Solid Organ Transplant Recipients Exhibit More TET2-Mutant Clonal Hematopoiesis of Indeterminate Potential Not Driven by Increased Transplantation Risk.

PURPOSE: Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk factor for hematologic malignancy and this study describes the prevalence and patterns of CHIP mutations across several types of solid organ transplants. EXPERIMENTAL DESIGN: We use two national biobank cohorts comprised of >650,000 participants with linked genomic and longitudinal phenotypic data to describe the features of CHIP across 2,610 individuals who received kidney, liver, heart, or lung allografts. RESULTS: We find individuals with an allograft before their biobank enrollment had an increased prevalence of TET2 mutations (OR, 1.90; P = 4.0e-4), but individuals who received transplants post-enrollment had a CHIP mutation spectrum similar to that of the general population, without enrichment of TET2. In addition, we do not observe an association between CHIP and risk of incident transplantation among the overall population (HR, 1.02; P = 0.91). And in an exploratory analysis, we do not find evidence for a strong association between CHIP and rates of transplant complications such as rejection or graft failure. CONCLUSIONS: These results demonstrate that recipients of solid organ transplants display a unique pattern of clonal hematopoiesis with enrichment of TET2 driver mutations, the causes of which remain unclear and are deserving of further study.

Long-Term Physical HRQOL Decreases After Single Lung as Compared With Double Lung Transplantation.

BACKGROUND: Single lung transplantation (SLT) and double lung transplantation (DLT) are associated with differences in morbidity and mortality, although the effects of transplant type on patient-reported outcomes are not widely reported and conclusions have differed. Previous studies compared mean health-related quality of life (HRQOL) scores but did not evaluate potentially different temporal trajectories in the context of longitudinal follow-up. To address this uncertainty, this study was designed to evaluate longitudinal HRQOL after SLT and DLT with the hypothesis that temporal trajectories differ between SLT and DLT. METHODS: Patients transplanted at a single institution were eligible to be surveyed at 1 month, 3 months, 6 months, and then annually after transplant using the Short Form 36 Health Survey, with longitudinal physical component summary (PCS) and mental component summary (MCS) scores as the primary outcomes. Multivariable mixed-effects models were used to evaluate the effects of transplant type and time posttransplant on longitudinal PCS and MCS after adjusting age, diagnosis, rejection, Lung Allocation Score quartile, and intubation duration. Time by transplant type interaction effects were used to test whether the temporal trajectories of HRQOL differ between SLT and DLT recipients. HRQOL scores were referenced to general population norms (range, 40 to 60; mean, 50 ± 10) using accepted standards for a minimally important difference (½ SD, 5 points). RESULTS: Postoperative surveys (n = 345) were analyzed for 136 patients (52% male, 23% SLT, age 52 ± 13 years, LAS 42 ± 12, follow-up 37 ± 29 months [range, 0.6 to 133]) who underwent lung transplantation between 2005 and 2016. After adjusting for model covariates, overall posttransplant PCS scores have a significant downward trajectory (p = 0.015) whereas MCS scores remain stable (p = 0.593), with both averaging within general population norms. The time by transplant type interaction effect (p = 0.002), however, indicate that posttransplant PCS scores of SLT recipients decline at a rate of 2.4 points per year over the total observation period compared to DLT. At approximately 60 months, the PCS scores of SLT recipients, but not DLT recipients, fall below general population norms. CONCLUSIONS: The trajectory of physical HRQOL in patients receiving SLT declines over time compared with DLT, indicating that, in the longer term, SLT recipients are more likely to have physical HRQOL scores that fall substantively below general population norms. Physical HRQOL after 5 years may be a consideration for lung allocation and patient counseling regarding expectations when recommending SLT or DLT.

Patient-reported outcomes in liver transplant recipients with hepatocellular carcinoma.

