Potential Role for Observation in Small Solid Pseudopapillary Neoplasm (SPN).

BACKGROUND: Solid pseudopapillary neoplasms (SPN) are rare tumors of the pancreas, typically affecting young women. Resection is the mainstay of treatment but is associated with significant morbidity and potential mortality. We explore the idea that small, localized SPN could be safely observed. METHODS: This retrospective review of the Pancreas National Cancer Database from 2004 to 2018 identified SPN via histology code 8452. RESULTS: A total of 994 SPNs were identified. Mean age was 36.8 ± 0.5 years, 84.9% (n = 844) were female, and most had a Charlson-Deyo Comorbidity Coefficient (CDCC) of 0-1 (96.6%, n = 960). Patients were most often staged clinically as cT2 (69.5%, n = 457) followed by cT3 (17.6%, n = 116), cT1 (11.2%, n = 74), and cT4 (1.7%, n = 11). Clinical lymph node and distant metastasis rates were 3.0 and 4.0%, respectively. Surgical resection was performed in 96.6% of patients (n = 960), most commonly partial pancreatectomy (44.3%) followed by pancreatoduodenectomy (31.3%) and total pancreatectomy (8.1%). In patients clinically staged as node (N0) and distant metastasis (M0) negative, occult pathologic lymph node involvement was found in 0% (n = 28) of patients with stage cT1 and 0.5% (n = 185) of patients with cT2 disease. The risk of occult nodal metastasis significantly increased to 8.9% (n = 61) for patients with cT3 disease. The risk further increased to 50% (n = 2) in patients with cT4 disease. CONCLUSIONS: Herein, the specificity of excluding nodal involvement clinically is 99.5% in tumors ≤ 4 cm and 100% in tumors ≤ 2 cm. Therefore, there may be a role for close observation in patients with cT1N0 lesions to mitigate morbidity from major pancreatic resection.

Ampullary Neuroendocrine Tumors: Insight into a Rare Histology.

BACKGROUND: Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs. METHODS: The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression. RESULTS: Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n = 149, 17%) than patients with duodenal (n = 197, 2%) or pancreatic head (n = 740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n = 297, 34%) than patients with duodenal (n = 950, 10%) or pancreatic head (n = 1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p < 0.0001), Charlson-Deyo score of 2 (HR 2.3, p = 0.001) or ≥3 (HR 2.9, p = 0.013), grade 2 (HR 1.9, p = 0.007) or grade 3 tumors (HR 4.0, p < 0.0001), and metastatic disease (HR 2.0, p = 0.001) were associated with decreased survival. At 5 years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p < 0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p < 0.0001). CONCLUSIONS: Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.

Robotic vs open distal pancreatectomy: A multi-institutional matched comparison analysis.

BACKGROUND: Pancreatic surgery is still a challenge even in high-volume centers. Clinically relevant postoperative pancreatic fistula (CR-POPF) represents the greatest contributor to major morbidity and mortality, especially following pancreatic distal resection. In this study, we compared robotic distal pancreatectomy (RDP) to open distal pancreatectomy (ODP) in terms of CR-POPF development and analyzed oncologic efficacy of RDP in the subgroup of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We collected data from five high-volume centers for pancreatic surgery and performed a matched comparison analysis to compare short and long-term outcomes after ODP or RDP. Patients were matched with a 2:1 ratio according to age, ASA (American Society of Anesthesiologists) score, body mass index (BMI), final pathology, and TNM (Tumour, Node, Metastasis) staging system VIII ed. RESULTS: Two hundred and forty-six patients who underwent 82 RDPs and 164 ODPs were included. No differences were found in the incidence of CR-POPF. In the PDAC group, median DFS and OS were 10.8 months and 14.8 months in the ODP group and 10.4 months and 15 months in the RDP group, respectively. CONCLUSIONS: Robotic distal pancreatectomy is a safe surgical strategy for PDAC and incidence of CR-POPF is equivalent between RDP and ODP. RDP should be considered equivalent to ODP in terms of oncological efficacy when performed in high-volume and proficient centers.

