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.

Distrofia quística de páncreas en paciente con un solo quiste previo / No disponible

Introducción: la distrofia quística de páncreas en una enfermedad rara. Su diagnóstico es difícil y su tratamiento se halla en debate. Caso clínico: describimos el caso de un paciente de 46 años con distrofia quística de páncreas que ingresa por pancreatitis alcohólica en estado de deprivación alcohólica. Entre sus antecedentes destaca dos pancreatitis agudas y en un TC de 18 meses previo al ingreso un quiste de 9 mm en primera porción duodenal. Se realizó resonancia magnética y ecoendoscopia hallando imagen compatible con distrofia quística de páncreas sin estenosis, por lo que se inició tratamiento con octreótido. Discusión: se cree que se trata de una enfermedad causada por la obstrucción de los ductos del páncreas heterotópico y se asocia a pancreatitis alcohólica. Su tratamiento se encuentra todavía en debate pero requiere en última instancia de pancreatectomía. Conclusión: la distrofia quística de páncreas es una enfermedad rara y se debe intentar aunar todos los casos descritos para incrementar nuestro conocimiento sobre la enfermedad(AU)

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(AU)

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.

Pseudoquiste pancreático de localización hepática / Pancreatic pseudocyst located in the liver

El pseudoquiste pancreático es una complicación frecuente dela pancreatitis aguda y de la pancreatitis crónica. Se han descritopseudoquistes pancreáticos en múltiples localizaciones extra-pancreáticas,como hígado, cavidad pleural, mediastino y pelvis. Sinembargo, el pseudoquiste pancreático de localización hepática esuna entidad infrecuente. Presentamos el caso de un paciente de46 años con un pseudoquiste pancreático de localización hepáticaque apareció en el curso de la agudización de una pancreatitis crónica.Durante el ingreso, se realizó una tomografía computarizada(TC) abdominal, que mostraba una masa en cabeza y cuerpo depáncreas y una trombosis de la vena esplénica. Se practicó unapunción-aspiración con aguja fina (PAAF) guiada por TC de lamasa pancreática, que resultó negativa para células atípicas. A las48 horas de la punción, el paciente presentó dolor abdominal yelevación de la amilasa sérica. Una resonancia magnética (RM)pancreática reveló la existencia de dos pseudoquistes pancreáticos,uno en lóbulo hepático izquierdo y otro en cola de páncreas.También se detectaron signos de pancreatitis crónica. Tras la administraciónde nutrición enteral nasoyeyunal durante dos semanas,se produjo la desaparición del pseudoquiste en cola pancreáticay la casi resolución del pseudoquiste pancreático delocalización hepática. Hasta la fecha, se han publicado 27 casosde pseudoquiste pancreático de localización hepática, la mayoríade ellos tratados mediante drenaje percutáneo o quirúrgico

Pancreatic pseudocyst is a common complication of acute andchronic pancreatitis. Extrapancreatic locations of pancreaticpseudocyst in the liver, pleura, mediastinum, or pelvis have beendescribed. However, a pancreatic pseudocyst located in the liver isan infrequent condition. We present the case of a 46-year-oldman with pancreatic pseudocyst located in the liver secondary tochronic alcoholic pancreatitis. During admission, the patient underwentan abdominal CT scan that showed a mass located in thehead and body of the pancreas, as well as a thrombosis of thesplenic vein. A percutaneous needle aspiration biopsy of the pancreaswas obtained under CT guidance, which showed no tumoralinvolvement. Fourty-eight hours after the procedure the patientdeveloped abdominal pain and elevated serum amylase levels. Apancreatic MRI exam showed two pancreatic pseudocysts, one ofthem located in the left hepatic lobe, the other in the pancreatictail. Chronic pancreatitis signs also were found. Enteral nutritionvia a nasojejunal tube was administered for two weeks. The disappearanceof the pancreatic pseudocyst located in the pancreatictail, and a subtotal resolution of the pancreatic pseudocyst locatedin the liver were observed. To date twenty-seven cases of pancreaticpseudocyst located in the liver have been published, most ofthem managed with percutaneous or surgical drainage

Genotype-phenotype correlation for pulmonary function in cystic fibrosis.

