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1.
Eur Radiol ; 34(4): 2374-2383, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37812295

ABSTRACT

OBJECTIVES: To evaluate safety and effectiveness of selective internal radiation therapy (SIRT) using yttrium-90 for localized and locally advanced intrahepatic cholangiocarcinoma (iCCA). METHODS: A retrospective review was performed of patients with localized iCCA treated with SIRT at a single institution. Overall survival (OS), local tumor response, progression-free survival (PFS), and toxicity were collected. Stratified analysis was performed based on surgical resection. Predictor analysis of OS was performed using the Fine-Grey regression analysis model with patients bridged to surgery regarded as competing events. RESULTS: A total of 28 consecutive patients with localized iCCA were treated with a total of 38 sessions of SIRT (17 segmental, 13 lobar, and 8 combined deliveries) and a mean dominant target dose per session of 238.4 ± 130.0 Gy. The cumulative radiologic response rate was 16/28 (57.1%) with a median PFS of 265 days. Median survival time (MST) was 22.9 months for the entire cohort with 1-year and 3-year survival of 78.4% and 45.1%, respectively. Ten patients (34.5%) were downstaged to surgical intervention (7 resection, 3 transplant) and showed longer OS (p = 0.027). The 1-year and 3-year OS for patients who received surgery were 100% and 62.5% (95% CI: 14.2-89.3%), respectively. Age (p = 0.028), Eastern Cooperative Oncology Group performance status (p = 0.030), and objective radiologic response (p=0.014) are associated with OS. Two ≥grade 3 hyperbilirubinemia, anemia, and one pleuro-biliary fistula occurred post-SIRT. CONCLUSIONS: SIRT for localized iCCA is safe and effective in achieving radiological response, downstaging to surgery and transplant, and resulting in pathologic necrosis. CLINICAL RELEVANCE STATEMENT: Selective internal radiation therapy should be considered for patients with localized and locally advanced intrahepatic cholangiocarcinoma. KEY POINTS: • The effectiveness of radioembolization for intrahepatic cholangiocarcinoma (iCCA) can be underestimated given the inclusion of extrahepatic disease. • Radioembolization is safe and effective for local and locally advanced iCCA. Age, Eastern Cooperative Oncology Group performance status, and radiologic response are associated with survival. • Radioembolization should be considered for patients with localized and locally advanced iCCA.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Liver Neoplasms , Humans , Microspheres , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/radiotherapy , Yttrium Radioisotopes/therapeutic use , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/radiotherapy , Bile Duct Neoplasms/pathology , Retrospective Studies , Treatment Outcome , Liver Neoplasms/pathology
2.
J Vasc Interv Radiol ; 35(7): 989-997.e2, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38490364

ABSTRACT

PURPOSE: To assess the safety and effectiveness of using modified radiation lobectomy (mRL) to treat primary hepatic tumors located in the right hepatic lobe (Segments V-VIII) and to determine future liver remnant (FLR) hypertrophy. MATERIALS AND METHODS: A retrospective review was performed at a single institution to include 19 consecutive patients (7 females, 12 males) who underwent single-session mRL for right-sided primary hepatic tumors: 15 received segmentectomy plus lobectomy (segmental dose of >190 Gy and lobar dose of >80 Gy); 4 were treated with the double-segmental approach (dominant segments of >190 Gy and nondominant segments of >80 Gy). Treated tumors included 13 hepatocellular carcinoma (HCC), 4 cholangiocarcinoma (CCA), and 2 mixed-type HCC-CCA with a median dominant tumor size of 5.3 cm (interquartile range [IQR], 3.7-7.3 cm). FLR of the left hepatic lobe was measured at baseline, T1 (4-8 weeks), T2 (2-4 months), T3 (4-6 months), and T4 (9-12 months). RESULTS: Objective tumor response and tumor control were achieved in 17 of the 19 (89.5%) and 18 of the 19 (94.7%) patients, respectively. FLR hypertrophy was observed at T1 (median, 47.8%; P = .025), T2 (median, 48.4%; P = .012), T3 (median, 50.4%; P = .015), and T4 (median, 59.1%; P < .001). Patients without cirrhosis demonstrated greater hypertrophy by 6 months (median, 55.8% vs 47.2%; P = .031). One patient developed a Grade 3 adverse event (ascites requiring paracentesis) at 1-month follow-up. Grade ≥2 serum toxicities were associated with worse baseline Child-Pugh Score, serum albumin, and total bilirubin (P < .05). Among 7 patients who underwent neoadjuvant mRL, 2 underwent resection and 1 received liver transplant. CONCLUSIONS: mRL appears safe and effective for treatment of right-sided primary hepatic tumors with the benefit of promoting FLR hypertrophy.


