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No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Partial hepatectomy, one of a few curative therapeutic modalities, is plagued by high recurrence rate of up to 70% at 5 years. Throughout the past 3 decades, many clinical trials have attempted to improve HCC recurrence rate following partial hepatectomy using adjuvant and neoadjuvant treatment modalities such as antiviral therapy, brachytherapy, systemic chemotherapy, immunotherapy, transarterial chemoembolization and radioembolization, and radiotherapy. The goal of this review is to discuss the clinical trials pertaining to resectable HCC including surgical technique considerations, adjuvant, and neoadjuvant treatment modalities.

Pts with gastric cancer in US-Mexico border counties receive less guideline-concordant care and have worse OS.

BackgroundTumour growth patterns have important implications for surveillance intervals, prognostication and treatment decisions but have not been well described for hepatocellular carcinoma (HCC). The aim of our study was to characterise HCC doubling time and identify correlates for indolent and rapid growth patterns.MethodsWe performed a systematic literature review of Medline and EMBASE databases from inception to December 2019 and national meeting abstracts from 2010 to 2018. We identified studies reporting HCC tumour growth or tumour volume doubling time (TVDT), without intervening treatment, and abstracted data to calculate TVDT and correlates of growth patterns (rapid defined as TVDT <3 months and indolent as TVDT >9 months). Pooled TVDT was calculated using a random-effects model.ResultsWe identified 20 studies, including 1374 HCC lesions in 1334 patients. The pooled TVDT was 4.6 months (95% CI 3.9 to 5.3 months I2=94%), with 35% classified as rapid, 27.4% intermediate and 37.6% indolent growth. In subgroup analysis, studies from Asia reported shorter TVDT than studies elsewhere (4.1 vs 5.8 months). The most consistent correlates of rapid tumour growth included hepatitis B aetiology, smaller tumour size (continuous), alpha fetoprotein doubling time and poor tumour differentiation. Studies were limited by small sample sizes, measurement bias and selection bias.ConclusionTVDT of HCC is approximately 4–5 months; however, there is heterogeneity in tumour growth patterns, including more aggressive patterns in Asian hepatitis B-predominant populations. Identifying correlates of tumour growth patterns is important to better individualise HCC prognostication and treatment decisions.

Racial/ethnic and socioeconomic disparities are assumed to negatively affect treatment and outcomes for hepatocellular carcinoma (HCC). Our aim was to investigate the interaction of racial/ethnic and socioeconomic factors with stage of disease and type of treatment facility in receipt of treatment and overall survival (OS) of patients with HCC.

Background Hepatitis C virus (HCV) has historically been the most common cause of cirrhosis and hepatocellular carcinoma (HCC) in the United States. With improved HCV treatment, cirrhosis secondary to other etiologies is increasing. Given this changing epidemiology, our aim was to determine the impact of cirrhosis etiology on overall survival (OS) in patients with HCC.Methods All patients with cirrhosis and primary HCC from the US Safety Net Collaborative (2012-2014) database were included. Patients were grouped into “safety net” and “academic” based on where they received their care. The primary outcome was the OS.Results 1479 patients were included. The average age was 60 years and 78% (n = 1156) were male. 56% (n = 649) received care at academic and 44% (n = 649) at safety net hospitals. The median model for end-stage liver disease (MELD) was 10 (IQR 8-16). Median OS was 23 months. Etiology of cirrhosis was viral hepatitis 56% (n = 612), alcohol abuse 14% (n = 152), alcohol and hepatitis 23% (n = 251), and other 7% (n = 85). Patients with alcohol-related cirrhosis (alcohol alone or with hepatitis) were younger (59 vs 62 years), more likely to be male (86% vs 75%), treated at a safety net facility (45% vs 35%), uninsured (17% vs 13%), and had a higher MELD (median 12 vs 10) (all P< .003). They were less likely to have been screened for HCC within 1 year of diagnosis (20% vs 29%) and to receive treatment (69% vs 81%), and more likely to present with stage IV disease (21% vs 15%) (all P< .001). Patients with alcohol-related cirrhosis had decreased OS (5-year OS 24% vs 40%, P< .001), which persisted in a subset analysis of both academic and safety net populations.Conclusion Although not significant on MVA, alcohol-related cirrhosis is associated with all factors that correlate with decreased survival from HCC. Efforts must focus on this vulnerable patient population to optimize screening, treatment, and outcomes.

