Repeat Transanal Advancement Flap Repair: Impact on the Overall Healing Rate of High Transsphincteric Fistulas and on Fecal Continence

PURPOSE: Transanal advancement flap repair (TAFR) has been advocated as the treatment of choice for transsphincteric fistulas passing through the upper or middle third of the external anal sphincter. It is not clear whether previous attempts at repair adversely affect the outcome of TAFR. The purpose of the present study was to evaluate the success rate of a repeat TAFR and to assess the impact of such a second procedure on the overall healing rate of high transsphincteric fistulas and on fecal continence. METHODS: Between January 2001 and January 2005, a consecutive series of 87 patients (62 males; median age, 49 (range, 27-73) years) underwent TAFR. Median follow-up was 15 (range, 2-50) months. Patients in whom the initial operation failed were offered two further treatment options: a second flap repair or a long-term indwelling seton drainage. Twenty-six patients (male:female ratio, 5:2; median age, 51 (range, 31-72) years) preferred a repeat repair. Continence status was evaluated before and after the procedures by using the Rockwood Faecal Incontinence Severity Index (RFISI). RESULTS: The healing rate after the first TAFR was 67 percent. Of the 29 patients in whom the initial procedure failed, 26 underwent a repeat TAFR. The healing rate after this second procedure was 69 percent, resulting in an overall success rate of 90 percent. Both before and after the first attempt of TAFR, the median RFISI was 7 (range, 0-34). In patients who underwent a second TAFR, the median RFISI before and after this procedure was 9 (range, 0-34) and 8 (range, 0-34), respectively. None of these changes were statistically significant. CONCLUSIONS: Repeat TAFR increases the overall healing rate of high transsphincteric fistulas from 67 percent after one attempt to 90 percent after two attempts without a deteriorating effect on fecal continence

On the evolutionary ecology of symbioses between chemosynthetic bacteria and bivalves

Mutualistic associations between bacteria and eukaryotes occur ubiquitously in nature, forming the basis for key ecological and evolutionary innovations. Some of the most prominent examples of these symbioses are chemosynthetic bacteria and marine invertebrates living in the absence of sunlight at deep-sea hydrothermal vents and in sediments rich in reduced sulfur compounds. Here, chemosynthetic bacteria living in close association with their hosts convert CO2 or CH4 into organic compounds and provide the host with necessary nutrients. The dominant macrofauna of hydrothermal vent and cold seep ecosystems all depend on the metabolic activity of chemosynthetic bacteria, which accounts for almost all primary production in these complex ecosystems. Many of these enigmatic mutualistic associations are found within the molluscan class Bivalvia. Currently, chemosynthetic symbioses have been reported from five distinct bivalve families (Lucinidae, Mytilidae, Solemyidae, Thyasiridae, and Vesicomyidae). This brief review aims to provide an overview of the diverse physiological and genetic adaptations of symbiotic chemosynthetic bacteria and their bivalve hosts

"It doesn't do any harm, but patients feel better": a qualitative exploratory study on gastroenterologists' perspectives on the role of antidepressants in inflammatory bowel disease

Background: Interest in psychological factors in patients with inflammatory bowel disease (IBD) has increased in recent years. It has even been proposed that treating psychological co-morbidities with antidepressants may control disease activity and improve quality of life. Despite this, there is no data on gastroenterologists' attitudes to, and experiences with, antidepressant therapy in patients with IBD. Methods: We conducted semi-structured interviews with 18 gastroenterologists associated with metropolitan teaching hospitals. Qualitative content analysis was used to examine their responses. Results: Seventy-eight percent of gastroenterologists had treated IBD patients with antidepressants for pain, depression and/or anxiety, and insomnia. Antidepressants were reported to be useful in improving psychosocial well-being, quality of life, and self-management of the disease by patients. However, in this group of gastroenterologists, there appears to be skepticism towards psychological disorders themselves or antidepressant therapy having a central role in either the causation of IBD or its clinical course. Nevertheless, these gastroenterologists were receptive to the idea of conducting a trial of the role of antidepressants in IBD. Conclusion: While the majority of specialists have treated IBD patients with antidepressants, there is considerable skepticism with regard to efficacy of antidepressive therapy or the role of psychological factors in the outcome of IBD patients.Antonina A Mikocka-Walus, Deborah A Turnbull, Nicole T Moulding, Ian G Wilson, Jane M Andrews and Gerald J Holtman

The In Vivo Role of the RP-Mdm2-p53 Pathway in Signaling Oncogenic Stress Induced by pRb Inactivation and Ras Overexpression

The Mdm2-p53 tumor suppression pathway plays a vital role in regulating cellular homeostasis by integrating a variety of stressors and eliciting effects on cell growth and proliferation. Recent studies have demonstrated an in vivo signaling pathway mediated by ribosomal protein (RP)-Mdm2 interaction that responds to ribosome biogenesis stress and evokes a protective p53 reaction. It has been shown that mice harboring a Cys-to-Phe mutation in the zinc finger of Mdm2 that specifically disrupts RP L11-Mdm2 binding are prone to accelerated lymphomagenesis in an oncogenic c-Myc driven mouse model of Burkitt's lymphoma. Because most oncogenes when upregulated simultaneously promote both cellular growth and proliferation, it therefore stands to reason that the RP-Mdm2-p53 pathway might also be essential in response to oncogenes other than c-Myc. Using genetically engineered mice, we now show that disruption of the RP-Mdm2-p53 pathway by an Mdm2C305F mutation does not accelerate prostatic tumorigenesis induced by inactivation of the pRb family proteins (pRb/p107/p130). In contrast, loss of p19Arf greatly accelerates the progression of prostate cancer induced by inhibition of pRb family proteins. Moreover, using ectopically expressed oncogenic H-Ras we demonstrate that p53 response remains intact in the Mdm2C305F mutant MEF cells. Thus, unlike the p19Arf-Mdm2-p53 pathway, which is considered a general oncogenic response pathway, the RP-Mdm2-p53 pathway appears to specifically suppress tumorigenesis induced by oncogenic c-Myc