Ischemic preconditioning vs adenosine vs prostaglandin E1 for protection against liver ischemia/reperfusion injury.

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.

Ischemic preconditioning vs adenosine vs prostaglandin E1 for protection against liver ischemia/reperfusion injury

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.

Umbilical endometriosis associated with large umbilical hernia. Case report.

Umbilical endometriosis is a rare condition, usually following laparoscopic and surgical procedures involving the umbilicus.Spontaneous umbilical endometriosis occurring without any previous abdominal or uterine surgery is extremely rare. The maximal depth of penetration of the umbilical endometriosis described is up to fascial level. There have been only two cases of endometriosis reported arising within umbilical hernia. The authors report a case of a patient with spontaneous umbilical endometriosis associated with a large umbilical hernia, treated by surgical excision and mesh repair of the abdominal wall. To the best of our knowledge, this is the first described case of the association of umbilical endometriosis with a large umbilical hernia that requires prosthetic mesh repair of the abdominal wall defect.

Tuberculous lymphadenitis as a cause of obstructive jaundice.

Obstructive jaundice secondary to abdominal tuberculosis is extremely rare. We present a patient with jaundice secondary to compression of the common bile duct by TB lymphadenitis. A 49-year-old woman was admitted to our department for nausea,epigastric pain and jaundice. Abdominal ultrasonography and computer tomography scan were suggestive of stenosis of the distal common bile duct caused by a retro pancreatic mass. At laparotomy, an enlarged lymph node behind the head of the pancreas was found, causing compression and stenosis of the distal parts of the choledochus. The lymph node frozen section analysis showed epithelioid granuloma with caseous necrosis,strongly suggesting tuberculous origin. Choledochoduodenal anastomosis was performed. Definitive pathohistological examination confirmed TB lymphadenitis. ATB should be considered as a potential cause of jaundice especially in immuno compromised patients and endemic areas. Diagnosing abdominal tuberculosis can be a challenging task. No satisfactory diagnostic gold standard is available so that in most cases the diagnosis cannot be reached before exploratory laparotomy.Early detection enables successful conservative treatment and eliminates the necessity of surgery.

Age dependent influence of external temperature on the pathogenesis of idiopathic lower extremity deep vein thrombosis.

AIM: The aim of the present study was to investigate the relationship between the incidence of idiopathic lower extremity deep vein thrombosis (DVT), age, location of the thrombus, and changes of temperature. MATERIAL AND METHOD: During the two year period between May 2009 and April 2011, inclusive, 124 consecutive patients were diagnosed as having idiopathic lower extremity DVT at the Vascular Surgery Clinic, Clinical Center of Nis, Serbia. RESULTS: In patients younger than 45 years, the increase in average daily temperature with 1 degree C 7 days before the event took place was associated (p 0.05) with a decrease of the risk of occurrence of idiopathic DVT of the lower limbs of 3.6% (0.4 6.7%) as well as DVT above the knees (p 0.01) of 4.7 % (1.3 8.0%). In patients of the age of 45 years and over the age of 45 years the increase of average daily temperature with 1 degree C 7 days before the event took place was associated (p 0.01) with the increase of the risk of occurrence of DVT below the knees of 9.4% (3.3 15.9%). CONCLUSION: According to the results of this study, one can conclude that the influence of external temperature change on DVT incidence and location is based on age.

Advantages of isolated application of fibrin glue over suture in preservation of second-grade spleen lesion.

OBJECTIVES: The aim of this procedure was to assess the safety and efficiency of glue application in the treatment of lienal second-degree lesions, compared with traditional suture method of treatment. BACKGROUND: The spleen is the most frequently injured intra-abdominal structure regardless of injury mechanisms. Fibrin glue is a useful bio-adhesive for safe and efficient treatment of diffuse parenchymatous spleen haemorrhages. METHODS: Seventy dogs under intravenous anaesthesia were subdued to spleen incision in length of 5 cm and depth of 2 cm. Forty animals from the experimental group were treated with fibrin glue preservation, and 30 animals from the control group were treated with suture. Removed spleens were histologically analyzed. No animal was sacrificed. RESULTS: The application of fibrin glue allowed reparation to be accomplished in all cases. The effectiveness of primary repair was registered in 95 %, with only 5 % of cases requiring an application of fibrin omentoplasty. Secondary bleeding was registered only in 1 (2.5 %) case. Preservation with suture is primarily effective only in 40 %, requires additional repair in 23 %, and even 37 % of cases are not feasible. This method is characterized by mortality of 21 %, secondary haemorrhage (32 %), appearance of focal necrosis (42 %) and abscess (11 %). CONCLUSIONS: Application of FG is a method of choice in cases of second-degree transcapsular spleen lesions and it has a considerable advantage over suture (Tab. 4, Fig. 6, Ref. 24).

