Caustic Esophageal Burns Research Articles

Outcomes of Colonic and Gastric Tube Transplants after Caustic Esophageal Burn in Children: A 33-Year Review.

Introduction: Accidental caustic burns of the esophagus in children represent a significant global health challenge, often necessitating esophageal reconstruction. The aim of this study is to compare the efficacy and morbidity related to esophagus replacement with colonic and gastric tube transplants in a pediatric population followed for caustic stenosis. Methods: This retrospective study was conducted at a tertiary pediatric surgery unit for children treated from January 1989 to December 2022. We compared colonic and gastric tube esophageal replacement. Short term (within 30 days) and mid-term outcomes and complications were reviewed. Statistical evaluation was considered using a Chi-square test for categorical data analysis. Results: A total of 124 children with caustic esophageal burns were included. Among them, 23 (18.5%) had a gastric tube transplant for esophagus replacement and 101 (81.5%) a colonic transplant. During surgical intervention, we found a significantly higher risk of complications when using a colonic transplant (34%, p < 0.001). There was no significant statistical difference in postoperative short term and mid-term complications between the two techniques. Twenty-six (26%) of the children required a reoperation, with a higher risk in the gastric tube transplant group (p < 0.001). Endoscopic dilatation after surgery was also performed on a higher number of children who had received a gastric tube transplant (p = 0.005). Overall, 97.6% recovered full normal oral feeding. Conclusions: We found that colonic and gastric tube replacement are both good options for pediatric esophageal replacement after a caustic injury and show effectiveness over time. Gastric tube transplants carried a slightly higher risk of reoperations and a higher number of dilatations post-surgery. However, our groups are not really comparable, due to the much higher number of colonic transplants. Both surgical options have to be considered during surgery, and the choice depends on the anatomy of the patient. Our future research will focus on assessing long term quality of life and the potential risk of neoplastic complications.

Utilization of chest tube as an esophagus stent in pediatric caustic injuries: A retrospective study.

BACKGROUNDThe management of caustic esophageal burns in the pediatric population has changed over the years, while the most optimal management with regards to effectiveness, availability, and cost-beneficent stays controvertible. AIMTo describe how to utilize a chest tube for esophageal stenting in pediatrics.METHODSData regarding the etiology, treatment, and complications of caustic injury in pediatrics over 10 years was collected retrospectively. Furthermore, data regarding the patient's follow-up who underwent esophageal chest tube (ECT) were collected. The ECT was prepared by carving a narrowed section in the chest tube while maintaining the radiopaque section. The ECT will then be positioned from the cricopharyngeal and exited through the nostril and fixed on the patient's cheek.RESULTSDuring the period of our study, data from 57 patients with an average age of 2.5 years (range 1-12; SD = 1.7) were obtained. The results showed that 89% of esophageal injury was due to alkaline and 9.4% were caused by acidic agents. The treatment methods showed that 29 patients (50.8%) recovered with dilatation alone. In 16 patients (28.06%), the esophageal repair was performed by using the colon, and in 5 patients (8.7%), other surgical methods were used and in 7 patients (12.2%), the ECT stents were used. ECT was inserted in 7 cases with a mean age of 2 (range: 1.5-3) years who were classified as grade IIB or III. Grading was performed by endoscopy assessment on the first day. Antibiotics and corticosteroids were administrated as initial medical management for all patients. ECT implantation was done during the first 8 d for 5 out of 7 cases (mean: 3.8 d). For the 2 patients, ECT was used after 27 (patient 6) d and 83 (patient 7) d. The reason for late stenting in these patients was a postponed referral to our center, in which patient 7 even received 4 dilation episodes before visiting our center. ECT was removed after an average of 44 d in the first 5 patients, while in the other 2 patients (6 and 7) was 2 and 1 wk, respectively. There was no complication related to, or failure of, stent placement. It is worth mentioning that none of the 7 ECT cases required gastrostomy or jejunostomy.CONCLUSIONThe ECT method introduced in our study can be used as a broadly available, economic, and easy-use facility for esophageal stenting, particularly in developing countries and emergency departments which have limited access to modern equipment. Further multicenter studies with higher volume patients are required for further deployment of this method.

