Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction.

The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.

Porcine small intestinal submucosa biomaterial graft for repair of a congenital pleuroperitoneal hernia in a kitten.

In this case, porcine small intestinal submucosa (pSIS) was used to repair a large congenital diaphragmatic hernia in a kitten. The pSIS was moistened in saline, folded in half, and sutured to the remnant of the right hemidiaphragm. The animal was determined to be doing well clinically and radiographically 12 wk after procedure. At 8.5 mo of age, the kitten was spayed, and the diaphragm was inspected, revealing a thin, semitransparent membrane at the central region of the previous pSIS graft. Serial thoracic radiographs may be an effective way to reach a diagnosis of a diaphragmatic hernia if not clearly identifiable on initial radiographs. Surgeons should be prepared to use alternative techniques to close large diaphragmatic defects. Porcine SIS was demonstrated to be a strong, easy-to-use, readily available, and effective technique to close a large defect in the diaphragm with excellent results in the short and medium terms. When hernia repair is employed in juvenile animals, reassessment of the diaphragmatic repair should be considered if future abdominal surgeries, such as ovariohysterectomies, are necessary. A functional 8-ply pSIS should be considered in cats and dogs as it has a lower complication and graft failure rate. Key clinical message: When serial radiographs fail to diagnose a diaphragmatic hernia when one is highly suspected, other modalities, such as ultrasonography or other contrast modalities, should be considered. A functional 8-ply pSIS should be considered to reconstruct the diaphragm, particularly in growing animals, as it is an effective graft with low complication and graft failure rates.

Greffe de biomatériau de sous-muqueuse intestinale porcine pour la réparation d'une hernie pleuropéritonéale congénitale chez un chatonDans ce cas, la sous-muqueuse intestinale porcine (pSIS) a été utilisée pour réparer une grande hernie diaphragmatique congénitale chez un chaton. La pSIS a été humidifiée dans une solution saline, pliée en deux et suturée au reste de l'hémidiaphragme droit. L'animal s'est avéré se porter bien cliniquement et radiographiquement 12 semaines après l'intervention. À l'âge de 8,5 mois, le chaton a été stérilisé et le diaphragme a été inspecté, révélant une fine membrane semi-transparente dans la région centrale de la greffe pSIS précédente. Des radiographies thoraciques en série peuvent être un moyen efficace de poser un diagnostic d'hernie diaphragmatique si elle n'est pas clairement identifiable sur les radiographies initiales. Les chirurgiens doivent être prêts à utiliser des techniques alternatives pour fermer les gros défauts diaphragmatiques. La SIS porcine s'est avérée être une technique solide, facile à utiliser, facilement disponible et efficace pour fermer un gros défaut du diaphragme avec d'excellents résultats à court et moyen terme. Lorsque la réparation d'une hernie est utilisée chez les animaux juvéniles, une réévaluation de la réparation diaphragmatique doit être envisagée si de futures chirurgies abdominales, telles que des ovariohystérectomies, sont nécessaires. Une pSIS fonctionnelle à 8 plis doit être envisagée chez les chats et les chiens car elle présente un taux de complications et d'échec de greffe plus faible.Message clinique clé :Lorsque les radiographies en série ne permettent pas de diagnostiquer une hernie diaphragmatique alors qu'elle est fortement suspectée, d'autres modalités, telles que l'échographie ou d'autres modalités de contraste, doivent être envisagées. Une pSIS fonctionnelle à 8 plis doit être envisagée pour reconstruire le diaphragme, en particulier chez les animaux en croissance, car il s'agit d'une greffe efficace avec un faible taux de complications et d'échec de greffe.(Traduit par Dr Serge Messier).

Post-stapedotomy reparative granuloma following use of acellular porcine small intestinal submucosa.

