Racial Disparities in Liver Transplant for Hepatitis C-Associated Hepatocellular Carcinoma.

BACKGROUND: In the United States, hepatitis C virus-associated hepatocellular carcinoma incidence and mortality are highest among minorities. Socioeconomic constraints play a major role in inequitable treatment. We evaluated the association between race/ethnicity and outcomes in a population that overcame treatment barriers. METHODS: We report a retrospective cohort study of 666 patients across 20 institutions in the United States Hepatocellular Carcinoma Liver Transplantation Consortium from 2015 to 2019 with hepatitis C virus-associated hepatocellular carcinoma who completed direct-acting antiviral therapy and underwent liver transplantation. Patients were excluded if they had a prior liver transplantation, hepatocellular carcinoma recurrence, no prior liver-directed therapy, or if race/ethnicity data were unavailable. Patients were stratified by race/ethnicity. Primary outcomes were recurrence-free survival and overall survival, and secondary outcome was major postoperative complication. RESULTS: Race/ethnicity was not associated with differences in 5-year recurrence-free survival (White 90%, Black 88%, Hispanic 92%, Other 87%; p = 0.85), overall survival (White 85%, Black 84%, Hispanic 84%, Other 93%; p = 0.70), or major postoperative complication. CONCLUSIONS: Race/ethnicity was not associated with worse oncologic or postoperative outcomes among those who completed direct-acting antiviral therapy and underwent liver transplantation, suggesting that overcoming socioeconomic constraints equalizes outcomes across racial/ethnic groups. Eliminating barriers that prohibit care access among minorities must be a priority.

Liver transplantation: expanding the donor and recipient pool.

Liver transplantation is an exemplar model of complex surgery and the only curative option for patients with end-stage liver disease. Although historically associated with poor outcomes, liver cancer management has also been revolutionised with liver transplantation and in some instances, survival outcomes are comparable to surgical resection. As such, the key elements underpinning the major advances in surgical technique, immunological therapies and allocation policies combined with improved patient and graft survival outcomes have created a huge demand for organ donation. Despite improvements in donor and recipient selection, there is a persistent disparity between organ supply and demand. Candidate wait-list mortality and dropout rates remain problematic and this concern has resulted in increased efforts to expand the donor pool to meet the unmet needs of the population. This is even more challenging when coupled with an ever-growing recipient pool, candidate waiting lists and an ageing population. Over the past two decades, there has been a considerable focus on extended criteria organs, donations after cardiac death and alternative avenues for marginal liver use. With careful donor selection and recipient matching, these livers may help bridge the gap between supply and demand and placate the ever-expanding recipient pool. Here, we present a summary of recent developments by the transplant community addressing the issues of a growing donor and recipient pool.

Surgical Considerations of Hilar Cholangiocarcinoma.

Cholangiocarcinoma is an aggressive malignancy of the extrahepatic bile ducts. Hilar lesions are most common. Patients present with obstructive jaundice and intrahepatic bile duct dilation. Cross-sectional imaging reveals local, regional, and distant extent of disease, with direct cholangiography providing tissue for diagnosis. The consensus of a multidisciplinary committee dictates treatment. Resection of the extrahepatic bile duct and ipsilateral hepatic lobe with or without vascular resection and transplantation after neoadjuvant protocol are options for curative treatment. The goal of surgery is to remove the tumor with negative margins. Patients with inoperable tumors or metastatic disease are best served with palliative chemoradiotherapy.

Mini-incision versus hand-assisted laparoscopic donor nephrectomy in living-donor kidney transplantation: A retrospective cohort study.

BACKGROUND: Increasing use of Living Donor Kidney Transplantation (LDKT) would decrease the discrepancy between patients awaiting transplantation and organ availability. Minimally invasive surgical approaches attempt to improve outcomes and foster living donation. This report compares outcomes of open minimal incision nephrectomy (Mini N) and a hand assisted laparoscopic nephrectomy (HALN). METHODS: This is a retrospective analysis of a prospectively maintained clinical database of LDKT using HALN or Mini N at a single institution between July 2007 and December 2015. Donor and recipient demographics, relevant pre-, intra- and post-operative factors, outcomes such as patient and graft survival rates, and complications were evaluated. RESULTS: Four hundred and fifty-four adult LDKT (243 Mini N, 211 HALN) were performed during the study period. Recipient and donor demographics were comparable except for higher BMI (p = 0.027) in HALN donors. One-, 3- and 5-year patient and graft survival rates were comparable. Six HALN donors experienced infectious wound complications or superficial skin dehiscence; none did in the Mini N group (p = 0.009). Eight HALN donors and one Mini N donor required an incisional hernia repair (p = 0.014). Recipients had similar warm ischemia times (33 v. 35 min, p = 0.491), but recipient surgeons of HALN nephrectomies subjectively noted higher anastomotic difficulty (10.4% v. 4.5%, p = 0.0183). Other parameters were similar between groups. CONCLUSION: Both Mini N and HALN provide similar long term recipient and donor outcomes. Offering techniques such as Mini N and HALN for living donor kidney procurement facilitates the opportunity to provide living donors safer and better tolerated nephrectomy procedures.