The effect of melanin on the proteolytic potential of blood under alkali esophageal burn

Caustic esophageal burns are among serious medical problems of global significance. Due to a key role in biological processes proteolytic enzymes actively involved in the pathological mechanisms underpinning the development and progression of burn-related complications. Since melanin possesses a broad spectrum of biological activities we have investigated whether this compound can influence the proteolytic activity and level of proteinase inhibitors in the blood of rats with an alkali esophageal burn. Alkaline esophageal burns, which correspond to the first and second degree of burn, were induced by 10% and 20% NaOH, respectively. White, nonlinear, immature (4 weeks old) rats were used in the experiment. Total proteolytic activity was measured using casein as a substrate. The activities of α1- antitrypsin and α2-macroglobulin were measured considering the degree of inhibition of hydrolysis of N-benzoyl-L-arginineethyl ester. The fraction of serine proteinases was obtained by affinity chromatography on a benzamidine sepharose column. The qualitative composition of serine proteinases fraction was analyzed by zymography technique. According to the data obtained, the pathogenesis of alkaline esophageal burn is accompanied by a significant increase in the total proteolytic activity, activity of serine proteinases, and activity of α1-antitrypsin and α2-macroglobulin compared with the control rats. The present results clearly indicated that melanin is able to normalize the proteolytic homeostasis by affecting the activity of serine proteinases and the level of proteinase inhibitors in the plasma of rats with alkali esophageal burns.

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

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. In this study, 24 Wistar-albino rats were divided into 4 groups. CEB was initiated with an instillation of 1mL of 10% NaOH solution into the an isolated esophageal segment for 3min. 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 200mg/kg/d, respectively, of Contractubex® for 4weeks 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 4weeks after the experiment. 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. 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.

Halofuginone improves caustic-induced oxidative injury of esophagus in rats.

The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats. Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity. GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone. In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

Hypermetabolism Correlated with Subsequent Stricture Formation in Esophageal Caustic Burn Injury in Children

Objective: Hypermetabolism is commonly found in esophageal caustic injury. Our aim was to assess metabolic conditions in children after esophageal caustic burn and to investigate their outcome prediction with treatment impact. Design: Retrospective medical review study. Setting: One tertiary academic center. Patients: Children with caustic esophageal burn admitted to Chang Gung Children’s Hospital during 1993 to 2013 were enrolled and medically reviewed. Interventions: None. Measurements and Main Results: A score system based on clinical and metabolic condition with total 5 items and the highest score of 6 was designed and applied to predict esophageal stricture and medical assessment after corrosive injury. Using SAS system software version 8 for Windows, continuous and dichotomous variables were analyzed. A total of 57 children were enrolled during the 20-year period. High-grade esophageal burn was diagnosed in 36 patients (63%). Fourteen (24.6%) of them subsequently developed esophageal stricture formation. Thirteen of the 14 patients (92.9%) manifested at least 1 of the hypermetabolic signs. Statistical analysis showed significant risk factors for stricture were hyperthermia (P= 0.011), hyperglycemia (P=0.001), and high grade burn injury (P=0.001). By our scoring system, the positive prediction of stricture formation was: 3 of 4 patients (75%) scored 6, 6 of 10 patients (60%) scored 5 or higher, 11 of 20 patients (55%) scored 4 or higher, 14 of 29 patients (48%) scored 3 or higher, and 14 of 43 patients (33%) scored 2 or higher. Ten of the 30 patients (33%) treated with antibiotics and 11 of the 34 patients (32 %) given steroids finally developed esophageal stricture. Conclusions: Hypermetabolism is commonly found and correlated to subsequent esophageal stricture after caustic burn injury in children. The score system included metabolic factors provide an objective way for predict stricture formation. The application of corticosteroid should be carefully evaluated for its impact on hypermetabolism, risky for subsequent stricture formation.

Protective effect of early placement of nasogastric tube with solid dilator on tissue damage and stricture formation after caustic esophageal burns in rabbits

BackgroundThe ingestion of caustic substances remains an important public health issue worldwide. Children represent 80% of the ingestion injury population globally. Accidental alkaline material accounts for most caustic ingestions. There is no conclusive evidence of tissue damage and stricture protection of a nasogastric-tube with a solid dilator in the literature, therefore it was hypothesized that early intraesophageal tube placement does not cause additional histopathologic damage and prevents strictures. MethodsAn exploratory study on experimental caustic esophageal burns in a rabbit model was designed. In the treated group a silicone tube was placed immediately after causing the burns, while the untreated group followed the natural course of the burn. On the twenty-secondday, an esophagectomy was performed on all animals for microscopic (Histopathologic Damage Score and Stenosis Index) and macroscopic analysis. ResultsForty animals were randomly divided into two groups. The Histopathologic Damage Score was 3.7±1.1 in the treated group versus 3.9±1.2 in the untreated group (p=.9690). The Stenosis Index was 0.6±0.1 in treated rabbits versus 2.3±0.2 in untreated (p<.0001). ConclusionThe early placement of an intraesophageal tube with solid dilator prevents stenosis formation and does not produce greater tissue damage.