BACKGROUND: Since the CFTR gene was cloned, more than 1000 mutations have been identified. To date, a clear relationship has not been established between genotype and the progression of lung damage. A study was undertaken of the relationship between genotype, progression of lung disease, and survival in adult patients with cystic fibrosis (CF). METHODS: A prospective cohort of adult patients with CF and two CFTR mutations followed up in an adult cystic fibrosis unit was analysed. Patients were classified according to functional effects of classes of CFTR mutations and were grouped based on the CFTR molecular position on the epithelial cell surface (I-II/I-II, I-II/III-V). Spirometric values, progression of lung disease, probability of survival, and clinical characteristics were analysed between groups. RESULTS: Seventy four patients were included in the study. Patients with genotype I-II/I-II had significantly lower current spirometric values (p < 0.001), greater loss of pulmonary function (p < 0.04), a higher proportion of end-stage lung disease (p < 0.001), a higher risk of suffering from moderate to severe lung disease (odds ratio 7.12 (95% CI 1.3 to 40.5)) and a lower probability of survival than patients with genotype I-II/III, I-II/IV and I-II/V (p < 0.001). CONCLUSIONS: The presence of class I or II mutations on both chromosomes is associated with worse respiratory disease and a lower probability of survival.

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.

Digestive system involvement in cystic fibrosis.

Cystic fibrosis is a hereditary disease well known to paediatricians. Over recent years, its prevalence among the adult population has dramatically increased; thus becoming a disease increasingly seen in adult practice. Cystic fibrosis is a multi-organ disease, with a wide spectrum of clinical manifestations involving many organs. The aim of this article is to review the digestive system manifestations of this disease: the involvement of the gastrointestinal tract, liver, biliary system and pancreas, with a special emphasis on the adult population.

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.

Cystic fibrosis transmembrane regulator (CFTR) DeltaF508 mutation and 5T allele in patients with chronic pancreatitis and exocrine pancreatic cancer. PANKRAS II Study Group.

BACKGROUND: An increased risk of chronic pancreatitis has been described among carriers of the cystic fibrosis transmembrane regulator (CFTR) mutation. In addition, patients with cystic fibrosis may have a higher risk of exocrine pancreatic cancer. AIMS: To determine the prevalence of the DeltaF508 mutation and 5T allele, the most common CFTR disease related variants, and to assess their association with lifestyle factors in an unselected series of patients with chronic pancreatitis or pancreatic cancer. SUBJECTS: Patients recruited to the multicentre PANKRAS II study with a diagnosis of chronic pancreatitis and pancreatic cancer from whom normal DNA was available. METHODS: The DeltaF508 mutation and 5T allele were analysed using polymerase chain reaction amplified normal DNA. Information on clinical and lifestyle factors was obtained through personal interviews. RESULTS: Among patients with pancreatitis, no DeltaF508 alleles were found and the prevalence of the 5T allele was 10.5%, similar to that described in the general population. Among patients with pancreatic cancer, the prevalence of the DeltaF508 mutation and the 5T allele was 2.4% and 5.5%, respectively. 5T allele carriers with cancer consumed significantly less alcohol than non-carriers (p=0.038). CONCLUSIONS: Our findings do not support the view that the DeltaF508 mutation and 5T allele confer a higher risk of chronic pancreatitis or pancreatic cancer. Nevertheless, our data suggest that interactions between CFTR polymorphism and environmental factors may play a role in the pathogenesis of these diseases. Our study emphasises the need for a multinational study to conclusively establish the role of CFTR variants as genetic susceptibility factors for chronic pancreatitis and pancreatic cancer.

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.

Achalasia presenting as acute airway obstruction.

Achalasia presenting as acute airway obstruction is an uncommon complication. We report the case of an elderly woman with previously undiagnosed achalasia who presented with acute respiratory distress due to megaesophagus. Emergency endotracheal intubation and insertion of a catheter into the esophagus, with continuous aspiration was required. Upon introduction of the esophageal catheter an abruptand audible air decompression occurred, with marked improvement of the clinical picture. Endoscopic injection of botulinum toxin was chosen as the definitive treatment with good clinical result. The pathophysiology of the phenomenon of esophageal blowing in achalasia is unclear, but different hypothetical mechanisms have been suggested. One postulated mechanism is an increase in upper esophageal sphincter (UES) residual pressure or abnormal UES relaxation with swallowing in achalasia patients. We reviewed the UES manometric findings in 50 achalasia patients and compared it with measurement performed in 45 healthy controls. We did not find any abnormalities in UES function in any of our achalasia patients group, or in the case under study. An alternative hypothesis postulates that airway compromise in patients with achalasia results from the loss UES belch reflex (abnormal UES relaxation during esophageal air distension), and in fact, an abnormal UES belch reflex was evidenced in our case.

Validity of the hospital discharge diagnosis in epidemiologic studies of biliopancreatic pathology. PANKRAS II Study Group.

