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Testoni PA, Testoni S. Endoscopic Management of Recurrent Acute Pancreatitis. J Clin Med 2025; 14:2150. [PMID: 40217601 PMCID: PMC11989922 DOI: 10.3390/jcm14072150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 02/28/2025] [Accepted: 03/05/2025] [Indexed: 04/14/2025] Open
Abstract
This review aims to summarize the role of endoscopic therapy in the management and outcomes of recurrent acute pancreatitis (RAP). RAP is a clinical entity characterized by repeated episodes of acute pancreatitis in the setting of a normal gland or chronic pancreatitis (CP). The aetiology of RAP can be identified in about 70% of cases; for the remaining cases, the term "idiopathic" (IRAP) is used. However, advanced diagnostic techniques may reduce the percentage of IRAP to 10%. Recognized causes of RAP are gallstone disease, including microlithiasis and biliary sludge, sphincter of Oddi dysfunction (SOD), pancreatic ductal abnormalities (either congenital or acquired) interfering with pancreatic juice or bile outflow, genetic mutations, and alcohol consumption. SOD, as a clinical entity, was recently revised in the Rome IV consensus, which only recognized type 1 dysfunction as a true pathological condition, while type 2 SOD was defined as a suspected functional biliary sphincter disorder requiring the documentation of elevated basal sphincter pressure to be considered a true clinical entity and type 3 was abandoned as a diagnosis and considered functional pain. Endoscopic therapy by retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) has been proven effective when a mechanical obstruction is found and can be removed. If an obstruction is not documented, few treatment options are available to prevent the recurrence of pancreatitis and progression toward chronic disease. In gallstone disease, endoscopic biliary sphincterotomy (EBS) is effective when a dilated common bile duct or biliary sludge/microlithiasis is documented. In type 1 SOD, biliary or dual sphincterotomy is generally successful, while in type 2 SOD, endotherapy should be reserved for patients with documented sphincter dysfunction. However, in recent years, doubts have been expressed about the real efficacy of sphincterotomy in this setting. When sphincter dysfunction is not confirmed, endotherapy should be discouraged. In pancreas divisum (PD), minor papilla sphincterotomy is effective when there is a dilated dorsal duct, and the success rate is the highest in RAP patients. In the presence of obstructive conditions of the main pancreatic duct, pancreatic endotherapy is generally successful if RAP depends on intraductal hypertension. However, despite the efficacy of endotherapy, progression toward CP has been shown in some of these patients, mainly in the presence of PD, very likely depending on underlying genetic mutations. In patients with IRAP, the real utility of endotherapy still remains unclear; this is because several unknown factors may play a role in the disease, and data on outcomes are few, frequently contradictory or uncontrolled, and, in general, limited to a short period of time.
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Affiliation(s)
- Pier Alberto Testoni
- Gastroenterology and Gastrointestinal Endoscopy, La Madonnina Clinic, Vita-Salute San Raffaele University, 20100 Milan, Italy
| | - Sabrina Testoni
- Unit of Gastroenterology and Gastrointestinal Endoscopy, IRCCS Policlinico San Donato, Vita-Salute San Raffaele University, 20100 Milan, Italy;
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Etheridge JC, Cooke RM, Castillo-Angeles M, Jarman MP, Havens JM. Disparities in uptake of cholecystectomy for idiopathic pancreatitis: A nationwide retrospective cohort study. Surgery 2022; 172:612-616. [PMID: 35568585 DOI: 10.1016/j.surg.2022.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 04/01/2022] [Accepted: 04/07/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND The majority of cases of idiopathic acute pancreatitis (IAP) are thought to result from occult biliary disease. A growing body of evidence suggests that cholecystectomy for IAP reduces the risk of recurrence by up to two thirds. This study examined nationwide uptake and disparities in adoption of cholecystectomy for IAP. METHODS The National Inpatient Sample was queried to identify admissions for IAP between October 2015 and December 2018. Patients who underwent cholecystectomy before discharge and those that did not were compared using Wald χ2 tests for categorical variables and Student's t test for continuous variables. Patient- and hospital-level predictors of cholecystectomy were identified using weighted multivariable logistic regression. RESULTS Of 62,305 estimated admissions for IAP, only 665 (1.1%) underwent cholecystectomy before discharge. Female sex, initiation of total parenteral nutrition (TPN), insurance status, and hospital type were associated with cholecystectomy on univariable analysis. On multivariable analysis, Hispanic patients (odds ration [OR] 1.60, 95% confidence interval [CI] 1.01-2.56), patients on TPN (OR 2.70, 95% CI 1.17-6.24), and those with private insurance (OR 2.18, 95% CI 1.48-3.21 versus Medicare/Medicaid) were more likely to receive operations. Small hospitals and hospitals in rural areas were least likely to perform empiric cholecystectomies. CONCLUSION Despite increasing evidence supporting cholecystectomy after IAP, the practice remains rare in the United States. Educational efforts and active implementation efforts are needed to promote adoption. Particular attention should be focused on small, rural centers and those that disproportionately care for uninsured patients and patients with public insurance.
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Affiliation(s)
- James C Etheridge
- Department of Surgery, Brigham and Women's Hospital, Boston, MA; Ariadne Labs at Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health, Boston, MA.
| | - Ryan M Cooke
- Department of Biological Sciences, University of Alabama, Tuscaloosa, AL
| | - Manuel Castillo-Angeles
- Department of Surgery, Brigham and Women's Hospital, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA
| | - Molly P Jarman
- Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA
| | - Joaquim M Havens
- Department of Surgery, Brigham and Women's Hospital, Boston, MA; Ariadne Labs at Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA
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Li H, Wen W, Luo J. Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis. Biomedicines 2022; 10:biomedicines10010108. [PMID: 35052788 PMCID: PMC8773075 DOI: 10.3390/biomedicines10010108] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/28/2021] [Accepted: 12/30/2021] [Indexed: 02/04/2023] Open
Abstract
Pancreatitis and alcoholic pancreatitis are serious health concerns with an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here, we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR in developing novel therapeutic strategies for the disease.
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Affiliation(s)
- Hui Li
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
| | - Wen Wen
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
| | - Jia Luo
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
- Iowa City VA Health Care System, Iowa City, IA 52246, USA
- Correspondence: ; Tel.: +1-319-335-2256
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García de la Filia Molina I, García García de Paredes A, Martínez Ortega A, Marcos Carrasco N, Rodríguez De Santiago E, Sánchez Aldehuelo R, Foruny Olcina JR, González Martin JÁ, López Duran S, Vázquez Sequeiros E, Albillos A. Biliary sphincterotomy reduces the risk of acute gallstone pancreatitis recurrence in non-candidates for cholecystectomy. Dig Liver Dis 2019; 51:1567-1573. [PMID: 31151894 DOI: 10.1016/j.dld.2019.05.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 04/28/2019] [Accepted: 05/01/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Population aging and comorbidity are leading to an increase in patients unfit for cholecystectomy. AIMS To evaluate whether endoscopic biliary sphincterotomy after a first episode of acute gallstone pancreatitis reduces the risk of pancreatitis recurrence and gallstone-related events in non-surgical candidates. METHODS Retrospective study of patients admitted for a first episode of acute gallstone pancreatitis rejected for cholecystectomy between 2013-2018. The role of endoscopic sphincterotomy was evaluated by adjusting for age, severity of pancreatitis, and presence of choledocholithiasis. RESULTS We included 247 patients (mean age 80 ± 12 years; Charlson index: 5; severity of pancreatitis: 72% mild). Sphincterotomy was performed in 23.9%. Recurrence of pancreatitis occurred in 17.4% patients (median follow-up: 426 days). The one-year cumulative incidence of a new episode of pancreatitis was 1.8% (95% confidence interval [CI]: 0.2-12%) and 23% (95% CI: 17-31%) in patients with and without sphincterotomy, respectively (p = 0.006). In multivariate analysis, sphincterotomy showed a protective role for recurrence of pancreatitis (adjusted hazard ratio [HR]: 0.29, 95% CI: 0.08-0.92, p = 0.037) and for any gallstone-related event (HR 0.46, 95% CI: 0.21-0.98, p = 0.043). CONCLUSIONS Endoscopic biliary sphincterotomy reduced the risk of gallstone pancreatitis recurrence and other biliary-related disorders in patients with a first episode of pancreatitis non-candidates for cholecystectomy.
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Affiliation(s)
- Irene García de la Filia Molina
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain
| | - Ana García García de Paredes
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain; Ramón y Cajal Institute of Biosanitary Research (IRYCIS), Madrid, Spain.
| | - Antonio Martínez Ortega
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain
| | - Natalia Marcos Carrasco
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain
| | - Enrique Rodríguez De Santiago
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain; Ramón y Cajal Institute of Biosanitary Research (IRYCIS), Madrid, Spain
| | - Rubén Sánchez Aldehuelo
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain
| | - Jose Ramón Foruny Olcina
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain; Ramón y Cajal Institute of Biosanitary Research (IRYCIS), Madrid, Spain
| | - Juan Ángel González Martin
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain; Ramón y Cajal Institute of Biosanitary Research (IRYCIS), Madrid, Spain
| | - Sergio López Duran
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain
| | - Enrique Vázquez Sequeiros
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain; Ramón y Cajal Institute of Biosanitary Research (IRYCIS), Madrid, Spain
| | - Agustín Albillos
- Gastroenterology and Hepatology Department, Ramón y Cajal University Hospital, Madrid, Spain; University of Alcalá, Madrid, Spain; Ramón y Cajal Institute of Biosanitary Research (IRYCIS), Madrid, Spain; Biomedical Research Center in Liver and Digestive Diseases Network (CIBERehd), Carlos III Health Institute, Madrid, Spain
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Reichstein JB, Patel V, Mekaroonkamol P, Dacha S, Keilin SA, Cai Q, Willingham FF. Practice Patterns and Use of Endoscopic Retrograde Cholangiopancreatography in the Management of Recurrent Acute Pancreatitis. Clin Endosc 2019; 53:73-81. [PMID: 31273969 PMCID: PMC7003016 DOI: 10.5946/ce.2019.052] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 04/11/2019] [Indexed: 12/11/2022] Open
Abstract
Background/Aims There are conflicting opinions regarding the management of recurrent acute pancreatitis (RAP). While some physicians recommend endoscopic retrograde cholangiopancreatography (ERCP) in this setting, others consider it to be contraindicated in patients with RAP. The aim of this study was to assess the practice patterns and clinical features influencing the management of RAP in the US.
