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Background: Lymph node (LN) involvement is a well-known poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). However, there have been conflicting results on the significance of the mechanism of LN involvement, "direct" tumor invasion versus "metastatic," disease on patient survival., Methods: Clinicopathologic records from all patients who underwent resection for PDAC from 1990 to 2014 at a single-institution were reviewed., Results: Of the 385 total patients, there was tumor invasion outside of the pancreas in 289 (75.1%) patients. Overall, 239 (62.1%) had node-positive disease: 220 (92.0%) by "metastatic" involvement, 14 (5.9%) by "direct" tumor extension, and five (2.1%) by a mix of "metastatic" and "direct". There were no significant differences in clinicopathologic factors associated with PDAC survival between "metastatic" and "direct" LN patients. The median overall survival for the whole cohort was 31.1 months. Compared to overall survival in patients with LN-negative disease (median 40.7 months), those with LNs involved by "metastatic" spread was significantly shorter (median 25.7 months, P < 0.001), yet "direct" LN extension was similar (median 48.1 months, P = 0.719)., Conclusions: The mechanism of LN involvement affects PDAC prognosis. Patients with LNs involved by direct extension have similar survival to those with node-negative disease., (© 2015 Wiley Periodicals, Inc.)

Objective: To assess the impact of postoperative complications on the receipt of adjuvant chemotherapy., Background: Randomized trials have demonstrated that adjuvant chemotherapy is associated with improved long-term survival. However, pancreatic surgery is associated with significant morbidity and the degree to which complications limit subsequent treatment options is unknown., Methods: Patients from the American College of Surgeons National Surgical Quality Improvement Program and the National Cancer Data Base who underwent pancreatic resection for cancer were linked (2006-2009). The associations between complications and adjuvant chemotherapy use or treatment delay (≥ 70 days from surgery) were assessed using multivariable regression methods., Results: From 149 hospitals, 2047 patients underwent resection for stage I-III pancreatic adenocarcinoma of which 23.2% had at least 1 serious complication. Overall adjuvant chemotherapy receipt was 57.7%: 61.8% among patients not experiencing any complication and 43.6% among those who had a serious complication. Serious complications increased the likelihood of not receiving adjuvant therapy over twofold [odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.73-2.80]. Specific complications associated with adjuvant chemotherapy omission were reintubation (OR = 7.79, 95% CI: 3.59-16.87), prolonged ventilation (OR = 5.92, 95% CI: 3.23-10.86), pneumonia (OR = 2.83, 95% CI: 1.63-4.90), sepsis/shock (OR = 2.76, 95% CI: 2.02-3.76), organ space/deep surgical site infection (OR = 2.19, 95% CI: 1.53-3.13), venous thromboembolism (OR = 1.92, 95% CI: 1.08-3.43), and urinary tract infection (OR = 1.61, 95% CI: 1.02-2.54). Serious complications also doubled the likelihood of delaying adjuvant treatment administration (OR = 2.08, 95% CI: 1.42-3.05). Sensitivity analysis in a younger, healthier patient cohort demonstrated similar associations., Conclusions: Postoperative complications are common following pancreatic surgery and are associated with adjuvant chemotherapy omission and treatment delays.

Background: Pancreatic ductal adenocarcinoma (PDAC) patients demonstrate highly variable survival within each stage of the American Joint Committee on Cancer (AJCC) staging system. We hypothesize that tumor grade is partly responsible for this variation. Recently our group developed a novel tumor, node, metastasis, grade (TNMG) classification system utilizing Surveillance Epidemiology and End Results (SEER) data in which the presence of high tumor grade results in advancement to the next higher AJCC stage. This study's objective was to validate this TNMG staging system utilizing single-institution data., Methods: All patients with PDAC who underwent resection at UCLA between 1990 and 2009 were identified. Clinicopathologic data reviewed included age, sex, node status, tumor size, grade, and stage. Grade was redefined as a dichotomous variable. The impact of grade on survival was assessed by Cox regression analysis. Disease was restaged into the TNMG system and compared to the AJCC staging system., Results: We identified 256 patients who underwent resection for PDAC. Patients with low-grade tumors experienced a 13-month improvement in median survival compared to those with high-grade tumors. On multivariate analysis, tumor grade was the strongest predictor of survival with a hazard ratio of 2.02 (p = 0.0005). Restaging disease according to the novel TNMG staging system resulted in improved survival discrimination between stages compared to the current AJCC system., Conclusions: We were able to demonstrate that grade is one of the strongest independent prognostic factors in PDAC. Restaging with our novel TNMG system demonstrated improved prognostication. This system offers an effective and convenient way of adding grade to the current AJCC staging system.

