Effect of surgery versus chemotherapy in pancreatic cancer patients: a target trial emulation.

PURPOSE: To estimate the causal effect of surgery vs chemotherapy on survival in patients with T1-3NxM0 pancreatic cancer in a rigorous framework addressing selection bias and immortal time bias. METHODS: We used population-based Danish healthcare registries to conduct a cohort study emulating a hypothetical randomized trial to estimate the absolute difference in survival, comparing surgery with chemotherapy. We included pancreatic cancer patients diagnosed during 2008-2021. Exposure was surgery or chemotherapy initiated within a 16-week grace period after diagnosis. At the time of diagnosis, data of each patient was duplicated; one copy was assigned to the surgery protocol and one copy to the chemotherapy protocol of the hypothetical trial. Copies were censored when the assigned treatment deviated from the observed treatment. To account for informative censoring, uncensored patients were weighted according to confounders. For comparison, we also applied a more conventional analysis using propensity score-based inverse probability weighting. RESULTS: We included 1,744 patients with a median age of 68 years; 73.6% underwent surgery and 18.6% had chemotherapy without surgery. 7.8% received no treatment. The 3-year survival was 39.7% (95% CI 36.7% to 42.6%) after surgery and 22.7% (95% CI: 17.7% to 28.4%) after chemotherapy, corresponding to an absolute difference of 17.0% (95% CI: 10.8% to 23.1%). In the conventional survival analysis, this difference was 23.0% (95% CI: 17.0% to 29.0%). CONCLUSION: Surgery was superior to chemotherapy in achieving long-term survival for pancreatic cancer. The difference comparing surgery and chemotherapy was substantially smaller when using the clone-censor-weight approach than conventional survival analysis.

Beta-blocker use and survival after pancreatic cancer surgery: A nationwide population-based cohort study.

PURPOSE: We examined the association between use of beta-blockers and survival in pancreatic cancer patients after curative-intent surgery. METHODS: Using Danish healthcare registries, we conducted a population-based cohort study of all patients undergoing curative-intent surgery for pancreatic cancer in Denmark 1997-2021. We defined beta-blocker use according to exposure before surgery as current (≤90 days), recent (91-365 days), or former (366-730 days) use, requiring at least one filled prescription. Patients were followed from the date of surgery for up to 5 years. We used Cox regression to compute hazard ratios (HRs) of deaths with 95% confidence intervals (CIs), adjusting for age, sex, year of diagnosis, cardiovascular disease, diabetes, liver disease, alcohol, and smoking. We also conducted an active comparator analysis, where we used angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers as comparators instead of nonusers. RESULTS: We included 2592 patients, of which 16.7% were beta-blocker users. Median survival for the entire population was 24.4 months. Beta-blocker use was associated with increased mortality (adjusted HR: 1.18; 95% CI: 1.04-1.34). This was evident in current (adjusted HR: 1.19; 95% CI: 1.02-1.38) and recent (adjusted HR: 1.29; 95% CI: 1.04-1.59) but not former (adjusted HR: 0.91; 95% CI: 0.64-1.43) users. In the active comparator analysis, the association between beta-blocker exposure and mortality attenuated slightly (adjusted HR: 1.12; 95% CI: 0.93-1.35). CONCLUSIONS: We observed an association between beta-blocker use and increased mortality in patients operated for pancreatic cancer. Findings are likely explained by confounding by indication.

Effect of adjuvant chemotherapy after pancreatectomy in patients with node-negative pancreatic cancer: target trial emulation.

