Gastric secretion in patients with caustic ingestion: A prospective study.

BACKGROUND: Caustic ingestion can lead to structural changes in the upper gastrointestinal tract. However, there are limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine the changes in gastric acid output in patients with caustic ingestion. METHODS: It was a prospective study done at a tertiary care center in northern India. Twenty consecutive patients in chronic phase of caustic ingestion were evaluated for the study. The gastric secretory function was estimated in the basal state and following pentagastrin stimulation. These results were compared with normal values for our laboratory. RESULTS: The mean age of the included patients (n = 20) was 27.35 ± 2.96 years and 14 patients were male. Sixteen (80%) patients had a history of acid ingestion. Patients with caustic ingestion had significantly lower mean gastric acid secretion (0.8 ± 0.4 mEq/h vs. 4 ± 0.4 mEq/h; p < 0.001) compared to controls. After pentagastrin stimulation, the mean gastric juice volume (31.8 ± 6 mL/h vs. 62.3 ± 11.7 mL/h; p < 0.01) and acidity (15.3 ± 5.1 mEq/L vs. 39.6 ± 9.3 mEq/L; p < 0.001) increased in patients with caustic ingestion, but were lower than those in control subjects. Patients with a lower esophageal stricture (n = 6) had decreased maximum acid output (0.62 ± 0.32 mEq/h vs. 6.05 ± 0.55 mEq/h; p < 0.05) compared to patients with stricture in the upper or middle esophagus. CONCLUSION: Caustic ingestion is associated with reduced gastric juice volume and acid output. Patients with stricture in the lower one third of the esophagus are at a higher risk of hypochlorhydria compared to patients with stricture in either the upper or middle esophagus.

Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions.

Eosinophilic esophagitis (EoE) is an antigen-driven disease associated with epithelial barrier dysfunction and chronic type 2 inflammation. Eosinophils are the defining feature of EoE histopathology but relatively little is known about their role in disease onset and progression. Classically defined as destructive, end-stage effector cells, eosinophils (a resident leukocyte in most of the GI tract) are increasingly understood to play roles in local immunity, tissue homeostasis, remodeling, and repair. Indeed, asymptomatic esophageal eosinophilia is observed in IgE-mediated food allergy. Interestingly, EoE is a potential complication of oral immunotherapy (OIT) for food allergy. However, we recently found that patients with peanut allergy may have asymptomatic esophageal eosinophilia at baseline and that peanut OIT induces transient esophageal eosinophilia in most subjects. This is seemingly at odds with multiple studies which have shown that EoE disease severity correlates with tissue eosinophilia. Herein, we review the potential role of eosinophils in EoE at different stages of disease pathogenesis. Based on current literature we suggest the following: (1) eosinophils are recruited to the esophagus as a homeostatic response to epithelial barrier disruption; (2) eosinophils mediate barrier-protective activities including local antibody production, mucus production and epithelial turnover; and (3) when type 2 inflammation persists, eosinophils promote fibrosis.

MicroRNA expression profiles in the esophagus of children with caustic stenosis: A pathway towards esophageal cancer?

BACKGROUND: Eighty percent of caustic ingestions occur in children and esophageal neoplasms may develop as a late complication of such injury. The identification of biomarkers is a promising strategy to improve early diagnosis of esophageal cancer or caustic lesions that are at an increased risk of progression. STUDY DESIGN/AIMS: This study aimed at identifying global microRNA (miRNA) expression changes in esophageal mucosa from children with caustic stenosis. The study included 27 biopsy samples from 15 patients. Samples were divided into two groups, according to the time elapsed after injury (N = 15 in Group A, with less than five years of follow-up and N = 12 in Group B, with more than five years of follow-up). miRNA expression profiles were determined in each lesion, compared with normal esophageal tissues from control group. We used the TaqMan Human MicroRNA Arrays (Thermo Fisher) platform. Furthermore, bioinformatic algorithms were used to identify miRNA target genes and biological pathways including miRNAs and their target genes potentially associated with esophageal disease. RESULTS: Thirteen miRNAs were significantly deregulated (9 over- and 4 underexpressed) in patients from Group A. In patients from Group B, two miRNAs were over- and two were underexpressed. Of note, miR-374 and miR-574 were deregulated in Group B patients and have been linked to esophageal tumorigenesis. We identified signal transduction and transcription factor networks with genes strongly related to development and progression of esophageal cancer. CONCLUSION: miRNAs identified here contribute to a better understanding of pathways associated with malignant transformation from caustic stenosis to neoplastic lesions. This study may serve as a basis for validation of miRNAs, including miR-374 and miR-574, as potential biomarkers of early cancer detection.

