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Debate persists regarding the need for shaking during hyperthermic intraperitoneal chemotherapy. Studies assessing the thermal behaviors of the perfusate throughout the abdomen during hyperthermic intraperitoneal chemotherapy are limited.A closed hyperthermic intraperitoneal chemotherapy technique was performed in an institutional International Animal Care and Use Committee approved porcine model targeting a 41°C outflow temperature. Continuous temperature monitoring was conducted. Abdominal shaking was performed for 60 second intervals and temperatures were allowed to equilibrate without shaking between intervals. Temperature distributions and changes due to shaking were evaluated. These findings were validated against human subjects' data.The experimental procedure was conducted in 2 different animals and with 6 total shaking intervals assessed. Without shaking, temperatures were highly variable ranging between 38.0 to 42.2°C. Shaking the abdomen reduced the mean range of temperatures across all locations observed from 3.9°C to 0.8°C (P.01). The locations of the most divergent temperatures varied based on perfusion cannula position. The point of minimum temperature heterogeneity was achieved in 28.3 (19.1-37.5) seconds. After shaking stopped, heterogeneity equal to the baseline measurements was seen on average within 25.7 (13.3-38.0) seconds. The outflow catheter differed from the system mean temperature by 1.4°C and from the coldest-reading probe by 2.8°C and outperformed the inflow catheter for all time points. With shaking these were significantly reduced to 0.4°C (P.01) and 0.6°C (P.01). The patient data mirrored that of the pig data.Shaking significantly reduces temperature variability within the abdomen during hyperthermic intraperitoneal chemotherapy, and significantly improves the ability of the outflow catheter to estimate internal temperatures.

The aim of this study is to present radiologically designated LAPC found to be resectable upon surgical exploration and evaluate the outcomes of such resections.Sequential LAPC patients between 2013 and 2019 were staged and underwent resection were included in the analysis of both perioperative and long-term outcomes.Twenty-eight patients with radiologically-designated LAPC underwent surgical resection after chemotherapy with a median follow-up of 31.7 m,75% underwent pancreaticoduodenectomy. The margin positivity and local recurrence rates were 21.4% and 35.7%, respectively. When compared to the 30 BRPC controls, the LAPC group had a higher rates of an arterial resection (11vs.1; p = 0.002), but the groups were similar with regard to all other preoperative and intraoperative variables (p 0.05). Perioperative morbidity rates were similar (25.9%vs21.4%; p = 0.53). The LAPC and BRPC groups were also equivalent with respect to median recurrence-free survival (9.0mo; 95%CI 6.3, 11.7vs.8.3mo; 95%CI 5.4, 11.2) and median overall survival (19.9mo; 95%CI 17.0, 22.7 vs. 19.9mo; 95%CI 14.8, 25.1), respectively.Despite a radiologic designation of locally advanced pancreatic cancer, certain subtypes of LAPC warrant surgical exploration provided the operative surgeon is prepared for major arterial and/or venous resection. Pancreatectomy in these patients has acceptable morbidity and oncologic outcomes, similar to patients who are radiologically borderline resectable.

There is concern regarding the competency of today's general surgery graduates as a large proportion defer independent practice in favor of additional fellowship training. Little is known about the graduates who directly enter general surgery practice and if their operative experiences during residency differ from graduates who pursue fellowship.Nineteen Accreditation Council for Graduate Medical Education-accredited general surgery programs from the US Resident OPerative Experience Consortium were included. Demographics, career choice, and case logs from graduates between 2010 to 2020 were analyzed.There were 1,264 general surgery residents who graduated over the 11-year period. A total of 248 (19.6%) went directly into practice and 1,016 (80.4%) pursued fellowship. Graduates directly entering practice were more likely to be a high-volume resident (43.1% vs 30.5%, P.01) and graduate from a high-volume program (49.2% vs 33.0%, P.01). Direct-to-practice graduates performed 53 more cases compared with fellowship-bound graduates (1,203 vs 1,150, P.01). On multivariable analysis, entering directly into practice was positively associated with total surgeon chief case volume (odds ratio = 1.47, 95% confidence interval 1.18-1.84, P.01) and graduating from a US medical school (odds ratio = 2.54, 95% confidence interval 1.45-4.44, P.01) while negatively associated with completing a dedicated research experience (odds ratio = 0.31, 95% confidence interval 0.22-0.45, P.01).This is the first multi-institutional study exploring resident operative experience and career choice. These data suggest residents who desire immediate practice can tailor their experience with less research time and increased operative volume. These data may be helpful for programs when designing their experience for residents with different career goals.

BACKGROUND This study aims to compare the LACE + readmission index to a novel hepatopancreatobiliary readmission risk score (HRRS) in predicting post-operative hepatopancreatobiliary (HPB) cancer patient readmissions. METHODS A retrospective review of 104 postoperative HPB cancer patients from January 2017 to July of 2019 was performed. Univariable and multivariable analyses were utilized. RESULTS The LACE + index did not predict 30-day (OR 1.01, 95% CI, 0.97-1.05, p = 0.81, c-statistic = 0.52) or 90-day (OR 1.02, 95% CI, 0.98-1.05, p = 0.43) readmission. Patients readmitted within 30 days had significantly increased HRRS scores compared to those who were not (0 vs 34, p

Supplementary Data from Single‐Cell Immune Mapping of Melanoma Sentinel Lymph Nodes Reveals an Actionable Immunotolerant Microenvironment

Purpose:Improving our understanding of the immunologic response to cancer cells within the sentinel lymph nodes (SLN) of primary tumors is expected to identify new approaches to stimulate clinically meaningful cancer immunity.Experimental Design:We used mass cytometry by time-of-flight (CyTOF), flow cytometry, and T-cell receptor immunosequencing to conduct simultaneous single-cell analyses of immune cells in the SLNs of patients with melanoma.Results:We found increased effector-memory αβ T cells, TCR clonality, and γδ T cells selectively in the melanoma-bearing SLNs relative to non–melanoma-bearing SLNs, consistent with possible activation of an antitumor immune response. However, we also observed a markedly immunotolerant environment in the melanoma-bearing SLNs indicated by reduced and impaired NK cells and increased levels of CD8+CD57+PD-1+ cells, which are known to display low melanoma killing capabilities. Other changes observed in melanoma-bearing SLNs when compared with non–melanoma-bearing SLNs include (i) reduced CD8+CD69+ T cell/T regulatory cell ratio, (ii) high PD-1 expression on CD4+ and CD8+ T cells, and (iii) high CTLA-4 expression on γδ T cells.Conclusions:Our data suggest that these immunologic changes compromise antimelanoma immunity and contribute to a high relapse rate. We propose the development of clinical trials to test the neo-adjuvant administration of anti–PD-1 antibodies prior to SLN resection in patients with stage III melanoma.See related commentary by Lund, p. 1996

