one of the ACA and one of B2G is
positive in analyzed parallel series in interval of 12 weeks. When
Table 5 Positive separate antibodies in male patients samples
Incidence of anticardiolipin antibodies evaluated by elisa method on hytec 288
Figure 6 Percentage of positive separate antibodies in male
patients samples
DISCUSSION
We analyzed a total of 158 samples, of which 124 samples were
of female patients and 34 male patients. This proportion of female
patients fits in so far known data that is the higher proportion of
female patients in all autoimmune diseases such as antiphospholipid
syndrome. Additionally, the proportion of positive samples is also
on the female side.
Positive and strongly-positive results for IgG and IgM phospholipid (cardiolipin) antibodies (>40 GPL and/or >40 MPL) are diagnostic criteria for antiphospholipid syndrome (APS). Lower levels
of IgG and IgM phospholipid (cardiolipin) antibodies and antibodies of the IgA isotype may occur in patients with clinical signs of
APS but the results are not considered diagnostic. Phospholipid
(cardiolipin) antibodies must be detected on two or more occasions at least 12 weeks apart to fulfill the laboratory diagnostic
criteria for APS. Detection of phospholipid (cardiolipin) antibodies
is not affected by anticoagulant treatment. The immunoassay for
phospholipid (cardiolipin) antibodies does not distinguish between
autoantibodies and antibodies produced in response to infectious
agents or as epiphenomena following thrombosis. For this reason,
a single positive test result is not sufficient to meet accepted serologic criteria for the diagnosis of antiphospholipid syndrome (APS).
In 158 analyzed samples we had two cases of strongly positive results in female patients’ and the results were ACAG: 100, ACAM:
60, B2GG: 3,79 and B2GM: 34,38, and for other female patient we
had ACAG: 100, ACAM 60, B2GG 12,88 and for B2GM 12,39. Except of these laboratory results clinician should consider clinical
signs and symptoms in inclusion criteria for APS. The presence of
serum anticardiolipin (aCL) antibody without clinical symptoms does
not support a diagnosis of antiphospholipid syndrome (APS). A positive result supports the diagnosis only in the presence of thrombosis
or fetal loss.A higher aCL titer indicates more frequent clinical manifestations among individuals with APS.
Patients with primary or secondary APS may have a negative
aCL result but may be positive for LA or occasionally anti-B2GPI.
In APS the antibody titers correlate with the severity of the disease
in a patient group, it is established that in the low range of antibody
titers some patients have significant clinical disease: as the patients’
antibody level may fluctuate over time into the normal range and
11
may also fall at the time of thrombosis (23, 24,25), patient may not
be diagnosed with the syndrome. Recurrent thrombosis may even
occur at the time of a normalized aCL level (27,28,29).
The combined aCL and LA tests, although assumed to be highly
sensitive, are not specific. aCL are also found in infections (26) such
as hepatitis C (30,31,32), malaria, lyme disease, syphilis, and HIV;
leukemias and solid-organ malignancies; and frequently in alcoholic
cirrhosis. LA is also found in children with infections, such as varicella, in elderly patients, and in cases of drug reactions. Repeating
the test in 6 weeks may help in acute infections, as in this instance
the aPL are temporary. Elevated aCL levels are commonly found
in the elderly, and 51% of a well, medication-free nursing home
population with a mean age of 81 years was positive. Positive test
result (for aCL, LA, or both) for a person without clinical features
need not to be a false-positive result. APS does not appear to be
a uniform predilection to thrombosis but, rather, a spectrum of
severity that may depend not only on antibody isotype and titer
but also on antibody avidity and other “hits”, such as: activated
protein C resistance, smoking, oral contraceptive use, serum homocysteine level (the other prothrombotic state that can produce
arterial, venous, and cerebral sinus thrombosis), and acute factors
such as trauma or immobilization (33,34,35).
One of the most difficult clinical issues in APS is the lack of
specificity of the aCL for the diagnosis, leading to the possibility
of false-positive diagnoses, both obscuring the true diagnosis and
possibly leading to unnecessary anticoagulation. A clinically useful
increase in specificity can be achieved with a phospholipid-free
anti-B2GPI ELISA. We had 46 serum samples positive for ACAG
and 68 serum samples positive for ACAM, but most of these were
not specific enough because we had negative B2G values and we
could not determine their role in diagnosing APS. The aCL assay is
only one of the methods used to detect aPL, and the test should
be administered with the LA and anti-B2GPI assays. The aCL assay
is reasonably sensitive but not at all specific; therefore, clinicians
should treat the clinical state and not an incidentally found antibody. Although, there is an association between antibody titer
and risk of thrombosis, this is not a ground for ignoring or not
reporting weakly positive results. False-positive results that are difficult to interpret are particularly likely to occur when there are
other causes of thrombosis such as atherosclerosis in the elderly;
therefore, screening widely should not be encouraged (36,37,38).
CONCLUSION
Antiphospholipid syndrome is an autoimmune disease that is
recognized as very serious and not so rare condition. Diagnostics
of anticardiolipin antibodies is available and should be considered
in cases of recurrent thrombosis or recurrent fetal loss and miscarriages. It is also important to note that these antibodies are not
specific and they have large sensitivity so clinician must recognize
the syndrome and treat the patients with not accidentally higher
antibody levels.
Conflict of interest: none declared.
12
REFERENCES
1. Bevers EM, Comfurius P, Dekkers DW, Zwaal RF. Lipid translocation across the
plasma membrane of mammalian cells. Biochim Biophys Acta 1999;1439(3):317330.
2. Arnout J,Vermylen J. Current status and implications of autoimmune antiphospholipid antibodies in relation to thrombotc disease. J Thromb Haemost 2003;1(5):931942.
3. Proven A, Bartlett RP, Moder KG, Chang-Miller A, Cardel LK, Heit JA, et al. Clinical importance of positive test results for lupus anticoagulant and anticardiolipin
antibodies. Mayo Clin Proc 2004;79:467-475.
4. Wilson WW, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, et al. International consensus statement on preliminary classification criteria for definite
antiphospholipid syndrome. Arthritis Rheum 1999;42(7):1309-1311.
5. Fontaine MJ, Jacob GL, Nichols WL, et al. Comparative evaluation of three assays
for anti-cardiolipin antibodies. J Autoimmun 2000;15(2):A56.
6. Favaloro EJ, Wong RC, Silvertrini R, McEvoy R, Jovanovich S, Roberts-Thomson P.
A multilaboratory peer assessment quality assurance program-based evaluation of
anticardiolipin antibody, and beta 2 glycoprotein 1 antibody testing. Semin Thromb
Hemost 2005;31(1):73-84.
7. Harris EN. Special report.The Second International Anti-cardiolipin Standardization
Workshop/the Kingston Anti-Phospholipid Antibody Study (KAPS) group. Am J
Clin Pathol 1990;94(4):476-84.
8. Wong RC, Gillis D, Adelstein S, Baumgart K, Favaloro EJ, Hendle MJ, et al. Consensus guidelines on anti-cardiolipin antibody testing and reporting. Pathology
2004;36(1):63-8.
9. Lakos G, Favaloro EJ, Harris EN, Meroni PL,Tincani A,Wong RC, et al. International
consensus guidelines on anticardiolipin and anti-ß2-glycoprotein I testing: report
from the 13th International Congress on Antiphospholipid Antibodies. Arthritis
Rheum 2012;64(1):1-10.
10. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite
antiphospholipid syndrome (APS). J Thromb Haemost 2006;4(2):295-306.
11. Caronti B, Calderaro C, Alessandri C, Conti F, Tinghino R, Palladini G, et al. Beta
2 glycoprotein 1 (beta 2 GP1) mRNA is expressed by several cell types involved in anti-phospholipid syndrome-related tissue damage. Clin Exp Immunol
1999;115:214-219
12. Lozier J, Takahashi N, Putnam F. Complete amino acid sequence of human plasma
beta 2 glycoprotein 1. Proc Natl Acad Sci USA 1984;81:3640-3644.
13. Kra-Oz Z, Lorber M, Shoenfeld Y, Scharff Y. Inhibitor(s) of natural anti-cardiolipin
autoantibodies. Clin Exp Immunol 1993;93(2):265-268.
14. Audrain Ma, El-Kouri D, Hamidou MA, Mioche L, Ibara A, Langlois ML, et al. Value
of autoantibodies to beta(2)-glycoprotein 1 in the diagnosis of antiphospholipid
syndrome. Rheumatology (Oxford) 2002;41(5):550-553.
15. Wong RCW, Flavaloro EJ, Adelstein S, Baumgart K, Bird R, Brighton TA, et al. Consensus guidelines on anti-beta 2 glycoprotein I testing and reporting. Pathology
2008;40(1):58-63.
16. Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet 2010;376(9751):1498-1509.
17. Kumar,Vinay, Abul K. Abbas, Nelson Fausto, Stanley L. Cotran. In: Robbins, Ramzi S.
Robbins and Cotran Pathologic Basis of Disease. Philadelphia: Elsevier Saunders;
2005.
18. Arnout J, Vermylen J. Current status and implications of autoimmune antiphospholipid antibodies in relation to thrombotic disease. J Thromb Haemost
2003;1(5):931-42.
19. Lockshin MD. Pregnancy loss and antiphospholipid antibodies. Lupus 1998;7 (Suppl
2):S86-9.
20. Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al.Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease
expression in a cohort of 1,000 patients. Arthritis Rheum 2002;46(4):1019-27.
21. Reisner SA, Brenner B, Haim N, Edoute Y, Markiewicz W. Echocardiography in
nonbacterial thrombotic endocarditis: from autopsy to clinical entity. J Am Soc
Echocardiogr 2000;13(9):876-81.
22. Gharavi AE, Harris EN, Asherson RA, Hughes GRV. Anticardiolipin antibody isotype
distribution and phospholipid specificity. Ann Rheum Dis 1987;46(1):1-6.
23. Molina JF, Gutierrez-Urena S, Molina J, Uribe O, Richards S, De Ceulaer C, et al.Variability of anticardiolipin antibody isotype distribution in 3 geographic populations
of patients with systemic lupus erythematosus. J Rheumatol 1997;24(2):291-6.
24. Harris EN, Chan JK, Asherson RA, Aber VR, Gharavi AE, Hughes GR. Thrombosis,
recurrent fetal loss, and thrombocytopenia. Predictive value of the anticardiolipin
antibody test. Arch Intern Med 1986;146(11):2153-6.
25. Pierangeli SS, Harris EN. A quarter of a century in anticardiolipin antibody testing
and attempted standardization has led us to here, which is? Semin Thromb Hemost
2008;34(4):313-28.
26. Agopian MS, Boctor FN, Peter JB. False-positive test result for IgM anticardiolipin
antibody due to IgM rheumatoid factor. Arthritis Rheum 1988;31(9):1212-3.
27. Favaloro EJ, Wong RC, Silvestrini R, McEvoy R, Jovanovich S, Roberts-Thomson P.
A multilaboratory peer assessment quality assurance program-based evaluation of
anticardiolipin antibody, and beta2-glycoprotein I antibody testing. Semin Thromb
Hemost 2005;31(1):73-84.
28. Cabiedes J, Cabral AR, Alarcon-Segovia D. Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more
strongly with anti-β2-glycoprotein-I than with antiphospholipid antibodies. J Rheumatol 1995; 22(10):1899–1906.
29. Drenkard C, Sanchez-Guerrero J, Alarcon-Segovia D. Fall in antiphospholipid antibody at time of thromboocclusive episodes in systemic lupus erythematosus. J
Rheumatol 1989;16(5):614–617.
30. Drouvalakis KA, Buchanan RR. Phospholipid specificity of autoimmune and drug
induced lupus anticoagulants; association of phosphatidylethanolamine reactivity
with thrombosis in autoimmune disease. J Rheumatol 1998;25(2):290–295.
31. Escalante A, Brey RL, Mitchell BD, Dreiner U. Accuracy of anticardiolipin antibodies
in identifying a history of thrombosis among patients with systemic lupus erythematosus. Am J Med 1995;98(6):559–565.
32. Hunt JE, McNeil HP, Morgan GJ, Crameri RM, Krilis SA. A phospholipid-β2glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in
autoimmune disease but not with infection. Lupus 1992;1(2):75–81.
33. Jude B, Goudemand J, Dolle I, Caron C, Watel A, Tiry C, Cosson A. Lupus anticoagulant: a clinical and laboratory study of 100 cases. Clin Lab Haematol 1988;
10(1):41–51.
34. Schousboe I. β2-Glycoprotein I: a plasma inhibitor of the contact activation of the
intrinsic blood coagulation pathway. Blood 1985;66(5):1086–1091.
35. Schulman S, Svenungsson E, Granqvist S. Anticardiolipin antibodies predict early
recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med. 1998;104(4):332–338.
36. Vlachoyiannopoulos PG, Petrovas C, Tektonidou M, Krilis S, Moutsopoulos HM.
Antibodies to β2-glycoprotein-I: urea resistance, binding specificity and association
with thrombosis. J Clin Immunol 1999;18(6):380–391.
37. Willems GM, Janssen MP, Pelsers MM, Comfurius P, Galli M, Zwaal RF, Bevers
EM. Role of divalency in the high-affinity binding of anticardiolipin antibody-β2glycoprotein I complexes to lipid membranes. Biochemistry 1996; 35(43):13833-42.
38. Cacoub P, Musset L, Amoura Z, Guilani P, Chabre H, Lunel F, Poynard T, Opolon
P, Piette JC. Anticardiolipin, anti-β2-glycoprotein I, and antinucleosome antibodies in hepatitis C virus infection and mixed cryoglobulinemia. J Rheumatol 1997;
24(11):2139–2144.
Reprint requests and correspondence:
Marina Delić-Šarac, MD
Department for Clinical Immunology
Bolnička 25, 71000 Sarajevo
Phone: +387 33 297 000
Email: marina772003@hotmail.com
Original article
Appearance of N-metastases in presence of peritumoral lymphovascular infiltration at lung cancer
Pojava N-metastaza u prisustvu peritumoralne limfovaskularne infiltracije kod karcinoma pluća
Kemal Grbić1*, Safet Guska1, Alma Alihodžić-Pašalić1, Alen Pilav1, Ferid Krupić2
Clinic of Thoracic Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; 2Department of Orthopaedics,
Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
1
ABSTRACT
SAŽETAK
Basic charesteristic of epithelical lung cancer is possibility of
early lymphatic spreading or in other words intaking of regional
lymphic nodes, which statistically proved represents the most significant individual prognostic factor of therapeutic result and survival of those who are suffering from it, and in pre operational
stage it is a possibility or limitation of resectional treatment. Aim
of work is analysis of frequences of peritumoral lymphovascular infiltration and its possible influence on more frequent appearence of
N- metastases at lung cancer. Retrospective research has included
239 surgicaly treated patients at Clinic for Thoracic Surgery CCU
Sarajevo in period from 01.01.2010. to 01.01.2013. with pre diagnosed lung cancer. Datas were collected from the existing medical documentation, including definite pathohistological tests which
contein presence/absence of peritumoral lymphovascular infiltration and status of lymphic nodes, and according to present TNM
classification. Average age of hospitalized patients is 62.72± 7.68
years, where is proportion in relation to gender 3.8:1 on behalf of
men. Statistically there is significant difference of age in relation to
gender at those who suffer, where patients of male gender in relation to female gender are in average older ( t-student test=2.12 and
p<0.03517). Presence of PLV infiltration was evidented in 68.2%
cases. Malignant negative nodes (N0) were 56,1%, N1-positive were
38,9%, while N2 nodes were caught in 5,0% cases. At pathohistologically proved N0 cases peritumoral lymphovascular infiltration
is present at 46,3% patients (χ2=3.25; p>0.07). At patohistologically proved lymphic nodes (N1,N2) , peritumoral lymphovascular
infiltration is present at 96.2% patients (χ2=0.29; p<0.0000019481).
Conclusion: Significantly greater representation of peritumoral
lymphovascular infiltration, and significant connection of existing of
the same and intaking of regional lymphic nodes.
Bazna osobina epitelnog plućnog karcinoma je mogućnost
ranog limfogenog širenja, odnosno zahvaćenost regionalnih limfnih
čvorova, koji statistički dokazanao, predstavljaju najbitniji pojedinačni
prognostički faktor terapijskog ishoda i preživljavanja oboljelih, a u
preoperativnom stejdžingu mogućnost, odnosno limitiranost resekcionog tretmana. Analiza učestalosti peritumoralne limfovaskularne
infiltracije i njenog mogućeg uticaja na češću pojavu N-metastaza kod
plućnog karcinoma. Pacijenti i metode: Retrospektivno istraživanje je
obuhvatilo 239 hiruški tretiranih pacijenata na Klinici za torakalnu
hirurgiju KCU Sarajevo u periodu od 01.01.2010 do 01.01.2013 godine sa prethodno dijagnostikovanim plućnim karcinomom. Podaci
su prikupljeni iz postojeće medicinske dokumentacije, uključujući
definitivne patohistološke nalaze koji sadrže prisustvo/odsustvo
peritumoralne limfovaskularne infiltracije i status limfnih čvorova,
a prema važećoj TNM-klasifikaciji. Prosječna starost hospitaliziranih
pacijenata je bila 62.72±7.68 godina, gdje je omjer u odnosu na spol
3.8:1 u korist muškaraca. Statistički postoji značajna razlika starosne
dobi u odnosu na spol kod oboljelih, pri čemu su osobe muškog
u odnosu na osobe ženskog spola, prosječno starije životne dobi
(t – Student test = 2.12 i p < 0.03517). Prisustvo PLV infiltracije je
evidentirano u 68.2% slučajeva. Maligno negativnih nodusa (N0) je
bilo 56.1%, N1-pozitivnih 38.9% , dok su N2 nodusi zahvaćeni u
5.0% slučajeva. Kod patohistološki potvrđenih N0 slučajeva peritumoralna limfovaskularna infiltracija je prisutna kod 46.3% pacijenata
(χ22=3.25; p>0.07). Od ukupnog broja metastatskih promjenjenih
limfnih nodusa (N1,N2), peritumoralna limfovaskularna infiltracija je
prisutna kod 96.2% slučajeva (χ22=0.99; p<0.0000019481).
Zaključak: Znatno veća zastupljenost peritumoralne limfovaskularne
infiltracije, te bitna veza postojanja iste i zahvaćenosti regionalnih limfnih čvorova.
Key words: lung cancer, peritumoral lymphovascular infiltration,
N metastases
Ključne riječi: karcinom pluća, peritumoralna limfovaskularna infiltracija, N metastaze
INTRODUCTION
cially in undeveloped countries, and with move of border of age to
younger life age and those of female gender. According to the newest data of American Cancer Society, there is more than 170.000 of
new diagnosed cases anually in the USA (1,2,3).
Lung cancer presents significant health problem nowadays , with
permanent increase of incidence of morbidity and mortality espe-
14
Anaplastically changed station of lung cancer leads to loss of
morphofunctional organisation of neoplastical tissue, with great authonomy of malignant station, which are not linked as in a normal
tissue, and it gives them possibility to perfore basal membrane and
to get access to blood and lymph vessels , and what is a good predisposition to further spreading of cancer and building of secondary deposits (4). Intaking of dreinagal regional lymph nodes with
metastases is manifesting with their increase which is preoperationally discovered most frequently by CT scaning of thorax, or by
postoperationally with definite pathohistological tests (4,5). Analysis of international base of data from The International Association
for the Study of Lung Cancer- IASLC shows that so far existing descriptors represent the most significant individual factor in relation
to survival of those who suffer from lung cancer (Table 1) (3,6,7,8).
K. Grbić et al.
datas of relevant researches which are presented in today referent
literature with presentation of discussion and comments.
RESULTS
Table 1 Rate of survival at NSCLC on the base of pathologic
analysis of lymph nodes (comparison between 6th and 7th
TNM classification)
In period from 01.01.2010. to 01.01.2013. at Clinic for Thoracic
Surgery CCUS in total of 239 patients under diagnosis of lung cancer were treated with some of resectional operations. Average
age of all hospitalized patients was 62.72± 7.68 years. From the
total number of patients 79.08 % (189/239) were men, and 20.92%
(50/239) were women while proportion was 3.8 : 1 (189/50) for
men. Average age for male patients was 63.46± 7.67 (from 42 to
84) and for female 59.94± 7.86 (from 21 to 80) years. Statistically
there is significant difference of age in relation to gender of patients
who suffer from lung cancer (t- Student = 2.12; p< 0.035) while
patients of male gender in relation to female gender are in average
older. State of regional lymphic nodes (of N- disease) at anylized
patients is shown on Figure 1.
The aim of work is to make evidence of frequency of appearence
of peritumoral lymphovascular infiltration, intaking of regional lymphic nodes and to anylise possible connection of the mentioned
variables, and their statistical significance.
Figure 1 Representation of N- disease at patients who suffer
from lung cancer.
This work has analised all surgically treated patients who were
hospitalised at Clinic for Thoracic Surgery CCUS (Clinical Center
University of Sarajevo) with diagnossis of lung cancer in period
from 01.01.2010. to 01.01.2013. Research has included 239 patients of all ages both genders. The patients who were undergone
explorative thoracotomy were excluded. Research is retrospective,
clinically-manipulative and descriptivlly-analitical. For each patient
there is a record of workup of definite datas from existing history of diseases. Pahtohistilogical workup of unloaded operational
preparations was done at Department for Pathology CCUS. Definitive pathohistological diagnosis in minimum consisted from: sort,
size and degree of differentation of cancer, presence/absence of
peritumoral lymphovascular (PLV) infiltration and status of lymph
nodes (N0, N1 and N2). Results are demonstrated in texts, in numerals , in charts and in graphics. Statistical workup was done on
PC in functions of MS Excel programme by applying coresponding
statistical methods. Parametric datas were done by demonstration of absolute and procentual values, arithmetic mean was done
by counting standard deviation and t- Student test in relation to
set variables, while nonparametrical datas were done by chi-square
test. Define level of significance is p< 0.05. There are also defined
own results and there was done comparison of these results with
The most representative patients were those without presence
of malignant cells in lymphic nodes (N0), with share of 56.06%
(134/239), while presence of N metastases is found at 43.94%
(105/239) of those who suffer, where N1 level is intaken with
38.91% (93/105), and N2 with 5.03% (12/105) of secondary deposit of primary disease.
Frequency of peritumoral lymphovascular infiltration of patients in
total is shown on Figure 2.
Figure 2 Representation of peritumoral lymphovascular
infiltration.
Peritumoral lymphovascular infiltration at patients who suffer
from lung cancer is represented at 68.20%(163/239) cases, while at
31.80% (76/239) it did not exist.
Appearance of N metastases in presence of peritumoral lymphovascular infiltration at lung cancer
Figure 3. shows cumulative relation of states of lymphic nodes and
existance of lymphovascular peritumoral infiltration of lung cancer.
15
Table 3. shows data on whose base thr relative risk of appearence
of N metastasis in relation to PLV infiltration was worked out.
Table 3 Diagram of frequency of appearence of N metastases
in relation to lymphovascular peritumoral infiltration
Figure 3 Relation of state of lymphic nodes and existance of
PLV infiltration
At case with negative lymphic nodes (N0) (134/239), lymphovascular peritumoral infiltration was present at 46.27% (62/134) while
at 53.73% (72/134) cases it was absent while the mentioned difference is not statistically significant (chi-square test=3.25; p>0.07).
From the total number of N1 metastases 95.70% (89/93) case had
presence of lymphovascular infiltration, while only 4.30% (4/93)
case did not have it. At intaking of N2 level of secondary deposit,
lymphovascular infiltration was present at 100% of cases. Statistically there is a significant difference in intaking of lymphic nodes in
relation to existance of PLV infiltration (chi-square test=0.99; p<
0.00000000000000019).
Sensitivity, specifity, positive and negative predictive value of peritumoral lymphovascular infiltration in relation to frequency of appearance of N metastases are counted on the base of data given
in the Table 2.ž
Table 2 Diagram of frequency of appearance of N metastases
in relation to lymphovascular peritumoral infiltraton.
Sensitivity is defined as proportion or procentage of intaken
lymphic nodes at existance of peritumoral lymphovascular infiltration and equals 96.1%. Specifity is defined as proportion or
procentage of lymphic nodes which are not intaken in relation to
existing peritumoral lymphovascular infiltration and equals 53.7%.
PPV (positive predictable value) is defined as proportion of intaken
lymphic nodes at existance of peritumoral lymphovascular infiltration and equals 61.9%. NPV (negative predictable value) is proportion pf patients who do not have intaking of lymphic nodes and
where there is no existance of peritumoral lymphovascular infiltration and it equals 94.7%.
Risk among positives : 101/4=25.2 (risk of coming into being of
metastasis in lymph nodes at patient with presence of PLV infiltration). Risk among negatives:62/72=0.86 (risk of coming into being
of metastasis in lymph nodes at patients where there is no presence of PLV infiltration). Total relative risk 101/4 : 62/72 =29.3 (risk
of coming into being of metastasis in lymph nodes at patients with
presence of PLV infiltration).
DISCUSSION
Lung cancer is definitely becomming the most frequent diagnosed malignic disease all over the world and is leading cause of
cancers linked to mortality at women the same as men. It represents fatal disease with in the USA so far the highest noted rate
of 5-years period survival of 14%, while in Europe similar as in
the rest of the developed world the rate is about 8% (1,3,9). The
most important surgical prognistic factor in curing lung cancer is
state of lymphic nodes of mediastinumwhish significantly influence
survival of five years period for patients with this disease (Table 1)
(3,6,7,8,9).
It was shown that presence of N1 disease significantly influence
on survival of 5-years period while it was noted that the same
depends of the number of N1 lymphic nodes which were intaken.
Presence of N2 disease is still subject of many discussions whose
results is that majority of surgens and oncoligists decide to choose
combined access to disease (6,7,8,10).
Within period from 01.01.2010. to 01.01 2013. at Clinic for
Thoracic Surgery CCUS, total of 239 patients with diagnosis of
lung cancer were undergone some of resectional operations. From
total number of patients , lung cuncer was diagnosed at 79.08%
(189/239) patients of male gender and 20.92% (50/239) at patients
of female gender, while the proportion was 3.8:1 for men. Given
data are corresponding to reports collected from relevant and accessable literature where there is mentioned similar proportion
(3-5 : 1) of appearance of lung cancer among male and female
gender (1,9,11). Average age of all hospitalised patients was 62.72±
7.68 (from 21 to 84) years. This detail shows a little bit lower age
of patients analised in this work in relation to date from available
literature where there is mentioned that frequency of appearence
of lung cancer in the USA has its peak among patients older than
70 years. The mentioned difference in frequency of appearence of
lung cancer in relation to age, among the data worked out in this
16
work and in available literature is most possibly partly result of the
fact that in this work we only analised patients who were surgically
treated, while in literature the data are related to the total number of patients who suffer from lung cancer. We should also bear in
mind the fact that the average length of life in developed countries
is longer (1,9,11). Average age for men was 63.46± 7.67 (from 42
to 84), and for women 59.94± 7.86 (from 21 to 80) years. It was
calculated that statistically there is a significant difference (p<0.035)
in average age in relation to gender while male gender is statistically older in relation to female gender what is relevant to majority of
literal reports (1,3,11). Analysis od definite pathohistological tests
showed that the intaking og regional lymphic nodes in metastases
of primary disease (Ndisease) was 43.94% (105/239), from which
in level N1 there was 38.92% (93/105), and in N2 5.03% (12/105)of
secondary deposit. The most representative patients were those
without presence of malignic cells in lymphic nodes (N0) with participation of 56.06% (134/239). These data are comparativly identical to data available in medical literature (6,7,12,13,14). From the
total number of analized patients peritumoral lymphovascular infiltration is present at 68.20% (163/239) what leads to the conclusion that infiltration of basal membrane is present in about 2/3
of cases and it proves the fact of high potential of metastasing of
epithel lung malignom. The mentioned fact is proved also on the
base of the fact that from total number of metastatically changed
lymph nodes (N1,N2), peritumoral lymphovascular infiltration was
present at 96.19% (101/105) of cases (5,6,7,13,14).
At pathologicaly proved N1 cases (93/239), PLV infiltration was
present at 95.70% (89/93), while at N2 cases (12/239) PLV infiltration is present at all patients 100% (12/12). On the base of earlier
shown results it was worked out that there is statistically significant relation (chi- square test = 0.99; p< 0.00000000000000019) of
intaking of lymph nodes in relation to existance of PLV infiltration.
At pathohistologically proved N0 cases (134/239), PLV infiltration was present at 46.27% (62/134). From the above mentioned
we come to the conclusion that at non-existing of N disease there
is significantly less part of existance of PLV infiltration, and that
also at existance of the same it is not rule that there must be the
appearence of N1 and N2 metastasis. (5,12,13,14) Relation between non-existing of N disease and existance of PLV infiltration
is not statistically significant (chi–square test =3.25; p>0.07). The
calculated sensitivity (96.1%), specificity (53.7%), positive (61.9%)
and negative predictive value (94.7%) the same as total relative
risk which shows that there is a chance of intaking of lymph nodes
nearly 30 times higher at presence of PLV infiltration and they can
also be indirect indicators of dependency of mentioned variables
and predictors of limitation of theraupetic treatment and postresectional survival.
CONCLUSION
Presence of peritumoral lymphovascular infiltration in more
than 2/3 of postresectional definite pathohistological tests, leads to
the fact that there is statistically significant connection between the
mentioned charateristic of lung cancer and frequency of regional
lymphonodular metastatic invasion.
