Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients.

BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. AIM: To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. METHODS: Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis.

BACKGROUND: Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis. AIM: To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease. METHODS: Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid (n = 5073). RESULTS: A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n = 46, mesalazine (mesalamine) n = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3-9.3; P = 0.012) and Crohn's disease (CD) (OR 5.8 95% CI: 1.6-20.6; P = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP (n = 1477) (OR 5.2 95% CI: 1.8-14; P = 0.002). CONCLUSIONS: The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.

[Gastrointestinal bleeding after endoscopic treatment of polypoid hamartoma (adenoma of Brunner's glands)]. / Hemorragia digestiva tras tratamiento endoscópico de hamartoma polipoide (adenoma de glándulas de Brunner).

The incidence of polypoidal tumors in the duodenum is scarce and Brunner's gland tumors represent 11% of these proliferations. Brunner's gland polypoid hamartoma or adenoma is a highly infrequent benign polypoid proliferation of Brunner's glands that is usually asymptomatic, although gastrointestinal bleeding or intestinal obstruction may sometimes occur. We present the case of a woman with an incidental diagnosis of duodenal polypoid hamartoma. The lesion was resected with polypectomy loop and at 48 h, the patient presented gastrointestinal bleeding as a complication. We describe the endoscopic treatment of the lesion and this complication.

[Macromolecular creatinine kinase in patients diagnosed with ulcerative colitis]. / Macrocreatincinasa tipo 1 en pacientes diagnosticados de colitis ulcerosa.

Macromolecular creatinine kinase (macro-CK) type 1 is a macroenzyme formed by the union of an immunoglobulin with a creatinine kinase (CK) enzyme. Its presence in the blood may lead to misdiagnosis of heart disease. This macromolecule has been described in various diseases and is relatively more frequent those with autoimmune etiology. We describe three cases of ulcerative colitis that presented elevated MB-isoenzyme of CK activity greater than the total CK quantified by the immunoinhibition method. Electrophoresis revealed an atypical band that corresponded with the presence of a type 1 macroenzyme. Detection of this macromolecule could be useful in cases of ulcerative colitis when results of blood testing lead to suspicion of ischemic disease.

[Esophageal fibrovascular polyp: report of 2 cases]. / Pólipo fibrovascular esofágico: a propósito de 2 casos.

Fibrovascular esophageal polyps are benign intraluminal tumors that, although of slow growth, may become large. We describe the features of two cases, diagnosed in our department, and emphasize the endoscopic aspects of the lesion.

[Prognostic factors for survival following transarterial chemoembolization in advanced hepatocellular carcinoma]. / Factores pronósticos de supervivencia del carcinoma hepatocelular avanzado tras quimioembolización transarterial.

The efficacy of transarterial chemoembolization in the palliative treatment of non-resectable hepatocellular carcinoma is controversial. To determine the possible existence of clinical and analytical variables with independent predictive value for survival related to the tumor and the treatment given, a multivariate analysis in a series of 111 patients who underwent transarterial chemoembolization was carried out. Overall actuarial survival was 54%, 31% and 24% at 1, 2 and 3 years respectively. Child-Pugh score (p < 0.05), tumor size (p < 0.05) and arterial occlusion after intraarterial chemotherapy (p < 0.05) reached independent predictive value. The group of patients in whom two or three of these factors were simultaneously present had a very poor prognosis with a survival of 20% and 0% at 1 and 2 years respectively, compared with 60%, 50% and 37% at 1, 2 and 3 years respectively in the group with one or none of these factors (p < 0.01). Grouping on the basis of these variables may be useful in the design of future controlled prospective studies that aim to determine the efficacy of transarterial chemoembolization.

[The prolonged administration of intravenous immunoglobulins as a treatment for refractory fistulous Crohn's diseases]. / Administración prolongada de inmunoglobulinas intravenosas como tratamiento de la enfermedad de Crohn fistulosa refractaria.

Fistulating Crohn's disease is present in 17-35% of non-surgically treated patients and in up to 45% of surgically treated ones. Among the several therapeutic alternatives for this disease is intravenous immunoglobulin administration. We present a 28-year-old woman with refractory fistulating Crohn's disease who improved after prolonged immunoglobulin administration (32 months).

[The endoscopic placement of self-expanding metal prostheses as palliative treatment in colorectal stenosis of tumor origin]. / Colocación de prótesis metálicas autoexpandibles por vía endoscópica como tratamiento paliativo en estenosis colorrectales de origen tumoral.

