Our series of patients with idiopathic pancreatitis (IP) found a cystic fibrosis (CF) gene abnormality in 19% compared with 3.5% in patients without pancreatitis.
Objective
The objective was to determine whether the CF gene predicts more severe ERP findings.
Design
This was a retrospective case-control study.
Setting and Patients
From July 1998 to August 2004, CF gene analysis was performed in 819 patients with IP via Genzyme Genetics. The panel tests for 70 to 87 alleles and has a detection rate of more than 90% of the cases. Sixty-nine patients (8.4%) who had at least one CF gene positive mutation were the study cohort. A total of 218 patients with IP and negative CF gene mutation were randomly selected from our database to be in the control group.
Main Outcome Measurements
Pancreatograms were evaluated for chronic pancreatitis (CP) based on Cambridge criteria. The results of the gene analysis were not available at the time of pancreatogram interpretation.
Results
Among patients positive for the CF gene, 42 (61%) were women. The mean age at intervention was 40 years (range 14-80 years), and 48 patients (70%) had cholecystectomy. Among patients who were negative for the CF gene, 147 (67%) were women. The mean age at intervention was 41 years (range 9-89 years), and 125 patients (57%) had cholecystectomy. Compared with controls, cases had higher incidence of CP (62% vs. 48%, p = 0.05), grade III CP (35% vs. 18%, p = 0.004), pseudocysts (12% vs. 4%, p = 0.036) and pancreatic strictures (20% vs. 8%, p = 0.008).
Limitations
The limitations of the study were (1) retrospective design and (2) the panel used tests only for 70 to 87 alleles (of approximately, 900 CF transmembrane conductance regulator genes known).
Conclusions
The mean age at intervention in both groups was similar. CP, grade III CP, pseudocysts, and pancreatic strictures were more common among patients who were CF gene positive.
Section snippets
Patients and methods
The Institutional Review Board of Indiana University Purdue University of Indianapolis approved this study. A case-control study design was used, in which patients with IP and with a positive CFTR mutation (cases) were compared with a control group (patients with IP and negative CFTR mutation analysis). The control group was selected by computer randomization.
Cases and controls were taken from a database of patients referred to the Indiana University Medical Center for evaluation with ERCP from
Results
From July 1998 to August 2004, CF gene analysis was performed in 819 patients with IP via Genzyme's expanded mutation panel. Sixty-nine patients (8.4%), who had a single (n = 64) or who were compound heterozygous (n = 5) for CF gene mutation, were the study cohort. A total of 218 patients undergoing ERCP in association with a diagnosis of IP and negative CF gene mutation analysis were randomly selected from our database to be the control group.
Discussion
Several studies have addressed the association between CFTR gene mutations and pancreatitis.6, 7, 8, 14, 15, 16, 17, 18 Selected published series, including the present study, reporting CFTR mutation frequencies in patients with IP are summarized in Table 5. A total of 1239 patients with IP were described. The number of CFTR mutations tested varied among these series and ranged from 13 to 135. The frequency of CFTR mutations ranged from 8.4% to 38.7%, with a mean of 12.8%. Some series7, 14, 18
It is thus appropriate to regularly quantify fecal elastase, particularly if there is a change in body weight and/or intestinal transit [2]. Certain complications of acute pancreatitis are reported to be more marked in the context of cystic fibrosis such as Cambridge classification grade III pancreatitis and pseudocysts [6]. In theory, the risk of secondary cancer of the pancreas is real but this risk has been little elucidated.
The gastrointestinal tract is a major source of morbidity in adults with cystic fibrosis (CF), with a wide range of complications, some of them being specific to the underlying disease.
Abnormal CFTR function, with reduced bicarbonate and other ion transport levels through the apical surface of epithelial cells, affects the intestinal tract including the pancreas and the liver. Similarly to what is observed in the respiratory tract, gastrointestinal CFTR dysfunction leads to mucus accumulation, dysmotility, small bowel bacterial overgrowth and inflammation with alteration of innate immune responses, all of which being likely to be interrelated. In developed countries, almost half of patients with CF are adults followed in multidisciplinary CF care centres by pneumologists who often have to manage gastrointestinal complications.
It therefore appears essential that adult gastroenterologists develop the expertise needed for managing CF gastrointestinal complications in close collaboration with multidisciplinary CF care centre teams to improve the quality of life of adults with CF.
