Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416.

Endoscopic versus surgical ampullectomy: an algorithm to treat disease of the ampulla of Vater.

OBJECTIVE: The objective of this study was to compare the effectiveness, morbidity, and mortality associated with endoscopic ampullectomy (EA) and surgical ampullectomy (SA). BACKGROUND: The proposed management of benign ampullary lesions includes local resection (EA or SA) and en bloc resection (pancreaticoduodenectomy). Most agree that en bloc resection entails a significant morbidity and mortality. No study has previously compared EA and SA for the treatment of benign ampullary lesions. METHODS: Medical records of patients selected for ampullectomy at Duke University Medical Center from 1991 to 2010 were reviewed. RESULTS: After review, 109 patients were confirmed to have undergone ampullectomy for a suspected benign ampullary lesion. Sixty-eight patients underwent EA, whereas 41 patients underwent SA. Patients in each group were identical in terms of age, sex, race, and comorbid conditions, except that EA had a higher rate of severe obesity (body mass index >35). Endoscopic ampullectomy was found to have a significantly reduced length of stay, lower morbidity, and readmission rates, but it had similar rates of mortality, margin-positive excisions, and reinterventions. CONCLUSIONS: In patients selected for ampullectomy for benign ampullary lesions, EA was found to have equivalent efficacy when compared with SA. Moreover, EA had lower morbidity and identical mortality. These findings suggest that patients would likely benefit from an aggressive endoscopic approach before consideration for surgery.

For patients with predicted low risk for choledocholithiasis undergoing laparoscopic cholecystectomy, selective intraoperative cholangiography and postoperative endoscopic retrograde cholangiopancreatography is an effective strategy to limit unnecessary procedures.

BACKGROUND: There is debate about whether intraoperative cholangiography (IOC) should be performed routinely or selectively during laparoscopic cholecystectomy (LC) in patients with suspected choledocholithiasis. The timing of endoscopic retrograde cholangiopancreatography (ERCP) in these patients also is an issue. We reviewed the experience in our center, where a management algorithm limiting ERCP in relation to LC was adopted. METHODS: We retrospectively reviewed every LC performed by one surgeon during 6 years and the related ERCPs. RESULTS: A total of 264 LCs were performed. In 30 patients, stones were cleared or excluded by preoperative ERCP. In the remaining 234 LCs, 31 of 34 IOCs were successfully performed. Two of 31 IOCs were positive for bile duct stones; stone removal was successful in each patient at subsequent ERCP. Only 10 of 201 patients who did not have IOC required postsurgical ERCP within 10 weeks of LC, 3 of whom had common bile duct stones at ERCP. CONCLUSIONS: For patients who underwent LC, we performed selective IOC with postoperative ERCP for positive studies. Review of our experience using this algorithm showed it to be a powerful tool in limiting unnecessary ERCPs. Our data suggest that routine preoperative ERCP cannot be justified. Selective IOC during LC misses relatively few cases of biliary stones; these can be managed quickly by experienced endoscopists.

Focal or diffuse "fullness" of the pancreas on CT. Usually benign, but EUS plus/minus FNA is warranted to identify malignancy.

CONTEXT: The role of EUS to evaluate subtle radiographic abnormalities of the pancreas is not well defined. OBJECTIVE: To assess the yield of EUS+/-FNA for focal or diffuse pancreatic enlargement/fullness seen on abdominal CT scan in the absence of discrete mass lesions. DESIGN: Retrospective database review. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Six hundred and 91 pancreatic EUS exams were reviewed. Sixty-nine met inclusion criteria of having been performed for focal enlargement or fullness of the pancreas. Known chronic pancreatitis, pancreatic calcifications, acute pancreatitis, discrete mass on imaging, pancreatic duct dilation (greater than 4 mm) and obstructive jaundice were excluded. MAIN OUTCOME MEASUREMENT: Rate of malignancy found by EUS+/-FNA. RESULTS: FNA was performed in 19/69 (27.5%) with 4 new diagnoses of pancreatic adenocarcinoma, one metastatic renal cell carcinoma, one metastatic colon cancer, one chronic pancreatitis and 12 benign results. Eight patients had discrete mass lesions on EUS; two were cystic. All malignant diagnoses had a discrete solid mass on EUS. CONCLUSIONS: Pancreatic enlargement/fullness is often a benign finding related to anatomic variation, but was related to malignancy in 8.7% of our patients (6/69). EUS should be strongly considered as the next step in the evaluation of patients with focal enlargement of the pancreas when clinical suspicion of malignancy exists.

