Necrosis esofágica aguda (esófago negro) asociado a neoplasias digestivas / Acute esophageal necrosis (black esophagus) associated with digestive neoplasms

INTRODUCCIÓN. La necrosis esofágica aguda es un síndrome raro que se caracteriza endoscópicamente por una apariencia negra circunferencial irregular o difusa de la mucosa esofágica intratorácica, la afectación es generalmente del esófago distal y la transición abrupta de mucosa normal en la unión gastroesofágica, con extensión proximal variable. CASOS. Se presentan dos casos con diferentes comorbiliades, presentación de signos y síntomas, antecedentes y tratamiento, teniendo en común el diagnóstico a través de endoscopía digestiva alta. RESULTADOS. Caso clínico 1: tratamiento clínico basado en hidratación, suspensión de vía oral, omeprazol intravenoso y sucralfato; mala evolución clínica caracterizada por: disfagia, intolerancia oral y recurrencia del sangrado digestivo alto, se realiza colocación de gastrostomía endoscópica. Caso clínico 2: esófago con mucosa con fibrina y parches de necrosis extensa, se realiza compensación tanto de foco infeccioso pulmonar como hidratación y nutrición, en estudios complementarios se observa masa colónica, con estudio histopatológico confirmatorio de adenocarcinoma de colon en estado avanzado. DISCUSIÓN. La esofagitis necrotizante aguda es una entidad inusual, de baja prevalencia e incidencia, asociada con estados de hipoperfusión sistémica y múltiples comorbilidades que favorezcan un sustrato isquémico. Al revisar los reportes de casos que hay en la literatura médica, los casos que reportamos se correlaciona con las características clínicas, epidemiológicas, endoscópicas y factores de riesgo causales de la enfermedad. La presentación clínica más frecuente es el sangrado digestivo alto, que se debe correlacionar con el hallazgo endoscópico clásico. Nuestro primer caso reportado termina con la colocación de una gastrostomía para poder alimentarse. CONCLUSIÓN. El pronóstico de la necrosis esofágica aguda es malo y se requiere un alto índice de sospecha clínica y conocimiento de esta infrecuente patología para un diagnóstico temprano y un manejo oportuno. Se requiere una evaluación por endoscopia digestiva alta. Es una causa de sangrado gastrointestinal que conlleva tasas altas de mortalidad, principalmente en adultos mayores frágiles. El reconocimiento temprano y la reanimación agresiva son los principios fundamentales para un mejor resultado de la enfermedad.

INTRODUCTION. Acute esophageal necrosis is a rare syndrome that is characterized endoscopically by an irregular or diffuse circumferential black appearance of the intrathoracic esophageal mucosa, the involvement is generally of the distal esophagus and the abrupt transition of normal mucosa at the gastroesophageal junction, with variable proximal extension. CASES. Two cases are presented with different comorbidities, presentation of signs and symptoms, history and treatment, having in common the diagnosis through upper gastrointestinal endoscopy. RESULTS. Clinical case 1: clinical treatment based on hydration, oral suspension, intravenous omeprazole and sucralfate; poor clinical evolution characterized by: dysphagia, oral intolerance and recurrence of upper digestive bleeding, endoscopic gastrostomy placement was performed. Clinical case 2: esophagus with mucosa with fibrin and patches of extensive necrosis, compensation of both the pulmonary infectious focus and hydration and nutrition is performed, in complementary studies a colonic mass is observed, with a confirmatory histopathological study of colon adenocarcinoma in an advanced state. DISCUSSION. Acute necrotizing esophagitis is an unusual entity, with low prevalence and incidence, associated with states of systemic hypoperfusion and multiple comorbidities that favor an ischemic substrate. When reviewing the case reports in the medical literature, the cases we report correlate with the clinical, epidemiological, endoscopic characteristics and causal risk factors of the disease. The most common clinical presentation is upper gastrointestinal bleeding, which must be correlated with the classic endoscopic finding. Our first reported case ends with the placement of a gastrostomy to be able to feed. CONCLUSION. The prognosis of acute esophageal necrosis is poor and a high index of clinical suspicion and knowledge of this rare pathology is required for early diagnosis and timely management. Evaluation by upper gastrointestinal endoscopy is required. It is a cause of gastrointestinal bleeding that carries high mortality rates, mainly in frail older adults. Early recognition and aggressive resuscitation are the fundamental principles for a better outcome of the disease.