BACKGROUND: The effect of adjuvant therapy in node-negative pancreatic cancer is uncertain. The aim of this study was to estimate the effect of adjuvant chemotherapy on survival after surgery for pancreatic cancer in patients with node-negative (pN0) and node-positive (pN+) disease using target trial emulation. METHODS: This was an observational cohort study emulating a hypothetical RCT by the clone-censor-weight approach using population-based Danish healthcare registries. The study included Danish patients undergoing curative-intent surgery for pancreatic cancer during 2008-2021, who were discharged alive no more than 4 weeks after surgery. At the time of discharge after surgery, the data for each patient were duplicated; one copy was assigned to the adjuvant chemotherapy strategy and the other to the no adjuvant chemotherapy strategy of the hypothetical trial. Copies were censored when the assigned treatment was no longer compatible with the observed treatment. To account for informative censoring, uncensored patients were weighted according to measured confounders. The primary outcomes were absolute difference in 2-year survival and median overall survival, comparing adjuvant with no adjuvant chemotherapy. RESULTS: Some 424 patients with pN0 and 953 with pN+ disease were included. Of these, 62.0 and 74.6% respectively initiated adjuvant chemotherapy within the 8-week grace period. Among patients with pN0 tumours, the difference in 2-year survival between those with and without adjuvant therapy was -2.2 (95% c.i. -11.8 to 7.4)%. In those with pN+ disease, the difference in 2-year survival was 9.9 (1.6 to 18.1)%. Median overall survival was 24.9 (i.q.r. 12.8-49.4) and 15.0 (8.0-34.0) months for patients having adjuvant and no adjuvant therapy respectively. CONCLUSION: In a target trial emulation using observational data, adjuvant chemotherapy did not improve survival after surgery for node-negative pancreatic cancer.

Impact on Survival of Early Versus Late Initiation of Adjuvant Chemotherapy After Pancreatic Adenocarcinoma Surgery: A Target Trial Emulation.

BACKGROUND: We examined the impact of early (0-4 weeks after discharge) versus late (> 4-8 weeks after discharge) initiation of adjuvant chemotherapy on pancreatic adenocarcinoma survival. METHODS: We used Danish population-based healthcare registries to emulate a hypothetical target trial using the clone-censor-weight approach. All eligible patients were cloned with one clone assigned to 'early initiation' and one clone assigned to 'late initiation'. Clones were censored when the assigned treatment was no longer compatible with the actual treatment. Informative censoring was addressed using inverse probability of censoring weighting. RESULTS: We included 1491 patients in a hypothetical target trial, of whom 32.3% initiated chemotherapy within 0-4 weeks and 38.3% between > 4 and 8 weeks after discharge for pancreatic adenocarcinoma surgery; 206 (13.8%) initiated chemotherapy after > 8 weeks, and 232 (15.6%) did not initiate chemotherapy. Median overall survival was 30.4 and 29.9 months in late and early initiators, respectively. The absolute differences in OS, comparing late with early initiators, were 3.2% (95% confidence interval [CI] - 1.5%, 7.9%), - 0.7% (95% CI - 7.2%, 5.8%), and 3.2% (95% CI - 2.8%, 9.3%) at 1, 3, and 5 years, respectively. Late initiators had a higher increase in albumin levels as well as higher pretreatment albumin values. CONCLUSIONS: Postponement of adjuvant chemotherapy up to 8 weeks after discharge from pancreatic adenocarcinoma surgery is safe and may allow more patients to receive adjuvant therapy due to better recovery.

Real-Time Identification of Pancreatic Cancer Cases Using Artificial Intelligence Developed on Danish Nationwide Registry Data.