Supplementary Figure from Single‐Cell Immune Mapping of Melanoma Sentinel Lymph Nodes Reveals an Actionable Immunotolerant Microenvironment

Supplementary Table from Single‐Cell Immune Mapping of Melanoma Sentinel Lymph Nodes Reveals an Actionable Immunotolerant Microenvironment

Purpose: Improving our understanding of the immunologic response to cancer cells within the sentinel lymph nodes (SLN) of primary tumors is expected to identify new approaches to stimulate clinically meaningful cancer immunity. Experimental Design: We used mass cytometry by time-of-flight (CyTOF), flow cytometry, and T-cell receptor immunosequencing to conduct simultaneous single-cell analyses of immune cells in the SLNs of patients with melanoma. Results: We found increased effector-memory αβ T cells, TCR clonality, and γδ T cells selectively in the melanoma-bearing SLNs relative to non–melanoma-bearing SLNs, consistent with possible activation of an antitumor immune response. However, we also observed a markedly immunotolerant environment in the melanoma-bearing SLNs indicated by reduced and impaired NK cells and increased levels of CD8+CD57+PD-1+ cells, which are known to display low melanoma killing capabilities. Other changes observed in melanoma-bearing SLNs when compared with non–melanoma-bearing SLNs include (i) reduced CD8+CD69+ T cell/T regulatory cell ratio, (ii) high PD-1 expression on CD4+ and CD8+ T cells, and (iii) high CTLA-4 expression on γδ T cells. Conclusions: Our data suggest that these immunologic changes compromise antimelanoma immunity and contribute to a high relapse rate. We propose the development of clinical trials to test the neo-adjuvant administration of anti–PD-1 antibodies prior to SLN resection in patients with stage III melanoma. See related commentary by Lund, p. 1996

PURPOSE To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early disease recurrence after major hepatectomy for metastatic colorectal cancer in order to improve patient selection and prevent futile hepatectomy. Sequential major (four or more segments) liver resections performed for metastatic colorectal cancer between 1995 and 2019 were selected from our prospectively maintained database. Univariate analyses, multivariable regression modelling, and survival analyses were used to identify predictors of futile resection (recurrence within 6 months of hepatectomy). Of 259 patients included, the median age was 61.3 years (interquartile range [IQR] 15.3) and the median number of liver tumors was 3.0 (IQR 2.0); 78.0% of patients received prehepatectomy chemotherapy. Surgeries were right (56.4%), left (19.3%), and extended hepatectomy (24.3%). Futile resection occurred in 26 (12.6%) patients. Margin positivity was similar in the futile resection group compared with the non-futile resection group (11.5% vs. 11.4%). Extrahepatic disease that disappeared with chemotherapy was present in 23.1% of patients with a futile resection and 7.2% of those without (p = 0.019). After multivariable regression, the factors predictive of futile resection were extrahepatic disease (odds ratio [OR] 5.6; p = 0.004), more than three liver lesions (OR 4.9; p = 0.001), and extended hepatectomy (OR 2.6; p = 0.038). Notably, 70.8% of futile recurrences occurred within the liver remnant and 20.8% were pulmonary metastases. Overall survival was 11.7 months (95% confidence interval [CI] 7.1–16.2) for the futile resection cohort versus 45.6 (95% CI 39.1–52.1) for non-futile hepatectomies (p

Locally-advanced pancreatic cancer (LAPC) is traditionally considered stage III unresectable disease. Advances in induction systemic therapy regimens, surgical technique, and perioperative care have led to successful resection of an increasing number of these tumors with reasonable perioperative outcomes and disease-free intervals. Certain anatomic characteristics that meet criteria for locally-advanced disease, however, are more likely to result in a successful surgical outcome. A practical and consistent system is needed to communicate such nuance between surgical and nonsurgical oncologists for optimal treatment planning and to improve recording for cancer registries and research studies. The present study proposes a novel subclassification system for stage III pancreatic cancers based on their pattern of vascular involvement and examines the current evidence for resection in each scenario. Introducing needed detail into the current catch-all stage III categorization will help to direct patient referrals and increase the body of knowledge about the variable presentations of this complex malignancy. This proposed staging revision for LAPC is designed to convey more actionable tumor descriptions for treating oncologists, clinical trial eligibility, and surgical patient selection in the era of effective induction systemic therapy.

The purpose of this study was to present the optimal patient selection for esophageal stenting after esophageal resection to investigate possible factors leading to treatment success or treatment failure in these patients. This was a prospective, observational study of patients from January 2005 to May 2019 with an esophageal anastomotic leak that were treated with a self-expandable stent (SES). A total of 34 patients were treated. All achieved technical success (100%); 33 (97%) achieved clinical success. No patient had to have reoperative surgery based on their leak management. The stenting in-hospital mortality was 0% with 1 patient (2%) with a 90-day mortality from possible leak-related death. Patients had their stents removed with a median of 106 days. Stenting for an anastomotic leak after resection offers a safe and effective method of treatment and is successful in the majority of cases. Critical to success is optimal patient selection, adequate leak drainage, and optimal stent selection and placement.

The purpose of this study was to evaluate the rates of local recurrence and margin positivity in patients with borderline resectable pancreatic cancer after pancreatectomy with or without irreversible electroporation with margin accentuation.Prospective data for preoperative stages IIB (borderline resectable) and III were evaluated, with 75 patients undergoing pancreatectomy with irreversible electroporation with margin accentuation compared to 71 patients who underwent pancreatectomy alone from March 2010 to November 2020.Both irreversible electroporation with margin accentuation and pancreatectomy-alone groups were similar for body mass index, Charleston comorbidity index, and sex. The irreversible electroporation with margin accentuation group had significantly greater preoperative stage III (irreversible electroporation 83% vs pancreatectomy alone 51%; P = .0001), with similar tumor location (head 64% vs 72%) and tumor size (median 2.9 vs 2.8). Neoadjuvant/induction chemotherapy and prior radiation therapy was similar in both groups (irreversible electroporation with margin accentuation 89% vs 72%). Surgical therapy included a greater percentage of pancreaticoduodenectomy in the pancreatectomy-alone group. Despite greater stage and greater percentage of margin positivity (irreversible electroporation with margin accentuation 27% vs 20%; P = not significant), rates of local recurrence were similar. The mean disease-free interval for local recurrence from time of diagnosis was similar (irreversible electroporation with margin accentuation 15.8 vs 16.5 pancreatectomy alone; P = not significant) and time of treatment (irreversible electroporation with margin accentuation 9.4 vs 10.5 months; P = not significant). Overall survival was improved with the irreversible electroporation with margin accentuation group, with a mean of 34.2 months versus 27.9 months in the pancreatectomy-alone group.Irreversible electroporation with margin accentuation is safe and effective in stages IIB and III pancreatic adenocarcinomas that are technically resectable. Despite higher margin positivity rates, the time to local recurrence and the effects of recurrence were the same in the pancreatectomy-alone group.

