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Recruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such preemptive and detailed planning can help prospective, longitudinal studies focusing on exocrine and endocrine complications of AP in accurately measuring outcomes. This manuscript highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly attributed to late diagnosis. We assessed the predictive performance of our previously reported urine biomarker panel for earlier detection of PDAC (LYVE1, REG1B and TFF1) in prediagnostic samples, alone and in combination with plasma CA19-9. This nested case-control study included 99 PDAC cases with urine samples prospectively collected up to 5 years prior to PDAC diagnosis and 198 matched controls. The samples were obtained from the Shanghai Women's Health Study (SWHS), the Shanghai Men's Health Studies (SMHS) and the Southern Community Cohort Study (SCCS). The urine biomarkers were measured by ELISA. Plasma CA19-9 was quantified by Luminex. Multiple logistic regression and Wilcoxon rank-sum and Mann-Whitney test were used for analysis. The internal validation approach was applied and the validated AUC estimators are reported on. The algorithm of urinary protein panel, urine creatinine and age named PancRISK, displayed similar AUC as CA19-9 up to 1 year before PDAC diagnosis (AUC = 0.79); however, the combination enhanced the AUCs to 0.89, and showed good discriminative ability (AUC = 0.77) up to 2 years. The combination showed sensitivity (SN) of 72% at 90% specificity (SP), and SP of 59% at 90% SN up to 1 year and 60% SN with 80% SP and 53% SP with 80% SN up to 2 years before PDAC diagnosis. Adding the clinical information on BMI value resulted in the overall improvement in performance of the PancRISK score. When combined with CA19-9, the urinary panel reached a workable model for detecting PDAC cases up to 2 years prior to diagnosis.

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Gastric carcinoma (GC) disproportionately affects Asian Americans. We examined whether history of upper gastrointestinal (GI) endoscopy was associated with lower stage at GC diagnosis among Asian Americans and whether origin of providers influenced referral for endoscopy. We employed Surveillance Epidemiology and End Results–Medicare data on Asian Americans diagnosed with GC in 2004–2013 (n = 1,554). Stage distribution, GI conditions at diagnosis, and history of endoscopy were compared between Asian ethnic groups. Multivariate logistic regression adjusting for age, sex, poverty level, tumor location, and histology was used to examine the association of ethnicity and endoscopic history with stage I disease at diagnosis of GC. Koreans were more likely to be diagnosed with stage I, T1a GC and have prior history of endoscopy, compared with other Asian ethnicities (24% vs. 8% for stage I, T1a; 40% vs. 15% for endoscopy). Patients with primary care providers of concordant ethnic origin were more likely to have history of endoscopy. Asian American patients with GC with history of endoscopy were more likely to be diagnosed with GC at stage I disease (adjusted OR, 3.07; 95% confidence interval, 2.34–4.02). Compared with other Asian Americans, Koreans were diagnosed with GC at earlier stages owing to common history of endoscopy, which was more often undergone by patients with primary care providers of concordant ethnic origin. Overall, upper GI endoscopy was associated with early detection of GC in Asian Americans. Novelty and Impact. It is well-established that Asian Americans in the United States are disproportionately affected by gastric cancer. In our study we found that Asian American patients treated by physicians of similar ethnic background are more likely to undergo upper GI endoscopy in the United States, leading to early detection of gastric cancer and longer survival. Given this, targeted endoscopic screening in Asian Americans should be considered for early detection of GC.

Selection of Medicare patients diagnosed with hepatocellular carcinoma for investigation of the association of statin use and survival

Procedure and diagnosis codes used to extract data on factors related to hepatocellular carcinoma prognosis

Background: Limited clinical and epidemiologic data suggest that statins may improve the outcomes of hepatocellular carcinoma (HCC), which has poor prognosis.Methods: We identified 1,036 stage I or II HCC patients, diagnosed between 2007 and 2009, through the linked Surveillance, Epidemiology, and End Results (SEER) Program and Medicare claims database. Of these, 363 patients were using statin either at the time of their HCC diagnosis or afterwards. We conducted multivariable Cox regression analysis to estimate the time-dependent effect of statin on survival. The analysis included age, sex, resection, transarterial chemoembolization, transplantation, cirrhosis, cardiovascular disease, diabetes, dyslipidemia, and hepatitis B and C.Results: Over a median follow-up time of 21 months, 584 HCC patients died. Statin users had a longer median survival compared with nonusers: 23.9 versus 18.9 months (P = 0.047). However, after accounting for immortal time bias and confounding, statin use was not associated with survival (HR, 0.98; 95% confidence interval, 0.80–1.20). The associations did not vary by hepatitis C or intensity of statin use.Conclusion: Statin treatment after HCC diagnosis was not associated with survival in elderly patients with stage I/II disease.Impact: Our study of nationally representative elderly patients with stage I or II HCC in the United States shows that statin treatment does not improve survival with liver cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 686–92. ©2016 AACR.

