Search

The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013).Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/5 cm and 39.1% in NoDS/5 cm, P 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P 0.001).In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.

OBJECTIVE The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.

Biliary tract and primary liver tumors can be divided into intrahepatic and extrahepatic sites. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma are the most common primary liver malignancies, making up 75% and 15% of cases, respectively. In the United States, there has been an increase in incidence of HCC and cholangiocarcinoma over the last 2 decades, and it is probable that the incidence of both will continue to climb. Gallbladder cancer, however, is the most frequent biliary tract cancer, comprising 80% to 90% of biliary tract cancers worldwide. Underlying epidemiology and cause are discussed.

To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC).Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited.Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013).Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P0.001; 4+ LRTs: HR 2.5, P0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044).Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.

Over the last several years, liver transplantation has evolved to become a widely used treatment for hepatocellular carcinoma (HCC). The criteria used were developed in order to have acceptable outcomes for transplant with survival similar to other indications for transplant. These criteria are discussed in detail along with alternate options, including surgical resection and downstaging of HCC in cirrhotics. Technical considerations of liver transplantation must be considered, and living donor liver transplant is a possibility for treatment.

Hepatic retransplantation has been surgically challenging since the beginning of liver transplant. Outcomes have improved over time, but patient survival with retransplant continues to be significantly worse than that of primary transplant. Many studies have focused on factors to predict outcomes. Models have been developed to help predict risk, but the decision for retransplant must be a multidisciplinary transplant team decision. The question of "when is too much?" can be guided by recipient and donor factors but is an ethical decision that must be made by the liver transplant team.

To assess survival after liver resection and transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan criteria.The role of liver resection and transplantation remains controversial for patients with HCC beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center.Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival.Of 608 patients beyond Milan without vascular invasion, 480 (79%) patients underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (P0.001). Resection patients had larger tumors [median 9 cm, interquartile range (IQR): 6.5-12.9 cm vs. median 4.1, IQR: 3.4-5.3 cm, P0.001]; transplant patients were more likely to have multiple tumors (78% vs 28%, P0.001).Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all P0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared with propensity-matched liver resection patients (P ≥ 0.176); DFS in this propensity matched cohort was greater after liver transplantation (P ≤ 0.017).Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.

With surgery for hepatic malignancy, there are poor options for chemotherapy; many patients are deemed unresectable because of vascular involvement or location of tumors. Over the past few decades, advances in surgical technique have allowed resection of these tumors with vascular reconstruction to achieve negative margins and improve chances for survival. This article reviews those reconstruction techniques and outcomes in detail, including in situ perfusion and ex vivo liver surgery, and provides a discussion of implications and operative planning for patients with hepatic malignancy in order to provide surgeons with better understanding of these complicated operations.

PURPOSE:Gadoxetate-disodium (Gd-EOB-DTPA)-enhanced 3D T1- weighted (T1w) MR cholangiography (MRC) is an efficient method to evaluate biliary anatomy due to T1 shortening of excreted contrast in the bile. A method that exploits both T1 shortening and T2* effects may produce even greater bile duct conspicuity. The aim of our study is to determine feasibility and compare the diagnostic performance of two-dimensional (2D) T1w multi-echo (ME) spoiled gradient-recalled-echo (SPGR) derived R2* maps against T1w MRC for bile duct visualization in living liver donor candidates. MATERIALS AND METHODS:Ten potential living liver donor candidates underwent pretransplant 3T MRI and were included in our study. Following injection of Gd-EOBDTPA and a 20-min delay, 3D T1w MRC and 2D T1w ME SPGR images were acquired. 2D R2* maps were generated inline by the scanner assuming exponential decay. The 3D T1w MRC and 2D R2* maps were retrospectively and independently reviewed in two separate sessions by three radiologists. Visualization of eight bile duct segments was scored using a 4-point ordinal scale. The scores were compared using mixed effects regression model. RESULTS:Imaging was tolerated by all donors and R2* maps were successfully generated in all cases. Visualization scores of 2D R2* maps were significantly higher than 3D T1w MRC for right anterior (p = 0.003) and posterior (p = 0.0001), segment 2 (p

At a recently concluded Americas Hepato-Pancreato-Biliary Association Annual Meeting, a Clinical Practice Guidelines Conference Series was convened with the topic focusing on Venous Thromboembolism (VTE) Prophylaxis in Liver Surgery. The symposium brought together hepatobiliary surgeons from three continents as well as medical experts in hematology and coagulation.The content of the discussion included literature reviews, evaluation of multi-institutional VTE outcome data, and examination of practice patterns at multiple high-volume centers.Literature review demonstrated that, within gastrointestinal surgery, liver resection patients are at particularly high-risk for VTE. Recent evidence clearly indicates a direct relationship between the magnitude of hepatectomy and postoperative VTE rates, however, the PT/INR does not accurately reflect the coagulation status of the post-hepatectomy patient. Evaluation of available data and practice patterns regarding the utilization and timing of anticoagulant VTE prophylaxis led to recommendations regarding preoperative and postoperative thromboprophylaxis for liver surgery patients.This conference was effective in consolidating our knowledge of coagulation abnormalities after liver resection. Based on the expert review of the available data and practice patterns, a number of recommendations were developed.

Living donor hepatectomy (LDH) is high risk to a healthy donor and remains controversial. Living donor nephrectomy (LDN), conversely, is a common practice. The objective is to examine the outcomes of LDH and compare this risk profile to LDN. The Nationwide Inpatient Sample was queried for hepatectomies and nephrectomies from 1998 to 2011. LDH or LDN were identified by donor ICD-9 codes. Outcomes included in-hospital mortality and complications. Bivariate analysis compared nondonor hepatectomy or nondonor nephrectomy (NDN). Multivariate analyses adjusted for baseline organ disease, malignancy, or benign lesions. There were 430 LDH and 9211 nondonor hepatectomy. In-hospital mortality was 0 and 6 per cent, respectively ( P < 0.001); complications 4 and 33 per cent ( P < 0.001). LDH had fewer complications [odds ratio (OR) 0.15 (0.08–0.26)]. There were 15,631 LDN and 117,966 NDN. Mortality rates were 0.8 per cent LDN and 1.8 per cent NDN ( P < 0.001). Complications were 1 and 21 per cent ( P < 0.001). LDN had fewer complications [OR 0.06 (0.05–0.08)] and better survival [OR 0.32 (0.18–0.58)]. Complication rates were higher in LDH than LDN (4% vs 1%, P < 0.001), but survival was similar (0% vs 0.8% mortality, P = 0.06). In conclusion, morbidity and mortality rates of LDH are significantly lower than hepatectomy for other disease. This study suggests that the risk profile of LDH is comparable with the widely accepted LDN.

