Pre-emptive resection for intraductal papillary mucinous neoplasia - Long-term outcome is similar between non-invasive and early invasive lesions in a tertiary single center.

BACKGROUND: Pre-emptive resection for intraductal papillary mucinous neoplasm (IPMN) aims to reduce the risk before invasive transformation has taken place. Pancreatic resections are highly associated with major morbidity and mortality. Long-term overall survival (OS) after resection for invasive IPMN (inv-IPMN) in early stages is favorable. Comparison of long-term OS for resected non-invasive IPMN and early staged inv-IPMN is poorly delineated. This study aims to compare outcomes for resected non-invasive IPMN and T1-staged inv-IPMN. METHODS: All patients ≥18 years of age resected for IPMN up to stage T1 at Karolinska University Hospital between 2008 and 2020 were included. Two-year OS were compared between groups by chi-squared test, and 5-year OS was estimated using Kaplan-Meier method. Covariates associated with death was assessed in multivariable Cox regression model. RESULTS: We included 284 patients, 264 (93%) non-invasive IPMN and 20 (7%) T1-staged inv-IPMN. Dysplasia of low grade (LGD) and high grade, i.e., tumor in situ (Tis) were present in 190 (67%) and 75 (26%) patients respectively. The 2-year OS for the entire cohort was 96%, and there were no differences between non-invasive and inv-IPMN (96% vs 92%, p = 0.203), nor between IPMN with LGD and Tis-T1b-staged IPMN (96% vs 95%, p = 0.734). CONCLUSION: Two thirds of the specimen from pre-emptive resections were of LGD and did not involve superior OS than in situ or early cancer. Due to high complication burden, efforts should be made to avoid resection when LGD is probable and rather identify more accurate predictors for surgery.

Antipsychotic drugs and risk of acute pancreatitis: A nationwide case-control study.

INTRODUCTION: Use of antipsychotic drugs, especially second-generation agents, has been suggested to cause acute pancreatitis in multiple case reports; however, such an association has not been corroborated by larger studies. This study examined the association of antipsychotic drugs with risk of acute pancreatitis. METHODS: Nationwide case-control study, based on data from several Swedish registers and including all 52,006 cases of acute pancreatitis diagnosed in Sweden between 2006 and 2019 (with up to 10 controls per case; n = 518,081). Conditional logistic regression models were used to calculate odds ratios (ORs) in current and past users of first-generation and second-generation antipsychotic drugs (dispensed prescription <91 and ≥91 days of the index date, respectively) compared with never users of such drugs. RESULTS: In the crude model, first-generation and second-generation antipsychotic drugs were associated with increased risk of acute pancreatitis, with slightly higher ORs for past use (1.58 [95% confidence interval 1.48-1.69] and 1.39 [1.29-1.49], respectively) than for current use (1.34 [1.21-1.48] and 1.24 [1.15-1.34], respectively). The ORs were largely attenuated in the multivariable model-which included, among others, alcohol abuse and the Charlson comorbidity index-up to the point where only a statistically significant association remained for past use of first-generation agents (OR 1.18 [1.10-1.26]). CONCLUSION: There was no clear association between use of antipsychotic drugs and risk of acute pancreatitis in this very large case-control study, indicating that previous case report data are most likely explained by confounding.

Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study.

BACKGROUND AND AIMS: Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation-wide population-based cohort in Sweden. APPROACH AND RESULTS: Using nation-wide registries, we identified all adults who received maintenance PPIs (≥180 days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow-up of 5.3 years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37-1.81), 1.77 (95% CI, 1.56-2.00), and 1.88 (95% CI, 1.57-2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17-1.57) and 1.47 (95% CI, 1.19-1.80) for extra- and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5 years of PPIs use, ruling out confounding by indication. CONCLUSIONS: In this study, long-term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.

