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An increased awareness of IgG4-related diseases has led to an escalation in the number of sites known to be involved by this fibroinflammatory disease. We report three cases of IgG4-related cholecystitis which were thought to represent biliary malignancies both clinically and radiographically. All three cases underwent surgery tailored towards presumed malignant neoplasms. Only following pathologic examination was the true nature of the disease identified. Recognition of the clinical, radiographic, and pathologic presentation of IgG4-related cholecystitis is essential for the consideration of this disease process prior to surgical management for suspected gallbladder malignancies. However, the pre-operative diagnosis remains challenging and extensive surgical intervention is often necessary given the distressing presentation of IgG4-related cholecystitis.

Background The surgical management of esophageal perforation (EP) often results in mortality and significant morbidity. Recent less invasive approaches to EP management include endoscopic luminal stenting and minimally invasive surgical therapies. We wished to establish therapeutic efficacy of minimally invasive therapies in a consecutive series of patients. Study Design An IRB-approved retrospective review of all acute EPs between 2007 and 2013 at a single institution was performed. Patient demographic, clinical outcomes data, and hospital charges were collected. Results We reviewed 76 consecutive patients with acute EP presenting to our tertiary care center. Median age was 64 ± 16 years (range 25 to 87 years), with 50 men and 26 women. Ninety percent of EPs were in the distal esophagus, with 67% of iatrogenic perforations occurring within 4 cm of the gastroesophageal junction. All patients were treated within 24 hours of initial presentation with a removable covered esophageal stent. Leak occlusion was confirmed within 48 hours of esophageal stent placement in 68 patients. Median lengths of ICU and hospital stay were 3 and 10 days, respectively (range 1 to 86 days). One-third of the patients were noted to have prolonged intubation (>7 days) and pneumonia that required a tracheostomy. One in-hospital (1.3%) mortality occurred within 30 days. Median total hospital charges for EP were $85,945. Conclusions Endoscopically placed removable esophageal stents with minimally invasive repair of the perforation and feeding access is an effective treatment method for patients with EP. This multidisciplinary method enabled us to care for severely ill patients while minimizing morbidity and mortality and avoiding open esophageal surgery.

A complete surgical excision with negative tumor margins is the single most important factor in the prediction of long-term survival for most cancer patients with solid tumors. We hypothesized that image-guided surgery using nanoparticle-enhanced photoacoustic and fluorescence imaging could significantly reduce the rate of local recurrence.A murine model of invasive mammary carcinoma was utilized. Three experimental groups were included: (1) control; (2) tumor-bearing mice injected with non-targeted nanoprobe; and (3) tumor-bearing mice injected with targeted nanoprobe. The surgeon removed the primary tumor following the guidance of photoacoustic imaging (PAI), then inspected the surgical wound and removed the suspicious tissue using intraoperative near-infrared (NIR) fluorescence imaging. The mice were followed with bioluminescence imaging weekly to quantify local recurrence.Nanoprobe-enhanced photoacoustic contrast enabled PAI to map the volumetric tumor margins up to a depth of 31 mm. The targeted nanoparticles provided significantly greater enhancement than non-targeted nanoparticles. Seven mice in the group injected with the targeted nanoprobes underwent additional resections based upon NIR fluorescence imaging. Pathological analysis confirmed residual cancer cells in the re-resected specimens in 5/7 mice. Image-guided resection resulted in a significant reduction in local recurrence; 8.7 and 33.3 % of the mice in the targeted and control groups suffered recurrence, respectively.These results suggest that photoacoustic and NIR intraoperative imaging can effectively assist a surgeon to locate primary tumors and to identify residual disease in real-time. This technology has promise to overcome current clinical challenges that result in the need for second surgical procedures.

TPS476 Background: Neoadjuvant treatment for borderline resectable pancreatic cancer (PCa) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Irinotecan liposomal injection (Nal-IRI) is FDA approved with a very tolerable safety profile in refractory metastatic PCa. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen and demonstrate safe and effective delivery in the neoadjuvant setting. Methods: This phase II, open-label, single-arm study targets patients with borderline resectable PCa without metastatic disease. Other key eligibility criteria include age ≥ 18 years, measurable disease by RECIST v1.1, adequate cardiac, renal, hepatic function, and Eastern Cooperative Oncology Group performance status of 0 to 1. Patients receive FOLFNal-IRINOX regimen as per table every two weeks for four months followed by disease reassessment. Patients who remain surgical candidates will undergo surgical resection within four to eight weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable patients to demonstrate a reduction in historical 30 day postoperative complication rate. FOLFNal-IRINOX regimen. Clinical trial information: NCT03483038. [Table: see text]

Objectives Evidence‐based guidelines for the treatment of severe acute pancreatitis have been established. This study was conducted to investigate the hypothesis that deviation from guidelines occurs frequently. Methods With institutional review board approval, the outside medical records of patients with severe pancreatitis who were transferred to the study institution during the period from July 2005 to May 2012 were reviewed. Severe pancreatitis was defined using the Atlanta Classification criteria. Records were reviewed with respect to published guidelines defining the appropriate use of imaging, antibiotics and nutritional support. Results A total of 538 patients with acute pancreatitis were identified. Of 67 patients with severe acute pancreatitis, 44 (66%) were male. The mean age of the patients was 55 years. Forty‐five of 61 (74%) patients for whom relevant data were available were imaged upon admission, but only 15 (31%) patients were imaged appropriately by computerized tomography with i.v. contrast to assess the presence of necrosis or other complications. In patients for whom relevant data were available, prophylactic antibiotics were initiated in the absence of culture data or a specific infectious target in 26 (53%) patients. Total parenteral nutrition (TPN) was administered to 38 (60%) of 63 patients for whom relevant data were available; only 10 (17%) patients received enteric feeding. No nutritional support was provided to 15 (23%) patients. Conclusions Adherence to best practice guidelines in the treatment of severe pancreatitis is poor. The consistent application of current knowledge might improve outcomes in these patients.

Perhaps the greatest barrier to adoption of laparoscopic pancreaticoduodenectomy by experienced pancreatic surgeons is the technical challenge of constructing the pancreaticojejunostomy (PJ). The authors present a less demanding PJ technique they have developed that creates an end-to-end intussuscepting anastomosis using a running monofilament suture. This method reduces technical complexity and operative time while producing acceptably comparable outcomes.