Daidzein ameliorates experimental acute reflux esophagitis in rats via regulation of cytokines.

Context: Daidzein is a secondary metabolite derived from plants, has a flavonoid structure and is known for its protective activity in gastrointestinal disorders. Objective: The current work determines the preventive effect of daidzein against injury in the esophagus mucosa induced by esophageal reflux (RE) in an animal model. Methods: Adult male Wistar rats were classified into six groups: normal control, ER + different doses of daidzein and ER + omeprazole. RE was induced in all animals except controls and supplemented with daidzein and standard drugs orally for 6 hours. Serum and tissue were used for further biochemical parameters. Results: Daidzein as a flavonoid has antioxidant properties and shows in vitro antioxidant activity. The outcomes also reveal an elevation in lipid peroxidation and a decline in the levels of sulphhydryl groups and glutathione, along with the depletion in the activities of enzymatic antioxidants in the oxidative stress state. In a dose-dependent manner daidzein and omeprazole amended all macroscopic and biochemical variations and protected against the raised level of hydrogen peroxide (H2O2), calcium and free iron levels in esophageal tissue induced during RE. It also improved the expression and level of proinflammatory cytokines. Conclusion: The finding reports that daidzein has a potential to show a shielding effect against esophagus damage induced by RE in rats, at least in part via alteration of inflammatory cytokines.

Wide Area Transepithelial Sampling with Computer-Assisted Analysis (WATS3D) Is Cost-Effective in Barrett's Esophagus Screening.

BACKGROUND: Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance. AIMS: To examine the cost-effectiveness of adding WATS3D to the Seattle protocol in screening patients for BE. METHODS: A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS3D. The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year. RESULTS: Between 320 and 337 people would need to be screened with WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY. CONCLUSIONS: Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.

Protective and regenerative effects of a novel medical device against esophageal mucosal damage using in vitro and ex vivo models.

Gastroesophageal reflux disease (GERD) is a common digestive disorder that causes esophagitis and injuries to the esophageal mucosa. GERD symptoms are recurrent during pregnancy and their treatment is focused on lifestyle changes and nonprescription medicines. The aim of this study was to characterize the mechanism of action of a new patented medical device, an oral formulation containing hyaluronic acid, rice extract, and amino acids dispersed in a bioadhesive polymer matrix, by assessing its protective effects in in vitro and ex vivo models of esophageal mucosa damage. Acidic bile salts and pepsin cocktail (BSC) added to CP-A and COLO-680 N esophagus cells were used as an in vitro GERD model to evaluate the binding capacities, anti-inflammatory effects and reparative properties of the investigational product (IP) in comparison to a viscous control. Our results showed that the IP prevents cell permeability and tight junction dysfunction induced by BSC. Furthermore, the IP was also able to down-regulate IL-6 and IL-8 mRNA expression induced by BSC stimulation and to promote tissue repair and wound healing. The results were confirmed by ex vivo experiments in excised rat esophagi through the quantification of Evans Blue permeability assay. These experiments provided evidence that the IP is able to bind to the human esophagus cells, preventing the damage caused by gastroesophageal reflux, showing potential anti-irritative, soothing, and reparative properties.

Weak acids induce PGE2 production in human oesophageal cells: novel mechanisms underlying GERD symptoms.

