Emrah Otan

Cytoprotective effects of amifostine,ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

AIM To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity. METHODS An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of 20 mg/kg MTX. Eleven of the rats were left untreated (Model group; n = 11), and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX + NAC group; n = 11), 50 mg/kg per single dose AMF (MTX + AMF group; n = 11), or 10 mg/kg per day ASC (MTX + ASC group; n = 11). Eleven rats that received no MTX and no treatments served as the negative control group. Structural and functional changes related to MTX- and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione (GSH) and xanthine oxidase activities and of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. RESULTS Exposure to MTX caused structural and functional hepatotoxicity, as evidenced by significantly worse histopathological scores [median (range) injury score: control group: 1 (0-3) vs 7 (6-9), P = 0.001] and significantly higher MDA activity [409 (352-466) nmol/g vs 455.5 (419-516) nmol/g, P < 0.05]. The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents, but only the reduction in hepatotoxicity scores reached statistical significance [4 (3-6) for NAC, 4.5 (3-5) for AMF and 6 (5-6) for ASC; P = 0.001, P = 0.001 and P < 0.005 vs model group respectively]. Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues [control group: 3.02 (2.85-3.43) μmol/g and 71.78 (61.88-97.81) U/g vs model group: 2.52 (2.07-3.34) μmol/g and 61.46 (58.27-67.75) U/g, P < 0.05]; however, only the NAC treatment provided significant increases in these antioxidant enzyme activities [3.22 (2.54-3.62) μmol/g and 69.22 (61.13-100.88) U/g, P < 0.05 and P < 0.01 vs model group respectively]. CONCLUSION MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress, and cytoprotective agents (NAC > AMF > ASC) may alleviate MTX hepatotoxicity.

Management of Giant Splenic Artery Aneurysm: Comprehensive Literature Review

AbstractTo provide an overview of the medical literature on giant splenic artery aneurysm (SAA).The PubMed, Medline, Google Scholar, and Google databases were searched using keywords to identify articles related to SAA. Keywords used were splenic artery aneurysm, giant splenic artery aneuryms, huge splenic artery aneurysm, splenic artery aneurysm rupture, and visceral artery aneurysm. SAAs with a diameter ≥5 cm are considered as giant and included in this study. The language of the publication was not a limitation criterion, and publications dated before January 15, 2015 were considered.The literature review included 69 papers (62 fulltext, 6 abstract, 1 nonavailable) on giant SAA. A sum of 78 patients (50 males, 28 females) involved in the study with an age range of 27–87 years (mean ± SD: 55.8 ± 14.0 years). Age range for male was 30–87 (mean ± SD: 57.5 ± 12.0 years) and for female was 27–84 (mean ± SD: 52.7 ± 16.6 years). Most frequent predisposing factors were acute or chronic pancreatitis, atherosclerosis, hypertension, and cirrhosis. Aneurysm dimensions were obtained for 77 patients with a range of 50–300 mm (mean ± SD: 97.1 ± 46.0 mm). Aneurysm dimension range for females was 50–210 mm (mean ± SD: 97.5 ± 40.2 mm) and for males was 50–300 mm (mean ± SD: 96.9 ± 48.9 mm). Intraperitoneal/retroperitoneal rupture was present in 15, among which with a lesion dimension range of 50–180 mm (mean ± SD; 100 ± 49.3 mm) which was range of 50–300 mm (mean ± SD: 96.3 ± 45.2 mm) in cases without rupture. Mortality for rupture patients was 33.3%. Other frequent complications were gastrosplenic fistula (n = 3), colosplenic fistula (n = 1), pancreatic fistula (n = 1), splenic arteriovenous fistula (n = 3), and portosplenic fistula (n = 1). Eight of the patients died in early postoperative period while 67 survived. Survival status of the remaining 3 patients is unclear. Range of follow-up period for the surviving patients varies from 3 weeks to 42 months.Either rupture or fistulization into hollow organs risk increase in compliance with aneurysm diameter. Mortality is significantly high in rupture cases. Patients with an evident risk should undergo either surgical or interventional radiological treatment without delay.