PURPOSE: There have been multiple proposed etiologies of reparative granuloma following stapes surgery. In this report, we present the first case of post-stapedectomy reparative granuloma following the use of Biodesign (Cook Medical, Bloomington, IN) otologic graft material, an acellular matrix derived from porcine small intestinal submucosa, and review the literature of post-stapes surgery reparative granuloma. PATIENT: 50-year-old woman who developed a reparative granuloma following stapedotomy with acellular porcine intestinal submucosa presenting with profound hearing loss and vertigo. INTERVENTION: Middle ear exploration with excision of granuloma and revision stapedotomy. MAIN OUTCOME MEASURES: Audiologic outcomes as measured by pure-tone air and bone conduction thresholds and word recognition scores. Improvement in vertigo. MAIN FINDINGS: Surgical excision of the reparative granuloma with revision stapedotomy resolved vertigo. Hearing has improved progressively postoperatively. CONCLUSIONS: We report the first case of post-stapedotomy reparative granuloma following the use of acellular porcine intestinal submucosa. Although exact etiology cannot be determined from a single case report, this illustrates the need for careful use of novel foreign graft material. This case additionally confirms that removal of granuloma and inciting materials can salvage serviceable hearing.

Correction of Defective T-Regulatory Cells From Patients With Crohn's Disease by Ex Vivo Ligation of Retinoic Acid Receptor-α.

BACKGROUND & AIMS: Crohn's disease (CD) is characterized by an imbalance of effector and regulatory T cells in the intestinal mucosa. The efficacy of anti-adhesion therapies led us to investigate whether impaired trafficking of T-regulatory (Treg) cells contributes to the pathogenesis of CD. We also investigated whether proper function could be restored to Treg cells by ex vivo expansion in the presence of factors that activate their regulatory activities. METHODS: We measured levels of the integrin α4ß7 on Treg cells isolated from peripheral blood or lamina propria of patients with CD and healthy individuals (controls). Treg cells were expanded ex vivo and incubated with rapamycin with or without agonists of the retinoic acid receptor-α (RARA), and their gene expression profiles were analyzed. We also studied the cells in cytokine challenge, suppression, and flow chamber assays and in SCID mice with human intestinal xenografts. RESULTS: We found that Treg cells from patients with CD express lower levels of the integrin α4ß7 than Treg cells from control patients. The pathway that regulates the expression of integrin subunit α is induced by retinoic acid (RA). Treg cells from patients with CD incubated with rapamycin and an agonist of RARA (RAR568) expressed high levels of integrin α4ß7, as well as CD62L and FOXP3, compared with cells incubated with rapamycin or rapamycin and all-trans retinoic acid. These Treg cells had increased suppressive activities in assays and migrated under conditions of shear flow; they did not produce inflammatory cytokines, and RAR568 had no effect on cell stability or lineage commitment. Fluorescently labeled Treg cells incubated with RAR568 were significantly more likely to traffic to intestinal xenografts than Treg cells expanded in control medium. CONCLUSIONS: Treg cells from patients with CD express lower levels of the integrin α4ß7 than Treg cells from control patients. Incubation of patients' ex vivo expanded Treg cells with rapamycin and an RARA agonist induced expression of α4ß7 and had suppressive and migratory activities in culture and in intestinal xenografts in mice. These cells might be developed for treatment of CD. ClinicalTrials.gov, Number: NCT03185000.

Long-term follow-up of neurogenic bladder patients after bladder augmentation with small intestinal submucosa.

PURPOSE: To evaluate the long-term effect of using small intestinal submucosa (SIS) for bladder augmentation in patients with neurogenic bladder. MATERIALS AND METHODS: A total of 15 patients (age range 14-65 years; mean age 29.6 years) were enrolled in our study. The patients had poor bladder capacity and compliance caused by a neurogenic disorder requiring bladder augmentation. A small intestinal submucosa (SIS) cystoplasty was performed alone or in combination with ureter reimplantation. We prospectively followed the cohort to assess the urodynamics parameters, morphologic changes and patient satisfaction and evaluate the clinical benefit of the SIS procedure in long term. The surgical indications and complications were analyzed. RESULTS: The duration of follow-up ranged from 4.5 to 8.3 years (mean 6.3 years). Nine patients had expected long-term benefit, leading to an overall success rate of 60%. Two patients experienced immediate failure, and four patients slowed decrease in bladder capacity over time. Compared with the baseline data, there were significant increases in bladder capacity (163.5 ± 80.90-275.6 ± 159.5 ml, p < 0.05) and a significant decrease in maximum detrusor pressure (45.07 ± 29.03-17.60 ± 10.34 cmH2O, p < 0.05). Histologic examinations showed a complete conversion of SIS, leaving the urothelial lining and bladder wall containing muscular, vascular, and relatively thick connective tissue. Major complications included vesicoureteral reflux in five patients, bladder stone formation in one patient, and bladder perforation in one patient. CONCLUSION: Bladder augmentation with an SIS graft offers a partial long-term success rate in neurogenic bladder patients. This procedure cannot be recommended as a substitute for enterocystoplasty, especially in patients with severe upper urinary tract deterioration and/or bladder fibrosis.

