Lymphomatoid granulomatosis with pulmonary and gastrointestinal involvement.

We present a rare case of grade II lymphomatoid granulomatosis (LYG) with pulmonary and gastrointestinal involvement. LYG is considered an Epstein-Barr virus-driven lymphoproliferative disorder that often presents with multiple nodular lesions in the lungs and sometimes involvement of skin and the central nervous system. Although the aetiology is unknown, it is associated with the use of immunosuppressives. Involvement of other organ systems is very rare. We successfully treated our patients with 6 cycles of R-CHOP and autologous stem cell transplantation with a major response at 20 months follow-up.

PTEN in colorectal cancer: a report on two Cowden syndrome patients.

Heterozygous germline PTEN mutations cause Cowden syndrome. The risk of colorectal cancer in Cowden patients, however, remains a matter of debate. We describe two patients presenting with colorectal cancer at a young age (28 and 39 years) and dysmorphisms fitting the Cowden spectrum. Heterozygous germline mutations in PTEN were found in both patients. Moreover, analysis of the resected colorectal cancer specimens revealed loss of heterozygosity at the PTEN locus with retention of the mutated alleles, and greatly reduced or absent PTEN expression. Histologically and molecularly, the tumours showed resemblance with sporadic colorectal cancers, although they had prominent fibrotic stroma. Our data indicate that PTEN loss was involved in carcinogenesis in the two patients, supporting that colorectal cancer is part of the Cowden syndrome-spectrum. This is in line with data on sporadic colorectal cancer, mice studies and emerging epidemiological data on Cowden syndrome. Although the exact role of germline PTEN mutations in the carcinogenesis of colorectal cancer remains unclear, we think that Cowden syndrome should be in the differential diagnosis of colorectal cancer certainly in view of the possible prognostic and therapeutic consequences. Prospective follow-up and surveillance of PTEN mutation carriers from the age of 25 to 30 years in a study setting should clarify this issue.

Predictors for neoplastic progression in patients with Barrett's Esophagus: a prospective cohort study.

OBJECTIVES: Patients with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors. METHODS: We included 713 patients with BE (≥ 2 cm) with no dysplasia (ND) or low-grade dysplasia (LGD) in a multicenter, prospective cohort study. Data on age, gender, body mass index (BMI), reflux symptoms, tobacco and alcohol use, medication use, upper gastrointestinal (GI) endoscopy findings, and histology were prospectively collected. As part of this study, patients with ND underwent surveillance every 2 years, whereas those with LGD were followed on a yearly basis. Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance. RESULTS: After 4 years of follow-up, 26/713 (3.4%) patients developed HGD or EAC, with the remaining 687 patients remaining stable with ND or LGD. Multivariable analysis showed that a known duration of BE of ≥ 10 years (risk ratio (RR) 3.2; 95% confidence interval (CI) 1.3-7.8), length of BE (RR 1.11 per cm increase in length; 95% CI 1.01-1.2), esophagitis (RR 3.5; 95% CI 1.3-9.5), and LGD (RR 9.7; 95% CI 4.4-21.5) were significant predictors of progression to HGD or EAC. In a prediction model, we found that the annual risk of developing HGD or EAC in BE varied between 0.3% and up to 40%. Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC (<1%), whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression (18-40%). CONCLUSIONS: In patients with BE, the risk of developing HGD or EAC is predominantly determined by the presence of LGD, a known duration of BE of ≥10 years, longer length of BE, and presence of esophagitis. One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE.

[Inflammatory bowel disease and Clostridium difficile: be prepared]. / Clostridium difficile bij chronische inflammatoire darmziekten.

In this report we describe 3 female patients, aged 38, 29 and 91, with inflammatory bowel disease (IBD) and suffering from an episode of abdominal symptoms and diarrhoea. This raised suspicion of a flare-up of IBD, but all three proved to have Clostridium difficile-associated disease (CDAD). This diagnosis led to a change in management, medication being changed from ciprofloxacin into metronidazole in 2 patients. Patients known to have IBD often present with abdominal pain and diarrhoea. In such a situation an exacerbation of the IBD usually seems most likely. However, an infection with C. difficile always has to be considered, since this infection can mimic a flare-up of IBD. There is a rising incidence of C. difficile in patients with IBD. C. difficile infections in IBD-patients tend to run a more severe course. Therefore, early diagnosis of CDAD in IBD patients is important and has distinct therapeutic implications.

Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn's disease with infliximab: a double-blind placebo-controlled study.

BACKGROUND: Ciprofloxacin is effective in perianal Crohn's disease but after treatment discontinuation symptoms reoccur. Infliximab is effective but requires maintenance therapy. AIM: To evaluate the effect of combined ciprofloxacin and infliximab in perianal Crohn's disease. METHODS: A double-blind placebo-controlled study was conducted. Patients were randomly assigned to receive 500-mg ciprofloxacin twice daily or a placebo for 12 weeks. All patients received 5-mg/kg infliximab in week 6, 8 and 12 and were followed for 18 weeks. Primary end-point was clinical response, defined as a 50% or greater reduction from baseline in the number of draining fistulae. Secondary end-points were the change in Perianal Disease Activity Index and hydrogen peroxide enhanced three-dimensional endoanal ultrasonography findings. Analysis was by intention-to-treat. RESULTS: Twenty-four patients were included but two discontinued treatment. At week 18, response was 73% (eight of 11) in the ciprofloxacin group and 39% (five of 13) in the placebo group (P = 0.12). Using logistic regression analysis patients treated with ciprofloxacin tended to respond better (OR = 2.37, CI: 0.94-5.98, P = 0.07). The Perianal Disease Activity Index score only improved (P = 0.008) in the ciprofloxacin group. Three-dimensional endoanal ultrasonography improved in three patients with a clinical response. CONCLUSIONS: A combination of ciprofloxacin and infliximab tended to be more effective than infliximab alone.