Sezai Yilmaz

Liver transplantation for HBV-related cirrhosis in Europe: an ELTR study on evolution and outcomes.

BACKGROUND & AIMS HBV-related chronic liver disease is one of the most common indications for liver transplantation (LT) in Europe. The ELTR database was used to evaluate outcomes and evolution over 20 years (01/1988 and 12/2010). METHODS HBV transplanted patients were analysed according to indication for LT: decompensated cirrhosis (HBVdec) or hepatocellular carcinoma (HBV/HCC). These groups were compared with co-infected patients HBV/HDV (HBDV), HBV/HCV (HBCV), HBV/HDV/HCV (HBDCV); n = 16,664 and with HCV patients (n = 2452) according to LT indication. RESULTS 5912 patients were transplanted for HBV (78% HBVdec, 22% HBV/HCC), with HBV/HCC patients who increased from 15.8% in 1988-1995 to 29.6% in 2006-2010 (p < 0.001). In HBVdec patients, 1, 3, 5, and 10 year patient and graft survival was 83%, 78%, 75%, 68%, and 80%, 74%, 71%, 64%, respectively, significantly better than HBV/HCC (84%, 73%, 68%, 61%, and 81%, 70%, 65%, 58% respectively; p = 0.001 and p = 0.026). In 2006-2010 patient and graft survival significantly improved compared to 1988-1995, both for HBVdec and HBV/HCC (each p < 0.001). A better patient and graft survival was seen in HBV/HCC patients with HBV-DNA(-) compared to HBV-DNA(+) at the time of LT (p < 0.001). Disease recurrence, as cause of death/graft loss, was significantly reduced in recent years compared to the past: currently <1% for HBVdec and 3% for HBV/HCC. CONCLUSIONS Outcomes of LT for HBV have improved in recent years, with disease recurrence being no longer a significant cause of death/graft loss. HBV-DNA at the time of LT seems to influence survival only in HBV/HCC patients.

Spontaneous Small Bowel Perforations Due to Intestinal Tuberculosis Should Not Be Repaired by Simple Closure

Intestinal tuberculosis is a major problem in many regions of the world. The incidence of it is rising in Western countries due to immigration from Third World countries and human immunodeficiency virus infection. The difference between the simple closure and resection and anastomosis was evaluated in this study. Retrospectively, 12 patients with intestinal tuberculosis diagnosed histopathologically among 50 patients with free intestinal perforations operated on between 1995 and 2003 at Turgut Ozal Medical Center were evaluated. Each patient underwent routine laboratory tests and radiologic studies. The most common symptoms of patients were abdominal pain, night sweats, and weight loss. Sites of perforation were ileum in 10 patients (multiple perforation in 4) and jejunum in 2 patients (both had multiple perforations). The perforation was closed by primary closure in 7 patients. Resection-anastomosis was performed in 5 patients. Leaks occurred in overall 3 of 7 patients with primary closure. Three of the 7 patients with leaks due to septicemia died. The mortality rate among all patients was 25%. Intestinal tuberculosis should be kept in mind as a cause in free intestinal perforations. Because of high mortality rate, the resection of the affected area and anastomosis may be the treatment of choice rather than primary closure.

Spontaneous Intestinal Perforation Due to Non-Hodgkin's Lymphoma: Evaluation of Eight Cases

Primary intestinal lymphoma with spontaneous perforation and after systemic chemotherapy is rare. The present study summarizes retrospectively the outcome of eight free intestinal perforated patients diagnosed with intestinal non-Hodgkins lymphoma. Two patients had a history of systemic chemotherapy before perforation. The most common symptoms of the patients were abdominal pain, nausea, vomiting, weight loss, and fever. Sites of perforation were ileum in four, jejunum in two, cecum in one, and sigmoid colon in one patient. Synchronous lymphoma was present in three patients. The perforation was closed by primary closure in three patients. Resection/anastomosis was performed in four patients and sigmoid colostomy was performed in one patient. Three patients were lost due to leakage or septicemia. Intestinal lymphoma might be kept in mind as a cause in free intestinal perforations. Because of the high mortality rate early diagnosis and treatment are important to improve the prognosis of bowel perforation in patients with non-Hodgkins lymphoma.