Pirfenidone prevents rat esophageal stricture formation

BackgroundAccidental ingestion of caustic substances induces esophageal injuries and stenosis formation. The main aim for acute phase treatment is to prevent esophageal stenosis. Pirfenidone (PFD) is a pyridone with antifibrotic and anti-inflammatory effects. Esophagus stenosis takes place after a strong inflammation process where proinflammatory and profibrogenic cytokines play an important role. The present study investigates the efficacy of PFD on the prevention of stricture development after esophageal caustic injuries in a rat model. Material and methodsCaustic esophageal burn was produced by application of 32% of NaOH to the distal esophagus of healthy rats. PFD in the form of 8% gel was administered at a dose of 200 mg/kg/d. Animals were divided in three experimental groups as follows: healthy rats, animals injured with NaOH without PFD treatment, and rats injured with NaOH and treated with PFD. Efficacy of the treatment was assessed by measuring image esophagoscopy and esophagography with contrast barium at the 21st d. Histology staining with Sirius-red was performed to evaluate collagen deposition and stenosis area. Gene expression of transforming growth factor β1, collagen-1, plasminogen activator inhibitor-1, connective tissue growth factor, and matrix metalloproteinase 2 were measured by quantitative reverse transcription polymerase chain reaction. ResultsThere was significant difference in means of stenosis by esophagoscopy and esophagogram. Collagen deposition in the damaged area increased significantly when rats were burned with NaOH, and decreased notably in PFD treated group. Profibrogenic key molecules transforming growth factor β1, collagen 1, plasminogen activator inhibitor-1 and connective tissue growth factor expression were significantly lower respect to control group without PFD treatment where matrix metalloproteinase 2 expression was no different in all groups. ConclusionsThis study suggests that PFD reduces stenosis on caustic esophageal burn by decreasing profibrogenic genes expression and ameliorates fibrosis significantly in the chronic phase.

Efficacy of keratinocyte growth factor (palifermin) for the treatment of caustic esophageal burns.

Current treatment strategies against the development of corrosive esophageal strictures remain unsatisfactory. Thus, the aim of the present study was to investigate the efficacy of keratinocyte growth factor, in the form of palifermin, for the prevention of stricture development following esophageal caustic injuries in a rat model. A total of 32 female Wistar albino rats were divided into four groups, which included the control (C), burn (B), steroid (S) and steroid plus palifermin (S/P) groups. An experimental corrosive esophageal burn model was established in the B, S and S/P groups. Weight gain was recorded and histopathological evaluation was performed for each group. Weight gain in the S and B groups was compared with the control group and statistically significant differences were observed. In addition, statistically significant differences in weight gain were observed between the S/P group and the B group. Histopathologically, statistically significant differences were identified with regard to submucosal collagen deposition, muscularis mucosa and tunica muscularis damage when comparing the B group with the C group. In addition, statistically significant differences were observed when comparing the S and S/P groups with the B group. Furthermore, significant submucosal collagen deposition and tunica muscularis damage were observed in the S group when compared with the S/P group. The stenosis indexes in the C and S groups were significantly lower compared with the B group. In addition, the stenosis index in the S/P group was significantly lower compared with the S group. To the best of our knowledge, the present study is the first to investigate the effect of palifermin on corrosive esophageal burns. The addition of palifermin to the corrosive esophageal burn standard treatment regimen was found to reduce the degree of fibrosis and ameliorate histopathological damage in an experimental model of corrosive esophagitis in rats.

High doses of methylprednisolone in the management of caustic esophageal burns.

