Outcomes of Colectomy and Proctectomy According to Surgeon Training: General vs Colorectal Surgeons.

BACKGROUND: Colectomies and proctectomies are commonly performed by both general surgeons (GS) and colorectal surgeons (CRS). The aim of our study was to examine the outcomes of elective colectomy, urgent colectomy, and elective proctectomy according to surgeon training. STUDY DESIGN: Data were obtained from the Vizient database for adults who underwent elective colectomy, urgent colectomy, and elective proctectomy from 2020-2022. Operations performed in the setting of trauma and patients within the database's highest relative expected mortality risk group were excluded. Outcomes were compared according to surgeon's specialty: GS vs. CRS. The primary outcome was in-hospital mortality. The secondary outcome was in-hospital complication rate. Data were analyzed using multivariate logistic regression. RESULTS: Of 149,516 elective colectomies, 75,711(50.6%) were performed by GS and 73,805(49.4%) by CRS. Compared to elective colectomies performed by CRS, elective colectomies performed by GS had higher rates of complications(4.9% vs. 3.9%, OR1.23, 95%CI 1.17-1.29,p<.01) and mortality(0.5% vs. 0.2%, OR2.06, 95%CI 1.72-2.47,p<.01). Of 71,718 urgent colectomies, 54,680(76.2%) were performed by GS, while 17,038(23.8%) were performed by CRS. Compared to urgent colectomies performed by CRS, urgent colectomies performed by GS were associated with higher rates of complications(12.1% vs. 10.4%, OR1.14, 95%CI 1.08-1.20,p<.01) and mortality (5.1% vs. 2.3%, OR2.08, 95%CI 1.93-2.23,p<.01). Of 43,749 elective proctectomies, 28,458(65.0%) were performed by CRS and 15,291(35.0%) by GS. Compared to proctectomies performed by CRS, those performed by GS were associated with higher rates of complications (5.3% vs. 4.4%, OR1.16, 95%CI 1.06-1.27,p<.01) and mortality(0.3% vs. 0.2%, OR1.49, 95%CI 1.02-2.20,p=.04). CONCLUSIONS: In this nationwide study, colectomies and proctectomies performed by CRS were associated with improved outcomes compared to GS. Hospitals without a CRS on staff should consider prioritizing recruiting CRS specialists.

Endometrial Adenocarcinoma with Discordant Microsatellite Stability Status Treated with First-Line Pembrolizumab: A Case Report and Narrative Review.

BACKGROUND Microsatellite instability (MSI) is a hallmark of specific cancers and can be diagnosed using both tissue- and liquid-based approaches. When these tissue- and liquid-based approaches give differing results, they are known as discordant or being at variance. MSI-H tumors are well-researched candidates for treatment with programmed cell death protein 1 (PD-1) inhibitor-based immunotherapy, but the efficacy of immunotherapy in MSI-H discordant endometrial cancer, especially as first-line therapy, is not yet well documented in the literature. CASE REPORT A 67-year-old woman presented with a retroperitoneal mass positive for recurrent adenocarcinoma of endometrial origin. Her stage I endometrial adenocarcinoma 7 years ago demonstrated microsatellite stable (MSS) by immunohistochemical (IHC) stain and indeterminant due to insufficient tissue by Caris Next-Generation Sequencing (NGS). She then presented with a retroperitoneal mass that was MSI-H on IHC stain and Caris NGS, as well as MSI high on liquid biopsy @Guardant360 (@G360). The patient proceeded with pembrolizumab treatment 1 year ago and has sustained a complete clinical response at the time of writing. CONCLUSIONS Our case provides further evidence for the need to retest the microsatellite stability of metastatic sites, especially after a long disease-free survival. Here, we providing a literature review of case reports and a review of studies outlining discordance of testing modalities. Our case also highlights the importance of considering the use of immunotherapy as a first-line agent in patients who may have a poor ECOG performance status, as it can significantly improve their quality of life and reduce the number of adverse effects compared to chemotherapy.

Surgical Management of Crohn's Disease.