To determine per-lesion sensitivity and positive predictive value (PPV) of gadoxetic acid-enhanced 3-T magnetic resonance (MR) imaging for the diagnosis of malignant lesions by using matched (spatially correlated) hepatectomy pathologic findings as the reference standard. Materials andIn this prospective, institutional review board-approved, HIPAA-compliant study, 20 patients (nine men, 11 women; mean age, 59 years) with malignant liver lesions who gave written informed consent underwent preoperative gadoxetic acid-enhanced 3-T MR imaging for surgical planning. Two image sets were independently analyzed by three readers to detect liver lesions (set 1 without and set 2 with hepatobiliary phase [HBP] images). Hepatectomy specimen ex vivo MR imaging assisted in matching gadoxetic acid-enhanced 3-T MR imaging findings with pathologic findings. Interreader agreement was assessed by using the Cohen κ coefficient. Per-lesion sensitivity and PPV were calculated.Cohen κ values were 0.64-0.76 and 0.57-0.84, and overall per-lesion sensitivity was 45% (42 of 94 lesions) to 56% (53 of 94 lesions) and 58% (55 of 94 lesions) to 64% (60 of 94 lesions) for sets 1 and 2, respectively. The addition of HBP imaging did not affect interreader agreement but significantly improved overall sensitivity for one reader (P.05) and almost for another (P = .05). Sensitivity for 0.2-0.5-cm lesions was 0% (0 of 26 lesions) to 8% (two of 26 lesions) for set 1 and 4% (one of 26 lesions) to 12% (three of 26 lesions) for set 2. Sensitivity for 0.6-1.0-cm lesions was 28% (nine of 32 lesions) to 59% (19 of 32 lesions) for set 1 and 66% (21 of 32 lesions) to 69% (22 of 32 lesions) for set 2. Sensitivity for lesions at least 1.0 cm in diameter was at least 81% (13 of 16 lesions) for set 1 and was not improved for set 2. PPV was 98% (56 of 57 lesions) to 100% (60 of 60 lesions) for all readers without differences between image sets or lesion size.Gadoxetic acid-enhanced 3-T MR imaging provides high per-lesion sensitivity and PPV for preoperative malignant liver lesion detection overall, although sensitivity for 0.2-0.5-cm malignant lesions is poor.

Improved outcomes have been associated with various methods of size matching between expanded criteria (ECD) donors and recipients. A novel method for improved functional based matching was developed utilizing manipulation of Cockcroft-Gault estimated creatinine clearances for donor and recipient. We hypothesized that optimal clearance-based matches would have superior outcomes for both immediate graft function and long-term graft survival. For the analysis, recipients of ECD kidneys in the Scientific Registry of Transplant Recipients (SRTR) transplanted between October 1, 1987 and August 31, 2011 were included. Univariate and multivariate analyses predicted the hazard ratio of graft failure and the odds ratio of requiring dialysis within the first week. A total of 25,640 ECD kidney transplants were analyzed. On multivariate analysis, higher creatinine clearance match ratio (CCMR) was associated with increased graft failure and odds of requiring dialysis within the first week (comparing highest ratio quintile versus lowest ratio quintile: HR 1.43, p < 0.001; OR 2.08, p < 0.001). This study suggests that ECD kidneys have improved outcomes when the recipient/donor CCMR is optimized.

The incidence of hepatocellular cancer (HCC) is increasing dramatically worldwide. Optimal management remains undefined, especially for well-compensated cirrhosis and HCC.This retrospective analysis included 5 US liver cancer centers. Patients with surgically treated HCC between 1990 and 2011 were analyzed; demographics, tumor characteristics, and survival rates were included.There were 1,765 patients who underwent resection (n = 884, 50.1%) or transplantation (n = 881, 49.9%). Overall, 248 (28.1%) resected patients were transplant eligible (1 tumor5 cm or 2 to 3 tumors all3 cm, no major vascular invasion); these were compared with 496 transplant patients, matched based on year of transplantation and tumor status. Overall survivals at 5 and 10 years were significantly improved for transplantation patients (74.3% vs 52.8% and 53.7% vs 21.7% respectively, p0.001), with greater differences in disease-free survival (71.8% vs 30.1% at 5 years and 53.4% vs 11.7% at 10 years, p0.001). Ninety-seven of the 884 (11%) resected patients were within Milan criteria and had cirrhosis; these were compared with the 496 transplantation patients, with similar results to the overall group. On multivariate analysis, type of surgery was an independent variable affecting all survival outcomes.The increasing incidence of HCC stresses limited resources. Although transplantation results in better long-term survival, limited donor availability precludes widespread application. Hepatic resection will likely remain a standard therapy in selected patients with HCC. In this large series, only about 10% of patients with cirrhosis were transplant-eligible based on tumor status. Although liver transplantation results are significantly improved compared with resection, transplantation is available only for a minority of patients with HCC.

Liver transplantation creates the perfect storm for the development of massive, uncontrolled hemorrhage. The pathophysiology of liver disease, including portal hypertension, leads to high-pressure collaterals that course through all of the abdominal tissue planes. In addition, liver disease also results in severe coagulopathy from the lack of clotting synthesis and platelet sequestration in the spleen. The location of liver makes things worse, as it is located in the “surgical soul” of the abdomen where all of the major blood vessels convene. Over the last several decades, improvements in the technical skill set needed for liver transplantation, as well as anesthesiology techniques and understanding of coagulation, have all led to liver transplantation being a successful operation and the only cure for end-stage liver disease and hepatocellular carcinoma in patients with cirrhosis. The chapter will discuss the treatment of hemorrhage in patients undergoing liver transplantation.