Data defining the optimal management of abdominal compartment syndrome resulting from acute pancreatitis are lacking. We investigated the outcomes of patients with acute pancreatitis who underwent surgery for treatment of abdominal compartment syndrome at a tertiary referral center. An electronic database was searched to identify patients with acute pancreatitis who underwent laparotomy between January 1, 2000, and December 31, 2009, for treatment of abdominal compartment syndrome. Twelve patients underwent decompressive laparotomy for abdominal compartment syndrome. The median interval between onset of pancreatitis and laparotomy was 4.5 days. Nine patients underwent a laparotomy within seven days of onset of pancreatitis. As a result of cardiopulmonary instability, four decompressive laparotomies were performed in the intensive care unit. In 11 patients, cardiopulmonary improvement was observed. Statistically significant improvements were seen across multiple physiologic parameters. Despite this initial improvement, six patients (50%) died from multisystem organ failure. Two patients survived without need for pancreatic débridement. Abdominal compartment syndrome is an uncommon but likely underrecognized and highly lethal complication of acute pancreatitis that should be considered in patients who become critically ill early in the course of their pancreatitis. Prompt recognition and decompressive laparotomy may rescue some of these patients and does not mandate future débridement.

Background:Laparoscopic distal pancreatectomy (LDP) reduces postoperative morbidity, hospital stay, and recovery as compared with open distal pancreatectomy. Technical limitations of laparoscopic surgery may limit patient eligibility and require conversion to open or hand-assisted surgery to maintai

Background: Targeted therapy with anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody in patients with HER2 overexpressed esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Some studies suggest that cMet overexpression provides cross talk for epidermal growth factor receptor (EGFR) and HER2 inhibition. We sought to characterize the expression profile of the EGFR family and cMet receptors in untreated, resected EGA. Methods: This retrospective analysis included all sequential patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma who underwent primary resection, without neoadjuvant therapy or HER2 inhibition, with adequate tissue, at the University of Florida from 2001 to 2011. Central blinded immunohistochemistry (IHC) was performed on tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low (0, 1+) or high (2+, 3+). Demographic and tumor characteristics were compared using Fisher exact test. Kaplan-Meier curves and univariate analysis compared survival among different receptors. Results: Total 52 patients were included in the study with median age 66 years. High expression of EGFR (73%), HER2 (40%), HER3 (75%), HER4 (35%) and cMet (69%) was detected among the study group. HER3 and HER4 co-expression was found in 18 (35%) cases. Pan expression of all four EGFR family members with cMet was noted in only 17% of cases. On univariate analysis, tumor stage and depth correlated with survival, while cMet + HER3 +/– EGFR receptor co-expression trended towards a worse survival. Conclusions: EGFR family and cMet are frequently co-expressed in treatment naive resected EGA or GEJ tumors. Although our data do not significantly show receptor status as a prognostic factor, the co-expression profiles support for further investigation to improve targeting of this signal transduction axis.

The relationship between myopenia, nutritional status, and long-term oncologic outcomes remains poorly characterized in patients with clinically resectable pancreatic cancer. We sought to reliably quantify prognostic indicators of preoperative cachexia in a manner applicable to any clinical setting.Preoperative computed tomographies were available electronically and suitable for analysis in 73 of 82 consecutive patients with pancreatic cancer undergoing pancreatoduodenectomy between November 2010 and February 2014. The psoas index was computed from the cross-sectional area of the psoas muscles normalized to vertebral body area at the third lumbar vertebra. Correlation and proportional hazards analyses were performed to identify relationships between muscularity, preoperative nutritional markers, clinicopathologic parameters, and long-term survival.The psoas index correlated strongly with preoperative hemoglobin and albumin levels (P = .001 and .014, respectively) identifying a pattern of preoperative frailty. High psoas index and the albumin and hemoglobin levels were associated with improved long-term survival (hazard ratio 0.014, P .001; hazard ratio 0.43, P .001; and hazard ratio = 0.80, P = .014); however, on multivariate analysis, the psoas index proved to be the only independent predictor of survival (hazard ratio 0.021; P = .003). Rapid decreases in the psoas index during neoadjuvant chemotherapy were associated with poor postoperative outcomes, as were decreases in the psoas index during the postoperative period.The data indicate that the psoas index, a calculation derived from a clinically mandated, preoperative computed tomography, is a statistically powerful and easily calculated predictor of survival in pancreatic cancer when compared to tumor grade and stage as well as previously validated nutritional parameters.

With a 5-year survival rate of just 8%, pancreatic cancer (PC) is projected to be the second leading cause of cancer deaths by 2030. Most PC patients are not eligible for surgery with curative intent upon diagnosis, emphasizing a need for more effective therapies. However, PC is notoriously resistant to chemoradiation regimens. As an alternative, immune modulating strategies have recently achieved success in melanoma, prompting their application to other solid tumors. For such therapeutic approaches to succeed, a state of immunologic tolerance must be reversed in the tumor microenvironment and that has been especially challenging in PC. Nonetheless, knowledge of the PC immune microenvironment has advanced considerably over the past decade, yielding new insights and perspectives to guide multimodal therapies. In this review, we catalog the historical groundwork and discuss the evolution of the cancer immunology field to its present state with a specific focus on PC. Strategies currently employing immune modulation in PC are reviewed, specifically highlighting 66 clinical trials across the United States and Europe.

Objective:To evaluate surgical performance in pancreatoduodenectomy using clinically relevant postoperative pancreatic fistula (CR-POPF) occurrence as a quality indicator.Background:Accurate assessment of surgeon and institutional performance requires (1) standardized definitions for the outcome of

Acute gastrointestinal (GI) bleeding is a common emergency condition requiring immediate medical attention and multidisciplinary team approach. We developed a management algorithm for acute GI bleeding in our hospital. Our preplanned acute GI bleeding protocol significantly facilitated patient management and improved communication between medical providers, patients, and their families. Management algorithm can greatly facilitate patient care and improve outcomes in acute GI bleeding situations. Our approach can serve as a framework for the establishment of similar quality improvement protocols in other institutions.