Treatment of Crohn's disease (CD) focuses on providing acceptable quality of life for the affected individual by optimizing medical therapy, endoscopic procedures, and surgical intervention. Biologics have changed the medical management of moderate to severe CD. However, despite their introduction, the need for surgical resection in CD has not drastically changed, with two-thirds of the patients still requiring an intestinal resection. Patient outcomes are optimized by focusing on preoperative management and intraoperative technical aspects to maximize bowel preservation. This article reviews some of the important principles of Crohn's surgery to help guide surgeons when approaching this challenging patient population.

How We Do It: Implementing a Virtual, Multi-Institutional Collaborative Education Model for the COVID-19 Pandemic and Beyond.

OBJECTIVE: To describe the implementation of a virtual, multi-institutional educational collaboration involving over 50 general surgery residency programs during the COVID-19 pandemic that enabled enhanced learning for surgical residents despite social-distancing requirements. DESIGN: Description of Virginia Commonwealth University's virtual educational augmentation program and the development of a collaborative teaching network during the coronavirus pandemic. SETTING: This collaboration was initiated by Virginia Commonwealth University's Department of Surgery, Richmond, VA, and grew to include general surgery residency programs from across the nation. PARTICIPANTS: General surgery residents and faculty from Departments of General Surgery were recruited locally via direct emails and nationally via the Association of Program Directors' listserv and Twitter. In total, 52 institutions participated from every part of the country. RESULTS: A virtual, multi-institutional collaborative lecture series was initiated that grew to involve over 50 general surgery residency programs, allowing for daily didactics by experts in their fields during the initial surge of the COVID-19 pandemic, while maintaining social distancing and the provision of essential clinical care. CONCLUSION: A multi-institutional collaboration enabled continued didactic education during the coronavirus pandemic, vastly broadening the expertise, scope and variety available to residents, while decreasing burden on faculty. We believe this can serve as a framework for future multi-institutional collaborations that extend beyond the COVID-19 era.

Efficacy of Virtual Case-Based General Surgery Clerkship Curriculum During COVID-19 Distancing.

OBJECTIVE: The COVID-19 pandemic created a paradigm shift in medical education with a reliance upon alternative teaching methods to deliver meaningful surgery clerkship content. This study examines the efficacy of a novel, case-based virtual surgery clerkship curriculum to determine its impact on student experience during quarantine. STUDY DESIGN: Sixteen third-year medical students enrolled in the General Surgery clerkship between April through June 2020 during COVID-19 distancing at a quaternary medical center (Cleveland Clinic, Cleveland, OH) participated in this study. Course surveys, including a 10-question curriculum-based multiple-choice assessment, were administered before and after the clerkship. Analyses include student self-perception of readiness to see a surgical consult independently, students' interest in pursuing a General Surgery residency, and improvement of surgical knowledge. RESULTS AND CONCLUSION: On a 5-point Likert scale, students felt significantly more assured in their ability to independently assess a surgical consult by the end of the course. Five (31%) students reported an influence of the curriculum on their personal interest in a career in General Surgery. Mean scores on the curriculum-based knowledge assessment increased. These findings highlight that a virtual platform can be a reliable alternative adjunct that delivers surgical content and positively impacts student experience. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-020-01126-5.

Survival impact based on hepatic artery lymph node status in pancreatic adenocarcinoma: A study of patients receiving modern chemotherapy.

BACKGROUND: Chemotherapy for pancreatic adenocarcinoma (PDAC) has significantly improved in recent years. While the involvement of the hepatic artery lymph node (HALN; station 8a lymph node) likely represents advanced disease, a comparison to patients with metastases on modern chemotherapy is lacking. METHODS: Patients who underwent pancreatoduodenectomy with HALN sent for pathologic review at a single institution from 2003 to 2018 were reviewed. Patients who presented with liver-only metastases at the time of PDAC diagnosis (Stage IV) and received chemotherapy were identified. Multivariate Cox proportional hazards regression modeling was utilized and overall survival (OS) was estimated using Kaplan-Meier analysis. RESULTS: Of the 112 patients with a HALN sent for analysis, 17 (15%) were positive and 13 (76%) received chemotherapy. Ninety-four stage IV patients were identified and were significantly more likely to have received a multiagent rather than single-agent chemotherapy regimen compared to HALN positive patients (79.8% vs. 38.5%, p < .001). Median OS was significantly longer in all patients who underwent surgical resection, regardless of HALN status, compared to stage IV patients. CONCLUSIONS: Patients undergoing pancreatoduodenectomy with HALN positivity have significantly improved OS compared to patients with stage IV disease. HALN involvement does not significantly alter survival among resected patients and does not warrant preoperative endoscopic ultrasound-guided biopsy.

