Localized Photodynamic Therapy Using a Chlorin e6-Embedded Silicone-Covered Self-Expandable Metallic Stent as a Palliative Treatment for Malignant Esophageal Strictures.

Localized photodynamic therapy (PDT) uses a polymeric-photosensitizer (PS)-embedded, covered self-expandable metallic stent (SEMS). PDT is minimally invasive and a noteworthy potential alternative for treating esophageal strictures, where surgery is not a viable option. However, preclinical evidence is insufficient, and optimized irradiation energy dose ranges for localized PDT are unclear. Herein, we validated the irradiation energy doses of the SEMS (embedded in a PS using chlorin e6 [Ce6] and covered in silicone) and PDT-induced tissue changes in a rat esophagus. Cytotoxicity and phototoxicity in the Ce6-embedded SEMS piece with laser irradiation were significantly higher than that of the silicone-covered SEMS with or without laser and the Ce6-embedded silicone-covered SEMS without laser groups (all p < 0.001). Moreover, surface morphology, atomic changes, and homogeneous coverage of the Ce6-embedded silicone-covered membrane were confirmed. The ablation range of the porcine liver was proportionally increased with the irradiation dose (all p < 0.001). The ablation region was identified at different irradiation energy doses of 50, 100, 200, and 400 J/cm2. The in vivo study in the rat esophagus comprised a control group and 100, 200, and 400 J/cm2 energy-dose groups. Finally, histology and immunohistochemistry (TUNEL and Ki67) confirmed that the optimized Ce6-embedded silicone-covered SEMS with selected irradiation energy doses (200 and 400 J/cm2) effectively damaged the esophageal tissue without ductal perforation. The polymeric PS-embedded silicone-covered SEMS can be easily placed via a minimally invasive approach and represents a promising new approach for the palliative treatment of malignant esophageal strictures.

Toxic Effects of Volume-modulated Arc Therapy for Esophageal Squamous Cell Cancer: Preliminary Clinical Results.

BACKGROUND/AIM: To evaluate the toxic effects associated with various factors, including the presence or absence of concurrent chemotherapy with volume-modulated arc therapy (VMAT) and dose parameters for esophageal cancer (EC), and to assess the safety and feasibility of the VMAT protocol. PATIENTS AND METHODS: Patients with EC who received definitive VMAT between December 2016 and December 2020 were retrospectively analyzed. VMAT plans were designed to deliver 60 Gy to the primary tumor, 54 Gy to high-risk sites, and 51.3 Gy to regional lymph node sites. Toxic effects were evaluated for esophagitis, neutropenia, esophageal stricture, pericardial effusion, radiation-associated pneumonia. RESULTS: Forty-five patients received concurrent chemoradiotherapy (CCRT), while 29 were treated with radiation therapy (RT) alone. The following grade 3 complications were detected: Neutropenia in four patients (5.4%), esophagitis in two (2.7%), and esophageal stricture in one (1.4%). Grade 4 or more complications were not observed. The median age of the CCRT group (67 years) was significantly lower than that of the RT-alone group (77 years) (p<0.0001). The incidence of esophagitis was significantly higher in the CCRT group (75.5%) than in the RT group (48.3%) (p=0.033). The univariate analysis identified increasing mean dose to the pericardium as a significant risk factor for pericardial effusion, and CCRT and performance status ≥1 as significant for radiation-associated pneumonia. These factors were not significant in the multivariate analysis. Neutropenia and esophageal stricture were not associated with any factor examined. CONCLUSION: VMAT alone and in CCRT performed with our protocol was safe and feasible in patients with esophageal squamous cell cancer.

[The effective analysis of refractory esophageal stricture after endoscopic mucosal dissection of early esophageal cancer treated by endoscopic radiotomy combined with local injection of triamcinolone acetonide].

Refractor esophageal stenosis after endoscopic submucosal dissection of early esophageal carcinoma is a difficult clinical problem. To verify the effect of endoscopic radial incision combined local triamcinolone injection to treat refractory esophageal stenosis, we retrospectively analyzed 7 patients diagnosed with refractory esophageal stricture after endoscopic mucosal dissection of early esophageal cancer in this study, of whom 4 male and 3 female patients, aged 50-76 years, with the mean age of 63 years. We performed the endoscopic radial incision in the thickness point of the scar stricture and injected the triamcinolone locally. The results showed it was safe and effective. The follow-up showed no esophageal stenosis occured and no adverse reaction such as hemorrhage, perforation, tumor-recurrence and triamcinolone-allergy occured.