BACKGROUND/OBJECTIVES: Black Americans are at increased risk of chronic pancreatitis (CP) compared to their White counterparts. We aimed to describe the race-specific smoking history and lifetime drinking in patients diagnosed with CP. METHODS: We analyzed data on 334 Black and White CP participants of the North American Pancreatitis Study 2 Continuation and Validation Study and Ancillary Study. Lifetime drinking history and lifetime smoking history were collected through in-person interviews. Intensity, frequency, duration and current status of drinking and smoking were compared between Black and White CP participants, stratified by physician-defined alcohol etiology. In addition, drinking levels at each successive decades in life (20s, 30s, 40s) were compared by race and graphically portrayed as heat diagrams. RESULTS: Among patients with alcoholic CP, current smoking levels were not different by race (67-70%), but a smaller proportion of Black patients reported having smoked 1 or more packs per day in the past (32%) as compared to White patients (58%, p

Acute pancreatitis (AP), an acute inflammatory disorder of the exocrine pancreas, is one of the most common gastrointestinal diseases encountered in emergency departments with no specific treatments. Laboratory-based research has formed the cornerstone of endeavours to decipher the pathophysiology of AP, because of the limitations of such study in human beings. While this has provided us with substantial understanding, we cannot answer several pressing questions. These are: (a) Why is it that only a minority of individuals with gallstones, or who drink alcohol excessively, or are exposed to other causative factors develop AP? (b) Why do only some develop more severe manifestations of AP with necrosis and/or organ failure? (c) Why have we been unable to find an effective therapeutic for AP? This manuscript provides a state-of-the-art review of our current understanding of the pathophysiology of AP providing insights into the unanswered clinical questions. We describe multiple protective factors operating in most people, and multiple stressors that in a minority induce AP, independently or together, via amplification loops. We present testable hypotheses aimed at halting progression of severity for the development of effective treatments for this common unpredictable disease.

Gastric carcinoma (GC) disproportionately affects Asian Americans. We examined whether history of upper gastrointestinal (GI) endoscopy was associated with lower stage at GC diagnosis among Asian Americans and whether origin of providers influenced referral for endoscopy. We employed Surveillance Epidemiology and End Results–Medicare data on Asian Americans diagnosed with GC in 2004–2013 (n = 1,554). Stage distribution, GI conditions at diagnosis, and history of endoscopy were compared between Asian ethnic groups. Multivariate logistic regression adjusting for age, sex, poverty level, tumor location, and histology was used to examine the association of ethnicity and endoscopic history with stage I disease at diagnosis of GC. Koreans were more likely to be diagnosed with stage I, T1a GC and have prior history of endoscopy, compared with other Asian ethnicities (24% vs. 8% for stage I, T1a; 40% vs. 15% for endoscopy). Patients with primary care providers of concordant ethnic origin were more likely to have history of endoscopy. Asian American patients with GC with history of endoscopy were more likely to be diagnosed with GC at stage I disease (adjusted OR, 3.07; 95% confidence interval, 2.34–4.02). Compared with other Asian Americans, Koreans were diagnosed with GC at earlier stages owing to common history of endoscopy, which was more often undergone by patients with primary care providers of concordant ethnic origin. Overall, upper GI endoscopy was associated with early detection of GC in Asian Americans. Novelty and Impact. It is well-established that Asian Americans in the United States are disproportionately affected by gastric cancer. In our study we found that Asian American patients treated by physicians of similar ethnic background are more likely to undergo upper GI endoscopy in the United States, leading to early detection of gastric cancer and longer survival. Given this, targeted endoscopic screening in Asian Americans should be considered for early detection of GC.

OBJECTIVESThere is currently no widely accepted approach to screening for pancreatic cancer (PC). We aimed to develop and validate a risk prediction model for PC across two health systems using electronic health records (EHR).METHODSThis retrospective cohort study consisted of patients 50-84 years of age meeting utilization criteria in 2008-2017 at Kaiser Permanente Southern California (KPSC, model training, internal validation) and the Veterans Affairs (VA, external validation). ‘Random survival forests’ models were built to identify the most relevant predictors from >500 variables and to predict PC within 18 months of cohort entry. A prospective study was then conducted in KPSC to assess feasibility of the model for real-time implementation.RESULTSThe KPSC cohort consisted of 1.8 million patients (mean age 61.6) with 1,792 PC cases. The estimated 18-month incidence rate of PC was 0.77 (95% CI 0.73-0.80)/1,000 person-years. The three models containing age, abdominal pain, weight change and two laboratory biomarkers (ALT change/HgA1c, rate of ALT change/HgA1c, or rate of ALT change/rate of HgA1c change) had comparable discrimination and calibration measures (c-index: mean=0.77, SD=0.01-0.02; calibration test: p-value 0.2-0.4, SD 0.2-0.3). The VA validation cohort consisted of 2.6 million patients (mean age 66.1) with an 18-month incidence rate of 1.27 (1.23-1.30). A total of 606 patients were screened in the prospective pilot study at KPSC with 9 patients (1.5%) diagnosed with a pancreatic or biliary cancer.CONCLUSIONSUsing widely available parameters in EHR, we developed a population-based parsimonious model for early detection of sporadic PC suitable for real-time application.Study HighlightsWhat Is KnownPatients with pancreatic cancer are often diagnosed at late stages.Early detection is needed to impact the natural history of disease progression and improve patient survival.What Is New HereMachine-learning was used to develop a population-based model for early detection of pancreatic cancer. The model was internally and externally validated in cohorts of 1.8 million and 2.6 million individuals, respectively.Calibration was excellent in prospective pilot testing for detection of pancreatic malignancy.