Background: Colonoscopic screening has increased detection of malignant colonic polyps (MPs). The goal of this study was to analyze trends and patterns in the surgical treatment of MPs and to assess outcomes as measured by lymph node retrieval and patient survival., Methods: The Surveillance, Epidemiology, and End Results (SEER) registry was queried to identify 19,743 patients with MPs from 1988 to 2003., Results: The majority of MPs were present in the sigmoid and descending colon (54%), and 38% were tubular, 40% were tubulovillous, and 22% were villous. During the study period, the incidence of MPs increased from 29% to 42% and surgical resection (SR) was increasingly used for treatment, from 54% to 70%. Predictors of SR were aged <70 years (odds ratio [OR], 1.3; 95% confidence interval [95% CI], 1.2-1.4), high-grade tumors (OR, 1.5; 95% CI, 1.2-1.9), diagnosis in 1999 through 2003 (OR, 1.7; 95% CI, 1.5-1.9), villous subtype (OR, 2.3; 95% CI, 2.0-2.6), and right colon location (OR, 8.1; 95% CI, 7.0-9.4). In patients undergoing SR, the mean and median number of lymph nodes was only 4 and 1, respectively. A significant percentage of patients (49%) had no lymph nodes retrieved and a worse overall survival at 5 years compared with patients who had at least 1 lymph node examined (64% vs 74%; P <.001)., Conclusions: MPs appear to be increasing in incidence, and there is a trend toward increased use of SR for treatment. However, patients undergoing SR for MPs undergo suboptimal assessment of lymph nodes, with a detrimental impact on survival. Adequate lymphadenectomy and lymph node evaluation are crucial to improve outcomes in patients with these potentially curable lesions. Cancer 2011. © 2010 American Cancer Society., (Copyright © 2010 American Cancer Society.)

Background: AJCC staging of pancreatic cancer (PAC) is used to determine prognosis, yet survival within each stage shows wide variation and remains unpredictable. We hypothesized that tumor grade might be responsible for some of this variation and that the addition of grade to current AJCC staging would provide improved prognostication., Methods: The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was used to identify 8082 patients with resected PAC. The impact of grade on overall and stage-specific survival was assessed using Cox regression analysis. Variables in the model were age, sex, tumor size, lymph node status, and tumor grade., Results: For each AJCC stage, survival was significantly worse for high-grade versus low-grade tumors. On multivariate analysis, high tumor grade was an independent predictor of survival for the entire cohort (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.31-1.48) as well as for stage I (HR 1.28, 95% CI 1.07-1.54), stage IIA (HR 1.43, 95% CI 1.26-1.61), stage IIB (HR 1.38, 95% CI 1.27-1.50), stage III (HR 1.28, 95% CI 1.02-1.59), and stage IV (HR 1.58, 95% CI 1.21-2.05) patients. The addition of grade to staging results in a statistically significant survival discrimination between all stages., Conclusions: Tumor grade is an important prognostic variable of survival in PAC. We propose a novel staging system incorporating grade into current AJCC staging for pancreas cancer. The improved prognostication is more reflective of tumor biology and may impact therapy decisions and stratification of future clinical trials.