[Outcomes of implanting porcine small intestinal submucosa mesh in rabbit vesicovaginal space].

Objective: To assess surgical outcomes of implanted porcine small intestinal submucosa (SIS) mesh in the rabbit vesicovaginal space (VVS) and explore its application value in pelvic floor reconstruction surgery. Methods: Sixteen male rabbits were randomly divided into four groups, and each group had four rabbits. All groups of rabbits were implanted with SIS mesh in the vesicovaginal space. They were humanely killed after a postoperative period of 7, 30, 90 and 180 days by group. The grafted area was removed with the surrounding bladder and vaginal tissues. The specimens were embedded in paraffin and then stained with HE and Masson's trichrome stains for visual observations, cells counts, and assessment of tissues and collagen fibers. Results: (1) After HE staining, a large number of inflammatory response cells mainly eosinophils and lymphocytes infiltrated around the SIS mesh in 7 days group, and neovascularization was observed, the infiltration area of inflammatory response cells further increased in 30 days group, the infiltration area of inflammatory response cells significantly reduced in 90 days group, while the inflammatory response basically subsided in 180 days group. (2) After Masson's trichromestaining, the collagen structure of SIS mesh in 7 days group was clear and intact. While, the collagen structure of SIS mesh was partially degraded in 30 days group, the SIS meshes of 4 rabbits were completely degraded, but the collagen fragments of SIS remained in 90 days group. In 180 days group, the SIS mesh of all rabbits was degraded, and one of them had the formation of new collagen fibers. Conclusions: SIS mesh implanted into the VVS of rabbits can lead to a transient non infective inflammatory reaction, which could be completely degraded and a small amount of new collagen fibers could be produced after 180 days of implantation. Which shown that SIS mesh should be used cautiously in pelvic floor reconstruction surgery.

Multi-Institutional Outcomes of Minimally Invasive Harvest of Rectal Mucosa Graft for Anterior Urethral Reconstruction.

PURPOSE: We report multi-institutional outcomes in patients who underwent urethroplasty with a rectal mucosa graft. MATERIALS AND METHODS: We used the TURNS (Trauma and Urologic Reconstructive Network of Surgeons) database to identify patients who underwent urethral reconstruction with transanal harvest of a rectal mucosa graft. We reviewed preoperative demographics, stricture etiology, previous management and patient outcomes. RESULTS: We identified 13 patients from April 2013 to June 2017. Median age at surgery was 54 years. The stricture etiology was lichen sclerosus in 6 of 13 patients (46%), idiopathic in 2 (15%), hypospadias in 1 (7%), prior gender confirming surgery in 3 (23%) and rectourethral fistula after radiation for prostate cancer in 1 (7%). Prior procedures included failed urethroplasty with a buccal mucosa graft in 9 of 13 patients (69%), direct vision internal urethrotomy in 2 (15%) and none in 2 (15%). Median stricture length was 13 cm. Stricture location in the 9 cisgender patients was panurethral in 5 (56%), bulbopendulous in 2 (22%) and bulbar in 2 (22%). It was located at the junction of the fixed urethra extending into the neophallus in all 3 patients (100%) who underwent prior gender confirming surgery. Mean rectal mucosa graft length for urethroplasty was 10.6 cm (range 3 to 16). Repair types included dorsal or ventral onlay, or 2-stage repair. Stricture recurred at a median followup of 13.5 months in 2 of 13 patients (15%). Postoperative complications included glans dehiscence, urethrocutaneous fistula and compartment syndrome in 1 patient each (7%). No rectal or bowel related complications were reported. CONCLUSIONS: Urethral reconstruction with a transanal harvested rectal mucosa graft is a safe technique when a buccal mucosa graft is unavailable or not indicated.

Donor mucosal immunocytes perpetuate refractory GVHD after intestinal transplantation without engrafting in recipient bone marrow: Case report and review of the literature.