BACKGROUND: The aim of this study was to retrospectively analyze the endoscopic placement of autoexpandible metallic prostheses of the colon carried out in our department as palliative treatment in patients with colorectal stenosis of tumoral origin. PATIENTS AND METHODS: From may, 1995 to august, 1998, autoexpandible metallic prostheses were placed in 14 patients (11 males and 3 females, mean age 64.5 years, range 41-92). All the patients presented tumoral stenosis by adenocarcinoma, 5 of which had been previously treated by surgery. RESULTS: All the stenoses were found in the rectum/sigma at less than 35 cm from the anal margin. In 7 patients endoscopic dilatation was performed prior to placement of the autoexpandible metallic prostheses. The prostheses used had a diameter of 18 mm and were of variable length. The placement of the prostheses was successfully achieved in all the patients except 2 (one due to technical difficulties and in the other because of early migration of the same, in both the autoexpandible metallic prostheses was placed without complications within 24 h). In two cases early complications were observed (14%): one case due to perforation and one to early migration. In two patients stenosis of the prostheses was observed during follow up and in a third patient late migration occurred. CONCLUSIONS: Endoscopic placement of autoexpandible metallic prostheses in patients with colorectal stenosis of tumoral origin is a simple technique with few complications and may be used as a definitive palliative treatment in these patients.

[The usefulness of transjugular hepatic biopsy in the evaluation of liver disease in candidates for heart transplantation]. / Utilidad de la biopsia hepática transyugular en la evaluación de la hepatopatía en el paciente candidato a trasplante cardíaco.

Heart transplantation is a universally accepted procedure in the treatment of terminal heart diseases. However, the presence of advanced liver disease in the potential receptors represents a contraindication for heart transplantation. On the other hand, the true diagnosis of liver disease not secondary to heart disease may be difficult requiring confirmatory liver biopsy. Nonetheless, percutaneous liver biopsy may be difficult to perform due to presence of coagulation alterations, marked dilatation of the hepatic veins, etc. The aim of this study was to evaluate the efficacy and safety of transjugular hepatic biopsy in the presence of severe coagulopathy in potential heart transplantation receptors with suspicion of liver disease and contraindication of percutaneous liver biopsy. Over a 9-year period, 350 potential heart transplantation patients were evaluated. In 23 patients (6.7%) transjugular hepatic biopsy was performed with aspiration needle followed by a hemodynamic study in 17 cases. The transjugular hepatic biopsy was completed in 22 cases (95.6%) with adequate material for the diagnosis being obtained in 21 (91.3% of the total cases indicated). Histologic study showed significant inflammatory infiltrates or alteration of the hepatic architecture in 4 patients (18%), all being positive for some viral markers (AgHBs or anti-HCV). The obtaining of a certain histologic diagnosis modified the consideration of liver disease as a definitive contraindication and allowed the performance of heart transplantation in 17 patients (73.9%). No complications were observed in association with the procedure. The transjugular hepatic biopsy is a feasible, effective and safe alternative for obtaining liver tissue in patients under evaluation for heart transplantation with suspicion of severe liver disease. The establishment of a correct histologic diagnosis may modify the clinical decision in an important number of patients.

Pulmonary complications following orthotopic liver transplant.

Pulmonary complications after orthotopic liver transplant (OLT) are frequent, involving high morbidity and mortality. We have determined the pulmonary complication incidence in 187 patients submitted to OLT at the General University Hospital "Gregorio Marañón" in the last 4 years, analyzing the type of infection, evolution, diagnostic and therapeutic measures and their influence on OLT mortality. A total of 120 patients had pulmonary complications, the most frequent being pleural effusion (61.94%), pneumonia (43.36%), and pneumothorax (11.5%). Serious pulmonary hypertension was diagnosed by invasive methods in two patients at the time of surgery (unidentified before OLT); both died at early post postoperative times. Pleural effusion was noted in 70 patients, 31.42% of them requiring thoracic tube drainage, complications developing in 22.72%. Thirteen patients were diagnosed of pneumothorax, the most frequent etiologies being percutaneous liver biopsy, thoracic tube drainage for pleural effusion, and postoperative complications in 41.6, 33.3, and 23.3%, respectively. Pneumonia was diagnosed in the 1st month after OLT in 45 patients. Tests to diagnose and identify the etiological agent were made in 71.1% of diagnosed pneumonia patients, identification being obtained in 62.5%. Telescope catheter culture identified the agent in 48%, fiber optic bronchoscopy in 50%, and lung or pleural biopsy in 100%. Respiratory insufficiency was noted in 64 patients (34.22% of transplanted patients). Factors involved in their development were pneumonia (42.18%), graft dysfunction (39.06%, pleural effusion (34.37%), sepsis (28.18%), and poor nutritional status (7.81%). Fifty patients (41.66%) died, pulmonary pathology being the determinant factor in 28.8%. Patient mortality with respiratory insufficiency was greater, especially in those with three factors involved the development of respiratory insufficiency.