The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Cystic dystrophy of the pancreas in patient with only one previous cyst.

CASE REPORT: we describe the case of a 46-year-old patient with cystic dystrophy of the pancreas admitted for alcoholic pancreatitis in a state of alcohol deprivation. The patient's background includes two cases of acute pancreatitis and a computed tomography taken 18 months prior to admittance reveals a 9 mm cyst in the first duodenal portion. Magnetic resonance imaging and endoscopic ultrasonography were consistent with cystic dystrophy of the pancreas without stenosis, for which reason treatment with octreotide was initiated. DISCUSSION: it is believed to be a disease caused by obstruction of the ducts of the heterotopic pancreas and is associated with alcoholic pancreatitis. Its treatment is still under debate, but it requires pancreatectomy as a last option. CONCLUSION: cystic dystrophy of the pancreas is a rare disease and an effort should be made to bring together all of the described cases to increase our understanding of the disease.

Pancreatic pseudocyst located in the liver.

Pancreatic pseudocyst is a common complication of acute and chronic pancreatitis. Extrapancreatic locations of pancreatic pseudocyst in the liver, pleura, mediastinum, or pelvis have been described. However, a pancreatic pseudocyst located in the liver is an infrequent condition. We present the case of a 46-year-old man with pancreatic pseudocyst located in the liver secondary to chronic alcoholic pancreatitis. During admission, the patient underwent an abdominal CT scan that showed a mass located in the head and body of the pancreas, as well as a thrombosis of the splenic vein. A percutaneous needle aspiration biopsy of the pancreas was obtained under CT guidance, which showed no tumoral involvement. Fourty-eight hours after the procedure the patient developed abdominal pain and elevated serum amylase levels. A pancreatic MRI exam showed two pancreatic pseudocysts, one of them located in the left hepatic lobe, the other in the pancreatic tail. Chronic pancreatitis signs also were found. Enteral nutrition via a nasojejunal tube was administered for two weeks. The disappearance of the pancreatic pseudocyst located in the pancreatic tail, and a subtotal resolution of the pancreatic pseudocyst located in the liver were observed. To date twenty-seven cases of pancreatic pseudocyst located in the liver have been published, most of them managed with percutaneous or surgical drainage.

Toxic megacolon in typhoid fever.

A 40-year-old man with bacteriologically documented typhoid fever who was receiving correct antibiotic treatment developed toxic megacolon. Because of progressive clinical deterioration, the patient underwent surgical treatment, with quick postoperative improvement while receiving antibiotics and total parenteral nutrition.

Phenotypic variability in a Spanish family with MNGIE.

Clinical, biochemical, and genetic features of a Spanish family with mitochondrial neurogastrointestinal encephalomyopathy are reported. The proband presented with severe gastrointestinal dysmotility and the affected sister had extraocular muscle weakness. In both affected individuals, biochemical defects of thymidine phosphorylase and a pathogenic G-to-A transition mutation at nucleotide 435 in the thymidine phosphorylase gene were identified. The first thymidine phosphorylase mutation identified in Spain showed phenotypic variability at onset.

A multicentre, randomized, double-blind study comparing nocte famotidine or ranitidine for the treatment of active duodenal ulceration.

The efficacy and safety of famotidine and ranitidine in the treatment of active duodenal ulcer were compared in a multicentre, randomized, double-blind study. The study was carried out in five centres which included a total of 143 patients with endoscopically documented active duodenal ulcer. The patients received either famotidine (one tablet of 40 mg at night) or ranitidine (two tablets of 150 mg at night). Endoscopic examinations were performed at 4 and 6 weeks of active treatment. Daytime and nocturnal pain were also monitored, and the laboratory and clinical profiles evaluated. One hundred and thirty-three patients fulfilled the evaluation criteria (66 patients in the famotidine group and 67 in the ranitidine group). Healing rates at 4 or 6 weeks of treatment showed no significant differences between the famotidine and ranitidine groups. The healing rates were 80% at week 4 and 97% at week 6 in the famotidine group, and 77% at week 4 and 96% at week 6 in the ranitidine group. Similar results were observed in both treatment groups with regard to pain resolution, decrease in antacid intake and safety profile.

Learning from case reports: diagnostic issues in an epidemiologic study of pancreatic cancer.