GVHD as a complication of SOT presents both a diagnostic and therapeutic challenge. Typically affecting the skin, gastrointestinal tract, and liver, GVHD occurs when donor lymphocytes engrafted in recipient tissues are activated by host antigen-presenting cells resulting in cytokine release and donor cell-mediated cytotoxicity to host tissue. Here, we describe a 5-year-old girl who developed fatal, refractory GVHD after isolated intestinal transplantation when recipient immune cells failed to repopulate the allograft in the setting of CMV viremia. Persistence of the donor immune cells in the allograft mucosa, rather than engraftment in the recipient bone marrow, likely perpetuated this refractory GVHD. Early diagnosis and intervention are critical to reduce morbidity and mortality. Thus, periodic monitoring of peripheral blood and allograft mucosal chimerism with sensitive detection methods may allow early detection and potentially curative enterectomy in similar cases of refractory GVHD.

Robotic transanal minimally invasive rectal mucosa harvest.

INTRODUCTION: Buccal mucosal grafts (BMG) are traditionally used in urethral reconstruction. There may be insufficient BMG for applications requiring large grafts, such as urethral stricture after gender-affirming phalloplasty. Rectal mucosa in lieu of BMG avoids oral impairment, while potentially affording less postoperative pain and larger graft dimensions. Transanal minimally invasive surgery (TAMIS) using laparoscopic instruments has been described. Due to technical challenges of harvesting a sizable graft within the rectal lumen, we adopted a new robotic approach. We demonstrate the feasibility and safety of a novel technique of Robotic TAMIS (R-TAMIS) in the harvest of rectal mucosa for the purpose of onlay graft urethroplasty. METHODS: Six patients (ages 28-60) presenting with urethral stricture and one vaginal stricture underwent robotic rectal mucosal harvest. The procedure, which was first studied on an inanimate bovine colon model, was performed under general anesthesia in lithotomy position using the GelPOINTTM Path Transanal Access. Mucosa was harvested robotically after submucosal hydrodissection. Graft size harvested correlated with surface area needed for urethral or vaginal reconstruction. Following specimen retrieval, flexible sigmoidoscopy confirmed hemostasis. The graft was placed as an onlay for urethroplasty. RESULTS: There were no intraoperative or postoperative complications. Mean graft size was 11.4 × 3.0 cm. All reconstructions had excellent graft take. All patients recovered without morbidity or mortality. They reported minimal postoperative pain and all regained bowel function on postoperative day one. Patients with prior BMG harvests subjectively self-reported less postoperative pain and greater quality of life. There have been no long-term complications at a median follow-up of 17 months. CONCLUSIONS: To our knowledge, this is the first use of R-TAMIS for rectal mucosa harvest. Our preliminary series indicates this approach is feasible and safe, constituting a promising minimally invasive technique for urethral reconstruction. Prospective studies evaluating graft outcomes and donor site morbidity with more long-term follow-up are needed.

Combined Laparoscopic and Vaginal Cervicovaginal Reconstruction Using Acellular Porcine Small Intestinal Submucosa Graft in a Patient with Mayer-Rokitansky-Küster-Hauser Syndrome (U5aC4V4).

