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Immune checkpoint blockade (ICB) with programmed cell death protein-1(PD-1)/programmed death ligand -1(PD-L1) antibodies has revolutionized the management of several cancers, especially non-small cell lung cancer, melanoma, urothelial, and renal cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers associated with high morbidity and mortality. Based on available data, it’s obvious that ICB has limited success in PDACs, which can be explained by the low immunogenicity and immunosuppressive tumor microenvironment of these tumors. In this review article, we focus on PD-L1 expression and microsatellite instability (MSI) in PDAC, and their roles as prognostic and predictive markers. We also discuss data supporting combination therapies to augment cancer immunity cycle. Combining anti-PD-1/PD-L1 agents with other modalities such as vaccines, chemotherapy, and radiation could potentially overcome resistance patterns and increase immune responsiveness in PDAC.

Merkel cell carcinoma is a cutaneous neuroendocrine neoplasm that has been poorly studied in contemporary cohorts. Patients with Merkel cell carcinoma from 1986 to 2011 were identified in the Surveillance Epidemiology and End Results registry. A total of 5211 patients met the inclusion criteria. The mean age was 74.9 years; majority were male (61.4%) and white (94.9%). Patients were divided into two cohorts: Group 1 (1986 and 1999) and Group 2 (1999–2010). Group 2 was more likely to have Stage III disease (14.6 vs 23.3%, P < 0.001) and less likely to have Stage I/II disease (71.8 vs 65.1%, P < 0.0001). The increase in Stage III was likely secondary to increased use of sentinel lymph node biopsy. Disease-specific five-year survival for Stages I/II was 78.1 per cent and Stage III was 54 per cent. Disease-specific five-year survival was unchanged between Groups 1 and 2, 69.9 versus 66.6 per cent, respectively ( P = 0.44). Both incidence and mortality significantly increased over the study period with P value for both trends <0.0001. In 1986, incidence and mortality rates per 100,000 were 0.22 and 0.03, respectively, and increased to 0.79 and 0.43 in 2011, respectively. There has been a greater than 333 per cent increase in mortality from Merkel cell carcinoma.

Background Although sentinel lymph node biopsy (SNB) has become a standard for Merkel cell carcinoma (MCC), the impact on survival is unclear. To better define the staging and therapeutic value of SNB, we compared SNB with nodal observation. Methods Patients with clinical stage I and II MCC in the Surveillance, Epidemiology, and End Results (SEER) registry undergoing surgery between 2003 and 2009 were identified and divided into two groups—SNB and observation. Results A total of 1,193 patients met the inclusion criteria (SNB 474 and Observation 719). The median age was 78 years, and the majority were White (95.3 %), male (58.8 %), received radiation therapy (52.9 %) and had T1 tumors (65.3 %). Twenty-four percent had a positive SNB. SNB patients were younger (73 vs. 81 years; p  < 0.0001), had T1 tumors (69.6 vs. 62.5 %; p  = 0.04) and received radiotherapy (57.8 vs. 40 %; p  < 0.0001). Among biopsy patients, a negative SNB was associated with improved 5-year MCC-specific survival (84.5 vs. 64.6 %; p  < 0.0001). Univariate analysis demonstrated an increased 5-year MCC-specific survival for the SNB group versus the Observation group (79.2 vs. 73.8 %; p  = 0.004), female gender (83.2 vs. 70.4 %; p  = 0.0004), and lower T stage ( p  < 0.0001). On Cox regression, diminished survival was noted for the Observation group (risk ratio [RR] 1.43; p  = 0.04), male gender (RR 2.06; p  < 0.0001), and a higher T stage. Conclusion SNB for MCC provides prognostic information and is associated with a significant survival advantage.