PURPOSE: Pancreatic cancer is expected to be the second leading cause of cancer-related deaths worldwide within few years. Most patients are not diagnosed in time for curative-intent treatment. Accelerating the time of diagnosis is a key component of reducing pancreatic cancer mortality. We developed and tested a dynamic algorithm aiming at proactively identifying patients with a substantially elevated risk of having undiagnosed pancreatic cancer. METHODS: Machine learning methodology was applied to a live stream of nationwide Danish registry data. A hybrid case-control and prospective cohort design relying on incidence density sampling was used. Three models with minimal tuning were tested. All performance evaluation metrics were based on out-of-sample, out-of-time data in a monthly walk-forward strategy to avoid any temporal biases or inflation of performance metrics. Outcome was a diagnosis of pancreatic cancer. RESULTS: Subgroups identified had a 10.1% risk of being diagnosed with pancreatic cancer within 1 year, corresponding to a number needed to screen of 9.9. When considering competing, potentially computed tomography-detectable GI cancers, this number is reduced to 5.7. The time of diagnosis can be accelerated by up to 142 days. CONCLUSION: Currently available nationwide live data and computational resources are sufficient for real-time identification of individuals with at least 10.1% risk of having undiagnosed pancreatic cancer and 17.7% risk of any GI cancer in the Danish population. For prospective identification of high-risk patients, the area under the curve is not a useful indication of the positive predictive values achieved. Viable design solutions are demonstrated, which address the main shortfalls of the existing cancer prediction efforts in relation to temporal biases, leaks, and performance metric inflation. Efficacy evaluations with resection rates and mortality as end points are needed.

Impact of prior cancer diagnosis on pancreatic cancer outcomes: A Danish Nationwide, population-based Cohort study.

BACKGROUND: The overall survival of pancreatic cancer (PC) remains low, underlining the need of further research to improve PC directed therapy. Some patients with PC may have experienced a prior cancer, refraining them from inclusion in clinical trials, despite not knowing the precise effect of a prior cancer on disease course of PC. OBJECTIVE: To examine the influence of prior cancer on the disease course in patients with PC. METHODS: We conducted a cohort study including Danish patients diagnosed with PC between 2004 and 2020 crosslinking data from the Danish Cancer Registry, the Danish National Patient Registry among several other databases. Using the Kaplan-Meier estimator, we calculated the overall and American Joint Committee on Cancer (AJCC) disease stage stratified survival, comparing patients with and without prior cancer. Furthermore, using inverse probability of treatment weighting (IPTW), we presented a covariate-adjusted model of the average treatment effect in the treated (ATT) of prior cancer on the overall PC survival and stratified for AJCC disease stage. RESULTS: We included 11,147 patients diagnosed with PC, of which 906 (8.1%) had a prior cancer. Comparing patients with and without prior cancer, the IPTW-adjusted survival, indicated a slightly better survival (ATT: 1.5 months; 95% CI: 0.7; 2.2 months). After stratifying by PC tumor stage, the difference was restricted to patients with stage IV PC disease (ATT: 1.1 months; 95% CI: 0.5; 1.7 months). Patients with prior cancer were slightly less prone to present with stage IV PC disease and were more likely to not receive active treatment compared with patients without prior cancer. CONCLUSION: Prior cancer was associated with a slightly better survival in patients with PC, but only in patients with stage IV PC disease. This is likely explained by lead time bias.

Biochemical and morphological responses to post-hepatectomy liver failure in rats.

The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.

Clinical implications of multidisciplinary team pancreatic cyst evaluation.

INTRODUCTION: The detection of incidental pancreatic cysts (PCs) is increasing due to frequent use of imaging. The aim of the present study was to evaluate the clinical consequences of regular multidisciplinary team (MDT) conferences for patients with PCs. METHODS: All patient data were obtained by review of patient medical records. PCs were assessed at the weekly MDT in accordance with the revised Fukuoka guidelines. RESULTS: A total of 455 patients were evaluated within 12 months. A large proportion of the cysts could not be characterised and was handled as branch duct (BD)-intraductal papillary mucinous neoplasia (IPMN). A total of 245 patients were included in a follow-up programme, whereas 175 patients were excluded. Further diagnostic work-up was recommended for 31 patients. A total of 66 patients were reviewed on MDT a second time during the study period, eight of whom received a diagnosis different from that given at the first MDT. A total of 35 patients with mucinous PC or cysts treated as BD-IPMN had either worrisome features (WF) or high-risk stigmata (HRS), four of these patients had a PC ≤ 10 mm. Indication for surgery was WF or HRS and, in the course of 12 months, six patients were recommended surgery taking their PS into account. Two patients had a malignant and two had a premalignant lesion. CONCLUSION: In all, 455 patients were evaluated to find 35 patients with suspected premalignant PCs. This means that almost 8% of the referred patients had suspicious lesions, which indicates a need for a regular MDT conference. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Validation of a surgical model for posthepatectomy liver failure in rats.

