Machine learning for the prediction of post-ERCP pancreatitis risk: A proof-of-concept study.

BACKGROUND: Predicting Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis (PEP) risk can be determinant in reducing its incidence and managing patients appropriately, however studies conducted thus far have identified single-risk factors with standard statistical approaches and limited accuracy. AIM: To build and evaluate performances of machine learning (ML) models to predict PEP probability and identify relevant features. METHODS: A proof-of-concept study was performed on ML application on an international, multicenter, prospective cohort of ERCP patients. Data were split in training and test set, models used were gradient boosting (GB) and logistic regression (LR). A 10-split random cross-validation (CV) was applied on the training set to optimize parameters to obtain the best mean Area Under Curve (AUC). The model was re-trained on the whole training set with the best parameters and applied on test set. Shapley-Additive-exPlanation (SHAP) approach was applied to break down the model and clarify features impact. RESULTS: One thousand one hundred and fifty patients were included, 6.1% developed PEP. GB model outperformed LR with AUC in CV of 0.7 vs 0.585 (p-value=0.012). GB AUC in test was 0.671. Most relevant features for PEP prediction were: bilirubin, age, body mass index, procedure time, previous sphincterotomy, alcohol units/day, cannulation attempts, gender, gallstones, use of Ringer's solution and periprocedural NSAIDs. CONCLUSION: In PEP prediction, GB significantly outperformed LR model and identified new clinical features relevant for the risk, most being pre-procedural.

Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, is increasing in incidence. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We, therefore, investigated the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS). METHODS: Between 2000 and 2016, we retrospectively enrolled 236 PDAC patients treated with curative-intent pancreatic surgery at Helsinki University Hospital. All pancreatic transection margin slides were re-reviewed and histological findings were evaluated applying international guidelines. RESULTS: DSS among patients with no fibrosis, acinar atrophy or chronic inflammation identified on pathology slides was significantly better than DSS among patients with fibrosis, acinar atrophy and chronic inflammation [median survival: 41.8 months, 95% confidence interval (CI) 26.0-57.6 vs. 20.6 months, 95% CI 10.3-30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19-9 > 37 kU/l [hazard ratio (HR) 1.48, 95% CI 1.02-2.16], lymph node metastases N1-2 (HR 1.71, 95% CI 1.16-2.52), tumor size > 30 mm (HR 1.47, 95% CI 1.04-2.08), the combined effect of fibrosis and acinar atrophy (HR 1.91, 95% CI 1.27-2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR 1.63, 95% CI 1.03-2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular fibrosis (p = 0.655), intralobular fibrosis (p = 0.587), acinar atrophy (p = 0.584) or chronic inflammation (p = 0.453). CONCLUSIONS: Our results indicate that the pancreatic stroma is associated with PDAC patients' DSS. Additionally, the more severe the fibrosis, acinar atrophy and chronic inflammation, the worse the impact on DSS, thereby warranting further studies investigating stroma-targeted therapies.

Chronic use of statins and acetylsalicylic acid and incidence of post-endoscopic retrograde cholangiopancreatography acute pancreatitis: A multicenter, prospective, cohort study.

OBJECTIVES: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP. METHODS: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated. RESULTS: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P = 0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94-2.99, P = 0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P = 0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49-2.13), P = 0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20 minutes, were risk factors. CONCLUSIONS: The use of statins or ASA is not associated with a lower risk or a milder course of PEP.

Association between chronic pancreatitis and pancreatic cancer: A 10-year retrospective study of endoscopically treated and surgical patients.

Pancreatic cancer (PC) has a poor prognosis. Chronic pancreatitis (CP) associates with high morbidity and mortality, and serves as a risk factor for PC. Our study aimed to assess the association between endoscopically treated CP patients and PC, and to establish the rate of CP among patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC). We retrospectively analyzed 458 CP patients undergoing endoscopic treatment (ET) between 2000 and 2010 and 349 PDAC patients undergoing pancreatic resection between 2000 and 2014 at the Helsinki University Hospital. The likelihood of diagnosing PC was highest within 2 years of a CP diagnosis: 21 of 30 PC diagnoses occurred during this time. After 2 years follow-up: 9 of 30 PC diagnoses occurred 2-12 years from CP diagnosis. Two patients were diagnosed with CP before PDAC. Multivariate analysis showed two prognostic factors indicative of PC development: biliary stricture (HR 9.21; 95% CI 3.76-22.08) and a higher age (per 5-year increases) at CP onset (HR 1.55; 95% CI 1.30-1.85). Among 458 CP patients, the median overall survival without PC was 14.7 years (95% CI 12.0-17.3), falling to 1.6 years (95% CI 1.2-2.0) with PC. The high incidence of PC among CP patients at the beginning of follow-up likely reflected an initially missed PC diagnoses. In long-term follow-up, an increasing PC incidence might reflect the PC-predisposing impact of CP. Thus, we recommend careful follow-up for patients presenting with a recently diagnosed CP and risk factors for PC.

Fully covered self-expanding metal stents for benign refractory pancreatic duct strictures in chronic pancreatitis.

