Association of Glycated Hemoglobin With a Risk of Pancreatic Cancer in High-Risk Individuals Based on Genetic and Family History.

INTRODUCTION: Screening for pancreatic cancer (PC) is suggested for high-risk individuals. Additional risk factors may enhance early detection in this population. METHODS: Retrospective cohort study among patients with germline variants and/or familial pancreatic cancer in an integrated healthcare system between 2003 and 2019. We calculated the incidence rate (IR) by risk category and performed a nested case-control study to evaluate the relationship between HbA1C and PC within 3 years before diagnosis (cases) or match date (controls). Cases were matched 1:4 by age, sex, and timing of HbA1c. Logistic regression was performed to assess an independent association with PC. RESULTS: We identified 5,931 high-risk individuals: 1,175(19.8%) familial PC, 45(0.8%) high-risk germline variants ( STK11, CDKN2A ), 4,097(69.1%) had other germline variants ( ATM, BRCA 1, BRCA 2, CASR, CDKN2A, CFTR, EPCAM, MLH1, MSH2, MSH6, PALB2, PRSS1, STK11, and TP53 ), and 614(10.4%) had both germline variants and family history. Sixty-eight patients (1.1%) developed PC; 50% were metastatic at diagnosis. High-risk variant was associated with greatest risk of PC, IR = 85.1(95% confidence interval: 36.7-197.6)/10,000 person-years; other germline variants and first-degree relative had IR = 33 (18.4, 59.3), whereas IR among ≥2 first-degree relative alone was 10.7 (6.1, 18.8). HbA1c was significantly higher among cases vs controls (median = 7.0% vs 6.4%, P = 0.02). In multivariable analysis, every 1% increase in HbA1c was associated with 36% increase in odds of PC (odds ratio 1.36, 95% confidence interval: 1.08-1.72). Pancreatitis was independently associated with a risk of PC (odds ratio 3.93, 95% confidence limit 1.19, 12.91). DISCUSSION: Risk of PC varies among high-risk individuals. HbA1c and history of pancreatitis may be useful additional markers for early detection in this patient population.

Gastric Cancer Screening in First-Degree Relatives: A Pilot Study in a Diverse Integrated Healthcare System.

INTRODUCTION: Family history of gastric cancer has been shown as an independent risk factor of gastric cancer development and is associated with increased risk of progression to gastric cancer among patients with gastric intestinal metaplasia (GIM). METHODS: Between 2017 and 2020, we conducted a prospective pilot screening program of patients with a confirmed first-degree relative with gastric cancer to evaluate the feasibility of screening and prevalence of precursor lesions (e.g., GIM or dysplasia) on biopsy. RESULTS: A total of 61 patients completed screening by upper endoscopy with a mapping biopsy protocol: 27 (44%) were found to have GIM and 4 (7%) were found with low-grade dysplasia. DISCUSSION: Our pilot screening program identified a high prevalence of precursor lesions for gastric cancer among asymptomatic patients with a first-degree relative with gastric cancer. Careful endoscopic inspection and standardized biopsy protocols may aid in prompt identification of these precursor lesions in those at risk of gastric cancer.

Satisfaction With Telehealth Among Patients With Irritable Bowel Syndrome During COVID-19: Cross-Sectional Survey Findings.

INTRODUCTION: Coronavirus disease 2019 rapidly shifted health care toward telehealth. We assessed satisfaction with and preferences for telehealth among patients with irritable bowel syndrome (IBS). METHODS: We conducted a cross-sectional survey in an integrated healthcare system in Southern California with members aged 18-90 years with an International Classification of Diseases 9 and 10 codes for IBS from office-based encounters between June 1, 2018, and June 1, 2020. Eligible patients were emailed a survey assessing telehealth satisfaction overall and by patient-related factors, IBS characteristics, health and technologic literacy, utilization, and coronavirus disease 2019 perceptions. We identified perceived telehealth benefits and challenges. Multivariable logistic regression identified predictors of telehealth dissatisfaction. RESULTS: Of 44,789 surveys sent, 5,832 (13.0%) patients responded and 1,632 (3.6%) had Rome IV IBS. Among 1,314 (22.5%) patients with IBS and prior telehealth use (mean age 52.6 years [17.4]; 84.9% female; and 59.4% non-Hispanic White, 29.0% Hispanic, and 5.6% non-Hispanic Black), 898 (68.3%) were satisfied, 130 (9.9%) were dissatisfied, and 286 (21.8%) felt neutral. In addition, 78.6% would use telehealth again. Independent predictors of telehealth dissatisfaction include social media use of once a week or less (adjusted odds ratio [OR] = 2.1; 1.3-3.5), duration of IBS for <1 year (adjusted OR = 8.2; 1.9-35.8), and willingness to travel 60 plus minutes for face-to-face visits (adjusted OR = 2.6; 1.4-3.7). Patients' main concern with telehealth was a lack of physical examination. DISCUSSION: Most of the patients with IBS are satisfied with telehealth. Shorter duration of IBS diagnosis, comfort with technology, and increased willingness to travel were associated with telehealth dissatisfaction. These predictors may help identify a target population for a focused IBS-telehealth program.

