[33 year old Libanese woman with recurrent haemoptysis and cystic lesion of the lung]. / 33-jährige Libanesin mit rezidivierenden Hämoptysen und zystischer Raumforderung in der Lunge.

A 33 year old woman from Lebanon presented with recurrent hemoptysis, subfebrile temperature, dyspnoe in stress, fatigue, weight loss, and pruritus. Serological tests and results from chest X-ray and computer tomography revealed cystic echinococcosis with pulmonary involvement. After refusal of surgical therapy a medical treatment with albendazole was implemented. Two months after the start of the therapy only a small fibrotic residuum in the lung was seen. A spontaneous healing success seems unlikely because of the duration of the pulmonary cyst and the progressive symptoms before treatment.

Candidate genes colocalized to linkage regions in inflammatory bowel disease.

BACKGROUND/AIMS: The genes encoding for tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor receptor (EGFR) and the vitamin D receptor (VDR) are colocalized to inflammatory bowel disease-associated linkage regions on chromosomes 6, 7 and 12. An association study of these gene polymorphisms with ulcerative colitis or Crohn's disease and a stratification according to disease phenotypes was performed in order to identify genetically homogenous subgroups. PATIENTS AND METHODS: 119 healthy, unrelated controls, 95 patients with Crohn's disease and 93 patients with ulcerative colitis were genotyped for the (G to A) -308 TNF-alpha promoter polymorphism on chromosome 6, the codon 497 EGFR polymorphism on chromosome 7 and the TaqI polymorphism of the VDR gene on chromosome 12. After genotyping, patients were stratified according to the respective disease phenotype. RESULTS: A disequilibrium in the distribution of the VDR genotypes was found in patients with ulcerative colitis compared to controls (p = 0.024). In fistulizing and fibrostenotic Crohn's disease the 'TT' genotype was significantly reduced compared with other phenotypes (p = 0.006), whereas the 'tt' genotype was found more frequently (p = 0.04). The frequency of the WT allele of the EGFR gene was significantly higher in ulcerative colitis (p = 0.04) than in controls. Further significant differences, concerning the associations of the different polymorphisms and disease susceptibility or clinical phenotypes, were not observed. CONCLUSIONS: Regardless of the disease phenotype, the associations between the polymorphisms and inflammatory bowel disease investigated herein are modest, even after stratification for the disease phenotypes. Hence, these polymorphisms are unlikely to confer the reported linkage between inflammatory bowel disease and chromosomes 6, 7 and 12.

K-ras mutations in sera of patients with colorectal neoplasias and long-standing inflammatory bowel disease.

BACKGROUND: About 50% of colorectal carcinomas and adenomas display K-ras mutations, which have also been described in stool or colonic lavage fluid. Moreover, the presence of K-ras mutations in plasma samples originating from patients with colorectal cancer has been reported recently. METHODS: DNA was extracted from sera of 16 patients with colorectal carcinomas, 6 with large adenomas, 3 with Crohn disease and 4 with ulcerative colitis. Sera of 20 healthy blood donors served as negative controls. K-ras mutations at the first or second position of codon 12 were detected by an enriched RFLP-PCR method and confirmed by sequencing. RESULTS: Mutations were found in sera of 5 patients with colorectal carcinomas (31%) and 2 patients with long-standing ulcerative pancolitis (50%), but not in patients with adenomas, Crohn disease or the controls. CONCLUSIONS: K-ras mutations can be detected in serum samples from patients with manifest colorectal cancer and in patients who display an increased risk for malignant transformation of the colonic mucosa. This observation may have clinical application concerning noninvasive surveillance of these patients. Because of the low sensitivity of this approach it may be useful to combine it with other molecular markers.

[Duodenosigmoidal fistula in a patient with Crohn's disease]. / Duodenosigmoidale Fistel bei Morbus Crohn.

The development of enteral fistulas - internal and external - is common in Crohn's disease with a frequency of about 45 % in large series of patients. Most internal fistulas arise in the small bowel, but internal large bowel fistulas occur in about one fourth of all patients with fistulas in Crohn's disease. Colonic gastroduodenal fistulas do occur, but are very rare. Of the 35 cases of colonic-duodenal fistulas that we found in the literature, most have been described to involve either a previous ileocolostomy site or the ascending or transverse colon. There are only three cases displaying sigmoidoduodenal fistulas. To these we add a fourth case with this report. A 42-year-old woman presented with upper abdominal pain, loss of appetite and regurgitations with a foul smell as well as abdominal gas complaints. A duodenosigmoidal fistula was diagnosed by local application of contrast and the fistula tract was excised in typical fashion by resection of the colonic fistula and primary closure of the duodenum. The patient experienced a good recovery with relief of symptoms.

K-ras and p53 mutations in colonic lavage fluid of patients with colorectal neoplasias.

