Onur Yaprak

Utilization of elderly donors in living donor liver transplantation: When more is less?†

An accepted definition of donor exclusion criteria has not been established for living donor liver transplantation (LDLT). The use of elderly donors to expand the living donor pool raises ethical concerns about donor safety. The aims of this study were (1) the comparison of the postoperative outcomes of living liver donors by age (≥50 versus <50 years) and (2) the evaluation of the impact of the extent of right hepatectomy on donor outcomes. The study group included 150 donors who underwent donor right hepatectomy between October 2004 and April 2009. Extended criteria surgery (ECS) was defined as right hepatectomy with middle hepatic vein (MHV) harvesting or right hepatectomy resulting in an estimated remnant liver volume (RLV) less than 35%. The primary endpoints were donor outcomes in terms of donor complications graded according to the Clavien classification. Group 1 consisted of donors who were 50 years old or older (n = 28), and group 2 consisted of donors who were less than 50 years old (n = 122). At least 1 ECS criterion was present in 74% of donors: 57% had 1 criterion, and 17% had 2 criteria. None of the donors had grade 4 complications or died. The overall and major complication rates were similar in the 2 donor age groups [28.6% and 14.3% in group 1 and 32% and 8.2% in group 2 for the overall complication rates (P = 0.8) and the major complication rates (P = 0.2), respectively]. However, there was a significant correlation between the rate of major complications and the type of surgery in donors who were 50 years old or older. In LDLT, extending the limits of surgery comes at the price of more complications in elderly donors. Right hepatectomy with MHV harvesting and any procedure causing an RLV less than 35% should be avoided in living liver donors who are 50 years old or older. Liver Transpl 17:548–555, 2011.

Use of middle hepatic vein in right lobe living donor liver transplantation

The harvesting of the middle hepatic vein (MHV) with the right lobe graft for living‐donor liver transplantation allows an optimal venous drainage for the recipient; however, it is an extensive operation for the donor. This is a prospective, nonrandomized study evaluating liver functions and early clinical outcome in donors undergoing right hepatectomy with or without MHV harvesting. From August 2005 to July 2007, a total of 100 donor right hepatectomies were performed with (n = 49) or without (n = 51) the inclusion of the MHV. The decision to take MHV was based on an algorithm that considers various donor and recipient factors. There was no donor mortality in donors in either group. Overall complication rate was higher in MHV (+) donor group, however when remnant liver volume was kept above 30%, complication rates were similar between the groups. The results of this study show that right hepatectomy including the MHV neither affects morbidity nor impairs early liver function in donors when remnant volume is kept above 30%. The decision, therefore, of the extent of right lobe donor hepatectomy should be tailored to the particular conditions considering the graft quality and metabolic demand of the recipient.

AFP level and histologic differentiation predict the survival of patients with liver transplantation for hepatocellular carcinoma.

BACKGROUND In liver transplantation or resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features. In patients with HCC, we performed a clinicopathological analysis of risk factors that affected survival after liver transplantation. METHODS In 389 liver transplantations performed from 2004 to 2010, 102 were for HCC patients. Data were collected retrospectively from the Organ Transplantation Center Database. Variables were as follows: age, gender, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, prognostic staging criteria (Milan and UCSF), etiology, number of tumors, the largest tumor size, total tumor size, multifocality, intrahepatic portal vein tumor thrombosis, bilobarity, and histological differentiation. RESULTS One hundred and two patients were evaluated. The 5-year overall survival rate was 56.5%. According to the UCSF criteria, 63% of the patients were within and 37% were beyond UCSF (P=0.03). Ten patients were excluded (one with fibrolamellary HCC and 9 because of early postoperative death without HCC recurrence), and 92 patients were assessed. The mean age of the patients was 56.5+/-6.9 years. Sixty-two patients underwent living donor liver transplantations. The mean follow-up time was 29.4+/-22.6 months. Fifteen patients (16.3%) died in the follow-up period due to HCC recurrence. Univariate analysis showed that AFP level, intrahepatic portal vein tumor thrombosis, histologic differentiation and UCSF criteria were significant factors related to survival and tumor recurrence.The 5-year estimated overall survival rate was 62.2% in all patients. According to the UCSF criteria, and the 5-year overall survival rate was 66.7% within and 52.7% beyond the criteria (P=0.04). Multivariate analysis showed that AFP level and poor differentiation were independent factors. CONCLUSIONS For proper patient selection in liver transplantation for HCC, prognostic criteria related to tumor biology (especially AFP level and histological differentiation) should be considered. Poor differentiation and higher AFP levels are indicators of poor prognosis after liver transplantation.

