ABSTRACT
BACKGROUND AND AIMS: Although pancreatic endotherapy (PET) is commonly used for treating adverse events of chronic pancreatitis, data on the frequency and factors associated with the use of PET are limited. Our aim was to define the use of and factors predictive for receiving PET in a well-characterized chronic pancreatitis cohort. METHODS: This is a cross-sectional analysis of data from PROCEED, a multicenter U.S. cohort study of chronic pancreatitis. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after completion of the last course. Multivariable logistic regression identified predictive factors for receiving PET, and proportional rates model assessed risk factors for repeat PET. RESULTS: Of 681 subjects, 238 (34.9%) received PET. Factors associated with receiving PET included female sex (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.03-1.53), lower education (OR, 1.30; 95% CI, 1.04-1.62), income ≤$50,000 per year (OR, 1.35; 95% CI, 1.07-1.71), and prior acute pancreatitis (OR, 1.74; 95% CI, 1.31-2.32). Of 238 subjects, 103 (43.3%) underwent repeat PET at a median duration of 2 years, with 23.1% receiving 2 courses, 9.7% receiving 3 courses, and 10.4% receiving ≥4 courses. CONCLUSIONS: Nearly half of patients with chronic pancreatitis who undergo PET received 1 or more repeat courses within 2 to 3 years. In addition to a prior history of acute pancreatitis, demographic and socioeconomic factors were associated with receiving PET.
Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Pancreatitis, Chronic , Humans , Pancreatitis, Chronic/therapy , Female , Male , Middle Aged , United States , Cross-Sectional Studies , Adult , Sex Factors , Cohort Studies , Aged , Logistic Models , Educational Status , Income , Risk Factors , Retreatment/statistics & numerical data , Multivariate AnalysisABSTRACT
BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is the standard of care for the management of choledocholithiasis but carries risk of complications which may result in significant morbidity and mortality. While currently available guidelines endorse the use of ERCP for the management of symptomatic common bile duct stones, the need for ERCP in incidentally found asymptomatic choledocholithiasis is more controversial, and practice varies on a geographic and institutional level. This systematic review and meta-analysis is conducted to compare post-ERCP adverse events between asymptomatic and symptomatic choledocholithiasis patients. METHODS: We searched PubMed/Embase/Web of Science databases to include all studies comparing post-ERCP outcomes between asymptomatic and symptomatic choledocholithiasis patients. The primary outcome was post-ERCP pancreatitis (PEP), while secondary outcomes included post-ERCP cholangitis, bleeding, and perforation. We calculated pooled risk ratios (RR) and 95% confidence intervals (CIs) using the Mantel-Haenszel method within a random-effect model. RESULTS: Our analysis included six observational studies, totaling 2,178 choledocholithiasis patients (392 asymptomatic and 1786 symptomatic); 53% were female. Asymptomatic patients exhibited a higher risk of PEP compared with symptomatic patients (11.7% versus 4.8%; RR 2.59, 95% CI 1.56-4.31, p ≤ 0.001). No significant difference was observed in post-ERCP cholangitis, bleeding, or perforation rates between the two groups. CONCLUSIONS: Asymptomatic patients with choledocholithiasis appear to have a higher risk of PEP than symptomatic patients, while the risk of other post-ERCP adverse events is similar between the two groups. Interventional endoscopists should thoroughly discuss potential adverse events (particularly PEP) with asymptomatic patients before performing ERCP and utilize PEP-prevention measures more liberally in this subgroup of patients.
Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Choledocholithiasis , Pancreatitis , Humans , Choledocholithiasis/surgery , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Pancreatitis/etiology , Pancreatitis/epidemiology , Asymptomatic Diseases , Cholangitis/etiology , Cholangitis/epidemiology , Risk Factors , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/diagnosisABSTRACT
BACKGROUND: Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control. OBJECTIVE: In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP. METHODS: Using the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0). RESULTS: As of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025. CONCLUSIONS: This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP. TRIAL REGISTRATION: Clinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50513.