Methods An anonymous 35-question survey instrument was developed and refined through multiple iterations, and its use was approved by our Institutional Review Board. The survey was distributed via email to 408 gastroenterologists to assess the practice patterns in the management of RAP in multiple clinical scenarios.
Results The survey was completed by 65 participants representing 36 of the top academic/tertiary care centers across the country. Approximately 90.8% of the participants indicated that they might offer or recommend ERCP in the management of RAP. Multinomial logistic regression analysis revealed that ductal dilatation and presence of symptoms were the most predictive variables (p<0.001) for offering ERCP.
Conclusions A preponderance of the respondents would consider ERCP among patients with RAP presenting to tertiary care centers in the US. Ductal dilatation, presence of symptoms, and pancreas divisum significantly increased the likelihood of a recommendation for ERCP.
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Affiliation(s)
| | - Vaishali Patel
- Division of Digestive Disease, Department of Medicine, Emory University, Atlanta, GA, USA
| | - Parit Mekaroonkamol
- Division of Digestive Disease, Department of Medicine, Emory University, Atlanta, GA, USA
| | - Sunil Dacha
- Division of Digestive Disease, Department of Medicine, Emory University, Atlanta, GA, USA
| | - Steven A Keilin
- Division of Digestive Disease, Department of Medicine, Emory University, Atlanta, GA, USA
| | - Qiang Cai
- Division of Digestive Disease, Department of Medicine, Emory University, Atlanta, GA, USA
| | - Field F Willingham
- Division of Digestive Disease, Department of Medicine, Emory University, Atlanta, GA, USA
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Sánchez Rodríguez E, García García de Paredes A, Albillos A. Current management of acute idiopathic pancreatitis and acute recurrent pancreatitis. Rev Clin Esp 2019. [DOI: 10.1016/j.rceng.2019.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Sánchez Rodríguez E, García García de Paredes A, Albillos A. Manejo actual de la pancreatitis aguda idiopática y la pancreatitis aguda recurrente. Rev Clin Esp 2019; 219:266-274. [DOI: 10.1016/j.rce.2018.12.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 12/28/2018] [Indexed: 02/07/2023]
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8
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Idiopathic acute pancreatitis: a review on etiology and diagnostic work-up. Clin J Gastroenterol 2019; 12:511-524. [DOI: 10.1007/s12328-019-00987-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 04/19/2019] [Indexed: 12/17/2022]
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9
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Wang HH, Portincasa P, Liu M, Tso P, Wang DQH. Similarities and differences between biliary sludge and microlithiasis: Their clinical and pathophysiological significances. LIVER RESEARCH (BEIJING, CHINA) 2018; 2:186-199. [PMID: 34367716 PMCID: PMC8341470 DOI: 10.1016/j.livres.2018.10.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The terms biliary sludge and cholesterol microlithiasis (hereafter referred to as microlithiasis) were originated from different diagnostic techniques and may represent different stages of cholesterol gallstone disease. Although the pathogenesis of biliary sludge and microlithiasis may be similar, microlithiasis could be preceded by biliary sludge, followed by persistent precipitation and aggregation of solid cholesterol crystals, and eventually, gallstone formation. Many clinical conditions are clearly associated with the formation of biliary sludge and microlithiasis, including total parenteral nutrition, rapid weight loss, pregnancy, organ transplantation, administration of certain medications, and a variety of acute and chronic illnesses. Numerous studies have demonstrated complete resolution of biliary sludge in approximately 40% of patients, a cyclic pattern of disappearing and reappearing in about 40%, and progression to gallstones in nearly 20%. Although only a minority of patients with ultrasonographic demonstration of biliary sludge develop gallstones, it is still a matter of controversy whether microlithiasis could eventually evolve to cholesterol gallstones. Biliary sludge and microlithiasis are asymptomatic in the vast majority of patients; however, they can cause biliary colic, acute cholecystitis, and acute pancreatitis. Biliary sludge and microlithiasis are most often diagnosed ultrasonographically and bile microscopy is considered the gold standard for their diagnosis. Specific measures to prevent the development of biliary sludge are not practical or cost-effective in the general population. Laparoscopic cholecystectomy offers the most definitive therapy on biliary sludge. Endoscopic sphincterotomy or surgical intervention is effective for microlithiasis-induced pancreatitis. Ursodeoxycholic acid can effectively prevent the recurrence of solid cholesterol crystals and significantly reduce the risk of recurrent pancreatitis.
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Affiliation(s)
- Helen H. Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica “A. Murri”, University of Bari “Aldo Moro” Medical School, Bari, Italy
| | - Min Liu
- Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Patrick Tso
- Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - David Q.-H. Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
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Abstract
Patients with recurrent acute pancreatitis (RAP) have few treatment options available to them to manage their symptoms or prevent progression to chronic pancreatitis. At present, endotherapy is typically pursued as a means to achieve symptom remission and reduce rates of recurrence, hospitalization, abdominal pain, narcotic use, and surgical intervention. However, evidence that endotherapy effectively alters the natural history of disease remains limited. This article reviews the recent literature on the efficacy of endoscopic intervention in the treatment RAP with a focus on high-quality prospective randomized controlled studies. Additional studies are needed to corroborate these findings.
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Affiliation(s)
- Averill Guo
- Columbia University Medical Center, 161 Fort Washington Avenue, Suite 852, New York, NY 10032, USA
| | - John M Poneros
- Columbia University Medical Center, 161 Fort Washington Avenue, Suite 852, New York, NY 10032, USA.
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Jagannath S, Garg PK. Recurrent Acute Pancreatitis: Current Concepts in the Diagnosis and Management. ACTA ACUST UNITED AC 2018; 16:449-465. [PMID: 30232693 DOI: 10.1007/s11938-018-0196-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW There have been significant developments in the diagnosis, clinical approach, and management of patients with recurrent acute pancreatitis (RAP) in the last decade. This review systematically summarizes our current understanding of RAP. NEW FINDINGS Gallstones and alcohol are common causes of RAP. Non-alcohol non-biliary RAP (nAnB RAP) is a difficult group of patients after excluding these two causes because extensive workup is required to elucidate the etiology. Idiopathic RAP is diagnosed after excluding all the known causes and recurrence is noted to be higher in such patients. Patients with non-biliary RAP are prone to develop chronic pancreatitis (CP) suggesting a continuum from acute to recurrent to chronic pancreatitis. Often, patients destined to develop CP present at an earlier stage with RAP. Endoscopic ultrasound and magnetic resonance cholangiopancreatography (MRCP) are the investigations of choice to detect microlithiasis, choledocholithiasis, ductal abnormalities, peri-ampullary malignancies, and early changes of chronic pancreatitis. The role of pancreas divisum, sphincter of Oddi dysfunction, and anomalous pancreatobiliary union in causing RAP is controversial. Genetic testing may be advisable in younger patients. CONCLUSION With a focused approach and appropriate investigations, the etiology of RAP can be identified in a significant proportion of patients. Therapeutic options are limited and future research is needed to improve understanding of the disease.
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Affiliation(s)
- Soumya Jagannath
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Pramod Kumar Garg
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
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Abstract
Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research.
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Somani P, Navaneethan U. Role of ERCP in Patients With Idiopathic Recurrent Acute Pancreatitis. ACTA ACUST UNITED AC 2016; 14:327-39. [PMID: 27371265 DOI: 10.1007/s11938-016-0096-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OPINION STATEMENT Recurrent acute pancreatitis (RAP) is defined based on the occurrence of two or more episodes of acute pancreatitis. RAP is differentiated from chronic pancreatitis based on the presence of a normal morphological appearance of the pancreas between episodes. RAP can be due to a variety of etiologies including common bile duct stones or sludge, sphincter of Oddi dysfunction (SOD), pancreas divisum (PD), anomalous pancreaticobiliary junction, genetic mutations, and alcohol related. In approximately 30 % of patients, the etiology of RAP is unclear and the term "idiopathic" is used. Endoscopic retrograde cholangiopancreatography (ERCP) can be utilized in both the diagnosis and the initial management of RAP, but it has known limitations and risks. Since gallbladder sludge and SOD account for most cases with RAP, cholecystectomy and, eventually, endoscopic biliary and/or pancreatic sphincterotomy are performed as a part of management. In patients with PD-associated RAP, data from uncontrolled and primarily retrospective studies point toward a benefit from minor papillary endoscopic intervention. However, given the lack of quality data from prospective randomized controlled trials (RCTs), endoscopic management in such patients remains an individualized decision, and RCTs are needed to ascertain its true long-term benefit. Future studies to investigate the role of endoscopic therapy in preventing progression to chronic pancreatitis are needed.
