The Toronto Upper Gastrointestinal Cleaning Score: a prospective validation study.

BACKGROUND : Assessment of mucosal visualization during esophagogastroduodenoscopy (EGD) can be improved with a standardized scoring system. To address this need, we created the Toronto Upper Gastrointestinal Cleaning Score (TUGCS). METHODS : We developed the TUGCS using Delphi methodology, whereby an international group of endoscopy experts iteratively rated their agreement with proposed TUGCS items and anchors on a 5-point Likert scale. After each Delphi round, we analyzed responses and refined the TUGCS using an 80 % agreement threshold for consensus. We used the intraclass correlation coefficient (ICC) to assess inter-rater and test-retest reliability. We assessed internal consistency with Cronbach's alpha and item-total and inter-item correlations with Pearson's correlation coefficient. We compared TUGCS ratings with an independent endoscopist's global rating of mucosal visualization using Spearman's ρ. RESULTS : We achieved consensus with 14 invited participants after three Delphi rounds. Inter-rater reliability was high at 0.79 (95 %CI 0.64-0.88). Test-retest reliability was excellent at 0.83 (95 %CI 0.77-0.87). Cronbach's α was 0.81, item-total correlation range was 0.52-0.70, and inter-item correlation range was 0.38-0.74. There was a positive correlation between TUGCS ratings and a global rating of visualization (r = 0.41, P = 0.002). TUGCS ratings for EGDs with global ratings of excellent were significantly higher than those for EGDs with global ratings of fair (P = 0.01). CONCLUSION : The TUGCS had strong evidence of validity in the clinical setting. The international group of assessors, broad variety of EGD indications, and minimal assessor training improves the potential for dissemination.

Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial.

OBJECTIVE: Endoscopic pyloromyotomy (G-POEM) is a minimally invasive treatment option with promising uncontrolled outcome results in patients with gastroparesis. DESIGN: In this prospective randomised trial, we compared G-POEM with a sham procedure in patients with severe gastroparesis. The primary outcome was the proportion of patients with treatment success (defined as a decrease in the Gastroparesis Cardinal Symptom Index (GCSI) by at least 50%) at 6 months. Patients randomised to the sham group with persistent symptoms were offered cross-over G-POEM. RESULTS: The enrolment was stopped after the interim analysis by the Data and Safety Monitoring Board prior to reaching the planned sample of 86 patients. A total of 41 patients (17 diabetic, 13 postsurgical, 11 idiopathic; 46% male) were randomised (21 G-POEM, 20-sham). Treatment success rate was 71% (95% CI 50 to 86) after G-POEM versus 22% (8-47) after sham (p=0.005). Treatment success in patients with diabetic, postsurgical and idiopathic gastroparesis was 89% (95% CI 56 to 98), 50% (18-82) and 67% (30-90) after G-POEM; the corresponding rates in the sham group were 17% (3-57), 29% (7-67) and 20% (3-67).Median gastric retention at 4 hours decreased from 22% (95% CI 17 to 31) to 12% (5-22) after G-POEM and did not change after sham: 26% (18-39) versus 24% (11-35). Twelve patients crossed over to G-POEM with 9 of them (75%) achieving treatment success. CONCLUSION: In severe gastroparesis, G-POEM is superior to a sham procedure for improving both symptoms and gastric emptying 6 months after the procedure. These results are not entirely conclusive in patients with idiopathic and postsurgical aetiologies. TRIAL REGISTRATION NUMBER: NCT03356067; ClinicalTrials.gov.

Lactated Ringers Does Not Reduce SIRS in Acute Pancreatitis Compared to Normal Saline: An Updated Meta-Analysis.

BACKGROUND: We aimed to compare outcomes according to a Lactated Ringers (LR) versus Normal Saline (NS)-based strategy for acute pancreatitis. METHODS: A database search through November 2020 was done to identify studies comparing LR to NS for fluid rehydration in AP. The primary endpoint was systemic inflammatory response syndrome (SIRS) at 24 h. Mantel-Haenszel pooled odds ratios (OR) and 95% confidence intervals were constructed using a random effects model. Heterogeneity was assessed using the I2 statistic. Publication bias was assessed using funnel plots. RESULTS: Six studies were included totaling 549 patients. No difference in the odds of developing SIRS was noted at 24 h (pooled OR 0.59, 95% CI 0.22-1.62, P = 0.31) between LR and NS. I2 indices showed low heterogeneity between the groups, and a funnel plot showed no obvious publication bias. There was no difference between LR and NS found for SIRS at 48 and 72 h, mortality, and other secondary outcomes. LR was associated with a decreased need for ICU admission. CONCLUSIONS: This updated meta-analysis does not support the previously published finding that the use of LR (rather than NS) leads to a statistically significant decreased odds of SIRS in acute pancreatitis.

Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. RESULTS: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76-1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80-2.12) were not associated independently with mechanical ventilation or death. CONCLUSIONS: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

Evaluating the impact of frailty on periprocedural adverse events and mortality among patients with GI bleeding.

BACKGROUND AND AIMS: Frailty is a known predictor of mortality and adverse events in the inpatient setting; however, it has not been studied as a modality to assess risk among patients undergoing endoscopy for GI bleeding (GIB). We aimed to determine the association between frailty status and risk of adverse events in hospitalized patients with GIB who underwent endoscopy. METHODS: We performed a cohort study using the 2016 and 2017 National Inpatient Sample database, using International Classification of Diseases diagnostic codes to identify adult patients with GIB who underwent endoscopic procedures within 2 days of admission and the Hospital Frailty Risk Score to classify patients as frail or nonfrail. Univariable and multivariable logistic regression models were constructed to assess the predictors of periprocedural adverse events, and marginal standardization analysis was performed to assess for possible interaction between age and frailty. RESULTS: A total of 757,920 patients met inclusion criteria, of which 44.4% (336,895) were identified as frail and 55.6% (421,025) as nonfrail; 49.2% of frail patients had composite periprocedural adverse events compared with 25.5% of nonfrail patients (P < .001). Frail patients notably had more cardiovascular (32.1% vs 17.1%, P < .001), pulmonary (18.5% vs 4.3%, P < .001), GI (10.1% vs 6.1%, P < .001), and infectious (9.9% vs .7%, P < .001) adverse events compared with nonfrail patients. Frail patients also had higher all-cause inpatient mortality rates (4.8% vs .5%, P < .001). On multivariable analysis, positive frailty status was associated with a 2.13 times increased likelihood of having composite periprocedural adverse events. CONCLUSIONS: In hospitalized patients undergoing endoscopy for GIB, frailty status is associated with increased periprocedural adverse events including all-cause mortality. The use of frailty assessments can thus further guide clinical decision-making when considering endoscopy and risk of adverse events in adult patients with GI hemorrhage.

The role of endoscopy and findings in COVID-19 patients, an early North American Cohort.

BACKGROUND AND AIMS: Gastrointestinal manifestations in patients with COVID-19 are common but the role of endoscopy in this patient population remains unclear. We investigated the need for endoscopic procedures, their findings, and impact on patient care in a systematic and geographically diverse sample of patients hospitalized with COVID-19. METHODS: As part of the North American Alliance for the Study of Digestive Manifestations of COVID-19, we identified consecutive patients hospitalized with COVID-19 at 36 medical centers in the USA and Canada. We performed a secondary analysis of patients who underwent endoscopy, collecting information on endoscopic indications, findings, interventions, staffing, procedure location, anesthesia utilization, and adverse events. RESULTS: Data were collected on 1992 patients; 24 (1.2%) underwent 27 endoscopic procedures (18 upper endoscopies, 7 colonoscopies, 2 endoscopic retrograde cholangiopancreatographies). The most common indications were: gastrointestinal bleeding (13) and enteral access (6). The most common findings were erosive or inflammatory changes. Ten patients underwent an endoscopic intervention for hemostatic therapy (2), enteral access (6), or biliary obstruction (2). Half of cases employed anesthesiology support; no sedation-related adverse events were reported. One-third of cases were performed in the intensive care setting and one quarter in the endoscopy unit. CONCLUSIONS: In this large, systematic, geographically diverse cohort of patients hospitalized with COVID-19 in North America, very few patients underwent endoscopy despite a high prevalence of gastrointestinal manifestations. Almost all endoscopic findings and interventions were thought related to critical illness rather than direct viral injury. This systematic assessment of endoscopic necessity and outcomes may help guide resource allocation in the event of ongoing and future surges.

Impact of COVID-19 on endoscopy trainees: an international survey.