Congenital esophageal stenosis: a rare malformation of the foregut.

Congenital esophageal stenosis (CES) is a type of esophageal stenosis, and three histological subtypes (tracheobronchial remnants, fibromuscular thickening or fibromuscular stenosis, and membranous webbing or esophageal membrane) are described. Symptoms of CES usually appears with the introduction of the semisolid alimentation. Dysphagia is the most common symptom, but esophageal food impaction, respiratory distress or failure to thrive can be clinical manifestations of CES. Wide spectrum of differential diagnoses leads to delayed definitive diagnosis and appropriate treatment. Depends on hystological subtype of CES, some treatment procedures (dilation or segmental esophageal resection) are recommended, but individually approach is still important in terms of frequency and type of dilation procedures or type of the surgical treatment. Dysphagia can persist after the treatment and a long follow-up period is recommended. In 33% of patients with CES, a different malformations in the digestive system, but also in the other systems, are described.

Esophageal reconstruction using a pedicled jejunum following esophagectomy for metastatic esophageal stricture from breast cancer in a patient with previous pancreatoduodenectomy.

A 71-year-old woman with dysphagia was diagnosed with thoracic esophageal squamous cell carcinoma by endoscopic biopsy at another hospital. She had previously undergone partial breast excision with axillary lymph node dissection for right breast cancer eleven years earlier and subtotal stomach-preserving pancreatoduodenectomy with Child's reconstruction for ampullary cancer ten years earlier. Gastrointestinal endoscopy showed a stricture due to a bulging submucosal tumor in the mid-thoracic esophagus. The tumor was diagnosed as an esophageal metastasis from breast cancer by endoscopic ultrasound-guided fine-needle aspiration biopsy. After six courses of fulvestrant, the tumor progressed, completely impeding her ability to swallow. An esophagectomy was planned in a one-stage operation because of the expectation of a prolonged survival and her strong hope of regaining oral intake. Unfortunately, she underwent emergent omental patch repair for perforation of the gastrojejunostomy site due to an anastomotic ulcer one day before the scheduled operation. Due to postoperative impairment of her performance status, she subsequently underwent a two-stage esophageal operation. In the first surgical stage, prone position thoracoscopic esophagectomy and cervical esophagostomy were performed and she was discharged with enteral nutrition on postoperative day 15. Sixty-one days after the first surgical stage, esophageal reconstruction was performed using a pedicled jejunum with microvascular anastomosis via the subcutaneous route. She was discharged without any complications 20 days after the second operation.

Evaluation of the efficacy of Hypericum perforatum (St. John's wort) oil in the prevention of stricture due to esophageal corrosive burns.

BACKGROUND/PURPOSE: The inflammatory response that follows the caustic burns results in fibrosis on the esophageal wall leading to esophageal stricture, dysphagia, and malnutrition. The controversy over the use of corticosteroids warrants alternative therapeutic interventions. We investigated the effect of extracts from St. John's wort (SJW) with known wound-healing activity on stricture formation in rat esophageal injury models. METHODS: Five experimental groups were involved: sham group with no injury, control group with injury without treatment, and three different treatment groups (methylprednisolone, SJW extract, and combination of the two). Histopathological examination of esophageal damage and collagen accumulation, stenosis index, and tissue hydroxyproline levels were used to assess stricture and the effect of treatments. RESULTS: There was a significant weight loss in all groups except for those without injury and those treated with SJW extract, the latter gained weight albeit not significant. Stenosis index was increased in all groups compared to sham but not significantly in those treated with SJW extract. Histopathological and biochemical analyses produced mixed results. CONCLUSIONS: Some of the experimental indicators such as weight gain and stenosis index suggested the treatment of esophageal injury models using extracts of St. John's wort effective while other histopathological indicators show no significant benefit.

Adipose Tissue-Derived Stem Cell Sheet Application for Tissue Healing In Vivo: A Systematic Review.