K. Grbić et al.
REFERENCES
1. American Cancer Society. Cancer Facts and Figures 2009.
2. Guska S. Osnovni principi savremene torakohiruške prakse, Medicinski fakultet Sarajevo. Sarajevo; 2012:55-57.
3. European mortality database - MDB, WHO Regional Office for Europe, Copenhagen, Denmark, 2010;http://data.euro.who.int/hfadb-pristupljeno: juli.2013.
4. Shields TW. Pathology of Carcinoma of the Lung. In: General Thoracic Surgery. Lippincott Williams and Wilkins. 2005;6(2):455-480.
5. Heerma van Voss MR, van der Groep P, Bart J, van der Wall E, van Diest. Lymphovascular invasion in BRCA related breast cancer compared to sporadic controls. BMC
Cancer 2010; (10):145.
6. Saeed M, Dilip O, Yalda A, Andrea C, Erwin JR van Beek E. Tth lung cancer TNM
classification and staging system: Review of the changes and implications. World J
Radiol 2012;28;4(4):128-134.
7. Gurleyik G, Aker F, Aktekin A, Saglam A. Tumor characteristics influencing non-sentinel lymph node involvement in clinically node negative patients with breast cancer.
J Breast Cancer 2011;14(2):124-128.
8. De la Guerra A. New TNM Classification for Lung Cancer. Part II:A review. Doctors
Lounge Website. Dostupno na: http://www.doctorslounge.com/index.php/ articles/
page/342. Pristupljeno: juli. 2013.
9. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, eds.World Health Organisation classification of tumours. Tumours of the lung, pleura and heart. Lyon:
IARC Press 2004;3: 778-791.
10. Rami-Porta R, Crowley JJ, Goldstraw P. The Revised TNM Staging System for Lung
Cancer. Ann Thorac Cardiovasc Surg 2009;(1):4-9.
11. Mostertz W, Stevenson M, Acharya C, Chan I, Walters K, Lamlertthon W, et
al. Age and sex specific genomic profiles in non-small cell lung cancer. JAMA
2010;303(6):535-43.
12. Bačić I. i sur. Retrospektivni prikaz kirurškog liječenja primarnog karcinoma pluća.
Med Jad 2007;37(3–4):77-79.
13. Gurleyik G, Aker F, Aktekin A, Saglam A. Tumor characteristics influencing non –
sentinel lymph node involvement in clinically node negative patients with breast
cancer. J Breast Cancer. 2011;14(2):124-128.
14. Marra A, Hillejan L, Zaboura G, Fujimoto T, Greschuchna D, Stamatis G.Pathologic
N1 non – small cell lung cancer: Correlation between pattern of lymphatic spread
and prognosis. J Thorac Cardiovasc Surg 2003;125:543-553.
Kemal Grbić, MD
Clinic of Thoracic Surgery
Phone: + 387 33 297 000
Email: kemal_grbic@hotmail.com
Appearance of N metastases in presence of peritumoral lymphovascular infiltration at lung cancer
Our contribution to the reduction of cardiovascular disease in Bosnia and Herzegovina!
Naš prilog redukciji kardiovaskularnih bolesti u Bosni i Hercegovini!
17
Original article
The usefulness of penile compression-release index
for diagnosing bladder outlet obstruction in patients
with benign prostatic enlargement
Korisnost indeksa penilne kompresije-otpuštanja u
dijagnozi opstrukcije bešičnog izlaza kod pacijenata sa
benignim prostatičnim uvećanjem
Damir Aganović*1, Alden Prcić1, Munira Hasanbegović1, Osman Hadžiosmanović1,
Hajrudin Spahović2
1
Clinic of Urology, University Clinical Centre Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 2General Hospital Sarajevo “Prim.dr. Abdulah
Nakaš”, 71000 Sarajevo, Bosnia and Herzegovina
ABSTRACT
SAŽETAK
Objective: to determine the discriminatory power of penile urethral compression-release (PCR) index for the detection of bladder
outlet obstruction and the associated bladder abnormality in patients
with benign prostatic enlargement (BPE). Material and methods: 135
patients with proven BPE from daily urological practice underwent
urodynamic measurement (UDM) and PCR maneuver. PCR Index
was calculated following the formula: PCRI = (Qs-Qss/Qss) x 100
(%).UDM results were plotted on Schafer and URA nomograms. Results: High sensitivity and specificity have been shown (74% and 94%,
respectively), as well as positive predictive value (93%) of PCR index
(PCRI) in diagnosing infravesical obstruction with cut-off point of
96%. PCRI clearly distinguishes obstructed patients with normocontractile detrusor and the presence of detrusor overactivity (161%
and 187%, respectively) versus those unobstructed (PCRI=63%) or
obstructed patients with detrusor underactivity (DUA; PCRI=83%).
Further on, there is a statistically significant difference between obstructed patients with DUA and those unobstructed (ANOVA test;
F=3.8; p=0.03). Conclusion: PCRI is a very good noninvasive urodynamic test for group-wise detection of bladder outlet obstruction in
patients with BPE. The understanding and application of this index
can serve as a good transition toward introducing penile cuff test in
daily urological practice.
Cilj: odrediti diskriminantnu moć Indexa penilne kompresijeotpuštanja (PCRI) u detekciji opstrukcije bešičnog izlaza kod pacijenata sa benignim prostatičnim uvećanjem (BPU). Materijali i metode: 135 pacijenata sa dokazanim BPU iz svakodnevne urološke
prakse podvrgnuto je urodinamskom mjerenju (UDM) i PCR manevru. PCR Indeks je izračunat prema formuli: PCRI= (Qs-Qss/
Qss) x 100 (izraženo u procentima). Rezultati UDM su plotirani
na Schafferov i URA nomogram. Rezultati: Pokazana je visoka senzitivnost i specifičnost (74% i 94%, odnosno), te pozitivna prediktivna vrijednost (93%) PCR indeksa u dijagnozi infravezikalne opstrukcije, sa graničnom vrijednošću od 96%. PCRI jasno razdvaja
pacijente u opstrukciji sa normokontraktilnim detruzorom i postojanjem detruzorske hiperaktivnosti (161% i 187%, odnosno) u
odnosu na pacijente van opstrukcije (PCRI=63%) ili u opstrukciji
sa detruzorskom hipokontraktilnošću (DUA; PCRI=83%). Nadalje,
postoji statistički signifikantna razlika između pacijenata sa DUA
u opstrukciji u odnosu na pacijente van opstrukcije (ANOVA
test; F=3, 8; p=0,03). Zaključak: PCR indeks predstavlja veoma dobar neinvazivni urodinamski test u grupnoj detekciji opstrukcije
bešičnog izlaza kod pacijenata sa BPU. Shvatanje i aplikacija ovoga
indeksa služe kao dobar prelaz prema uvođenju testa sa penilnom
manžetnom u svakodnevnu urološku praksu.
Key words: benign prostatic enlargement, bladder outlet obstruction, non invasive urodynamics
Ključne riječi: benigno uvećanje prostate, opstrukcija bešičnog
izlaza, neinvazivna urodinamika
INTRODUCTION
in the diagnosis of this disease, but from the therapy optimization
perspective it is very important to prove bladder outlet obstruction (infravesical obstruction). In patients with LUTS and suspected
bladder outlet obstruction, the obstruction is urodynamically proven only in 50% to 66% of cases (1).
Benign prostatic enlargement (BPE) is an aging disease, causing
considerable deterioration in quality of life, expressed by lower
urinary tract symptoms (LUTS). There are a number of algorithms
The usefulness of penile compression-release index for diagnosing bladder outlet obstruction in patients with benign
prostatic enlargement
Uroflowmetry is an additional test for diagnosing the disease,
but it is not sufficiently sensitive or specific since a low flow is
not necessarily caused by the obstruction, it can also be caused
by detrusor underactivity (DUA) (2). For the time being, pressureflow studies (PFS) are the only method for an accurate diagnosis of
infravesical obstruction. This urodynamic test is reliable, reproducible, but also time-consuming and invasive, causing discomfort and
pain to patients. This is why numerous noninvasive techniques have
been developed and validated, including penile compression-release
index, condom catheter method, and penile cuff technique (3), to
replace invasive testing. The penile urethral compression-release
(PCR) maneuver is a test which determines a possible infravesical
obstruction by a simple gradual squeezing of penile urethra during urination (4). The theory is based on isobaric conduit (bladder
and urethra) and the generation of isovolumetric detrusor pressure, when flow rate reduction amounts to zero, i.e. when the flow
stops completely. The flow generated after the release maneuver
represents surge flow (Qs), and once the flow has stabilized, quasi
steady-state flow appears (Qss) (Figure 1). PCR index is determined from these reference points. In such a way, it is possible to
distinguish, with a high discrimination value, between obstructed
patients and those unobstructed; however, there are difficulties in
diagnosing unobstructed patients with DUA or another bladder
abnormality. This is why this prospective study was conducted – to
examine the sensitivity of this parameter in patients with BPE accompanied by the above-mentioned abnormalities. The difference
in PCR index in obstructed patients was specifically focused on,
depending on the presence of detrusor overactivity (DO).
Figure 1 Uroflow examination. After PCR maneuver, high
Qsurge was reached. After the stabilization of the flow, steadystate flow emerged (Qss=7,8 ml/sec.). Patient is in the region
of clear defined obstruction (URA= 39 cmH2O), with normal
contractility of detrusor. PCRI= 117%. Qsurge (Qs)=17 ml/sec,
steady-state flow (Qss)=7.8 ml/sec.
During the period 2011-2013, the prospective study was carried
out on 140 patients with lower urinary tract symptoms (LUTS)
due to BPE at the Urology Clinic of the Sarajevo University Hospital. Finally, 135 patients were covered by the analysis. The exclusion
criteria were all conditions, illnesses, neurological abnormalities
19
and medication that could interfere with the act of micturition.The
transabdominal ultrasound (TAUS) determined the patients’ prostate volume, as well as intravesical protrusion of the prostate (IPP)
at the bladder volume of 150-200 ml.The intravesical prostatic protrusion (IPP) and bladder wall thickness (BWT) were measured
applying standard methodology described elsewhere (5, 6). The patients completed International Prostatic Symptom Score (IPSS) and
signed the Informed Consent Form. After that, it was explained to
the patients how the penile compression-release (PCR) maneuver
is performed. During the examination of flow, once the urinary
stream started, the patient should gradually squeeze the penis to
abort the flow with complete relaxation of the pelvic floor. After 2-3 seconds, the patient released the compressed urethra and
voiding was continued till the end. Two main points were taken;
surge flow after releasing the urethra (marked as the reference
point Qs), and the second point was taken when the flow was
stabilized (marked as the reference point of the steady-state flow
- Qss). PCR Index was calculated for each patient, following the
formula: PCRI = (Qs-Qss/Qss) x 100. The index was expressed
as a percentage (4). Patients with the voided volume of less than
150 ml during PCR testing were excluded because of proven poor
reliability (7). The next day, the patients underwent conventional
urodynamic studies (UDS) using the Andromeda Ellipse 4 apparatus. Urodynamic studies were done according to the “good urodynamic practices” by the International Continence Society (ICS)
(8). Then, the findings of pressure/flow studies (PFS) were plotted
on the Schafer obstruction class nomogram (9) and URA-group
specific urethral resistance factor (10). Each patient had their bladder outlet obstruction index (BOOI= PdetQmax -2Qmax) determined, as well as bladder contractility index (BCI= PdetQmax
+5Qmax) and bladder voiding efficiency (BVE=voided volume/total
bladder capacity x100) calculated (11).
Statistical analysis was performed applying ANOVA test, Pearson correlation coefficient, calculation of area under the receiver
operating characteristic (ROC) curve for predicting obstruction,
while AUCs were compared via the method of DeLong (12). The
Bland-Altman plot, or difference plot (13) was used as a graphical method to compare the two measurement techniques; in this
study to determine the possible differences between the values of
Qmax and Qss. Statistic analysis was made using Medcalc program
for Windows version 12. The level of significance (two-tailed) was
set at p <0.05.
RESULTS
Out of the 140 patients that underwent the PCR maneuver, 135
of them were finally covered by the analysis.The drop-out 4% were
the patients unable to initiate the stream (restore the flow) following the PCR maneuver, probably due to reflex inhibition of the
resulting pelvic floor contraction. Only eleven patients (8%) experienced pain and discomfort in the perineum, within the pubic space,
and in the urethra, following the PCR maneuver (they all belonged
to the unobstructed group). 70 patients (52%) had urodynamically
proven obstruction, according to URA nomogram.
The mean age of subjects was 66 years, the average IPSS (17.1)
fell within the 2nd category (moderate symptoms).The mean pros-
20
tate volume amounted to 47.1 ccm, while postvoid residual urine
amounted to 66 ml (0-286 range). The average bladder contractility index (BCI) amounted to 103.5, therefore, on the borderline
towards the region of detrusor underactivity (DUA), and the average PCR Index amounted to 100.3% (26-266 range). The data are
shown in Table 1.
D. Aganović et al.
rate (Qmax), detrusor contraction duration (DCD), detrusor pressure at maximum flow (PdetQmax) and maximum detrusor pressure (Pdetmax). The correlation with bladder contractility index
(BCI) is not shown (p=0.36), although there is a very strong correlation with the grade of detrusor contraction (GDC), according
to Schafer nomogram. Also, PCRI correlates very well with the
degree of urodynamic obstruction, expressed as BOOI (Figure 2).
Table 1 Summary statistics
IPSS- International prostatic symptom score, PV-prostate volume, PVR-post void residual urine, IPP –intravesical protrusion of prostate, PCR Index- penile compressionrelease index, BCI- bladder contractility index.
In order to determine the correlation of the observed variable
(PCRI) according to physiological, radiologic and urodynamic parameters, a correlation matrix was done for the observed variables.
The most important results are shown in Table 2.
Figure 2 Linear regression for BOOI and PCR Index
Table 2 Correlation coefficient for PCRI and observed
variables
Since a good statistical correlation of PCR index with age was
shown, patients were subgrouped into three age categories. The
category under 60 years of age included 21 patients (15.5%), the
category under 70 years of age included 63 patients (47%), while the
category of oldest patients – those over 70 years of age, included
51 patients (37.5%). ANOVA test (F=5.9; p 0.003) showed age dependence of PCRI value, including the dependence on a higher degree of infravesical obstruction. The average PCRI for the youngest
age group amounts to 67% (most patients unobstructed), followed
by the medium-age and the oldest groups with PCRI amounting to
an average of 98.4% and of 116.2%, respectively (Figure 3).
PV-prostate volume, Qmax –maximum urinary flow, BWT-bladder wall thickness,
IPP –intravesical protrusion of prostate, PVR-post void residual urine, IPSS- International prostatic symptom score, DCD-detrusor contraction duration, GDC- grade
of detrusor contraction, BCI- bladder contractility index, BVE –bladder voiding
efficiency*Spearman’s coefficient of rank correlation (rho)
There is a statistically significant correlation of PCRI with patient’s age and the size of intravesical protrusion as a factor of
infravesical obstruction. Observed from urodynamic point of view,
there is a strong correlation of this parameter with maximum flow
Figure 3 Age depending PCR index
Then, the predicted probability of this noninvasive urodynamic
factor was determined according to urodynamic bladder outlet
obstruction, defined based on URA nomogram. Cut-off point for
PCRI of 96.4% gives the sensitivity and specificity of 74.3% and
93.8%, respectively, according to the obstruction, with a high positive predictive value (PPV) of 93%, and negative predictive value
(NPV) of 77.2% (95% CI 0.777 to 0.904).
Figure 4 Interactive dot diagram for PCR Index and URA
nomogram NO-no obstruction, OB-obstruction
Since the high predictive power of this factor according to the
obstruction was proven, it was compared with other obstruction
factors, i.e. maximum flow rate (Qmax) and intravesical prostatic protrusion (IPP). A comparative analysis was made using ROC
curves, and again the best discriminatory power of PCR Index according to the obstruction was shown. The area under the curve
(AUC) for PCRI is 0.85, while AUC for Qmax is 0.8 (sensitivity and
specificity 67.1% and 80%, respectively; 95% CI 0.72-0.78), while for
IPP 0.71 (sensitivity and specificity 69% and 74%, respectively; 95%
CI 0.621-0.701), Figure 5. Pair-wise comparison of ROC curves
by DeLong method showed a statistically significant difference between areas for PCR Index and IPP (a=0.143; p=0.007), Table 3.
21
Table 3 Pair wise comparison of ROC curves
The patients were then divided into five groups, depending
on detrusor contractility and obstruction: the first group of 27
patients with normal detrusor contractility and no obstruction
(20%), the second group of 38 patients with impaired detrusor
contractility and no obstruction (28%), the third group of 34 patients in the region of clear obstruction with normal contractility
(25%), the fourth group of 19 patients with obstruction and with
normal contractility and detrusor overactivity (14%), and the fifth
group of 26 patients with obstruction and with impaired detrusor contractility (19%) (Figure 6.). A clear difference was shown in
obstructed patients with preserved contractility with or without
detrusor overactivity (PCRI=161% and 187%, respectively; ANOVA
test; F=9.2, p=0.005), and in relation to the non-obstructed group
and the group of patients with obstruction and impaired detrusor contractility (PCRI= 63% and PCRI=83%, respectively; ANOVA
test; F=43, p<.00001).The obstructed patients with impaired detrusor contractility based on PCR Index (PCRI=83%) as a group could
be statistically different from the group of unobstructed patients
with or without impaired detrusor contractility, using ANOVA test
(F=3.8, p=0.03).
Figure 6 Average values of PCR Index depending on detrusor contractility, obstruction and the presence of DO. IC-NO
impaired contractility-no obstruction, NC-NO normal contractility -no obstruction, NC-OB normal contractility with
obstruction, IC-OB impaired contractility with obstruction,
NC-OB +DOA normal contractility with obstruction and detrusor overactivity
Figure 5 Comparison of ROC curves in the prediction of obstruction Qmax-maximum flow rate, PCR Index- penile compression- release index, IPP –intravesical protrusion of prostate
In order to analyze PRC index only with obstruction, patients
from this category (No=70), were divided according to detrusor
contractility and the presence of DO. Of 44 patients with preserved detrusor contractility (63%), 19 patients (43,1%) had detrusor overcontractility (DO). Of 26 patients with impaired detrusor
contractility, 10 patients (38%) had DO (Figure 7). There is a clear
distinction in PCR index in patients with the presence of DO and
preserved detrusor contractility (PCRI= 187% and 141%, respectively) compared with those with impaired detrusor contractility
and the presence of DO, where there is no clear statistical difference (PCRI=80% and 86%, respectively; ANOVA test; F=2, p=0.16).
22
Figure 6 Average values of PCR Index depending on detrusor contractility and the presence of DO in the region of obstruction. NC;DOA normal contractility without detrusor
overactivity, NC;DOA + normal contractility with detrusor
overactivity, IC;DOA impaired contractility without detrusor
overactivity, IC- DOA + impaired contractility with detrusor
overactivity
The patients were also analyzed for maximum flow rate and
PCRI reference points, i.e. Qs and Qss (Table 4). What clearly distinguishes the patients without obstruction and with normal detrusor contractility is a clearly higher Qmax, compared with the other
two categories, while the patients with impaired detrusor contractility, regardless of the condition regarding obstruction, have both
Qs and Qss far lower, compared with the other categories. The
patients with obstruction and with preserved detrusor contractility and the presence of DO have the highest Qs.
Table 4 Group wise values of maximum urinary flow (Qmax),
surge flow (Qs), and steady-state flow (Qss). IC-NO impaired
contractility-no obstruction, NC-NO normal contractility no
obstruction, IC-OB impaired contractility with obstruction,
NC-OB normal contractility with obstruction, NC-OB +DOA
normal contractility with obstruction and detrusor overactivity
Since there was a strong similarity between the values of maximum urinary flow (Qmax) and Qss during the PCR index, these
two variables were comparatively analyzed, using Bland-Altman plot
(Figure 8.). The mean value of Qmax is 8.8 ml/sec, while the mean
value of Qss is 7.7 ml/sec, giving the average difference of -1.1 ml/
sec (SD 1.8; 95%CI -1.318 to -0.0773). The agreement was further
confirmed by defining the correlation coefficient for these two
variables with a strong r=0.88 (95% CI 0.8314 to 0.9111; p<.0001).
D. Aganović et al.
Figure 8 Bland-Altman plot of difference between Qss and
Qmax as a function of mean
DISCUSSION
In the pioneer research of Sullivan and Yalla (4), it was shown that
PCR Index clearly distinguished patients with obstruction (PCRI=
183%) from those without obstruction, but with the presence of DO
(PCRI=157%), as well as from those with impaired detrusor contractility (PCRI=70%) or those with normal detrusor contractility
without obstruction (PCRI=67%). Also, younger volunteers without
obstruction did not have a high PCR index. Sullivan, using PCR index
cut-off of 100%, shows the sensitivity and specificity according to the
obstruction of 91% and 70%, respectively. However, this study does
not emphasize the obstructive status of patients with DUA or DO.
Harding et al. (14), while comparing standard pressure/flow studies
with penile cuff test, also determined PCR Index. They found the
optimal threshold for the detection of obstruction with PCR Index
of 160%, with PPV of 69% according to bladder outlet obstruction.
Such an increase in the cut-off value can be explained by the use of
automated penile cuff, since it was proven that external control of
compression produces higher values of isovolumetric pressure than
the voluntary mechanical compression, perhaps due to the inhibition
of detrusor contraction in patients performing the manual compression. PCR index, as confirmed by this study as well, provides twice as
high values in obstructed patients than in those not obstructed or
those obstructed, having impaired detrusor contractility. Formerly, it
was viewed that there is no difference in patients with obstruction
or another bladder abnormality just because patients with DO were
clearly distinguished, without being classified into obstructed or nonobstructed group. The originality of this study lies in the fact that
obstructed patients were dichotomized into those with the presence or absence of DO. A statistically more significant increase in
PCR index was shown in patients having normocontractile detrusor
with DO than in those having normocontractile muscle but without
DO (average value 187.2% vs. 161 %, p= 0.005). Further on, our
study has shown a strong discriminatory power of PCRI according
to the obstruction with sensitivity and specificity of 75% and 94%,
respectively, and excellent PPV (93%), with the most optimal PCR
Index cut-off of 96%.
23
There are weak statistically significant differences in patients
without obstruction and those with impaired detrusor contractility.
That is why it is very important to follow both Qmax and uroflow
curve in the conditions of low flow, for the detection of DUA. It is
also very important to follow reference points during the determination of PCRI, i.e. Qs and Qss, since they provide very important information. Patients with detrusor overactivity (DO) without
obstruction have a typical curve during PCR maneuver. High Qs is
also characteristic, accompanied with a high Qss, which is similar
to that in patients without obstruction and normal contractility.
Qs has an increasing tendency in patients with DO, compared with
those having normal flow, which correlates with enhanced contractility in the presence of DO. Patients without clearly obstructive pathology have a higher Qss, which corresponds to a higher
maximum flow rate. Patients with detrusor underactivity neither
have high Qs nor do they have high Qmax (Qss). (15). As emphasized in earlier studies, the increase of PCRI points to increased
contractility and velocity of the detrusor. PCRI correlates very well
with urodynamic determinants of obstruction (Qmax, PdetQmax,
Pdetmax). Since the dependence of PCRI on detrusor contractility has been proven, it is logical that this variable strongly correlates with the grade of detrusor contraction (GDC), derived from
Schafer nomogram (rho=0. 44, p<0.0001), however, correlation
with bladder contractility index (BCI) is not shown (p=0.16). Again,
there is very strong correlation between BCI and GDC (rho=0.6;
p<0.0001), suggesting that in similar research studies GDC should
be used as a measure for detrusor contractility. Further on, better
sensitivity and specificity of PCR Index have been shown compared
with the maximum flow rate (Qmax) or the volume of intravesical
prostatic protrusion (IPP), being good predictors of obstruction
(16, 17). Again, PCRI correlates well with age, since the group-wise
increase of PCR Index has been shown with age; thus, the mean
PCR Index in the youngest age group of patients with BPE is only
67%, compared with patients over seventy years of age, having almost twice as high mean PCR Index of 116%. Harding et al. (14) did
not find differences between Qmax measured during conventional
PF studies and Qss, determined during PCR maneuver. The mean
difference between these two parameters was 0.4 ml/sec (SD 4.5).
This study also showed significant agreement between Qmax and
Qss (mean difference 1.1 ml/sec; SD 1.8), along with excellent correlation coefficient (r=0.88); thus, these two parameters can be
used interchangeably in daily practice, particularly in diagnosing the
state of obstruction with low detrusor contractility, along with additional uroflow curve monitoring.
The results of the study suggest that PCR index combines the
measure of detrusor contractility (Qs) with the actual maximum
flow rate (Qss). Qs, therefore, is an important measure of detrusor
contractility (isovolumetric strenght).
physiology, detrusor contractility and isovolumetric pressure generation in patients with BPE. The test is easy to perform; drop-out
rate is very low, while side effects are rare and tolerable.
CONCLUSION
Damir Aganović, MD, PhD
Clinic of Urology, CCUS,
Bolnička 25, 71000 Sarajevo,
Bosnia and Herzegovina,
Phone: +387 33 297 754
Email: dagano@lol.ba
PCR Index is shown to be a very good diagnostic instrument
for the detection of infravesical obstruction. It represents a very
good introduction to noninvasive urodynamic diagnostics since it
shows significant specificity and PPV in the condition of infravesical
obstruction caused by BPE, and is useful in the study of urethra
REFERENCES
1. Schafer W, Rubin H, Nopeney R, et al. Obstructed and non-obstructed prostatic
obstruction: a plea for urodynamic objectivism of bladder outflow obstruction in
benign prostatic hyperplasia. World J Urol 1989;6:198-203.
2. Griffiths D. Detrusor contractility-order out of chaos. Scand J Urol Nephrol Suppl
2004; 215:93-100.
3. Griffiths D, Abrams P, D’Ancona CA, van Kerrebroeck P, Nishizawa O, Nitti VW
et al.: Urodynamic evaluation of lower urinary tract symptoms in men. Current
Bladder Dysfunction Reports 2008;3:49-5.
4. Sullivan MP and Yalla SV. Penile Urethral Compression-Release Maneuver as a Noninvasive Screening Test for Diagnosing Prostatic Obstruction. Neurourol Urodynam 2000;19:657-669.
5. Reis LO, Barreior GC, Baracat J, Prudente A, D’Ancona CA: Intravesical protrusion
of the prostate as a predictive method of bladder outlet obstruction. Inter Braz J
Urol 2008;34(5): 627-37.
6. Franco G, De Nunzio C, Leonardo C, Tubaro A, Ciccariello M, De Dominicis C,
Miano L, Laurenti C. Ultrasound assessment of intravesical prostatic protrusion and
detrusor wall thickness-new standards for noninvasive bladder outlet obstruction
diagnosis? J Urol 2010;183(6):2270-4.
7. McIntosh, SL, Drinnan, MJ, Griffiths CJ, Robson W A, Ramsden P D, Pickard RS.:
Non-invasive assessment of bladder contractility in men. J Urol 2004;172:954
8. Schaefer W, Abrams P, Liao L, Mattiasson A, Pesce F, Spangberg A et al.: Good
urodynamic practices: uroflowmetry, filling cystometry and pressure-flow studies.
Neurourol Urodyn 2002;21:261-74.
9. Schaefer W. Analysis of bladder-outlet function with the linearized passive urethral
resistance relation, linPURR, and a disease-specific approach for grading obstruction: from complex to simple. World J Uro 1995;13:47-58.
10. Griffiths D, van Mastrigt R, and Bosch R. Quantification of urethral resistance and
bladder function during voiding, with special reference to the effects of prostate
size reduction on urethral obstruction due to benign prostatic hyperplasia. Neurourol Urodyn 1989;8:17–27.
11. Abrams P. Bladder outlet obstruction index, bladder contractility index and bladder
voiding efficiency: three simple indices to define bladder voiding dysfunction. BJU
Inter 1999;84: 14-15.
12. DeLong ER, DeLong DM, and Clarke-Pearson DL. Comparing the areas under two
or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837-45.
13. Bland JM, Altman DG. Measuring agreement in method comparison studies. Statistical Methods in Medical Research 1999;8:135-160
14. Harding CK, Robson W, Drinnan WMJ, Griffiths CJ, Ramsden PD and Pickard
RS: An automated penile compression release maneuver as a noninvasive test for
diagnosis of bladder outlet obstruction. J Urol 2004;172:2312–2315.
15. Blake C, Abrams P. Noninvasive techniques for the measurement of isovolumetric
bladder pressure. J Urol 2004;171(1):12-19.