On June 18, 2013, the United Network for Organ Sharing (UNOS) instituted a change in the liver transplant allocation policy known as "Share 35." The goal was to decrease waitlist mortality by increasing regional sharing of livers for patients with a model for end-stage liver disease (MELD) score of 35 or above. Several studies have shown Share 35 successful in reducing waitlist mortality, particularly in patients with high MELD. However, the MELD score at transplant has increased, resulting in sicker patients, more complications, and longer hospital stays. Our study aimed to explore factors, along with Share 35, that may affect the cost of liver transplantation. Our results show Share 35 has come with significantly increased cost to transplant centers across the nation, particularly in regions 2, 5, 10, and 11. Region 5 was the only region with a median MELD above 35 at transplant, and cost was significantly higher than other regions. Several other recipient factors had changes with Share 35 that may significantly affect the cost of liver transplant. While access to transplantation for the sickest patients has improved, it has come at a cost and regional disparities remain. Financial implications with proposed allocation system changes must be considered.

Author(s): Caussy, Cyrielle; Soni, Meera; Cui, Jeffrey; Bettencourt, Ricki; Schork, Nicholas; Chen, Chi-Hua; Ikhwan, Mahdi Al; Bassirian, Shirin; Cepin, Sandra; Gonzalez, Monica P; Mendler, Michel; Kono, Yuko; Vodkin, Irine; Mekeel, Kristin; Haldorson, Jeffrey; Hemming, Alan; Andrews, Barbara; Salotti, Joanie; Richards, Lisa; Brenner, David A; Sirlin, Claude B; Loomba, Rohit; Familial NAFLD Cirrhosis Research Consortium | Abstract: BackgroundThe risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.MethodsThis is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).ResultsThe prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438).ConclusionUsing a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.Trial registrationUcsd irb140084.FundingNational Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

Background Postoperative or remnant liver volume (RLV) after hepatic resection is a critical predictor of perioperative outcomes. This study investigates whether the accuracy of liver surgical planning software for predicting postoperative RLV and assessing early regeneration. Study Design Patients eligible for hepatic resection were approached for participation in the study from June 2008 to 2010. All patients underwent cross-sectional imaging (CT or MRI) before and early after resection. Planned remnant liver volume (pRLV) (based on the planned resection on the preoperative scan) and postoperative actual remnant liver volume (aRLV) (determined from early postoperative scan) were measured using Scout Liver software (Pathfinder Therapeutics Inc.). Differences between pRLV and aRLV were analyzed, controlling for timing of postoperative imaging. Measured total liver volume (TLV) was compared with standard equations for calculating volume. Results Sixty-six patients were enrolled in the study from June 2008 to June 2010 at 3 treatment centers. Correlation was found between pRLV and aRLV ( r = 0.941; p r = 0.953; p Conclusions Preoperative virtual planning of future liver remnant accurately predicts postoperative volume after hepatic resection. Early postoperative liver regeneration is measureable on imaging beginning at 5 days after surgery. Measuring TLV directly from CT scans rather than calculating based on equations accounts for extremes in TLV.

The aim of the present study was to determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). A retrospective chart review was performed for patients diagnosed with ICC between 2000 and 2009 at a single institution. We identified a total of 105 patients with ICC. Among them, 63.8% were older than 60 years of age, 50.5% were male and 88.6% were Caucasian. By preoperative imaging approximately half of the patients (50.5%) were surgical candidates and underwent resection. The other half of the patients (49.5%) were unresectable. The unresectable group received chemoradiotherapy (53%) and transarterial chemoembolization (7.7%) as palliative treatments while 23.0% of the patients (12/52) received best supportive care alone. The median survival rates were 16.1 months (13.1‑19.2) for the entire cohort, 27.6 months (17.7-37.6) for curative resection, 12.9 months (6.5-19.2) for palliative chemoradiotherapy and 4.9 months (0.4-9.6) for best supportive care (p0.001). Independent predictors on multivariate analysis were advanced stage at diagnosis and treatment received. In those patients who underwent resection, advanced AJCC stage and presence of microvascular invasion were also independent predictors of poor survival. We concluded that surgery offers the most beneficial curative option and outcome, emphasizing the importance of resectability as a major prognostic factor. The present study also revealed that use of chemoradiotherapy in the adjuvant setting failed to improve survival but its palliative use in those patients with unresectable ICC offered a modest survival advantage over best supportive care. The overriding factors influencing outcome were stage and the presence of microvascular invasion on pathology.

With primary and metastatic cancers to the liver, the optimal therapy remains curative surgical resection. Various non-anatomical and anatomical liver resections are common practice, but when tumors are in difficult locations, surgeons may require the use of vascular resection with portal venous or arterial reconstruction to obtain negative resection margins. In situations where tumors involve the inferior vena cava (IVC) or hepatic veins, other techniques may be employed for resection that was developed from liver transplant techniques. Ex vivo resection remains the most dramatic of these complex resection techniques and is used for the most difficult tumors to resect, including malignant disease such as hepatocellular carcinoma, cholangiocarcinoma, colorectal metastasis, benign obstructive disease, or echinococcal cysts. Ex vivo resection carries a 10–15% mortality, with a high chance of surgical complications and postoperative liver failure, but offers a potential for cure in otherwise unresectable patients. This chapter outlines the technique of ex vivo resection and highlights two cases where it was used.

IMT, previously known as IPT, is a relatively rare tumor that was originally described in the lungs, but case reports have reported the tumor in almost every organ system. Surgical resection is typically the mainstay of therapy; however, tumors have also been shown to respond to chemotherapy or anti-inflammatory therapy and some have spontaneously regressed. We present a literature review and case report representing the first documentation to date of liver transplant combined with PD for surgical resection of a myofibroblastic tumor non-responsive to medical therapy.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide, and its incidence has been increasing in the last decade largely in parallel to the incidence and duration of exposure to hepatitis B and C. The widespread implementation of hepatitis B vaccine, hepatitis B antivirals, and the introduction of direct antiviral therapies for hepatitis C virus may have a substantial impact in reducing the incidence of HCC. This report reviews the risk factors and underlying mechanisms associated with the development of HCC in hepatitis B, along with advances in the diagnosis, imaging, and management of HCC.