BACKGROUND: The upper limit for liver resections in rats is approximately 90%. In the early postoperative phase, mortality increases. The aim of the present study was to validate the rat model of 90% partial hepatectomy (PH) as a model of post-hepatectomy liver failure (PHLF). Further, we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats. METHODS: Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further, block randomization was performed based on time of euthanization: 12, 24, or 48 h after surgery. A general distress score (GDS) ≥10 during the day or ≥6 at midnight prompted early euthanization and classification as nonsurvivor. Animals euthanized as planned were classified as survivors. During euthanization, blood and liver tissue were collected, and liver-specific biochemistry was evaluated. RESULTS: Based on the biochemical results, all animals subjected to 90% PH experienced PHLF. Seventeen rats were euthanized due to irreversible PHLF. The GDS increased for nonsurvivors within 12-18 h after surgery. The mean time for euthanization was 27 h after surgery. CONCLUSION: Based on the GDS and liver-specific biochemistry, we concluded that the model of 90% PH seems to be a proper model for investigating PHLF in rats. As a high GDS is associated with increased mortality, the GDS appears to be valuable in detecting lethal outcomes caused by PHLF in rats.

Trends in pancreatic cancer incidence, characteristics, and outcomes in Denmark 1980-2019: A nationwide cohort study.

OBJECTIVE: To describe time-trends in incidence, characteristics, treatments, and survival in pancreatic cancer patients in Denmark during 1980-2019. DESIGN: A nationwide population-based cohort study of all Danish patients diagnosed with exocrine pancreatic cancer during the study period. Data was obtained from individual-level cross linkage between Danish healthcare registries. We present descriptive characteristics and survival estimates, which was obtained using the Kaplan-Meier estimator and Cox proportional hazards regression models. RESULTS: During the study period, 32,107 patients were diagnosed with pancreatic cancer. In the most recent period, the age-standardized incidence rate was 17.7 per 100,000 person-years. Throughout the study period, between 18.4% and 27.5% of patients had no tumor staging performed, and approximately half of the patient were only offered best supportive care. The proportion of patients treated with surgery doubled during the study period, and the use of adjuvant and neoadjuvant oncological therapy increased substantially. Median survival after surgical resection also increased to 25.8 months in the most recent time period. CONCLUSION: Pancreatic cancer incidence is increasing in Denmark, and this increase is projected to continue. The proportion of patients offered curative-intent treatment increased, which translates into an increase in overall survival. All numbers are comparable to best international standards.

Disparity in use of modern combination chemotherapy associated with facility type influences survival of 2655 patients with advanced pancreatic cancer.

AIM: Academic and high volume hospitals have better outcome for pancreatic cancer (PC) surgery, but there are no reports on oncological treatment. We aimed to determine the influence of facility types on overall survival (OS) after treatment with chemotherapy for inoperable PC. MATERIAL AND METHODS: 2,657 patients were treated in Denmark from 2012 to 2018 and registered in the Danish Pancreatic Cancer Database. Facilities were classified as either secondary oncological units or comprehensive, tertiary referral cancer centers. RESULTS: The average yearly number of patients seen at the four tertiary facilities was 71, and 31 at the four secondary facilities. Patients at secondary facilities were older, more frequently had severe comorbidity and lived in non-urban municipalities. As compared to combination chemotherapy, monotherapy with gemcitabine was used more often (59%) in secondary facilities than in tertiary (34%). The unadjusted median OS was 7.7 months at tertiary and 6.1 months at secondary facilities. The adjusted hazard ratio (HR) of 1.16 (confidence interval 1.07-1.27) demonstrated an excess risk of death for patients treated at secondary facilities, which disappeared when taking type of chemotherapy used into account. Hence, more use of combination chemotherapy was associated with the observed improved OS of patients treated at tertiary facilities. Declining HR's per year of first treatment indicated improved outcomes with time, however the difference among facility types remained significant. DISCUSSION: Equal access to modern combination chemotherapy at all facilities on a national level is essential to ensure equality in treatment results.

