Ibrahim Astarcioglu

Risk Factors for Early Bacterial Infections in Liver Transplantation

OBJECTIVE Our aim was to determine perioperative risk factors for early bacterial infection after liver transplantation. METHODS Retrospectively examining medical records using Centers for Disease Control and Prevention (CDC) definitions to identify nosocomial infections, we analyzed data on 367 adult patients. RESULTS The incidence of infection was 37.3% (n = 137): namely, surgical site (n = 74; 20.2%) [corrected], blood stream (n = 64; 17.4%), pulmonary (n = 49; 13.4%), urinary system (n = 26; 7.1%). Significant risk factors within the first 30 days were as follows: deceased donor, Model for End-Stage Liver Disease (MELD) >20, albumin level <2.8 g/dL, intraoperative erythrocyte transfusion >6 U, intraoperative fresh frozen plasma >12 U, bilioenteric anastomosis, postoperative intensive care unit stay >6 days, and postoperative length of stay >21 days. Significant risk factors detected within the first 90 days were as follows: MELD >20, preoperative length of stay >7 days, reoperation, postoperative length of intensive care unit stay >6 days, and postoperative length of stay >21 days. Variability was observed in risk factors according to localization of infection. As a result, except for MELD, type of donor, and biliary anastomosis, the others are preventable factors for early bacterial infection. In addition, the same risk factors showed variability according to the site of infection.

Epidemiology and survival of hepatocellular carcinoma in Turkey: outcome of multicenter study.

OBJECTIVE Hepatocellular cancer (HCC) is one of the important health problems in Turkey. We aimed to determine the clinical and demographic features of HCC in the Turkish population and to evaluate the prognostic and survival features. METHOD Two hundred and twenty-one patients with HCC from five hospitals in Turkey are included in this study. RESULTS In 44.4% of the 221 patients with hepatitis B virus and in 21.3% of the 221 patients with hepatitis C virus were found to be responsible for HCC etiology. It has been shown that HCC developed on cirrhosis basis in 74.2% of the patients. HCC was presented with single solitary nodule in 69.2% of the patients. Non-liver metastasis was present in 12.5% of the patients. In 21.7% of the patients, alpha-fetoprotein (AFP) levels were above the diagnostics level of 400 ng/ml. The median overall survival (OS) of 221 patients was 14 months. The median OS of the patients with Child-Pugh A class was significantly longer than that with Child-Pugh B and C classes. The OS of the individuals with normal AFP levels was also longer than that with high AFP levels. The OS of the patients with Stage I HCC according to tumor node metastasis (TNM) classification, the female patients and the treated patients group was found to be significantly good. CONCLUSIONS In conclusion, the viral etiology (hepatitis B and C infections) in Turkish population is found to be an important factor in HCC development. The Child-Pugh classification, AFP levels, TNM classification, being female and treatment were determined to be important prognostic factors in HCC patients.

Immunohistochemical detection of pS2 protein and heat shock protein-70 in pancreatic adenocarcinomas. Relationship with disease extent and patient survival.

