Evaluation of the effectiveness of mother milk exosomes in the experimental corrosive esophagitis model.

PURPOSE: We aimed to examine the effectiveness of mother milk exosomes in treating corrosive esophageal burns. MATERIALS AND METHODS: 32 rats were separated into four equal groups and weighed individually before the procedure. A corrosive esophageal burn model was created with 12.5% sodium hydroxide by a 3F Fogarty catheter. Group 1 did not apply any process or treatment, Group 2 was burned, and no treatment was performed. Group 3 was burned, and then 0.5 cc/day of mother milk exosome extract was given. Group 4 was not applied any process, and 0.5 cc/day mother milk exosome extract was given. All rats were weighed again and sacrificed. Biopsy samples were sent to the pathology laboratory for histopathological examination (in terms of inflammation, fibrosis, and necrosis).Kindly check and confrm all email ids.The e-mail addresses and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. RESULTS: A significant difference was found in the results of inflammation and fibrosis. There was a meaningful difference in fibrosis between the 2nd and 3rd groups. There was weight gain in groups 1, 3 and 4. Statistical evaluations for each group were significant. CONCLUSION: It was observed that breast milk exosomes may be effective in inflammation and fibrosis formation in treating corrosive esophageal burns. This suggested that breast milk exosomes reduce stricture formation due to esophageal corrosion.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [specify authors given name] Last name [specify authors last name]. Also, kindly confirm the details in the metadata are correct.The names and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. Also we confirm the details in the metadata.

Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial.

INTRODUCTION: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure. METHODS: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed. RESULTS: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm. DISCUSSION: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

Clinicopathologic Features, Treatment Response, and Outcomes of Immune Checkpoint Inhibitor-Related Esophagitis.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) have provided practice-changing outcomes in treating many cancers, ICI-related gastrointestinal toxicity can limit their use. Upper gastrointestinal toxicity is not common nor as well described as lower gastrointestinal toxicity. We aimed to characterize the clinical presentation, endoscopic and histologic features, treatment response, and outcomes of ICI-related esophagitis. METHODS: We retrospectively studied patients at The University of Texas MD Anderson Cancer Center in whom esophagitis developed after receiving ICIs from June 2011 through January 2020. We included patients with endoscopic evidence of esophagitis and excluded those with other obvious causes of esophagitis. A chi-square test was used to assess associations between categorical variables. The Mann-Whitney U test was used to compare differences between continuous variables. RESULTS: Of 657 consecutive patients who underwent esophagogastroduodenoscopy (EGD) during or within 6 months of completing ICI-based therapy, 21 (3%) had esophagitis deemed to be from ICIs. Of these patients, 1 (5%) received an inhibitor of CTLA-4 alone, 15 (71%) received anti-PD-1 or PD-L1 monotherapy, and 5 (24%) received a combination of these. Median time from ICI initiation to onset of esophagitis was 4 months. Upon evaluation with EGD, only 3 patients (14%) had isolated esophageal involvement; 18 (86%) had concurrent involvement of the stomach, duodenum, or both. Most patients (67%) were treated with proton pump inhibitors, and 4 (19%) received steroids (prednisone or budesonide). The mortality rate was 38% (median follow-up, 15 months). CONCLUSIONS: Esophagitis associated with ICI use is rare. The diagnosis is one of exclusion because its clinical presentation appears similar to that of inflammation resulting from other causes. It often occurs in conjunction with other upper gastrointestinal toxicity. Symptoms are mild and respond well to nonimmunosuppressive treatment, with few severe complications.

Acute phlegmonous esophagitis: apropos of a case.

A 43-year-old male with an uneventful history presented with fever and ingestion-triggered retrosternal chest pain of a three-day duration, which was aggravated by deep breathing and the supine position. When asked regarding the possible ingestion of a foreign body he recalled having accidentally swallowed tiny glass shards from a broken bottle.

Non gastro-esophageal reflux disease related esophagitis: an overview with a histologic diagnostic approach.