Caustic substance ingestion in childhood is a public health issue in developing countries, and several management protocols have been proposed to prevent the resulting esophageal strictures. The role of corticosteroids in preventing corrosive-induced strictures is controversial. Our aim was to study the influence of high doses of corticosteroids in preventing esophageal strictures. Eighty-three children with a mean age of 4.10 6 2.63 years and with grade IIb esophageal burns (an esophagogastroscopy was performed within 24–48 hours of injury) due to corrosive substance ingestion were enrolled in our study between 2005 and 2008. Forty-two children (study group) received methylprednisolone (1 g/1.73 m2 per day for 3 days), ranitidine, ceftriaxone, and total parenteral nutrition. Forty-one children (control group) were administered the same regimen excluding methylprednisolone. Stricture development was compared between groups based on endoscopic and radiologic findings. During the endoscopic examination, stricture development was observed in 4 patients (10.8%) in the study group and in 12 patients (30%) in the control group. The difference was statistically significant (P = .038). The stricture development rate in the upper gastrointestinal system with barium meal was 14.3% and 45.0% in the study and control groups, respectively. The difference was statistically significant (P = .004). The duration of total parenteral nutrition was shorter in the study group compared with the control group (P = .001). High doses of methylprednisolone were well tolerated in the study group without any side effects. High doses of methylprednisolone used for the management of grade IIb esophageal burns may reduce stricture development.

The efficacy of mesenchymal stem cell transplantation in caustic esophagus injury: an experimental study.

Introduction. Ingestion of corrosive substances may lead to stricture formation in esophagus as a late complication. Full thickness injury seems to exterminate tissue stem cells of esophagus. Mesenchymal stem cells (MSCs) can differentiate into specific cell lineages and have the capacity of homing in sites of injury. Aim and Methods. We aimed to investigate the efficacy of MSC transplantation, on prevention of esophageal damage and stricture formation after caustic esophagus injury in rats. 54 rats were allocated into four groups; 4 rats were sacrificed for MSC production. Group 1, untreated controls (n: 10). Group 2, membrane labeled MSCs-treated rats (n: 20). Group 3, biodistribution of fluorodeoxyglucose labeled MSCs via positron emission tomography (PET) imaging (n: 10). Group 4, sham operated (n: 10). Standard caustic esophageal burns were created and MSCs were transplanted 24 hours after. All rats were sacrificed at the 21st days. Results. PET scan images revealed the homing behavior of MSCs to the injury site. The histopathology damage score was not significantly different from controls. However, we demonstrated Dil labeled epithelial and muscle cells which were originating from transplanted MSCs. Conclusion. MSC transplantation after caustic esophageal injury may be a helpful treatment modality; however, probably repeated infusions are needed.

Indwelling esophageal balloon catheter for benign esophageal stenosis in infants and children

Balloon dilatation of benign esophageal strictures is an established mode of therapy in adults and children. There remains a group of patients with refractory stenosis despite dilatation at regular intervals. An indwelling balloon catheter may offer an alternative. This is a retrospective study of 19 children who underwent esophagoscopy between 2004 and 2012 with placement of an indwelling balloon catheter for refractory esophageal stenosis. Total number of endoscopies, number of endoscopies with indwelling balloon catheter, as well as complications, reoperations, and mortality due to use of the balloon catheter were studied. Patient age ranged from 4 weeks to 15 years. The indwelling balloon catheter was used to treat refractory stenosis after corrective surgery of long gap esophageal atresia (n = 5), esophageal atresia with distal fistula (n = 2), refractory esophageal stenosis due to caustic esophageal burns (n = 7), reflux (n = 2), and stenosis of unknown cause (n = 3). With the indwelling balloon catheter in place, the mean number of endoscopies equalled four. Complications were restenosis after a symptom-free period for which a new indwelling balloon catheter was necessary (n = 3). Two others needed two to five additional dilations: balloon leakage requiring replacement (n = 7 in 5 patients), sputum retention (n = 1), and dislodgement (n = 5 in 4 patients). More importantly, there was no mortality or the need for any patient to undergo a surgical resection. The indwelling balloon catheter is safe to use and can be used by parents at home. More importantly it obviates the need for rethoracotomy/-scopy or esophageal replacement.

