Burden of bone disease in chronic pancreatitis:A systematic review and meta-analysis

BACKGROUND Bone disease is an under-recognized cause of morbidity in chronic pancreatitis(CP).Over the past decade,publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem.AIM To quantify the prevalence of osteopenia,osteoporosis,and fragility fractures in CP patients and investigate the associated clinical features and outcomes.METHODS A systematic search identified studies investigating bone disease in CP patients from Cochrane Library,Embase,Google Scholar,Ovid Medline,PubMed,Scopus,and Web of Science,from inception until October 2022.The outcomes included prevalence of osteopenia,osteoporosis,and fragility fractures,which were metaanalyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features.RESULTS Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis.The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2%(95%CI:35.2%-47.3%)and 20.9%(95%CI:14.9%-27.6%),respectively.The pooled prevalence of fragility fractures described among CP was 5.9%(95%CI:3.9%-8.4%).Metaregression revealed significant association of pancreatic enzyme replacement therapy(PERT)use with prevalence of osteoporosis[coefficient:1.7(95%CI:0.6-2.8);P<0.0001].We observed no associations with mean age,sex distribution,body mass index,alcohol or smoking exposure,diabetes with prevalence of osteopenia,osteoporosis or fragility fractures.Paucity of data on systemic inflammation,CP severity,and bone mineralization parameters precluded a formal metaanalysis.CONCLUSION This meta-analysis confirms significant bone disease in patients with CP.Other than PERT use,we observed no patient or study-specific factor to be significantly associated with CP-related bone disease.Further studies are needed to identify confounders,at-risk population,and to understand the mechanisms of CP-related bone disease and the implications of treatment response.

Evaluating the accuracy of American Society for Gastrointestinal Endoscopy guidelines in patients with acute gallstone pancreatitis with choledocholithiasis

BACKGROUND Acute gallstone pancreatitis(AGP) is the most common cause of acute pancreatitis(AP) in the United States. Patients with AGP may also present with choledocholithiasis. In 2010, the American Society for Gastrointestinal Endoscopy(ASGE) suggested a management algorithm based on probability for choledocholithiasis, recommending additional imaging for patients at intermediate risk and endoscopic retrograde cholangiopancreatography(ERCP) for patients at high risk of choledocholithiasis. In 2019, the ASGE guidelines were updated using more specific criteria to categorize individuals at high risk for choledocholithiasis. Neither ASGE guideline has been studied in AGP to determine the probability of having choledocholithiasis.AIM To determine compliance with ASGE guidelines, assess outcomes, and compare 2019 vs 2010 ASGE criteria for suspected choledocholithiasis in AGP.METHODS We conducted a retrospective cohort study of 882 patients admitted with AP to a single tertiary care center from 2008-2018. AP was diagnosed using revised Atlanta criteria and AGP was defined as the presence of gallstones on imaging or with cholestatic pattern of liver injury in the absence of another cause. Patients with chronic pancreatitis and pancreatic malignancy were excluded as were those who went directly to cholecystectomy prior to assessment for choledocholithiasis. Patients were assigned low, intermediate or high risk based on ASGE guidelines. Our primary outcomes of interest were the proportion of patients in the intermediate risk group undergoing magnetic resonance cholangiopancreatography(MRCP) first and the proportion of patients in the high risk group undergoing ERCP directly without preceding imaging. Secondary outcomes of interest included outcome differences based on if guidelines were not adhered to. We then evaluated the diagnostic accuracy of 2019 in comparison to the 2010 ASGE criteria for patients with suspected choledocholithiasis. We performed the t test or Wilcoxon rank sum test, as appropriate, to analyze if there were outcome differences based on if guidelines were not adhered to. Kappa coefficients were calculated to measure the degree of agreement between pairs of variables.RESULTS In this cohort, we identified 235 patients with AGP of which 79 patients were excluded as they went directly to surgery for cholecystectomy without prior MRCP or ERCP. Of the remaining 156 patients, 79 patients were categorized as intermediate risk and 77 patients were high risk for choledocholithiasis according to the 2010 ASGE guidelines. Among 79 intermediate risk patients, 54(68%) underwent MRCP first whereas 25 patients(32%) went directly to ERCP. For the 54 patients with intermediate risk who had MRCP first, 36 patients had no choledocholithiasis while 18 patients had evidence of choledocholithiasis prompting ERCP. Of these patients, ERCP confirmed stone disease in 11 patients. Of the 25 intermediate risk patients who directly underwent ERCP, 18 patients had stone disease. One patient with a normal ERCP developed post ERCP pancreatitis. Patients undergoing MRCP in this group had a significantly longer length of stay(5.0 vs 4.0 d, P = 0.02). In the high risk group, 64 patients(83%) had ERCP without preceding imaging, of which, 53 patients had findings consistent with choledocholithiasis, of which 13 patients(17%) underwent MRCP before ERCP, all of which showed evidence of stone disease. Furthermore, all of these patients ultimately had an ERCP, of which 8 patients had evidence of stones and 5 had normal examination.RESULTS Our cohort also demonstrated that 58% of all 156 patients with AGP had confirmed choledocholithiasis(79% of the high risk group and 37% of the intermediate group when risk was assigned based on the 2010 ASGE guidelines). When the updated 2019 ASGE guidelines were applied instead of the original 2010 guidelines, there was moderate agreement between the 2010 and 2019 guidelines(kappa = 0.46, 95%CI: 0.34-0.58). Forty-two of 77 patients were still deemed to be high risk and 35 patients were downgraded to intermediate risk. Thirty-five patients who were originally assigned high risk were reclassified as intermediate risk. For these 35 patients, 26 patients had ERCP findings consistent with choledocholithiasis and 9 patients had a normal examination. Based on the 2019 criteria, 9/35 patients who were downgraded to intermediate risk had an unnecessary ERCP with normal findings(without a preceding MRCP).CONCLUSION Two-thirds in intermediate risk and 83% in high risk group followed ASGE guidelines for choledocholithiasis. One intermediate-group patient with normal ERCP had post-ERCP AP, highlighting the risk of unnecessary procedures.

