The effect of neoadjuvant chemoradiation on pancreatic cancer-associated diabetes mellitus.

OBJECTIVES: Pancreatic cancer-associated diabetes mellitus (PaCDM) occurs in approximately 50% of patients. In patients with new-onset PaCDM undergoing neoadjuvant chemoradiation therapy before surgical resection, we hypothesized that pancreatic tumor destruction would lead to improvement in fasting glucose levels. METHODS: A retrospective chart review was performed on patients with newly diagnosed pancreatic adenocarcinoma without a history of DM treated with neoadjuvant therapy at our center. All patients underwent combined modality neoadjuvant chemoradiation therapy, followed by surgical excision of the primary tumor. RESULTS: Sixty-nine patients (31 with PaCDM) met inclusion criteria for the study; 18 had Evans grade II tumor kill response, 10 had grade III response, and 3 had grade IV response. In patients with grade IV response, the odds ratio (OR) for achieving a normal preoperative glucose was 5.0 (95% confidence interval [CI], 0.4-63.2), compared with grade III (OR, 0.5; 95% CI, 0.1-3.0) and grade II (OR, 1.1; 95% CI, 0.2-5.2). When adjusted for percent kilogram weight loss and tumor size in a multivariable regression model, the grade IV response became significant to an OR of 6.5 (95% CI, 1.2-77.3). CONCLUSIONS: In patients with new-onset PaCDM undergoing neoadjuvant chemoradiation therapy, fasting glucose response may mirror the extent of tumor destruction.

Pancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US adults.

OBJECTIVES: The presence of a pancreatic cyst often prompts concern, although the rate of malignant transformation to mucin-producing adenocarcinoma is not known. We aimed to determine the prevalence rate of mucin-producing adenocarcinoma in US adults with pancreatic cysts. METHODS: This retrospective, population-based cross-sectional study calculated the annual number of mucin-producing adenocarcinomas using the Surveillance Epidemiology and End Results (SEER 18) database and the 2010 US census. The overall prevalence rate of cysts in the population was found using data from large cross-sectional imaging studies of incidental cyst prevalence. Prevalence rates were then calculated by dividing the annual number of mucin-producing adenocarcinomas by the cyst prevalence rate. RESULTS: Between 2005 and 2009, 1,137 mucin-producing adenocarcinomas were estimated to be found annually in a US adult population of 137,154,960. The total number of pancreas cysts, given a cyst prevalence rate of 2.5%, was 3,428,874. Therefore, the prevalence rate of mucin-producing adenocarcinoma arising in patients with pancreatic cysts was 33.2 per 100,000 (95% confidence interval (CI): 21.9-44.5). The prevalence rate was 32.8 per 100,000 (95% CI: 21.6-44.0) in women and 33.5 per 100,000 (95% CI: 22.2-44.8) in men. As expected, the rate of malignant transformation increased linearly with advancing age (highest 38.6 per 100,000 in 80- to 84-year-old men). CONCLUSIONS: Malignant transformation of pancreatic cysts into mucin-producing adenocarcinoma in US adults is a very rare event. Current clinical guidelines and resource allocation for pancreatic cyst disease should be reconsidered given these findings.

The clinical relevance of the increasing incidence of intraductal papillary mucinous neoplasm.

BACKGROUND & AIMS: The incidence of intraductal papillary mucinous neoplasm (IPMN) is believed to be increasing; we investigated whether this is the result of increasing burden of disease or more diagnostic scrutiny. METHODS: In a retrospective cohort study, we calculated a trend in reported incidence of IPMN using data collected from Olmsted County, Minnesota, from 1985 to 2005. Total IPMN cases from the Olmsted database were identified through a keyword and International Classification of Diseases, 9th revision, search using a database from the Rochester Epidemiology Project, with all cases verified by subsequent chart review. The subsequent rate of IPMN-related carcinoma was calculated using data from the national Surveillance Epidemiology and End Results-9 database, reflecting trends from 1982 to 2007. Cases of IPMN-related carcinoma were identified in the Surveillance Epidemiology and End Results-9 database by limiting the search to histology codes for noninvasive and invasive IPMN. RESULTS: Between 1985 and 2005, there was a 14-fold increase in the age- and sex-adjusted incidence of IPMN, from 0.31 to 4.35 per 100,000 persons. From 2000 to 2001, the rate of reported carcinoma increased from 0.008 to 0.032 per 100,000 persons, but stabilized afterward, with a rate of 0.06 per 100,000 persons in 2007. Mortality from all causes of pancreatic cancer was stable between 1975 and 2007 (approximately 11 deaths per 100,000 individuals). CONCLUSIONS: The incidence of IPMN has increased in the absence of an increase in IPMN-related or overall pancreatic cancer-related mortality, so it likely results from an increase in diagnostic scrutiny, rather than greater numbers of patients with clinically relevant disease.

Synergistic targeting with bone marrow-derived cells and PDGF improves diabetic vascular function.

Diabetes mellitus is associated with an increased risk of vascular disease, with significant alterations in systemic endothelial progenitor cells (EPCs) and peripheral vascular function. To identify the contribution of the different vascular compartments in the diabetic impairment of vascularization, we employed streptozotocin- and control-treated 3-mo-old C57Bl/6 mice in an isogeneic pinnal cardiac allograft model, revealing a significant delay in vascularization of wild-type cardiac tissue transplanted into diabetic mice. To investigate the basis of this impairment, the function of diabetic bone marrow cells was tested by transplantation of bone marrow cells isolated from diabetic and control mice into intact, unirradiated 18-mo-old C57Bl/6 mice, which have impaired function of both EPCs and peripheral endothelial cells. Importantly, cells derived from control, but not diabetic, bone marrow integrated into transplanted cardiac allografts. To assess the contribution of diabetic changes in the local vasculature, diabetic mice were treated with pinnal injections of platelet-derived growth factor (PDGF)-AB, which promotes cardiac angiogenesis in wild-type mice. However, whereas PDGF-AB enhanced allograft function in control mice, the activity of the cardiac transplants in the PDGF-AB-treated diabetic mice was significantly decreased. To decipher the potential interactions between systemic bone marrow-derived cells and local vascular pathways, diabetic mice were transplanted with wild-type bone marrow cells with or without PDGF-AB pinnal pretreatment, resulting in improved allograft function and donor cell recruitment only in the combination treatment arm. Overall, these studies show that the diabetic impairment in cardiac angiogenesis can be reversed by targeting the synergism between local trophic pathways and systemic cell function.