BACKGROUND: The effect of awarding MELD exception points for hepatocellular carcinoma (HCC) on patient-reported outcomes (PROs) is unknown. We evaluated the physical and mental health-related quality of life (HRQOL) and symptoms of anxiety and depression in liver transplant recipients with HCC compared to patients without HCC. METHODS: The single-center sample measured PROs before and after transplant, which included 1521 multisurvey measurement points among 502 adults (67% male, 28% HCC, follow-up time: <1-131 months). Data were analyzed using multivariable mixed-effects models. RESULTS: Longitudinal PRO values did not differ between persons who received HCC exception points and those who did not have HCC. Patients with HCC who did not receive exception points had reduced physical HRQOL (P=.016), a late decline in mental HRQOL, and delayed reduction in anxiety (time-by-outcome interaction P<.050) compared to patients with HCC who received exception points. CONCLUSION: Transplant recipients who received HCC exception points had PROs that were comparable to those of patients without HCC, and reported better physical HRQOL and reduced symptoms of anxiety compared to patients with HCC who did not receive exception points. These analyses demonstrate the impact of HCC exception points on PROs, and may help inform policy regarding HCC exception point allocation.

Is liver transplantation using organs donated after cardiac death cost-effective or does it decrease waitlist death by increasing recipient death?

OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness in liver transplantation (LT) of utilizing organs donated after cardiac death (DCD) compared with organs donated after brain death (DBD). METHODS: A Markov-based decision analytic model was created to compare two LT waitlist strategies distinguished by organ type: (i) DBD organs only, and (ii) DBD and DCD organs. The model simulated outcomes for patients over 10 years with annual cycles through one of four health states: survival; ischaemic cholangiopathy; retransplantation, and death. Baseline values and ranges were determined from an extensive literature review. Sensitivity analyses tested model strength and parameter variability. RESULTS: Overall survival is decreased, and biliary complications and retransplantation are increased in recipients of DCD livers. Recipients of DBD livers gained 5.6 quality-adjusted life years (QALYs) at a cost of US$69 000/QALY, whereas recipients on the DBD + DCD LT waitlist gained 6.0 QALYs at a cost of US$61 000/QALY. The DBD + DCD organ strategy was superior to the DBD organ-only strategy. CONCLUSIONS: The extension of life and quality of life provided by DCD LT to patients on the waiting list who might otherwise not receive a liver transplant makes the continued use of DCD livers cost-effective.

A cost-effectiveness analysis of early vs late reconstruction of iatrogenic bile duct injuries.

BACKGROUND: Controversy exists regarding the optimal timing of repair after iatrogenic bile duct injuries (BDI). Several studies advocate late repair (≥6 weeks after injury) with mandatory drainage and resolution of inflammation. Others indicate that early repair (<6 weeks after injury) produces comparable or superior clinical outcomes. Additionally, although most studies have reported inferior outcomes with primary surgeon repair, this practice continues. With disparate published recommendations and rising health care costs, decision analysis was used to examine the cost-effectiveness of BDI repair. STUDY DESIGN: A Markov model was developed to evaluate primary surgeon repair (PSR), late repair by a hepatobiliary surgeon (LHBS), and early repair by a hepatobiliary surgeon (EHBS). Baseline values and ranges were collected from the literature. Sensitivity analsyses were conducted to test the strength of the model and variability of parameters. RESULTS: The model demonstrated that EHBS was associated with lower costs, earlier return to normal activity, and better quality of life. Specifically, 1 year after repair, PSR yielded 0.53 quality adjusted life years (QALYs) ($120,000/QALY) and LHBS yielded 0.74 QALYs ($74,000/QALY); EHBS yielded 0.82 QALYs ($48,000/QALY). Sensitivity analyses supported these findings at clinically meaningful probabilities. CONCLUSIONS: This cost-effectiveness model demonstrates that early repair by a hepatobiliary surgeon is the superior strategy for the treatment of BDI in properly selected patients. Although there is little clinical difference between early and late repair, there is a great difference in cost and quality of life. Ideally, costs and quality of life should be considered in decisions regarding strategies of repair of injured bile ducts.

An urban-rural blight? Choledocholithiasis presentation and treatment.

