Yildiray Yuzer

Donor Safety and Remnant Liver Volume in Living Donor Liver Transplantation

Living donor liver transplantation is now a common practice in countries in which the availability of cadaveric organs is limited. The preoperative preparation, intraoperative surgical technique, and postoperative care of donors and recipients have evolved in recent years. We retrospectively compared 67 donors with a remnant liver volume equal to or more than 30% (group 1) with 14 donors who had less than 30% remnant liver volume (group 2) for donor outcomes. All the complications in donors were systematically classified. Donors with less than 30% remnant liver volume showed significantly higher peak aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and bilirubin levels. There were 6 complications in group 1 and 4 complications in group 2. The difference between the 2 groups in terms of donor complications did reach statistical significance (P = 0.043); donors with a remnant liver volume < 30% had a 4 times greater relative risk of morbidity. In conclusion, the use of donors with less than 30% remnant liver volume is highly debatable as donor safety should be of utmost importance in living donor liver transplantation. Liver Transpl 14:1174–1179, 2008.

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 (nu2003=u200349) or without (nu2003=u200351) 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.

BACKGROUNDnIn 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.nnnMETHODSnIn 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.nnnRESULTSnOne 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.nnnCONCLUSIONSnFor 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.

Gemcitabine treatment in patients with inoperable locally advanced/metastatic pancreatic cancer and prognostic factors

Objective. Most patients with pancreatic cancer show an inoperable locally advanced/ metastatic tumour at the time of diagnosis. The present study was aimed at determining the prognostic factors in patients with advanced pancreatic carcinoma treated with gemcitabine. Material and methods. Sixty-seven unresectable or metastatic pancreatic cancer patients treated with gemcitabine were included in the study and a total of 258 cycles of treatment were applied. Results. The overall response rate was 5%. Thirty-one percent of the patients had stable disease, whereas progressive disease was seen in 49%. Clinical benefit response rate was 15%. The median duration of response was 7.3 months. Median progression-free survival was 3 months, while median overall survival was 9 months. Univariate analysis revealed that worse results were found in patients with performance status (PS)u200a=u200a2, and in patients with primary tumour location in the body or tail of the pancreas (p<0.05). Multivariate analysis of data revealed that the most important factor was PS of the patient, as the patients with PSu200a=u200a2 had worse results than the patients with PSu200a=u200a0–1 (p<0.05). Conclusions. Low PS is a negative predictive factor for the survival of patients with advanced pancreatic carcinoma treated with gemcitabine.

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 .

Hepatic arterial mapping by multidetector computed tomographic angiography in living donor liver transplantation.

Purpose: Our aims were to present the hepatic arterial variations that were detected with computed tomographic angiography (CTA) and confirmed by operation in living liver donors and to emphasize the usefulness of CTA in the assessment of hepatic arterial anatomy. Materials and Methods: The donors of 100 patients (46 women and 54 men) who had undergone a living donor liver transplantation in a (blinded) hospital between July 2004 and June 2007 were evaluated. The age of the donors ranged from 18 to 63 years (mean, 39 years). The CTA images obtained by a 16-slice multidetector CT before the transplantation procedure were retrospectively evaluated for arterial variations, and the results were compared with the results of the operation. Results: In 59 donors (59%), classic hepatic arterial anatomy was observed. In the remaining 41 donors (41%), various arterial variations were determined. In 11 of the donors (11%), variations were not compatible with the description of Michels classification. In all of our patients, CTA findings were confirmed with operational findings. Our complication rate was 1%. Only 1 of the patients who had undergone the transplantation developed hepatic arterial thrombus, and the remaining 99 patients had no arterial complications. Conclusions: The course of the vascular structures before live donor liver transplantation is essential for planning and success of the operation. Our study showed that multidetector CTA can be used successfully in hepatic artery imaging of liver transplantation donors as a noninvasive method.

Leiomyosarcoma of the inferior vena cava: report of a case.

We report a case of leiomyosarcoma of the inferior vena cava, which was successfully treated by surgical en bloc resection and reconstruction of the inferior vena cava, followed by adjuvant radiation therapy. A 39-year-old man presented with nausea, vomiting, epigastric pain, and weight loss. Radiologic examinations showed a mass originating from the inferior vena cava and surgical resection was performed. Histopathological examination of the specimen revealed a moderately differentiated (grade II) leiomyosarcoma arising from the inferior vena cava. We believe that radical resection with clear surgical margins followed by adjuvant radiation therapy is a good curative strategy for achieving any chance of long-term survival.

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 (32.1u2009±u20091.6 versus 23.2u2009±u20091.9 kg/m2, Pu2009<u20090.001) and received larger actual grafts (918.9u2009±u2009173 versus 839.4u2009±u2009162 g, Pu2009=u20090.002) than recipients with normal BMI values. Donors who donated to O recipients had a greater mean BMI (26.3u2009±u20093.8 kg/m2) than those who donated to N recipients (24.4u2009±u20093.2 kg/m2, Pu2009=u20090.001). 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)u2009=u20090.955, 95% confidence interval (CI)u2009=u20090.474‐1.924, Pu2009=u20090.90] or recipient survival (HRu2009=u20090.90, 95% CIu2009=u20090.56‐1.5, Pu2009=u20090.67) 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 (Pu2009=u20090.26). 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

BACKGROUNDnVaried 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.nnnMETHODSnTwo 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.nnnRESULTSnClassical 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.nnnCONCLUSIONSnLiving 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.