Bone disease in chronic pancreatitis

Bone disease(osteopenia or osteoporosis)is a highly prevalent condition in society and presents a tremendous,preventable public health burden.Screening procedures,such as,dual-energy X-ray absorptiometry scans,have allowed early identification and intervention to improve bone health,and reduce the risk of osteoporotic fractures,which carry significant morbidity and mortality.The association of bone disease has been recognized in several diseases of the gastrointestinal tract,resulting in established guidelines for screening in patients with malabsorptive disorders such as inflammatory bowel disease and celiac disease.Increasingly,the risk of bone disease has been recognized in patients with chronic pancreatitis(CP),who share similar risk factors as patients with other high gastrointestinal disorders.As a result,there have been a number of studies examining the prevalence and risks of bone disease and fractures in patients with CP.This review aims to summarize the recent literature and current recommendations related to bone disease in CP.

Natural history,clinical characteristics,outcomes,and long-term follow-up of pain-free chronic pancreatitis

Background:Chronic pancreatitis(CP)is characterized by chronic abdominal pain and functional insufficiency.However,a small subset of patients with prior acute pancreatitis(AP)and/or underlying risk factors for developing CP may be pain-free at diagnosis and may have a different clinical course.We aimed to compare the clinical characteristics,outcomes,and healthcare utilization between CP patients with and without pain.Methods:Reviewed patients with established CP were followed in our Pancreas Center between January 2016 and April 2021.Patients without risk factors for developing CP and/or without AP prior to their diagnosis and only with incidental radiologic features of CP were excluded,so as tominimize confounding factors of pancreatopathy unrelated to CP.Patients were divided into painful and pain-free groups to analyze differences in demographics,outcomes,and healthcare utilization.Results:Of 368 CP patients,49(13.3%)were pain-free at diagnosis and had remained so for>9 years.There were no significant differences in body mass index,race,sex,or co-morbidities between the two groups.Pain-free patients were older at diagnosis(53.9 vs 45.7,P=0.004)and had less recurrent AP(RAP)(43.8%vs 72.5%,P<0.001)and less exocrine pancreatic insufficiency(EPI)(34.7%vs 65.7%,P<0.001).Pain-free patients had less disability(2.2%vs 22.0%,P=0.003),mental illness(20.4%vs 61.0%,P<0.001),surgery(0.0%vs 15.0%,P=0.059),and therapeutic interventions(0.0%vs 16.4%,P=0.005)for pain.Conclusions:We described a unique subset of patients with underlying risk factors for CP and/or prior AP who were painfree at diagnosis.They were older at diagnosis,had less EPI and RAP,and overall favorable outcomes with minimal resource utilization.