Imaging of the Pancreas in New-Onset Diabetes: A Prospective Pilot Study.

INTRODUCTION: The aim of this study was to assess the feasibility of cross-sectional imaging for detection of pancreatic cancer (PDAC) in patients with new-onset hyperglycemia and diabetes (NOD). METHODS: We conducted a prospective pilot study from November 2018 to March 2020 within an integrated health system. Patients aged 50-85 years with newly elevated glycemic parameters without a history of diabetes were invited to complete a 3-phase contrast-enhanced computed tomography pancreas protocol scan while participating in the Prospective Study to Establish a NOD Cohort. Abnormal pancreatic findings, incidental extrapancreatic findings, and subsequent clinical evaluation were identified. Variability in clinical reporting between medical centers based on descriptors of pancreatic duct and parenchyma was assessed. RESULTS: A total of 130 of 147 participants (88.4%) consented to imaging; 93 scans were completed (before COVID-19 stay-at-home order). The median age was 62.4 years (interquartile range 56.3-68.8), 37.6% women; Hispanic (39.8%), White (29.0%), Black (14.0%), and Asian (13.3%). One (1.1%) case of PDAC (stage IV) was diagnosed, 12 of 93 participants (12.9%) had additional pancreatic findings: 5 fatty infiltration, 3 cysts, 2 atrophy, 1 divisum, and 1 calcification. There were 57 extrapancreatic findings among 52 of 93 (56%) unique patients; 12 of 57 (21.1%) prompted clinical evaluation with 2 additional malignancies diagnosed (nonsmall cell lung and renal oncocytoma). Reports from 1 participating medical center more frequently provided description of pancreatic parenchyma and ducts (92.9% vs 18.4%), P < 0.0001. DISCUSSION: High proportion of incidental findings and variability in clinical reports are challenges to be addressed for a successful NOD-based early detection strategy for PDAC.

Validation of the Enriching New-Onset Diabetes for Pancreatic Cancer Model in a Diverse and Integrated Healthcare Setting.

BACKGROUND: The risk of pancreatic cancer is elevated among people with new-onset diabetes (NOD). Based on Rochester Epidemiology Project Data, the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) model was developed and validated. AIMS: We validated the END-PAC model in a cohort of patients with NOD using retrospectively collected data from a large integrated health maintenance organization. METHODS: A retrospective cohort of patients between 50 and 84 years of age meeting the criteria for NOD in 2010-2014 was identified. Each patient was assigned a risk score (< 1: low risk; 1-2: intermediate risk; ≥ 3: high risk) based on the values of the predictors specified in the END-PAC model. Patients who developed pancreatic ductal adenocarcinoma (PDAC) within 3 years were identified using the Cancer Registry and California State Death files. Area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated. RESULTS: Out of the 13,947 NOD patients who were assigned a risk score, 99 developed PDAC in 3 years (0.7%). Of the 3038 patients who had a high risk, 62 (2.0%) developed PDAC in 3 years. The risk increased to 3.0% in white patients with a high risk. The AUC was 0.75. At the 3+ threshold, the sensitivity, specificity, PPV, and NPV were 62.6%, 78.5%, 2.0%, and 99.7%, respectively. CONCLUSIONS: It is critical that prediction models are validated before they are implemented in various populations and clinical settings. More efforts are needed to develop screening strategies most appropriate for patients with NOD in real-world settings.

Characterization of patients with advanced chronic pancreatitis using natural language processing of radiology reports.