BACKGROUND AND AIMS: Although coronavirus disease 2019 (COVID-19) has affected endoscopy services globally, the impact on trainees has not been evaluated. We aimed to assess the impact of COVID-19 on procedural volumes and on the emotional well-being of endoscopy trainees worldwide. METHODS: An international survey was disseminated over a 3-week period in April 2020. The primary outcome was the percentage reduction in monthly procedure volume before and during COVID-19. Secondary outcomes included potential variation of COVID-19 impact between different continents and rates and predictors of anxiety and burnout among trainees. RESULTS: Across 770 trainees from 63 countries, 93.8% reported a reduction in endoscopy case volume. The median percentage reduction in total procedures was 99% (interquartile range, 85%-100%), which varied internationally (P < .001) and was greatest for colonoscopy procedures. Restrictions in case volume and trainee activity were common barriers. A total of 71.9% were concerned that the COVID-19 pandemic could prolonged training. Anxiety was reported in 52.4% of respondents and burnout in 18.8%. Anxiety was independently associated with female gender (odds ratio [OR], 2.15; P < .001), adequacy of personal protective equipment (OR, 1.75; P = .005), lack of institutional support for emotional health (OR, 1.67; P = .008), and concerns regarding prolongation of training (OR, 1.60; P = .013). Modifying existing national guidelines to support adequate endoscopy training during the pandemic was supported by 68.9%. CONCLUSIONS: The COVID-19 pandemic has led to restrictions in endoscopic volumes and endoscopy training, with high rates of anxiety and burnout among endoscopy trainees worldwide. Targeted measures by training programs to address these key issues are warranted to improve trainee well-being and support trainee education.

Preoperative Endoscopic Retrograde Cholangiopancreatography Is Not Associated With Increased Pancreatic Cancer Mortality.

BACKGROUND & AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) before surgery for pancreatic cancer has been associated with infectious complications after surgery. Little is known about the effects of preoperative ERCP on the survival of patients with pancreatic cancer. We investigated whether ERCP before surgery affects overall survival, after controlling for confounding factors. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) and linked Medicare claims data to identify patients older than 65 years with cancer localized to the head of the pancreas, from 2000 through 2011. We used inverse propensity-weighted Cox proportional hazard models to assess the effects of ERCP on the survival of patients who underwent surgery for pancreatic cancer. RESULTS: Among 16,670 patients with cancer of the head of the pancreas, 2890 (17.3%) underwent surgical resection; 1864 (64.5%) of these patients received preoperative ERCP. After we adjusted for confounders, we found that patients who received preoperative ERCP did not have an increased risk of death compared with patients who underwent resection alone (hazard ratio, 1.02; 95% CI, 0.96-1.08). CONCLUSIONS: Patients with pancreatic cancer who underwent ERCP before surgery did not have an increased risk of death compared with patients who proceeded directly to surgery. Studies are needed to identify subsets of patients who may benefit from this procedure.

Role of Fluorescent In Situ Hybridization, Cholangioscopic Biopsies, and EUS-FNA in the Evaluation of Biliary Strictures.

BACKGROUND AND AIMS: Our goal was to compare the diagnostic accuracy of FISH in the detection of malignancy compared with other standard diagnostic modalities, including brush cytology and biopsy specimens over a 10-year period of prospective data collection. METHODS: We conducted a review of all consecutive biliary strictures evaluated between 2006 and 2016. Patients with a final pathologic diagnosis or conclusive follow-up were included. We evaluated the performance of FISH polysomy (CEP 3, 7, and 17) and 9p21 deletion as well as cholangioscopic biopsy (CBx) and EUS-FNA. Statistical analysis was performed with the Mann-Whitney U and Fisher's exact tests. RESULTS: Of 382 patients with indeterminate strictures, 281 met inclusion criteria. Forty-nine percent were malignant. Cytology, FISH polysomy, and FISH polysomy/9p21 showed a specificity of 99.3%. FISH polysomy/9p21 as a single modality was the most sensitive at 56% (p < 0.001). The sensitivity of FISH polysomy/9p21 and cytology was significantly higher than cytology alone at 63 versus 35% (p < 0.05). EUS-FNA for distal strictures and CBx for proximal strictures increased sensitivity from 33 to 93% (p < 0.001) and 48-76% (p = 0.05) in cytology-negative strictures. CONCLUSIONS: The high specificity of FISH polysomy/9p21 suggests that a positive result is sufficient for diagnosing malignancy in indeterminate strictures. The significantly higher sensitivity of FISH polysomy/9p21 compared to cytology supports the use of FISH in all non-diagnostic cases. Although both EUS-FNA and CBx were complimentary, our results suggest that distal strictures should be evaluated by EUS initially. Proximal strictures may be evaluated by FISH first and then by CBx if inconclusive.

Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study.

BACKGROUND AND AIMS: The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. METHODS: This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. RESULTS: A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). CONCLUSIONS: TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs.

Building the Toolbox of Devices to Optimize a Practice in Submucosal Endoscopy.