Mortality, length of stay (LOS), patient safety indicators (PSIs), and hospital-acquired conditions (HACs) are routinely reported by the University HealthSystem Consortium (UHC) to measure quality at academic health centers. We hypothesized that a clinical quality measurable goal assigned to individual faculty members would decrease UHC measures of mortality, LOS, PSIs, and HACs. For academic year (AY) 2010–2011, faculty members received a clinical quality goal related to mortality, LOS, PSIs, and HACs. The quality metric constituted 25 per cent of each faculty member's annual evaluation clinical score, which is tied to compensation. The outcomes were compared before and after goal assignment. Outcome data on 6212 patients from AY 2009–2010 were compared with 6094 patients from AY 2010–2011. The mortality index (0.89 vs 0.93; P = 0.73) was not markedly different. However, the LOS index decreased from 1.01 to 0.97 ( P = 0.011), and department-wide PSIs decreased significantly from 285 to 162 ( P = 0.011). Likewise, HACs decreased from 54 to 18 ( P = 0.0013). Seven (17.9%) of 39 faculty had quality grades that were average or below. Quality goals assigned to individual faculty members are associated with decreased average LOS index, PSIs, and HACs. Focused, relevant quality assignments that are tied to compensation improve patient safety and outcomes.

There has not been an appraisal of outcomes of appendectomy for more than 10 years. More reliable diagnostic techniques and minimally invasive surgery are now in widespread use, yet the impact of these advances remains unknown.A retrospective review was performed of 453 patients who underwent appendectomy for appendicitis at a single hospital from 2004 to 2009. Patient demographics, operative characteristics, procedure cost, and pathologic diagnoses were analyzed.The overall rate of complicated appendicitis was 13%, with a negative appendectomy rate of 4.9%. The average age was significantly greater for patients with complicated versus uncomplicated appendicitis (47 vs. 33 years, respectively; p0.001), and by logistic regression, age (as a continuous variable) was a significant factor for complicated appendicitis (p0.001). The hospital length of stay was 2.3 times longer for patients with complicated appendicitis (4.4 vs. 1.9 days; p0.001), and the average cost was 86% higher ($14,125 vs. $7,595; p0.001), the difference in cost being attributable mostly to pharmacy and nursing costs.Advances in diagnostic and surgical technique may be altering traditionally accepted rates of complicated appendicitis and negative appendectomy. For the first time, age is shown to be related to the rate of complicated appendicitis as a continuous variable rather than simply an extreme. Patients with complicated appendicitis still stay in the hospital longer, and there is a large cost difference as a result.

Background The role of nonacidic reflux contents on the pathophysiology of Barrett's esophagus remains poorly understood. We hypothesized that esophageal squamous epithelium differs from Barrett's columnar epithelium in response to bile salts with respect to subsequent changes in the cell surface expression of CD95 (Fas/Apo-1) and sensitivity to CD95-mediated apoptosis. Methods Immortalized esophageal squamous cells (HET-1A) and Barrett's esophagus cells (BAR-T), and esophageal adenocarcinoma cells (Flo-1) were treated with toxic and nontoxic bile salts at concentrations observed in gastroesophageal refluxate. CD95 cell-surface expression and apoptotic response to activating anti-CD95 antibody treatment was determined by FACScan analysis. Results Bile salt exposure resulted in a dose-dependent increase in CD95 cell-surface expression in HET-1A cells, but not BAR-T or Flo-1 cells. This response occurred rapidly, within a time-frame inconsistent with de novo protein synthesis and was blocked by protein kinase C (PKC) inhibition. Surprisingly, PKC inhibition in Flo-1 cells resulted in an increase in CD95 cell surface expression. Following bile salt exposure, a corresponding increase in the induction of CD95-mediated apoptosis was observed in HET-1A cells; PKC inhibition sensitized Flo-1 cells to apoptosis. Conclusions Our findings suggest that esophageal squamous cells are sensitized to CD95-mediated apoptosis following bile salt exposure. This differential response, compared with columnar epithelial cells, could exert a selection pressure that contributes to the pathophysiology of Barrett's esophagus.

Background Financial pressures drive efforts to optimize hospital resource use, but inefficiencies occur in systems as volume nears total capacity. We examined how operating room use impacts efficiency and costs of treating an urgent surgical condition. Methods A retrospective review of patients who underwent appendectomy for appendicitis at a single hospital from 2004 to 2009 was performed. Patient demographics, operative characteristics, pathologic diagnoses, hospital time intervals, and costs were analyzed. Gap time (time from case booking to surgery start) was used to measure operating room availability. Results In all, 453 patients met inclusion criteria. Longer gap times were associated with increased hospital-based costs. A gap time of greater than 2 h was associated with 39% higher costs to the hospital, which could not be accounted for by any single cost center. The patients in the 2 groups had similar medical and surgical complexity, as well as similar clinical outcomes and hospital duration of stay. Gap times were greatest during peak elective operating room activity (7 am to 11 pm ); however, the total hospital costs were not related to the time of day of the case. Conclusion A short delay in operating room availability for urgent cases is associated with significantly increased total hospital costs. Our data suggest this finding is attributable to inefficient care when the operating room volume nears total capacity.

Cancer cachexia is a debilitating condition seen frequently in patients with pancreatic ductal adenocarcinoma (PDAC). The underlying mechanisms driving cancer cachexia are not fully understood but are related, at least in part, to the immune response to the tumor both locally and systemically. We hypothesize that there are unique differences in cytokine levels in the tumor microenvironment and systemic circulation between PDAC tumors and that these varying profiles affect the degree of cancer cachexia observed. Patient demographics, operative factors, oncologic factors, and perioperative data were collected for the two patients in the patient derived xenograft (PDX) model. Human pancreatic cancer PDX were created by implanting fresh surgical pancreatic cancer tissues directly into immunodeficient mice. At PDX end point, mouse tumor, spleen and muscle tissues were collected and weighed, muscle atrophy related gene expression measured, and tumor and splenic soluble proteins were analyzed. PDX models were created from surgically resected patients who presented with different degrees of cachexia. Tumor free body weight and triceps surae weight differed significantly between the PDX models and control (P &lt, 0.05). Both PDX groups had increased atrophy related gene expression in muscle compared to control (FoxO1, Socs3, STAT3, Acvr2b, Atrogin-1, MuRF1, P &lt, 0.05). Significant differences were noted in splenic soluble protein concentrations in 14 of 15 detected proteins in tumor bearing mice when compared to controls. Eight splenic soluble proteins were significantly different between PDX groups (P &lt, 0.05). Tumor soluble proteins were significantly different between the two PDX groups in 15 of 24 detected proteins (P &lt, 0.05). PDX models preserve the cachectic heterogeneity found in patients and are associated with unique cytokine profiles in both the spleen and tumor between different PDX. These data support the use of PDX as a strategy to study soluble cachexia protein markers and also further efforts to elucidate which cytokines are most related to cachexia in order to provide potential targets for immunotherapy.