Proton pump inhibitors and survival in patients with colorectal cancer: a Swedish population-based cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) are associated with microbiome changes of the gut, which in turn may affect the progression of colorectal cancer (CRC). This study aims to assess the associations between PPI use and all-cause and CRC-specific mortality. METHODS: We selected all patients registered in the Swedish Prescribed Drug Registry who were diagnosed with CRC between 2006 and 2012 (N = 32,411, 54.9% PPI users) and subsequently followed them through register linkage to the Swedish Causes of Death Registry until December 2013. PPI users were patients with ≥1 post-diagnosis PPI dispensation. Time-dependent Cox-regression models were performed with PPI use as time-varying exposure. RESULTS: Overall 4746 (14.0%) patients died, with an aHR of 1.38 (95% CI 1.32-1.44) for all-cause mortality comparing PPI users with PPI nonusers. Higher-magnitude associations were observed among male, cancer stage 0-I, rectal cancer and patients receiving CRC surgery. The PPI-all-cause mortality association was also more pronounced comparing new users to non-users (aHR = 1.47, 95%CI 1.40-1.55) than comparing continuous users to non-users (aHR = 1.32, 95%CI 1.24-1.39). The risk estimates for CRC-specific mortality comparing PPI users to PPI nonusers were similar to those for all-cause mortality. CONCLUSION: PPI use after the CRC diagnosis was associated with increased all-cause and CRC-specific mortality.

Pancreatic Cancer Following Acute Pancreatitis: A Population-based Matched Cohort Study.

BACKGROUND: Acute pancreatitis is linked to pancreatic cancer, but the direction of this association is not fully elaborated. METHODS: This was a population-based cohort study including all Swedish residents diagnosed with a first-time episode of acute pancreatitis between 1997 and 2013 and corresponding matched pancreatitis-free individuals from the general population. Hazard ratios for the association between acute pancreatitis and pancreatic cancer were estimated using multivariable Cox regression models. RESULTS: Overall, 49,749 individuals with acute pancreatitis and 138,750 matched individuals without acute pancreatitis were followed up for 1,192,134 person-years (median 5.3 years). A total of 769 individuals developed pancreatic cancer, of whom 536 (69.7%) had a history of acute pancreatitis. The risk of pancreatic cancer was substantially increased during the first few years after a diagnosis of acute pancreatitis but declined gradually over time, reaching a level comparable to the pancreatitis-free population after >10 years of follow-up. In those with non-gallstone-related acute pancreatitis, the risk of pancreatic cancer declined to a level comparable to the pancreatitis-free population only when follow-up time was censored for a second episode of acute pancreatitis or a diagnosis of chronic pancreatitis. Increasing number of recurrent episodes of acute pancreatitis was associated with increased risk of pancreatic cancer. CONCLUSION: These findings imply a delay in the diagnosis of pre-existing pancreatic cancer, if clinically presented as acute pancreatitis. Any association between non-gallstone-related acute pancreatitis and pancreatic cancer in the long-term (>10 years) could be mediated through recurrent acute pancreatitis or chronic pancreatitis.

Overall diet quality and risk of recurrence and progression of non-gallstone-related acute pancreatitis: a prospective cohort study.

PURPOSE: An incident episode of acute pancreatitis is often followed by recurrent attacks and/or progression to chronic pancreatitis, especially if the etiology is non-gallstone-related. We examined whether overall diet quality influences the natural history of non-gallstone-related acute pancreatitis. METHODS: Three hundred and eighty-six individuals (born 1914-1952) were included in a prospective study, all of whom had an incident diagnosis of non-gallstone-related acute pancreatitis in the Swedish National Patient Register between 1998 and 2013. Participants were already enrolled in two population-based cohorts and had completed a food frequency questionnaire in 1997. Overall diet quality was calculated using a recommended food score (RFS), which was based on 25 food items. Post-diagnosis follow-up was conducted throughout 2014 for recurrence of acute pancreatitis and/or progression to chronic pancreatic disease (including cancer). Hazard ratios were estimated using Cox models. RESULTS: During 1859 person-years of follow-up, 23.3% of the study population (n = 90) developed recurrent or progressive pancreatic disease. An inverse association was observed between the RFS and risk of recurrent and progressive pancreatic disease after adjustment for age and sex (hazard ratio for each 2-unit increase 0.90, 95% confidence interval 0.81-1.01) (P overall association = 0.06). However, the association became weaker and was not statistically significant after adjustment for other potential confounders, including alcohol drinking and cigarette smoking (P overall association = 0.27). CONCLUSIONS: In this prospective study of individuals with non-gallstone-related acute pancreatitis, there was no clear association between overall diet quality and risk of recurrent and progressive pancreatic disease.