Subject(s)
Carcinoma, Hepatocellular , Embolization, Therapeutic , Hepatectomy , Liver Neoplasms , Humans , Male , Female , Liver Neoplasms/radiotherapy , Liver Neoplasms/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Retrospective Studies , Middle Aged , Aged , Treatment Outcome , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Hepatectomy/adverse effects , Embolization, Therapeutic/adverse effects , Cholangiocarcinoma/radiotherapy , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/surgery , Cholangiocarcinoma/pathology , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/adverse effects , Time Factors , Tumor Burden , Bile Duct Neoplasms/radiotherapy , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/surgery , Yttrium Radioisotopes/administration & dosage , Yttrium Radioisotopes/adverse effects , Hypertrophy , Adult , Liver Regeneration
3.
J Vasc Interv Radiol ; 34(4): 702-709, 2023 04.
Article in English | MEDLINE | ID: mdl-36521794

ABSTRACT

PURPOSE: To determine the safety and effectiveness of yttrium-90 transarterial radioembolization (TARE) combined with systemic gemcitabine, cisplatin, and capecitabine for the first-line treatment of locally advanced intrahepatic cholangiocarcinoma (iCCA). MATERIALS AND METHODS: Data of 13 patients with treatment-naïve, locally advanced iCCA treated with a downstaging protocol using gemcitabine, cisplatin, TARE, and capecitabine were retrospectively reviewed. Overall survival (OS), local tumor response (modified Response Evaluation Criteria in Solid Tumors), progression-free survival (PFS), technical adverse events, and toxicity were measured. RESULTS: Calculated from the time of diagnosis, the median OS was 29 months (95% confidence interval [CI], 15 to not reached), with a 1-year OS of 84.6% (95% CI, 52.2%-95.9%) and 2-year OS of 52.9% (95% CI, 20.3%-77.5%). The median OS values were 24 months (95% CI, 8 to not reached) and 21 months (95% CI, 5 to not reached) from the time of initial cycle of chemotherapy and TARE, respectively. Patients who were downstaged to surgery (n = 7, 53.8%) had a more favorable OS (median OS, not reached vs 15 months; P = .0221). Complete and partial radiologic responses were achieved in 5 (38.5%) and 6 (46.2%) patients, respectively. The median PFS was 13 months (95% CI, 12 to not reached). Although no serum toxicity with Grade >2 occurred within 3 months after TARE, 1 patient was no longer a surgical candidate given suboptimal nutrition status despite successful downstage on imaging studies. Two patients required a reduced dose or delay of post-TARE chemotherapy. CONCLUSIONS: First-line combination therapy with TARE and systemic gemcitabine, cisplatin, and capecitabine is an effective treatment with an acceptable safety profile for iCCA with a high rate of downstaging to resection.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Gemcitabine , Capecitabine/adverse effects , Cisplatin/adverse effects , Retrospective Studies , Yttrium Radioisotopes , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/therapy , Treatment Outcome , Bile Ducts, Intrahepatic , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/therapy
4.
J Vasc Interv Radiol ; 34(11): 1970-1976.e1, 2023 11.
Article in English | MEDLINE | ID: mdl-37532096

ABSTRACT

Radiation segmentectomy with a dose of >190 Gy using yttrium-90 (90Y) glass microspheres for intrahepatic cholangiocarcinoma (iCCA) has been shown to be safe and effective. The present study further increased the dose to >400 Gy for treatment of iCCA as complete pathologic necrosis has been shown in hepatocellular carcinoma using this ablative approach. A total of 10 patients with 13 tumors (median size, 5.3 cm; range, 1.5-13.6 cm) at a single institution underwent >400-Gy segmental radioembolization. Objective response was achieved in all tumors (13 of 13, 100%). One patient developed a Grade 3 or greater major adverse event (stroke and hepatic decompensation). One patient was bridged to transplant (>95% pathologic necrosis), whereas another underwent resection (>99% necrosis). Contralateral hypertrophy was observed in 6 out of 6 patients treated with modified lobectomy dosing, with a functional liver reserve increase from a median of 31.5% to 57.1%. The present report suggests that segmental transarterial radioembolization with >400 Gy is feasible in terms of safety and effectiveness for treating iCCA.