Exocrine pancreatic insufficiency (EPI) occurs when pancreatic enzyme activity in the intestinal lumen is insufficient for normal digestion to occur. The true incidence and diagnosis of EPI after pancreatectomy has not been fully understood and optimized. The aim of this study was to present incidence and diagnostic criteria for EPI after pancreatectomy for cancer and provide a guide for management and optimal therapy in pancreatectomy patients with cancer. A comprehensive review of the literature with publication dates from 2014 to 2019 was performed. A comprehensive diagnostic and treatment algorithm was then created based on literature review and current treatment options. In total, 30 studies were included, 19 combined both pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), 9 for central pancreatectomy, and 2 others. EPI was defined subjectively without definitive testing using any of the established diagnostic studies in the majority of studies 23 (76%). Preoperative EPI was calculated to be 11.52%. Most studies assessed exocrine function at least 6 months postoperatively with four studies extending the follow-up period beyond 12 months. EPI diagnosed postoperatively at 1 month (40.27%), 3 months (30.94%), 6 months (36.06%), and 12 months (34.69%). After PD, the median prevalence of postoperative EPI was 43.14%, CP, the median prevalence was 4.85%, DP, median prevalence of postoperative EPI of 11.94%. EPI is a frequent outcome that is often misdiagnosed or under-reported by the patient post-pancreatectomy. Given the increasing overall survival in pancreatectomy patients for cancer, surgeon awareness and assessment is critical to improving patients’ overall quality of life.

Hepatocellular carcinoma (HCC), the most common primary hepatic malignancy worldwide, is the second leading cause of cancer-related death. Underlying liver dysfunction and advanced stage of disease require treatments to be optimally timed and implemented to minimize hepatic parenchymal damage while maximizing disease response and quality of life. Locoregional therapies (LRTs) such as trans-arterial chemo- and radio-embolization remain effective for intermediate liver-only and advanced HCC disease (i.e., Barcelona-Clinic liver cancer stages B and C) not amendable to primary resection or ablation. Additionally, these minimally invasive interventions have been shown to augment the immune system. This and the recent success of immune-oncologic treatments for HCC have generated interest in applying these therapies in combination with such locoregional interventions to improve patient outcomes and response rates. This report reviews the use of trans-arterial LRTs with immunotherapy for stages B and C HCC, potential biomarkers, and imaging methods for assessing the response and safety of such combinations.

The optimal timing of treatment of liver metastases from low-grade neuroendocrine tumors (LG-NELM) varies significantly due to numerous treatment modalities and the literature supporting various treatment(s). This study sought to create and validate a literature-based treatment algorithm for LG-NELM.A treatment algorithm to maximize overall survival (OS) was designed using peer-reviewed articles evaluating treatment of LG-NELM. This algorithm was retrospectively applied to patients treated for LG-NELM at our institution. Deviation was determined based on whether or not a patient received treatment consistent with that recommended by the algorithm. Patients who did and did not deviate from the algorithm were compared with respect to OS and number of treatments.Applying our algorithm to a 149-patient cohort, 57 (38%) deviated from recommended treatment. Deviation occurred in the form of alternative (28, 49%) versus additional procedures (29, 51%). Algorithm deviators underwent significantly more procedures than non-deviators (median 1 vs. 2, p 0.001). Cox model indicated no difference in OS associated with algorithm deviation (HR 1.19, p = 0.58) when controlling for age and tumor characteristics.This literature-based algorithm helps standardize treatment protocols in patients with LG-NELM and can reduce cost and risk by minimizing unnecessary procedures. Prospective implementation and validation is required.

Background: Nonalcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD) and a potential precursor of hepatocellular carcinoma (HCC). In our previous studies, we found that endocrine fibroblast growth factor 21 (FGF21) played a key role in preventing the development of NASH, however, the FGF15/19 mediated-FGFR4 signaling worsened NASH and even contributed to the NASH-HCC transition. The aim of this study is to determine whether FGF15/FGFR4 signaling could alleviate or aggravate NASH in the FGF21KO mice. Methods: NASH models were established in FGF21KO mice fed with high fat methionine-choline deficient (HFMCD) diet to investigate FGF15/FGFR4 signaling during early stage NASH and advanced stage NASH. Human hepatocytes, HepG2 and Hep3B cells, were cultured with human enterocytes Caco-2 cells to mimic gut-liver circulation to investigate the potential mechanism of NASH development. Results: Significant increase of FGF15 production was found in the liver of the NASH-FGF21KO mice, however the increased FGF15 protein was unable to alleviate hepatic lipid accumulation. In contrast, up-regulated FGF15/19/FGFR4 signaling was found in the FGF21KO mice with increased NASH severity, as evident by hepatocyte injury/repair, fibrosis and potential malignant events. In in vitro studies, blockage of FGFR4 by BLU9931 treatment attenuated the lipid accumulation, up-regulated cyclin D1, and epithelial-mesenchymal transition (EMT) in the hepatocytes. Conclusion: The increased FGF15 in NASH-FGF21KO mice could not substitute for FGF21 to compensate its lipid metabolic benefits thereby to prevent NASH development. Up-regulated FGFR4 signaling in NASH-FGF21KO mice coupled to proliferation and EMT events which were widely accepted to be associated with carcinogenic transformation.

Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common treatment for peritoneal surface malignancies but no standard carrier solution currently exists for the procedure. This study compared a standard low-dextrose perfusate to a higher-dextrose dialysate that has previously shown favorable impact on perioperative patient outcomes in trauma settings. Materials and methods A single-center retrospective study identified patients undergoing CRS/HIPEC from 2008 to 2019 with recorded dextrose concentration of administered perfusate. An institutional shift to a higher-dextrose solution was made in late 2015. Comparisons of preoperative factors, intraoperative and postoperative glucose levels, and postoperative outcomes were made using the chi-square test, Fisher's exact test, Wilcoxon rank sum test, or repeated measures analysis of variance. Results There were 97 patients in the study, 73 (75%) in the low-dextrose group and 24 (25%) in the high-dextrose group. There was no significant difference in peak intraoperative blood glucose levels between the 1.5% (mean 230 mg/dL) and the 2.5% group (mean 199 mg/dL, P = 0.15). Daily postoperative glucose values were also not statistically different (repeated measures analysis of variance, P = 0.18). Median length of stay was slightly lower for the high-dextrose group (10 d, interquartile range 8-15) than that for the low-dextrose group (12 d, interquartile range 9-17), but was not statistically significant (P = 0.29). Return of bowel function and resumption of diet were similar between the groups. The high-dextrose group had a lower rate of overall complications (20.8%) than the low-dextrose group (49.3%, P = 0.0143). Ninety-day mortality was equivalent between the two groups (2.7% low-dextrose, 4.2% high-dextrose, P = 1.0). Conclusions Use of 2.5% dextrose-containing perfusate appears safe for CRS/HIPEC operations, does not negatively impact intraoperative or postoperative glucose levels, and may be associated with a decreased risk of complications.

