Faculty Bibliography

CONTEXT/BACKGROUND:Molecular analysis of pancreatic cyst fluid obtained by EUS-FNA may increase diagnostic accuracy. We evaluated the utility of cyst-fluid molecular analysis, including mutational analysis of K-ras, loss of heterozygosity (LOH) at tumor suppressor loci, and DNA content in the diagnoses and surveillance of pancreatic cysts. METHODS:We retrospectively reviewed the Columbia University Pancreas Center database for all patients who underwent EUS/FNA for the evaluation of pancreatic cystic lesions followed by surgical resection or surveillance between 2006-2011. We compared accuracy of molecular analysis for mucinous etiology and malignant behavior to cyst-fluid CEA and cytology and surgical pathology in resected tumors. We recorded changes in molecular features over serial encounters in tumors under surveillance. Differences across groups were compared using Student's t or the Mann-Whitney U test for continuous variables and the Fisher's exact test for binary variables. RESULTS:Among 40 resected cysts with intermediate-risk features, molecular characteristics increased the diagnostic yield of EUS-FNA (n=11) but identified mucinous cysts less accurately than cyst fluid CEA (P=0.21 vs. 0.03). The combination of a K-ras mutation and ≥2 loss of heterozygosity was highly specific (96%) but insensitive for malignant behavior (50%). Initial data on surveillance (n=16) suggests that molecular changes occur frequently, and do not correlate with changes in cyst size, morphology, or CEA. CONCLUSIONS:In intermediate-risk pancreatic cysts, the presence of a K-ras mutation or loss of heterozygosity suggests mucinous etiology. K-ras mutation plus ≥2 loss of heterozygosity is strongly associated with malignancy, but sensitivity is low; while the presence of these mutations may be helpful, negative findings are uninformative. Molecular changes are observed in the course of cyst surveillance, which may be significant in long-term follow-up.

BACKGROUND: This prospective study was undertaken to assess toxicity, resectability, and survival in pancreatic adenocarcinoma patients presenting with locally advanced, unresectable disease treated with neoadjuvant gemcitabine, docetaxel, and capecitabine (GTX) and gemcitabine and capecitabine (GX)/radiation therapy (RT). METHODS: All patients presenting to the Pancreas Center were evaluated for eligibility. Forty-five patients (mean age, 64 years; range, 44-83 years)-34 patients deemed unresectable because of arterial involvement and 11 patients deemed unresectable because of extensive venous involvement-were treated with 6 cycles of GTX. Those with arterial involvement were treated with GX/RT after chemotherapy. RESULTS: The GTX and GX/RT treatments were tolerated with the expected drug-related toxicities. There were no bowel perforations, cases of pancreatitis, or delayed strictures. Among those with arterial involvement, 29 underwent subsequent resection, with 20 (69%) achieving R0 resections. All 11 patients with venous-only involvement underwent resection, with 8 achieving R0 resections and 3 achieving complete pathologic responses. For the arterial arm, the 1-year survival rate was 71% (24 of 34 patients), and the median survival was 29 months (95% confidence interval, 21-38 months). Thirteen patients (38%) have not relapsed (range, 5-49+ months). For the venous arm, the median survival has not been reached at more than 42 months. Six patients (55%) in the venous arm did not experience recurrence (range, 6.2-42+ months). CONCLUSIONS: GTX plus GX/RT is an effective neoadjuvant regimen that can be safely administered to patients up to at least the age of 83 years. It is associated with a high response rate, a high rate of R0 resections, and prolonged overall survival. Cancer 2015;121:673-680. (c) 2014 American Cancer Society.

OBJECTIVE:The study aim was to quantify the burden of complications of pancreatoduodenectomy (PD). BACKGROUND:The Postoperative Morbidity Index (PMI) is a quantitative measure of the average burden of complications of a procedure. It is based on highly validated systems--ACS-NSQIP and the Modified Accordion Severity Grading System. METHODS:Nine centers contributed ACS-NSQIP complication data for 1589 patients undergoing PD from 2005 to 2011. Each complication was assigned a severity weight ranging from 0.11 for the least severe complication to 1.00 for postoperative death, and PMI was derived. Contribution to total burden by each complication grade was used to generate a severity profile ("spectrogram") for PD. Associations with PMI were determined by regression analysis. RESULTS:ACS-NSQIP complications occurred in 528 cases (33.2%). The non-risk-adjusted PMI was 0.115 (SD = 0.023) for all centers and 0.113 (SD = 0.005) for the 7 centers that contributed at least 100 cases. Grade 2 complications were predominant in frequency, and the most common complication was postoperative bleeding/transfusion. Frequency and burden of complications differed markedly. For instance, severe complications (grades 4/5/6) accounted for only about 20% of complications but for more than 40% of the burden of complications. Organ space infection had the highest burden of any complication. The average burden in cases in which a complication actually occurred was 0.346. CONCLUSIONS:This study develops a quantitative non-risk-adjusted benchmark for postoperative morbidity of PD. The method quantifies the burden of types and grades of postoperative complications and should prove useful in identifying areas that require quality improvement.