Intra-observer agreements in multidisciplinary team assessments of pancreatic cancer patients.

BACKGROUND AND METHODS: Treatment strategies for pancreatic cancer patients are made by a multidisciplinary team (MDT) board. We aimed to assess intra-observer variance at MDT boards. Participating units staged, assessed resectability, and made treatment allocations for the same patients as they did two years earlier. We disseminated clinical information and CT images of pancreatic cancer patients judged by one MDT board to have nonmetastatic pancreatic cancer to the participating units. All units were asked to re-assess the TNM stage, resectability, and treatment allocation for each patient. To assess intra-observer variance, we computed %-agreements for each participating unit, defined as low (<50%), moderate (50%-75%), and high (>75%) agreement. RESULTS: Eighteen patients were re-assessed by six MDT boards. The overall agreement was moderate for TNM-stage (ranging from 50%-70%) and resectability assessment (53%) but low for treatment allocation (46%). Agreement on resectability assessments was low to moderate. Findings were similar but more pronounced for treatment allocation. We observed a shift in treatment strategy towards increasing use of neoadjuvant chemotherapy, particularly in patients with borderline resectable and locally advanced tumors. CONCLUSIONS: We found substantial intra-observer agreement variations across six different MDT boards of 18 pancreatic cancer patients with two years between the first and second assessment.

Splenectomy and risk of COVID-19 infection, hospitalisation, and death.

OBJECTIVES: Splenectomy is a common surgical procedure, and splenectomized patients have shown to be severely more affected by certain infections than patients with a preserved splenic function. We investigated the risk of COVID-19 infection and subsequent hospitalisation and death in splenectomized patients. METHODS: We conducted a case-control study of all individuals with a microbiologically verified COVID-19 infection in Denmark through December 31, 2020. To each case, we matched three controls on age, sex, and region of residence. We examined the association between previous splenectomy and the risk of COVID-19 infection, hospitalisation, and death using a logistic regression model. RESULTS: We identified 165,623 individuals with a positive COVID-19 test and 493,300 matched controls. Mean age was 38 years. 130 and 422 splenectomies were performed in the COVID-19 positive individuals and controls, respectively. Splenectomized patients did not have a higher risk of COVID-19 infection than non-splenectomized patients (adjusted OR: 0.89; 95% CI: 0.73-1.08). Among COVID-19 positive individuals, splenectomized patients may have an increased risk of hospitalisation or death (adjusted OR for combined endpoint: 1.44; 95% CI: 0.79-2.61). CONCLUSIONS: Splenectomized patients are not at an increased risk of COVID-19 infection, but they may have a higher risk of hospitalisation or death among COVID-19 positive individuals. This may be attributed to higher comorbidity levels.

Predictors of underlying pancreatic cancer in patients with acute pancreatitis: a Danish nationwide cohort study.