Epidemiologic studies on exocrine pancreatic cancer show a large heterogeneity in diagnostic criteria applied to define "caseness." Reanalyses conducted after review of diagnostic information have yielded substantially different results than those based on more crude classifications of disease. During a multicenter prospective study on mutations in the K-ras gene in pancreatic and biliary diseases, hospital diagnoses from 602 patients were reviewed by a panel of experts. There were two main motivations to do so: a generic interest for the quality of the diagnostic data, and the anticipation that a firm diagnosis could be needed to assess whether patients whose tumors did not harbor the mutation were true negatives or false negatives. In addition, the review of diagnoses was helpful to minimize tissue misclassification, and it had a high educational value for clinicians and epidemiologists. This article illustrates why and how this was so through a brief presentation of the 10 most significant cases. With respect to selection and classification of subjects, the main issues that studies on pancreatic cancer need to address are the differential diagnosis of exocrine pancreatic cancer and pancreatitis, the differential diagnosis of exocrine pancreatic cancer and other abdominal tumors, and the use of survival as a hallmark of pancreatic cancer. In epidemiologic studies of pancreatic cancer, it is warranted that a panel of experts centrally reviews all the existing diagnostic evidence (cytohistological and other) of all patients, regardless of whether they have cytohistological confirmation and of their hospital discharge diagnosis.

Occupation and pancreatic cancer in Spain: a case-control study based on job titles. PANKRAS II Study Group.

BACKGROUND: Occupational exposures may increase the risk of exocrine pancreatic cancer. This study aimed to identify occupations that in Spain may be associated with such risk. METHODS: Incident cases of pancreatic cancer and hospital controls were prospectively identified and interviewed during their hospital stay. Occupational history was obtained by direct interview with the patient and was available for 164 (89%) of 185 pancreatic cancer cases and for 238 (90%) of 264 controls. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. RESULTS: A significant increased odds ratio (OR) was observed in men for 'physical, chemistry and engineering science technicians'. Elevated risks were also found for 'metal moulders, sheet-metal workers, structural metal workers, welders and related workers', 'painters and varnishers' and 'machinery mechanics and fitters'. 'Agricultural workers' did not present an increased risk for pancreas cancer in men. In women, however, high OR were observed for 'agricultural workers' and for 'textile and garment workers'. Most associations remained unchanged after considering long duration of the exposure and the period 5-15 years before diagnosis. CONCLUSIONS: Few occupations were at increased risk for pancreatic cancer, and the associations observed are in accordance with previous studies. The increases in risk observed for women in agricultural and textile jobs, and for men in the manufacture of dyes and pigments may deserve further attention.

Gastrointestinal, liver, and pancreatic involvement in adult patients with cystic fibrosis.

BACKGROUND: The clinical prevalence of cystic fibrosis (CF) in adults continues to rise, with a consequent impact on adult gastroenterology practice. AIM: To characterize the gastrointestinal manifestations of CF in adult patients. PATIENTS AND METHODS: The clinical records of 89 adult CF patients treated at our institution from 1992 to 1999 were reviewed. Patients were distributed into two groups: group A (39 patients), which consisted of patients who were diagnosed with CF at when they were younger than 14 years old and who survived into adulthood; and group B (50 patients), who were diagnosed with CF at the age of 14 years or older. Data on CF genetic mutations, nutritional state, evidence of pulmonary, gastrointestinal, liver, or pancreatic involvement were collected for each patient. RESULTS: The most prevalent genetic mutation in our series was deltaF508, present in 50 patients (56.2%), 29 of whom belonged to group A and 21 who belonged to group B. In group A, the deltaF508 mutation was associated with exocrine pancreatic insufficiency (PI) in 26 of 29 patients (89.6%), whereas in group B it was associated with PI in only four patients (19%). Overall, PI was present in 33 of 39 patients (84.6%) in group A and in eight of 50 patients (16%) in group B. Four patients in group B had experienced previous episodes of acute pancreatitis; two of them had associated PI. Of the 89 patients, 12 (10 in group A) were malnourished. Malnutrition was invariably associated with PI. Hepatic and biliary tree abnormalities were particularly prevalent in patients in group A and was usually associated with PI. Intestinal manifestations were uncommon. CONCLUSIONS: Diagnosis of CF before the age of 14 years is associated with greater gastrointestinal compromise than diagnosis at an older age, particularly with regard to PI. CF carriers of the deltaF508 mutation have an increased risk of developing gastrointestinal manifestations.

Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts.