Endoscopic submucosal dissection (ESD) is a technically complex and still evolving procedure. As a result, there are many advances in the technology and tools available to assist the endoscopist. This article delves into the various tools developed for ESD including electrosurgical knives, caps, injection agents, and traction devices. The authors discuss tools available as well as their respective pros, cons, and technical considerations for use. Overall, the choice of tools depends on a multitude of factors from availability, cost, lesion characteristics, and the endoscopist's familiarity and proficiency.

No difference in outcomes with 15 mm vs. 20 mm lumen-apposing metal stents for endoscopic ultrasound-guided gastroenterostomy for gastric outlet obstruction: a meta-analysis.

BACKGROUND/AIMS: We compared outcomes between use of 15 vs. 20 mm lumen-apposing metal stents (LAMSs) in endoscopic ultrasound-guided gastroenterostomy (EUS-GE) for gastric outlet obstruction. METHODS: Databases were queried for studies that used LAMS for EUS-GE to relieve gastric outlet obstruction, and a proportional meta-analysis was performed. RESULTS: Thirteen studies were included. The 15 mm and 20 mm LAMS had pooled technical success rates of 93.2% (95% confidence interval [CI], 90.5%-95.2%) and 92.1% (95% CI, 68.4%-98.4%), clinical success rates of 88.6% (95% CI, 85.4%-91.1%) and 89.6% (95% CI, 79.0%-95.1%), adverse event rates of 11.4% (95% CI, 8.1%-15.9%) and 14.7% (95% CI, 4.4%-39.1%), and reintervention rates of 10.3% (95% CI, 6.7%-15.4%) and 3.5% (95% CI, 1.6%-7.6%), respectively. Subgroup analysis revealed no significant differences in technical success, clinical success, or adverse event rates. An increased need for reintervention was noted in the 15 mm stent group (pooled odds ratio, 3.59; 95% CI, 1.40-9.18; p=0.008). CONCLUSION: No differences were observed in the technical, clinical, or adverse event rates between 15 and 20 mm LAMS use in EUS-GE. An increased need for reintervention is possible when using a 15 mm stent compared to when using a 20 mm stent.

Intragastric Balloon Significantly Improves Metabolic Parameters at 6 Months: a Meta-Analysis.

INTRODUCTION: It is estimated that by 2030, 38% of the world population will be overweight, and another 20% will be people with obesity. Intragastric balloons (IGBs) are an option in conjunction with lifestyle modification for the treatment of obesity. We sought to investigate the effects of IGB therapy on hemoglobin A1c (A1c), systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs). METHODS: PubMed, Embase, and Google Scholar were queried through November 2021 to identify studies that evaluated the effects of IGB therapy on selected variables at 6 months. A total of 17 studies and 1198 patients met inclusion criteria. Results were pooled using a random-effects model. RESULTS: At 6-month post-IGB insertion, patients had a significant reduction in A1c (mean difference (MD): - 0.62, 95% confidence interval (CI): - 0.884 to - 0.355, p < 0.001), SBP (MD: - 8.39, 95% CI: - 11.39 to - 5.386, p < 0.001), DBP (MD: - 5.807, 95% CI: - 8.852 to - 2.76, p < 0.001), TC (MD: - 9.189, 95% CI: - 15.763 to - 2.616, p = 0.006), LDL (MD: - 5.20, 95% CI: - 9.05 to - 1.35, p = 0.008), and TGs (MD: - 25.35, 95% CI: - 40.30 to - 10.10, p = 0.001). There was no significant difference in HDL (MD: 1.245, 95% CI: - 0.11 to 2.60, p = 0.071). CONCLUSIONS: Our meta-analysis suggests that IGB therapy is associated with improvements in insulin resistance, blood pressure, and dyslipidemia at 6 months. The results of this analysis suggest that IGB placement can be a viable treatment option to improve important metabolic parameters beyond weight loss alone.