Background: Data-driven patient selection guidelines are not available to optimize outcomes in minimally invasive pancreaticoduodenectomy (MIPD). We aimed to define risk factors associated with conversion from MIPD to open PD and to determine the impact of conversion on post-operative outcomes. Methods: We conducted a retrospective review of MIPD using NSQIP from 2014 to 2015. Propensity score was used to match patients who underwent completed MIPD to converted MIPD. Results: 467 patients were included: 375 (80.3%) MIPD and 92 (19.7%) converted. Converted patients were more often male (64% vs. 52%, p= 0.030), had higher rates of dyspnea (10% vs. 3%, p= 0.009), underwent more vascular (44% vs. 14%, p&lt; 0.001) or multivisceral resection (19% vs. 6%, p= 0.0005), and were more likely attempted laparoscopically compared to robotically (76% vs. 51%, p&lt; 0.001). Robotic approach was independently associated with reduced risk of conversion (OR 0.40, 95% CI 0.23–0.69), while male gender (OR 1.70, 95% CI 1.02–2.84), history of dyspnea (OR 3.85, 95% CI 1.49–9.96), vascular resection (OR 4.32, 95% CI 2.53–7.37), and multivisceral resection (OR 2.18, 95% CI 1.05–4.52) were associated with increased risk. Major complications were more common in converted patients (68% vs. 37%, p&lt; 0.001). Converted patients had increased odds of non-home discharge (OR 3.25, 95% CI 1.06–9.97) and an associated increased length of stay of 3 days (95% CI 0.1–6.7). Conclusion: Patients with a history of dyspnea or tumors requiring vascular or multivisceral resection were at increased risk of conversion, and the robotic platform was associated with a lower rate of conversion. Conversion was independently associated with increased overall complications, increased length of stay, and non-home discharge.

Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC.

Operative blood loss is associated with postoperative morbidity and mortality in surgery. Hemostatic agents are used as adjuncts for hemostasis during surgery and help to prevent postoperative bleeding. We evaluated the safety and efficacy of an investigational polysaccharide hemostatic (PH) topical product compared to a U.S. Food and Drug Administration (FDA)-approved control in clinical use comprising microporous polysaccharide hemospheres (MPH) to achieve hemostasis of bleeding surfaces during surgery.

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Minimally invasive pancreaticoduodenectomy (MIPD) is being performed with increasing frequency for pancreatic cancer, but the most oncologically efficacious surgical platform, whether robotic or laparoscopic, is yet to be determined. Currently, there are no national studies comparing the oncological outcomes between robotic (RPD) and laparoscopic (LPD) pancreaticoduodenectomy. This was a retrospective study using the National Cancer Database between 2010 and 2013. We compared the perioperative, pathological, and mid-term oncological outcomes between RPD and LPD. There were 1623 MIPD cases, of which 90% were LPD and 10% were RPD. Most LPD (63%) and RPD (51%) cases were performed at institutions with a volume of ≤ 5 MIPDs per year. There were no differences in patient- and tumor-related factors between the groups. The majority of treated tumors were adenocarcinoma (90.1% for RPD and 89.1% for LPD). RPDs were more likely to be performed at academic centers (89.1%) compared to LPDs (68.1%, P< 0.001) and at higher-volume centers (median MIPD/year of 4.7 for RPD vs 3.6 for LPD, P< 0.001). There was no difference in the median number of examined lymph nodes, margin status, median length of stay, 90-day mortality, or 30-day readmission between groups. There was no difference in median overall survival for pancreatic adenocarcinoma between LPD (20.7 months) and RPD (22.7 months; log-rank P= 0.445). The 1- and 3-year overall survival rates were 74 and 31% for LPD and 71 and 33% for RPD. In this national cohort of patients, LPD and RPD were associated with equivalent perioperative, pathological, and mid-term oncological outcomes.