Intermittent or continuous occlusion of hepatic inflow.

THE AIM OF THE STUDY: The aim was to compare the effects of intermittent and continuous inflow occlusion on liver I/R injury in an experimental model. METHOD: The experiment was done using the Wistar rats that underwent continuous and intermittent inflow liver vascular occlusion. Blood and liver tissue samples were taken and parameters of hepatic ischemia/reperfusion injury were analyzed and compared. RESULTS: Serum activities of ALT, AST and LDH were significantly higher and ALP activity and albumin concentration were markedly lower in rats with continuous liver ischemia. Also, histopathological examination revealed more severe changes in animals with continuous liver vascular occlusion. CONCLUSION: The results of biochemical assay and histopathological examination were concurrent, both indicating more serious parenchymatous damage caused by continuous hepatic pedicle clamping. Study results clearly demonstrated a better tolerance of the liver to intermittent Pringle maneuver (Tab. 1, Fig. 5, Ref. 9).

Malignant biliary stenosis treated with two percutaneous stents--case report.

INTRODUCTION: During last three decades interventional radiology became most powerfull tool in palliative treatment of patients with malignant biliary stenosis. CASE REPORT: We report a case of 62-year-old patient with malignant biliary obstruction caused by recidivant tumor of common bile duct remnant with infiltration of previously created hepaticojejunostomia. Biliary decompression was achieved by placement of two self-expanding metallic stents. DISCUSSION: In presented patient, due to previous surgery percutaneous approach was mandatory. Also, considering the unresectability of recidivant lesion and poor prognosis, definitive, preferable internal biliary drainage was to be achieved. Therefore the placement of metallic self-expanding stent was the therapeutic method of choice. CONCLUSION: The aim of percutaneous minimally invasive radiological interventions is to achieve effective biliary decompression with internal bile drainage if possible.

Hepatitis C virus-related hepatocellular carcinoma and liver cirrhosis.

PURPOSE: The aim of this study was to compare patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection with patients with liver cirrhosis associated with HCV virus infection. METHODS: Forty-five patients were prospectively analyzed, all with HCV infection. Patients were divided into 2 groups. The first group consisted of 21 patients with histologically proven HCC and the second one consisted of 24 patients with liver cirrhosis without HCC. PCR was carried out in order to diagnose active HCV infection and HCV genotyping. RESULTS: There was no statistically significant difference in the structure of the compared groups of patients in relation to sex and age. In 76.19% of the patients with HCC cirrhosis preceded HCC, while 23.81% of the patients had chronic hepatitis. The prevalence of genotypes in the HCC group was 1a in 4.76%, 1b in 80.95% and 2a in 14.29%. In the group with liver cirrhosis 1a was detected in 20.83%, 1b in 45.83%, 2a in 12.50%, 2b in 4.17% and 3a in 16.67% of the patients. The prevalence of genotype 1b was significantly higher among HCV RNA positive patients with HCC compared to the group with liver cirrhosis and HCV RNA positive patients (x(2)=4.48; p=0.034). In the group where cirrhosis preceded HCC, genotype 1b was found in 75% of the cases, genotype 2a in 18.75%, and genotype 1a in 6.25%. Genotype 1b was detected in 100% of patients with chronic hepatitis and HCC. CONCLUSION: The role of HCV infection in the development of HCC has not been fully clarified. Most authors evaluate the role of individual genotypes in the pathogenesis of HCC. This study has shown that the dominant genotype found in patients with HCC is 1b.

Molecular response to imatinib in patient with Ph negative p190 BCR-ABL transcript positive chronic myeloid leukemia with cyclic leukocytosis.

An atypical case of Philadelphia (Ph) negative, e1a2 BCR-ABL transcript positive chronic myeloid leukemia (CML) characterized with cyclic periodic leukocytosis and spontaneous remissions is reported. The patient was treated with imatinib and good hematology response with molecular remission was achieved. So far, only few Ph positive CML patients expressing p190 BCR-ABL protein and different clinical characteristics and treatment have been described in the literature. This is the first report of Philadelphia negative, p190 BCR-ABL positive CML with cyclic spontaneous oscillation of white blood cell count (WBC), and excellent response to imatinib treatment.

Molecular characteristics and prognostic significance of Bcl-2/IgH gene rearrangement in Serbian follicular lymphoma patients.

