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

Role of yttrium-90 selective internal radiation therapy in the treatment of liver-dominant metastatic colorectal cancer: An evidence-based expert consensus algorithm

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments)

Economic evaluation of the specialized donor care facility for thoracic organ donor management

Background: Over the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown. Methods: We performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.S. transplant centers over a 2-year study period. In this analysis, we utilized nationwide data from the Scientific Registry of Transplant Recipients and controlled for donor characteristics and patterns of organ sharing across the nation\u27s organ procurement organizations (OPOs). Subgroup analysis was performed to determine the impact of the SDCF model on thoracic organ transplants. Results: A total of 38,944 organ transplants were performed in the U.S. during the study period from 13,539 donors with an observed total organ cost of $1.36 billion. If every OPO assumed the cost and effectiveness of the SDCF model, a predicted 39,155 organ transplants (+211) would have been performed with a predicted total organ cost of$1.26 billion (-$100 million). Subgroup analysis of thoracic organs revealed that the SDCF model would lead to a predicted 156 additional transplants with a cost saving of$24.6 million. Conclusions: The U.S. SDCF model may be a less costly and more effective means of multi-organ donor management, particularly for thoracic organ donors, compared to the conventional hospital-based model

Utility of the Gyrus open forceps in hepatic parenchymal transection

AbstractObjectiveThis study aimed to evaluate if the Gyrus open forceps is a safe and efficient tool for hepatic parenchymal transection.BackgroundBlood 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.MethodsWe 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.ResultsOf 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 220min (range 97–398min). Inflow occlusion was required in nine patients (19%) for a median time of 12min (range 3–30min). Median total estimated blood loss was 400ml (range 10–2000ml) 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.ConclusionsUse 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

MR-guided radiation therapy with concurrent gemcitabine / nab-paclitaxel chemotherapy in inoperable pancreatic cancer: a TITE-CRM phase I trial

BACKGROUND: Ablative radiation therapy for borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) may limit concurrent chemotherapy dosing and usually is only safely deliverable to tumors distant from gastrointestinal organs. MR-guided radiation therapy (MRgRT) may safely permit radiation and chemotherapy dose escalation. METHODS: We conducted a single-arm phase I study to determine the maximum tolerated dose (MTD) of ablative hypofractionated radiation with full-dose gemcitabine/nab-paclitaxel in patients with BR/LA-PDAC. Patients were treated with gemcitabine/nab-paclitaxel (1000/125 mg/m(2)) x 1c then concurrent gemcitabine/nab-paclitaxel and radiation. Gemcitabine/nab-paclitaxel and radiation doses were escalated per time-to-event continual reassessment method from 40-45 Gy / 25 fxs with chemotherapy (600-800/75 mg/m(2)) to 60-67.5 Gy / 15 fractions and concurrent gemcitabine/nab-paclitaxel (1000/100 mg/m(2)). The primary endpoint was MTD of radiation as defined by 60-day dose limiting toxicity (DLT). DLT was treatment-related G5, G4 hematologic or G3 gastrointestinal requiring hospitalization \u3e3 days. Secondary endpoints included resection rates, local progression free survival (LPFS), distant metastasis free survival (DMFS), and overall survival (OS). RESULTS: Thirty patients enrolled (3/2015-2/2019), with 26 evaluable patients (2 progressed before radiation, 1 determined ineligible for radiation during planning, 1 withdrew consent). One DLT was observed. The DLT rate was 14.1% [3.3%-24.9%] with a maximum tolerated dose of gemcitabine/nab-paclitaxel (1000/100 mg/m(2)) and 67.5 Gy / 15 fractions. At a median follow-up of 40.6 months for living patients the median OS was 14.5 months (95% CI, 10.9-28.2 months). The median OS for patients with ECOG 0 and CA 19-9 \u3c90 were 34.1 (95% CI, 13.6-54.1) and 43.0 (95% CI, 8.0-not reached) months, respectively. 2-year LPFS and DMFS were 85% (95% CI, 63-94%) and 57% (95% CI, 34-73%), respectively. CONCLUSIONS: Full-dose gemcitabine/nab-paclitaxel with ablative MRgRT dosing is safe in patients with BR/LA-PDAC, with promising LPFS and DMFS. CLINICALTRIALS: gov NCTXXXXXXXX