A prospective cohort study on the association between coffee drinking and risk of non-gallstone-related acute pancreatitis.

Only one previous study has examined the association between coffee consumption and risk of acute pancreatitis, and it found a reduced risk for alcohol-related episodes among high consumers of coffee. Therefore, we examined (1) the association between coffee consumption and risk of non-gallstone-related acute pancreatitis and (2) whether this association was modified by alcohol intake. Data were obtained from two prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, including 76 731 men and women (born 1914-1952). Coffee consumption was assessed at baseline with a FFQ, and the cohorts were followed up between 1998 and 2012 via linkage to national health registries. Hazard ratios were estimated using Cox models, with adjustment for potential confounding factors. During 1 035 881 person-years of total follow-up, 383 cases (246 in men and 137 in women) of incident non-gallstone-related acute pancreatitis were identified. Overall, and irrespective of whether a categorical or a continuous exposure model was used, we observed no association between coffee consumption and risk of non-gallstone-related acute pancreatitis (e.g. the multivariable-adjusted hazard ratio for each 1 cup/d increase in coffee consumption was 0·97; 95 % CI 0·92, 1·03). There was no evidence of effect modification by alcohol intake (P interaction=0·77). In conclusion, coffee consumption was not associated with risk of non-gallstone-related acute pancreatitis in this large prospective cohort study. Because of the limited number of epidemiological studies and their conflicting results, further research is needed to elucidate this potential association.

Exogenous estrogen and the risk of biliary tract cancer - a population-based study in a cohort of Swedish men treated for prostate cancer.

BACKGROUND: To assess the role of exogenous estrogen in the etiology of biliary tract cancer, a nationwide population-based cohort study in Sweden was performed. METHODS: The study included all men in Sweden with prostate cancer diagnosed in 1961-2008. Due to treatment standards, patients diagnosed in 1961-1980 were considered more exposed to estrogen, while those diagnosed in 1981-2008 were regarded less exposed. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated to estimate the risk of biliary tract cancer in cohort members compared to the corresponding Swedish male population. RESULTS: After 849 307 person-years of follow-up in 203 131 prostate cancer patients, there were 41 incident gallbladder cancers and 36 cancers of the extra-hepatic bile ducts. In overall, there were no apparent differences in the risk of gallbladder cancer or bile duct cancer between patients diagnosed in 1961-1980 and patients diagnosed in 1981-2008. However, in patients diagnosed in 1961-1980, there was a statistically non-significant increased risk of gallbladder cancer (SIR 1.34; 95% CI 0.71-2.29) and extra-hepatic bile duct cancer (SIR 1.20; 95% CI 0.55-2.28) > 5 years of follow-up after the prostate cancer diagnosis. No such association was found for patients diagnosed in 1981-2008. Sensitivity analyses excluding prostate cancer patients exposed to potential confounding factors did not change the SIRs. CONCLUSIONS: Long exposure to high doses of exogenous estrogen might increase the risk of biliary tract cancer. However, any potential excess risk of bile duct cancer resulted by prolonged exposure to high doses of exogenous estrogen seems to be small.

Polypharmacy and risk of acute pancreatitis.

PURPOSE: Drug-induced pancreatitis is receiving increased medical and epidemiological attention. However, as no study has examined the role of polypharmacy per se in the development of acute pancreatitis, we examined the association between polypharmacy and risk of acute pancreatitis. METHODS: A nationwide case-control study was conducted between 2006 and 2008 of Swedish people aged 40-84 years. The Swedish Patient Register was used to identify 6161 cases of first-episode acute pancreatitis. The Swedish Register of the Total Population was used to randomly select 61 637 controls from the general population using frequency-based density sampling, matched for age, sex, and calendar year. The Swedish Prescribed Drug Register was used to assess polypharmacy, defined as the number of unique drugs prescribed during the last 6 months before the index date (i.e. the date of acute pancreatitis for cases and a random date for controls). Odds ratios (ORs), with 95% confidence intervals (CIs), of acute pancreatitis were estimated by unconditional logistic regression, adjusted for matching variables and potential confounding factors. RESULTS: The number of prescribed drugs was associated with a dose-dependent increase in the risk of acute pancreatitis. In the multivariable-adjusted model, compared to those without any prescriptions, the OR was 1.69 (95%CI: 1.55-1.86) for persons with 1-2 drugs, 2.40 (2.20-2.62) for 3-5 drugs, 3.17 (2.88-3.48) for 6-9 drugs, and 4.57 (4.12-5.06) for 10 or more drugs. CONCLUSION: This population-based case-control study shows a dose-dependent association between increasing polypharmacy and risk of acute pancreatitis. These findings provide further insights into drug-induced pancreatitis. Copyright © 2016 John Wiley & Sons, Ltd.