Temporal changes and risk factors for esophageal stenosis after salvage radiotherapy in superficial esophageal cancer following non-curative endoscopic submucosal dissection.

BACKGROUND AND PURPOSE: Radiotherapy (RT) has recently received increasing attention as an additional treatment for organ preservation after non-curative endoscopic submucosal dissection (ESD) in patients with superficial esophageal cancer. Esophageal stenosis is an adverse event related to RT after ESD that is not widely studied. The aim of this study was to investigate esophageal stenosis related to salvage RT in superficial esophageal cancer after non-curative ESD. MATERIALS AND METHODS: Fifty patients who received salvage RT after non-curative ESD at a single institution between 2011 and 2018 were included in this study. The Common Terminology Criteria for Adverse Events, version 5.0, was used to assess esophageal stenosis. Data were compared using Fisher's exact test. Statistical significance was set at P < 0.05. RESULTS: Median follow-up time was 48 months (range, 12-95 months). Grade 2 and 3 esophageal stenosis were observed in 17 (34%), and 3 patients (6%), respectively. The frequency of grade 2 or worse esophageal stenosis decreased over time (before RT, 6 months, 1 year, and 2 years after RT: 16 (32%), 13 (26%), 10 (20%), and 6 (12%) patients, respectively). Only one patient required endoscopic balloon dilation (EBD) 1 year after RT. All grade 3 esophageal stenosis improved grade 2 or less by EBD. In univariate analysis, only tumor location was a significant risk factor for grade 3 esophageal stenosis. CONCLUSIONS: Esophageal stenosis, after salvage RT in patients with esophageal cancer who received non-curative ESD, improved naturally or after EBD; only a few cases required long-term EBD.

EFFICACY OF ENDOSCOPIC TOPICAL MITOMYCIN C APPLICATION IN CAUSTIC ESOPHAGEAL STRICTURES IN THE PEDIATRIC POPULATION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

BACKGROUND: Caustic ingestion and development of esophageal strictures are recognized major public health problems in childhood. Different therapeutic methods have been proposed in the management of such strictures. OBJECTIVE: To evaluate efficacy and risk of endoscopic topical application of mitomycin C in the treatment of caustic esophageal strictures. METHODS: We searched MEDLINE, EMBASE, Central Cochrane, and LILACS databases. The outcomes evaluated were dysphagia resolution rate, number of dilations performed in resolved cases, and the number of dilations performed in all patients. RESULTS: Three randomized clinical trials were included for final analysis with a total of 190 patients. Topical mitomycin C application group showed a significant increase in dysphagia resolution rate, corresponding to a 42% higher dysphagia resolution as compared to endoscopic dilation alone, with statistical significance between the two groups (RD: 0.42 - [CI: 0.29-0.56]; P-value <0.00001). The mean number of dilations performed in resolved cases were significantly less in the topical mitomycin C application group, compared to endoscopic dilations alone, with statistical significance between the two groups (MD: 2.84 [CI: 1.98-3.69]; P-value <0.00001). When comparing the number of dilations in all patients, there was no statistical difference between the two groups (MD: 1.46 [CI: -1.53-4.44]; P-value =0.34). CONCLUSION: Application of topical mitomycin C with endoscopic dilations in caustic esophageal strictures was more effective in dysphagia resolution than endoscopic therapy alone in the pediatric population. Moreover, topical mitomycin C application also reduced the number of dilation sessions needed to alleviate dysphagia without rising morbidity.

