Vermillion Reconstruction With Anal Verge Transitional Epithelium: Turning Things Upside Down.

Postburn lip deformities pose a significant set of challenges to reconstructive burn surgeons because of the complex anatomy, diverse functions, and specialized nature of the lip tissues. There has been a paucity of literature on restoration of the vermillion to date. The authors report on two patients who suffered burn injuries resulting in significant lip deformities who underwent a novel method of vermillion reconstruction with a full thickness anal verge skin graft. Both patients tolerated the procedure well without complications. One patient had slight hyperpigmentation of the graft which was treated with a phenol peel to cause intentional lightening. Overall, both patients had a restored vermillion border and improved color match and contour of the lip. Histologic analysis of the anal verge demonstrates that it has a nonkeratinized, transitional epithelial architecture which is nearly identical to that of the vermillion tissue. Skin grafting remains one of the cornerstones of tissue replacement in acute burn care and burn reconstruction. The vermillion represents an area of specialized tissue that is not well reconstructed with simple skin grafts. Other methods for reconstruction involve lip switch operations or local flaps, like a ventral tongue flap. These procedures are not without limitation and can often cause microstomia among other issues. With no donor site morbidity, a full thickness anal verge skin graft represents the closest approximation of actual vermillion tissue found anywhere else in the body and should be considered a viable option in the reconstruction of these challenging patients.

A novel method for treatment of chronic anal fissure: adipose-derived regenerative cells - a pilot study.

AIM: The purpose of this study was to investigate the safety and feasibility of autologous adipose-derived regenerative cells (ADRC) in the treatment of chronic anal fissure. METHOD: A prospective pilot study was conducted in six patients with chronic anal fissures at the First Surgical Clinic, Clinical Center of Serbia and at the BelPrime Clinic, Belgrade, Serbia. All patients were candidates for surgical treatment. The average duration of symptoms was 24 months. Pain assessment was quantified using a visual analogue scale and bowel continence was assessed using the Wexner incontinence score. Both were assessed before treatment and during each postoperative outpatient visit. Liposuction was performed under local or general anaesthesia. Extraction of ADRC was achieved with a closed automated medical device. The fat and ADRC were injected subcutaneously into the edge of the fissure. The rest of the pellet was infiltrated into the internal anal sphincter. The study has been registered at ClinicalTrials.gov (NCT02628522). RESULTS: Complete healing of the anal fissure and the disappearance of symptoms was achieved in all patients. The average time to complete pain cessation was 33.7 ± 15.0 days. All fissures healed after 3 months and remained healed 12 months after the procedure. There were no complications related to the procedure. CONCLUSION: The application of ADRC may be an alternative to lateral sphincterotomy and a reliable procedure which avoids faecal incontinence.

Allogeneic anorectal transplantation in rats: technical considerations and preliminary results.

Fecal incontinence is a challenging condition with numerous available treatment modalities. Success rates vary across these modalities, and permanent colostomy is often indicated when they fail. For these cases, a novel potential therapeutic strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum was retrieved with a vascular pedicle containing the aorta in continuity with the inferior mesenteric artery and portal vein in continuity with the inferior mesenteric vein. In the recipient, the native anorectal segment was removed and the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses and end-to-end colorectal anastomosis. Recipients were sacrificed at the experimental endpoint on postoperative day 30. Surviving animals resumed normal body weight gain and clinical performance within 5 days of surgery. Isografts and 42.9% of allografts achieved normal clinical evolution up to the experimental endpoint. In 57.1% of allografts, signs of immunological rejection (abdominal distention, diarrhea, and anal mucosa inflammation) were observed three weeks after transplantation. Histology revealed moderate to severe rejection in allografts and no signs of rejection in isografts. We describe a feasible model of ATx in rats, which may allow further physiological and immunologic studies.

Functional outcome of autologous anorectal transplantation in an experimental model.

