Heterotopic gastric mucosa of the proximal esophageal (HGMPE) and its potential role in pediatric dysphonia and dysphagia.

OBJECTIVE: Despite a reported incidence of HGMPE of 10%, proof of acid production, and an increased incidence of respiratory symptoms, the pediatric otolaryngology, swallowing and voice care literature is silent on this entity. This case series describes pediatric patients confirmed to have HGMPE with dysphonia and/or dysphagia. METHODS: Retrospective case series of Pediatric Voice, Resonance, and Swallowing Center patients at a tertiary Children's Hospital in 2019. SETTING: Tertiary academic medical center. SUMMARY OF RESULTS: Three patients who underwent triple endoscopy for dysphonia or dysphagia were histologically diagnosed with HGMPE. Esophageal biopsies were otherwise normal. Two of the three patients resolved their primary aerodigestive symptoms following treatment with acid suppression and a protectant (sucralfate). The third patient reported significant improvement in symptoms by phone. The significance of this case series cannot be understated: 1) A need for increased awareness among pediatric otolaryngologists, voice care and swallowing professionals of this entity given its relatively common incidence of 10% offset by a dearth of presentations & scientific publications in our literature clearly exists. 2) Otolaryngologists have abandoned operative upper aerodigestive tract endoscopy in lieu of office-based less comprehensive videolaryngostroboscopy and fiberoptic endoscopic evaluation of swallowing. HGMPE & other esophageal disorders (i.e. eosinophilic esophagitis) support revisiting triple endoscopy in select patients where office endoscopy has failed to diagnose and successfully treat such patients. 3) Both acid suppression therapy and a protectant (sucralfate) may be useful in these patients. 4) Modification of rigid esophagoscopy technique to carefully assess the introitus and superior esophageal segment is paramount 5) Otolaryngologists over-diagnose & over-treat laryngopharyngeal reflux. The pediatric & adult literature is replete with significant safety warnings associated with acid suppression therapy and guidelines admonish their indiscriminate use, raising the liability bar of empiric treatment. Large scale prospective, randomized and controlled studies are needed to confirm the pathophysiologic role of this entity in pediatric aerodigestive disorders. CONCLUSION: HGMPE is a clinical entity that can be easily missed upon swift entry into the esophagus with rigid endoscopy. Careful scrutiny and visualization of the proximal esophagus is critical in order to identify HGMPE, as there is a higher rate of laryngospasm, stricture, and potentially neoplasm in this population.

Nobiletin alleviates endometriosis via down-regulating NF-κB activity in endometriosis mouse model.

Nobiletin exhibits protective potential on inflammation and inhibits the activation of transcription factors nuclear factor-κB (NF-κB). However, its effects on the progression of endometriosis remain unsettled. The present study aimed to explore the in vivo alleviation of nobiletin on endometriosis and its mechanism of action. The mouse model of endometriosis was established and administered with nobiletin. The ectopic lesion size was measured and the hotplate test was performed to assess the amelioration of nobiletin on endometriosis. The expression of proliferation and angiogenesis relevant genes including proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and E-cadherin was measured by immunostaining and the mRNA expression of proinflammatory mediators including interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, matrix metalloproteinases (MMP)-1, and MMP-3 was measured by RT-PCR. The change of NF-κB activity in endometriotic cells was evaluated by Western blotting and confirmed by luciferase assay. Administration of nobiletin significantly reduced lesions size and pain in endometriosis mice. Nobiletin significantly altered the expression of PCNA, VEGF, and E-cadherin in ectopic endometrium, as well as the levels of IL-6, IL-1ß, TNF-α, MMP-1, and MMP-3. Nobiletin also showed remarkably impairment on the activation of NF-κB in promoting endometriotic cells, likely targeting on the activity of IκB kinases (IKKs). The present study provides the first evidence that nobiletin exerts protection on endometriosis via inhibition the activation of NF-κB, specifically on the activity of IκB kinases.

Intravitreal bevacizumab monotherapy for choroidal neovascularisation secondary to choroidal osteoma.

PurposeThe purpose of this study is to present the outcomes of a series of patients with choroidal neovascular membrane (choroidal neovascularisation (CNV)) secondary to a choroidal osteoma undergoing anti-VEGF monotherapy.Patients and methodsRetrospective series of patients with choroidal neovascularization secondary to choroidal osteoma. All patients underwent clinical and imaging assessment (fundus photo, B-scan ultrasonography, fluorescein angiography, and optical coherence tomography-where available), and were managed with intravitreal anti-VEGF injections (Bevacizumab). Visual acuity and central retinal thickness were recorded pre treatment and at the end of the follow-up period.ResultsEight patients were included in this study. Of this, 6/8 had predominantly classic or classic and 2/8 patients had minimally classic or occult CNV. Each patient received 3-10 injections of bevacizumab. Median follow-up was 9 months (3-15 months). Visual acuity improved in 5 patients, by 2-6 Snellen lines. CNV completely regressed in 5 cases and partially regressed in 3 cases. Mean CRT reduction was 122 µm (6 to -230 µm).ConclusionIntravitreal bevacizumab can be an effective treatment modality in the management of vision threatening CNV secondary to choroidal osteoma.