Impact of Surgery Program Characteristics on Fate of Non-designated Preliminary Surgery Interns.

OBJECTIVE: Non-designated preliminary (NDP) general surgery residents face the daunting challenge of obtaining a categorical residency position while undertaking the rigors of a general surgery residency. This additional application cycle represents a stressful time for these trainees and limited data exists to help guide applicants and program directors regarding the factors predictive of application success. While previous studies have focused solely on applicant related factors, no study to date has evaluated the effect of the residency program structure, institutional resources, or administrative support on these outcomes. DESIGN/SETTING: A multicenter retrospective review of 10 general surgery residency programs over a 5-year period from 2014 to 2019 was performed. Applicant related information was compiled from NDP general surgery residents and the results of their attempted second application into a categorical position. Applicant factors including age, gender, standardized test scores (USMLE/ABSITE), and professional training were examined. Program and administrative structure including residency class size, number of NDP PGY-2 positions, number of assistant program directors and program director (PD) background were also examined. Primary success was defined as a NDP resident successfully obtaining a categorical position within general surgery or a surgical subspecialty. Secondary success was obtaining a categorical residency position in any field of medical practice other than surgery or a surgical subspecialty in the United States. RESULTS: A total of 260 NDP trainees were evaluated with an average age of 29.1. Almost seventy percent of applicants were male, 40% graduated from a non-U.S. medical school and 24.2% required a visa to work in the United States. Thirty 4 percent of NDPs successfully obtained a categorical surgery position and an additional 35% obtained a categorical residency position in a nonsurgical field for an overall match success rate of 68.9%. Factors associated with primary success included ABSITE score (p < 0.001), US medical school graduation (p = 0.02), visa status (p = 0.03), presence of preliminary PGY-2 positions (p = 0.02), and PD professional development time (p = 0.004). Overall success was associated USMLE Step 1 scores (p = 0.02), number of approved chiefs (p = 0.03), presence of dedicated faculty researchers (p = 0.001), and PD professional development time (p < 0.001). CONCLUSIONS: Applicant, program-related, and administrative factors all have a significant impact on the success of NDP general surgery residents in obtaining a categorical surgical position. Trainees should consider all of these factors when applying to NDP residencies and in approaching their second application cycle to maximize their likelihood of a successful match.

Effect of critical care complications on perioperative mortality and hospital length of stay after hepatectomy: A multicenter analysis of 21,443 patients.

OBJECTIVE: To determine predictors of critical care complications (CCC) in patients undergoing hepatectomy. METHODS: All hepatectomy patients in NSQIP from 2012 to 2016 were analyzed. CCC included prolonged ventilation (>48 h), sepsis/septic shock, renal failure/insufficiency, cardiac arrest/AMI and pulmonary embolism. RESULTS: A total of 21,443 patients underwent hepatectomy during the study period. Overall rate of CCC was 11%, with the most common being sepsis/septic shock (6.1%) and respiratory failure (4.9%). On multivariate analysis the preoperative risk factors associated with CCC included ASA Class IV-V (OR:2.04, p < 0.0001), diabetes (OR = 1.28, p = 0.0001), pre-operative ventilator use (OR: 17.75, p = 0.0003); COPD (OR: 1.65, p < 0.0001); pre-operative weight loss >10% (OR: 1.35, p = 0.0026); pre-operative sepsis (OR: 2.14, p < 0.0001). Propensity score matched analysis demonstrated a significant increased risk of mortality in patients with CCC (OR: 26.75, p < 0.0001) and a prolonged LOS of 10.5 days above the mean (ß Estimate: 10.51, p < 0.0001). CONCLUSIONS: ASA class, diabetes, COPD, pre-operative weight loss >10% and pre-operative sepsis are the strongest predictors of CCC after hepatectomy. The presence of CCC significantly increased the risk of peri-operative mortality 26-fold.