STUDY AIM: To develop and apply a natural language processing algorithm for characterization of patients diagnosed with chronic pancreatitis in a diverse integrated U.S. healthcare system. METHODS: Retrospective cohort study including patients initially diagnosed with chronic pancreatitis (CP) within a regional integrated healthcare system between January 1, 2006 and December 31, 2015. Imaging reports from these patients were extracted from the electronic medical record system and split into training, validation and implementation datasets. A natural language processing (NLP) algorithm was first developed through the training dataset to identify specific features (atrophy, calcification, pseudocyst, cyst and main duct dilatation) from free-text radiology reports. The validation dataset was applied to validate the performance by comparing against the manual chart review. The developed algorithm was then applied to the implementation dataset. We classified patients with calcification(s) or ≥2 radiographic features as advanced CP. We compared etiology, comorbid conditions, treatment parameters as well as survival between advanced CP and others diagnosed during the study period. RESULTS: 6,346 patients were diagnosed with CP during the study period with 58,085 radiology studies performed. For individual features, NLP yielded sensitivity from 88.7% to 95.3%, specificity from 98.2% to 100.0%. A total of 3,672 patients met cohort inclusion criteria: 1,330 (36.2%) had evidence of advanced CP. Patients with advanced CP had increased frequency of smoking (57.8% vs. 43.0%), diabetes (47.6% vs. 35.9%) and underweight body mass index (6.6% vs. 3.6%), all p<0.001. Mortality from pancreatic cancer was higher in advanced CP (15.3/1,000 person-year vs. 2.8/1,000, p<0.001). Underweight BMI (HR 1.6, 95% CL 1.2, 2.1), smoking (HR 1.4, 95% CL 1.1, 1.7) and diabetes (HR 1.4, 95% CL 1.2, 1.6) were independent risk factors for mortality. CONCLUSION: Patients with advanced CP experienced increased disease-related complications and pancreatic cancer-related mortality. Excess all-cause mortality was driven primarily by potentially modifiable risk factors including malnutrition, smoking and diabetes.

Association of Glycated Hemoglobin Levels With Risk of Pancreatic Cancer.

Importance: New-onset diabetes after the age of 50 years is a potential indicator of pancreatic cancer. Understanding the associations between hyperglycemia, diabetes, and pancreatic cancer, including pancreatic ductal adenocarcinoma, is key to developing an approach to early detection. Objective: To assess the association of elevation in glycated hemoglobin (HbA1c) with the risk of pancreatic cancer. Design, Setting, and Participants: This cohort study was conducted using data collected from an integrated health care system in California. A total of 851 402 patients aged 50 to 84 years who had HbA1c measurements taken between 2010 and 2014 were identified as the base cohort, with 12 contemporaneous cohorts created based on varying HbA1c thresholds (ie, 6.1%, 6.3%, 6.5%, and 6.7%) and prior diabetes status. Data analysis was conducted from August 2018 to September 2019. Main Outcomes and Measures: New cases of pancreatic cancer identified through cancer registry and California death files during a 3-year period. Three-year risk, incidence rate, sensitivity, number of patients needed to screen to detect 1 case, timing, and stage at diagnosis were determined. Results: Among 851 402 patients in the base cohort, 447 502 (52.5%) were women, 255 441 (30.0%) were Hispanic participants, 383 685 (45.1%) were non-Hispanic white participants, 100 477 (11.8%) were Asian participants, and 88 969 (10.4%) were non-Hispanic black participants, with a median (interquartile range) age of 62 (56-69) years and a median (interquartile range) HbA1c level of 6.0% (5.7%-6.6%). The incidence rate of pancreatic cancer was 0.45 (95% CI, 0.43-0.49) per 1000 person-years. After excluding prior diabetes as well as confirmation of new-onset hyperglycemia based on an HbA1c level of 6.5%, a total of 20 012 patients remained, with 74 of 1041 pancreatic ductal adenocarcinoma cases (7.1%) from the base cohort included. The rate of pancreatic cancer was 0.72 (95% CI, 0.32-1.42) per 1000 person-years among Asian patients, 0.83 (95% CI, 0.35-1.71) per 1000 person-years among non-Hispanic black patients, 0.84 (95% CI, 0.48-1.37) per 1000 person-years among Hispanic patients, and 2.37 (95% CI, 1.75-3.14) per 1000 person-years among non-Hispanic white patients. Overall, 42 of 74 cancers (56.8%) were diagnosed within 1 year of the index laboratory test. Among 1041 total cases, 708 (68.0%) had staging information available, of whom 465 (65.7%) had stage III or IV disease at diagnosis. In the base cohort, the number needed to undergo evaluation to identify a single case of pancreatic ductal adenocarcinoma was 818 (95% CI, 770-869), with estimates ranging from 206 (95% CI, 160-264) to 600 (95% CI, 540-666) in the subcohorts. Conclusions and Relevance: The findings of this study suggest that screening patients for pancreatic cancer based solely on elevation in HbA1c level is unlikely to represent an effective strategy. Future efforts to identify a high-risk population based on changes in glycemic parameters should account for racial/ethnic differences.