There is currently no consensus about the most effective adjuvant therapy for adenocarcinoma of the pancreas. Both gemcitabine and erlotinib have been demonstrated to improve survival in patients with metastatic disease. This study was designed to evaluate the efficacy of gemcitabine and erlotinib as adjuvant therapy, and to explore potential biomarkers associated with response. An institutional review board–approved single-center phase II trial of adjuvant biweekly fixed-dose rate gemcitabine (1500 mg/m2) and daily erlotinib (150 mg/day) for 4 months followed by maintenance erlotinib (150 mg/day) over 8 months was initiated. Primary end point was recurrence-free survival (RFS). Epidermal growth factor receptor (EGFR) expression in the resected tumors was assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The study completed planned accrual of 25 patients. Median follow-up was 18.2 (range 11.6–23.5) months. Recurrences were observed in 17 subjects (68%). Median RFS was 14.0 months (95% confidence interval [95% CI], 8.2–24.5) with 1-year and 2-year RFS of 56% (95% CI, 35–73) and 26% (95% CI, 6–52), respectively. Median overall survival was not reached. Estimated 1-year and 2-year overall survival was 84% (95% CI, 63–94) and 53% (95% CI, 22–76), respectively. Nine patients (36%) had a grade 3 event and only 1 (4%) had a grade 4 (neutropenia). Most toxicities were dermatologic, gastrointestinal, and constitutional. There were nonsignificant trends to longer RFS and lower recurrence rates while receiving therapy in subjects with fluorescence in situ hybridization-positive tumors and greater immunohistochemistry expression. Our phase II results suggest that adjuvant gemcitabine and erlotinib is a promising regimen that merits further investigation.

We read with great interest the findings from Palanivelu et al . comparing laparoscopic versus open pancreaticoduodenectomy (PD) for periampullary tumors. This study addresses a critical gap in the field.

318 Background: The collection and enumeration of circulating tumor cells (CTCs) are feasible in metastatic breast, prostate and colorectal cancers. CTCs have diagnostic, prognostic and treatment monitoring implications, but have been challenging to detect in pancreatic cancer (PCa). We have proven feasibility of CTCs in PCa. This study is a pilot to assess use of CTCs as a surrogate for imaging response. Methods: Blood samples (7-10mL) from newly diagnosed metastatic PCa were collected within 1 month of treatment initiation (T0) and at repeat scan after 2mo of treatment (T1). Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). CTC enumeration and changes were correlated with scan RECIST results at T0 and T1. The study was approved by the UF IRB. Results: A total of 16 patients had matched pair CTCs collected and analyzed (Table 1). For the entire cohort, the median CTC count at T0 was 7/mL of blood (range 2-11.5/mL) and decreased to 4.5/mL (range 2-8.5/mL) at T1 (36% reduction). CTCs were reduced to some degree in all patients with therapy. Disease control at T1 was confirmed in 13/16 (81%) with stable disease (n=11), partial (n=1) or complete (n=1) response. Progressive disease was noted in 3 patients. CTCs were reduced by 35% in radiographic stable or responders vs 24% in those with clear progressive disease. Conclusions: This study demonstrated the feasibility of microfluidic technology to reliably and consistently identify CTCs in advanced PCa. While all patients had reduced CTCs with therapy, a trend towards higher reductions were in those with radiographic stable or improved disease. Continued assessment of CTCs in PCa for treatment monitoring are warranted and are ongoing. [Table: see text]

304 Background: Circulating tumor cells (CTCs) represent real time dissemination of solid tumors. Historically, CTC enumeration has been challenging to perform successfully in pancreatic cancer (PCa). Using a previously published microfluidic device designed to increase cell capture, we analyzed CTC characteristics in a cohort of newly diagnosed patients with metastatic PCa. Methods: After provision of informed consent, blood samples (7-10mL) were collected within 1 month of treatment initiation. Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). Statistical analysis was performed using Scheffe’s method along with analysis of variance to test interactions between the clinical demographics and groups. The study was approved by the UF IRB. Results: A cohort of 27 patients had CTC determination at treatment onset with multi-agent chemotherapy for metastatic PCa. Cohort characteristics included: median age 65 (range 29-76), 63% male, 92% white, 85% with intact primary pancreatic tumor, pancreatic tumor location: head (n = 12), body (n = 5), tail (n = 6), number of sites of metastasis: 1 (n = 18), 2 (n = 7), 3 (n = 2), and median albumin 3.9 g/dl. Median CTC for the entire cohort was 7/mL of blood (range 2-12). CTCs were detected and quantified in all patients analyzed. In those with intact primary tumors, there were no significant differences in CTCs based on age (≥65), sex, albumin (≥3.5 g/dl), or number of metastatic organ sites (1, 2, or 3). However, primary tumor location in the head vs. tail was different (mean 7.7 vs. 4.3/mL; p = 0.02; CI -5.78 – [-] 0.41). Conclusions: This analysis demonstrates the feasibility of measuring CTCs in patients with metastatic PCa. CTC amount does not appear impacted by systemic tumor burden or demographic differences. However, anatomic differences in primary tumor location may be important in CTC studies. Further analysis of a larger and more diverse patient data set is planned.

