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Previous studies have reported healthcare disparities in the Texas-Mexico border population. Our aim was to evaluate treatment utilization and oncologic outcomes of colon cancer patients in this vulnerable population.Patients with localized and regional colon cancer (CC) were identified in the Texas Cancer Registry (1995-2016). Clinicopathological data, hospital factors, receipt of optimal treatment, and overall survival (OS) were compared between Texas-Mexico Border (TMB) and the Non-Texas-Mexico Border (NTMB) cohorts. Multivariable analysis was performed to identify risk factors associated with decreased survival.We identified 43,557 patients with localized/regional CC (9% TMB and 91% NTMB). TMB patients were more likely to be Hispanic (73% versus 13%), less likely to have private insurance (13% versus 21%), were more often treated at safety net hospitals (82% versus 22%) and less likely at ACS-CoC accredited hospitals (32% versus 57%). TMB patients were more likely to receive suboptimal treatment (21% versus 16%) and had a lower median OS for localized (8.58 versus 9.58 y) and regional colon cancer (5.75 versus 6.18 y, all P0.001). In multivariable analysis, TMB status was not associated with worse OS. Factors associated with worse survival included receipt of suboptimal treatment, Medicare/insured status, and treatment in safety net and non-accredited ACS-CoC hospitals (all P0.001) CONCLUSIONS: While TMB CC patients had worse OS, TMB status itself was not found to be a risk factor for decreased survival. This survival disparity is likely associated with higher rate of suboptimal treatment, Medicare/Uninsured status, and decreased access to ACS-CoC accredited hospitals.

Background Patients with metastatic hepatocellular carcinoma (HCC) suffer symptoms of both end-stage liver disease and cancer. Palliative care (PC) enhances the quality of life via symptom control and even improves survival for some cancers. Our study characterized rates of PC utilization among metastatic HCC patients and determined factors associated with PC receipt. Methods We conducted a retrospective review of adult National Cancer Database patients diagnosed with metastatic HCC between 2004 and 2016. Chi-square tests were used to analyze two cohorts: those who received PC and those who did not. Logistic regression was performed to assess the impact of clinicodemographic factors on the likelihood of receiving PC. Results PC utilization was low at just 17%. Later year of diagnosis, insured status, and higher education level were associated with an increased likelihood of receiving PC. Treatment at academic centers or integrated network cancer programs increased the likelihood of receiving PC compared to treatment at a community center (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03-1.33 and OR = 1.25, 95% CI = 1.07-1.45; respectively). Hispanics were significantly less likely to received PC than non-Hispanic Whites (OR = 0.73, 95% CI = 0.64-0.82). Conclusions PC utilization among patients with metastatic HCC remains low. Targeted efforts should be enacted to increase the delivery of PC in this group.

Background: Delays in diagnosis and treatment have been reported for many cancers, with resultant stage migration and worse survival; however, few data exist in patients with hepatocellular carcinoma (HCC). These data are of particular importance in light of the COVID-19 pandemic, which has caused disruptions in healthcare processes and may continue to impact cancer care for the foreseeable future. The aim of our study was to characterize the prevalence and clinical significance of diagnostic and treatment delays in patients with HCC. Methods: We performed a retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and July 2017 at 2 US health systems. Diagnostic and treatment delays were defined as >90 days between presentation and HCC diagnosis and between diagnosis and treatment, respectively. We used multivariable logistic regression to identify factors associated with diagnostic and treatment delays and Cox proportional hazard models to identify correlates of overall survival. Results: Of 925 patients with HCC, 39.0% were diagnosed via screening, 33.1% incidentally, and 27.9% symptomatically. Median time from presentation to diagnosis was 37 days (interquartile range, 18–94 days), with 120 patients (13.0%) experiencing diagnostic delays. Median time from HCC diagnosis to treatment was 46 days (interquartile range, 29–74 days), with 17.2% of patients experiencing treatment delays. Most (72.5%) diagnostic delays were related to provider-level factors (eg, monitoring indeterminate nodules), whereas nearly half (46.2%) of treatment delays were related to patient-related factors (eg, missed appointments). In multivariable analyses, treatment delays were not associated with increased mortality (hazard ratio, 0.90; 95% CI, 0.60–1.35); these results were consistent across subgroup analyses by Barcelona Clinic Liver Cancer stage and treatment modality. Conclusions: Diagnostic and therapeutic delays exceeding 3 months are common in patients with HCC; however, observed treatment delays do not seem to significantly impact overall survival.

Professional society guidelines recommend semiannual screening for hepatocellular carcinoma (HCC) in patients with cirrhosis; however, studies suggest underuse of screening in clinical practice. Our study’s aim was to characterize reasons for HCC screening underuse among patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis diagnosed with HCC in two large health systems from 2011 to 2019. We classified screening receipt as consistent, inconsistent, or no screening in the year before HCC diagnosis. We categorized reasons for screening underuse as a potential failure at each of the following steps required for HCC screening: receipt of regular outpatient care, recognition of liver disease, recognition of cirrhosis, screening orders in patients with cirrhosis, and adherence to screening ultrasound appointments. Among 1,014 patients with cirrhosis with HCC, only 377 (37.2%) had regular outpatient care in the year before HCC presentation. Consistent screening was observed in 93 (24.7%) patients under regular outpatient care, whereas 161 (42.7%) had inconsistent screening and 123 (32.6%) no screening. We found screening underuse related to failures at each step in the screening process, although nearly half (49.6%) were due to lack of screening orders in patients with known cirrhosis. Conclusion: The most common reasons for HCC screening underuse in patients with cirrhosis are lack of regular outpatient care and lack of screening orders in those with known cirrhosis, highlighting the need for interventions targeted at these steps to increase HCC screening use., In a retrospective cohort study of 1014 cirrhosis patients diagnosed with HCC in two large health systems, we categorized reasons for screening underuse: receipt of regular outpatient care, recognition of liver disease, recognition of cirrhosis, screening orders in patients with cirrhosis, and adherence to screening ultrasound appointments. Only 377 (37.2%) patients had regular outpatient care in the year prior to HCC presentation, of whom 93 (24.7%) had consistent screening, 161 (42.7%) had inconsistent screening, and 123 (32.6%) no screening. We found screening underuse related to failures at each step in the screening process, although nearly half (49.6%) were due to lack of screening orders in patients with known cirrhosis.

Portal vein tumor thrombus (PVTT) remains a common presentation in patients with hepatocellular carcinoma (HCC). Approximately 30–50% of patients newly diagnosed with HCC will present with a concomitant PVTT. Current guidelines recommend systemic therapy for treatment of HCC with PVTT. Real-world application of partial hepatectomy in HCC patients with PVTT has increased over the past two decades, as perioperative complications have declined. However, it is unclear if there is an association between the extent of PVTT and overall survival and rates of recurrence and whether the perioperative morbidity outweighs these potential benefits. Partial hepatectomy with en bloc resection of PVTT in second-order branches and distal can offer significant benefits in carefully selected patients; however, once the HCC-associated PVTT extends into first-order portal venous branches or more proximal into the superior mesenteric vein, the risks of surgical resection outweigh the benefits. The aim of this review is to determine which patients with HCC presenting with PVTT benefit from surgical resection. We will discuss the classification systems of PVTT and review both outcome and perioperative measures in patients undergoing partial hepatectomy with extirpation of HCC-related PVT.

