Lower Rates of Hepatocellular Carcinoma Observed Among Cannabis Users: A Population-Based Study.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the fourth leading cause of cancer deaths in the world. The association between HCC and cannabis has been identified in mice; however, to our knowledge has not been identified in humans. Therefore, we aim to investigate the relation between HCC and cannabis use in humans. METHODS: Using data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified the patients with HCC and cannabis use diagnosis using the International Classification of Disease 9th version codes (ICD-9). Then, we identified patients without cannabis use as the control group. We adjusted for multiple potential confounders and performed multivariable logistic regression analysis to determine the association between cannabis abuse and HCC. RESULTS: A total of 101,231,036 patients were included in the study. Out of the total, 996,290 patients (1%) had the diagnosis of cannabis abuse versus 100,234,746 patients (99%) in the control group without cannabis abuse. We noticed that patients with cannabis abuse were younger (34 vs 48 years), had more males (61.7% vs 41.4%) and more African Americans (29.9% vs 14.2%) compared with the control group (P<0.001 for all). Besides, patients with cannabis use had more hepatitis B, hepatitis C, liver cirrhosis, and smoking, but had less obesity and gallstones, (P<0.001 for all). Using multivariable logistic regression, and after adjusting for potential confounders, patients with cannabis abuse were 55% less likely to have HCC (adjusted Odds Ratio {aOR}, 0.45, 95% Confidence Interval {CI}, 0.42-0.49, P<0.001) compared with patients without cannabis abuse. CONCLUSION: Based on our large database analysis, we found that cannabis use patients were 55% less likely to have HCC compared to patients without cannabis use. Further prospective studies are needed to assess the role of cannabis use on HCC.

Rates of Intestinal Resection and Colectomy in Inflammatory Bowel Disease Patients After Initiation of Biologics: A Cohort Study.

BACKGROUND & AIMS: 50% to 80% Crohn's disease (CD) and 10% to 30% ulcerative colitis (UC) patients require surgery over their lifetime. Biologic therapies may alter this natural history, but data on the effect of biologics on surgery rates in this patient population are mixed. We sought to investigate the influence of biologics on surgery prevalence in CD and UC. METHODS: We used a commercial database (Explorys Inc, Cleveland, OH), which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients who were diagnosed with CD or UC that were treated with any biologics between 2015 and 2020. The primary outcome was to examine the association between biologics therapy and the prevalence of bowel resection. Also, we identified the factors associated with surgery in IBD patients on biologics. RESULTS: Of 32,904,480 patients in the database, we identified 140,540 patients with CD and 115,260 patients with UC, of whom 25,840 (18%) and 9,050 (7.8%) patients received biologics, respectively. The prevalence of intestinal resection was significantly lower in biologics-treated CD patients (9.3%) compared to those who did not receive biologics (12.1%) (p < .001). Similarly, biologic-treated UC patients were significantly less likely to undergo colectomy (7.3%) compared to UC patients who did not receive biologic therapy (11.0%) (p < .001). Tobacco use, Clostridium difficile infection, and perianal disease were associated with intestinal resection in CD. Colon neoplasm and Clostridium difficile infection were associated with colectomy in UC. CONCLUSIONS: In this study of a large healthcare administrative database, inflammatory bowel disease (IBD) patients treated with biologics were significantly less likely to undergo bowel resection when compared to those who never received biologics. This data suggests that biologics may impact surgical rates in IBD.

Simplified 6-month prediction scores for primary biliary cholangitis patients treated with ursodeoxycholic acid.

OBJECTIVES: To develop a prognostic score evaluating treatment response at 6 months after ursodeoxycholic acid (UDCA) initiation in primary biliary cholangitis (PBC) patients. METHODS: Adult PBC patients who were newly prescribed UDCA at our institution (n = 292) were included. Significant determinants of liver-related adverse events in the multivariable Cox model were used for score development, weighted by ß-coefficients. Discrimination ability was assessed using Harrell's C-statistic. The performance of our model was compared to the previous models. RESULTS: Our model included the following variables evaluated at 6 months: (1) alkaline phosphatase decline of less than 50% from baseline and >upper limit normal (ULN) (2 points); (2) bilirubin >ULN (2 points); (3) albumin

Hepatocellular carcinoma in nonalcoholic fatty liver disease with or without cirrhosis: a population-based study.