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Affiliation(s)
- Piyush Somani
- Center for Interventional Endoscopy, University of Central Florida College of Medicine, Florida Hospital, 601 E Rollins Street, Orlando, FL, 32803, USA
| | - Udayakumar Navaneethan
- Center for Interventional Endoscopy, University of Central Florida College of Medicine, Florida Hospital, 601 E Rollins Street, Orlando, FL, 32803, USA.
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Das R, Clarke B, Tang G, Papachristou GI, Whitcomb DC, Slivka A, Yadav D. Endoscopic sphincterotomy (ES) may not alter the natural history of idiopathic recurrent acute pancreatitis (IRAP). Pancreatology 2016; 16:770-7. [PMID: 27450967 DOI: 10.1016/j.pan.2016.07.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2016] [Revised: 07/09/2016] [Accepted: 07/11/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The role of endoscopic sphincterotomy (ES) in idiopathic recurrent acute pancreatitis (IRAP) is unclear. We hypothesized that ES will alter the natural history of IRAP. METHODS We retrospectively studied the course of 50 IRAP patients from the NAPS2 study from UPMC based on whether they underwent ES or were managed medically. Data included age at first AP, rate of attacks, and history of severe AP. Primary outcomes were any subsequent AP and rate of attacks; secondary outcome was chronic pancreatitis (CP) diagnosis during follow-up. Similar data was abstracted for alcoholic RAP. RESULTS When compared with medically managed IRAP patients (n = 24, 48%), those who underwent ES (n = 26, 52%) had similar rate of attacks/year (median 1.54 vs. 1.41, p = 0.63), but significantly more attacks (median 3 vs. 2, p = 0.04) at baseline. During follow-up (median 7 years), rate of attacks/year decreased significantly, and were similar in both groups (median 0.16 vs. 0, p = ns). Predictors for rate of attacks during follow-up were sex (ratio 0.54 in females, p = 0.045) and rate of attacks at baseline (ratio for doubling 1.2, p = 0.025), but not ES. Alcoholic RAP patients had lower rate of attacks at baseline, but higher risk of subsequent AP (80 vs. 46%, p = 0.021) and rate of attacks/year (median 0.25 vs. 0, p = 0.016) during follow-up. Progression to CP occurred in IRAP and ES, medically managed IRAP, and alcoholic RAP in 27%, 8% and 27% respectively (p = ns). CONCLUSIONS ES, chosen in patients with higher burden of attacks, does not seem to impact the natural history of IRAP.
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Affiliation(s)
- Rohit Das
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Bridger Clarke
- South Hills Gastroenterology Associates, Clairton, PA, USA
| | - Gong Tang
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Georgios I Papachristou
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Adam Slivka
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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Hill PA, Harris RD. Clinical Importance and Natural History of Biliary Sludge in Outpatients. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2016; 35:605-610. [PMID: 26903661 DOI: 10.7863/ultra.15.05026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 07/09/2015] [Indexed: 06/05/2023]
Abstract
OBJECTIVES Gallbladder sludge is a common diagnosis on routine abdominal sonography, yet its clinical importance is uncertain, especially in outpatients. To determine its natural history and potential future complications in this setting, we reviewed the imaging and clinical histories of nonhospitalized patients with a diagnosis of sludge on sonography. METHODS We conducted a retrospective search of our institutional radiology information system for all sonographic reports using the key words "biliary sludge without gallstones" over a 3-year period. For each of the 104 patients with isolated biliary sludge on initial sonography, we reviewed the electronic medical records and all imaging for the development of pancreaticobiliary complications. RESULTS We found an overall prevalence of biliary sludge in outpatients of 1.8%. Of the 104 patients reviewed with a mean follow up of 630 days (21 months), 25 developed a pancreaticobiliary complication, including cholelithiasis, cholecystitis, choledocholithiasis, and pancreatitis. The most frequent complication was cholecystitis, with a total of 14 diagnoses (12 chronic acalculous and 2 acute with gallstones). An additional 6 patients developed gallstones without cholecystitis features; 4 patients developed pancreatitis; and 1 developed choledocholithiasis. Biliary sludge remained quiescent or resolved in 76% of patients. CONCLUSIONS Biliary sludge always represents a pathologic process, but its clinical implications among outpatients have not been previously investigated. Our ambulatory population developed pancreaticobiliary complications at similar rates as prior mixed-patient setting studies. Regardless of the patient setting, biliary sludge is likely of more clinical importance than previously regarded.
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Affiliation(s)
- Paul Armstrong Hill
- Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire USA.
| | - Robert D Harris
- Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire USA
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Can Laparoscopic Cholecystectomy Prevent Recurrent Idiopathic Acute Pancreatitis?: A Prospective Randomized Multicenter Trial. Ann Surg 2016; 262:736-41. [PMID: 26583660 DOI: 10.1097/sla.0000000000001469] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The aim of the present trial was to ascertain whether laparoscopic cholecystectomy (LCC) can prevent recurrent attacks of idiopathic acute pancreatitis (IAP). SUMMARY Up to 50% to 75% of IAP may be due to microlithiasis, which is undetectable by conventional imaging methods. METHODS This randomized, prospective trial included 85 patients (39 in the LCC and 46 in the control group) in 8 hospitals in Finland. We included adult patients (over 18 years) with their first attack of IAP. The diagnosis of IAP was based on the exclusion of common etiological reasons for acute pancreatitis (AP), whereafter the patients were randomized into conservative watchful waiting (controls) or LCC group. The primary end point was the number of patients with recurrent AP during the follow-up. All recurrent attacks of AP after an initial IAP episode were registered. RESULTS During a median follow-up of 36 (5-58) months, the recurrence of IAP was significantly higher in the control group than in LCC group (14/46 vs. 4/39, P = 0.016), as was also the number of recurrences (23/46 vs. 8/39, P = 0.003). In the subgroup of patients with at least 24 months' follow-up, the recurrence was still higher among controls (14/37 vs. 4/35, P = 0.008). In patients with normal liver function, recurrence was also significantly higher in the control than in the LCC group (13/46 vs. 4/39, P = 0.026). During surgery, 23/39 (59%) of the gallbladders were found to contain biliary stones or sludge. CONCLUSIONS LCC can effectively prevent the recurrence of IAP when all other possible etiologies of pancreatitis are carefully excluded. A total of 5 patients needed to be treated (NNT-value) to prevent 1 IAP.
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Katona M, Hegyi P, Kui B, Balla Z, Rakonczay Z, Rázga Z, Tiszlavicz L, Maléth J, Venglovecz V. A novel, protective role of ursodeoxycholate in bile-induced pancreatic ductal injury. Am J Physiol Gastrointest Liver Physiol 2016; 310:G193-G204. [PMID: 26608189 DOI: 10.1152/ajpgi.00317.2015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Accepted: 11/23/2015] [Indexed: 01/31/2023]
Abstract
We have previously shown that chenodeoxycholic acid (CDCA) strongly inhibits pancreatic ductal HCO3 (-) secretion through the destruction of mitochondrial function, which may have significance in the pathomechanism of acute pancreatitis (AP). Ursodeoxycholic acid (UDCA) is known to protect the mitochondria against hydrophobic bile acids and has an ameliorating effect on cell death. Therefore, our aim was to investigate the effect of UDCA pretreatment on CDCA-induced pancreatic ductal injury. Guinea pig intrainterlobular pancreatic ducts were isolated by collagenase digestion. Ducts were treated with UDCA for 5 and 24 h, and the effect of CDCA on intracellular Ca(2+) concentration ([Ca(2+)]i), intracellular pH (pHi), morphological and functional changes of mitochondria, and the rate of apoptosis were investigated. AP was induced in rat by retrograde intraductal injection of CDCA (0.5%), and the disease severity of pancreatitis was assessed by measuring standard laboratory and histological parameters. Twenty-four-hour pretreatment of pancreatic ducts with 0.5 mM UDCA significantly reduced the rate of ATP depletion, mitochondrial injury, and cell death induced by 1 mM CDCA and completely prevented the inhibitory effect of CDCA on acid-base transporters. UDCA pretreatment had no effect on CDCA-induced Ca(2+) signaling. Oral administration of UDCA (250 mg/kg) markedly reduced the severity of CDCA-induced AP. Our results clearly demonstrate that UDCA 1) suppresses the CDCA-induced pancreatic ductal injury by reducing apoptosis and mitochondrial damage and 2) reduces the severity of CDCA-induced AP. The protective effect of UDCA against hydrophobic bile acids may represent a novel therapeutic target in the treatment of biliary AP.
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Affiliation(s)
- Máté Katona
- Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine and First Department of Medicine, University of Pécs, Pécs, Hungary; First Department of Medicine, University of Szeged, Szeged, Hungary; MTA-SZTE Translational Gastroenterology Research Group, University of Szeged, Szeged, Hungary
| | - Balázs Kui
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Zsolt Balla
- Department of Pathophysiology, University of Szeged, Szeged, Hungary; and Department of Pathophysiology, University of Szeged, Szeged, Hungary; and
| | - Zoltán Rakonczay
- First Department of Medicine, University of Szeged, Szeged, Hungary; Department of Pathophysiology, University of Szeged, Szeged, Hungary; and
| | - Zsolt Rázga
- Department of Pathology, University of Szeged, Szeged, Hungary
| | | | - József Maléth
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Viktória Venglovecz
- Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;
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Das R, Yadav D, Papachristou GI. Endoscopic Treatment of Recurrent Acute Pancreatitis and Smoldering Acute Pancreatitis. Gastrointest Endosc Clin N Am 2015; 25:737-48. [PMID: 26431601 DOI: 10.1016/j.giec.2015.06.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Recurrent acute pancreatitis (RAP) is a challenging condition that can lead to chronic pancreatitis and long-term morbidity. Etiology-based treatment can potentially have an impact on the natural history of RAP and its progression to chronic pancreatitis. In cases of divisum-associated RAP and idiopathic RAP, several studies have been performed to evaluate the efficacy of endoscopic therapy in alleviation of symptoms and frequency of AP events. This review discusses the literature available on these topic as well as touching on the role of endoscopic therapy in smoldering acute pancreatitis.