Hepatic Artery Thrombosis–Related Risk Factors After Living Donor Liver Transplantation: Single-Center Experience From Turkey

AIM The purpose of this retrospective study is to evaluate the risk factors hepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT) in a consecutive series from a single center. MATERIALS AND METHODS Between January 2010 and May 2012, we performed 278 living donor liver transplantations, including 189 males and 89 females. We compared the risk factors between HAT and non-HAT groups according to the following variables: age, gender, body mass index (BMI), graft weight, use of graft, Child-Pugh and model for end stage liver disease score, level of hemoglobin, blood pressure, operation time, blood transfusion, presence of ascites, international normalized ratio (INR) level, and etiology. RESULTS Eighteen patients, including 15 males and 3 female, had HAT after the operation (mean age, 45.1 years; age range, 22-60 years). There were no pediatric patients in the HAT group. HAT rate was 6.5% in our series. Graft loss and retransplantation due to HAT was 38.7% in a 2-year period. Biliary leakage was observed in 72 (25.8%) living donor liver transplantations; this rate was higher in patients with HAT (n = 8; 44.4%). The infection rate was 50% (n = 9) in the HAT group and was 32.7% (n = 91) in the non-HAT group. Mean INR value was 2.15 in the HAT group and 1.72 in the non-HAT group. When we compared the groups according to use of graft for anastomosis, biliary lekage, infection, and INR value, the differences were statistically significant (P < .05). CONCLUSION Although the results of OLT have improved over the past years, HAT is still associated with substantial morbidity, high incidence of graft failure, and high mortality rates. The most important findings associated with HAT in our series were found as INR levels, bile leakage, and resistant infections. Use of vascular graft for hepatic artery anastomosis was found to increase HAT risk.

Postoperative Pulmonary Complications After Liver Transplantation: Assessment of Risk Factors for Mortality

BACKGROUND The aim of this study was to identify the risk factors related to mortality in liver transplant (LT) patients with post-transplantation pulmonary complications. METHOD Patients who underwent liver transplantation in our clinic between January 2010 and January 2012 were retrospectively reviewed for post-transplantation pulmonary complications. Demographic, clinical, radiologic, and postoperative chart data of 153 patients with pulmonary complications were analyzed using an independent samples Student t test, Pearsons χ(2) test, Fishers exact test, and Yates corrected χ(2) test. Mortality was analyzed using a multiple logistic regression model. The best-fit breakpoint resulting in a cut-off value for the variables of interest was determined using ROC curves and the Youden index. RESULTS The 153 patients with pulmonary complication were divided into 2 groups: mortality (n = 53) and survival (n = 100). Univariate analyses showed significant differences between these 2 groups with respect to MELD score (P = .035), duration of mechanical ventilation (P > .001), pneumonia (P = .01), and endotracheal culture results (P = .001). In the multivariate analysis, hemoglobin (P = .03, odds ratio [OR]: 1.239), MELD score (P = .027, OR: 1.064), duration of mechanical ventilation (P = .003, OR: 1.091), and age (P = .042, OR: 1.001) were significant risk factors for mortality. The best-fit breakpoint analysis yielded cut-off values for hemoglobin (>11.2, sensitivity: 50.9%, specificity: 70%), MELD score (>16, sensitivity: 73.6%, specificity: 42%) and duration of mechanical ventilation (>3, sensitivity: 62.3%, specificity: 76%). CONCLUSION Advanced age, high hemoglobin level, high MELD score, and long-term mechanical ventilation are significant risk factors for mortality in liver transplant patients with postoperative pulmonary complications.

Effects of antioxidant agents against cyclosporine-induced hepatotoxicity

BACKGROUND To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity. METHODS Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol. RESULTS CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase. CONCLUSIONS UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system.

Storage of allogeneic vascular grafts: experience from a high-volume liver transplant institute.

