Changing paradigm of sacral neuromodulation and external anal sphincter repair for faecal incontinence in specialist centres.

AIM: The aim of this study was to determine whether the paradigm of surgical intervention for faecal incontinence (FI) has changed between 2000 and 2013. METHOD: This was a multi-centre retrospective study of patients who had undergone either sacral neuromodulation (SNM) or delayed sphincter repair or sphincteroplasty (SR) as a primary surgical intervention for FI in five centres in Europe and one in the United States. The flow of patients according to the intervention, sustainability of the treatment at a minimum follow-up of 5 years, complications and requirement for further interventions were recorded. RESULTS: A total of 461 patients (median age 56 years, range 24-90 years, 41 men) had either SNM or SR as an index operation during the study period [SNM 284 (61.6%), SR 177 (38.4%)]. Among SNM patients, there were 169 revisional operations (change of battery and/or lead, re-siting or removal). At the time of last follow-up 203 patients (71.4%) continued to use SNM. Among SR patients, 30 (16.9%) had complications, most notably wound infection (22, 12.4%). During follow-up 32 patients (18.1%) crossed over to SNM. Comparing two 4-year periods (2000-2003 and 2007-2010), the proportion of patients operated on who had a circumferential sphincter defect of less than 90° was 48 (68%) and 45 (46%), respectively (P = 0.03), while those who had SNM as the primary intervention increased from 29% to 89% (P < 0.05). CONCLUSION: The paradigm of surgical intervention for FI has changed with increasing use of SNM.

Thermochemotherapy for non-muscle-invasive bladder cancer: is there a chance to avoid early cystectomy?.

OBJECTIVES: Non-muscle-invasive bladder cancer is characterized by a high recurrence rate after primary transurethral resection. In case of bacillus Calmette-Guérin-refractory neoplasms, cystectomy is the gold standard. In this study the effects of thermochemotherapy with mitomycin C were evaluated in high-risk bladder cancer nonresponders to previous therapy. PATIENTS AND METHODS: Between January 2006 and December 2009, 30 patients were enrolled with recurrent stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder cancer refractory to chemotherapy or immunotherapy and so becoming suitable for radical cystectomy. All patients underwent endovesical thermochemotherapy: 16 patients underwent a prophylactic scheme and 14 patients underwent an ablative scheme. RESULTS: All the patients completed the study. The mean follow-up for all the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were disease free and 17 patients (56.70%) had recurrence. In the prophylactic group, 7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor recurrence; no progression was observed. In the ablative group, 3 patients (17, 64%) had progression to muscle-invasive disease. Side effects were generally mild. CONCLUSIONS: Thermochemotherapy could be considered an additional tool in patients refractory to intravesical therapies before considering early cystectomy.

GABA (gamma-amino-butyric acid) neurotransmission: identification and fine mapping of the human GABAB receptor gene.

GABA (gamma-amino-butyric acid) receptors are a family of proteins involved in the GABAergic neurotransmission of the mammalian central nervous system (CNS). They have physiological importance and clinical relevance in several diseases. We report the identification, cloning, and fine mapping of the human cDNA for GABAB receptor. A 4.2-Kb cDNA containing an open reading frame for a predicted protein of 960 aa was isolated from a fetal brain cDNA library. It had a strong identity (91.5%) with the rat GABAB receptor (rGB1A) nucleotide sequence, that corresponded to 98.6% identity at the amino acid level. Expression of the GABAB at the transcription level was detected by Northern analysis in all brain areas examined. The GABAB receptor has been mapped to human chromosome 6p21.3 within the HLA class I region close to the HLA-F gene. Susceptibility loci for multiple sclerosis, epilepsy, and schizophrenia have been suggested to map in this region.

Generation of a transcription map of a 1 Mbase region containing the HFE gene (6p22).

A transcription map was generated of a 1 Mb interval including the HFE gene on 6p22. Thirty-seven unique cDNA fragments were characterised following their retrieval from hybridisation of immobilised YACs to primary pools of cDNAs prepared from RNA of foetal brain, human liver, foetal human liver, placenta, and CaCo2 cell line. All cDNA fragments were positioned on the physical map on the basis of presence in aligned and overlapping YACs and cosmid clones of the region. The isolated cDNAs together with established or published sequence tagged sites (STSs) and markers provided sufficient landmark density to cover approximately 90% of the 1 Mb interval with cosmid clones. The precise localisation of two known genes (NPT1 and RING finger protein) was established. A minimum of 14 additional transcription units has also been integrated. Twenty-eight cDNA fragments showed no similarity with known sequences, but 20 of these detected discrete mRNAs upon northern analysis. Their characterisation is still under investigation. Eleven new polymorphisms were also identified and localised, and the HFE genomic structure was better defined. This integrated transcription map considerably extends a recently published map of the HFE region. It will be useful for the identification of genetic defects mapping to this region and for providing template resources for genomic sequencing.