Aim The aim of this study is to clarify the association between hepatitis C virus (HCV) infection and post-transplant lymphoproliferative disease (PTLD) in the liver allograft. Methods Of the 933 adults who underwent liver transplantation (LT) between 1990 and 2005, 10 patients developed PTLD. Seven of the 10 patients that were HCV(+) (group 1) were compared with three HCV-negative recipients (group 2). Results The mean time between LT and PTLD was 24.5 months. There were no differences between in Epstein–Barr virus antibody status or tumor lymphocyte subsets. In five of the seven HCV-positive recipients who developed PTLD, PTLD recurred preferentially in the liver allograft, whereas none of the three HCV-negative patients who developed PTLD did so in the liver (71.4 vs. 0%, respectively, P=0.038). In all five patients with graft PTLD, HCV recurred within 12 months followed by PTLD. There were significant differences between groups 1 and 2 in mean lymphocyte infiltrate scores (6.0±2.1 vs. 2.0±0.7, P=0.037), fibrosis stage (2.4±0.5 vs. 0.7±0.5, P=0.029), and frequency of lymphoid follicles in portal areas (33.6±14.8% vs. 1.1±2.3%, P=0.0002). Conclusion When PTLD occurs in patients with HCV recurrence after LT, it does so preferentially in the liver allograft.

Background: The literature suggests that blood product transfusions have a negative impact on the survival of liver transplant patients. We investigated the impact of intraoperative blood product usage on the survival of liver transplantation patients being transplanted for hepatitis C-related end-stage liver disease. In addition, we analyzed a potentially more sensitive metric, namely disease recurrence and fibrosis progression, obtained from follow-up liver biopsies. Methods: We retrospectively studied 194 consecutive patients with hepatitis C virus (HCV) undergoing liver transplantation. To investigate the effect of red blood cell (RBC) or platelet transfusions on post-transplant HCV recurrence, hepatic biopsy data from 4 months and 1 year after transplantation were studied. In addition, survival data were analyzed. Results: There was no effect of intraoperative RBC or platelet transfusion on either 1- or 5-year patient survival following liver transplantation. There was no difference in HCV disease recurrence or progression of hepatic fibrosis at 4 months or 1 year attributable either to RBC or to platelet transfusion. Conclusion: This study was not able to confirm an effect on the survival of HCV-infected liver transplant patients related to intraoperative transfusion of RBCs or platelets. In addition, these transfusions had no effect on HCV recurrence or fibrosis progression. This is not to condone a liberal transfusion practice, but rather to reassure that when clinically indicated, transfusion does not have a significant impact on patient survival or disease recurrence in HCV-infected liver transplant patients.

Fulminant hepatic failure is a life-threatening condition that can lead to rapid deterioration and death if timely treatment is not instituted. Many patients recover with supportive care. Patients with deteriorating signs and laboratory parameters require prompt assessment and listing for liver transplantation. Outcome following transplantation is a function of severity of illness before transplantation, timeliness of liver transplantation and graft quality and function. With appropriate immunosuppression and close follow-up most patients can lead near normal lives following liver transplantation.

Background Combined resection of both the liver and pancreas for malignancy remains a controversial procedure. To many, the need for such an extended procedure implies an extent of disease that is usually not amenable to surgical control, and the extent of the procedure exposes the patients to substantial operative risks. The purpose of this study was to assess our results with combined resection of the liver and pancreas. Study Design Forty patients underwent combined liver and pancreas resection from 1996 to 2009. Patient ages ranged from 39 to 69 years (mean 53 years). Underlying diagnoses were neuroendocrine tumor (13), cholangiocarcinoma (13), gallbladder carcinoma (9), gastrointestinal stromal tumor (3), colorectal cancer (1), and metastatic ocular melanoma (1). Pancreatic resections included 26 pancreaticoduodenectomies (PD) and 14 distal pancreatic resections. Liver resections included 18 trisectionectomies (13 right, 5 left), 10 lobectomies (8 right, 2 left), and 12 segmental resections. Results There was no perioperative mortality. One patient who underwent PD with right trisegmentectomy for gallbladder cancer developed postoperative liver failure that improved with supportive management. Two patients developed bile leaks that resolved with conservative management. One patient developed a pancreatic leak/hemorrhage and required a completion pancreatectomy. Mean hospital stay was 14 days (range 7 to 42 days). Median follow-up was 30 months (range 3 to 76 months). Patients undergoing resection for neuroendocrine tumors had a better 5-year survival than those with hepatobiliary malignancies (100% vs 37% p=0.01). Conclusions Combined resection of the liver and pancreas can be performed safely. The need for combined partial hepatectomy and pancreatectomy to remove malignancy should not be considered a contraindication to resection in selected patients.

Introduction Strategies to reduce red blood transfusion utilization in cancer patients undergoing operation are needed. Hypothesis Postoperative epoetin alfa (40,000 units subcutaneous on postoperative days 1 and 7) is associated with improved hematologic parameters in patients undergoing major abdominal surgery for malignancy. Materials and methods Prospective, blinded, randomized trial of epoetin alfa (40,000 units subcutaneous on postoperative days 1 and 7) versus placebo in patients undergoing major abdominal operation for malignancy. Primary endpoints were immature reticulocyte fraction, reticulocyte count, and hemoglobin, which were measured on postoperative days 4, 7, and between 14 and 20. Secondary endpoints were transfusions and complications in the 2 groups. Results Forty patients were enrolled. There were no significant differences in immature reticulocyte fraction (P = 0.78), reticulocyte count (P = 0.42), or hemoglobin (0.35) in patients randomized to receive epoetin alfa versus placebo. There was no significant difference in red blood cell transfusion rate or postoperative complications in patients who received epoetin alfa compared with placebo. Discussion The use of postoperative epoetin alfa (40,000 units subcutaneous on postoperative days 1 and 7) in patients undergoing major operation for abdominal or pelvic malignancy is not supported by this randomized trial.