Identification of Individuals at Increased Risk for Pancreatic Cancer in a Community-Based Cohort of Patients With Suspected Chronic Pancreatitis.

OBJECTIVES: We lack reliable methods for identifying patients with chronic pancreatitis (CP) at increased risk for pancreatic cancer. We aimed to identify radiographic parameters associated with pancreatic cancer in this population. METHODS: We conducted a retrospective cohort study of patients with suspected CP within an integrated healthcare system in Southern California in 2006-2015. Patients were identified by a diagnostic code and confirmed by imaging findings (parenchymal calcification, ductal stones, glandular atrophy, pseudocyst, main duct dilatation, duct irregularity, abnormal side branch, or stricture) defined by the natural language processing of radiographic reports. We used Cox regression to determine the relationship of smoking, alcohol use, acute pancreatitis, diabetes, body mass index, and imaging features with the risk of incident pancreatic cancer at least 1 year after abnormal pancreas imaging. RESULTS: We identified 1,766 patients with a diagnostic code and an imaging feature for CP with a median follow-up of 4.5 years. There were 46 incident pancreatic cancer cases. Factors that predicted incident pancreatic cancer after 1-year of follow-up included obesity (hazard ratio 2.7, 95% confidence interval: 1.2-6.1) and duct dilatation (hazard ratio 10.5, 95% confidence limit: 4.0-27). Five-year incidence of pancreatic cancer in this population with duct dilatation was 6.3%. DISCUSSION: High incidence of pancreatic cancer in suspected patients with CP with pancreatic duct dilatation warrants regular surveillance for pancreatic cancer.

Factors Associated With Opioid Use in Patients Hospitalized for Acute Pancreatitis.

Importance: Limited guidance exists regarding the optimal approach to management of pain in acute pancreatitis (AP). Objectives: To investigate sources of variability in opioid use for treatment of acute pain in patients hospitalized for AP and to explore a potential association of opioid prescribing patterns with length of stay. Design, Setting, and Participants: This retrospective cohort study included 4307 patients 18 years and older hospitalized for AP in a community-based integrated health care system, from January 1, 2008, to June 30, 2015. Analysis began in November 2017. Exposures: Opioid use was quantified by morphine equivalent dose (MED). Main Outcomes and Measures: Three analyses were performed: (1) factors associated with increased opioid administration during the initial 12 hours of hospitalization (baseline), (2) association of baseline opioid use with length of stay, and (3) frequency of opioid use 90 days after hospital discharge (persistent use). Results: The cohort included 4307 patients (median [interquartile range] age, 57.4 [44.0-70.2] years; 2241 women [52.0%]) with AP. At baseline, 3443 patients (79.9%) received opioids, and 388 patients (9.6%) had persistent opioid use after discharge. After adjusting for pain and other clinical factors, women received less MED than men (adjusted event ratio, 0.83; 95% CI, 0.79-0.86; P < .001). Hispanic and Asian patients received less MED than non-Hispanic white patients (adjusted event ratio, 0.85; 95% CI, 0.81-0.90; P < .001; and adjusted event ratio, 0.79; 95% CI, 0.72-0.86; P < .001, respectively). Alcohol-related AP etiology was associated with increased MED vs gallstone disorders (adjusted event ratio, 1.11; 95% CI, 1.05-1.18; P < .001). Two of 13 hospitals administered significantly less opioids compared with the others. Median (interquartile range) length of stay was independently associated with MED at baseline, with 3.0 (2.1-4.5) days among patients not receiving opioids vs 5.0 (3.2-8.7) days among patients in the highest quintile of MED (P < .001). Conclusions and Relevance: In addition to pain and disease severity, opioid use varied by etiology of AP, sex, race/ethnicity, and institution of treatment. Increased opioid use at baseline was associated with longer hospitalization. These findings suggest opportunities for improved approaches to pain control for patients with AP.