Role of endoscopic ultrasound in the characterization of solid pseudopapillary neoplasm of the pancreas.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) is an uncommon pathology of the pancreas with unpredictable malignant potential. Endoscopic ultrasound (EUS) assessment plays a vital role in lesion characterization and confirmation of the tissue diagnosis. However, there is a paucity of data regarding the imaging assessment of these lesions. AIM: To determine the characteristic EUS features of SPN and define its role in preoperative assessment. METHODS: This was an international, multicenter, retrospective, observational study of prospective cohorts from 7 large hepatopancreaticobiliary centers. All cases with postoperative histology of SPN were included in the study. Data collected included clinical, biochemical, histological and EUS characteristics. RESULTS: One hundred and six patients with the diagnosis of SPN were included. The mean age was 26 years (range 9 to 70 years), with female predominance (89.6%). The most frequent clinical presentation was abdominal pain (80/106; 75.5%). The mean diameter of the lesion was 53.7 mm (range 15 to 130 mm), with the slight predominant location in the head of the pancreas (44/106; 41.5%). The majority of lesions presented with solid imaging features (59/106; 55.7%) although 33.0% (35/106) had mixed solid/cystic characteristics and 11.3% (12/106) had cystic morphology. Calcification was observed in only 4 (3.8%) cases. Main pancreatic duct dilation was uncommon, evident in only 2 cases (1.9%), whilst common bile duct dilation was observed in 5 (11.3%) cases. One patient demonstrated a double duct sign at presentation. Elastography and Doppler evaluation demonstrated inconsistent appearances with no emergence of a predictable pattern. EUS guided biopsy was performed using three different types of needles: Fine needle aspiration (67/106; 63.2%), fine needle biopsy (37/106; 34.9%), and Sonar Trucut (2/106; 1.9%). The diagnosis was conclusive in 103 (97.2%) cases. Ninety-seven patients were treated surgically (91.5%) and the post-surgical SPN diagnosis was confirmed in all cases. During the 2-year follow-up period, no recurrence was observed. CONCLUSION: SPN presented primarily as a solid lesion on endosonographic assessment. The lesion tended to be located in the head or body of the pancreas. There was no consistent characteristic pattern apparent on either elastography or Doppler assessment. Similarly SPN did not frequently cause stricture of the pancreatic duct or common bile duct. Importantly, we confirmed that EUS-guided biopsy was an efficient and safe diagnostic tool. The needle type used does not appear to have a significant impact on the diagnostic yield. Overall SPN remains a challenging diagnosis based on EUS imaging with no pathognomonic features. EUS guided biopsy remains the gold standard in establishing the diagnosis.

Incidence of subsequent pancreatic adenocarcinoma in patients with a history of nonpancreatic primary cancers.

BACKGROUND: Several environmental risk factors are known to predispose individuals to pancreatic cancer, and up to 15% of pancreatic cancers have an inherited component. Understanding metachronous cancer associations can modify pancreas cancer risk. The objective of this study was to investigate the association of nonpancreatic cancers with subsequent pancreatic adenocarcinoma. METHODS: The authors used data from the US Surveillance, Epidemiology, and End Results (SEER) registries to identify 1,618,834 individuals who had a primary malignancy and subsequent pancreatic adenocarcinoma (n = 4013). Standardized incidence ratios were calculated as an approximation of relative risk (RR) for the occurrence of pancreatic adenocarcinoma after another primary malignancy. RESULTS: Among patients who were diagnosed with a first primary malignancy at ages 20 to 49 years, the risk of subsequent pancreatic adenocarcinoma was increased among patients who had cancers of the ascending colon (relative risk [RR], 4.62; 95% confidence interval [CI], 1.86-9.52), hepatic flexure (RR, 5.42; 95% CI, 1.12-15.84), biliary system (RR, 13.14; 95% CI, 4.27-30.66), breast (RR, 1.32; 95% CI, 1.09-1.59), uterine cervix (RR, 1.61; 95% CI, 1.02-2.41), testes (RR, 2.78; 95% CI, 1.83-4.05), and hematopoietic system (RR, 1.83; 95% CI, 1.28-2.53). Among patients who had a first malignancy at ages 50 to 64 years, the risk was increased after cancers of the stomach (RR, 1.88; 95% CI, 1.13-2.93), hepatic flexure (RR, 2.25; 95% CI, 1.08-4.13), lung and bronchus (RR, 1.46; 95% CI, 1.16-1.82), pharynx (RR, 2.26; 95% CI, 1.13-4.04), and bladder (RR, 1.24; 95% CI, 1.03-1.48). Among patients who had a primary cancer after age 65 years, the risk was increased after cancers of the stomach (RR, 1.79; 95% CI, 1.23-2.53), hepatic flexure (RR, 1.76; 95% CI, 1.06-2.75), biliary system (RR, 2.35; 95% CI, 1.17-4.20), and uterus (RR, 1.23; 95% CI, 1.03-1.47). CONCLUSIONS: The results from the current population-based data set suggested that pancreatic adenocarcinoma is associated with certain primary cancers. Genetic predisposition and common environmental and behavioral risk factors all may contribute to this observation. Specific tumor associations will guide future risk-stratification efforts.