Patients undergoing major hepatectomy are at increased risk for post-operative morbidity and mortality, and changes in the phenotype of effector cells may predispose these patients to infectious sequelae.To better understand post-hepatectomy immune responses, peripheral blood from 15 hepatectomy patients was drawn immediately before and after liver resection and on post-operative days 1, 3, and 5. Circulating monocytes and dendritic cells were analyzed by flow cytometry for quantity, phenotype, activation status, human leukocyte antigen DR (HLA-DR) expression, and toll-like receptor-2 and -4 expression.Major hepatectomy increased the numbers of activated CD16(bright) blood monocytes and the percentage of activated dendritic cells, although monocyte HLA-DR expression was reduced. These results may represent both dysfunctional antigen presentation and pending anergy, as well as cellular priming of immune effector cells. Better understanding of the alterations in innate immunity induced by hepatectomy may identify strategies to reduce infectious outcomes.

Background The definition of what is unresectable in liver surgery is controversial. Problems that many believe render patients unresectable can currently be resected using advanced techniques of liver surgery. This study assesses liver resection in patients who were unresectable with standard liver resection but were potentially resectable using an aggressive approach to liver surgery. Study Design From 1997 to 2007, 830 adult patients undergoing hepatectomy were reviewed. Patients were categorized as having unresectable disease by standard resection if the disease could not be resected without resection of the IVC, hepatic vasculature, or because of tumor extent. Results One hundred sixteen patients were initially believed to have unresectable disease but went on to laparotomy. Eighteen patients were unresectable at operation, although 98 patients were resected. Seventy-eight trisectionectomies; 18 lobectomies; 1 mesohepatectomy; and 1 segment 5, 6 resection, combined with pancreaticoduodenectomy, nephrectomy, and colectomy, were performed. Fourteen patients also had pancreatic resections. Vascular reconstructions were performed on the IVC (n = 35), hepatic veins (n = 21), portal vein (n = 34), and hepatic artery (n = 5). Hypothermic perfusion of the liver was used in 12 patients (4 ex vivo, 8 in situ cold perfusion). Patients undergoing resection had 6% mortality with a morbidity of 35%. Median survival was 37 months (95% CI, 34–42 months). Five-year actuarial survival was 32%. Conclusions Patients with liver tumors considered "unresectable" by standard liver resection should be considered for resection with an aggressive approach to liver surgery. Five-year survival of approximately one-third of patients can be expected.

Autoimmune pancreatocholangitis is characterized by sclerosing inflammation of the biliary tree or pancreatic duct and can mimic pancreaticobiliary malignancy. Serum immunoglobin (Ig) G4 values seem to be helpful in distinguishing autoimmune pancreatocholangitis from pancreatic malignancy in the Japanese population; however, its significance in the Western population has not been well studied.We report a retrospective analysis of 7 consecutive patients with autoimmune pancreatocholangitis and compare them to 23 patients with pancreatic malignancy. Clinical presentation, diagnostic tests, and preoperative IgG4 levels were reviewed in all patients. Presence of autoimmune pancreatocholangitis or pancreatic malignancy was determined by pathologic analysis in all patients and reviewed by a single pathologist.In all patients, autoimmune pancreatocholangitis manifested in a similar fashion to pancreatic malignancy. Median IgG4 levels were far lower in pancreatic cancer patients with localized, resectable disease (24 mg/dL), locally advanced disease (24 mg/dL), and metastatic disease (28 mg/dL) as compared with patients with autoimmune pancreatocholangitis (142 mg/dL, P.05). Only one patient with pancreatic cancer had an IgG4 level that was100 mg/dL. In contrast, all patients with autoimmune pancreatitis or cholangitis had levels100 mg/dL. However, in five of these seven patients, IgG4 levels were below the upper limits of normal.Autoimmune pancreatocholangitis mimics pancreatobiliary malignancy. Serum IgG4 values seem to be helpful in distinguishing autoimmune pancreatocholangitis from malignancy in the Western population. However, absolute values seem to be lower in the United States compared with Japan. The upper limit of normal as reported in laboratories in the United States may not be useful in identifying abnormally high IgG4 values. A new upper limit of normal may need to be defined because IgG subclass determinations are being used more frequently in Western patients with biliary obstruction.

Background & Aims: Hepatitis C virus (HCV) has a tendency to cause chronic viral infection. Viral evasion of host immune systems plays a key role in the pathogenesis of HCV. However, the interaction between HCV and hepatocyte innate antiviral defense systems is not understood. The aim of this study was to examine how human hepatocytes respond to HCV infection. Methods: We have established a novel human hepatoma cell line, LH86, from a well-differentiated hepatocellular carcinoma tissue. An infectious HCV isolate, JFH-1, was used to infect LH86 cells. HCV replication and apoptosis after viral infection were examined. Mechanisms of HCV-induced apoptosis were determined. Type I interferon induction and the relevant signaling molecules were examined. Results: LH86 cells permitted JFH-1 HCV infection. The viral infection caused massive apoptosis. The apoptosis was related to viral replication, because blocking viral entry with anti-CD81 or suppressing viral replication with interferon protected cells from HCV-induced apoptosis. The HCV-induced apoptosis appeared to be triggered by tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and its receptors, death receptor 4 and death receptor 5, which were up-regulated in HCV infection. HCV also activated interferon response factor 3, which induced expression of interferon and TRAIL in LH86 cells. Conclusions: Our study showed that a specific HCV isolate, JFH-1, is cytopathic in this new hepatoma cell line. LH86 cells mount an intact innate antiviral defense through induction of interferon and triggering apoptosis of infected cells. This study reveals a novel mechanism by which host hepatocytes respond to acute HCV infection.