Preliminary study of efficacy of hyaluronic acid on caustic esophageal burns in an experimental rat model

BackgroundThe aim of this study was to investigate the effectiveness of hyaluronic acid on the prevention of esophageal damage and stricture formation after experimental caustic (alkaline) esophageal injury in rats. Materials and MethodsTwenty-one Wistar albino rats were randomly divided into three groups. A caustic esophageal burn was created following the Gehanno model: Group l (n=7) underwent operation, but no injury; Group 2 (n=7) was injured and left untreated; and Group 3 (n=7) was injured and treated with hyaluronic acid, first topically and then orally by gavage (2×0.3mL; 12.5mg/mL for 7days). The caustic esophageal burn was created by instilling 25% NaOH into the distal esophagus. All rats were euthanized on day 22 for evaluation. The efficacy of hyaluronic acid treatment was assessed histopathologically and biochemically via blood determination of the total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and sulfhydryl group (SH) and lipid hydroperoxidase (LOOH) levels. Statistical analyses were performed. ResultsWeight gain was significantly lower in Group 2 than in the other two groups (P<0.05). The mean stenosis index, histopathologic damage score, TAS, TOS, OSI, and SH and LOOH levels were higher in Group 2 than in the other two groups. The mean stenosis index, inflammation, TAS, SH and OSI in Group 2 were significantly different than those in the other two groups (P<0.05). ConclusionHyaluronic acid treatment is effective in treating damage and preventing strictures after caustic esophageal burn in rats.

The Effect of Beta-Aminopropionitrile and Prednisolone on the Prevention of Fibrosis in Alkali Esophageal Burns: An Experimental Study

Objective. The aim of this study was to investigate the efficacy of beta-aminopropionitrile (BAPN) and prednisolone on the prevention of esophageal damage and stricture formation after caustic esophageal burn. Method. Twenty-eight rats were divided into four equal groups. In groups 1, 2, and 3, caustic esophageal burns were generated by applying NaOH to the 1.5 cm segment of the abdominal esophagus. Group 4 was for the sham. Normal saline to group 1, BAPN to group 2, and prednisolone to group 3 were administered intraperitoneally as a single daily dose. Results. Treatment with BAPN decreased the stenosis index (SI) and histopathologic damage score (HDS) seen in caustic esophageal burn rats. The SI in group 4 was significantly lower compared with groups 1, 2, and 3. Group 2 had the minimum SI value in corrosive burn groups. The differences related to SI between groups 1, 2, and 3 were not statistically significant. The HDS was significantly lower in group 4 compared with groups 1, 2, and 3. The HDS in group 2 was significantly lower compared with groups 1 and 3. Conclusion. This study demonstrated that BAPN was able to decrease the development of stenosis and tissue damage better than prednisolone.

The efficacy of single-dose 5-fluorouracil therapy in experimental caustic esophageal burn

Introduction Accidental ingestion of caustic substances may cause serious problems in children. Approximately 20% of caustic ingestions result in esophageal stricture formation, resulting from excessive collagen synthesis to the extracellular matrix by fibroblasts. Recent studies showed that a single application of 5-fluorouracil (5-FU) is a very effective inhibitor of fibroblast proliferation and differentiation for prolonged periods. Using an experimental model, we investigated the efficacy of single-dose 5-FU on stricture formation after caustic esophageal burn. Materials and methods Forty Wistar-Albino rats were divided randomly into 4 equal groups: group 1 (sham-operated group), the esophagus was uninjured and untreated; group 2 (control group), the esophagus was injured and left untreated; group 3 (intraperitoneal treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraperitoneal dose (20 mg/kg) of 5-FU; group 4 (local treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraesophageal application of 5-FU at a concentration of 25 mg/mL. Caustic esophageal burn was produced by instilling 10% NaOH in the distal esophagus. The distal esophagi were harvested at 28 days postoperatively. Histologic sections were assessed by measuring the stenosis index (SI) and histopathologic damage score. Hydroxyproline (HP) levels in the tissues were determined biochemically. Results There were significant reductions in the SI ( P < .05), histopathologic damage score ( P < .05), and HP level ( P < .05) in the intraperitoneal treatment group when compared with the control group. No significant differences in the SI and histopathologic damage score were detected between the control and local treatment groups ( P > .05), whereas significant reduction in the HP level was determined between these groups ( P < .05). Conclusion A single intraperitoneal dose of 5-FU had a preventive effect on stricture formation after caustic esophageal burn. This observation suggests that 5-FU may prevent this undesirable complication in the clinical setting. Clinical studies are now required to verify this form of treatment. Local intraesophageal application of 5-FU immediately after the burn injury was not effective. Further investigations are required to determine the appropriate timing of application of 5-FU at the local site of injury.