Expression of Matrix Metalloproteinases 2 and 9 in Donor Liver, Cirrhotic Liver, and Acute Rejection After Human Liver Transplantation

Matrix proteinases are known to play an important role in the cell migration during cancer invasion, in organ development, and in tissue damage during inflammatory process. Among the matrix proteinases, matrix metalloproteinases (MMP) are the most powerful proteinases. Changes at the extracellular matrix components play an essential role in acute rejection after orthotopic liver transplantation (OLT). This prospective clinical study investigated the alterations in the expression of MMP-2 (72-kd gelatinase type IV collagenase [gelatinase A]) and MMP-9 (92-kd gelatinase type IV collagenase [gelatinase B]) in patients with acute cellular rejection (ACR) compared with the biopsies of cirrhotic livers (CL) of patients who underwent OLT, and with healthy livers (HL) of the donors. Although MMP-2 expression was not present in the hepatocytes of the HL, it was in the endothelium; it was moderate in CL and severe in the livers suffering from ACR. MMP-9 expression, on the other hand, is found to be present only in the inflammatory cells, with an increasing intensity in HL, CL, and in livers suffering from ACR. The results suggest that MMP-2 and MMP-9, beside their roles in liver injury with tissue remodeling and fibrosis as mentioned in the previous studies, can be a marker of acute rejection.

Effect of resveratrol and melatonin on oxidative stress enzymes, regeneration, and hepatocyte ultrastructure in rats subjected to 70% partial hepatectomy.

AIM We sought to compare the antioxidant effects of resveratrol (R) and melatonin (M) after 70% partial hepatectomy (PH) as evidenced by ultrastructural alterations and effects on hepatocyte proliferation and apoptosis. METHODS Twenty-six male Wistar albino rats were randomized into four groups: group A (n = 8) resveratrol (R); group B (n = 8) melatonin (M); group C (n = 5) control PH; group D (n = 5) sham operated animals. The rats that received either R or M were sacrificed a week after PH. The malondialdehyde, glutathione, glutathione S-transferase, and nitric oxide levels were estimated in liver homogenates. The morphological changes were investigated using light and electron microscopy (EM). Cell proliferation was detected by immunohistochemical staining with monoclonal antibodies to Ki-67. Apoptosis was detected by the transferase-mediated dUTP nick end-labeling method. RESULTS PH induced hepatic LP, decreased GSH and NO, and inhibited GST activity (P < .05). R and M completely prevented PH-induced lipid peroxidation, decreased hepatic GSH and NO levels (P < .05). The inhibition of GST activity was prevented by R (P < .05), but not with M (P > .05). In the PH group EM showed severe morphological changes: mitochondrial degeneration, vacuoles, lipid droplets, and myelin-like figures. In both the R and M groups, morphological alterations repaired protective effects more prominently in the R group. Ki-67 indices (KI) were increased in the PH group and decreased in both R and M groups (P < .001). In the M group, KI was the lowest, but the difference compared with R was not significant (P > .05). Apoptosis was slightly increased in PH, but in either the R or M groups, apoptosis was intensively increased (P < .001). Increased apoptosis was greatest in the M group and the difference compared with the R group was statistically significant (P < .05). CONCLUSION R and M suppressed PH-induced oxidative damage, attenuated proliferation, and stimulated apoptosis. When we compared R and M, R showed more potent antioxidative effects and was morphologically more protective to hepatocytes. Antiproliferative effects of M were more potent. Because of their potent antioxidative effects, R and M can be effective for oxidative damage like ischemia-reperfusion injury; however, because of the adverse effects on proliferation and apoptosis more studies are needed in states in which regeneration is critical.