There is currently no widely accepted approach to screening for pancreatic cancer (PC). We aimed to develop and validate a risk prediction model for pancreatic ductal adenocarcinoma (PDAC), the most common form of PC, across 2 health systems using electronic health records.This retrospective cohort study consisted of patients aged 50-84 years having at least 1 clinic-based visit over a 10-year study period at Kaiser Permanente Southern California (model training, internal validation) and the Veterans Affairs (VA, external testing). Random survival forests models were built to identify the most relevant predictors from500 variables and to predict risk of PDAC within 18 months of cohort entry.The Kaiser Permanente Southern California cohort consisted of 1.8 million patients (mean age 61.6) with 1,792 PDAC cases. The 18-month incidence rate of PDAC was 0.77 (95% confidence interval 0.73-0.80)/1,000 person-years. The final main model contained age, abdominal pain, weight change, HbA1c, and alanine transaminase change (c-index: mean = 0.77, SD = 0.02; calibration test: P value 0.4, SD 0.3). The final early detection model comprised the same features as those selected by the main model except for abdominal pain (c-index: 0.77 and SD 0.4; calibration test: P value 0.3 and SD 0.3). The VA testing cohort consisted of 2.7 million patients (mean age 66.1) with an 18-month incidence rate of 1.27 (1.23-1.30)/1,000 person-years. The recalibrated main and early detection models based on VA testing data sets achieved a mean c-index of 0.71 (SD 0.002) and 0.68 (SD 0.003), respectively.Using widely available parameters in electronic health records, we developed and externally validated parsimonious machine learning-based models for detection of PC. These models may be suitable for real-time clinical application.

Background: Worsening glycemic control indicates elevated risk of pancreatic ductal adenocarcinoma (PDAC). We developed prediction models for PDAC among those with worsening glycemic control after diabetes diagnosis. Methods: In 2000–2016 records within the Veterans Affairs Health System (VA), we identified three cohorts with progression of diabetes: (i) insulin initiation (n = 449,685), (ii) initiation of combination oral hypoglycemic medication (n = 414,460), and (iii) hemoglobin A1c (HbA1c) ≥8% with ≥Δ1% within 15 months (n = 593,401). We computed 12-, 36-, and 60-month incidence of PDAC and developed prediction models separately for males and females, with consideration of >30 demographic, behavioral, clinical, and laboratory variables. Models were selected to optimize Akaike's Information Criterion, and performance for predicting 12-, 36-, and 60-month incident PDAC was evaluated by bootstrap. Results: Incidence of PDAC was highest for insulin initiators and greater in males than in females. Optimism-corrected c-indices of the models for predicting 36-month incidence of PDAC in the male population were: (i) 0.72, (ii) 0.70, and (iii) 0.71, respectively. Models performed better for predicting 12-month incident PDAC [c-index (i) 0.78, (ii) 0.73, (iii) 0.76 for males], and worse for predicting 60-month incident PDAC [c-index (i) 0.69, (ii) 0.67, (iii) 0.68 for males]. Model performance was lower among females. For subjects whose model-predicted 36-month PDAC risks were ≥1%, the observed incidences were (i) 1.9%, (ii) 2.2%, and (iii) 1.8%. Conclusions: Sex-specific models for PDAC can estimate risk of PDAC at the time of progression of diabetes. Impact: Our models can identify diabetes patients who would benefit from PDAC screening.

Background: Endoscopy of the upper gastrointestinal tract is an effective way to screen for gastric cancer (GC) and benefits of screening are evident in countries that have implemented nationwide screening. Despite being disproportionately affected by GC, Asian Americans lack knowledge of GC risk factors and resources to make informed decision on GC screening. Experts recommend shared decision making between providers and patients regarding endoscopy for GC screening. However, we lack decision support tools for providers and patients at high risk for GC. Objective: This qualitative study aims to 1) explore patient experiences and perspectives on GC screening with endoscopy on concepts such as perceived GC risk, risk factors, early detection methods, and healthcare navigation, 2) explore provider knowledge, beliefs, and practice patterns regarding GC screening and GC prevention, and 3) develop a decision aid to support shared decision making for GC screening in the Asian American population. Methods: We interviewed primary care providers [PCP] and gastroenterologists in medical networks in Southern California that primarily serve Asian American communities, and patient populations in these medical networks with an initial focus on Korean and Vietnamese Americans who face the highest risk of GC among Asian Americans. Qualitative data was collected using one-on-one interviews with patients and providers. The interview was then transcribed and coded following reflexive thematic analysis. Results: To date, we have interviewed 6 patients and 5 providers and data collection continues. Several key themes were identified during the interviews: Among patients there is a lack of understanding of Helicobacter pylori (H. pylori) as a risk factor for GC, while dietary factors were frequently perceived as risk factors. Providers found GC screening to be beneficial for Korean and Vietnamese populations, and recommended GC screening simultaneous to screening colonoscopy, to reduce patient burden and cost. Patients who had experience with upper endoscopy found it to be acceptable. On the other hand, patients’ desired costs for upper endoscopy were much lower than market out-of-pocket costs of endoscopy. A preliminary decision aid was developed and edited in response to the results. The decision aid presents educational information including risk of GC in Korean and Vietnamese American relative to the general U.S. population, risk factors of GC, GC screening procedures, and risks and benefits of screening. The decision aid offers opportunity to assess personal attitudes towards GC screening, and allows for patients to indicate their intentions for GC screening for discussion with their providers. The decision aid will be further refined with additional qualitative data. Conclusion: Perceptions towards GC screening is generally positive among Asian patients and providers, but the costs of screening are a concern. Patients need education on H. pylori as a risk factor for GC. Citation Format: Simon Kim, Christie Y. Jeon, Celina Shirazipour. Perceptions of gastric cancer screening in Asian Americans [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B049.