To examine the outcome of technical variant liver transplant techniques relative to whole organ liver transplantation in pediatric liver transplant recipients.Technical variant liver transplant techniques comprising split, reduced, and live-donor liver transplantation evolved to address the need for timely and size appropriate grafts for pediatric recipients.Analysis of data from the Studies of Pediatric Liver Transplantation (SPLIT) registry, a multicenter database of 44 North American pediatric liver transplant programs. The outcome (morbidity and mortality) of each of the technical variants were compared with that of whole organ recipients.Data were available on 2192 transplant recipients (1183 whole, 261 split, 388 reduced, and 360 live donor). Recipients of all technical variant graft type were significantly younger than whole organ recipients, but on average spent 2.3 months less on the waiting list. Thirty-day post-transplant morbidity was increased for each type of technical variant relative to whole organ (45.1% whole, 66.7% split, 65.5% reduced, 51.9% live-donor). Biliary complications (30 day: 7.5% whole, 18.8% split, 16% reduced, 17.5% live-donor) and portal vein thrombosis (30 day: 3.6% whole, 8% split, 8% reduced, 7.5% live-donor) were more common in all technical variant types. Graft type was an independent predictor of graft loss (death or retransplantation) in a multivariate analysis. Split and reduced (relative risk = 1.74 and 1.77, respectively) grafts had a worse outcome when compared with whole organ recipients.Technical variant techniques expand the pediatric donor pool and reduce time from listing to transplant, but they are associated with increased morbidity and mortality.

BACKGROUND: The aim of this study was to compare the ability of staging systems (American joint Committee on Cancer/Union Internationale contre le Cancer [AJCC/UICC], Japanese TNM, Pittsburgh, United Network for Organ Sharing [UNOS], Cancer of the Liver Italian Program [CLIP], Japan Integrated Staging [JIS], and Barcelona Clinic Liver Cancer [BCLC]) to predict survival after liver transplantation for hepatocellular carcinoma. STUDY DESIGN: Four hundred ninety consecutive patients who underwent liver transplantation for hepatocellular carcinoma at 4 centers (1985 to 2005) were identified using a registry (US, Belgium, Germany). End points were overall (OS) and recurrence-free survival (RFS). Survival by stage was compared with the log-rank test. Sequential stage-wise discrimination of each system was evaluated using Cox regression. RESULTS: Three- and 5-year overall survival rates were 71% and 64%, respectively; recurrence-free survival rates were 67% and 61%, respectively. Median followup among 327 living and 308 recurrence-free patients was 40 months. In only three systems-AJCC/UICC, Japanese TNM, and Pittsburgh-were overall and recurrence-free survivals longer for patients with low stage versus more advanced stage. For overall and recurrence-free survivals, sequential stages were different only for AJCC/UICC. In the Japanese TNM system, stages II and I were similar; for Pittsburgh, grades 3 and 2 were similar. For the United Network for Organ Sharing system, stages II and I and stages IVAI and III were similar. All stages were similar for the Cancer of the Liver Italian Program. For the Japan Integrated Staging, scores 2 and I and scores 4 and 3 were similar. In the Barcelona Clinic Liver Cancer, stage D patients had significantly better survival than patients at stage C. CONCLUSIONS: The AJCC/UICC staging system provides the best stratification of prognosis for patients undergoing liver transplantation for hepatocellular carcinoma. This confirms previous analyses in patients treated with hepatic resection. The AJCC/UICC staging system should be considered for uniform prediction of outcomes after surgery for hepatocellular carcinoma.

Background Tumor recurrence remains the major cause of death after curative resection for hepatocellular carcinoma (HCC). The purpose of this study was to identify risk factors for the recurrence of HCC and to examine long-term outcomes after resection. Methods From July 1992 to July 2004, 193 consecutive patients who underwent hepatic resection as primary therapy with curative intent for HCC were included in this single-center analysis. The perioperative mortality rate was 5%. Time to recurrence (disease-free survival) and overall survival were determined by Kaplan-Meier analysis. Demographic, tumor, and treatment characteristics were tested for their prognostic significance by univariate and multivariate analysis with the log-rank test and the Cox proportional hazards model, respectively. Results Median overall survival for the entire cohort was 71 ± 11 months; disease-free survival was 34 months (range, 1-149 months). After a median follow-up time of 34 months, 98 patients (51%) experienced recurrent cancer; initial tumor recurrence was confined to the liver in 86 patients (88%). With the use of multivariate analysis, preoperative vascular invasion detected on radiologic imaging studies; postoperative vascular invasion found on pathologic assessment, and intermediate and poor tumor differentiation and tumor size and number were significant predictors of disease-free survival. Of the 98 patients who had tumor recurrence, 53 patients (54%) underwent additional therapy (ablation, 31 patients; re-resection, 11 patients; transarterial chemoembolization, 8 patients; liver transplantation, 3 patients) with improvement in survival. Conclusion Despite recurrences in >50% of patients, long-term survival can be achieved after resection of HCC. Identification of risk factors, close follow-up evaluation, and early detection are mandatory because recurrences that are confined to the liver may be amenable to treatment with an additional survival benefit.

This study examines the results of liver transplantation (LT) in children 5 kg or less. Reports suggest an increased morbidity and mortality in children weighing 5 kg or less as compared to larger children. However, over half of all children needing LT are1 year old. Improving outcomes in very small children is a major goal of liver transplantation.All children under 21 years of age transplanted from January 1990 to June 2005 were included in this study. One hundred sixty-eight primary liver transplants were done: 61 in children less than one year of age and 20 in infants weighing 5 kg or less at LT (2 to 5 kg). These 20 infants underwent 23 transplants. Whole organs were used in 39% of transplants, and reduced or split grafts were used in 61%. Arterial reconstruction using aortic conduits was done in 22%. Analysis included Fischer's exact or Chi square test for non-parametric analysis while patient survival was calculated using the Kaplan-Meier method test with differences in survival assessed using the log rank test.Five-year survival for infants 5 kg or less was 74%, and graft survival was 60%, which was not different from patients transplanted that were5 kg. There were three perioperative deaths, one from primary graft non-function, and two from portal vein thrombosis. There were no bile leaks or hepatic artery thromboses. Bacterial, fungal, and viral infections made up the vast majority of the postoperative complications (65%), with viral infections resulting in two graft losses requiring re-transplantation. Rejection occurred in 25% of patients, of which one required OKT3. Five of the 23 liver transplants in infants less than 5 kg were done prior to 1996, with a five-year graft survival of only 20%. Improvements in technique and postoperative care after 1996 led to improved graft and patient survival of 77% and 86% respectively.Liver transplantation for infants weighing less than 5 kilograms can be technically challenging but can have equivalent graft and patient survival when compared to larger children requiring liver transplantation. Infants should not be denied liver transplantation based on weight alone.

