The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.

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.

This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19-20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.

Due to increasing use of allografts from donation after cardiac death (DCD) donors, we evaluated DCD liver transplants and impact of recipient and donor factors on graft survival. Liver transplants from DCD donors reported to UNOS were analyzed against donation after brain death (DBD) donor liver transplants performed between 1996 and 2003. We defined a recipient cumulative relative risk (RCRR) using significant risk factors identified from a Cox regression analysis: age; medical condition at transplantation; regraft status; dialysis received and serum creatinine. Graft survival from DCD donors (71% at 1 year and 60% at 3 years) were significantly inferior to DBD donors (80% at 1 year and 72% at 3 years, p < 0.001). Low-risk recipients (RCRR ≤ 1.5) with low-risk DCD livers (DWIT < 30 min and CIT < 10 h, n = 226) achieved graft survival rates (81% and 67% at 1 and 3 years, respectively) not significantly different from recipients with DBD allografts (80% and 72% at 1 and 3 years, respectively, log-rank p = 0.23). Liver allografts from DCD donors may be used to increase the cadaveric donor pool, with favorable graft survival rates achieved when low-risk grafts are transplanted in a low-risk setting. Whether transplantation of these organs in low-risk recipients provides a survival benefit compared to the waiting list is unknown.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.

The receptor tyrosine kinase EphB2 is expressed by colon progenitor cells; however, only 39% of colorectal tumors express EphB2 and expression levels decline with disease progression. Conversely, EphB4 is absent in normal colon but is expressed in all 102 colorectal cancer specimens analyzed, and its expression level correlates with higher tumor stage and grade. Both EphB4 and EphB2 are regulated by the Wnt pathway, the activation of which is critically required for the progression of colorectal cancer. Differential usage of transcriptional coactivator cyclic AMP-responsive element binding protein-binding protein (CBP) over p300 by the Wnt/Bcatenin pathway is known to suppress differentiation and increase proliferation. We show that the B-catenin-CBP complex induces EphB4 and represses EphB2, in contrast to the B-catenin-p300 complex. Gain of EphB4 provides survival advantage to tumor cells and resistance to innate tumor necrosis factor-related apoptosis-inducing ligand-mediated cell death. Knockdown of EphB4 inhibits tumor growth and metastases. Our work is the first to show that EphB4 is preferentially induced in colorectal cancer, in contrast to EphB2, whereby tumor cells acquire a survival advantage.

Importance A combined objective and subjective wireless monitoring program of patient-centered outcomes can be carried out in patients before and after major abdominal surgery. Objective To conduct a proof-of-concept study of a wireless, patient-centered outcomes monitoring program before and after major abdominal cancer surgery. Design Patients wore wristband pedometers and completed online patient-reported outcome surveys (symptoms, QOL) 3 to 7 days before surgery, through hospitalization, and for two weeks post-discharge. Alerts were generated for all moderate to severe scores for symptoms and QOL. Surgery-related data was collected via electronic medical chart and complications were calculated using the Clavien-Dindo classification. Setting The study was carried out in the inpatient and outpatient surgical oncology unit of one NCI designated comprehensive cancer center. Participants Eligible patients were scheduled to undergo curative resection for hepatobiliary and gastrointestinal malignancies, English-speaking, and 18 years or older. Twenty participants were enrolled over 4 months. Main Outcomes and Measures Outcomes included 1) adherence with wearing the pedometer; 2) adherence with completing the surveys (MDASI and EQ-5D-5L), and 3) satisfaction with the monitoring program. Results Pedometer adherence (88% pre-op versus 83% post-discharge) was higher than survey adherence (75% completed). The median number of steps at day 7 was 1689 (19% of steps at baseline). This correlated with the comprehensive complication index (CCI), for which the median was 15/100 (r = −0.64, p<0.05). Post-discharge overall symptom severity (2.3/10) and symptom interference with activities (3.5/10) were mild. Pain, fatigue, and appetite loss were moderate after surgery (4.4, 4.7, 4.0). QOL scores were lowest at discharge (66.6/100), but improved at week 2 (73.9/100). While patient-reported outcomes returned to baseline at 2 weeks, the number of steps was only one third of pre-operative baseline. Conclusions and Relevance Wireless monitoring of combined subjective and objective patient-centered outcomes can be carried out in the surgical oncology setting. Pre- and post-operative patient-centered outcomes have the potential of identifying high risk populations who may need additional interventions to support postoperative functional and symptom recovery.

IMPORTANCE In patients with intrahepatic cholangiocarcinoma (ICC), the oncologic benefit of surgery and perioperative outcomes for large multifocal tumors or tumors with contiguous organ involvement remain to be defined. OBJECTIVES To develop and externally validate a simplified prognostic score for ICC and to determine perioperative outcomes for large multifocal ICCs or tumors with contiguous organ involvement. DESIGN, SETTING, AND PARTICIPANTS This study of a contemporary cohort merged data from the California Cancer Registry (January 1, 2004, through December 31, 2011) and the Office of Statewide Health Planning and Development inpatient database. Clinicopathologic variables were compared between tumors that were intrahepatic, small (<7 cm), and solitary (ISS) and those that had extrahepatic extension and were large (≥7 cm) and multifocal (ELM). External validation of the prognostic model was performed using an independent data set from the National Cancer Institute’s Surveillance, Epidemiology, and End Results database from January 1, 2004, through December 31, 2013. MAIN OUTCOMES AND MEASURES Patient overall survival after hepatectomy. RESULTS A total of 275 patients (123 men [44.7%] and 152 women [55.3%]; median [interquartile range] age, 65 [55–72] years) met the inclusion criteria. No significant differences in overall complication rate (ISS, 48 [34.5%]; ELM, 37 [27.2%]; P = .19) and mortality rate (ISS, 10 [7.2%]; ELM, 6 [4.4%]; P = .32) were found. A multivariate Cox proportional hazards model demonstrated that multifocality, extrahepatic extension, grade, node positivity, and age greater than 60 years are independently associated with worse overall survival. These variables were used to develop the MEGNA prognostic score. The prognostic separation/discrimination index was improved with the MEGNA prognostic score (0.21; 95% CI, 0.11–0.33) compared with the staging systems of the American Joint Committee on Cancer sixth (0.17; 95% CI, 0.09–0.29) and seventh (0.18; 95% CI, 0.08–0.30) editions. CONCLUSIONS AND RELEVANCE The MEGNA prognostic score allows more accurate and superior estimation of patient survival after hepatectomy compared with current staging systems.