Adipose tissue-derived stem cells (ASCs) are known to be tissue-healing promoters due to their cellular plasticity and secretion of paracrine factors. Cultured ASC sheets provide a novel method of ASC application and can retain ASCs at the targeted tissue. The purpose of this systematic review is to evaluate preclinical studies using ASC sheet transplantation therapy for promoting tissue healing. First, we searched databases to identify studies of ASC sheet therapy in different experimental animal models, and then determined the quality score of studies using SYRCLE's risk bias tool. A total of 18 included studies examined the role of ASC sheets on tissue healing and function in models for myocardial infarction, dilated cardiomyopathy, full-thickness skin wounds, hind limb ischemia, esophageal strictures, and oral ulcers. ASC sheet application after myocardial infarction improved survival rate, cardiac function, and capillary density and reduced the extent of fibrosis. Application of ASC sheets to a full-thickness skin wound decreased the wound size and stimulated wound maturation. In the hind limb ischemia model, ASC sheet application improved limb perfusion and capillary density, and decreased the amount of ischemic tissue and inflammation. ASC sheet application to mucosal wounds of the digestive tract accelerated wound healing and decreased the degree of stricture and fibrosis. Taken together, transplanted ASC sheets had a positive effect on tissue healing and reconstruction in these preclinical studies. The reported favorable effects of ASC sheet therapy in various tissue healing applications may be implemented in future translational studies. It is suggested that future preclinical animal model studies of ASC sheet therapy should concern standardization of culture techniques and investigate the mechanisms of action. In addition, clearly indicated experimental setups according to the SYRCLE's guidelines should improve study quality and validity.

Biodegradable stents for the treatment of refractory or recurrent benign esophageal stenosis.

INTRODUCTION: Esophageal stents are used for the treatment of refractory and recurrent dyphagias. In 2007, esophageal biodegradable stents (EBS) were authorised as an alternative to existing metal and plastic stents in Europe. The advantages claimed for EBS are fewer complications concerning tissue ingrowth, stent migration and stent removal. AREAS COVERED: We performed a systematic review to evaluate the efficacy and safety of EBS compared to fully-covered self-expanding metal stents, self-expanding plastic stents, and esophageal dilation for the treatment of refractory or recurrent benign esophageal stenosis. Three comparative studies (one randomized controlled trial and two cohort studies) were assessed. The studies used different inclusion criteria, had a very small (sample) size and the quality of the evidence was very low. Expert commentary: The current evidence is insufficient to determine the relative efficacy or safety of esophageal biodegradable stents. The results of this systematic review should be updated once new evidence is available.

[Not Available].

Introduction: Caustic ingestion (CI) in children and adolescents may lead to esophageal burns, esophageal stenosis and secondary dysphagia. These complications may limit the normal feeding process leading to malnutrition and growth impairment. Aims: Our aim was to evaluate the nutritional status and its association with dysphagia and esophageal stenosis in children with CI. Methods: Sixty-two patients with caustic ingestion treated at a pediatric referral hospital were included in this cross-sectional study. Independent variables were dysphagia/normal swallowing and esophageal stenosis/normal barium-swallow. The dependent variables were growth and nutritional status evaluated by anthropometry. Analysis: c2 test, OR, 95% CI, kappa test and Student's t-test. Results: The average age at the time of CI was 39.7 months; 38.7% of the patients were girls. Endoscopy performed upon admission revealed erosive esophagitis (II-b, III-a, and III-b) in 46 (77.8%) of the patients, dysphagia in twenty-four (38.7%) and esophageal stenosis in forty (64.5%). Both complications occurred simultaneously in 20 children (32.3%, kappa = 0.3, p = 0.014).The z-score of height-for-age was below -2 SD in five children (8.1%). The z score of body mass index (BMI) was < -2 SD in three children (4.8%) and it was above +1 SD in 24.2%. The z-score means of the arm anthropometric indicators of fat stores and muscle mass in both the dysphagia and esophageal stenosis groups were located in the negative area of the z-score curve and their values differed significantly from the z-scores of the non-dysphagia and non-stenosis groups. Conclusions: The proportion of erosive esophagitis, esophageal stenosis and dysphagia was high. Children with dysphagia and/or esophageal stenosis associated with CI had lower fat stores and muscle mass than the cases without esophageal complications.