Background: Pancreatic duct (PD) stricture is a common adverse event in chronic pancreatitis (CP). Primary treatment for refractory PD strictures is endotherapy (ET), including the insertion of multiple plastic stents. In addition, fully covered self-expandable metal stents (FC-SEMSs) have also been successfully used. More long-term studies are necessary to clarify the complication rate and efficiency, however. Methods: This retrospective study was comprised of 17 patients with symptomatic CP and refractory fibrotic main pancreatic duct (MPD) stricture treated with FC-SEMSs between 2010-2018 at the Helsinki University Hospital. Treated strictures were located in the pancreatic head. Technical success was defined as the accurate positioning of the stent and resolution of the MPD stricture. Clinical success was defined as pain relief at the end of the follow-up. Results: In 12 patients (71%), stricture resolution was accomplished. Clinical success was achieved in 12 patients (71%). The median duration of stenting was 169 days (range 15-804). Ten patients (58.8%) underwent a follow-up of two years or more. Early complications (≤7 days) occurred in two patients (12%): one pancreatitis and one cholestasis. Late complications (≥7 days) included severe abdominal pain (n = 2, 12%), pancreatitis (n = 3, 18%), cholestasis (n = 1, 6%) and stent migration (n = 7, 35%). Significant differences in stricture resolution and pain improvement were evident in patients with stent migration compared to patients without stent migration [1(14.3%) vs. 11(84.6%), p = .004 and 2(28.6%) vs. 11(84.6%), p = .022]. Conclusion: FC-SEMS placement is a safe and potentially effective treatment for this challenging group of patients. However, stent migration appears to affect the clinical and technical outcome.

Statin use is not associated with an increased risk of acute pancreatitis-A meta-analysis of observational studies.

BACKGROUND: Statins are perceived as potential etiological factors for acute pancreatitis (AP), but recent evidence suggests the opposite. Our aim was to evaluate the association between statin use and risk of AP in observational studies. METHODS: Medline, Scopus, and Web of Science were searched for cohort (C) and case-control (CC) studies evaluating statins as intervention and AP as outcome. Pooled adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. RESULTS: Thirteen studies (seven CC, six C) with 34,899 AP patients and 5,377,894 controls were included. Prevalence of statin use was 9.8% among AP patients and 25% among controls. Pooled adjusted OR was 1.00 (95% CI = 0.63 to 1.59) with considerable heterogeneity (I 2 = 98%). CC studies were associated with increased AP risk (OR = 1.33; 95% CI = 1.20 to 1.47), unlike C studies (OR = 0.69; 95% CI = 0.37 to 1.31). No association with increased risk was found for studies from Western countries (OR = 0.90; 95% CI = 0.52 to 1.56), unlike for studies conducted in Asia (OR = 1.39; 95% CI = 1.10 to 1.75). CONCLUSION: Statin use is not associated with increased risk of AP. Increased risk was limited to CC studies, which are more prone to bias, while C studies showed no global effect. Further research is needed to clarify whether statin type, dosage, treatment duration or AP etiology might account for this difference.

Chronic use of statins and risk of post-ERCP acute pancreatitis (STARK): Study protocol for an international multicenter prospective cohort study.

BACKGROUND: Acute pancreatitis (AP) is the most common complication after endoscopic retrograde cholangiopancreatography (ERCP). Statins have been traditionally associated to an increased risk of AP, however, recent evidence suggests that statins may have a protective role against this disease. AIMS: Our primary aim is to investigate whether the use of statins has a protective effect against post-ERCP pancreatitis (PEP). Secondary outcomes are: to evaluate the effect of other drugs on the incidence of PEP; to ascertain the relationship between the use of statins and the severity of PEP; and to evaluate the effect of other risk and protective factors on the incidence of PEP. METHODS: STARK is an international multicenter prospective cohort study. Centers from Spain, Italy, Croatia, Finland and Sweden joined this study. The total sample size will include about 1016 patients, which was based on assuming a 5% incidence of PEP among non-statin (NSt) users, a 1-3 ratio of statin (St) and NSt consumers respectively, a 70% decrease in PEP among St consumers, an alpha-error of 0.05 and beta-error of 0.20. All patients aged ≥18 years scheduled for ERCP will be offered to enter the study. DISCUSSION: STARK study will ascertain whether statins, a safe, widely used and inexpensive drug, can modify the incidence of PEP.

Long-term results of combined ESWL and ERCP treatment of chronic calcific pancreatitis.

OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) combined with endotherapy (ET) is the standard treatment for pancreatic duct stones (PDS) in chronic pancreatitis (CP). Our aim was to report the short- and long-term results of ESWL and ET. MATERIAL AND METHODS: Consecutively treated 83 patients with symptomatic PDS using ESWL and ET. Success was defined (i) technically: PDS fragmentation and clearance obtained and (ii) clinically: improvement/resolution of pain. To get information on quality of life, we conducted a phone survey whereby we contacted 64 (89%) patients. The long-term results are presented in those patients with ≥2 years follow-up. RESULTS: Treated PDS with median size of 10 (5-25) mm were located in the head, body, or the tail of the pancreas in 78, 4, and 1 patients, respectively. The primary results were that technical success was achieved in 69 patients (83%) and clinical success in 66 patients (80%). Fourteen patients had technical failure, but eight of them became free of pain. Thus, clinical success can be considered to have been achieved in 74 of 83 patients (89%). In patients with persistent pseudocyst (PC) at the time of ESWL (n = 19), the PC disappeared in a year in 14 patients (74%). The long-term results were obtained from 61 (73%) ESWL- and ET-treated patients. The median follow-up for them was 53 months (range: 24-124) and 57 patients (93%) became pain-free or had less pain. CONCLUSIONS: For patients with CP and PDS ESWL combined with ET is an effective and safe treatment giving favorable long-term results.