Optimal extent of surgical and pathologic lymph node evaluation for resected intrahepatic cholangiocarcinoma.

BACKGROUND: Lymph node (LN) status is an important predictor of overall survival for resected IHCC, yet guidelines for the extent of LN dissection are not evidence-based. We evaluated whether the number of LNs resected at the time of surgery is associated with overall survival for IHCC. METHODS: Patients undergoing curative-intent (R0 or R1) resection for IHCC between 2004 and 2012 were identified within the US National Cancer Database. LN thresholds were evaluated using maximal chi-square testing and five-year overall survival was modeled using Kaplan-Meier and Cox regressions. RESULTS: 57% (n = 1,132) of 2,000 patients had one or more LNs resected and pathologically examined. In the 631 patients undergoing R0 resection with pN0 disease, maximal chi-square testing identified ≥3 LNs as the threshold most closely associated with overall survival. Only 39% of resections reached this threshold. On multivariable survival analysis, no threshold of LNs was associated with overall survival, including ≥3 LNs (p = 0.186) and the current American Joint Committee on Cancer recommendation of ≥6 LNs (p = 0.318). CONCLUSION: In determining the extent of lymphadenectomy at the time of curative-intent resection for IHCC, surgeons should carefully consider the prognostic yield in the absence of overall survival benefit.

Liver Transplantation for Advanced Hepatocellular Carcinoma after Downstaging Without Up-Front Stage Restrictions.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) continues to increase dramatically worldwide. Liver transplantation (LT) is now the standard and optimal treatment for patients with HCC in the setting of cirrhosis, but only for tumors within Milan criteria. In patients presenting beyond Milan criteria, locoregional therapy (LRT) can downstage to within Milan criteria for consideration for LT. Although controversial, the current study aims to evaluate the outcomes of LT in patients presenting with advanced-stage HCC who underwent downstaging and compare these outcomes with those of patients who met Milan criteria at presentation. STUDY DESIGN: Our protocol does not set a priori limitations as long as HCC is confined to the liver. In this retrospective study between January 1, 2002 and December 31, 2014, we reviewed outcomes associated with 284 patients who presented within Milan criteria and patients who presented with more-advanced stage tumor who were potential transplantation candidates. The patients with advanced disease were then subdivided into those who were within or beyond University of California San Francisco criteria. Imaging, details of LRT, recurrence, and survival were compared between the groups. RESULTS: Sixty-three of 210 (30%) eligible patients were downstaged and underwent transplantation; 14 additional downstaged and listed patients were withdrawn for the following reasons: death while waiting (n = 4), disease progression (n = 8), development of other malignancy (n = 1), and declined LT (n = 1). Twelve patients underwent resection after downstaging and did not require LT. Survival for patients who were downstaged was similar to those who were within Milan criteria initially. Recurrence of HCC at 5 years was similar between groups (10.9% vs 10.8%; p = 0.84). CONCLUSIONS: Patients with beyond-Milan criteria HCC who are otherwise candidates for LT should undergo aggressive attempts at downstaging without a priori exclusion. This highly selective approach allows for excellent long-term results, similar to patients presenting with earlier-stage disease.

Biphenotypic Primary Liver Carcinomas: Assessing Outcomes of Hepatic Directed Therapy.