We investigated pS2 and HSP-70 protein expression in 36 pancreatic adenocarcinomas for their effect on disease extent and patient outcome. The cases were reviewed, histologically diagnosed, typed, graded, and staged. Lymphatic vessel, blood vessel and perineural invasion as well as lymph node, resection margin and adjacent organ involvements were re-evaluated. The standard streptavidin biotin immunperoxidase method was used for immunostaining with pS2 and HSP-70 antibodies. Cytoplasmic staining with both antibodies was scored semiquantitatively. The scores were compared with histopathological prognostic parameters using statistical methods. Standard prognostic parameters and staining scores were tested by survival analysis in terms of their effect on survival. All the tumors showed a positive cytoplasmic reaction with HSP-70 antibody. Seventy-seven percent of the tumors showed positive cytoplasmic staining with pS2 antibody (22.2% +, 13.9% ++ and 41.7% +++). There was a statistically significant difference between HSP-70 staining scores with N status and final stages of the tumors (Chi-square, p = 0.03 and p = 0.026, respectively), while neither direct nor inverse correlation was detected for both parameters. PS2 staining scores showed no statistically significant relationship with tumor grade T, M status, perineural invasion, lymph and blood vessel invasion. In tumors with extensive staining with pS2, tumor stage tended to be low (Chi square, p = 0.024, Kendall Tau-b, r: -0.336, p = 0.036). There was a statistically significant difference and inverse correlation between tumors with extensive pS2 staining and tumors with less intense staining in terms of lymph node metastasis (Chi-square, p = 0.041, Kendall Tau: p = 0.024, r = -0,373). In the R0 resection group, in univariate analysis, we found that with higher scores of HSP-70 staining, the prognosis of the patient tended to improve. (Cox regression, p = 0.013). In multivariate analysis, HSP-70 expression was found to be an independent prognostic factor. We found no relationship between pS2 staining and patient survival.

Expression of transforming growth factor-beta-1 and p27Kip1 in pancreatic adenocarcinomas: relation with cell-cycle-associated proteins and clinicopathologic characteristics

BackgroundThe purpose of our study was to investigate the immunohistochemical expression of TGF-β1 and p27 in pancreatic adenocarcinomas and to compare the findings with the clinicopathological features and survival. We also aimed to evaluate the expression of TGF-β1 and p27 in the context of other cell cycle and proliferation markers such as cyclin D1 and Ki-67.MethodsWe examined TGF-β1 and p27 expression immunohistochemically in 63 cases of invasive ductal adenocarcinoma of the pancreas. Standard streptavidin-biotin immunperoxidase method was used for immunostaining and the stained slides were examined microscopically using semiquantitative criteria.ResultsTGF-β1 stained the cytoplasms of the tumor cells in 43 cases [68.3%]. There was a statistically significant difference among TGF-β1 staining scores in terms of clinicopathologic factors such as blood vessel invasion, stage and distant metastasis [p < 0.05]. Of the 63 tumors evaluated 23 [36.5%] were positive for p27 within the nucleus. An inverse correlation was found between p27 immunoreactivity and grade [p < 0.05]. But no significant correlation was found between p27 and other parameters. Among the patients with survival data 27 patients had RO resections and these cases were considered in survival analysis. In the univariate analysis, neither TGF-β1 nor p27 expression was related with patient survival.ConclusionOur findings suggest that in pancreatic carcinoma, TGF-β1 expression is related to tumor growth and metastasis. But it is not associated with cell cycle proteins. p27 expression is reduced in pancreatic adenocarcinomas and decreased protein levels of p27 may play a role in the differentiation of pancreatic cancer.

BENEFICIAL EFFECTS OF PENTOXIFYLLINE PRETREATMENT IN NON-HEART-BEATING DONORS IN RATS

BACKGROUND Pentoxifylline (PTX) pretreatment of recipients was shown to protect against liver graft failure from ischemia-reperfusion injury after orthotopic rat liver transplantation. It has also been shown that PTX protects against normothermic ischemia-reperfusion injury to the liver in lobar ischemia model in the rat. Whether PTX can benefit the liver procured from non-heart-beating donors (NHBDs) with up to 9 hr of cold ischemia is unknown. METHODS Donor and recipient rats were pretreated with intraperitoneal PTX (50 mg/kg) 1 hr before cardiac arrest and transplantation, respectively. Grafts were transplanted 0, 30, and 60 min after cardiac arrest with additional 1 and 9 hr of cold ischemia in both PTX-pretreated or untreated (control) groups (10 rats per group). PTX (25 mg/kg/day) was continuously given to the surviving rats for 5 days postoperatively. Recipient survival rates, serum enzyme levels, and histopathological examination of postreperfusion liver biopsies were all analyzed. RESULTS The survival rates, serum enzyme levels, and postreperfusion histology were significantly improved in groups pretreated with PTX compared to the controls. CONCLUSION Donor and recipient PTX pretreatment significantly improves the viability of the liver grafts procured from NHBDs.