Mercaptoethylguanidine attenuates caustic esophageal injury in rats: a role for scavenging of peroxynitrite

Introduction After ingestion of caustic material, tissue damage is caused by reactive oxygen species and reactive nitrogen species such as peroxynitrite. Mercaptoethylguanidine (MEG) is a well-known scavenger of peroxynitrite. This study was designed to determine whether MEG has a beneficial effect on caustic esophageal injury. Materials and Methods Forty-five rats were allocated into 3 groups: sham-operated, untreated, and treated groups. Caustic esophageal burn was created by instilling 15% NaOH in the distal esophagus. The rats were left untreated or treated with 10 mg/kg per day MEG intraperitoneally for 5 days. All rats were killed at 28 days. Efficacy of the treatment was assessed both histopathologically and biochemically. Results Of 15 rats, 6 (40%) died in the untreated group, and only 1 (7%) rat died in the treated group. The stenosis index (SI) and the histopathologic damage score were significantly lower in the MEG treatment group than the untreated group, which showed a correlation with tissue hydroxyproline level. In the untreated group, tissue oxidative stress parameters (malondialdehyde and protein carbonyl content) were significantly higher; and antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) were significantly lower. Administration of MEG ameliorated oxidative stress parameters and antioxidant enzyme activities. Urinary nitrate and nitrite levels increased in the treated and untreated groups in the first 3 days, suggesting increased nitrosative stress; but at the fourth day, nitrate and nitrite level reached control values in the treated group. Conclusion Peroxynitrites play an important role in the healing process of caustic esophagitis. As a peroxynitrites scavenger, MEG potentially might be a useful adjuvant agent in the treatment of esophageal caustic burn by modulating the antioxidant defense mechanism.

Effect of Stent Placement, Balloon or Cutting Balloon Dilatation on Stricture Formation after Caustic Esophageal Burn in Rats

This study aimed to evaluate the effects of stent placement prior to stricture development following caustic esophageal burn (CEB) in an animal model. The outcomes after stent placement were also compared with those after balloon dilatation and cutting balloon dilatation performed after stricture development. Groups were compared with regard to stricture development and weight loss. 40 rats were divided into 5 groups. CEB was created as described by Gehanno etal. In Group A (control) no CEB was performed and the esophagus was only rinsed with saline. Group B rats underwent CEB with no subsequent treatment. Group C rats underwent CEB followed by balloon dilatation in the 3 (rd) and 4 (th) week. Group D rats underwent CEB followed by cutting balloon dilatation in the 3 (rd) week. Group E rats underwent CEB with subsequent placement of a silicon stent in the same session. The animals were sacrificed in the 6 (th) week, and the stenosis index (SI), collagen deposition, and hydroxyproline (HP) levels were determined in the esophageal segments and statistically compared. Although weight loss occurred in Group C and Group B rats (238.87±15.95 g vs. 233.83±19.01 g), weight loss in Group C rats was less marked compared to Group B. Similarly, the SI in Group C was lower compared to that of Group B and the difference was statistically significant. Although there was no difference in weight between the rats in Group C and Group B before the procedure (p=0.318), there was statistically significant difference thereafter (p=0.002). The SI of Group D was also lower compared with that of Group B, and the difference was statistically significant. Weight gain in Group E rats was similar to that noted in Group A rats and was higher compared to Group B; this difference was statistically significant. The SI for Group E was lower compared to that of Group B. Stenting performed at the time of corrosive injury and cutting balloon dilatation performed after stricture formation had a positive effect with regard to SI and weight gain in an animal model.

Mercaptoethylguanidine Attenuates Caustic Esophageal Injury in Rats; A Role for Scavenging of Peroxynitrite

IntroductionAfter ingestion of caustic material, tissue damage is caused by reactive oxygen species and reactive nitrogen species. Mercaptoethylguanidine (MEG) is a scavenger of peroxynitrite. Thus, this study was designed whether MEG has a beneficial effect on caustic esophageal injury.Methods45 rats were allocated into 3 groups; sham‐operated, untreatment and treatment groups. Caustic esophageal burn was created by instilling 15% NaOH in the distal esophagus. The treatment group treated with 10 mg/kg/day MEG i.p. for 5 days. All rats were killed at 28 days. Efficacy of the treatment was assessed by histopathologically and biochemically.ResultsThe stenosis index and the histopathologic damage score were significantly lower in the MEG‐treatment group which showed a correlation with tissue hydroxyproline level. In the untreatment group, tissue oxidative stres parameters (malondialdehyde and protein carbonyl content) were significantly higher, antioxidant enzymes activities (SOD and GSH‐Px) were significantly lower than trreatment group. Urinary Nitrate and Nitrite (NOx) levels increased in the treatment and un‐treatment group at the first three days.ConclusionPeroxynitrites play an important role in the healing process of caustic esophagitis. MEG might be used a potential adjuvant agent in treatment of esophageal caustic burn by modulating antioxidant defense mechanism.