The role of weak acids with pH values in the range of 4-7 has been implicated in the symptoms of gastroesophageal reflux disease (GERD). Prostaglandin E2 (PGE2) is associated with heartburn symptom in GERD patients; however, the precise productive mechanisms remain unclear. In this study, we revealed that exposure to weak acids increases PGE2 production with a peak at pH 4-5, slightly in human normal oesophageal cells (Het-1A), and robustly in oesophageal squamous carcinoma cells (KYSE-270). Release of PGE2 from the oesophageal mucosa was augmented by weak acid treatment in rat. Chenodeoxycholic acid (CDCA), a bile acid, upregulated cyclooxygenase-2 (COX-2) expression in Het-1A and KYSE-270 and induced PGE2 production in KYSE-270 cells. Weak acid-induced PGE2 production was significantly inhibited by cytosolic phospholipase A2 (cPLA2), ERK, and transient receptor potential cation channel subfamily V member 4 (TRPV4), a pH-sensing ion channel, inhibitors. Hangeshashinto, a potent inhibitor of COX-2, strongly decreased weak acid- and CDCA-induced PGE2 levels in KYSE-270. These results indicated that weak acids induce PGE2 production via TRPV4/ERK/cPLA2 in oesophageal epithelial cells, suggesting a role in GERD symptoms like heartburn. Interventions targeting pH values up to 5 may be necessary for the treatment of GERD.

In Barrett's epithelial cells, weakly acidic bile salt solutions cause oxidative DNA damage with response and repair mediated by p38.

The frequency of esophageal adenocarcinoma is rising despite widespread use of proton pump inhibitors (PPIs), which heal reflux esophagitis but do not prevent reflux of weakly acidic gastric juice and bile in Barrett's esophagus patients. We aimed to determine if weakly acidic (pH 5.5) bile salt medium (WABM) causes DNA damage in Barrett's cells. Because p53 is inactivated frequently in Barrett's esophagus and p38 can assume p53 functions, we explored p38's role in DNA damage response and repair. We exposed Barrett's cells with or without p53 knockdown to WABM, and evaluated DNA damage, its response and repair, and whether these effects are p38 dependent. We also measured phospho-p38 in biopsies of Barrett's metaplasia exposed to deoxycholic acid (DCA). WABM caused phospho-H2AX increases that were blocked by a reactive oxygen species (ROS) scavenger. WABM increased phospho-p38 and reduced bromodeoxyuridine incorporation (an index of S phase entry). Repair of WABM-induced DNA damage proceeded through p38-mediated base excision repair (BER) associated with reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease I (Ref-1/APE1). Cells treated with WABM supplemented with ursodeoxycholic acid (UDCA) exhibited enhanced p38-mediated responses to DNA damage. All of these effects were observed in p53-intact and p53-deficient Barrett's cells. In patients, esophageal DCA perfusion significantly increased phospho-p38 in Barrett's metaplasia. WABM exposure generates ROS, causing oxidative DNA damage in Barrett's cells, a mechanism possibly underlying the rising frequency of esophageal adenocarcinoma despite PPI usage. p38 plays a central role in oxidative DNA damage response and Ref-1/APE1-associated BER, suggesting potential chemopreventive roles for agents like UDCA that increase p38 activity in Barrett's esophagus.NEW & NOTEWORTHY We found that weakly acidic bile salt solutions, with compositions similar to the refluxed gastric juice of gastroesophageal reflux disease patients on proton pump inhibitors, cause oxidative DNA damage in Barrett's metaplasia that could contribute to the development of esophageal adenocarcinoma. We also have elucidated a critical role for p38 in Barrett's metaplasia in its response to and repair of oxidative DNA damage, suggesting a potential chemopreventive role for agents like ursodeoxycholic acid that increase p38 activity in Barrett's esophagus.

Acute chest pain and esophageal mucosal injury following an extreme yoga position Case report.

A young lady complained of the sudden onset of intense chest pain, in consequence of an extreme hyperextension of the back in a yoga position. At endoscopy a large lesion of the esophageal epithelium was detected, involving the middle third of the anterior wall of the esophagus. Other symptoms reported by the patient were dysphagia and odynophagia, depicting the typical features of intramural hematoma, also known as intramural dissection or intramural perforation of the oesophagus. The patient was managed conservatively and symptoms disappeared within a week. A barium swallow at six months reported normal findings. Different types of accidents occurring during yoga practice are reported in the literature, mainly involving musculoskeletal or nervous systems. Visceral lesions are exceptional and no similar cases have been reported in the literature. KEYWORDS: Acute chest pain, Esophageal lesion, Intramural hematoma, Management of esophageal lesion.