BACKGROUND: Exploration of urban-rural (UR) and regional differences is critical to developing effective healthcare delivery systems. Choledocholithiasis (CDL) remains a common problem with a range of therapeutic options and potentially severe complications. This study evaluated UR and regional differences of CDL presentation and treatment. We hypothesized that UR status contributes to differences in treatment of CDL. METHODS: This study examined patients from the 2007 Healthcare Cost and Utilization Project dataset. Inpatient discharges and interventions for CDL patients were identified. UR and regional designations were determined from National Center for Health Statistics guidelines. Patients with pancreatitis or cholangitis were designated as complicated CDL (cCDL) patients. Interventions for CDL were classified as endoscopic, surgical, or percutaneous. Complex-sample proportion analyses were performed. RESULTS: A total of 111,021 patients with CDL were identified; 81% of these patients lived in urban areas compared with 19% in rural areas; 61% had uncomplicated choledocholithiasis (uCDL) and 39% had cCDL. The overall distribution of uCDL and cCDL did not differ by UR status or region. A higher proportion of rural patients did not receive an intervention 45.1% (95%CI 41.8%-48.4%) versus urban patients 30.5% (28.8%-32.2%), P < 0.05. Interventions for urban patients were more likely endoscopic 87.7% (86.8%-88.6%) compared with rural 82.0% (79.3%-84.7%), P < 0.05. Rural patients were more likely to undergo surgery 10.5% (8.6%-12.4%) than urban patients 4.9% (4.4%-5.4%), P < 0.05. Regional variations did not impact the type of intervention received. CONCLUSION: Rural patients received CDL interventions less often and had a higher proportion of surgical interventions regardless of severity of presentation.

Which is more cost-effective under the MELD system: primary liver transplantation, or salvage transplantation after hepatic resection or after loco-regional therapy for hepatocellular carcinoma within Milan criteria?

OBJECTIVE: The optimal strategy for treating hepatocellular carcinoma (HCC), a disease with increasing incidence, in patients with Child-Pugh class A cirrhosis has long been debated. This study evaluated the cost-effectiveness of hepatic resection (HR) or locoregional therapy (LRT) followed by salvage orthotopic liver transplantation (SOLT) vs. that of primary orthotopic liver transplantation (POLT) for HCC within the Milan Criteria. METHODS: A Markov-based decision analytic model simulated outcomes, expressed in costs and quality-adjusted life years (QALYs), for the three treatment strategies. Baseline parameters were determined from a literature review. Sensitivity analyses tested model strength and parameter variability. RESULTS: Both HR and LRT followed by SOLT were associated with earlier recurrence, decreased survival, increased costs and decreased quality of life (QoL), whereas POLT resulted in decreased recurrence, increased survival, decreased costs and increased QoL. Specifically, HR/SOLT yielded 3.1 QALYs (at US$96 000/QALY) and LRT/SOLT yielded 3.9 QALYs (at US$74 000/QALY), whereas POLT yielded 5.5 QALYs (at US$52 000/QALY). Sensitivity analyses supported these findings at clinically meaningful probabilities. CONCLUSIONS: Under the Model for End-stage Liver Disease (MELD) system, in patients with HCC within the Milan Criteria, POLT increases survival and QoL at decreased costs compared with HR or LRT followed by SOLT. Therefore, POLT is the most cost-effective strategy for the treatment of HCC.

Health insurance status affects staging and influences treatment strategies in patients with hepatocellular carcinoma.

BACKGROUND: Lack of health insurance is associated with poorer outcomes for patients with cancers amenable to early detection. The effect of insurance status on hepatocellular carcinoma (HCC) presentation stage and treatment outcomes has not been examined. We examined the effect of health insurance status on stage of presentation, treatment strategies, and survival in patients with HCC. METHODS: The Tennessee Cancer Registry was queried for patients treated for HCC between January 2004 and December 2006. Patients were stratified by insurance status: (1) private insurance; (2) government insurance (non-Medicaid); (3) Medicaid; (4) uninsured. Logistic, Kaplan-Meier, and Cox models tested the effects of demographic and clinical covariates on the likelihood of having surgical or chemotherapeutic treatments and survival. RESULTS: We identified 680 patients (208 private, 356 government, 75 Medicaid, 41 uninsured). Uninsured patients were more likely to be men, African American, and reside in an urban area (all P < 0.05). The uninsured were more likely to present with stage IV disease (P = 0.005). After adjusting for demographics and tumor stage, Medicaid and uninsured patients were less likely to receive surgical treatment (both P < 0.01) but were just as likely to be treated with chemotherapy (P ≥ 0.243). Survival was significantly better in privately insured patients and in those treated with surgery or chemotherapy (all P < 0.01). Demographic adjusted risk of death was doubled in the uninsured (P = 0.005). CONCLUSIONS: Uninsured patients with HCC are more likely to present with late-stage disease. Although insurance status did not affect chemotherapy utilization, Medicaid and uninsured patients were less likely to receive surgical treatment.