Top Ten Tips Palliative Care Clinicians Should Know About Interventional Symptom Management Options When Caring for Patients with Gastrointestinal Malignancies.

Patients diagnosed with advanced stages of gastrointestinal (GI) malignancies are often quite symptomatic, with symptoms primarily related to anatomic sites of obstruction. Endoscopic approaches to the palliation of GI malignancies have begun to overtake surgical approaches as first line in interventional management. We brought together a team of interventional gastroenterologists and palliative care experts to collate practical pearls for the types of endoscopic interventions used for symptom management in patients with GI malignancies. In this article, we use a "Top 10" format to highlight issues that may help palliative care physicians recognize common presentations of advanced GI malignancies, address interventional approaches to improve symptom burden, and improve the quality of shared decision making and goals-of-care discussions.

Endoscopic ultrasound-guided fine-needle aspiration for non-small cell lung cancer staging: A systematic review and metaanalysis.

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive alternative technique for mediastinal staging of non-small cell lung cancer. A metaanalysis was performed to estimate the diagnostic accuracy of EUS-FNA for staging mediastinal lymph nodes (N2/N3 disease) in patients with lung cancer. METHODS: Relevant studies were identified using Medline (1966 to November 2005), CINAHL, and citation indexing. Included studies used histology or adequate clinical follow-up (> 6 months) as the "gold standard," and provided sufficient data for calculating sensitivity and specificity. Summary receiver operating characteristic curves metaanalysis was performed to estimate the pooled sensitivity and specificity. RESULTS: In 18 eligible studies, EUS-FNA identified 83% of patients (95% confidence interval [CI], 78 to 87%) with positive mediastinal lymph nodes (pooled sensitivity) and 97% of patients (95% CI, 96 to 98%) with negative mediastinal lymph nodes (pooled specificity). In eight studies that were limited to patients who had abnormal mediastinal lymph nodes seen on CT scans, the sensitivity was 90% (95% CI, 84 to 94%) and the specificity was 97% (95% CI, 95 to 98%). In patients without abnormal mediastinal lymph nodes seen on CT scans (four studies), the pooled sensitivity was 58% (95% CI, 39 to 75%). Minor complications were reported in 10 cases (0.8%). There were no major complications. CONCLUSIONS: EUS-FNA is a safe modality for the invasive staging of lung cancer that is highly sensitive when used to confirm metastasis to mediastinal lymph nodes seen on CT scans. In addition, among lung cancer patients with normal mediastinal adenopathy seen on CT scans, despite lower sensitivity, it has the potential to prevent unnecessary surgery in a large proportion of cases missed by CT scanning.

The impact of cystic fibrosis and PSTI/SPINK1 gene mutations on susceptibility to chronic pancreatitis.

This article reviews current concepts regarding the pathobiology of cystic fibrosis pancreatic disease. It summarizes recent studies on the relationship between CFTR mutations and pancreatitis, and it reviews several unresolved issues in the field.

Rotational assisted endoscopic retrograde cholangiopancreatography in patients with reconstructive gastrointestinal surgical anatomy.

AIM: To evaluate the success rates of performing therapy utilizing a rotational assisted enteroscopy device in endoscopic retrograde cholangiopancreatography (ERCP) in surgically altered anatomy patients. METHODS: Between June 1, 2009 and November 8, 2012, we performed 42 ERCPs with the use of rotational enteroscopy for patients with altered anatomy (39 with gastric bypass Roux-en-Y, 2 with Billroth II gastrectomy, and 1 with hepaticojejunostomy associated with liver transplant). The indications for ERCP were: choledocholithiasis: 13 of 42 (30.9%), biliary obstruction suggested on imaging: 20 of 42 (47.6%), suspected sphincter of Oddi dysfunction: 4 of 42 (9.5%), abnormal liver enzymes: 1 of 42 (2.4%), ascending cholangitis: 2 of 42 (4.8%), and bile leak: 2 of 42 (4.8%). All procedures were completed with the Olympus SIF-Q180 enteroscope and the Endo-Ease Discovery SB overtube produced by Spirus Medical. RESULTS: Successful visualization of the major ampulla was accomplished in 32 of 42 procedures (76.2%). Cannulation of the bile duct was successful in 26 of 32 procedures reaching the major ampulla (81.3%). Successful therapeutic intervention was completed in 24 of 26 procedures in which the bile duct was cannulated (92.3%). The overall intention to treat success rate was 64.3%. In terms of cannulation success, the intention to treat success rate was 61.5%. Ten out of forty two patients (23.8%) required admission to the hospital after procedure for abdominal pain and nausea, and 3 of those 10 patients (7.1%) had a diagnosis of post-ERCP pancreatitis. The average hospital stay was 3 d. CONCLUSION: It is reasonable to consider an attempt at rotational assisted ERCP prior to a surgical intervention to alleviate biliary complications in patients with altered surgical anatomy.

