Small intestinal submucosa graft bulbar urethroplasty is a viable technique: results compared to buccal mucosa graft urethroplasty after propensity score matching.

PURPOSE: Small intestinal submucosa (SIS) graft urethroplasty has been employed to decrease buccal mucosa morbidity and facilitate the procedure. The first published series had a short follow-up, inhomogeneous patient selection, and a lack of a control group. Our purpose is to report treatment outcomes at 13 years in a propensity score-matched cohort comparing bulbar urethroplasty with SIS (SISU) or buccal mucosa (BMU). METHODS: From our institutional database of 1132 bulbar urethroplasties, we used propensity score matching with the nearest-neighbor method without replacement to generate a study sample of 25 BMU and 25 SISU. Failure was defined as any treatment after urethroplasty. Survival analyses were used to analyze treatment failure occurrence with data censored at 156mo. RESULTS: Matching resulted in a complete correction of bias between the two samples except for the follow-up duration, which was slightly longer in the SIS group. The cumulative treatment success probability of BMU and SISU at 156mo was 83.4% and 68%, respectively. At multivariable Cox regression, SIS graft, previous urethrotomy, stricture length, and lower postoperative Qmax (within 2mo after catheter removal) were predictors of failure. Stricture length had a more remarkable effect in SISU, with estimated survival probabilities from the Cox model lower than 80% in strictures > = 3 cm. CONCLUSION: SIS has poorer outcomes compared to BM but may still be useful when BM grafting is not possible. The best candidates for SISU, with similar success to BMU, are patients with strictures shorter than 3 cm, preferably without a history of DVIU.

Outcomes of Ventral Onlay Buccal Mucosal Graft Urethroplasty in Bulbomembranous Urethral Strictures Post-transurethral Resection of the Prostate.

OBJECTIVE: To evaluate the outcomes of ventral onlay buccal mucosal graft urethroplasty (VOBMGU) in bulbomembranous urethral strictures after transurethral resection of the prostate. METHODS: After approval of the institutional ethical committee, we retrospectively examined the database of patients diagnosed with post-TURP urethral stricture (PTS) and treated by VOBMGU from January 2020 to January 2022. The patients were evaluated by retrograde urethrogram and voiding cystourethrogram. Follow-up evaluation included assessment of lower urinary tract symptoms, physical examination, uroflowmetry (Q-max and International Prostate Symptom Score) 3, 6, and 12months of follow-up. RESULTS: A total of 30 patients underwent VOBMGU for bulbomembranous PTS were included. The median age of the patients was 63.5 (11.25). The median stricture length was 3.5 (1.5) cm. During follow-up, the mean Q-max significantly increased to 21.1 ± 5.5 mL/s (P < .0001), 20.1 ± 5.4 mL/s (P < .001), and 19.1 ± 5.3 mL/s (P < .003) at 3, 6, and 12months, respectively. IPSS significantly decreased to 8.93 ± 6.37 at the 12-month follow-up mark (P < .0001). Three patients developed stricture recurrence and two patients developed postoperative urinary incontinence. CONCLUSION: VOBMGU in cases of bulbomembranous urethral PTS offered excellent functional outcomes with low stricture recurrence and minimal risk of incontinence. Further prospective studies are warranted to confirm the results.

Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

PURPOSE: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy. MATERIALS AND METHODS: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed. The primary outcomes were stenosis recurrence and development of de novo stress urinary incontinence. Secondary outcomes were surgical complications, changes in voiding, and patient-reported satisfaction. RESULTS: Forty-five men were treated with D-BMGU for stenosis following prostatectomy and radiation. There was a total of 7 recurrences. Median follow-up in patients without recurrence was 21 months (IQR 12-24). There were no incidents of de novo incontinence, 28 patients were incontinent pre- and postoperatively, and of the 6 patients managed with suprapubic catheter preoperatively, 4 were continent after repair. Following repair, men had significant improvement in postvoid residual, uroflow, International Prostate Symptom Score, and International Prostate Symptom Score quality-of-life domain. Overall satisfaction was +2 or better in 86.6% of men on the Global Response Assessment. CONCLUSIONS: D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.