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Affiliation(s)
- Rohit Das
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, PUH, M2, C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, PUH, M2, C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA
| | - Georgios I Papachristou
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, PUH, M2, C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
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Testoni PA. Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment. World J Gastroenterol 2014; 20:16891-16901. [PMID: 25493002 PMCID: PMC4258558 DOI: 10.3748/wjg.v20.i45.16891] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 06/19/2014] [Accepted: 09/19/2014] [Indexed: 02/06/2023] Open
Abstract
Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches.
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Surgical treatment of chronic pancreatitis in young patients. JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY. MEDICAL SCIENCES = HUA ZHONG KE JI DA XUE XUE BAO. YI XUE YING DE WEN BAN = HUAZHONG KEJI DAXUE XUEBAO. YIXUE YINGDEWEN BAN 2014; 34:701-705. [PMID: 25318880 DOI: 10.1007/s11596-014-1339-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Revised: 08/14/2014] [Indexed: 10/24/2022]
Abstract
The main treatment strategies for chronic pancreatitis in young patients include therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) intervention and surgical intervention. Therapeutic ERCP intervention is performed much more extensively for its minimally invasive nature, but a part of patients are referred to surgery at last. Historical and follow-up data of 21 young patients with chronic pancreatitis undergoing duodenum-preserving total pancreatic head resection were analyzed to evaluate the outcomes of therapeutic ERCP intervention and surgical intervention in this study. The surgical complications of repeated therapeutic ERCP intervention and surgical intervention were 38% and 19% respectively. During the first therapeutic ERCP intervention to surgical intervention, 2 patients developed diabetes, 5 patients developed steatorrhea, and 5 patients developed pancreatic type B pain. During the follow-up of surgical intervention, 1 new case of diabetes occurred, 1 case of steatorrhea recovered, and 4 cases of pancreatic type B pain were completely relieved. In a part of young patients with chronic pancreatitis, surgical intervention was more effective than therapeutic ERCP intervention on delaying the progression of the disease and relieving the symptoms.
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Abstract
PURPOSE OF REVIEW Acute pancreatitis is associated with alcohol abuse, gallstones and bacterial infection. Its basic cause is tissue destruction accompanied by an innate immune response, which induces epithelial stress pathways. Recent studies have focused on some of the integral cellular pathways shared between multiple pancreatitis models that also suggest new approaches to detection and treatment. RECENT FINDINGS Several models of pancreatitis have been associated with stress responses, such as endoplasmic reticulum and oxidative stress together with the induction of a defective autophagic pathway. Recent evidence reinforces the critical role of these cellular processes in pancreatitis. A member of the toll-like receptor family, toll-like receptor 4, which is known to contribute to disease pathology in many models of experimental pancreatitis, has been found to be a promising target for treatment of pancreatitis. Interestingly, a direct activator of toll-like receptor 4, the bacterial cell wall component in gram-negative bacteria lipopolysaccharide, contributes to the onset and severity of disease when combined with additional stressors, such as chronic alcohol feeding; however, recent studies have shown that acute infection of mice with live bacteria is alone sufficient to induce acute pancreatitis. SUMMARY In the last several months, the convergent roles of acinar cell stress, autophagy and proinflammatory signaling initiated by the toll-like receptors have been emphatically reinforced in the onset of acute pancreatitis.
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Neri V, Lapolla F, Di Lascia A, Giambavicchio LL. Defining a therapeutic program for recurrent acute pancreatitis patients with unknown etiology. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2014; 7:1-7. [PMID: 24833943 PMCID: PMC4019227 DOI: 10.4137/cgast.s13531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Revised: 11/28/2013] [Accepted: 12/12/2013] [Indexed: 12/17/2022]
Abstract
AIM To define a therapeutic program for mild-moderate acute pancreatitis (AP), often recurrent, which at the end of the diagnostic process remains of undefined etiology. MATERIAL AND METHODS In the period 2011-2012, we observed 64 cases of AP: 52 mild-moderate, 12 severe; biliary 39, biliary in alcoholic chronic pancreatitis 5, unexplained recurrent 20. The clinical and instrumental evaluation of the 20 cases of unexplained AP showed 6 patients with biliary sludge, 4 microlithiasis, 4 sphincter of Oddi dysfunction, and 6 cases that remained undefined. RESULTS Among 20 patients with recurrent, unexplained AP at initial etiological assessment, we performed 10 video laparo cholecystectomies (VLCs), 2 open cholecystectomies and 4 endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomies (ERCP/ES) in patients who had undergone previous cholecystectomy; 4 patients refused surgery. Among these 20 patients, 6 had AP that remained unexplained after second-level imaging investigations. For these patients, 4 VLCs and 2 ERCP/ES were performed. Follow-up after six months was negative for further recurrence. CONCLUSION The recurrence of unexplained acute pancreatitis could be treated with empirical cholecystectomy and/or ERCP/ES in cases of previous cholecystectomy.
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Affiliation(s)
- Vincenzo Neri
- General Surgery, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Francesco Lapolla
- General Surgery, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Alessandra Di Lascia
- General Surgery, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
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Nutritional status in patients with chronic pancreatitis. Eur J Clin Nutr 2013; 67:1271-6. [PMID: 24129361 DOI: 10.1038/ejcn.2013.199] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 08/30/2013] [Accepted: 08/30/2013] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Chronic pancreatitis (CP) patients have an increased risk of malnutrition. Information about nutritional status of CP outpatients is scarce, and simple, sensitive methods to identify patients at risk are lacking. This explorative cross-sectional study was performed to survey the nutritional status of CP outpatients. SUBJECTS Fifty patients with chronic or recurrent acute pancreatitis (RAP) had a nutritional assessment performed. Scores on nutritional screening tools and a quality of life questionnaire were assessed. General observations and relations between parameters were described. RESULTS Thirty-nine patients had CP and eleven patients had RAP. According to the nutritional screening tools, 28-50% of the patients had a moderate or high risk of malnutrition. All domains of the Short Form Health Survey were significantly lowered in CP patients (all P0.001) compared with the Dutch norm values. A considerable number of patients scored below the 5th percentile on anthropometric measures. Mini Nutritional Assessment could not identify all patients with very low anthropometric scores. Substantial weight loss was not a sensitive indicator for functional impairment. CONCLUSION CP outpatients are at risk of malnutrition. Currently used screening methods (for example, weight loss) are likely to be not sensitive enough to identify all patients with impaired body composition and restricted function. Therefore, some patients with objective decline in nutritional status will remain unidentified. An extended nutritional assessment is recommendable in CP patients.
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Etiology of recurrent acute pancreatitis, with special emphasis on pancreaticobiliary malformation. Adv Med Sci 2013. [PMID: 23183766 DOI: 10.2478/v10039-012-0041-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE This study was aimed to investigate etiology and clinical profiles of recurrent acute pancreatitis (RAP), particularly from the morphology of the pancreaticobiliary duct system. MATERIAL AND METHODS Pancreaticobiliary morphology was examined in 230 of 381 patients with acute pancreatitis (AP) using endoscopic retrograde cholangiopancreatography. We analyzed factors associated with RAP including the pancreaticobiliary duct system. RESULTS RAP was diagnosed in 74 patients (19%). Major etiologies of RAP were alcoholic (38%), idiopathic (26%) and pancreaticobiliary malformation (22%). Patients with alcoholic RAP were significantly younger (47.2±11.6 years) than those with gallstone RAP (67.3±16.8; p<0.05). RAP with pancreaticobiliary malformation (male-to-female ratio: 1:4.3; p<0.01) and gallstone RAP (1:1.7; p<0.05) occurred predominantly in females in comparison with alcoholic RAP (1:0.2). Recurrence rate was 80% for AP with pancreaticobiliary malformation, significantly higher than for the others (p<0.01). Pancreas divisum was suspected as the etiology of mild RAP in 7 patients. Four RAP patients with pancreas divisum underwent endoscopic minor papilla sphincterotomy and improved. Pancreaticobiliary maljunction with biliary dilatation (choledochal cyst) was suspected as the etiology of mild RAP in 3 patients. The 3 RAP patients with choledochal cyst underwent prophylactic flow diversion surgery with complete resection of the dilated common bile duct, and achieved improvement. High confluence of pancreaticobiliary ducts was suspected as the etiology of mild RAP in 6 patients. CONCLUSION Pancreaticobiliary malformation is one of the major causes of RAP. As some of them benefit from endoscopic or surgical treatment, morphology of the pancreaticobiliary duct system should be examined where possible in RAP patients.
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Endoscopic approach to the patient with motility disorders of the bile duct and sphincter of Oddi. Gastrointest Endosc Clin N Am 2013; 23:405-34. [PMID: 23540967 DOI: 10.1016/j.giec.2012.12.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Since its original description by Oddi in 1887, the sphincter of Oddi has been the subject of much study. Furthermore, the clinical syndrome of sphincter of Oddi dysfunction (SOD) and its therapy are controversial areas. Nevertheless, SOD is commonly diagnosed and treated by physicians. This article reviews the epidemiology, clinical manifestations, and current diagnostic and therapeutic modalities of SOD.