STUDY OBJECTIVE: To introduce a creation that combines laparoscopic and Wharton-Sheares-George cervicovaginal reconstruction using a small intestinal submucosa (SIS) graft in a patient with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome who had a rudimentary cavity (U5aC4V4) [1]. DESIGN: A video article introducing a new surgical technique. SETTING: A university hospital. PATIENTS: A 24-year-old patient had primary amenorrhea and irregular lower abdominal pain for 9 years. The patient was Tanner stage 3 for pubic hair and Tanner stage 4 for breast development. The physical examination revealed no vagina. A primordial uterus and a uterus with a rudimentary cavity were detected by magnetic resonance imaging [2,3]. However, the rudimentary cavity had no hematometra. Magnetic resonance imaging also found a left solitary kidney. The diagnosis was MRKH syndrome with a rudimentary cavity (U5aC4V4) [4]. The patient desired resumption of menses and possible future fertility. INTERVENTIONS: Combined laparoscopic and Wharton-Sheares-George cervicovaginal reconstruction using an SIS graft was performed. MEASUREMENTS AND MAIN RESULTS: With the Wharton-Sheares-George neovaginoplasty, a vaginal mold with a surrounding SIS graft was inserted into the newly created cavity [5]. Using laparoscopy, the lower uterine segment was incised by shape dissection. The proximal segment of the SIS graft to the lower uterine segment was sutured. A T-shaped intrauterine device with a Foley catheter was fixed in the uterine cavity by the delay of absorbed sutures to prevent cervical or vaginal stenosis. The distal segment of the SIS graft was sutured with the high vaginal or vestibular mucosa vaginally. The operation was successfully completed. The operating time was 2 hours. Hospitalization was 4 days. There were no blood transfusions or complications. The patient had resumption of menses for 2 cycles postoperatively, and she had no dysmenorrhea. The patient did not have sexual intercourse because of the mode in the vagina to prevent vagina stenosis. No cervical stenosis occurred because of the Foley catheter. CONCLUSION: In the past, a uterus with a rudimentary cavity in patients with MRKH was always excised, and patients lost the chance of menstrual onset and fertility. Combined laparoscopic and Wharton-Sheares-George cervicovaginal reconstruction using an SIS graft provided a minimally invasive, safe, and effective surgical option for the young patient with MRKH syndrome with a rudimentary cavity. The technique is not complex, is easy to learn and perform, and provided a result with functional and anatomic satisfaction. No special surgical apparatus is needed with this technique.

Comparison of neovaginoplasty using acellular porcine small intestinal submucosa graft or Interceed in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

OBJECTIVE: To compare using the acellular porcine small intestinal submucosa (SIS) graft or the Interceed in patients with MRKH syndrome undergoing creation of a neovagina. METHODS: In this retrospective study, patients with MRKH syndrome undergoing creation of a neovagina from 2016 to 2018 were retrospectively investigated. Wharton-Sheares-George neovaginoplasty was performed using the acellular porcine SIS graft or the Interceed. RESULTS: Overall, 67 patients were included for analysis. The operating time, the estimated blood loss and return of bowel activity were similar between the two groups. However, the total cost in the SIS group was significantly higher than that in the Interceed group due to the cost of the SIS graft. The mean length and width of the neovagina were similar between the two groups. However, the incidence of granulation in vaginal apex was higher in the SIS graft group than that in the Interceed group. There was no statistically significant difference in the total FSFI scores between the two groups who became sexually active postoperatively. CONCLUSIONS: Our results demonstrated that Wharton-Sheares-George method provided the patients to have satisfactory sexual intercourse. The Interceed played a role in the reconstruction of neovagina no less than the SIS graft.

Intestinal Preservation Injury: A Comparison Between Rat, Porcine and Human Intestines.

Advanced preservation injury (PI) after intestinal transplantation has deleterious short- and long-term effects and constitutes a major research topic. Logistics and costs favor rodent studies, whereas clinical translation mandates studies in larger animals or using human material. Despite diverging reports, no direct comparison between the development of intestinal PI in rats, pigs, and humans is available. We compared the development of PI in rat, porcine, and human intestines. Intestinal procurement and cold storage (CS) using histidine-tryptophan-ketoglutarate solution was performed in rats, pigs, and humans. Tissue samples were obtained after 8, 14, and 24 h of CS), and PI was assessed morphologically and at the molecular level (cleaved caspase-3, zonula occludens, claudin-3 and 4, tricellulin, occludin, cytokeratin-8) using immunohistochemistry and Western blot. Intestinal PI developed slower in pigs compared to rats and humans. Tissue injury and apoptosis were significantly higher in rats. Tight junction proteins showed quantitative and qualitative changes differing between species. Significant interspecies differences exist between rats, pigs, and humans regarding intestinal PI progression at tissue and molecular levels. These differences should be taken into account both with regards to study design and the interpretation of findings when relating them to the clinical setting.

The bolster technique utilising small intestinal submucosa wound matrix: A novel approach to wound treatment.