16. Aganović D. The role of uroflowmetry in diagnosis of infravesical obstruction in the
patients with benign prostatic enlargement. Med Arh 2004;58(1):109-12
17. Aganović D, Hasanbegović M, Prcić A, Kulovac B, Hadžiosmanović O. Which Is a
Better Indicator of Bladder Outlet Obstruction in Patients with Benign Prostatic
Enlargement - Intravesical Protrusion of Prostate or Bladder Wall Thickness? Med
Arh 2012;66(4): 296-300
Original article
Evaluation activities of daily living in patient’s rehabilitation with osteoporosis
Procjena aktivnosti svakodnevnog života u rehabilitaciji pacijenata sa osteoporozom
Edina Tanović1*, Aldijana Kadić1, Haris Tanović2, Dževad Vrabac1
Clinic for Physical Medicine and Rehabilitation, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina;
Clinic for Abdominal Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina
1
2
ABSTRACT
SAŽETAK
The objectives are to evaluated the length of stay in hospital
(LOH), and Barthel index (BI) at admission and discharge from rehabilitation, in patients with osteoporosis as comorbidity.We were
conducted a retrospective study in the period from January, 1st to
the December, 31th 2012 and as a source of data we used medical records. The study included 39 patients with osteoporosis and
who were hospitalized at the Clinic for Physical Medicine and Rehabilitation, Clinical Center University of Sarajevo. We have evaluated activities of daily living by Barthel index. Descriptive statistical
methods were used: frequency and relative frequency, median and
interquartile range (iqr). Results: Out of a total number of patients
(n=39), 31 (79.5%) were females and 8 (20.5%) were males. The
median age for females was 70.0 years (IQR=61.0 to 74.0), and
for males 72.5 years (IQR=48.3 to 79.5). The median of LOH was
29.0 days (IQR=22.5 to 36.0). The median of BI at admission was
16.0 (IQR=11.0 to 19.5) and the median of BI at discharge was
17.0 (IQR=13.0 to 20.0). Conclusion: Osteoporosis as comorbidity
didn’ t influence on longer length of stay in hospital and there was
not a clinicaly significant improvement in activities of daily living in
these patients.
Cilj rada je procijeniti koliko osteoporoza utiče na dužinu hospitalizacije, te vrijednosti Barthel indeksa-a na prijemu i na otpustu kod
pacijenata sa osteoporozom kao komorbiditetom. Provedena je retrospektivna studija koja uključuje 39 pacijenata sa osteoporozom kao
komorbiditetom, hospitaliziranih na Klinici za fizijatriju i rehabilitaciju,
Klinički centar Univerziteta u Sarajevu u periodu janaur-decembar
2012. godine. Kao izvor podataka su analizirane istorije bolesti pacijenata. Aktivnosti svakodnevnog života su procjenjene prema Barthel
indeksu. Korištene su deskriptivne statističke metode: apsolutna i relativna frekvencija, mjere centralne tendencije (medijana i interkvartilni
raspon - IQR).Rezultati: Od ukupanog broja pacijenata (n=39), 31
(79,5%) su bili ženskog spola i 8 (20,5%) su bili muškog spola. Medijana
starosne dobi za žene iznosi 70,0 godina (IQR=61,0 do 74,0 godine) i
za muškarce 72,5 godine (IQR=48,3 do 79,5 godina). Medijana dužine
hospitalizacije iznosi 29,0 dana (IQR=22,5 do 36,0 dana). Medijana
vrijednosti Barthel indexa-a na prijemu iznosi 16,0 dana (IQR=11,0
do 19,5 dana), a na otpustu 17,0 dana (IQR=13,0 do 20,0). Zaključak:
Osteoporosa kao komorbiditena bolest nije značajno uticala na dužu
hospitalizaciju, a u aktivnostima svakodnevnog života nije evidentirano
klinički signifikantno poboljšanje kod pacijenata na rehabilitaciji.
Key words: osteoporosis, Length of Stay in Hospital (LOH), Activities of Daily Living (ADL), Barthel index (BI)
Ključne riječi: osteoporoza, dužina hospitalizacije, aktivnosti svakodnevnog života, Barthel indeks
INTRODUCTION
tion. Throughout youth, the body uses these minerals to produce
bones. If calcium intake is not sufficient, or if the body does not
absorb enough calcium from the diet, bone production and bone
tissues may suffer (3). As people age, calcium and phospate may
be reabsorbed back into the body from the bones, which makes
the bone tissue weaker. Both situations can result in brittle, fragile
bones that are subject to fractures, even in the absence of trauma.
Researchers estimate that about 20% of American women over
the age of 50 have osteoporosis. In addition, another 30% of them
have osteopenia, which is abnormally low bone density that may
eventually deteriorate into osteoporosis, if not treated. About half
of all women over the age of 50 will suffer a fracture of the hip,
wrist, or vertebra (3,4). Now we know that 1 in 5 people with a
hip fracture do not walk again. The results show the importance
of the rehabilitation of these patients, as well as the significant ef-
Osteoporosis is characterized by low bone mass and structural
deterioration of bone tissue, which leads to bone fragility and an
increased propensity to fractures (1). In the U.S. 44 million people over 55 years of age are diagnosed with osteoporosis. In BiH
currently affects 162 000 women. The World Health Organization
estimates that by 2025. the number of hip fractures will grow up
to 3 million a year. Epidemiological studies which confirm that
subjects who are born light and whose growth falters in the first
year of postnatal life, have significantly lower bone size and
mineral content, at age 60 to 75 years (1,2). Osteoporosis occurs
when the body fails to form enough new bone, or when too much
old bone is reabsorbed by the body, or both. Calcium and phosphate are two minerals that are essential for normal bone forma-
25
Evaluation activities of daily living in patient’s rehabilitation with osteoporosis
fects on the patient, the family and their economic status (3,5).
Preventive strategies against osteoporotic fracture can be targeted
throughout the life course. Although there is evidence to suggest
that peak bone mass is inherited, current genetic markers are able
to explain only a small proprostion of the variation in individual
bone mass or fracture risk. Evidence has begun to accrue that
fracture risk might be modified by environmental influences during
intrauterine or early postnatal life (1).
The rapid development and availability of effective therapies
for osteoporosis over the last 20 years has been one of the grest
success stories- many might therefore belive that the problem of
osteoporosis is largely solved. But the full impact of therapeutic
strategies, both pharmacological and non- pharmacological (e.g.
exercise, falls prevention) can only be achieved by widespread,
systemic application of best clinical practice targeting to best
therapies to those most at risk (2). One of the best indicators
that a skeleton will fail in the future in the fact that is has failed
in the past. Those patients thet suffer a fragility fracture today
are much more likely to suffer fractures in the future (2,3). The
objectives are to evaluated the length of stay in hospital (LOH),
and Barthel index (BI) at admission and discharge from hospital, in
patients with osteoporosis as comorbidity.
Figure 2 Distribution of patients according to age
The median age for females was 70.0 years (IQR=61.0 to 74.0), and
for males 72.5 years (IQR=48.3 to 79.5) for males (Figure 2).
The median of length of stay in hospital (LOH) was 29.0 days
(IQR=22.5 to 36.0).
We were conducted a retrospective study in the period from
January, 1st to the December, 31th 2012 and as a source of data
we used medical records. The study included 39 patients with osteoporosis who were hospitalized at the Clinic for Physical Medicine and Rehabilitation, Clinical Center University of Sarajevo. We
analyzed socio-demographic variables such as gender and age and
also the length of stay in hospital on rehabilitation.We have evaluated activities of daily living by Barthel index at admission and at
discharge.
Stastical analysis
Descriptive statistical methods were used: frequency and relative frequency, median and interquartile range (IQR).
RESULTS
Figure 3 Box plot of Barthel index at admission and discharge
The median of BI at admission was 16.0 (IQR=11.0 to 19.5) and
the median of BI at discharge was 17.0 (IQR=13.0 to 20.0) (Fig.3).
DISCUSSION
Figure 1 Distribution of patients according to gender
Out of a total number of patients (n=39), 31/39 (79.5%) were females and 8/39 (20.5%) were males (Figure 1).
In our stady we analyzed a 39 patients. The frequency of males
was 79.5% and 20.5% were males.These results are consistent with
others similar studies ( 3,5,6 ). The median age for females was
70.0 years (IQR=61.0 to 74.0), and for males 72.5 years (IQR=48.3
to 79.5) for males. Garcia et al. published that the median age for
women was 72.1 years, which coincides with the data in our study
(5). Boskovic and al. mentioned that the quality of life of patients
with the osteoporosis observes the role of physical functioning,
which leads to the need for adequate assessment of the quality
of life through specific surveys (6). Spica and colleagues in their
study published in 2008 stress that patients who were treated with
only physical procedures didn’t experience an increase in bone
26
density, but there was no increase in the number of fractures,
which is considered a positive effect of physical therapy (7). The
median of length of stay in hospital was 29.0 days (IQR=22.5 to
36.0).The rehabilitation of these patients are usualy longer because
they need more help and rehabilitation would continue at home
(3). The median of BI at admission was 16.0 and the median of BI
at discharge was 17.0.In our work, after assessing activities of daily
living, we determined that was no significant recovery by Barhel
index. Patients with osteoporosis can not be rehabilitated in the
period as they treated our patients. This period was used to assist
and guide patients in the rehabilitation process that they will continue at home (3,7). Rauter in a paper published in 2008 highlights
the shortcomings of measuring activities of daily living. Bojnec and
associates in the work of 2011 emphasis that there is no general
consensus on the evaluation activities of daily living of patients with
ostoporosis (8,9). Physical activities continue to stimulate increases
in bone diameter throughout the lifespan.(10) These exercise-stimulated increases in bone diameter diminish the risk of fractures by
mechanically counteracting the thinning of bones and increases in
bone porosity.(11) Exercise should be dynamic, exceed a threshold
intensity and strain frequency, be relatively brief but intermittent,
and also be supported by unlimited nutrient energy and adequate
calcium and vitamin D3 supplements (12,13). Prevention of osteoporosis is necessary and when it is identified as a co-morbidity.
Further analysis in this regard, especially the application of appropriate questionnaires to verify the effects on activities of daily living,
would be useful.
E. Tanović et al.
4. Avdić D. Pad u trećoj životnoj dobi. Sarajevo: OKO; 2004.
5. Garcia-Martin A, Reyes-Garcia R, Garcia-Catsro JM, Munoz-Tormes M. Diabetes
and osteoporosis: action of gastrointestinal hormones on the bone. Rev Clin
Esp 2013;213(6):294-7.
6. Bošković K, Protić-Glava B, Grajić M, Madić D, Obradović B. Adapted physical activity in the prevention of therapy of osteoprosis. Med pregl 2013;66(56):221-224.
7. Romano-Spica V, Partalo A, Partalo D, Lorenzo E, et all. Health promotion through
physicals activity: teritories models and experiens. Ann Ig 2008;20(3):291-11.
8. Rauter T, Pugartnik T. Outcome Measuerment of Hip Fracture. Rehabilitacija:
Inštitut Republike Slovenije za rehabilitacijo. 2008;7(2):35-39.
9. Bojnec V, Celan D, Palfy M, Turk Z. Efects of exercise on quality of life in patients with osteopenia or osteoporosis-implementation of the qualeffo-41 quastionare in Slovenia. Rehabilitacija: Inštitut Republike Slovenije za rehabilitacijo.
2011;10(12):37-44.
10. Tanović E. Opća kineziterapija. Sarajevo: V-Graf; 2012.
11. Shava H, Favela E, Diaz J. Knowledge of osteoporosis among men in the primary
care setting. South Med J 2011;104(8):584-588.
12. Park J, Linde K, Maucimer E, Malsberger A, Sherman K, Smith C, et al. The Status
and Future of Acunptucture Clinical Research. J Altern Complement Med
2008;14(7):871-881.
13. Maliberger A, Straeilberger K, Kraemer J, Brittinger C, Witte S, Boewing G, et
al. Desinging and Acupuncture study II.The Nationwide, Randomized, Controled
German Acupuncture Trials of Low Back Pain and Goanrthrosis. J Altern Complement Med 2006;12(8):733-742.
CONCLUSION
Osteoporosis as comorbidity did not influence on longer length
of stay in hospital and there was not a clinicaly significant improvement in activities of daily living in these patients.
REFERENCES
1. Cooper C. Epigenetics and developmental originis of osteoporosis. Osteoporosis Int 2013;24 (Suppl 1):27-31.
2. McCloskey E. Secondary prevention: a call to action. Osteoporosis Int 2013;24
(Supp 1):27-31.
3. Tanović E, Čelik D, Kadić A, Vrabac Dž. One Year Prevalence Rate for Osteoporosis as a Comorbidity in Patients on Rehabilitation. Osteoporosis Int 2013;24
(Supp 1):310.
Edina Tanović, MD, PhD
Clinic for Physical Medicine and Rehabilitation
Clinical Centar University of Sarajevo
Bolnička 25,
71000 Sarajevo
Phone: +387 33 298 465
Email: tanovicedina@hotmail.com
Original article
Testicular volume in healthy prepubertal boys
Zlatan Zvizdić1*, Denisa Zvizdić2, Sandra Vegar Zubović3, Amra Džananović3,
Faris Fočo4
1
Clinic of Pediatric Surgery, Clinical Centre University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; 2Clinic of Ophthalmology, Clinical
Centre University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; 3Clinic of Radiology, Clinical Center University of Sarajevo, Bolnička 25,
71000 Sarajevo, Bosnia and Herzegovina; 4Clinic for Maxillofacial Surgery, Clinical Center University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina
* Corresponding author
ABSTRACT
SAŽETAK
Estimation of prepubertal testicular volume is important to
define the onset of puberty as well as in the evaluation of boys
with a variety of disorders affecting testicular growth and development, such as varicocele and undescended testis, and after
testicular torsion. In this study, we determined the baseline testicular volume measured by ultrasonography (USG) and using the
Prader orchidometer. In addition, we assessed the validity of the
Prader orchidometer per age group by correlating it with volume
measurement by ultrasonography. Our study included 60 healthy
boys, aged 0.5 to 12 years, divided into fourth groups according the age: 0.5-3, 4-6, 7-10 and 11-12 years. The ultrasonography
measurements of testicular volume were calculated using Lambert formula (length x width x height x 0.71.). Mean testicular
volume was compared between the different age categories. The
results showed that the mean testicular volume in boys aged 0.53 years was 1.032ml ± 0.12, in boys aged 4-6 years was 1.163ml ±
0.12, in boys aged 7-10 years was 1.257ml ± 0.09 while testicular
volume in boys aged 11-12 years was significantly higher than in
all younger age groups.
Određivanje volumena prepubertalnog testisa je važno u definisanju javljanja puberteta kao i u evaluaciji dječaka s različitim
poremećajima koji uzrokuju poremećaj rasta i razvoja zahvaćenog
testisa, kao što su varikokela i nespušteni testis, kao i poslije torzije
testisa. U ovom istraživanju smo utvrđivali referentne vrijednosti
testikularnog volumena dobijene ultrasonografski i korištenjem
Praderovog orhidometra. Osim toga, procjenjivali smo validnost
rezultata dobijenih Praderovim orhidometrom za dobne grupe,
koreliranjem sa volumenima izmjerenim ultrasonografski. Naše
istraživanje je uljučilo 60 zdravih dječaka, u dobi od 5 mjeseci do 12
godina, podijeljeni u četiri grupe po dobu: 0,5-3, 4-6, 7-10 i 11-12
godina. Ultrazvučno određivanje volumena testisa je izračunavano
korištenjem Lamberove formule (dužiba x širina x debljina x 0,71).
Srednji testikularni volumen je kompariran između različitih dobnih
grupa. Rezultati su pokazali da je srednji testikularni volumen kod
dječaka starosti 0,5-3 godine bio 1.032ml ± 0.12, kod dječaka starosti 4-6 godina 1.163ml ± 0.12, kod dječaka starosti 7-10 godina
1.257ml ± 0.09, dok je volumen testisa kod dječaka u dobi 11-12
godina signifikantno veći nego u svim mlađim dobnim grupama.
Key Words: testicular volume, measurement, prepubertal boys
Ključne riječi: testikularni volumen, mjerenje, prepubertalni dječaci
INTRODUCTION
composed of a series of 12 consecutive testicular samples with a
size ranging from 1 to 25 ml which are made of different materials
including plastic or wood (4) (Figure1).
Testicular volume is related to various reproductive endocrine
parameters (1). Furthermore, testicular volume significantly correlated with the testicular function, since seminiferous tubules and
germinal elements comprise approximately 98% of testicular mass
(2). Estimation of prepubertal testicular volume is important to
define the onset of puberty as well as in the evaluation of boys with
a variety of disorders affecting testicular growth and development,
such as varicocele and undescended testis, hypogonadism with respect to tubular function and after testicular torsion (3).Therefore,
the measurement of testicular volume represents important indirect indicator of functional status of the measured prepubertal
testicle.
A number of clinical methods have been used for the measurement of testicular volumes, including a centimeter ruler, orchidometers (4,5), sliding caliper or ultrasonography. Probably the
most common orchidometer among the ones used currently is
the orchidometer developed by Prader, described in 1966, which is
Figure 1 Prader orchidometer
28
In accordance with the Helsinki declaration, the Institutional
Review Board (IRB), and the Independent Ethics Committee of
Clinical Center University of Sarajevo approved all aspects of this
study. 60 healthy boys whose families gave consent were included
in the study. The participans were divided into four groups according to age: 0.5 to 3, 4 to 6, 7 to 10 and over 10 years. The ages of
the children were calculated using decimal age table. All children
were examined by the same physicians. The volume of 120 testes
in 60 prepubertal boys with a mean age of 6,1 years (range 0.5 to
12 years) was measured by ultrasonography and using the Prader
orchidometer. Testicular volumes (ml) were calculated using the
empiric formula of Lambert (length x width x height x 0.71) (6). Ultrasound studies were performed by experienced sonog¬raphers
using linear array probe 7.5 - 10 MHz.
Data analyses
Statistical analyses was done using the Statistical Package for
Social Sciences (SPSS) version 17.0. Simple frequencies were determined for the age, while descriptive statistics were used for the
testicular volume measurements.The paired sample t-test was used
for evaluating the significance of testicular volumes, while the correlation was determined using the Pearson correlation coefficient.
RESULTS
We found no statistically significant differences in the results of
measurements by different techniques (ultrasonography vs Prader
orchidometer). Actually, statistical correlation of measured results
between the two methods showed statistically significant correlation correlation (P < 0.01).
Figure 2 Mean testicular volume between the different age
categories.
There are presented average (X+SEM) of the testicular volumes of examinees aged
0,5-3 years (N =32); 4-6 years (N =24); 7-10 years (N =40); and > 10 years (N =24),
p< - probability
The mean testicular volume ( ± SD) per age category is shown
in Figure 2. The results showed no significant differences in the
testicular volume between groups of the healthy boys aged 0.53 years (1.032 ± 0.12), 4-6 years (1.163 ± 0.12) and 7-10 years
(1.257 ± 0.09). Inversely, there was statistically significant difference
Z. Zvizdić et al.
between testicular volume of the each of aforementioned groups
respectively to the group of the healthy children older than 10
years in whom the maen testicular volume ( ± SD) was 1.82 ± 0.15.
Thus the boys aged 0.5-3 years had the maen testiculare volume
decreased by 43% (P < 0.0002), the boys aged 4-6 years decreased
by 36% (P < 0.001) and the boys aged 7-10 years by 31% (P <
0.002) compared to the mean testicular volume in boys older than
10 years.
DISCUSSION
Different methods have been used for the clinical measurement
of testicular volumes: measurements of the testis in the scrotum
by a ruler, by a caliper, by orchidometers or by ultrasonography. A
number of orchidometers have been described such as the Prader
orchidometer (4) and the Takihara (also known as the Rochester
orchidometer) (5), and they are still the most commonly used.
Currently, ultrasonographic determination of testicular volume is
emerging as the most accurate method because of the ability to enable one to distinguish the testis from the adjacent soft tissues (7).
Althouth numerous studies have shown that ultrasonography provides more accurate volumes than those obtained by orchidometer especially in small testicles (7,8,9), we found no statistically
significant differences in the results of measurements by different
techniques (ultrasonography vs Prader orchidometer). Our results
are in accordance with those studies that have found a significant
correlation between the values of testicular volume obtained by
Prader orchidometer and by ultrasound (10,11).
Various formulas have been used in the ultrasonography assessment of testicular volume: the formula for an ellipsoid (L × W × H
× 0.52), the formula for a prolate spheroid (L × W2 × 0.52), and
the empirical formula of Lambert (6) (L × W × H × 0.71). However,
few studies have made direct comparisons of their accuracy and
precision. Paltiel et al. (9) as well as Sakamoto et al. (12) found that
the formula in which testicular volume is calculated by L × W × H
× 0.71 has the smallest mean bias relative to actual volume over
the entire volume range and concluded that this formula is the
most accurate for calculating the testicular volume. Therefore, in
our study we used the empiric formula of Lambert (6) to calculate
testicular volumes.
The results of our research in terms of getting normal testicular
volume values in the different age groups in prepubertal boys could
serve as reference values. We found that there is a slight increase in
testicular volume to ten years of age but without a statistically significant values. These our results are in accordance with the results
of previous studies that have also found that there is no significant
increase in testicular volume in the first 10 years of life (13,14). Previous studies have found that testicular growth occurs during the
fetal period and in infants and then remains static from about 1 year
until early puberty (14). Reasons for the growth of the testes in the
early postnatal period lie in the existence of so- called ‘mini-puberty’
which describes a peak in gonadotropic hormones (LH, FSH, inhibin
B and testosteron) around 3 to 4 months of age (15,16). Such an
increase in levels of gonadotropins after delivery is caused by suppresion of placental negative feedback and activation of the hypothalamic–pituitary–testicular axis (17). Testosterone and LH return to a
29
Testicular volume in healthy prepubertal boys
minimum again at 6–9 months. It takes slightly longer for FSH and
inhibin B to reach the low pre-pubertal levels (17).
For all these reasons, it is very difficult to assess the functional
status of prepubertal testes. In contrast to adults in whom testicular size correlates with hormonal and function status as well
as spermatogenesis (12), the only objective indicator of testicular function in childhood represents testicular biopsy with histopathologic analysis. Since seminiferous tubules and germinal elements comprise approximately 98% of testicular mass, estimation
of testicular volume has become an important method of indirect
assessment of the functional status of the testes (18). Most children
have similar left-and right-hand side testicular volumes; however, it
is common for the left-hand side testicle to have a slightly lower
volume than the right-hand side one.
Our results indicate that maesurement of testicles is able to detect such a small biologically relevant change in testicular volume,
which indicates that this is a highly valuable and accurate method
to measure the size of pre-pubertal testicles.
CONCLUSIONS
Our research has provided normal values for testicular volume
measured by ultrasonography and Prader orchidometer in boys
aged 0.5 - 12 years. Ultrasonography method and method of measurements with Prader orchidometer have similar diagnostic value
in comparing the size of both testes. Intensive growth of testes
starts in the 11th year of life. The formula L x W x H x 0.71 provides a superior estimate of testicular volume and should be used
in clinical practice.
REFERENCES
1. Bahk JY, Jung JH, Jin LM, Min SK. Cut-off value of testes volume in young adults
and correlation among testes volume, body mass index, hormonal level, and seminal
profiles. Urology 2010;75(6):1318-1323.
2. Kollin C, Hesser U, Ritzen EM, Karpe B. Testicular growth from birth to two years
of age, and the effect of orchidopexy at age nine months: a randomized, controlled
study. Acta Paediatr 2006;95:318-324.
3. Goede J, Hack WW, Sijstermans K, van der Voort-Doedens LM, Van der Ploeg T,
Meij-de Vries A et al. Normative values for testicular volume measured by ultrasonography in a normal population from infancy to adolescence. Horm Res Paediatr 2011;76(1):56-64.
4. Prader A. Testicular size: assessment and clinical importance. Triangle 1966;7:240243.
5. Takihara H, Cosentino MJ, Sakatoku J, Cockett ATK. The significance of testicular
size measurement in andrology correlation of testicular size with testicular function. J Urol 1987;137:416-419.
6. Lambert B. The frequency of mumps and mumps orchitis and the consequences for
sexuallity and fertility. Acta Genet Stat Med 1951;2:1-166.
7. Hsieh ML, Huang ST, Huang HC, Chen Y, Hsu YC.The reliability of ultrasonographic
measurements for testicular volume assessment: comparison of three common
formulas with true testicular volume. Asian J Androl 2009;11(2):261-265.
8. Shiraishi K, Takihara H, Kamiryo Y, Naito K. Usefulness and limitation of punchedout orchidometer in testicular volume measurement. Asian J Androl 2005;7:77-80.
9. Paltiel HJ, Diamond DA, Di Canzio J, Zurakowski D, Borer JG, Atala A. Testicular
volume: comparison of orchidometer and US measurements in dogs. Radiology
2002; 222(1):114-119.
10. Taskinen S, Taavitsainen M, Wikström S. Measurement of testicular volume: comparison of 3 different methods. J Urol 1996;155(3):930-933.
11. Schiff JD, Li PS, Goldstein M. Correlation of ultrasonographic and orchidometer
measurements of testis volume in adults. BJU Int 2004;93(7):1015-1017.
12. Sakamoto H, Yajima T, Nagata M, Okumura T, Suzuki K, Ogawa Y. Relationship
between testicular size by ultrasonography and testicular function: measurement of testicular length, width, and depth in patients with infertility. Int J Urol
2008;15(6):529-533.
13. Cendron M, Huff DS, Keating MA, Snyder HMcC, Duckett JW. Anatomical, morphological and volumetric analysis: a review of 759 cases of testicular maldescent. J
Urol 1993;149:570-573.
14. Main KM, Toppari J, Skakkebeak NE. Gonadal development and reproductive hormones in infant boys. Eur J Endocrinol 2006;155:S51-S57.
15. Hadžiselimović F, Živković D, Bica DT, Emmons LR. The importance of minipuberty for fertility in cryptorchidism. J Urol 2005;174:1536-1539.
16. Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab 2005;90:3122-3127.
17. Chada M, Prusa R, Bronsky J, Kotaska K, Sidlova K, Pechova M, Lisa L. Inhibin B, follicle stimulating hormone, luteinizing hormone and testosterone during childhood
and puberty in males: changes in serum concentrations in relation to age and stage
of puberty. Physiol Res 2003;52:45-51.
18. Kollin C, Hesser U, Ritzen EM, Karpe B. Testicular growth from birth to two years
of age, and the effect of orchidopexy at age nine months: a randomized, controlled
study. Acta Paediatr 2006;95:318-324.
Zlatan Zvizdić, MD, PhD
Clinic of Pediatric Surgery
Clinical Center University of Sarajevo,
Phone: +387 33 297 144
Email: zlatanzvizdic@yahoo.com
Original article
Correlation of gastroesophageal reflux disease and
Helicobacter pylori infection
Korelacija gastroezofagealnog refluksa i Helicobacter
pylori infekcije
Nenad Vanis1*, Amila Mehmedović1, Rusmir Mesihović1, Amir Redžepović2, Aida Saray1
Clinic for Gastroenterohepatology, Clinical Centre University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina,
Emergency Medical Services, Sarajevo, Bosnia and Herzegovina.
1
2
ABSTRACT
The nature of the relationship between Helicobacter pylori
(HP) and reflux oesophagitis is still not clear. Aim of the study is to
investigate the correlation between Helicobacter pylori infection
and gastroesophageal reflux disease (GERD) taking into account
endoscopic data. Materials and methods: the study was perfomed
from Jan. 2013 to Jan. 2014. as a prospective study in total of 146
patients with GERD in order to determine the prevalence of Helicobacter pylori infection in GERD patients. Further the value endoscopic parameters of the patients with and without Helicobacter pylori infection were studied and statistically compared. Finally,
univariate analysis of the above mentioned data were performed in
order to evaluate the statistical correlation with reflux esophagitis.
Results: there were no statistically significant differences between
the two groups, HP infected and HP negative patients, regarding
age and gender. There was statistical difference between the two
groups regarding severity of symptoms of regurgitation, dysphagia and epigastric pain, which were more registred in Helicobacter
pylori positive group. We observed that hiatal hernia (p=0,01), LES
size (p=0,05) and pathological reflux number (p=0,05) were significantly related to the presence of reflux oesophagitis. Conclusion:
based on these findings, we found statistical difference regarding
presence and severity of reflux esophagitis between patients with
and without Helicobacter pylori infection.
Key words: Helicobacter pylori, GERD, symptoms.
INTRODUCTION
Helicobacter pylori (HP) has been demonstrated the causative
factor of various gastrointestinal diseases; nevertheless, the relationship between HP infection and gastroesophageal reflux disease
(GERD) is still debated (1).To date, different studies have examined
the relationship between atrophic gastritis due to HP infection and
reflux oesophagitis with conflicting results. HP infection has been
associated to inflammation of gastric mucosa that increases cellular apoptosis and epithelium proliferation. The excessive apoptosis, leads to the atrophy of epithelial cells and glands and could
contribute to carcinogenesis (2). Some authors have found an in-
crease of reflux oesophagitis after HP eradication. On the contrary,
other authors suggested a correlation between HP infection and
presence and severity of reflux esophagitis (3). It was suggested
that HP could contribute to GERD through different mechanisms:
cardias inflammation causing sphincter weakness; increased acid
secretion due to antral gastritis; delayed gastric emptying and citotoxin production causing esophageal epithelium injury. Conversely,
other authors believe that HP infection may even protect against
GERD and HP eradication may lead to an accelerated development
of GERD in ulcer disease patients (4-6). Further, previous studies
have shown an increased effect of proton pump inhibitors on intragastric pH in HP-infected patients suffering from GERD with rapid
heartburn relief and lack of relapse (7). HP could play a protective
role through different mechanisms: decrease of acid secretion resulting from chronic gastritis of the gastric body; improvement of
gastro-oesophageal junction due to proximal gastritis and finally
production of ammonium by the gastric colonization of HP that
could be a potential stopgap system (7-10). The present prospective study was performed in 146 patients with GERD in order to
determine the prevalence of Helicobacter pylori (HP) infection at
gastric mucosa; furthermore the correlation between HP infection
and endoscopic and histological findings was studied through the
statistical comparison of endoscopic and histological data between
subjects with and without HP infection. Finally, we analysed the
statistical correlation between reflux esophagitis and HP infection
and endoscopic data.