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Coté GA, Imperiale TF, Schmidt SE, Fogel E, Lehman G, McHenry L, Watkins J, Sherman S. Similar efficacies of biliary, with or without pancreatic, sphincterotomy in treatment of idiopathic recurrent acute pancreatitis. Gastroenterology 2012; 143:1502-1509.e1. [PMID: 22982183 DOI: 10.1053/j.gastro.2012.09.006] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2012] [Revised: 08/28/2012] [Accepted: 09/06/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The role of sphincter of Oddi manometry (SOM) in the management of patients with idiopathic recurrent acute pancreatitis requires clarification. We evaluated the therapeutic effects of endoscopic sphincterotomy in patients with recurrent acute pancreatitis and the prognostic significance of pancreatic sphincter dysfunction (SOD). METHODS We performed a randomized trial of endoscopic retrograde cholangiopancreatography with SOM for patients with idiopathic recurrent acute pancreatitis. Patients with pancreatic SOD (n = 69) were assigned randomly to groups that received only biliary sphincterotomy (BES) or a combination of biliary and pancreatic sphincterotomy (DES); patients who underwent normal SOM (n = 20) were assigned randomly to groups that received BES or a sham surgery. The primary outcome was incidence of recurrent acute pancreatitis during the follow-up period (minimum, 1 year; maximum, 10 years). We also determined the incidence of chronic pancreatitis and analyzed factors associated with recurrence of acute pancreatitis. RESULTS Among the 69 patients with SOD, 48.5% who received BES and 47.2% who received DES had recurrent acute pancreatitis (95% confidence interval, -22.3 to 24.9; P = 1.0). In patients with normal SOM (n = 20), 27.3% of those who received BES and 11.1% of those who received the sham surgery had recurrent acute pancreatitis (95% confidence interval, -49.5 to 17.2; P = .59). Overall, 16.9% of subjects developed chronic pancreatitis during a median follow-up period of 78 months (interquartile range, 35-108 mo). The odds of recurrent acute pancreatitis during follow-up evaluation were significantly greater among patients with SOD than those with normal SOM (unadjusted hazard ratio, 3.5; 95% confidence interval, 1.07-11.4; P < .04), and remained so after adjusting for potential confounders (hazard ratio, 4.3; 95% confidence interval, 1.3-14.5; P < .02). CONCLUSIONS Among patients with pancreatic SOD, DES and BES have similar effects in preventing recurrence of acute pancreatitis. Pancreatic SOD is an independent prognostic factor, identifying patients at higher risk for recurrent acute pancreatitis. CLINICAL TRIALS REGISTRATION Clinicaltrials.gov (NCT01583517).
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Affiliation(s)
- Gregory A Coté
- Division of Gastroenterology & Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
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Buxbaum J. The role of endoscopic retrograde cholangiopancreatography in patients with pancreatic disease. Gastroenterol Clin North Am 2012; 41:23-45. [PMID: 22341248 DOI: 10.1016/j.gtc.2011.12.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Given the significant risk of pancreatitis and the advent of high-fidelity diagnostic techniques, ERCP is now reserved as a therapeutic procedure for those with pancreatic disease. Early ERCP benefits those with gallstone pancreatitis who present with or develop cholangitis or biliary obstruction. Among those with idiopathic pancreatitis, ERCP may be used to confirm and treat SOD, microlithiasis, and structural anomalies, including pancreas divisum. Pancreatic endotherapy is a consideration to decrease pain in those with pancreatic duct obstruction, although surgical decompression may be more durable, particularly in those with severe disease. Pancreatic duct leaks may respond to endoscopic drainage, but optimal therapy is achieved if a bridging stent can be placed. Finally, using a wire-guided technique and pancreatic duct stents in high-risk patients, particularly in cases of suspected SOD, may minimize the risk of post-ERCP pancreatitis.
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Affiliation(s)
- James Buxbaum
- Los Angeles County Hospital, Division of Gastroenterology and Liver Diseases, The University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
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Seyhun E, Malo A, Schäfer C, Moskaluk CA, Hoffmann RT, Göke B, Kubisch CH. Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis. Am J Physiol Gastrointest Liver Physiol 2011; 301:G773-82. [PMID: 21778463 DOI: 10.1152/ajpgi.00483.2010] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In acute pancreatitis, endoplasmic reticulum (ER) stress prompts an accumulation of malfolded proteins inside the ER, initiating the unfolded protein response (UPR). Because the ER chaperone tauroursodeoxycholic acid (TUDCA) is known to inhibit the UPR in vitro, this study examined the in vivo effects of TUDCA in an acute experimental pancreatitis model. Acute pancreatitis was induced in Wistar rats using caerulein, with or without prior TUDCA treatment. UPR components were analyzed, including chaperone binding protein (BiP), phosphorylated protein kinase-like ER kinase (pPERK), X-box binding protein (XBP)-1, phosphorylated c-Jun NH(2)-terminal kinase (pJNK), CCAAT/enhancer binding protein homologues protein, and caspase 12 and 3 activation. In addition, pancreatitis biomarkers were measured, such as serum amylase, trypsin activation, edema formation, histology, and the inflammatory reaction in pancreatic and lung tissue. TUDCA treatment reduced intracellular trypsin activation, edema formation, and cell damage, while leaving amylase levels unaltered. The activation of myeloperoxidase was clearly reduced in pancreas and lung. Furthermore, TUDCA prevented caerulein-induced BiP upregulation, reduced XBP-1 splicing, and caspase 12 and 3 activation. It accelerated the downregulation of pJNK. In controls without pancreatitis, TUDCA showed cytoprotective effects including pPERK signaling and activation of downstream targets. We concluded that ER stress responses activated in acute pancreatitis are grossly attenuated by TUDCA. The chaperone reduced the UPR and inhibited ER stress-associated proapoptotic pathways. TUDCA has a cytoprotective potential in the exocrine pancreas. These data hint at new perspectives for an employment of chemical chaperones, such as TUDCA, in prevention of acute pancreatitis.
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Affiliation(s)
- Ersin Seyhun
- Department of Internal Medicine II, Campus Grobhadern, University of Munich, Germany
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Recurrent acute pancreatitis: clinical profile and an approach to diagnosis. Dig Dis Sci 2010; 55:3610-6. [PMID: 20232145 DOI: 10.1007/s10620-010-1175-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2009] [Accepted: 02/19/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Though recurrent acute pancreatitis is often seen in clinical practice, there are few comprehensive articles on this entity. The aim of this study therefore was to assess the etiological and clinical profile as well as diagnostic yield of non-invasive and invasive tests in this group of patients. METHODS All patients with recurrent acute pancreatitis seen from 2002 to 2007 were included in the study, retrospectively. Clinical information, investigation, and treatment data were collected for all patients by a standardized review of medical charts. Diagnostic tests were grouped into level one (non-invasive) and level two (invasive) tests and their yield was assessed. Comparison was made between the group with known etiology and idiopathic group to look for significant differences. RESULTS A total of 188 patients with recurrent acute pancreatitis were seen during the study period. Common etiological factors were biliary disease (37%), pancreas divisum (8.5%) and alcohol (6.4%). Multiple etiologies were seen in 7% of cases, and no cause was found in 32.4%. The diagnostic yield of level-one investigation (non-invasive) was 29.3%. Level-two tests (invasive) identified presumptive etiologies in 38.3% of cases. Complications developed in 12.2% and there was no mortality. Clinical features and complications were similar in the idiopathic group and those with known etiology. CONCLUSIONS Etiological diagnosis was obtained in 67.6% of patients after comprehensive diagnostic work up. Diagnosis in the majority of patients could only be reached after invasive tests (bile crystal analysis, EUS, ERCP). Early diagnosis and etiology-based therapy is the key to optimum patient outcome.
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Tabata T, Kamisawa T, Takuma K, Anjiki H, Fujiwara J, Egashira H, Koizumi K, Egawa N. Does a patent accessory pancreatic duct prevent acute pancreatitis? Dig Endosc 2010; 22:297-301. [PMID: 21175482 DOI: 10.1111/j.1443-1661.2010.01004.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
BACKGROUND AND AIM The role of the accessory pancreatic duct (APD) in pancreatic pathophysiology has been unclear. We previously examined the patency of the APD in 291 control cases who had a normal pancreatogram in the head of the pancreas by dye-injection endoscopic retrograde pancreatography (ERP). APD patency was 43% and was closely related with the shape of the terminal portion of the APD. The present study aimed to clarify the clinical implications of a patent APD. METHODS Based on the underlying data, the patency rate of the APD was estimated from the terminal shape of the APD on ERP in 167 patients with acute pancreatitis. RESULTS In patients with acute pancreatitis, stick-type APD, spindle-type APD, and cudgel-type APD, which showed a high patency, were rare, and branch-type APD and halfway-type or no APD, which showed quite low patency, were frequent in acute pancreatitis patients. Accordingly, the estimated patency of the APD in acute pancreatitis patients was only 21%. There was no significant relationship between the estimated APD patency and etiology or severity of acute pancreatitis. CONCLUSIONS The terminal shapes of the APD with low patency were frequent in acute pancreatitis patients, and estimated APD patency was only 21% in acute pancreatitis. A patent APD may function as a second drainage system to reduce the pressure in the main pancreatic duct and prevent acute pancreatitis.