Influence of Ambulatory Triglyceride Levels on Risk of Recurrence in Patients with Hypertriglyceridemic Pancreatitis.

BACKGROUND AND AIMS: To evaluate impact of ambulatory triglyceride levels on risk of recurrent pancreatitis in patients with hypertriglyceridemic pancreatitis. METHODS: We conducted a longitudinal retrospective cohort study of patients with serum triglyceride level ≥ 500 mg/dL during index hospitalization for acute pancreatitis within a regional integrated healthcare system between 2006 and 2013 (follow-up through 2015). Cases were identified based on combination of diagnosis codes and serum amylase/lipase. We used multivariable robust Poisson regression to determine independent effect of baseline (first outpatient) triglyceride measurement on risk of recurrent pancreatitis. Ambulatory triglyceride levels were categorized as normal (0-200 mg/dL), moderately elevated (201-500 mg/dL), and highly elevated (> 500 mg/dL). We further assessed factors related to likelihood of normalization of serum triglycerides (< 200 mg/dL) in the outpatient setting. RESULTS: One hundred and fifty-one patients met study inclusion criteria with median follow-up of 3 years. Overall, 45 (29.8%) patients experienced at least 1 recurrent attack with 25 (16.6%) experiencing multiple episodes. In multivariable analysis, patients that continued to have moderately elevated ((adjusted rate ratio RR 5.47 (95% CL 1.80, 16.65)) as well as highly elevated (RR 8.45 (2.55, 27.96)) triglycerides were at increased risk of disease recurrence compared to patients that achieved normalization. Patients with triglyceride measurement performed within 30 days from discharge were more likely to achieve normalization, 40 versus 26%, p = 0.03. CONCLUSIONS: For patients with hypertriglyceridemic pancreatitis, even modest elevation in subsequent triglyceride levels was associated with increased risk of recurrence. Future efforts should focus on ensuring timely care in the outpatient setting with a goal of normalizing triglycerides.

Impact of Integrated Health Care Delivery on Racial and Ethnic Disparities in Pancreatic Cancer.

OBJECTIVES: The objective of this study was to evaluate whether disparities in pancreatic cancer diagnosis, treatment, and survival are reduced in an integrated health system. METHODS: We conducted a retrospective study (2006-2014) among patients with pancreatic cancer from Kaiser Permanente Southern California. Racial ethnic groups included non-Hispanic whites (NHW), non-Hispanic blacks (NHB), Hispanics, and Asians. We used multivariable and Cox regression analyses to evaluate disparities in diagnosis and treatment utilization (oncology care, surgery, time to surgery, chemotherapy) and overall survival, respectively. RESULTS: Among 2103 patients, 54% were diagnosed with stage IV disease, 80% received oncology consultation, 20% received surgery with mean time to surgery 27 days (standard deviation, 36.8), 50.4% received chemotherapy. Mean overall survival was 8.6 months (standard deviation, 11.5). There were no differences in odds of stage IV diagnosis, oncology consultation, surgery, or time to surgery by racial ethnic group. Asians were more likely to receive chemotherapy (odds ratio, 1.59; 95% confidence interval [CI], 1.09-2.32) compared to NHW. NHB (hazard ratio, 0.78; 95% CI, 0.67-0.91) and Asians (hazard ratio, 0.81; 95% CI, 0.66-1.00) had improved survival compared to NHW. CONCLUSIONS: Minorities were not disadvantaged in pancreatic cancer care. Improved health care coordination may improve current disparities.

Effect of Serum Triglycerides on Clinical Outcomes in Acute Pancreatitis: Findings From a Regional Integrated Health Care System.

OBJECTIVES: The aim of this study was to evaluate the effect of serum triglycerides on the development of multiple or persistent organ failure in patients with acute pancreatitis. METHODS: A retrospective cohort study was conducted among patients hospitalized for acute pancreatitis between 2006 and 2013. Triglyceride levels measured before and within 72 hours of admission were compared. In addition, the effect of triglyceride levels on the development of multiple or persistent organ failure during hospitalization for acute pancreatitis was assessed. RESULTS: Among 2519 patients, 267 patients (10.6%) developed organ failure, of which 75 patients developed multiple system organ failure and 82 patients developed persistent organ failure. Triglyceride levels in patients who developed organ failure were initially much higher than in patients who did not develop organ failure, but by 72 hours into admission, approached levels of patients who did not develop organ failure. Approximately 8% of patients had triglyceride levels greater than 500 mg/dL, the majority of which had similarly high levels before admission. CONCLUSIONS: Increased triglyceride levels were associated with the development of multiple or persistent organ failure among patients hospitalized with acute pancreatitis. Patients with high triglyceride levels at the time of admission were likely to have high triglyceride levels before admission.