National guidelines suggest routine intraoperative esophagogastroduodenoscopy (EGD) during laparoscopic Heller myotomy (LHM) to assess for mucosal perforation and myotomy adequacy, but the utility of this is unknown. This study aimed to evaluate the effect of intraoperative EGD on outcomes after LHM. Patients who underwent LHM in a single center were retrospectively identified. Outcomes were compared between patients who did and did not undergo intraoperative EGD. Sixty-one patients were reviewed: 46 (75%) underwent intraoperative EGD and 15 (25%) did not. Mucosal perforations occurred in 2 (4%) of the EGD group and 3 (20%) of the non-EGD group (p = 0.06). All perforations, regardless of EGD use, were recognized laparoscopically. There were no postoperative leaks. Failed myotomy occurred in 5 (11%) who underwent EGD and 1 (7%) who did not (p = 0.64). Because EGD does not appear to improve outcomes after LHM, we emphasize its selective, rather than routine, use.

Few studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC.Patients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed.Seventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2-112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8-11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75-1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01-1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03-1.25, p = 0.018).Pre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.

Background The preoperative and intraoperative factors that could predict a higher risk of anastomotic/staple line leak for gastric cancer patients has not been accurately defined. Methods Patients who underwent surgery with curative intent for gastric malignancies between 2002 and 2018 were evaluated from a single prospective database. Results A total of 195 patients were evaluated with an overall complication rate of 40%. Anastomotic/staple line leak occurred in 13%, with 4% undergoing reoperation during the same hospitalization. Significant risk factors affecting postoperative complications (POC) were identified in the patients including number of comorbidities (≥2) (HR, 5.30; 95% CI, 1.1–15.3; P = 0.037) and operation type (Total vs Distal) (HR, 2.5; CI 1.08–8.5; p = 0.048). Subset analysis of gastric adenocarcinoma patients demonstrates a five-year overall survival (OS) for patients without perioperative complications was 68%, compared with 41% for patients with POCs (p 0.001). Conclusions In a large single-institutional study, POCs were associated with decreased survival in patients undergoing surgery for gastric adenocarcinoma. Optimizing these patients post-operatively with limited anastomotic stress and enteral feeding tube may allow for a less complicated course.

BACKGROUND Primitive neuroectodermal tumors (PNETs) comprise less than 1% of all sarcomas. The rarity of this disease has resulted in a paucity of information about disease process and management. This study sought to evaluate the incidence, treatment patterns, and outcomes among patients with PNET. METHODS The National Cancer Database was queried for diagnoses of PNET between 2004 and 2014. Patients were dichotomized based on tumor type (central [cPNET] vs peripheral [pPNET]). Demographic, tumor, treatment, and outcome variables were analyzed for the entire patient cohort and by type of PNET. RESULTS White (86.4%) males (56.6%) represented the majority of patients. The incidence of PNET remained stable over the study period (r2 = 0.0821). A total of 70.7% underwent surgical resection of the primary site, 50.3% received radiation, and 74.7% received systemic chemotherapy. Compared to those with pPNET, patients with cPNET more often received radiation treatment (P

The aim of this prospective trial was to assess the compliance of a prehabilitation protocol on post-operative outcome after major abdominal and head and neck surgery. A single-arm, prospective 7-day intervention trial was approved by our local IRB for patients undergoing major abdominal and head-and-neck (H&N) surgery from 8/2018 to 3/2019. This was a 7-day intervention trial at the time of pre-admission testing to assess compliance for pulmonary, nutritional, and physical activity prior to surgery. Seventy-six patients were enrolled in this compliance with IS use that was 85%, with a median of 2200 cc (range 1500–2500cc), pre-operative nutritional drink (89.5%), and chlorhexidine gluconate use was 92%. Ambulation/step compliance was only 32 patients (44%), with median steps of 7500 (range 400–15,000). Compared with the non-prehabilitation patients, we found significant improvement in immediate post-operative mobility (OR 0.73, 95% CI 0.46–0.97, p = 0.04), and improvement in prevention of pulmonary morbidity (OR 0.82, 95% CI 0.23–1.18, p = 0.07) was observed in the prehabilitation group. No significant difference in overall infectious complications (18% vs 27%), surgical site infections (14% vs 22%), length of stay (median 6 days vs 6), or readmissions (18% vs 22%). A simple 7-day prehabilitation protocol at the time of pre-admission testing is feasible with a high degree of compliance regardless of a patient’s disease type, education, or socioeconomic background.

Introduction Surgical site infections (SSIs) lead to increased morbidity and cost. Negative-pressure wound therapy (NPWT) removes wound exudate and improves local blood flow, but its effect on SSI is unproven following hepatectomy and pancreatectomy. The aim of this trial was to evaluate the effect of NPWT on SSI in this population. Methods Patients were randomized to incisional NPWT or sterile island dressing following surgery. SSI predictive factors were recorded as well as patient comorbidities. Wound complications and type of SSI were recorded prospectively. Results Forty patients received the standardized perioperative bundle. Twenty patients received sterile island: 11 hepatic and 9 pancreatic resections; 20 patients received NPWT: 11 hepatic and 9 pancreatic resections; 23 patients were male; mean age 60.8 years (SD ±10.3); mean BMI 31.7 (SD ±7.0). There were three incisional wound infections: two with sterile island, one with NPWT; six organ space infections: four sterile island and two NPWT. There were no significant differences in SSI rates between groups (P = .57). Conclusion NPWT does not improve SSI rates over simple sterile dressing following hepatectomy or pancreatectomy. Improvements in SSI must be directed toward organ-space infections, which are unaffected by NPWT.

