Faculty Bibliography

BACKGROUND:The diagnosis of serous cystadenoma (SCA), a rare benign pancreatic neoplasm, can alter the management of patients with pancreatic masses. Although characteristic imaging findings and fluid chemical analysis have been described, SCAs are not always recognized preoperatively. Furthermore, scant cellular yield on fine-needle aspiration (FNA) often leads to a nondiagnostic or nonspecific benign diagnosis. α-Inhibin (AI), a sensitive marker for SCA, is infrequently required for diagnosis in surgical specimens due to their characteristic histologic appearance. The objective of the current study was to determine whether AI staining can improve SCA diagnosis on FNA specimens. METHODS:Fifteen confirmed cases of SCA with prior FNA specimens were selected for this study. FNAs were evaluated for cellularity, cellular arrangement, and cytomorphology. Resection specimens were reviewed. RESULTS:Of the 15 FNA cases, approximately 75% demonstrated scant cellularity (11 of 15 cases). On smears, the cells were arranged as flat sheets, corresponding to strips of cells on cell block sections. The cells were small and round to cuboidal, with clear cytoplasm; occasional plasmacytoid cells and oncocytic cells were identified. Flattened cells, corresponding to attenuated epithelial cells lining macrocysts on the resections, were also noted. Stromal fragments were present in 5 FNAs and correlated with the hyalinized stroma in the resection specimens. AI immunostaining was positive in 88% of cases (7 of 8 of cases), thereby supporting the diagnosis of SCA. CONCLUSIONS:The results of the current study indicate that low cellularity and bland cytology are inherent to SCAs. Performing cell blocks and AI staining on FNA specimens is useful for establishing the diagnosis of SCA. An immunohistochemical panel including AI, chromogranin, and synaptophysin may enhance the diagnostic accuracy of pancreatic FNA specimens.

BACKGROUND:Pancreatic surgery with vascular reconstruction is increasingly performed to offer the benefits of surgical resection to patients with locally advanced disease. The short- and long-term patency rates and the clinical significance of thrombosis of such reconstructions are unknown. METHODS:We reviewed pancreatectomies requiring venous reconstruction from 1994 to 2011. We sought to identify predictors of acute (within 30 days) and late thrombosis. We compared survival of patients with thrombosis to patients with patent reconstructions. RESULTS:Of 203 pancreatectomies requiring venous reconstruction, acute thrombosis occurred in nine (4.4 %) cases and was associated with increased perioperative mortality (22.2 versus 4.6 %, p = 0.023). Even when nonfatal, acute thrombosis was associated with decreased median survival (7.1 versus 15.9 months, p = 0.011) and increased hazard of death (hazard ratio 8.6, confidence interval 3.7-19.9, p < 0.001). A late loss of patency was seen in 31.2 % of cases at a median of 9.5 months. Later loss of patency was not associated with decreased median survival or increased hazard of death. CONCLUSIONS:Acute thrombosis of the portal venous reconstructions after pancreatectomy is associated with increased perioperative mortality and, even when nonfatal, is associated with decreased survival. Late loss of patency occurs in one-third of patients but does not affect survival.

PURPOSE/OBJECTIVE:Previously, we reported PIK3CA gene mutations in high-grade intraductal papillary mucinous neoplasms (IPMN). However, the contribution of phosphatidylinositol-3 kinase pathway (PI3K) dysregulation to pancreatic carcinogenesis is not fully understood and its prognostic value unknown. We investigated the dysregulation of the PI3K signaling pathway in IPMN and its clinical implication. EXPERIMENTAL DESIGN/METHODS:Thirty-six IPMN specimens were examined by novel mutant-enriched sequencing methods for hot-spot mutations in the PIK3CA and AKT1 genes. PIK3CA and AKT1 gene amplifications and loss of heterozygosity at the PTEN locus were also evaluated. In addition, the expression levels of PDPK1/PDK1, PTEN, and Ki67 were analyzed by immunohistochemistry. RESULTS:Three cases carrying the E17K mutation in the AKT1 gene and one case harboring the H1047R mutation in the PIK3CA gene were detected among the 36 cases. PDK1 was significantly overexpressed in the high-grade IPMN versus low-grade IPMN (P = 0.034) and in pancreatic and intestinal-type of IPMN versus gastric-type of IPMN (P = 0.020). Loss of PTEN expression was strongly associated with presence of invasive carcinoma and poor survival in these IPMN patients (P = 0.014). CONCLUSION/CONCLUSIONS:This is the first report of AKT1 mutations in IPMN. Our data indicate that oncogenic activation of the PI3K pathway can contribute to the progression of IPMN, in particular loss of PTEN expression. This finding suggests the potential employment of PI3K pathway-targeted therapies for IPMN patients. The incorporation of PTEN expression status in making surgical decisions may also benefit IPMN patients and should warrant further investigation.

BACKGROUND:Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients. METHODS:Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR. RESULTS:Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167). DISCUSSION/CONCLUSIONS:Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment's surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.

OBJECTIVES/OBJECTIVE:We examined long-term outcomes in patients with surgically treated intraductal papillary mucinous neoplasm (IPMN) to determine if any clinical or histologic features could predict risk of recurrent disease. METHODS:We reviewed 183 margin-negative surgical resections performed for IPMN between 1994 and 2011 with documented postoperative abdominal imaging. We calculated time to recurrent disease as indicated by radiographic change and created a multivariable Cox proportional hazards model to assess the relationship between patient characteristics and histopathologic tumor features and disease recurrence. RESULTS:Among patients with margin-negative resections and adequate imaging follow-up, we observed a recurrence rate of 13% over a median follow-up of 32.0 months. Individuals with invasive tumors on original pathology were more likely to recur (HR 5.2, 95% CI 2.2-12.2); however, original pathology did not predict disease severity on recurrence. Controlling for invasive pathology, no other histologic feature of the original tumor, including dysplasia at the surgical margin, predicted recurrence. Among non-invasive IPMN, pancreatitis was associated with disease recurrence (HR 3.6, 95% CI 1.2-10.7). CONCLUSIONS:The frequency of recurrent disease in this population and the inability to predict recurrence argues for universal and continuous surveillance after resection for IPMN. The relationship between pancreatitis and disease recurrence should be investigated further.