Eficácia da aplicação endoscópica tópica de mitomicina C em estenoses esofágicas cáusticas na população pediátrica: uma revisão sistemática e meta-análise de ensaios clínicos randomizados / Efficacy of endoscopic topical mitomycin c application in caustic esophageal strictures in the pediatric population: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT BACKGROUND: Caustic ingestion and development of esophageal strictures are recognized major public health problems in childhood. Different therapeutic methods have been proposed in the management of such strictures. OBJECTIVE: To evaluate efficacy and risk of endoscopic topical application of mitomycin C in the treatment of caustic esophageal strictures. METHODS: We searched MEDLINE, EMBASE, Central Cochrane, and LILACS databases. The outcomes evaluated were dysphagia resolution rate, number of dilations performed in resolved cases, and the number of dilations performed in all patients. RESULTS: Three randomized clinical trials were included for final analysis with a total of 190 patients. Topical mitomycin C application group showed a significant increase in dysphagia resolution rate, corresponding to a 42% higher dysphagia resolution as compared to endoscopic dilation alone, with statistical significance between the two groups (RD: 0.42 - [CI: 0.29-0.56]; P-value <0.00001). The mean number of dilations performed in resolved cases were significantly less in the topical mitomycin C application group, compared to endoscopic dilations alone, with statistical significance between the two groups (MD: 2.84 [CI: 1.98-3.69]; P-value <0.00001). When comparing the number of dilations in all patients, there was no statistical difference between the two groups (MD: 1.46 [CI: -1.53-4.44]; P-value =0.34). CONCLUSION: Application of topical mitomycin C with endoscopic dilations in caustic esophageal strictures was more effective in dysphagia resolution than endoscopic therapy alone in the pediatric population. Moreover, topical mitomycin C application also reduced the number of dilation sessions needed to alleviate dysphagia without rising morbidity.

RESUMO CONTEXTO: A ingestão de soda cáustica e o desenvolvimento de estenoses esofágicas são reconhecidos como importantes problemas de saúde pública na infância. Diferentes métodos terapêuticos têm sido propostos no manejo dessas estenoses. OBJETIVO: Avaliar a eficácia e o risco da aplicação endoscópica tópica de mitomicina C no tratamento de estenoses esofágicas cáusticas. MÉTODOS: Buscamos as bases de dados MEDLINE, EMBASE, Central Cochrane e LILACS. Os desfechos avaliados foram taxa de resolução da disfagia, número de dilatações realizadas nos casos resolvidos e número de dilatações realizadas em todos os pacientes. RESULTADOS: Três ensaios clínicos randomizados foram incluídos para análise final com um total de 190 pacientes. O grupo de aplicação de mitomicina C tópica apresentou aumento significativo na taxa de resolução da disfagia, correspondendo a uma resolução da disfagia 42% maior em comparação à dilatação endoscópica isolada, com significância estatística entre os dois grupos (RD: 0,42 - [IC: 0,29-0,56]; P-valor <0,00001). O número médio de dilatações realizadas em casos resolvidos foi significativamente menor no grupo de aplicação tópica de mitomicina C, em comparação com as dilatações endoscópicas isoladas, com significância estatística entre os dois grupos (MD: 2,84 [IC: 1,98-3,69]; P-valor <0,00001). Ao comparar o número de dilatações em todos os pacientes, não houve diferença estatística entre os dois grupos (MD: 1,46 [IC: -1,53-4,44]; valor de P=0,34). CONCLUSÃO: A aplicação de mitomicina C tópica com dilatações endoscópicas em estenoses esofágicas cáusticas foi mais eficaz na resolução da disfagia do que a terapia endoscópica isolada na população pediátrica. Além disso, a aplicação tópica de mitomicina C também reduziu o número de sessões de dilatação necessárias para aliviar a disfagia sem aumentar a morbidade.

Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects.

PURPOSE: To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. METHODS: Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. RESULTS: Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). CONCLUSIONS: The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

Biological testing of chitosan-collagen-based porous scaffolds loaded with PLGA/Triamcinolone microspheres for ameliorating endoscopic dissection-related stenosis in oesophagus.

OBJECTIVES: Endoscopic submucosal dissection (ESD), a preferential approach for early oesophageal neoplasms, inevitably results in oesophageal strictures in patients. Clinical use of glucocorticoids through submucosal injection is beneficial for inhibiting oesophageal stricture following injury; however, it also has limitations, such as dose loss and perforation. Hence, alternatives to glucocorticoid therapy should be developed. METHODS: A novel porous composite scaffold, ChCo-TAMS, composed of chitosan, collagen-I and triamcinolone acetonide (TA) loaded into poly (lactic-co-glycolic) acid (PLGA) microspheres (TAMS), was successfully constructed and subjected to biological testing to ameliorate oesophageal ESD-related stenosis. RESULTS: The synthesized biomaterials displayed unique properties in inhibiting the activation of macrophages, chemokine-mediated cell recruitment and fibrogenesis of fibroblasts. Further application of the scaffolds in the rat dermal defect and porcine oesophageal ESD model showed that these novel scaffolds played a robust role in inhibiting wound contracture and oesophageal ESD strictures. CONCLUSIONS: The developed composite scaffolds provide a promising clinical medical device for the prevention of post-operative oesophageal stricture.

