Background As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy (LDP) affords improved perioperative outcomes. The role of LDP for patients with pancreatic ductal ...adenocarcinoma (PDAC) is not defined. Study Design Records from patients undergoing distal pancreatectomy (DP) for PDAC from 2000 to 2008 from 9 academic medical centers were reviewed. Short-term (node harvest and margin status) and long-term (survival) cancer outcomes were assessed. A 3:1 matched analysis was performed for ODP and LDP cases using age, American Society of Anesthesiologists (ASA) class, and tumor size. Results There were 212 patients who underwent DP for PDAC; 23 (11%) of these were approached laparoscopically. For all 212 patients, 56 (26%) had positive margins. The mean number of nodes (± SD) examined was 12.6 ±8.4 and 114 patients (54%) had at least 1 positive node. Median overall survival was 16 months. In the matched analysis there were no significant differences in positive margin rates, number of nodes examined, number of patients with at least 1 positive node, or overall survival. Logistic regression for all 212 patients demonstrated that advanced age, larger tumors, positive margins, and node positive disease were independently associated with worse survival; however, method of resection (ODP vs. LDP) was not. Hospital stay was 2 days shorter in the matched comparison, which approached significance (LDP, 7.4 days vs. ODP, 9.4 days, p = 0.06). Conclusions LDP provides similar short- and long-term oncologic outcomes as compared with OD, with potentially shorter hospital stay. These results suggest that LDP is an acceptable approach for resection of PDAC of the left pancreas in selected patients.
Background Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy. There have been no large prospective randomized trials evaluating PF rates comparing ...invagination versus duct to mucosa pancreaticojejunostomy. We tested the hypothesis that a duct to mucosa pancreaticojejunostomy would reduce the PF rate. Study Design Between August 2006 and May 2008, 197 patients at two institutions underwent pancreaticoduodenectomy by a total of 8 experienced pancreatic surgeons as part of this prospective randomized trial (clinical trial no. NCT00359320 ). All patients were stratified by pancreatic texture and randomized to either an invagination or a duct to mucosa pancreaticojejunal anastomosis. Recorded variables included pancreatic duct diameter, operative time, blood loss, complications, and pathology. Primary end point was PF rate, as defined by the International Study Group on Pancreatic Fistula. Secondary end points included PF grade, postoperative length of hospital stay, other morbidities, and mortality. Results Rate of PF for the entire cohort was 17.8%. There were 23 fistulas (24%) in the duct to mucosa cohort and 12 fistulas (12%) in the invagination cohort (p < 0.05). The greatest risk factor for a PF was pancreas texture: PF developed in only 8 patients (8%) with hard glands, and in 27 patients (27%) with a soft gland. There were two perioperative deaths (both in the duct to mucosa group), with the proximate causes of death being PF, followed by bleeding and sepsis. Conclusions This dual-institution prospective randomized trial reveals considerably fewer fistulas with invagination compared with duct to mucosa pancreaticojejunostomy after pancreaticoduodenectomy. Results confirm increased PF rates in soft as compared with hard glands. Additional studies are needed to define the optimal technique of pancreatic reconstruction after pancreaticoduodenectomy.