Subject(s)
Bile Duct Neoplasms , Carcinoma, Hepatocellular , Cholangiocarcinoma , Embolization, Therapeutic , Liver Neoplasms , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapy , Liver Neoplasms/drug therapy , Microspheres , Carcinoma, Hepatocellular/pathology , Yttrium Radioisotopes/adverse effects , Embolization, Therapeutic/adverse effects , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/radiotherapy , Necrosis/chemically induced , Necrosis/drug therapy , Bile Ducts, Intrahepatic , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/radiotherapy , Treatment Outcome , Retrospective Studies
5.
Ann Surg ; 275(1): 166-174, 2022 01 01.
Article in English | MEDLINE | ID: mdl-32224747

ABSTRACT

OBJECTIVE: Evaluating the perioperative outcomes of minimally invasive (MIV) donor hepatectomy for adult live donor liver transplants in a large multi-institutional series from both Eastern and Western centers. BACKGROUND: Laparoscopic liver resection has become standard practice for minor resections in selected patients in whom it provides reduced postoperative morbidity and faster rehabilitation. Laparoscopic approaches in living donor hepatectomy for transplantation, however, remain controversial because of safety concerns. Following the recommendation of the Jury of the Morioka consensus conference to address this, a retrospective study was designed to assess the early postoperative outcomes after laparoscopic donor hepatectomy. The collective experience of 10 mature transplant teams from Eastern and Western countries was reviewed. METHODS: All centers provided data from prospectively maintained databases. Only left and right hepatectomies performed using a MIV technique were included in this study. Primary outcome was the occurrence of complications using the Clavien-Dindo graded classification and the Comprehensive Complication Index during the first 3 months. Logistic regression analysis was used to identify risk factors for complications. RESULTS: In all, 412 MIV donor hepatectomies were recorded including 164 left and 248 right hepatectomies. Surgical technique was either pure laparoscopy in 175 cases or hybrid approach in 237. Conversion into standard laparotomy was necessary in 17 donors (4.1%). None of the donors died. Also, 108 experienced 121 complications including 9.4% of severe (Clavien-Dindo 3-4) complications. Median Comprehensive Complication Index was 5.2. CONCLUSIONS: This study shows favorable early postoperative outcomes in more than 400 MIV donor hepatectomy from 10 experienced centers. These results are comparable to those of benchmarking series of open standard donor hepatectomy.


Subject(s)
Hepatectomy/methods , Laparoscopy/methods , Liver Transplantation , Living Donors , Tissue and Organ Harvesting/methods , Adolescent , Adult , Aged , Carcinoma, Hepatocellular/surgery , Conversion to Open Surgery , Female , Hepatectomy/adverse effects , Hepatitis, Viral, Human/surgery , Humans , Laparoscopy/adverse effects , Liver Neoplasms/surgery , Male , Middle Aged , Outcome Assessment, Health Care , Postoperative Complications , Retrospective Studies , Tissue and Organ Harvesting/adverse effects , Young Adult
6.
Hepatology ; 73(3): 998-1010, 2021 03.
Article in English | MEDLINE | ID: mdl-32416631