Systemic steroids have a role in treating esophageal strictures in pediatric eosinophilic esophagitis.

BACKGROUND: The role of systemic steroids in the treatment of esophageal strictures in children with Eosinophilic Esophagitis (EoE) is poorly defined. AIMS: To describe a cohort of children with EoE-associated esophageal strictures responding to systemic steroids. METHODS: Retrospective review of medical records of children with EoE and moderate (<9 mm) to severe (<6 mm) strictures, who responded clinically and endoscopically to systemic steroids. RESULTS: Twenty children (median age 10.6 ±â€¯4.2 years; 17 males) from nine centers in six countries were included in the analysis; 16 had moderate and four, severe strictures; 18 had dysphagia or bolus impaction; median diagnostic delay was 8 months (IQR 3.5-35). Eighteen patients received oral systemic steroids (mean dose 1.4 mg/kg/day) for a median of 4 weeks, while two initially received IV steroids. All patients showed clinical improvement and 15/20 became asymptomatic. Stricture resolution at endoscopy was found in 19/20, while histological resolution of EoE (<15 eos/hpf) in 13/20. Only minor side effects were reported: hyperphagia (10/20); weight gain (5/20); hyperactivity (2/20) and acne (1/20). Esophageal dilation was required in 3/20 patients during a median follow-up of 48.5 months (IQR 26.7-73.2). CONCLUSION: Children with EoE and esophageal strictures, may benefit from the use of a short course of systemic steroids, avoiding mechanical dilation.

Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects

ABSTRACT Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

Protective Effects of Contractubex® on Stricture Formation after Experimental Corrosive Esophageal Burns in Rats.

AIM/BACKGROUND: Although many agents have been tested as treatment options for caustic esophageal burn (CEB), none have successfully suppressed the formation of strictures. Thus,the purpose of this study was to determine the efficacy of Contractubex® gel (10% onion extract, 50 U/gr heparin, and 1% allantoin) in stricture preventing after CEB. METHODS: In this study, 24 Wistar-albino rats were divided into 4 groups. CEB was initiated with an instillation of 1 mL of 10% NaOH solution into the an isolated esophageal segment for 3 min. Group C (control) was uninjured and untreated. In Group CEB, was initiated but no treatment was given. In Groups CTX1 and CTX2, the animals received 100 and 200 mg/kg/d, respectively, of Contractubex® for 4 weeks via gavage after CEB was initiated. The stenosis indices (SI), histopathologic damage scores, tissue hydroxyproline (HP) levels, and weights of the rats were taken before the experiment and 4 weeks after the experiment. RESULTS: The Mean SI levels, HP levels, and histopathologic damage scores were statistically lower in Groups CTX1 and CTX2 when compared with Group CEB (p <0.05). The treatment groups increased in weight when compared to Group CEB. The results were similar between Group CTX1 and Group CTX2 (p >0,05); the efficacy of the treatment was not dose-dependent. CONCLUSION: For the first time, Contractubex® was used for its antifibrotic, antioxidant, anti-inflammatory, and wound healing effects to treat caustic esophageal burn in rats. It was effective in reducing stricture formation by decreasing the HP levels and histopathologic damage as well as preventing stenosis and weight gain in the treatment groups.

Short-term Effects of Mitomycin C Infiltration for Caustic Oesophageal Strictures in Children.

OBJECTIVES: The aim of this study was to investigate the efficacy and safety of endoscopic local infiltration of mitomycin C (MMC) after oesophageal dilation for children suffering from refractory postcorrosive oesophageal stricture (OS). METHODS: Children referred to Cairo University Specialized Paediatric Hospital with refractory postcorrosive OS during the period from March 2016 to August 2017 were included in this study. MMC was infiltrated endoscopically at the stricture site by the end of the dilation session. The measured outcomes were dysphagia score (DS) and periodic dilation index (PDI). RESULTS: During the inclusion period of the presented study, 17 children met the inclusion criteria. There were 7 boys and 10 girls. During the follow-up period, an average of 3.8 dilation sessions with MMC infiltration per case were performed, using a total dose of 1 mg each session. The median follow-up period was 9.5 months. The median DS improved from DS 3 before application of MMC to DS 0 at the last follow-up (P < 0.001). Additionally, the median PDI declined from 1 to 0.75 after MMC application (P = 0.052). Sixteen cases (94%) became dysphagia free after 6 months. Seven patients experienced postdilation minor bleeding that was spontaneously resolved, not triggering blood transfusion. There were no infiltration-related complications in the included series. CONCLUSION: Stricture-site MMC endoscopic infiltration by the end of a dilation session proved to be safe and effective in improving the DS and PDI.