ABSTRACT
INTRODUCTION: Acute necrotizing pancreatitis (ANP) complicates 15 % of acute pancreatitis cases and is associated with prolonged length of stay (LOS). There are limited studies exploring potential predictors. METHODS: We carried out a retrospective study of all consecutive patients presenting to a large referral healthcare system with ANP. Patients younger than 18 years of age, without confirmed glandular necrosis and with in-hospital mortality were excluded. Poisson regression was carried out to identify potential predictors of prolonged hospital stay. RESULTS: One hundred and sixty-two patients hospitalized between December 2016 and June 2020 were included. The median LOS was 12 days (range: 1-155 days). On multivariate analysis, organ dysfunction at presentation (Incidence rate ratio (IRR) 1.21, p = 0.01) or during admission (IRR 1.32, p = 0.001), Charlson Comorbidity Index scores (IRR 1.1 per CCI point, p < 0.001), known chronic pancreatitis (IRR 1.19, p = 0.03), concurrent (non-pancreas related) infections (IRR 1.13, p = 0.04), need for enteral tube placement (IRR 3.42, p < 0.001) and in-hospital interventions (IRR 1.48-2.85 depending on intervention, p < 0.001) were associated with increased LOS. For patients in the cohort to whom this applied, delayed hospital transfers (IRR 1.02, p < 0.001) and delayed start of enteral feeds (IRR 1.01, p = 0.017) contributed to increased overall LOS. CONCLUSION: We demonstrate that multiple factors including delayed transfers to hospitals with pancreaticobiliary expertise lead to increased length of hospitalization. We suggest various strategies that can be considered to target those gaps and may have a favorable effect on LOS.
Subject(s)
Pancreatitis, Acute Necrotizing , Humans , Length of Stay , Retrospective Studies , Acute Disease , HospitalsABSTRACT
BACKGROUND AND AIMS: Extracorporeal shock wave lithotripsy (ESWL) is performed to fragment large main pancreatic duct (MPD) stones in symptomatic patients. Subsequent endoscopic retrograde cholangiopancreatography (ERCP) is often performed to clear the stone fragments. Edema of surrounding tissue after ESWL theoretically affects the ability to perform ERCP. However, the optimal timing of ERCP after ESWL is not clearly defined. The aim of this study is to determine the efficacy and safety of same-day ERCP after ESWL and to determine if the timing of ERCP after ESWL affects outcomes. METHODS: This is a retrospective study of consecutive patients from January, 2013 to September, 2019 who received ESWL for MPD stones at our center. Included patients received subsequent same-day ERCP under the same general anesthesia session or later session ERCP (1-30 days after ESWL). Demographics, anatomical findings, history, and outcomes were collected. Success was defined as complete or near complete (> 80%) stone fragmentation with clearance. RESULTS: 218 patients were treated with ESWL and subsequent ERCP. 133 (61.0%) received ERCP on the same day immediately after ESWL, while 85 (39.0%) returned for ERCP at a later day (median 3.0 days after ESWL). Baseline characteristics demonstrated patients who received same-day ERCP had a higher rate of pain at baseline (94.7% vs 87.1%, p = 0.045). Main outcomes demonstrated an overall successful MPD stone clearance rate of 90.4%, with similar rates between same-day ERCP and later session ERCP (91.7% vs 88.2%, p = 0.394). Additionally, successful cannulation at ERCP, adverse events, and post-procedure admission rates were similar. CONCLUSIONS: Delaying ERCP to allow peripancreatic tissue recovery after ESWL does not affect outcomes. Same-day ERCP after ESWL is safe and effective.
Subject(s)
Calculi , Lithotripsy , Pancreatic Diseases , Humans , Cholangiopancreatography, Endoscopic Retrograde/methods , Retrospective Studies , Treatment Outcome , Lithotripsy/adverse effects , Lithotripsy/methods , Pancreatic Diseases/therapy , Pancreatic Diseases/etiology , Pancreatic DuctsABSTRACT
OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.