A Life-saving but Inadequately Discussed Procedure: Tube Duodenostomy. Known and Unknown Aspects

ObjectiveThe most successful method of managing the difficult duodenum, including the stump leakage, has been the tube duodenostomy technique, but it has not gained wide acceptance and is rarely used. The purpose of this study is to describe the details of the procedure for indication, technical approach, and postoperative care.MethodsDuring the period from 1998 to 2006, a tube duodenostomy was performed in 31 patients for possible insecure duodenal stump closure during gastric resection, postoperative duodenal stump leakage, duodenal leak after primary closure of duodenum for perforation or injury, or anostomotic leak after choledochoduodenostomy. All of the tube duodenostomies were performed through the open end of the duodenum. We also inserted a T-tube into the common bile duct in 19 of 31 patients (61.2 %) with tube duodenostomy.ResultsA tube duodenostomy was performed in the primary operation in 15 of 31 patients. None of those 15 patients required a second operation, and there were no leaks and no deaths. Among the larger group (31 patients), there was one (3.2 %) duodenal stump leak after tube duodenostomy, and it ceased spontaneously; one patient had a subhepatic collection after removal of the duodenostomy tube, and three patients had associated incisional infections. Two patients died; one after a myocardial infarction and the other from irreversible sepsis. The mean length of hospital stay was 26.9 days.ConclusionsWe conclude that tube duodenostomy is a simple, effective, and safe method to prevent rupture of an insecure duodenal stump or to treat the leakage from the duodenal stump or primary repair on the duodenum.

Unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis

AIM To investigate the prevalence and implications of unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis. METHODS The demographic and histopathological data of 1621 patients (≥ 16 years-old) who underwent appendectomy to treat an initial diagnosis of acute appendicitis between January 1999 and November 2011 were retrospectively assessed. Microscopic findings were used to classify the patients under six categories: appendix vermiformis, phlegmonous appendicitis, gangrenous appendicitis, perforated appendicitis, supurative appendicitis, and unusual histopathologic findings. The demographic and clinicopathologic characteristics of patients with unusual histopathologic findings were evaluated in detail, and re-analysis of archived resected appendix specimens was carried out. RESULTS A total of 912 males and 709 females, from 16 to 94 years old, were included in the study and comprised 789 cases of suppurative appendicitis, 370 cases of appendix vermiformis, 243 cases of perforated gangrenous appendicitis, 53 cases of flegmaneous appendicitis, 32 cases of gangrenous appendicitis, and 134 (8.3%) cases of unusual histopathological findings. The unusual histopathological findings included fibrous obliteration (n = 62), enterobius vermicularis (n = 31), eosinophilic infiltration (n = 10), mucinous cystadenoma (n = 8), carcinoid tumor (n = 6), granulomatous inflammation (n = 5), adenocarcinoma (n = 4; one of them mucinous), and mucocele (n = 3), adenomatous polyp (n = 1), taenia sup (n = 1), ascaris lumbricoides (n = 1), appendiceal diverticula (n = 1), and B cell non-hodgkin lymphoma (n = 1). None of the 11 patients with subsequent diagnosis of tumor were suspected of cancer prior to the appendectomy. CONCLUSION Even when the macroscopic appearance of appendectomy specimens is normal, histopathological assessment will allow early diagnosis of many unusual diseases.

Protective Effect of Resveratrol Against Renal Oxidative Stress in Cholestasis

Background/aims. This experimental study was designed to evaluate histological changes of the kidney and renal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) and the effect of resveratrol on these metabolites after bile duct ligation in rats. Methods. Secondary biliary cirrhosis was induced by bile duct ligation for 28 days. Swiss albino rats were divided into three groups. Group 1: Sham (n = 7), Group 2: Bile duct ligation (n = 7), Group 3: Bile duct ligation plus resveratrol (n = 7). Bile duct ligation (BDL) plus resveratrol group received 10 mgr/kg dose of resveratrol intraperitoneally daily throughout 28 days. Kidney tissues were harvested to determine the tissue levels of MDA, GSH, and NO activity. Liver and kidney tissues were removed for light microscopic evaluation. Results. Cholestasis was determined by biochemical and pathologic examination. In the resveratrol-treated rats, levels of MDA were significantly lower than those of the BDL group (p < 0.04). The levels of GSH in the resveratrol-treated rats were significantly higher than those in the BDL group (p < 0.01). The levels of NO in the resveratrol group were significantly lower than those in the BDL group (p < 0.01). Conclusion. The present study demonstrates that intraperitoneal administration of resveratrol in bile duct ligated rats maintains antioxidant defenses and reduces kidney oxidative damage. This effect of resveratrol may be useful in the preservation of renal oxidative stress in cholestasis.