Aims Cumulative consumption of alcohol and variations of alcohol intake by age are unknown in chronic pancreatitis (CP) patients in North America. This study summarizes the lifetime drinking history (LDH) by physician attribution of alcohol etiology, smoking status and sex in persons with CP. Methods We analyzed data on 193 CP participants who completed the LDH questionnaire in the North American Pancreatitis Continuation and Validation Study (NAPS2-CV). We collected data on frequency of drinking and drinks per drinking day for each drinking phase of their lives. We examined differences in total number of alcoholic drinks and weight of ethanol consumed by physician’s assessment of CP etiology, sex and smoking status. We also compared intensity of drinking in 20, 30 and 40s by timing of CP diagnosis. Results Persons diagnosed with alcoholic CP consumed median of 34,488 drinks (interquartile range 18,240–75,024) prior to diagnosis of CP, which occurred earlier than in persons with CP of other etiology (47 vs. 52 years). Cumulative drinking was greater in male vs. female patients. Male CP patients with a diagnosis of CP before the age of 45 drank more intensely in their 20s as compared to those with later onset of disease. Current smoking was prevalent (67%) among those diagnosed with alcoholic CP. Twenty-eight percent of patients without physician attribution of alcohol etiology reported drinking heavily in the past. Conclusions Lifetime cumulative consumption of alcohol and prevalence of current smoking are high in persons diagnosed with alcoholic pancreatitis. Intense drinking in early years is associated with earlier manifestation of the disease.

BACKGROUND/OBJECTIVE: Smoking prevalence in patients with chronic pancreatitis [CP] is high. We aimed to understand lifetime history of smoking and cohort trends in CP patients to inform effective strategies for smoking cessation. METHOD: Data on 317 CP patients from the North American Pancreatitis Study 2 [NAPS2] Continuation and Validation Study and the NAPS2 Ancillary Study were analyzed. Smoking history was assessed for each phase of life from the onset of smoking to study enrollment. Data on second-hand smoke and drinking history were also collected. We compared demographic factors, drinking history, pain level and pancreas morphology by smoking status at age 25 (non-smoking

Background/Objectives Alcohol is the most common etiology of recurrent acute pancreatitis and chronic pancreatitis. The extent and timing of drinking that increases the transient risk of acute pancreatitis is yet unknown. Methods We designed a case-crossover study to determine the effective hazard period of drinking in relation to episodes of pancreatitis. We aim to evaluate the dose-response relationship between excess drinking and pancreatitis comparing the extent of drinking during case and control periods from the same individual. We aim to recruit 160 patients hospitalized with acute pancreatitis, whose AUDIT-C score reaches 3 or higher. Interviews of each enrolled patient to define their 15-day history of alcohol consumption employing the timeline follow-back method. Long-term drinking and smoking will be investigated as modifiers of the impact of short-term excess drinking. Patients are followed-up for evaluation of usual alcohol consumption during asymptomatic periods following the index hospitalization. Blood and urine specimens are collected while the patients are hospitalized and during a standard-of-care follow-up visit. Results We have recruited 31 patients to date, with a median age of 33 years. Females and non-White participants make up 26% and 35% of the enrolled population, respectively. Forty-eight % of patients have had a prior history of acute pancreatitis. Conclusions Our study will shed light on the impact of short-term changes in drinking on triggering acute pancreatitis. It will provide data on other covarying factors of drinking and behaviors changes after acute pancreatitis.

Objectives Abnormalities of the main pancreatic duct may be an early indicator of pancreatic ductal adenocarcinoma (PDAC). We develop and validate algorithms that predict the risk of PDAC using features identified on cross-sectional imaging and other clinical characteristics collected through electronic medical records. Methods Adult patients with abdominal computed tomography or magnetic resonance imaging in January 2006 to June 2016 demonstrating dilatation of main pancreatic duct were identified. Pancreas-related morphologic features were extracted from radiology reports using natural language processing. The cumulative incidence of PDAC with death as a competing risk was estimated using multistate models. Model discrimination was assessed using c-index. The models were internally validated using bootstrapping. Results The cohort consisted of 7819 patients (mean age, 71 years; 65% female). A total of 781 patients (10%) developed PDAC within 3 years after the first eligible imaging study. The final models achieved reasonable discrimination (c-index, 0.825-0.833). The 3-year average risk of PDAC in the top 5% of the total eligible patients was 56.0%, more than 20 times of the average risk among the bottom 50% of patients. Conclusions Prediction models combining imaging features and clinical measures can be used to further stratify the risk of pancreatic cancer among patients with pancreas ductal dilatation.

Pancreatic ductal adenocarcinoma is most frequently detected at an advanced stage. Such late detection restricts treatment options and contributes to a dismal 5-year survival rate of 3-15%. Pancreatic ductal adenocarcinoma is relatively uncommon and screening of the asymptomatic adult population is not feasible or recommended with current modalities. However, screening of individuals in high-risk groups is recommended. Here, we review groups at high risk for pancreatic ductal adenocarcinoma, including individuals with inherited predisposition and patients with pancreatic cystic lesions. We discuss studies aimed at finding ways of identifying pancreatic ductal adenocarcinoma in high-risk groups, such as among individuals with new-onset diabetes mellitus and people attending primary and secondary care practices with symptoms that suggest this cancer. We review early detection biomarkers, explore the potential of using social media for detection, appraise prediction models developed using electronic health records and research data, and examine the application of artificial intelligence to medical imaging for the purposes of early detection.

PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and translational stuDies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis in the US. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in chronic pancreatitis. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of chronic pancreatitis - controls, Suspected chronic pancreatitis and Definite chronic pancreatitis. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium to study Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC) are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of chronic pancreatitis. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of chronic pancreatitis.

Background: People with new-onset diabetes face higher risk of pancreatic cancer (PC). However, data on PC risk in people with more advanced stages of diabetes are lacking. We aimed to identify factors associated with PC among people with progressing diabetes. Methods: We conducted a retrospective cohort study on veterans aged ≥50, who were treated with either combination oral hypoglycemic therapy (n=578,543) or insulin (n=609,687) at the VA in 2000-2016. Incident PC was determined through the electronic health records and cancer registries. We examined the association of multiple risk factors with PC using Cox regression analyses. Results: In both people initiating combination therapy and in those initiating insulin, increasing age, male sex, non-Hispanic ancestry, current smoking, acute and chronic pancreatitis, abdominal pain, alcoholism, increase in A1c, and decrease in weight were associated with increased risk of PC (Table). Based on the multivariable model, we can identify sub-populations with ≥5% risk of PC, such as ≥75 year-old non-Hispanic white males initiating insulin who have a history of alcoholism, and who show ≥2% increase in A1c and ≥15% decrease in weight prior to insulin initiation. Conclusion: We identified risk factors associated with PC among people initiating combination oral hypoglycemics or insulin, which may be useful for stratifying people who may benefit from screening for PC. Disclosure C.Y. Jeon: None. M.O. Goodarzi: None. Y. Lin: None. S. Kim: None. T. Moin: None. J.R. Pisegna: None. Funding National Cancer Institute (R21CA220073)

Author(s): Baecker, Aileen; Kim, Sungjin; Risch, Harvey A; Nuckols, Teryl K; Wu, Bechien U; Hendifar, Andrew E; Pandol, Stephen J; Pisegna, Joseph R; Jeon, Christie Y | Abstract: Background and objectiveEarly detection methods for pancreatic cancer are lacking. We aimed to develop a prediction model for pancreatic cancer based on changes in health captured by healthcare claims data.MethodsWe conducted a case-control study on 29,646 Medicare-enrolled patients aged 68 years and above with pancreatic ductal adenocarcinoma (PDAC) reported to the Surveillance Epidemiology an End Results (SEER) tumor registries program in 2004-2011 and 88,938 age and sex-matched controls. We developed a prediction model using multivariable logistic regression on Medicare claims for 16 risk factors and pre-diagnostic symptoms of PDAC present within 15 months prior to PDAC diagnosis. Claims within 3 months of PDAC diagnosis were excluded in sensitivity analyses. We evaluated the discriminatory power of the model with the area under the receiver operating curve (AUC) and performed cross-validation by bootstrapping.ResultsThe prediction model on all cases and controls reached AUC of 0.68. Excluding the final 3 months of claims lowered the AUC to 0.58. Among new-onset diabetes patients, the prediction model reached AUC of 0.73, which decreased to 0.63 when claims from the final 3 months were excluded. Performance measures of the prediction models was confirmed by internal validation using the bootstrap method.ConclusionModels based on healthcare claims for clinical risk factors, symptoms and signs of pancreatic cancer are limited in classifying those who go on to diagnosis of pancreatic cancer and those who do not, especially when excluding claims that immediately precede the diagnosis of PDAC.

Background: Limited clinical and epidemiologic data suggest that statins may improve the outcomes of hepatocellular carcinoma (HCC), which has poor prognosis. Methods: We identified 1,036 stage I or II HCC patients, diagnosed between 2007 and 2009, through the linked Surveillance, Epidemiology, and End Results (SEER) Program and Medicare claims database. Of these, 363 patients were using statin either at the time of their HCC diagnosis or afterwards. We conducted multivariable Cox regression analysis to estimate the time-dependent effect of statin on survival. The analysis included age, sex, resection, transarterial chemoembolization, transplantation, cirrhosis, cardiovascular disease, diabetes, dyslipidemia, and hepatitis B and C. Results: Over a median follow-up time of 21 months, 584 HCC patients died. Statin users had a longer median survival compared with nonusers: 23.9 versus 18.9 months (P = 0.047). However, after accounting for immortal time bias and confounding, statin use was not associated with survival (HR, 0.98; 95% confidence interval, 0.80–1.20). The associations did not vary by hepatitis C or intensity of statin use. Conclusion: Statin treatment after HCC diagnosis was not associated with survival in elderly patients with stage I/II disease. Impact: Our study of nationally representative elderly patients with stage I or II HCC in the United States shows that statin treatment does not improve survival with liver cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 686–92. ©2016 AACR.

Objectives Both in vitro and clinical trial data suggest that cardiac glycosides demonstrate a synergistic anti-tumor effect when administered with platinum chemotherapy. Epidemiologic studies have also demonstrated improved cancer survival in colorectal, breast, head and neck and hepatocellular carcinoma patients on digoxin therapy at the time of cancer treatment. We sought to determine whether digoxin improves survival in epithelial ovarian cancer patients treated with platinum. Methods Surveillance, Epidemiology and End-Results (SEER) tumor registries program data on ovarian cancer patients diagnosed in 2007–2009 were linked to Medicare claims data to capture platinum administration, digoxin use and cardiac comorbidities. We analyzed 762 patients who underwent cancer-directed surgery and received platinum chemotherapy. Patients were considered digoxin users during platinum administration if a prescription was filled within 6months of cancer diagnosis. Cox proportional hazards regression models were used to determine the impact of digoxin use on overall survival (OS). Results Among 762 epithelial ovarian cancer patients treated with surgery and platinum chemotherapy, 53 (7%) used digoxin ever and 38 (5%) used digoxin specifically during platinum administration. Adjusting for age, heart disease and Charlson comorbidity score, digoxin use was not associated with OS (HR=1.29, 95% CI 0.81, 2.06). Conclusions In this SEER-Medicare database analysis, digoxin use during chemotherapy was not associated with improved OS outcomes in patients with epithelial ovarian cancer treated with surgery and platinum chemotherapy. These conclusions are limited, however, by a small sample size and bias intrinsic to claims-based data and should be further evaluated in a larger cohort.

