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Author(s): Angela Nebbioso [1]; Nicole Clarke [2]; Emilie Voltz [2]; Emmanuelle Germain [2]; Concetta Ambrosino [1]; Paola Bontempo [1]; Rosana Alvarez [3]; Ettore M Schiavone [4]; Felicetto Ferrara [4]; Francesco [...]

The Paraganglioma is the most common extra-adrenal pheochromocytoma arising from neural crest (1) (It will better to write: The paraganglioma is an extra-adrenal pheocromocytoma arising from the neural crest. 10% of pheocromocytomas are extra-adrenal and can arise form chromaffin tissue derived from primitive neuroectoderm). Minimally invasive techniques allow surgeons to perform the procedure without wide exposure and mobilization of intra abdominal organs. To our knowledge we present the third case of robotic excision of a retroperitoneal paraganglioma.

Introduction: The standard treatment of colo-vesical fistula is the exeresis of fistula, suture of bladder wall, colic resection with or without temporary colostomy. Usually the approach is open because conversion rates and morbidity are lower than laparoscopy. The aim of video is to show the steps of a new mini-invasive approach of colo-vesical fistula without colic resection., Materials and Methods: A 69 years old male underwent laparoscopic conservative treatment of colo-vesical fistula due to endoscopic polipectomy in sigmoid diverticulum. 12 mm trocar for the camera was placed at the umbilicus, two 10 mm trocars were placed along bisiliac line and 5 mm port was placed along left emiclavear line; Trendelenburg position was 20°. The fistulous loop was carefully isolated, clipped with Hem-o-lock clips and removed. Since diverticular disease appeared slight and no inflammation signs were evident, colon resection was not performed. We sutured and sinked the sigmoid wall; after curettage of the fistula site, the bladder wall was sutured. Fat tissue was placed between sigmoid and bladder wall to reduce the risk of fistula recurrence., Results: Operative time, estimated blood loss, catheterization time, time to flatus and hospital stay were respectively 210 minutes, 300 mL, 10 days, 48 h and 8 days. The histological examination showed colonic inflammatory and necrotic tissue. No complications or fistula recurrence occurred at 54 months follow-up., Conclusions: The laparoscopic conservative treatment of colo-vesical fistula is a safe and feasible technique, in particular when the diverticular disease is limited and the fistula is not due to diverticulitis.

Cytochrome P450 3A4 (CYP3A4) plays a prominent role in the metabolism of a vast array of drugs and xenobiotics and exhibits broad substrate specificities. Most cytochrome P450-mediated reactions follow simple Michaelis-Menten kinetics. These parameters are widely accepted to predict pharmacokinetic and pharmacodynamic consequences in vivo caused by exposure to one or multiple drugs. However, CYP3A4 in many cases exhibits allosteric (sigmoidal) characteristics that make the Michaelis constants difficult to estimate. In the present study, diazepam, temazepam and nordiazepam were employed as substrates of CYP3A4 to propose a kinetic model. The model hypothesized that CYP3A4 contains two substrate-binding sites in a single active site that are both distinct and co-operative, and the resulting velocity equation had a good fit with the sigmoidal kinetic observations. Therefore, four pairs of the kinetic estimates (KS1, kalpha, KS2, kbeta, KS3, kdelta, KS4 and kgamma) were resolved to interpret the features of binding affinity and catalytic ability of CYP3A4. Dissociation constants KS1 and KS2 for two single-substrate-bound enzyme molecules (SE and ES) were 3-50-fold greater than KS3 and KS4 for a two-substrate-bound enzyme (SES), while respective rate constants kdelta and kgamma were 3-218-fold greater than kalpha and kbeta, implying that access and binding of the first molecule to either site in an active pocket of CYP3A4 can enhance the binding affinity and reaction rate of the vacant site for the second substrate. Thus our results provide some new insights into the co-operative binding of two substrates in the inner portions of an allosteric CYP3A4 active site.