BACKGROUND AND OBJECTIVES Irreversible electroporation (IRE) is a nonthermal electrical tumor ablative strategy for unresectable tumors. IRE is relatively safe around critical structures but may induce cardiac arrhythmia when its delivery is not synchronized to the cardiac cycle. We performed a systematic literature review to determine rates of arrhythmia when IRE was utilized with or without cardiac synchronization. METHODS An online literature search was conducted with additional hand selection of articles. Data were extracted and pooled analyses were performed. RESULTS Twelve articles were included in analysis. IRE was performed for 481 patients; 46% hepatic tumors (n = 223), 36% pancreatic lesions (n = 168), and multiple other locations including prostate. Synchronization was performed on 422 patients. Arrhythmias were noted in 3.7% of cases (n = 18/481); cardiac synchronization: 1.2% (n = 5/422) vs unsynchronized: 22.0% (n = 13/59), P

Background Peritoneal carcinomatosis of colorectal adenocarcinoma (CRC) origin is common and is the second-most frequent cause of death in colorectal cancer. There is survival benefit to surgical resection plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with metastatic CRC. However, there remains controversy between oxaliplatin (Oxali) and mitomycin C (MMC), as the agent of choice. Methods A review of our 285 patients prospective HIPEC database from July 2007 to May 2018 identified 48 patients who underwent cytoreductive surgery plus HIPEC with MMC or Oxali. Patients were stratified based on preoperative and postoperative peritoneal cancer indices (PCI). The primary outcomes of survival and progression-free survival were compared. Results Type of HIPEC chemotherapy was not found to be predictive of overall survival. Preoperative PCI (P = .04), preoperative response to chemotherapy (P = .0001), and postoperative PCI (P = .05) were predictive for overall survival. Conclusions MMC or Oxali based HIPEC chemotherapy are both safe and effective for the management of peritoneal only metastatic CRC. Both perfusion therapies should be considered with all patients receiving modern induction chemotherapy.

Liver-directed hepatic arterial therapies are associated with improved survival and effective symptom control for patients with unresectable neuroendocrine liver metastases (NELM). Whether transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) with yttrium-90 (y-90) are associated with improved short- or long-term outcomes is unknown.A retrospective review was performed of all patients with NELM undergoing transarterial therapies, from 2000 to 2018, at 2 academic medical centers. Postoperative morbidity, radiographic response according to response evaluation criteria in solid tumors (RECIST) criteria, and long-term outcomes were compared between patients who underwent TACE vs TARE.Among 248 patients with NELM, 197 (79%) received TACE and 51 (21%) received TARE. While patients who underwent TACE were more likely to have carcinoid syndrome, larger tumors, and higher chromogranin A levels, there was no difference in tumor differentiation, primary site, bilobar disease, or synchronous presentation. Nearly all TARE treatments (92%) were performed as outpatient procedures, while 99% of TACE patients spent at least 1 night in the hospital. There were no differences in overall morbidity (TARE 13.7% vs TACE 22.6%, p = 0.17), grade III/IV complication (5.9% vs 9.2%, p = 0.58), or 90-day mortality. The disease control rate (DCR) on first post-treatment imaging (RECIST partial/complete response or stable disease) was greater for TACE compared with TARE (96% vs 83%, p0.01). However, there was no difference in median overall survival (OS, 35.9 months vs 50.1 months, p = 0.3) or progression-free survival (PFS, 15.9 months vs 19.9 months, p = 0.37).In this retrospective multi-institutional analysis, both TACE and TARE with Y-90 were safe and effective liver-directed therapies for unresectable NELM. Although TARE was associated with a shorter length of hospital stay, TACE demonstrated improved short-term DCR, and both resulted in comparable long term outcomes.

Adequate perioperative nutrition is critical for the success of surgical outcomes. Jejunostomy feeding tube placement may ensure enteral feeding access; however, these types of tubes have had variable reported rates of dysfunction/morbidity. The aim of our study was to report our experience with jejunostomy feeding tube placement and the long-term outcomes following complex foregut surgery. We performed a review of all of our jejunostomy feeding tube placement patients from 1/1/2010 until 7/1/2018. The indication for surgery and primary operation were recorded. All adverse events related to the jejunostomy were recorded during the entire duration of tube access. Social “hassle-factor” issues were also reported, including the number of “jejunostomy-related” phone calls, reinsertion and related placement studies, and readmissions pertaining to jejunostomy-associated complications. During the study period, 542 primary procedures were performed with secondary jejunostomy placement. Jejunostomy-related adverse events occurred in 22.0% of patients (n = 119/542); 12.0% (n = 65/542) were dislodged tubes, 6.0% (n = 30/542) clogged tubes; 5% (n = 25/542) leaking tubes, and 2.8% (n = 15/542) site infections. Tube dysfunctions initiated 244 reinsertion/placement studies in 107 patients, 20 jejunostomy tube-related readmissions, and 78 phone calls to providers for tube dysfunction. Adverse event rates differed significantly between groups (p

BACKGROUND: Assimilating diagnostic radiology education into undergraduate medical education remains a challenge. This challenge places a greater emphasis in surgical residency to ensure this education occurs. The objective of this study is to determine whether a 3D-reconstruction may improve surgical residents’ assessment of resectability of pancreatic lesions METHODS: Four cases were identified of patients with a pancreatic lesion; high-quality, triphasic abdominal CT scans were obtained and evaluated to ensure sufficient resolution and slice thickness. The images then were used for 3D-reconstruction of the cases. RESULTS: PGY3–5 residents had a statistically-significant higher percentage of correct answers on objective questionnaire items using CT in conjunction with 3D-reconstruction software versus CT only. PGY1–2 residents had a higher percentage of correct answers using 3D-reconstruction software, but the difference was not statistically significant. statistically significant. CONCLUSIONS: 3D-reconstruction software could be a viable tool to augment radiology education within a surgery residency, especially in CT interpretation, but there appears to be a minimum threshold of knowledge needed for meaningful improvement; therefore, this software may be more useful for PGY3–5 residents than PGY1–2 residents.