Allogeneic vascular grafts are often required for vascular reconstruction during living donor liver transplantation. Such grafts are obtained prior to use, making storage conditions a critical issue for maintaining the integrity of the tissue to ensure a successful transplantation. This study describes an optimized storage protocol currently in use at a high-volume liver transplant center. Twenty-nine allogeneic vascular graft tissues obtained during cardiovascular surgery or from cadaveric donors were stored respectively in sterile 50 mL of Ringer lactate solution, without any preservation solutions or antimicrobials, at -22°C for a maximum of 3 months. Prior to use in vascular reconstruction, grafts were thawed in 0.9% NaCl solution at 37°C, and 1 × 0.5-cm(2) tissue samples were collected for microbial culturing and viral serology. ABO compatibility was not performed for any patients receiving vascular grafts. During this prospective study, all 29 allogeneic vascular grafts were used for back-table vascular reconstruction in living donor liver transplantation procedures. A total of 16 grafts were from the saphenous vein, 10 were from the iliac vein, and 3 were from the iliac artery. Bacterial growth was not detected in any tissue samples taken from the stored grafts. No vascular graft-related complications occurred during the 5 months of follow-up. The successful vascular reconstructions achieved with all 29 study grafts demonstrate that the simple, inexpensive storage method described herein is feasible and safe. Randomized, controlled studies should be carried out to further optimize and standardize the technique.

Reconstruction of Anomalous Portal Venous Branching in Right Lobe Living Donor Liver Transplantation: Malatya Approach

Reconstruction of anomalous portal vein branching (APVB) during right lobe living donor liver transplantation (LDLT) can be challenging. The goal of this article is to describe our surgical technique, named the Malatya Approach, in case of APVB during right lobe LDLT. The technique unifies the APVB and obtains a funnel‐shaped common extension with a circumferential fence by a saphenous vein conduit. In total, 126 (10.6%) of 1192 right lobe grafts had APVB that were divided into 2 groups according to the adopted surgical techniques: the Malatya Approach group (n = 91) and the previously defined other techniques group (n = 35). Both groups were compared regarding portal vein thrombosis (PVT), postoperative 90‐day mortality and survival. PVT developed in 3 patients (3.3%) in the Malatya Approach group and developed in 10 (28.6%) patients for the other group (P < 0.001). There were 8 (8.8%) 90‐day mortalities in the Malatya Approach group (1 PVT related) and 15 patients (9 PVT related) died in the other techniques group (P < 0.001). Mean follow‐up time for both groups was similar (999.1 days for the Malatya Approach group versus 1024.7 days for the other group; P = 0.47), but longterm survival in the Malatya Approach group was better than in the other group (84.6% versus 40%; P < 0.001). Multivariate analysis revealed that the Malatya Approach group showed less PVT development and longer survival (P < 0.001). This technique is promising to avoid PVT and mortalities in cases of APVB during right lobe LDLT. Liver Transplantation 23 751–761 2017 AASLD.

Acinetobacter Infection in a Liver Transplantation Intensive Care Unit

OBJECTIVE Despite the advances in surgical technique and postoperative care, infectious complications are associated with high mortality rates. Acinetobacter species are emerging as a leading worldwide nosocomial pathogen in intensive care unit (ICU) patients. This study was designed to evaluate the results of the patients who developed Acinetobacter infection in the ICU after liver transplantation. METHODS We retrospectively analyzed 220 patients who had undergone liver transplantation between August 2011 and August 2012. Among the 55 positive culture results with clinical signs of infection, Acinetobacter was the single infectious agent for 10 of them, who were included in the study. RESULTS The mean age of the patients was 43.1 ± 11.79 years with a male dominance (70%, n = 7). Eighty percent of the patients underwent living donor liver transplantations (n = 8). Mean Model for End-stage Liver Disease score was 28.5 ± 14.99. Graft dysfunction was present in 50% (n = 5), all of whom had a history of preoperative hospitalization (100%, n = 10). Forty percent (n = 4) of patients had a history of diabetes mellitus and 60% were subject to extended mechanical ventilation. Mean platelet count was 20.32 ± 8.1 × 10(9)/mL. The majority of the patients had multiple culture-positive sites (90%, n = 9). Positive culture results for Acinetobacter species included bloodstream (n = 8), drain fluid (n = 5), sputum (n = 3), paracenthesis material (n = 3), and catheter (n = 1). The mean period of postoperative positive culture results was 12.7 ± 9.5 days. Mortality was 90% (n = 9). CONCLUSION Acinetobacter infections in the ICU after liver transplantation were asociated with a high mortality presenting with thrombocytopenia.