Between January 2013 and January 2014, 146 consecutive patients
with daily reflux symptoms were evaluated at the Clinic for gastroenterology and hepatology, Clinical Centre University of Sarajevo.
Exclusion criteria were the following;
1. Previous therapy to eradicate HP,
2. Concomitant assumption of aspirin and non-steroidal
anti-inflammatory drugs,
3. Previous surgical procedures on digestive tract.
All patients were underwent to the protocol, which included anamnesis, clinical examination, esophagogastroduodenoscopy and
HP determination. Symptoms (heartburn, pain, and regurgitation)
were assessed by patients visits. At endoscopy lower oesophageal
31
Correaltion of gastroesophageal reflux disease and Helicobacter pylori infection
sphingter (LES) opening, presence of hiatus hernia, evident refluxes
and esophagitis were evaluated.
Esophagitis was graded by endoscopy according to the SavaryMiller classification:
Grade 0; no lesions;
Grade 1; erythema of the mucosa with multiple erythematous and
exudative lesions;
Grade 2; multiple erosions affecting multiple folds, not confluent;
Grade 3; multiple linear or circumferential erosions that may be
confluent;
Grade 4; ulcer, stricture, or esophageal shortening, Barrett’s epithelium. Barrett’s esophagus has been defined as the presence of
squamo-columnar metaplasia localized at least 3 cm above the
oesophagus-gastric junction; 2–3 samples of the lower oesophagus
(last 3 cm) were obtained. Endoscopic biopsy both of the gastric
body and of the antrum was performed in order to diagnose HP
infection and to obtain histological evaluation of the mucosa.
Statistical analyses
All statistical elaborations were obtained by using SPSS 17.0 Results are expressed as mean values and standard deviation (SD).
Quantitative variables between the two groups (HP positive and
HP negative patients) were compared using the Student’s t-test;
qualitative parameters were compared between the two groups
using chi-squared test. Results were considered statistically significant at P < 0.05.
RESULTS
The study included 146 patients, 58 males and 88 females with a
mean age of 51,5 ± 15,2 years (range 23–89). HP infection was diagnosed in 35 patients (24%), 13 males and in 22 females, while 111
patients (76%), 45 males and 66 females, were HP negative. Patients
with and without HP infection were statistically compared. There
were no significant differences between the two groups regarding
age and gender. Hiatal hernia was found in 97 cases out of 146
patients (66.4%); 25 patients were HP positive (25.7%) and 72 were
HP negative (74.3%); p< 0,05. Reflux esophagitis was evidenced by
endoscopy in 41 patients (28%); according the Savary-Miller classification, out of 146 patients, 105 were graded 0;
Table 1 Clinical parameters of 146 GERD patients
14 patients were graded 1–3 (3 HP positive patients and 11 HP
negative) and finally 27 patients were graded 4 (9 HP positive patients and 18 HP negative) p< 0,05 (Table 1).
We observed that hiatal hernia (p = 0,01), LES opening (p< 0,05)
and pathological reflux number (p = 0,05) were significantly related to the presence of oesophagitis.
Regarding the severity of symptoms statistical difference complained by the patients between the two groups, was found as
follows:
DISCUSSION
The incidence of HP infection in the patients with GERD, varies
widely in literature from 30% to 90% and is approximately of 35%
in most series (11). It was suggested that HP could contribute to
GERD through different mechanisms: development of antral gastritis
that increases acid production, decrease of LES pressure and impairment of gastric filling (12). Nevertheless, the decreasing prevalence
of HP infection and related diseases (ulcer disease, gastric cancer)
in western countries has been paralleled by an increased incidence
of gastro-esophageal reflux and related complications. These epidemiological data do not support a causative role of HP for reflux
disease, but suggest a negative association (13). Further, most trials
on correlation between HP infection and GERD have indicated no
causal relationship (14,15) Some other authors have even found a
lower prevalence of HP infection in patients with reflux symptoms
and have suggested a ‘protective’ role of HP infection against the development of esophageal diseases (16,17). Patients with HP-related
corpus-predominant gastritis may have reduced gastric acid probably
mediated by cytokines such as interleukin 1 (13). In our trial, out of
146 GERD patients, only 24% were HP infected while 76% were HP
negative; in addition we found statistical difference regarding presence and severity of reflux esophagitis between patients with and
without HP infection ( p< 0,05). Most trials on correlation between
HP infection and GERD are based only on endoscopic observations
(18-20). We found significant correlation between HP infection and
hiatal hernia, considered by some authors as a supporting element
of GERD and significantly associated with the development of oesophagitis (21,22). Finally, the relationship between HP infection and
Barrett’s oesophagus and oesophageal adenocarcinom is still contraversary (22).
CONCLUSION
Based on these findings, we found statistical difference regarding presence and severity of reflux esophagitis between patients
with and without Helicobacter pylori infection. However, this is
an evolving area with ongoing research and further assessments in
prospective large studies are warranted.
REFERENCES
1. Harry HX, Yi Yang, Benjamin Chun-Yu Wong: Relationship between Helicobacter
pylori infection and gastroesophageal reflux disease. Chinese J Digestive Disease
2012;5:1-6.
32
2. Kohli Y, Tanaka Y, Ito S. Endoscopic diagnosis of Helicobacter pylori distribution
in human gastric mucosa by phenol red dye spraying method. Nippon Rinsh
2013;51:182-186.
3. Nordenstedt H, Nilsson M, Johnsen R, Lagergren J, Hveem K. Helicobacter pylori
infection and gastroesophageal reflux in a population-based study. Helicobacter
2010;12:16-22.
4. Labenz J, Blum AL, Bayerdörffer E, Meining A, Stolte M, Börsch G. Curing helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis.
Gastroenterology 1997;112:1442-1447.
5. DeVault KR, Castell DO. American College of Gastroenterology: Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J
Gastroenterology 2005; 100:190-200.
6. Tee W, Lambert JR, Dwyer B. Cytotoxin production by helicobacter pylori from
patients with upper gastrointestinal tract disease. J Clin Microbiol 1995;33:12031205.
7. Calleja JL, Suarez M, De Tejada AH, Navarro A. Pantogerd Group. Helicobacter pylori infection in patients with erosive esophagitis is associated with rapid heartburn relief and lack of relapse after treatment with pantoprazole. Dig Dis Sci 2005;
50:432-439.
8. Cammarota G, Gasbarrini GB. Helicobacter pylori and gastro-oesophageal reflux
disease: information underlying pathology is not given. BMJ 2004; 14:402.
9. Thor PT, Blaut U:. Helicobacter pylori infection in pathogenesis of gastroesophageal reflux disease. J Physiology and Pharmacology 2006; 57(S3):81-90.
10. Dore MP, Fastame L, Tocco A, Negrini R, Delitala G, Realdi G. Immunity markers in
patients with Helicobacter pylori infection: effect of eradication. Helicobacter 2005;
10:391-397.
11. Smout AJPM:. Endoscopy-negative acid reflux disease. Aliment Pharmacol Ther
1997; 11(S2):81-85.
12. Gisbert JP, Pajares JM, Losa C. Helicobacter pylori and gastroesophageal reflux
disease: friends or foes? Hepatogastroenterology 1999; 46:1023-1029.
13. Sharma P, Vakil N. Helicobacter pylori and reflux disease. Aliment Pharmacol Ther
2003; 17:297-305.
14. Lord RV, Frommer DJ, Inder S, Tran D, Ward RL. Prevalence of Helicobacter pylori
infection in 160 patients with Barrett’s oesophagus or Barrett’s adenocarcinoma.
Aust NZJ Surg 2000; 70:26-33.
N. Vanis et al .
15. Wu JC, Sung JJ, Ng EK, Chan FK, Ching JY, Ng AC, Go MY, Wong SK, Ng EK, Chung
SC. Helicobacter pylori infection is associated with milder gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2000;14:427-432.
16. Ohara S, Sekine H, Iijima K, Moriyama S, Nakayama Y, Kinpara T, Kato K, Asaki S,
Katakura T, Ikeda T, Toyota T. Gastric mucosal atrophy and prevalence of Helicobacter pylori in reflux esophagitis of the elderly. Nippon Shokakibyo Gakkai Zasshi
1996;93:235-9.
17. Moayyedi P, Talley NJ. Gastro-oesophageal reflux disease. Lancet 2006; 367:20862100.
18. Fennerty MB, Sampliner RE, Grewal HS. Barrett’s oesophagus-cancer risk, biology
and therapeutic management. Aliment Pharmacol Ther 1993; 7:339-345.
19. Güliter S, Kandilci U. The effect of Helicobacter pylori eradication on gastroesophageal reflux disease. J Clin Gastroenterol 2004;38:750-755.
20. Oberg S, Peters JH, Nigro JJ, Theisen J, Hagen JA, DeMeester SR, Bremner CG,
DeMeester TR. Helicobacter pylori is not associated with the manifestations of
gastroesophageal reflux disease. Arch Surg 1999;134:722-726.
21. Schwizer W, Thumshirn M, Dent J, Guldenschuh I, Menne D, Cathomas G, Fried M.
Helicobacter pylori and symptomatic relapse of gastro-esophageal reflux disease: a
randomized controlled trial. Lancet 2001;357:1738-1742
22. Sharma VK, Howden CW. Decreased prevalence of H. pylori and cagA+ H. pylori in
GERD and Barrett’s esophagus (BE) with or without dysplasia or adenocarcinoma
(D/AC): a meta-analysis. Gastroenterology 2002;122:A291.
Nenad Vanis, MD, PhD
Clinic for Gastroenterohepatology,
Phone: +387 33 297 911
Email: vanis@bih.net.ba
Original article
A prospective comparison of preperitoneal with prefascial herniorrhaphy for the treatment of inguinal hernias
Prospektivna komparacija preperitonealne i prefascijalne hernioplastike u tretmanu ingvinalnih hernija
Ismar Rašić*, Goran Akšamija, Adi Mulabdić, Adis Kandić
Clinic for General and Abdominal Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina
ABSTRACT
SAŽETAK
Inguinal hernia repair is the most common operation in general
surgery. The fact is that in the field of inguinal repairs are several different surgical methods, but it is still a current issue of choice in the
operative treatment of inguinal hernias and places the best position
for the prostetic mesh. The aim of this study was to evaluate and
compare the outcome and postoperative complications of open inguinal hernia repair by using Rives and the Lichtenstein tension-free
technique, and to determine their association with the technique
and placing prostetic meshes. A prospective clinical study was carried during 2012 at the Clinic for General and Abdominal Surgery,
Clinical Center University of Sarajevo. From 60 patients with inguinal hernia, 30 patients were surgically treated by Rives technique,
while other 30 patients were undergoing hernia repair by Lichtenstein technique. For all patients it were collected planned clinical
data from the medical and surgical protocols, the length of follow-up
surgery, length of hospitalization, surgical outcomes and appearing of
postoperative complications untill one year after surgery.The results
showed that the duration of surgery significantly shorter in patients
operated using Lichtenstein technique (p<0.001), while the length
of hospitalisation is significantly less in patients operated by Rives
technique (p<0.001). The significantly lower rate of pain (p<0.01),
infection (p=0.019), fever (p= 0.006) was found in the early postoperative period, as well as the occurrence of seroma (p=0.038) at patients treated by Rives technique with preperitoneal mesh position.
None of the patients in both groups did not develop recurrence of
inguinal hernia during the study period (up to twelve months after
surgery), while the varicocele occurred in one patient one year after
Lichtenstein herniorrhaphy. In patients who were underwent surgery
using Lichtenstein technique, four (13.3%) patients were developed
hydrocele for a period of one year follow-up, while two patients
(6.6%) developed ischemic orchitis with accompanying atrophy of
the testes.The results of this study indicate that there are significant
differences in the incidence of postoperative complications between
the observed tension-free techniques of inguinal hernia repair with
prosthetic mesh on different locations, emphasizing hernioplastics
Rives with preperitoneal mesh setting as a safer and more efficient
method of operative solving of inguinal hernia.
Ingvinalna hernioplastika je najčešća operacija u opštoj hirurgiji. Činjenica je da na polju ingvinalne hernioplastike postoji više
različitih operativnih metoda, ali je i dalje aktualno pitanje izbora
tehnike u operativnom tretmanu preponske kile i mjesta najbolje
pozicije za mrežicu. Cilj ovog rada je bio komparirati ishod i postoperativne komplikacije otvorene netenzione ingvinalne hernioplastike
tehnikom po Rivesu i tehnikom po Lichtensteinu, te utvrditi njihovu
povezanost sa operativnom tehnikom mjestom postavljanja mrežice.
Ova klinička studija prospektivnog karaktera provedena je na Klinici
za opštu i abdominalnu hirurgiju Kliničkog centra Univerziteta u Sarajevu tokom 2012. godine. Ispitivanjem je bilo obuhvaćeno 60 pacijenata sa ingvinalnom hernijom, od kojih je 30 pacijenata operisano
tehnikom po Rivesu, a ostalih 30 tehnikom po Lichtensteinu. Svim
pacijentima sakupljani su planirani klinički podaci iz istorija bolesti i
operativnog protokola, uz praćenje dužine operacije, dužine hospitalizacije, operativnog ishoda i pojave postoperativnih komplikacija
do godine dana nakon operacije. Rezultati ispitivanja ukazuju da je
trajanje operacije značajno kraće kod pacijenata operisanih Lichtenstein tehnikom (p<0.001), a da je dužina hospitalizacije značajno
manja kod pacijenata operisanih Rives tehnikom (p<0.001). U ranom
postoperativnom periodu je nađena signifikantno manja učestalost
boli (p<0.01), infekcije (p=0.019) i febrilnosti (p=0.006), kao i pojave
seroma (p=0.038) kod pacijenata tretiranih Rives tehnikom sa preperitonealnom pozicijom mrežice. Ni jedan pacijent iz obje grupe nije
razvio rekurenciju ingvinalne hernie tokom praćenog perioda, dok
se varikokela javila u jednog pacijenta godinu dana nakon urađene
Lichtenstein hernioplastike. U pacijenata operisanih Lichtenstein metodom hidrokela se razvila kod četiri pacijenta (13.3%) nakon perioda praćenja od godinu dana. U istoj grupi pacijenata u navedenom
vremenskom periodu kod dva pacijenta (6.6%) se razvio ishemični
orhitis sa pratećom atrofijom testisa. Rezultati ovog ispitivanja ukazuju na postojanje značajnih razlika u učestalosti postoperativnih
komplikacija između posmatranih netenzionih tehnika ingvinalne
hernioplastike sa različitom lokacijom mrežice, ističući hernioplastiku
po Rivesu sa preperitonealnim postavljanjem mrežice kao sigurniju i
efikasnu metoda u operativnom rješavanju ingvinalne hernije.
Key wods: inguinal hernia, hernia repair, Rives, Lichtenstein
Ključne riječi: ingvinalne hernije, hernioplastika, Rives, Lichtenstein
34
INTRODUCTION
A hernia of the abdominal wall is the protrusion of parietal peritoneum through congenital or acquired opening of the abdominal
wall, in which, as in a bag, enter organs of abdominal cavity. Inguinal
hernias are the most common pathology in the field of surgery and
make up around two thirds of all hernias of the abdominal wall. All
inguinal hernias are the result of the weakness of the inguinal region
as the lowest part of the abdominal wall, or weakened transverse fascia in the region of myopectineal orifice of the inguinal canal, which
is the passage from the abdomen into the scrotum. As a result of
the testis passage through the inguinal region of the anterior abdominal wall, in this wall remains the inguinal canal as his weak point
(1). Repair of inguinal hernia is one of the most performed surgical
procedures. These surgical techniques can be devided into tension
and tension free procedures. Tension free techniques can be classic open procedures like Lichtenstein and Rives or endoscopic like
transabdominal preperitoneal herniorrhaphy (TAPP) and total extraperitoneal herniorrhaphy (TEP) (2). First tension free techniques are
starting to develop in the mid sixties, while the first successful and
widely used Lichtenstein method with prefascial setting the mesh
used since 1986 (3). Amid with his associates found that the Lichtenstein method is safe, easy and efficient way of hernia repair with the
recurrence rate of only 0.12 at 3.250 were done hernioplastics (4).
Various prosthetic materials can be used for tension free procedures
like dacron and polypropylene mesh.The meta-analysis, done by the
EU Hernia Trialists, has been shown that hernia repair with the use
of mesh reduces the relapse rate by 50% (2% of the mesh versus
4.9% without mesh) (5). Position meshes with nontension methods
can be at different levels. Some believe that the front subaponeurotic
approach is superior because it is technically feasible, and when done
correctly, is associated with a lower incidence of recurrence. By placing nonresorptive mesh between mioaponeurotic ports up and inguinal canal down reinforces the posterior wall of the inguinal canal
without tension. Others argue that the mesh should be placed in the
preperitoneal position (Rives technique), where the intra-abdominal
pressure will hold it in place (6,7). Aim of this study was to compare
outcome of two tension free technique in the treatment of primary
inguinal hernia: Rives with preperitoneal setting the mesh and Lichtenstein with prefascial setting the mesh.
I. Rašić et al .
the same education. Lichtenstein technique is based on prefascial
mesh position, with its fixation to the pubic tubercle, along ligamentum Pouparty and the internal oblique muscle, while Rives technique is based on the preperitoneal mesh position with its fixation
to Cooper’s ligament, along iliopubic tract laterally and medially for
transversal muscular arch. In all patients polypropylene mesh 6 x 11
cm was applied using 2-0 Prolene suture. Antibiotic prophylaxis with
cefotaxim 2 g i.v. was performed in all patients of both groups prior
to surgery, while prophylactic anticoagulant therapy was given to all
patients during hospitalization. Patients were monitored on occurrence of early postoperative complications (hematoma of wound,
hematoma of scrotum, infection of wound, urinary retention, urinary
tract infection, postoperative wound pain) during the first 7 and after
30 postoperative days, and late postoperative complications six and
12 months after surgery (persistent postoperative pain, testicular
atrophy, hydrocele, varicocele, relapse). The protocol of study was
approved by the local Ethics Committee. Informed consents was also
obteined from all patients.
Statisical analyses
All statistical analyses were conducted using statistical program
SPSS Version 15. Data are expressed as numbers, percentage (%),
means with standard deviation (SD). Student’s t-test was used for
comparison of mean values of the variables with normal, while MannWhitney U test was used for comparison of variables without normal distribution. Chi-square test was used to determine the existence of differences in categorical variables between groups. Pearson
correlation test was used to determine the correlation between
monitored variables in the selected surgical techniques. Statistical
significance was considered with p<0.05.
RESULTS
All the patients in both groups were males. The average age of
the patients surgically treated with Lichtenstein procedure (group
1) was 58.0±11.7 years, and patients undergoing Rives hernia repair
(group 2) 55.7±11.8 years (Figure 1). Most of the respondents in
both groups of patients were over 60 years of age. No significant
differences in the number of patients by age groups in both patient
groups (X2=0.725, p=0.948).
This prospective clinical study was conducted during 2012 years
in the Clinic for General and Abdominal Surgery of Clinical Center
University of Sarajevo. After excluding cases of severe comorbidity,
previous lower abdominal or retropubic surgery that might interfere with placement of the mesh, previous contralateral hernia repair
with preperitoneal prosthetic material, reccurent hernia, incarcerate
inquinal hernia, proven abdominal neoplasms with a short term survival and refusal of surgical treatment, 60 patients with primary inguinal hernia were included in the study. All patients were devided randomly into two groups: 30 patients for surgical treatement by Rives
technique and 30 patients for surgical treatement by Lichtenstein
technique. Both surgical procedures were performed under general
anasthesia and done by a team of surgeons who have undergone
Figure 1 The age of the respondents in relation to surgical
technique
1 - Lichtenstein group, 2 - Rives group
Data are presented as median and interquartile range.
In relation to the type of hernia, 30% of patients treated with
Lichtenstein technique were had indirect hernia, 63.3% direct hernia, while the combined inguinal hernia was present in 6.7% of
patients of this group (Table 1). In the group of patients treated
by Rives surgical technique the most patients (43.3%) were had a
direct hernia. Indirect inguinal hernia was present in 33.3% of patients, while 23.3% of patients were had a combined hernia. There
were no statistically significant differences in the frequency of different types of hernia between the two groups of patients followed
(X2=3.955, p=0.138).
Table 1 Type of inguinal hernias
X2=3.955; p=0.138
According to the Nyhus classification, the highest number of
hernias of both groups were Nyhus III a grade (63.33% vs. 43.33%),
followed by Nyhus II (20% vs. 30%), while the least was Nyhus III
b grade (16.66% vs. 26.7%). No patients had a hernia classified as
Nyhus I or Nyhus IV. There were no statistically significant differences in the incidence of hernia by Nyhus classification between
these groups of patients (p=0.298). Mean surgery duration was
significantly shorter in the Lichtenstein group (36.37±5.49 minutes) compared to subjects of Rives group (46.03±6.29 minutes),
p<0.001 (Figure 2). The average of hospitalization length in the
Lichtenstein group was 3.05±1.27 days, while in Rives group was
2.87±0.82, a statistically significant difference (p<0.001).
Figure 2 The time of surgery duration in relation to the
applied surgical technique
patients monitored groups in the early postoperative period. Namely, 30% of patients in the Lichtenstein group were febrile compared
to 3.33% in the Rives group (X2=7.68, p=0.006). Infections of surgical wound were significantly higher in the first seven days in the
Lichtenstein group patients (p=0.019) compared to a comparative
group of patients. It was diagnosed in 16.7% of patients from the
Lichtenstein group, while patients surgically treated Rives technique
did not have detected infection of wound in any of case. In patients
who underwent hernia repair by using Lichtenstein technique seroma was found in 13.3% of patients, whereas in patients with initial Rives hernioplastics has been free of seroma as postoperative
complications (p=0.038). In the first seven days postoperatively there
was no significant differences in the frequency of occurrence of hematoma of wounds between the two groups of patients (X2=0.162,
p=0.687), but swelling of scrotum was found in 20% of patients in
the Lichtenstein group compared to 3.3% in Rives group (X2=4.043,
p=0.044). The occurrence of urinary tract infections and urinary
retention has not been recorded in these groups of patients. Significant intergroup differences in the intensity of pain in the groin
area was confirmed after the first, sixth and twelfth postoperative
month (p <0.001). One year after surgery varicocele is registered in
one (3.33%) patients in the Lichtenstein group, while patients from
Rives group did not develop this kind of complications. One year
after surgery hydrocele is registered in 4 (13.3%) patients in the Lichtenstein group, without the appearance in Rives group. Ischemic
orchitis with subsequent testicular atrophy was found in two (6.66%)
patients in the Lichtenstein group, without the appearance of Rives
group. Relapse hernia has not been verified in any of the operated
patients after a follow-up period of twelve months. There was a statistically significant positive correlation between the presence of pain
of the first and sixth (r=0.549, p=0.002), and the sixth and twelfth
months (r=0.771, p<0.001) after Lichtenstein hernioplastics done. In
this group of patients demonstrated a statistically significant association between early infection and fever (r=0.683, p<0.01), infection
of wound and length of hospitalization (r=0.703, p<0.01), and the
association between surgical intervention and duration of hospitalization (r=0.613, p<0.01). Length of hospitalization was also in direct
significant correlation with the occurrence of postoperative hematoma (r=0.381, p<0.05), table 2. A significant positive correlation in
the early postoperative period was confirmed between the occurrence of hematoma of wound and length of hospitalization (r=0.469,
p<0.01) in patients with Rives herniorrhaphy, as well as between the
appearance of the swelling of scrotum and length of hospitalization
(r=0.492, p<0.01), Table 3.
Table 2 Correlation of early postoperative complications in
patients with Lichtenstein herniorrhaphy
1 - Lichtenstein group, 2 - Rives group
Data are presented as median and interquartile range.
Using a pain scale (Visual Analogue Pain Scale) significant intergroup difference in the intensity of pain in the area of the surgical incision was observed on the second day (5.53±1.1 vs. 3.2±1.24,
p<0.01), and the third day (4.87±1.36 vs. 2.74±0.99, p<0.01) in the
Lichtenstein patient group compared to the Rives group. There was
significant difference in the frequency of occurrence of fever among
35
** Correlation is significant at p<0.01.
* Correlation is significant at p<0.05.
36
Table 3 Correlation of early postoperative complications in
patients with Rives herniorrhaphy
** Correlation is significant at p<0.01.
* Correlation is significant at p<0.05.
Analysis of monitored variables one year after surgery indicates
a statistically significant negative correlation between Lichtenstein
herniorrhaphy and the presence of chronic postherniorrhaphy pain
(r=-0302, p<0.05). It was observed a statistically significant positive
correlation between chronic postherniorrhaphy pain in this group of
patients and the occurrence of varicocele (r=0.432, p<0.01) as well
as a significant positive correlation between chronic postherniorrhaphy pain and the occurrence of hydrocele (r=0.280, p<0.05) and
ischemic orchitis / testicular atrophy (r=0.280, p<0.05).
DISCUSSION
Numerous studies have compared the Lichtenstein technique
with other surgical treatment of inguinal hernia. The European collaborative study on hernia (The European Union Hernia Trialists
Collaboration), which analyzed all randomized studies that compared the open inguinal hernia repair with mesh-type Lichtenstein
with methods without mesh, included 4.005 treated patients (8).The
study indicated that the results of surgical treatment were far better
with methods that are used mesh, including faster return work activity and lower incidence of hernia recurrence.All hernioplastics in our
study were performed as elective surgery.There were no statistically
significant differences in the incidence of hernia by Nyhus classification between these groups of patients (p=0.298). The average age
of patients surgically treated with Lichtenstein or Rives procedure
was not significantly different, with the largest number of patients in
both groups older than 60 years (60% vs. 56.7%), which is consistent
with published data on the average age of patients with initial inguinal
hernia repair in the world (9,10).
The operating procedure was significantly shorter in the Lichtenstein group of patients in comparison to Rives hernia repair, but the
duration of hospitalization was significantly shorter in patients after
Rives hernioplastics. The length of hospitalization after Lichtenstein
hernioplastics was significantly associated with the occurrence of infection of wound, fever and hematoma of wound, while the length of
hospitalization after Rives hernioplastics was significantly associated
with hematoma of wound and swelling of the scrotum. Muldoon and
colleagues have compared the results Lichtenstein inguinal hernia
repair with mesh subaponeurotic position in 126 surgically treated
patients with the results of Read-Rives technique with preperitoneal mesh position in 121 patients (11). The average time operation
in Read-Rives reparation was 9 minutes longer than in Lichtenstein
reparation. In study by Zejbek and associates the average duration of
the operation by Lichtenstein procedure was 56 minutes and the av-
I. Rasić et al .
erage time restore routine activities of 20 days, with post-operative
complications registered in 11.7% of patients and hernia recurrence
in 0.6% of treated patients (10). In study from Güner and associates the average length of preperitoneal inguinal hernia repair was
significantly longer with significantly shorter length of hospitalization compared to patients with initial hernia repair by Lichtenstein
method (12). In contrast to these results, Fricano and associates in
a sample of 406 patients mean age of 52±12.7 years, found that the
average time for Lichtenstein procedure with minor modifications
was 65±13.8 minutes, which is almost twice as long compared to
duration of the same procedures in our sample (13).
In our research, we found significant differences in the intensity
of early postoperative pain between groups, with significantly lower
pain intensity after Rives hernioplastics (p<0.01), which can be explained by preperitoneal mesh position and its separation from funicular elements in the inguinal canal with repaired transversal fascia
and absence of fibrous tissue reactions to the mesh. No patient in
Rives group had infection of wound, whereas in the first seven days
infection of wound had 16.7% of patients in the Lichtenstein group.
Infection is one of the most common complications after hernioplastics done. It can be recognized only as a minimal occurrence of pus
around a cutaneous suture, or as a process that can be extensive and
require prolongation of hospitalization, intravenous antibiotics or
surgical re-intervention with debridement, drainage and eventual extraction of mesh. The ratio of infection of wound after hernioplasty
of inguinal hernia was ranging from 0.9 to 9%, depending on the
clinical variables of the population, as well as whether to use mesh
or antibiotic prophylaxis. Several studies in the United Kingdom
have announced a relatively high incidence of infections of surgical
wound after inguinal groin repairs. Holmes and Readman reported
the occurrence of infection of wound in 4% patients after the first
postoperative month (14). Despite the opinion of some authors that
the mesh increases the risk of infection, Gilbert and Felton found
no difference in the proportion of infections in hernia repair with
and without the use of mesh (15). According to the results of this
study, the two most important variables in reducing local complications in the surgical wound were antibiotic prophylaxis and techniques of closing. The introduction of antibiotic prophylaxis resulted
in reducing the ratio of infection from 1.2% (in patients who did not
receive antibiotic prophylaxis) to 0.2% (in those who received antibiotic prophylaxis). In contrast to these findings, the results of Perez
and authors have shown that preoperative administration of singledose antibiotic does not reduce significantly the risk of infection of
wound (16). However, most authors agree that the prophylactic use
of antibiotics is justified (17).Antibiotic prophylaxis as a single variant
are applied in all our patients. However, the incidence of infections
of wound in the early postoperative period was higher after the Lichtenstein hernia repair compared to Rives. In doing so, none of the
patients after Rives hernioplastics had no drainage. All patients after
Lichtenstein hernioplastics had subaponeurotic drainage, which can
be coupled with the onset of fever and a higher incidence of infection
of wound in this group of patients.