Splenic injury during resection for esophageal cancer: risk factors and consequences.

OBJECTIVE: Esophageal cancer surgery carries a risk of splenic injury, which may require splenectomy, but predictors of such events remain uncertain. Moreover, the hypothesis that incidental splenectomy carries a worse prognosis deserves attention. DESIGN: A population-based, nationwide cohort study was conducted on 1679 patients who underwent resection for esophageal cancer in Sweden in 1987 to 2010, with follow-up until February 2012. Predictors of splenic injury and incidental splenectomy were analyzed using multivariable logistic regression, providing odds ratios (ORs) with 95% confidence intervals (CIs). Associations between incidental splenectomy and risk of mortality and severe infections were analyzed using multivariable Cox regression, providing hazard ratios (HRs) with 95% CIs. RESULTS: Higher surgeon volume of esophageal cancer resection decreased the risk of splenic injury and incidental splenectomy (OR: 0.58; 95% CI: 0.41-0.80; and OR: 0.41; 95% CI: 0.25-0.66, respectively, comparing the highest to lowest category). In patients with splenic injury, progression to incidental splenectomy decreased by 92% during the study period. Sex, age, tumor stage, previous abdominal surgery, neoadjuvant therapy, and surgical radicality did not influence these risks. Incidental accidental splenectomy increased the overall risk of mortality (HR: 1.29; 95% CI: 1.03-1.61) and severe infections (HR: 2.79; 95% CI: 1.35-5.79). CONCLUSION: The inverse association between surgeon volume and splenic injury supports centralization of esophageal cancer surgery. The increased risk of mortality and severe infections after incidental splenectomy should be kept in mind during surgery, and we should encourage efforts to preserve an injured spleen and stress the relevance of vaccination after splenectomy.

Pattern of increasing HbA1c levels in patients with diabetes mellitus before clinical detection of pancreatic cancer - a population-based nationwide case-control study.

BACKGROUND: Diabetes mellitus is a risk factor for pancreatic cancer. Impaired insulin resistance might precede the clinical detection of this cancer by several years. METHODS: This was a nested case-control population-based study assessing the pattern of glycated hemoglobin (HbA1c) change before clinical detection of pancreatic cancer in a population of individuals with diabetes mellitus. All patients registered in the Swedish National Diabetes Register with a prescription of an anti-diabetic drug between 2005 and 2011 were identified. For each case of pancreatic cancer, 10 controls were randomly selected, matched for age, sex, and factors related to diabetes mellitus. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between HbA1c and pancreatic cancer. RESULTS: In total, 391 cases and 3910 matched controls were identified. The risk of pancreatic cancer was increased more than two-fold in individuals with the highest HbA1c quartile compared with the lowest (OR 1.96, 95% CI 1.40-2.75). The risk of pancreatic cancer remained elevated when comparing the highest HbA1c quartile measured within five years from the clinical detection of pancreatic cancer to the lowest HbA1c quartile (p-value for trend < 0.05). No association was found between HbA1c and pancreatic cancer if HbA1c was measured > 5 years before the clinical detection of pancreatic cancer. CONCLUSIONS: The pattern of increasing HbA1c in patients with diabetes mellitus preceded the clinical detection of pancreatic cancer by up to five years. These findings indicate that there is a lead time of several years during which the development of pancreatic cancer might be detectable through screening in patients with diabetes mellitus.

Reproductive factors and risk of biliary tract cancer in a population-based study.