IMPORTANCE: Distant recurrence following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma is common. Adjuvant chemotherapy may improve survival. OBJECTIVE: To compare adjuvant chemotherapy with postoperative observation following preoperative chemoradiotherapy and resection in patients with gastroesophageal adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: Propensity score–matched analysis using the National Cancer Database. We included adult patients who received a diagnosis between 2006 and 2013 of clinical stage T1N1-3M0 or T2-4N0-3M0 adenocarcinoma of the distal esophagus or gastric cardia who were treated with preoperative chemoradiotherapy and curative-intent resection. Patients receiving adjuvant chemotherapy were matched by propensity score to patients undergoing postoperative observation. EXPOSURES: Adjuvant chemotherapy and postoperative observation. MAIN OUTCOMES AND MEASURES: Overall survival. RESULTS: We identified 10 086 patients (8840 [88%] male; mean [SD] age, 61 [9.5] years), 9272 in the postoperative observation group and 814 in the adjuvant chemotherapy group. Patients receiving adjuvant chemotherapy were younger (18-54 years: 252 [31%] vs 1989 [21%]; P &lt; .001) and were more likely to have advanced disease (ypT3/4: 458 [62%] vs 3531 [46%]; P &lt; .001; ypN+: 572 [72%] vs 3428 [39%]; P &lt; .001), as well as shorter postoperative inpatient stays (>2 weeks: 94 [13%] vs 1589 [20%]; P &lt; .001). A total of 732 patients in the adjuvant chemotherapy group were matched by propensity score to 3660 patients in the postoperative observation group. Adjuvant chemotherapy was associated with improved overall survival compared with postoperative observation (median survival: 40 months; 95% CI, 36-46 months vs 34 months; 95% CI, 32-35 months; stratified log-rank P &lt; .001; hazard ratio, 0.79; 95% CI, 0.72-0.88). Overall survival at 1, 3, and 5 years was 88%, 47%, and 34% in the observation group, and 94%, 54%, and 38% in the adjuvant chemotherapy group, respectively. Adjuvant chemotherapy was associated with a survival benefit compared with postoperative observation in most patient subgroups. CONCLUSIONS AND RELEVANCE: For patients with locally advanced gastroesophageal adenocarcinoma treated with preoperative chemoradiotherapy and resection, adjuvant chemotherapy was associated with improved overall survival. Our findings have important implications for the postoperative treatment of this patient group for which few data are available.

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) 51.0–2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7–5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5–4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1–3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1–12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9–6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Peri-operative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

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Hepatic resection is one of the mainstays of curative therapy for HCC. The appropriate selection of resectable candidates requires careful consideration of a multitude of factors including tumor burden (size and number of nodules, presence of vascular involvement, extrahepatic spread), patient factors (performance status, underlying liver function), and availability of other therapies (access to transplantation, interventional procedures, immunotherapies). Historically, hepatic resection for HCC has been reserved for patients with solitary tumors without vascular invasion. However, in well selected patients HCC tumors multifocal in nature or with vascular invasion should be considered for hepatic resection.

OBJECTIVES:The association between hospital volume and outcome following high-risk low volume cancer surgery is well documented. However, this association is not well understood in cancer patients undergoing non-surgical therapies. We explored this association in a cohort of newly diagnosed patients with hepatocellular carcinoma (HCC).METHODS:Data from the 2000 through 2011 in Texas Cancer Registry were used to study adults with newly diagnosed HCC (17,231 patients from 322 hospitals). Hospital volume was stratified into low and high volume using Contal’s outcome-based method. A multivariable Cox regression with shared frailty was used to evaluate the association between hospital volume and overall survival. The relationship between treatment modality and hospital volume was explored using mixed effects logistic regression.RESULTS:The majority (61%) of HCC patients were seen in 21 high-volume hospitals. An annual hospital volume cutoff point of 24 patients was determined to stratify between high- and low-volume hospitals. Patients at high-volume hospitals presented more commonly with localized disease (56 vs. 50%, P<0.01) and were more likely to receive curative therapies including surgical resection, liver transplantation, or ablation (22 vs. 12%, P<0.01). High-volume hospitals were significantly associated with improved survival (HR=0.96, 95% CI=0.94–0.98). In multivariable analysis, hospital volume was associated with increased overall treatment utilization (OR=1.3, 95% CI=1.2–1.4).CONCLUSIONS:Hospital volume is associated with improved overall survival, particularly in localized HCC. Improved survival may be mediated by increased utilization of treatments in high HCC volume hospitals.

IMPORTANCE: Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES: To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS: Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES: The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS: In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P &lt; .001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02-3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS). CONCLUSIONS AND RELEVANCE: Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.

Understanding trafficking and migration of antigen-presenting cells and T cells is important to uncover the anatomic domains where lymphocytes interact with alloantigen during the tolerization process and whether the interactions for immunity and rejection are anatomically separate from those important for tolerance.