504 Background: Systemic chemotherapy for pancreatic adenocarcinoma (PCa) improves survival but most targeted agents have consistently failed to demonstrate clinical benefits. Src is overexpressed in PCa and promotes an aggressive cancer phenotype. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation through inhibition of Src, Bcr-Abl, CKit and other pathways. Inhibition of Src is associated with biologic modifications favorably modifying the PCa phenotype and has synergy with restoring inherent chemosensitivity. Src inhibition can also increase oxaliplatin activity and modulate Tcell responses. The addition of D to the well-established backbone of FOLFOX represents a multifaceted line of scientific investigation. Methods: This single arm phase II trial is to determine activity and toxicity of FOLFOX + D in previously untreated metastatic PCa. Pts must have at least 1 RECIST measurable target lesion, ECOG PS 0-2, normal QTc and adequate organ function. Treatment is standard q14d cycles of mFOLFOX6 with continuous D (150mg PO daily). Tumor assessments occur q8w. Endpoints are PFS (primary), objective and biochemical response rates, clinical benefit rate, freedom from metastases, overall survival (OS), toxicity, and quality of life. Exploratory tissue, circulating tumor cell and serum analyses to identify predictors of response are planned, particularly in those with durable disease control or exceptional response. Sample size is based on a 50% improved median PFS from 4 (historical) to 6 months. Results: Enrollment is now closed on this prospective phase II study with 42 of 42 evaluable pts. Baseline demographics are in Table 1. Toxicity and outcomes continue to be assessed. Conclusions: Final toxicity data will be presented at the meeting for this novel combination treatment in advanced PCa. Clinical trial information: NCT01652976. [Table: see text]

The financial impact of laparoscopic colectomy remains poorly defined. We report the short-term costs of laparoscopic colectomy (LC) as compared with open colectomy (OC) in a high-volume tertiary care hospital, and are the first to incorporate the costs of late, colectomy-related complications in an analysis of long-term costs. A retrospective analysis of patients undergoing elective laparoscopic (n = 76) or open (n = 162) colon resection between January 2004 and December 2006 was performed. Primary endpoints were total hospital cost of the index admission and total hospital cost for any subsequent admission for treatment of a colectomy-related complication. Two-hundred thirty-eight patients met inclusion criteria. Mean total hospital cost was significantly greater for patients undergoing OC (US $17,686 per patient versus US $14,518, P = 0.0003). Mean total operative costs were equivalent (US $7,451 OC versus US $7,794 LC, P = 0.274). Average length of stay was shorter for LC (5.2 versus 6.9 days, P

The authors report the safety and efficacy of using a percutaneous minimal-access insertion technique for distal shunt catheter placement in 100 cases. From June 2007 to March 2008, they attempted 100 minimal-access insertions of distal shunt catheters in 91 patients who required ventriculoperitoneal shunting. Using the minimal-access approach, they avoided utilizing laparoscopic assistance or a mini-laparotomy in 91% of the cases. There were no bowel injuries or misplaced distal catheters. Additional outcomes in terms of operative times, cases that required conversion to open or laparoscopically assisted implantation, and infection rates are presented. They conclude that intraperitoneal shunt catheter placement can be safely and effectively accomplished using a simplified percutaneous minimal-access insertion method that does not require direct laparoscopic visualization.

Few methods exist to measure declarative (explicit) memory in children during the toddler and preschool stages of development. We report the development and psychometric properties of a new measure of declarative memory for this age group, the Color Object Association Test (COAT). In pilot testing and large scale application of the test, the COAT was demonstrated to be a reliable and a valid measure of declarative memory for healthy children ages 18-36 months, living in a disadvantaged community. The test shows a linear developmental trajectory, which allows longitudinal examination of the development of declarative memory in children.

The clinical significance of micrometastasis of colorectal cancer (CRC) to regional lymph nodes remains controversial. In this review, we analyze publications that have evaluated the clinical significance of occult lymph node metastasis in CRC. An extensive literature search identified 19 publications that evaluated the clinical significance of micrometastatic CRC by various methods, including immunohistochemistry (IHC; n = 13) and reverse transcription-polymerase chain reaction (RT-PCR, n = 6). These studies were reviewed for methodology and findings. Significant limitations in methodology were identified, including inconsistent histological definitions of micrometastatic disease, poor sampling because of an inadequate number of lymph nodes or number of sections per lymph node analyzed, lack of conformity with respect to IHC antibody or RT-PCR marker, and inadequate power because of small sample size. Micrometastatic lymph node metastasis identified by RT-PCR was consistently found to be prognostically significant, but this was not true of micrometastatic disease identified by IHC. RT-PCR analysis of lymph nodes with specific markers can help identify pN0 (pathological-negative lymph node) CRC patients at increased risk for recurrence. The identification of occult disease by IHC techniques may also ultimately prove to be associated with worse outcome, but a number of inadequately powered studies have concluded conversely.

The Mortality and Morbidity (MM) conference is a staple of surgical training programs. With reduced resident work hours, maximizing limited educational opportunities has become essential. We attempted to determine whether increasing the perceived educational value in MM conference is associated with enhanced confidence levels in the future. We analyzed which features of MM case reviews are associated with greater perceived educational value and enhanced confidence to deal with similar future clinical scenarios.Educational process variables were prospectively collected for 47 consecutive cases reviewed over a 16-week period at a single institution's surgical MM conference. General surgery residents completed self-reporting surveys rating the educational value of cases and impact on confidence in managing similar future clinical situations. Univariate regression analysis and multivariate regression analysis were calculated to study the relationship between various process variables and perceived educational and confidence values surveyed by residents.Tertiary academic medical center.General surgery residents PGY1 to PGY5.Increased perceived educational value was associated with increased confidence (p0.001). Perceived educational value was increased with more questioning of the audience, increasing explanations of cases, use of slides, increase in number of questions directed to attendings, use of radiologic images, the more junior the resident surveyed, and when teaching points were made specifically for the medical students in attendance. (p0.05) Level of confidence was increased with increased questioning to the audience, increased explanations, increased questioning of the attendings, and more junior the resident surveyed. Increased questioning of presenter did not increase perceived educational value or resident perceived confidence value.These data demonstrate that audience interaction, not directed questioning of the presenter, may improve surgical resident perceived educational value and confidence in managing problems discussed at MM. These data suggest that MM moderators can play a central role in maximizing audience interaction and improve the educational value of this important conference.

Background: The detection of circulating tumor cells (CTCs) may prove useful for screening, prognostication, and monitoring of response to therapy. However, given the large background of circulating cells, it is probably necessary to detect 1 cancer cell in >106 leukocytes. Although reverse transcription (RT)-PCR is potentially sensitive and specific enough to achieve this goal, success will require the use of appropriate mRNA markers. The goal of this study was to identify optimal marker combinations for detection of CTCs.Methods: An extensive literature and internet database survey was conducted to identify potential markers. We then used real-time quantitative RT-PCR to test for expression of selected potential markers in tissue samples from primary tumors of breast, colon, esophagus, head and neck, lung, and melanoma and normal blood samples. Markers with high expression in tumors and a median 1000-fold lower expression in normal blood were considered potentially useful for CTC detection and were tested further in an expanded sample set.Results: A total of 52 potential markers were screened, and 3–8 potentially useful markers were identified for each tumor type. The mRNAs for all but 2 markers were found in normal blood. Marker combinations were identified for each tumor type that had a minimum 1000-fold higher expression in tumors than in normal blood.Conclusions: Several mRNA markers may be useful for RT-PCR–based detection of CTCs from each of 6 cancer types. Quantification of these mRNAs is essential to distinguish normal expression in blood from that due to the presence of CTCs. Few markers provide adequate sensitivity individually, but combinations of markers may produce good sensitivity for detection of the presence of these 6 neoplasms.