BACKGROUND: Although anorectal transplantation is a challenging procedure, it is a promising option for patients who have completely lost anorectal function or in whom it failed to develop, as in congenital malformations. The paucity of animal models with which to test functional outcomes was addressed in this study of anorectal manometry in rats. METHODS: Wistar rats were assigned randomly to four groups: orthotopic anorectal transplantation, heterotopic transplantation, sham operation, or normal control. Bodyweight and anal pressure were measured immediately before and after operation, and on postoperative days 7 and 14. ANOVA and Tukey's test were used to compare results for bodyweight, anal manometry and length of procedure. RESULTS: Immediately after the procedure, mean(s.d.) anal pressure in the orthotopic group (n = 13) dropped from 31·4(13·1) to 1·6(13·1) cmH2 O (P < 0·001 versus both sham operation (n = 13) and normal control (n = 15)), with partial recovery on postoperative day 7 (14·9(13·9) cmH2 O) (P = 0·009 versus normal control) and complete recovery on day 14 (23·7(12·2) cmH2 O). Heterotopic rats (n = 14) demonstrated partial functional recovery: mean(s.d.) anal pressure was 26·9(10·9) cmH2 O before operation and 8·6(6·8) cmH2 O on postoperative day 14 (P < 0·001 versus both sham and normal control). CONCLUSION: Orthotopic anorectal transplantation may result in better functional outcomes than heterotopic procedures. Surgical relevance Patients with a permanent colostomy have limited continence. Treatment options are available, but anorectal transplantation may offer hope. Some experimental studies have been conducted, but available data are currently insufficient to translate into a clinical option. This paper details functional outcomes in a rat model of anorectal autotransplantation. It represents a step in the translational research that may lead to restoration of anorectal function in patients who have lost or have failed to develop it.

Anorectal autotransplantation in a canine model: the first successful report in the short term with the non-laparotomy approach.

Colostomy is conventional treatment for anal dysfunction. Recently, a few trials of anorectal transplantation in animals have been published as a potential alternative to colostomies; however, further development of this technique is required. In this study, we utilized a canine model of anorectal transplantation, evaluated the patency of our microsurgical anastomoses, and assessed the perfusion of the transplanted anus. We designed a canine anorectal transplantation model, wherein anorectal autotransplantation was performed in four healthy beagle dogs by anastomoses of the lower rectum, the bilateral pudendal arteries (PAs) and veins (PVs), and pudendal nerves (PNs). Postoperative graft perfusion was measured by indocyanine green (ICG) angiography and histological examination. The length of the anorectal graft including perianal skin, anal sphincter muscle, bilateral PAs, PVs, and PNs was 4.9 ± 0.3 cm. All diameters of the PAs, PVs, and PNs were large enough to be microscopically anastomosed. Both ICG angiography and histological examination demonstrated good graft perfusion, except for one case that lead to venous congestion. These results show that anastomosis of the bilateral PAs, PVs, and PNs is required for anorectal transplantation. This is the first successful report of canine anorectal autotransplantation.

Anorectal transplantation in human cadavers: mock anorectal allotransplantation.

BACKGROUND: Anorectal transplantation is a method for patients who have lost their anorectal function or suffer from congenital anorectal dysfunction to recover this function, and this has been investigated in experimental animal models using pigs, dogs, and rats. In this study, we performed an examination of anorectal transplantation in human cadavers to investigate whether this procedure could be performed in patients. METHODS: A 77-year-old woman cadaver 1 was used as the donor and a 98-year-old woman cadaver 2 was used as the recipient. Initially, abdominoperineal excision of the anus and rectum (the Miles' operation) was performed on the recipient. Next, an anorectal graft containing the pudendal nerve (PN), pudendal artery (PA), pudendal vein (PV), inferior mesenteric artery (IMA), and inferior mesenteric vein (IMV) was harvested from the donor. The donor graft was transplanted into the recipient by intestinal anastomosis and microneurovascular anastomoses orthotopically. RESULTS: The diameters of the PN (right/left), IMA, and IMV were 2.5 mm/2.5 mm, 2.0 mm, and 1.5 mm, respectively, in cadaver 1, and 2.0 mm/2.0 mm, 2.0 mm, and 2.0 mm, respectively, in cadaver 2. The length of the PN, PA, PV, IMA, and IMV in the graft was sufficient to allow proper anastomosis. CONCLUSION: This preliminary study indicated that human anorectal transplantation was possible anatomically and technically. We anticipate our study will aid in the potential future application of this procedure to human patients.