BACKGROUND: Access to health insurance and curative interventions [surgery/liver directed therapy (LDT)] affects survival for early-stage hepatocellular carcinoma (HCC). The aim of this multi-institutional study of high-volume safety-net hospitals (SNHs) and their tertiary-academic-centers (AC) was to identify the impact of type/lack of insurance on survival disparities across hospitals, particularly SNHs whose mission is to minimize insurance related access to care barriers for vulnerable populations. METHODS: Early-stage HCC patients (2012-2014) from the US Safety-Net Collaborative were propensity-score matched by treatment at SNH/AC. Overall survival (OS) was the primary outcome. Multivariable Cox proportional-hazard analysis was performed accounting for sociodemographic and clinical parameters. RESULTS: Among 925 patients, those with no insurance (NI) had decreased curative surgery, compared to those with government insurance (GI) and private insurance [PI, (PI-SNH:60.5% vs. GI-SNH:33.1% vs. NI-SNH:13.6%, p

The neutrophil–lymphocyte ratio (NLR) has been proposed as a prognostic biomarker for cirrhosis and non-liver malignancies. We aimed to evaluate the prognostic value of NLR in a diverse cohort of patients with hepatocellular carcinoma (HCC). We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at two large US health systems. We used Cox proportional hazard and multivariable ordinal logistic regression models to identify factors associated with overall survival and response to first HCC treatment, respectively. Primary variables of interest were baseline NLR and delta NLR, defined as the difference between pre- and post-treatment NLR. Among 1019 HCC patients, baseline NLR was 200 ng/mL (45.6% vs 33.8%). Baseline NLR ≥ 5 was independently associated with higher mortality (median survival 4.3 vs 15.1 months; adjusted HR 1.70, 95%CI 1.41–2.06), with differences in survival consistent across BCLC stages. After adjusting for baseline covariates including NLR, delta NLR > 0.26 was also independently associated with increased mortality (HR 1.42, 95%CI 1.14–1.78). In a secondary analysis, high NLR was associated with lower odds of response to HCC treatment (20.2% vs 31.6%; adjusted OR 0.55, 95%CI 0.32–0.95). In a large Western cohort of patients with HCC, high baseline NLR and delta NLR were independent predictors of mortality. NLR is an inexpensive test that may be a useful component of future HCC prognostic models.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study.Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 postprotocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control.Median imaging follow-up for the combined cohort (n = 33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for postprotocol patients. Median lesion size was 2.0 cm (range, 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only 3 grade 2 toxicities were observed in the entire cohort, with no grade ≥3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%, 100% in the protocol group and 92.9% in the subsequent patients. Two-year overall survival for all treated patients was 82.0%.For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long-term follow-up; results in subsequent patients treated with single-fraction SABR doses of 40 Gy confirmed our earlier results.

To evaluate the inter-reader reproducibility and prognostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (LR-TR) at the time of initial post-treatment evaluation following drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC). This retrospective study included patients with HCC who underwent first-line DEB-TACE between January 2011 and December 2015. Six readers (three fellowship-trained radiologists and three radiology trainees) independently assessed lesion-level response in up to two treated lesions per LR-TR and modified Response Evaluation Criteria in Solid Tumors (mRECIST)-target criteria, as well as patient-level response per mRECIST-overall criteria, on the initial post-treatment CT/MRI. Inter-reader agreement was calculated by Fleiss’ multi-reader κ. We tested whether LR-TR, mRECIST-target, and mRECIST-overall response were associated with overall survival using Kaplan–Meier and Cox proportional hazard model analyses. A total of 82 patients with 113 treated target lesions were included. Inter-reader agreement was moderate for LR-TR and mRECIST-overall (κ range 0.42–0.57), and substantial for mRECIST-target (κ range 0.62–0.66), among all three reader-groups: all readers, experienced readers, and less-experienced readers. LR-TR and mRECIST-target response were not significantly associated with overall survival regardless of reader experience (P > 0.05). In contrast, mRECIST-overall response was significantly associated with overall survival when assessed by all readers (P = 0.02) and experienced readers (P = 0.03), but not by the less-experienced readers (P = 0.35). Although LR-TR algorithm has moderate inter-reader reproducibility, it alone may not predict overall survival on the initial post-treatment CT/MRI after first-line DEB-TACE for HCC.

BACKGROUND: Widespread HCV treatment for hepatocellular carcinoma (HCC) patients remains limited. Our aim was to evaluate the association of HCV treatment with survival and assess barriers to treatment. METHODS: Patients in the U.S. Safety Net Collaborative with HCV and HCC were included. Primary outcome was overall survival (OS). Secondary outcomes were recurrence-free survival (RFS) and barriers to receiving HCV treatment. RESULTS: Of 941 patients, 57% received care at tertiary referral centers (n=533), 74% did not receive HCV treatment (n=696), 6% underwent resection (n=54), 17% liver transplant (n=163), 50% liver-directed therapy (n=473), and 7% chemotherapy (n=60). HCV treatment was associated with improved OS compared to no HCV treatment (70 vs 21 months, p

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan–Meier method and log-rank test. Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

Performance of technically complex surgery at high-volume (HV) centers is associated with improved outcomes. The aim of this study was to assess whether hospital gastrectomy volume is associated with surgical outcomes, and what threshold of case volume meaningfully impacts surgical outcomes. We conducted a retrospective review of adult NCDB patients with gastric adenocarcinoma undergoing gastrectomy between 2004 and 2015. A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital gastrectomy volume and overall survival. Bootstrap simulation was used to estimate the cut-point corresponding to maximum change in log hazard ratio. Hospitals were divided into HV (≥ 17 cases/year) and low-volume (LV

Accurate clinical staging (CS) of gastric cancer is critical for appropriate treatment selection and prognostication, but CS remains highly imprecise. Our study evaluates factors associated with inaccurate CS, the impact of inaccurate CS on outcomes, and utilization of adjuvant therapy in patients who are understaged. We conducted a retrospective review of NCDB patients diagnosed with clinical early stage gastric adenocarcinoma (cT1-2N0M0) between 2004 and 2016. Patients not undergoing upfront gastrectomy or with missing pathologic staging were excluded. Patients were classified as accurately staged, inaccurately staged with receipt of adjuvant therapy (IS+), and inaccurately staged with no receipt of adjuvant therapy (IS−). Logistic regression was utilized to assess the impact of factors on CS accuracy and receipt of adjuvant therapies. Kaplan–Meier and Cox proportional hazard methods were used for survival analysis. Approximately 40% of patients were inaccurately staged (IS). cT2, moderately/poorly differentiated, and site-overlapping tumors were associated with increased likelihood of being IS. Treatment at an academic facility was associated with decreased likelihood of understaging. Only 54% of patients who were IS received adjuvant therapy. Accurate CS of gastric cancer remains inadequate. Understaging is associated with detrimental effects on receiving guideline-concordant care and, possibly, patient outcomes. Targeted interventions reducing the proportion of understaged patients and ensuring receipt of appropriate therapy is needed to optimize outcomes. Patients with high-risk disease that are frequently understaged may benefit from selective neoadjuvant therapy. Centralization of gastric cancer care may also be a key strategy in improving receipt of guideline-concordant therapies.