Subject(s)
Pancreatic Cyst , Pancreatic Neoplasms , Humans , RNA , Early Detection of Cancer , Pancreatic Cyst/diagnosis , Pancreatic Cyst/genetics , Pancreatic Cyst/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , DNA , High-Throughput Nucleotide Sequencing , Pancreatic NeoplasmsABSTRACT
BACKGROUND AND AIMS: Post-ERCP pancreatitis (PEP) is the most frequent adverse event of ERCP. Various prophylactic measures are endorsed by the American Society for Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy to both lower the incidence of PEP and to decrease its severity. The extent to which these interventions are practiced throughout the United States is unclear. The aim of this study was to describe the utilization pattern of various PEP measures and determine factors that affect utilization of these measures. METHODS: A 27-question electronic survey was distributed using a cloud-based program (Qualtrics). The questions assessed ERCP training, practice setting, experience, practice patterns, and perceptions for PEP prophylaxis interventions. Endoscopists with practices based in the United States listed in the American Society for Gastrointestinal Endoscopy member directory received a survey invitation via e-mail. The invitation outlined the study and contained a link with instructions to complete the voluntary survey if they had an active ERCP practice. Data were de-identified for the purposes of analysis. RESULTS: Of survey respondents (N = 319), 46% reported therapeutic endoscopy fellowship training and 37% practiced in teaching programs. Annualized ERCP volume of >100 cases per year were reported by 47%, with pancreatic ERCP comprising ≤5% of procedure volume reported by the majority of respondents (61%). The majority of respondents used prophylactic pancreatic stent (PPS), and 54% reported frequent use during high-risk ERCP. The most common indications for PPS were difficult cannulation, to assist biliary access, and multiple pancreatic duct injections. Most respondents reported frequent use of indomethacin (89%). Of physicians who did not use PPS, use of indomethacin was the most common reason (80%). Variables associated with frequent use of PPS were ERCP fellowship training (P ≤ .001), practice at a teaching program (P ≤ .001), <10 years in practice (P = .005), higher procedure volume (P ≤ .001), and higher proportion of pancreatic cases (P ≤ .001). CONCLUSIONS: Physicians with higher annual ERCP volume, who teach at hospital-based ERCP practices, and who regularly perform pancreatic ERCP are more likely to use PPS. Therapeutic ERCP fellowship training and recent entry into practice were also associated with PPS utilization. Indomethacin use seems to be more frequent than PPS. Our findings suggest that indomethacin is supplanting PPS as the preferred method of PEP prophylaxis.
Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Pancreatitis , Humans , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/methods , Pancreatitis/etiology , Pancreatitis/prevention & control , Pancreatitis/epidemiology , Pancreatic Ducts , Catheterization , Indomethacin/therapeutic use , Stents/adverse effects , Risk FactorsABSTRACT
BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.
Subject(s)
Cystadenoma, Serous , Pancreatic Cyst , Pancreatic Neoplasms , Humans , Retrospective Studies , Cystadenoma, Serous/diagnosis , Prospective Studies , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/surgery , Pancreatic Cyst/diagnosis , Pancreatic Cyst/genetics , Pancreatic Cyst/therapy , High-Throughput Nucleotide Sequencing , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Genomics , Mitogen-Activated Protein Kinases/geneticsABSTRACT
Young adults who have experienced recurrent acute pancreatitis and chronic pancreatitis as children or adolescents are vulnerable to poor follow-up and disease management during the transfer from the pediatric to adult healthcare system. Although formalized transition programs for young adults have been developed and described for other disease conditions, no such program has been described for young adults with pancreatic disease. This document is the first expert opinion outlining the important aspects of a transitional care and transfer program tailored to youth with recurrent acute and chronic pancreatitis. We emphasize the unique needs of these patients as they transfer to adult health care and the need for further research. The goal of improved transitional care and transfer is to enhance the services provided to adolescents/young adults with pancreatic disease in both healthcare settings and improve continuity of follow-up care.
Subject(s)
Pancreatic Diseases , Pancreatitis, Chronic , Transition to Adult Care , Adolescent , Young Adult , Humans , Child , Acute Disease , Pancreatitis, Chronic/therapy , PancreasABSTRACT
OBJECTIVE: We evaluated a protocolized endoscopic necrosectomy approach with a lumen-apposing metal stent (LAMS) in patients with large symptomatic walled-off pancreatic necrosis (WON) comprising significant necrotic content, with or without infection. SUMMARY BACKGROUND DATA: Randomized trials have shown similar efficacy of endoscopic treatment compared with surgery for infected WON. DESIGN: We conducted a regulatory, prospective, multicenter single-arm clinical trial examining the efficacy and safety of endoscopic ultrasound -guided LAMS with protocolized necrosectomy to treat symptomatic WON ≥6 cm in diameter with >30% solid necrosis. After LAMS placement, protocolized WON assessment was conducted and endoscopic necrosectomy was performed for insufficient WON size reduction and persistent symptoms. Patients with radiographic WON resolution to ≤ 3 cm and/or 60-day LAMS indwell had LAMS removal, then 6-month follow-up. Primary endpoints were probability of radiographic resolution by 60 days and procedure-related serious adverse events. RESULTS: Forty consecutive patients were enrolled September 2018 to March 2020, of whom 27 (67.5%) were inpatients and 19 (47.5%) had clinical evidence of infection at their index procedure. Mean WON size was 15.0 ± 5.6 cm with mean 53.2% ± 16.7% solid necrosis. Radiographic WON resolution was seen in 97.5% (95% CI, 86.8%, 99.9%) by 60 days, without recurrence in 34 patients with 6-month follow-up data. Mean time to radiographic WON resolution was 34.1 ± 16.8 days. Serious adverse events occurred in 3 patients (7.5%), including sepsis, vancomycin-resistant enterococcal bacteremia and shock, and upper gastrointestinal bleeding. There were no procedure-related deaths. CONCLUSIONS: Endoscopic ultrasound-guided drainage with protocolized endoscopic necrosectomy to treat large symptomatic or infected walled-off necrotic pancreatic collections was highly effective and safe. Clinicaltrials.-gov no: NCT03525808.