BACKGROUND: The strong female predominance of biliary tract cancer (BTC) may be related to reproductive factors. We aimed to clarify whether parity or age at first birth influence the risk of BTC. METHODS: This was a population-based, case-control study including Swedish female and male cases of cancer of the gallbladder (GBC), extra hepatic bile ducts (EHCC), or the ampulla of Vater (AVC) between 1960 and 2008. For each case, 10 age- and sex-matched controls were randomly selected. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounders. RESULTS: In total, 1169 cases of GBC, 432 cases of EHCC and 295 cases of AVC were included. Multi- and nulliparous women and men had an increased risk of all tumor locations in the biliary tract compared to uniparous women and men, respectively. Whereas higher age at first birth was associated with a decreased risk of GBC in women, no such association was found in men. There were no clear differences in the risk of EHCC and AVC between women and men. CONCLUSION: Sex hormones may play a role in the etiology of GBC. The associations between reproductive factors and EHCC and AVC are similar in women and men, which do not support the sex hormone hypothesis.

Mortality after a cholecystectomy: a population-based study.

BACKGROUND: The trade-off between the benefits of surgery for gallstone disease for a large population and the risk of lethal outcome in a small minority requires knowledge of the overall mortality. METHODS: Between 2007 and 2010, 47 912 cholecystectomies for gallstone disease were registered in the Swedish Register for Cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) (GallRiks). By linkage to the Swedish Death Register, the 30-day mortality after surgery was determined. The age- and sex-standardized mortality ratio (SMR) was estimated by dividing the observed mortality with the expected mortality rate in the Swedish general population 2007. The Charlson Comorbidity Index (CCI) was estimated by International Classification of Diseases (ICD) codes retrieved from the National Patient Register. RESULTS: Within 30 days after surgery, 72 (0.15%) patients died. The 30-day mortality was close [SMR = 2.58; 95% confidence interval (CI): 2.02-3.25] to that of the Swedish general population. In multivariable logistic regression analysis, predictors of 30-day mortality were age >70 years [odds ratio (OR) 7.04, CI: 2.23-22.26], CCI > 2 (OR 1.93, CI: 1.06-3.51), American Society of Anesthesiologists (ASA) > 2 (OR 13.28, CI: 4.64-38.02), acute surgery (OR 10.05, CI:2.41-41.95), open surgical approach (OR 2.20, CI: 1.55-4.69) and peri-operative complications (OR 3.27, CI: 1.74-6.15). DISCUSSION: Mortality after cholecystectomy is low. Co-morbidity and peri-operative complications may, however, increase mortality substantially. The increased mortality risk associated with open cholecystectomy could be explained by confounding factors influencing the decision to perform open surgery.

High dietary glycemic load increases the risk of non-gallstone-related acute pancreatitis: a prospective cohort study.

BACKGROUND & AIMS: Obesity and type 2 diabetes--diseases linked to glucose intolerance and insulin resistance--have been positively associated with the risk of acute pancreatitis. However, it is unclear whether consumption of foods that increase postprandial glycemia and insulinemia have similar associations. We examined the association between dietary glycemic load and risk of non-gallstone-related acute pancreatitis. METHODS: We performed a prospective study of 44,791 men and 36,309 women (aged 45-84 years), without a history of acute pancreatitis, from the Cohort of Swedish Men and the Swedish Mammography Cohort. Glycemic loads were calculated from food frequency questionnaire data collected in 1997, and participants were followed for the development of non-gallstone-related acute pancreatitis through 2010 via linkage to the Swedish National Patient Register. Hazard ratios (HRs) were estimated using Cox proportional hazard models. RESULTS: During a total follow-up of 967,568 person-years, there were 364 cases of incident non-gallstone-related acute pancreatitis (236 in men and 128 in women). Incidence rates, standardized for age and sex, were 49 cases per 100,000 person-years in the highest quartile of glycemic load and 33 cases per 100,000 person-years in the lowest. The multivariate-adjusted HR of non-gallstone-related acute pancreatitis was 1.60 (95% confidence interval [CI], 1.17-2.18) for the highest compared with the lowest quartile. Every 50-unit increase in glycemic load per day (∼ 3 servings of white bread) had an HR of 1.38 in men (95% CI, 1.11-1.72) and women (95% CI, 1.02-1.86). CONCLUSIONS: Based on a large, prospective cohort study, diets with high glycemic load are associated with an increased risk of non-gallstone-related acute pancreatitis.

Postmenopausal hormone replacement therapy and risk of acute pancreatitis: a prospective cohort study.