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Affiliation(s)
- Taku Tabata
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
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Malo A, Krüger B, Seyhun E, Schäfer C, Hoffmann RT, Göke B, Kubisch CH. Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini. Am J Physiol Gastrointest Liver Physiol 2010; 299:G877-86. [PMID: 20671193 DOI: 10.1152/ajpgi.00423.2009] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Endoplasmic reticulum (ER) stress leads to accumulation of un- or misfolded proteins inside the ER and initiates the unfolded protein response (UPR). Several UPR components are physiologically involved in pancreatic development and are pathophysiologically activated during acute pancreatitis. However, the exact role of ER stress in exocrine pancreatic acini is mainly unclear. The present study examined the effects of tauroursodeoxycholic acid (TUDCA), a known ER chaperone, on acinar function and UPR components. Isolated rat pancreatic acini were stimulated by increasing concentrations of cholecystokinin (CCK-8) with or without preincubation of TUDCA. UPR components were analyzed, including chaperone binding protein (BiP), protein kinase-like ER kinase (PERK), X-box binding protein (XBP)-1, c-Jun NH(2)-terminal kinase (JNK), CCAAT/enhancer binding protein homologues protein (CHOP), caspase 3 activation, and apoptosis. In addition, TUDCA effects were measured on amylase secretion, calcium signaling, trypsin, and cathepsin B activation. TUDCA preincubation led to a significant increase in amylase secretion after CCK-8 stimulation, a 50% reduction of intracellular trypsin activation, and reduced cathepsin B activity, although the effects for cathepsin B were not statistical significant. Furthermore, TUDCA prevented the CCK-8-induced BiP upregulation, diminished PERK and JNK phosphorylation, and prohibited the expression of CHOP, caspase 3 activation and apoptosis. XBP-1 splicing was not altered. ER stress response mechanisms are activated in pancreatic inflammation. Chemical chaperones enhance enzyme secretion of pancreatic acini, reduce ER stress responses, and attenuate ER stress-associated apoptosis. These data hint new perspectives for an employment of chemical chaperones in the therapy of acute pancreatitis.
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Affiliation(s)
- A Malo
- Dept. of Internal Medicine, University of Munich, Germany
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Fischer M, Hassan A, Sipe BW, Fogel EL, McHenry L, Sherman S, Watkins JL, Schmidt S, Lazzell-Pannell L, Lehman GA. Endoscopic retrograde cholangiopancreatography and manometry findings in 1,241 idiopathic pancreatitis patients. Pancreatology 2010; 10:444-52. [PMID: 20720445 DOI: 10.1159/000264675] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2009] [Accepted: 11/12/2009] [Indexed: 12/11/2022]
Abstract
BACKGROUND 10-30% of patients with pancreatitis are classified as idiopathic after the initial evaluation. Our aim was to assess the diagnostic yield of endoscopic retrograde cholangiopancreatography (ERCP) and sphincter of Oddi manometry in patients with idiopathic pancreatitis in a tertiary referral center. METHODS A single-center, retrospective study analyzing the ERCP and manometry results of 1,241 patients who were classified as having idiopathic pancreatitis based upon their initial evaluation. RESULTS A single episode of pancreatitis occurred in 20.4%, acute recurrent pancreatitis in 56.3% and chronic pancreatitis in 23.3% of the patients undergoing ERCP. Sphincter of Oddi dysfunction was found in 40.3% and pancreas divisum in 18.8% of the patients. Biliary stone disease was found in 3.0%. Intraductal papillary mucinous neoplasms were identified in 52 patients with increasing frequency in older age groups. The overall diagnostic yield of ERCP and sphincter of Oddi manometry to elucidate a potential cause of pancreatitis was 65.8%. Of these, 91.9% patients had findings amenable to endoscopic therapy. The complication rate was 11.5%. CONCLUSIONS In this large series, ERCP with manometry frequently identified conditions which probably caused or contributed to the idiopathic pancreatitis. Long-term studies are awaited to determine outcomes after correctable factors are addressed. and IAP.
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Affiliation(s)
- Monika Fischer
- Department of Medicine, Indiana University, Indianapolis, Ind 46202, USA.
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Romagnuolo J, Guda N, Freeman M, Durkalski V. Preferred designs, outcomes, and analysis strategies for treatment trials in idiopathic recurrent acute pancreatitis. Gastrointest Endosc 2008; 68:966-74. [PMID: 18725158 DOI: 10.1016/j.gie.2008.05.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2007] [Accepted: 05/05/2008] [Indexed: 12/13/2022]
Affiliation(s)
- Joseph Romagnuolo
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425-2900, USA
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Ursodeoxycholic acid treatment for patients with postcholecystectomy pain and bile microlithiasis. Gastrointest Endosc 2008; 68:69-74. [PMID: 18577477 DOI: 10.1016/j.gie.2007.09.046] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2007] [Accepted: 09/20/2007] [Indexed: 02/08/2023]
Abstract
BACKGROUND Microlithiasis has been identified as a cause of idiopathic acute pancreatitis in patients with an intact gallbladder. Microlithiasis has also been identified in the bile of some patients who have undergone cholecystectomy. However, it is unknown whether bile microlithiasis causes postcholecystectomy pain. OBJECTIVE To identify bile microlithiasis in patients with postcholecystectomy pain and to investigate the therapeutic effect of ursodeoxycholic acid (urso) on such patients with microlithiasis in the bile. DESIGN Prospective randomized trial. SETTING Tertiary medical center. PATIENTS Patients with postcholecystectomy pain and bile crystals. INTERVENTIONS Urso treatment. MAIN OUTCOME MEASUREMENTS The severity and frequency of right upper-quadrant abdominal pain were compared with and without urso treatment, and before and after urso treatment. RESULTS A total of 118 patients with postcholecystectomy pain were screened for the study. Twelve patients (10%) were identified with bile crystals. In the first phase, 6 of these patients received urso treatment, whereas the other 6 patients did not receive urso treatment. In the second phase, the latter 6 patients were given the urso treatment. After using urso for a few months, their biliary-type abdominal pain significantly improved or resolved. In the control group, there was no improvement in symptoms. There was a significant difference between the 2 groups (P = .01). LIMITATIONS Single-center, small number of patients. CONCLUSIONS This study provided evidence that supports the hypothesis that bile microlithiasis is indeed a cause for postcholecystectomy pain. Patients with such postcholecystectomy pain may benefit from a microscopic examination of bile for crystals or microlithiasis, and urso treatment if bile crystals are identified.
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MRCP-secretin test-guided management of idiopathic recurrent pancreatitis: long-term outcomes. Gastrointest Endosc 2008; 67:1028-34. [PMID: 18179795 DOI: 10.1016/j.gie.2007.09.007] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2006] [Accepted: 09/04/2007] [Indexed: 02/08/2023]
Abstract
BACKGROUND In patients with recurrent pancreatitis of unknown etiology and nondilated ducts, accurate morphofunctional evaluation of the pancreaticobiliary ductal system and sphincter of Oddi function is important in the diagnostic workup. However, ERCP and sphincter of Oddi manometry may be nondiagnostic and postprocedure complications may be frequent. OBJECTIVE Our purpose was to assess the diagnostic accuracy of the magnetic resonance cholangiopancreatography with secretin test (MRCP-S) in patients with recurrent acute pancreatitis of unknown etiology. Accuracy was established on the basis of ERCP findings and a minimum of 24 months' clinical follow-up. DESIGN Thirty-seven consecutive patients with intact gallbladder and a nondilated pancreaticobiliary ductal system with nonpathologic EUS findings entered a prospective MRCP-S-guided and ERCP-guided diagnostic and therapeutic study protocol. RESULTS Patients were followed up for a mean of 31.3 months (range 26-38 months). MRCP-S identified some pancreatic outflow impairment, suggesting morphofunctional dysfunction of either the major or minor papilla, in 12 of 37 patients (32.4%). The addition of ERCP to MRCP-S did not substantially improve the diagnostic yield for the etiology of recurrent pancreatitis, and 13.6% of cases had mild postprocedure pancreatitis. The S-test was abnormal in 12 of 20 cases (60%) in whom some dysfunction of the sphincter of Oddi or minor papilla was assumed on the basis of follow-up findings. The outcome was successful after biliary or pancreatic sphincterotomy in all patients with an abnormal S-test result. Sensitivity, specificity, and positive and negative predictive values of the S-test for the diagnosis of pancreatic outflow impairment at the major or minor papilla were, respectively, 57.1%, 100%, 100%, and 64%. When the test showed an abnormal result, we were unable to distinguish between biliary and pancreatic segment dysfunction of the sphincter of Oddi. CONCLUSIONS In idiopathic recurrent pancreatitis with nondilated ducts, the MRCP-S-guided approach gave diagnostic accuracy comparable to ERCP with regard to morphologic lesions, and it can be used as an alternative, avoiding ERCP-related complications in the diagnostic phase. An abnormal S-test result showed an excellent positive predictive value and somewhat disappointing negative predictive value for sphincter of Oddi or minor papilla dysfunction and for clinical success of therapeutic endoscopic approach.
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Testoni PA. Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases. World J Gastroenterol 2008; 13:5971-8. [PMID: 18023085 PMCID: PMC4250876 DOI: 10.3748/wjg.v13.45.5971] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangio-pancreatography (ERCP) or endoscopic ultrasound (EUS), or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute pancreatitis, recurrent idiopathic pancreatitis, and in the prevention of post-ERCP pancreatitis. These stents are currently routinely placed to reduce intraductal hypertension, bypass obstructing stones, restore lumen patency in cases with dominant, symptomatic strictures, seal main pancreatic duct disruption, drain pseudocysts or fluid collections, treat symptomatic major or minor papilla sphincter stenosis, and prevent procedure-induced acute pancreatitis. The present review aims at updating and discussing techniques, indications, and results of endoscopic pancreatic duct stent placement in acute and chronic inflammatory diseases of the pancreas.