The development of a canine anorectal autotransplantation model based on blood supply: a preliminary case report.

Colostomy is conventionally the only treatment for anal dysfunction. Recently, a few trials of anorectal transplantation in animals have been published; however, further development of this technique is required. Moreover, it is crucial to perform this research in dogs, which resemble humans in anorectal anatomy and biology. We designed a canine anorectal transplantation model, wherein anorectal autotransplantation was performed by anastomoses of the rectum, inferior mesenteric artery (IMA) and vein, and pudendal nerves. Resting pressure in the anal canal and anal canal pressure fluctuation were measured before and after surgery. Graft pathology was examined three days after surgery. The anal blood supply was compared with that in three beagles using indocyanine green (ICG) fluorescence angiography. The anorectal graft had sufficient arterial blood supply from the IMA; however, the graft's distal end was congested and necrotized. Functional examination demonstrated reduced resting pressure and the appearance of an irregular anal canal pressure wave after surgery. ICG angiography showed that the pudendal arteries provided more blood flow than the IMA to the anal segment. This is the first canine model of preliminary anorectal autotransplantation, and it demonstrates the possibility of establishing a transplantation model in dogs using appropriate vascular anastomoses, thus contributing to the progress of anorectal transplantation.

Vascularized anal autotransplantation model in rats: preliminary report.

Ostomy has served as an effective surgery for various anorectal disfunctions. However, it must also be noted that those patients suffered greatly from stresses caused by their stoma. Many alternative therapies have been developed, but none have solved this critical issue. Meanwhile, due to the improvements in operative methods and immunosuppressive therapy, allotranplantation has gained great popularity in recent years. Therefore, we began development of an anal transplantation model. The operation was performed in six adult Wistar rats that were divided into two groups. Group 1 underwent vascular anastomoses, while group 2 did not Group 1 grafts survived, fully recovering anal function. However, many of the group 2 grafts did not survive; those that did survive showed major defects in their anus, never recovering anal function. We succeeded in establishing the rat anal transplantation model utilizing super-microsurgery. While research in anal transplantation was behind compared to that in other fields, we hope that this model will bring significant possibilities for the future.

Successful implantation of bioengineered, intrinsically innervated, human internal anal sphincter.

BACKGROUND & AIMS: To restore fecal continence, the weakened pressure of the internal anal sphincter (IAS) must be increased. We bioengineered intrinsically innervated human IAS to emulate sphincteric physiology in vitro. METHODS: We cocultured human IAS circular smooth muscle with immortomouse fetal enteric neurons. We investigated the ability of bioengineered innervated human IAS, implanted in RAG1-/- mice, to undergo neovascularization and preserve the physiology of the constituent myogenic and neuronal components. RESULTS: The implanted IAS was neovascularized in vivo; numerous blood vessels were observed with no signs of inflammation or infection. Real-time force acquisition from implanted and preimplant IAS showed distinct characteristics of IAS physiology. Features included the development of spontaneous myogenic basal tone; relaxation of 100% of basal tone in response to inhibitory neurotransmitter vasoactive intestinal peptide (VIP) and direct electrical field stimulation of the intrinsic innervation; inhibition of nitrergic and VIPergic electrical field-induced relaxation (by antagonizing nitric oxide synthesis or receptor interaction); contraction in response to cholinergic stimulation with acetylcholine; and intact electromechanical coupling (evidenced by direct response to potassium chloride). Implanted, intrinsically innervated bioengineered human IAS tissue preserved the integrity and physiology of myogenic and neuronal components. CONCLUSIONS: Intrinsically innervated human IAS bioengineered tissue can be successfully implanted in mice. This approach might be used to treat patients with fecal incontinence.

In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival.