Despite being a common disease in humans, little is known about the etiopathogenesis of and effective therapeutic approaches to chronic pancreatitis, due mainly to the fact that few simple animal models suitable to study inflammatory and fibrogenetic processes have been described in the pancreas. Trinitrobenzene sulfonic acid (TNBS) induces chronic colitis and cholangitis in the rat. We hypothesized that TNBS instillation into the pancreatic ducts could also result in the development of a chronic pancreatic disease. The biliopancreatic duct of rats was cannulated and tied close to the liver. TNBS [0.4 ml of 2% TNBS in phosphate-buffered saline (PBS)-10% ethanol, pH 8] was infused into the pancreas under a continuous controlled-pressure system. Control rats underwent the same procedure using vehicle only. Pathology assessment of TNBS-treated rats examined at 48 h was consistent with severe acute necrotizing pancreatitis, having a morality rate of 31% and serum amylase activity of 37.4 +/- 8.8 U/ml at 24 h and 13.3 +/- 1.7 U/ml at 48 h (p < 0.01 for both time points compared to PBS/ethanol-treated rats). Groups of 10 rats each were killed at 3, 4, and 6 week after the surgical procedure. Morphological examination revealed changes mimicking features of chronic pancreatitis in humans in 80% (32 of 40) of TNBS-treated rats, consisting in various degrees of periductal and lobular fibrosis, duct stenosis, patchy acute and chronic inflammatory cell infiltrates, and signs of gland atrophy. Animals developing chronic disease had a weight gain rate significantly lower than that of control rats. Serum amylase, fasting glucose, and a glucose tolerance test were not different in diseased or control rats. In conclusion, we were able to induce chronic fibrogenetic inflammatory disease in the pancreas after a single pulse instillation of TNBS into the pancreatic ducts. This might be a useful animal model to study the pathophysiology of inflammatory, fibrogenetic, and reparative processes in pancreatic tissue.

Hydrogen breath test with glucose in exocrine pancreatic insufficiency.

The present study was designed to investigate the prevalence of bacterial overgrowth in patients with exocrine pancreatic insufficiency by using the hydrogen breath test with glucose. Thus, in 30 patients with exocrine pancreatic insufficiency (in 15 due to chronic pancreatitis and in 15 associated to primary immunodeficiency), established by quantifying trypsin output before and after stimulation with cerulein using a duodenal perfusion technique, a glucose test was performed by administering 50 g of glucose and quantifying H2 in the breath by gas chromatography. The glucose test was positive in six of 15 patients with chronic pancreatitis but in only one of 15 immunodeficient patients (p < 0.05). Age, sex, etiology, time of evolution, associated diabetes, pancreatic calcifications, duodenal pH, or duodenal trypsin output did not differ between patients with and those without bacterial overgrowth. Previous gastroduodenal surgery was more common in chronic pancreatitis patients with overgrowth (six of six vs. four of nine; p < 0.05). Five patients with a positive glucose test were treated with antibiotics for 2 weeks and became negative in two of them. These results suggest that a positive glucose test indicating overgrowth is relatively common in exocrine pancreatic insufficiency due to chronic pancreatic, especially in patients with previous gastroduodenal surgery.

Association between coffee drinking and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group.

STUDY OBJECTIVE: To analyse the relation between coffee consumption and mutations in the K-ras gene in exocrine pancreatic cancer. DESIGN: Case-case study. Consumption of coffee among cases with the activating mutation in the K-ras gene was compared with that of cases without the mutation. SETTING AND PATIENTS: All cases of pancreatic cancer newly diagnosed at five hospitals in Spain during three years were included in the PANKRAS II Study (n = 185, of whom 121 whose tissue was available for molecular analysis are the object of the present report). Over 88% were personally interviewed in hospital. DNA was amplified from paraffin wax embedded tissues, and mutations in codon 12 of K-ras were detected by the artificial RFLP technique. MAIN RESULTS: Mutations were found in tumours from 94 of 121 patients (77.7%). Mutations were more common among regular coffee drinkers than among non-regular coffee drinkers (82.0% v 55.6%, p = 0.018, n = 107). The odds ratio adjusted by age, sex, smoking and alcohol drinking was 5.41 (95% CI 1.64, 17.78). The weekly intake of coffee was significantly higher among patients with a mutated tumour (mean of 14.5 cups/week v 8.8 among patients with a wild type tumour, p < 0.05). With respect to non-regular coffee drinkers, the odds ratio of a mutated tumour adjusted by age, sex, smoking and alcohol drinking was 3.26 for drinkers of 2-7 cups/week, 5.77 for drinkers of 8-14 cups/week and 9.99 for drinkers of > or = 15 cups/week (p < 0.01, test for trend). CONCLUSIONS: Pancreatic cancer cases without activating mutations in the K-ras gene had drank significantly less coffee than cases with a mutation, with a significant dose response relation: the less they drank, the less likely their tumours were to harbour a mutation. In exocrine pancreatic cancer the K-ras gene may be activated less often among non-regular coffee drinkers than among regular drinkers. Caffeine, other coffee compounds or other factors with which coffee drinking is associated may modulate K-ras activation.