We sought to determine whether the prophylactic use of amphotericin B products (conventional amphotericin B and liposomal amphotericin B) reduces the incidence of fungal infections in high-risk liver transplant recipients, and if so, whether this lowers the cost of care. The study sample comprised 232 adult orthotopic liver transplants performed from 1994 to 2005 at a single center for patients classified as being at high risk for fungal infections. High-risk patients who received transplants with a prophylaxis regimen of amphotericin B (n=58 transplants) were compared with high-risk patients who received no prophylaxis (n=174 transplants). Fungal infections occurred in 3 transplants (5.17%) of those who received amphotericin B and 28 transplants (16.09%) in those without prophylaxis (P=0.0432). Regression models were used to analyze fungal infection and costs for the 232 high-risk transplants. Failure to offer prophylaxis conferred a 4-fold greater risk of fungal infection (P=0.046) compared with those who received amphotericin B. A fungal infection in a high-risk recipient increased mean costs by 46.48%. The indirect effect of prophylaxis (operating through infection reduction) is estimated to reduce overall costs in high-risk patients by 8.73%.

Pompe disease results from inherited deficiency of the enzyme acid alpha-glucosidase resulting in lysosomal accumulation of glycogen primarily in skeletal muscle. Reported is the first case in which a donor with late onset Pompe disease (LOPD) was successfully used for deceased donor liver and kidney transplantation. This case demonstrates co-operative transplant surgery and genetic medicine evaluation and risk estimation for donors with inherited metabolic disorders some of which may be suitable for donation of selected organs for transplantation.

Liver resections that require ex vivo techniques occur rarely, but when done are generally performed on veno-veno bypass to maintain venous return and decompress the portal circulation during the anhepatic phase of the procedure. We describe an ex vivo extended left hepatectomy that was performed with preservation of the inferior vena cava and the use of a temporary portacaval shunt to eliminate the need for veno-venous bypass. Ex vivo resection allowed reconstruction of right hepatic vein branches, using the patient's reversed portal vein bifurcation as a graft to provide venous outflow.

Ischemic preconditioning has been shown to protect the liver from ischemia/reperfusion injury. We hypothesized that IL-6 directly modulates the protective effects of ischemic preconditioning.Three weeks after undergoing splenic transposition, wild-type C57BL/6 and IL-6 null mice underwent 75 minutes of total hepatic ischemia with or without prior ischemic preconditioning (10 minutes of ischemia followed by 15 minutes of reperfusion). After reperfusion, serum ALT, serum IL-6, hepatic IL-6 mRNA, hepatic pSTAT3, and liver histology were evaluated.In wild-type mice, survival at 24 hours was greater in the preconditioned group compared with the non-preconditioned group (75% vs 40%, P.05). In IL-6 null mice, however, ischemic preconditioning did not improve survival when compared with the non-preconditioned group. Preconditioning significantly reduced hepatocellular injury in wild-type mice (P.05) when compared with IL-6 null animals. This protection was associated with significant increases in serum IL-6, hepatic IL-6 mRNA, and hepatic pSTAT3 levels (P.05). The protective effects of ischemic preconditioning that correlated with significant increases in systemic IL-6, hepatic IL-6 mRNA abundance, and pSTAT3 levels, were not observed in IL-6 null mice.The protective effects of ischemic preconditioning during total hepatic ischemia/reperfusion injury are dependent on IL-6 signaling and are associated with increased phosphorylation of hepatic STAT3.

We describe the novel use of radiofrequency ablation (RFA) in combination with surgical resection for treatment of multifocal hepatic adenoma. We show three cases without recurrent lesions detected in follow-up examination. Two of the patients have subsequently gone on to carry pregnancies successfully to term.

Duodenal gastrointestinal stromal tumors (GIST) have been described primarily in isolated case reports. In order to learn more about duodenal GIST, a retrospective review of patients with GIST managed at a single institution between 2000 and 2005 was conducted. Thirty-eight GIST of the stomach and small bowel were analyzed. Eight (21%) were duodenal GIST. The median size of duodenal GIST (6.0 cm) and small bowel GIST (6.3 cm) was larger than the median size of gastric GIST (3.0 cm). The most common presentation of duodenal GIST was bleeding (50%) which was similar to other small bowel GIST (49%) but different from gastric GIST which were most commonly an incidental finding (62%). Two patients (25%) with duodenal GIST had a history of neurofibromatosis. The duodenal GIST were located in the 2nd (n = 5, 63%) and 3rd portion of duodenum (n = 3, 37%). Seven of 8 patients underwent complete resection of duodenal GIST. Pancreaticoduodenectomy was the most common operation performed (n = 5); 2 patients were treated with partial duodenal resection. No patients undergoing pancreaticoduodenectomy (n = 5) were found to have lymph node metastases. No patients received neo-adjuvant or adjuvant therapy with Imatinib. Following resection, 2 patients have recurred (12 and 48 mo.), 4 patients are without disease (1, 6, 6, and 24 mo.), 1 patient died postoperatively. Duodenal GIST are relatively rare tumors that present most commonly with gastrointestinal bleeding. Duodenal GIST are associated with neurofibromatosis. Many duodenal GIST require pancreaticoduodenectomy for complete removal.