Despite advances in treatment options for hepatocellular carcinoma (HCC), 5-year survival for HCC remains below 20%. This poor survival is multifactorial but is partly related to underuse of curative treatment in clinical practice. In light of growing treatment options, delivered by different types of providers, optimal management requires input from multiple specialties. A multidisciplinary approach has been evolving over the past couple of decades, bringing different specialists together to develop a therapeutic plan to treat and manage HCC, which significantly increases timely guideline-concordant treatment and improves overall survival. The present review attempts to highlight the need for such a multimodal approach by providing insights on its potential structure and impact on the various aspects of HCC management.

BACKGROUND: Prophylactic drainage following hepatectomy is frequently performed despite evidence that drainage is unnecessary. It is unknown to what extent drain use is influenced by hospital practice patterns. The objectives of this study were to identify factors associated with the use of prophylactic drains following hepatectomy and assess hospital variation in drain use. METHODS: Retrospective cohort study of patients following hepatectomy without concomitant bowel resection or biliary reconstruction from the ACS NSQIP Hepatectomy Targeted Dataset. Factors associated with the use of prophylactic drains were identified using multivariable logistic regression and hospital-level variation in drain use was assessed. RESULTS: Analysis included 10,530 patients at 130 hospitals. Overall, 42.3% of patients had a prophylactic drain placed following hepatectomy. Patients were more likely to receive prophylactic drains if they were ≥65 years old (adjusted odds ratio [aOR]: 1.34, 95%CI: 1.16–1.56), underwent major hepatectomy (aOR: 1.42, 95%CI 1.15–1.74), or had an open resection (aOR 1.94, 95%CI 1.49–2.53). There was notable hospital variability in drain use (range: 0% to 100% of patients), and 77.5% of measured variation in drain placement was at the hospital level. CONCLUSION: Prophylactic drains are commonly placed in both major and minor hepatectomy. While some patient factors are associated with drain use, hospital-specific patterns appear to be a major driver and represent a target for improvement.

A paucity of data exists regarding adenosquamous carcinoma of the gallbladder, a histology comprising under 10% of gallbladder cancer diagnoses. The aim of this study is to characterize the clinicopathological features of these tumors utilizing a population-based dataset compared with gallbladder adenocarcinoma. We identified patients with gallbladder adenosquamous and adenocarcinoma from the National Cancer Database from 2004 to 2015. Patient demographics, tumor characteristics, treatment regimens, and overall survival were analyzed between the groups. We identified 13,158 patients: 12,455 (95%) with a diagnosis of gallbladder adenocarcinoma and 703 (5%) with adenosquamous carcinoma. Adenosquamous tumors were larger, poorly differentiated, and presented with Stage III/IV disease (75% vs 69%, p

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.

Hispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes compared with patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients have been included in previous studies. To determine the genomic landscape of gastric cancer in Hispanic/Latino patients, we performed whole-exome sequencing (WES) and RNA sequencing on tumor samples from 57 patients; germline analysis was conducted on 83 patients. The results were compared with data from Asian and White patients published by The Cancer Genome Atlas. Hispanic/Latino patients had a significantly larger proportion of genomically stable subtype tumors compared with Asian and White patients (65% vs. 21% vs. 20%, P < 0.001). Transcriptomic analysis identified molecular signatures that were prognostic. Of the 43 Hispanic/Latino patients with diffuse-type cancer, 7 (16%) had germline variants in CDH1. Variant carriers were significantly younger than noncarriers (41 vs. 50 years, P < 0.05). In silico algorithms predicted five variants to be deleterious. For two variants that were predicted to be benign, in vitro modeling demonstrated that these mutations conferred increased migratory capability, suggesting pathogenicity. Hispanic/Latino patients with gastric cancer possess unique genomic landscapes, including a high rate of CDH1 germline variants that may partially explain their aggressive clinical phenotypes. Individualized screening, genetic counseling, and treatment protocols based on patient ethnicity and race may be necessary. Significance: Gastric cancer in Hispanic/Latino patients has unique genomic profiles that may contribute to the aggressive clinical phenotypes seen in these patients.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Once considered an experimental treatment with dismal survival rates, liver transplantation for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. In the modern post‐Milan‐criteria era, 5‐year survival outcomes are now upwards of 70% in select patients. Liver transplantation (LT) is now considered the optimal treatment for patients with moderate to severe cirrhosis and HCC, and the rates of transplantation in the United States are continuing to rise. Several expanded selection criteria have been proposed for determining which patients with HCC should be candidates for undergoing LT with similar overall and recurrence‐free survival rates to patients within the Milan criteria. There is also a growing experience with downstaging of patients who fall outside conventional LT criteria at the time of HCC diagnosis with the goal of tumor shrinkage via locoregional therapies to become a candidate for transplantation. The aim of this review article is to characterize the various patient selection criteria for LT, discuss balancing organ stewardship with outcome measures in HCC patients, present evidence on the role of downstaging for large tumors, and explore future directions of LT for HCC., Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Once considered experimental treatment with dismal survival rates, liver transplantation for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. The aim of this review article is to characterize the various patient selection criteria for liver transplantation, discuss balancing organ stewardship with outcome measures in HCC patients, present evidence on the role of downstaging for large tumors, and explore future directions of liver transplantation for HCC.

Lessons Learned The fibrolamellar carcinoma-associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and, thus, overexpression of Aurora kinase A. ENMD-2076 showed a favorable toxicity profile. The limited results, one patient (3%) with a partial response and 57% of patients with stable disease, do not support further evaluation of ENMD-2076 as single agent. Future studies will depend on the simultaneous targeting approach of DNAJB1-PRKACA and the critical downstream components. Background Fibrolamellar carcinoma (FLC) represents approximately 0.85% of liver cancers. The associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and overexpression of Aurora kinase A (AURKA). ENMD-2076 is a selective anti-AURKA inhibitor. Methods Patients aged >12 years with pathologically confirmed incurable FLC, with measurable disease, Eastern Cooperative Oncology Group performance status 0–2 or Lansky 70–100, and adequate organ function were eligible. Patients were prescribed ENMD-2076 based on body surface area. The primary endpoint was overall objective response rate by RECIST v1.1, with a null hypothesis of true response rate of 2% versus one-sided alternative of 15%. Secondary endpoints included 6-month progression-free survival (PFS) rate (Fig. 1), median PFS, time to progression (TTP), and overall survival (OS). Safety was evaluated throughout the study. Results Of 35 patients who enrolled and received treatment, 1 (3%) had a partial response (PR) and 20 (57%) had stable disease (SD). Median TTP, PFS, and OS were 5, 3.9, and 19 months, respectively. The most frequently reported drug-related serious adverse event was hypertension in three patients. Three deaths were reported on-study—two due to disease progression and one due to pulmonary embolism not related to ENMD-2076. Conclusion The study provided no rationale for further studying ENMD-2076 as a single agent in FLC.