PURPOSE: Our laboratory has developed and implanted a novel bioengineered internal anal sphincter (IAS) to treat anal incontinence. Fibroblast growth factor-2 (FGF-2) has been used in mice; however, the optimal growth factor for successful IAS implantation is unclear. This study compares several growth factors in order to optimize IAS viability and functionality. METHODS: Bioengineered IAS rings were implanted subcutaneously into the dorsum of wildtype C57Bl/6 mice, with an osmotic pump dispensing FGF-2, vascular endothelial growth factor (VEGF), or platelet-derived growth factor (PDGF) (n = 4 per group). Control mice received IAS implants but no growth factor. The IAS was harvested approximately 25 days post-implantation. Tissue was subjected to physiologic testing, then histologically analyzed. Muscle phenotype was confirmed by immunofluorescence. RESULTS: All implants supplemented with growth factors maintained smooth muscle phenotype. Histological scores, blood vessel density and muscle fiber thickness were all markedly better with growth factors. Neovascularization was comparable between the three growth factors. Basal tonic force of the constructs was highest with VEGF or PDGF. CONCLUSION: All growth factors demonstrated excellent performance. As our ultimate goal is clinical implantation, our strong results with PDGF, a drug approved for use in the United States and the European Union, pave the way for translating bioengineered IAS implantation to the clinical realm.

Anorectal transplantation.

BACKGROUND: Anorectal transplantation is a valid procedure for the treatment of anorectal dysfunction; however, the lack of a suitable animal model has hampered the development of this method. We describe a simple technique for anorectal transplantation in the rat and compare this procedure with colostomy. METHODS: The anorectal segment including the skin surrounding the anus were freed by abdominal and perineal dissection. In a heterotopically transplanted group the segment was exteriorized by the formation of an anus through an abdominal incision. In an orthotopically transplanted group the segment was replaced in its original position and reimplanted by suturing. In another group a distal colostomy was performed. A sham-treated control group (simulated surgical procedure) was also included. Changes in behavior, characteristics of the stool, body weight and survival rate were assessed by daily clinical examination. Moribund animals, those with a weight loss of more than 30%, and those surviving at 1 month were killed by an overdose of anesthetic. The results were analyzed using the Mann Whitney, Student's t and chi-squared tests, and p<0.05 was considered significant. RESULTS: Within 4 days after the operation, animals submitted to orthotopic or heterotopic transplantation had achieved normal defecation, body weight gain and clinical evolution similar to the sham-treated group. The overall mortality in these groups was 4.16%. In contrast, colostomized animals showed a high incidence of diarrhea, intestinal obstruction, stress posture and violent behavior (p

Functional reconstruction of large anogenital defects with bilateral V-Y advancement posterior thigh fasciocutaneous flaps.

BACKGROUND: In patients with perianal extramammary Paget's disease, wide local excision is recommended. In the reconstruction of the resulting large defects not only the closure of the defect but also the preservation of anogenital function need to be considered. METHODS: We used bilateral V-Y advancement posterior thigh fasciocutaneous flaps for reconstructing three large anogenital defects, including the total anal canal, resulting from wide local excisions attributed to extramammary Paget's disease. A temporary anus was constructed at the same time to allow the wound of the reconstructed anus to heal. After the surgery, the course of bowel function was followed up through interviews and manometric examinations. RESULTS: All defects were successfully reconstructed with the flaps, and bowel function recovered satisfactorily. Manometric examinations were carried out in two cases; anal pressures were recorded regularly and used as parameters of the recovery of bowel function before closing the artificial anus. Eventually, the patients recovered the function of defecation. CONCLUSIONS: We recommend the bilateral V-Y advancement posterior thigh fasciocutaneous flaps together with manometric studies as one of the most effective techniques for managing large anogenital defects. The use of sensate flaps, the restoration of original structures and manometric studies are conducive to successful outcomes.