Background: Although invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. The authors compared survival and identify prognostic factors after resection for invasive IPMN versus stage-matched PAC., Methods: The Surveillance, Epidemiology, and End Results database (1991-2005) was used to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection., Results: Patients with resected invasive IPMN experienced improved overall survival when compared with resected PAC (median survival, 21 vs 14 months; P<.001). Stratification by nodal status demonstrated no difference in survival among lymph node-positive patients; however, median survival of resected, lymph node-negative, invasive IPMN was significantly improved compared with lymph node-negative PAC (34 vs 18 months; P<.001). On multivariate analysis, PAC histology was an adverse predictor of overall survival (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.50) compared with invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR, 1.98; 95% CI, 1.50-2.60), high tumor grade (HR, 1.74; 95% CI, 1.31-2.31), tumor size>2 cm (HR, 1.50; 95% CI, 1.04-2.19), and age>66 years (HR, 1.33; 95% CI, 1.03-1.73) were adverse predictors of survival., Conclusions: Although lymph node-negative invasive IPMN showed improved survival after resection compared with lymph node-negative PAC, the natural history of lymph node-positive invasive IPMN mimicked that of lymph node-positive PAC. The authors also identified adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis after resection of invasive IPMN., (Copyright (c) 2010 American Cancer Society.)

Introduction: Complications following pancreaticoduodenectomy (PD) often necessitate nutritional support. This study analyzes the utilization of parenteral nutrition (TPN) during the surgical admission as evidence for or against routine jejunostomy placement., Methods: The California Cancer Registry (1994-2003) was linked to the California Inpatient File; PD for adenocarcinoma was performed in 1,873 patients. TPN use and enterostomy tube placement were determined and preoperative characteristics predictive of TPN use during the surgical admission were identified., Results: Fourteen percent of patients received TPN, 23% underwent enterostomy tube placement, and 63% received no supplemental nutritional support. TPN was associated with longer hospital stay (18 vs. 13 days, P < 0.0001). The Charlson Comorbidity Index (CCI) > or = 3 had nearly two-fold greater odds of receiving TPN (odds ratio [OR] = 1.85, P < 0.005)., Conclusion: Approximately 1 in 6 patients undergoing PD received TPN, which was associated with prolonged hospital stay. CCI > or = 3 was associated with increased odds of TPN utilization. Selected jejunostomy placement in patients with high CCI is worthy of consideration.

Evaluation of 12 lymph nodes has been mandated to prevent colon cancer understaging. Given that the probability of node metastases is largely associated with T-stage, are <12 nodes substandard for T1 and T2 lesions? We evaluated if survival for T1 and T2 tumors varies by nodes examined. In SEER, 61,237 patients undergoing colon cancer resection were identified. For each T-stage, 5-year survival rates were compared for node-negative cancers by using stepwise node cut-point comparisons (4 nodes, <4, etc.). Survival impact was determined by log-rank test and hazard regression. For T1 tumors, 4 nodes had 24% lower hazard of death compared to <4. For T2 tumors, 10 nodes had the biggest survival impact, 15% lower hazard of death. In conclusion, the number of nodes to stage T1 and T2 lesions may be <12.

Procedure complexity and volume-outcome relationships have led to increased regionalization of pancreaticoduodenectomy (PD) for pancreas cancer. Knowledge regarding outcomes after PD comes from single-institutional series, which may be limited if a significant number of patients follow up at other hospitals. Thus, readmission data may be underreported. This study utilizes a population-based data set to examine readmission data following PD. California Cancer Registry (1994-2003) was linked to the California's Office of Statewide Health Planning and Development (OSHPD) database; patients with pancreatic adenocarcinoma who had undergone PD, excluding perioperative (30-day) mortality, were identified. All hospital readmissions within 1 year following PD were analyzed with respect to timing, location, and reason for readmission. Our cohort included 2,023 patients who underwent PD for pancreas cancer. Fifty-nine percent were readmitted within 1 year following PD and 47% were readmitted to a secondary hospital. Readmission was associated with worse median survival compared with those not readmitted (10.5 versus 22 months, p<0.0001). Multivariate analysis revealed that increasing T-stage, age, and comorbidities were associated with increased likelihood of readmission. Diagnoses associated with high rates of readmission included progression of disease (24%), surgery-related complications (14%), and infection (13%). Diabetes (1.4%) and pain (1.5%) were associated with low rates of readmission. We found a readmission rate of 59%, which is much higher than previously reported by single institutional series. Concordantly, nearly half of patients readmitted were readmitted to a secondary hospital. Common reasons for readmission included progression of disease, surgical complications, and infection. These findings should assist in both anticipating and facilitating postoperative care as well as managing patient expectations. This study utilizes a novel population-based database to evaluate incidence, timing, location, and reasons for readmission within 1 year following pancreaticoduodenectomy. Fifty-nine percent of patients were readmitted within 1 year after pancreaticoduodenectomy and 47% were readmitted to a secondary hospital.