BACKGROUND: Cancer cachexia is a wasting syndrome associated with functional impairment and reduced survival that impacts up to 50% of patients with gastrointestinal cancers. However, data are limited on the prevalence and clinical significance of cachexia in patients with hepatocellular carcinoma (HCC). METHODS: We performed a retrospective cohort study of patients diagnosed with HCC at two U.S. health systems between 2008 – 2018. Patient weights were recorded six months prior and at HCC diagnosis. Cachexia was defined as >5% weight loss (or >2% weight loss if BMI

Summary Background 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. Methods A serum protein-based prognostic liver secretome signature (PLSec) was bioinformatically derived from previously validated hepatic transcriptome signatures and optimized in 79 patients with advanced liver fibrosis. We independently validated PLSec for HCC risk in 331 cirrhosis patients with mixed etiologies (validation set 1 [V1]) and thereafter developed a score with clinical prognostic variables. The score was then validated in 2 independent cohorts: V2, 164 patients with advanced liver fibrosis due to hepatitis C virus (HCV) infection cured after direct-acting antiviral therapy, and V3, 146 patients with advanced liver fibrosis with successfully treated HCC and cured HCV infection. Findings An 8-protein blood-based PLSec recapitulated transcriptome-based hepatic HCC risk status. In V1, PLSec was significantly associated with incident HCC risk (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.30–4.23). A composite score with serum α-fetoprotein (PLSec-AFP) was defined in V1 and validated in V2 (adjusted odds ratio, 3.80 [95% CI, 1.66–8.66]) and V3 (aHR, 3.08 [95% CI, 1.78–5.31]; c-index, 0.74). PLSec-AFP outperformed AFP alone (Brier score, 0.165 versus 0.186 in V2 and 0.196 versus 0.206 in V3, respectively). Conclusions The blood-based PLSec-AFP can accurately stratify patients with advanced liver fibrosis for long-term HCC risk and thereby guide risk-based tailored HCC screening. Funding Uehara Memorial Foundation, US NIH (DK099558, CA233794, CA226052, CA222900, CA230694, CA230669, and CA237659), European Commission (ERC-2014-AdG-671231), Cancer Prevention and Research Institute of Texas (RR180016), LABEX HepSYS (ANR-10-LABX-0028_HEPSYS), ARC Foundation (IHU201901299), IUF, Inserm Plan Cancer (HCCMICTAR), and MGH Research Scholars Program.

BACKGROUND AND OBJECTIVES The clinical presentation of gastric cancer varies between racial and ethnic groups. While historically studied as a monolithic population, the Hispanic ethnicity is comprised of heterogenous groups with considerable biologic, socioeconomic, and cultural variability; therefore, intragroup differences among Hispanic gastric cancer patients may have been overlooked in past research. METHODS We conducted a retrospective review of the National Cancer Database (NCDB) to compare Hispanic patients with gastric adenocarcinoma diagnosed between 2004 and 2015, by NCDB-reported location of patient ancestry. RESULTS We identified a cohort of 3811 patients. There were higher proportions of females, patients with early disease onset, and stage 4 disease among patients of Mexican and South/Central American ancestry. Additionally, a significantly larger proportion of Mexican (15%) and South/Central American patients (11%) were diagnosed before age 40, in contrast to Cubans (2%), Dominicans (6%), and Puerto Ricans (3%; p

Background & Aims Identifying patients in whom ultrasound may be inadequate to exclude the presence of hepatocellular carcinoma (HCC) can inform interventions to improve screening effectiveness. We aimed to characterize correlates of suboptimal ultrasound quality and changes in ultrasound quality over time in patients with cirrhosis undergoing HCC screening. Methods We performed a retrospective cohort study of patients with cirrhosis who underwent ultrasound examination at 2 large health systems between July 2016 and July 2019. Exam adequacy was graded by radiologists using the LI-RADS Visualization Score (A, B, C); we evaluated changes in visualization over time among patients with >1 ultrasound exams. We performed multivariable logistic regression to identify characteristics associated with limited ultrasound visualization (scores B or C). Results Of 2053 cirrhosis patients, 1685 (82.1%) had ultrasounds with score A, 262 (12.8%) had score B, and 106 (5.2%) had score C. Limited visualization was associated with alcohol-related or nonalcoholic fatty liver disease cirrhosis and presence of class II-III obesity. Among 1546 patients with >1 ultrasounds, 1129 (73.0%) had the same visualization score on follow-up (1046 score A, 60 score B, 23 score C). However, 255 (19.6%) of 1301 with score A at baseline had limited visualization when repeated (230 score B, 25 score C), and 130 (53.1%) of 245 patients with baseline limited visualization had good visualization when repeated. Conclusions Nearly 1 in 5 patients with cirrhosis had moderately-severely limited ultrasound visualization for HCC nodules, particularly those with obesity or alcohol-related or nonalcoholic fatty liver disease cirrhosis. Ultrasound quality can change between exams, including improvement in many patients with limited visualization.

PURPOSE: Telehealth has been an integral response to the COVID-19 pandemic. However, no studies to date have examined the utility and safety of telehealth for oncology patients undergoing systemic treatments. Concerns of the adequacy of virtual patient assessments for oncology patients include the risk and high acuity of illness and complications while on treatment. METHODS: We assessed metrics related to clinical efficiency and treatment safety after propensity matching of newly referred patients starting systemic therapy where care was in large part replaced by telehealth between March and May 2020, and 206 newly referred patients from a similar time period in 2019 where all encounters were in-person visits. RESULTS: Patient-initiated telephone encounters that capture care or effort outside of visits, time to staging imaging, and time to therapy initiation were not significantly different between cohorts. Similarly, 3 month all-cause or cancer-specific emergency department presentations and hospitalizations, and treatment delays were not significantly different between cohorts. There were substantial savings in travel time with virtual care, with an average of 211.4 minutes saved per patient over a 3-month interval. CONCLUSION: Our results indicate that replacement of in-person care with virtual care in oncology does not lead to worse efficiency or outcomes. Given the increased barriers to patients seeking oncology care during the pandemic, our study indicates that telehealth efforts may be safely intensified. These findings also have implications for the continual use of virtual care in oncology beyond the pandemic.