Protective Effects of Dexpanthenol and Y-27632 on Stricture Formation in a Rat Model of Caustic Esophageal Injury

This experimental study was conducted to investigate the effect of dexpanthenol (converted in the body to pantothenic acid) and Y-27632 (a selective Rho-kinase inhibitor) on stricture formation after caustic (alkaline) esophageal injury in rats. Sixty male Wistar albino rats were randomly allocated into six groups. In group 1 (sham) the distal esophagus was isolated and cannulated but no caustic injury was induced. In all remaining groups, a caustic esophageal burn was induced with 50% sodium hydroxide solution for 90 s and drug treatment was given by daily intraperitoneal injection, beginning 24 h after injury and continuing for 21 d. In group 2 (controls), animals were treated with 0.9% saline; in groups 3 and 4, with 50 and 500 mg/kg/d of dexpanthenol, respectively; and in groups 5 and 6, with 0.3 and 3 mg/kg/d of Y-27632, respectively. Rats were sacrificed 22 d after caustic injury and the distal esophagus was isolated for histopathology and biochemical investigation. Stenosis index and collagen deposition scores were significantly lower in both the dexpanthenol and Y-27632 treated groups (P<0.05). Dexpanthenol and Y-27632 treatment markedly depressed esophageal tissue malondialdehyde and hydroxyproline levels. In this experimental model of caustic esophageal stricture, dexpanthenol and Y-27632 significantly attenuated esophageal stricture formation. These findings indicate that inhibition of Rho-kinase or dexpanthenol administration may offer novel therapeutic approaches in the treatment of caustic esophageal injury.

Protective effects of ibuprofen against caustic esophageal burn injury in rats

The aim of this study was to investigate the efficacy of ibuprofen on the healing of esophagus and the prevention of stricture development after esophageal caustic injuries in rats. Rats were divided into three groups as: group 1(sham), group 2(esophageal burn injury), group 3(injury + ibuprofen). In groups 2 and 3, a standard esophageal burn injury was created by applying 10% NaOH solution to distal esophagus of about 3 cm. To rats in the sham group, isotonic solution was given instead of NaOH. Ibuprofen (90 mg/kg/day) was given via oral route to group 3 rats. Normal saline as placebo was given via the same route to rats in groups 1 and 2. 28 days later, all the live rats were killed. The distal esophageal segments of all rats were removed and divided into two equal parts for biochemical and histopathologic examination. In the tissue samples, biochemically hydroxyproline and histopathologically collagen content and stenosis indices were evaluated for efficacy of treatment. The hydroxyproline level (microg/mg wet tissue) in the groups was 1.54 +/- 0.08, 4.82 +/- 0.60, and 3.28 +/- 0.27, respectively. The hydroxyproline level increased significantly in group 2 compared with group 1 (P < 0.01). Although the hydroxyproline level was significantly increased in group 3 compared with group 1, it decreased significantly in group 3 compared with group 2 (P < 0.05) by treatment of ibuprofen. In group 3, the collagen content score (1.50 +/- 0.26) was significantly lower than in group 2 (2.62 +/- 0.37) (P < 0.05). The stenosis index was found as 0.37 +/- 0.02 in group 1, 0.84 +/- 0.02 in group 2, and 0.67 +/- 0.03 in group 3. The stenosis index in group 2 was significantly higher than group 1 and group 3 (P < 0.01). Although the stenosis index was significantly higher than in group 1, a significant decrease in stenosis index was found in group 3 compared with group 2, by ibuprofen treatment (P < 0.01). Based on these results, we concluded that the treatment with ibuprofen in acute phase esophageal burn injury has beneficial effects on healing of esophagus and may decrease the stricture formation. For these reasons, ibuprofen may effectively be used in the acute phase treatment of caustic esophagus injury and after esophageal dilatation procedures.