Robot-Assisted Ureteroplasty with Labial Mucosal Onlay Grafting for Long Left-Sided Proximal Ureteral Stenosis in Children and Adolescents: Technical Tips and Functional Outcomes.

Purpose: To evaluate functional outcomes of robot-assisted ureteroplasty with labial mucosa grafting for long proximal ureteral stenosis (LPUS) in children and adolescents. Methods: Included in this study were 15 patients who underwent robot-assisted ureteroplasty with labial mucosal grafting in our center between July 2017 and September 2021. The left affected stenotic ureter was repaired using labial mucosal grafting. If the ureter was simply strictured but not obliterated, the ureter was spatulated longitudinally along the ventral side and the labial mucosa graft was interposed and anastomosed in a continuous manner. Faced with the obliterated segment, it was excised and the spatulated portion re-anastomosed with a pelvic flap as the dorsal wall. The labial mucosa graft was placed as the ventral wall. The preoperative clinical data and follow-up outcomes were collected and evaluated. Results: Labial mucosa graft onlay ureteroplasty was well performed in all the 15 patients with no occurrence of intraoperative complications or surgical conversion. Five patients underwent an onlay ureteroplasty, and 10 patients underwent a dorsally augmented pelvic flap anastomotic ureteroplasty. The mean (range) stricture length was 7.1 (3-10) cm. The mean operative time was 371.2 (216-480) minutes, and the median blood loss was 40 mL. At the median follow-up of 35 months (range 12-58 months), the overall success rate was 93.3%. Conclusions: Labial mucosa grafting appears to be safe and feasible for repairing long ureteral strictures in pediatric and adolescent patients. Our experience may provide beneficial references and conveniences to solve complex problems in LPUS. This study was approved by the institutional review board, and written informed consent was obtained from each participant (ethics number: 2017-30).

Early Postoperative Complications of One-Stage Substitution Urethroplasty with Oral Mucosa Graft: A Monocentric Retrospective Study.

INTRODUCTION: We report early postoperative complications (PCs) (≤90 days) of one-stage oral mucosa graft (OMG) urethroplasty in treatment of acquired anterior urethral strictures. MATERIAL AND METHODS: In this study, we evaluated 530 males who underwent one-stage substitution urethroplasty (SU) between September 1996 and October 2020. Medical records were reviewed to identify and classify early PCs based on the Clavien-Dindo classification (CDC). We subdivided the PCs into three groups with different kinds of complications which allowed us a more detailed analysis concerning general surgical complications (GSCs), donor site morbidity (DSM) and complications specific for free graft urethroplasty (CSUs). The influence of patient demographics, stricture characteristics and operative procedure on the occurrence of PCs was analysed. RESULTS: Early (90-day) PCs occurred in 90 (16.98%) patients, whereas only 19 patients (3.58%) experienced serious events (CDC grades III and IV). Early complications include 4.5% GSCs, 1.7% DSM and 10.8% CSUs. Only stricture length turned out to be an independent statistically significant risk factor for the occurrence of early PCs. There was a trend towards a higher rate of complications in patients with ASA III compared to ASA I. CONCLUSION: The incidence of severe early complications in patients undergoing one-stage SU with OMG is low.

Comparison of oral morbidity and mid-term efficacy of anterior urethroplasty using an autologous tissue-engineered graft (MukoCell®) versus native oral mucosa graft.