Development of a Mucoadhesive and an in Situ Gelling Formulation Based on κ-Carrageenan for Application on Oral Mucosa and Esophagus Walls. II. Loading of a Bioactive Hydroalcoholic Extract.

The aim of the present work was to load a Hibiscus sabdariffa (HS) hydroalcoholic extract into in situ gelling formulations for the treatment of oral mucositis and esophagitis. Such formulations, selected as the most promising options in a previous work of ours, were composed by κ-carrageenan (κ-CG), a sulfated marine polymer able to gelify in presence of saliva ions, hydroxypropyl cellulose (HPC), used as mucoadhesive agent, and CaCl2, salt able to enhance the interaction κ-CG/saliva ions. HS extract, which is rich in phytochemicals such as polyphenols, polysaccharides and organic acids, was selected due to its antioxidant and anti-inflammatory properties. For HS extraction, three different methodologies (maceration, Ultrasound Assisted Extraction (UAE) and Microwave Assisted Extraction (MAE)) were compared in terms of extraction yield and extract antioxidant activity, revealing that MAE was the best procedure. Rheological and mucoadhesive properties of HS-loaded formulations were investigated. Such formulations were characterized by a low viscosity at 25 °C, guaranteeing an easy administration, a proper in situ gelation behavior and marked elastic and mucoadhesive properties at 37 °C, functional to a protective action towards the damaged mucosa. Finally, the biocompatibility and the proliferative effect of HS-loaded formulations, as well as their antioxidant and anti-inflammatory properties, were proved in vitro on human dermal fibroblasts.

A pilot study of the impact of Vitamin C supplementation with neoadjuvant chemoradiation on regulators of inflammation and carcinogenesis in esophageal cancer patients.

AIMS: Vitamin C plays a role in chemoprevention in cancer treatment, and Vitamin C modulates many regulators of inflammation in in vitro studies. The aim of this study is to assess the effect of Vitamin C supplementation with neoadjuvant chemoradiation in esophageal adenocarcinoma on the nuclear factor-kappa B (NF-κB) and associated cytokines. MATERIALS AND METHODS: A total of 20 patients undergoing multimodal treatment for esophageal adenocarcinoma were randomized to receive Vitamin C (1000 mg/day) orally for 4 weeks or no supplementation. Pre- and post-Vitamin C endoscopic biopsies were used for the study of NF-κB activity and cytokine analysis. RESULTS: NF-κB activity along with cytokines was activated in the cancer tissue pretreatment. Down-regulation in NF-κB activity was observed in 25% of cases, two from the Vitamin C arm posttreatment. There was a significant reduction in cytokines levels in the cancer group, and this effect was more pronounced in the Vitamin C group (P < 0.05). CONCLUSIONS: Vitamin C supplementation had a mild protective effect in modulating of regulators of inflammation and carcinogenesis. Further studies with larger numbers of endpoints are needed to evaluate its effect on modulation of chemoradiation responses.