Efficacy and Safety of the Local Application of Mitomycin C to Recurrent Esophageal Strictures in Children.

OBJECTIVES: Research on long-term use of mitomycin C (MC) for recurrent esophageal stenoses is limited. We assessed the long-term efficacy and safety of local application of MC for recurrent esophageal stenoses in children. METHODS: This was a retrospective study of 39 patients (17 girls) with a median age of 19.5 months (range: 2.4-196.0) at the time of MC application. The etiologies of stenosis were esophageal atresia (n = 25), caustic ingestion (n = 9), congenital esophageal stenosis (n = 3), and other causes (n = 2). Stenosis was single in 35 (90%) patients and multiple in 4 (10%). Before MC, patients underwent multiple repeated dilations (median: 3 dilations per child [range: 2-26]) over a median period of 7 months (range: 2.6-49.3). Treatment success was defined a priori as a reduction in the number of dilations over the same period from before to after the application of MC. RESULTS: For 26 (67%) patients, the application of MC was considered a success: 102 versus 17 dilatations (P < 0.0001). Sixteen (41%) patients never required additional dilation during the follow-up after MC application (median: 3.1 years [range: 0.6-8.5]). No complication related to MC was observed. Biopsies at the site of MC application were performed at maximal follow-up in 16 patients and revealed no dysplasia. Three factors were associated with success of MC: single stenosis, short stenosis, and esophageal atresia type III. CONCLUSIONS: This study is the largest series reported showing that topical application of MC is an efficient and safe treatment for recurrent esophageal stenosis in children.

Effectiveness of an orally administered steroid gel at preventing restenosis after endoscopic balloon dilation of benign esophageal stricture.

BACKGROUND: Restenosis occurs in 10% to 30% of patients after endoscopic balloon dilation (EBD) of benign esophageal stricture. This study aimed to investigate whether an orally administered steroid/gel mixture would inhibit restenosis after EBD for benign esophageal stricture. METHODS: This retrospective analysis included patients with benign esophageal stricture treated with EBD at the Peking University Third Hospital, China (September 2005 to October 2017). The patients were divided into an EBD alone group (EBD only) and EBD/OHA group (EBD plus oral hydrocortisone sodium succinate/aluminum phosphate gel mixture). Patients were followed-up for 3 months. EBD was repeated for persistent dysphagia. The outcome measures included the restenosis rate and the number of additional EBD sessions required during follow-up. Any side effects were noted. RESULTS: Thirty-two patients were included (EBD alone group, n = 12; EBD/OHA group, n = 20). Baseline demographic and clinical characteristics (including age, sex, etiology, stricture location, and diameter of narrowest segment) did not differ between groups. Restenosis rate was significantly lower in the EBD/OHA group than in the EBD alone group (5/20, 25.0% vs 8/12, 66.7%; P = .025). The median number of EBD sessions required was numerically lower in the EBD/OHA group (median, 1.0; interquartile range, 1.0-1.8) than in the EBD alone group (median 2.0, interquartile ranged 1.0-2.5), but statistical significance was not attained (P = .071). The only side effects occurred in the EBD/OHA group: hypokalemia in 4/20 (20.0%) and apathy/somnolence in 1/20 (5.0%). CONCLUSIONS: An orally administered steroid/gel mixture might reduce the incidence of restenosis after EBD for benign esophageal stricture, but it requires confirmation by prospective trials.

A severe case of refractory esophageal stenosis induced by nivolumab and responding to tocilizumab therapy.

