James W. Marsh

Orthotopic liver transplantation for primary sclerosing cholangitis.

The incidence or diagnostic rate of sclerosing cholangitis is increasing. Because of the lack of effective medical or surgical therapy for patients with end-stage liver disease and sclerosing cholangitis, results with orthotopic liver transplantation were examined. The results of 55 consecutive liver replacements for this disease were reviewed. The 1− and 2-year actuarial survival rates are 71% and 57%, respectively. Orthotopic liver transplantation for end-stage liver disease from sclerosing cholangitis has emerged as the most effective therapy.

Complications of right lobe living donor liver transplantation

BACKGROUND/AIMS Right lobar living donor liver transplantation (LDLT) has been controversial because of donor deaths and widely variable reports of recipient and donor morbidity. Our aims were to ensure full disclosure to donors and recipients of the risks and benefits of this procedure in a large University center and to help explain reporting inconsistencies. METHODS The Clavien 5-tier grading system was applied retrospectively in 121 consecutive adult right lobe recipients and their donors. The incidence was determined of potentially (Grade III), actually (Grade IV), or ultimately fatal (Grade V) complications during the first post-transplant year. When patients had more than one complication, only the seminal one was counted, or the most serious one if complications occurred contemporaneously. RESULTS One year recipient/graft survival was 91%/84%. Within the year, 80 (66%) of the 121 recipients had Grade III (n=54) Grade IV (n=16), or Grade V (n=10) complications. The complications involved the grafts biliary tract (42% incidence), graft vasculature (15%), or non-graft locations (9%). Complications during the first year did not decline with increased team experience, and adversely affected survival out to 5 years. All 121 donors survive. However, 13 donors (10.7%) had Grade III (n=9) or IV (n=4) complications of which five were graft-related. CONCLUSIONS Despite the satisfactory recipient and graft survival at our and selected other institutions, and although we have not had a donor mortality to date, the role of right lobar LDLT is not clear because of the recipient morbidity and risk to the donors.

Reversal of hypersplenism following orthotopic liver transplantation

The purpose of this study was to clarify the effect of orthotopic liver transplantation on hypersplenism. In a 1-year period from July 1, 1986 to June 30, 1987, 196 adult patients underwent 233 orthotopic liver transplantations. Of the 58 patients with hypersplenism who were analyzed in this study, hypersplenism was more commonly associated with postnecrotic cirrhosis than other kinds of liver disease (55.3% (47/85) vs. 14.5% (11/76); p less than 0.001). Postoperative platelet counts were statistically higher than preoperative values (p less than 0.05). The latest platelet counts were more than 100,000/mm3 in 53 patients (91.4%). Of the eight patients whose preoperative and postoperative spleen volumes could be compared, all showed the reduction in the spleen size (p less than 0.02). We conclude that orthotopic liver transplantation, which is a radical surgical procedure for portal hypertension, reverses hypersplenism.

Intrahepatic bile duct strictures after human orthotopic liver transplantation: Recurrence of primary sclerosing cholangitis or unusual presentation of allograft rejection?

Abstract. One of 55 patients transplanted for sclerosing cholangitis during the cyclosporin‐steroid era (March 1980‐June 1986) developed intrahepatic biliary strictures in the absence of allograft rejection within the 1st year posttransplantation. Although many causes underlie biliary pathology in the postoperative period (i.e., arterial injury, ischemia, chronic rejection, cholangitis), recurrent disease remains a possibility.

Comparison of surgical methods in liver transplantation: retrohepatic caval resection with venovenous bypass (VVB) versus piggyback (PB) with VVB versus PB without VVB.

Use of piggyback technique (PB) and elimination of venovenous bypass (VVB) have been advocated in adult liver transplantation (LT). However, individual contribution of these two modifications on clinical outcomes has not been fully investigated. We performed a retrospective review of 426 LTs within a 3‐year period, when three different surgical techniques were employed per the surgeons’ preference: retrohepatic caval resection with VVB (RCR + VVB) in 104 patients, PB with VVB (PB + VVB) in 148, and PB without VVB (PB‐Only) in 174. The primary outcomes were intraoperative blood transfusion and the patient and graft survivals. Demographic profiles were similar, except younger recipient age in RCR + VVB and fewer number of grafts with cold ischemic time over 16 h in PB‐Only. PB‐Only required lesser intraoperative red blood cells (P = 0.006), fresh frozen plasma (P = 0.005), and cell saver return (P = 0.007); had less incidence of acute renal failure (P = 0.001), better patient survival (P = 0.039), and graft survival (P = 0.003). The benefits of PB + VVB were only found in shortened total surgical time (P = 0.0001) and warm ischemic time (P = 0.0001), and less incidence of acute renal failure (P = 0.001) than RCR + VVB. PB‐Only method seemed to provide the best clinical outcome. The benefit of PB was not fully achieved when it was used with VVB.