Germination of pollen grains in the oesophagus of individuals with eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) is characterized by oesophageal dysfunction and, histologically, by eosinophilic inflammation. There is no a clear aetiologic treatment. EoE exacerbations are often seasonal. We hypothesized that the inflammatory response of the oesophageal mucosa in patients with high levels of antibodies to pollen allergens and worsened seasonal EoE might be due to swallowing airborne pollen and the intrusion into the oesophageal mucosa of pollen allergens and pollen tubes, which encounter a pH and humidity resembling the stigma at pollination. OBJECTIVE: The aim of our study was to demonstrate the possible pathogenic role of environmental allergens in EoE through molecular and anatomopathological studies METHODS: One hundred and twenty-nine patients with EoE were tested for environmental and food allergens. Component resolved diagnosis (CRD), histological and botanical analysis was performed. Microscopic examination of oesophageal biopsies of 129 adults patients with EoE, 82 of them with seasonal exacerbation, and 100 controls, with gastroesophageal reflux without eosinophilic infiltrate, were made to verify the presence of callose (polysaccharide abundant in pollen tubes but absent in animal tissues) in the oesophagus. RESULTS: Component resolved diagnosis detected pollen allergens in 87.6% of patients with EoE. The predominant allergens were group 1 grass (55%), Art v 3 (11.3%) and lipid transfer proteins (LTPs) (19.4%) of common Mediterranean foods such as peach, hazelnuts, walnuts and wheat. Callose from pollen tubes was found in 65.6% of biopsies. CONCLUSION: Alteration of the mucosal barrier in EoE might cause the penetration of pollen grains into the oesophageal tissues. In EoE patients, anatomopathological studies searching for intrusion to plant foods and pollen, and specific-guided diet and immunotherapy after plant structures detection in biopsies, might be effective. CLINICAL RELEVANCE: It is possible to see the intrusion into animal tissues (oesophagus mucosa) of plant structures (pollen grains or pollen tubes) using an adecuate histologic botanical analysis. Molecular and anatomopathological studies can help to demonstrate a possible pathogenic role of environmental allergens in EoE.

Anti-apoptotic effect of banhasasim-tang on chronic acid reflux esophagitis.

AIM: To evaluate the anti-apoptotic effect of banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CARE) using a rat model. METHODS: A surgically-induced CARE model was established in Sprague-Dawley rats. The modeled rats were divided into a treatment group or untreated group, and given BHSST (1 g/kg body weight per day) or water, respectively, for 15 consecutive days (n = 7 each group). Changes in expression of proteins related to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and apoptosis were assessed by western blotting. Changes in esophageal pathology were analyzed by gross and histological examinations. RESULTS: The CARE exposure modeled rats showed increased levels of the NADPH oxidase subunit, NOX4 and p47phox in the esophagus. The BHSST treatment completely resolved these CARE-related increases. The CARE rats also showed markers of cytokine stress, including elevated levels of TNF-α and reactive oxygen species as well as of the consequent increase in JNK activation, and subsequent decrease in pro-survival gene expression, such as of Bcl-2. BHSST treatment resolved the CARE-related changes. BHSST also exerted an anti-apoptotic effect, as evidenced by altered expression of the apoptosis-related genes for bax, cytochrome c, and caspase 3. Finally, the BHSST treatment markedly ameliorated the CARE-related esophageal mucosal ulcerations. CONCLUSION: In the rat model of CARE, BHSST can suppress development of esophageal mucosal ulceration via regulation of reactive oxygen species-dependent apoptosis.

Association between coffee or tea drinking and Barrett's esophagus or esophagitis: an Italian study.

BACKGROUND/OBJECTIVES: Only a few papers have treated of the relationship between Barrett's esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We evaluated the role of these beverages in BE and E occurrence. SUBJECTS/METHODS: Patients with BE (339), E (462) and controls (619) were recruited. Data on coffee and tea and other individual characteristics were collected using a structured questionnaire. RESULTS: BE risk was higher in former coffee drinkers, irrespective of levels of exposure (cup per day; ⩽1: OR=3.76, 95% CI 1.33-10.6; >1: OR=3.79, 95% CI 1.31-11.0; test for linear trend (TLT) P=0.006) and was higher with duration (>30 years: OR=4.18, 95% CI 1.43-12.3; TLT P=0.004) and for late quitters, respectively (⩽3 years from cessation: OR=5.95, 95% CI 2.19-16.2; TLT P<0.001). The risk of BE was also higher in subjects who started drinking coffee later (age >18 years: OR=6.10, 95% CI 2.15-17.3). No association was found in current drinkers, but for an increased risk of E in light drinkers (<1 cup per day OR =1.85, 95% CI 1.00-3.43).A discernible risk reduction of E (about 20%, not significant) and BE (about 30%, P<0.05) was observed in tea drinkers. CONCLUSIONS: Our data were suggestive of a reduced risk of BE and E with tea intake. An adverse effect of coffee was found among BE patients who had stopped drinking coffee. Coffee or tea intakes could be indicative of other lifestyle habits with protective or adverse impact on esophageal mucosa.