Abstract Background Accurate differentiation of pancreatic cystic lesions is important for pancreatic cancer early detection and prevention as well as avoidance of unnecessary surgical intervention. ...Serous cystic neoplasms (SCN) have no malignant potential, but may mimic premalignant mucinous cystic lesions: mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN). We recently identified vascular endothelial growth factor (VEGF)-A as a novel pancreatic fluid biomarker for SCN. We hypothesize that combining cyst fluid carcinoembryonic antigen (CEA) with VEGF-A will improve the diagnostic accuracy of VEGF-A. Methods Pancreatic cyst/duct fluid was collected from consenting patients undergoing surgical cyst resection with corresponding pathologic diagnoses. Pancreatic fluid VEGF-A and CEA levels were detected by ELISA. Results One hundred forty-nine patients with pancreatic cystic lesions met inclusion criteria. Pathologic diagnoses included pseudocyst (n=14), SCN (n=26), MCN (n=40), low/moderate grade IPMN (n=34), high grade IPMN (n=20), invasive IPMN (n=10) and solid pseudopapillary neoplasm (n=5). VEGF-A was significantly elevated in SCN cyst fluid compared to all other diagnoses (p<0.001). With a threshold of >5,000 pg/ml, VEGF-A alone has 100% sensitivity and 83.7% specificity to distinguish SCN from other cystic lesions. With a threshold of ≤10ng/ml, CEA alone identifies SCN with 95.5% sensitivity and 81.5% specificity. Sensitivity and specificity of the VEGF-A/CEA combination are 95.5% and 100% respectively. The c-statistic increased from 0.98 to 0.99 when CEA was added to VEGF-A alone in the ROC analysis. Conclusions Although VEGF-A alone is a highly accurate test for SCN, the combination of VEGF-A with CEA approaches the gold-standard of pathologic diagnosis, thus importantly avoiding false positives. Patients with a positive test indicating benign SCN can be spared a high risk surgical pancreatic resection.
Background Mucinous pancreatic cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) have the potential to progress to invasive pancreatic adenocarcinoma, presenting an ...opportunity for early detection, prevention, and cure. Serous cystic neoplasms (SCN) have no malignant potential, but can mimic mucinous pancreatic cysts on imaging. Therefore, identification of biomarkers that can distinguish between cystic lesions is critically important. We hypothesize that vascular endothelial growth factor (VEGF)-A levels in pancreatic fluid correlate with pathologic diagnosis. Study Design Pancreatic cyst/duct fluid samples were prospectively collected from patients undergoing pancreatic resection and correlated with surgical pathology. VEGF levels were detected by ELISA. VEGF-A and VEGF receptor 2 expression in pancreatic tissue was localized by immunohistochemistry. Genetic alterations of the von Hippel-Lindau gene were determined by targeted next-generation sequencing. Results Eighty-seven patients met inclusion criteria for enrollment. Final pathologic diagnoses included pseudocyst (n = 9), SCN (n = 17), mucinous cystic neoplasm (n = 24), low/moderate grade intraductal papillary mucinous neoplasm (n = 16), high-grade/invasive intraductal papillary mucinous neoplasm (n = 10), and pancreatic ductal adenocarcinoma (n = 11). VEGF-A was significantly upregulated in SCN cyst fluid compared with all other diagnoses (p < 0.0001). With a cut-off of 8,500 pg/mL, VEGF-A has 100% sensitivity and 97% specificity as an SCN biomarker. VEGF-A and VEGF receptor 2 are overexpressed in SCN cyst tissue. VEGF-C was also significantly elevated in SCN cyst fluid (p < 0.0001). With a cut-off set at 200 pg/mL, VEGF-C identifies SCN with 100% sensitivity and 90% specificity. The presence of a von Hippel-Lindau mutation in SCN cyst tissue correlates with elevated cyst fluid VEGF levels. Conclusions This is the first report of a cyst fluid protein biomarker that can positively identify SCN. The ability to distinguish SCN from premalignant/malignant pancreatic cysts can spare the cost and risk of surveillance and surgical intervention in select patients.