Characterization of a Novel Entity of G3 (High-grade Well-differentiated) Colorectal Neuroendocrine Tumors (NET) in the SEER Database.

OBJECTIVES: Small studies suggest that a new entity of high-grade (HG) (G3, by Ki-67 or mitotic index) well-differentiated (histologically) gastrointestinal neuroendocrine tumors (NETs) exists, but prognosis and characteristics are unknown. We further characterized demographics and prognosis of patients with colorectal G3 NETs. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results (SEER) database to study colorectal NETs diagnosed from 2000 to 2015. We evaluated demographic, clinical, and tumor characteristics. We compared overall survival (OS) for G1-2 NET, G3 NET, and NEC (neuroendocrine carcinoma). We used logistic regression to detect grade associations and Cox proportional hazards models to examine predictors of survival. RESULTS: We identified 5894 cases with colorectal NET (5780 [98.1%] G1-2 and 114 [1.9%] G3); the cohort was 66% white, 47% male, and had a median age of 54. Patients with G3 NET were likely to be older (odds ratio [OR]: 2.23; 95% confidence interval [CI]: 1.19-4.19 for 60 to 69 vs. <50), unmarried (OR: 1.56; 95% CI: 1.02-2.38), and less likely to be diagnosed after 2010 (OR: 0.09; 95% CI: 0.06-0.15). OS for G3 NET (median, 36 mo; 95% CI: 13-92) fell between OS for NEC (median, 7 mo; 95% CI: 6-8), and G1-2 NET (median not reached, >120 mo). Among G1-3 NETs, black patients (hazard ratio [HR]: 1.30; 95% CI: 1.03-1.62), older patients (HR: 3.63; 95% CI: 2.63-5.01 for age 60 to 69 vs. <50), unmarried patients (HR: 1.40; 95% CI: 1.17-1.68), and those with HG features (HR: 3.97; 95% CI: 3.15-4.99) had worse survival. CONCLUSIONS: We defined a subset of G3 NETs that are HG and well differentiated, more common in older, unmarried patients, with a prognosis between that of NEC and G1-2 NETs. Our analysis adds the first national registry study in support of a new classification of nonpancreatic HG and well-differentiated NETs.

Perioperative Gemcitabine + Erlotinib Plus Pancreaticoduodenectomy for Resectable Pancreatic Adenocarcinoma: ACOSOG Z5041 (Alliance) Phase II Trial.

BACKGROUND: There is considerable interest in a neoadjuvant approach for resectable pancreatic ductal adenocarcinoma (PDAC). This study evaluated perioperative gemcitabine + erlotinib (G+E) for resectable PDAC. METHODS: A multicenter, cooperative group, single-arm, phase II trial was conducted between April 2009 and November 2013 (ACOSOG Z5041). Patients with biopsy-confirmed PDAC in the pancreatic head without evidence of involvement of major mesenteric vessels (resectable) were eligible. Patients (n = 123) received an 8-week cycle of G+E before and after surgery. The primary endpoint was 2-year overall survival (OS), and secondary endpoints included toxicity, response, resection rate, and time to progression. Resectability was assessed retrospectively by central review. The study closed early due to slow accrual, and no formal hypothesis testing was performed. RESULTS: Overall, 114 patients were eligible, consented, and initiated protocol treatment. By central radiologic review, 97 (85%) of the 114 patients met the protocol-defined resectability criteria. Grade 3+ toxicity was reported in 60% and 79% of patients during the neoadjuvant phase and overall, respectively. Twenty-two of 114 (19%) patients did not proceed to surgery; 83 patients (73%) were successfully resected. R0 and R1 margins were obtained in 67 (81%) and 16 (19%) resected patients, respectively, and 54 patients completed postoperative G+E (65%). The 2-year OS rate for the entire cohort (n = 114) was 40% (95% confidence interval [CI] 31-50), with a median OS of 21.3 months (95% CI 17.2-25.9). The 2-year OS rate for resected patients (n = 83) was 52% (95% CI 41-63), with a median OS of 25.4 months (95% CI 21.8-29.6). CONCLUSIONS: For resectable PDAC, perioperative G+E is feasible. Further evaluation of neoadjuvant strategies in resectable PDAC is warranted with more active systemic regimens.