A multicenter, randomized, double-blind study comparing once-daily bedtime administration of famotidine and ranitidine in the short-term treatment of active duodenal ulcer.

The efficacy and safety of famotidine and ranitidine in the treatment of active duodenal ulcer were compared in a multicenter, randomized double-blind study. The study was carried out at 5 centers and involved a total of 143 patients with endoscopically documented active duodenal ulcer. The patients received either famotidine (1 40 mg tablet at night) or ranitidine 2 150 mg tablets at night). Endoscopic examinations were performed at 4 and 6 weeks of active treatment. Day and nocturnal pain were also monitored, and the laboratory and clinical profiles evaluated. One hundred and thirty-three patients fulfilled the evaluation criteria (66 patients in the famotidine group and 67 in the ranitidine group). Healing rates at weeks 4 or 6 of treatment showed no significant differences between the famotidine group and the ranitidine group. The healing rates were 78% at week 4 and 96% at week 6 in the famotidine group, and 76% at week 4 and 95% at week 6 in the ranitidine group. Similar results were observed in both treatment groups with regard to pain resolution, decrease in antacid intake and safety profile.

Acute necrotizing pancreatitis: a multicenter study.

A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

[Acute gastroenteritis due to Vibrio parahaemolyticus in Spain. Presentation of 8 cases]. / Gastroenteritis aguda por Vibrio parahaemolyticus en España. Presentación de 8 casos.

Eight cases of acute gastroenteritis caused by Vibrio parahaemolyticus in humans are described; to our knowledge, they are the first such reported cases in Spain. All cases appeared between August 20th and October 15th, with a frequency of 8.3% regarding the overall adult patients with acute gastroenteritis, and 11.5% regarding the overall patients with positive stool culture for any enteropathogenic organism. The eight strains were Kanagawa positive and in three patients other enteropathogenic organisms were isolated in addition to Vibrio parahaemolyticus, i.e. Aeromonas hydrophila in two and Salmonella serovariety enteritidis in another. In all cases fish or shellfish had been ingested outside the patients' homes; except for one patient, who ate living clams in the seaside of Galicia, all patients ingested them at seaside restaurants from the Barcelona province. The clinical features of acute gastroenteritis were definite in all patients, but no patients had significant electrolyte losses or required hospital admission. Recovery was spontaneous and no antimicrobial agents were required. All strains were sensitive to tetracyclines, aminoglycosides, cefotaxime, ceftazidime and nearly always to co-trimoxazole.

[Thrombocytopenia onset in acute episodes of pancreatitis]. / Aparición de trombocitopenia en los episodios agudos de pancreatitis.

BACKGROUND: The objective of this study was to determine the prevalence of thrombocytopenia in acute pancreatitis and its value as a prognostic marker for complications. METHODS: The records of all patients admitted to our institution between January and June 1993 were reviewed. After exclusion of other possible causes of thrombocytopenia, 104 patients were evaluated. The prognostic value of thrombocytopenia was determined by evaluation of the length of hospital stay, radiologic severity, complications, need for ICU care, need for surgery and mortality. RESULTS: The etiology of pancreatitis was as follows: gallstone-induced in 49 patients, alcoholic in 35, idiopathic in 12 and due to other causes in the remaining 8 cases. Thrombocytopenia developed early, within the first 48 hours and was moderate (106 +/- 27 x 10(9)/l). Alcoholic pancreatitis was associated to a higher probability to develop thrombocytopenia (43% vs 36% in gallstone-induced pancreatitis and 4% in idiopathic pancreatitis, p = 0.02). Thrombocytopenic patients had a greater radiologic severity (Balthazar's scores D or E 78% vs 49%, p = 0.04), a higher number of acute complications (28% vs 10%, p = 0.05) and a more frequent need for ICU care (25% vs 7%, p = 0.01). No differences were seen in length of hospital stay, need for surgery and mortality between the two groups of patients. CONCLUSIONS: Thrombocytopenia is frequent in acute pancreatitis, especially in cases of alcoholic origin. Its presence suggests a higher risk to develop complications.