Hilar cholangiocarcinoma remains a difficult challenge for the surgeon. Achieving negative surgical margins when resecting this relatively uncommon tumor is technically demanding as a result of the close proximity of the bile duct bifurcation to the vascular inflow of the liver. A recent advance in surgical treatment is the addition of portal vein resection to the procedure. Resection of the portal vein increases the number of patients offered a potentially curative approach but is technically more difficult and may increase the risk of the procedure. This study reviews the results of portal vein resection for hilar cholangiocarcinoma. Between 1998 and 2005, 60 patients underwent potentially curative resections of hilar cholangiocarcinoma. Mean patient age was 64 ± 12 years (range, 24–85 years). Liver resections performed along with biliary resection included 49 trisegmentectomies (37 right, 12 left) and 10 lobectomies (8 left, 2 right). One patient had only the bile duct resected. Four patients also had simultaneous pancreaticoduodenectomy performed. Twenty-six patients required portal vein resection and reconstruction to achieve negative margins, 3 of which also required reconstruction of the hepatic artery. Operative mortality was 8 per cent with an overall complication rate of 40 per cent. Patients who underwent portal vein resection had an operative mortality of 4 per cent, which was not different from the 12 per cent mortality in patients who did not undergo portal vein resection (P = 0.39). There was no difference in actuarial patient survival between patients who underwent portal vein resection and those who did not (5-year survival 39 per cent vs. 41 per cent, P = not significant). Negative margins were achieved in 80 per cent of cases and were associated with improved survival (P < 0.01). Five-year actuarial survival in patients undergoing resection with negative margins was 45 per cent. There was no difference in margin status or long-term survival between those patients who underwent portal vein resection and those who did not. Only negative margin status was associated with improved survival by multivariate analysis. Portal vein resection for hilar cholangiocarcinoma is safe and allows a chance for long-term survival in otherwise unresectable patients.

Cholangiocarcinoma is a relatively rare tumor with an estimated incidence of 3000 cases in the United States in 2002.1 A review of 294 patients with cholangiocarcinoma by Nakeeb et al2 demonstrated that two thirds of patients had hilar tumors, 27% of tumors were in the distal bile duct, and 6% were intrahepatic. It is difficult to accurately estimate the proportion of patients with hilar cholangiocarcinoma (HCCA) that are amenable to surgical resection. This is because the majority of series published reflect only patients that are referred for surgical management and do not include patients that present with unresectable disease that are never seen by a surgeon. Perhaps the best current estimate is presented in a series by Jarnagin et al;3 approximately 30% of patients with HCCA seen at their multidisciplinary hepatobiliary cancer center presented with unresectable disease, while 70% went on to some attempt at surgical management. Of those patients managed surgically, only 50% had an attempted curative resection. The low number of patients amenable to curative resection results in few surgeons outside of specialized centers gaining experience in the management of this formidable disease. Early reports of resection of HCAA consisted mainly of resections of the biliary tree and bilioenteric anastomosis to the intrahepatic ducts.4,5 Blumgart and Launois, pioneers of modern hepatobiliary surgery, were early proponents of the addition of liver resection to bile duct resection for this disease;6,7 however, the concept was greeted with little enthusiasm by surgeons at the time that had a relatively nihilistic view of any surgical treatment of HCAA. Advances in liver surgery over the last 2 decades have led to a more aggressive approach to HCAA. Partial liver resection was added to biliary resection to manage those tumors with direct hepatic invasion, as well as to obtain oncologic margins on tumors that frequently extend longitudinally out the hepatic ducts.3,8–10 However, major liver resection in the setting of liver dysfunction caused by biliary obstruction can be associated with increased mortality.11 With relatively few exceptions, reports to date by necessity include case series that extend over a prolonged time period. These reports incorporate patients that underwent bile duct resection alone who would currently be managed with the addition of liver resection. This study examines the results of surgical management of HCAA during a time period when liver resection in addition to bile duct resection was considered the standard management for curative resection of HCAA.

The objective of the current study was to define the optimal treatment for patients with retroperitoneal soft tissue sarcomas (RPS). The authors conducted a review of the pertinent literature and found that the majority of patients had locally advanced RPS at the time of diagnosis. Surgery was the mainstay of treatment, and macroscopic total excision was feasible in approximately 50-67% of patients. The 5-year probability of local control was approximately 50%, and the likelihood of developing distant metastasis was approximately 20-30%. The 5-year survival rate was approximately 50%, and deaths due to recurrent RPS continued to occur after 5 years. Postoperative radiotherapy (RT) decreased the likelihood of local recurrence, although it demonstrated no impact on survival. Adjuvant chemotherapy had no proven efficacy. The factor that was found to have the greatest impact on the prognosis for patients with RPS was the ability to achieve a macroscopic total resection. The authors concluded that RPS usually is advanced at the time of diagnosis. The optimal treatment was complete resection. Most patients experienced recurrent disease after surgery, and the most common site of failure was local. Adjuvant RT reduced the risk of local recurrence, but its impact on survival was questionable.

Background Dendritic cells (DCs) are potent antigen-presenting cells that induce and regulate immune responses. Recent advances allow accurate quantification of peripheral blood (PB) myeloid and plasmacytoid DC populations (mDC and pDC, respectively), although the response to renal transplantation (RT) remains unknown. Methods Using flow cytometry, PBDC levels were quantified in patients with end-stage renal disease (ESRD) undergoing renal transplantation. Results PBDC levels were significantly reduced in ESRD patients pretransplantation compared to healthy controls, with further reduction noted immediately following a hemodialysis session. RT resulted in a dramatic decrease in both subsets, with a greater reduction of pDC levels. Both subset levels were significantly lower than in control patients undergoing abdominal surgery without RT. Subgroup analysis revealed significantly greater mDC reduction in RT recipients receiving antilymphocyte therapy, with preferential binding of antibody preparation to this subset. Samples from later time points revealed a gradual return of PBDC levels back to pretransplant values concurrent with overall reduction of immunosuppression. Finally, PBDC levels were significantly reduced in patients with BK virus nephropathy compared to recipients with stable graft function, despite lower overall immunosuppression. Conclusions Our findings suggest that PBDC levels may reflect the degree of immunosuppression in renal allograft recipients. Furthermore, PBDC monitoring may represent a novel strategy to predict important outcomes such as acute rejection, long-term graft loss, and infectious complications.

Acetaminophen overdose is the most rapidly growing cause of fulminant hepatic failure in Western countries. Pregnant women are counseled that acetaminophen is safe during pregnancy and an alternative to nonsteroidal anti-inflammatory medications. This report describes a case of acetaminophen overdose during the second trimester of pregnancy with resultant fulminant hepatic failure requiring liver transplantation. The fetus was previable at the time of liver transplantation, and methods to preserve viability during and after transplantation are discussed. Despite the best attempts of the team, the fetus expired. The challenges and outcomes of fulminant hepatic failure in pregnancy are discussed in detail.