BACKGROUND: There are limited data regarding the factors associated with hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. We sought to determine the prevalence and factors associated with HCC in NAFLD patients with or without cirrhosis. METHODS: Adults with NAFLD (June 2015 to May 2020) were identified using the electronic health record database (Explorys Inc, Cleveland, OH) from 26 major integrated US healthcare systems. The prevalence of HCC was calculated. Multivariable analyses adjusting for covariates were performed to evaluate the associated risk factors and the presence of HCC. RESULTS: A total of 392,800 NAFLD patients were identified. Among 1110 patients with HCC, 170 (15.3%) had no cirrhosis. The prevalence of HCC in non-cirrhotic and cirrhotic NAFLD patients was 4.6/10,000 persons (95% CI 3.9-5.3), and 374.4/10,000 persons (95% CI 350.9-398.8), respectively. Age > 65 years (adjusted OR; 3.37, 95% CI 2.47-4.59), ever had elevated alanine aminotransferase (2.69; 2.14-3.37), male gender (2.57; 1.88-3.49), smoker (1.75; 1.23-2.49), and diabetes (1.56; 1.15-2.11) were associated with HCC in non-cirrhotic NAFLD (all P < 0.05). The prevalence of HCC in the non-cirrhotic with all five risk factors was 45.5/10,000 persons (95% CI 17.4-73.6). The factors associated with HCC in cirrhotic NAFLD included clinical decompensation, age > 65 years, male gender, Hispanic race, elevated alanine aminotransferase, diabetes and smoker (all P < 0.05). CONCLUSIONS: These data identified the major risk factors for the development of HCC in NAFLD patients. In the non-cirrhotics, older male patients with smoking history, diabetes and an elevated alanine aminotransferase had highest risk and may need increased judicious monitoring.

Epidemiology of neuroendocrine tumors of the appendix in the USA: a population-based national study (2014-2019).

BACKGROUND: The appendix is the third most common place for neuroendocrine tumors (NETs) along the digestive tract and NETs are the most common neoplasms of the appendix. However, there are limited population-based data on the epidemiology of this disease. Using a large database, we sought to describe the epidemiology and risk association of NETs of the appendix. METHOD: We queried a multi-institutional database (Explorys Inc., Cleveland, OH, USA), comprising 360 hospitals in the United States (US), for patients with a diagnosis of NETs of the appendix from 2014-2019. RESULTS: Of the 30,324,050 individuals in the database, 2020 patients had an appendiceal NET diagnosis (0.007%). The most common presenting symptoms included abdominal pain, nausea, vomiting and diarrhea. Patients with appendiceal NETs were more likely to be female (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.24-1.49), Caucasian (OR 2.71, 95%CI 2.40-3.07), with a history of smoking (OR 1.82, 95%CI 1.65-2.01), family history of primary gastrointestinal malignancy (OR 7.26, 95%CI 6.31-8.33), diagnosis of multiple endocrine tumor type 1 (OR 52.31, 95%CI 23.15-118.23), or neurofibromatosis type 1 (OR 16.37, 95%CI 7.24-37.01). CONCLUSIONS: In a population-based study in the US, using the Explorys database, we found the overall prevalence of NETs of the appendix to be 7 per 100,000 persons. The incidence in the year January 2019-January 2020 was 0.4 per 100,000 individuals. These rates are higher than previously reported and may be more accurate, given the more comprehensive nature of the Explorys database.

Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy.

BACKGROUND: Chronic inflammation is a key factor for the development of colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD). Despite the increased use of biologic agents in patients with IBD, their impact on colorectal carcinogenesis remains unclear. With the use of a large database, we sought to describe the effect of biologics on CRC among patients with IBD. METHODS: We evaluated a multicenter database (Explorys) consisting of electronic medical records from several U.S. hospitals between 1999 and 2020. A cohort of patients with a diagnosis of IBD was identified. We performed a multivariate analysis to adjust for multiple factors including medical and surgical therapies. RESULTS: There were a total of 62,007,510 patients in the database between 1999 and 2020. Amongst those, 225,090 (0.36%) individuals had Crohn's disease and 188,420 (0.30%) had ulcerative colitis. After adjusting for confounding factors using multivariate analysis, patients with IBD were more likely to develop CRC. Among the IBD cohort, patients treated with anti-TNF agents were less likely to develop CRC; patients with Crohn's disease: odds ratio, 0.69; 95% confidence interval, 0.66-0.73; P < 0.0001 vs patients with ulcerative colitis: odds ratio, 0.78; 95% confidence interval, 0.73-0.83; P < 0.0001. CONCLUSIONS: Patients with IBD who were treated with anti-tumor necrosis factor agents were less likely to develop CRC. Prospective studies are needed to evaluate whether anti-tumor necrosis factor drugs provide a chemoprotective effect in patients with IBD by inflammation control and mucosal healing.