Bavituximab, an immunomodulator, targets phosphatidylserine (PS), a membrane lipid externalized on tumor and endothelial cells in response to sorafenib.The objective of this phase II study was to assess the efficacy of combination bavituximab and sorafenib in advanced hepatocellular carcinoma (HCC).In this single-arm phase II study, patients with HCC determined to be unresectable with Eastern Cooperative Oncology Group (ECOG) score ≤ 2, Child-Pugh score A/B7 received intravenous bavituximab 3 mg/kg weekly and oral sorafenib 400 mg twice daily until disease progression or intolerable toxicity. We investigated time to progression (TTP) for patients receiving combination bavituximab and sorafenib compared with that for sorafenib-only historical controls.In total, 38 patients were accrued. The median follow-up was 6.1 months. Patient characteristics were as follows: median age 61 years; male 82%; hepatitis C virus 79%; Black 39%, Hispanic 26%, White 29%; previous treatment 39%; macrovascular invasion 84%; and extrahepatic metastases 24%. The median TTP was 6.7 months (95% confidence interval [CI] 4-17). The median overall survival was 6.1 months (95% CI 5-8), and the median disease-specific survival was 8.6 months (95% CI 6-14). Two patients experienced partial responses; none had a complete response. The disease control rate was 58%. Treatment-related adverse events were observed in 63% of patients, with the most commonly reported therapy-related symptoms being diarrhea (32%), fatigue (26%), and anorexia (24%).The efficacy of adding bavituximab to sorafenib for the treatment of advanced HCC was inconclusive; however, the combination regimen did not exacerbate toxicities associated with single-agent sorafenib. CLINICALTRIALS.NCT01264705.

Pringle maneuver (PM) is used for inflow vascular control during hepatectomy, but its use remains controversial. We aimed to report its pattern of use and association with postoperative outcomes.We identified hepatectomy patients using the liver-targeted National Surgical Quality Improvement Program database (2014-2016). Associations between PM and posthepatectomy liver failure (PHLF), receipt of blood transfusion, and total hospital length of stay (LOS) were evaluated.We identified 7870 patients (74.9%) with no Pringle maneuver and 2632 (25.1%) with PM. PM patients were older (median age 61 versus 60 y, P = 0.002) and had higher ASA scores (76.1% versus 71.4% were ASA 3-4, P 0.001). PM had more malignancy (83.0% versus 73.0%, P 0.001), neoadjuvant therapy (37.7% versus 28.8%, P 0.001), total lobectomy (30.6% versus 23.2%, P 0.001), open resection (90.8% versus 74.9%, P 0.001), and longer operations (246 min versus 212 min, P 0.001). PM was associated with longer LOS (0.36 d, 95% confidence interval [CI] 0.11-0.60) and increased risk of PHLF (odds ratio [OR] 1.36, 95% CI 1.11-1.66), although not clinically significant grade B/C PHLF (OR 0.82, 95% CI 0.57-1.19), but was not associated with receipt of perioperative blood transfusions (OR 1.00, 95% CI 0.69-1.64).PM is associated with similar clinically significant PHLF and transfusion requirements but longer LOS compared with no Pringle maneuver.

Background The high operational cost of MRI limits its utility for hepatocellular carcinoma (HCC) screening. Abbreviated-protocol dynamic contrast-enhanced MRI (aMRI) may help lower cost while maintaining the high accuracy of complete-protocol diagnostic MRI (cMRI). Purpose To compare aMRI to cMRI for HCC detection in cirrhosis patients. Study type Cross-sectional study. Study population Cirrhosis patients undergoing MRI for suspected HCC. Field strength/sequence 1.5T and 3T; aMRI (coronal T2 -weighted, axial dynamic contrast-enhanced T1 -weighted fat-suppressed sequences); cMRI (aMRI sequences and unenhanced axial T2 -, T1 -, and diffusion-weighted sequences). Assessment From each cMRI, an abbreviated exam was created by extracting only the aMRI sequences. Five radiologists independently reviewed aMRI and cMRI and assigned per-patient screening results by the presence/absence of any actionable observation per Liver Imaging and Reporting Data System v2018 (LI-RADS 4, 5, M, or TIV categories). Per-patient HCC status was determined by the composite reference standard of histopathology, follow-up imaging, consensus expert panel imaging review, and clinical follow-up. Statistical tests Interreader agreement between aMRI and cMRI was compared with that of cMRI and tested for interchangeability against a tolerance margin of 0.05. Per-patient screening sensitivity, specificity, and accuracy were compared between aMRI and cMRI and tested for equivalence against a tolerance margin of 0.05. Results In 93 cirrhosis patients, five radiologists recorded on average 121 liver observations. Interreader screening agreement probability (and 95% confidence interval confidence interval [CI]) was 0.914 [0.900, 0.926] between aMRI and cMRI, and 0.927 [0.908, 0.942] for cMRI; their difference was within the 0.05 margin for interchangeability. In 86 patients in whom a final HCC status could be determined, the detection sensitivity and specificity of aMRI was 0.921 [0.864, 0.956] and 0.886 [0.844, 0.918], within the 5% equivalence margin to cMRI, 0.936 [0.881, 0.965] and 0.883 [0.840, 0.915], respectively. Data conclusion Abbreviated-protocol screening MRI is interchangeable with, and equivalent to, complete-protocol diagnostic MRI for per-patient HCC detection in cirrhosis. Level of evidence 4 Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2020;51:415-425.

36 Background: Two recent South Korean studies showed adjuvant therapy (AT) was not associated with improved survival in pT1N1 gastric adenocarcinoma (GAC). We aimed to establish the prognostic utility of lymph node status, determine the pattern of use of AT, and compare survival stratified by type of AT in pT1N1 GAC in a Western patient population. Methods: We identified patients with pT1N0 and pT1N1 GAC using the National Cancer Database from 2004 to 2012. Clinicopathologic variables, treatment regimens, and overall survival (OS) were compared. Results: We compared 4,516 (86.6%) pT1N0 to 696 (13.4%) pT1N1 patients. pT1N1 tumors were larger (median size 2.5 vs. 1.8 cm, p < 0.001), more often poorly differentiated (56.2% vs. 39.6%, p < 0.001), and had higher median retrieved lymph nodes (RLN) (14 vs. 12, p < 0.001) compared to pT1N0. pT1N1 was associated with worse median OS (6.9 years vs. 9.9 years for pT1N0, p < 0.001). pN1 was independently associated with worse OS (HR 2.17 95% CI 1.84-2.56). Increased RLN was associated with improved OS (HR 0.73, 95% CI 0.65-0.83). Among pT1N1 patients, 330 (47.4%) had observation (OBS), 77 (11.1%) received adjuvant chemotherapy (ACT), 68 (9.8%) received adjuvant radiation therapy (ART), and 221 (31.8%) received adjuvant chemoradiation therapy (ACRT). ACT and ACRT were independently associated with improved OS (HR 0.37, 95% CI 0.22-0.65 and HR 0.40, 95% CI 0.28-0.57). Conclusions: pN1 was associated with worse survival and RLN ≥ 15 was associated with improved survival in pT1 GAC. ACT and ACRT were independently associated with improved survival in pT1N1 gastric cancer suggesting a valuable role in Western patients.