Follicular lymphoma (FL) is characterized by the presence of a t(14;18) chromosomal translocation that results in overexpression of bcl-2 protein. Bcl-2/IgH gene rearrangement is detected in 80-90% of follicular lymphomas in Western countries. The aim of this study was to analyze the bcl-2/IgH rearrangement in FL lymphoma patients in Serbia, by PCR technique, correlate molecular findings with clinical characteristics and outcome and assess the prognostic significance of these rearrangements. One hundred-seven patients (median age, 54 years; male/female ratio:60/47) diagnosed with FL were included in the study. DNA samples were obtained from paraffin embedded lymphoid tissue of patients. Bcl-2/IgH rearrangement was assessed for the major breakpoint region (MBR), 5' MBR and the minor cluster region (mcr) breakpoints by PCR technique. We detected a t(14;18) in 81.3% (87/107) of patients. The distribution of bcl-2-IgH rearrangement was as follows: 88,5% (77/87) in MBR breakpoint, 10,35% (9/87) in 5' MBR, whereas mcr bcl-2-IgH rearrangement was observed in one patient (1.15%). No rearrangements were detected in remaining 20 patients (18.7%). This is the first analyses of the frequency of the bcl-2/IgH gene rearrangement in Serbian FL patients, as well as in Eastern European countries. There was no correlation between presence of bcl-2/IgH gene rearrangement and clinical outcome of disease. Incidence of bcl-2/IgH gene rearrangement in Serbian FL patients is relatively high, and similar to frequency in Western countries. Presence of this rearrangement in tumor tissue is not of prognostic significance.

PCR amplification on whole blood samples treated with different commonly used anticoagulants.

The aim of this study was to explore the influence of different anticoagulants on PCR amplification, as well as to optimize PCR amplification of blood samples for successful mutation detection. For the purpose of this study the amplification of part of methylenetetrahydrofolate reductase (MTHFR) gene exon 4, in which mutation C677T is located, was performed. With the exception of sodium heparin, the presence of other commonly used anticoagulants (sodium citrate, K3EDTA, lithium heparin) made it possible to obtain satisfactory amplification. The described method, apart from saving time and material, enables successful PCR-based analysis even when a very small amount of blood sample is available.

Predictive value of prognostic indices in patients with follicular lymphomas.

PURPOSE: The aim of this study was to compare which of three indices--International Prognostic Index (IPI), Italian Lymphoma Intergroup (ILI) index, Follicular Lymphoma adapted International Prognostic Index (FLIPI)--is the most useful in predicting outcome in follicular lymphoma (FL) patients and to identify other clinical and laboratory prognostic factors that influence survival. PATIENTS AND METHODS: Clinical and prognostic studies were carried out in 99 patients with FL. RESULTS: The distribution of patients in IPI risk groups was 44.4%, 19.2%, and 36.4% of cases classified as low, intermediate, and high risk. According to ILI, low-, intermediate-, and high-risk scores were present in 34.3%; 27.3%, and 38.4% of FL patients. After applying the FLIPI index, the patients were divided into three risk groups: low (21.2% of cases), intermediate (39.4%), and high (39.4%) of FL patients. Survival curves demonstrated a high significant difference for the low- and high-risk group according to IPI and FLIPI (log rank=91.13 and 82.17 respectively; p < 0.0001). Difference in overall survival (OS) and failure-free survival (FFS) among low-, intermediate-, and high-risk groups according to ILI was statistically significant (log rank test p < 0.0001). CONCLUSION: All three indices are important tools for prognostic evaluation of FL patients, as well as useful in identifying FL patients with poor outcome. IPI and FLIPI classify patients into two risk groups (low/intermediate- and high-risk groups) with significance difference in OS and FFS, but ILI is more reliable in stratifying patients in low-, intermediate-, and high-risk groups.

Busulfan-induced loss of Ph chromosome in chronic myeloid leukemia.

We report a 44-yr-old female with Philadelphia chromosome positive chronic myeloid leukemia who was initially treated with busulfan, and clinical remission has been achieved. After 4 yr, low-dose busulfan therapy was started again and induced bone marrow aplasia. The patient spontaneously has recovered from aplasia, and complete cytogenetic remission with loss of Ph+ chromosome in bone marrow has been achieved. However, reverse-transcription-polymerase chain reaction analysis showed presence of the bcr-abl transcript in bone marrow.

Failure to detect colonic mucosal hyperproliferation in mutation positive members of a family with hereditary non-polyposis colorectal cancer.