Peroral Endoscopic Myotomy Is Safe and Highly Effective Treatment for Advanced Achalasia With Sigmoid Esophagus.

BACKGROUND AND AIMS: In advanced achalasia patients with sigmoid esophagus, peroral endoscopic myotomy (POEM) might be technically challenging and its outcomes are not well known in western population. Hence, our study aims were to assess and compare the safety and efficacy of POEM in achalasia patients with and without sigmoid esophagus. MATERIALS AND METHODS: Medical records of achalasia patients who had POEM at our institution between April 2014 and December 2019 were reviewed. Patients who underwent work-up comprising timed barium esophagram (TBE) and high-resolution esophageal manometry (HREM) before POEM along with 2-month post-POEM esophageal pH study, TBE and HREM were included in the final analysis. Patients were categorized as either sigmoid or no sigmoid esophagus based on the morphology of esophagus on TBE as per Japan Esophageal Society guidelines. Treatment success was defined as reduction of post-POEM Eckardt score to ≤3. RESULTS: A total of 168 patients (sigmoid esophagus=20; no sigmoid esophagus=148) were included. Esophageal width on TBE at 1 minute was significantly higher in sigmoid esophagus group compared with no sigmoid esophagus group (4.9 vs. 3.0 cm, P<0.001). Procedural outcomes and complications were similar in both groups. At 2-month follow-up, both groups had significant improvement in Eckardt scores, TBE, and HREM parameters. Treatment success was high and similar in both sigmoid and no sigmoid groups (94.4% vs. 93.2%, P=0.84). The rates of gastroesophageal reflux disease were also similar in both groups. CONCLUSIONS: Our study findings suggest that POEM is safe and highly effective treatment for achalasia patients with sigmoid esophagus similar to those without sigmoid esophagus in western population. POEM should be considered as the treatment of choice in advanced achalasia with sigmoid esophagus.

Peroral endoscopic myotomy is highly effective for achalasia patients with recurrent symptoms after pneumatic dilatation.

BACKGROUND: Previous interventions in achalasia such as pneumatic dilation (PD) might lead to difficulties with peroral endoscopic myotomy (POEM) along with sub-optimal outcomes. There are limited data in the literature on outcomes of POEM after PD, especially from the western hemisphere. Hence, we aimed to determine the safety and efficacy of POEM for recurrent symptoms after PD compared to treatment naïve achalasia patients. METHODS: Medical records of achalasia patients who underwent POEM at our institution between April 2014 and October 2019 were reviewed. Patients who had POEM for recurrent symptoms after prior PD were matched at 1:2 ratio with treatment naïve achalasia patients using propensity score matching. Patients who had prior Heller myotomy were excluded. Patient demographics, Eckardt scores, timed barium swallow (TBE), high-resolution esophageal manometry (HREM), and pH study findings were compared between the two groups, pre- and 2 months post-POEM. Treatment success was defined as reduction of Eckardt score to ≤ 3. RESULTS: A total of 39 patients (prior PD = 13; treatment naïve = 26) were included. Patient demographics, procedural, and peri-procedural outcomes were similar in both groups. Treatment success was similar in both groups, 100.0% in prior PD vs 91.7% in treatment naïve group (p = 0.53). On adjusted analysis, there was no significant difference in the pre-post-POEM improvement in Eckardt scores, TBE, and HREM parameters in the two groups. Gastroesophageal reflux disease rates were also similar in both groups. CONCLUSIONS: In achalasia with recurrent symptoms after PD, POEM is a safe and highly effective treatment modality. Prior PD does not seem to influence the outcomes or efficacy of POEM.

The Risk of Acute and Chronic Pancreatitis in Celiac Disease.