CD4 + CD25 + regulatory T cells (Tregs) are potent suppressors, playing important roles in autoimmunity and transplantation tolerance. Understanding the signals necessary for the generation and expansion of Tregs is important for clinical cellular therapy, but only limited progress has been made. Recent reports suggest a role for TGF-β in the generation of Tregs from CD4 + CD25 − precursors, but the mechanism remains unknown. Here, we demonstrate that TGF-β2 triggers Foxp3 expression in CD4 + CD25 − precursors, and these Foxp3 + cells act like conventional Tregs. The generation of Foxp3 + Tregs requires stimulation of the T-cell receptor, the IL-2R and the TGF-β receptor. More importantly, strong costimulation through CD28 prevents Foxp3 expression and suppressive function in an IL-4-dependent manner. Furthermore, TGF-β-driven Tregs inhibit innate inflammatory responses to syngeneic transplanted pancreatic islets and enhance islet transplant survival. Thus, TGF-β is a key regulator of the signaling pathways that initiate and maintain Foxp3 expression and suppressive function in CD4 + CD25 − precursors. TGF-β and signaling through TGF-β receptor, CD28 costimulation and IL-4 may be key components for the manipulation of Treg. The de novo generation of Foxp3 + cells from CD4 + cells has the potential to be used for treatment of autoimmune diseases and induction of transplant tolerance.

CD4 + CD25 + regulatory T cells (Tregs) are potent suppressors, playing important roles in autoimmunity and transplantation tolerance. Understanding the signals necessary for the generation and expansion of Tregs is important for clinical cellular therapy, but only limited progress has been made. Recent reports suggest a role for TGF-β in the generation of Tregs from CD4 + CD25 − precursors, but the mechanism remains unknown. Here, we demonstrate that TGF-β2 triggers Foxp3 expression in CD4 + CD25 − precursors, and these Foxp3 + cells act like conventional Tregs. The generation of Foxp3 + Tregs requires stimulation of the T-cell receptor, the IL-2R and the TGF-β receptor. More importantly, strong costimulation through CD28 prevents Foxp3 expression and suppressive function in an IL-4-dependent manner. Furthermore, TGF-β-driven Tregs inhibit innate inflammatory responses to syngeneic transplanted pancreatic islets and enhance islet transplant survival. Thus, TGF-β is a key regulator of the signaling pathways that initiate and maintain Foxp3 expression and suppressive function in CD4 + CD25 − precursors. TGF-β and signaling through TGF-β receptor, CD28 costimulation and IL-4 may be key components for the manipulation of Treg. The de novogeneration of Foxp3 + cells from CD4 + cells has the potential to be used for treatment of autoimmune diseases and induction of transplant tolerance.

CD4+CD25+regulatory T cells (Treg) are potent suppressors, and play important roles in autoimmunity and transplantation. Recent reports suggest that CD4+CD25+Treg are not a homogeneous cell population, but the differences in phenotype, function, and mechanisms among different subsets are unknown. Here, we demonstrate CD4+CD25+Treg cells can be divided into subsets according to cell-surface expression of CD62L. While both subsets express foxp3 and are anergic, the CD62L+population is more potent on a per cell basis, and proliferates and maintains suppressive function far better than the CD62L– population and unseparated CD4+CD25+Treg. The CD62L+population preferentially migrates to CCL19, MCP-1 and FTY720. Both CD62L+and CD62L– subsets prevent the development of autoimmune gastritis and colitis induced by CD4+CD25–CD45RBhighcells in severe combined immunodeficiency (SCID) mice. Overall, these results suggest CD4+CD25+Treg are not a homogenous cell population, but can be divided into at least two subsets according to CD62L expression. The CD62L+subset is a more potent suppressor than the CD62L– population or unfractionated CD4+CD25+Treg cells, can be expanded far more easily in culture, and is more responsive to chemokine-driven migration to secondary lymphoid organs. These properties may have significant implications for the clinical manipulation of the CD4+CD25+CD62L+cells.

Accurate non-invasive prediction of long-term hepatocellular carcinoma (HCC) risk in advanced liver fibrosis is urgently needed for cost-effective HCC screening; however, this remains an unmet need.

Normal hepatic arterial anatomy occurs in approximately 50–80% of cases; for the remaining cases, multiple variations have been described. Knowledge of these anomalies is especially important in hepatobiliary and pancreatic surgery in order to avoid unnecessary complications. We describe two cases of patients undergoing pancreatoduodenectomy for abnormalities in the head of the pancreas. Preoperative contrast-enhanced cross-sectional imaging demonstrated relevant, rare hepatic arterial variants: (1) a completely replaced hepatic arterial system with a gastroduodenal artery (GDA) arising directly from the celiac axis and (2) a replaced right hepatic artery originating from the superior mesenteric artery and traveling anterior to the pancreatic uncinate process and head. These findings were confirmed during pancreatoduodenectomy. Both of these variants have been rarely described with an incidence of <1.0%. In the present paper, we describe the hepatic arterial anomalies commonly encountered and clarify the important details associated with these variants as they pertain to pancreatoduodenectomy.