Necrotizing pancreatitis continues to challenge clinicians, and few other medical subjects currently elicit as much debate. Host characteristics or underlying differences in pathophysiology that lead to pancreatic necrosis remain poorly understood. Severe pancreatitis follows a two-phase clinical course. The early first phase manifests the features of the systemic inflammatory response syndrome, and the second late phase is characterized by infectious complications. This article presents a multidisciplinary literature-based approach to the treatment of patients with necrotizing pancreatitis.

Purpose: The relationship between smoking and pancreatic cancer biology, particularly in the context of the heterogeneous microenvironment, remains incompletely defined. We hypothesized that nicotine exposure would lead to the augmentation of paracrine growth factor signaling between tumor-associated stroma (TAS) and pancreatic cancer cells, ultimately resulting in accelerated tumor growth and metastasis. Experimental Design: The effect of tobacco use on overall survival was analyzed using a prospectively maintained database of surgically resected patients with pancreatic cancer. Nicotine exposure was evaluated in vitro using primary patient–derived TAS and pancreatic cancer cells independently and in coculture. Nicotine administration was then assessed in vivo using a patient-derived pancreatic cancer xenograft model. Results: Continued smoking was associated with reduced overall survival after surgical resection. In culture, nicotine-stimulated hepatocyte growth factor (HGF) secretion in primary patient-derived TAS and nicotine stimulation was required for persistent pancreatic cancer cell c-Met activation in a coculture model. c-Met activation in this manner led to the induction of inhibitor of differentiation-1 (Id1) in pancreatic cancer cells, previously established as a mediator of growth, invasion and chemoresistance. HGF-induced Id1 expression was abrogated by both epigenetic and pharmacologic c-Met inhibition. In patient-derived pancreatic cancer xenografts, nicotine treatment augmented tumor growth and metastasis; tumor lysates from nicotine-treated mice demonstrated elevated HGF expression by qRT-PCR and phospho-Met levels by ELISA. Similarly, elevated levels of phospho-Met in surgically resected pancreatic cancer specimens correlated with reduced overall survival. Conclusions: Taken together, these data demonstrate a novel, microenvironment-dependent paracrine signaling mechanism by which nicotine exposure promotes the growth and metastasis of pancreatic cancer. Clin Cancer Res; 22(7); 1787–99. ©2015 AACR.

International Study Group of Pancreatic Fistula (ISGPF) grade C postoperative pancreatic fistulas (POPF) are the greatest contributor to major morbidity and mortality following pancreatoduodenectomy (PD); however, their infrequent occurrence has hindered deeper analysis. This study sought to develop a predictive algorithm, which could facilitate effective management of this challenging complication. Data were accrued from 4301 PDs worldwide. Demographics, postoperative management, and microbiological characteristics of grade C POPFs were evaluated. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) preoperative and intraoperative variables were compared between grade C POPFs and a 639-case sample of non-grade C POPFs. Risk factors for grade C POPF formation were identified using regression analysis. Grade C POPFs developed in 79 patients (1.8 %). Deaths (90 days) occurred in 2.0 % (N = 88) of the overall series, with 35 % (N = 25) occurring in the presence of a grade C POPF. Reoperations occurred 72.2 % of the time. The rates of single- and multi-system organ failure were 28.2 and 39.7 %, respectively. Mortality rates escalated with pulmonary, renal, and neurologic organ failure, but they were unaffected by reoperation(s). The median number of complications incurred was four (IQR: 2–5), and the median duration of hospital stay was 32 (IQR: 21–54) days. Warning signs for impending grade C POPFs most often presented on postoperative day (POD) 6. Adjuvant chemotherapy might have benefited 55.7 % of grade C POPF patients, yet it was delayed in 25.6 % and never delivered in 67.4 % of these patients. Predictive models for grade C POPF occurrence based on preoperative factors alone and preoperative and intraoperative factors yielded areas under the receiver operating characteristic curve of 0.73 and 0.84 (both P

Recent advances demonstrate a critical yet poorly understood role for the pancreatic stellate cell (PSC) in the pathogenesis of chronic pancreatitis (CP) and pancreatic cancer (PC). Progress in this area has been hampered by the availability, fidelity, and/or reliability of in vitro models of PSCs. We examined whether outgrowth cultures from human surgical specimens exhibited reproducible phenotypic and functional characteristics of PSCs. PSCs were cultured from surgical specimens of healthy pancreas, CP and PC. Growth dynamics, phenotypic characteristics, soluble mediator secretion profiles and co-culture with PC cells both in vitro and in vivo were assessed. Forty-seven primary cultures were established from 52 attempts, demonstrating universal α-smooth muscle actin and glial fibrillary acidic protein but negligible epithelial surface antigen expression. Modification of culture conditions consistently led to cytoplasmic lipid accumulation, suggesting induction of a quiescent phenotype. Secretion of growth factors, chemokines and cytokines did not significantly differ between donor pathologies, but did evolve over time in culture. Co-culture of PSCs with established PC cell lines resulted in significant changes in levels of multiple secreted mediators. Primary PSCs co-inoculated with PC cells in a xenograft model led to augmented tumor growth and metastasis. Therefore, regardless of donor pathology, outgrowth cultures produce PSCs that demonstrate consistent growth and protein secretion properties. Primary cultures from pancreatic surgical specimens, including malignancies, may represent a reliable source of human PSCs.