Subject(s)
Pancreatitis, Acute Necrotizing , Humans , Drainage/methods , Endosonography , Metals , Necrosis/etiology , Necrosis/surgery , Pancreatitis, Acute Necrotizing/diagnostic imaging , Pancreatitis, Acute Necrotizing/surgery , Prospective Studies , Retrospective Studies , Stents/adverse effects , Treatment OutcomeABSTRACT
ABSTRACT: Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study.
Subject(s)
Diabetes Mellitus, Type 1 , Pancreatitis , Acute Disease , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Humans , Incidence , Pancreatitis/complications , Pancreatitis/epidemiology , Prospective StudiesABSTRACT
ABSTRACT: 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 pre-emptive and detailed planning can help prospective, longitudinal studies focus on exocrine and endocrine complications of AP in accurately measuring outcomes. This article 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, which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.
Subject(s)
Diabetes Mellitus, Type 1 , Pancreatitis , Acute Disease , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/therapy , Humans , Pancreatitis/complications , Pancreatitis/diagnosis , Prospective StudiesABSTRACT
BACKGROUND: The cornerstone of treatment for acute cholangitis is source control with biliary drainage and early antibiotics. The primary aim of this study was to describe the microbiology of bile aspirate pathogens obtained at the time of endoscopic retrograde cholangiopancreatography (ERCP) in patients suspected of having acute cholangitis. METHODS: In this single-center retrospective study, patients were included if a bile aspirate was collected at ERCP for suspicion of acute cholangitis, from 1 January 2010 to 31 December 2016. RESULTS: There were 721 ERCP procedures for suspected acute cholangitis with bile culture results, with 662 positive bile cultures (91.8â%). Pathogens included: Enterococcus species (spp.) 448 (67.7â%); Klebsiella spp.â295 (44.6â%); Escherichia coli 269 (40.6â%); Pseudomonas spp.â52 (7.9â%); and anaerobes 64 (9.7â%). Susceptibility of Klebsiella pneumoniae and E.coli isolates to ciprofloxacin was 88â% and 64â%, respectively. Extended-spectrum beta-lactamases and carbapenem resistance were found in 7.9â% and 3.6â% of Enterobacteriaceae, respectively. There were 437 concurrent blood cultures, of which 174 were positive (39.8â% of cultures drawn). Prior biliary endoscopic sphincterotomy (ES) was evident in 459 ERCP cases (63.7â%), and was associated with increased frequency of Klebsiella spp., Pseudomonas aeruginosa, Enterobacter spp., and Enterococcus spp.âPrior biliary ES significantly increased the probability of vancomycin-resistant Enterococcus (VRE). CONCLUSIONS: The vast majority of bile cultures (91.8â%) were positive. The susceptibilities of E.coli and K.pneumoniae to ciprofloxacin are lower than historically noted. A notable portion of cultures contained pathogenic drug-resistant organisms. Prior biliary ES is associated with a higher frequency of certain organisms and higher frequency of VRE.
Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Cholangitis , Humans , Cholangiopancreatography, Endoscopic Retrograde/methods , Bile/microbiology , Retrospective Studies , Cholangitis/drug therapy , Anti-Bacterial Agents/therapeutic use , Ciprofloxacin , EnterococcusABSTRACT
BACKGROUND/OBJECTIVES: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. METHODS: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. RESULTS: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent. CONCLUSION: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Pancreatitis/epidemiology , Acute Disease , Adult , Aged , Diabetes Mellitus, Type 2/complications , Female , Hospitalization , Humans , Male , Middle Aged , Pancreatitis/complications , Prevalence , Registries , Retrospective Studies , Severity of Illness Index , Systemic Inflammatory Response Syndrome/epidemiologyABSTRACT
BACKGROUND & AIMS: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. METHODS: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. RESULTS: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). CONCLUSION: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.