BACKGROUND: Several case reports have suggested that women's use of exogenous sex hormones is associated with acute pancreatitis; however, relevant epidemiologic data are sparse. We examined the association between postmenopausal hormone replacement therapy and risk of acute pancreatitis. METHODS: We conducted a prospective study involving 31,494 postmenopausal women (aged 48-83 yr) from the population-based Swedish Mammography Cohort. Participants completed a baseline questionnaire in 1997 assessing their use of hormone replacement therapy. We linked the cohort to the hospital-based Swedish National Patient Register to determine hospital admissions for acute pancreatitis through 2010. Relative risks (RRs) were calculated using Cox proportional hazard models. RESULTS: Over a total follow-up of 389,456 person-years, we identified 237 cases of incident acute pancreatitis. The age-standardized incidence rates per 100,000 person-years were 71 cases among women who had ever used hormone replacement therapy and 52 cases among women who had never used such hormones. Among ever users of hormone replacement therapy, the multivariable-adjusted RR of acute pancreatitis was 1.57 (95% confidence interval [CI] 1.20-2.05) compared with never users. The risk did not differ by current or past use, but it seemed to be higher among women who used systemic therapy (RR 1.92, 95% CI 1.38-2.66) and among those with duration of therapy of more than 10 years (RR 1.87, 95% CI 1.11-3.17). INTERPRETATION: Use of postmenopausal hormone replacement therapy was associated with increased risk of acute pancreatitis. Physicians should consider this potential increase in risk when prescribing such therapy.

Postmenopausal hormone replacement therapy and risk of cholecystectomy: a prospective cohort study.

OBJECTIVE: Our aim of this study was to examine the association between the use of postmenopausal HRT and risk of cholecystectomy in Sweden, where the most common regimen of HRT (oral oestradiol in combination with testosterone-like progestin) has been different from those investigated in previous studies. MATERIAL AND METHODS: We performed a prospective study of 27 892 postmenopausal women (aged 48-83 years) from the population-based Swedish Mammography Cohort. Use of HRT was assessed by a self-reported questionnaire at baseline in 1997, and the cohort was followed up through 2011 for procedures of cholecystectomy by linkage to the Swedish Patient Register. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: During 362 728 person-years of follow-up (median 14 years), 995 cases of cholecystectomy were recorded. After adjustment for potential confounders, the HR of cholecystectomy was 1.52 (95% CI, 1.33-1.74) among ever users of HRT compared with never users. The risk did not differ by current or past use (p = 0.38) or duration of use (p = 0.65), but it did differ by indication of use (p = 0.006). Women who used HRT for systemic symptoms had a higher risk of cholecystectomy than those who used it for local symptoms (HR, 1.62; 95% CI, 1.41-1.87 vs HR, 1.21; 95% CI, 0.97-1.50). CONCLUSIONS: This prospective study of postmenopausal women adds to the evidence that use of HRT may increase the risk of cholecystectomy.

Systematic underreporting of the population-based incidence of pancreatic and biliary tract cancers.

BACKGROUND: Incidence rates of cancers of the pancreas and biliary tract, typically derived from cancer registers, have been reported to be decreasing. This study tested whether pancreatic and biliary tract cancers are underreported in the Swedish Cancer Register (CR). METHODS: The concordance of pancreatic and biliary tract cancer diagnoses in 1990-2009 between CR and the Swedish Patient Register (PR) were evaluated through record linkage. To further assess the completeness of these cancer diagnoses in both CR and PR, record linkage was also made to the Swedish Causes of Death Register (DR). RESULTS: A total of 31 067 cases of pancreatic cancer and 14 273 cases of biliary tract cancer were identified in CR or PR. Altogether, 44% of the pancreatic cancers and 44% of the biliary tract cancers were registered in PR only, and not in CR. The concordance between CR and PR declined from 63% in the years 1990-1994 to 44% in 2005-2009 for pancreatic cancer. The corresponding figures for biliary tract cancer were 60% and 37%. This decline in concordance was also observed with increasing age, e.g. the concordance between CR and PR for pancreatic cancer declined from 62% in patients<60 years to 36% among patients≥80 years. The corresponding figures for biliary tract cancer were 52% and 38%. CONCLUSION: There is an overwhelming underreporting of pancreatic and biliary tract cancers within the Swedish Cancer Register, which has increased during recent years. The reported decreasing incidence rates for pancreatic and biliary tract cancers might therefore be incorrect.