ABSTRACT

BACKGROUND AND AIMS: Radioembolization (yttrium-90 [Y90]) is used in hepatocellular carcinoma (HCC) as a bridging as well as downstaging liver-directed therapy to curative liver transplantation (LT). In this study, we report long-term outcomes of LT for patients with HCC who were bridged/downstaged by Y90. APPROACH AND RESULTS: Patients undergoing LT following Y90 between 2004 and 2018 were included, with staging by United Network for Organ Sharing (UNOS) tumor-node-metastasis criteria at baseline pre-Y90 and pre-LT. Post-Y90 toxicities were recorded. Histopathological data of HCC at explant were recorded. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS), disease-specific mortality (DSM), and time-to-recurrence, were reported. Time-to-endpoint analyses were estimated using Kaplan-Meier. Univariate and multivariate analyses were performed using a log-rank test and Cox proportional-hazards model, respectively. During the 15-year period, 207 patients underwent LT after Y90. OS from LT was 12.5 years, with a median time to LT of 7.5 months [interquartile range, 4.4-10.3]. A total of 169 patients were bridged, whereas 38 were downstaged to LT. Respectively, 94 (45%), 60 (29%), and 53 (26%) patients showed complete, extensive, and partial tumor necrosis on histopathology. Three-year, 5-year, and 10-year OS rates were 84%, 77%, and 60%, respectively. Twenty-four patients developed recurrence, with a median RFS of 120 (95% confidence interval, 69-150) months. DSM at 3, 5, and 10 years was 6%, 11%, and 16%, respectively. There were no differences in OS/RFS for patients who were bridged or downstaged. RFS was higher in patients with complete/extensive versus partial tumor necrosis (P < 0.0001). For patients with UNOS T2 treated during the study period, 5.2% dropped out because of disease progression. CONCLUSIONS: Y90 is an effective treatment for HCC in the setting of bridging/downstaging to LT. Patients who achieved extensive or complete necrosis had better RFS, supporting the practice of neoadjuvant treatment before LT.


Subject(s)
Brachytherapy/methods , Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Liver Transplantation , Neoadjuvant Therapy/methods , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Liver Transplantation/mortality , Male , Middle Aged , Proportional Hazards Models , Survival Analysis , Yttrium Radioisotopes
7.
Clin Transplant ; 36(4): e14586, 2022 04.
Article in English | MEDLINE | ID: mdl-35041226

ABSTRACT

BACKGROUND: Until recently, combined heart-liver-kidney transplantation was considered too complex or too high-risk an option for patients with end-stage heart failure who present with advanced liver and kidney failure as well. AIMS: The objective of this paper is to present our institution's best practices for successfully executing this highly challenging operation. At our institution, referral patterns are most often initiated through the cardiac team. RESULTS: Determinants of successful outcomes include diligent multidisciplinary patient selection, detailed perioperative planning, and choreographed care transition and coordination among all transplant teams. The surgery proceeds in three distinct phases with three different teams, linked seamlessly in planned handoffs. The selection and perioperative care are executed with determined collaboration of all of the invested care teams. CONCLUSIONS: Combined heart-liver-kidney transplantation can be successfully done by careful selection, coordination, and execution.


Subject(s)
Heart Transplantation , Kidney Transplantation , Liver Transplantation , Heart Transplantation/adverse effects , Humans , Liver , Liver Transplantation/adverse effects , Retrospective Studies
8.
HPB (Oxford) ; 24(7): 1007-1018, 2022 07.
Article in English | MEDLINE | ID: mdl-35012876

ABSTRACT

BACKGROUND: Transarterial radioembolization (TARE) with yttrium-90 (90Y) glass microspheres is an efficacious option for converting appropriately selected patients with borderline-resectable hepatocellular carcinoma (HCC) to surgical candidacy. METHODS: In 2018 and 2019, a diverse multidisciplinary group of surgical and interventional experts with experience using 90Y for downstaging and bridging to liver transplant convened to review peer-reviewed literature and personal experience in the use of 90Y to convert borderline resectable liver cancer patients to surgical candidacy. The working group included surgical oncologists specializing in liver cancer, liver transplant surgeons with experience in complex hepatobiliary surgery, and interventional radiologists with experience using 90Y. RESULTS: This document presents expert recommendations based upon the group's experience and consensus. CONCLUSIONS: By combining related evidence from the literature with expert experiences with TARE in surgical candidates, these recommendations aim to demonstrate the safety, efficacy, and feasibility of TARE in converting borderline-resectable patients to surgical options. The document also addresses the concerns about potential complications associated with TARE during the surgical intervention.


Subject(s)
Brachytherapy , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Embolization, Therapeutic , Liver Neoplasms , Liver Transplantation , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/surgery , Embolization, Therapeutic/adverse effects , Humans , Liver Neoplasms/radiotherapy , Liver Neoplasms/surgery , Yttrium Radioisotopes/adverse effects
9.
Am J Transplant ; 21(5): 1838-1847, 2021 05.
Article in English | MEDLINE | ID: mdl-33107180