Comparison of Intracorporeal Knot-tying Suture (polyglactin) and Titanium Endoclips in Laparoscopic Appendiceal Stump Closure: A Prospective Randomized Study

Background: Laparoscopic appendectomy is a well-described surgical technique. However, concerns still exist regarding whether the closure of the appendiceal stump should be done with a clip, an endoloop, staples, or other techniques. Therefore, several modifications to the original technique with new materials have been introduced for appendiceal stump closure. The aim of this study was to compare intracorporeal (polyglactin) knot-tying suture with titanium endoclips in appendiceal stump closure during laparoscopic appendectomy. Methods: The study was carried out as a prospective randomized clinical trial between April 2010 and February 2011. Patients with a presentation of appendicitis were included into the study. Two groups were defined—patients with the titanium endoclip and patients with the knot-tying (polyglactin) suture. The results in terms of operating time, complication rates, and hospital stay were analyzed. Results: Sixty-one patients who underwent laparoscopic appendectomy were enrolled in the titanium endoclip group (n=30) or the knot-tying (polyglactin) suture group (n=31). No statistically significant differences were detected between the groups in terms of the distribution of age, sex percentage, appendix localization, and histopathologic diagnosis (P>0.05). One patient required a second operation on postoperative day 10 because of intraperitoneal abscess. The mean operative time for the endoclip group (41.27±12.2 min) was shorter than that for the knot-tying group (62.81±15.4 min) (P=0.001). No statistically significant differences were detected between the groups in terms of hospital stay, follow-up time, and preoperative and postoperative complications (P>0.05). Conclusions: In laparoscopic appendectomy, using a titanium endoclip for optimizing and controlling the appendiceal stump closure is safe and is associated with shorter operation time. This also simplifies the procedure, so it can be a useful alternative to intracorporeal knot-tying for appendiceal stump closure.

Graft-versus-host disease after liver transplantation： A comprehensive literature review

AIM To determine the factors affecting mortality in patients who developed graft-versus-host disease (GvHD) after liver transplantation (LT). METHODS We performed a review of studies of GvHD following LT published in the English literature and accessed the PubMed, Medline, EBSCO, EMBASE, and Google Scholar databases. Using relevant search phrases, 88 articles were identified. Of these, 61 articles containing most of the study parameters were considered eligible for the study. Risk factors were first examined using a univariate Kaplan-Meier model, and variables with a significant association (P < 0.05) were then subjected to multivariate analyses using a Cox proportional-hazards model. RESULTS The 61 articles reported 87 patients, 58 male and 29 female, mean age, 40.4 ± 15.5 years (range: 8 mo to 74 years), who met the inclusion criteria for the present study. Deaths occurred in 59 (67.8%) patients, whereas 28 (32.2%) survived after a mean follow-up period of 280.8 ± 316.2 d (range: 27-2285 d). Among the most frequent symptoms were rash (94.2%), fever (66.6%), diarrhea (54%), and pancytopenia (54%). The average time period between LT and first symptom onset was 60.6 ± 190.1 d (range: 2-1865 d). The Kaplan-Meier analysis revealed that pancytopenia (42.8% vs. 59.3%, P = 0.03), diarrhea (39.2% vs. 61.0%, P = 0.04), age difference between the recipient and the donor (14.6 ± 3.1 years vs. 22.6 ± 2.7 years, P < 0.0001), and time from first symptom occurrence to diagnosis or treatment (13.3 ± 2.6 mo vs. 15.0 ± 2.3 mo, P < 0.0001) were significant factors affecting mortality, whereas age, sex, presence of rash and fever, use of immunosuppressive agents, acute rejection before GvHD, etiological causes, time of onset, and donor type were not associated with mortality risk. The Cox proportional-hazards model, determined that an age difference between the recipient and donor was an independent risk factor (P = 0.03; hazard ratio, 7.395, 95% confidence interval, 1.2-46.7). CONCLUSION This study showed that an age difference between the recipient and donor is an independent risk factor for mortality in patients who develop GvHD after LT.