BACKGROUND AND AIMS: Celiac disease (CD) is a chronic immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals. A few studies reported a higher incidence of pancreatitis in the CD population. Using a large US database, we sought to describe the epidemiology, risk, and outcomes of acute pancreatitis (AP) and chronic pancreatitis (CP) in CD patients. METHODS: We queried a multiple health system data analytics and research platform (Explorys Inc, Cleveland, OH, USA). A cohort of patients with a diagnosis of CD was identified. Subsequently, individuals who developed a new diagnosis of AP and CP after at least 30 days of being diagnosed with CD were identified. A multivariate regression model was performed to adjust for multiple confounding factors. RESULTS: Of the 72,965,940 individuals in the database, 133,400 (0.18%), 362,050 (0.50%), and 95,190 (0.13%) had CD, AP, and CP, respectively. New diagnosis of AP and CP after at least 30 days of CD diagnosis was 1.06%, 0.52%, respectively, compared to non-CD patients with 0.49% for AP and 0.13% for CP, P < .0001. In multivariate regression analysis, patients with CD were at higher risk of developing AP [OR 2.66; 95% CI 2.55-2.77] and CP [OR 2.18; 95% CI 2.04-2.34]. Idiopathic AP was the most common etiology among CD patients [OR 1.54; 95% CI 1.34-1.77]. CONCLUSIONS: In this largest US population database and after adjusting for several confounders, patients with CD were at increased risk of developing AP and CP. Celiac disease patients had worse outcomes and higher medical burden compared to non-CD patients. Recurrent abdominal pain that suggests pancreatic etiology, idiopathic pancreatitis, or elevation of pancreatic enzymes should warrant investigation for CD as a potential cause of pancreatic disease.

Colorectal Cancer Epidemiology: Recent Trends and Impact on Outcomes.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related deaths in the world with an estimated number of 1.8 million new cases and about 881,000 deaths worldwide in 2018. The epidemiology of CRC varies significantly between different regions in the world as well as between different age, gender and racial groups. Multiple factors are involved in this variation, including risk factor exposure, demographic variations in addition to genetic susceptibility and genetic mutations and their effect on the prognosis and treatment response. In this mini-review, we discuss the recent epidemiological trend including the incidence and mortality of colorectal cancer worldwide and the factors affecting these trends.

The Epidemiology of Pancreatic Cancer and the Association With Acetylsalicylic Acid in the United States: A Population-Based Study.

OBJECTIVES: Pancreatic cancer (PaC) is the third leading cause of cancer-related death in the United States. Multiple studies have investigated the epidemiology and the association between PaC and acetylsalicylic acid (ASA) use, revealing mixed results. Using a large database, we sought to investigate the epidemiology of PaC. METHODS: Using a commercial database (Explorys Inc, Cleveland, Ohio), which includes electronic health record data from 26 major integrated US health care systems, all patients 18 years and older diagnosed with PaC for 5 years were identified based on Systematized Nomenclature Of Medicine-Clinical Terms. We determined the prevalence of PaC and the potential associated factors using univariable and multivariable analysis. RESULTS: Of the 32,970,850 individuals, we identified 30,250 individuals with PaC with an overall prevalence of 0.08%. Individuals with PaC were more likely to be males, seniors (age, >65 years), and White, compared with patients without PaC. In subgroup analysis of chronic pancreatitis, individuals on ASA, individuals >65 years, White, and White males were less likely to have PaC, and non-White females were more likely to have PaC. CONCLUSIONS: This is the largest population-based study evaluating the epidemiology of PaC. We observed a protective association of ASA on a subgroup of patients with PaC and chronic pancreatitis.

The Risk of Vitamin D Deficiency, Osteoporosis, and Fractures in Acute Pancreatitis.

OBJECTIVES: A few past studies have found increased utilization of 25-hydroxyvitamin D and prevalence of osteoporosis in acute pancreatitis (AP). Our aim was to obtain a survey of bone diseases after a sentinel episode of AP. METHODS: A database (Explorys), an aggregate of electronic health record from 26 integrated United States healthcare systems, was queried. A cohort of patients with a Systematized Nomenclature of Medicine-Clinical Terms diagnosis of AP between 2014 and 2019, after excluding patients with selected medical conditions and medications that are associated with poor bone health, was identified. The prevalence of new diagnoses of vitamin D deficiency (VDD), osteoporosis, and fractures in the study cohort was evaluated. Age-, race-, and sex-based distributions and risk factors were determined through univariate and multivariate analyses. RESULTS: Of the 36,087,380 individuals in the database, we identified 256,580 (0.71%) with AP. In multivariate analysis, patients with AP were more likely to develop VDD (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.24-1.26; P < 0.0001), osteoporosis (OR, 1.89; CI, 1.81-1.85; P < 0.0001), and fractures (OR, 1.58; 95% CI, 1.57-1.59; P < 0.0001). CONCLUSIONS: Acute pancreatitis was associated with increased risk of VDD, osteoporosis, and fractures.