The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 Expression in Hepatocellular Carcinoma

Background Hepatocellular carcinoma (HCC) is the fifth most common fatal cancer and an important healthcare problem worldwide. There are many studies describing the prognostic and predictive effects of epidermal growth factor receptor 2 (c-erb-B2) and epidermal growth factor receptor 1 (EGFR), transmembrane tyrosine kinases that influence cell growth and proliferation in many tumors. Objectives The current study aimed to investigate the expression levels of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 in hepatocellular carcinoma (HCC) and their correlation with other clinicopathologic features. Patients and Methods Fifty HCC cases were stained immunohistochemically with these markers. Correlations between the markers and clinicopathologic characteristics and survival rates were analyzed. Results No membranous c-erb-B2 staining was seen, whereas cytoplasmic positivity was present in 92% of HCC samples, membranous EGFR was observed in 40%, PI3K was found in all samples, and mTOR was seen in 30%, whereas reduced or absent PTEN expression was observed in 56% of samples and loss of p27 was seen in 92% of the cases. c-erb-B2 and mTOR overexpression, as well as reduced expression of p27, all correlated with multiple tumors (P = 0.041, P < 0.001, and P < 0.001, respectively). P27 loss, and mTOR and EGFR positivity were significantly correlated with AFP (P = 0.047, P = 0.004, and P = 0.008, respectively). Angiolymphatic invasion was more commonly seen in EGFR- and ERCC1-positive cases (P = 0.003 and P = 0.005). EGFR was also correlated with histological grade (P = 0.039). No significant correlations were found among PTEN , PI3K, and the clinicopathological parameters. Disease-free or overall survival rates showed significant differences among therapy modalities, AFP levels, angiolymphatic or lymph node invasions, and ERCC1 and p27 expression levels (P < 0.05). Conclusions c-erb-B2, EGFR, mTOR, ERCC1 overexpression levels, and loss of p27 may play roles in hepatocarcinogenesis and may be significant predictors of aggressive tumor behavior. These markers were found to be correlated with certain clinicopathologic features, therapy modalities, and survival rates in the current study. These findings may help in planning new, targeted treatment strategies .

Living donor liver transplantation for obese patients: Challenges and outcomes

Living donor liver transplantation (LDLT) is an accepted option for end‐stage liver disease, particularly in countries in which there are organ shortages. However, little is known about LDLT for obese patients. We sought to determine the effects of obesity on pretransplant living donor selection for obese recipients and their outcomes. On the basis of body mass index (BMI) values, 148 patients were classified as normal weight (N), 148 were classified as overweight (OW), and 74 were classified as obese (O). O recipients had significantly greater BMI values (32.1 ± 1.6 versus 23.2 ± 1.9 kg/m2, P < 0.001) and received larger actual grafts (918.9 ± 173 versus 839.4 ± 162 g, P = 0.002) than recipients with normal BMI values. Donors who donated to O recipients had a greater mean BMI (26.3 ± 3.8 kg/m2) than those who donated to N recipients (24.4 ± 3.2 kg/m2, P = 0.001). Although O recipients were more likely to face some challenges in finding a suitable living donor, there were no differences in graft survival [hazard ratio (HR) = 0.955, 95% confidence interval (CI) = 0.474‐1.924, P = 0.90] or recipient survival (HR = 0.90, 95% CI = 0.56‐1.5, P = 0.67) between the 3 groups according to an adjusted Cox proportional hazards model. There were no significant differences in posttransplant complication rates between the 3 recipient groups or in the morbidity rates for the donors who donated to O recipients versus the donors who donated to OW and N recipients (P = 0.26). Therefore, we recommend that obese patients undergo pretransplant evaluations. If they are adequately evaluated and selected, they should be considered for LDLT. Liver Transpl 20:311‐322, 2014.

Living donor liver hilar variations: surgical approaches and implications

BACKGROUND Varied vascular and biliary anatomies are common in the liver. Living donor hepatectomy requires precise recognition of the hilar anatomy. This study was undertaken to study donor vascular and biliary tract variations, surgical approaches and implications in living liver transplant patients. METHODS Two hundred living donor liver transplantations were performed at our institution between 2004 and 2009. All donors were evaluated by volumetric computerized tomography (CT), CT angiography and magnetic resonance cholangiography in the preoperative period. Intraoperative ultrasonography and cholangiography were carried out. Arterial, portal and biliary anatomies were classified according to the Michels, Cheng and Huang criteria. RESULTS Classical hepatic arterial anatomy was observed in 129 (64.5%) of the 200 donors. Fifteen percent of the donors had variation in the portal vein. Normal biliary anatomy was found in 126 (63%) donors, and biliary tract variation in 70% of donors with portal vein variations. In recipients with single duct biliary anastomosis, 16 (14.4%) developed biliary leak, and 9 (8.1%) developed biliary stricture; however more than one biliary anastomosis increased recipient biliary complications. Donor vascular variations did not increase recipient vascular complications. Variant anatomy was not associated with an increase in donor morbidity. CONCLUSIONS Living donor liver transplantation provides information about variant hilar anatomy. The success of the procedure depends on a careful approach to anatomical variations. When the deceased donor supply is inadequate, living donor transplantation is a life-saving alternative and is safe for the donor and recipient, even if the donor has variant hilar anatomy.