Ciliated hepatic foregut cysts in children.

Ciliated hepatic foregut cyst (CHFC) is a rare foregut developmental malformation usually diagnosed in adulthood; however, rare cases have been reported in the pediatric population. CHFC can transform into a squamous cell carcinoma resulting in death despite surgical resection of the isolated malignancy. We report the presentation, evaluation, and surgical management of a symptomatic 17-year-old girl found to have a 6.5 x 4.5 cm CHFC and suggest that all patients with suspected CHFC undergo prompt evaluation and complete cyst excision.

Implementation of a real-time compliance dashboard to help reduce SICU ventilator-associated pneumonia with the ventilator bundle.

BACKGROUND: Ventilator-associated pneumonia (VAP) causes significant morbidity and mortality in critically ill surgical patients. Recent studies suggest that the success of preventive measures is dependent on compliance with ventilator bundle parameters. HYPOTHESIS: Implementation of an electronic dashboard will improve compliance with the bundle parameters and reduce rates of VAP in our surgical intensive care unit (SICU). DESIGN: Time series analysis of VAP rates between January 2005 and July 2008, with dashboard implementation in July 2007. SETTING: Multidisciplinary SICU at a tertiary-care referral center with a stable case mix during the study period. PATIENTS: Patients admitted to the SICU between January 2005 and July 2008. MAIN OUTCOME MEASURES: Infection control data were used to establish rates of VAP and total ventilator days. For the time series analysis, VAP rates were calculated as quarterly VAP events per 1000 ventilator days. Ventilator bundle compliance was analyzed after dashboard implementation. Differences between expected and observed VAP rates based on time series analysis were used to estimate the effect of intervention. RESULTS: Average compliance with the ventilator bundle improved from 39% in August 2007 to 89% in July 2008 (P < .001). Rates of VAP decreased from a mean (SD) of 15.2 (7.0) to 9.3 (4.9) events per 1000 ventilator days after introduction of the dashboard (P = .01). Quarterly VAP rates were significantly reduced in the November 2007 through January 2008 and February through April 2008 periods (P < .05). For the August through October 2007 and May through July 2008 quarters, the observed rate reduction was not statistically significant. CONCLUSIONS: Implementation of an electronic dashboard improved compliance with ventilator bundle measures and is associated with reduced rates of VAP in our SICU.

Liver transplantation for iatrogenic porta hepatis transection.

Iatrogenic porta hepatis transection is a rare but devastating surgical complication. There are no systematic studies examining the best treatment strategy in patients with this injury. We report two cases of transection of all three portal structures, one during an open right adrenalectomy and another during a laparoscopic cholecystectomy, both of which were transferred to our tertiary care center hours postinjury. Diagnostic imaging and exploration revealed nonsalvageable livers, and both patients underwent total hepatectomies and portocaval shunting. Donor livers were available 12 to 20 hours after United Network for Organ Sharing Status 1 listing and both patients survived their postoperative course with 2- and 6-year follow up to date. Two-stage total hepatectomy with portocaval shunting followed by liver transplantation should be considered for patients presenting with porta hepatis transection.

Improvement of survival with response to neoadjuvant radiation therapy for rectal cancer.