Managing acute wounds with soft tissue loss can be very challenging for both patients and physicians. Successful wound healing depends on several factors including exudate control, prevention of infection, and moisture balance. In this case series, we describe a novel combination treatment method utilising small intestinal submucosa wound matrix (SISWM) with the bolster technique as a way of assisting the integration of collagen-based wound treatment products into the base of complex wounds with the intent of restoring a dysfunctional extracellular matrix. In case 1, a 44-year-old female presented with an acute wound resulting from a spider bite to the posterior aspect of the right knee. In case 2, a 12-year-old male sustained multiple injuries to his right foot from an all-terrain vehicle accident. In case 3, an 80-year-old female on anticoagulants sustained an avulsion injury to her left lower leg. In case 4, a 41-year-old female sustained a severe complex avulsion injury to the dorsal left forearm sustained from a dog bite. All patients were successfully treated with SISWM and the bolster technique, and their wounds healed completely within 6 weeks. The bolster technique, when combined with an SISWM, is a novel method designed to enable the SISWM to impart its wound healing properties to these complex traumatic wounds. This case series presents treating clinicians with a different treatment methodology to assist the patient in achieving a successful outcome.

Myeloid-derived suppressor cells increase and inhibit donor-reactive T cell responses to graft intestinal epithelium in intestinal transplant patients.

Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal and multivisceral transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33+ CD11b+ lineage(CD3/CD56/CD19)- HLA-DR-/low cells with 3 subsets, CD14- CD15- (e-MDSCs), CD14+ CD15- (M-MDSCs), and CD14- CD15+ (PMN-MDSCs), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs after ITx; among MDSC subsets, M-MDSC numbers were maintained at a high level after 2 months post ITx. The MDSC numbers decreased in ITx recipients with ACR. MDSC numbers were positively correlated with serum interleukin (IL)-6 levels and the glucocorticoid administration index. IL-6 and methylprednisolone enhanced the differentiation of bone marrow cells to MDSCs in vitro. M-MDSCs and e-MDSCs expressed CCR1, -2, and -3; e-MDSCs and PMN-MDSCs expressed CXCR2; and intestinal grafts expressed the corresponding chemokine ligands after ITx. Of note, the percentage of MDSCs among intestinal mucosal CD45+ cells increased after ITx. A novel in vitro assay demonstrated that MDSCs suppressed donor-reactive T cell-mediated destruction of donor intestinal epithelial organoids. Taken together, our results suggest that MDSCs accumulate in the recipient PBMCs and the grafted intestinal mucosa in ITx, and may regulate ACR.

Mesh, graft, or standard repair for women having primary transvaginal anterior or posterior compartment prolapse surgery: two parallel-group, multicentre, randomised, controlled trials (PROSPECT).