Percutaneous cholecystostomy in patients with acute cholecystitis: experience of 45 patients at a US referral center.

BACKGROUND: Standard treatment for acute cholecystitis is cholecystectomy, but some patients are at high risk for immediate surgery. Percutaneous cholecystostomy might be the procedure of choice in this group. We reviewed the experience of percutaneous cholecystostomy in a large tertiary center population. STUDY DESIGN: We performed a retrospective analysis of patients who underwent percutaneous cholecystostomy, and recorded indications for cholecystostomy, duration of tube placement, clinical outcome, death within 30 days of procedure, complications, bacteriology of aspirated bile, gallbladder contents, and performance of interval cholecystectomy. RESULTS: Forty-five patients (mean age 63 years) had cholecystostomy tubes placed from July 1999 to March 2002. All had confirmed or presumed acute cholecystitis. Mean duration of tube insertion was 54.3 days. Thirty-six patients improved clinically within 5 days. Nine patients died within 30 days; only one death was directly related to gallbladder sepsis. Nine patients subsequently had laparoscopic cholecystectomy, eight had open cholecystectomy, and two had cholecystoenterostomy. Cholecystectomy was planned in another five patients. Cholecystostomy tubes leaked in two patients, blocked in four, and dislodged in one. One patient developed a hemoperitoneum. Bile aspirated at cholecystostomy was culture positive in 12 patients, negative in 16, and not sent or recorded in 17. Twenty-two patients had gallstones, 10 had sludge, 9 had both, and 4 had neither. CONCLUSIONS: In experienced hands, percutaneous cholecystostomy is easy to perform, with low complication and high success rates. It is the procedure of choice in patients with acute cholecystitis unfit for emergency surgery. Patients often improve clinically, so that cholecystectomy can be done electively.

Idiopathic pancreatitis related to CFTR: complex inheritance and identification of a modifier gene.

Idiopathic chronic pancreatitis (ICP) is the leading cause of nonalcoholic chronic pancreatitis. This study examined a series of patients with ICP to determine the prevalence and role of mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI). Genetic testing was done in 39 patients with ICP. In this series, 17 patients had CFTR mutations and 9 had PSTI mutations. Pancreatitis risk was increased 14-fold by having the N34S PST1 mutation, 40-fold by having two abnormal copies of CFTR, and 600-fold by having both. In patients with two CFTR mutations, extrapancreatic clinical findings and nasal bioelectric responses suggested reduced residual CFTR protein function. Thus, pancreatitis risk showed complex inheritance and was highest in individuals who have abnormalities in both the pancreatic ducts (CFTR) and acini (PSTI). These findings indicate that PSTI is a modifier gene for CFTR-related ICP and have implications for the classification, diagnosis, and pathogenesis of pancreatitis.

Extensive investigation of patients with mild elevations of serum amylase and/or lipase is 'low yield'.

BACKGROUND: Serum amylase and lipase levels are widely used as markers of pancreatic inflammation. However, it would seem that mild elevations of amylase and lipase rarely predict significant pancreatic pathology. Pancreatic imaging tests are expensive. The gold standard, endoscopic retrograde cholangiopancreatography, carries risk of morbidity and mortality. OBJECTIVE: To determine whether extensive investigation of patients with mild, nonspecific abdominal symptoms and mild elevations of amylase and/or lipase results in a significant diagnostic yield. METHODS: Outpatient evaluations were retrospectively analyzed over 12 months. Inclusion criteria were nonspecific abdominal pain, and mild elevations (less than three times the upper limit of normal) of serum amylase or lipase, or both. Exclusion criteria included a history of chronic pancreatitis, elevation of liver tests and acute pain syndromes. RESULTS: Nineteen patients over the study period met the criteria. Of the nineteen patients, 58% had elevation of lipase alone, 21% amylase alone and 21% had elevations of both. In addition, 89.5% of the patients had nonspecific abdominal pain. After imaging with one or more of ultrasound, computed tomography, magnetic resonance cholangiopancreatography, endoscopic ultrasound and endoscopic retrograde cholangiopancreatography, small bowel follow through or hepatobiliary scanning, 78.9% patients were thought to have a normal pancreas. Of the remaining patients, 15.8% had mild or equivocal changes of chronic pancreatitis, and one patient was found to have a pancreatic tail pseudocyst. The average cost of investigation was US$2,255, taking only direct procedural costs into account. No patient was found to have malignancy. CONCLUSIONS: The majority of patients with nonspecific abdominal pain and isolated elevations of amylase and/or lipase (less than three times the upper limit of normal) had no identifiable pancreatic pathology. The diagnostic yield in patients with mild elevations of lipase alone was particularly poor. The cost effectiveness and risk-benefit ratio of extensive investigation of this group of patients warrants further study.