Background: Ampullary cancer is the second most common periampullary cancer, with a resection and survival rate more favorable than that for pancreatic cancer. However, most reports have been conducted at single institutions with small sample sizes, and results may not reflect the practices and outcomes in the community. Our objective was to complete a population-based analysis of patients undergoing resection for ampullary carcinoma and compare it with outcomes in the published literature., Methods: Patients diagnosed with ampullary cancer reported in the Surveillance, Epidemiology, and End Results program (1988-2003) were collected. Primary outcome was survival (5-year), and secondary outcome was stage at presentation. Comparisons were made with outcomes reported in the literature (resection rate, perioperative mortality, and 5-year survival)., Results: Of the 3292 ampullary cancer patients, 1301 (40%) underwent resection. Thirty-seven percent presented with stage I tumors. Perioperative mortality (30 day) was 7.6% after resection, and 5-year survival was 36.8%. Few patients died if they survived at least 5 years. The cancer registry data showed less early stage disease, higher perioperative mortality, and lower 5-year survival compared with published reports., Conclusions: This is the largest population-based analysis of ampullary carcinoma. Resection rates and survival at the national level are lower, in general, compared with cancer center reports, which may have implications for regionalizing these procedures. Many patients surviving at least 5 years seem to be cured by surgical resection.

Background: National efforts are underway to monitor the quality of patient care at Veterans Administration (VA) hospitals. The objective of this study was to examine treatment utilization and outcomes for localized pancreatic cancer at VA compared with non-VA hospitals., Methods: Using the National Cancer Data Base, patients with pretreatment clinical stage I/II pancreatic adenocarcinoma were identified. Treatment utilization and outcomes were assessed at VA compared with academic and community hospitals., Results: Of 35,009 patients, 2% were seen at VA, 38% at academic, and 54% at community hospitals. VA hospitals were more likely to use surgery (odds ratio 2.20, 95% confidence interval 1.73-2.79) and to administer adjuvant chemotherapy (odds ratio 1.77, confidence interval 1.28-2.46) compared with community hospitals. Adjusted perioperative mortality and 3-year survival rates after surgery were similar at VA and academic hospitals., Conclusions: For localized pancreatic cancer, patients treated at VA hospitals receive stage-specific treatments and have risk-adjusted perioperative and long-term survival rates that are comparable with those for patients treated at academic centers.

Background: Despite decreased perioperative morbidity and mortality and clinical trials suggesting improved outcomes with adjuvant therapy, national practice patterns in the management of pancreatic cancer remain poorly defined. The purpose of the current study was to evaluate multimodality therapy utilization and outcomes relative to hospital type and volume., Methods: Using the National Cancer Data Base, stage-specific treatment patterns were analyzed for 301,033 patients with pancreatic adenocarcinoma. Logistic regression was used to evaluate treatment utilization. Cox proportional hazards modeling was utilized to evaluate the effect of multimodality therapy on survival., Results: Stage at presentation did not differ from 1985-1994 to 1995-2003; however, the percentage of patients receiving cancer-directed treatment increased from 45.1% to 51.8% (P < .001). Pancreatectomy for localized disease (AJCC 6th edition stages I and II) increased from 36.9% to 49.3% (P < .001). After resection, the use of adjuvant chemotherapy alone increased from 4.1% to 5.7% (P < .001), but the use of adjuvant radiation alone decreased from 7.0% to 4.6% (P < .001). Adjuvant chemoradiation use increased from 26.8% to 38.7% (P < .001). The use of surgery alone decreased from 62.1% (5213 of 8400 cases) to 49.9% (10,807 of 21,679 cases) (P < .001). Patients with localized pancreatic cancer were more likely to receive pancreatectomy and adjuvant chemoradiation at academic and high-volume centers (P < .001). Survival for localized disease was better after surgery with adjuvant therapy (hazards ratio [HR], 0.44; 95% confidence interval [95% CI], 0.42-0.47) and surgical resection alone (HR, 0.54; 95% CI, 0.52-0.57) compared with no treatment., Conclusions: To the authors' knowledge, the current study is the largest study regarding pancreatic cancer performed to date, and the first to investigate national practice patterns for multimodality therapy utilization. Multimodality therapy utilization has increased over time and appears to have a beneficial impact on survival., ((c) 2007 American Cancer Society.)