Le tractus gastro-intestinal est une source importante de morbidité chez l’adulte atteint de mucoviscidose, avec un large panel de complications, certaines d’entre elles étant spécifiques de la maladie sous-jacente.
L’anomalie de fonctionnement de la protéine CFTR, avec la baisse du flux des bicarbonates pancréatiques et d’autres ions, perturbe les fonctions du tractus intestinal, du pancréas et du foie. Ainsi de façon identique à ce que l’on observe au niveau de l’appareil respiratoire, l’anomalie de la fonction CFTR entraîne au niveau gastro-intestinal une succession de perturbations liées les unes aux autres avec une accumulation de mucus, une dysmotricité, une pullulation microbienne et une inflammation avec une anomalie de la réponse immunitaire innée. Dans les pays développés, près de la moitié des personnes atteintes de mucoviscidose sont des adultes qui sont suivis dans des centres de soins multidisciplinaires par des pneumologues qui gèrent souvent les complications gastro-intestinales.
Dès maintenant, il est indispensable que des gastro-entérologues adultes développent l’expertise nécessaire à la prise en charge des complications gastro-intestinales en collaboration étroite avec les équipes des centres de soins multidisciplinaires pour améliorer la qualité de vie des adultes avec une mucoviscidose.
La pancreatitis es una rara complicación en la evolución de pacientes con fibrosis quística (FQ). Puede presentarse en forma de episodios agudos, aislados o repetidos, o evolucionar a cronicidad con progresiva destrucción de la glándula. El objetivo de este estudio fue describir las características de una cohorte de pacientes que habían padecido pancreatitis, conocer su frecuencia e intentar encontrar posibles factores de riesgo asociados.
Estudio retrospectivo descriptivo de pacientes controlados en unidades de FQ de cinco hospitales españoles que habían padecido pancreatitis. Se recogieron datos demográficos, clínicos y analíticos, y relativos al estado pancreático y el genotipo.
De 520 pacientes, 17 presentaron pancreatitis. Una prevalencia del 3,3%, superior a la descrita en la literatura. Analizando el estado pancreático, se observó que 8 de ellos eran insuficientes pancreáticos (47,06%), hecho que contrasta, en parte, con lo referido clásicamente al considerar esta complicación más típica de pacientes con cierto grado de reserva pancreática. No se encontraron factores de riesgo ni asociaciones significativas con la genética, edad, sexo u otras características.
En nuestra serie, la prevalencia de pancreatitis es superior a la descrita en la literatura, no tratándose de una complicación exclusiva de suficientes pancreáticos. Se produce más frecuentemente durante la adolescencia o en el inicio de la edad adulta. La enfermedad pulmonar es leve en la mayoría. La genética es variable, sin poder establecerse una clara relación genotipo-fenotipo. Se debe observar a largo plazo la evolución de esta patología intercurrente y diseñar estudios más amplios para obtener resultados más significativos.
Pancreatitis is an uncommon complication of cystic fibrosis (CF). Either single or recurrent acute episodes can occur and it occasionally may follow a protracted course with relentless destruction of the pancreas. Moreover mild mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been found in many cases of idiopathic chronic pancreatitis. We describe a group of patients with CF who had one or more episodes of pancreatitis. We have estimated its prevalence in a large population of patients with CF across Spain.
A retrospective descriptive study was conducted by collecting the demographic, clinical and laboratory data, pancreatic status and genotype of CF patients who attended the CF Units in 5 Spanish hospitals.
The overall number of CF patients under follow-up in the five centres was 520, of which 17 cases with pancreatitis were identified. The prevalence of pancreatitis in this population was 3.3%, higher than previously reported. Noticeably eight of the 17 patients (47.06%) had pancreatic insufficiency. This appears to be, partly, in contrast with that classically found, as this complication is usually associated with patients with a certain level of pancreatic reserve. No associations with genotype, age, gender or other factors were found.
The prevalence of pancreatitis in our CF patients was higher than that found in other CF populations, and was not limited to patients with pancreatic sufficiency. It occurred mostly in teenagers and young adults often with mild pulmonary disease. The CF genotype was variable. The course of the patients should be carefully monitored, and further information on the long-term outcome of larger cohorts of patients is needed.
