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Background: Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients., Experimental Design: A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies., Results: CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76-0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17-4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01-1.88, p = 0.040)., Conclusions: CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

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.

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: With increasing frequency, studies using cancer registries have evaluated the treatment effect of adjuvant radiation; however, these analyses generally do not include chemotherapy treatment data. Our objective is to evaluate the potential impact the absence of adjuvant chemotherapy data has on the estimated survival benefit attributed to adjuvant radiation therapy., Methods: Using the National Cancer Data Base, patients were identified who underwent surgery for cancers that often require radiation therapy: breast, esophageal, gastric, pancreatic, and rectal cancer. Cox proportional hazards modeling with and without chemotherapy as a predictor variable was used to assess the impact of radiation therapy on 5-year survival., Results: From 1998 to 1999, 295,206 patients underwent surgical resection for one of five cancers. Chemotherapy administration ranged from 27.5% for gastric to 56.1% for rectal cancer. For cancers where chemotherapy affected survival, the impact of radiation therapy was overestimated in the multivariate model when chemotherapy was not included. For example, radiation treatment for rectal cancer was associated with a 31% decrease in the risk of death in the model that did not control for chemotherapy; however, the addition of chemotherapy to the model resulted in only a 14% decrease in the risk of death associated with receiving radiation therapy., Conclusions: For selected tumor sites, the administration of chemotherapy is not evenly distributed among patients receiving and not receiving radiation. Survival analyses that do not include chemotherapy administration overestimate the beneficial impact of radiation on survival. Evaluating the effect of radiation on survival retrospectively without adjusting for chemotherapy administration should be done cautiously.