OBJECTIVES: To determine whether patients with a complete or near-complete response to neoadjuvant radiation therapy (XRT) have improved survival compared with those with less of a response and to compare survival between patients with disease downstaged after neoadjuvant XRT and patients with stage I disease undergoing resection alone. DESIGN, SETTING, AND PATIENTS: Retrospective cohort of 10,971 patients (3760 patients with neoadjuvant XRT; 7211 with stage I disease with resection alone) from the Surveillance, Epidemiology, and End Results registry using data from January 1, 1994, through December 31, 2003. MAIN OUTCOME MEASURES: Overall survival and disease-specific survival (DSS) of patients undergoing resection for nonmetastatic rectal adenocarcinoma receiving neoadjuvant XRT and patients with stage I disease undergoing surgical resection alone. RESULTS: The 5-year DSS and overall survival were 94% and 82%, respectively, for responders to neoadjuvant XRT, 78% and 60%, respectively, for nonresponders, and 97% and 79%, respectively, for patients with stage I disease undergoing resection alone. Responders had improved DSS (P < .001) and overall survival (P < .001) compared with nonresponders by Cox regression. Patients with stage I disease undergoing resection alone had improved DSS (P = .01) but not overall survival (P = .89) compared with XRT responders. CONCLUSIONS: Patients with rectal adenocarcinoma downstaged after neoadjuvant XRT have improved survival compared with nonresponders. While DSS is excellent for responders to neoadjuvant XRT, it did not equal the DSS of patients with stage I disease undergoing resection alone.

Correlation of health-related quality of life after liver transplant with the Model for End-Stage Liver Disease score.

OBJECTIVE: To determine whether a correlation exists between the Model for End-Stage Liver Disease (MELD) score and health-related quality of life (HRQOL) after liver transplant (LT). DESIGN: Prospective cohort. SETTING: University hospital. PATIENTS: Adult LT recipients (N = 209). MAIN OUTCOME MEASURES: Postoperative HRQOL over a 1-year period after LT as measured via multiple regression-based path analysis testing the effects of the MELD score, preoperative variables, and postoperative variables on scores on the physical component summary and mental component summary scales of the 36-Item Short Form Health Survey and on composite physical and mental HRQOL scores derived from multiple scales. RESULTS: The MELD score (beta = .16), cholestatic cirrhosis (beta = .12), autoimmune/metabolic disease (beta = .18), neoplasm (beta = .23), time after LT (beta = .16), and the Karnofsky score (beta = .49) had significant effects on the physical component summary scale score. Autoimmune/metabolic disease (beta = .16) and the Karnofsky score (beta = .25) had significant effects on the mental component summary scale score. The MELD score (beta = .15), high school education (beta = .15), college education (beta = .17), autoimmune/metabolic disease (beta = .15), neoplasm (beta = .23), time after LT (beta = .11), and the Karnofsky score (beta = .51) had significant effects on the composite physical HRQOL score. Autoimmune/metabolic disease (beta = .23), neoplasm (beta = .15), and the Karnofsky score (beta = .42) had significant effects on the composite mental HRQOL score. CONCLUSIONS: An increasing MELD score, when computed without any diagnosis-based exception points, was associated with improved physical HRQOL in the first year after LT. The MELD score did not affect mental HRQOL.

The impact of tumor extent (T stage) and lymph node involvement (N stage) on survival after surgical resection for gallbladder adenocarcinoma.

INTRODUCTION: Tumor extent (T stage) and lymph node involvement (N stage) have a known combined negative effect on survival in patients with gallbladder adenocarcinoma, but the independent effects of these factors have been less well described. We investigated whether T stage and N stage independently predict survival after surgery for gallbladder adenocarcinoma. METHODS: We queried the Surveillance, Epidemiology and End Results database for patients treated with surgical resection for gallbladder adenocarcinoma between 1988 and 2004. Cases were stratified by disease severity based on tumor extent and nodal involvement. Kaplan-Meier and Cox regression methods were used to test the effect of disease severity and to develop multivariate models of the effects of demographic and clinical covariates on survival. Univariate and multivariate models were tested in the entire cohort and in a subsample with pathologically confirmed lymph node status. RESULTS: Four thousand and forty-eight patients who survived the immediate perioperative period comprised the full cohort. The subsample with pathologically confirmed lymph node status included 1298 patients. Age, gender, radiation treatment, tumor grade, tumor extent and lymph node status had statistically significant independent effects on survival in both models (all p<0.03). After accounting for T by N stage interactions, both tumor extent (1.21 < or = HR < or = 3.81, all p < or = 0.005) and lymph node involvement (1.80 < or = HR < or = 2.84, p<0.001) had independent effects on survival. CONCLUSIONS: Tumor extent and lymph node metastases are independent predictors of survival after surgical resection for gallbladder adenocarcinoma. Tumor penetration of the gallbladder wall and pathologically confirmed lymph node involvement each carry poor prognosis.