BACKGROUND: Primary liver carcinomas with hepatocellular and cholangiocellular differentiation (b[HB]-PLC) are rare. Surgery offers the best prognosis, but there is a paucity of literature to guide therapy for patients with advanced or unresectable disease. This study aimed to evaluate outcomes of hepatic-directed therapy compared with those of systemic chemotherapy and surgery. METHODS: A retrospective evaluation of patients with b(HB)-PLC from 1 January 2008 to 1 September 2014 was conducted. The patients were divided into the following four groups: transplantation (TX) group, surgical resection (SX) group, hepatic directed (HD) group, and systemic chemotherapy alone (SC) group. Overall and progression-free survival, treatment response, and clinicopathologic data were analyzed. RESULTS: The study included 79 patients (37 females) with an average age of 62 years. The number of patients in each group were as follows: TX group (n = 6), SX group (n = 27), HD group (n = 18), and SC group (n = 28). The mean follow-up periods were 33 months for the TX group, 17 months for the SX group, 14 months for the HD group, and 7 months for the SX group. Overall, 28 % of the patients had cirrhosis and 35 % had viral hepatitis. The candidates for surgery comprised 42 % of the patients. The HD group (n = 18) had a significantly greater objective response than the SC group (n = 28) (47 vs. 6 %; p = 0.02). Two patients who underwent hepatic arterial infusion pump treatment were downstaged to resection. A trend toward improved OS/PFS was observed in the HD group versus the SC group, although statistically significant. The SX group had significantly improved survival (p < 0.001) as did the transplanted patients. CONCLUSIONS: Although surgery offers the best survival for b(HB)-PLC patients, only a minority are candidates for surgery. Because HD therapy showed a superior objective response over SC therapy, it may offer a survival advantage and may downstage patients for surgical resection or transplantation.

Liver transplantation for hepatocellular carcinoma: long-term results suggest excellent outcomes.

BACKGROUND: Selected 5-year survival results after liver transplantation for hepatocellular carcinoma (HCC) have been reported to be 70%. Our hypothesis was that liver transplantation is effective for long-term cancer control for HCC. STUDY DESIGN: A 20-year retrospective review of a prospectively collected database was carried out. Demographic data and patient survival were calculated. RESULTS: There were 1,422 liver transplantations performed between January 1990 and April 2011. Of these, 264 had HCC and 157 (59%) were pretreated with transarterial chemoembolization. Recipient age was 55.9 (± 7.9) years and 208 (79%) of patients were male. The underlying disease was hepatitis C virus in 155 (58.7%), hepatitis B virus in 16 (6%), alcohol in 21 (8%), and miscellaneous in the remaining 72 cases. The mean number of tumors was 1.8 (± 1.7) and the mean largest tumor diameter was 2.3 (± 1.3) cm in the explanted liver. One, 5, and 10-year patient survival was 88.5%, 69.1%, and 40.5%, respectively; disease-specific survival was 99.1%, 94.4% and 87.9%; and disease-free survival was 86.0%, 64.6%, and 40.1%. One, 5, and 10-year graft survival was 87.3%, 68.0%, and 41.8%. Nine (3.4%) patients required retransplantation; 75 patients (28.4%) have died, but only 10 of 75 (13.3%) died of recurrent HCC (3.7% of all HCC patients receiving a transplant) and 6 (8%) died of recurrent viral hepatitis. An additional 9 recipients developed recurrence (total HCC recurrence, n = 19 [7%]), 4 of whom died of causes other than HCC. The remaining 5 are disease-free post-treatment (mean 5.5 years after orthotopic liver transplantation). CONCLUSIONS: Orthotopic liver transplantation offers an effective treatment strategy for HCC in the setting of cirrhosis, even in the setting of hepatitis C virus. Hepatocellular carcinoma recurrence is uncommon in properly selected patients and disease-specific long-term survival approaches 90%.

Short- and long-term outcomes after steatotic liver transplantation.

OBJECTIVE: To determine if the use of steatotic grafts adversely affects outcomes in liver transplantation. DESIGN: A retrospective review of a prospectively maintained database. SETTING: A single center. PATIENTS: Four hundred ninety adults who underwent liver transplantation from January 1, 2002, to December 31, 2008, at a single center. Graft biopsies were available in 310 (63.3%) cases. Grafts were classified based on amount of macrovesicular steatosis: 5% or less (n = 222), more than 5% to less than 35% (n = 66), and 35% or more (n = 22). MAIN OUTCOME MEASURES: Recipient demographics, Model for End-Stage Liver Disease (MELD) score, patient/graft survival, complications, transfusion rates, and liver function test results. RESULTS: One-, 3-, and 5-year patient and graft survivals, respectively, were similar (90.38%, 84.7%, and 74.4%, respectively, P = .3; and 88.7%, 82.5%, and 73.3%, respectively, P = .15). Median follow-up was 25 months. Recipient age, sex, body mass index, laboratory MELD score, and ischemia times were similar among all groups. Packed red blood cell (3 vs 8 U, P < .001), fresh frozen plasma (2 vs 4 U, P = .007), and cryoprecipitate transfusion rates were significantly increased in grafts with 35% or more steatosis. Intensive care unit (5 vs 11 days, P = .02) and hospital (11 vs 21 days, P < .001) stay was also increased in those with grafts with 35% or more steatosis compared with those with 5% or less steatosis. The grafts with 35% or more steatosis had higher transaminase peaks and longer times for bilirubin to normalize (P < .001). CONCLUSIONS: Use of carefully selected steatotic grafts was not associated with higher rates of primary nonfunction or poorer outcomes. However, the use of steatotic grafts is associated with increased resource use in the perioperative period.

