Citations

INTRODUCTION: Chronic pancreatitis (CP) is a debilitating chronic disease and significantly impacts patient's quality of life. There is evidence that cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells; Cannabis is becoming increasingly popular and there are currently 33 states in the US that have approved medical cannabis while 10 states have approved cannabis for recreational use. We investigated the national trends in prevalence, mortality, length of stay (LOS), hospitalization charges and cost of chronic pancreatitis patients and compared between cannabis-exposed (CE) and non-cannabis-exposed (non-CE). METHODS: The National Inpatient Sample (NIS) database from 2005 to 2014 was queried for all patients with a primary discharge diagnosis of CP as per the International Classification of Diseases 9 th revision (ICD-9) code 5771. Active exposure to cannabis was ascertained based on ICD-9 code 304.3X and 305.2X. We compared CE vs. non-CE patients. Outcomes included in-hospital mortality, length of stay (LOS), inflation adjusted charges and cost. Propensity match analysis for age, gender, race, median income quartile, hospital characteristics and Elixhauser comorbidity index and multivariable logistic regression models were performed using STATA 14 software. RESULTS: Over 31,481 patients with CP as the primary diagnosis were analyzed. Cannabis-exposure prevalence was 1.4% (447 patients). The mean age of CP patients was 49. Patients exposed to cannabis were younger (42 vs 49-year-old, P < 0.001) and mostly males (69% vs 49.7%, P < 0.001). After adjusting for these factors, CE patients had lower total charges compared to non-CE (US$ 21,589 vs. 30,291 P < 0.001) (Figure 1a). CE patients were also hospitalized for fewer number of days when compared to non-CE patients (3.84 vs 5.19 days). There was a significant downward trend in the prevalence of chronic pancreatitis admissions ( P < 0.001) amongst non-CE patients while there was an upward trend in the prevalence of chronic pancreatitis admissions amongst CE patients (Figure 2a, b). Interestingly, after matching for age, gender and comorbidities – CE patients had lower inpatient mortality ( P = 0.059). CONCLUSION: In patients admitted with a primary diagnosis of CP, CE patients had fewer length of stay, hospitalization cost and inpatient mortality. The interplay of these factors remains unknown and studies looking at cannabis strength/dose, route and consumption frequency are needed.

INTRODUCTION: Chronic pancreatitis (CP) does not currently have a cure and it leads to multiple complications (pain, exocrine pancreatic insufficiency, steatorrhea, bone disease), its management is still a challenge. There is evidence that stimulating the endocannabinoid system may reduce inflammation and fibrosis in pancreatic stellate cells. Cannabis is the most frequently used recreational drug in the US and in recent years its legalization has increased. There are currently multiple States in the US that have approved medical cannabis for CP. We investigate the prevalence and outcomes of CP-related complications amongst cannabis-exposed (CE) and non-cannabis-exposed (non-CE) CP patients. METHODS: The National Inpatient Sample (NIS) database from 2005 to 2014 was queried for all patients with a primary or secondary discharge diagnosis of chronic pancreatitis as per the International Classification of Diseases 9 th revision (ICD-9) code 577.1 and a complication related to chronic pancreatitis. Active exposure to cannabis was ascertained based on ICD-9 code 304.3X and 305.2X. We compared CE vs. non-CE patients. Outcomes included pancreatic cancer diagnosis, biliary stricture, pancreatic duct stricture, cholangitis, endoscopic retrograde cholangiopancreatography (ERCP) use for either diagnostic or therapeutic purpose. Propensity match analysis for age, gender, race, median income quartile, hospital characteristics and Elixhauser comorbidity index and multivariable logistic regression models were performed using SAS software (STATA 14). RESULTS: 109,326 patients with CP were analyzed (Figure 1). Prevalence of CE was 2.2% (2360 patients). The mean age of CP patients was 49. When comparing CE vs. non-CE, the CP-related complications amongst matched cohorts were as follows chronic abdominal pain 5.2% vs 0.3% ( P < 0.001), steatorrhea/diarrhea 1.2% vs 13.5% ( P < 0.001), biliary stricture 0.3% vs. 7.1% ( P < 0.001), pancreatic cancer 0.4% vs. 11.8% ( P < 0.001), cholangitis (0.1% vs 2.6%; P < 0.001), pancreatic cancer (0.4 vs 11.8; P < 0.001). Cannabis users also required less diagnostic ERCP (1.4% vs 5.5%; P < 0.001) and therapeutic ERCP (3.5% vs 9.3%; P < 0.001) (Figure 2). CONCLUSION: In CP patients admitted to the hospital, CE patients had lower rates of CP-related complications and importantly pancreatic cancer. These effects could possibly be through the effect of cannabis in the endocannabinoid system as previously shown in mice studies in Germany. More studies are needed to corroborate our findings.

Abstract Pancreatic ductal adenocarcinoma (PDA) affects over 44,000 people in the United States every year and carries a dismal prognosis, with a 5-year survival rate of just 5%. A subset of these patients (5-10%) report a familial history of the disease. The genetic etiology in these familial cases is poorly defined, with known susceptibility genes, such as: BRCA2, PALB2, CDKN2A, BRCA1, PRSS1 and STK11, accounting for only 10-15% of familial pancreatic cancer. In an effort to identify previously unappreciated pancreatic cancer susceptibility genes, we used next generation sequencing technology to evaluate the whole genome and whole exome sequences of 16 (6 families) and 22 individuals (10 families) respectively. All of these families enrolled into one of the familial pancreatic cancer registries participating in the Pancreatic Cancer Genetic Epidemiology (PacGene) Consortium, all had at least three members with PDA, and DNA was available from at least two affected members in each kindred. Using this approach, we identified heterozygous, inactivating, ATM mutations in two kindreds with familial pancreatic cancer (c.8266A&gt;AT; p.K2756X and c.170G&gt;GA; p.W57X). These mutations were previously reported as disease causing variants in patients with ataxia-telangiectasia, an autosomal recessive condition resulting from bi-allelic deleterious mutations of ATM. Interestingly, heterozygotes of deleterious ATM mutations have an increased risk of breast cancer. However, there have been no previous reports of deleterious ATM mutations in the germline of familial PDA patients. In our study, mutations segregated with disease in both kindreds and tumor analysis demonstrated Loss of heterozygosity (LOH) of the wild-type allele. Sequence analysis of the entire ATM gene in an additional 166 familial pancreatic cancer probands indentified four additional patients with deleterious mutations in the ATM gene (c.3214G&gt;GT; p.E1072X, c.6095G&gt;GA; p.R2032K, IVS41-1G&gt;GT and c.3801delG), while no deleterious mutations were identified in 190 spouse controls (p=0.046). When considering only the mostly severely affected families, those with three or more pancreatic cancer cases, four deleterious mutations were found in 87 families (P=0.009). These results indicate that ATM mutations play an important role in familial pancreatic cancer predisposition and have significant implications in the management of affected individuals and the risk assessment of family members. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2628. doi:1538-7445.AM2012-2628

Abstract Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with &gt;200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition. Significance: The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes. Cancer Discovery; 2(1): 41–6. ©2011 AACR. Read the Commentary on this article by Bakker and de Winter, p. 14 This article is highlighted in the In This Issue feature, p. 1