Beneficial effects of Eurocollins as aortic flush for the procurement of human livers.

A review of 550 consecutively transplanted liver grafts stored in University of Wisconsin solution (UW) was performed during a 4-year period to ascertain whether graft function was impaired by flushing the aorta with Eurocollins (EC) rather than UW during the harvesting. The outcome of 255 liver grafts flushed with UW in both the aorta and portal vein (group UW/UW) was compared with 295 liver grafts flushed with EC through the aorta and UW through the portal vein (group ECUW). Liver grafts in both groups were flushed with 1 L of UW during the back table procedure and subsequently stored in UW at 4 degrees C before transport. Donor and recipient characteristics, cold and warm ischemia times, and methods of transplantation were similar in both groups, except that the recipient prothrombin time (PT) before liver transplantation (LT) was lower in the UW/UW group. There was no significant difference between the groups with peak transaminases aspartate aminotransferase (AST) and alanine aminotransferase, maximum value of serum bilirubin within 10 days following LT, incidence of primary nonfunction, need for retransplantation, and patient and graft survival at 1 month. Results were improved, however, in the EC/UW group in regard to PT after LT, operative bleeding and proportion of grafts with histologic lesions at the reperfusion biopsy (P<0.001). These better results in the EC/UW group were confirmed when grafts transplanted in urgent situations were excluded from analysis and by multivariate analysis assessing the effects of pretransplant PT and AST values of the recipients combined with the method of liver cooling with each of the aforementioned criteria. In conclusion, the method of using EC for the aortic flush during liver procurement reduces the amount of UW solution by 50% with improved graft function. This method seems justified in that it is less expensive while affording improved graft function.

A new technique of one-stage total hepatectomy in the rat

BACKGROUND A small animal model of one-stage total hepatectomy is needed for the study of the consequences of fulminant liver failure and to investigate the extrahepatic metabolism of drugs metabolized by the liver. The models of hepatectomy described previously in the rat have the disadvantage of multiple stages, technical difficulty, or achievement of only an incomplete removal of the liver tissue. METHODS A Y-shaped graft was prepared from the inferior vena cava and the left renal vein of a donor rat. A total hepatectomy was performed in a recipient rat. The graft was placed and the portorenal and lower cavocaval anastomoses were performed by means of the polyethylene cuff technique. The upper cavocaval anastomosis was fashioned with a continuous suture. The procedure was performed on 49 rats, and the animals were studied for survival and biochemical profiles. RESULTS The surgical procedure took a mean of 40 +/- 5 minutes and was not associated with any operative deaths. The portal clamping time did not exceed 15 minutes. Spontaneous mean survival of the anhepatic rats was 360 +/- 30 minutes, and glucose supplemented animals had a mean survival time of 20 +/- 5 hours. The anhepatic state was associated with significant metabolic and biochemical alterations. CONCLUSIONS This procedure is quick to perform and does not require considerable microsurgical expertise. It provides a reproducible small animal model of total hepatectomy that is particularly useful for metabolic studies.

Comparison of Milan and UCSF criteria for liver transplantation to treat hepatocellular carcinoma

AIM To assess the validity of the Milan and University of California San Francisco (UCSF) criteria and examine the long-term outcome of orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) in a single-center study. METHODS This study is a retrospective review of prospectively collected data. Between 1998 and 2009, 56 of 356 OLTs were performed in patients with HCC. Based on pathological examination of liver explants, patients were retrospectively categorized into 3 grou-ps: Milan + (n = 34), Milan -/UCSF + (n = 7) and UCSF - (n = 14). RESULTS Median follow-up period was 39.5 (1-124) mo. The 5-year overall survival rates in the Milan +, Milan -/UCSF + and UCSF-groups were 87.7%, 53.6% and 33.3%, respectively (P < 0.000). Within these groups, tumor recurrence was determined in 5.8%, 14.3% and 40% of patients, respectively (P < 0.011). Additionally, the presence of microvascular invasion within the explanted liver had a negative effect on the 5-year disease free survival (74.7% vs. 46.7%, P < 0.044). CONCLUSION The Milan criteria are reliable in the selection of suitable candidates for OLT for the treatment of HCC. For cases of OLT involving living donors, the UCSF criteria may be applied.