Background An absolute bilirubin level where preoperative biliary decompression (PBD) is indicated before pancreaticoduodenectomy has been elusive. Our goal was to identify a total bilirubin level whereby biliary decompression provides clear benefit, despite associated expenses and potential complications. Materials and Methods We reviewed a prospectively collected database of patients undergoing pancreaticoduodenectomy at the Vidant Medical Center between 2007 and 2016. Patients were arbitrarily subdivided into 3 groups based on presenting bilirubin level (≤10 mg/dL, 10.1-14.9 mg/dL, and ≥15 mg/dL) to determine the presence of overall complications, severe complications (Clavien-Dindo classification ≥3), prolonged length of stay (>1 SD), readmissions, or mortality. Results Common bile duct stenting independently predicted a higher incidence of complications in patients presenting with bilirubin ≤10 mg/dL (P = .03) vs. those patients going directly to surgery. No differences were observed for patients with bilirubin between 10.1 mg/dL and 14.9 mg/dL. Biliary decompression in patients with bilirubin ≥15 mg/dL independently predicted fewer overall (73.8% vs. 100%, P = .0082) and less severe complications (14.3% vs. 44.5%, P = .03) and lower readmission rates (15.8% vs. 55.6%, P = .03) vs. those going directly to surgery. Patients not undergoing biliary decompression underwent pancreaticoduodenectomy sooner than those decompressed (4.7 days vs. 17.2 days, P = .01). Discussion All patients presenting with bilirubin ≥15 mg/dL should undergo PBD, while those with bilirubin ≤10 mg/dL should forego stent placement to avoid stent-related complications. The decision to stent between 10.1 and 14.9 mg/dL should be made on a case-by-case basis keeping in mind timeliness to definitive cancer treatment.

Background The Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) failed to demonstrate a survival advantage for sentinel lymph node biopsy (SNB) in melanoma. This may have been secondary to inadequate statistical power. This study was designed to determine the impact of SNB on melanoma-specific survival (MSS) in a larger patient cohort. Methods From 2003–2008, patients with tumors 1–4 mm in thickness and clinically negative nodes were identified within the SEER registry. Propensity score was used to create two matched cohorts: those who underwent a wide excision with SNB or wide excision alone. Result A total of 15,274 met inclusion criteria and 7,910 comprised the match cohort. Average age was 67.4 years. The majority were male (62.3 %) and white (97.2 %). Primary tumors were most frequently nonulcerated (77.1 %), located on the extremity (42.3 %), and T2 (64.1 %). There were 3,955 patients in both the SNB and observation groups. There was no significant difference in gender, ethnicity, ulceration status, primary site, or T-classification between the groups. Improved 5-year MSS was associated with SNB (85.7 vs. 84.0 %), female gender (88.3 vs. 82.7 %), absence of ulceration (87.5 vs. 75.7 %), extremity location (87.4 %), T2 disease (88.6 vs. 77.9 %), and a negative SNB (88.9 vs. 64.8 %). The relationships between observation [hazard ratio (HR) 1.18], male gender (HR 1.33), ulceration (HR 1.77), head-and-neck location (HR 1.34), and T3 disease (HR 1.82) persisted on multivariate analysis. Conclusions Status of the sentinel node is the strongest predictor of survival in patients with intermediate thickness melanoma. SNB compared with observation was associated with a modest survival advantage.

The role of surgical resection in low-grade pancreatic neuroendocrine tumors (P-NET) is unclear. The patients diagnosed with low-grade P-NET from 1988 to 2012 were identified in SEER. Five hundred and sixty-one patients met the inclusion criteria. A majority were white (82.9%), and node negative (69.9%). Univariate analysis revealed that tumor size (<2 cm 8.3%, 2–4 cm 38.5%, and >4 cm 40.3%; P < 0.0001) and surgery (30.9% vs 25.3%; P = 0.0014) were associated with the risk of lymph node metastases (LNM). In contrast, age (P = 0.8360), gender (P = 0.4903), and race (P = 0.4235) were not. Five-year disease-free survival was associated with size (<2 cm 89.4%, 2–4 cm 80.0%, and >4 cm 74.5%; P = 0.0089), LNM (72.4% vs 82.9%; P = 0.0025), and surgery (84.3% vs 47.5%; P < 0.0001). Cox regression model showed that the association with LNM (P = 0.0025) and surgery (P < 0.0001) was significant. Surgery was associated with an improved disease-free survival for tumors >2 cm (2–4 cm, 84.4% vs 26.0% at five years; P = 0.0003, and >4 cm, 80.5% vs 49.5% at five years; P < 0.0001) but not for those with tumor size <2 cm (P = 0.4525). In conclusions, low-grade P-NETs in patients with tumor size >2 cm showed an increased risk of LNM and improved survival with resection.

