Complex rectovaginal fistulas after pelvic organ prolapse repair with synthetic mesh: a multidisciplinary approach to evaluation and management.

OBJECTIVES: The use of synthetic mesh for transvaginal pelvic organ prolapse (POP) repair is associated with the rare complication of mesh erosion into hollow viscera. This study presents a single-institution series of complex rectovaginal fistulas (RVFs) after synthetic mesh-augmented POP repair, as well as strategies for identification and management. METHODS: Institutional review board approval was obtained for this retrospective study. Data were collected and analyzed on all female patients undergoing RVF repair from 2000 to 2011 at our institution. RESULTS: Thirty-seven patients underwent RVF repair at our multidisciplinary center for restorative pelvic medicine. Of these, 10 (27.0%) were associated with POP repairs using mesh. The POP repairs resulting in RVF were transvaginal repair with mesh (n = 8), laparoscopic sacrocolpopexy with concomitant traditional posterior repair (n = 1), and robotic-assisted laparoscopic sacrocolpopexy (n = 1). Time to presentation was an average of 7.1 months after POP repair. Patients underwent a mean of 4.4 surgeries for definitive RVF repair, with 40% of patients requiring a bowel diversion (3 temporary ileostomies and 1 long-term colostomy). Mean follow-up time after last surgery was 9.2 months. On follow-up, 1 patient has a persistent fistula with vaginal mesh extrusion. One patient has persistent pelvic pain. CONCLUSIONS: This series highlights the significant impact of synthetic mesh complications in the posterior compartment. These complications should be cautionary for synthetic graft use by those with limited experience, particularly when an alternate choice of traditional repair is available. When symptoms of RVF are present, collaboration with a colon and rectal specialist should be initiated as soon as possible for evaluation and definitive repair.

Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors.

Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2' subsite within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f, a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported.

Design and synthesis of morpholine derivatives. SAR for dual serotonin & noradrenaline reuptake inhibition.

Single enantiomer (SS) and (RR) 2-[(phenoxy)(phenyl)methyl]morpholine derivatives 5, 8-23 are inhibitors of monoamine reuptake. Target compounds were prepared using an enantioselective synthesis employing a highly specific enzyme-catalysed resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (26) as the key step. Structure-activity relationships established that serotonin and noradrenaline reuptake inhibition are functions of stereochemistry and aryl/aryloxy ring substitution. Consequently, selective SRI, selective NRI and dual SNRIs were all identified. One of these compounds, a potent and selective dual SNRI, (SS)-5a was selected as a candidate for further pre-clinical evaluation.

Stereoselective synthesis of 2-dienyl-substituted piperidines using an eta4-dienetricarbonyliron complex as the stereocontrolling element in a double reductive amination cascade.

In the presence of NaBH(OAc)(3), a 1,5-keto-aldehyde, contained within a side-chain of an eta(4)-dienetricarbonyliron complex, undergoes a double reductive amination sequence with a series of primary amines, to provide the corresponding piperidine products in good to excellent yield. The dienetricarbonyliron complex functions as a powerful chiral auxiliary in this cascade process, exerting complete control over the stereoselectivity of the reaction, with the formation of a single diastereoisomeric product. The sense of stereoinduction has been confirmed by X-ray crystallography. Removal of the tricarbonyliron moiety can be effected with CuCl(2) to afford the corresponding 2-dienyl-substituted piperidine in excellent yield. Attempted extension of this cyclisation strategy to the corresponding azepane ring system using a 1,6-keto-aldehyde as the cyclisation precursor was unsuccessful; in this case, the reaction stopped after a single reductive amination on the aldehyde to provide an acyclic keto-amine product.

Rectal erosion of synthetic mesh used in posterior colporrhaphy requiring surgical removal.

Treatment of pelvic organ prolapse with transvaginally placed synthetic mesh has recently increased. Several reports of complications have surfaced raising the overall question of safety regarding its use for vaginal prolapse repair. This case report describes a rectal erosion and dyspareunia that resulted from mesh placed into the posterior vaginal wall. A 47-year-old woman underwent a laparoscopic supracervical hysterectomy and a posterior repair with polypropylene mesh resulting in a rectal erosion. Despite removal of all of the mesh that could be excised rectally resulting in a healed rectal mucosa, the patient had persistent dyspareunia and pain requiring complete removal of the mesh using a vaginal approach. After surgery, the patient had resolution of all her symptoms. Further studies of transvaginally placed synthetic mesh need to be performed to determine its safety and efficacy.

Stereoselective synthesis of 2-dienyl-substituted pyrrolidines using an eta4-dienetricarbonyliron complex as the stereodirecting element: Elaboration to the pyrrolizidine skeleton.

Primary amines react with keto-aldehyde functionality located in the side-chain of an eta4-dienetricarbonyliron complex to provide the corresponding pyrrolidines in excellent diastereoselectivity. Two of the pyrrolidine products, 1i and 1k, have been elaborated into pyrrolizidines using a 1,5-C-H insertion and radical cyclization strategy, respectively.