Socioeconomic factors as predictors of organ donation.

BACKGROUND: Despite numerous initiatives to increase solid organs for transplant, the gap between donors and recipients widens. There is little in the literature identifying socioeconomic predictors for donation. We evaluate the correlation between socioeconomic factors and familial authorization for donation. METHODS: A retrospective analysis of adult potential donor referrals between 2007 and 2012 to our organ procurement organization (OPO) was performed. Potential donor information was obtained from the OPO database, death certificates, and the US Census Report. Data on demographics, education, residence, income, registry status, cause and manner of death, as well as OPO assessments and approach for donation were collected. End point was familial authorization for donation. RESULTS: A total of 1059 potential donors were included, with an overall authorization rate of 47%. The majority was not on the donor registry (73%). Younger donors (18-39 y: odds ratio [OR] = 4.9, P < 0.001; 40-60 y: OR = 2.1, P < 0.001), higher levels of education (college: OR = 2.5, P = 0.005; graduate studies: OR = 3.9, P = 0.002), prior listing on the donor registry (OR = 10.3, P < 0.001), and residence in counties with lower poverty rates than the US rates (OR = 1.7, P = 0.02) were independently associated with higher authorization rates. Decoupling (OR = 3.1, P < 0.001) and donation first mentioned by the local health care provider (OR = 1.8, P = 0.01) were also independently associated with higher authorization rates. CONCLUSIONS: Donor registration correlated most strongly with the highest authorization rates. These results indicate that public educational efforts in populations with unfavorable socioeconomic considerations may be beneficial in improving donor registration. Collaborations with local providers as well as OPO in-hospital assessments and approach techniques can help with improving authorization rates.

Evidence of the immunomodulatory role of dual PI3K/mTOR inhibitors in transplantation: an experimental study in mice.

The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative. Here we show that dual PI3K/mTOR PI-103 and PKI-587 inhibitors interfered IL-2-dependent responses in T-cells. However, in contrast to the inhibitory effects in non-Treg T-cell proliferation and effector functions, dual inhibitors increased the differentiation, preferential expansion, and suppressor activity of iTregs. Rapamycin, PI-103, and PKI-587 targeted different signaling events and induced different metabolic patterns in primary T-cells. Similar to rapamycin, in vivo administration of PI-103 and PKI-587 controlled effectively the immunological response against allogeneic skin graft. These results characterize specific regulatory mechanisms of dual PI3K/mTOR inhibitors in T-cells and support their potential as a novel therapeutic option in transplantation.

Sorafenib and FH535 in combination act synergistically on hepatocellular carcinoma by targeting cell bioenergetics and mitochondrial function.

Treatment of advanced hepatocellular carcinoma (HCC) remains a challenge due to the high tumor heterogeneity. In the present study, we aim to evaluate the impact of the ß-catenin inhibitor, FH535, alone or in combination with the Ras/Raf/MAPK inhibitor Sorafenib, on the bioenergetics profiles of the HCC cell lines Huh7 and PLC/PRF/5. Single low-dose treatments with FH535 or Sorafenib promoted different effects on mitochondrial respiration and glycolysis in a cell type specific manner. However, the combination of these drugs significantly reduced both mitochondrial respiration and glycolytic rates regardless of the HCC cells. The significant changes in mitochondrial respiration observed in cells treated with the Sorafenib-FH535 combination may correspond to differential targeting of ETC complexes and changes in substrate utilization mediated by each drug. Moreover, the bioenergetics changes and the loss of mitochondrial membrane potential that were evidenced by treatment of HCC cells with the combination of FH535 and Sorafenib, preceded the induction of cell apoptosis. Overall, our results demonstrated that Sorafenib-FH535 drug combination induce the disruption of the bioenergetics of HCC by the simultaneous targeting of mitochondrial respiration and glycolytic flux that leads the synergistic effect on inhibition of cell proliferation. These findings support the therapeutic potential of combinatory FH535-Sorafenib treatment of the HCC heterogeneity by the simultaneous targeting of different molecular pathways.