BACKGROUND: The prevalence of esophageal stenosis caused by immune checkpoint inhibitors in the context of induced immune mucositis and esophagitis is extremely rare. CASE PRESENTATION: We report the case of a patient with stage IV pulmonary adenocarcinoma treated for 6 months with nivolumab who developed bilateral sterile conjunctivitis followed by oropharyngeal mucositis and esophagitis complicated by a severe esophageal stenosis. The laryngeal margin and hypopharyngeal mucosa appeared highly inflammatory with fibrinous deposits. Esophagogastroduodenoscopy revealed mucositis with a scar-like structure immediately below the upper esophageal sphincter with nonulcerative mucosa and an inflammatory aspect of the entire esophagus. No involvement of the stomach was observed. Oropharynx biopsies displayed marked lymphocytic T cell-infiltration with several foci of monocellular necrosis in the squamous epithelium. No morphologic evidence of adenocarcinoma and no signs of mycotic, bacterial or viral infection were noted. A blood sample revealed a discrete increase in the erythrocyte sedimentation rate (ESR) with no eosinophilia or leukocytosis. Liver and kidney function panel tests were normal. A thoracoabdominal CT scan reported no evidence of disease recurrence. Despite multiple boluses of methylprednisolone and high doses of prednisone continued for several months, the patient experienced very rapid symptomatological reappearance during three steroid tapering attempts and aggravation of his esophageal stenosis to an aphagic stage, requiring a nasogastric tube. This long course of high-dose corticosteroid treatment was complicated with osteoporosis-induced fractures with several spontaneous compressions of thoracolumbar vertebrae requiring an enlarged T10 to L5 cementoplasty. Anti-IL-6 blockade therapy with tocilizumab resulted in excellent clinical response, allowing the total resolution of the immune-related adverse events (irAEs) and leading to successful steroid tapering. CONCLUSIONS: Herein, we describe the first case of a patient who developed autoimmune mucositis and esophagitis complicated by a severe refractory esophageal stenosis induced during treatment by nivolumab, which completely resolved after personalized treatment with tocilizumab, suggesting a role of IL-6 blockade in the management of severe steroid refractory esophageal stenosis and more broadly in refractory immune-related adverse events.

A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa - case report and literature review.

BACKGROUND: Epidermolysis bullosa (EB) constitutes a heterogenous group of rare multisystem genetically transmitted disorders comprising several blistering muco-cutaneous diseases with a monogenic basis and either autosomal dominant or autosomal recessive mode of inheritance. EB manifestation is not only limited to the skin. Systemic signs might involve the nose, ear, eye, genitourinary tract and upper gastrointestinal tract. The presence of particular symptoms is directly determined by a type of altered skin protein. Gastrointestinal manifestation of EB is most commonly reflected by esophageal stenosis due to recurrent esophageal blistering, followed by consequent scarring. CASE PRESENTATION: Here we present a case of a man with dystrophic EB and dysphagia, skin blistering, joints contractures and missing nails. To our knowledge, the presented man is the oldest one diagnosed with EB living in Poland. CONCLUSIONS: Management of an esophageal stricture in such circumstances is based on endoscopic dilatation. However, in most severe cases, placement of a gastrostomy tube is required. Despite great advances in medicine, a targeted therapy in the course of EB has not been established yet.

Topical Mitomycin C Application in Pediatric Patients with Recurrent Esophageal Strictures-Report on Unfavorable Results.

OBJECTIVE: Recurrent esophageal strictures (ESs) following esophageal atresia repair or caustic ingestion represent a common clinical problem. Recently, Mitomycin C was reported to improve the outcome of patients by reducing the number of endoscopic dilatations. However, other groups failed to exhibit a beneficial effect. We report on our experience with topic Mitomycin C application following endoscopic dilatation for recurrent ES. METHODS: Retrospective chart review of patients with ES treated at the Hannover Medical School (Location A) and the University of Leipzig (Location B) between 2009 and 2015. A Mitomycin C-soaked cotton swab was endoscopically placed at the area of stricture in all subjects. Successful treatment was defined as resolution of stricture after Mitomycin C therapy with not more than three dilatations thereafter. Our results were compared with published outcomes of alternative studies that involved 10 or more patients. RESULTS: A total of 11 children received Mitomycin C concurrently with endoscopic dilatations. Seven children (64%) had gross type C esophageal atresia, two patients (18%) gross type A esophageal atresia, and two children (18%) caustic injury.After a median follow-up of 34 months (range, 14-75 months) and a median number of 3 ± 2.5 dilatations with Mitomycin C application per patient (range, 1-9), 6 of 11 patients (55%) achieved a resolution of their strictures. Five patients (45%) did not respond to Mitomycin C therapy, of which two needed esophageal redo-surgery. CONCLUSION: We failed to confirm the high success rates of Mitomycin C treatment for recurrent ESs. Given the fact that there is limited data to prove the beneficial effect of Mitomycin C treatment, pediatric surgeons should carefully consider whether the advantages of this therapy outweigh the necessity of life-long endoscopic follow-ups. Further randomized controlled studies are recommended.