ABSTRACT

COVID-19 has profoundly affected the American health care system; its effect on the liver transplant (LT) waitlist based on COVID-19 incidence has not been characterized. Using SRTR data, we compared observed LT waitlist registrations, waitlist mortality, deceased donor LTs (DDLT), and living donor LTs (LDLT) 3/15/2020-8/31/2020 to expected values based on historical trends 1/2016-1/2020, stratified by statewide COVID-19 incidence. Overall, from 3/15 to 4/30, new listings were 11% fewer than expected (IRR = 0.84 0.890.93 ), LDLTs were 49% fewer (IRR = 0.37 0.510.72 ), and DDLTs were 9% fewer (IRR = 0.85 0.910.97 ). In May, new listings were 21% fewer (IRR = 0.74 0.790.84 ), LDLTs were 42% fewer (IRR = 0.39 0.580.85 ) and DDLTs were 13% more (IRR = 1.07 1.151.23 ). Centers in states with the highest incidence 3/15-4/30 had 59% more waitlist deaths (IRR = 1.09 1.592.32 ) and 34% fewer DDLTs (IRR = 0.50 0.660.86 ). By August, waitlist outcomes were occurring at expected rates, except for DDLT (13% more across all incidences). While the early COVID-affected states endured major transplant practice changes, later in the pandemic the newly COVID-affected areas were not impacted to the same extent. These results speak to the adaptability of the transplant community in addressing the pandemic and applying new knowledge to patient care.


Subject(s)
COVID-19 , Liver Transplantation/statistics & numerical data , Humans , Liver Transplantation/trends , Pandemics , Retrospective Studies , United States/epidemiology , Waiting Lists
10.
Clin Transplant ; 35(4): e14246, 2021 04.
Article in English | MEDLINE | ID: mdl-33555058

ABSTRACT

Adverse clinical outcomes related to SARS-CoV-2 infection among liver transplant (LTx) recipients remain undefined. We performed a meta-analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID-19. A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines. Twelve studies comprising 517 hospitalized LTx recipients with COVID-19 were analyzed. Common presenting symptoms were fever (71%), cough (62%), dyspnea (48%), and diarrhea (28%). Approximately 77% (95% CI, 61%-93%) of LTx recipients had a history of liver cirrhosis. The most prevalent comorbidities were hypertension (55%), diabetes (45%), and cardiac disease (21%). In-hospital mortality was 20% (95% CI, 13%-28%) and rose to 41% (95% CI, 19%-63%) (P < 0.00) with ICU admission. Additional subgroup analysis demonstrated a higher mortality risk in the elderly (>60-65 years) (OR 4.26; 95% CI, 2.14-8.49). There was no correlation in respect to sex or time since transplant. In summary, LTx recipients with COVID-19 had a high prevalence of dyspnea and gastrointestinal symptoms. In-hospital mortality was comparable to non-transplant populations with similar comorbidities but appeared to be less than what is reported elsewhere for cirrhotic patients (26%-40%). Importantly, the observed high case fatality in the elderly could be due to age-associated comorbidities.


Subject(s)
COVID-19/epidemiology , Liver Transplantation , Transplant Recipients , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/surgery , Female , Hospitalization , Humans , Liver Neoplasms/surgery , Male , Middle Aged
11.
Clin Transplant ; 34(12): e14086, 2020 12.
Article in English | MEDLINE | ID: mdl-32918766

ABSTRACT

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19-positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.


Subject(s)
COVID-19/prevention & control , Health Services Accessibility/trends , Organ Transplantation/trends , Organizational Policy , Practice Patterns, Physicians'/trends , Telemedicine/trends , Tissue and Organ Procurement/trends , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/etiology , COVID-19 Testing , Clinical Decision-Making , Follow-Up Studies , Health Care Surveys , Health Services Accessibility/organization & administration , Humans , Incidence , Infection Control/methods , Infection Control/trends , Organ Transplantation/methods , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Postoperative Complications/virology , Tissue and Organ Procurement/organization & administration , United States/epidemiology
12.
J Card Surg ; 35(6): 1357-1359, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32333435

ABSTRACT

We report a case of successful heart and liver transplantation requiring intraoperative extracorporeal membrane oxygenation (ECMO) for primary cardiac allograft dysfunction in a patient with Fontan failure. A successful outcome for both the heart and the liver can be achieved with the timely management of ECMO support. In describing our experiences treating a Fontan patient requiring multiorgan transplantation, we have shown that challenging cases such as this one can have successful outcomes if multidisciplinary collaborations and proper treatment strategies are utilized at the optimal timing, along with family support and patient cooperation.