Decreased graft survival in liver transplant recipients of donors with positive blood cultures: a review of the United Network for Organ Sharing dataset.

Liver transplantation using blood culture positive donors (BCPD) has allowed a significant expansion of the donor pool. We aimed to characterize BCPD and assess the outcomes of BCPD liver transplant recipients. We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single-organ deceased-donor liver transplantation in the USA between 2008 and 2013. Patients were classified into two cohorts: the BCPD cohort and the non-BCPD cohort. One-year graft and patient survival were compared between cohorts using Kaplan-Meier estimates and Cox models. A total of 28 961 patients were included. There were 2316 (8.0%) recipients of BCPD. BCPD were more likely to be older, female, black, diabetic, hypertensive, and obese compared to non-BCPD. Graft survival was significantly lower in BCPD recipients compared to non-BCPD recipients (Kaplan-Meier, 0.85 vs. 0.87; P = 0.009). Results remained significant in propensity-matched analysis (P = 0.038). BCPD was independently associated with decreased graft survival (adjusted HR; 1.10, 95% CI 1.01-1.20; P = 0.04). There were no significant differences in patient survival between study groups. BCPD was associated with decreased graft survival in liver transplant recipients. Studies are needed to identify subgroups of BCPD with the highest risk of graft failure and characterize the underlying pathogenic mechanisms.

Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma.

BACKGROUND: The cancer stem cell hypothesis provides an explanation for hepatocellular carcinoma (HCC) heterogeneity. We investigated the expression of CD44 and CD133 alone and in combination with microvascular invasion (MVI) as predictors of prognosis in patients undergoing liver transplantation for HCC. METHODS: Explanted livers from 95 patients transplanted for HCC were analyzed. Marker expression was evaluated by immunofluorescence. RESULTS: Seventy-seven patients were male with a mean age of 56 years. The most common etiologies of cirrhosis were hepatitis C (50%) and alcoholic liver disease (41%). Forty-one patients had laboratory model for end-stage liver disease score greater than 15. Overall survival (OS) at 1-, 3-, and 5-years was 86%, 75%, and 64%, respectively. Recurrence rate was 13% with a median follow-up of 64 months. The 5-year OS was significantly lower in those patients with MVI and CD44 (36.9%) or CD133 (40%). CD44(+) and CD133(+) correlated with increased risk of poorly differentiated HCC, and elevated alpha-fetoprotein levels. In combination with MVI, both markers were independently associated with increased recurrence and worse OS (recurrence P < .003, odds ratio = 8.05; P = .001, odds ratio = 9.5, survival P = .001, HR = 3.7; P = .004, HR = 3.2 respectively). CONCLUSIONS: CD44 or CD133 alone and in combination with MVI are independent predictors of poor prognosis in patients undergoing transplantation for HCC.

Liver transplantation for the treatment of neuroendocrine liver metastases.

Neuroendocrine neoplasms represent a heterogeneous group of cancers arising from a variety of neuroendocrine cell types. In general, these tumors (NET) are asymptomatic and are discovered late once metastatic disease is present (40-80%). The liver is the most common organ involved when metastases occur (40-93%), followed by bone (12-20%) and lungs (8-10%). A number of different therapeutic options are available for patients with hepatic metastases including surgical resection, transplantation, transarterial chemoembolization, radiofrequency and microwave ablation, radioembolization (Y90), chemotherapy, somatostatin analogues and molecular targeted therapies. Surgical resection is still considered the treatment of choice and provides excellent disease control with an overall survival of 47-92%. Liver transplantation has been advocated in selected patients with bilateral unresectable symptomatic liver metastases. The aim of this study is to review the existing literature emphasizing on the role of transplantation to treat patients with liver metastases from NET.

Donor positive blood culture is associated with delayed graft function in kidney transplant recipients: a propensity score analysis of the UNOS database.