We found that the incidence of seroma and scrotal swelling in the
early postoperative period was significantly greater after Lichtenstein
hernioplastics compared to Rives technique. Also, prefascial position
of the mesh in Lichtenstein procedure was statistically significantly
associated with the development of varicocele and hydrocele with
ischemic orchitis one year after surgery. There were no reported
recurrence of inguinal hernia in any groups of patients during the
studied period.
In a large prospective clinical study which was conducted from
1989 to 2007 Just and his colleagues were included 2.002 inguinal
hernia repair by Lichtenstein technique and found that 7.7% cases
were accompanied by complications, of which 3.7% were hematomas, 2.2% infections, 1.3% seroma and 0.5% complications of
other causes (18). Muldoon and colleagues, comparing the results
of Lichtenstein inguinal hernia repair in 126 patients with results of
Read-Rives technique in 121 patients, did not register infections of
wound, and frequency of other early and late complications was low
and similar in both groups of patients (11). Hematoma of scrotum
was found in 3.5% of patients in the Lichtenstein versus 3.7% in the
Read-Rives group, hematoma of wound in 2.6% vs. 4.6%, testicular
atrophy in 2.6% vs. 0.9%, inguinal discomfort and pain in 9.3% vs.
6.1% of patients, confirming that both the operational procedures
provide a low ratio of postoperative complications and good longterm outcome.
CONCLUSION
Results of the study indicate the justification preperitoneal setting
mesh, considering the significantly lower incidence of postoperative
complications, especially infection of wound and seroma formation
in the early postoperative period as well as absence of varicocele
and hydrocele formation during one year follow-up. Preperitoneal
mesh setting close to all the weak spots of myopectineal orifice.This
surgical technique can be especially recommended for addressing
inguinal hernia in patients with increased intra-abdominal pressure
when other techniques may be insufficient due to the protrusion of
the mesh.
5. The EU Hernia Trialists Collaboration. Repair of groin hernia with synthetic mesh:
meta-analysis of randomized controlled trials. Ann Surg 2002;235(3):322-332.
6. Bringman S, Ramel S, Heikkkinen TJ, England T, Westman B, Anderberg B. Tensionfree inguinal hernia repair: TEP versus mesh plug versus Lichtenstein: a prospective
randomized controlled trial. Ann Surg 2003;237(1):142-147.
7. Bhat MG, Somasundaram SK. Preperitoneal mesh repair of incisional hernias: A
seven year retrospective study. Indian J Surg 2007;69:95-98.
8. EU Hernia Triallists Collaboration. Mesh compared with non-mesh methods of
open groin hernia repair: Systematic Review of randomized controlled trials. Br J
Surg 2000; 87(7):854-859.
9. Kingsnorth A, LeBlanc K. Hernias: inguinal and incisional. Lancet 2003;
362(9395):1561-1571.
10. Zejbek N, Tas H, Peker Y, Yildiz F, Akdeniz A, Tufan T. Comparison of Modified
Darn Repair and Lichtenstein Repair of Primary Inguinal Hernias. J Surg Res
2008;146(2):225-229.
11. Muldoon RL, Marchant K, Johnson DD, Yoder GG, Read RC, Hauer-Jensen M. Lichtenstein vs anterior preperitoneal prosthetic mesh placement in open inguinal
hernia repair: A prospective, randomized trial. Hernia 2004;8(2):98-103.
12. Güner A, Güler K, Bozkurt S, Kaya MA, Leblebici IM. Anterior Lichtenstein Repair
versus Posterior Preperitoneal Repair Techniques for Recurrent Inguinal Hernia.
Erciyes Medical Journal 2009;31(1):37-43.
13. Fricano S, Fiorentino E, Cipolla C, Matranga D, Bottino A, Mastrosimone A, Bonanno E, Latteri MA. A minor modification of Lichtenstein repair of primary inguinal
hernia: postoperative discomfort evaluation. Am Surg 2010;76(7):764-769.
14. Holmes J, Readman R. A study of wound infection following inquired hernia repair.
J Hosp Infect 1994;28(2):153-156.
15. Gilbert AJ, Felton LL. Infection in inguinal hernia repair considering bacterial and
antibiotics. Surg Gynecol Obstet 1993;177(2):126-130.
16. Perez AR, Roxas MF, Hilvano SS. A randomized, double-blind, placebo-controlled
trial to determine the effectiveness of antibiotic profilaxis for tension-free mesh
herniorraphy. J Am Coll Surg 2005;200(3):392-398.
17. Sanabria A, Dominguez LC, Valdivieso E, Gomez G. Prophylactic antibiotics for
mesh inguinal hernioplasty. A meta-analysis. Ann Surg 2007;245(3):392-394.
18. Just E, Botet X, Martinez S, Escola D, Moreno I, Duque E. Reduction of the
complication rate in Lichtenstein hernia repair. International Journal of Surger
2010;8(6):462-465.
REFERENCES
1. Gluhović A, Parčević Z, Popović M. Hirurgija preponskih kila. Novi Sad-Sombor:
Visio Mundi Academic Press; 2005.
2. Kurzer M, Kark A, Hussain T. Inguinal hernia repair. J Perioper Pract 2001;17(7):318330.
3. Lichtenstein IG, Shulman AG. Ambulatory (outpatient) hernia surgery including a
new concept: introducing tension-free repair. Int Surg 1986;71(1):1-4.
4. Amid PK, Shulman AG, Lichtenstein H. A clinical evaluation of the Lichtenstein
tension-free hernioplasty. Int Surg 1994;79(1):76-79.
37
Ismar Rašić, MD
Clinic for General and Abdominal Surgery
Phone: +387 33 297 326
Email: fijukan@gmail.com
Original article
Assessment of initial diagnostic procedures in isolated
thoracic injuries
Procjena inicijalnih dijagnostičkih procedura kod
izolovanih povreda grudnog koša
Alma Alihodžić-Pašalić*, Safet Guska, Ademir Hadžismailović, Alen Pilav, Kemal Grbić
Clinic of Thoracic Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina
ABSTRACT
SAŽETAK
Thoracic injuries are the cause of 20 - 25% of all deaths caused
by trauma and the second most common cause of mortality and
the main contributing factor in the 50% of all deaths. A large number
of patients with chest injuries are not hospitalized but are treated
on an outpatient basis. Chest injuries must be treated properly to
avoid potential complications that may be life threatening. The most
serious thoracic injuries often occur in the absence of damage to
the chest wall. Therefore it is very important to fully understand the
different events that occur as a result of thoracic injury in respect of
which it is possible to define the severity of injury. Two factors are
very important: time and a type of surgical help. We retrospectively
analyzed the conducted initial diagnostic procedures of injured persons with isolated injuries of the chest. At the Clinic for Thoracic
Surgery, Clinical Center University of Sarajevo were analyzed 320
patients between January 2007 and January 2012 years. The initial
diagnostic procedures were performed at 67.81% (217/320) injured.
After secondary examination or shorter monitoring, additional
diagnostic procedures were indicated and performed in only 5%
(16/320) of injured. Initial diagnostic sensitivity was 98.1%, specificity
98.6%, positive predictive value 97.1% and negative predictive value
of 99.0%. Conclusion: the defined initial diagnostic procedures in the
majority of patients with isolated thoracic injuries were sufficient to
assess the type and severity of injury.
Torakalne povrede su uzrok kod 20 25% svih smrtnih slučajeva
uzrokovanih traumom, a na drugom su mjestu uzroka smrtnosti i
glavni doprinoseći faktor u ostalih 50% smrtnih slučajeva. Veliki broj
pacijenata sa povredama grudnog koša se ne hospitalizira već se tretira ambulantno. Povrede grudnog koša moraju biti ispravno tretirane
da bi se izbjegle potencijalne komplikacije koje mogu ugroziti život
povrijeđenog. Najteže torakalne povrede se često pojavljuju u odsustvu oštećenja zida grudnog koša. Zbog toga je jako važno detaljno
poznavanje različitih manifestacija koje mogu nastati kao posljedica
torakalne povrede, a na osnovu kojih se mogu ustanoviti pojedine lezije. Treba voditi računa o dva faktora: faktor vrijeme i faktor hirurška
pomoć. Istraživanjem je obuhvaćeno 320 pacijenata hospitaliziranih na
Klinici za torakalnu hirurgiju Kliničkog centra Univerziteta Sarajevo
sa isključivo izolovanim torakalnim povredama što je ujedno i osnovni kriterij uključivanja pacijenata u provedeno istraživanje.Inicijalna
dijagnostička obrada je provedena kod 67,81%(217/320) povrijeđenih.
Nakon sekundarnog pregleda ili kraćeg praćenja stanja povrijeđenog
dodatna dijagnostika je bila indicirana i urađena kod samo 5% (16/320)
povrijeđenih. Senzitivitet inicijalne dijagnostike je 98,1%, specificitet
98,6%, pozitivna prediktivna vrijednost 97,1% i negativna prediktivna
vrijednost 99,0%. Zaključak: definisana inicijalna dijagnostička obrada
je kod većine pacijenata sa izolovanim torakalnim povredama bila dovoljna za procjenu vrste i težine povrede.
Key words: isolated thoracic injuries, the initial diagnostic procedures
Ključne riječi: izolovana torakalna povreda, inicijalne dijagnostičke
procedure
INTRODUCTION
Primary aim of the first examination of the patients with isolated thoracic injuries is to identify life-threatening conditions
which are necessary to be disposed of immediately (1,4,5,6,7,8).
The first review should start trying to obtain appropriate medical history or hetero-history data associated with the violation.
Getting the data should be accompanied by physical examination
(inspection, palpation, percussion and auscultation) and the concomitant use of basic laboratory tests (including blood sample to
determine the blood Group and cross-reaction) and if the patient’s
condition permits continues with diagnostic procedures (standard
chest radiography, FAST) (1,6,9,10,11,12). Many health centers, in
addition to the above procedures, as the initial diagnostic proce-
Thoracic trauma is a major diagnostic and therapeutic challenge
for surgeons (1,2,3). In diagnostic evaluation there are precisely
defined sequence of procedures for patients with isolated thoracic
trauma. Committee on Trauma American College of Surgeons in
1997. adopted ATLS (Advanced Trauma Life Support) (1.2) which
includes:
1. First examination
2. Resuscitation
3. Secondary examination and
4. Treatment
39
Assessment of initial diagnostic procedures in isolated thoracic injuries
dure use CT of the thorax (7,13,14,15). At the Clinic for Thoracic
Surgery UCC Sarajevo initial diagnostic procedures include: history and heteroamnesis,physical examination (inspection, palpation,
percussion and auscultation) standard chest radiography,setting a
standard laboratory, blood group and cross reacting, abdominal ultrasound and lung bases.
The aim
1. Analysis ofthe conducted initial diagnostic procedures and
their valuation in the diagnosis of the type and severity of isolated thoracic injuries.
2. Calculat specificity, sensitivity, positive and negative predictive
value of total initial diagnostic evaluation of patients with isolated thoracic injuries.
Retrospective analysis included 320 patients hospitalized at the
Clinic for Thoracic Surgery, Clinical Center University of Sarajevo
in the period between January 2007 and January 2012 with only
isolated thoracic injuries. Defined criteria for inclusion of patients
in the survey include:
RESULTS
Total of 320 patients with isolated chest trauma was hospitalized
and treated for at the Clinic for Thoracic Surgery UCC Sarajevo.
Male [78.44% (251/320)] to female [21.56% (69/320)] ratio was
3.64:1. The average age of hospitalized patients was 43.17 ± 17.9
(2-98 years). Average age of men was 46.83 ± 17.80 (range 14 to
90 years), and women 54.91 ± 18, 54 (2 to 98 years) and there is
a statistically significant difference (p<0.001634) in relation to the
age by gender. The initial diagnostic procedures; history, clinical
examination, PA chest radiography, standard laboratory and ultrasonic examination of the thorax and abdomen, was performed in
67.81% (217/320) injured (Table 1). In patients with fractures of
the sternum was mandatory made cardiological examination with
ECG and determination of biohumoral enzyme status and was perfomed in 15,31% (49/320). The initial diagnostics procedures complemented with CT scan of the thorax was performed in 14,06%
(45/320) injured.
Table 1 Performed the initial diagnostic procedures
1. General information (name, age, sex, date of admission and
discharge, injury mechanism, type and severity of injury).
2. Diagnostic procedures were performed in all patients were
divided into two groups:
Initial (standardized) diagnostic procedures (medical history, physical examination, standard PA or AP chest radiography, depending
on the condition of the patient, and the lateral radiogram if the
patient’s condition permits, standard laboratory tests, ultrasound
examination of the abdomen and thorax bases.
Additional diagnostic procedures according to the type of injury
and the patient’s condition are:
- in patients with fractures of the sternum was mandatory made
cardiological examination with ECG and determination of biohumoral enzyme status.
Initial treatment that could be performed after the initial diagnostic procedures confirmed their sufficiency in assessment of
the type and severity of injury. Initial treatment (Figure 1) was conservative in 63.75% (204/320) of cases while surgical treatment was
carried out in 36.25% (116/320) injured.
- CT with contrast in order to resolve diagnostic problems unexplained by the previous standard treatment, -endoscopic examinations
(bronchoscopy in suspected rupture of a major airway, esophagography and esophagoscopy for suspected possible esophageal injury)
The results are presented numerically, graphically and in tables. Statistical analysis was performed by statistical software MS Excel by
using the appropriate statistical methods (parametric data were
analyzed by calculating the absolute and the percentage value, the
arithmetic mean with standard deviations, and t - Student test; nonparametric data are processed in absolute and percentages values
and with corresponding chi square test). A defined level of significance was p <0.05. Our results were identified and compared with
the results of relevant research data presented in contemporary
literature.
Figure 1 Types of initial treatment
Secondary examination is much more detailed and complete review, and aims to identify all violations on the basis of which it will
be planned further diagnostic procedures and appropriate treatment. Additional diagnostic procedures (Figure 2) were indicated in
only 5% (16/320) of cases.
40
Figure 2 Additional diagnostic procedures.
The average period of the hospitalization for all injured with isolated thoracic trauma was 5,9±4,0 days (from 6 hours to 16 days).
In relation to the type of injury (Table 2), penetrating vs. blunt, the
average length of hospitalization was 5.4 ± 3.36 and 6.07 ± 4.26
days respectively. Statistically, there is no significant difference in
relation to the duration of hospitalization between penetrating vs.
blunt trauma (0,2766 > 0,05).
Table 2 Length of hospitalization in relation to the type of injury
Pneumothorax was the most common [51.72% (75/145)] endopleural disorder established in blunt injuries and hemato - pneumothorax [37.72% (46/145)] in penetrating injuries (Table 3).
Table 3 Types endopleural disorders in relation to the violation
Sensitivity, specificity, positive and negative predictive value of
total initial diagnosis of isolated thoracic injuries of all patients
treated in the study period at the Clinic of Thoracic Surgery CCU
are: SENZITIVITY = 98,1%; SPECIFICITY = 98,6%; PPV = 97,1%
and NPV = 99,0%.
DISCUSSION
At the Clinic for Thoracic Surgery CCU Sarajevo initial diagnostic procedures include: history and heteroanamnaesis, physical
examination (inspection, palpation, percussion and auscultation)
standard chest radiography, a standard laboratory, blood group and
A. Alihodžić-Pašalić et al.
cross reacting, abdominal ultrasound and lung bases. In the fiveyear study, previously described initial diagnostic procedure was
performed at 67.81% (217/320) injured. With the existence of an
infringement sternal region initial diagnostic evaluation is mandatory supplemented with lateral radiogram sternum, ECG with
analysis of biohumoral status and cardiologist consultation , and
carried out at 15.31% (49/320) of injured. Initial diagnostic work
was complemented by CT of the chest in 14.06% (45/320) patients.
In 2.50% (8/320) patients with superficial chest injuries were only
done standard radiography and basic laboratories, and one patient
[0.32% (1/320)] initially underwent standard radiography and CT
of the spine, because he had an extremely strong pain in the area
of the thoracic spine, caused by a fall on the back.Today is not a
small number of health care institutions, especially those with organized trauma centers, which in the initial diagnostic procedure
inevitably and routinely indicate chest CT (10,11,16). As demonstrated, CT in patients with isolated thoracic injury is done only in
the strictly indicated cases [14.06% (45/320)], based on the clinical
assessment of the severity of the patient and the possible existence of severe injuries that could not be excluded on the basis of
previously conducted initial diagnostic procedures.The reason for
this selective use of CT of the chest can be explained with: First
of all it is a time-consuming diagnostic procedure that may delay
the necessary initial treatment for at least 20 - 30 minutes which
in severe cases of thoracic injuries may represent unnecessary loss
of valuable time. If we keep in mind that the radiation dose during
CT of the chest is equivalent to radiation dose of 50-450 pairs of
radiography one should consider the benefits versus the justification of the additional radiation exposure. The effective radiation
dose for standard and lateral radiography ranges from 0.06 to 0.25
milli sievert (mSv). Corresponding dose of conventional CT of the
thorax is 3 - 27mSv, and from 0.3 to 0.55 mSv if someone uses a
CT scan with low-dose radiation. International Commission of Radiological Protection (ICRP) in a publication of 1990. suggests that
low doses of radiation may be carcinogenic, especially in children.
The situation is further complicated by the fact that radiation has
a cumulative effect.
Today we can speak about the invasion of lawsuits and litigation aimed in respect of justification of medical protocols and
procedures, including diagnostic procedures. The above-mentioned
trends have resulted in almost regular and mandatory professional
liability insurance of health workers. However it must be emphasized that it is necessary to define precisely the legal protection
from judicial prosecution of health workers to provide health care
services. In countries with developed legal and judicial systems (UK,
USA), jurisprudence and law follow the development of medical
science and practice in order to quickly and accurately define acceptable procedures and protocols that are mandatory for health
care workers in specific cases. In the initial treatment of injuried
with isolated thoracic injuries at the Clinic of Thoracic Surgery, in
the five-year study, the conservative treatment was more frequently applied and was sufficient in 63.75% (204/320) of the patients.
Such treatment consisted of: continuous observation of the condition, pharmacological treatment, physical therapy and thoracentesis. Initial surgical treatment was necessary in 36.25% (116/320) injured. Based on the results of the study for the majority of patients
41
Assessment of initial diagnostic procedure in isolated thoracic injuries
the initial diagnostic procedures (history, physical examination,
standard PA or AP chest radiography, standard laboratory tests and
ultrasound examination) are usually sufficient for an initial assessment of the injured and the application of appropriate treatment
and there is rarely a need for more complicated, time-consuming
and expensive diagnostic procedures. Bearing in mind the results
of this study, chest CT should be selectively indicate as the part of
the initial diagnostic procedures of injuried with isolated thoracic
trauma. Secondary examination is much more detailed and aims
to identify all injuries. On this basis should be planned further
diagnostic procedures and appropriate treatment (1,15,16,17). Further testing may include: CT scan of the chest, CT angiography,
esophagoscopy, esophagography, bronchoscopy as well as all other
available diagnostic procedures depending on the type of injury
(1,14,17,18,19). After secondary examination or shorter monitoring of injured an additional diagnostic procedures were indicated
and performed in only 5% (16/320) injured. The analysis showed
that necessary additional diagnostic procedures were as follows :
bronchoscopy in 1,25%(4/320), chest CT in 2,18(7/320), ultrasound
of the heart in 0,93%(3/320), CT aortography in 0,31%(1/320) and
esophagoscopy in 0,31(1/320) injuried. Bronchoscopy as an additional diagnostic procedure is indicated in 1.25% (4/320) injuried
because of suspected rupture of a major airway (large air fistula,
absence of lung reexpansion after pleural drainage, radiologically proven subcutaneous and mediastinal emphysema and etc.) In
two patients was confirmed the existence of a large airway rupture (rupture of trachea, rupture of the intermediate bronchus).
It is relatively rare indicated additional CT of the chest [2.18%
(7/320)], the most common indication was assessment of the
state of lung parenchyma. Ultrasound of the heart was indicated at
0.93% (3/320) injured with verified sternal fracture accompanied
by changes in the ECG and changes in the biohumoral status. After
ultrasound of the heart we could excluded the existence of severe
injuries of the heart and the possible existence of pericardial tamponade. Due to the expansion of the upper mediastinal shadow CT
aortography was indicated in one patient [0.31% (1/320)] which
excluded the possible existence of aortic rupture. Esophagoscopy
was indicated in [0.31% (1/320)] because of the low down paravertebral stab wound of left hemithorax, which excluded esophagus
lesion. The results obtained in this study correspond to the most
data of the other centers in which a secondary examination or
shorter observation with further diagnostic tests are used to confirm or rule out specific violations (1,4,5,7,11,20,21,22,23). Overall
value of performed initial diagnostic procedures was assessed after:
initially perfomed therapeutic procedures, secondary examination,
additional diagnostic procedures and continuous monitoring of the
injured. The average period of the hospitalization for all injured
with isolated thoracic trauma was 5,9±4,0 days (from 6 hours to
16 days). In relation to the type of injury, penetrating vs. blunt, the
average length of hospitalization was 5.4 ± 3.36 and 6.07 ± 4.26
days respectively. Statistically, there is no significant difference in
relation to the duration of hospitalization between penetrating vs.
blunt trauma (0,2766>0,05). Initial diagnostic sensitivity in comparison to the indication for active treatment, which is the percentage or proportion of correctly identified injuries was 98.1%.
Initial diagnostic specificity represents a percentage or proportion
of correctly identified patients in whom there was no indication
for active treatment and was 98.6%.The positive predictive value as
the proportion of patients who had an indication for active treatment and whom the initial treatment confirmed indication was
97.1%. The negative predictive value as the proportion of patients
for whom there was no indication for active treatment was 99.0%.
Sensitivity, specificity, positive and negative predictive values of the
total initial diagnostic procedures of all injured with isolated thoracic trauma showed that the initial diagnostic procedures (history,
clinical examination, standard and lateral chest radiography, ultrasound abdomen and basic laboratory findings) were sufficient to
assess the severity of most isolated chest injuries.
CONCLUSION
Initial diagnostic evaluation (medical history, clinical and physical
examination, standard chest radiography, ultrasound examination
of the abdomen and the base of the thorax and standard laboratory tests) in the majority of patients with isolated thoracic injuries
were sufficient (sensitivity, 98.1%; specificity 98.6%; positive predictive value of 97.1% and a negative predictive value of 99.0%) for
an initial assesment of the type and severity of injury. Based on
the above results of initial diagnostic work of most injuried with
isolated thoracic injuries it is possible to carry out the necessary
and appropriate initial therapeutic procedures.
REFERENCES
1. Guska S. Torakalna trauma. U: Guska S. Opšti principi savremene torakohirurške
prakse. Sarajevo: Medicinski fakultet Univerziteta u Sarajevu; 2012; 629-680.
2. Guska S, Hadžismailović A, Čerimagić Z. Vodič za torakalnu traumu. Sarajevo: Ministarstvo zdravstva Kantona Sarajevo: Institut za naučno-istraživački rad i razvoj
KCU Sarajevo; 2007.
3. Schelzig H, Kick J, Orend KH, Sunder-Plassmann L. Thorax injuries. Chirurg
2006;77(3):281-96.
4. Miller LA. Chest wall, lung, and pleural space trauma. Radiol Clin North Am
2006;44(2):213-24.
5. Guska S, Pilav A, Banjanović B, Mušanović S. Primary surgical repair of traumatic rupture of the bronchus intermedius in closed chest trauma. Scripta Medica
2008;39(1,1 Suppl):227–233.
6. Degiannis E, Bonanno F, Titius W, Smith M, Doll D. Treatment of penetrating
injuries of neck, chest and extremities. Chirurg 2005;76(10):945-58.
7. Alihodžić-Pašalić A, Guska S, Hadžismailović A, Pilav A, Pilav I, Mušanović S, et al..
Ubodna rana grudnog koša sa lezijom aorte. Scripta Medica 2008;39(1 Suppl):333
-337.
8. Liener UC, Sauerland S, Knoferl MW, Bartl C, Riepl C, Kinzl L, et al. Emergency surgery for chest injuries in the multiply injured: A systematic review. Unfallchirurg
2006;109(6):447-452.
9. Guska S. Izolirane povrede grudnog koša kod pacijenata hospitaliziranih na Klinici
za torakalnu hirurgiju KCU Sarajevo u periodu od 01.01.1999. do 08.10.2000.
godine. Med Žurnal 2000;6(2)117–125.
10. Cander B, Kalkan E, Girisgin S, Gul M, Coskun F. Emergency operation indications
in emergency medicine clinic (model of emergency medicine in Turkey). Adv Ther
2006;23(2):359-63.
11. Plurad D, Demetriades D, Gruzinski G, Preston C, Chan L, Gaspard D,et al. Pedestrian injuries: the association of alcohol consumption with the type and severity of injuries and outcomes. J Am Coll Surg 2006;202(6):919-27.
12. Guska S, Pilav I, Mušanović S. Clinical Significance of Isolated Sternal Fracture. Med
42
A. Alihodžić-Pašalić et al.
Arh 2010;64(1):17–21.
13. Sarquis G,Velez SE, Suizer A, Reche F. Diagnostic and therapeutic options for traumatic sternal fractures. Rev Fac Cien Med Univ Nac Cordoba 2003;60(1):13-8.
14. Pilav I, Guska S, Banjanović B, Ćerimagić Z, Mušanović S. Javno zdravstveni značaj
povreda grudnog koša u Kantonu Sarajevo. HealthMED 2007;1(1):22–26.
15. Greingor JL, Lazarus S. Chest and abdominal injuries caused by seat belt wearing.
South Med J 2006;99(5):534-5.
16. Cryer HM. Chest radiography in blunt trauma patients: is it necessary? Ann Emerg
Med 2006;47(5):422-3.
17. Rodriguez RM, Hendey GW, Marek G, Dery RA, Bjoring A. A pilot study to derive clinical variables for selective chest radiography in blunt trauma patients. Ann
Emerg Med 2006;47(5):415-8.
18. Mušanović S, Guska S, Hadžismailović A, Alihodžić-Pašalić A, Pilav I, Pilav A, et al..
Penetrantna povreda torakasa - smt in situ. Scripta Medica 2008;39(1,1 Suppl):37–43.
19. Farooq U, Raza W, Zia N, Hanif M, Khan MM. Classification and management of
chest trauma. J Coll Physicians Surg Pak 2006;16(2):101-3.
20. Shoemaker WC, Bayard DS, Wo CC, Chan LS, Chien LC, Lu K, et al. Outcome
prediction in chest injury by a mathematical search and display program. Chest
2005;128(4):2739-48.
21. Vermeulen B, Konstantinidis P. Apparently benign thoracic trauma: what to be
aware of? Rev Med Suisse 2005;1(29):1910-3.
22. Demetriades D, Kimbrell B, Salim A, Velmahos G, Rhee P, Preston C, et al.Trauma
deaths in a mature urban trauma system: is “trimodal” distribution a valid concept?
J Am Coll Surg 2005;201(3):343-8.
23. Propper BW, Gifford SM, Calhoon JH, McNeil JD. Wartime Thoracic Injury: Perspectives in Modern Warfare. Ann Thorac Surg 2010;89(4):1032-6.
Alma Alihodžić-Pašalić, MD
Clinic of Thoracic Surgery
Email: alma_ap68@yahoo.com
Our contribution to the reduction of cardiovascular disease in Bosnia and Herzegovina!
Naš prilog redukciji kardiovaskularnih bolesti u Bosni i Hercegovini!
Original article
Medicamentous abortion induction in the second
trimester in pathological pregnancies
Medikamentozna indukcija pobačaja u drugom
trimestru kod patoloških trudnoća
Naima Imširija1*, Zulfo Godinjak2, Lejla Imširija1, Edin Idrizbegović2, Fatima
Gavrankapetanović1, Admir Rama1, Muhamed Ardat2
Clinic for Obstetrics, Clinical Center University of Sarajevo, Patriotske lige 81, 71000 Sarajevo, Bosnia and Herzegovina;
Clinic for Gynecology, Clinical Center University of Sarajevo, Patriotske lige 81, 71000 Sarajevo, Bosnia and Herzegovina
1
2
ABSTRACT
Optimal modern methods of abortion include instrumental methods and methods of abortion by the means of medications, according to certain schemes and protocols depending on the age of the
pregnancy. In the late sixties of the past century, there were natural
prostaglandins available for abortions, such as carboprost (PGF2alpha) and dinoprostone (PGE2). Misoprostol is a synthetic analogue
of prostaglandin E 1 and it is in use since the early nineties of the past
century. Mifepristone is a synthetic derivative of the norethindrone
progestin, it is progesterone receptor antagonist, it causes contractions, softens the cervix and makes endometrium sensitive to the
effects of prostaglandins that stimulate uterine contractions and expulsion of the fetus. A clinical study aims to show the efficiency of
prepidil gel as well as mifepristone, misoprostol and prostin M-15 in
the induction of abortion in pathological pregnancies in the second
trimester. The study included 90 subjects in whom the medicationinduced abortion was performed in the second trimester of patological pregnancy at the Department of Obstetrics, Clinical Center University of Sarajevo. In relation to the combination of medications by
which the abortion was induced all patients have been divided into
three groups of 30 subjects. Group I was induced with prepidil gel
and prostin M-15, Group II with prepidil gel and misoprostol, group
III with mifepristone and misoprostol. Results:The highest number of
pregnancies was terminated because of the foetus mortus in utero
diagnosis, a total of 79 ( 87.8 % ) in comparison to the entire specimen. The percentage in group I (patients treated with prepidil gel
and prostin M-15) amounted to 83.33 %, and in group II (patients
induced with prepidil gel and misoprostol) together with group III
(patients treated with mifepristone and misoprostol) amounted to
90 % each. Down syndrome was present in five pregnancies, while
multiple anomalies and malformations were represented at 3.33 %.