BACKGROUND: The use of transvaginal mesh and biological graft material in prolapse surgery is controversial and has led to a number of enquiries into their safety and efficacy. Existing trials of these augmentations are individually too small to be conclusive. We aimed to compare the outcomes of prolapse repair involving either synthetic mesh inlays or biological grafts against standard repair in women. METHODS: We did two pragmatic, parallel-group, multicentre, randomised controlled trials for our study (PROSPECT [PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trials]) in 35 centres (a mix of secondary and tertiary referral hospitals) in the UK. We recruited women undergoing primary transvaginal anterior or posterior compartment prolapse surgery by 65 gynaecological surgeons in these centres. We randomly assigned participants by a remote web-based randomisation system to one of the two trials: comparing standard (native tissue) repair alone with standard repair augmented with either synthetic mesh (the mesh trial) or biological graft (the graft trial). We assigned women (1:1:1 or 1:1) within three strata: assigned to one of the three treatment options, comparison of standard repair with mesh, and comparison of standard repair with graft. Participants, ward staff, and outcome assessors were masked to randomisation where possible; masking was obviously not possible for the surgeon. Follow-up was for 2 years after the surgery; the primary outcomes, measured at 1 year and 2 years, were participant-reported prolapse symptoms (i.e. the Pelvic Organ Prolapse Symptom Score [POP-SS]) and condition-specific (ie, prolapse-related) quality-of-life scores, analysed in the modified intention-to-treat population. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN60695184. FINDINGS: Between Jan 8, 2010, and Aug 30, 2013, we randomly allocated 1352 women to treatment, of whom 1348 were included in the analysis. 865 women were included in the mesh trial (430 to standard repair alone, 435 to mesh augmentation) and 735 were included in the graft trial (367 to standard repair alone, 368 to graft augmentation). Because the analyses were carried out separately for each trial (mesh trial and graft trial) some women in the standard repair arm assigned to all treatment options were included in the standard repair group of both trials. 23 of these women did not receive any surgery (15 in the mesh trial, 13 in the graft trial; five were included in both trials) and were included in the baseline analyses only. Mean POP-SS at 1 year did not differ substantially between comparisons (standard 5·4 [SD 5·5] vs mesh 5·5 [5·1], mean difference 0·00, 95% CI -0·70 to 0·71; p=0·99; standard 5·5 [SD 5·6] vs graft 5·6 [5·6]; mean difference -0·15, -0·93 to 0·63; p=0·71). Mean prolapse-related quality-of-life scores also did not differ between groups at 1 year (standard 2·0 [SD 2·7] vs mesh 2·2 [2·7], mean difference 0·13, 95% CI -0·25 to 0·51; p=0·50; standard 2·2 [SD 2·8] vs graft 2·4 [2·9]; mean difference 0·13, -0·30 to 0·56; p=0·54). Mean POP-SS at 2 years were: standard 4·9 (SD 5·1) versus mesh 5·3 (5·1), mean difference 0·32, 95% CI -0·39 to 1·03; p=0·37; standard 4·9 (SD 5·1) versus graft 5·5 (5·7); mean difference 0·32, -0·48 to 1·12; p=0·43. Prolapse-related quality-of-life scores at 2 years were: standard 1·9 (SD 2·5) versus mesh 2·2 (2·6), mean difference 0·15, 95% CI -0·23 to 0·54; p=0·44; standard 2·0 (2·5) versus graft 2·2 (2·8); mean difference 0·10, -0·33 to 0·52; p=0·66. Serious adverse events such as infection, urinary retention, or dyspareunia or other pain, excluding mesh complications, occurred with similar frequency in the groups over 1 year (mesh trial: 31/430 [7%] with standard repair vs 34/435 [8%] with mesh, risk ratio [RR] 1·08, 95% CI 0·68 to 1·72; p=0·73; graft trial: 23/367 [6%] with standard repair vs 36/368 [10%] with graft, RR 1·57, 0·95 to 2·59; p=0·08). The cumulative number of women with a mesh complication over 2 years in women actually exposed to synthetic mesh was 51 (12%) of 434. INTERPRETATION: Augmentation of a vaginal repair with mesh or graft material did not improve women's outcomes in terms of effectiveness, quality of life, adverse effects, or any other outcome in the short term, but more than one in ten women had a mesh complication. Therefore, follow-up is vital to identify any longer-term potential benefits and serious adverse effects of mesh or graft reinforcement in vaginal prolapse surgery. FUNDING: UK National Institute of Health Research.

Refractory Urethral Stricture Management: Indications for Alternative Grafts and Flaps.

PURPOSE OF REVIEW: Urethral strictures that are refractory to initial management present unique challenges to the reconstructive surgeon. Treatment trends have shifted as new tissue resources are becoming available. There is renewed interest in old methods as skill and technique have improved. We describe the scope of the surgical armamentarium available to develop creative approaches and successful outcomes. RECENT FINDINGS: We discuss techniques to maximize the availability of oral mucosa, harvest and use of rectal mucosa, and developments in tissue engineering. Evolving methods to assess success of repair are also described. Urethral reconstruction for refractory urethral strictures requires proficiency with multiple methods as these strictures often require combining techniques for successful treatment.

Barriers to Epineural Scarring: Role in Treatment of Traumatic Nerve Injury and Chronic Compressive Neuropathy.

The physiological limitations of neural regeneration make peripheral nerve surgery challenging to both the surgeon and the patient. Presence of nerve gaps and local wound factors may all influence outcome, suggesting that barriers to reduce perineural scarring, minimize fibrosis, and avoid ischemia would be beneficial. To examine the evidence supporting their use, we reviewed the autologous and commercially-available options for barriers against scarring around a nerve. Numerous clinical case series demonstrated the effectiveness and safety of local/rotational flaps and autologous vein wrapping when used in the presence of recurrent compressive neuropathy. Translational research in animal models supports the biocompatibility of commercially available nerve wraps following nerve repair. To date, there are no reports of clinical use of commercially available nerve wraps in acute nerve repair, but a growing number of case series demonstrate their effectiveness and safety in chronic compressive neuropathy. Limited clinical evidence exists to support the efficacy of vein or flap coverage in acute nerve repairs.