A Quest for Optimization of Postoperative Triage After Major Surgery.

INTRODUCTION: Innovative strategies to reduce costs while maintaining patient satisfaction and improving delivery of care are greatly needed in the setting of rapidly rising health care expenditure. Intensive care units (ICUs) represent a significant proportion of health care costs due to their high resources utilization. Currently, the decision to admit a patient to the ICU lacks standardization because of the lack of evidence-based admission criteria. The objective of our research is to develop a prediction model that can help the physician in the clinical decision-making of postoperative triage. MATERIALS AND METHODS: Our group identified a list of index events that commonly grants admission to the ICU independently of the hospital system. We analyzed correlation among 200 quantitative and semiquantitative variables for each patient in the study using a decision tree modeling (DTM). In addition, we validated the DTM against explanatory models, such as bivariate analysis, multiple logistic regression, and least absolute shrinkage and selection operator. RESULTS: Unlike explanatory modeling, DTM has several unique strengths: tree models are easy to interpret, the analysis can examine hundreds of variables at once, and offer insight into variable relative importance. In a retrospective analysis, we found that DTM was more accurate at predicting need for intensive care compared with current clinical practice. DISCUSSION: DTM and predictive modeling may enhance postoperative triage decision-making. Future areas of research include larger retrospective analyses and prospective observational studies that can lead to an improved clinical practice and better resources utilization.

Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria.

BACKGROUND & AIMS: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSIONS: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

Can we downstage locally advanced pancreatic cancer to resectable? A phase I/II study of induction oxaliplatin and 5-FU chemoradiation.

BACKGROUND: Half of patients with pancreatic adenocarcinoma (PC) present with regionally advanced disease. This includes borderline resectable and locally advanced unresectable tumors as defined by current NCCN guidelines for resectability. Chemoradiation (CH-RT) is used in this setting in attempt to control local disease, and possibly downstage to resectable disease. We report a phase I/II trial of a combination of 5FU/Oxaliplatin with concurrent radiation in patients presenting with borderline resectable and locally advanced unresectable pancreatic cancer. METHODS: Patients with biopsy-proven borderline resectable or locally advanced unresectable PC were eligible. Chemotherapy included continuous infusion 5FU (200 mg/m2) daily and oxaliplatin weekly for 5 weeks in dose escalation cohorts, ranging from 30 to 60 mg/m2. Concurrent radiation therapy consisted of 4,500 cGy in 25 fractions (180 cGy/fx/d) followed by a comedown to the tumor and margins for an additional 540 cGy ×3 (total dose 5,040 cGy in 28 fractions). Following completion of CH-RT, patients deemed resectable underwent surgery; those who remained unresectable for cure but did not progress (SD, stable disease) received mFOLFOX6 ×6 cycles. Survival was calculated using Kaplan-Meier analysis. End-points of the phase II portion were resectability and overall survival. RESULTS: Overall, 24 subjects (15 men and 9 women, mean age 64.5 years) were enrolled between June 2004 and December 2009 and received CH-RT. Seventeen patients were enrolled in the Phase I component of the study, fifteen of whom completed neoadjuvant therapy. Reasons for not completing treatment included grade 3 toxicities (1 patient) and withdrawal of consent (1 patient). The highest dose of oxaliplatin (60 mg/m2) was well tolerated and it was used as the recommended phase II dose. An additional 7 patients were treated in the phase II portion, 5 of whom completed CH-RT; the remaining 2 patients did not complete treatment because of grade 3 toxicities. Overall, 4/24 did not complete CH-RT. Grade 4 toxicities related to initial CH-RT were observed during phase I (n=2, pulmonary embolism and lymphopenia) and phase II (n=3, fatigue, leukopenia and thrombocytopenia). Following restaging after completion of CH-RT, 4 patients had progressed (PD); 9 patients had SD and received additional chemotherapy with mFOLFOX6 (one of them had a dramatic response after two cycles and underwent curative resection); the remaining 7 patients (29.2%) were noted to have a response and were explored: 2 had PD, 4 had SD, still unresectable, and 1 patient was resected for cure with negative margins. Overall 2 patients (8.3%) in the study received curative resection following neoadjuvant therapy. Median overall survival for the entire study population was 11.4 months. Overall survival for the two resected patients was 41.7 and 21.6 months. CONCLUSIONS: Combined modality treatment for borderline resectable and locally advanced unresectable pancreatic cancer with oxaliplatin, 5FU and radiation was reasonably well tolerated. The majority of patients remained unresectable. Survival data with this regimen were comparable to others for locally advanced pancreas cancer, suggesting the need for more novel approaches.