BACKGROUND: To identify demographic characteristics, comorbidities, medical procedures, and prescription drug use that may act as predictors of underlying pancreatic cancer in acute pancreatitis. METHODS: A cohort study of all patients admitted to Danish hospitals with incident acute pancreatitis during 1999-2015. The ability of age, sex, selected comorbidities, medical procedures, and prescription drug use to predict underlying pancreatic cancer in acute pancreatitis (i.e., pancreatic cancer diagnosed up to one year after acute pancreatitis) was examined. The absolute risk and odds ratio (OR) with 95% confidence interval (CI) of cancer was computed for each variable. RESULTS: 28,231 patients with incident acute pancreatitis, of which 283 (1.0%) had underlying pancreatic cancer, were included. Age >50 years was a predictor of pancreatic cancer with highest risk in patients aged 56-70 years. New-onset chronic pancreatitis (multivariable OR: 2.36 [95% CI: 1.35-4.14]) and new-onset diabetes (multivariable OR: 1.94 [95% CI: 1.30-2.92]) were also predictors of pancreatic cancer. Diagnoses of biliary or alcohol-related diseases were predictors of no underlying pancreatic cancer. Most variables examined had no or limited predictive ability. CONCLUSION: Age, new-onset chronic pancreatitis, new-onset diabetes, and absence of biliary or alcohol-related diseases were predictors of underlying pancreatic cancer in acute pancreatitis patients.

Statins and pancreatic cancer risk in patients with chronic pancreatitis: A Danish nationwide population-based cohort study.

Statins (HMG-CoA reductase inhibitors) have antiinflammatory and possibly anticancer properties. We hypothesized that statin use is associated with lower risk of pancreatic cancer in patients with chronic pancreatitis. This nationwide population-based cohort study included all Danish patients diagnosed with incident chronic pancreatitis from 1 January 1996 to 31 December 2012. We used the Danish National Prescription Registry to ascertain information on statin prescriptions for members of the study population before and after their pancreatitis diagnosis. We computed crude incidence rates, incidence rate ratios (IRRs) and adjusted hazard ratios (HRs) with associated 95% confidence intervals (CIs) for pancreatic cancer, comparing statin users with nonusers. We computed HRs using Cox proportional hazards regression with statins treated as a time-varying exposure lagged by 1 year, adjusting for age, sex, socioeconomic status and individual comorbidities. The study included 8,311 chronic pancreatitis patients with a median age of 54 years. We observed 153 pancreatic cancers during 60,365 person-years of follow-up. The unadjusted IRR comparing statin users with nonusers was 1.00 (95% CI: 0.60-1.60). Adjustment for potential confounders only had a small impact on the estimate (adjusted HR: 0.90; 95% CI: 0.56-1.44). Our findings suggest that statin use is not associated with pancreatic cancer risk in patients with chronic pancreatitis.

Positive predictive value of acute and chronic pancreatitis diagnoses in the Danish National Patient Registry: A validation study.

Aims: To examine the validity of the diagnoses of acute and chronic pancreatitis registered in the Danish National Patient Registry. Methods: We identified all patients in the Danish National Patient Registry admitted to two Danish hospitals with acute or chronic pancreatitis from 1996 to 2013. From this population, we randomly sampled 100 patients with acute pancreatitis and 100 patients with chronic pancreatitis. For each cohort, we computed the positive predictive values and associated 95% confidence intervals (CIs) for the discharge diagnosis of acute or chronic pancreatitis using medical records as the gold standard. Results: We identified 2617 patients with acute pancreatitis and 1284 patients with chronic pancreatitis discharged from either of the two hospitals during the study period. Of these, 776 (19.9%) had a diagnosis of both acute and chronic pancreatitis and are thus present in both cohorts. From the 200 sampled patients, a total of 138 (69.0%) medical records were available for review. The positive predictive value for a diagnosis of acute pancreatitis in the Danish National Patient Registry was 97.3% (95% CI 90.5-99.2%) and for chronic pancreatitis 83.1% (95% CI 72.2-90.3%). Conclusions: The validity of diagnoses of acute and chronic pancreatitis registered in the Danish National Patient Registry since 1996 is generally high.

Cholecystitis and risk of pancreatic, liver, and biliary tract cancer in patients undergoing cholecystectomy.