BACKGROUND: The effect of blood culture positive donor (BCPD) on delayed graft function (DGF) in kidney transplant recipients has not been well established. METHODS: We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single organ deceased-donor kidney transplantation in US between 2008 and 2013. Patients were classified in two cohorts: the BCPD cohort and the non-BCPD cohort. We used propensity scores for 1:1 matching of BCPD and non-BCPD cohorts. DGF, graft and patient survival at one yr were compared between cohorts using multivariable logistic and Cox regression models. DGF was defined as requiring dialysis within the first week post-transplant. RESULTS: There were 4126 (8.1%) recipients of BCPD during the study period. DGF was associated with BCPD (aOR; 1.15, 95% CI 1.07-1.24). This association was maintained in the propensity-score matched analysis (p < 0.01). No association was found between BCPD and graft survival (aHR; 1.01, 95% CI, 0.92-1.09) or patient survival (aHR; 0.92, 95% CI, 0.82-1.04). CONCLUSION: Blood culture positive donor was associated with DGF but did not impact graft or patient survival in deceased-donor kidney transplants. This suggests a transient negative effect of BCPD that does not appear to translate into a more persistent deleterious outcome.

Targeting Wnt/ß-catenin pathway in hepatocellular carcinoma treatment.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/ß-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. A great effort in developing selective drugs to target components of the ß-catenin pathway with anticancer activity is underway but only a few of them have reached phase I clinical trials. We aim to review the role of ß-catenin pathway on hepatocarcinogenesis and liver cancer stem cell maintenance. We also evaluated the use of small molecules targeting the Wnt/ß-catenin pathway with potential application for treatment of HCC.

Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database.

BACKGROUND: Mixed hepatocellular and cholangiocarcinoma (HCC-CC) have been associated with a poor prognosis after liver transplantation (LT). We aimed to evaluate long-term outcomes in patients undergoing LT for HCC-CC versus patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC). METHODS: Retrospective analysis of the United Network for Organ Sharing (UNOS) database from 1994-2013. Overall survival (OS) in patients with HCC-CC, HCC, and CC, were compared. RESULTS: We identified 4049 patients transplanted for primary malignancy (94 HCC-CC; 3515 HCC; 440 CC). Mean age of patients with HCC-CC was 57 ± 10 years, and 77% were male. MELD score did not differ among the groups (p = 0.637). Hepatitis C virus was the most common secondary diagnosis within the HCC-CC (44%) and HCC (36%) cohorts, with primary sclerosing cholangitis in the CC (16%) cohort. OS rates at 1, 3 and 5 years for HCC-CC (82%, 47%, 40%) were similar to CC (79%, 58%, 47%), but significantly worse than HCC (86%, 72%, and 62% p = 0.002). DISCUSSION: Patients undergoing LT for HCC had significantly better survival compared to those transplanted for HCC-CC and CC. LT for mixed HCC-CC confers a survival rate similar to selected patients with CC. Efforts should be made to identify HCC-CC patients preoperatively.

Nonalcoholic steatohepatitis is strongly associated with sarcopenic obesity in patients with cirrhosis undergoing liver transplant evaluation.