OBJECTIVE: Our study aimed to compare surgical success rate (SR) and oral morbidity of augmentation urethroplasty for anterior urethral strictures using autologous tissue-engineered oral mucosa graft (TEOMG) named MukoCell® versus native oral mucosa graft (NOMG). METHODS: We conducted a single-institution observational study on patients undergoing TEOMG and NOMG urethroplasty for anterior urethral strictures >2 cm in length from January 2016 to July 2020. SR, oral morbidity, and potential risk factors of recurrence were compared between groups were analyzed. A decrease of maximum uroflow rate < 15 mL/s or further instrumentation was considered a failure. RESULTS: Overall, TEOMG (n = 77) and NOMG (n = 76) groups had comparable SR (68.8% vs. 78.9%, p = 0.155) after a median follow-up of 52 (interquartile range [IQR] 45-60) months for TEOMG and 53.5 (IQR 43-58) months for NOMG. Subgroup analysis revealed comparable SR according to surgical technique, stricture localization, and length. Only following repetitive urethral dilatations, TEOMG achieved lower SR (31.3% vs. 81.3%, p = 0.003). Surgical time was significantly shorter by TEOMG use (median 104 vs. 182 min, p < 0.001). Oral morbidity and the associated "burden" in patients' quality of life were significantly less at 3 weeks following the biopsy required for TEOMG manufacture, compared to NOMG harvesting and totally absent at 6 and 12 months postoperatively. CONCLUSIONS: The SR of TEOMG urethroplasty appeared to be comparable to NOMG at a mid-term follow-up but taking into account the uneven distribution of stricture site and the surgical techniques used in both groups. Surgical time was significantly shortened, since no intraoperative mucosa harvesting was required, and oral complications were diminished through the preoperative biopsy for MukoCell® manufacture.

Urethroplasty Outcomes for Pars Fixa Urethral Strictures Following Gender-affirming Phalloplasty and Metoidioplasty: A Retrospective Study.

OBJECTIVE: To evaluate outcomes of three urethroplasty techniques for pars fixa (PF) urethral strictures and provide a treatment algorithm based on stricture characteristics. The PF is an essential anatomic region of the neourethra created in gender-affirming phalloplasty and metoidioplasty. Urethral strictures in this region present a reparative challenge given its unique anatomy and vascularization. METHODS: A total of 41 urethroplasties performed on 41 patients between March 2018 and June 2021 were reviewed at two surgical centers. A Heineke-Mikulicz (HM) repair was done for strictures under 20 mm when the proximal and distal urethral segments were mobile and supported a tension-free closure. Substitution urethroplasty with ventral onlay buccal mucosal graft was utilized for strictures under 40 mm not suitable for HM repair. Complex or long (≥40 mm) strictures were treated by two-stage Johansen urethroplasty. Success of each surgical approach was defined by a minimum of 12-month follow-up without the need for a repeat intervention. RESULTS: Mean follow-up was 30.2 months (range: 12.4-52.0 months). Mean stricture length was 16.9 mm (range: 2-55 mm). Most strictures (46%) were located at the distal PF. HM urethroplasty had a success rate of 44% (n = 16). Substitution urethroplasty had a success rate of 92% (n = 13). Two-stage Johansen urethroplasty had a success rate of 75% (n = 12). CONCLUSION: The success rates of PF urethral stricture repair ranged from 44% to 92% depending on the surgical approach, and the best reparative procedure depends on stricture length, severity, and local tissue mobility.

Laparoscopic ventral onlay ureteroplasty with buccal mucosa graft for complex proximal ureteral stricture.

INTRODUCTION: There is lack of papers dedicated to the laparoscopic buccal mucosa graft (BMG) ureteroplasty of the complex upper ureteral stricture. The aim of this study is to evaluate the results of laparoscopic BMG ureteroplasty in patients with complex proximal ureteral stricture. MATERIAL AND METHODS: Twenty-four patients underwent laparoscopic ventral onlay BMG ureteroplasty for long or recurrent proximal ureteral stricture not amenable to uretero-ureteral anastomosis over 2019-2022. Patient demographics, operative time, estimated blood loss, length of stay, follow-up, intra- and postoperative complication rate and percentage of stricture-free at last visit were analyzed. RESULTS: The mean stricture length was 3.6 cm. The mean operative time was 208.3 min, while mean blood loss was 75.8 mL. The length of hospital stay was 7.3 days. No intraoperative complications were observed. Postoperatively, seven patients developed complications (29.2%). Five patients experienced a Grade II (according to Clavien nomenclature). Two patients developed a Grade IIIa complication, which included leakage of the anastomosis site. The mean follow-up was on the 22 months with stricture free rate 87.5%. CONCLUSION: Patients with proximal ureteral strictures could be effectively treated by laparoscopic ventral onlay ureteroplasty with a buccal mucosa graft.

Mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty: a ventral modification for obliterative strictures.

OBJECTIVES: To present a surgical modification for the repair of bulbar urethral strictures containing short, highly obliterative segments and report on long-term objective and patient-reported outcomes. PATIENTS AND METHODS: We considered patients undergoing bulbar buccal mucosal graft urethroplasty (BMGU) between July 2016 and December 2019. Eligibility criteria for mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty were strictures of ≥2 cm with an obliterative segment of ≤1.5 cm. The stricture is approached ventrally to avoid extensive dissection and mobilisation. Dorsally, the scar is superficially excised and the spongiosum is left intact. Dorsal mucomucosal anastomosis is complemented by ventral onlay graft. Perioperative characteristics were prospectively collected including uroflowmetry data and validated patient-reported outcome measures on voiding, erectile, and continence function. We evaluated functional follow-up, incorporating patient-reported (lower urinary tract symptoms [LUTS] score) and functional success. Recurrence was defined as need of re-treatment. RESULTS: Of 641 men treated with anterior BMGU, 54 (8.4%) underwent MANTA urethroplasty. Overall, 26 (48%) and 45 (83%) had a history of dilatation and urethrotomy, respectively, and 14 (26%) were redo cases. Location was bulbar in 38 (70%) and penobulbar in 16 patients (30%), and the mean (SD) graft length was 4.5 (1.4) cm. At a median (interquartile range) follow-up of 41 (27-53) months, the functional success rate was 93%. Whereas the median LUTS score significantly improved from baseline to postoperatively (13 vs 3.5; P < 0.001), there was no change in erectile function (median International Index of Erectile Function - erectile function domain score 27 vs 24) or urinary continence (median International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form sum score 0 vs 0; all P ≥ 0.4). All patients were 'satisfied' (27%) or 'very satisfied' (73%) with the outcome of their operation. CONCLUSION: With excellent long-term objective and patient-reported outcomes, MANTA urethroplasty adds to the armamentarium for long bulbar strictures with a short obliterative segment.

[Ureteroplasty using onlay graft for long ureteral strictures].

Full-text articles published in peer-reviewed journals dedicated to the results of onlay ureteroplasty using various materials, as well as monographs on surgical treatment of long ureteral strictures are presented in the article. Over the past decade, onlay technique for the treatment of long ureteral strictures using flaps or grafts on a vascular pedicle have been introduced. Experimental data on the results of onlay ureteroplasty using autologous vein or bladder mucosa, as well as the small intestine submucosa (SIS) have been published in the literature. Due to the availability and good survival rate, buccal and tongue mucosal flaps are widely recognized as the optimal graft for onlay ureteroplasty. There are also studies on the results of ureteroplasty using SIS or appendix graft onlay for the upper and middle ureteral strictures. A use of tissue-engineered flaps for ureteroplasty remains contradictory. Further research in this direction may allow to obtain optimal grafts for onlay ureteroplasty. However, oral mucosa or appendix are predominant materials, which are used for onlay ureteroplasty.

Preliminary results of a new surgical technique: bladder mucosal graft harvested with holmium:YAG (HO:YAG) laser. A new option in bulbar replacement urethroplasty?