Outcome of endoscopic minor papillotomy in patients with symptomatic pancreas divisum.

CONTEXT: Pancreas divisum has been associated with recurrent acute pancreatitis, chronic abdominal pain without elevated pancreatic enzymes, and chronic pancreatitis. Prior studies suggest that endoscopic minor papillotomy benefits certain symptomatic pancreas divisum patients. However, the data are quite limited and there is a lack of long-term follow-up. OBJECTIVE: To describe a retrospective study of endoscopic minor papillotomy for pancreas divisum. PATIENTS: Eighty-nine adult patients who underwent endoscopic minor papillotomy at our referral center were included in the study. Median follow-up was 29 months. INTERVENTION: We conducted a telephone survey. Fifty-three patients were available for the telephone survey. RESULTS: Thirty-two patients (60.4%) reported immediate improvement: however, symptoms recurred in 17 (53.1% of the immediate responders). Repeat endoscopic interventions were performed in 8 patients, with long-term improvement in two. Overall long-term improvement was achieved in 17 patients (32.1%). Results of minor papillotomy were more favorable for patients with recurrent, well-defined bouts of pancreatitis (immediate improvement: P=0.036; long-term improvement: P=0.064) compared to those with pancreatitis who reported continuous pain and those without clinical evidence of pancreatitis (immediate improvement: 73.3%, 42.9% and 44.4%, respectively; long-term improvement: 43.3%, 21.4%, and 11.1%, respectively). CONCLUSIONS: The long-term benefit from endoscopic minor papillotomy using strict criteria is poorer than suggested from previous studies. However, pancreas divisum patients with well-defined bouts of pancreatitis are more likely to benefit from endoscopic minor papillotomy than those without symptom-free intervals between "attacks" and those with pain that is not associated with elevated pancreatic enzymes.

A wolf in sheep's clothing: a non-functioning islet cell tumor of the pancreas masquerading as a microcystic (serous cystic) adenoma.

CONTEXT: The endosonographic appearance of a microcystic "honeycomb" lesion of the pancreas usually indicates a serous cystic adenoma. CASE REPORT: We report a case of a non-functioning islet cell tumor that has the typical microcystic "honeycomb" appearance of a serous cystic adenoma. The implications for endoscopic ultrasound diagnosis and management of cystic pancreatic lesions are discussed. CONCLUSION: Islet cell tumors are a rare differential diagnosis of microcystic pancreatic lesions. If fine needle aspiration remains non-diagnostic preoperative distinction from serous cystic adenomas may be impossible.

Repeat Procedures Within 30 days in Patients Stented for Malignant Distal Biliary Strictures: Experience of 508 Patients at a Tertiary Referral Center.

BACKGROUND: Stent related occlusion and migration remains a problem despite attempts to improve stent design over this time period. Flanged polyethylene plastic stents (FPS) remains the stent of choice in most centers. Early failure of stents placed for malignant extrahepatic biliary strictures (MEBS) has not previously been studied in detail. We set out to determine the incidence and reasons for biliary stent change within 30 days of the index procedure in a large tertiary center population during a period where (FPS) was the sole plastic stent used. METHODS: Retrospective analysis of endoscopic retrograde cholangiography (ERCP) was undertaken in patients who were stented for presumed or known MEBS between 1993 and 2001. Patients who required repeat stenting within 30 days were identified. RESULTS: All 508 patients were stented for MEBS. 5.7% of patients had a total of 34 repeat stenting procedures within 30 days of the index procedure; 27of 29 index stents were plastic, 2 were self-expandable metal stents (SEMS), 20 (3.9%) patients had stent failure as the reason for a stent exchange (plastic stent occlusion n = 15, mean time to stent change 14 ± 8.3 days; metal stent occlusion n = 2, mean time to stent change 24.5 ± 7.8 days; plastic stent migration n = 3, mean time to stent change 25 ± 5.3 days). There was a statistically significant difference in the time to stent change between the occluded plastic stent and migrated plastic stent cases (P = 0.045, 95% CI -21.7 to -0.29). 6 patients spent at least 2 additional days in hospital as a result of stent failure. CONCLUSIONS: Early stent failure is an uncommon problem, especially in patients with SEMS. Early plastic stent failure appears to occur sooner with stent occlusion than with stent migration. Early stent failure is associated with significant morbidity and bears an economic impact in additional procedures and hospital stay.