MRI-Based Apparent Diffusion Coefficient for Predicting Pathologic Response of Rectal Cancer After Neoadjuvant Therapy: Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to assess the use of apparent diffusion coefficient (ADC) during DWI for predicting complete pathologic response of rectal cancer after neoadjuvant therapy. MATERIALS AND METHODS: A systematic review of available literature was conducted to retrieve studies focused on the identification of complete pathologic response of locally advanced rectal cancer after neoadjuvant chemoradiation, through the assessment of ADC evaluated before, after, or both before and after treatment, as well as in terms of the difference between pretreatment and posttreatment ADC. Pooled mean pretreatment ADC, posttreatment ADC, and Δ-ADC (calculated as posttreatment ADC minus pretreatment ADC divided by pretreatment ADC and multiplied by 100) in complete responders versus incomplete responders were calculated. For each parameter, we also pooled sensitivity and specificity and calculated the area under the summary ROC curve. RESULTS: We found 10 prospective and eight retrospective studies. Overall, pathologic complete response was observed in 22.2% of patients. Pooled mean pretreatment ADC in complete responders was 0.84 × 10-3 mm2/s versus 0.89 × 10-3 mm2/s in incomplete responders (p = 0.33). Posttreatment ADC values were 1.51 × 10-3 mm2/s and 1.29 × 10-3 mm2/s, in complete and incomplete responders, respectively (p = 0.00001). The Δ-ADC percentages were also significantly higher in complete responders than in incomplete responders (59.7% vs 29.7%, respectively, p = 0.016). Pooled sensitivity, specificity, and AUC were 0.743, 0.755, and 0.841 for pretreatment ADC; 0.800, 0.737, and 0.782 for posttreatment ADC; and 0.832, 0.806, and 0.895 for Δ-ADC. CONCLUSION: Use of ADC during DWI is a promising technique for assessment of results of neoadjuvant treatment of rectal cancer.

Delivery of adjuvant chemotherapy among stage III colon cancer patients at a public versus private hospital in New York City.

PURPOSE: Prior studies of timeliness of adjuvant chemotherapy (AC) initiation in stage III colon cancer have suggested longer time to AC at public compared with private hospitals. Few studies have explored differences in AC completion. We investigated whether timely initiation and completion of AC differed between a public and private hospital, affiliated with the same academic institution in a large, urban setting. METHODS: We conducted a retrospective cohort study of stage III colon cancer patients who had surgery and AC at the same medical center between 2008 and 2015, either at its affiliated public hospital (n = 43) or private hospital (n = 79). We defined timely initiation as receiving AC within 60 days postoperatively, and completion as receiving ≥ 75% of planned AC. Univariate and stepwise multivariable logistic regressions were used to identify factors associated with AC delivery. RESULTS: Median number of days to AC was significantly greater among patients at the public (53, range 31-231) compared with the private hospital (43, range 25-105; p = 0.002). However, the percentage of patients with timely AC initiation did not differ substantially by hospital (74 vs 81%, p = 0.40). In multivariable analysis, age (OR 0.95/year, 95% CI 0.91-0.99) and laparoscopic versus open surgery (OR 5.65, 95% CI 1.92-16.62) were significant factors associated with timely AC initiation. Moreover, AC completion did not differ significantly between public (83.7%) and private (89.9%) hospital patients (p = 0.32). CONCLUSIONS: The proportions of patients with timely initiation and completion of AC were similar at a public and private hospital affiliated with a large, urban medical center. Future research should investigate how specific system-level factors help alleviate this expected difference in timely care delivery.