In breast cancer and other malignancies, involvement of regional lymph nodes is a strong prognostic indicator and greatly influences staging and clinical management.1–4 One benefit from the implementation of sentinel lymph node biopsy (SLNB) techniques is the identification of metastatic foci of cancer in 10% to 15% of patients that would have been previously staged as node-negative (pN0) by conventional methods.5,6 This improved sensitivity is attributed to both the addition of immunohistochemical staining (IHC) and to an increase in sampling volume.5,6 Many of these additional positive nodes contain only micrometastatic foci of tumor. However, the clinical significance of micrometastatic disease identified by SLNB techniques is highly controversial.7–11 Nonetheless, SLNB techniques are now widely used in breast cancer and melanoma and are being applied with increasing frequency to other tumors, including colorectal, oropharyngeal, prostate, lung, and other solid organ cancers.12–15 Another clear advantage to the SLNB technique is that in the majority of breast cancer patients, SLNB safely avoids axillary lymph node dissection (ALND) and the associated morbidity when the SLN is negative for metastatic disease.16 However, rapid, frozen-section analysis of SLN for metastasis is only 50% to 70% sensitive for the detection of metastasis compared with the permanent histologic sections and IHC of the same lymph node,17,18 and complete analysis of the SLNB specimen currently requires extensive preparation and time-consuming review.8 Even in experienced hands, 10% of SLNB specimens are later found to contain metastases.19 As a result, these patients have required a second surgical procedure to complete the ALND. This is clearly an undesirable algorithm for the patient, the healthcare provider, and the healthcare payer, and this dilemma has contributed to a new controversy; if the SLNB is positive, does a completion ALND confer a therapeutic or staging benefit to the patient? Until ongoing multicenter trials determine whether completing the ALND when the SLNB is positive for metastasis benefits the patient, it is clear that the time required to accurately evaluate SLNB specimens has significant implications.20 It must also be recognized that, even with adequate time, the accurate histologic analysis of lymph nodes for metastatic disease is challenging, and discordance in the interpretation of these materials is a well-known clinical problem. Indeed, a recent study found alarming disparity among pathologists in the analysis of SLNB specimens.21 Furthermore, protocols for SLNB specimen analysis vary widely between healthcare centers.22 Thus, current methods of lymph node analysis clearly lack standardization, are dependent in part on subjective criteria, and are subject to human error. We and others have shown that a real-time, quantitative RT-PCR (QRT-PCR) analysis of lymph nodes can be more accurate than conventional histologic analysis in predicting prognosis for solid organ malignancies,23,24 and we have previously reported our development of a rapid QRT-PCR procedure that can be completed (including RNA isolation) in less than 25 minutes.25 Importantly, a revolutionary tool for molecular-based assays called the GeneXpert (Cepheid, Sunnyvale, CA) is in the final stages of development. This instrument fully automates sample preparation, RNA isolation and purification, and QRT-PCR in a single-use, cartridge-based format that removes the major obstacles limiting routine use of molecular-based assays. Thus, we aimed to determine if a rapid, fully automated, internally controlled QRT-PCR assay performed by a prototype GeneXpert instrument could produce equivalent results to histologic techniques of SLNB analysis, including IHC. This assay could produce significant benefits to patients and healthcare providers by definitively analyzing lymph nodes using objective criteria in a time frame that allows intraoperative use, reduces patient psychologic distress, and improves standardization between healthcare centers.

IL-21 is a cytokine that can promote the anti-tumor responses of the innate and adaptive immune system. Mice treated with IL-21 reject tumor cells more efficiently, and a higher percentage of mice remain tumor-free compared with untreated controls. In this study, we demonstrate that in certain tumor models IL-21-enhanced tumor rejection is NKG2D dependent. When engagement of the NKG2D receptor was prevented, either due to the lack of ligand expression on the tumor cells or due to direct blocking with anti-NKG2D mAb treatment, the protective effects of IL-21 treatment were abrogated or substantially diminished. Specifically, IL-21 only demonstrated a therapeutic effect in mice challenged with a retinoic acid early inducible-1δ-bearing lymphoma but not in mice bearing parental RMA tumors lacking NKG2D ligands. Furthermore, treatment with a blocking anti-NKG2D mAb largely prevented the therapeutic effect of IL-21 in mice challenged with the 4T1 breast carcinoma, the 3LL lung carcinoma, and RM-1 prostate carcinoma. By contrast, IL-21 did mediate beneficial effects against both the parental DA3 mammary carcinoma and DA3 tumors transfected with H60, a NKG2D ligand. We also observed that IL-21 treatment could enhance RMA-retinoic acid early inducible-1δ tumor rejection in RAG-1−/− deficient mice, thereby demonstrating that the IL-21-induced protective effect can be mediated by the innate immune system and that, in this case, IL-21 does not require the adaptive immune response. Collectively, these findings suggest that IL-21 therapy may work optimally against tumors that can elicit a NKG2D-mediated immune response.

Purpose: This study was designed to evaluate molecular markers for the detection of micrometastasis in esophageal adenocarcinoma, define algorithms to distinguish positive from benign lymph nodes and to validate these findings in an independent tissue set and in patients with pN0 esophageal adenocarcinoma. Experimental Design: Potential markers were identified through literature and database searches. All markers were analyzed by quantitative reverse transcription (QRT)-PCR on a limited set of primary tumors and benign lymph nodes. Selected markers were further evaluated on a larger tissue set and classification algorithms were generated for individual markers and combinations. Algorithms were statistically validated internally as well as externally on an independent set of lymph nodes. Selected markers were then used to identify occult disease in lymph nodes from 34 patients with pN0 esophageal adenocarcinoma. Results: Thirty-nine markers were evaluated, six underwent further analysis and five were analyzed in the external validation study. Two markers provided perfect classification in both the screening and validation sets, although parametric bootstrap analysis estimated 2% to 3% optimism in the observed classification accuracy. Several marker combinations also gave perfect classification in the observed data sets, and estimates of optimism were lower, implying more robust classification than with individual markers alone. Five of thirty-four patients with esophageal adenocarcinoma had positive nodes by multimarker QRT-PCR analysis and disease-free survival was significantly worse in these patients (P = 0.0023). Conclusions: We have identified novel QRT-PCR markers for the detection of occult lymph node disease in patients with esophageal adenocarcinoma. The objective nature of QRT-PCR results, and the ability to detect occult metastases, make this an attractive alternative to routine pathology.