BACKGROUND:While contemporary studies demonstrate decreasing complication rates following total pancreatectomy (TP), none have quantified the impact of post-TP complications. The Postoperative Morbidity Index (PMI)-a quantitative measure of postoperative morbidity-combines ACS-NSQIP complication data with severity weighting derived from Modified Accordion Grading System. We establish the PMI for TP in a multi-institutional cohort. METHODS:Nine institutions contributed ACS-NSQIP data for 64 TPs (2005-2011). Each complication was assigned an Accordion severity weight ranging from 0.110 (grade 1/mild) to 1.00 (grade 6/death). PMI equals the sum of complication severity weights ("Total Burden") divided by total number of patients. RESULTS:Overall, 29 patients (45.3 %) suffered 55 ACS-NSQIP complications; 15 (23.4 %) had >1 complication. Thirteen patients (20.3 %) were readmitted and one death (1.6 %) occurred within 30 days. Non-risk adjusted PMI was 0.151, while PMI for complication-bearing cases rose to 0.333. Bleeding/Transfusion and Sepsis were the most common complications. Discordance between frequency and burden of complications was observed. While grades 4-6 comprised only 18.5 % of complications, they contributed 37.1 % to the series' total burden. CONCLUSION/CONCLUSIONS:This multi-institutional series is the first to quantify the complication burden following TP using the rigor of ACS-NSQIP. A PMI of 0.151 indicates that, collectively, patients undergoing TP have an average burden of complications in the mild to moderate severity range, although complication-bearing patients have a considerable reduction in health utility.

BACKGROUND:Accurate assessment of complications is critical in analysing surgical outcomes. The post-operative morbidity index (PMI), derived from the Modified Accordion Severity Grading System and American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), is a quantitative measure of post-operative morbidity. This study utilizes PMI to establish the complication burden for a distal pancreatectomy (DP). METHODS:From 2005-2011, nine centres contributed ACS-NSQIP complication data for 655 DPs. Each complication was assigned an Accordion severity weight ranging from 0.11 for grade 1 to 1.00 for grade 6 (death). The PMI is the sum of complication severity weights divided by the total number of patients. RESULTS:ACS-NSQIP complications occurred in 177 patients (27.0%). The non risk-adjusted PMI for DP is 0.087. Bleeding/Transfusion and Organ Space Infection were the most common complications. Frequency and burden differed across Accordion grades. While grade 4-6 complications represented only 15.4% of complication occurrences, they accounted for 30.4% of the burden. Subgroup analysis demonstrates that the PMI did not vary based on laparoscopic versus open approach or the performance of a splenectomy. DISCUSSION/CONCLUSIONS:This study uses two validated systems to quantitatively establish the morbidity of a DP. The PMI allows estimation of both the frequency and severity of complications and thus provides a more comprehensive assessment of risk.

BACKGROUND:Positron emission tomography (PET) as an adjunct to conventional imaging in the staging of pancreatic adenocarcinoma is controversial. Herein, we assess the utility of PET in identifying metastatic disease and evaluate the prognostic potential of standard uptake value (SUV). METHODS:Imaging and follow-up data for patients diagnosed with pancreatic adenocarcinoma were reviewed retrospectively. Resectability was assessed based on established criteria, and sensitivity, specificity, and accuracy of PET were compared to those of conventional imaging modalities. RESULTS:For 123 patients evaluated 2005-2011, PET and CT/MRI were concordant in 108 (88 %) cases; however, PET identified occult metastatic lesions in seven (5.6 %). False-positive PETs delayed surgery for three (8.3 %) patients. In a cohort free of metastatic disease in 78.9 % of cases, the sensitivity and specificity of PET for metastases were 89.3 and 85.1 %, respectively, compared with 62.5 and 93.5 % for CT and 61.5 and 100.0 % for MRI. Positive predictive value and negative predictive value of PET were 64.1 and 96.4 %, respectively, compared with 75.0 and 88.9 % for CT and 100.0 and 91.9 % for MRI. Average difference in maximum SUV of resectable and unresectable lesions was not statistically significant (5.65 vs. 6.5, p = 0.224) nor was maximum SUV a statistically significant predictor of survival (p = 0.18). CONCLUSION/CONCLUSIONS:PET is more sensitive in identifying metastatic lesions than CT or MRI; however, it has a lower specificity, lower positive predictive value, and in some cases, can delay definitive surgical management. Therefore, PET has limited utility as an adjunctive modality in staging of pancreatic adenocarcinoma.