Técnicas novedosas en el tratamiento de la incontinencia anal / Novel techniques in the treatment of anal incontinence

La incontinencia fecal es un problema que puede condicionar la vida sociolaboral del paciente. Hasta hace poco, la mayoría de enfermos con incontinencia anal grave, en los que habían fracasado medidas conservadoras y/o quirúrgicas, eran sometidos a una colostomía. Actualmente, estos pacientes pueden beneficiarse de alguna técnica innovadora de reciente aparición. Así, disponemos del esfínter anal artificial y de la graciloplastia dinámica, cada una con sus indicaciones específicas. Ambos procedimientos consiguen buenos resultados funcionales, pero con cifras de complicaciones no despreciables y con reintervenciones en bastantes ocasiones. La neuromodulación sacra ha supuesto un avance importante por su relativa sencillez y porque permite, mediante un test de estimulación temporal, discriminar qué pacientes se beneficiarán definitivamente de su aplicación. Otras técnicas, como la inyección de agentes aumentadores de volumen o la radiofrecuencia, son tan recientes y hay tan poca experiencia que su papel todavía está por definir. Al ser tan novedosas las técnicas descritas, además de su elevado coste económico, conviene utilizarlas en grupos de estudio que dispongan de laboratorio de fisiología anorrectal y dentro de ensayos clínicos, hasta que la experiencia demuestre que puede generalizarse, o no, su aplicación (AU)

Fecal incontinence can negatively affect the patient's occupational and social life. Until recently, most patients with severe anal incontinence unresponsive to conservative medical and/or surgical treatments underwent colostomy. Currently, these patients can benefit from one of the innovative techniques that have recently been developed. Thus, the artificial anal sphincter and dynamic graciloplasty are now available, each with specific indications. Both procedures achieve good functional results but complication and reintervention rates are not inconsiderable. Sacral neuromodulation represents an important advance due to its relative simplicity and because, through a period of test stimulation, patients who can definitively benefit from its application can be identified. Other techniques, such as injectable bulking agents or radiofrequency ablation are so recent that experience is limited and their role remains to be defined. Since these techniques are so novel and their economic cost is high, their use should be restricted to study groups with an anorectal physiology laboratory and within the context of clinical trials until experience shows whether or not their application can become widespread (AU)

Experimental model of anorectal transplantation.

BACKGROUND: Anorectal transplantation with pudendal nerve anastomosis after rectal excision is a possible strategy that would avoid a colostomy and recreate potentially normal anorectal function. This study investigates the technical feasibility of anorectal transplantation with pudendal nerve and inferior mesenteric artery and vein anastomosis in a porcine model. METHODS: Four female pigs (22-42 kg) provided donor anorectum for four male recipients (29-39 kg) under standard general anaesthesia. The donor operation involved abdominoperineal excision of rectum (APR) taking the anal sphincter, pudendal neurovascular bundle and inferior mesenteric vessels. The recipient underwent APR, transperineal introduction of the donor graft, anastomoses of the rectum, inferior mesenteric vessels and pudendal neurovascular bundle, and perineal closure. Recorded variables were duration of each step of transplantation, ischaemic time, dimensions of anastomosed structures and postoperative graft viability. Animals were killed at 24 h, the state of the graft was noted and tissue was taken for confirmatory histology. RESULTS: Mean operation time was 372 (range 303-435)min. Mean ischaemic time was 118 (100-130)min. Before death, observation at laparotomy revealed two pink grafts, one slightly dusky but healthy graft and one outright failure, reflecting the state of the mesenteric vessels, which were patent in three and thrombosed in one. Histological examination showed no difference between control biopsies and the three cases with satisfactory mesenteric flow. Gross ischaemia was present histologically in the failed case. CONCLUSION: Anorectal transplantation is technically feasible in a pig model. Longer-term studies are now needed to assess return of function and overcome rejection issues.

Perineal anal transplant in anorectal malformation in female patients.

Results of perineal anal transplant in 25 patients with anorectal malformations in female children have been analyzed. The present study shows that the operation is ill advised in patients with intermediate anomalies but can be undertaken safely in patients with low anomalies. In our series best results were obtained when the transplant was performed in patients who were past 5 years of age. Colostomy, though helpful in reducing the severity of the immediate complications, does not influence the late results.