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Testoni PA. Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases. World J Gastroenterol 2008. [PMID: 18023085 DOI: 10.3748/wjg.13.5971] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangio-pancreatography (ERCP) or endoscopic ultrasound (EUS), or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute pancreatitis, recurrent idiopathic pancreatitis, and in the prevention of post-ERCP pancreatitis. These stents are currently routinely placed to reduce intraductal hypertension, bypass obstructing stones, restore lumen patency in cases with dominant, symptomatic strictures, seal main pancreatic duct disruption, drain pseudocysts or fluid collections, treat symptomatic major or minor papilla sphincter stenosis, and prevent procedure-induced acute pancreatitis. The present review aims at updating and discussing techniques, indications, and results of endoscopic pancreatic duct stent placement in acute and chronic inflammatory diseases of the pancreas.
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Elta GH. Sphincter of Oddi dysfunction and bile duct microlithiasis in acute idiopathic pancreatitis. World J Gastroenterol 2008; 14:1023-6. [PMID: 18286682 PMCID: PMC2689403 DOI: 10.3748/wjg.14.1023] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Although there are numerous causes of acute pancreatitis, an etiology cannot always be found. Two potential etiologies, microlithiasis and sphincter of Oddi dysfunction, are discussed in this review. Gallbladder microlithiasis, missed on transcutaneous ultrasound, is reported as the cause of idiopathic acute pancreatitis in a wide frequency range of 6%-80%. The best diagnostic technique for gallbladder microlithiasis is endoscopic ultrasound although biliary crystal analysis and empiric cholecystectomy remain as reasonable options. In contrast, in patients who are post-cholecystectomy, bile duct microlithiasis does not appear to have a role in the pathogenesis of acute pancreatitis. Sphincter of Oddi dysfunction is present in 30%-65% of patients with idiopathic acute recurrent pancreatitis in whom other diagnoses have been excluded. It is unclear if this sphincter dysfunction was the original etiology of the first episode of pancreatitis although it appears to have a causative role in recurring episodes since sphincter ablation decreases the frequency of recurrent attacks. Unfortunately, this conclusion is primarily based on small retrospective case series; larger prospective studies of the outcome of pancreatic sphincterotomy for SOD-associated acute pancreatitis are sorely needed. Another problem with this diagnosis and its treatment is the concern over potential procedure related complications from endoscopic retrograde cholangiopancreatography (ERCP), manometry and pancreatic sphincterotomy. For these reasons, patients should have recurrent acute pancreatitis, not a single episode, and have a careful informed consent before assessment of the sphincter of Oddi is undertaken.
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Delhaye M, Matos C, Arvanitakis M, Devière J. Pancreatic ductal system obstruction and acute recurrent pancreatitis. World J Gastroenterol 2008; 14:1027-33. [PMID: 18286683 PMCID: PMC2689404 DOI: 10.3748/wjg.14.1027] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acute recurrent pancreatitis is a clinical entity largely associated with pancreatic ductal obstruction. This latter includes congenital variants, of which pancreas divisum is the most frequent but also controversial, chronic pancreatitis, tumors of the pancreaticobiliary junction and sphincter of Oddi dysfunction. This review summarizes current knowledge about diagnostic work-up and therapy of these conditions.
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Abstract
Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins, autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted.
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41
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Kinney TP, Punjabi G, Freeman M. Technology insight: applications of MRI for the evaluation of benign disease of the pancreas. ACTA ACUST UNITED AC 2007; 4:148-59. [PMID: 17339852 DOI: 10.1038/ncpgasthep0760] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2006] [Accepted: 01/15/2007] [Indexed: 12/18/2022]
Abstract
This article reviews the role of MRI in the evaluation of benign pancreatic disease. Although MRI and magnetic resonance cholangiopancreatography (MRCP) are most often used to evaluate the liver and bile duct, technical advances such as the use of secretin stimulation also allow for high-quality imaging of the pancreas and pancreatic ductal system. Secretin-stimulated MRCP (S-MRCP) can aid the diagnosis of acute and chronic pancreatitis, and delineate ductal pathology such as benign strictures and duct leaks. There seems to be a role for S-MRCP in the assessment of pancreatic function and (possibly) sphincter of Oddi dysfunction. When endoscopic or surgical therapy is planned, S-MRCP can help to establish a diagnosis as well as offer a 'road map' to guide therapy. S-MRCP is noninvasive and almost entirely without risk to the patient, which gives it a distinct advantage over traditional endoscopic methods of diagnosis for conditions such as pancreas divisum and other ductal pathology. The information provided by S-MRCP, obtained before endoscopic or surgical therapy is attempted, can assist the patient and physician in making a fully informed decision with regard to the risks and probable benefits of any planned intervention.
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Affiliation(s)
- Timothy P Kinney
- Division of Gastroenterology, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA.
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42
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Gao YJ, Li YQ, Wang Q, Li SL, Li GQ, Ma J, Zeng XZ, Huang LY, Yuan SA, Liu CA, Wang FX. Analysis of clinical features of acute pancreatitis in Shandong Province, China. J Gastroenterol Hepatol 2007; 22:340-4. [PMID: 17295764 DOI: 10.1111/j.1440-1746.2006.04545.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIM To investigate and obtain a more comprehensive view of the etiology and clinical features of acute pancreatitis in China. METHOD The study comprised 1471 patients in 10 cites of China who were admitted to hospitals for acute pancreatitis from January 1992 to December 2002. Data for each patient were collected on a standardized form. RESULTS Of the 1471 patients (854 men, 617 women; mean age 43.3 years; range 13-82 years), 1280 had mild pancreatitis and 191 had the severe form. Cholelithiasis (20.2%), alcohol (17.3%) and diet-induced (12.4%) were the most frequent etiological factors, followed by biliary tract infections (5.6%), hyperlipidemia (2.3%) and other factors (5.1%). However, in about 36.1% of cases, the etiology of acute pancreatitis still remained unexplained. In coastal regions, cholelithiasis was the most frequent factor but alcohol ranked first in interior regions. In males, a small predominance of alcohol over cholelithiasis was seen (27.4%vs 14.3%) and there was a clear predominance of cholelithiasis over alcohol (28.4%vs 3.2%) in females. The differences in the frequency of cholelithiasis and alcohol between coastal regions and interior regions and males and females were statistically significant (P < 0.01). According to their frequency, complications of acute pancreatitis were pancreatic pseudocyst, pancreatic ascites and bacterial peritonitis, pulmonary infections, multiple organ failure, diabetes mellitus type 2 and shock. CONCLUSION Cholelithiasis, alcohol and diet-induced factors were the main etiological factors seen in China, whereas cholelithiasis alone predominated in females and alcohol ranked first in males. In about 36.1% of cases, the etiology of acute pancreatitis remained unknown. More attention should be paid to studying the etiologies of acute pancreatitis that remain unknown.
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Affiliation(s)
- Yan Jing Gao
- Shandong University Qi-Lu Hospital, Ji-Nan City, Japan
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Ewald N, Marzeion AM, Bretzel RG, Kloer HU, Hardt PD. Endoscopic sphincterotomy in patients with stenosis of ampulla of Vater: Three-year follow-up of exocrine pancreatic function and clinical symptoms. World J Gastroenterol 2007; 13:901-5. [PMID: 17352020 PMCID: PMC4065926 DOI: 10.3748/wjg.v13.i6.901] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate retrospectively the long-term effect of endoscopic sphincterotomy (ES) including exocrine pancreatic function in patients with stenosis of ampulla of Vater.
METHODS: After diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and ES because of stenosis of the ampulla of Vater (SOD Type I), follow-up examinations were performed in 60 patients (mean follow-up time 37.7 mo). Patients were asked about clinical signs and symptoms at present and before intervention using a standard questionnaire. Before and after ES exocrine pancreatic function was assessed by determination of immunoreactive fecal elastase 1. Serum enzymes indicating cholestasis as well as serum lipase and amylase were measured.
RESULTS: Eighty percent of patients reported an improvement in their general condition after ES. The fecal elastase 1 concentrations (FEC) in all patients increased significantly after ES. This effect was even more marked in patients with pathologically low concentrations (< 200 μg/g) of fecal elastase prior to ES. The levels of serum lipase and amylase as well as serum alcaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGT) decreased significantly after ES.
CONCLUSION: The results of this study demonstrate that patients with stenosis of the ampulla of Vater can be successfully treated with endoscopic sphincterotomy. The positive effect is not only indicated by sustained improvement of clinical symptoms and cholestasis but also by improvement of exocrine pancreatic function.
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Affiliation(s)
- Nils Ewald
- Third Medical Department and Policlinic, University Hospital Giessen and Marburg, Giessen Site, D-35392 Giessen, Germany.