Subject(s)
Pancreatitis , Acute Disease , Cohort Studies , Female , Humans , Male , Middle Aged , Pancreatitis/diagnosis , ROC Curve , Severity of Illness IndexABSTRACT
BACKGROUND AND AIMS: Endoscopic management of large main pancreatic ductal (MPD) stones often require treatment with lithotripsy. Extracorporeal shock wave lithotripsy (ESWL) has been the mainstay therapy, and single-operator pancreatoscopy with intraductal (intracorporeal) lithotripsy (SOPIL) is an emerging technique. However, no comparative studies between these techniques exist. We therefore aimed to compare ESWL to SOPIL for the treatment of large MPD stones. METHODS: This is a retrospective cohort study comparing patients who were treated with ESWL or SOPIL from September 2013 to September 2019 at a single tertiary center. Logistic regression was performed to identify factors associated with technical success and efficient stone clearance (≤ 2 procedures to clear stones). RESULTS: There were 240 patients who were treated with ESWL and 18 treated with SOPIL. The overall technical success rate of stone clearance was 224/258 (86.8%), which was similar between the ESWL and SOPIL groups (86.7% vs 88.9%, p = 1.000). A SOPIL approach required fewer total procedures (1.6 ± 0.6 vs 3.1 ± 1.5, p < 0.001) and less aggregate procedure time (101.6 ± 68.2 vs 191.8 ± 111.6 min, p = 0.001). Adverse event rates were similar between the groups (6.3% vs 5.6%, p = 1.000). The use of SOPIL was independently associated with greater efficiency compared to ESWL (OR 5.241 [1.348-20.369], p = 0.017). Stone size > 10 mm was associated with less efficient stone clearance (OR 0.484 [0.256-0.912], p = 0.025). CONCLUSION: Both ESWL and SOPIL are safe and effective endoscopic adjunct modalities for treating large pancreatic duct stones. SOPIL is an emerging alternative to ESWL that is potentially more efficient for lithotripsy and MPD stone clearance.
Subject(s)
Calculi , Lithotripsy , Pancreatic Diseases , Calculi/therapy , Cholangiopancreatography, Endoscopic Retrograde/methods , Humans , Lithotripsy/methods , Pancreatic Diseases/etiology , Pancreatic Diseases/therapy , Pancreatic Ducts , Retrospective Studies , Treatment OutcomeABSTRACT
MicroRNA-29 (miR-29) is a critical regulator of fibroinflammatory processes in human diseases. In this study, we found a decrease in miR-29a in experimental and human chronic pancreatitis, leading us to investigate the regulatory role of the miR-29a/b1 cluster in acute pancreatitis (AP) utilizing a conditional miR-29a/b1-KO mouse model. miR-29a/b1-sufficient (WT) and -deficient (KO) mice were administered supramaximal caerulein to induce AP and characterized at different time points, utilizing an array of IHC and biochemical analyses for AP parameters. In caerulein-induced WT mice, miR-29a remained dramatically downregulated at injury. Despite high-inflammatory milieu, fibrosis, and parenchymal disarray in the WT mice during early AP, the pancreata fully restored during recovery. miR-29a/b1-KO mice showed significantly greater inflammation, lymphocyte infiltration, macrophage polarization, and ECM deposition, continuing until late recovery with persistent parenchymal disorganization. The increased pancreatic fibrosis was accompanied by enhanced TGFß1 coupled with persistent αSMA+ PSC activation. Additionally, these mice exhibited higher circulating IL-6 and inflammation in lung parenchyma. Together, this collection of studies indicates that depletion of miR-29a/b1 cluster impacts the fibroinflammatory mechanisms of AP, resulting in (a) aggravated pathogenesis and (b) delayed recovery from the disease, suggesting a protective role of the molecule against AP.