The longest induction of abortion have had the subjects in group and
was at 52.93 ± 10.87h , followed with the subjects in group II with
52.06 ± 10.56h and shortest induction was present in group III with
47.7 ± 12.27h . Of the total number of subjects and groups, complete
abortion was present in 86.7 %, in group II there was a total of 90 %
of complete abortions, while the percentage in group III was 96.7 % .
By analyzing the frequency of side effects (bleeding, nausea, diarrhea),
it was shown that the patients in group III had the lowest number of
treatment complications and side effects. Conclusion: Medicamentous non-surgical interruption of pathological pregnancies in the
second trimester has significant advantages in relation to the surgical
method.The combination of mifepristone and misoprostol is a more
efficient way to end pathological pregnancies in the second trimester
compared to induced abortions by combination of misoprostol with
prepidil gel or prepidil gel with prostin M-15.
Key words: medicamentous abortion, pathological pregnancy, prostaglandins, mifepristone
SAŽETAK
Optimalne savremene metode prekida trudnoće podrazumijevaju
instrumentalne metode i metode prekida trudnoće lijekovima, po
određenim šemama i protokolima u zavisnosti od starosti trudnoće.
Za prekide trudnoće, prirodni prostaglandini, kasnih šezdesetih godina prošlog vijeka bili su dostupni kao karboprost (PGF2alfa) i dinoproston (PGE2). Mizoprostol (misoprostol) je, sintetski analog prostaglandina E 1 i u upotrebi je od početka devedesetih prošlog vijeka.
Mifepriston je sintetički derivat progestina noretindrona; antagonista
je progesteronskih receptora; izaziva kontrakcije materice, omekšava
grlić materice i senzibiliše endometrijum na dejstvo prostaglandina
koji stimulišu kontrakcije materice i ekspulziju ploda. Klinička studija
ima za cilj da prikaže efikasnost prepidil gela, mifepristona, mizoprostola i prostina M-15 u indukciji pobačaja kod patoloških trudnoća u
drugom trimestru. Istraživanje je obuhvatilo 90 ispitanica kod kojih
je na Klinici za ginekologiju Kliničkog centra Univerziteta u Sarajevu
urađen medikamentozni pobačaj, u drugom trimestru patološke
trudnoće. U odnosu na kombinaciju lijekova kojima je indukovan
abortus sve pacijentice smo podjelili u tri skupine po 30 ispitanica.
Skupina I je inducirana prepidil gelom i prostinom M-15, skupina II
prepidil gelom i misoprostolom, skupina III mifepristonom i misoprostolom. Rezultati: Najveći broj trudnoća je prekinuto zbog postavljene dijagnoze foetus mortus in utero i to ukupno 79 (87.8%) u
odnosu na čitav uzorak.Taj procenat u skupini I (pacijentice tretirane
prepidil gelom i prostinom M-15) je iznosio 83.33%, u skupini II (pacijentice inducirane prepidil gelom i misoprostolom) i III (pacijentice
tretirane mifepristonom i misoprostolom) po 90%. Down sindrom
44
N. Imširija et al.
je bio prisutan u 5 trudnoća, dok su multiple anomalije i malformacije bile zastupljene po 3.33%. Najdužu indukciju pobačaja imale
su ispitanice skupine I iznosila je 52.93±10.87h, zatim ispitanice skupine II 52.06±10.56h, a najkraću ispitanice skupine III 47.7±12.27h.
Od ukupnog broja ispitanica skupine I, kompletan pobačaj je imalo
86.7%, u skupini II bilo je ukupno 90% kompletnih pobačaja, dok je taj
procenat u skupini III iznosio 96.7%. Analizom učestalosti nus pojava
(krvarenje, mučnina, proljev) ustanovljeno je da su ispitanice skupine
III imale najmanji broj komplikacija i neželjenih efekata primjenjene
terapije. Zaključak: Medikamentozni nehirurški prekid patoloških
trudnoća u drugom trimestru ima znatne prednosti u odonosu na
hirurški način. Kombinacija mifepristona i mizoprostala je efikasniji
način prekida patoloških trudnoća u II trimestru u odnosu na indukciju pobačaja kombinacijom misoprostola i prepidil gela i prepidil
gela i prostina M-15.
INTRODUCTION
used was used for qualitative variables, and the Anova test for quantitaive ones.The level of significance was p <0.05.The largest number
of pathological pregnancies (total of 79 87.8 % ) refers to the fetus in
utero mortus diagnosis, Down syndrome was present in 5 pregnancies ( 5:56 % ), and multiple anomalies were diagnosed in 3 pregnancies (33.3 % ). In relation to the combination of medications which
induced abortion, all patients have been divided into three groups of
30 subjects.The first group was given prepidil intracervical gel and after “cervical ripening“ we proceeded with induction of prostin M-15
intramuscularly, up to 5 doses every 3 hours. In the second group we
used prepidil intracervical gel and misoprostol 200μg, up to five doses every 4 hours, and in the third group we used mifepristone 600
mg per os, and misoprostol 200μg, up to five doses every four hours.
There are about 46 million abortions carried out (1) annually in
the world, although recent data from the 2011 point to the fact that
their number is decreasing and that it is closer to number of 41 million (2). Of this number, about 48 % falls under unsafe abortions, performed by non professionals by inadequate techniques in inadequate
conditions (3). Uunsafe abortions are mainly present in countries
where abortion is prohibited or restrictively permitted because of
certain medical indications and such abortions are the cause of high
morbidity and mortality in women (4). Optimal modern methods
of abortion include instrumental methods and medication-induced
abortion methods, according to certain schemes and protocols depending on the age of the pregnancy, the available methods and other
conditions affecting the general health condition of women and local
conditions. Medicamentous way of abortion occurred in response
to attempts to reduce the risks associated with abortion performed
by surgical intervention, mainly those related to accidents related
to anesthesia (mortality up to 1 %), infection (and possible sterility)
as well as genital and other organs injuries during the intervention
(5). Natural prostaglandins PGF2 alpha and PGE2 play an important
role in the regulation of uterine activity. PGE2 has a stronger effect
on the cervix and causes its softening and dilatation, and PGF2 alpha
has greater effect on inducing uterine contractions. Misoprostol, a
synthetic analogue of prostaglandin E1, is used in over 80 countries
worldwide. Because of its effects on the cervix, it can be applied in
preparing the cervix - for softening and dilatation of the cervix prior
to the instrumental abortion or before hysteroscopy. For abortions
in the first and second trimester, it is applied in various schemes (6).
Mifepristone is a synthetic derivative of the norethindrone progestin,
it is progesterone receptor antagonist, and it causes contractions, it
softens the cervix and makes endometrium sensitive to the effects
of prostaglandins that stimulate uterine contractions and expulsion
of the concept. In the absence of progesterone, mifepristone acts as
a partial agonist of progestine. At doses higher than those used for
abortion, it has antiglucocorticoid and weak antiandrogenic effect (7).
The clinical study was aimed to show the efficiency of prepidil
gel, mifepristone, misoprostol and prostin M-15 in the induction of
abortion in pathological pregnancies in the second trimester.The
study included 90 subjects in whom the medicamentous abortion
was performed by the application of prostaglandins in the second
trimester of patological pregnancy at the Department of Obstetrics,
Clinical Center University of Sarajevo. After the research, data were
analyzed by statistical software SPSS, version 20.0. Chi square test
Ključne riječi: medikamentozni abortus, patološka trudnoća, prostaglandini, mifepriston
RESULTS
The oldest gestational age had the patients in group III (patients
induced with mifepristone and misoprostol) and it amounted to
18.56 ± 2.89 weeks, followed by group I (patients induced with prepidil gel and prostin M-15) 18.06 ± 3.21 weeks, and the lowest had
the patients in group II (patients induced with Prepidil gel and misoprostol), 17.83 ± 2.40 weeks. Anova test showed that there was
no statistically significant difference in the length of gestational age
during pregnancy termination between the examined groups, F =
0.384, p = 0.682.
Table 1 Average gestational age during pregnancy termination
There was a statistically significant difference in the length of the
abortion induction in relation to test group F=1.034, p=0.039. The
longest abortion induction was present in group I patients (patients
induced with prepidil gel and prostin M-15) and it amounted to 52.93
± 10.87h, followed with group II patients (patients induced with prepidil gel and misoprostol) 52.06 ± 10.56h and shortest induction was
in group III patients (patients induced with mifepristone and misoprostol) 47.7 ± 12.27h.
Table 2 The average length of the abortion induction
Medicamentous abortion induction in the second trimester in pathological pregnancies
From the total number of respondents in group I (patients induced with prepidil gel and prostin M-15), complete abortion occured in 86.7%, in group II (patients induced with prepidil gel and
misoprostol) there were a total of 90% of complete abortions, while
the same percentage in group III (patients induced with mifepristone
and misoprostol) amounted to 96.7%. In other women abortion also
occured, but because of incomplete abortions, in a total of 8.9% of
the patients, we underwent revision of the uterine cavity.
Table 3 Success of induction as compared to the
experimental group
45
tion was shorter. Honkanen et al. states that oral administration of
600 mg dose of mifepristone causes more frequent diarrhea, nausea
and vomiting, than when it is used in lower doses of 200 mg and
pelvic pain after oral administration of misoprostol occurs on average one hour earlier (9). Guengant et al. states that a dose of 600
mg mifepristone administered orally is successful in 95.4%, with the
likelihood of side effects in the form of bleeding and vomiting in 8.2%
(10). Spitz et al. specify nausea in 30%, vomiting in 16-21% and pelvic
pain in 80, the incidence of hemostatic curettage at 1:45 %, as well as
the need for transfusion at 0.15% and analgesics in 16% of pregnant
women in the event of termination of pregnancy up to 49 days of
amenorrhea (10). In this study, patients in group III (patients treated
with mifepristone and misoprostol) had the lowest number of treatment complications and side effects.
CONCLUSION
By analyzing the frequency of side effects (bleeding, nausea, diarrhea) a statistically significant difference was shown in the incidence of therapy side effects and complications, where the patients
in group III (patients induced with mifepristone and misoprostol) had
the lowest number of complications (infections, residues and post
abortum perforations) and treatment side effects. Group I patients
(patients induced with prepidil gel and prostin M-15) had significantly
higher incidence of side effects (nausea and diarrhea), and complications (infections and post abortum residues) as compared to the
other two groups.
Table 4 The frequency of side effects caused by medications
and the treatment complications
Medicamentous non-surgical interruption of pathological pregnancies in the second trimester has considerable advantages over
the surgical method. It reduces the number of complications (infection, bleeding, residue post abortum) and subsequent cervical
incompetence in subsequent pregnancies, as well as adverse effects
(bleeding, nausea, vomiting). The psychological aspects of fear were
significantly lower in the medicamentous abortion. The combination
of mifepristone and mizoprostal is a more efficient way to break
pathological pregnancies in the second trimester compared to induced abortion combination of mifepristone with prepidil gel or
prepidil gel with prostin M-15.
REFERENCES
DISCUSSION
Modern methods of abortion by medications are nowadays available to women in many countries by the range of different protocols.
The discovery of synergistic action of the antiprogestin (mifepristone) and its synthetic analogue, prostaglandin E1 (misoprostol) on
abortions in the second trimester, has developed a new, highly effective and safe method of abortion with medicaments. Existing today,
there are established schemes of administering these medications,
provided by the World Health Organization, at various gestational
age on the basis of many studies done in this area. If an unwanted
pregnancy or pathological pregnancy occur, it is necessary to enable women to have a choice as well as these modern methods of
medicamentous abortion on which about half of women actually
decides on in countries where it is available (8). In the first group
treated with prepidil gel and prostin M–15, abortion occured in 86.7
% of the patients, in the second group treated with prepidil gel and
misoprostol that percentage was higher, and amounted to 90 %. The
analysis of the success in the third group treated with mifepristone
in combination with misoprostol in the second trimester, showed
that the success was much higher ( 96.7 % ), and duration of induc-
1. Alan Guttmacher Institute. Sharing responsibility: women, society and abortion
worldwide. New York: The Alan Guttmacher Institute; 2009.
2. Sedgh G, Henshaw S, Singh S, Lhman E, Shah IH. Induced abortion: rates and trends
worldwide. Lancet 2007;370(9595): 1338-45.
3. Safe abortion: technical and policy guidance for health systems. Geneva: WHO;
2003.
4. WHO Scientific Group. Medical methods for termination of pregnancy: report.
Geneva: WHO; 2007.
5. Misoprostol AHFS drug information 2001:2837-42.
6. Schcepcrs HC, van Erp EJ, van den Bergh AS. Use of misoprostol in first and
second trimester abortion: a review. Obstet Gynecol Surv 1999;54(9): 592-600.
7. Song J. Use of misoprostol in obstetrics and gynecology. Obstet Gynecol Surv
2000;55(8):1-12.
8. Kapamadzija A, Vukelic J, Bjelica A, Kopitovic V. Abortus lekovima - savremena
metoda prekida trudnoće. Med Pregl 2010;53(1-2): 63-67.
9. Honkanen H, Piaggio G, Hertzen H, Bartfai G, Erdenetungalag R, Gemzell-Danielsson K, et al. WHO multinational study of three misoprostol regimens after
mifepristone for early medical abortion. BJOG 2004;111(7):715–25.
10. Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 2008;338(18):1241–7.
Naima Imširija, MD
Clinic for Gynecology and Obstetrics
Patriotske brigade 81, 71000 Sarajevo
Phone: +387 33 250 250
Email: naimaimsirija@hotmail.com
Endoscopic retrograde cholangiopancreatography: our
experience
Endoskopska retrogradna holangiopankreatografija:
naša iskustva
Kenan Nahodović*, Rusmir Mesihović, Nenad Vanis, Amra Puhalović,
Srdjan Gornjaković, Amila Mehmedović, Alma Nahodović
Clinic for Gastroenterohepatology, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina
ABSTRACT
SAŽETAK
Introduction: ERCP is a technique that combines endoscopic
and radiological procedures in diagnosis and treatment of biliopancreatic diseases. ERCP is used in the diagnosis and treatment
of choledocholithiasis, various stenosis of biliopancreatic system,
carcinoma treatment. Today ERCP is mainly used for therapeutic
purposes, and as such carries the risk of a large number of complications. Objective: To evaluate the number of patients who underwent ERCP, ERCP success, the most common diagnosis, and
the rate of complications. Methods: we retrospectively analyzed
570 patients who were admitted during 2011. at the Clinic of Gastroenterohepatology CCUS. The patients were on admission underwent the basic lab findings and diagnostic procedures followed
by indicated ERCP. Statistically analyzed demographic structure of
patients diagnosed during ERCP, the performance of the procedure
and the emergence of post ERCP complications. Results: during
year 2011., 570 patient were admitted at our Clinic of Gastroenterohepatology for endoscopic retrograde cholangiopancreatography. The largest number of patients was more than 50 yrs of age
(82.1%), and at least between 20 and 29 years of age (2.1%). ERCP
was successful in 556 or 97.54% of the cases and unsuccessful in
14 or 2.5% of cases. The most common diagnosis verified during
ERCP was choledocholithiasis, 303 patients (53.2%), followed by
tumors of the head of the pancreas, 112 patients (19.6%).The most
common complication was the occurrence of mild pancreatitis in
35 patients, or 6.1% of cases, and severe in only 1 case or 0.2%.
Conclusion: ERCP is a safe method that is used in the treatment
of diseases of biliopancreatic system, especially choledocholithiasis
and malignant obstruction. The percentage of post ERCP complications is very small and is in accordance to global standards. The
mortality rate is extremely low.
Uvod: ERCP je tehnika koja kombinira endoskopske i radiološke
procedure u dijagnostici i tretmanu bolesti biliopankreatičnog sistema.ERCP se koristi u dijagnostici I tretmanu holedoholitijaze,
raznih stenoza biliopankreatičnog sistema, tretmana carcinoma.
Danas se ERCP uglavnom koristi u terapeutske svrhe, I kao takva
nosi rizik od velikog broja komplikacija. Cilj: evaluirati broj pacijenata kod kojih je radjen ercp, uspješnost ercp, najčešća dijagnoza, i
procenat komplikacija. Metod rada: retrospektivno smo analizirali
570 pacijenata koji su primljeni tokom 2011. godine na Kliniku
za Gastroenterohepatologiju KCUS. Pacijentima su pri prijemu
urađeni osnovni laboratorijski nalazi i dijagnostičke procedure nakon čega je indiciran ERCP. Statistički smo analizirali demografsku
strukturu pacijenata, dijagnozu prilikom ERCP, uspješnost izvođenja
procedure i nastanak post ERCP komplikacija. Rezultati: tokom
2011. godine na Kliniku za Gastroenterohepatologiju je primljeno
570 pacijenata kojima je urađena endoskopska retrogradna holangiopankreatografija. Najveći broj pacijenata je bio preko 50 godina
starosti (82,1%), a najmanje između 20 i 29 godina starosti (2,1%).
ERCP je bio upješan u 556 ili 97,54% slučajeva a neuspješan u 14 ili
2,5% slučajeva. Najčešća dijagnoza koja je verificirana tokom ERCP
je bila holedoholitijaza, 303 pacijenta (53,2%), potom neoplazma
glave pankreasa, 112 pacijenata (19,6%). Najčešća komplikacija je
bila pojava pankreatitisa blagog pankreatisita, 35 pacijenata ili 6,1%
slučajeva, te teški pankraetitis u samo jednom slučaju ili 0,2%. Stopa
mortaliteta je iznosila 0,3%.
Zaključak: ERCP je sigurna metoda koja se koristi u tretmanu
oboljenja biliopankreatičnog sistema, posebno holedoholitijaze i
malignih opstrukcija. Procenat post ERCP komplikacija je vrlo
mali i u skladu je svjetskim standarima. Stopa mortaliteta je izrazito niska.
Key words: ERCP, complication, pancreatitis, bleeding.
Ključne riječi: ERCP, komplikacije, pankreatitis, krvarenje.
INTRODUCTION
have improved, endoscopic retrograde cholangiopancreatography
(ERCP) has evolved from primarily a diagnostic procedure into
primarily a therapeutic procedure (4-7). ERCP is helpful in diagnosing and treating choledocholithiasis, benign and malignant biliary
strictures, operative and traumatic ductal injuries, and sphincter of
Oddi dysfunction. However, this diagnostic technique may lead to
potential complications, even post-ERCP mortality, which should
be reduced by avoidance of its unnecessary use (8,9).
The first endoscopic pancreatogram was obtained in 1968, and
in 1974, biliary sphincterotomy was first described (1-2). This was
followed by the first report of papillotomy for the management of
choledocholithiasis (3) and in subsequent years, numerous endoscopic techniques evolved to address pancreaticobiliary disease. As
computerized axial tomography and magnetic resonance imaging
47
Endoscopic retrograde cholangiopancreatography: our experience
We retrospectively analyzed 570 patients who were admitted during 2011. at the Clinic of Gastroenterohepatology Clinical Center University of Sarajevo (CCUS).The patients were on
admission underwent the basic laboratory findings and diagnostic
procedures followed by indicated ERCP. We statistically analyzed
demographic structure of patients diagnosed during ERCP, the
performance of the procedure and the emergence of post ERCP
complications. Basic demographic parameters are given in Figure 1.
The most common diagnosis during ERCP was choledoholithiasis, 303 patients (53,2%), and pancreatic cancer 112 patients
(19,6%). Nine patients (1,65%) had normal findings, and only 2 patients (0,4%) had billiar leakage (Figure 2).
Figure 3 Post ERCP pancreatitis
Figure 1 Demographic parameters
As for the demographics of patients most patients had more
than 50 years of age (82.1%), and at least between 20 and 29 years
of age (2.1%).
Pancreatitis has appeared as of mild in 35 (6.1%) of cases and
severe in only 1 case (0.2%). Patients who had verified mild pancreatitis were successfully treated with conservative therapy, while
in patient who developed severe pancreatitis surgical treatment
was indicated (Figure 3).
Table 2 ERCP age distribution
RESULTS
Table 1 ERCP efficacy
ERCP was succesfully performed in 556 patients (97,4%), unsuccesfully in 14 patients (2,5%). Majority of patients in whom ERCP
could not be perfomed had altered digestive anatomy of previous operations (hepatico jejuno anastomosis (0,7%) and Billroth
II anastomosis ( 0,4%). The least patients, 1 or 0,2%, had diffuse
malignancy caused by pancreatic cancer who could not had been
treated endoscopicaly and they were reffered to surgery (Table 1).
hi=2,928; p=1,000
Relationship to the occurrence of pancreatitis vintage and endoscopic diagnosis, which indicates that there is no significant difference between the incidence of pancreatitis in relation to age and
endoscopic diagnosis (p=1.000) (Table 2.)
Figure 4 Post ERCP bleeding
Figure 2 ERCP diagnosis during procedure
Bleeding was reported in 4 cases or 0.5% of the total sample.
48
Figure 5 Post ERCP perforation
Duodenal perforation was recorded in the 4 cases or 0.5%
of the total sample (N=870). According to the diagnosis, duodenal perforation was observed more frequently in diagnosis of neo
pancreatic head (3 or 75%) compared to 1, or 25% of diagnosis
choledocholithiasis slots within the total number of slots (Figure 5).
Mortality rate of the total 870 patients was observed in 3 cases
or 0.3%.
DISCUSSION
ERCP is an established diagnostic and therapeutic tool for pancreatobiliary diseases including choledocholithiasis, malignant opstruction, biliar leakage. The rate of technical success, complete
duct clearance, early/late complications, and mortality are reportedly 80.5%-100%, 86.0%-98.0%, 5.0%-6.3%, 0-5.0%, and 0-3.2%, respectively (10,11,12,13). The largest number of patients that was
hospitalized, had over 50 years of age, the most common indication
for ERCP was choledocholithiasis and obstructive jaundice caused
by malignancy of the pancreatic head.The success of the ERCP was
97.54%, which is consistent with studies in the world where it describes the performance of up to 97% (10,11). The largest number
of patients in whom we could not perform ERCP had deteriorated
anatomy after previous surgery (Billroth II anastomosis and hepaticojejunoanastomosis), and are referred to the PTC or surgical treatment. Since its introduction in 1968., ERCP has become a
commonly performed endoscopic procedure (14). The diagnostic
and therapeutic utility of ERCP has been well demonstrated for a
variety of disorders, including the management of choledocholithiasis, diagnosis and management of biliary and pancreatic neoplasms,
and the postoperative management of biliary perioperative complications (15,16,17). Performing ERCP is associated with numerous
complications (perforation, bleeding, pancreatitis). Numerous studies have helped determine the expected rates of complications,
potential contributing factors for these adverse events, and possible methods for improving the safety of ERCP. Recognition and
understanding of potential complications of ERCP are vital in the
acquisition of appropriate informed consent (18). Pancreatitis is the
most common serious ERCP complication (19,20,21). Although
transient increase in serum pancreatic enzymes may occur in as
many as 75% of patients,16 such an increase does not necessarily constitute pancreatitis. A widely used consensus definition for
K. Nahodović et al.
post ERCP pancreatitis is (1) new or worsened abdominal pain, (2)
new or prolongation of hospitalization for at least 2 days, and (3)
serum amylase 3 times or more the upper limit of normal, measured more than 24 hours after the procedure (22). By using this
or similar definitions, the incidence of PEP in a meta-analysis of
21 prospective studies was approximately 3.5%, but ranges widely
(1.6%-15.7%) depending on patient selection (23,24). Our study
showed that post ERCP pancreatitis had 36 patients (6,3%), majority of them had mild form (6,1%) and only one patient had severe
pancreatitis (0,2%). Patients with mild pancreatitis were treated
conservative, while patient with severe form of pancreatitis needed
further surgical treatment. Most ERCP-associated bleeding is intraluminal, although intraductal bleeding can occur and hematomas
(hepatic, splenic, and intra-abdominal) have been reported (26,27).
Hemorrhage is primarily a complication related to sphincterotomy
rather than diagnostic ERCP. In a meta-analysis of 21 prospective
trials, the rate of hemorrhage as a complication of ERCP was 1.3%
(95% CI, 1.2%-1.5%) with 70% of the bleeding episodes classified
as mild (23). Hemorrhagic complications may be immediate or delayed, with recognition occurring up to 2 weeks after the procedure. In our case bleeding rate was 0,5%. Bleeding was immediate
after sphincterotomy and was treated with injection of adrenalin
solution or heater probe. Perforation rates with ERCP range from
0.1% to 0.6% (19, 20, 28, 29,30). Three distinct types of perforation
have been described: guidewire-induced perforation, periampullary
perforation during sphincterotomy, and luminal perforation at a
site remote from the papilla (30). Risk factors for perforation determined in a large retrospective study included the performance
of a sphincterotomy, Billroth II anatomy, the intramural injection of
contrast, prolonged duration of procedure, biliary stricture dilation, and SOD (28,31). In our study 3 patients had perforation as
a major complication. Two of them had luminal perforation at site
remote from the papila and one had perforation that occured during sphincterotomy. All three of them were treated surgicaly with
good outcome.
CONCLUSION
Endoscopic retrograde cholangiopankreatography is safe and
very succesfull method for treatment of bilio pancreatic disorders.
It is very invasive procedure that is used only in therapeutic purpose. For endoscopists to accurately assess the clinical appropriateness of ERCP, it is important to have a thorough understanding
of the potential complications of this procedure. Rate of complications is very low as well as mortality rate. Most common complication is post ERCP pancreatitis.
REFERENCES
1. McCune WS, Shorb PE, Moscovitz H. Endoscopic cannulation of the ampulla of
vater: a preliminary report. Ann Surg 1968;167:752-756.
2. Peel AL, Hermon-Taylor J, Ritchie HD. Technique of transduodenal exploration
of the common bile duct. Duodenoscopic appearances after biliary sphincterotomy. Ann R Coll Surg Engl 1974;55:236-244.
49
Endoscopic retrograde cholangiopancreatography: our experience
3. Zimmon DS, Falkenstein DB, Kessler RE. Endoscopic papillotomy for choledocholithiasis. N Engl J Med 1975;293:1181-1182.
4. Zimmon DS, Falkenstein DB, Riccobono C, Aaron B. Complications of endoscopic
retrograde cholangiopancreat ography. Analysis of 300 consecutive cases. Gastroenterology 1975;69:303-309.
5. Bilbao MK, Dotter CT, Lee TG, Katon RM. Complications of endoscopic retrograde cholangiopancreatography (ERCP). A study of 10,000 cases. Gastroenterology 1976;70:314-320.
6. Deschamps JP, Allemand H, Janin Magnificat R, Camelot G, Gillet M, Carayon P.
Acute pancreatitis following gastrointestinal endoscopy without ampullary cannulation. Endoscopy 1982;14:105-106.
7. Odes HS, Novis BN, Barbezat GO, Bank S. Effect of calcitonin on the serum amylase levels after endoscopic retrograde cholangiopancreatography. Digestion
1977;16: 180-184.
8. Mallery JS, Baron TH, Dominitz JA, Goldstein JL, Hirota WK, Jacobson BC, et al.
Complications of ERCP. Gastrointest Endosc 2003;57:633-638.
9. Masci E, Toti G, Mariani A, Curioni S, Lomazzi A, Dinelli M, et al. Complications of
diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001;96:417-423.
10 Sugiyama M, Atomi Y. Endoscopic sphincterotomy for bile duct stones in patients
90 years of age and older. Gastrointest Endosc 2000;52:187-191.
11. Koklu S, Parlak E, Yuksel O, Sahin B. Endoscopic retrograde cholangiopancreatography in the elderly: a prospective and comparative study. Age and Ageing
2005;34:572-577.
12. Fritz E, Kirchgatterer A, Hubner D. ERCP is safe and effective in patients 80
years of age and older compared with younger patients. Gastrointest Endosc
2006;64:899-905.
13. Katsinelos P, Paroutogou G, Kountouras J, Zavos C, Beltsis A,Tzovaras G. Efficacy
and safety of therapeutic ERCP in patients 90 years of age and older. Gastrointest Endosc 2006;63:417-423.
14. McCune WS, Shorb PE, Moscovitz H. Endoscopic cannulation of the ampulla of
Vater: a preliminary report. Ann Surg 1968;167:752-6.
15. Maple JT, Ben-Menachem T, Anderson MA.. The role of endoscopy in the evaluation of suspected choledocholithiasis. Gastrointest Endosc 2010;71:1-9.
16. Baron TH, Mallery JS, Hirota WK.. The role of endoscopy in the evaluation and
treatment of patients with pancreaticobiliary malignancy. Gastrointest Endosc
2003;58:643-9.
17. Costamagna G, Shah SK, Tringali A. Current management of postoperative
complications and benign biliary strictures. Gastrointest Endosc Clin N Am
2003;13:635-48.
18. Zuckerman MJ, Shen B, Harrison ME 3rd. Informed consent for GI endoscopy.
Gastrointest Endosc 2007;66:213-8.
19. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorscher PJ,
et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med
1996;335:909-18.
