Recurrent anal fistulae:Limited surgery supported by stem cells

AIM:To study the results of stem-cell therapy under a Compassionate-use Program for patients with recurrent anal fistulae.METHODS:Under controlled circumstances,and approved by European and Spanish laws,a Compassionate-use Program allows the use of stem-cell therapy for patients with very complex anal fistulae.Candidates had previously undergone multiple surgical interventions that had failed to resolve the fistulae,and presented symptomatic recurrence.The intervention consisted of limited surgery(with closure of the internal opening),followed by local implant of stem cells in the fistula-tract wall.Autologous expanded adipose-derived stem cells were the main cell type selected for implant.The first evaluation was performed on the 8th postoperative week;outcome was classified as response or partial response.Evaluation one year after the intervention confirmed if complete healing of the fistula was achieved.RESULTS:Ten patients(8 male)with highly recurrent and complex fistulae were treated(mean age:49years,range:28-76 years).Seven cases were nonCrohn’s fistulae,and three were Crohn’s-associated fistulae.Previous surgical attempts ranged from 3to 12.Two patients presented with preoperative incontinence(Wexner scores of 12 and 13 points).After the intervention,six patients showed clinical response on the 8th postoperative week,with a complete cessation of suppuration from the fistula.Three patients presented a partial response,with an evident decrease in suppuration.A year later,six patients(60%)remained healed,with complete reepithelization of the external opening.Postoperative Wexner Scores were 0 in six cases.The two patients with previous incontinence improved their scores from12 to 8 points and from 13 to 5 points.No adverse reactions or complications related to stem-cell therapy were reported during the study period.CONCLUSION:Stem cells are safe and useful for treating anal fistulae.Healing can be achieved in severe cases,sparing fecal incontinence risk,and improving previous scoring.

Stem cell therapy applied for digestive anastomosis: Current state and future perspectives

BACKGROUND Digestive tract resections are usually followed by an anastomosis.Anastomotic leakage,normally due to failed healing,is the most feared complication in digestive surgery because it is associated with high morbidity and mortality.Despite technical and technological advances and focused research,its rates have remained almost unchanged the last decades.In the last two decades,stem cells(SCs)have been shown to enhance healing in animal and human studies;hence,SCs have emerged since 2008 as an alternative to improve anastomoses outcomes.AIM To summarise the published knowledge of SC utilisation as a preventative tool for hollow digestive viscera anastomotic or suture leaks.METHODS PubMed,Science Direct,Scopus and Cochrane searches were performed using the key words“anastomosis”,“colorectal/colonic anastomoses”,“anastomotic leak”,“stem cells”,“progenitor cells”,“cellular therapy”and“cell therapy”in order to identify relevant articles published in English and Spanish during the years of 2000 to 2021.Studies employing SCs,performing digestive anastomoses in hollow viscera or digestive perforation sutures and monitoring healing were finally included.Reference lists from the selected articles were reviewed to identify additional pertinent articles.METHODS Given the great variability in the study designs,anastomotic models,interventions(SCs,doses and vehicles)and outcome measures,performing a reliable meta-analysis was considered impossible,so we present the studies,their results and limitations.RESULTS Eighteen preclinical studies and three review papers were identified;no clinical studies have been published and there are no registered clinical trials.Experimental studies,mainly in rat and porcine models and occasionally in very adverse conditions such as ischaemia or colitis,have been demonstrated SCs as safe and have shown some encouraging morphological,functional and even clinical results.Mesenchymal SCs are mostly employed,and delivery routes are mainly local injections and cell sheets followed by biosutures(sutures coated by SCs)or purely topical.As potential weaknesses,animal models need to be improved to make them more comparable and equivalent to clinical practice,and the SC isolation processes need to be standardised.There is notable heterogeneity in the studies,making them difficult to compare.Further investigations are needed to establish the indications,the administration system,potential adjuvants,the final efficacy and to confirm safety and exclude definitively oncological concerns.CONCLUSION The future role of SC therapy to induce healing processes in digestive anastomoses/sutures still needs to be determined and seems to be currently far from clinical use.