Introducción: la ingestión de cáusticos (IC) en niños y adolescentes puede ocasionar esofagitis erosiva, estenosis esofágica y disfagia, entidades que pueden alterar el proceso de alimentación y originar desnutrición y retraso en el crecimiento. Objetivos: evaluar el estado nutricio de niños con IC y su asociación con disfagia y estenosis esofágica. Métodos: estudio transversal analítico en el que se incluyó a 62 niños atendidos en un hospital pediátrico de referencia que sufrieron IC. Lasvariables independientes fueron la presencia/ausencia de disfagia y/o estenosis esofágica; las dependientes fueron el crecimiento y el estado nutricio evaluados mediante antropometría. Análisis estadístico: c2, OR, IC 95%, kappa y t de Student. Resultados: la edad promedio fue 39,7 meses, el 39,7% eran niñas. Cuarenta y dos (77,8%) presentaron esofagitis erosiva (II-b, III-a, and III-b) en la endoscopia. En 24 (38,7%) ocurrió disfagia y en 40 (64,5%) estenosis esofágica. El puntaje z de la talla para la edad fue <-2 DE en cinco niños (8,1%) y el puntaje z del IMC < -2 DE en tres (4,8%). En 24.2% la z-IMC fue > +1 DE. El puntaje z de los indicadores del brazo relacionados a reservas grasa y masa muscular tanto en el grupo de estenosis como de disfagia se localizó en el lado negativo de la curva y ambos fueron significativamente menores a los del grupo sin disfagia o estenosis. Conclusiones: la proporción de esofagitis erosiva, estenosis o disfagia fue elevada. En los niños con disfagia o estenosis esofágica se identificaron reservas de grasa y masa muscular menores a las de los niños sin estas complicaciones.

Enfermedades esofágicas: enfermedad por reflujo gastroesofágico, Barrett, acalasia y esofagitis eosinofílica / Esophageal diseases: GERD, Barrett, achalasia and eosinophilic esophagitis

En la Digestive Disease Week 2014 se han presentado importantes novedades en patología esofágica. A destacar, respecto de la enfermedad por reflujo gastroesofágico, la utilidad de la impedanciometría para el diagnóstico de la enfermedad por reflujo, o la eficacia de los inhibidores de la bomba de protones para el tratamiento del dolor torácico no coronario. Respecto del esófago de Barrett, que su prevalencia es idéntica en pacientes con y sin síntomas de reflujo, que el < 1 cm probablemente no precisa seguimiento y que en pacientes de edad y con Barrett largo, la endoscopia inicial pasa por alto hasta un 2% de lesiones significativas. Respecto de la acalasia, la miotomía quirúrgica no es superior a la dilatación endoscópica y podría ser menos efectiva que la miotomía endoscópica peroral (POEM). Respecto de la esofagitis eosinofílica, es importante tomar biopsias sistemáticamente en pacientes con disfagia, para no pasar por alto casos de esofagitis eosinofílica y que, en esta patología, la dilatación endoscópica rutinaria no solamente no parece útil para mejorar el curso de la enfermedad, sino que incluso podría empeorar la respuesta al tratamiento médico

At Digestive Disease Week (DDW) 2014, developments in esophageal disease were presented. Highlights include: the usefulness of impedancemetry to diagnose reflux disease, or the effectiveness of PPIs for treating non-cardiac chest pain. Concerning Barrett's esophagus, its prevalence is identical in patients with and without reflux symptoms, Barrett segments less than 1cm probably do not require follow-up, and in older patients with long-segment Barrett, initial endoscopies overlooked up to 2% of significant lesions. Regarding achalasia, surgical myotomy is no more effective than endoscopic dilation and may even be less effective than peroral endoscopic myotomy (POEM). In terms of eosinophilic esophagitis, it is important to systematically take biopsies in patients with dysphagia so that cases of eosinophilic esophagitis are not overlooked. In addition, for this condition, routine endoscopic dilations not only do not seem useful in improving the course of the disease, but could also worsen the response to medical treatment

Effect of oral tamoxifen on the healing of corrosive oesophageal burns in an experimental rat model.