OBJECTIVE: To compare the survival outcomes associated with clinical and pathological response in pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant chemotherapy (NAC) with FOLFIRINOX (FLX) or gemcitabine/nab-paclitaxel (GNP) followed by curative-intent pancreatectomy. BACKGROUND: Newer multiagent NAC regimens have resulted in improved clinical and pathological responses in PDAC; however, the effects of these responses on survival outcomes remain unknown. METHODS: Clinicopathological and survival data of PDAC patients treated at 7 academic medical centers were analyzed. Primary outcomes were overall survival (OS), local recurrence-free survival (L-RFS), and metastasis-free survival (MFS) associated with biochemical (CA 19–9 decrease ≥50% vs

The risk of sentinel lymph node (SLN) metastasis in melanoma is related directly to tumor thickness and inversely to age. The authors hypothesized that for T2 (thickness 1.1–2.0 mm) melanoma, age, and other factors may be able to identify a cohort of patients with a low risk of SLN metastases. The authors developed logistic regression models to predict positive SLNs in patients undergoing SLN biopsy for T2 melanoma using the National Cancer Database. Classification and regression-tree analysis were used to identify groups of patients with high and low risk for SLN metastases. The prediction model then was applied to a separate data set from a multicenter randomized clinical trial. The study identified 12,918 patients with T2 melanoma undergoing SLN biopsy with clinically node-negative melanoma. In the multivariable analysis, increasing thickness, younger age, lymphovascular invasion (LVI), mitotic rate of 1/mm2 or more, axial location, and Clark level of 4 or 5 were independent risk factors for SLN metastases. A cohort based on age (> 56 years) and no LVI was identified with a relatively low risk (7.8%; 95% confidence interval 7.2–8.4%) of SLN metastases. The independent data set of 1531 patients with T2 melanoma confirmed these findings. Among elderly patients (age > 75 years) with melanoma 1.2 mm or smaller and no LVI, the risk of a positive SLN was 4.9% (95% confidence interval 3.3–7.1%). Younger age and LVI are powerful predictors of SLN metastases for patients with T2 melanoma. This prediction model can inform shared decision-making regarding whether to perform SLN biopsy for older patients with otherwise low-risk T2 melanoma.

Patients undergoing irreversible electroporation (IRE) for locally advanced pancreatic cancer (LAPC) may experience biliary obstruction owing to inflammation generated by tumor ablation. This study assessed the safety, efficacy, and technical details of endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression after IRE. A single-institution database of patients undergoing IRE for LAPC between 2012 and 2017 was queried for patients requiring post-IRE ERCP. Patients were evaluated along demographic, laboratory, procedural, and outcome measures. Of 113 patients with LAPC who underwent IRE, 6 (5.3%) required subsequent ERCP for biliary obstruction. A total of 12 ERCPs were performed. Two patients (33%) had duodenal bulb narrowing requiring dilation, and one patient (17%) had a pancreatic head cyst complicating guidewire passage. Biliary cannulation was achieved in all patients in a median time of 30 min. Four patients (67%) underwent sphincterotomy, and 5 (83%) underwent stent placement. Post-procedurally, all showed liver test improvement. None developed pancreatitis. Four patients underwent a 2nd ERCP. All were successful and included stent placement. For patients with biliary obstruction after IRE, ERCP with sphincterotomy and stent placement can safely relieve this obstruction. Duodenal dilation and careful guidewire manipulation may be required to maximize technical success in these patients.

Traditionally, intraductal papillary mucinous neoplasms (IPMNs) of the pancreas with "high risk stigmata" (HRS) or "worrisome features" (WF) are referred for resection. We aim to assess if IPMN location is predictive of harboring either high grade dysplasia (HGD) or invasive cancer (IC).Patients undergoing resection for IPMN from seven institutions between 2000 and 2015 (n = 275) were analyzed. HRS and WF were defined by the 2012 Fukuoka international consensus guidelines.168 (61%) patients had head/uncinate cysts, while 107 (39%) had neck/body/tail cysts. No differences were noted between groups with regard to age, duct type, cyst size, or presence of at least one WF. Patients with cysts in the head/uncinate were more often male (55% vs. 40%), had at least one HRS (24% vs. 11%), and more often harbored HGD or IC(49% vs. 27%)[all p 0.05]. On multivariate analysis, only cyst location in the head/uncinate remained associated with presence of HGD or IC(odds ratio 4.76, p = 0.02).Cyst location is predictive of HGD or IC in patients with IPMNs. Head/uncinated cysts are more likely to harbor malignancy compared to those of the neck/body/tail. Additional studies are needed to confirm these findings, however, cyst location should be considered part of the decision making process for surveillance vs. resection for IPMNs.

Background In the 8th edition of the American Joint Committee on Cancer melanoma staging system, the T1b category has been redefined based solely on thickness and ulceration. National Comprehensive Cancer Network guidelines recommend consideration of sentinel lymph node biopsy (SLNB) for all patients with T1b melanomas (0.8 to 1.0 mm thick). We hypothesized that the new staging system would lead to excessive use of SLNB in patients with non-ulcerated T1b melanomas with a low risk of positive sentinel lymph nodes. Study Design The National Cancer Database 2015 Melanoma Public Use File was used to select patients undergoing SLNB for thin T1 cutaneous melanoma from 2010 to 2015. Clinicopathologic risk factors for having a positive SLNB were evaluated. Univariable and multivariable logistic regression models and classification and regression tree analysis were performed to identify groups with high and low risk of positive SLNB. Results We selected patients undergoing SLNB without ulceration with thickness 0.75 to 1.04 mm, staged T1b in the new 8th edition American Joint Committee on Cancer by thickness criteria alone (6,894 patients). Independent risk factors for a positive sentinel lymph node were age 56 years or younger (odds ratio [OR] 1.74; 95% CI 1.38 to 2.17), thickness 1.0 vs 0.8 to 0.9 mm (OR 1.36; 95% CI 1.09 to 1.70), female sex (OR 1.36; 95% CI 1.09 to 1.69), and mitotic rate ≥1/mm2 (OR 2.01; 95% CI 1.54 to 2.64). Classification and regression tree analysis identified 2 groups based on age, mitotic rate, and thickness with a risk of positive SLNB Conclusions The new 8th edition American Joint Committee on Cancer melanoma staging system T1b category should not be used to determine use of SLNB in thin melanoma, as more than one half of T1b lesions without ulceration have a low risk of positive sentinel lymph nodes.

BACKGROUND. Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in multiple malignancies. The effect of blood transfusion on recurrence and survival in distal cholangiocarcinoma (DCC) is not known. METHODS. All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000 to 2015 were included. Primary outcomes were recurrence-free (RFS) and overall survival (OS). RESULTS. Among 314 patients with DCC, 191 (61%) underwent curative-intent pancreaticoduodenectomy. Fifty-three patients (28%) received perioperative blood transfusions, with a median of 2 units. There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups. Compared with no-transfusion, patients who received a transfusion were more likely to have (+) margins (28 vs 14%; p = 0.034) and major complications (46 vs 16%; p < 0.001). Transfusion was associated with worse median RFS (19 vs 32 months; p = 0.006) and OS (15 vs 29 months; p = 0.003), which persisted on multivariable (MV) analysis for both RFS [hazard ratio (HR) 1.8; 95% confidence interval (CI) 1.1–3.0; p = 0.031] and OS (HR 1.9; 95% CI 1.1–3.3; p = 0.018), after controlling for portal vein resection, estimated blood loss (EBL), grade, lymphovascular invasion (LVI), and major complications. Similarly, transfusion of ≥ 2 pRBCs was associated with lower RFS (17 vs 32 months; p < 0.001) and OS (14 vs 29 months; p < 0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95% CI 1.4–4.5; p = 0.001) and OS (HR 4.0; 95% CI 2.2–7.5; p < 0.001). The RFS and OS of patients transfused 1 unit was comparable to patients who were not transfused. CONCLUSION. Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit was not associated with the same adverse effects as ≥ 2 units.