Comparison of Plasmapheresis and Molecular Adsorbent Recirculating System Efficacy in Graft Failure After Living Donor Liver Transplantation

INTRODUCTION Liver transplantation may result in graft failure, requiring time and supportive treatment for regeneration of the graft. The aim of this study was to compare the laboratory parameter changes after single-session molecular adsorbent recirculating system (MARS) and plasmapheresis procedures among living donor liver transplantation patients experiencing graft failure. PATIENTS AND METHOD We analyzed retrospectively the results in 45 liver transplantation patients treated with plasmapheresis and/or MARS between June 2011 and July 2012: (plasmapheresis, n = 17; MARS, n = 15; MARS + plasmapheresis, n = 13). When cadaveric donor cases (n = 11) were excluded, the remaining 34 included patients, underwent. MARS (n = 18) or plasmapheresis (n = 16) at the first session. FINDINGS Both groups were similar in age, sex, and body mass index features. The MARS group displayed significantly higher levels of international normalized ratio, blood urea nitrogen, and Model for End-stage Liver Disease score. The plasmapheresis cohort, displayed significantly higher levels of initial direct bilirubin and gamma glutamyl transferase (P < .05). The plasmapheresis group showed a significant decrease in GGT after treatment (P < .05). RESULTS An initial MARS session provided significantly greater decrease in renal function associated with graft failure after living donor liver transplantation.

Natural orifice specimen extraction (NOSE) and transanal extracorporeal anvil placement during laparoscopic low anterior resection

Natural orifice specimen extraction allows laparoscopic colorectal resections only through 5–12-mm trocar orifices on the abdominal wall without any additional incisions [1, 2]. Here, we describe a technique that facilitates laparoscopic coloanal anastomosis after retrieval of the colorectal specimen through the anus. A 62-year-old male presented with abdominal pain and rectal bleeding. He had no history of surgery and no severe comorbidity. His body mass index was less than 30 kg/m. A mobile mass was palpated on digital rectal examination. Colonoscopy revealed an ulcerated vegetating tumor 5 cm in diameter located 10 cm from the anal verge. The pathologist reported adenocarcinoma. Computed tomography scanning showed a rectal tumor not invading surrounding tissues. No preoperative radiotherapy was planned. The patient was hospitalized for surgical treatment. Following preoperative mechanical bowel preparation and antibiotic prophylaxis, the patient was placed in the modified lithotomy position. A 10–12-mmHg pneumoperitoneum was established. We used a five-port technique: Two 5-mm ports were placed in the upper and lower left quadrants, and a 10-mm umbilical port and two 12-mm ports were placed in the upper and lower right quadrants. The peritoneum was incised on the promontory, and dissection extending to the inferior mesenteric artery and vein was commenced. These vascular structures were transected after clip placement. The left and sigmoid colons were mobilized with medial-to-lateral dissection. The rectum was suspended in the cranial direction, sharp dissection was extended along the avascular plane between the presacral fascia and mesorectum, and dissection with Ligasure (Covidien, Mansfield USA) was carried out laterally up to the levator ani muscle. Following mobilization, the rectum was transected at the rectosigmoid junction using a 60-mm laparoscopic stapler. The anus was dilated gently using two fingers, and the stapled stump was retracted transanally using an ovarian clamp (Figs. 1a, 2). The rectum was transected 5 cm distally from the mass (Fig. 1b). The proximal closed colonic segment in the abdomen was delivered transanally using an ovarian clamp under laparoscopic guidance. The closed end of the proximal bowel was opened, and following placement of the anvil, and fixation with 2–0 prolene sutures, it was returned to the abdomen (Fig. 1c). The rectum was closed using a stapler device (TA 60 mm, Covidien), and the closed stump was inverted back into the abdomen (Figs. 1d, 3). Using a transanally placed 28-mm circular stapler, anatomic continuity was provided under laparoscopic guidance (Fig. 1e). Intraoperative air leak testing of the anastomosis was negative. We created a diverting loop ileostomy for protection of the distal anastomosis. The patient’s postoperative course was uneventful except for urinary incontinence that was treated conservatively. He was discharged after 5 days. The histopathology findings were adenocarcinoma T2N0M0. The patient underwent two courses of postoperative chemotherapy and radiotherapy for 25 days. His ileostomy was reversed after 5 months, and there was no anal or urinary incontinence at 7-month follow-up. A. H. Alam Rabia Balkhi Hospital, Kabul, Afghanistan