Constance M. Mobley

Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series

BACKGROUND At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy. METHODS In this prospective case-series, patients with locally advanced, unresectable intrahepatic cholangiocarcinoma, without extrahepatic disease or vascular involvement, were treated at a single liver transplant centre according to a non-randomised, centre-approved clinical management protocol with neoadjuvant chemotherapy followed by liver transplantation. Neoadjuvant therapy consisted of gemcitabine-based chemotherapy, such as gemcitabine-cisplatin or gemcitabine-capecitabine, with second-line or third-line therapies given per institutional standards. Patients with a minimum of 6 months of radiographic response or stability were listed for liver transplantation. The primary endpoints were overall survival and recurrence-free survival after liver transplantation, assessed with Kaplan-Meier analysis. This report includes interim data from the initial case-series treated under this ongoing clinical management protocol, censored on Dec 1, 2017. FINDINGS Between Jan 1, 2010, and Dec 1, 2017, 21 patients were referred for evaluation and 12 patients were accepted, of whom six patients have undergone liver transplantation for intrahepatic cholangiocarcinoma. Three patients received livers from extended criteria deceased donors that would otherwise have been discarded, two from domino living donors, and one from a standard criteria liver donor. Median duration from diagnosis to transplantation was 26 months (IQR 17-33) and median follow-up from transplantation was 36 months (29-51). All patients received neoadjuvant chemotherapy while awaiting liver transplantation. Overall survival was 100% (95% CI 100-100) at 1 year, 83·3% (27·3-97·5) at 3 years, and 83·3% (27·3-97·5) at 5 years. Three patients developed recurrent disease at a median of 7·6 months (IQR 5·8-8·6) after transplantation, with 50% (95% CI 11·1-80·4) recurrence-free survival at 1, 3, and 5 years. Adverse events after liver transplantation included one patient with postoperative ileus (grade 3) and one patient with acute kidney injury requiring temporary dialysis (grade 4). INTERPRETATION Selected patients with locally advanced intrahepatic cholangiocarcinoma who show pre-transplant disease stability on neoadjuvant therapy might benefit from liver transplantation. FUNDING None.

Impact of Pretransplant Bridging Locoregional Therapy for Patients with Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients from the US Multicenter HCC Transplant Consortium

Objective: 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). Summary Background Data: 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. Methods: 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). Results: 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, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), 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, P < 0.001) 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). Conclusions: 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.

Strongyloides stercoralis in solid organ transplantation: early diagnosis gets the worm

Purpose of review Strongyloidiasis is a parasitic infection affecting millions of people worldwide. Complications of infection are strongly associated with alcoholism, immunosuppression, and organ transplantation. Delayed diagnosis results in hyperinfection syndrome and disseminated strongyloidiasis leading to mortality rates approaching 80%. Early detection, and prevention of infection and transmission are key to diminish this illness. Recent findings In this review, we cover the basic concepts in immunity, immunosuppression, and disorder necessary for understanding the infectious syndromes associated with Strongyloides stercoralis infection. Focused discussion on donor-derived transmission and recipient risk in solid organ transplantation is presented. Current methodology for diagnosis, screening algorithms, and treatment are also reviewed. Summary Strongyloidiasis complicated by hyperinfection and dissemination remains associated with a poor outcome. The poor outcome pleads for a high level of suspicion and aggressive treatment in at-risk patients. As the population of transplant patients continues to increase, the risk of infection also increases, compelling us to address this highly fatal infectious complication in solid organ transplantation (SOT). Here we review the pathology, immunology, diagnosis, and treatment of strongyloides infection in the immunosuppressed SOT population.

Portable device for the analysis of liver function: a boon to liver surgery and critical care

Liver biology, liver disease and its management present a myriad of challenges to clinicians. Difficulties arise in determining liver functional capacity, which must be effectively measured in a quantitative reproducible manner. Measurement of indocyanine green (ICG) clearance, an exceptional tool that has been used for decades to assess liver function, has traditionally been cumbersome to perform. New technology now allows for rapid and noninvasive determination of ICG clearance making it clinically accessible. This adds ICG clearance measurement to the armamentarium of physiologic monitors that could be routinely used in the evaluation of patients undergoing liver surgery or in the intensive care setting.

Management of the critically ill liver failure patient: Surpassing our limitations to reach transplantation

PURPOSE OF REVIEW Patients with liver failure and liver-related diseases are often critically ill. Here, we review advances in donor organ management, tools for patient selection and highlight ICU management of liver transplant (LT) recipients. A focused discussion on the impact each of these factors have on critical care management of liver failure patients is presented. RECENT FINDINGS Artificial liver assist devices to increase donor organ utilization are broadening the potential for transplantation of critically ill patients. Additionally, prognostication tools continue to improve and identify patients salvageable with transplantation despite severely deranged physiology. Most importantly, early recognition of liver failure combined with proactive critical care management reduces the incidence of failure-to-rescue and increases the likelihood of transplantation. SUMMARY Liver transplantation is often the only hope for cure, and despite the presence of profound physiologic disturbances surgery remains the goal. In this review, we cover topics key in ICU management of LT recipients. A focused discussion on development of artificial liver assist devices to increase donor organs, prognostic scoring systems to define appropriate transplant recipients, critical care management of liver failure physiology, and bridging modalities and supportive measures are presented.