BACKGROUND: The aim was to analyse the magnitude, direction and predictors of change in the main hospital discharge diagnosis (HDD) after a clinical expert review, among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases. METHODS: A total of 602 patients with a suspicion diagnosis of pancreas cancer (PC), cancer of the extrahepatic biliary system (CEBS) or benign biliopancreatic pathologies (BPP) were prospectively recruited at five general hospitals. A structured form was used to collect information from medical records. A panel of experts revised all diagnostic information and established the main clinicopathological diagnosis (CPD) by consensus. RESULTS: Of the 204 cases with a HDD of PC, 176 (86%) were deemed to have a CPD of PC, eight of CEBS, twelve a neoplasm of different origin, four BPP and four syndromic diagnoses. Thus, 28 cases (14%) were false positives. Of the 129 patients with a HDD of CEBS, 15 (12%) were false positives. Nine of the 396 cases with a HDD of non-PC (2%) had a CPD of PC (false negatives), whilst 14 of 471 patients with a HDD of non-CEBS (3%) were deemed to have CEBS. Overall, sensitivity and specificity of HDD for PC were, respectively, 95 and 93%, and for CEBS, 89 and 97%. Cytohistological confirmation and laparotomy were independent predictors of diagnostic change. CONCLUSIONS: Validity of the HDD was high, but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results, and highlights the need to review all HDDs. Alternatively, only patients at high risk of misdiagnosis could be reviewed: primarily, those lacking a cytohistological diagnosis or a laparotomy. No exclusions appear warranted solely on the basis of age, gender or tumour spread.

[Cerebrovascular accident as the form of presentation of a pancreatic cystadenocarcinoma: an unusual form of presentation in a rare tumor]. / Accidente cerebrovascular como forma de presentación de un cistoadenocarcinoma de páncreas: una forma de presentación inusual en un tumor infrecuente.

Pancreatic cystadenocarcinoma is an uncommon neoplasm of the pancreas. Mucinous cystadenocarcinoma is the most frequent pancreatic cystadenocarcinoma. Symptoms are often non-specific but abdominal pain and jaundice are common in tumors localized in the head of the pancreas. Thromboembolic manifestations of pancreatic neoplasm have been described but are infrequent. The commonest manifestations are migratory thrombophlebitis, mesenteric venous thrombosis and pulmonary embolism. Cerebral stroke as the first manifestation of pancreatic carcinoma is exceptional. The mechanism by which pancreatic carcinoma induces stroke is unclear, although Trousseau's syndrome, complications of mucinous cancer or blood disorders could play a role. We report the case of a young woman with transient stroke and paraneoplastic thrombocytosis in whom pancreatic cystadenocarcinoma was diagnosed.

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.

¿La Ciclosporina A empeora la función hepática de pacientes con enfermedad inflamatoria intestinal y nutrición parenteral total? / Does cyclosporin A worsen liver function in patients with inflammatory bowel disease and total parenteral nutrition?

INTRODUCCIÓN: la Nutrición Parenteral Total (NPT), el tratamiento inmunosupresor con Ciclosporina A (CsA) y la Enfermedad Inflamatoria Intestinal (EII) son factores conocidos de disfunción hepática. Su asociación, sin embargo, ha sido escasamente analizada. MÉTODOS: se estudian de forma retrospectiva las alteraciones en la bioquímica hepática (GOT, GPT, FAI, GGT y Bt) de pacientes ingresados, consecutivamente, en nuestro centro por brote grave de EII y analítica basal normal, desde Enero 1992 a Julio 1997: n = 50, 29 V/21 H, edad 32 a (16-78), 76 por ciento Colitis Ulcerosa (CU), 24 por ciento Enf. Crohn (EC), 28 por ciento formas de debut. Todos los pacientes recibieron 6metilprednisolona (MP) ev (0,75-1 mg/kg/d) y NPT, como tratamiento estándar. El 42 por ciento (21/50) requirió tratamiento adicional con CsA ev (5 mg/kg/d) al inicio o en el transcurso de la primera semana de NPT, durante 7 a 24 días, para el control de su enfermedad por falta de respuesta clínica. En base al tratamiento recibido se definieron dos grupos de estudio: Grupo I = MP + NPT (n = 29) y Grupo Il = MP + NPT + CsA (n = 21), -ambos homogéneos en todos los parámetros analizados-. Se realizaron controles analíticos semanales durante el periodo de tratamiento. RESULTADOS: el 62 por ciento de los pacientes (31/50) presentó alteración en la bioquímica hepática -definida previamente como alteración de 2 o más parámetros, 2 o más veces los valores de normalidad-. No se observaron diferencias estadísticamente significativas entre los grupos 1 y 11 (15/29 vs 16/21, p = NS). Las enzimas GGT y GPT fueron los parámetros que más se alteraron; la máxima elevación apareció en el transcurso de la 3ª semana de tratamiento y no superó en seis veces los valores de normalidad. Al suspender la NPT y el tratamiento inmunosupresor, dichas alteraciones desaparecieron. CONCLUSIONES: estos resultados nos permiten concluir que, en este grupo de pacientes, la asociación de NPT y CsA no provoca más disfunción hepática que la ocasionada por la NPT (AU)