Serum carbohydrate antigen (CA19-9) is known to correlate with stage, resectability, and prognosis of pancreatic cancer. The goal of pancreaticoduodenectomy is to achieve an R0 resection because worse outcomes are reported in the presence of positive margins. The purpose of this study was to evaluate the predictive utility of CA19-9 for pancreaticoduodenectomy margin status. A retrospective review of patients with pancreatic adenocarcinoma undergoing pancreaticoduodenectomy between October 2007 and November 2018 at our institution was performed. Patient demographics, preoperative CA19-9, and tumor characteristics were analyzed. Univariate and mul-tivariate logistic regression was performed to determine factors associated with positive margins. A total of 184 patients were included. The mean age was 65 years; most patients were male and white. Majority had a positive preoperative CA19-9 (69%). There were nearly twice as many patients with negative as positive margins. Groups had similar demographics and preoperative CA19-9. A greater proportion of patients with negative margins had smaller tumors and early disease. On univariate and multivariate analysis, larger and higher stage tumors had greater odds of positive margins (P < 0.05). There was no significant association between margin status and preoperative CA19-9. Preoperative CA19-9 is not predictive of margin status. These results suggest that although preoperative CA19-9 values are associated with both resectability and prognosis, positive margins may not be a contributing mechanism.

Readmission rates after pancreaticoduodenectomy (PD) are among the highest of any surgical procedure. The purpose of this study was to identify those factors present at discharge that may predict readmission after PD. All patients undergoing PD between 2010 and 2015 at a very high (>35 PD/year) volume center were entered into a prospective database. Twenty factors present at discharge from index admission identified on univariate analysis were subjected to multivariate analysis to identify those independently predictive of 30-day hospital readmission. A total of 220 patients underwent PD during the study period, 88 per cent of which had cancer. Mean age was 64.4 ± 11.7 years with slight male preponderance (54.5%) and significant African American representation (33.2%). Surgical complications occurred in 67.3 per cent of patients the most common of which included infectious/leak (30%), gastrointestinal (29%), cardiorespiratory (13%), other (13%), minor complications (7%), multi system failure (5%), and new onset diabetes (3%). The 30-day readmission rate was 27.3 per cent and was due to infection (89%), failure to thrive (32%), nausea/vomiting (15%), or other (15%). On multivariate analysis, presence of pancreatic leak/fistula at discharge was the only significant predictor of readmission, present in 62.5 per cent of all readmitted patients (P = 0.001). Comorbidities, length of stay, insurance status, obesity, smoking, and discharge to a care venue other than home did not predict readmission. Patients manifesting pancreatic fistula after PD are at high risk for hospital readmission. Enhanced scrutiny regarding suitability for discharge should be exercised in these patients and measures taken to minimize readmission whenever possible.

Few data exist regarding outcomes after resection versus embolic treatment of symptomatic metastatic carcinoid and neuroendocrine tumors. The purpose of this study was to determine whether cytoreduction provides any benefit over embolic management of diffuse neuroendocrine tumors. A prospective database of 734 patients treated at our institution was retrospectively queried for symptomatic metastatic tumors treated with embolization or cytoreduction. Patients were compared with regard to pretreatment performance status, relief of symptoms, and survival. A total of 120 patients were identified: 59 undergoing embolization and 61 undergoing cytoreduction. Twenty-three patients had palliative cytoreduction (gross residual disease). Pretreatment performance status (Eastern Cooperative Oncology Group) was similar for both groups: .7+/-.70 (embolization) versus .8+/-.72 (cytoreduction; P=.27). Complete symptomatic relief was observed in 59% and partial relief in 32% of patients who underwent embolization, with a mean symptom-free interval of 22+/-13.6 months. A total of 69% of patients who underwent cytoreduction had complete symptomatic relief, and 23% had partial relief (P=.08 vs. embolization). The mean duration of relief was 35+/-22.0 months (P<.001 vs. embolization). The mean survival for the patients who underwent embolization was 24+/-15.8 months versus 43+/-26.1 months for those who underwent cytoreduction (P<.001). Survival in patients who underwent palliative cytoreduction was 32+/-18.9 months (P<.001 vs. embolization), whereas it was 50+/-27.6 months in patients who underwent curative resection (P<.001 vs. embolization; P<.001 vs. palliative). Cytoreduction for metastatic neuroendocrine tumors resulted in improved symptomatic relief and survival when compared with embolic therapy in this nonrandomized study. Cytoreduction should be pursued whenever possible even if complete resection may not be achievable.

Pancreatic cancer is the 5th leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells. In addition, the MVA virus has oncolytic properties in vitro as it can replicate in and kill Panc02 pancreatic adenocarcinoma cell line tumor cells, even though it is unable to replicate in most mammalian cells. Deletion of the A35 gene in MVA improved T cell responses as expected. However, we were unable to demonstrate inhibition of Panc02 tumor growth in immunocompetent mice with pre-vaccination of mice, boosts, or even intratumoral injections of the recombinant viruses. Vaccine efficacy may be limited by shedding of mesothelin from tumor cells thus creating a protective screen from the immune system.