Background Survival after resection for invasive intraductal papillary mucinous neoplasm (inv-IPMN) is superior to pancreatic ductal adenocarcinoma (PDAC). This difference may be explained by earlier ...presentation of inv-IPMN. We hypothesized that inv-IPMN has survival comparable with PDAC after resection when matched by stage. Study Design From 1999 to 2009, 113 patients underwent resection for inv-IPMN at 2 large academic institutions. These data were compared with 845 patients during the same period undergoing resection for PDAC. Demographics, pathology, and overall survival (OS) were compared according to current American Joint Committee on Cancer stage. Results Mean age with inv-IPMN and PDAC was 68 and 65 years, respectively. Follow-up was 33 and 24 months for inv-IPMN and PDAC, respectively. Median OS was 32 months for inv-IPMN and 17 months in PDAC (p < 0.001). Median OS in lymph node−negative inv-IPMN was 41 months and 24 months in PDAC (p = 0.003), with the greatest absolute difference in stage Ia patients with OS of 80 and 50 months in inv-IPMN and PDAC, respectively (p = 0.03). In node-positive patients, OS was 20 months in inv-IPMN and 15 months in PDAC (p = 0.06). Of inv-IPMN, 24% was colloid versus 75% of tubular subtype; 37(85%) of node-positive inv-IPMN were tubular subtype. Median OS was 23 and 127 months for tubular and colloid subtypes, respectively (p < 0.001). Conclusions When matched by stage, inv-IPMN has superior survival after resection compared with PDAC. This disparity is greatest in node-negative and least in node-positive disease. These findings suggest the behaviors of inv-IPMN and PDAC, although different, converge with advancing American Joint Committee on Cancer stage because of a greater proportion of tubular subtype.
Background Splenic preserving distal pancreatectomy (SPDP) can be accomplished with splenic artery and vein preservation or ligation. However, no data are available on the relative merits of these ...techniques. The aim of this analysis was to compare the outcomes of splenic preserving distal pancreatectomy with and without splenic vessel preservation. Study Design From 2002 through 2009, 434 patients underwent distal pancreatectomy and 86 (20%) had splenic preservation. Vessel preservation (VP) was accomplished in 45 and ligation (VL) was performed in 41. These patients were similar with respect to age, American Society of Anesthesiologists class, pathology, surgeons, and minimally invasive approach (79%). For comparison, a matched group of 86 patients undergoing distal pancreatectomy with splenectomy (DP+S) was analyzed. Results The VP-SPDP procedure was associated with less blood loss than VL-SPDP or DP+S (224 vs 508 vs 646 mL, respectively; p < 0.05). The VP-SPDP procedure also resulted in fewer grade B or C pancreatic fistulas (2% vs 12% vs 14%; p = NS) and splenic infarctions (5% vs 39%; p < 0.01), less overall morbidity (18% vs 39% vs 38%, respectively; p < 0.05) and need for drainage procedure (2% vs 15% vs 16%; p < 0.05), and shorter post-operative length of stay (4.5 vs 6.2 vs 6.6 days; p < 0.05). Conclusions This analysis suggests that outcomes are (1) best for VP-SPDP and (2) VL-SPDP provides no short-term advantage over distal pancreatectomy with splenectomy. We conclude that splenic VP is preferred when SPDP is performed.
Background The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with ...resected pancreatic cancer in a large, multiinstitutional cohort of patients. Study Design Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. Results There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n = 374) and those receiving adjuvant CRT (n = 299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p = 0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p = 0.034). Conclusions This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival.
Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a propensity for early metastasis that is often encountered unexpectedly at operation. Our objective was to examine ...the effect of the time interval between preoperative imaging and attempted resection and the venue in which imaging was performed on the frequency of unanticipated metastasis (UM) encountered at operation. We hypothesize that imaging obtained locally at our hospital and within 4 weeks of operation will result in a lesser frequency of UM encountered at operation. Methods Between January 2004 and December 2009, records of patients undergoing planned pancreatic resection for PDAC at a high volume pancreatic surgery center were compiled. Exclusion criteria included neoadjuvant therapy, prior pancreatic resection, or evidence of metastasis on imaging. Review and analysis of clinical, radiographic, operative, and pathologic data were undertaken. Frequency of UM and outcome of resection was compared with the interval between most recent cross-sectional imaging (dual-phase contrast-enhanced CT or MRI) and operation defined as imaging-to-operation interval (IOI). Results Four-hundred eighty-seven patients met eligibility requirements for the study: 431 (88%) proximal and 56 (12%) distal PDAC. 202 (41%) patients had their most recent imaging performed at an outside institution, and no difference in the rates of UM was observed whether imaging was conducted at our institution or at an outside institution ( P > .05). Of 329 with complete imaging information for analysis, UM were discovered in 60 (18%): 52 (18%) of 293 proximal PDAC and 8 (22%) of 36 distal PDAC. In proximal PDAC, there was a linear relationship in the frequency of UM as a function of the weekly IOI ( R2 = .99; P = .006). For distal PDAC, no significant difference in the frequency of UM as a function of IOI was observed. Conclusion For proximally located PDAC, the frequency of UM increases with greater imaging-to-operation interval. Performing imaging at a high volume, pancreatic surgery center compared with elsewhere was not associated with a decrease in the rate of UM. Obtaining timely diagnostic imaging for proximal PDAC may improve the accuracy of preoperative staging, and thereby reduce the number of operations not producing oncologic benefit.