Subject(s)
Extracorporeal Membrane Oxygenation , Fontan Procedure , Heart Transplantation , Intraoperative Care , Liver Transplantation , Primary Graft Dysfunction/therapy , Adult , Allografts , Female , Humans , Interdisciplinary Communication , Patient Compliance , Treatment Failure , Treatment Outcome
13.
Liver Transpl ; 24(10): 1470-1475, 2018 10.
Article in English | MEDLINE | ID: mdl-30080954

ABSTRACT

Liver transplantation was made a reality through the bravery, innovation, and persistence of Dr. Thomas Starzl. His death in 2017, at the age of 90, makes us pause to consider how far the field has come since its inception by this remarkable pioneer. It also is an opportunity to evaluate the continued novel innovations which contribute to the growth and potential for liver transplantation in the future. The liver transplant community in 2017 continued to be most significantly challenged by an overwhelming disparity between the need for liver transplant and the shortage of donor organs. The many ways in which this critical shortage are being addressed are examined in this article. The continued debate about equitable and efficacious organ allocation, "the liver wars," has dominated much of the recent past, while efforts to optimize current organ availability have also been aggressively pursued. Efforts to optimize the use of marginal and expanded criteria organs have escalated in recent years and have been accompanied by rigorous scientific evaluation. The ongoing opioid epidemic, combined with the approval and availability of highly effective hepatitis C treatment options, has allowed the increased use of HCV positive organs in HCV positive and negative recipients. Machine perfusion, both cold and warm, has moved solidly into the liver transplant world potentiating optimization of marginal donors and also offering potential modulation of liver grafts (ie, gene therapy, stem cell therapy, and defatting). Finally, pharmacological and mechanical interventions in DCD procurement techniques have contributed to improved outcomes in DCD transplants. All of these are explored in this article as a tribute to innovative spirit of Dr. Starzl and his continued impact on liver transplant today.


Subject(s)
End Stage Liver Disease/surgery , Liver Transplantation/trends , Tissue and Organ Procurement/standards , End Stage Liver Disease/diagnosis , End Stage Liver Disease/mortality , History, 20th Century , History, 21st Century , Humans , Liver Transplantation/history , Liver Transplantation/methods , Liver Transplantation/standards , Organ Preservation/methods , Organ Preservation/trends , Severity of Illness Index , Tissue and Organ Procurement/trends , Treatment Outcome , United States/epidemiology , Waiting Lists/mortality
15.
J Vasc Interv Radiol ; 29(11): 1502-1510.e1, 2018 11.
Article in English | MEDLINE | ID: mdl-30268638

ABSTRACT

PURPOSE: To longitudinally study clinical and radiologic outcomes of patients with hepatocellular carcinoma (HCC) who underwent yttrium-90 transarterial radioembolization (TARE) as a bridge to surgical resection. MATERIALS AND METHODS: TARE was performed in 31 patients with HCC before resection. Of patients, 25 underwent major hepatic resection (16 received right hepatectomy and 9 received trisegmentectomy), and 6 underwent partial hepatectomy. Clinical outcomes after TARE and after resection were recorded. Future liver remnant (FLR) was calculated before and after TARE, and actual liver remnant volume was calculated after resection. Radiologic response after TARE and pathologic necrosis were assessed. Overall and recurrence-free survivals after resection were estimated. RESULTS: Median time between TARE and resection was 2.9 months (interquartile range [IQR]: 2-5 months). Median FLR hypertrophy after TARE (and before resection) was 23.3% (IQR:10%-48%) for patients who had radiation lobectomy and 9% (IQR: 6%-25%) for patients who had radiation segmentectomy (P = .037). Median augmented hypertrophy of the liver remnant 3 months after resection was 72% (IQR:45%-88%) in patients who had radiation lobectomy and 94% (IQR: 72%-146%) in patients who had radiation segmentectomy. Complete, 50%-99%, and < 50% pathologic tumor necrosis was identified in 14 (45%), 10 (32%), and 7 (23%) tumors. Disease control was achieved in all 31 patients. Survival rates at 1 and 3 years were 96% and 86%, respectively. Median recurrence-free survival was 34.2 months (95% confidence interval,18.7-34.2). CONCLUSIONS: TARE can serve as a safe bridge to resection providing FLR hypertrophy and disease control.


Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/surgery , Embolization, Therapeutic/methods , Hepatectomy , Liver Neoplasms/radiotherapy , Liver Neoplasms/surgery , Radiopharmaceuticals/administration & dosage , Yttrium Radioisotopes/administration & dosage , Adult , Aged , Biopsy , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/secondary , Embolization, Therapeutic/adverse effects , Female , Hepatectomy/adverse effects , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Regeneration , Magnetic Resonance Imaging , Male , Middle Aged , Necrosis , Neoplasm Recurrence, Local , Progression-Free Survival , Radiopharmaceuticals/adverse effects , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Yttrium Radioisotopes/adverse effects
17.
Gastroenterology ; 151(6): 1155-1163.e2, 2016 12.
Article in English | MEDLINE | ID: mdl-27575820

ABSTRACT

BACKGROUND & AIMS: Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. METHODS: From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child-Pugh A) or cTACE (n = 21; 71% Child-Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan-Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. RESULTS: Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P = .0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027-0.557; P = .007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P = .031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P < .001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P = .433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3-not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4-32.5) (P = .99). CONCLUSIONS: In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Yttrium Radioisotopes/therapeutic use , Aged , Antineoplastic Agents/therapeutic use , Chemoembolization, Therapeutic/adverse effects , Diarrhea/etiology , Disease Progression , Disease-Free Survival , Ethiodized Oil/therapeutic use , Female , Humans , Hypoalbuminemia/etiology , Intention to Treat Analysis , Liver Transplantation , Male , Middle Aged , Necrosis , Neoplasm Staging , Prospective Studies , Survival Rate , Yttrium Radioisotopes/adverse effects
18.
Liver Transpl ; 23(12): 1519-1530, 2017 12.
Article in English | MEDLINE | ID: mdl-28926171

ABSTRACT

Living donor liver transplantation (LDLT) is a technically demanding endeavor, requiring command of the complex anatomy of partial liver grafts. We examined the influence of anatomic variation and reconstruction techniques on surgical outcomes and graft survival in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Data from 272 adult LDLT recipients (2011-2015) included details on anatomic characteristics and types of intraoperative biliary reconstruction. Associations were tested between reconstruction technique and complications, which included first biliary complication (BC; leak, stricture, or biloma) and first vascular complication (VC; hepatic artery thrombosis [HAT] or portal vein thrombosis [PVT]). Time to patient death, graft failure, and complications were estimated using Kaplan-Meier curves and tested with log-rank tests. Median posttransplant follow-up was 1.2 years. Associations were found between the type of biliary reconstruction and the incidence of VC (P = 0.03) and BC (P = 0.05). Recipients with Roux-en-Y hepaticojejunostomy had the highest probability of VC. Recipients with biliary reconstruction involving the use of high biliary radicals on the recipient duct had the highest likelihood of developing BC (56% by 1 year) compared with duct-to-duct (42% by 1 year). In conclusion, the varied surgical approaches in the A2ALL centers offer a novel opportunity to compare disparate LDLT approaches. The choice to use higher biliary radicals on the recipient duct for reconstruction was associated with more BC, possibly secondary to devascularization and ischemia. The use of Roux-en-Y biliary reconstruction was associated with VCs (HAT and PVT). These results can be used to guide biliary reconstruction decisions in the setting of anatomic variants and inform further improvements in LDLT reconstructions. Ultimately, this information may contribute to a lower incidence of technical complications after LDLT. Liver Transplantation 23 1519-1530 2017 AASLD.


Subject(s)
Bile Duct Diseases/epidemiology , Bile Ducts/anatomy & histology , Biliary Tract Surgical Procedures/methods , End Stage Liver Disease/surgery , Liver Transplantation/adverse effects , Plastic Surgery Procedures/methods , Postoperative Complications/epidemiology , Adult , Aged , Anastomosis, Roux-en-Y/adverse effects , Anastomosis, Roux-en-Y/methods , Anatomic Variation , Bile Duct Diseases/etiology , Bile Ducts/pathology , Bile Ducts/surgery , Biliary Tract Surgical Procedures/adverse effects , Cohort Studies , Constriction, Pathologic/epidemiology , Constriction, Pathologic/etiology , Female , Graft Survival , Humans , Incidence , Liver/blood supply , Liver/surgery , Liver Transplantation/methods , Liver Transplantation/statistics & numerical data , Living Donors , Male , Middle Aged , Postoperative Complications/etiology , Prospective Studies , Plastic Surgery Procedures/adverse effects , Thrombosis/epidemiology , Thrombosis/etiology , Treatment Outcome , United States/epidemiology
19.
J Vasc Interv Radiol ; 28(12): 1714-1721.e2, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29050854