BACKGROUND: The adenoma-carcinoma sequence has its molecular basis in several gene mutations of which K-ras and p53 are of paramount importance. The aims of this study were to evaluate whether these genetic alterations can be detected in colonic lavage fluid from patients with colorectal adenomas and carcinomas. METHODS: In 45 patients with adenomas, 20 patients with colorectal carcinomas and 38 patients with non-neoplastic and noninflammatory diseases of the colon p53 and K-ras mutations were evaluated in colonic lavage fluid employing single-strand confirmation polymorphism analysis and dot-blot hybridization, respectively. RESULTS: Mutations of the K-ras and the p53 gene were found in 15.6% (p = 0.065) of patients with adenomas, in 25.0 % (p = 0.016) of patients with carcinomas and in 2.6% in the control group. CONCLUSION: Genetic alterations in the colonic lavage fluid could be an additional diagnostic tool for the surveillance of patients with colorectal neoplasias.

Delta 32 mutation of the chemokine-receptor 5 gene in inflammatory bowel disease.

The gene encoding chemokine receptor 5 (CCR5) is colocalized to the microsatellite marker D3S1573, which was linked with inflammatory bowel disease. Genetic heterogeneity in inflammatory bowel disease might be defined by a combination of the p-ANCA status and immunoregulatory genes. One hundred and twenty healthy unrelated controls, 101 patients with Crohn's disease, and 99 patients with ulcerative colitis were genotyped for the Delta 32 mutation of the CCR5 gene. The presence of p-ANCA was determined by the use of indirect immunofluorescence. After genotyping, patients were stratified according to p-ANCA status. The frequency of the Delta 32 mutation was not significantly different in controls and patients with Crohn's disease or ulcerative colitis (P 0.207 or more). Moreover, the frequency of the mutation was not significantly different in patients with inflammatory bowel disease after stratification for the p-ANCA status (P 0.482). Regardless of the p-ANCA status, Crohn's disease and ulcerative colitis are not associated with the Delta 32 mutation of the CCR5 gene.

Molecular screening of patients with long standing extensive ulcerative colitis: detection of p53 and Ki-ras mutations by single strand conformation polymorphism analysis and differential hybridisation in colonic lavage fluid.

BACKGROUND: In patients with long standing ulcerative colitis at risk of developing malignancy, mutations of the p53 and Ki-ras gene were investigated in lavage solution obtained at surveillance colonoscopy. METHODS: DNA was isolated from 31 consecutive patients with total or subtotal ulcerative colitis and a disease duration of between seven and 26 years. Twenty seven control patients showed no macroscopic or microscopic inflammation on colonoscopy. Exons 5-8 of the p53 gene and exon 1 of the Ki-ras gene were amplified by polymerase chain reaction. Mutations of the p53 gene were detected by single strand conformation polymorphism analysis. Point mutations of the Ki-ras gene were hybridised on dot blots with oligonucleotides marked with digoxigenin. RESULTS: In all cases of ulcerative colitis and in all of the 27 control patients, wild type p53 and wild type Ki-ras could be detected. In four patients with ulcerative colitis, a mutation in exon 5 to 7 of the p53 gene was found, and two patients had a mutation of the Ki-ras gene (Gly to Asp-12, Gly to Val-12). None of these patients had dysplasia in serial biopsy specimens, and all but one had had the disease for more than 10 years. One control patient had a mutation. CONCLUSIONS: Mutations were more frequent in patients with long standing ulcerative colitis (19%) than in control patients (3%, p = 0.07). The technique may be useful for screening for early malignancy in ulcerative colitis.

Detection of Ki-ras mutations by PCR and differential hybridization and of p53 mutations by SSCP analysis in endoscopically obtained lavage solution from patients with long-standing ulcerative colitis.

OBJECTIVES: The goal of this study was the early detection of malignant transformation in patients with long-standing ulcerative colitis; therefore, mutations of the Ki-ras and p53 gene were analyzed in lavage solution and biopsies obtained at surveillance colonoscopy. METHODS: DNA was isolated from 14 patients (nine female, five male) with a history of pancolitis for more than 10 yr. Exon 1 of the Ki-ras gene and exons 5-8 of the p53 gene were amplified via polymerase chain reaction. Mutations of the p53 gene were detected via single-strand conformation polymorphism analysis; point mutations of the Ki-ras gene were hybridized on dot blots with oligonucleotides marked with digoxigenin. RESULTS: Wild-type Ki-ras and wild-type p53 were detected in all cases of ulcerative colitis and in four of seven control patients. In two ulcerative colitis patients, a mutation was found in the Ki-ras gene (Gly --> Asp 12 and Gly --> Val 12), and in one patient, a mutation in exon 5 of the p53 gene. Mutations were found only in the lavage fluid, whereas random biopsies were negative. CONCLUSIONS: From colonic lavage fluid, it is possible to extract DNA of sufficient quantity and quality for polymerase chain reaction-based amplification and subsequent analysis via single-strand conformation polymorphism or hybridization. Mutations were found in three of 14 patients with long-standing ulcerative colitis but were not found in controls. The method may be useful for the screening of such patients.