BACKGROUND AND OBJECTIVES Little is known regarding the difference in prognosis among patients who have an incidentally discovered adrenocortical carcinoma (ACC) vs those who present with signs or symptoms. We aimed to explore differences in the outcomes of these two populations. METHODS Data were collected on patients who underwent resection of ACC at 1 of 13 institutions between January 1993 and December 2014. Presentations were categorized as incidental vs symptomatic and outcomes were compared. RESULTS Among 227 patients, 100 were diagnosed incidentally while 127 patients presented with symptoms/signs. Clinical and pathological features were comparable among incidental vs nonincidental patients with ACC following the exceptions. Patients with incidentalomas were more likely to have a T1/T2 tumor (55.8% vs 34.8%; P

IntroductionAlthough antibiotic prophylaxis is established in reducing postoperative surgical site infections (SSIs), the optimal antibiotic for prophylaxis in pancreatoduodenectomy (PD) remains unclear. The study objective is to evaluate if administration of piperacillin–tazobactam as antibiotic prophylaxis results in decreased 30-day SSI rate compared with cefoxitin in patients undergoing elective PD.Methods and analysisThis study will be a multi-institution, double-arm, non-blinded randomised controlled superiority trial. Adults ≥18 years consented to undergo PD for all indications who present to institutions participating in the National Surgical Quality Improvement Program Hepato-Pancreato-Biliary (NSQIP HPB) Collaborative will be included. Data collection will use the NSQIP HPB Collaborative Surgical Clinical Reviewers. Patients will be randomised to either 1–2 g intravenous cefoxitin or 3.375–4.5 g intravenous piperacillin–tazobactam within 60 min of surgical incision. The primary outcome will be 30-day postoperative SSI rate following PD. Secondary outcomes will include 30-day postoperative mortality; specific postoperative complication rate; and unplanned reoperation, length of stay, and hospital readmission. A subset of patients will have bacterial isolates and sensitivities of intraoperative bile cultures and SSIs. Postoperative SSIs and secondary outcomes will be analysed using logistic regression models with the primary predictor as the randomised treatment group. Additional adjustment will be made for preoperative biliary stent presence. Additionally, bacterial cultures and isolates will be summarised by presence of bacterial species and antibiotic sensitivities.Ethics and disseminationThis study is approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center. This trial will evaluate the effect of piperacillin–tazobactam compared with cefoxitin as antibiotic prophylaxis on the hazard of postoperative SSIs. The results will be disseminated regardless of the effect of the intervention on study outcomes. The manuscript describing the effect of the intervention will be submitted to a peer-reviewed journal when data collection and analyses are complete.Trial registration numberNCT03269994.

Background and Aims Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related death in the United States; however, HCC incidence and mortality are not equally distributed among racial-ethnic groups. Our aim was to characterize the direction and magnitude of racial-ethnic disparities in overall survival and early tumor detection among patients with HCC. Methods We searched MEDLINE, EMBASE and Cochrane databases from inception through August 2020 for studies reporting HCC outcomes (early stage presentation and overall survival) by race and ethnicity. We calculated pooled hazard ratios (HRs) and odds ratios (ORs) for each racial-ethnic group (White, Black, Hispanic, Asian) using the DerSimonian and Laird method for a random-effects model. Results We identified 35 articles comprising 563,097 patients (53.0% White, 17.3% Black, 18.4% Hispanic, 5.0% Asian). Compared with White patients, Black patients had worse survival (pooled HR 1.08; 95% CI, 1.05 – 1.12), whereas Hispanic (pooled HR 0.92; 95% CI, 0.87 – 0.97) and Asian (pooled HR 0.81; 95% CI, 0.73 – 0.88) patients had better survival. Among articles reporting tumor stage (n = 20), Black patients had lower odds of early stage HCC compared with White patients (OR, 0.66; 95% CI, 0.54 – 0.78). Conversely, there was no difference in odds of early HCC detection for Asian (OR, 1.01; 95% CI, 0.97 – 1.05) or Hispanic patients (OR, 0.87; 95% CI, 0.74 – 1.01) compared with White patients. The most common limitation of studies was risk of residual confounding from socioeconomic status and liver dysfunction. Conclusions There are significant racial and ethnic disparities in HCC prognosis in the United States, with Black patients having worse overall survival and Hispanic and Asian patients having better overall survival compared with White patients. Interventions are needed to reduce disparities in early HCC detection to improve HCC prognosis.

BACKGROUND AND OBJECTIVES Surgical resection is indicated for hepatocellular carcinoma (HCC) patients with Child A cirrhosis. We hypothesize that surgical intervention and survival are limited by advanced HCC presentation at safety net hospitals (SNHs) versus academic medical centers (AMCs). METHODS Patients with HCC and Child A cirrhosis in the US Safety Net Collaborative (2012-2014) were evaluated. Demographics, clinicopathologic features, operative characteristics, and outcomes were compared between SNHs and AMCs. Liver transplantation was excluded. Kaplan-Meier and Cox proportional-hazards models were used to identify the effect of surgery on overall (OS). RESULTS A total of 689 Child A patients with HCC were identified. SNH patients frequently presented with T3/T4 stage (35% vs. 24%) and metastases (17% vs. 8%; p

BACKGROUND AND AIMS There are limited data on hepatocellular carcinoma (HCC) growth patterns, particularly in Western cohorts, despite implications for surveillance, prognosis, and treatment. Our study's aim was to quantify tumor doubling time (TDT) and identify correlates associated with indolent and rapid growth. APPROACH AND RESULTS We performed a retrospective multicenter cohort study of patients with cirrhosis diagnosed with HCC from 2008 to 2017 at six US and European health systems with two or more contrast-enhanced imaging studies performed ≥ 30 days apart prior to HCC treatment. Radiologists independently measured tumors in three dimensions to calculate TDT and specific growth rate (SGR). We used multivariable ordinal logistic regression to identify factors associated with indolent (TDT > 365 days) and rapid (TDT