OBJECTIVE: To describe the technique of transurethral harvesting of bladder mucosal graft using the Holmium:YAG (Ho-YAG) laser and describe the preliminary results from 7 cases where this graft was used for urethroplasty. MATERIALS AND METHODS: We performed a single-stage dorsal onlay urethroplasty using bladder mucosal graft in 7 patients with anterior urethral stricture. Transurethral harvesting was performed with the Ho-YAG laser. We performed a prospective and descriptive analysis with uroflowmetry performed at 30, 90 and 180 days after surgery and applied the PROM translated into Portuguese before and 6 months after urethroplasty. RESULTS: Seven patients were included, 2 (28.5%) with penile urethral stricture, and 5 (71.5%) with bulbar urethral stricture. Mean stricture length was 50mm (range 35-60mm). Stricture etiology was trauma in 3 (42.9%) patients, iatrogenic in 1 (14.3%) patient, and idiopathic in 3 (42.9%) patients. Two patients (28.6%) had previously undergone ventral buccal mucosa urethroplasty. Mean bladder mucosal graft length was 52.86mm (± 13.801), and mean harvest time was 46.43min (± 14.639). Dorsal onlay urethroplasty using bladder mucosa was successfully completed in 5 patients (71.4%). Two patients (28.6%) couldn't have the procedure completed using bladder mucosa, one due to thermal damage of the graft during harvesting, and one due to insufficient graft length. In both cases the procedure was completed using buccal mucosa. Two patients (28.6%) experienced minor hematuria between the twelfth and eighteenth postoperative day, but neither required hospitalization and/or additional procedures. All patients achieved normalization of peak flow, and this was maintained throughout the follow-up period. Mean peak flow was 17.8 ml/s (± 3.271) at 30 days, 20.6 ml/s (± 5.413) at 90 days, and 19.6 ml/s (± 8.019) 180 days. Mean IPSS score decreased from 19.3 to 5.4. Similar improvements were also seen in the ICIQ-MLUTS Score (a mean drop from 3.8 to 2.0) and Peeling's Voiding Picture Score (a mean drop from 4.0 to 2.2). Quality of Life improved post urethroplasty, with increases in EQ-5D (from 0.6371 to 0.7285) and EQ-VAS (from 58.0 to 84.0). CONCLUSION: Transurethral harvesting of bladder mucosa using the Holmium laser (Ho-YAG) is feasible and reproducible. Our preliminary experience suggests that bladder mucosa grafts achieve comparable results to other grafts when used for dorsal onlay urethroplasty. Further research is needed to confirm these results.

Lateral incision 1-stage urethroplasty with oral mucosal graft for patients with penile urethral stricture after hypospadias repair-a preliminary report.

PURPOSE: To report our early experience of a novel surgical approach for penile urethral strictures after hypospadias repair, using a lateral incision to keep the ventral tissue and vasculature of the penis intact and to avoid the need for tissue interposition. PATIENTS AND METHODS: A total of 21 patients underwent lateral incision 1-stage urethroplasty with oral mucosal graft. The median age of the patients was 21 years old (range, 13-47). The median number of prior procedures for hypospadias repair was 3 (range, 1-9) with 18 of 21 patients (85.7%) undergoing greater than 1 prior reconstructive procedure. The mean length of the penile urethral strictures was 4.5 ± 1.7 cm, with a range of 1.0 to 8.0 cm. Selection criteria for lateral incision 1-stage urethroplasty include: non-obliterative stricture, no or mild penile curvature and no urethrocutaneous fistula. RESULTS: Median follow-up was 30 months (range, 6-73). Success was achieved in 17 of 21 patients (80.9%). The 4 (19.0%) patients with treatment failure developed recurrent urethral strictures. Of the 4 men with recurrent strictures, 3 were ultimately treated successfully by DVIU (2) or two-stage urethroplasty (1), and one patient chose repeated dilation. CONCLUSIONS: For patients with penile urethral stricture after hypospadias repair with non-obliterative stricture, no significant penile curvature and no urethrocutaneous fistula, a lateral approach with oral mucosal graft is a simple technique that avoids the need for tissue interposition and keeps the penile ventral tissue and vasculature intact, resulting in a low risk of complications.

Buccal mucosa graft vaginoplasty: A viable option demonstrated step-by-step.