Several pathological conditions, other than gastro-esophageal reflux disease and its complications, can affect the esophagus. While some of these can present with unspecific lesions (i.e. ulcers and epithelial damage) and require clinico-pathological correlation for diagnosis (i.e. drug-induced esophagitis and corrosive esophagitis) other conditions show distinctive histological lesions which enable the pathologist to reach the diagnosis (i.e. some specific infectious esophagites and Crohn's disease). In this context eosinophilic esophagitis is the condition which has been increasingly studied in the last two decades, while lymphocytic esophagitis, a relatively new entity, still represents an enigma. This overview will focus on and describe histologic lesions which allow pathologists to differentiate between these conditions.

[Patient with Recurrent Breast Cancer Who Developed Radiation Esophagitis with Severe Esophageal Stenosis after Combined Bevacizumab and Paclitaxel Therapy-A Case Report].

Severe stenosis rarely occurs with radiation esophagitis after irradiation. We report our recent experience of a case of recurrent breast cancer in which the patient developed severe esophageal stenosis after receiving combined bevacizumab (Bev)-paclitaxel(PTX)therapy following radiotherapy for a thoracic vertebral metastasis. A 59-year-old woman with Stage ⅢB left breast cancer had undergone total mastectomy with axillary lymph node dissection after receiving neoadjuvant therapy. Elevated carcinoembryonic antigen levels were observed 23 months postoperatively, and multiple bone metastases were detected on PET-CT. After 5 sessions of irradiation with 20 Gy at the Th8-L1 level, combined Bev and PTX plus zoledronic acid was administered. The patient developed dysphagia at the end of the 4 cycles of combined Bev and PTX therapy, and her condition exacerbated subsequently. Therefore, upper gastrointestinal endoscopy was performed, which revealed a circumferential stenosis 31-37 cm from the incisors. We decided to perform the endoscopic treatment. After 3 balloon dilatations, her condition improved, and oral ingestion was possible. The esophageal stenosis might have been caused by the exacerbation of esophagitis because of the delayed wound healing effect of Bev in addition to radiation.

[Ibero-Latinamerican Clinical Practical Guidelines on pediatric caustic esophagitis: Therapeutical aspects (Part 2)]. / Guía de práctica clínica Ibero-Latinoamericana sobre la esofagitis cáustica en Pediatría: Aspectos terapéuticos (2a. Parte).

Caustic ingestion represents a serious social-medical problem due to the devastating and irreversible consequences it can produce in the upper digestive tract. In Ibero-America, there are no published reliable data on the incidence or prevalence of caustic-induced injuries, and most of the available information on clinical presentation, diagnosis, treatment, and prognosis is based on retrospective clinical series and, indeed, its clinical management is often based primarily on expert opinion. Re cently as an initiative of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) and with the cooperation of the Spanish Society for Pediatric Gastroente rology, Hepatology and Nutrition (SEGHNP), we have designed a Clinical Practice Guideline that include a series of statements and recommendations aimed at optimizing patient medical care which is based on the systematic review of evidence. Two (2) separate papers focused on the evaluation of physiopathological and clinical-endoscopic diagnostic features of caustic esophagitis in children (1st. Paper) and, on the other hand, the most relevant therapeutic considerations (2nd. Paper). We expect this guideline to become a useful tool for the physician in the difficult decision-making process when assessing patients after caustic ingestion.

Crizotinib-induced erosive esophagitis in a pediatric patient with neuroblastoma.

