New onset diabetes predicts progression of low risk pancreatic mucinous cysts.

BACKGROUND: Patients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts. METHODS: We evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method. RESULTS: The 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5-57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%-20.2%), compared to only 0.8% (95%CI, 0.0%-2.3%) for patients without NODM. Among patients with the largest cysts (20-29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%-89.9%) compared to only 7.5% (95%CI, 1.6%-15.2%) for patients without NODM. CONCLUSION: New onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.

New-Onset Diabetes Is a Potential Marker for the Malignant Transformation of Pancreatic Cysts: A Real-World Population Cohort Study.

OBJECTIVES: New-onset diabetes mellitus has been shown to be associated with pancreatic cancer (PC) in the general population. Our objective was to leverage real-world data to assess the association of new-onset diabetes (NODM) with malignant transformation in a large longitudinal cohort of pancreatic cyst patients. METHODS: A retrospective longitudinal cohort study was conducted using IBM's MarketScan claims databases from 2009 to 2017. From 200 million database subjects, we selected patients with newly diagnosed cysts without prior pancreatic pathology. RESULTS: Of the 137,970 patients with a pancreatic cyst, 14,279 had a new diagnosis. Median follow-up was 41.6 months. Patients with NODM progressed to PC at nearly 3 times the rate of patients without a diabetes history (hazard ratio, 2.80; 95% confidence interval, 2.05-3.83) and at a significantly higher rate than patients with preexisting diabetes (hazard ratio, 1.59; 95% confidence interval, 1.14-2.21). The mean interval between NODM and cancer diagnosis was 7.5 months. CONCLUSIONS: Cyst patients who developed NODM progressed to PC at 3 times the rate of nondiabetics and at a greater rate than preexisting diabetics. The diagnosis of NODM preceded cancer detection by several months. These results support the inclusion of diabetes mellitus screening in cyst surveillance algorithms.

Prevalence, Incidence, and Risk of Progression of Asymptomatic Pancreatic Cysts in Large Sample Real-world Data.

OBJECTIVES: Using large-sample, real-world administrative claims data, we evaluated the prevalence of putatively asymptomatic pancreatic cysts, the historical growth in their incident diagnosis, and their risk of malignant progression. METHODS: Data were sourced from IBM MarketScan administrative claims databases of more than 200 million patients. Period prevalence was assessed using 700,000 individuals without conditions that predispose to pancreatic cyst. The standardized cumulative incidence was compared with the cross-sectional abdominal imaging rate from 2010-2017. The risk of progression to pancreatic cancer for 14,279 newly diagnosed patients with a cyst was estimated using Kaplan-Meier analysis. RESULTS: Standardized prevalence increased exponentially with age and was 1.84% (95% confidence interval, 1.80%-1.87%) for patients older than 45. Standardized incidence nearly doubled from 2010-2017 (6.3 to 11.4 per 10,000), whereas the imaging rate changed from only 8.0% to 9.4%. The cumulative risk of pancreatic cancer at 7 years was 3.0% (95% confidence interval, 2.4%-3.5%), increasing linearly (R2 = 0.991) with an annual progression risk of 0.47%. CONCLUSIONS: Using large-sample data, we show a significant burden of asymptomatic pancreatic cysts, with an annual risk of progression to cancer of 0.47% for 7 years. Rapid growth in cyst diagnosis over the last decade far outpaced increases in the imaging rate.

Development of a stratification tool to identify pancreatic intraductal papillary mucinous neoplasms at lowest risk of progression.

BACKGROUND: Because most pancreatic intraductal papillary mucinous neoplasms (IPMNs) will never become malignant, currently advocated long-term surveillance is low-yield for most individuals. AIM: To develop a score chart identifying IPMNs at lowest risk of developing worrisome features or high-risk stigmata. METHODS: We combined prospectively maintained pancreatic cyst surveillance databases of three academic institutions. Patients were included if they had a presumed side-branch IPMN, without worrisome features or high-risk stigmata at baseline (as defined by the 2012 international Fukuoka guidelines), and were followed ≥ 12 months. The endpoint was development of one or more worrisome features or high-risk stigmata during follow-up. We created a multivariable prediction model using Cox-proportional logistic regression analysis and performed an internal-external validation. RESULTS: 875 patients were included. After a mean follow-up of 50 months (range 12-157), 116 (13%) patients developed worrisome features or high-risk stigmata. The final model included cyst size (HR 1.12, 95% CI 1.09-1.15), cyst multifocality (HR 1.49, 95% CI 1.01-2.18), ever having smoked (HR 1.40, 95% CI 0.95-2.04), history of acute pancreatitis (HR 2.07, 95% CI 1.21-3.55), and history of extrapancreatic malignancy (HR 1.34, 95% CI 0.91-1.97). After validation, the model had good discriminative ability (C-statistic 0.72 in the Mayo cohort, 0.71 in the Columbia cohort, 0.64 in the Erasmus cohort). CONCLUSION: In presumed side branch IPMNs without worrisome features or high-risk stigmata at baseline, the Dutch-American Risk stratification Tool (DART-1) successfully identifies pancreatic lesions at low risk of developing worrisome features or high-risk stigmata.

Variability in Motor and Language Recovery during the Acute Stroke Period.

BACKGROUND: Most stroke recovery occurs by 90 days after onset, with proportional recovery models showing an achievement of about 70% of the maximal remaining recovery. Little is known about recovery during the acute stroke period. Moreover, data are described for groups, not for individuals. In this observational cohort study, we describe for the first time the daily changes of acute stroke patients with motor and/or language deficits over the first week after stroke onset. METHODS: Patients were enrolled within 24-72 h after stroke onset with upper extremity hemiparesis, aphasia, or both, and were tested daily until day 7 or discharge with the upper-extremity Fugl-Meyer Assessment of Motor Recovery after Stroke, the Boston Naming Test, and the comprehension domain from the Western Aphasia Battery. Discharge scores, and absolute and proportional changes were examined using t-tests for pairwise comparisons and linear regression to determine relative contributions of initial impairment, lesion volume, and age to recovery over this period. RESULTS: Thirty-four patients were enrolled: 19 had motor deficits alone, 8 had aphasia alone, and 7 had motor and language deficits. In a group analysis, statistically significant changes in absolute scores were found in the motor (p < 0.001) and comprehension (p < 0.001) domains but not in naming. Day-by-day recovery curves for individual patients displayed wide variation with comparable initial impairment. Proportional recovery calculations revealed that, on average, patients achieved less than 1/3 of their potential recovery by the time of discharge. Multivariate regression showed that the amount of variance accounted for by initial severity, age, and lesion volume in this early time period was not significant for motor or language domains. CONCLUSIONS: Over the first week after stroke onset, recovery of upper extremity hemiparesis and aphasia were not predictable on the basis of initial impairment, lesion volume, or age. In addition, patients only achieved about 1/3 of their remaining possible recovery based on the anticipated 70% proportion found at 90 days. These findings suggest that the complex interaction between poststroke structural repair, regeneration, and functional reorganization during the first week after stroke has yet to be elucidated.