IMPORTANCE/OBJECTIVE:Research has been limited on the incidence, mechanisms, etiology, and treatment of symptoms that require palliation in patients with terminal cancer. Bowel obstruction (BO) is a common complication of advanced abdominal cancer, including colon cancer, for which small, single-institution studies have suggested an incidence rate of 15% to 29%. Large population-based studies examining the incidence or risk factors associated with BO in cancer are lacking. OBJECTIVE:To investigate the incidence and risk factors associated with BO in patients with stage IV colon cancer. DESIGN AND SETTING/METHODS:Retrospective cohort, population-based study of patients in the Surveillance, Epidemiology, and End Results and Medicare claims linked databases who were diagnosed as having stage IV colon cancer from January 1, 1991, through December 31, 2005. PATIENTS/METHODS:Patients 65 years or older with stage IV colon cancer (n = 12 553). MAIN OUTCOMES AND MEASURES/METHODS:Time to BO, defined by inpatient hospitalization for BO. We used Cox proportional hazards regression models to determine associations between BO and patient, prior treatment, and tumor features. RESULTS:We identified 1004 patients with stage IV colon cancer subsequently hospitalized with BO (8.0%). In multivariable analysis, proximal tumor site (hazard ratio, 1.22 [95% CI, 1.07-1.40]), high tumor grade (1.34 [1.16-1.55]), mucinous histological type (1.27 [1.08-1.50]), and nodal stage N2 (1.52 [1.26-1.84]) were associated with increased risk of BO, as was the presence of obstruction at cancer diagnosis (1.75 [1.47-2.04]). A more recent diagnosis was associated with decreased risk of subsequent obstruction (hazard ratio, 0.84 [95% CI, 0.72-0.98]). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:In this large population of patients with stage IV colon cancer, BO after diagnosis was less common (8.0%) than previously reported. Risk was associated with site and histological type of the primary tumor. Future studies will explore management and outcomes in this serious, common complication.

BACKGROUND:Bowel obstruction is a common complication of late-stage abdominal cancer, especially colon cancer, which has been investigated predominantly in small, single-institution studies. OBJECTIVE:We used a large, population-based data set to explore the surgical treatment of bowel obstruction and its outcomes after hospitalization for obstruction among patients with stage IV colon cancer. DESIGN/METHODS:This was a retrospective cohort study. SETTING AND PATIENTS/METHODS:We identified 1004 patients aged 65 years or older in the Surveillance, Epidemiology and End Results-Medicare database diagnosed with stage IV colon cancer January 1, 1991 to December 31, 2005, who were later hospitalized for bowel obstruction. MAIN OUTCOME MEASURES/METHODS:We describe outcomes after hospitalization and analyzed the associations between surgical treatment of obstruction and outcomes. RESULTS:Hospitalization for bowel obstruction occurred a median of 7.4 months after colon cancer diagnosis, and median survival after obstruction was approximately 2.5 months. Median hospitalization for obstruction was about 1 week and in-hospital mortality was 12.7%. Between discharge and death, 25% of patients were readmitted to the hospital at least once for obstruction, and, on average, patients lived 5 days out of the hospital for every day in the hospital between obstruction diagnosis and death. Survival was 3 times longer in those whose obstruction claims suggested an adhesive obstruction origin. In multivariable models, surgical compared with nonsurgical management was not associated with prolonged survival (p = 0.134). LIMITATIONS/CONCLUSIONS:Use of an administrative database did not allow determination of quality of life or relief of obstruction as an outcome, nor could nonsurgical interventions, eg, endoscopic stenting or octreotide, be assessed. CONCLUSIONS:In this population-based study of patients with stage IV colon cancer who had bowel obstruction, overall survival following obstruction was poor irrespective of treatment. Universally poor outcomes suggest that a diagnosis of obstruction in the setting of advanced colon cancer should be considered a preterminal event.

BACKGROUND: Hospital readmission has been proposed as a metric for quality of medical and surgical care. We examined our institutional experience with readmission after pancreatic resection, and assessed factors predictive of readmission. METHODS: We reviewed 787 pancreatic resections performed at a single institution between 2006 and 2010. Univariate and multivariate logistic regression models were used to assess the relationships between preoperative and postoperative characteristics and readmission. Reasons for hospital readmission were examined in detail. RESULTS: We found the 30-day readmission rate after pancreatic resection to be 11.6 %. In univariate analysis, young age, pancreaticoduodenectomy versus other operations, open versus laparoscopic technique, fistula formation, the need for reoperation, and any complication during the index hospitalization were predictive of readmission. In multivariate analysis, only young age and postoperative complication were predictive of readmission. Vascular resection, postoperative ICU care, length of stay, and discharge disposition were not associated with readmission. The most common reasons for readmission were leaks, fistulas, abscesses, and wound infections (45.1 %), delayed gastric emptying (12.1 %), venous thrombosis (7.7 %), and GI bleeding (7.7 %). CONCLUSIONS: We found the vast majority of readmissions after pancreatic resection were to manage complications related to the operation and were not due to poor coordination of care or poor discharge planning. Because evidence-based measures to prevent these surgical complications do not exist, we cannot support the use of readmission rates themselves as a quality indicator after pancreatic surgery.