Anatomical variations of donor portal vein in right lobe living donor liver transplantation: the safe use of variant portal veins

In right lobe (RL) living donor liver transplantation (LDLT), portal vein (PV) variations are of immense clinical significance. In this study, we describe in detail our PV reconstruction techniques in RL grafts with variant PV anatomy and evaluate the impact of accompanying biliary variations on the recipient outcomes. In a total of 386 RL LDLTs performed between July 2004 and July 2012, the clinical data on 52 (13%) transplants using RL grafts with variant PV anatomy were retrospectively analyzed. Portal vein anatomy was classified as type 2 in 20 patients, type 3 in 24 patients, and type 4 in eight patients. The PV reconstruction techniques utilized included back‐wall plasty (n = 21), back‐wall plasty with saphenous vein graft interposition (n = 6), saphenous vein graft interposition (n = 5), cryopreserved iliac vein Y‐graft interposition (n = 6), and quiltplasty (n = 3). There was no donor mortality. In a median follow‐up of 29 months, none of the recipients had vascular complications. Anomalous PV anatomy was associated with a high (54%) incidence of biliary variations; however, these variations did not result in increased biliary complication rate. Overall, the 1‐ and 3‐year patient survival rates of recipients were 91% and 81%, respectively. Vascular and biliary variations in RL grafts render LDLT technically more challenging. By employing appropriate reconstruction techniques, it is possible to successfully use RL grafts with PV variations without endangering recipient and donor safety.

Biliary complications after right lobe living donor liver transplantation: a single-centre experience

BACKGROUND Biliary complications that developed after right lobe liver transplantation from living donors were studied in a single centre. METHODS From 2004 to 2010, 200 consecutive living donor right lobe liver transplantations were performed. The database was evaluated retrospectively. Biliary complications were diagnosed according to clinical, biochemical and radiological tests. The number of biliary ducts in the transplanted graft, the surgical techniques used for anastomosis, biliary strictures and bile leakage rates were analysed. RESULTS Of a total of 200 grafts, 117 invloved a single bile duct, 77 had two bile ducts and in six grafts there were three bile ducts. In 166 transplants, the anastomosis was performed as a single duct to duct, in 21 transplants double duct to ducts, in one transplant, three duct to ducts and in 12 transplants as a Roux-en-Y reconstruction. In all, 40 bile leakages (20%) and 17 biliary strictures (8.5%) were observed in 49 patients resulting in a total of 57 biliary complications (28.5%). Seventeen patients were re-operated (12 as a result of bile leakages and five owing to biliary strictures). CONCLUSION Identification of more than one biliary orifice in the graft resulted in an increase in the complication rates. In grafts containing multiple orifices, performing multiple duct-to-duct (DD) or Roux-en-Y anastomoses led to a lower number of complications.

Splenic Abscess After Splenic Artery Ligation in Living Donor Liver Transplantation : A Case Report

Although recent developments in living donor liver transplantation (LDLT) yield promising results, a size mismatch between the weights of the graft and the recipient remains a significant problem. Recipients of LDLT may have hyperdynamic splanchnic circulations resulting in graft hyperperfusion and increased portal vein flow leading to small-for-size syndrome. Splenic artery ligation is one of the least invasive measures to prevent occurrence of this syndrome. Despite its potentially devastating consequences, splenic infarction following splenic artery ligation has received little attention to date. Herein we have reported a patient who developed a splenic abscess due to a splenic infarction following splenic artery ligation during LDLT.

Which Incision Is Better for Living-Donor Right Hepatectomy? Midline, J-Shaped, or Mercedes

Incision-related morbidity for donors is a major concern in living-donor right hepatectomy (LDRH). Open approaches use midline, J-shaped, and Mercedes incisions for LDRH. We retrospectively studied 95 consecutive donors who underwent LDRH between January 2009 and November 2010. They underwent midline (n = 32), J-shaped (n = 28), or Mercedes (n = 35) incisions. We studied resection times, perioperative bleeding, postoperative hospital stay, and postoperative pain assessed by the visual analog scale (VAS) and by analgesic requirements as well as laboratory data and complications. Postoperative analgesic requirements and postoperative VAS scores were significantly lower in the midline group (P < .05) upon univariate but not multivariate analyses. The postoperative complications as well as other parameters were similar between the groups. In conclusion, compared with a J-type shaped or not for Mercedes incision, a donor hepatectomy can be satisfactorily performed via a midline incision by experienced surgeons without increased risk.