Crizotinib is an oral tyrosine kinase inhibitor, approved by the FDA in 2011, for use in anaplastic lymphoma kinase positive, metastatic, non-small cell lung cancer. Crizotinib inhibits oncogenic protein expression and impairs cellular proliferation in tumors with an overexpressed anaplastic lymphoma kinase gene. Currently used most frequently in the adult patient population, pediatric use is becoming more prominent, specifically in disease states exhibiting anaplastic lymphoma kinase-positive, metastatic disease, such as neuroblastoma. Approximately 8% of neuroblastomas have activating anaplastic lymphoma kinase-mutations, making this a promising target for a difficult-to-treat disease. Studies in the pediatric population are limited. However, targeted anaplastic lymphoma kinase-inhibitor therapies have shown improved outcomes at both one-year and two-year marks in both overall survival and progression free survival in anaplastic lymphoma kinase-positive adult patients with non-small cell lung cancer. One Children's Oncology Group phase I trial examined toxicities associated with anaplastic lymphoma kinase inhibitor therapy in pediatric patients. Results revealed varying grades in severity of neutropenia, dizziness, and liver function test elevation. In the adult population, severe toxicities reported by the manufacturer include effects on liver, cardiac and lung function. Additionally, several cases of severe, erosive, pill-esophagitis due to crizotinib therapy have been documented in the adult population. Erosive esophagitis is common in the pediatric population due to a variety of factors. Ingestion of medications or other corrosive agents accounts for approximately 3-5% (5000-10,000 cases per year) of esophagitis presentation in the pediatric population. Common causative medications include non-steroidal anti-inflammatory drugs, antibiotics such as doxycycline and tetracycline, and ferrous sulfate. Presented here is the first reported case of crizotinib-induced pill esophagitis in a pediatric patient.

[Gastroesophageal reflux disease and esophagitis associated with the use of drugs: the modern state of the problem].

From the standpoint of evidence - based medicine, the ability of various drugs to induce the development of gastroesophageal reflux disease and esophagitis is considered. Thus, all known drugs can be divided into 3 groups: drugs that have the ability to reduce pressure in the lower esophageal sphincter, for example, ß-adrenoreceptor agonists, α-adrenoreceptor antagonists, anticholinergics, calcium channel blockers, nitrates, benzodiazepines (diazepam), estrogen, progesterone, aminophylline (theophylline), tricyclic antidepressants, selective serotonin reuptake inhibitors, glucocorticosteroids; means providing a direct damaging effect on the esophageal mucosa, as well as lowering its resistance reflyuktatu, e.g., bisphosphonates, acetylsalicylic acid / non - steroidal anti - inflammatory agents, anticoagulants, antiplatelet drugs, iron preparations, ascorbic acid, potassium chloride, quinidine, phenytoin, calcium dobesilate, 131I sodium iodide, antibiotics (tetracycline, doxycycline, clindamycin, ciprofloxacin, ornidazole, clindamycin, rifampicin), antitumor agents; drugs that impede gastric emptying: calcium channel blockers, anticholinergics. These data can be used in practice in the choice of treatment tactics, especially in individuals with a diagnosis of gastroesophageal reflux disease or heartburn.

Symptomatic exfoliative esophagitis induced by dabigatran.

Dabigatran is an oral anticoagulant prescribed as an alternative to warfarin which has been associated with exfoliative esophagitis and esophageal ulcer. We report a new case of dabigatran-induced exfoliative esophagitis where the mucosal injury improved after prescribing proton-pump inhibitors and ingesting medication with sufficient water.

Phase I study of evofosfamide, an investigational hypoxia-activated prodrug, in patients with advanced leukemia.

Tumor hypoxia causes resistance to radiation and chemotherapy. Evofosfamide (TH-302) has exhibited specific hypoxia-dependent cytotoxicity against primary acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) samples in vitro. Based on these findings, a Phase I study of evofosfamide was designed for patients with relapsed/refractory leukemia (NCT01149915). In this open-label study, patients were treated with evofosfamide as a 30-60 min/day infusion on Days 1-5 of a 21-day cycle (Arm A, n = 38) or as a continuous infusion over 120 hr over Days 1-5 of a 21-day cycle (Arm B, n = 11). Forty-nine patients were treated including 39 (80%) with AML and 9 (18%) with ALL. Patients had received a median of five prior therapies. In Arm A, the dose-limiting toxicities (DLTs) were grade 3 esophagitis, observed at a dose of 550 mg/m(2) . The maximum tolerated dose (MTD) was a daily dose of 460 mg/m(2) . In Arm B, the DLTs were grade 3 stomatitis and hyperbilirubinemia, observed at a daily dose of 460 mg/m(2) . The continuous infusion MTD was a daily dose of 330 mg/m(2) . Hypoxia markers HIF-1α and CAIX were highly expressed in leukemic bone marrow and were significantly reduced after evofosfamide therapy. The combined overall response rate in Arms A and B was 6% (2 CR/CRi and 1 PR), with all responses seen in Arm A. Evofosfamide has shown limited activity in heavily pretreated leukemia patients. Further evaluation investigating evofosfamide in combination with cytotoxic or demethylating agents is warranted. Am. J. Hematol. 91:800-805, 2016. © 2016 Wiley Periodicals, Inc.