Predictors and Prognostic Implications of Perioperative Chemotherapy Completion in Gastric Cancer.

BACKGROUND: Perioperative chemotherapy in gastric cancer is increasingly used since the "MAGIC" trial, while clinical practice data outside of trials remain limited. We sought to evaluate the predictors and prognostic implications of perioperative chemotherapy completion in patients undergoing curative-intent gastrectomy across multiple US institutions. METHODS: Patients who underwent curative-intent resection of gastric adenocarcinoma between 2000 and 2012 in eight institutions of the US Gastric Cancer Collaborative were identified. Patients who received preoperative chemotherapy were included, while those who died within 90 days or with unknown adjuvant chemotherapy status were excluded. Predictors of chemotherapy completion and survival were identified using multivariable logistic regression and Cox proportional hazards. RESULTS: One hundred sixty three patients were included (median age 63.3, 36.8% female). The postoperative component of perioperative chemotherapy was administered in 112 (68.7%) patients. Factors independently associated with receipt of adjuvant chemotherapy were younger age (odds ratio (OR) 2.73, P = 0.03), T3 tumors (OR 14.3, P = 0.04), lymph node metastasis (OR 5.82, P = 0.03), and D2 lymphadenectomy (OR 4.12, P = 0.007), and, inversely, postoperative complications (OR 0.25, P = 0.008). Median overall survival (OS) was 25.1 months and 5-year OS was 36.5%. Predictors of OS were preexisting cardiac disease (hazard ratio (HR) 2.7, 95% CI 1.13-6.46), concurrent splenectomy (HR 4.11, 95% CI 1.68-10.0), tumor stage (reference stage I; stage II HR 2.62; 95% CI 0.99-6.94; stage III HR 4.86, 95% CI 1.81-13.02), and D2 lymphadenectomy (HR 0.43, 95% CI 0.19-0.95). After accounting for these factors, adjuvant chemotherapy administration was associated with improved OS (HR 0.33, 95% CI 0.14-0.82). CONCLUSION: Completion of perioperative chemotherapy was successful in two thirds of patients with gastric cancer and was independently associated with improved survival.

Management of Incidental Pancreatic Cysts: A White Paper of the ACR Incidental Findings Committee.

The ACR Incidental Findings Committee (IFC) presents recommendations for managing pancreatic cysts that are incidentally detected on CT or MRI. These recommendations represent an update from the pancreatic component of the JACR 2010 white paper on managing incidental findings in the adrenal glands, kidneys, liver, and pancreas. The Pancreas Subcommittee-which included abdominal radiologists, a gastroenterologist, and a pancreatic surgeon-developed this algorithm. The recommendations draw from published evidence and expert opinion, and were finalized by informal iterative consensus. Algorithm branches successively categorize pancreatic cysts based on patient characteristics and imaging features. They terminate with an ascertainment of benignity and/or indolence (sufficient to discontinue follow-up), or a management recommendation. The algorithm addresses most, but not all, pathologies and clinical scenarios. Our goal is to improve quality of care by providing guidance on how to manage incidentally detected pancreatic cysts.

Minimally Invasive Management of Ectopic Pancreas.