20. Masci E, Toti G, Mariani A. Complications of diagnostic and therapeutic ERCP: a
prospective multicenter study. Am J Gastroenterol 2001;6:417-23.
21. Freeman ML, DiSario JA, Nelson DB. Risk factors for post-ERCP pancreatitis: a
prospective, multicenter study. Gastrointest Endosc 2001;54:425-34.
22. Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, et al. Endoscopic sphincterotomy complications and their management: an attempt at
consensus. Gastrointest Endosc 1991;37:383-93.
23. Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F et al. Incidence rates of post-ERCP
complications: a systematic survey of prospective studies. Am J Gastroenterol
2007;102:1781-8.
24. Cotton PB, Garrow DA, Gallagher J, Joseph Romagnuolo. Risk factors for complications after ERCP: a multivariate analysis of 11,497 procedures over 12 years.
Gastrointest Endosc 2009;70:80-8.
25. Barthet M, Lesavre N, Desjeux A, Gasmi M, Berthezene P, Berdah S et al. Complications of endoscopic sphincterotomy: results from a single tertiary referral
center. Endoscopy 2002;34:991-7.
26. Costa Macedo T, Maldonado R, Valente A. Hemobilia in hereditary hemorrhagic
telangiectasia: an unusual complication of endoscopic retrograde cholangiopancreatography. Endoscopy 2003;35:531-3.
27. Kingsley DD, Schermer CR, Jamal MM. Rare complications of endoscopic retrograde cholangiopancreatography: two case reports. JSLS 2001;5:171-3.
28. Loperfido S, Angelini G, Benedetti G, Chilovi F, Costan F, De Berardinis F et al.
Major early complications from diagnostic and therapeutic ERCP: a prospective
multicenter study. Gastrointest Endosc 1998;48:1-10.
29. Colton JB, Curran CC. Quality indicators, including complications, of ERCP in
a community setting: a prospective study. Gastrointest Endosc 2009;70:457-67.
30. Howard TJ, Tan T, Lehman GA. Classification and management of perforations
complicating endoscopic sphincterotomy. Surgery 1999;126:658-63;
31. Enns R, Eloubeidi MA, Mergener K, Jowell PS, Branch MS, Pappas TM et al. ERCPrelated perforations: risk factors and management. Endoscopy 2002;34:293-8.
Kenan Nahodović, MD
Clinic for Gastroenterohepatology,
Bolnička 25,
71000 Sarajevo,
Phone: +387 33 297 911
Email: kenannahodovic@hotmail.com
People with disabilities and their free access to hospital
facilities in the compound of Clinical Center University
of Sarajevo: special focus on Central Medical Building
Analiza kretanja osoba umanjenih tjelesnih
mogućnosti kroz objekte nove gradnje u Kliničkom
Centru Univerziteta u Sarajevu; poseban osvrt na
Centralni medicinski blok
Mirza Dilić1, Mustafa Hiroš2, Mirela Imširija3*, Naima Imširija-Galijašević3
1
Internal Clinics and Departments, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 2Surgical Clinics and Departments, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 1Technical Department, Clinical Center University of
Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, Clinic of Ginecology and optetrition, Clinical Center University of Sarajevo, Jezero
ABSTRACT
SAŽETAK
The reasons for this article lies in the fact that modern society is
not sufficiently sensitive to the population of persons with currently or
permanently reduced physical abilities. The involvement of the whole
community is required, to provide independent lifestyle for these people.The public institutions carry a special responsibility in overcoming
architectural, as well as every other barriers. Individual contribution
of each and one of us should be present in our local communities.
Clinical Center University of Sarajevo (CCUS) is a tertiary health care
institution, and as such it should and it must be an example for all other
public institutions in implementation of the principle of handicapped
friendly construction. The analyses of the post-war construction reveals that the movement of handicapped persons had been taken into
an account.This particularly applies to the new Central Medical Building (CMB), which is building of a 50,000 m2 gross area and whose
full construction is in progress. In current implementation of CMB’s
construction, this issue has been taken into an account, particularly
bearing in mind that the potential moves reduction may be of temporary (broken limbs, etc) and permanent character. The approach to
this issue in the analyses of future activities and creation of “free train
line” was multidisciplinary, and included the joint work of doctors and
engineers, which resulted in the establishment of the best and shortest
safe and dry lines (covered corridors, tunnels, etc.) connections within
the building. The backbone of the future construction of demanding
object, as a starting point and an important basis for the planning of
movement within other health institutions. The paper contains additional drawings and graphics of handicapped people’s movement plan,
which can be of a great help to the physically disabled persons, as a
movement lines within CCUS objects of the “Koševo“ location.
Razlozi za istraživanje ove teme leže u činjenici da savremeno
društvo nije dovoljno osjetljivo na populaciju osoba trenutno ili
trajno umanjenih tjelesnih sposobnosti. U omogućavanju samostalnog života ovih ljudi potreban je angažman cijele zajednice, ali
u javnim ustanovama leži posebna odgovornost u prevazilaženju
arhitektonskih kao i svakih drugih barijera. Pojedinačan doprinos
svakoga od nas treba da bude u našim lokalnim radnim sredinama.
Klinički Centar Univerziteta u Sarajevu (KCUS) je zdravstvena
ustanova tercijarnog nivoa i kao takva treba i mora da bude za
primjer svim drugim javnim ustanovama u provedbi humanističkih
principa gradnje. Analizom postratne izgradnje vidljivo je da se
vodilo računa o kretanju osoba umanjenih tjelesnih sposobnosti.To
se posebno odnosi na novi Centralni medicinski blok (CMB), koji
je objekat od 50.000 m2 brutto površine i čija puna izgradnja je u
toku. U dosadašnjoj realizaciji gradnje CMB-a, o ovoj problematici
se vodilo posebno računa imajući u vidu da umanjenje mogućnosti
kretanja može biti privremenog (lomovi ekstremiteta i sl.) i trajnog
karaktera. Pristup ovoj problematici kod analize budućih aktivnosti
i kreiranja „hodnih linija“ je bio multidisciplinaran i podrazumijevao
je zajednički rad doktora i inžinjera, što je rezultiralo uspostavljanjem najboljih i najkraćih toplih (pokrivenih, tunelskih, itd) veza unutar objekta. Okosnica je to buduće izgradnje ovog zahtjevnog objekta, kao polazna i važna osnova planiranja kretanja unutar drugih
zdravstvenih institucija. U radu su dati i grafički prilozi plana kretanja, što može biti od velike pomoći ljudima umanjenih tjelesnih
sposobnosti kao vodič za kretanje unutar dijela objekata KCUS-a
na lokalitetu „Koševo“.
Keywords: people of reduced physical abilities, newly built hospital facilities, Central Medical Building, Clinical Center University of Sarajevo
Ključne riječi: osobe umanjenih tjelesnih sposobnosti, novija gradnja
bolničkih kapaciteta, Centralni medicinski blok, Klinički Centar Univerziteta u Sarajevu
People with disabilities and their free access to hospital facilities in the compound of Clinical Center University of Sarajevo:
special focus on Central Medical Building
UVOD
Tretman osoba umanjenih tjelesnih sposobnosti u
javnim objektima s aspekta arhitektonskih barijera
Činjenica je da Bosna i Hercegovina nema zvaničan podatak o
broju osoba sa trajno umanjenim tjelesnim sposobnostima. Ulazni podatak može jedino da se pretpostavi na temelju istraživanja
Svjetske zdravstvene organizacije (SZO) i drugih međunarodnih
organizacija. Smatra se, na osnovu istraživanja SZO kao i procjene
specijalizovanih agencija i međunarodnih organizacija, da je krajem
sedamdesetih godina u svijetu bilo oko 450 miliona ljudi sa trajno
umanjenim sposobnostima. U tom momentu, to je iznosilo oko
10% ukupnog broja svjetskog stanovništva. Statistčki pokazatelji
morbiditeta jasno ukazuju na očekivano povećanje broja osoba sa
trajno umanjenim tjelesnim sposobnostima. Ovaj trend prvenstveno ima tendenciju rasta zahvaljujući napretku savremene medicine, čiji su izvanredni rezultati omogućili da veliki broj ljudi doživi
duboku starost, i da takođe veliki broj preživi teška, do prije koju
deceniju najčešće smrtonosna tjelesna oštećenja, ali sa smanjenom
tjelesnom sposobnošću kao posljedicom (1,2,3,4).Također je važno
napomenuti da su iz ovih numeričkih podataka izuzete sve druge osobe čije su umanjene sposobnosti kretanja privremenog karaktera.
To se odnosi na povrede čije izlječenje podrazumijeva privremenu
korištenje različitih vrsta ortopedskih pomagala; štake, štap, kolica i
dr. Bosna i Hercegovina trenutno se nalazi u postratnom periodu
koji je sasvim sigurno značajno uvećao broj ljudi iz ove kategorije
kao direktnu ili indirektnu posljedicu ranjavanja. Postavlja se realno
pitanje koliko mi zaista brinemo o njima, odnosno koliko svojim
nemarom i/ili nebrigom dodatno otežavamo život? Ova problematika svakako bi morala biti jače podržana od strane cijele zajednice,
međutim u konkretnim arhitektonskim barijerama s kojima se ova
populacija susreće svakodnevno, ne možemo i ne trebamo abolirati
arhitekte, urbaniste i sve ostale koji imaju mogućnost direktno intervenirati u određenim lošim arhitektonskim rješenjima. Kretanje
unutar već izgrađenih javnih, stambenih i drugih objekata najčešće
biva nemoguće bez pomoći trećih lica, što za posljedicu ima „zatvaranje u svoja četiri zida“ velikog broja ljudi iz ove kategorije što je
neprihvatljivo (2,3). Iako je na nivou države donesen veliki broj uredbi, pravilnika, odluka itd, provođenje njima predviđenih mjera još
uvijek je jako slabo. Sve javne ustanove morale bi imati u potpunosti
realiziranu mogućnost kretanja ove populacije, što sada nije slučaj.
U velikom broju primjera, vanjske rampe su neprimjerenih nagiba
i onemogućavaju samostalno kretanje, vanjske platforme (koje su
postavljene poštujući najčešće uvjete tehničkih prijema objekata),
ostanu prekrivene i van funkcije su. To znači da se ovakvo stanje
mora mijenjati (2,3,4). Klinički centar Univerziteta u Sarajevu je
ustanova tercijarne zdravstvene zaštite i kao takva jedna od krovnih
zdravstvenih institucija u Bosni i Hercegovini. To znači da veliki broj
ljudi sa privremeno ili trajno umanjenim tjelesnim mogućnostima
dolazi svakodnevno na ove lokalitete. To nameće dodatnu obavezu u promišljanju i projektiranju objekata koje će ova populacija
moći samostalno koristiti. Kroz KCUS ponuđene su najkvalitetnije
i konsultativno-specijalističke i hospitalne usluge najšireg spektra.
Klinički centar raspolaže sa 2030 bolesničkih postelja, raspoređenih
u 33 zgrade, te suvremenom medicinskom opremom (3,5,6,8,9,10).
51
Slika 1 Situacioni plan kompleksa Kliničkog centra Univerziteta u Sarajevu sa naznačenim nukleusom prostornog razvoja
novih objekata.
KONCEPT NOVE GRADNJE
Nova gradnja predstavlja tipični blokovski koncept po uzoru na
na velike bolničke sisteme u SAD-u, Evropi, Japanu, Australiji i
širem Azijskom regionu, a koji u svom sadržaju ima:
- Centralni medicinski blok sa stacionarom i funkcionalnim
dijelom (CMB)
- Objekat dijagnostike i poliklinike (DIP)
- Objekat za nauku i nastavu (NIN)
- Tehno-ekonomski blok (TEB)
Svi ovi objekti međusobno su povezani podzemnim i nadzemnim
komunikaciono-instalacionim koridorima. Sa postojećim objektima
novijeg datuma gradnje na kojima su izvedeni odgovarajući rekonstruktivni radovi čine okosnicu novog Kliničkog centra na lokalitetu
Koševo. Zadržavanjem dijela postojećih objekata i izgradnjom novih
mijenja se u prostornom smislu koncept bolnice u blok-paviljonski.
Skoro polovina posteljnih kapaciteta KCUS-a biće smještena u Centralnom medicinskom bloku, a druga polovina u postojećim objektima novijeg datuma gradnje. Stari nefunkcionalni objekti biće porušeni.
Neki od njih biće zadržani i restaurirani za nemedicinske namjene
(biblioteke, muzeji, klubovi i sl.).To znači da će nukleus buduće izgradnje biti Centralni medicinski blok (CMB), koji je prema svojoj i situacionoj i funkcionalnoj poziciji centralni. Zbog toga će u daljnjoj
analizi kretanja osoba sa umanjenim tjelesnim sposobnostima biti dat
poseban osvrt na mogućnosti kretanja unutar ovog objekta. U ovom
trenutku on ima “tople veze” sa objektom DIP-a, TEB-a, Ortopedije,
Magnetne rezonanse i Klinike za Urgentnu medicinu (4,5,6,7).
Slika 2 Fotografija makete kompleksa Koševo sa označenim
novim objektima (Maketa: „Arhitekt“ d.o.o. Sarajevo; Imširija M.)
52
Osnovni podaci o funkcijama novih objekata
M. Dilić. et al.
Slika 3 Maketa kompleksa sa naznačenom pozicijom objekta
CMB - KCUS (Tehnički sektor; Imširija M.)
Tehnoekonomski blok (TEB) je objekat u kome su smješteni
energetski i pogonski uređaji i servisi neophodni za funkcionisanje
KCUS-a. Unutrašnjim saobraćajnicama povezan je sa svim objektima na lokalitetu kao i sa gradskim saobraćajnicama. Na ovaj način
omogućeno je efikasno snabdijevanje robama, gorivom i materijalima. Sa većinom medicinskih sadržaja povezan je toplim vezama.U
okviru tehno-ekonomskih sadržaja izgrađeni su: Centralna kuhinja,
Centralna praonica rublja, servisi, radionice, Dispečerski centar,
procesno skladište i telefonska centrala.
Dijagnostika i poliklinika (DIP) je dio Centralnog medicinskog objekta (CMO). Objekat se sastoji iz međusobno povezanih
funkcionalnih cjelina: poliklinike, nuklearne medicine i Centralnog
laboratorija. Poliklinički sadržaji u okviru jedne djelatnosti osigurava im optimum interdisciplinarnog rada. Pored konsultativne
dijagnostičko-terapeutske djelatnosti, u ovim jedinicama se organizuje i praktična nastava za studente i liječnike kao i određena
naučno istraživačka istraživanja.
Nauka i nastava (NIN) je takođe dio Centralnog medicinskog objekta (CMO) i izgrađen je uz CMB i sa kojim ima neposrednu toplu vezu. U objektu NIN-a nalaze se dva savremena amfiteatra
namjenjena za održavanje nastave studentima Medicinskog fakulteta kao i za druge manifestacije.Tu je i glavni ulaz za sve studente koji
dolaze na ovu lokaciju.
OPIS CENTRALNOG MEDICINSKOG
BLOKA (CMB-a)
Centralni medicinski blok (CMB) je najveći objekat na lokalitetu
Koševo (Slika 3). Njegova ukupna brutto površina je oko 50.000 m2
i sastoji se iz šest samostalnih lamela, projektantski označenih kao:
A, B, C, D, E i F. Većim svojim dijelom objekat prati konfiguraciju
terena na kome je izgrađen (Slika 4).
Slika 4 Osnova CMB-a sa rasporedom lamela
CENTRALNI MEDICINSKI OBJEKAT (CMO)
Centralni medicinski objekat (CMO) je najveći objekat na lokalitetu Koševo. U njegov sastav ulazi (ranije opisani) objekat DIP-a i
Centralni medicinski blok (CMB), čija intenzivna gradnja je u toku.
Do ovog trenutka je izvedeno cca. 35% od ukupne površine objekta, koja iznosi cca. 50.000m2.
Iz funkcionalne šeme vidljivo je da sve discipline i djelatnosti
smještene u centralne objekte, moraju biti jasno diferencirane, a istovremeno međusobno povezane u jedinstvenu tehnološku cjelinu.
Centralni medicinski objekat ima šest ulaza primarnog značaja;
1. ulaz za osoblje i posjetioce,
2. ulaz za vanjske pacijente, koji koriste usluge dnevne bolnice,
polikliničko – dijagnostičkih i laboratorijskih jedinica. Ulaz mora
biti odvojen od ulaza za osoblje, studente i posjetioce,
3. ulaz za studente,
4. ulaz opskrbe u TEB,
5. urgentni ulaz,
6. ulaz u dijagnostiku pacijenata koji su stacionirani na lokalitetu
Koševo van Centralnog objekta i objekata povezanih toplim
vezama.
Unutarnje komuniciranje vanjskih pacijenata i hospitaliziranih
bolesnika treba vidno dodatnom vizuelnom signalizacijom usmjeriti.
Ovo se naročito odnosi na prostore poliklinike, dijagnostike i centralne laboratorije koje koriste i vanjski pacijenti (poseban ulaz, ulazni hol, čekaonice) i hospitalizirani bolesnici (veza sa stacionarom).
Hospitalni dio - stacionar je riješen u obliku slova H, koga
čine lamele A i C (prostori u kojima su smještene bolesničke sobe)
i spojna komunikaciona lamela B. U lameli B su projektovani vertikalni komunikacioni putevi (baterija od 9 liftova i dva stepeništa) i
zajednički prostori .
Dijagnostičko-terapijski dio objekta čine niski dijelovi lamela A, B i C, te interpolirane četverospratne lamele D i E.
One popunjavaju prostor između lamela A, B i C na etažama 04,
05, 06 i 07. Na etaži 06 smješten je Operacioni blok sa 15 OP
sala, hirurška intenzivna njega sa 26 kreveta, endoskopije i stacionar Kardiohirurgije. Na nižoj etaži (05) predviđeni su Centralna
sterilizacija, Apoteka, Restoran i Glavni ulazni hol sa recepcijom.
Etaža 04 planirana je za Patologiju i Centralne garderobe. Rtg dijagnostika i Radioterapija predviđeni su na etažama 03 i 02. Lamela
F je niski dvoetažni objekat koji spaja CMB sa starijim objektom
Ortopedsko-traumatološke klinike. Podaci o objektima sadržani su
u prethodnim studijama, u kojima su oni sa tehničko-tehnološkog
aspekta detaljno analizirani. (4)
53
Osvrt na način dosadašnje gradnje novih objekata
STACIONAR CMB-a - tipska etaža
Novi objekti Kliničkog centra Univerziteta u Sarajevu, prema postavljenim standardima kvaliteta moraju ispuniti maksimalne tehničkotehnološke uvjete savremene gradnje medicinskih objekata. Njihova
gradnja je izuzetno skupa, imajući u vidu veliki broj zahtjevnih instalacija. Osnovno opredjeljenje je da ono što se izgradi mora biti na
putu maksimalno humaniziranog, odnosno „friendly“ pristupa kada
su pacijenti, posjetioci i uposlenici u pitanju. Samo takav prostor čini
bolesnim ljudima, ali i njihovim obiteljima situaciju lakšom i s humanog
aspekta prihvatljivom. U tom smislu promišlja se i kada su u pitanju
osobe sa umanjenim tjelesnim mogućnostima. Uvažavajući činjenicu
da su tjelesna oštećenja dosta širok pojam, referentna skupina čije
kretanje se mora posebno analizirati su ljudi u invalidskim kolicima.
Kada se obezbijedi njihovo samostalno kretanje, određeni prostor
će biti bez arhitektonskih barijera i za ostale skupine ove populacije.
Da je to opredjeljenje primarno dokazuje i činjenica da je unutar Centralnog medicinskog bloka, uz prve dijagnostičko-polikliničke
prostore izgrađen najveći dio vertikalnih komunikacija, kao i kupatila za ove osobe. Ulazna vrata u sve stacionare i bolesničke sobe
su širine 120cm, što omogućava nesmetan ulaz/izlaz pacijenata sa
otežanim kretanjem, ali istovremeno omogućava obilazak pacijenata
od strane posjeta (koje mogu imati isti problem).
S obzirom da je izgrađen manji stepen ovog zahtjevnog objekta,
vidljiva je razvijena svijest o potrebama svih ljudi u obezbjeđivanju
njihovog samostalnog kretanja kroz njega. Međutim, dosta korisnika usluga Kliničkog centra još uvijek ne poznaje sve prostorne
mogućnosti u njihovom samostalnom kretanju do njihovih odredišta
unutar lokaliteta Koševo. Postavljanje posebnih obilježja o mogućim
pravcima kretanja i drugih usluga, ne odnosi se samo na ljude u kolicima. Potrebno je voditi računa i o drugim osobama sa poteškoćama
(npr. slabovidni). To je dovoljan razlog da se uradi poseban projekat
vizuelne signalizacije koja treba da im pomogne u tome. U tome
svakako mogu biti od pomoći piktogrami prikazani na Slici 5 (1,2).
Stacionar služi za smještaj, liječenje i njegu onih bolesnika čiji
medicinski tretman nije moguće u cjelosti sprovesti u polikliničkodijagnostičkim jedinicama, a organizovan je na principu progresivne njege.
Slika 5 Vizuelna signalizacija za različite potrebe ljudi sa umanjenim tjelesnim mogućnostima (Uvećana slika na strani 59)
Slika 6 Šematski prikaz stacionara CMB-a sa naznačenom
lamelom ”B” koja je glavna komunikaciona lamela za cijeli
objekat CMB-a
Stacionar je riješen u obliku slova „H“ sa četiri grupe njege od
po 26- 30 ležajeva, što zavisi od specifičnih potreba pojedinih OJ.
Grupa njege se sastoji od 6 kreveta postintenzivne (2 dvokrevetne
i 2 jednokrevetne) i 20-24 kreveta standardne njege.
Blok sa stacionarnim jedinicama biće povezan sa svim ostalim
dijelovima Kliničkog centra, a posebno sa prijemom i upućivanjem
bolesnika, polikliničko-dijagnostičkim jedinicama i laboratorijem,
kao i intenzivnom njegom i Centralnim OP blokom.
Osnovni tip jedinice je bolesnička jedinica sa 26-30 kreveta koja
se sastoji od:
- šest kreveta poluintenzivne njege
- 24 kreveta za standardnu njegu
- dvije sobe sa po dva radna mjesta za liječnike
- pult za centralni nadzor i prostor za odmor sestara
- prostor za intervencije sa priručnom apotekom
- prostor za pripremu terapije
- odgovarajući servisni i sanitarni prostori
Standardna njega se odvija u sedam trokrevetnih soba, jednoj
dvokrevetnoj i jednoj jednokrevetnoj sobi. Svaka soba opremljena
je jednim umivaonikom koji služi za pranje ruku liječnika ili sestre
nakon određenih radnji koje se obavljaju na krevetu. Svaka soba ima
zaseban sanitarni čvor (tuš, WC, umivaonik), koji se nalazi neposredno kraj ulaza u sobu.
Dvije grupe njege po 26-30 kreveta čine jednu jedinicu njege
sa 52-60 kreveta. Ona pored nabrojanih sadržaja ima i slijedeće
zajedničke prostore: prijemni pult, soba šefa jedinice, soba glavne
sestre, soba dežurnog liječnika, soba za sastanke i rad sa studen-
54
M. Dilić. et al.
tima, dnevni boravak za pacijente, katni terminal i odgovarajuće
sanitarne prostorije. Ovakav tipski raspored biće prilagođen
specifičnim potrebama odgovarajućih disciplina koje su uvjetovane
medicinskom tehnologijom rada. Na slikama 7-20 prikazani su već
izgrađeni prostori CMB-a po etažama i analizom mogućeg kretanja
osoba sa umanjenim tjelesnim mogućnostima.
Na slikama su prikazane potpuno ili djelomično izgrađene
etaže CMB-a. Iz njih se vidi da je moguće samostalno kretanje ljudi
umanjenih tjelesnih sposobnosti unutar objekta. Naime, do sada
je stepen izgrađenosti ovog objekta 15%, ali su i unutar tog dijela
novih prostora stvoreni uslovi za nesmetano kretanje. U grafičkom
prilogu će se detaljnije prikazati pravci kretanja osoba umanjenih
tjelesnih mogućnosti unutar objekta CMB-a. To su:
ETAŽA 02
ETAŽA 03
ETAŽA 05
ETAŽA 06
ETAŽA 13
- Hemoterapija i radioterapija.
- Onkologija, CT aparati i druga dijagnostika.
- Centralna sterilizacija i koridori, tople veze
CMB-a prema objektu TEB-a i Ortopedije.
- Tek izgrađeni dio etaže 06-Kardiohirurgija.
- Dio izgrađene prve stacionarne etaže 13
(na kojoj se nalazi 12 kreveta poluintenzivne
njege i 48 kreveta standardne njege)
Na tlocrtima izgrađenih etaža ili dijelova etaža CMB-a, označene
su komunikacije; vertikalne (liftovi), horizontalne (tople veze i koridori), i kupatila za osobe sa umanjenim tjelesnim sposobnostima
(kroz kompletno izgrađeni dio objekta).
CENTRALNI MEDICINSKI BLOK - ETAŽA 02
Slika 7 Šematski prikaz etaže 02 CMB-a - Hemoterapija i radioterapija
Slike 8, 9, 10. Kupatilo za osobe sa umanjenim tjelesnim mogućnostima
Slika 11 Liftovi - baterija od tri bolesnička lifta
Slika 12 Šematski prikaz etaže 03 CMB-a - Onkologija, CT aparati i druga dijagnostika
Slike 13,14 Izgled i pozicija vanjske rampe za ulaz na Onkologiju u CMB-a
55
56
M. Dilić. et al.
Slika 15 Šematski prikaz etaže 05 CMB-a - Glavni ulaz u CMB, Recepcija, i prateći sadržaji
Slika 16 Šematski prikaz etaže 06 CMB-a - Novi Operacioni blok, Kardiohirurgija
Dio etaže 06, koji je još uvijek u izgradnji koristiće Klinika za Kardiohirurgiju. Ona u svom sastavu ima 12 kreveta intenzivne njege i 24 kreveta
standardne njege. U okviru prostora standardne njege, planirano je i izgrađeno moderno kupatilo za nepokretne i osobe umanjenih tjelesnih
mogućnosti.
CENTRALNI MEDICINSKI BLOK - Etaža13 - izgrađeni obuhvat stacionara
Slika 17 Šematski prikaz etaže 13 CMB-a.
Slika 18, 19, 20 Kupatila za nepokretne i osobe umanjenih tjelesnih mogućnosti
Slika 21 Tipična stacionarna etaža s šematskim prikazom osnovnih jedinica
57
58
Stacionarni dio Centralnog medicinskog bloka (CMB) je izgrađen
samo jednom polovinom etaže 13 (lamele A i dio lamele B). Ostale
stacionarne etaže imaju oblik slova H sa ukupno 104-120 kreveta po
etaži. Za svaku jedinicu standardne i poluintenzivne njege (ukupno
26-30 kreveta) ide jedno kupatilo za nepokretne, odnosno osobe
umanjenih tjelesnih mogućnosti. To znači da će na jednoj etaži biti
4 takva kupatila, što potvrđuje opredjeljenost Kliničkog Centra Univerziteta u Sarajevu da poklanja dužnu pažnju ovom dijelu populacije.
ZAKLJUČAK
Zdravstveni objekti izgrađeni na lokalitetu Koševo u vrijeme austrougarskog perioda bili su paviljonskog tipa, međusobno odvojeni
i po pravilu sa ulazom denivelisanim stepenicima od nivoa ulice.
Takva gradnja bila je skupa s aspekta održavanja, uvezivanja različitih
medicinskih disciplina i otežavala je kretanje ljudi sa umanjenim tjelesnim sposobnostima (koji su najčešći korisnici bolničkih usluga).
Novi princip gradnje bolničkih objekata je blokovski, što podrazumijeva koncentraciju dijagnostičko-polikliničkih i stacionarnih prostora
unutar jednog objekta. Takav pristup ima za cilj obezbijediti što veću
koncentraciju zdravstvenih usluga onima kojima su one potrebne.
Istovremeno održavanje tako koncipiranih objekata je jeftinije i
lakše. Primjer ovakve gradnje je Centralni medicinski objekat (CMB),
koji i lokacijski i funkcionalno će biti centralna prostorna okosnica
razvoja. Ovakav koncept omogućava osobama umanjenih tjelesnih
mogućnosti sigurno kretanje i obezbjeđivanje korištenja svih prostora i uređaja bolnice (WC, telefon, šalteri i sl,). Strategija adekvatnog
planiranja je naročito važna obzirom na važnost tercijarnog nivoa
zdravstvene zaštite koji se provodi u Kliničkom centru Univerziteta u
Sarajevu. Uvažavajući potrebe ove populacije (čiji dio možemo biti svi
mi već sutra), a sa prirodnim procesom starenja svakako izgledno u
budućnosti, moramo biti posebno osjetljivi i obezbijediti im potpuno
samostalno kretanje. Referentna grupa za osobe umanjenih tjelesnih
sposobnosti su ljudi u invalidskim kolicima i sva dobra arhitektonska
rješenja podrazumijevaju njihovo kretanje bez ikakvih poteškoća. To
se ne smije doživljavati samo kao uvjet dobijanja upotrebnih dozvola novoizgrađenih dijelova objekta, već kao odraz lične savjesti i
inžinjerskih vještina da to izgradimo na pravi način. Samo oni objekti
koji obezbijede nesmetano kretanje svih ljudi u određenom prostoru
su dobri objekti, sve drugo su loša tehnička i arhitektonska rješenja.