Aims To provide updated systematic and quantitative summary of the association between depression and the risk of CVD events among individuals with type 2 diabetes. We also aimed to examine the sensitivity of the association to uncontrolled confounding. Methods Data sources included Medline, Embase, and PsycInfo through September 2019. Two independent reviewers selected cohort studies that evaluated the association between depression and fatal or non-fatal CVD events among individuals with type 2 diabetes. Bias analysis was performed using the bias formula approach. Results Of 2527 citations screened, 17 eligible studies with a total of 1,033,131 participants were identified. Based on random-effects meta-analysis, depression was associated with higher risks of non-fatal CVD events (relative risk 1.35, 95% confidence interval [CI] 1.20 to 1.53) and fatal CVD event (relative risk 1.47, 95% CI 1.21 to 1.77). Bias analysis indicated that unmeasured confounders alone may not explain the observed association between depression and CVD events among individuals with type 2 diabetes. Conclusions Depression was associated with a higher risk of non-fatal and fatal CVD events among individuals with type 2 diabetes. Our findings provide updated and robust evidence about the association between depression and CVD events among individuals with type 2 diabetes., Highlights • This meta-analysis includes 1,033,131 patients with type 2 diabetes from 17 studies. • We found the association between depression and increased risk of both fatal and non-fatal CVD events. • Our bias analysis indicates that the observed association is unlikely to be entirely due to uncontrolled confounding. • Further investigations are needed to validate our findings and evaluate the effectiveness of mental health management.

Background & Aims Observational studies of predominantly white populations have found new-onset diabetes to be associated with increased risk of pancreatic cancer. We sought to determine whether this relationship applies to other races or ethnicities and to identify metabolic profiles associated with increased risk of pancreatic cancer. Methods We conducted a population-based cohort study of Asian, black, Hispanic and white patients from Kaiser Permanente Southern California from 2006 through 2016 (n = 1,499,627). Patients with diabetes were identified based on glucose and hemoglobin A1c (HbA1c) measurements. We used Cox regression to assess the relationship between diabetes status and duration and pancreatic cancer. For patients with recent diagnoses of diabetes (1 year or less) we compared longitudinal changes in glucose, HbA1c, and weight, from time of diabetes diagnosis through 3 years prior to the diagnosis, in patients with vs without pancreatic cancer. Results We identified 2,002 incident cases of pancreatic cancer from nearly 7.5 million person-years of follow-up. Compared to patients without diabetes, individuals who received a recent diagnosis of diabetes had an almost 7-fold increase in risk of pancreatic cancer (relative risk, 6.91; 95% CI, 5.76–8.30). Among patients with a recent diagnosis of diabetes, those who developed pancreatic cancer had more rapid increases in levels of glucose (Δslope: cases, 37.47 mg/dL vs non-cases, 27.68 mg/dL) and HbA1c (Δslope: cases, 1.39% vs non-cases, 0.86%) in the month preceding the diagnosis of diabetes, and subtle weight loss in the prior years (slope: cases –0.18 kg/interval vs non-cases 0.33 kg/interval). These longitudinal changes in markers of metabolism were stronger for specific race and ethnic groups. Conclusions In a study of a large ethnically diverse population, we found risk of pancreatic cancer to be increased among patients with a diagnosis of diabetes in the past year among different races and ethnicities. Weight loss and rapid development of poor glycemic control were associated with increased risk of pancreatic cancer in multiple races.

Background: Hispanic and Black persons are at higher risk for gastric cancer (GC) in the United States, as compared to White counterparts. Economic analyses demonstrate that endoscopy for GC screening may be cost-effective in Hispanic and Black Americans, but no prevention guidelines support gastric cancer screening for these minorities in the U.S. Targeted Helicobacter pylori (H. pylori) testing and treatment may also help to prevent GC. It is unknown how common endoscopic history and H. pylori testing are among Hispanics and Blacks diagnosed with gastric cancer and how this is related to stage at diagnosis and survival. Methods: We employed SEER-Medicare data on Hispanic (n=1,428) and Black (n=1,774) patients diagnosed with GC in 2004-2013. We compared stage of disease by history of gastric imaging and H. pylori testing >18 months prior to GC diagnosis. Qualifying imaging included esophagogastroduodenoscopy, endoscopic ultrasound, upper gastrointestinal series. We tested for differences in proportions by Chi-squared tests and survival differences by log-rank test. We performed Cox regression analyses adjusting for age, sex, residence in large metropolitan areas, neighborhood poverty index, histology, and tumor location to determine the association of prior gastric imaging with survival. Results: Hispanic and Black GC patients shared similar histories of endoscopic imaging (17%, 16% respectively). Hispanics and Blacks who had a history of endoscopy were more likely to be diagnosed at Stage I (41% in both), as opposed to those without endoscopic history (26% and 29%; p Citation Format: Christie Y Jeon, Yu-Chen Lin, Bianca Luna-Lupercio, Robert Haile. Endoscopic history potentially explains survival differences in Hispanics and Blacks with gastric cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C113.