Influence of Statins and Cholesterol on Mortality Among Patients With Pancreatic Cancer.

Background: Recent studies have suggested associations between statins and enhanced survival among patients with pancreatic ductal adenocarcinoma (PDAC). However, the relationship between statins, cholesterol, and survival remains unclear. Methods: We conducted a retrospective cohort study on 2142 PDAC patients in a regional integrated healthcare system from 2006 to 2014. Electronic pharmacy records were used to abstract information on the type, length, and dosage of statin exposures starting in the year prior to diagnosis. The cumulative and individual effects of simvastatin, lovastatin, atorvastatin, pravastatin, and rosuvastatin on mortality were assessed using Cox proportional hazards regression. Statins were evaluated as any use (pre- and postdiagnosis as a time-dependent variable) and baseline use (prediagnosis only). We also evaluated whether low-density lipoprotein (LDL) cholesterol, measured at various time windows prior to diagnosis, had an independent influence on survival. Additional analyses were performed to examine whether cholesterol mediated the relationship between statins and mortality. All models included age, race, stage, surgery, gemcitabine-based chemotherapy, and the Charlson comorbidity index as covariates. Results: Any (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.79 to 0.97) and baseline (HR = 0.88, 95% CI = 0.79 to 0.98) statin use were both associated with a decreased risk in mortality. When assessing individual statins, we found reduced mortality among simvastatin (HR = 0.87, 95% CI = 0.77 to 0.98) and atorvastatin (HR = 0.58, 95% CI = 0.46 to 0.72) users. Cholesterol was not associated with mortality and did not mediate any relationships between statins and survival. Conclusions: Statin use rather than cholesterol level was associated with lower mortality risk in patients with pancreatic cancer. Statins appear to improve survival through a lipid-independent mechanism.

Racial and Ethnic Minorities at Increased Risk for Gastric Cancer in a Regional US Population Study.

BACKGROUND AND AIMS: Limited data are available on risk factors for gastric cancer in the United States. We aimed to characterize risk for gastric cancer based on race/ethnicity and additional established risk factors. METHODS: We conducted a retrospective cohort study from 2008 to 2014 from an integrated health care system in Southern California to assess incidence of gastric cancer by race/ethnicity. We then conducted an age- and sex-matched case-cohort study to evaluate additional risk factors: Helicobacter pylori infection, tobacco use, family history, obesity, language, and socioeconomic status. Subgroup analysis was performed for language and socioeconomic status by race/ethnicity. RESULTS: The incidence of gastric cancer in the reference (non-Hispanic white) population was 8.2 (95% confidence interval [CI], 7.7-8.7) cases per 100,000 person-years. Incidence values for Asians, Hispanics, and non-Hispanic black persons were higher: 12.7 (95% CI, 11.1-14.3), 12.7 (95% CI, 11.7-13.7), and 11.8 (95% CI, 10.3-13.2) cases per 100,000 person-years, respectively (all P < .0001). In logistic regression analysis, we found race/ethnicity to be an independent risk factor for gastric cancer; the odds ratio (OR) for non-Hispanic black persons was 1.5 (95% CI, 1.22-1.72; P < .0001), the OR for Hispanics was 1.4 (95% CI, 1.22-1.57; P < .0001), and the OR for Asians was 1.5 (95% CI, 1.28-1.81; P < .0001), compared with the non-Hispanic white population. Other independent risk factors included infection with H pylori (OR, 4.6; 95% CI, 3.8-5.7), smoking history (OR, 1.4; 95% CI, 1.3-1.6), and family history of gastric cancer (OR, 3.4; 95% CI, 2.6-4.4) (all P < .0001). Non-English language was a significant risk factor for gastric cancer in Asians (P = .05). Higher annual median income was associated with reduced risk (OR, 0.84; 95% CI, 0.75-0.95; P = .0004). CONCLUSIONS: In a population study in Southern California, we found racial/ethnic minorities to have a 40%-50% increase in risk of gastric cancer compared with the non-Hispanic white population. In addition to H pylori infection, smoking, family history, and low socioeconomic status were also associated with increased risk. Further characterization of high-risk groups may identify populations appropriate for targeted screening.