We developed a protocol to investigate and optimize the application of contrast-enhanced ultrasound (CEUS) to non-invasive diagnosis of progressing fatty liver disease in mouse models. Eighteen 4-wk-old male C57 L/J mice were randomly assigned to one of the three groups and placed on a control diet, high-fat diet or non-alcoholic steatohepatitis diet for the next 10 wk. After 14 wk, B-mode imaging and CEUS imaging using a VisualSonics Vevo2100 system were performed. CEUS imaging and data analysis using three different parameters-peak enhancement, wash-in rate and wash-in perfusion index-revealed a significant decrease in representative blood flow in the high-fat diet group versus controls and a further significant decrease in the non-alcoholic steatohepatitis group (p0.001; n = 6/group). In conclusion, compared with B-mode imaging, non-targeted CEUS imaging was more sensitive in diagnosing early-stage fatty infiltration-mediated vascularity changes in liver parenchyma and provided a more accurate steatohepatitis diagnosis in mouse models.

Background Anti-PDL-1 immunotherapy for Hepatocellular Carcinoma (HCC) demonstrated a mixed response. Polycomb Repressor Complex 2(PRC2) contributes to the initiation and progression of HCC by suppressing tumor antigens and inhibiting an immune response. Two components of epigenetic modulation are Enhancer of Zeste Homolog 2 (EZH2, the catalytic component of PRC2) and DNA Methyltransferase 1 (DNMT1). We aim to investigate the potential role of epigenetic therapy targeting EZH2 and DNMT1 as a novel strategy to modulate immunotherapy response in HCC. Methods HepG2, Hep3B, and Hepa1-6 HCC cell lines were treated with EZH2 inhibitor (DZNep) and DNMT1 inhibitor (5-Azacytidine) with and without anti-PDL-1. Quantitative RT-PCR and immunohistochemistry were performed to evaluate the expression of tumor suppressors, tumor antigens, and Th1 chemokines. In-vivo C57/LJ immunocompetent mice model with subcutaneous tumor inoculation was performed with intraperitoneal drug injections. Results There was a significant upregulation of Th1 chemokines in HepG2 (CXCL9 5.5 ± 0.2 relative fold change; CXCL10 1.44 × 103 ± 37 relative fold change) and Hep3B (CXCL 9 6.85 × 103 ± 1.3 × 103 relative fold change; CXCL 10 2.15 × 103 ± 3.1 × 102 relative fold change). Additionally, there was a significant induction of cancer testis antigens NY-ESO-1 (3.6–3.7 ± 0.3 relative fold change) and LAGE (8.3–11.7 ± 1.9 relative fold change). In vivo model demonstrated statistically significant tumor regression in the combination treatment group (0.02 g ± 0.02) compared to epigenetic therapy (0.63 g ± 0.61) or immunotherapy alone (0.15 g ± 0.21) with untreated control (2.4 g ± 0.71). There was significantly increased trafficking of cytotoxic T- lymphocytes and associated apoptosis for the combination treatment group compared to epigenetic or immunotherapy alone. Conclusions This study demonstrates that epigenetic modulation could be a novel potential strategy to augment immunotherapy for HCC by stimulating T cell trafficking into tumor microenvironment via activation of transcriptionally repressed chemokine genes responsible for T-cell trafficking, inducing previously silent neoantigens for immune targets, and allowing tumor regression as a result. A clinical trial of this feasible combination therapy of these clinically available agents is warranted.

Background Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors. Methods Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only. Discussion These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC. Trial registration Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019.

BackgroundPharmacological application of the endocrine fibroblast growth factor15/19 (FGF15/19) and FGF21 holds great promise to be effective therapeutic agents for treating nonalcoholic steatohepatitis (NASH), which is the most severe form of non-alcoholic fatty liver disease (NAFLD) and accepted as a potential precursor of hepatocellular carcinoma (HCC). In our previous studies, we found that FGF21 played a key role in preventing the development of NASH, however, the FGF15/19 mediated-FGFR4 signaling worsened NASH and even contributed to the NASH-HCC transition. MethodsNASH models were established in FGF21KO mice fed with high fat methionine-choline deficient (HFMCD) diet to investigate FGF15/FGFR4 signaling during NASH development. We sought to determine whether FGF15/FGFR4 signaling could alleviate or aggravate NASH in the FGF21KO mice challenged with HFMCD. ResultsSignificant increase of FGF15 production was found in the liver of the NASH-FGF21KO mice, however the increased FGF15 protein was unable to alleviate hepatic lipid accumulation. In contrast, the up-regulated hepatic FGFR4–β‑klotho was found during NASH progression, as evident by hepatocyte injury/repair, fibrosis and potential malignant events, in the NASH-FGF21KO mice. ConclusionThe increased FGF15 production in NASH-FGF21KO mice could not substitute for FGF21 to compensate its lipid metabolic benefits thereby to prevent NASH development. The up-regulated FGFR4/β-klotho was coupled to cellular and molecular events which might associate to carcinogenic transformation.

Background Outcomes after laparoscopic gastropexy (LG), performed as an alternative to formal paraesophageal hernia (PEH) repair in patients with giant PEH, have been rarely studied. This manuscript evaluates complications and long-term quality-of-life after LG. Methods An IRB-approved protocol was used to identify patients who underwent LG to alleviate symptoms of acute or chronic gastric obstruction secondary to a paraesophageal hernia. Postoperative outcomes and quality-of-life data were retrospectively collected via chart review and prospectively via phone interview. Results Twenty-six patients underwent LG, with a median age of 76 (52 - 91). Median follow-up was 28 (3 to 55) months. Gastropexy was the chosen intervention due to comorbid conditions (23, 88%), gastric inflammation (2, 8%), or intraoperative instability (1, 4%). Nine (35%) suffered postoperative complications, and 2 (8%) required reoperation. At the time of follow-up, 7 (27%) had died, 3 (11%) could not be reached. Sixteen (62%) completed the follow-up survey. Fourteen (88%) reported symptom resolution. Ten (62%) still required antireflux medication. Median Gastroesophageal Reflux Disease-Health Related Quality of Life score was 4.5 (0 to 19). Fourteen (88%) denied current dietary restrictions. All reported satisfaction with the operation. Conclusion Laparoscopic PEH repair remains the standard of care for the management of giant PEH. However, a subcategory of patients with high operative risk could be candidates for a shorter operative intervention. As our data infers, LG is a reasonable alternative in this patient population. While the continued use of antisecretory medications is sometimes required, LG restores the ability to tolerate full meals without restrictions and results in excellent patient satisfaction.