Objective: To determine the optimal number of lymph nodes to examine for accurate staging of node-negative pancreatic adenocarcinoma after pancreaticoduodenectomy., Design, Setting, and Patients: Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program (1988-2002) were used to identify 3505 patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreas, including 1150 patients who were pathologically node negative (pN0) and 584 patients with a single positive node (pN1a). Perioperative deaths were excluded. Univariate and multivariate survival analyses were performed., Main Outcome Measure: Examination of 15 lymph nodes appears to be optimal for accurate staging of node-negative adenocarcinoma of the pancreas after pancreaticoduodenectomy., Results: The number of nodes examined ranged from 1 to 54 (median, 7 examined nodes). Univariate survival analysis demonstrated that dichotomizing the pN0 cohort on 15 or more examined lymph nodes resulted in the most statistically significant survival difference (log-rank chi(2) = 14.49). Kaplan-Meier survival curves demonstrated a median survival difference of 8 months (P < .001) in favor of the patients who had 15 or more examined nodes compared with patients with fewer than 15 examined nodes. Multivariate analysis validated that having 15 or more examined nodes was a statistically significant predictor of survival (hazard ratio, 0.63; 95% confidence interval, 0.49-0.80; P < .0001). Furthermore, a multivariate model based on the survival benefit of each additional node evaluated in the pN0 cohort demonstrated only a marginal survival benefit for analysis of more than 15 nodes. Approximately 90% of the pN1a cohort was identified with examination of 15 nodes., Conclusions: Examination of 15 lymph nodes appears to be optimal to accurately stage node-negative adenocarcinoma of the pancreas after pancreaticoduodenectomy. Furthermore, evaluation of at least 15 lymph nodes of a pancreaticoduodenectomy specimen may serve as a quality measure in the treatment of pancreatic adenocarcinoma.

Purpose: Nomograms are statistically based tools that provide the overall probability of a specific outcome. They have shown better individual discrimination than the current TNM staging system in numerous patient tumor models. The pancreatic nomogram combines individual clinicopathologic and operative data to predict disease-specific survival at 1, 2, and 3 years from initial resection. A single US institution database was used to test the validity of the pancreatic adenocarcinoma nomogram established at Memorial Sloan-Kettering Cancer Center., Patients and Methods: The nomogram was created from a prospective pancreatic adenocarcinoma database that included 555 consecutive patients between October 1983 and April 2000. The nomogram was validated by an external patient cohort from a retrospective pancreatic adenocarcinoma database at Massachusetts General Hospital that included 424 consecutive patients between January 1985 and December 2003., Results: Of the 424 patients, 375 had all variables documented. At last follow-up, 99 patients were alive, with a median follow-up time of 27 months (range, 2 to 151 months). The 1-, 2-, and 3-year disease-specific survival rates were 68% (95% CI, 63% to 72%), 39% (95% CI, 34% to 44%), and 27% (95% CI, 23% to 32%), respectively. The nomogram concordance index was 0.62 compared with 0.59 with the American Joint Committee on Cancer (AJCC) stage (P = .004). This suggests that the nomogram discriminates disease-specific survival better than the AJCC staging system., Conclusion: The pancreatic cancer nomogram provides more accurate survival predictions than the AJCC staging system when applied to an external patient cohort. The nomogram may aid in more accurately counseling patients and in better stratifying patients for clinical trials and molecular tumor analysis.