BACKGROUND: The management of ectopic pancreas is not well defined. This study aims to determine the prevalence of symptomatic ectopic pancreas and identify those who may benefit from treatment, with a particular focus on robotically assisted surgical management. METHODS: Our institutional pathology database was queried to identify a cohort of ectopic pancreas specimens. Additional clinical data regarding clinical symptomatology, diagnostic studies, and treatment were obtained through chart review. RESULTS: Nineteen cases of ectopic pancreas were found incidentally during surgery for another condition or found incidentally in a pathologic specimen (65.5%). Eleven patients (37.9%) reported prior symptoms, notably abdominal pain and/or gastrointestinal bleeding. The most common locations for ectopic pancreas were the duodenum and small bowel (31% and 27.6%, respectively). Three out of 29 cases (10.3%) had no symptoms, but had evidence of preneoplastic changes on pathology, while one harbored pancreatic cancer. Over the years, treatment of ectopic pancreas has shifted from open to laparoscopic and more recently to robotic surgery. CONCLUSIONS: Our experience is in line with existing evidence supporting surgical treatment of symptomatic or complicated ectopic pancreas. In the current era, minimally invasive and robotic surgery can be used safely and successfully for treatment of ectopic pancreas.

Use of the surgical Apgar score to enhance Veterans Affairs Surgical Quality Improvement Program surgical risk assessment in veterans undergoing major intra-abdominal surgery.

BACKGROUND: We investigated whether the surgical Apgar score (SAS) may enhance the Veterans Affairs Surgical Quality Improvement Program (VASQIP) risk assessment for prediction of early postoperative outcomes. METHODS: We retrospectively evaluated demographics, medical history, procedure, SAS, VASQIP assessment, and postoperative data for patients undergoing major/extensive intra-abdominal surgery at the Manhattan Veterans Affairs between October 2006 and September 2011. End points were overall morbidity and 30-, 60- , and 90-day mortality. Pearson's chi-square, ANOVA, and multivariate regression modeling were employed. RESULTS: Six hundred twenty-nine patients were included. Apgar groups did not differ in age, sex, and race. Low SASs were associated with worse functional status, increased postoperative morbidity, and 30-, 60- , and 90-day mortality rates. SAS did not significantly enhance VASQIP prediction of postoperative outcomes, although a trend was detected. Multivariate analysis confirmed SAS as an independent predictor of morbidity and mortality. CONCLUSIONS: SAS effectively identifies veterans at high risk for poor postoperative outcome. Additional studies are necessary to evaluate the role of SAS in enhancing VASQIP risk prediction.

γδ T Cells Support Pancreatic Oncogenesis by Restraining αß T Cell Activation.

Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αßT cells. Although αßT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that γδT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe γδT cells as central regulators of effector T cell activation in cancer via novel cross-talk.

Stage-Specific Prognostic Effect of Race in Patients with Resectable Gastric Adenocarcinoma: An 8-Institution Study of the US Gastric Cancer Collaborative.

BACKGROUND: Gastric cancer constitutes a major public health problem. This study sought to evaluate the relevance of race in gastric cancer and its prognostic effect in the overall outcomes of patients with gastric adenocarcinoma. STUDY DESIGN: Patients who underwent curative intent resection of gastric adenocarcinoma in 8 institutions of the US Gastric Cancer Collaborative were included, from 2000 to 2012. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic data. Multivariate Cox proportional hazards regression was used to identify factors associated with recurrence-free survival and overall survival. RESULTS: There were 1,077 patients included in the study, the majority of whom were of Caucasian race (n = 698, 68%), followed by African-American (n = 164, 15%), Asian (n = 132, 12%), Hispanic (n = 34, 3.2%), and other (n = 49, 4.5%). Clinicopathologic data were similarly distributed among the 5 groups. Mean follow-up was 27.1 months. By multivariate, stage-specific analysis, Asian race was a significant predictor of recurrence (all stages hazard ratio [HR] 0.45 95% CI [0.23, 0.97], p = 0.041) and of overall survival (all stages HR 0.35 95% CI [0.18, 0.68], p = 0.002). Recurrence-free survival was significantly increased in the Asian population compared with the non-Asian population (25th percentile: 38.6 vs 17.7 months, p = 0.0096), as was overall median survival (141 vs 38.8 months, p < 0.001). CONCLUSIONS: Patients of Asian race undergoing curative gastrectomy for gastric adenocarcinoma appear to have a better prognosis stage for stage. Further studies are required to elucidate the underlying etiology of this phenomenon.