BACKGROUND. While hepatocellular carcinoma (HCC) is ideally diagnosed outpatient by screening at-risk patients, many are diagnosed in Emergency Departments (ED) due to undiagnosed liver disease and/or limited access-to-healthcare. This study aims to identify sociodemographic/clinical factors associated with being diagnosed with HCC in the ED to identify patients who may benefit from improved access-to-care. METHODS. HCC patients diagnosed between 2012 and 2014 in the ED or an outpatient setting [Primary Care Physician (PCP) or hepatologist] were identified from the US Safety-Net Collaborative database and underwent retrospective chart-review. Multivariable regression identified predictors for an ED diagnosis. RESULTS. Among 1620 patients, median age was 60, 68% were diagnosed outpatient, and 32% were diagnosed in the ED. ED patients were more likely male, Black/Hispanic, uninsured, and presented with more decompensated liver disease, aggressive features, and advanced clinical stage. On multivariable regression, controlling for age, gender, race/ethnicity, poverty, insurance, and PCP/navigator access, predictors for ED diagnosis were male (odds ratio [OR] 1.6, 95% confidence interval [CI]: 1.1–2.2, p = 0.010), black (OR 1.7, 95% CI: 1.2–2.3, p = 0.002), Hispanic (OR 1.6, 95% CI: 1.1–2.6, p = 0.029), > 25% below poverty line (OR 1.4, 95% CI: 1.1–1.9, p = 0.019), uninsured (OR 3.9, 95% CI: 2.4–6.1, p < 0.001), and lack of PCP (OR 2.3, 95% CI: 1.5–3.6, p < 0.001) or navigator (OR 1.8, 95% CI: 1.3–2.5, p = 0.001). CONCLUSIONS. The sociodemographic/clinical profile of patients diagnosed with HCC in EDs differs significantly from those diagnosed outpatient. ED patients were more likely racial/ethnic minorities, uninsured, and had limited access to healthcare. This study highlights the importance of improved access-to-care in already vulnerable populations.

Background & Aims Differences in outcomes of hepatocellular carcinoma (HCC) between countries have been largely attributed to variation in the conduct of surveillance and subsequent HCC treatment eligibility. However, differences in outcomes among those detected under surveillance have not been well described. We compared characteristics and prognosis between patients with surveillance-detected HCC from the United States (US) and Japan. Methods Patients in whom initial HCC was detected under surveillance between January 2006 and December 2015 from two centers in the US and two from Japan were included. Survival was compared between patients from the US and Japan using multivariable Cox regression analysis and propensity-score matched analysis. We performed subgroup analyses by liver disease etiology, tumor stage, and type of HCC treatment. Results Of 3788 HCC patients, 1797 (47.4%) were diagnosed under surveillance, 715 from the US and 1082 from Japan. Patients from the US diagnosed under surveillance had worse liver dysfunction and larger tumor burden than those from Japan. In multivariate analysis, US patients with surveillance-detected HCC had significantly worse survival than those from Japan (HR 1.17, 95% CI 1.00–1.35), which was also observed in propensity-score matched analysis. However, this difference was no longer significant after adjusting for treatment type (HR 1.07, 95% CI 0.92–1.25). When stratified by treatment type, survival was comparable between the two countries except lower survival among patients who underwent resection in the US versus Japan. Conclusions Prognosis of patients with surveillance-detected HCC is poorer in the US than Japan, primarily driven by differences in treatment delivery. Studies are necessary to elucidate reasons for these differences.

BACKGROUND Although consensus guidelines generally discourage any surgical management (ASM; i.e., resection and/or transplantation) in patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT), recent series from Asia have challenged this paradigm. METHODS Patients from the US Safety Net Collaborative database (2012-2014) with localized HCC and radiographically confirmed PVT were propensity-score matched based on demographic and clinicopathologic factors associated with receipt of ASM and overall survival (OS). OS was compared between patients undergoing ASM and those not selected for surgery. RESULTS Of 1910 HCC patients, 207 (14.5%) had localized disease and PVT. The majority received either liver-directed therapies (LDTs; 34%) and/or targeted systemic therapies (36%). Twenty-one patients (10.1%) underwent ASM (resection [n = 11], transplantation [n = 10]); a third experienced any complication with no 30-day mortalities. Independent predictors of undergoing ASM were younger age, recent hepatology consultation, and lower model of end-stage liver disease (MELD) score. After matching for age, comorbidities, MELD, tumor size, receipt of LDT, or systemic therapy, OS was significantly longer for patients selected for ASM versus non-ASM patients (median not reached vs. 5.8 months, p

Meckel’s diverticulum (MD) is an anomaly of the small intestine from which malignancy may arise. Among MD neoplasms, neuroendocrine tumors (NETs) are considered the most common. However, their metastatic potential and optimal surgical therapy remain ill-defined. In a retrospective analysis of the National Cancer Database (2004–2015), patients with a diagnosis of MD malignancy were identified. Clinicopathologic factors were extracted and tumors arising in MD were compared. In the subgroup of patients with NET, the association between tumor factors and node involvement was investigated. Three hundred twenty primary MD malignancies were captured in the National Cancer Database, consisting of 280 (87.5%) NET. The median age at diagnosis was 64 years. Patients were predominantly male (207, 73.9%) and white (269, 96.1%). Most tumors were well-differentiated (118, 42.1%) and sub-centimeter (median size, 0.7 cm). Distant metastasis was present in a minority (16, 5.7%), and the median overall survival was 114 months in the entire cohort. The regional lymph node status was known in 87 NET patients, out of which 39 (44.8%) harbored node metastasis. Although the risk of node involvement increased with larger tumor size, it remained significant even among sub-centimeter (9 out of 34, 26.5%) and well-differentiated (18 out of 44, 41%) tumors. Regional node involvement was associated with the presence of distant metastasis (p

Background & Aims The value of a cancer screening programs is defined by its balance of benefits and harms; however, there are few data evaluating both attributes for hepatocellular carcinoma (HCC) surveillance. We aimed to characterize benefits and harms of HCC surveillance in a large prospective cohort of patients with cirrhosis. Methods We conducted a secondary analysis of a clinical trial evaluating HCC surveillance among patients with cirrhosis at a safety-net health system enrolled between December 2014 and July 2015. We quantified surveillance-related benefits, defined as early HCC detection and curative treatment receipt, and physical harms, defined as diagnostic procedures for false positive or indeterminate results, over an 18-month period. Results Of 614 cirrhosis patients with ≥1 surveillance exam, abnormal results were observed in 118 (19.2%) patients. Twenty-six patients developed HCC during follow-up, of whom 16 (61.5%) were detected by surveillance. The proportion of HCC detected at BCLC stage 0/A (62.5% vs 50%, p = .69) and who underwent curative treatment (43.8% vs. 40.0%, p = 1.0) did not significantly differ between surveillance-detected patients and those diagnosed incidentally/symptomatically. Physical harms were observed in 54 (8.8%) patients who underwent surveillance – most of mild severity with only 1 diagnostic CT or MRI and none undergoing invasive testing such as biopsy. Incidental findings on follow-up imaging were found in 40 (6.5%) patients —23 of low clinical importance and 17 medium clinical importance. Conclusions In our cohort of patients with cirrhosis, HCC surveillance was associated with high early tumor detection and minimal physical harms.