ABSTRACT

PURPOSE: To report the final analysis of the safety and efficacy of portal vein (PV) recanalization (PVR) and transjugular intrahepatic portosystemic shunt (TIPS) creation (PVR-TIPS) in patients with PV thrombosis (PVT) in need of liver transplantation. MATERIALS AND METHODS: Sixty-one patients with cirrhosis and PVT underwent PVR-TIPS to improve transplantation candidacy. Median patient age was 58 years (range, 22-75 y), and median pre-TIPS Model for End-Stage Liver Disease score was 14 (range, 7-42). The most common etiologies of cirrhosis were nonalcoholic fatty liver disease in 18 patients (30%) and hepatitis C in 13 patients (21%). Twenty-seven patients (44%) had partial PVT, and 34 patients (56%) had complete thrombosis. Forty-nine patients (80%) had Yerdel grade 2 PVT, and 12 (20%) had Yerdel grade 3 PVT. Twenty-nine patients (48%) had cavernous transformation of the PV. RESULTS: PVR-TIPS was technically successful in 60 of 61 patients (98%). PV/TIPS patency was maintained in 55 patients (92%) at a median follow-up of 19.2 months (range, 0-105.9 mo). Recurrent PV/TIPS thrombosis occurred in 5 patients (8%), all of whom initially presented with complete PVT. The most common adverse events were TIPS stenosis in 13 patients (22%) and transient encephalopathy in 11 patients (18%). Twenty-four patients (39%) underwent transplantation, 23 of whom (96%) received an end-to-end anastomosis. There were no cases of recurrent PVT following transplantation, with a median imaging follow-up of 32.5 months (range, 0.4-75.4 mo). Five-year overall survival rate was 82%. CONCLUSIONS: PVR-TIPS is a safe, effective, and durable treatment option for patients with chronic PVT who need liver transplantation.


Subject(s)
Portal Vein/surgery , Portasystemic Shunt, Transjugular Intrahepatic , Venous Thrombosis/surgery , Adult , Aged , Chronic Disease , Female , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/surgery , Liver Transplantation , Male , Middle Aged , Retrospective Studies , Survival Rate , Treatment Outcome , Venous Thrombosis/etiology
20.
Liver Transpl ; 22(1): 103-10, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26202132

ABSTRACT

Following living donor liver transplantation (LDLT; and unlike deceased donor liver transplantation [DDLT]), the liver must rapidly regenerate, and sometimes segmental graft dysfunction (SGD) is observed. Hepatic regeneration requires substantial de novo lipid synthesis, and we previously reported that expression of lipid-related genes is dysregulated in LDLT. Here, we compare serum lipid measurements in 41 LDLT recipients and 43 DDLT recipients at baseline and at serial posttransplant time points. In addition, we examined whether serum lipid/apolipoprotein (apo) levels correlate with the degree of liver regeneration (measured using percent volume increase [%VI] at 3 months) or SGD in LDLT recipients. In contrast to DDLT, lipid levels declined early after LDLT but returned to baseline by 30 days. The odds ratio (OR) for achieving robust regeneration (>90 %VI) was 2.53 (95% confidence interval [CI], 1.15-5.52) for every 1 mg/dL increase in serum apoE at 30 days. The OR of SGD for every year increase in donor age was 1.19 (95% CI, 1.02-1.39), and 0.61 for every 1 mg/dL increase in serum high-density lipoprotein cholesterol at 7 days (95% CI, 0.34-1.11). No associations were detected between preoperative serum lipids/apos in LDLT donors and SGD or %VI in recipients. In conclusion, we suggest that initiation of regeneration prevents the liver from participating fully in lipid transport and metabolism. Inability to meet systemic metabolic needs may result in compromised liver function and SGD. Certain serum lipid concentrations correlate with extent of liver regeneration and function.


Subject(s)
Apolipoproteins/blood , Liver Regeneration , Liver Transplantation , Living Donors , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Young Adult
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