Background There is an increasing trend toward regionalization of emergency general surgery, which burdens patients. The absence of a standardized, emergency general surgery transfer algorithm creates the potential for unnecessary transfers. The aim of this study was to evaluate clinical reasoning prompting emergency general surgery transfers and to initiate a discussion for optimal emergency general surgery use. Methods Consecutive emergency general surgery transfers (December 2018 to May 2019) to 2 tertiary centers were prospectively enrolled in an institutional review board–approved protocol. Clinical reasoning prompting transfer was obtained prospectively from the accepting/consulting surgeon. Patient outcomes were used to create an algorithm for emergency general surgery transfer. Results Two hundred emergency general surgery transfers (49% admissions, 51% consults) occurred with a median age of 59 (18 to 100) and body mass index of 30 (15 to 75). Insurance status was 25% private, 45% Medicare, 21% Medicaid, and 9% uninsured. Weekend transfers (Friday to Sunday) occurred in 45%, and 57% occurred overnight (6:00 pm to 6:00 am). Surgeon-to-surgeon communication occurred with 22% of admissions. Pretransfer notification occurred with 10% of consults. Common transfer reasons included no surgical coverage (20%), surgeon discomfort (24%), or hospital limitations (36%). A minority (36%) underwent surgery within 24 hours; 54% did not require surgery during the admission. Median length of stay was 6 (1 to 44) days. Conclusion Conditions prompting emergency general surgery transfers are heterogeneous in this rural state review. There remains an unmet need to standardize emergency general surgery transfer criteria, incorporating patient and hospital factors and surgeon availability. Well-defined requirements for communication with the accepting surgeon may prevent unnecessary transfers and maximize resource allocation.

Irreversible electroporation (IRE) has been demonstrated as an effective local method for locally advanced (stage 3) pancreatic adenocarcinoma. Immune regulatory T cells (Tregs) induce immunosuppression of tumors by inhibiting patients’ anti-tumor adaptive immune response. This study aimed to evaluate the immunomodulation effect of IRE to identify an ideal time point for potential adjuvant immunotherapy. This study prospectively evaluated an institutional review board-approved study of patients undergoing either in situ IRE or pancreatectomy. Patient blood samples were collected at different time points (before surgery [preOP] and on postoperative day [POD] 1, POD3, and POD5). Peripheral blood mononuclear cells (PBMCs) were isolated and evaluated for three different CD4 + Treg subsets (CD25 + CD4 +, CD4 + CD25 + FoxP3 +, CD4 + CD25 + FoxP3 −) by flow cytometry and analyzed for median fold change (MFC) between each two consecutive time points (MFC = log2(T2/T1)). The study analyzed 15 patients with in situ IRE (n = 11) or pancreatectomy (PAN) (n = 4). In both groups, CD25 + CD4 + Tregs decreased on POD1 followed by a steady increase in pancreatectomy, whereas the trend in the IRE group reversed between D3 and D5 (MFC: IRE [− 0.01], PAN [+ 0.39]). For each period, CD4 + CD25 + FoxP3 + Tregs showed the most dramatic inverse effect, with D3 to D5 showing the most change (MFC: IRE [− 0.18], PAN [+ 0.39]). Also, CD4 + CD25 + FoxP3 − Tregs showed an inverse effect between D3 and D5 (MFC: IRE [− 0.25], PAN [+ 0.49]). Altogether, the Treg trend was inversely affected by the in situ IRE procedure, with the greatest cumulative significant change for all three Treg subsets between D3 and D5 (MFC ± SEM: IRE [− 0.24 ± 0.05], PAN [+ 0.37 ± 0.02]; p = 0.016). The study data suggest that in situ IRE procedure-mediated Treg attenuation between POD3 and POD5 can provide a clinical window of opportunity for potentiating clinical efficacy in combination with immunotherapy.

A novel highly biocompatible nanosystem made up of a chitosan matrix and filled with magnesium nanoparticles was synthesized using a simple and one-pot strategy, and tested as a promising, well-tolerated tool for photothermal therapy. Moreover, in vivo a proof of concept on hepatocarcinoma-bearing mice is presented.

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective, aggressive approach to treating intraperitoneal carcinomatosis. This study aimed to test the efficacy/safety of an enhanced recovery (ERAS) program after CRS-HIPEC surgery. METHODS: Review of an IRB-approved prospectively maintained HIPEC database from 2003–2019. Adverse events and outcomes related to the primary operation were noted. RESULTS. 125 HIPEC procedures performed met inclusion criteria, with 20 treated through ERAS. There was an improvement in LOS (ERAS: 9, 6.0–28.0; non-ERAS: 11.0, 6.0–45.1, P=0.5), a significant reduction in opioid use during hospitalization (ERAS Total Morphine Equivalents 156 vs Non-ERAS of 856, p

BACKGROUND Staging laparoscopy (SL) is used to avoid resection failure and thus increase the curative resection rate. SL utilization in extra-hepatic biliary tumors (EHBT) is variable. METHODS Data from 1090 patients with potentially resectable EHBT including gallbladder (GBC), distal (DC), and hilar (HC) subtypes were retrospectively collected from 10 academic centers (2000-2015). RESULTS The SL utilization rate increased over time and was significantly higher in GBC than DC and HC. SL yield was 16.8% and did not differ between groups or over time. In patients undergoing attempted resection with prior SL, the curative resection rate did not differ between subtypes. In patients undergoing attempted resection without prior SL, the curative resection rate was less in GBC compared with DC or HC. After matching cohorts by inverse probability weighting, prior SL was associated with curative resection in GBC only (odds ratio [OR], 2.41, 95% CI, 1.36-4.27). On multivariable regression analysis, elevated carbohydrate antigen 19-9 (CA 19-9), low serum albumin, and GBC were strong predictors of distant disease on SL. After categorizing patients undergoing SL into low, intermediate, and high-risk groups based on these parameters, SL yield improved progressively from 10.0% to 19.6% to 52.6%. CONCLUSIONS We recommend routine SL for patients with GBC, particularly with elevated CA19-9 level and/or decreased serum albumin.