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Gao YJ, Li YQ, Wang Q, Li SL, Li GQ, Ma J, Zeng XZ, Huang LY, Yuan SA, Liu CA, Wang FX. Analysis of the clinical features of recurrent acute pancreatitis in China. J Gastroenterol 2006; 41:681-5. [PMID: 16933006 DOI: 10.1007/s00535-006-1820-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2005] [Accepted: 03/22/2006] [Indexed: 02/04/2023]
Abstract
BACKGROUND Since few systematic studies have focused on recurrent acute pancreatitis in China, we sought to investigate its clinical features, including etiological factors and relative frequency. METHODS Patients were selected from a total 1471 patients with acute pancreatitis in ten cities of China. All had been admitted to a hospital with an attack of acute pancreatitis between January 1992 and December 2002. Data for each patient was recorded on a standardized form. RESULTS Of the 1471 patients with acute pancreatitis, 157 (10.7%) had recurrent acute pancreatitis. The majority (63%) were male, with a mean age of 41 years (range, 13-82 years). Regarding the etiology, alcohol (20.4%) and cholelithiasis (20.4%) were the most frequent causes, followed by diet (13.4%), hypertriglyceridemia (8.3%), biliary tract infection (5.7%), other (5.1%), and idiopathic factors (26.8%). Alcohol was most frequent in male patients (30.3%), whereas cholelithiasis was most frequent (34.5%) in female patients. The majority of patients (79.6%) presented with their second attack of pancreatitis. Complications of recurrent acute pancreatitis in order of frequency were pancreatic pseudocyst, multiple organ failure, diabetes mellitus type 2, and shock. CONCLUSIONS Recurrent acute pancreatitis remains a frequent disease, with cholelithiasis and alcohol being the most usual etiological factors. Alcohol is the primary etiological factor in male patients. In about 26.8% of cases, the etiology remains unknown.
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Affiliation(s)
- Yan Jing Gao
- Shandong University Qilu Hospital, Jinan, 250012, China
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45
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Evans WB, Draganov P. Is empiric cholecystectomy a reasonable treatment option for idiopathic acute pancreatitis? ACTA ACUST UNITED AC 2006; 3:356-7. [PMID: 16819478 DOI: 10.1038/ncpgasthep0527] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2006] [Accepted: 04/26/2006] [Indexed: 11/09/2022]
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Wilcox CM, Varadarajulu S, Eloubeidi M. Role of endoscopic evaluation in idiopathic pancreatitis: a systematic review. Gastrointest Endosc 2006; 63:1037-1045. [PMID: 16733122 DOI: 10.1016/j.gie.2006.02.024] [Citation(s) in RCA: 93] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2005] [Accepted: 02/11/2006] [Indexed: 02/07/2023]
Abstract
In approximately 20% of patients with acute pancreatitis, a cause is not established by history, physical examination, routine laboratory testing, and abdominal imaging. For those with a single unexplained attack, the role of invasive evaluation with endoscopic retrograde cholangiopancreatography is unsettled but has been generally limited to those patients with suspected bile duct stones or malignancy. Recent studies suggest that microlithiasis is causative in up to 75% of patients with an unexplained attack and gallbladder in situ, whereas sphincter of Oddi dysfunction is most prevalent in those with recurrent attacks who have previously undergone cholecystectomy. EUS has been shown to be highly accurate for the identification of gallbladder sludge, common bile duct stones, and pancreatic diseases. Given this apparent diagnostic utility, an EUS-based strategy may be a reasonable approach to evaluate patients with a single idiopathic attack. ERCP and sphincter of Oddi manometry should generally be reserved for patients with multiple unexplained attacks and negative EUS results, especially for those patients who have previously undergone cholecystectomy.
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Affiliation(s)
- C Mel Wilcox
- Division of Gastroenterology and Hepatology and Pancreaticobiliary Center, University of Alabama at Birmingham, 703 19th Street South, Birmingham, AL 35294, USA
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Venneman NG, Besselink MGH, Keulemans YCA, Vanberge-Henegouwen GP, Boermeester MA, Broeders IAMJ, Go PMNYH, van Erpecum KJ. Ursodeoxycholic acid exerts no beneficial effect in patients with symptomatic gallstones awaiting cholecystectomy. Hepatology 2006; 43:1276-83. [PMID: 16729326 DOI: 10.1002/hep.21182] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Ursodeoxycholic acid (UDCA) and impaired gallbladder motility purportedly reduce biliary pain and acute cholecystitis in patients with gallstones. However, the effect of UDCA in this setting has not been studied prospectively. This issue is important, as in several countries (including the Netherlands) scheduling problems result in long waiting periods for elective cholecystectomy. We conducted a randomized, double-blind, placebo-controlled trial on effects of UDCA in 177 highly symptomatic patients with gallstones scheduled for cholecystectomy. Patients were stratified for colic number in the preceding year (<3: 32 patients; > or =3: 145 patients). Baseline postprandial gallbladder motility was measured by ultrasound in 126 consenting patients. Twenty-three patients (26%) receiving UDCA and 29 (33%) receiving placebo remained colic-free during the waiting period (89 +/- 4; median [range]: 75[4-365] days) before cholecystectomy (P = .3). Number of colics, non-severe biliary pain, and analgesics intake were comparable. A low number of prior colics was associated with a higher likelihood of remaining colic-free (59% vs. 23%, P < .001), without effects on the risk of complications. In patients evaluated for gallbladder motility, 57% were weak and 43% were strong contractors (minimal gallbladder volume > respectively < or = 6 mL). Likelihood to remain colic-free was comparable in strong and weak contractors (31% vs. 33%). In weak contractors, UDCA decreased likelihood to remain colic-free (21% vs. 47%, P = .02). In the placebo group, 3 preoperative and 2 post-cholecystectomy complications occurred. In contrast, all 4 complications in the UDCA group occurred after cholecystectomy. In conclusion, UDCA does not reduce biliary symptoms in highly symptomatic patients. Early cholecystectomy is warranted in patients with symptomatic gallstones.
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Affiliation(s)
- Niels G Venneman
- Gastrointestinal Research Unit, Department of Gastroenterology, University Medical Center Utrecht, The Netherlands
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48
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van Minnen LP, Venneman NG, van Dijk JE, Verheem A, Gooszen HG, Akkermans LMA, van Erpecum KJ. Cholesterol crystals enhance and phospholipids protect against pancreatitis induced by hydrophobic bile salts: a rat model study. Pancreas 2006; 32:369-75. [PMID: 16670619 DOI: 10.1097/01.mpa.0000220861.78248.1f] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVES The role of bile composition in the pathogenesis of biliary pancreatitis is unknown. The objective of this experiment was to explore the potential role of bile salts, phospholipids, and cholesterol crystals in the pathogenesis of biliary pancreatitis in a rat model. METHODS Model systems composed of taurodeoxycholate (TDC), mixed bile salts (MBS), or tauroursodeoxycholate (TUDC) [in 10 mM phosphate-buffered saline (PBS), pH 7.4], with or without cholesterol crystals or phosphatidylcholine, were infused into bile ducts of male Sprague-Dawley rats. Twenty-four hours later, animals were killed for histopathologic scoring of (peri)pancreatic inflammation. RESULTS : Severity of acute pancreatitis depended on bile salt hydrophobicity (TDC > MBS >> TUDC = PBS; histopathologic scores: 25.6 +/- 0.5, 23.0 +/- 1.5, 14.4 +/- 2.2, 14.8 +/- 1.0, respectively; P < 0.001), with corresponding differences in serum lipase concentration. Phosphatidylcholine protected against detrimental effects of TDC at physiological, but not at low, concentrations (scores: 19.5 +/- 2.3 vs 28.3 +/- 1.9 in case of Phosphatidycholine/(TDC + Phosphatidycholine) ratios 0.25 or 0.05, respectively). Cholesterol crystals increased severity of pancreatitis in model systems containing TDC or MBS, but not TUDC or PBS (33.2 +/- 0.4, 29.6 +/- 1.2, 18.6 +/- 1.5, 18.5 +/- 2.2, respectively; P < 0.001). CONCLUSIONS In the rat model, hydrophobic bile salts and cholesterol crystals aggravate biliary pancreatitis, whereas phospholipids have a protective effect.
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Affiliation(s)
- L Paul van Minnen
- Gastrointestinal Research Unit, Departments of Gastroenterology and Surgery, University Medical Center Utrecht, The Netherlands.
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49
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Abstract
'Sludge' is the solid material which results from the slow settling of particles dispersed in a liquid medium. Biliary sludge in the gallbladder can be detected by transabdominal ultrasonography, and the typical echoes derive mainly from pigment precipitates mixed with cholesterol crystals. A portion of biliary sludge contains comparatively large particles (1-3 mm) called microliths, the formation of which is an obligatory intermediate step in the development of all types of gallstone. Microlithiasis and sludge in bile may cause colicky pain, cholecystitis, cholangitis, and acute pancreatitis, and are thus of clinical relevance. In these patients treatment follows the guidelines of symptomatic gallstone disease, and strategies include long-term application of ursodeoxycholic acid, endoscopic papillotomy, or preferably laparoscopic cholecystectomy.
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Affiliation(s)
- Christoph Jüngst
- Department of Medicine I, Universitätsklinikum Bonn, Sigmund-Freud Str. 25, 53105 Bonn, Germany
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50
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Abstract
Several risk factors for cholesterol gallstone formation in the general population have been identified. There is a strongly increased risk of gallstone disease during prolonged fasting, rapid weight loss, total parenteral nutrition, and somatostatin(-analogue) treatment. The annual risk of biliary colic and gallstone complications in asymptomatic gallstone carriers has been investigated sparsely. In asymptomatic and symptomatic gallstone carriers, treatment with the hydrophilic bile salt ursodeoxycholic acid (UDCA) has been claimed to reduce the risk of biliary colic and gallstone complications such as acute cholecystitis and acute pancreatitis. Also, prophylactic cholecystectomy could be beneficial in certain subgroups of asymptomatic gallstone carriers. However, randomized, double-blind, placebo-controlled trials are lacking. In this review, strategies for the prevention of gallstone formation in the general population and in high-risk conditions are dealt with. Also, strategies for the prevention of biliary colic and gallstone complications in asymptomatic and symptomatic gallstone carriers are discussed.
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Affiliation(s)
- Niels G Venneman
- Gastrointestinal Research Unit, Department of Gastroenterology, University Medical Center Utrecht, The Netherlands.
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