Risk of Gastric Cancer Among Patients With Intestinal Metaplasia of the Stomach in a US Integrated Health Care System.

BACKGROUND & AIMS: Gastric intestinal metaplasia (GIM) is a common finding from routine endoscopies. Although GIM is an early step in gastric carcinogenesis, there is controversy regarding routine surveillance of patients with GIM in regions with a low prevalence of gastric cancer. We aimed to determine the incidence of gastric cancer among patients with GIM and risk factors for gastric cancer. METHODS: We performed a retrospective cohort study of patients from the Kaiser Permanente Southern California region diagnosed with GIM from 2000 through 2011. GIM was identified by a keyword search of pathology reports; gastric cancer cases were identified by cross-reference with an internal cancer registry. The incidence of gastric cancer in patients with GIM (n = 923; median age at diagnosis, 68 y) was compared with that of an age- and sex-matched reference population (controls). Risk factors such as ethnicity, smoking status, history of Helicobacter pylori infection, and family history of gastric cancer were evaluated by individual Cox proportional hazards regression. We then performed a second case-cohort study to evaluate the risk of gastric cancer based on the location and extent of GIM. The median duration of follow-up evaluation was 4.6 years (interquartile range, 3.0-6.7 y). RESULTS: We identified 25 patients with GIM who developed gastric cancers. Seventeen cases of cancer were diagnosed at the same time as the diagnosis of GIM. Eight cases of cancer were identified within a median time period of 4.6 years after a diagnosis of GIM (interquartile range, 2-5.7 y). The overall incidence rate for the cohort was 1.72 (95% confidence interval, 0.74-3.39). Among the risk factors evaluated, only family history (hazard ratio, 3.8; 95% confidence interval, 1.5-9.7; P = .012) and extent of GIM (odds ratio, 9.4; 95% confidence interval, 1.8-50.4) increased the risk for gastric cancer. The incidence rate for gastric cancer in patients with a positive family history was 8.12 (95% confidence interval, 1.67-23.73). CONCLUSIONS: In an analysis of patients with GIM listed in the Kaiser Permanente Southern California database, 2.7% were diagnosed with gastric cancer; almost 70% of cases of gastric cancer were detected at the time of GIM diagnosis. Family history and extensive metaplasia were associated with an increased risk of subsequent gastric cancer. Targeted surveillance of patients with these criteria could increase early detection of gastric cancer.

Impact of statin use on survival in patients undergoing resection for early-stage pancreatic cancer.

OBJECTIVES: It has been suggested that statins exert potential anti-tumor effects. The relationship between statin use and outcomes in pancreatic cancer is controversial. We hypothesized that statin use at baseline would impact survival among patients with early-stage pancreatic cancer and that the effect might vary by individual statin agent. METHODS: We conducted a retrospective cohort study on data from an integrated healthcare system. We included patients with pancreatic cancer stage I-IIb who underwent resection for curative intent between January 2005 and January 2011. Baseline statin use was characterized as any prior use as well as active use of either simvastatin or lovastatin. Intensity of exposure was calculated as average daily dose prior to surgery. Overall and disease-free survival was assessed from surgery until the end of study (April 2014). We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the impact of baseline statin use on survival, adjusting for age, sex, Charlson comorbidity score, resection margin, disease stage, and receipt of adjuvant chemotherapy. RESULTS: Among 226 patients, 71 (31.4%) had prior simvastatin use and 27 (11.9%) had prior lovastatin use at baseline. Prior simvastatin but not lovastatin use was associated with improved survival (median 28.5 months (95% confidence limit (CL) 20.8, 38.4) for simvastatin vs. 12.9 months (9.6, 15.5) for lovastatin vs. 16.5 months (14.1, 18.9) for non-statin users; log-rank P=0.0035). In Cox regression, active simvastatin use was independently associated with reduced risk for mortality (adjusted hazard ratio (HR) 0.56 (95% CL 0.38, 0.83), P=0.004) and risk for recurrence (adjusted HR 0.61 (0.41, 0.89), P=0.01). Survival improved significantly among patients who received moderate-high-intensity (median 42.1 months (24.0,52.7)) doses compared with those who received low-intensity doses of simvastatin (median 14.1 months (8.6, 23.8), log-rank P=0.03). CONCLUSIONS: The effects of statins varied by agent and dose. Active use of moderate-high-dose simvastatin at baseline was associated with improved overall and disease-free survival among patients undergoing resection for pancreatic cancer.