[The use of human gamma globulin in the treatment of common variable immunodeficiency]. / Utilización de gammaglobulina humana en el tratamiento de la inmunodeficiencia común variable.

BACKGROUND: The indication for treatment with human gammaglobulin in patients with primary hypogammaglobulinemia is well established. Nonetheless, there are no uniform criteria with regard to dose, periodicity and route of administration. METHODS: Twenty-seven patients with common variable immunodeficiency (CVI) who received i.m. or i.v. treatment with gammaglobulin were studied, evaluating the secondary effects, stable levels of IgG achieved, control of symptomatology, clinical evolution and the need for adjuvant therapies. RESULTS: Intravenous administration was more effective than intramuscular administration to achieve higher total IgG serum levels (5.2 +/- 1.2 vs 3.5 +/- 1.6 g/l; p = 0.07) in a shorter period of time (2.1 +/- 1.6 months vs 6.3 +/- 2.8 months; p < 0.01) and with new few secondary effects. The dose and periodicity of the treatment was individualized in each patient on the basis of the needs of consumption and the speed of metabolism of the gammaglobulin, with patients with chronic bronchial suppuration and diarrhea being those requiring the greatest doses (p < 0.0001) and a short interdosis time interval (19.2 +/- 3.1 vs 23.6 +/- 3.6 days; p = 0.01). Treatment with human gammaglobulin allowed the control of recurrent bacterial infection; however, adjuvant treatment with respiratory physical measures and antibiotics were required in patients with chronic bronchial suppuration to avoid progressive alteration of respiratory function. CONCLUSIONS: The administration of human gammaglobulin at adequate doses and frequency is effective to control infection, avoid the development of chronic bronchial disease, alteration of pulmonary function and the appearance of other complications. Intravenous route is safer and produces fewer secondary effects than intramuscular administration with the doses and period of the treatment requiring individualization for each patient.

Does cyclosporin A worsen liver function in patients with inflammatory bowel disease and total parenteral nutrition?

OBJECTIVE: inflammatory bowel disease (IBD), total parenteral nutrition (TPN) and immunosuppressive treatment with cyclosporin A (CsA) are well known factors in hepatobiliary disorders. Their association, however, has been little studied. METHOD: we retrospectively analyzed the results of liver function tests (transaminases, AST. ALT), total bilirubin, alkaline phosphatase, and gamma-glutamyltransferase (GGT) in a consecutive series of 50 patients (29 men, 21 women, mean age 32 years, range 16-78 years) hospitalized for a severe attack of IBD between January 1992 and July 1997. Basal laboratory values in all patients were normal. Thirty-eight patients had ulcerative colitis (UC) and 12 had Crohn's disease (CD), which debuted in 28% of the patients. All patients were treated with methylprednisolone (MP) (0.75-1.0 mg/kg daily i.v., and received TPN. 42% (21/50) required additional treatment with CsA (5 mg/kg daily i.v.) at the beginning or during the first week of TPN and during 7-24 days, because on nonresponse to steroid treatment. Two study groups were defined according to treatment: Group I consisted of 29 patients given MP + TPN, and group II comprised 21 patients who received MP + TPN + CsA. The groups were otherwise similar in all other variables analyzed. Liver function tests were done weekly until the end of the study period. RESULTS: 62% of the patients (31/50) showed hepatobiliary dysfunction, defined previously as a 2-fold or greater elevation of two or more parameters. There was no statistically significant difference between the two groups in the incidence of dysfunction (15/29 vs 16/21, n.s.). The parameters that showed the greatest alterations were GGT and ALT; the greatest elevation appeared during the third week of immunosuppressive treatment, and did not exceed 6-fold the normal value. The alterations disappeared once TPN and immunosuppressive treatment were discontinued. CONCLUSIONS: the hepatobiliary dysfunction in patients treated with both TPN and CsA was no more severe than associated with TPN alone.

[Acute pancreatitis in cystic fibrosis]. / Pancreatitis aguda en la fibrosis quística.

Cystic fibrosis is the most prevalent hereditary disease in the Caucasian race. It is a multisystemic alteration that affects the quality and quantitative properties of exocrine secretions. The pancreas develops a progressive atrophy causing steatorrhoea and nutritive deficiencies. Acute pancreatitis is an unusual complication. The pancreatic atrophy prevents the inflammatory response. Published series suggest that pancreatitis in 0.5%, including patients without pancreatic insufficiency. We present two cases with cystic fibrosis, with and without pancreatic insufficiency, who developed acute pancreatitis.