Background and Aims: Despite an extensive search, no cause is found for recurrent acute/chronic pancreatitis (idiopathic pancreatitis (IP)) in about 20% of patients. In these patients, CFTR gene mutations may be identified. The aims of this study were (1) to describe the natural history of pancreatitis associated with the CFTR mutation, (2) to look for genotype-phenotype correlations, and (3) to examine the frequency of CFTR mutations in a population of patients with IP. Results: 100 consecutive patients with IP were included between 1998 and 2005. 50% had one of the 33 most frequent CFTR gene mutations (common CF mutations, uncommon mutations causing variable phenotypes and variants of unknown significance in 28, 44 and 28%, respectively). Patients with a CFTR gene mutation were significantly younger than those without (34 vs. 40 years, p = 0.03). Duration of follow-up (3.5 vs. 3 years), proportion of patients with acute pancreatitis as first symptom (76 vs. 74%) were not significantly different. Signs of chronic pancreatitis (ductal changes and pancreatic calcifications), pseudocysts, common bile duct stenosis, exocrine or endocrine insufficiency occurred in 36,26,4,10 and 12% of patients with CFTR gene mutations respectively, which was not different from patients without mutations. No phenotype-genotype correlation was observed. Conclusions: In patients with IP, clinical and radiological manifestations are not related to the presence of a CFTR gene mutation or to the type of mutation.
Although most patients with pancreas divisum are asymptomatic, this ductal anatomy is associated with idiopathic recurrent acute pancreatitis (IRAP) in a subset of patients.4,5 Although the pathophysiologic mechanisms underlying this association have not been fully elucidated, recent studies suggest that cystic fibrosis transmembrane conductance regulator (CFTR) protein function is impaired in patients with IRAP and pancreas divisum as compared with healthy controls,6 and that patients with pancreas divisum may have more CFTR mutations than healthy controls.7 Impaired CFTR function, causing diminished chloride and bicarbonate secretion into pancreatic juice, may predispose patients to more viscous pancreatic secretions, which may lead to ductal obstruction in patients with divisum anatomy.
Recommended techniques for minor papilla sphincterotomy include performing a standard pull-type sphincterotomy (PTS) or using a needle-knife over a stent. A wire-assisted access sphincterotomy (WAAS) technique may hold some technical advantages over these accepted methods, but has not been robustly described.
To describe the safety and efficacy of WAAS compared with PTS in a series of patients from our institution.
Retrospective audit of initial minor papilla sphincterotomies over a 6-year period. Demographic and procedural data were abstracted, and the medical record was reviewed for clinical follow-up.
A large tertiary referral center.
One hundred twenty-eight consecutive patients with pancreas divisum who underwent ERCPs between April 2001 and April 2007, 64 of whom underwent an initial minor papilla sphincterotomy.
WAAS was performed by deeply cannulating the dorsal duct with a guidewire and then passing a needle-knife sphincterotome alongside the wire and cutting the minor papilla by inserting the needle-knife beside the wire and cutting away from the wire.
Clinical procedural success and reported adverse events.
Thirty-two patients had recurrent acute pancreatitis, 15 had pain only, and 13 had chronic pancreatitis. Thirty-two underwent WAAS, 24 had PTS, and 8 had other types of sphincterotomies. Patients undergoing WAAS (32) versus PTS (24) were similar in age, sex, and procedural indication. Mild post-ERCP pancreatitis and mild intraprocedural bleeding occurred more commonly in the WAAS group, although the differences were not statistically significant.
Retrospective, nonrandomized study.
WAAS is an effective technique that may be used either to begin a minor papilla sphincterotomy or to perform the entire sphincterotomy. Complications appear similar to those seen with conventional methods but require a larger patient sample to fully evaluate.
The current study assessed the diagnostic accuracy of MRCP and the S-test in a standard diagnostic and therapeutic study protocol used routinely for patients with recurrent acute pancreatitis of unknown etiology and nondilated ducts as an effective alternative to ERCP and SOM. In these patients a detailed view of the pancreaticobiliary ductal system28,29 and assessment of sphincter of Oddi function are indispensable for a definite diagnosis and to decide on treatment. However, ERCP still gives normal pancreaticobiliary findings in a considerable proportion,30,31 and an objective diagnosis of sphincter of Oddi dysfunction (type 2) can be achieved by SOM in 50% to 72% of cases.32,33
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.
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.
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.
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.
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.