Nemamo pravo i dalje se komotno ponašati i na taj način ugrožavati
nečije pravo na dostojanstven i samostalan život.
CONCLUSION
Health facilities which were built at the Koševo area during the
Austro-Hungarian period, were pavilions in the compound of hospital, divided from each other, and with entrance with stairs sloping
from the street level. Such a construction was expensive in terms
of maintenance, binding various medical disciplines and with serious
difficulties regarding the movement of people with reduced physical
abilities (which are the most frequent users of hospital services).The
new principle of hospital facilities construction is single building i.e.
„all in one“, which means the concentration of diagnostic, polyclinic
and stationary departments within a single building. This approach
aims to ensure a most effective concentration of health services to
those who need it. At the same time, maintaining of facilities so
conceived is cheaper and easier. An example of such a construction
is our Central Medical Building (CMB), which will be a central spatial
M. Dilić. et al.
development framework by its function and location. This concept
allows safe movement to persons with disabilities, and it also provides them easy use of space and hospitals’ equipment (toilettes,
telephone, counters, etc.). That is an important strategy, especially
when taking into account the importance of the tertiary level of
health care that is provide at the Clinical Center University of Sarajevo.We must take into account the needs of this population, and we
must be particularly sensitive and provide them with a completely
independent movement. Within the broader group of handicapped
people, the reference group is the one of people in wheelchairs, and
all the functional architectural solutions should be (must be) adjusted
for their movement without any difficulties. It should not be perceived only as a condition of obtaining constructions’ licences for
new components of the object, but also as a reflection of our personal conscience as well as engineering skills to build those objects in
a right and functional way. Only those objects that provide easy and
smooth movement of all people in a certain area are good facilities,
everything else is a non-functional i.e. bad technical and architectural
solutions. We have no right to continue with comfortably manner
and without having in mind disabled persons and theis basic right to
a dignified and independent life.
REFERENCES
1. UN Convention on the rights of persons with disabilities (2006). http:/www. un.
org/ disabilities /convention/conventionfull.(access Dec. 2013)
2. Uredba o prostornim standardima, urbanističko-tehničkim uvjetima i normativima
za sprječavanje stvaranja arhitektonsko-urbanističkih prepreka za osobe sa umanjenim tjelesnim mogućnostima. Vlada Federacije Bosne i Hercegovine na 109. sjednici, 16.07.2009.
3. Fejzić E. Osobe umanjenih tjelesnih sposobnosti i arhitektonske barijere. Izdavač;
Expedito. Centar za održivi prostorni razvoj. Kotor. 2007.
4. Prijedlog za dogradnju, rekonstrukciju i povezivanje sa centralnim novim objektom.
Institut za socijalnu medicinu, organizaciju i ekonomiku zdravstva. Sarajevo;1987.
5. Građevinsko-arhitektonski i medicinski program za rekonstrukciju i adaptaciju
postojećih objekata Kliničkog centra na lokalitetu Koševo. Medicinski fakultet i Institut za socijalnu medicinu. Sarajevo; 1987.
6. Građevinsko-arhitektonski i medicinski program za projektiranje Kliničkog centra
- Centralni objekat Koševo. Arhitekt d.d. Sarajevo; 1986.
7. Analiza postojećeg građevinskog i medicinsko-tehnološkog stanja bolničkih objekata na lokalitetu “Koševo“. Institut za socijalnu medicinu, organizaciju i ekonomiku
zdravstva. -Sarajevo;1986.
8. http//www.kcus.ba/izlaz/08.06.2010./
9. Hospitals and People with Disabilities. http://www.nidirect.gov.uk/index/information-and-services/people-with-isabilities/health-and-support/hospitals-and-peoplewith-disabilities /in-hospital.htm (access Jan. 2014)
10. Access To Medical Care For Individuals With Mobility Disabilities. http.// www. ada.
gov /medcare_mobility_ta/medcare_ta.htm. (access Dec. 2013)
Mirza Dilić, MD, PhD
Internal Clinics and Departments,
Phone: +387 33 298 077
Email: mdilic@bih.net.ba
Vizuelna signalizacija za različite potrebe ljudi sa umanjenim tjelesnim mogućnostima
59
Case report
Intraluminal lipoma as a cause of intestinal obstruction
Intraluminalni lipom kao uzrok intestinalne opstrukcije
Amir Hadžibeganović1, Adnan Kulo1, Lana Sarajlić1*, Dijela Kulo2, Abdulah Efendić3
1
Clinic of General and Abdominal surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; 2Medical Faculty
University of Sarajevo, Čekaluša 90, 71000 Sarajevo, Bosnia and Herzegovina; 3General Hospital „Prim. dr Abdulah Nakaš“ Kranjčevićeva 12, 71000 Sarajevo,
ABSTRACT
SAŽETAK
Intestinal lipomas are rare benign tumors and intussusceptions
due to a gastrointestinal lipoma constitutes an infrequent clinical entity. Lipoma may develop as a benign tumor in all organs and rarely in
large or small intestine.The occurrence of intussusception in adults
is rare, accounting for less than 5% of all cases of intussusceptions
and almost 1%-5% of bowel obstruction. The condition is found in
less than 1 in 1300 abdominal operations and 1 in 100 patients operated for intestinal obstruction. The child to adult ratio is more than
20:1. Gastrointestinal lipomas are rare benign tumors that can occur
anywhere along the gut, and the small bowel is the second most
common site for gastrointestinal lipomas after the colon. We report
a rare case of jejunojejunal intussusception in an 32 year-old adult
secondary to an jejunal lipoma. The present report describes a case
of jejunojejunal intussusceptions in an adult with a colicky upper abdominal pain. Invagination was diagnosed by computed tomography
scan. Exploratory laparotomy revealed jejunojejunal intussusception
secondary to a lipoma which was successfully treated with tumor
resection. Surgical resection remains the recommended treatment
for nearly all cases, but there is controversy about whether or not
the intussusception should be initially reduced before resection.
Intestinalni lipomi su rijetki benigni tumori te intususcepcije
zbog gastrointestinalnog lipoma predstavlja rijedak klinički entitet. Lipom se može razviti kao benigni tumor u svim organima,
a rijetko u tankim i debelim crijevima. Pojava intususcepcije kod
odraslih je rijetka te čini manje od 5% svih slučajeva intususcepcije
i 1% -5% crijevne opstrukcije. Stanje se nalazi u manje od 1 na
1300 abdominalnih operacija te 1 od 100 bolesnika operisanih zbog
intestinalne opstrukcije. Odnos djece i odraslih je više od 20:01.
Gastrointestinalni lipomi su rijetki benignih tumora koji se mogu
pojaviti bilo gdje duž crijeva, a tanko crevo je druga najčešća lokalizacija gastrointestinalnih lipoma nakon kolona. Izvještavamo o rijetkom slučaju jejunojejunalne intususcepcije kod 32 godine starog
pacijenta sekundarno jejunalnoom lipomu. Ovaj rad opisuje slučaj
jejunojejunalne intususcepcije u odraslih sa količnom boli u trbuhu.
Invaginacija je dijagnosticirana CT skeniranjem. Explorativna laparotomija otkrila je jejunojejunalnu intususcepciju sekundarno zbog
lipoma koji je uspješno tretiran resekcijom tumora. Kirurška resekcija ostaje preporučeni tretman u gotovo svim slučajevima, ali
postoji kontroverza oko toga da li treba ili ne inicijalno smanjiti
intususcepciju prije resekcije.
Key words: intussusception, colon, lipoma.
Ključne riječi: intususcepcija, kolon, lipom.
INTRODUCTION
reported as a cause of adult intussusceptions (4). Gastrointestinal
lipomas are uncommon, slow growing, fatty tumors that can occur anywhere along the gut, and the small bowel is the second
most common site for gastrointestinal lipomas after the colon with
about 20~25% of the cases of lipoma occurring in the small bowel.
Approximately 90% to 95% of all lipomas are located in the submucosa and because of its usual position immediately superficial to
the muscularis propria, the underlying muscular contractions tend
to draw the tumor into the bowel lumen and form an intraluminal
polyp (5). This produces the intussusception as the leading point
or this creates intestinal obstruction by occlusion of the lumen (6,
7). We report a rare case of jejunojejunal intussusception in an 32
years old adult secondary to an jejunal lipoma. The present report
describes a case of jejunojejunal intussusceptions in an adult with a
colicky upper abdominal pain. Invagination was diagnosed by computed tomography scan. Exploratory laparotomy revealed jejunojejunal intussusception secondary to a lipoma which was successfully
treated with tumor resection.
Intestinal lipomas are rare benign tumors and intussusceptions
due to a gastrointestinal lipoma constitutes an infrequent clinical
entity (1). Lipoma may develop as a benign tumor in all organs and
rarely in large or small intestine (2).The occurrence of intussusception in adults is rare, accounting for less than 5% of all cases of
intussusceptions and almost 1%-5% of bowel obstruction.The condition is found in less than 1 in 1300 abdominal operations and 1 in
100 patients operated for intestinal obstruction. The child to adult
ratio is more than 20:1. In contrast to childhood intussusception,
adult intussusception has an underlying lesion within the intussusception in 83% to 95% of the cases that require surgical resection
(3). This disease usually has a subacute or chronic onset so that
the diagnosis can be delayed and it is frequently established only
when performing emergency laparotomy for treating the obstructive symptoms. Neoplasms are the most frequent causes of adult
intussusception, and gastrointestinal lipoma has been infrequently
61
Intraluminal lipoma as a cause of intestinal obstruction
CASE REPORT
A 32 year-old patient was admitted to the clinic in the emergency room because of severe abdominal pain, persistent vomiting
under clinical, laboratory, X-ray and CT-image of ileus. The patient
had no past history of peptic ulcer disease, alteration in bowel
habits, melena or weight loss. On examination, he was apyrexial
and hemodynamically stable. His abdomen was distended and no
palpable abdominal masses; bowel sounds were hyper audible. Initial rectal examination revealed no masses or blood.Abdominal
radiography revealed prominent dilatation of the small bowel with
air fluid levels (Figure 1). Abdominal CT showed a target sign- or
sausage-shaped lesion typical of an intussusceptions that varied in
appearance relative to the slice axis (Figure 2). The inner central
area represented the invigilated intussuscepted, surrounded by its
mesenteric fat and associated vasculature, and all surrounded by
the thick-walled intussuscipiens. More head-side scans showed a
low-density homogenous mass measuring 4 cm that was considered to be the leading point for the invagination (Figure 3).
Figure 3 Computed tomography scan of the abdomen without oral contrast
Figure 1 Abdominal X-Ray, in favor of bowel obstruction
These findings led to a diagnosis of intussusceptions induced by
a tumor most likely begin. Nasogastric probe is placed and after a
short resuscitation lines up an indication for prompt surgical treatment. The patient underwent an urgent exploratory laparotomy.
At laparotomy 20 cm below the Treitz’s ligament clear jejunal invagination was identified ,approximately 15 cm in length, and distally in the lumen of intestine is palpable soft tumorous formation. Enterotomy was done directly under intussusception and we
found intraluminal tumor size of tangerine on long stem that lead
to intussusception. Intestinal trophic was completely neat. Ligature
of tumor stem was made and tumor was fully removed and the
intestine was sewn in two layers. Removed tumor was sent to histopathology analysis. The histopathology report confirmed a submucosal lipoma in the jejunum as a cause for a 15-cm jejuno-jejunal
intussusception. There was no evidence of dysplasia or malignancy.
The postoperative period was uneventful, intestinal passage was
established spontaneously and the patient was discharged on the
sixth postoperative day with a good general condition and adequate local findings.
DISCUSSION
Figure 2 Abdominal computed tomography, showing a fatty
oval mass in the small intestine.
Intussusception occurs when a proximal segment of the bowel
telescopes into an adjacent distal segment (8). The typical symptoms found in adult patients with intussusceptions are often chronic; such as abdominal pain, fever, nausea, vomiting, melaena, weight
loss, and constipation (9). Physical examination may demonstrate
diffuse or localized abdominal tenderness, while an abdominal mass
is detected in a minority of cases. In our case, these symptoms and
signs did not occur, with a first presentation of acute large-bowel
obstruction (10). The use of computed tomography in the evaluation of patients with uncharacteristic abdominal pain may allow the
condition to be more reliably diagnosed (11, 12). However, in our
62
case a colonic malignancy could not be ruled out and therefore
the patient had an emergency laparotomy. Resection or reduction
of the colon involved is still controversial. However, many speculate against reduction before resection, especially when taking into
account cases where the bowel is nonviable or when malignancy
is suspected. Lipoma of the colon is an uncommon tumor of the
gastrointestinal tract. In general, colonic lipomas do not cause
symptoms and, therefore, are usually detected incidentally during
colonoscopy, surgery and autopsy. However, a minority of lipomas
can cause symptoms when the lesion is large, especially for those
with a diameter greater than 2cm. With the widespread application of colonoscopy, small lesions are found incidentally, and their
diagnosis and treatment are mainly dependent on endoscopy. Large
colonic lipomas are often mistaken for more serious pathology, as
a result of their rarity and variable presentation. Therefore, more
attention should be paid to how to increase the rate of preoperative diagnosis. Clinical features are still important, especially for
those large lesions.Many therapeutic interventions have been tried
for the treatment of colonic lipoma, which have varied from hemicolectomy to segmental resection and local excision, according
to the correct preoperative diagnosis and intraoperative findings.
With the advancement of colonoscopy, endoscopic cautery snare
resection of colonic lipomas has become popular and has been
proven to be a safe therapeutic method, especially for small lesions.
This is unlikely to be of value in large lipomas as in our case, and
resection would be recommended in large colonic lipomas. The
removal of colonic lipoma with the assistance of laparoscopy has
also been reported, but this would be contraindicated in a patient
with acute bowel obstruction (13).
CONCLUSION
Surgical resection remains the recommended treatment for
nearly all cases, but there is controversy about whether or not the
intussusception should be initially reduced before resection.
Conflict of interest: none declared
A. Hadžibeganović et al.
REFERENCES
1.
Kim CY, Bandres D, Tio TL, Benjamin SB, Al-Kawas FH. Endoscopic removal of
largecolonic lipomas. Gastrointest Endosc 200;55(7):929-931.
2. Liessi G, Pavanello M, Cesari S, Dell’Antonio C, Avventi P. Large lipomas of
the colon: CT and MR findings in three symptomatic cases. Abdom Imaging
2006;21(2):150-152.
3. Pfeil SA,Weaver MG, Abdul-Karim FW, Yang P. Colonic lipomas: outcome of endoscopic removal. Gastrointest Endosc 1990;36(5):435-438.
4. Ryan J, Martin JE, Pollock DJ. Fatty tumours of the large intestine: a clinicopathological review of 13 cases. Br J Surg 1989;76(8):793-796.
5. Radhi JM. Lipoma of the colon: self amputation. Am J Gastroenterol 1993; 88 (11):
1981-1982.
6. Jiang L, Jiang LS, Li FY, Ye H, Li N, Cheng NS, Zhou Y. Giant submucosal lipoma located in the descending colon: a case report and review of the literature. World J
Gastroenterol 2007; 13(42):5664-7.
7. Azar T, Berger DL. Adult intussusception. Ann Surg 1997;226(2):134-138.
8. Reijnen HA, Joosten HJ, de Boer HH. Diagnosis and treatment of adult intussusception. Am J Surg 1989;158(1):25-28.
9. Begos DG, Sandor A, Modlin IM. The diagnosis and management of adult intussusception. Am J Surg 1997;173(2):88-94.
10. Creasy TS, Baker AR, Talbot IC, Veitch PS. Symptomatic submucosal lipoma of the
large bowel. Br J Surg 1987;74(11):984-986.
11. Bar-Meir S, Halla A, Baratz M. Endoscopic removal of colonic lipoma. Endoscopy
1981; 13(3):135-136.
12. Michowitz M, Lazebnik N, Noy S, Lazebnik R. Lipoma of the colon. A report of 22
cases. Am J Surg 1985;51(8):449-454.
13. Scoggin SD, Frazee RC. Laparoscopically assisted resection of a colonic lipoma. J
Laparoendosc Surg 1992;2:185-189.
Lana Sarajlić, MD
Clinic of General and Abdominal Surgery
Email: elss@bih.net.ba
Case report
Entrapment syndrome of the left renal vein
Entrapment sindrom lijeve renalne vene
Zoran Roljić1*, Božina Radević1, Dušan Janičić1, Slavko Grbić1, Milan Žigić1, Jevrosima
Roljić1,Vladimir Keča1, Severin Dunović1, Novak Milović2
Clinic for Vascular Surgery, Clinical Center Banja Luka, Dvanaest beba 1, 78000 Banja Luka, Bosnia and Herzegovina;
Military Medical Academy, Crnotravska 17, 11000 Belgrade, Republic of Serbia
1
2
* Corresponding author
ABSTRACT
SAŽETAK
Symptomatic stenosis of the left renal vein in preaortic position
is consequence of compression of a. mesenterica superior to the
aorta, and in retroaortic position, by compresion of aorta to the
spine. Symptoms arise from hypertension in left renal vein. Our patient had pains in pelvis and in the left lumbal region for two years,
and recidivant hematuria. Hematuria in left urether was diagnosed
with cystoscopy. Color Doppler and CT angiography showed diametar of left renal vein retroaortic of 2 mm, and in proximal part of
14 mm.We decided for surgery and underwnt preaortic transposition of left renal vein preaortic with interposition of autovenous
panel vein graft of v.saphena magna. Our patient is without any
simptoms after operation.
Simptomatska stenoza lijeve renalne vene u preaortičnoj poziciji
nastaje kompresijom gornje mezenterične arterije prema aorti, a
retroaortične, kompresijom aorte prema kičmi. Simptomi nastaju
zbog hipertenzije u sistemu lijeve renalne vene. Naša bolesnica je
godinama imala bolove u maloj karlici i lijevoj slabinskoj loži, a nekoliko puta je imala hematuriju u posljednje dvije godine. Cistoskopijom je nađena hematurija iz lijevog uretera. Color Dopplerom i
CT angiografijom je prikazana lijeva renalna vena promjera 2 mm
u retroaortičnom i 14 mm u proksimalnom dijelu. Urađena je
preaortična transpozija lijeve renalne vene interpozicijom autovenskog grafta vene safene magne duplog lumena. Poslije operacije
bolesnica je bez tegoba.
Key words: compression, left renal vein, operative treatment
Ključne riječi: kompresija, lijeva renalna vena, operativni tretman
INTRODUCTION
METHODS
The left renal vain is circumaortic in the beginning of the embrional development, and like that staies in 5,7 to 15 % of the
population. With involution of preaortic part of the vein remains
retroaortic vein in 1.8 to 4% of the population, and with involution of the retroaortic part remains preaortic left renal vein in 92
% of the population. Preaortic left renal vein is compressed by
a.mesenterica sup. and aorta in 75%, and it makes stenosis in 50%
cases. his is not hemodynamicaly significant stenosis. Percentage of
stenosis of preaortic left renal vein depends of aortomesenteric
angle and kidney position due to left renal vein. If aortomesenteric
angle is smaller then 21 degree, then compression on the vein is
significant and can narrow the vein lumina. The same effect is compression of aorta and spina on the retroaortic left renal vein. This
stenosis of left renal vein is hemodynamicaly significant if diametar
of left renal vein in the stenotic part is 5 to 7 times smaller then
the diametar of proximal part, and if gradient of pressure in left
renal vein and in the v.cava inf. is 3 mmHg and higher. This pressure
makes dilatation in the system of left renal vein and symptoms
like pain in left lumbal region, in pelvis, hematuria, left varicocela,
and pelvical varices. Some of this symptoms are the part of the
another clinical entities, and early observation on this syndrome is
important for diagnosis (1,2,3,4).
We had a female patient, 44 years old, with chronic pain in left
lumbal region and pelvis. She had recidivant hematuria for last two
years. Cystoscopy showed bleading from left kidney and color doppler ultrasound showed high position of left kidney and retroaortic
left renal vein. MR and MSCT angiography showed retroaortic left
renal vein, which was compressed by aorta and first lumbal vertebra (Figure 1 and 2). That part of the vein was shown like stenosis
with diametar of 2 mm and lenght of 1,5 cm. Proximal part of
left renal vein had diametar of 14 mm. The branches of left renal
vein was dilated, especially v.ovarica with varices in pelvis.This findings was enough for diagnosis of symptomatic compression of left
renal vein, with indication for operation (5,6). The operation was
underwent in general anestesia. We made transversal laparathomy.
V.cava inferior, aorta, both renal arteries and left renal vein were
preparated. Retroaortic part of left renal vein was 2 mm in diameter and fixed with surrounding tissue up to v.cava. Proximal part
of vein was dilated like its branches with varices in pelvis.Transposition of left renal vein and direct anastomosis with v.cava inf. was
not able because of fixed vein and lenght of stenotic part of vein.
The stenotic part of left renal vein was resected and clossed with
sutturing, and preaortic transposition was made with interposition
of panel autograft v.saph.magnae with double lumen. Autovein graft
64
of v.saphena magna was anastomosed with v. renalis sin. and v.cava
inf. 2 cm lower then its natural position. Postoperative and control
findings were good and our patient is without symptoms (7).
Z. Roljić et al.
before and after stenosis. Stenosis of left renal vein is hemodynamicaly
significant if diametar of left renal vein in the stenotic part is 5 times
smaller then the diametar of proximal part, and if gradient of pressure in left renal vein proximal part and in the v. cava inf. is 3 mmHg
and higher, while the pressure in the v.cava inf. is smaller then 1 mmHg.
Our patient had pain in the pelvis left lumbal region, hematuria and
dismenorrhea. Hematuria was showen by the cystoscopy, and stenosis
with ultrasound. MR and MSCT angiography showed stenotic part of
vein in the lenght of 1,5 cm. and diametar of 2 mm, and proximal part
with diametar of 14 mm, and dilated v.ovarica and pelvic varices, as well
(8,9,10,11). Compression syndrome of the left renal vein described by
El Sadr et al.(1950), but De Schepper (1972) named this entitet. Medical treatmant and embolisation is selected for isolated pelvic vein hypertension.Operative anmd interventional procedures are indicate for
treatment in patient with renal and pelvic symptoms. Transposition of
vein is the method, from retroaortic position to preaortic or preaortic
with new influence in v.cava inf. 3 or 5 cm lower. Both procedures are
now feasible with open or laparascopic technique. Patients with congestive pelvical syndrome should underwent transection of v.ovarica
or v.testicularis. Autotransplatation is method for operation but it has
high risk and should be avoided. Endovascular procedure is dilatation
and stenting of the vein but with risk or restenosis and dislocation of
stent (12).
CONCLUSION
Our patient has retroaortic left renal vein with symptoms of vein
hypertension in left kidney and with syndrome or pelvic congestion.
We did resection of stenotic part of the left renal vein and make
preaortic transposition with autovein graft.
Figure I and 2 MRI scan and CT scan: Compression on left
renal vein
REFERENCES
DISCUSSION
1. Hollinshead WH.Textbook of Anatomy. 3rd ed. New York: Harper & Row; 1974. 521-
The left renal vein is lenght 8 to 10 cm. The left renal vein goes
in 92% cases between aorta and a. mesenterica sup, and in 1,8 to 4%
between aorta and spina to the influence in v.cava inf. It has many
branches and good connection with another veins. Left renal vein influents are: v. ovarica (v. spermatica), v.uretralis, vv.capsulares, vv.lumbales,
v.suprarenalis medialis, v.diafragmalis inf. There is connection with
v.azygos sin. and with internal and external vertebral plexus. Compression on renal vein, with significant reduction of flow, increases pressure
in proximal part of the vein, and in the kidney. Hypertension in the left
renal vein makes varices in kidney and varicocela in males. In females
there is varices of kidney, varices of the v.ovarica and pelvic congestion
syndrome, with chronic pain in pelvis, urinary problems and dismenorrhea.The problems arise when patient is in sitting or standing position.
Gluteal, perineal and femoral varices can be part of this syndrome. Ultrasound, MR and MSCT angiography can show position and stenosis
of the left renal vein. Hemodynamic degree of stenosis can be measured with ultrasound and with measuring of the pressure in the vein
2. Hilgard P, Oberholzer K, Meyer KH, Hohenfellner R, Gerken G. Das “Nuýknacker-
523.
Syndrom” der Vena renalis (Arteria-mesenterica-superior-Syndrom) als Ursache
gastrointestinaler Beschwerden. Dtsch Med Wochenschr 1998;123(31-32):936940.
3. Hohenfellner M, Steinbach F, Schultz-Lampel D, Schantzen W, Walter K, Cramer
BM, et al. The nutcracker syndrome: new aspects of pathophysiology, diagnosis and
treatment. J Urol 1991;146(3):685-688.
4. Andrianne R, Limet R, Waltregny D, de Leval J. Hematuria caused by nutcracker
syndrome: preoperative confirmation of its presence. Prog Urol 2002;12(6):13231326.
5. Rudloff U, Holmes RJ, Prem JT, Faust GR, Moldwin R, Siegel D. Mesoaortic compression of the left renal vein (nutcracker syndrome): case reports and review of the
literature. Ann Vasc Surg 2006;20(1):120-129.
6. Basile A, Tsetis D, Calcara G, Figuera D, Patti MT, Coppolino F, et al. Nutcracker
Syndrome Due to Left Renal Vein Compression by an Aberrant Right Renal Artery.
Am J Kid Dis 2007;50(2):326-329.
7. Thompson PN, Darling RC, Chang BB, Shah DM, Leather RP. A case of nutcracker
syndrome: treatment by mesoaortic transposition. J Vasc Surg 1992;16(4):663-665.
65
Entrapment syndrome of the left renal vein
8. Ming-Feng L,Tsung-Lung Y. Nutcracker syndrome. Nephrology 2011;16(1):118
9. Takebayashi S, Ueki T, Ikeda N, Fujikawa A. Diagnosis of the nutcracker syndrome
with color Doppler sonography: correlation with flow patterns on retrograde left
renal venography. Am J Roentgenol 1999;172(1):39-43.
10. Altugan FS, Ekim M, Fitöz S, Özçakar ZB, Burgu B,Yalçınkaya F, Soygür T. Nutcracker
syndrome with urolithiasis. J Ped Urology 2010;6(5):519-521.
11. De Schepper A. Nutcracker phenomenon of the renal vein causing left renal vein
pathology. J Belge Radiol 1972;55(5):507-511.
12. Shokeir AA, El-Diasty TA, Ghoniem MA.The nutcracker syndrome: new methods of
diagnosis and treatment. Br J Urol 1994;74(2):139-143.
Zoran Roljić, MD
Department of Vascular Surgery
Clinical Center of Banja Luka
Dvanaest beba 1
78000 Banja Luka, RS
Phone: + 387 65 673 135
Email: roljicas@spinter.net
66
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67
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68
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rada koji uz engleski trebaju biti napisani i na našim jezicima (bosanski, hrvatski i srpski). Autori su odgovorni za sve navode i stavove u njihovim radovima. Ukoliko je rad pisalo više autora, potrebno je navesti tačnu adresu (uz telefonski broj i e-mail adresu) onog autora s kojim
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-UVOD
-
MATERIJAL I METODE
-REZULTATI
-DISKUSIJA
-
ZAKLJUČAK
-LITERATURA
69
UVOD
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navesti glavni problem, cilj istraživanja i/ili glavnu hipotezu koja se provjerava.
MATERIJAL I METODE
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literaturi. U kliničko-epidemiološkim studijama opisuju se: uzorak, protokol i tip kliničkog istraživanja, mjesto i vrijeme istraživanja. Potrebno je opisati glavne karakteristike istraživanja (npr. randomizacija, dvostruko slijepi pokus, unakrsno testiranje, testiranje s placebom itd.),
standardne vrijednosti za testove, vremenski odnos (prospektivna, retrospektivna studija), izbor i broj ispitanika – kriterije za uključivanje i
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DISKUSIJA
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odnosno njihovim negiranjem.
ZAKLJUČAK
Treba da bude kratak, da sadrži najbitnije činjenice do kojih se došlo u radu tokom istraživanja i njihovu eventualnu kliničku primjenu, kao i
potrebne dodatne studije za potpuniju aplikaciju. Obavezno navesti i afirmativne i negirajuće zaključke.
LITERATURA - Upute za citiranje - pisanje literature
Literatura se obavezno citira po Vankuverskim pravilima.
Svaku tvrdnju, saznanje ili misao treba potvrditi referencom. Reference u tekstu treba označiti po redoslijedu unošenja arapskim brojevima
u zagradi na kraju rečenice. Ukoliko se kasnije u tekstu pozivamo na istu referencu, navodimo broj koji je referenca dobila prilikom prvog
unošenja/pominjanja u tekstu. Literatura se popisuje na kraju rada, rednim brojevima pod kojim su reference unesene u tekst (ulazni broj
reference), a naslov časopisa se skraćuje po pravilima koje određuje Index Medicus. Ukoliko je citirani rad napisalo više autora, navodi se
prvih šest i doda “et al.”.
Vrlo je važno ispravno oblikovati reference prema uputama koje se mogu preuzeti na adresama National Library of Medicine Citing Medicine http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=citmed.TOC&depth=2 , ili International Committee of Medical Journal Editors Uniform
Requirements for Manuscripts Submitted to Biomedical Journals:
Sample References http://www.nlm.nih.gov/bsd/uniform_requirements.html.

Evaluation activities of daily living in patient`s rehabili

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