Background: Breast cancer screening rates among Korean American women lag behind other populations in the US; additionally, this population has the lowest mammography adherence rates of all the Asian subgroups. The rates of invasive breast cancer among Korean women in Los Angeles County (LAC) have also increased dramatically, which leads to poor outcomes. Early detection of breast cancer provides a greater range of treatment options and often better survival rates. Given this, we want to understand the unique barriers that Korean women in LAC face in order to adequately serve our catchment area. Methods: To understand the context of cancer screening compliance among Koreans in LAC, the Research Center for Health Equity (RCHE) at Cedars-Sinai Medical Center conducted a culturally adapted survey within its catchment area. We developed a Cancer and Healthcare in Los Angeles Survey (CHILAS) with feedback from Korean community leaders. The survey targeting females has 31 questions and covers screening behavior, medical history, and health care access. The survey was adapted with feedback from Korean community leaders and printed in the Korean language. A free cancer education workshop was offered post survey. For the purposes of the current analyses, we focused on participants were Korean women >= 18 yrs who reside in LAC. Surveys were administered at seven different faith-based venues, such as churches and Buddhist temples, during a three-month period. Results: 126 female participants were age eligible (age 45 and above) to answer the mammography screening cancer question and 52 (41.3%) of them had their screening up to date. 113 participants answered both the question about mammography screening and knowing someone with cancer. Of those who ‘knew someone with cancer’ (N=75), 46% had their screening up to date (N=35). Of those who ‘did not know someone with cancer’ (N=38), 34% had their screening up to date (N=13), the difference was not significant (p-value =0.21). Two of the top reasons for not getting screened were 1) not feeling sick and 2) no health insurance. Moreover, speaking the same language as the primary provider, financial status, length of waiting for an appointment, and transportation were not associated with breast cancer screening. Although mammography rates were low, colonoscopy rates among age eligible participants in the survey were very high (94.5%), leading us to believe there are unique factors to low mammography screening in Korean women. Future direction: To our knowledge, there are no existing awareness programs to increase mammography screening for this population. We know that faith-based organizations can increase screening behaviors among parishioners and can be an effective avenue for improving health outcomes. Through the engagement with elders, RCHE has formed an extensive network of partnerships with faith-based organizations we will identify the unique barriers to mammography compliance in Korean Americans. Citation Format: Dong Hee Kim, Yu-Chen Lin, Christie Y. Jeon, Laurel Finster, A. Joan Levine, Zul Surani, Robert W. Haile. Addressing the needs of Cedars-Sinai Cancer’s catchment area: Cancer screening compliance among the Korean community in Los Angeles [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D020.

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.

BackgroundChronic inflammation and immune activation are reported to play a key role in the etiology of non-Hodgkin lymphoma (NHL). We conducted a meta-analysis on the associations between prediagnosis circulating levels of immune stimulatory markers, interleukin 6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), CXCL13, soluble CD23 (sCD23), sCD27, sCD30, and the risk of NHL.MethodsRelevant studies were identified from PubMed, EMBASE, and Web of Science up to January 1, 2017. We calculated summary odds ratio (OR) estimates for the association between one natural log increase in concentration of each biomarker and NHL using random-effects models for NHL as a composite outcome and for several histological subtypes of NHL.ResultsSeventeen nested case control studies were included. Elevated levels of several biomarkers were more strongly associated with increased odds of NHL: TNF-α, OR = 1.18 (95% confidence interval [CI] = 1.04 to 1.34); CXCL13, OR = 1.47 (95% CI = 1.03 to 2.08); sCD23, OR = 1.57 (95% CI = 1.21 to 2.05); sCD27, OR = 2.18 (95% CI = 1.20 to 3.98); sCD30, OR = 1.65 (95% CI = 1.22 to 2.22). In stratified analyses, IL-6, TNF-α, sCD27, and sCD30 were more strongly associated with NHL in HIV-infected individuals compared to HIV-uninfected individuals. Between-study heterogeneity was observed across multiple biomarkers for overall NHL and by subtypes.ConclusionThis meta-analysis provides evidence that elevated circulating levels of TNF-α, CXCL13, sCD23, sCD27, and sCD30 are consistently associated with an increased risk of NHL, suggesting the potential utility of these biomarkers in population risk stratification and prediction.

Objectives It is unclear whether long-standing diabetes or new-onset pancreatogenic diabetes contributes to poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). Methods We investigated the influence of diabetes diagnosed shortly before PDAC and long-term diabetes on overall survival in 2792 PDAC patients who had participated in 3 PDAC case-control studies in the Pancreatic Cancer Case-Control Consortium. There were 300 patients with long-term diabetes of more than 3 years' duration (11%) and 418 patients with recently diagnosed diabetes of 3-year duration or less (15%). We performed Cox regression to determine the association of long-term diabetes and recently diagnosed diabetes with overall survival, adjusting for study site, age, sex, race, stage of disease, surgery, chemotherapy, smoking history, and body mass index at diagnosis. Results In the overall population, neither long-term diabetes (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.97-1.26) nor recently diagnosed diabetes (HR, 1.06; 95% CI, 0.94-1.18) was associated with shorter survival. When stratified by stage of disease, long-term diabetes was associated with 42% increase in rate of death in persons with resectable PDAC (HR, 1.42; 95% CI, 1.13-1.78), whereas it was not associated with survival in PDAC patients with more advanced disease. Conclusion Long-term diabetes was associated with increased rate of death in patients with resectable PDAC.