Combined Liver-Kidney Transplantation and Follow-Up in Primary Hyperoxaluria Treatment: Report of Three Cases

INTRODUCTION Primary hyperoxaluria type-1 (PH1) is an autosomal recessive disorder caused by impaired activity of the hepatic peroxisomal alanine-glyoxilate aminotransferase, which leads to end-stage renal disease (ESRD) and requires combined liver-kidney transplantation (CLKT). Herein, we have reported 3 children diagnosed with PH1 who received CLKT. CASE 1: A 4.5-year-old boy with an elder brother diagnosed with PH1 was diagnosed during family screening when the sonography showed multiple calculi. Within 5 years he experienced flank pain, hematuria attacks, and anuric phases due to obstruction and received hemodialysis (HD) when ESRD appeared. CLKT was performed from his full-match sister at the age of 9.5. He is doing well at 5.5 years. CASE 2: A 7-year-old boy was admitted with polyuria, polydypsia, and stomach pain with renal stones on sonography. PD was instituted when serum creatinine and BUN levels were measured as high values. At the age of 10, CKLT was performed from his mother. His liver and renal function tests are well at 14 months after CKLT. CASE 3: A 2.5-year-old girl had attacks of dark urine without any pain; renal stones were imaged on sonography. She was diagnosed with PH1 and operated on several times due to obstruction. She received peritoneal dialysis and a cadaveric CLKT was performed when she was 9 years old. At the age of 16, she experienced chronic allograft nephropathy requiring HD and subsequent cadaveric donor renal transplantation at 1.5 years after initiation of HD. CONCLUSION Herein, we have presented the favorable clinical outcomes of patients with CKLT to indicate the validity of this treatment choice for PH1.

Acute Renal Injury Evaluation after Liver Transplantation: With RIFLE Criteria

BACKGROUND The aim of this study was to identify acute renal injury (ARI) through the use of RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria and to investigate perioperative risk factors for ARI in liver transplantation (LT). METHODS We reviewed medical records of adult LT patients retrospectively. Postoperative ARI was staged with RIFLE criteria by the 1st and 7th days of the surgery. RESULTS We analyzed 440 adult LT patients, categorized as risk (R), injury (I), or failure (F) according to the RIFLE criteria. In this study, in the first postoperative day, incidence of ARI was 7.95%; all of them were R-class, and, on the 7th day, the incidence of ARI was 7.27%, as R-class 6.59% and I-class 0.68%. Significant risk factors were detected within the first postoperative day including pre-operative hemoglobin levels <9 g/dL (P = .019), intra-operative transfusion of red blood cells (RBCs) (P = .049) and fresh-frozen plasma (FFP) (P = .049), blood loss (P = .011), and post-reperfusion syndrome (P = .023). Multivariate analysis revealed risk factors for ARI as RBCs (odds ratio [OR], 1.049; P = .247) and FFP (OR, 1.017; P = .627) transfusion and blood loss (OR, 1.000; P = .021) (blood loss OR: 0.9996952300184; 95% confidence interval: 0.9994356774026 to 0.999548500399). The only significant risk factor for the 7th postoperative day was the Model for End-Stage Liver Disease (MELD) score (>20) (P = .002). CONCLUSIONS This study showed that RBC and FFP transfusion, perioperative blood loss, and MELD score >20 are risk factors for LT-related ARI. Also normalization of hemoglobin levels with non-blood products in patients with preoperative low hemoglobin levels can diminish the need for RBC and that can prevent ARI.