Utility of the Gyrus open forceps in hepatic parenchymal transection.

OBJECTIVE: This study aimed to evaluate if the Gyrus open forceps is a safe and efficient tool for hepatic parenchymal transection. BACKGROUND: Blood loss during hepatic transection remains a significant risk factor for morbidity and mortality associated with liver surgery. Various electrosurgical devices have been engineered to reduce blood loss. The Gyrus open forceps is a bipolar cautery device which has recently been introduced into hepatic surgery. METHODS: We conducted a single-institution, retrospective review of all liver resections performed from November 2005 through November 2007. Patients undergoing resection of at least two liver segments where the Gyrus was the primary method of transection were included. Patient charts were reviewed; clinicopathological data were collected. RESULTS: Of the 215 open liver resections performed during the study period, 47 patients met the inclusion criteria. Mean patient age was 61 years; 34% were female. The majority required resection for malignant disease (94%); frequent indications included colorectal metastasis (66%), hepatocellular carcinoma (6%) and cholangiocarcinoma (4%). Right hemihepatectomy (49%), left hemihepatectomy (13%) and right trisectionectomy (13%) were the most frequently performed procedures. A total of 26 patients (55%) underwent a major ancillary procedure concurrently. There were no operative mortalities. Median operative time was 220 min (range 97-398 min). Inflow occlusion was required in nine patients (19%) for a median time of 12 min (range 3-30 min). Median total estimated blood loss was 400 ml (range 10-2000 ml) and 10 patients (21%) required perioperative transfusion. All patients had macroscopically negative margins. Median length of stay was 8 days. Two patients (4%) had clinically significant bile leak. The 30-day postoperative mortality was zero. CONCLUSIONS: Use of the Gyrus open forceps appears to be a safe and efficient manner of hepatic parenchymal transection which allows rapid transection with acceptable blood loss, a low rate of perioperative transfusion, and minimal postoperative bile leak.

Liver transplant for hepatitis C virus: effect of using older donor grafts on short- and medium-term survival.

HYPOTHESIS: Older donor grafts will provide suitable results of liver transplant, even in recipients with hepatitis C virus (HCV). Although HCV remains the leading indication for liver transplant in adults in the United States, it is associated with HCV recurrence, increased graft loss, and reduced survival. In addition, recent studies suggest that the use of older donors in recipients with HCV is associated with significantly worsened short- and long-term survival. DESIGN: Prospective database analysis. SETTING: Washington University School of Medicine. PATIENTS: Between January 1, 1997, and June 30, 2006, a total of 579 liver transplants were performed. Ninety pediatric transplants were excluded. Of the remaining 489 adult patients (84.5%), 187 (38.2%) had HCV and 302 (61.8%) had other indications. MAIN OUTCOME MEASURES: Patient and graft survival, recurrence of HCV, and need for and results of retransplant. RESULTS: At 1, 3, and 5 years, overall patient survival was 88.1%, 78.3%, and 69.2%, respectively, and graft survival was 85.6%, 75.6%, and 65.6%, respectively, in patients with HCV. There was no significant difference in patient or graft survival between patients with and those without HCV. Recurrent HCV with clinically significant disease was 20% at 1 year and 62% at 10 years. Seventy-two patients received transplants from donors 60 years or older (24 of 187 [12.8%] with HCV and 48 of 302 [15.9%] without HCV). No difference was demonstrated in short- or medium-term patient or graft survival in recipients of grafts from older donors. CONCLUSION: The increasing use of marginal donors, including carefully selected older donors, does not seem to adversely affect short- or medium-term results and may be a source of additional organs for expanding liver transplant waiting lists.