BACKGROUND: Sarcopenia is the most common complication of cirrhosis and adversely affects quality of life and outcomes before, during, and after liver transplantation. We studied predictors of sarcopenia and sarcopenic obesity in patients with cirrhosis undergoing liver transplant (LT) evaluation. METHODS: A retrospective analysis of 207 adult cirrhotic patients that underwent LT from January 2008 to December 2013 was performed at our institution. RESULTS: Two hundred seven patients were evaluated, 68% were male with a mean age of 54 ± 8 years. The most common etiology of cirrhosis was alcoholic liver disease (38.6%), followed by chronic hepatitis C (38.2%), nonalcoholic steatohepatitis (NASH) (21.7%), and hepatocellular carcinoma (HCC) (24.6%). The mean body mass index of the cohort was of 30.1 ± 5.7 kg/m(2) . Forty-eight percent of these patients were obese. Of the 207 patients, 88% had computed tomographic (CT) scans within 90 days before transplant; of these, 59% had sarcopenia found during LT evaluation. Of the patients with pretransplant sarcopenia, 59 had CT scan at 6 months posttransplant and 56 (95%) remained sarcopenic. Of the 56 patients who had sarcopenia at 6 months, 31 had available CT scans at 1 year, and 100% persisted with sarcopenia. These 31 subjects had a mean skeletal muscle index of 35 at 6 months and 36 at 1 year. SO was found in 41.7% of our patients. On multivariable regression analysis, obesity and age were found to be independently associated with pretransplant sarcopenia after controlling for gender and alcohol liver disease diagnosis (P = 0.00001, odds ratio [OR] 0.22, and P = 0.008, OR 2.0, respectively). A multivariable logistic regression analysis found that NASH as cause of cirrhosis and model of end-stage liver disease score are independent predictors of sarcopenic obesity after controlling for age, gender, alcoholic liver disease diagnosis, and HCC (P = 0.014 and 0.038, respectively; 95% confidence interval, 1.44-25.26 and 1.00-1.15, respectively; OR 6.03, 1.08, respectively). CONCLUSIONS: Sarcopenia and sarcopenic obesity is seen in a significant number of patients with cirrhosis undergoing LT evaluation. Sarcopenia progresses after LT initially and does not recover at least within the first year after surgery. Obesity is an independent predictor of pretransplant sarcopenia and NASH was associated with 6-fold increased risk of having sarcopenic obesity in cirrhotic patients in our cohort.

A prospective analysis of factors associated with decreased physical activity in patients with cirrhosis undergoing transplant evaluation.

BACKGROUND: Physical activity (PA) has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes. AIM: To evaluate predictors of PA and grip strength in patients with cirrhosis undergoing liver transplant evaluation. METHODS: Single-center, prospective analysis. RESULTS: One hundred patients were evaluated (54% male, mean age 53 ± 9). Common etiologies of liver disease were non-alcoholic steatohepatitis (27%), hepatitis C (22%) and alcoholic liver disease (21%). Mean model of end-stage liver disease (MELD) score was 13.5. Forty-one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire (IPAQ). The median total PA score was 33 metabolic equivalent (MET)-min/wk. The mean total grip strength was 62.1 ± 22 lb. Total grip strength was found to be an independent predictor of low-moderate PA (OR 4.7, 95% CI 1.4-16.2, p = 0.038), and smoking was the only significant factor associated with reduced grip strength (OR 3.4, 95% CI 1.4-8, p = 0.005). CONCLUSIONS: Patients with end-stage liver disease undergoing liver transplant evaluation have reduced total PA by IPAQ. Total grip strength was found to be a significant predictor of low-moderate PA in patients with cirrhosis. Smoking is a risk factor for reduced grip strength, an important indicator of muscle wasting in cirrhotics.

N-Aryl benzenesulfonamide inhibitors of [3H]-thymidine incorporation and ß-catenin signaling in human hepatocyte-derived Huh-7 carcinoma cells.

Structure-activity relationships (SAR) in 2,5-dichloro-N-(2-methyl-4-nitrophenyl)benzenesulfonamide (FH535) were examined as part of a program to identify agents that inhibit the Wnt/ß-catenin signaling pathway that is frequently upregulated in hepatocellular carcinoma (HCC). FH535 was reported as an inhibitor of both ß-catenin in the Wnt signaling pathway and the peroxisome proliferator-activated receptor (PPAR). A ß-catenin/T-cell factor (TCF)/Lymphoid-enhancer factor (LEF)-dependent assay (i.e., luciferase-based TOPFlash assay) as well as a [(3)H]-thymidine incorporation assay were used to explore SAR modifications of FH535. Although replacing the 2,5-dichlorophenylsulfonyl substituent in FH535 with a 2,6-dihalogenation pattern generally produced more biologically active analogs than FH535, other SAR modifications led only to FH535 analogs with comparable or slightly improved activity in these two assays. The absence of a clear SAR pattern in activity suggested a multiplicity of target effectors for N-aryl benzenesulfonamides.