INTRODUCTION: Persistent cloaca, defined as confluence of the rectum, the vagina and the urethra into a single common channel, has an estimated incidence of 1/50,000 live births. We describe the buccal mucosa graft vaginoplasty for a 11 year old female with cloaca, who underwent at the age of 11 months a Peña repair. We performed the vaginoplasty after the onset of uterine pain due to the beginning of menstruation. MATERIAL AND METHODS: We accessed the lower lip for superficial dissection to harvest the graft. The donor site has been kept with as much submucosal fat as possible to avoid damage to the buccinatoria muscles. A second graft was further obtained from the cheek. Both grafts were submitted to multiple small sections to produce a mesh graft and increase its size. A arciform incision anterior to the anal canal and posterior to the urethra was performed followed by consecutive dissection with eletrocautery to gain profundity. The mesh-graft was placed over the neovaginal cavity and sutured with 4.0 PDS monofilament suture used to suture and then quilt the graft in place. The vaginal capacity was confirmed by ease of a two-digit insertion. Haemostasis was confirmed before the insertion of a soft vaginal mold. The patient remained with an indwelling urinary catheter. The mold was equivalent to 24Fr and had 13 cm of profundity and Foley tube were removed after 14 days postoperatively. RESULTS: Patient had an excellent postoperative course and had been instructed to perform vaginal dilatation every 3 h during the day. Current follow up is 10 months. DISCUSSION: Buccal mucosal grafting has advantages over the use of keratinized skin flaps and intestinal flaps. Buccal mucosa is ideal for female genital reconstruction, given its color, texture, lack of hair and mild mucous production. In our particular case, we connected the neovagina after two months of adequate healing to the native 1/3 through laparoscopic approach. CONCLUSIONS: BMG vaginoplasty is a viable alternative to treat females with cloaca at adolescence.

Ventral-Onlay Buccal Mucosal Graft Urethroplasty of a Perineal Fistula in a 26-Year-Old Patient With 46 XX Male Syndrome: A Case Report.

Substitution urethroplasty with either a flap or graft is the gold standard for treating long segment urethral strictures. In 1992, Burger and colleagues rediscovered and popularized buccal mucosal graft (BMG). After that El-Kassaby and colleagues, in 1993, used BMG to repair anterior urethral stricture. De la Chapelle syndrome or 46 XX male syndrome is a rare genetic disorder found in 1 in 20,000-25,000 men. This condition described as a presentation of male phenotype along a 46 xx karyotype. In this case report, we report a reconstructive surgery of a 46 XX male syndrome with ambiguous genitalia who presented with the chief complaint of bulbar urethral fistula opened in the perineal space. In this case, we used a buccal mucous graft with the ventral-onlay urethroplasty technique for reconstructing the failed bulbar urethra and closure of the fistula.

Buccal mucosa graft urethroplasty for bulbar urethral stricture: Outcomes andpredictive factors affecting success.

INTRODUCTION AND OBJECTIVE: The bulbar urethra is the location where urethral stricture is most commonly observed. The most successful method for long and recurrent urethral stenosis is graft urethroplasty. The most successful graft source is buccal mucosa, with advantages like easy adaptation to the corporeal bed, thick epithelium, thin lamina propria with rich vascular structure and easy ability to obtain the graft. In this study we aimed to retrospectively assess the outcomes and predictive factors affecting surgical success of our buccal mucosal graft urethroplasty surgery performed for bulbar urethra stenosis with moderate length. MATERIAL AND METHOD: In this study, we monitored 51 patients with mean 4.4 cm bulbar urethral stricture length for mean 17 months follow-up. From operative and postoperative data, stenosis length, operation duration, Qmax, International Prostate Symptom Score, International Index of Erectile Function-Erectile Function and OF, success rates in total and in subgroups (age, according to DVIU, etiology, BMI and DM), follow-up duration, complications, re-stricture time and number were assessed. RESULTS: The total success of the operations was 86.3%. In 17 months, the re-stricture rate was 13.7%. Oral and urethral complications were all minor. The complications with longest duration (6 months) were ejaculation, erection problems and urethral fistula. Mean time to re-stricture was 11 months. All re-stricture patients were relieved by one DVIU session each. CONCLUSION: For bulbar urethral stricture longer than 2 cm and with recurrence, the dorsal buccal mucosa graft replacement is a very successful method with low complication rates.

Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis.

BACKGROUND: We performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy. METHODS: Epithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations. RESULTS: Subject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subjects 2 and 3 did not require EBD for 48 weeks after transplantation, during which time they were able to maintain a normal diet by mouth. CONCLUSIONS: Subjects 2 and 3 were free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; and find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis. TRIAL REGISTRATION: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393 .