Subject(s)
MicroRNAs/genetics , MicroRNAs/metabolism , Pancreatitis, Chronic/metabolism , Pancreatitis/genetics , Animals , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Fibrosis/genetics , Fibrosis/metabolism , Fibrosis/pathology , Humans , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Mice , Mice, Knockout , Pancreatitis/pathologyABSTRACT
OBJECTIVES: Select patients with anatomically favorable walled off pancreatic necrosis may be treated by endoscopic (Endo-TGD) or operative (OR-TGD) transgastric debridement (TGD). We compared our experience with these 2 approaches. SUMMARY BACKGROUND DATA: Select necrotizing pancreatitis (NP) patients are suitable for TGD which may be accomplished endoscopically or surgically. Limited experience exists contrasting these techniques exists. METHODS: Patients undergoing Endo-TGD and OR-TGD at a single, high-volume pancreatic center between 2008 and 2019 were identified from a prospective database. Patient characteristics, procedural details, and outcomes of these 2 groups were compared. RESULTS: Among 498 NP patients undergoing necrosis intervention, 160 (32%) had TGD: 59 Endo-TGD and 101 OR-TGD. The groups were statistically similar in age, comorbidity, pancreatitis etiology, necrosis anatomy, pancreatitis severity, and timing of TGD from pancreatitis insult. OR-TGD required 1.1â±â0.5 and Endo-TGD 3.0â±â2.0âdebridements/patient. Fewer hospital readmissions and repeat necrosis interventions, and shorter total inpatient length of stay were observed in OR-TGD patients. New-onset organ failure [Endo-TGD (13%); OR-TGD (13%); P = 1.0] was similar between groups. Hospital length of stay after TGD was significantly longer in patients undergoing Endo-TGD (13.8â±â20.8âdays) compared to OR-TGD (9.4â±â6.1âdays; P = 0.047). Mortality was 7% in Endo-TGD and 1% in OR-TGD (P = 0.04). CONCLUSIONS: Operative and endoscopic transgastric debridement achieve necrosis resolution with different temporal and procedural profiles. Clear multidisciplinary communication is essential to determine appropriate approach to individual necrotizing pancreatitis patients.
Subject(s)
Debridement/methods , Laparoscopy/methods , Laparotomy/methods , Pancreatitis, Acute Necrotizing/surgery , Female , Humans , Indiana , Length of Stay/statistics & numerical data , Male , Middle Aged , Pancreatitis, Acute Necrotizing/mortalityABSTRACT
BACKGROUND: Pancreatic cysts are incidentally detected in up to 13% of patients undergoing radiographic imaging. Of the most frequently encountered types, mucin-producing (mucinous) pancreatic cystic lesions may develop into pancreatic cancer, while nonmucinous ones have little or no malignant potential. Accurate preoperative diagnosis is critical for optimal management, but has been difficult to achieve, resulting in unnecessary major surgery. Here, we aim to develop an algorithm based on biomarker risk scores to improve risk stratification. STUDY DESIGN: Patients undergoing surgery and/or surveillance for a pancreatic cystic lesion, with diagnostic imaging and banked pancreatic cyst fluid, were enrolled in the study after informed consent (n = 163 surgical, 67 surveillance). Cyst fluid biomarkers with high specificity for distinguishing nonmucinous from mucinous pancreatic cysts (vascular endothelial growth factor [VEGF], glucose, carcinoembryonic antigen [CEA], amylase, cytology, and DNA mutation) were selected. Biomarker risk scores were used to design an algorithm to predict preoperative diagnosis. Performance was tested using surgical (retrospective) and surveillance (prospective) cohorts. RESULTS: In the surgical cohort, the biomarker algorithm outperformed the preoperative clinical diagnosis in correctly predicting the final pathologic diagnosis (91% vs 73%; p < 0.000001). Specifically, nonmucinous serous cystic neoplasms (SCN) and mucinous cystic neoplasms (MCN) were correctly classified more frequently by the algorithm than clinical diagnosis (96% vs 30%; p < 0.000008 and 92% vs 69%; p = 0.04, respectively). In the surveillance cohort, the algorithm predicted a preoperative diagnosis with high confidence based on a high biomarker score and/or consistency with imaging from ≥1 follow-up visits. CONCLUSIONS: A biomarker risk score-based algorithm was able to correctly classify pancreatic cysts preoperatively. Importantly, this tool may improve initial and dynamic risk stratification, reducing overdiagnosis and underdiagnosis.
Subject(s)
Biomarkers, Tumor/analysis , Pancreatic Cyst/diagnosis , Pancreatic Neoplasms/diagnosis , Adult , Aged , Algorithms , Female , Humans , Male , Middle Aged , Pancreatic Cyst/diagnostic imaging , Pancreatic Cyst/surgery , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Prospective Studies , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF. OBJECTIVE: We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF. METHODS: We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders. RESULTS: 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3-34.9) and three (48%, OR = 20.2, 5.9-68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality. CONCLUSION: In AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.