Vegetables, fruit and risk of non-gallstone-related acute pancreatitis: a population-based prospective cohort study.

OBJECTIVE: To examine the association of vegetable and fruit consumption with the risk of non-gallstone-related acute pancreatitis. DESIGN: A population-based prospective cohort of 80,019 women and men, aged 46-84 years, completed a food-frequency questionnaire at baseline and was followed up for incidence of non-gallstone-related acute pancreatitis from 1 January 1998 to 31 December 2009. Participants were categorised into quintiles according to consumption of vegetables and consumption of fruit. Cox proportional hazards models were used to estimate RRs and 95% CIs. RESULTS: In total, 320 incident cases (216 men and 104 women) with non-gallstone-related acute pancreatitis were identified during 12 years of follow-up (891,136 person-years). After adjustment for potential confounders, the authors observed a significant inverse linear dose-response association between vegetable consumption and risk of non-gallstone-related acute pancreatitis; every two additional servings per day were associated with 17% risk reduction (RR=0.83; 95% CI 0.70 to 0.98; p=0.03). Among participants consuming >1 drink of alcohol per day and among those with body mass index ≥25 kg/m2, the RR for the highest compared with the lowest quintile of vegetable consumption was 0.29 (95% CI 0.13 to 0.67) and 0.49 (95% CI 0.29 to 0.85), respectively. Fruit consumption was not significantly associated with the risk of non-gallstone-related acute pancreatitis; the RR comparing extreme quintiles of consumption was 1.20 (95% CI 0.81 to 1.78). CONCLUSIONS: Vegetable consumption, but not fruit consumption, may play a role in the prevention of non-gallstone-related acute pancreatitis.

Maintenance proton pump inhibitor use and risk of colorectal cancer: a Swedish retrospective cohort study.

OBJECTIVES: We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort. DESIGN: Retrospective cohort study. SETTING: This research was conducted at the national level, encompassing the entire population of Sweden. PARTICIPANTS: This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years. INTERVENTIONS: Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H2RA) use. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H2RA use. RESULTS: Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H2RA users (IRR 1.05, 95% CI=0.87 to 1.27, p<0.05). CONCLUSIONS: Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.

Exploring the association between acute pancreatitis and biliary tract cancer: A large-scale population-based matched cohort study.

BACKGROUND: Biliary tract cancer (BTC) often goes undetected until its advanced stages, resulting in a poor prognosis. Given the anatomical closeness of the gallbladder and bile ducts to the pancreas, the inflammatory processes triggered by acute pancreatitis might increase the risk of BTC. OBJECTIVE: To assess the association between acute pancreatitis and the risk of BTC. METHODS: Using the Swedish Pancreatitis Cohort (SwePan), we compared the BTC risk in patients with a first-time episode of acute pancreatitis during 1990-2018 to a 1:10 matched pancreatitis-free control group. Multivariable Cox regression models, stratified by follow-up duration, were used to calculate hazard ratios (HRs), adjusting for socioeconomic factors, alcohol use, and comorbidities. RESULTS: BTC developed in 0.94% of 85,027 acute pancreatitis patients and in 0.23% of 814,993 controls. The BTC risk notably increased within 3 months of hospital discharge (HR 82.63; 95% CI: 63.07-108.26) and remained elevated beyond 10 years of follow-up (HR 1.82; 95% CI: 1.35-2.47). However, the long-term risk of BTC subtypes did not increase with anatomical proximity to the pancreas, with a null association for gallbladder and extrahepatic tumors. Importantly, patients with acute pancreatitis had a higher occurrence of early-stage BTC within 2 years of hospital discharge than controls (13.0 vs. 3.6%; p-value <0.01). CONCLUSION: Our nationwide study found an elevated BTC risk in acute pancreatitis patients; however, the risk estimates for BTC subtypes were inconsistent, thereby questioning the causality of the association. Importantly, the amplified detection of early-stage BTC within 2 years after a diagnosis of acute pancreatitis underscores the necessity for proactive BTC surveillance in these patients.