Faculty Bibliography

BACKGROUND:Primary hyperparathyroidism is characterized by increased levels of serum calcium and parathyroid hormone. Recently, 2 additional mild biochemical profiles have emerged, normocalcemic and normohormonal primary hyperparathyroidism. We reviewed our surgical experience of mild biochemical profile patients and compared them with classic primary hyperparathyroidism patients. METHODS:test. A logistic regression was performed to identify significantly independent predictor variables for multigland disease. RESULTS:A total of 573 patients underwent parathyroidectomy for primary hyperparathyroidism (classic, n = 405; normohormonal, n = 96; normocalcemic, n = 72). Normocalcemic primary hyperparathyroidism was associated with multigland disease in 43 (45%, P < .001) patients as compared with the normohormonal (7, 10%) and classic (36, 9%) groups. On logistic regression, significant predictors for multigland disease were the normocalcemic subtype and positive family history. Twelve month biochemical normalization rates after operative treatment were >98% in all 3 groups. CONCLUSION:Our series shows that normocalcemic primary hyperparathyroidism is associated with a high incidence of multigland disease. Normohormonal disease is similar to classic disease patients with >90% presenting with single adenomas. Excellent rates of biochemical normalization can be obtained by operative treatment in all 3 groups.

CONTEXT/BACKGROUND:Endocrine and exocrine insufficiency after partial pancreatectomy affect quality of life, cardiovascular health, and nutritional status. However, their incidence and predictors are unknown. OBJECTIVE:To identify the incidence and predictors of new-onset diabetes and exocrine insufficiency after partial pancreatectomy. DESIGN/METHODS:We retrospectively reviewed 1165 cases of partial pancreatectomy, performed from 1998 to 2010, from a large population-based database. MAIN OUTCOME MEASURES/METHODS:Incidence of new onset diabetes and exocrine insufficiency RESULTS: Of 1165 patients undergoing partial pancreatectomy, 41.8% had preexisting diabetes. In the remaining 678 patients, at a median 3.6 months, diabetes developed in 274 (40.4%) and pancreatic insufficiency developed in 235 (34.7%) patients. Independent predictors of new-onset diabetes were higher Charlson Comorbidity Index (CCI; hazard ratio [HR] = 1.62 for CCI of 1, p = 0.02; HR = 1.95 for CCI ≥ 2, p < 0.01) and pancreatitis (HR = 1.51, p = 0.03). There was no difference in diabetes after Whipple procedure vs distal pancreatic resections, or malignant vs benign pathologic findings. Independent predictors of exocrine insufficiency were female sex (HR = 1.32, p = 0.002) and higher CCI (HR = 1.85 for CCI of 1, p < 0.01; HR = 2.05 for CCI ≥ 2, p < 0.01). Distal resection and Asian race predicted decreased exocrine insufficiency (HR = 0.35, p < 0.01; HR = 0.54, p < 0.01, respectively). CONCLUSION/CONCLUSIONS:In a large population-based database, the rates of postpancreatectomy endocrine and exocrine insufficiency were 40% and 35%, respectively. These data are critical for informing patients' and physicians' expectations.

OBJECTIVES/OBJECTIVE:Intraductal papillary mucinous neoplasms (IPMNs) are premalignant pancreatic cysts commonly found incidentally. Immunosuppression accelerates carcinogenesis.Thus, we aimed to compare IPMN progression in liver transplant (LT) recipients on chronic immunosuppression to progression among an immunocompetent population. METHODS:We retrospectively assessed adult LT recipients between 2008 and 2014 for imaging evidence of IPMN. Diagnosis of IPMN was based on history, imaging, and cyst fluid analysis. The immunocompetent control group consisted of nontransplant patients from our pancreatic cyst surveillance program with IPMN under surveillance for greater than 12 months between 1997 and 2013. Four hundred fifty-four patients underwent LT in the study period and had cross-sectional imaging. RESULTS:The prevalence of suspected IPMN was 6.6% (30 of 454). Compared with 131 controls, the transplant cohort was younger, with increased prevalence of diabetes and smoking. The prevalence of other risk factors for IPMN progression (history of pancreatitis, family history of pancreatic cancer) was similar. After an average follow-up of 31 months, most cysts increased in diameter, with a similar increase of dominant cyst (0.4 cm vs 0.5 cm; P = 0.6). Type of immunosuppression was not associated with the increased rate of cyst growth. CONCLUSIONS:Our findings suggest that LT recipients with incidental IPMN can be managed under similar guidelines as immunocompetent patients.

OBJECTIVES/OBJECTIVE:This study compares the progression of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs) to unifocal (UF) lesions. METHODS:We performed a retrospective review of demographics, risk factors, and cyst characteristics of a prospectively maintained database of 999 patients with pancreatic cysts. Patients included had IPMN under surveillance for 12 months or more. Those with high-risk stigmata were excluded. Cyst size progression and development of worrisome features were compared between MF and UF cohorts. We evaluated whether the dominant cyst in MF-IPMN had more significant growth than did the other cysts. RESULTS:Seventy-seven patients with MF-IPMN and 54 patients with UF-IPMN, with mean follow-up of 27 and 34 months, met the criteria. There were no significant differences between demographics, risk factors, or initial cyst sizes. Fifty-seven percent of MF dominant cysts and 48% of UF cysts increased in size (P = 0.31). Progression in MF was more likely in the dominant cyst (P < 0.05). There were no significant differences in the development of mural nodules or increase in cyst size to more than 3 cm. CONCLUSIONS:Demographics of both cohorts were similar, as was the overall incidence of worrisome features. Because meaningful size progression primarily occurred in the dominant cyst, our findings support surveillance based on the dominant cyst in MF disease.

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.