Epidemiology of Large Bowel Carcinoid Tumors in the USA: A Population-Based National Study.

BACKGROUND AND AIMS: Prior studies have shown that about 90% of all carcinoid tumors occur in the GI tract. However, epidemiological studies of these tumors have been limited by small sample size. Our aim was to obtain a more robust epidemiologic survey of large bowel carcinoids (LBC), using population-based data in order to more accurately identify risk factors for these tumors. METHODS: We used a commercial database (Explorys Inc, Cleveland, OH) which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients aged 18 and older who were diagnosed with LBC, excluding appendiceal carcinoids, between 1999 and 2018 based on Systematized Nomenclature Of Medicine-Clinical Terms (SNOMED-CT) and evaluated the prevalence of LBC. We also performed univariate analysis to describe age-, race-, and gender-based distributions and to identify potential risk factors. RESULTS: Of the 62,817,650 individuals in the database, 4530 were identified to have LBC with an overall prevalence of 7.21/100,000. Individuals with LBC were more likely to be elderly (age > 65) [OR 2.17, CI 2.05-2.31, p < 0.0001], smokers [OR 3.25; 95% CI 3.00-3.53, p < 0.0001], have a history of alcohol use [OR 3.75; 95% CI 3.52-3.99, p < 0.0001], diabetes mellitus (DM) [OR 4.42; 95% CI 4.14-4.72, p < 0.0001], obesity [OR 1.58; 95% CI 1.43-1.74, p < 0.0001], family history of cancer [OR 8.06; 95% CI 7.47-8.71, p < 0.0001], and personal history of ulcerative colitis [OR 6.93; 95% CI 5.55-8.64, p < 0.0001] or Crohn's disease [OR 6.45; 95% CI 5.24-7.95, p < 0.0001]. The prevalence of LBC was less among Caucasians compared to African-Americans [OR 0.57; 95% CI 0.53-0.61, p < 0.0001]. There was no statistically significant gender-based difference; men versus women [OR 1.02; 95% CI 0.96-1.08, p = 0.47]. The most common presenting symptoms included flushing, diarrhea, nausea, weight loss, and abdominal pain, while the most common GI associations included perforation, obstruction, hemorrhage, intussusception, and volvulus. CONCLUSION: This is the largest epidemiological study evaluating the prevalence of LBC. We estimated the prevalence rate of LBC to be 7.21/100,000. The presence of significant risk factors with the clinical picture suspicious for a LBC should warrant thorough evaluation as these tumors can lead to life-threatening complications. Further studies are needed to better understand the mechanism of association between these risk factors and LBC.

Characterization of patients with both alcoholic and nonalcoholic fatty liver disease in a large United States cohort.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS) and is characterized by steatosis in the absence of significant alcohol consumption. However, MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD. AIM: To assess the clinical characteristics of patients with both alcoholic and NAFLD (BAFLD) in a large cohort in the United States. METHODS: Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included. NAFLD was diagnosed based on elevated alanine aminotransferase (ALT) and being overweight or obese in the absence of other liver diseases. BAFLD patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of alcohol. Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score (FIB4 index). RESULTS: The prevalence of NAFLD was at 25.9% (95%CI; 25.1-26.8) and that of BAFLD was 0.84% (0.67, 1.02) which corresponds to an estimated 1.24 million Americans affected by BAFLD. Compared to NAFLD, patients with BAFLD were more likely to be male, smokers, have higher ALT, aspartate aminotransferase, triglycerides, and lower platelets; P < 0.01 for all. More importantly, after adjusting for MetS components, BAFLD patients were significantly more likely to have advanced fibrosis [adjusted OR (95%CI) based on FIB4 index > 2.67 was 3.2 (1.4, 7.0), P = 0.004]. CONCLUSION: A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.

Endoscopic Sinusotomy Using Needle Knife Technique for Treatment of H-Pouch With Leak and Sinus.

A 62-year-old patient with a history of ulcerative colitis and total colectomy with ileal pouch-anal anastomosis was referred to our pouch center for rectal pain, loose stool, and perianal swelling. He was diagnosed with chronic fistula and anastomotic stricture for which he had excision of J-pouch and creation of H-pouch. Surveillance workup after surgery revealed pouch sinus, which was treated with needle-knife sinusotomy (NKSi). This is the first case in the literature of an H-pouch complicated with anastomotic sinus successfully treated with NKSi. We propose using NKSi as the preferred technique for pouch sinuses.