Gene Deletions and Amplifications in Human Hepatocellular Carcinomas: Correlation with Hepatocyte Growth Regulation

Tissues from 98 human hepatocellular carcinomas (HCCs) obtained from hepatic resections were subjected to somatic copy number variation (CNV) analysis. Most of these HCCs were discovered in livers resected for orthotopic transplantation, although in a few cases, the tumors themselves were the reason for the hepatectomies. Genomic analysis revealed deletions and amplifications in several genes, and clustering analysis based on CNV revealed five clusters. The LSP1 gene had the most cases with CNV (46 deletions and 5 amplifications). High frequencies of CNV were also seen in PTPRD (21/98), GNB1L (18/98), KIAA1217 (18/98), RP1-1777G6.2 (17/98), ETS1 (11/98), RSU1 (10/98), TBC1D22A (10/98), BAHCC1 (9/98), MAML2 (9/98), RAB1B (9/98), and YIF1A (9/98). The existing literature regarding hepatocytes or other cell types has connected many of these genes to regulation of cytoskeletal architecture, signaling cascades related to growth regulation, and transcription factors directly interacting with nuclear signaling complexes. Correlations with existing literature indicate that genomic lesions associated with HCC at the level of resolution of CNV occur on many genes associated directly or indirectly with signaling pathways operating in liver regeneration and hepatocyte growth regulation.

Treatment of Hepatic Epithelioid Hemangioendothelioma: A Single-Institution Experience With 25 Cases

OBJECTIVE To examine treatment of hepatic epithelioid hemangioendothelioma (EHE), a rare vascular tumor with a variable course. Treatment modalities at our institution include liver resection, transplantation, and catheter-based therapies. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES Retrospective review of 25 patients treated for hepatic EHE (1976-2007). We examined treatment modality, overall survival, complications, and clinicopathologic characteristics. RESULTS Of the 25 patients treated for hepatic EHE, 17 underwent liver transplantation (LT); 4, transcatheter arterial chemoembolization (TACE); 2, resection; and 2, TACE followed by LT. Twelve patients (48%) were male. The median age at diagnosis was 38 years (range, 9 months to 72 years). Mean overall survival was 167 (95% confidence interval [CI], 123-212) months, with 172 (124-220) months in the LT group and 83 (54-112) months in the TACE group. The 2 patients in the resection group remain alive after 19 and 71 months. The 2 patients treated with TACE followed by LT died after 13 and 113 months. Extrahepatic disease was identified as a predictor of outcome. Patients with extrahepatic disease treated with TACE fared better than those treated with surgical approaches (mean survival, 83.0 [95% CI, 54.2-111.8] vs 38.8 [23.7-53.8] months; P = .12). CONCLUSIONS Hepatic EHE is a rare tumor that can be treated with surgical or nonsurgical approaches. In our experience, LT is used for patients with advanced local disease, whereas TACE is the primary modality when extrahepatic disease or comorbid conditions prohibiting LT are present. To our knowledge, this is the largest single-institution experience describing the various therapeutic modalities in the treatment of hepatic EHE.

Laparoscopic major hepatectomy: pure laparoscopic approach versus hand-assisted technique

Laparoscopic liver resections are being performed with increasing frequency, with several groups having reported minimally invasive approaches for major anatomic hepatic resections. Some surgeons favor a pure laparoscopic approach, while others prefer a hand-assisted approach for major laparoscopic liver resections. There are clear advantages and disadvantages to a hand-assisted technique. The purpose of this study is to summarize the literature comparing pure laparoscopic and hand-assisted approaches for minimally invasive hepatic resection, and to describe our approach in 432 laparoscopic liver resections.

Radiofrequency ablation compared to resection in early‐stage hepatocellular carcinoma

OBJECTIVES This study aimed to compare survival outcomes after hepatic resection (HR) and radiofrequency ablation (RFA) in early-stage hepatocellular carcinoma (HCC) at a Western hepatobiliary centre. METHODS Demographic details, clinicopathologic tumour characteristics and survival outcomes were compared among non-transplant candidate patients undergoing HR (n= 50) and RFA (n= 60) for early-stage HCC during 2001-2011. RESULTS Patients who underwent HR had larger tumours, a longer length of stay and a higher rate of postoperative complications. After a median follow-up of 29 months, there were no significant differences between the treatment groups in 1-, 3- and 5-year overall survival (OS) [RFA group: 86%, 50%, 35%, respectively; HR group: 88%, 68%, 47%, respectively (P= 0.222)] or disease-free survival (DFS) [RFA group: 68%, 42%, 28%, respectively; HR group: 66%, 42%, 34%, respectively (P= 0.823)]. The 58 patients who underwent RFA demonstrated ablation success on follow-up computed tomography at 3 months. Of these, 96.5% of patients showed sustained ablation success over the entire follow-up period. In a subgroup analysis of patients with tumours measuring 2-5 cm, no differences in OS or DFS emerged between the HR and RFA groups. Similarly, no significant differences in outcomes in patients with Child-Pugh class A cirrhosis were seen between the RFA and HR groups. CONCLUSIONS   Radiofrequency ablation is comparable with HR in terms of OS and DFS. It is a reasonable alternative as a first-line treatment for HCC in well-selected patients who are not candidates for transplant.

Intrahepatic bile duct strictures after human orthotopic liver transplantation

One of 55 patients transplanted for sclerosing cholangitis during the cyclosporin-steroid era (March 1980–June 1986) developed intrahepatic biliary strictures in the absence of allograft rejection within the 1st year posttransplantation. Although many causes underlie biliary pathology in the postoperative period (i.e., arterial injury, ischemia, chronic rejection, cholangitis), recurrent disease remains a possibility.