Dabigatran-induced esophagitis: The prevalence and endoscopic characteristics.

BACKGROUND AND AIM: There have been some descriptions of dabigatran-induced esophagitis in the literature. The aim of this study was to examine the prevalence and endoscopic characteristics of the disease. METHODS: We reviewed the endoscopic database and medical records of 91 patients with dabigatran internal use who underwent upper gastrointestinal endoscopy. The frequency of dabigatran-induced esophagitis and its endoscopic findings were retrospectively analyzed. In addition, the clinical characteristics were compared between patients with dabigatran-induced esophagitis and those without the disease. RESULTS: Dabigatran-induced esophagitis was found in 19 of 91 (20.9%) patients. Of the 19 patients with the esophagitis, 18 (94.7%) showed longitudinally sloughing epithelial casts in the mid and/or lower esophagus, which may be characteristic endoscopic findings of this disease. Symptomatic patients were more frequent in patients with dabigatran-induced esophagitis (68.4%) than those without (37.5%, P = 0.02). Other factors including age, gender, coexistence of hiatal hernia, gastroesophageal reflux disease, or concomitant other medications did not differ between the two groups. CONCLUSIONS: Dabigatran causes the esophageal mucosal injury in approximately 20% of patients. Longitudinally sloughing casts in the distal esophagus are characteristic of dabigatran-induced esophagitis.

Acid suppressing therapy as a risk factor for Candida esophagitis.

Studies were reviewed from PubMed for risk factors for the development, recurrence, prevention and therapy of Candida esophagitis, and for mechanisms induced by acid-suppressing therapy potentially influencing these factors. Documented observations included greatly increased Candida populations in the mouth, esophagus, stomach, and upper small intestine induced by acid-suppressing therapy. Among patients without HIV disease, PPI consumers more frequently had developed Candida esophagitis than did non-consumers and had also developed its recurrences more frequently. Similar phenomena associated with H2 -blocker use were less intense, and the possibility of similar phenomena in patients with HIV disease apparently had not yet been examined in spite of their high frequency of this disorder. PPI-induced elimination of the gastric acid barrier is a major mechanism leading to oro-pharyngeal and esophageal candida colonization, while PPI-induced impairment of absorption of most orally administered antifungal agents may limit the prophylactic and therapeutic success of these agents. These observations suggest potential value in limiting PPI use in populations of patients with Candida infections including esophagitis, as well as in patients at risk for their development, and also suggest that post-PPI rebound acid hypersecretion may provide additional anti-Candida benefit. Studies designed to develop the risk-benefit ratios of PPI use in these patients deserve investigation with high priority appropriate for studies in patients with HIV disease.

Candida Esophagitis Associated With Mycophenolate Mofetil Treatment of Atopic Dermatitis.

OBJECTIVE: To describe a case in which a patient developed Candida esophagitis (CE) after treatment of atopic dermatitis (AD) with mycophenolate mofetil (MMF) for 22 months. CASE SUMMARY: A 59-year-old Caucasian female with long-standing history of AD successfully treated with MMF presented to the dermatology clinic for follow-up appointment with 3 months' history of projectile vomiting, choking, and trouble swallowing. Patient underwent esophagogastroduodenoscopy (EGD) that demonstrated whitish plaques in esophagus consistent with CE, which was confirmed by biopsy and cytology. DISCUSSION AND CONCLUSION: MMF is a lymphocyte selective immunosuppressive agent that has demonstrated very good therapeutic effects against cutaneous inflammatory skin disease and proved to have good efficacy and bioavailability. Generally, MMF is a safe medication with relatively low side effects. There are no case reports to date that describe CE in patients treated with MMF. Clinicians should be aware of this rare complication to enable timely intervention and treatment.

J Drugs Dermatol. 2016;15(10):1267-1269.