OBJECTIVES: Corrosive oesophagitis is a common health problem in children. Scar tissue can develop during the recovery period, and as a result, serious narrowing of the oesophagus can develop, in turn causing morbidity and mortality. In previous studies, it was argued that tamoxifen (TAM) may have antifibrotic effects beyond its oestrogen antagonist or agonist properties. We aimed to examine the possible effects of TAM on fibrosis and stricture formation, which are complications of corrosive oesophagitis. METHODS: Three study groups were formed as follows: a non-oesophageal burn group (NON-EB, n = 6), an oesophageal burn group (EB, n = 6) and an oesophageal burn + tamoxifen group (EB-TAM, n = 6). In the NON-EB rats, the oesophageal lumen was washed with 0.9% NaCl while, in the EB and EB-TAM rats, the distal oesophagus was burned with a 50% NaOH solution. After application of this solution to the EB-TAM group rats, 0.4 mg/kg/day of TAM was administered via gavage for 7 days. Twenty-two days later, the rat oesophagi were examined histopathologically for inflammation, granulation, collagen deposition and stenosis. RESULTS: In the EB group rats, the inflammation, collagen deposition and stenosis scores increased compared with those of the other groups. In the EB-TAM group, these three scores were lower compared with those of the EB group rats, but higher compared with those of the NON-EB group rats. No significant difference was observed in the granulation scores between the EB and EB-TAM groups. It was also observed that the EB-TAM group rats gained more weight than those in the EB group. CONCLUSIONS: According to the data obtained, TAM use prevents inflammation, collagenization and stricture development. TAM may be a useful medicine in the treatment of corrosive oesophagitis.

[Enteral nutrition in patients with ulcerative and postburn cicatrix strictures of the esophagus and stomach outcome region].

Decompensated cicatrices stricture of upper alimentary canal is a complex disease clinically presenting a high mechanical blocking and leads to expressed abnormality of homeostasis, which requires its pathogenetic correction of urgency evidence. The greatest difficulty is correct protein-energy malnutrition and water-electrolyte metabolism. Prior to the imposition of stoma for feeding should begin immediately with standard parenteral nutrition solutions. In a subsequent it is nessesary to resort more physiologecal tube alimentasion. As with esophageal postambustion stricture electrical activity of the stomach inhibiting and in essentially remains small bowel function, preference should be given to ways of enteral threpsology support. This can be used as a balanced composition in breeding (primary breeding should be 1: 2) and special blends for intraintestinal alimentation (close chyme on line carrying the major components). In the case of postambustion struck of outlet termination stomach department when identified violations of the underlying functions of the digestive canal division, rational come to gentle tactics of enteral alimentation using mixtures, completely similar in composition to himus. At stricture janitor ulcer genesis appropriate tactics is enteral correction, similar to that used in the event of postambustion strictures of the zones when bowel function is largely preserved.

Prevention of stricture development after corrosive esophageal burn with a modified esophageal stent in dogs.

OBJECTIVE: We sought to test the feasibility and technical ease of a newly designed nitinol-based modified esophageal stent and its effects on preventing postcaustic stricture in mongrel dogs and to try to explain the result at the molecular level. METHODS: Twenty-four dogs were included in this controlled study. Stenosis index (wall thickness/intraluminal diameter), pathologic features, hydroxyproline quantities, esophageal compliance, and biomechanics were compared between the injured but unstented and stented dogs. Transforming growth factor beta1, Sma/Mad (Smad)3, and Smad7 mRNA expression and protein levels in esophageal tissue were detected by means of reverse transcriptase-polymerase chain reaction and Western blotting, respectively. RESULTS: The modified esophageal stent was able to be placed and retrieved successfully and conveniently and was not only intact but there was also no macroscopic esophageal mucosal injury after the stent removal 4 months later. In comparison with the injured but unstented group, esophageal compliance, biomechanics, and the stenosis index were significantly better in the stented group. Histopathologic study revealed that collagen bundles were thinner and its orientation tended toward a regular and parallel pattern. Transforming growth factor beta1 and Smad3 mRNA expression and protein levels increased and Smad7 mRNA expression and protein levels decreased significantly in esophageal tissue in the stented group. These variables showed no statistically significant difference 2 months after stent removal. CONCLUSIONS: The modified esophageal stent might be a promising stent in preventing stricture formation after corrosive esophageal burns clinically.

Role of allopurinol on oxidative stress in caustic burn: cure for stricture?