Summary Background Infection is the most common cause of mortality in end-stage liver disease (ESLD). The impact of obesity on infection risk in ESLD is not established. Aim To characterise the impact of obesity on infection risk in ESLD. Methods We evaluated the association between infection and obesity in patients with ESLD. Patients grouped as non-obese, obesity class I–II and obesity class III were studied using the Nationwide Inpatient Sample. Validated diagnostic code based algorithms were utilised to determine weight category and infections, including bacteraemia, skin/soft tissue infection, urinary tract infection (UTI), pneumonia/respiratory infection, Clostridium difficile infection (CDI) and spontaneous bacterial peritonitis (SBP). Risk factors for infection and mortality were assessed using multivariable logistic regression analysis. Results Of 115 465 patients identified, 100 957 (87.5%) were non-obese and 14 508 (12.5%) were obese, with 9489 (8.2%) as obesity class I–II and 5019 (4.3%) as obesity class III. 37 117 patients (32.1%) had an infection diagnosis. Infection was most prevalent among obesity class III (44.0%), followed by obesity class I–II (38.9%) and then non-obese (31.9%). In multivariable modelling, class III obesity (OR = 1.41; 95% CI 1.32–1.51; P < 0.001), and class I–II obesity (OR = 1.08; 95% CI 1.01–1.15; P = 0.026) were associated with infection. Compared to non-obese patients, obese individuals had greater prevalence of bacteraemia, UTI, and skin/soft tissue infection as compared to non-obese patients. Conclusions Obesity is newly identified to be independently associated with infection in end-stage liver disease. The distribution of infection sites varies based on weight category.

Primary sclerosing cholangitis (PSC) patients suffer from comorbidities unaccounted for by the model for end-stage liver disease scoring system and may benefit from the increased donor organ pool provided by donation after cardiac death (DCD) liver transplantation. However, the impact of DCD transplantation on PSC graft outcomes is unknown.We studied 41,018 patients using the United Network for Organ Sharing database from 2002 through 2012. Kaplan-Meier analysis and Cox regression were used to evaluate graft survival and risk factors for graft failure, respectively.The PSC patients receiving DCD livers (n=75) showed greater overall graft failure (37.3% vs. 20.4%, P = 0.001), graft failure from biliary complications (47.4% vs. 13.9%, P = 0.002), and shorter graft survival time (P = 0.003), compared to PSC patients receiving donation after brain death organs (n=1592). Among DCD transplants (n=1943), PSC and non-PSC patients showed similar prevalence of graft failure and graft survival time, though a trend existed toward increased biliary-induced graft failure among PSC patients (47.4 vs. 26.4%, P = 0.063). Cox modeling demonstrated that PSC patients have a positive graft survival advantage compared to non-PSC patients (hazard ratio [HR]=0.72, P0.001), whereas DCD transplantation increased risk of graft failure (HR = 1.28, P0.001). Furthermore, the interaction between DCD transplant and PSC was significant (HR = 1.76, P = 0.015), indicating that use of DCD organs impacts graft survival more in PSC than non-PSC patients.Donation after cardiac death liver transplantation leads to significantly worse outcomes in PSC. We recommend cautious use of DCD transplantation in this population.

Pancreatic cancer is projected to become the leading cause of cancer deaths by 2050. The risk for pancreatic cancer may be reduced by up to 27% by modifying lifestyle risk factors, most notably tobacco smoking. Based on analysis of more than 2 million unselected individuals from general population, this article quantified the risk of pancreatic cancer in relation to lifelong tobacco smoking and alcohol consumption status, both alone and in combination. It also provided a state-of-the-art review of animal studies on the effect of tobacco smoke and alcohol on genetically engineered mouse models of pancreatic precursor lesions, as well as the role of pancreatic stellate cells and immune cells in pancreatic carcinogenesis activated by tobacco and alcohol.

Observational studies suggest that statin therapy for cardio-protection is associated with improved survival in cancer patients. We sought to evaluate the impact of statin treatment on ovarian cancer survival in a nationally representative elderly population.The linked Surveillance, Epidemiology, and End Results (SEER) registries and Medicare claims data on patients diagnosed with epithelial ovarian cancer in 2007-2009 were used to extract data on statin prescription fills, population characteristics, primary treatment, comorbidity and survival. Cox regression models were used to examine the association between statin treatment and overall survival.Among the 1431 ovarian cancer patients who underwent surgical resection, 609 (42.6%) filled prescriptions for statin. The majority of statin-users (89%) were prescribed a lipophilic formulation. Mean overall survival among statin-users was 32.3months compared to 28.8months for non-users (p0.0001). A 34% reduction in death was associated with statin therapy, independent of age, race, neighborhood median household income, stage, platinum therapy and comorbid conditions (HR=0.66, 95% CI 0.55-0.81). Improved overall survival with statin use was observed for both serous (HR=0.69, 95% CI 0.54-0.87) and non-serous (HR=0.63, 95% CI 0.44-0.90) histologies. When statin treatment was categorized by lipophilicity and intensity, a significant survival benefit was limited to lipophilic statin users and those who took statins of moderate intensity.This SEER-Medicare analysis demonstrates improvement in overall survival with lipophilic statin use after surgery in elderly patients with epithelial ovarian cancer. A clinical trial to evaluate the impact of statin treatment in ovarian cancer survival is warranted.