Mucosal proliferation was studied in biopsies obtained from the ascending colon from four mutation positive members of a hereditary non-polyposis colorectal cancer family (group I) and compared to subjects with some positive family history of colorectal cancer but lacking the clinical and pathological features of hereditary non-polyposis colorectal cancer (group II). Labelling indices were derived through immunohistochemical staining of the cell cycle associated nuclear proteins proliferating cell nuclear antigen (PCNA) and Ki-67. Only perfectly longitudinally sectioned crypts were assessed and good intra- and interobserver reproducibility was demonstrated. The labelling indices and proliferative compartment locations were similar in both groups. The mean Ki-67 derived labelling indices (group I 18.0% and group II 17.5%) were similar to values obtained for normal subjects in other studies. PCNA derived labelling indices (group I 58.5% and group II 57.0%) were high, but probably reflect optimization of staining through methacarn fixation. The negative findings do not fit with most published data but critical appraisal of the literature indicates that they are likely to be correct.

[Non-Hodgkin's lymphoma: morphologic, immunologic and cytogenetic classification]. / Nehockinski limfomi: morfoloska, imunoloska i citogenetska klasifikacija.

Malignant lymphomas (ML) encompass about 1/6 of all malignant neoplasms. They have been divided into two major categories: Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). While the classification of Hodgkin's disease is clearly established, classification of non-Hodgkin's lymphomas is still a histopathological problem, and requires a great pathological experience. Many morphological classifications of NHL are used in different countries. In the last few years the "Working formulation for clinical usage" is widely used. Advances in immunology allowed immunological determination of different histopathological lymphoma cell types. Progress in the field of cytogenetics discovered particular cytogenetics abnormalities in patients with different types of NHL. Modern diagnostic procedures in each patient with NHL, besides clinical staging, require a detailed morphological-immunological-cytogenetical (MIC) classification. MIC classification provides the basis for the modern therapeutical management and better estimation of prognosis and evolution of the disease.

Assessment of invasive growth pattern and lymphocytic infiltration in colorectal cancer.

A total of 122 specimens of colorectal cancer were re-assessed in relation to the reporting of invasive growth pattern (expanding vs. infiltrating) and presence or absence of peritumoral lymphocytic infiltrate as used in the Jass prognostic classification. Jass agreed with 69% of cases reported as infiltrating and 90% of reported as expanding. This parameter was distributed similarly amongst Dukes B and C cases in the original assessment (P = 0.27), whereas in the reviewed data infiltrating cases were more likely to be staged as Dukes C (P = 0.04). Jass agreed with 44% of lymphocyte present and 94% of lymphocyte absent assessments. The original lymphocyte assessments showed no significant differences in distribution between Dukes A and B cases (P = 0.12) or B and C cases (P = 0.75), whereas the reviewed data showed significant differences for A vs. B (P = 0.015) and B vs. C cases (P = 0.0025). Criteria for assessment were circulated to eight observers who revisited 20 of the cases in which there was disagreement. Consensus agreement with Jass was achieved in nine of 10 cases for invasive growth pattern and seven of 10 cases for lymphocyte infiltration (with two being evenly split). Most observers showed at least fair levels of agreement with Jass and some achieved excellent levels of agreement. This study indicates that assessment of criteria used in the Jass prognostic system for colorectal cancer is less than optimal in routine practice, but is improved through the provision of simple guidelines.

[The role of T-lymphocyte subsets in susceptibility and resistance to induction of autoimmunity in the central nervous system]. / Uloga subpopulacija T limfocita u osetljivosti i otpornosti na indukciju autoimunosti u centralnom nervnom sistemu.

The importance of two major subsets of T cells (CD4 and CD8) for the induction of EAE was analysed in two strains of rats differing in susceptibility to EAE and the level of IL 2 production. It was found that CD8 cells do not play a role in the induction or in the inherent resistance to EAE. Additionally, the elimination of CD8 cells does not increase the IL 2 production in lymphoid cell cultures. Based on these and previous results showing that a low dose of cyclophosphamide readily abrogates the resistance to EAE and enhances the IL 2 production. Thus it was concluded that genetically determined differences in susceptibility to EAE are governed by immunoregulatory genes whose effect appears to be mediated at the level of cellular interaction of different subsets of CD4 T cells.

[Detection of human papilloma viruses using in situ hybridization]. / Detekcija humanih papiloma virusa in situ hibridizacijom.

First experiences in the diagnosis of human papilloma viruses are reported. The method of in situ hybridization was used together with biotin tests for types of HPV: 6/11, 16/18 and 31/33/51. The study was performed on the preparations of of the cervix tissue with displasmic proliferation and laryngeal papilloma tissues. There have been examined 37 specimens: in 6 were found sequence of HPV genoma for types 6/11 and in 1 specimen for types 16/18 and 31/33/51/.