Hepatocellular carcinoma recurs in 70–80% of cases following potentially curative resection or ablation and the immune component of the liver microenvironment plays a key role in recurrence. Many immunosuppressive mechanisms implicated in HCC recurrence are modulated by VEGF and/or immune checkpoints such as PD-L1. Atezolizumab (PD-L1 inhibitor) plus bevacizumab (VEGF inhibitor) has been shown to significantly improve overall survival, progression-free survival and overall response rate in unresectable HCC. Dual PD-L1/VEGF blockade may be effective in reducing HCC recurrence by creating a more immune-favorable microenvironment. We describe the rationale and design of IMbrave 050 (NCT04102098), a randomized, open-label, Phase III study comparing atezolizumab plus bevacizumab versus active surveillance in HCC patients at high-risk of recurrence following curative resection or ablation. The primary end point is recurrence-free survival. Clinical Trial Registration: NCT04102098

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. In early stage HCC, current practice guidelines recommend surgical resection with 5-year overall survival (OS) rates approaching 60%. Due to heterogeneity of the patient population and underutilization of HCC screening, in the past only 10-37% of patients were eligible for surgical resection at the time of initial HCC diagnosis. With recent implementation of HCC screening programs resulting in earlier diagnosis, the number of patients that might be candidates for curative surgical resection has increased. Factors determining outcome following HCC diagnosis are complex and heterogenous in nature and treatment decisions should be based on both tumor- and patient-related factors. Tumor characteristics including tumor size, macrovascular invasion (MVI), and multifocality must be balanced against measures of liver dysfunction including portal hypertension, liver function, and future liver remnant (FLR) to assess the applicability of hepatic resection in patients newly diagnosed with HCC. The aim of this article is to review the indications for curative HCC surgical resection as it pertains to underlying tumor- and patient-related factors. We also discuss adjunctive therapies that may allow for an increased role for hepatic resection in HCC patients with early stage disease who are ineligible for upfront resection due to small liver remnant size.

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 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.

BACKGROUND Although sex disparities in hepatocellular carcinoma (HCC) incidence have been well described, there are limited data examining sex disparities in HCC prognosis. AIM To characterise sex differences in HCC presentation and prognosis. METHODS We performed a retrospective study of consecutive patients (n = 1110, 23.5% women) diagnosed with HCC between 2008 and 2017 at two US health systems. We used Cox proportional hazard and multivariable logistic regression models to identify factors associated with overall survival, early tumour detection and response to HCC treatment (per the modified Response Evaluation Criteria in Solid Tumors [mRECIST] criteria). RESULTS Women were older at HCC diagnosis (mean 62.5 vs 59.2 years, P

Purpose To compare percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA) for treatment of Hepatocellular carcinoma (HCC) and to identify risk factors for treatment failure and local progression. Methods 145 unique HCC [87 (60%) RFA, 58 (40%) MWA] were retrospectively reviewed from a single tertiary medical center. Adverse events were classified as severe, moderate, or mild according to the Society of Interventional Radiology Adverse Event Classification system. Primary and secondary efficacy, as well as local progression, were determined using mRECIST. Predictors of treatment failure and time to local progression were analyzed using generalized estimating equations and Cox regression, respectively. Results Technical success was achieved in 143/145 (99%) HCC. There were 1 (0.7%) severe and 2 (1.4%) moderate adverse events. Of the 143 technically successful initial treatments, 136 (95%) completed at least one follow-up exam. Primary efficacy was achieved in 114/136 (84%). 9/22 (41%) primary failures underwent successful repeat ablation, so secondary efficacy was achieved in 128/136 (90%) HCC. Local progression occurred in 24 (19%) HCC at a median of 25 months (95% CI = 19–32 months). There was no difference in technical success, primary efficacy, or time to local progression between RFA and MWA. In HCC treated with MWA, same-day biopsy was associated with primary failure (RR = 9.0, 95% CI: 1.7–47, P = 0.015), and proximity to the diaphragm or gastrointestinal tract was associated with local progression (HR = 2.40, 95% CI:1.5–80, P = 0.017). Conclusion There was no significant difference in primary efficacy or time to local progression between percutaneous RFA and MWA.

Background: Differences in outcomes of hepatocellular carcinoma (HCC) between countries have been largely attributed to variation in the conduct of surveillance and subsequent HCC treatment eligibility; however, differences in outcomes among those detected under surveillance have not been well described. We compared characteristics and prognosis between patients with surveillance-detected HCC from the United States (US) and Japan. Methods: Patients in whom initial HCC was detected under surveillance between January 2006 and December 2015 from two centers in the US and two from Japan were included. Survival was compared between patients from the US and Japan using multivariable Cox regression analysis and propensity-score matched analysis. We performed subgroup analyses by liver disease etiology, tumor stage, and type of HCC treatment. Findings: Of 3788 HCC patients, 1797 (47.4%) were diagnosed under surveillance –715 from the US and 1082 from Japan. Patients from the US diagnosed under surveillance had worse liver dysfunction and larger tumor burden than those from Japan. In multivariate analysis, US patients with surveillance-detected HCC had significantly worse survival than those from Japan (HR 1.17, 95%CI 1.00–1.35), which was also observed in propensity-score matched analysis. However, this difference was no longer significant after adjusting for treatment type (HR 1.07, 95%CI 0.92–1.25). When stratified by treatment type, survival was comparable between the two countries except lower survival among patients who underwent resection in the US versus Japan. Interpretation: Prognosis of patients with surveillance-detected HCC is poorer in the US than Japan, primarily driven by differences in treatment delivery. Studies are necessary to elucidate reasons for these differences. Funding Statement: No funding on this study. Dr. Singal’s research is in part supported by U01CA230694. Dr. Parikh’s research is in part supported by U01CA230669. Declaration of Interests: Hidenori Toyoda has received lecturer fees from Gilead Sciences, AbbVie, MSD, and Bayer. Neehar Parikh has served as a consultant for Bristol Myers-Squibb, Exact Sciences, Eli Lilly, Freenome has served on advisory boards of Genentech, Eisai, Bayer, Exelixis, Wako/Fujifilm and has received research funding from Bayer, Target Pharmasolutions, Exact Sciences, and Glycotest. Amit Singal has been on advisory boards and served as a consultant for Wako Diagnostics, Roche, Exact Sciences, Glycotest, Genentech, Bayer, Eisai, BMS, Exelixis, Merck, AstraZeneca, and TARGET Pharmasolutions. The other authors have no conflict of interest. Ethics Approval Statement: This study was conducted after approval by the institutional review board of each participating institutions and was carried out in compliance with the Helsinki Declaration. Written informed consent was waived due to the retrospective nature of this study.

Data on the efficacy of adjuvant therapy (AT) in distal cholangiocarcinoma (dCCA) is limited. This study aimed to determine the role of AT in resected dCCA and identify subgroups that benefit from AT. We conducted a retrospective review of surgically resected dCCA in the NCDB from 2004 to 2013. Patients who received AT or observation (OB) were matched by propensity score. Log-rank test was used to compare OS. Of 1782 patients with resected dCCA, 840 (47%) were in the OB group and 942 (53%) in the AT group. AT was younger (64.0 vs. 68.7 years, p