An experimental study was conducted to investigate the effects of allopurinol, which inhibits the enzyme xanthine oxidase, on oxidative stress and on the prevention of stricture development after esophageal caustic injuries in rat. A randomized controlled study was conducted and 60 Wistar albino rats were divided into 6 equal groups, three groups for the acute phase and 3 groups for the chronic phase. Caustic esophageal burn was created by application of 37.5% NaOH to the distal esophagus. Allopurinol was administered at 40 mg/kg daily. Efficacy of the treatment for the acute phase was assessed by measuring tissue malondialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) at the 3rd day; and for the chronic phase by determining tissue hydroxyproline content and histopathologic damage score at the 28th day. We found an increase in XO, MDA and GSH levels and a decrease in NO levels in the acute phase. Allopurinol reinstated the increase in XO significantly, while MDA, GSH and NO levels were reinstated insignificantly. There was no significant difference in means of tissue hydroxyproline content. Histopathologic damage scores were significantly lower in the allopurinol treated group. This study, which is to our knowledge, the first in the literature investigating the influence of allopurinol on caustic esophageal burn, reveals that allopurinol effects MDA, GSH and NO levels insignificantly in the acute phase of caustic esophageal burn and decreases fibrosis significantly in the chronic phase.

[Restoration of nutritional status in patients with complicated course of ulcer during preoperative period]. / Vosstanovlenie pitatel'nogo statusa u patsientov s oslozhnennym techeniem iazvennoi bolezni v predoperatsionnom periode.

The comparative analysis of the efficiency of the enteral tube feeding and parenteral feeding in 52 patients with the subcompensated stenosis of the pylorus was carried out. Satisfactory results were received in all groups of patients taking enteral and parenteral feeding. Consequently, the differences in the parameters of the catabolic index and general protein in the patients taking balanced food mixes rich in calories and 'usual feeding' were statistically significant. Complications caused by enteral tube feeding were observed in 23.3%. None of the patients having such complications required food suspension. The frequency and significance of such complications were higher (54.5%) in the group of the patients taking parenteral feeding. This study has shown that the enteral tube feeding is just as efficient as the parenteral feeding. Besides, the enteral tube feeding is characterized by less significant side effects and is more cost-efficient.

Restenosis following balloon dilation of benign esophageal stenosis.

AIM: To elucidate the mechanism of restenosis following balloon dilation of benign esophageal stenosis. METHODS: A total of 49 rats with esophageal stenosis were induced in 70 rats using 5 ml of 50% sodium hydroxide solution and the double-balloon method, and an esophageal restenosis (RS) model was developed by esophageal stenosis using dilation of a percutaneous transluminal coronary angioplasty (PTCA) balloon catheter. These 49 rats were divided into two groups: rats with benign esophageal stricture caused by chemical burn only (control group, n=21) and rats with their esophageal stricture treated with balloon catheter dilation (experimental group, n=28). Imaging analysis and immunohistochemistry were used for both quantitative and qualitative analyses of esophageal stenosis and RS formation in the rats, respectively. RESULTS: Cross-sectional areas and perimeters of the esophageal mucosa layer, muscle layer, and the entire esophageal layers increased significantly in the experimental group compared with the control group. Proliferating cell nuclear antigen (PCNA) was expressed on the 5th day after dilation, and was still present at 1 month. Fibronectin (FN) was expressed on the 1st day after dilation, and was still present at 1 month. CONCLUSION: Expression of PCNA and FN plays an important role in RS after balloon dilation of benign esophageal stenosis.

Polyunsaturated phosphatidylcholine lowers collagen deposition in a rat model of corrosive esophageal burn.

Esophageal strictures are characterized by excess deposition of collagen in the esophageal wall. Polyunsaturated phosphatidyl-choline (PPC) stimulates collagen breakdown in experimental models of liver cirrhosis and colitis. This study was done in order to investigate the therapeutical effect of PPC in preventing esophageal strictures due to alkali-induced esophageal burns in rats. Fifty-five albino rats were divided into four groups as follows: control group (Group A, 10 rats), rats with sham operation and treated with saline (Group B, 15 rats), rats with esophageal burns only (Group C, 15 rats), and PPC-fed rats with esophageal burns (Group D, 15 rats). A standard esophageal burn was produced as described by Gehanno. PPC was administered orally to Group D rats in doses of 100 mg/day for four weeks. All animals were sacrificed on the 28th day of the experiment. Hydroxyproline levels in esophageal tissue was determined in each rat, and histopathologic evaluation was performed for each group. Hydroxyproline levels were significantly lower in the PPC-fed rats than in the rats with pure esophageal burns (p < 0.001). Histopathologically, collagen deposition in the submucosa and tunica muscularis was lower in Group D rats (PPC-fed rats with esophageal burn) than Group C rats (pure esophageal burn) (p < 0.05). As a result of our study, we concluded that PPC has an ameliorating effect on stricture formation after alkali-induced corrosive esophageal burns in rats.

Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD2-PL) gene therapy.