Inflammatory breast carcinoma (IBC) is characterized by florid tumor emboli within lymphovascular spaces termed lymphovascular invasion (LVI). Using a human-scid model of IBC (MARY-X), we have demonstrated using retrovirally-mediated dominant-negative E-cadherin mutant approaches (H-2K(d)-E-cad), that the tumor cell embolus (IBC spheroid) forms on the basis of an intact and overexpressed E-cadherin/alpha, beta-catenin axis which mediates tumor cell-tumor cell adhesion analogous to the embryonic blastocyst and accounts for the compactness of the embolus. The tumor cell embolus (IBC spheroid), in contrast, fails to bind the surrounding vascular endothelial cells both in vitro and in vivo because of markedly decreased sialyl-Lewis X/A carbohydrate ligand-binding epitopes on its overexpressed MUC1 which are necessary for binding endothelial cell E-selectin. This tumor cell-endothelial cell aversion further contributes to the compactness of the IBC spheroid and its passivity in metastasis dissemination. This passivity is manifested by a dramatic increase in metastatic pulmonary emboli following palpation of the primary tumor. In assessing this passivity of metastatic dissemination, we compared the effects of palpation on MARY-X with the effects of palpation on a derived dominant-negative E-cadherin mutant (H-2K(d)-E-cad), as well as other well known human tumoral xenografts exhibiting no (MCF-7, T47D), low (MDA-MB-231, MDA-MB-468) or high (C8161, M24(met)) levels of spontaneous metastasis but no LVI. Palpation of each xenograft similarly increased intratumoral pressure by 200% (10-->30 mmHg) but dramatically increased the numbers and sizes of pulmonary metastases 10-100-fold (P<0.001) only in MARY-X. The mechanism of this effect was through an immediate post-palpation release of circulating tumor emboli detected 2-3 min after palpation (P<0.01) by human cytokeratin 19 RT-PCR of extracted RNA from 300 microl of murine blood. Although circulating human tumor cell-derived growth factors (IGF-I, IGF-II, TGF-alpha and TGF-beta) and angiogenic factors (VEGF and bFGF) were detected by ELISA in murine serum of MARY-X, palpation did not further increase the circulating levels of these factors (P>0.1). Our findings support the cooperative role of E-cadherin and sialyl-Lewis X/A-deficient MUC1 in the passive dissemination of tumor emboli in IBC.

The natural history of pancreatic neuroendocrine tumors (PNET) remains poorly defined. Our objectives were to examine the clinicopathologic features of PNETs, to assess treatment trends over time, and to identify factors associated with undergoing resection. From the National Cancer Data Base (1985-2004), 9,821 patients were identified with PNETs. Clinicopathologic features and treatment trends were examined. Multivariable logistic regression was used to assess factors associated with undergoing resection. Of 9,821 patients with PNETs, 85% were nonfunctional, 7.1% were functional, and 7.9% were carcinoid tumors. Of the 3,851 (39.0%) patients who underwent pancreatectomy, 449 (11.7%) received adjuvant chemotherapy, and 254 (6.6%) received adjuvant radiation. From 1985 to 2004, utilization of pancreatectomy increased from 39.4 to 44.3% (P < 0.0001). Patients were less likely to undergo resection if they were > 55 years old, had tumors in the head of the pancreas, tumors > or = 4 cm, or had distant metastases (P < 0.0001). Patients treated at NCCN/NCI, academic, or high-volume hospitals were more likely to undergo resection. There are disparities in the utilization of pancreatectomy for PNETs. As PNETs have a better prognosis than adenocarcinoma, concerns regarding the morbidity and mortality of pancreatic surgery and neoplasms should not preclude resection. [ABSTRACT FROM AUTHOR]