Background Obesity is an established risk factor for pancreatic adenocarcinoma. No study has examined specifically the influence of obesity on malignant risk in patients with intraductal papillary ...mucinous neoplasm (IPMN), a group at substantial risk of pancreatic adenocarcinoma. We hypothesize that obesity is associated with a greater frequency of malignancy in IPMN. Methods Data on patients undergoing resection for IPMN between 1992 and 2012 at a high-volume university institution were collected prospectively. Clinicopathologic and demographic parameters were reviewed. Patients were classified according to World Health Organization categories of body mass index (BMI). Malignancy was defined as high-grade dysplastic or invasive IPMN. Results We collected data on 357 patients who underwent resection for IPMN. Of these, 274 had complete data for calculation of preoperative BMI and 31% had malignant IPMN. Of 254 patients with a BMI of <35 kg/m2 , 30% had malignant IPMN versus 50% in patients with BMI of ≥35 ( P = .08). In branch-duct IPMN, patients with a BMI of <35 had 12% of malignant IPMN compared with 46% in severely obese patients ( P = .01). Alternatively, in main-duct IPMN, no difference was found in the malignancy rate (48% vs 56%; P = .74). Conclusion These findings suggest that obesity is associated with an increased frequency of malignancy in branch-duct IPMN. Obesity is a potentially modifiable risk factor that may influence oncologic risk stratification, patient counseling, and surveillance strategy.
Introduction Pancreatitis is associated with intraductal papillary mucinous neoplasm (IPMN). This association is in part due to inflammation from pancreatic ductal obstruction. Although the ...correlation between pancreatitis and the malignant potential of IPMN is unclear, the 2012 International Consensus Guidelines (ICG) consider pancreatitis a “worrisome feature.” We hypothesized that serum pancreatic enzymes, markers of inflammation, are a better predictor of malignancy than pancreatitis in patients with IPMN. Methods Between 1992 and 2012, 364 patients underwent resection for IPMN at a single university hospital. In the past decade, serum amylase and lipase were collected prospectively as an inflammatory marker in 203 patients with IPMN at initial surveillance and “cyst clinic” visits. The latest serum pancreatic enzyme values within 3 months preoperatively were studied. Pancreatitis was defined according to the 2012 revision of the Atlanta Consensus. Results Of the 203 eligible patients, there were 76 with pancreatitis. Pancreatitis was not associated with an increased rate of malignancy ( P = .51) or invasiveness ( P = .08). Serum pancreatic enzymes categorically outside of normal range (high or low) were also not associated with malignancy or invasiveness. In contrast, as a continuous variable, the higher the serum pancreatic enzymes were, the greater the rate of invasive IPMN. Of the 127 remaining patients without pancreatitis, serum pancreatic enzymes outside of normal range (low and high) were each associated with a greater rate of malignancy ( P < .0001 and P = .0009, respectively). Serum pancreatic enzyme levels above normal range (high) were associated with a greater rate of invasiveness ( P = .02). Conclusion In patients with IPMN without a history of pancreatitis, serum pancreatic enzymes outside of the normal range are associated with a greater risk of malignancy. In patients with a history of pancreatitis, there is a positive correlation between the levels of serum pancreatic enzymes and the presence of invasive IPMN. These data suggest serum pancreatic enzymes may be useful markers in stratification of pancreatic cancer risk in patients with IPMN.
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