Octreotide for the treatment of diarrhoea in patients with ileal pouch anal anastomosis: a placebo-controlled crossover study.

AIM: Diarrhoea with urgency is a debilitating long-term complication of ileal pouch anal anastomosis (IPAA) after a proctocolectomy. Somatostatin analogues are used to control diarrhoea and high-output ostomies. Hence, we designed a prospective, double-blind, crossover trial to explore the efficacy and tolerability of octreotide to reduce diarrhoea in adult patients with IPAA. METHOD: Patients were randomized to octreotide subcutaneously (SC), 500 µg three times daily (t.i.d.), or matching placebo SC for 7 days. Responders (a reduction in stool frequency of three or more stools per 24-h period and with a reduction in stool frequency of at least 30% after 7 days of treatment compared with baseline; the primary end-point) remained in the same group and nonresponders could cross over to the alternative treatment for 7 days. Open-label octeotide LAR 30 mg was offered to all responders on day 14. Flexible pouchoscopy with biopsies was performed at baseline in all patients and was repeated on days 7 and 14 in patients with pouchitis. RESULTS: Fifteen patients (11 men, median age 52 years), all with ulcerative colitis, were randomized. Three patients were withdrawn for side effects during the blinded phase. Response was achieved by two of 12 and two of 11 patients treated with octreotide or placebo, respectively (including crossover, P = 0.9). The median stool frequency remained stable in both groups [Δoctreotide: 0 (IQR, -4 to 0), Δplacebo: -1 (IQR, -1 to 1), P = 0.45]. Octreotide had no effect on the modified pouch disease activity index (mPDAI), and pouchitis persisted in five of six subjects with pouchitis at onset. One subject received open-label octreotide LAR. CONCLUSION: Octreotide has no clear beneficial effect on the stool pattern or on pouchitis severity in patients with high stool frequency after IPAA.

Salvage Radiotherapy for Prostate Cancer.

For patients experiencing biochemical recurrence in the absence of distant metastasis, salvage radiotherapy (SRT) with or without androgen deprivation therapy (ADT) is currently the only possible curative treatment option. Prostate-specific antigen (PSA) monitoring and the selected use of SRT has some advantages when compared with adjuvant radiotherapy. The most important one is avoidance of a potential overtreatment of patients who would never have disease progression, even in the presence of high-risk pathological features. The identification of a specific PSA cut-off seems to be incorrect. In patients with more adverse pathological features, early SRT administered at the very first sign of a PSA rise granted better disease control. Dose-intensified SRT is feasible and well tolerated with no significant difference in grade 2 or more acute and late toxicity. At least 66 Gy must be given in the salvage setting. ADT has a radio-sensitising effect on the radiotherapy by inhibiting the repair of DNA double-strand breaks. The use of ADT in the salvage setting results in a better oncological outcome. Hormonal therapy is associated with a decrease in quality of life and side-effects depending on the duration of hormone therapy. The oncological benefit of hormone therapy duration depends on their clinical and pathological characteristics. 68-Ga-prostate-specific membrane antigen positron emission tomography-computed tomography is the gold standard in staging prostate cancer patients with biochemical persistence or recurrence after radical prostatectomy. The implementation of 18F-labelled PSMA tracers can provide a further improvement.

JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy?

BACKGROUND AND AIMS: Anti-alpha4 integrin therapy with natalizumab is efficacious in refractory Crohn's disease and in multiple sclerosis, but carries an estimated 1/1000 risk of progressive multifocal leukoencephalopathy (PML) caused by reactivation of latent JC virus infection. Although anti-alpha4 integrin therapies are likely to be introduced in the clinic, screening for the risk of PML has not been developed. METHODS: We prospectively collected urine, serum, plasma and buffy coats from 125 patients with Crohn's disease, 100 control subjects with gastrointestinal (GI) disease, and 106 healthy volunteers. Four to eight weeks after this first sample collection, we additionally collected a set of urine, serum, plasma and buffy coat samples from the 125 patients with Crohn's disease, and a next set of samples was collected 12-16 weeks after the first collection. JC viral loads were determined with quantitative real-time polymerase chain reaction (PCR), and JC virus seroprevalence with a specific enzyme-linked immunosorbant assay (ELISA). RESULTS: The overall JC virus seroprevalence was 65%. JC virus DNA copies were detected in the urine from 29-44% of subjects, both those with Crohn's disease and controls. Median viral loads were significantly higher in patients with Crohn's disease who were immunosuppressed (7.36x10(6) copies/ml) compared to healthy volunteers (2.77x10(5) copies/ml) and compared to GI controls (1.8x10(6) copies/ml). Clearance at any time point occurred in 4/107 (3.7%) subjects only. JC viraemia was found in two patients with Crohn's disease. CONCLUSIONS: The natural history of JC virus in patients with Crohn's disease is still unknown. Our study results show that JC virus latency and urine viral shedding is frequent in immunosuppressed patients with Crohn's disease. More prospective studies are needed in order to agree on possible recommendations concerning the exclusion of patients with JCV viraemia from anti-alpha4 integrin treatment.

The use of the Australian Basic Treatment Equivalent (BTE) workload measure for linear accelerators in Canada.

The Inter Society of Radiation Oncologists of North America (ISRON) workload standard for linear accelerators is the one most widely used; it regards the treatment of 250 or more patients per year as an acceptable limit. Nevertheless, there is concern that this standard does not represent the current workload of linear accelerators, given that the complexity of techniques and equipment has increased significantly since the ISRON model was developed in the late 1980s. Delaney et al. recently validated a workload indicator for Australian (AUS) centres, known as the basic treatment equivalent (BTE). They showed that this was a better predictor of workload and that there was less variation between centres using this model than there would have been by using fields/hour. This centre attempted to validate this model for use in a Canadian centre, by collecting treatment data on all linear accelerator-treated patients during February 1998. The linear accelerators at this centre delivered 2,295 fractions (6,928 fields) in 662 hours during February 1998. When 15 minutes was used as a denominator, the BTE model functioned as a better workload indicator than simple measures such as fields/hour. It also had better performance in reducing variability between machines. A BTE of 3,403 was calculated for these machines. The mean value for fields/hour, BTE/hour and BTE/fraction for this centre fell within the range of values quoted by AUS centres. The BTE/fraction value for this centre was relatively high compared with the AUS mean, indicating this centre's reliance on the use of a high number of complex techniques. We recommend that the model should be further refined for the Canadian context by developing BTE values with the use of local time and motion studies, including factors such as multileaf collimators and enhanced dynamic wedges.