A prognostic system applicable to patients with resectable liver metastasis from colorectal carcinoma staged by positron emission tomography with [18F]fluoro-2-deoxy-D-glucose: role of primary tumor variables.

BACKGROUND: The purpose of this study was to develop a prognostic system applicable to patients with hepatic metastasis from colorectal cancer in whom extrahepatic disease was excluded by preoperative PET with [(18)F]fluoro-2-deoxy-D-glucose (FDG-PET). Data from two institutions were analyzed separately and together to improve general applicability of results. STUDY DESIGN: Data were analyzed for 285 consecutive patients undergoing liver resection for colorectal metastases from 1995 to 2005 at 2 institutions routinely using preoperative FDG-PET with. Fifteen clinicopathologic variables of the primary and secondary tumors were examined to identify factors predictive of survival. RESULTS: Outcomes were correlated with poorly differentiated tumor grade in both data sets. Because patients with poorly differentiated tumors comprised a small proportion (16%) of the population, patients with well-differentiated or moderately differentiated tumors were analyzed independently. In this subgroup, positive lymph node status in the primary colorectal tumor resection specimen was the only characteristic that predicted survival of patients in both institutions. Consequently, patients were sorted into three prognostic categories: poor tumor differentiation; well-differentiated or moderately differentiated tumors and node positive; and well-differentiated or moderately differentiated tumors and node negative. These groups had significantly different overall survival on Kaplan-Meier analysis (p=0.0014). CONCLUSIONS: In patients with colorectal liver metastases staged with FDG-PET with overall survival can be predicted directly from data in the pathology report of the colorectal primary tumor. This study also indicates the need for new molecular tumor markers of prognosis to complement clinicopathologic markers if the goal of prediction of outcomes in individual patients is to be reached.

The effects of physical quality of life, time, and gender on change in symptoms of anxiety and depression after liver transplantation.

Previous research demonstrated that physical health-related quality of life (HRQOL) improves after liver transplantation, but improvements in mental HRQOL are less dramatic. The aim of this study was to test the effects of physical HRQOL, time post-transplant, and gender on pre- to post-transplant change in anxiety and depression. Longitudinal HRQOL data were prospectively collected at specific times before and after liver transplantation using the SF-36(R) Health Survey (SF-36), Center for Epidemiologic Studies Depression Scale (CES-D), and Beck Anxiety Inventory (BAI). Within-subject change scores were computed to represent the longest follow-up interval for each patient. Multiple regression was used to test the effects of baseline score, time post-transplant, gender, and SF-36 physical component summary scores (PCS) on change in BAI and CES-D scores. About 107 patients (74% male, age=54+/-8 years) were included in the analysis. Time post-transplant ranged 1 to 39 months (mean=9+/-8). Improvement in symptoms of anxiety and depression was greatest in those patients with the most severe pre-transplant symptoms. Significant improvement in symptoms of depression occurred after liver transplant, but the magnitude of improvement was smaller with time suggesting possible relapse of symptoms. Better post-transplant physical HRQOL was associated with a greater reduction in symptoms of anxiety and depression after liver transplantation. This demonstrates clear improvements in post-transplant mental HRQOL and the significant relationships between physical and mental HRQOL.

Model for end-stage liver disease: did the new liver allocation policy affect waiting list mortality?