Radiation of the esophagus of C3H/HeNsd mice with 35 or 37 Gy of 6 MV X rays induces significantly increased RNA transcription for interleukin 1 (Il1), tumor necrosis factor alpha (Tnf), interferon gamma inducing factor (Ifngr), and interferon gamma (Ifng). These elevations are associated with DNA damage that is detectable by a comet assay of explanted esophageal cells, apoptosis of the esophageal basal lining layer cells in situ, and micro-ulceration leading to dehydration and death. The histopathology and time sequence of events are comparable to the esophagitis in humans that is associated with chemoradiotherapy of non-small cell lung carcinoma (NSCLC). Intraesophageal injection of clinical-grade manganese superoxide dismutase-plasmid/liposome (SOD2-PL) 24 h prior to irradiation produced an increase in SOD2 biochemical activity in explanted esophagus. An equivalent therapeutic plasmid weight of 10 microgram ALP plasmid in the same 500 microliter of liposomes, correlated to around 52-60% of alkaline phosphatase-positive cells in the squamous layer of the esophagus at 24 h. Administration of SOD2-PL prior to irradiation mediated a significant decrease in induction of cytokine mRNA by radiation and decreased apoptosis of squamous lining cells, micro-ulceration, and esophagitis. Groups of mice receiving 35 or 37 Gy esophageal irradiation by a technique protecting the lungs and treating only the central mediastinal area were followed to assess the long-term effects of radiation. SOD2-PL-treated irradiated mice demonstrated a significant decrease in esophageal wall thickness at day 100 compared to irradiated controls. Mice with orthotopic thoracic tumors composed of 32D-v-abl cells that received intraesophageal SOD2-PL treatment showed transgenic mRNA in the esophagus at 24 h, but no detectable human SOD2 transgene mRNA in explanted tumors by nested RT-PCR. These data provide support for translation of this strategy of SOD2-PL gene therapy to studies leading to a clinical trial in fractionated irradiation to decrease the acute and chronic side effects of radiation-induced damage to the esophagus.

Reactive oxygen radical levels in caustic esophageal burns.

PURPOSE: This study was designed to determine the tissue levels of reactive oxygen radicals in caustic esophageal burns in a rat model. METHODS: Forty rats were divided into four groups of 10 animals each. The control rats were uninjured in group A, and the others were injured rats in groups B, C, and D. Through a median laparatomy incision, a 1.5-cm abdominal esophageal segment was isolated and tied with 2-0 chromic sutures in all groups as described by Gehanno. One milliliter of 10% sodium hydroxide solution in groups B, C, and D and 0.9% saline solution in group A were instilled through the isolated segment via a no. 24 cannula for 3 minutes, then the esophagus was rinsed for 1 minute with distilled water. The studied 1.5 cm of the abdominal esophagus was removed from each animal 24 hours after caustic injury in group B, 48 hours after in group C, and 72 hours after in group D. In group A, studied uninjured segments were removed for biochemical investigation. Tissue malondialdehyde (MDA) and glutathione (GSH) levels were determined for each group. RESULTS: The mean MDA levels in esophageal tissue were significantly higher in groups B, C, and D than in group A (P < .05). Moreover, the mean GSH levels in the same esophageal tissues were significantly lower in groups C and D than in groups A and B (P < .05). CONCLUSION: The reactive oxygen radicals may be play an important role in early phase of caustic esophageal burns by increasing the tissue damage.

[Enteral infusion-nutritional correction of homeostasis in patients with postburn cicatricial stenosis of the esophagus and stomach]. / Enteral'naia infuzionno-nutritivnaia korrektsiia gomeostaza u bol'nykh s postozhogovymi rubtsovymi suzheniiami pischevoda i zheludka.

The metabolic status was studied in 67 patients with postburn cicatricial strictures of the esophagus (39) and of the pyloric part of the stomach (28). The aim of the work was to find the methods of enteral nutrition with special mixtures. The composition of the mixtures must be close to that of the chyme. In addition to changes of the standard parameters (pH, enzymatic and electrical activity) the assessment of the state of the digestive tract included the estimation and description of certain disorders in the system of heterophasic hydrolysis in the gastrojejunal tract (enzyme activity in fractions of the duodenal juice, enzyme sorption on the flocular structures) in the both categories of the patients. The authors recommend to treat such patients with the special mixtures "Nutrichim" or using the new corrector "Flokozim".