Early outcomes of fluorescence angiography in the setting of endorectal mucosa advancement flaps.

BACKGROUND: Fistula-in-ano has a reported incidence of 31-34%. Besides fistulotomy, options for fistula repair are seton placement, endorectal advancement flap (ERAF), fibrin sealant, anal fistula plug and ligation of the intersphincteric fistula tract. Despite having a reported success rate as high as 75-98%, ERAF is not without complications, including flap breakdown, recurrence and fecal incontinence. Traditionally, maintaining a broad base to preserve blood supply has been advocated to reduce flap failure. And the aim of the present study was to evaluate outcomes of adult patients who underwent ERAF for complex fistula-in-ano with the use of intraoperative fluorescence angiography (FA) at our institution between July 2014 and July 2016. METHODS: We retrospectively reviewed consecutive cases of complex fistula-in-ano repair with ERAF and FA from a prospectively maintained dataset of adult patients with complex fistula-in-ano. Demographics, intraoperative data and 60-day outcomes were recorded and reviewed. RESULTS: Six patients [five males and one female with a mean age of 40 years (range 25-46 years)], with a total of seven fistulas, were identified. Six (85.7%) of these patients had undergone prior surgery for fistula-in-ano. No recurrences or complications of any type were noted at 2-week and 8-week follow-up. The majority of patients (71.4%) required flap revision based on intraoperative FA prior to flap fixation. CONCLUSIONS: FA is safe and offers real-time assessment of flap perfusion prior to and after fixation in anal fistula repair. The rate of flap ischemia may be underestimated, and therefore, to improve outcomes in ERAF, intraoperative FA should be included in the surgical armamentarium.

Ectopic intestinal mucosa implanted on the perianal skin of a patient with Crohn disease.

Intestinal mucosa implanted in skin is an exceedingly rare occurrence. Implantations are thought to occur during the creation of ostomy sites or other surgical procedures in which suture goes through bowel mucosa and then skin. Current ostomy literature reports this as a very uncommon complication. We present a 54-year-old man diagnosed with Crohn disease with severe perianal involvement who was referred to our outpatient clinic because of two persistent perianal cutaneous ulcerations. He previously underwent several interventions to drain complex perianal fistulas and abscesses, the last of them involved placing seton stitches to ensure continuous draining during the healing process. Physical examination revealed two painful ulcerations with bleeding on contact. A skin biopsy was performed, revealing ectopic intestinal mucosa with crypts, villi, and goblet cells. Perianal ulcerations characteristic of Crohn disease might be difficult to differentiate from ectopic implant of bowel mucosa secondary to a surgical procedure in the perianal area. Therefore, we believe a high degree of suspicion and skin biopsy are key to the diagnosis.

Early complications of biologic extracellular matrix patch after use for femoral artery repair.

BACKGROUND: The CorMatrix (CorMatrix Cardiovascular, Roswell, Ga) biologic extracellular patch derived from porcine small intestinal mucosa provides a biologic scaffold for cellular ingrowth and eventual tissue regeneration. It has been used in a variety of applications, including cardiac and vascular repair procedures. METHODS: CorMatrix was used as a patch arterioplasty for femoral artery repair in conjunction with endarterectomy for seven separate procedures in six patients (one patient underwent staged, bilateral femoral procedures). RESULTS: Patients were a median age of 67 years (interquartile range, 3.6 years). Six of seven procedures (86%) were performed on male patients. There were no operative deaths. Three of seven procedures (43%) resulted in significant early complications. Two procedures (29%) resulted in catastrophic biologic extracellular matrix patch disruption (11 and 19 days after initial procedure), requiring emergency exploration, patch removal, and definitive repair with vein patch arterioplasty. Both patches demonstrated an absence of growth on culture. One procedure (14%) resulted in groin pseudoaneurysm formation. Use of the CorMatrix patch was suspended upon recognition of significant complications. CONCLUSIONS: Use of CorMatrix patch in the femoral artery position demonstrates a high incidence of early postoperative complications, including catastrophic patch disruption and pseudoaneurysm formation.