Intravenous synthetic secretin reduces the incidence of pancreatitis induced by endoscopic retrograde cholangiopancreatography.

OBJECTIVES: This study aimed to evaluate whether synthetic secretin is effective in reducing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. METHODS: This is a single academic medical center, prospective, randomized, double-blind, placebo-controlled trial using secretin (dose of 16 µg) administered intravenously immediately before ERCP. Patients were evaluated for the primary outcome of post-ERCP pancreatitis as diagnosed by a single investigator. RESULTS: A total of 1100 patients were screened, of whom 869 were randomly assigned to receive secretin (n = 426) or placebo (n = 443) before ERCP and were evaluated after the procedure for efficacy of secretin. The incidence of pancreatitis in the secretin group compared with the placebo group was 36 (8.7%) of 413 patients versus 65 (15.1%) of 431 patients, respectively, P = 0.004. In the subgroup analysis, secretin was highly protective against post-ERCP pancreatitis for patients undergoing biliary sphincterotomy (6/129 vs 32/142, P < 0.001), patients undergoing cannulation of the common bile duct (26/339 vs 56/342, P < 0.001), and patients not undergoing pancreatic sphincterotomy (26/388 vs 57/403, P = 0.001). Analysis of the interaction between these groups reveals that the primary effect of secretin prophylaxis was prevention of post-ERCP pancreatitis in patients undergoing biliary sphincterotomy. CONCLUSIONS: Synthetic secretin reduces the risk of post-ERCP pancreatitis, particularly in patients in undergoing biliary sphincterotomy.

Pancreatic FNA in 1000 cases: a comparison of imaging modalities.

BACKGROUND: Image-guided FNA is a popular method for evaluating pancreatic lesions, but few large studies on pancreatic FNA exist. METHODS: Cytologic material, imaging reports, and clinical follow-up information were reviewed from pancreatic FNA cases performed over a 5-year period. RESULTS: A total of 1050 pancreatic FNAs were obtained by EUS (n = 843), US (n = 140), and CT (n = 67). On-site assessment was performed in 89.2% (n = 937) of cases. Findings were as follows: positive for neoplasm 48.9% (n = 503), negative 29.1% (n = 306), descriptive 10% (n = 105), suspicious 5.9% (n = 62), atypical/inconclusive 4.6% (n = 48), and nondiagnostic/inadequate 1.5% (n = 26). Follow-up in the form of histology or at least 6 months of clinical observation was available for 61.2% (n = 643). There was an overall false-positive rate of 0.3% and a false-negative rate of 14.3%. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were as follows: 79.4, 99.0, 99.4, 67.9, 84.5 for the total series, respectively; 79.9, 98.8, 99.2, 72.5, 86.5 for EUS, respectively; 77.9, 100, 100, 48.6, 81.7 for US, respectively; and 78.6, 100, 100, 47.1, 82.0 for CT, respectively. In general, accuracy was not influenced by lesion size or site, number of FNA passes, or number of procedures per patient. After controlling for lesion size, EUS resulted in greater accuracy than US or CT when evaluating lesions <3 cm ( p = 0.015). CONCLUSIONS: All imaging modalities showed moderate to high sensitivity, specificity, and accuracy. Logistic regression analysis showed that for lesions <3 cm, the EUS method had higher accuracy than US or CT. No statistically significant difference was seen for larger lesions or for the number of FNA passes.

Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer.

BACKGROUND: Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. METHODS: Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods. RESULTS: The estimated overall survival (median +/- SE) in the entire group of patients undergoing resection was 23 +/- 4.2 months, with an estimated 3-year survival of 37% +/- 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation. CONCLUSIONS: Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

The role of cystic fibrosis gene mutations in determining susceptibility to chronic pancreatitis.

This article reviews current concepts regarding the pathobiology of cystic fibrosis pancreatic disease. It summarizes recent studies on the relationship between CFTR mutations and pancreatitis, and it reviews several unresolved issues in the field.