BACKGROUND: Cholecystitis before cholecystectomy may increase risk of cancers in the hepato-pancreato-biliary area. METHODS: A population-based cohort study of all patients undergoing cholecystectomy in Denmark during 1996-2015, using nationwide healthcare registries. We retrieved information on cholecystitis within two years before the date of surgery and information on pancreatic cancer, hepatocellular carcinoma (HCC), and biliary tract cancer. We examined cancer risk using a Cox model to calculate the hazard ratios (HRs). We also computed cumulative incidence functions with 95% CIs, comparing patients with and without cholecystitis before cholecystectomy. RESULTS: We included 132,794 patients, of which 73.0% were women. In the first five years of follow-up, we observed an increased risk of biliary tract cancer, but not pancreatic cancer or HCC, in patients with prior cholecystitis. After more than five years of follow-up, patients with prior cholecystitis had an increased risk of pancreatic cancer (adjusted HR: 1.26; 95% CI: 0.98-1.63) and possibly biliary tract cancer (adjusted HR: 1.33; 95% CI: 0.64-2.77). Long-term risk of HCC was decreased in patients with prior cholecystitis. For all cancers, the 20-year absolute risks were less than 1%. CONCLUSION: In patients undergoing cholecystectomy, prior cholecystitis was associated with increased risk of pancreatic and possibly biliary tract cancer.

Acute pancreatitis as an early marker of pancreatic cancer and cancer stage, treatment, and prognosis.

BACKGROUND: We aimed to examine the association between acute pancreatitis, a potential early symptom of pancreatic cancer, and pancreatic cancer stage, treatment, and prognosis. METHODS: We conducted a cohort study of patients diagnosed with pancreatic cancer during 2004-2017 using population-based registry data from Denmark and Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims from the United States (US), which include individuals aged 65 + . We ascertained information on acute pancreatitis diagnoses up to 90 days before pancreatic cancer and followed them for a maximum of five years. We assessed overall survival difference at 30 days, six months, and one, three and five years, comparing patients with and without coexistence of acute pancreatitis. Secondary outcomes were cancer stage and treatment. RESULTS: We identified 12,522 Danish and 37,552 US patients with pancreatic cancer (median age 71 and 78 years, respectively). In the Danish cohort, 1.4 % had acute pancreatitis before pancreatic cancer vs. 5.9 % in the US cohort. After five years of follow-up, the survival difference was 6.1 % (95 % CI: [-0.4 %, 12.6 %]) in Danish and 1.7 % (95 % CI: [0.8 %, 2.7 %]) in US patients, comparing patients with and without acute pancreatitis. Patients with acute pancreatitis had lower prevalence of metastatic tumors at diagnosis (Denmark: 42.5 % vs. 48.7 %; US: 34.4 % vs. 45.9 %) and higher resection frequencies (Denmark: 20.1 % vs. 12.1 %; US: 16.1 % vs.11.3 %) than patients without acute pancreatitis. CONCLUSIONS: Pancreatic cancer patients with acute pancreatitis diagnosed up to 90 days before cancer diagnosis had earlier stage at diagnosis and better survival than patients without acute pancreatitis.

Antihypertensive drugs and pancreatic cancer risk in patients with chronic pancreatitis: a Danish nationwide population-based cohort study.

BACKGROUND: Antihypertensives may inhibit pancreatic carcinogenesis. We examined the association between use of these drugs and pancreatic cancer in patients with chronic pancreatitis. METHODS: We conducted a nationwide population-based cohort study of all chronic pancreatitis patients diagnosed in Denmark during 1996-2012. Using a Cox proportional hazards model with time-varying exposure lagged by 1 year, we examined the risk of pancreatic cancer according to antihypertensive drug use. RESULTS: We included 8,311 patients with chronic pancreatitis and observed 153 pancreatic cancers during follow-up. At baseline, 2197 patients (26.4%) were exposed to at least one class of antihypertensive drugs. We did not observe any measurable associations between the use of antihypertensive drugs and pancreatic cancer. CONCLUSIONS: Our findings suggest little evidence of an association between the use of antihypertensive drugs and pancreatic cancer risk in patients with chronic pancreatitis. Confirmation is warranted in future studies.