Background Decreased cell-surface expression of Fas (CD95) results in resistance to Fas-mediated apoptosis in esophageal adenocarcinoma (EA). Because p53 is known to increase transcription of Fas and also may induce trafficking of the protein to the plasma membrane, we investigated whether the loss of wild-type (wt)-p53 function accounts for our previous findings. Materials and methods Surgical specimens of Barrett’s Esophagus containing areas of dysplasia were immunostained for p53 and Fas protein expression. Three EA cell lines were transfected with a wt-p53 containing adenovirus to examine the effects of p53 overexpression. The p53 status of these EA cell lines was determined by sequence analysis. Results Regions of dysplasia where p53 protein accumulation was observed corresponded to areas of loss of Fas expression. Sequence analysis of the p53 coding sequence in three EA cell lines (Seg-1, Bic-1, and Flo-1) that retain Fas protein within the cytoplasm, demonstrated that Seg-1 contained wt-p53, but mutations were found in Flo-1 and Bic-1 cell lines. Adenoviral transduction of the cell lines with wt-p53 resulted in cell growth arrest in Seg-1 and Bic-1 and induced cell death in Flo-1, but did not result in an increase in Fas protein expression, cell-surface expression, or restoration of sensitivity to Fas-mediated apoptosis. Conclusions These data suggest that decreased cell-surface expression of Fas and resistance to Fas-mediated apoptosis may occur independently of loss of wt p53 expression.

We previously reported that within the pancreatic ductal adenocarcinoma (PDAC) microenvironment, miR-145 and miR-199a are exclusively expressed in tumor-associated stroma (TAS) cells, but these miRNAs are present in PDAC cells following co-culture with TAS cells. We hypothesized that miRNAs function as paracrine signals via exosomal exchange between TAS cells and adjacent PDAC cells. Primary cultures of human TAS and PDAC cells were employed. Membrane-bound microparticles were isolated from TAS conditioned, serum-free culture media by sequential ultracentrifugation followed by ultrafiltration. Exosomes and microvesicles were then assayed for particle size distribution using nanoparticle tracking analysis and electronic microscopy. miRNA expression levels were determined using quantitative PCR. miRNA transfection was performed with RNAiMax reagents. Cell viability was measured by Alamar Blue. Statistics were performed using Prism 6 software. Following transfection of human TAS cells with cel-miR-39, a nonhuman miRNA, we demonstrated that miRNA exchanges occurred between TAS cells and neighboring PDAC cells via a process that is not dependent upon cell-cell contact. We next confirmed the presence and enrichment of miR-145-5p in TAS-cell-derived exosomes (8-fold higher concentrations in exosomes than parental cells, p Taken together, our data suggest that stroma derived exosomes deliver miRNAs to adjacent PDAC cells and may function as tumor-suppressing paracrine signals in the case of miR-145. This finding provides a potential explanation for the observation that stroma depletion paradoxically accelerates PDAC progression in murine models. Citation Format: Song Han, Sayali Belsare, DongYu Zhang, Mark Beveridge, Carlos Rinaldi, Jose G. Trevino, Thomas D. Schmittgen, Steven J. Hughes. Exosomal delivery of stroma-derived miR-145 inhibits pancreatic cancer cell proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4322. doi:10.1158/1538-7445.AM2017-4322

TPS517 Background: Systemic chemotherapy for pancreatic adenocarcinoma improves survival and cancer related symptoms. Most targeted agents combined with gemcitabine have consistently failed to demonstrate clinical benefits. Src is overexpressed in pancreatic cancer and promotes an aggressive cancer phenotype. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation through inhibition of Src, Bcr-Abl, CKit and other pathways. Inhibition of Src is associated with biologic modifications favorably modifying the pancreatic cancer phenotype and has synergy with restoring inherent chemosensitivity. Src inhibition can also increase oxaliplatin activity and modulate Tcell responses. The addition of D to the well-established backbone of FOLFOX represents a multifaceted line of scientific investigation. Methods: This is a multicenter phase II trial to determine activity and toxicity of FOLFOX + D in previously untreated metastatic pancreatic adenocarcinoma. Eligible pts must have at least 1 measurable target lesion by RECIST, ECOG PS 0-2, normal QTc and adequate organ function. Pts received standard cycles of mFOLFOX6 repeated q14d with continuous D (150mg PO daily). Tumor assessments occur q8w. Endpoints included progression-free survival (primary; PFS), objective and biochemical response rates, clinical benefit rate, freedom from metastases, overall survival (OS), toxicity, and quality of life. Exploratory tissue, circulating tumor cell and serum analyses to identify predictors of response are planned, particularly in those demonstrating durable disease control or exceptional response. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months. NCT01652976. Results: Enrollment continues on this prospective phase II study with 38 of 42 evaluable patients. There are no unexpected toxicities noted thus far. Clinical trial information: NCT01652976. [Table: see text]

AIM To review surgical outcomes for patients undergoing pancreatectomy after proton therapy with concomitant capecitabine for initially unresectable pancreatic adenocarcinoma. METHODS From April 2010 to September 2013, 15 patients with initially unresectable pancreatic cancer were treated with proton therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients received 59.40 Gy (RBE) to the gross disease and 1 patient received 50.40 Gy (RBE) to high-risk nodal targets. There were no treatment interruptions and no chemotherapy dose reductions. Six patients achieved a radiographic response sufficient to justify surgical exploration, of whom 1 was identified as having intraperitoneal dissemination at the time of surgery and the planned pancreatectomy was aborted. Five patients underwent resection. Procedures included: Laparoscopic standard pancreaticoduodenectomy (n = 3), open pyloris-sparing pancreaticoduodenectomy (n = 1), and open distal pancreatectomy with irreversible electroporation (IRE) of a pancreatic head mass (n = 1). RESULTS The median patient age was 60 years (range, 51-67). The median duration of surgery was 419 min (range, 290-484), with a median estimated blood loss of 850 cm3 (range, 300-2000), median ICU stay of 1 d (range, 0-2), and median hospital stay of 10 d (range, 5-14). Three patients were re-admitted to a hospital within 30 d after discharge for wound infection (n = 1), delayed gastric emptying (n = 1), and ischemic gastritis (n = 1). Two patients underwent R0 resections and demonstrated minimal residual disease in the final pathology specimen. One patient, after negative pancreatic head biopsies, underwent IRE followed by distal pancreatectomy with no tumor seen in the specimen. Two patients underwent R2 resections. Only 1 patient demonstrated ultimate local progression at the primary site. Median survival for the 5 resected patients was 24 mo (range, 10-30). CONCLUSION Pancreatic resection for patients with initially unresectable cancers is feasible after high-dose [59.4 Gy (RBE)] proton radiotherapy with a high rate of local control, acceptable surgical morbidity, and a median survival of 24 mo.