Simvastatin is associated with reduced risk of acute pancreatitis: findings from a regional integrated healthcare system.

OBJECTIVE: To characterise the relationship between simvastatin and risk of acute pancreatitis (AP). DESIGN: We conducted a retrospective cohort study (2006-2012) on data from an integrated healthcare system in southern California. Exposure to simvastatin was calculated from time of initial dispensation until 60 days following prescription termination. AP cases were defined by ICD-9 CM 577.0 and serum lipase≥3 times normal. Patients were censored at death, last follow-up, and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin users was compared with the adult reference population. Robust Poisson regression was used to generate risk ratio (RR) estimates for simvastatin use adjusted for age, gender, race/ethnicity, gallstone-related disorders, hypertriglyceridaemia, smoking and alcohol dependence. Analysis was repeated for atorvastatin. RESULTS: Among 3,967,859 adult patients (median duration of follow-up of 3.4 years), 6399 developed an initial episode of AP. A total of 707,236 patients received simvastatin during the study period. Patients that received simvastatin were more likely to have gallstone-related disorders, alcohol dependence or hypertriglyceridaemia compared with the reference population. Nevertheless, risk of AP was significantly reduced with simvastatin use, crude incidence rate ratio 0.626 (95% CL 0.588, 0.668), p<0.0001. In multivariate analysis, simvastatin was independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95% CL 0.27, 0.31) after adjusting for age, gender, race/ethnicity, gallstone disorders, alcohol dependence, smoking and hypertriglyceridaemia. Similar results were noted with atorvastatin, adjusted RR 0.33(0.29, 0.38). CONCLUSIONS: Use of simvastatin was independently associated with reduced risk of AP in this integrated healthcare setting. Similar findings for atorvastatin suggest a possible class effect.

Surveillance colonoscopy in elderly patients: a retrospective cohort study.

IMPORTANCE: The risks and benefits of surveillance colonoscopy in elderly patients have not been well characterized. OBJECTIVE: To investigate the relative impact of surveillance colonoscopy in elderly patients compared with a reference cohort. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study from 2001 through 2010 of patients 50 years and older undergoing surveillance colonoscopy for a history of colorectal cancer (CRC) or adenomatous polyps at an integrated health care system in southern California. Patients were followed up from the surveillance examination until CRC diagnosis, death, disenrollment, IBD diagnosis, or study end date (December 31, 2010). MAIN OUTCOMES AND MEASURES: The primary outcome measure was incidence of CRC detected following surveillance colonoscopy. The secondary outcome was risk of procedure defined as postprocedure hospitalization within 30 days. Cox regression and multivariable logistic regression analyses were used to determine the impact of age on CRC incidence on surveillance examination as well as postprocedure hospitalization, respectively. RESULTS: The study cohort included 4834 elderly patients (age ≥75 years; 55.8% male) (median surveillance age, 79 years) and 22 929 individuals in the reference group (age 50-74 years; 57.7% male) (median surveillance age, 63 years). A total of 373 cancers were detected following surveillance colonoscopy (368 in the reference group and 5 among the elderly patients). There were a total of 711 postprocedure hospitalizations (184 in the reference group and 527 among the elderly patients). The CRC incidence among elderly patients undergoing surveillance was 0.24 per 1000 person-years vs 3.61 per 1000 person-years in the reference population (P < .001). In Cox regression analysis, the hazard ratio for CRC in the elderly patients compared with the reference group was 0.06 (95% CI, 0.02-0.13) (P < .001) after adjusting for comorbid illness, sex, and race/ethnicity. In logistic regression analysis, age 75 years and older was independently associated with increased risk of postprocedure hospitalization (adjusted odds ratio, 1.28 [95% CI, 1.07-1.53]; P = .006). Charlson score of 2 was also independently associated with increased risk of postprocedure hospitalization (adjusted odds ratio, 2.54 [95% CI, 2.06-3.14]; P < .001). CONCLUSIONS AND RELEVANCE: A low incidence of CRC and relatively high rate of postprocedure hospitalization were found among elderly patients undergoing surveillance colonoscopy. Recommendations for ongoing surveillance in the elderly population should take into consideration the impact of comorbid illness and increasing age on the anticipated risks and benefits of colonoscopy.