OBJECTIVE: To examine the impact of the Model for End-stage Liver Disease (MELD) on waiting list mortality. DESIGN: Interrupted time series with a nominal inception point of the intervention on February 27, 2002. SETTING: United Network for Organ Sharing Standard Transplant Analysis and Research file data from March 1, 1999, to July 30, 2004. PARTICIPANTS: All adult candidates on the waiting list for liver transplantation in the United States during the study period. INTERVENTION: Implementation of the MELD policy. MAIN OUTCOME MEASURES: Waiting list mortality, waiting time to transplantation, number of new registrants, and posttransplantation survival. RESULTS: Although no preintervention trend was identified, the policy change was associated with an immediate effect of increasing waiting list mortality by 2.2 deaths per 1000 registrants per month (from approximately 11 to 13 deaths per 1000 registrants per month; 95% confidence interval [CI], 1.1 to 3.4; P = .001) followed by a postintervention decline in waiting list mortality over time (-0.09 death per 1000 registrants per month; 95% CI, -0.16 to -0.03; P <.001). An immediate effect of decreased waiting time was also noted (from approximately 294 to 250 days; -44.4 days; 95% CI, -77.1 to -11.7 days; P <.001), which reached a new, lower postintervention steady state. The intervention had no effect on the number of new registrants listed per month or on 3- and 6-month posttransplantation survival. CONCLUSION: After an initial increase in waiting list mortality, the implementation of the MELD-based allocation policy was associated with an overall decline in waiting list mortality and time to transplantation.

Surgical management of polycystic liver disease.

Adult polycystic liver disease (PCLD) is an autosomal dominant condition commonly associated with autosomal dominant polycystic kidney disease (ADPKD). However in the last decade, it has been recognized that there is a distinct form of autosomal dominant PCLD that arises without concomitant ADPKD. Early knowledge of the pathogenesis was gained from the study of hepatic cysts in patients with ADPKD. Bile duct overgrowth after embryogenesis results in cystic hepatic dilatations that are known as biliary microhamartomas or von Meyenburg complexes. Further dilatation arises from cellular proliferation and fluid secretion into these cysts. There is a variable, broad spectrum of manifestations of PCLD. Although PCLD is most often asymptomatic, massive hepatomegaly can lead to disabling symptoms of abdominal pain, early satiety, persistent nausea, dyspnea, ascites, biliary obstruction, and lower body edema. Complications of PCLD include cyst rupture and cyst infection. Also, there are associated medical problems, especially intracranial aneurysms and valvular heart disease, which clinicians need to be aware of and evaluate in patients with PCLD. In asymptomatic patients, no treatment is indicated for PCLD. In the symptomatic patient, surgical therapy is the mainstay of treatment tailored to the extent of disease for each patient. Management options include cyst aspiration and sclerosis, open or laparoscopic fenestration, liver resection with fenestration, and liver transplantation. The surgical literature discussing treatment of PCLD, including techniques, outcomes, and complication rates, are summarized in this review.

Liver transplantation for non-hepatocellular carcinoma malignancy.

Liver transplantation (LT) for hepatocellular carcinoma is effective for selected patients. LT for other malignancies like cholangiocarcinoma (CCA), hepatoblastoma (HB), hepatic epithelioid hemangioepithelioma (HEHE), angiosarcoma (AS), and neuroendocrine tumors (NET) is being defined. For CCA, series that did not emphasize highly selected early stage disease and neoadjuvant or adjuvant chemoradiation had an average 5-year survival of 10%. However, emphasizing neoadjuvant radiation and chemosensitization in operatively confirmed stage I or II hilar CCA has led to improved 5-year survival, up to 82%. LT is indicated under strict research protocols at selected centers, for patients with early stage CCA and anatomically unresectable (Bismuth type IV) lesions. HB is typically sensitive to cisplatin-based chemotherapy. LT plays a role as primary surgical therapy for those individuals in whom tumors remain unresectable after chemotherapy or as rescue therapy for those who are incompletely resected, recur after resection, or develop hepatic insufficiency after chemotherapy and/or resection. Long-term survival is reported at 58-88%. HEHE is a multifocal tumor that lies somewhere between benign hemangiomas and malignant AS. The extensive multifocal nature makes resection difficult and LT an attractive option. Series on LT for HEHE report overall survival of 71-78% at 5 years. However, AS is an aggressive tumor and LT is contraindicated. For NET, resection of the primary tumor and all gross metastatic disease is reported to provide 5-year survival of 70-85%. LT has been employed for some patients for unresectable tumors or for palliation of medically uncontrollable symptoms with 5-year survival reported between 36% and 80%.