Effects of the hypoxia-inducible factor-1 inhibitor echinomycin on vascular endothelial growth factor production and apoptosis in human ectopic endometriotic stromal cells.

Recent evidence points to a possible role for hypoxia-inducible factor (HIF)-1 in the pathogenesis and development of endometriosis. The objectives of this study were to investigate the critical role of HIF-1 in endometriosis and the effect of the HIF-1 inhibitor echinomycin on human ectopic endometriotic stromal cells (eESCs). Ectopic endometriotic tissues were obtained from 20 patients, who received an operation for ovarian endometriomas. We examined vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) production, HIF-1 expression, cell proliferation and apoptosis of eESCs. Cobalt chloride (CoCl2) significantly induced expression of HIF-1α protein and VEGF production in a time-dependent manner in eESCs, but reduced SDF-1 production. VEGF production was significantly suppressed by treatment of 100 nM echinomycin without causing cell toxicity, but 0.1-10 nM echinomycin or 100 nM progestin had no significant effect. SDF-1 production was not affected by echinomycin treatment at any dose. Echinomycin inhibited cell proliferation and induced apoptotic cell death of the eESCs, and significantly inhibited expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL. Echinomycin inhibits VEGF production and induces apoptosis of eESCs by suppression of Bcl-2 and Bcl-xL. These findings suggest the unique therapeutic potential for echinomycin as an inhibitor of HIF-1 activation for endometriosis treatment.

Local delivery of the cationic steroid antibiotic CSA-90 enables osseous union in a rat open fracture model of Staphylococcus aureus infection.

BACKGROUND: Treatment of infected open fractures remains a major clinical challenge. In this study, we investigated the novel broad-spectrum antibiotic CSA-90 (cationic steroid antibiotic-90) as an antimicrobial agent. METHODS: CSA-90 was screened in an osteoblast cell culture model for effects on differentiation and mineralization. Local delivery of CSA-90 was then tested alone and in combination with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a mouse ectopic bone formation model (n=40 mice) and in a rat open fracture model inoculated with pathogenic Staphylococcus aureus (n=84 rats). RESULTS: CSA-90 enhanced matrix mineralization in cultured osteoblasts and increased rhBMP-2-induced bone formation in vivo. All animals in which an open fracture had been inoculated with Staphylococcus aureus and not treated with local CSA-90, including those treated with rhBMP-2, had to be culled prior to the experimental end point (six weeks) because of localized osteolysis and deterioration of overall health, whereas CSA-90 prevented establishment of infection in all open fractures in which it was used (p≤0.012). Increased union rates were seen for the fractures treated with rhBMP-2 or with the combination of rhBMP-2 and CSA-90 compared with that observed for the fractures treated with CSA-90 alone (p=0.04). CONCLUSIONS: CSA-90 can promote osteogenesis and be used for prevention of Staphylococcus aureus infection in preclinical models. CLINICAL RELEVANCE: Local delivery of CSA-90 represents a novel strategy for prevention of infection and may have specific benefits in the context of orthopaedic injuries.

Bilateral choroidal osteoma with choroidal neovascular membrane treated with bevacizumab in a child.

Choroidal osteoma is a rare benign tumor. We report a male child diagnosed with bilateral choroidal osteoma, high myopia and secondary choroidal neovascularization (CNV) membrane in one eye. Co-existence of posterior staphyloma made the clinical diagnosis of choroidal osteoma difficult due to the osteoma filling the depression of the posterior staphyloma. Typical findings on fundus fluorescein angiography, optical coherence tomography, B-scan and indocyanine green angiography confirmed the diagnosis. A review of literature was performed. CNV secondary to choroidal osteoma was treated with intravitreal bevacizumab and it responded well. Regular follow-up is essential for recurrence of CNV and decalcification of the osteoma.

Retinal pigment epithelium tear formation following intravitreal ranibizumab injection in choroidal neovascularization secondary to choroidal osteoma.

Choroidal osteoma is an extremely rare osseous tumor of the choroid where choroidal neovascularization (CNV) is the major cause of visual loss. We report the case of a 28-year-old female with CNV secondary to choroidal osteoma, who developed RPE tear after intravitreal ranibizumab treatment.

Combination use of ferulic acid, ligustrazine and tetrahydropalmatine inhibits the growth of ectopic endometrial tissue: a multi-target therapy for endometriosis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferulic acid (FA), ligustrazine (LZ) and tetrahydropalmatine (THP) are separately isolated from Chinese Angelica, Szechwan Lovage Rhizome and Rhizoma in the Jiawei-Foshou-San formula, a popular traditional Chinese medicine for irregular menses. It has been reported that the combination use of FA+LZ+THP has similar effect on endometriosis, but the underlying mechanisms are unclear. This study was to investigate the combination effects and mechanisms of FA+LZ+THP on endometriosis rats. MATERIALS AND METHODS: Fifty endometriosis rats were intragastricly treated with FA+LZ+THP for 4 wk. The volume of ectopic endometrial tissue was measured to evaluate the effects. Then the changes in hypothalamic-pituitary-ovarian axis and ERE pathway were indicated by the levels of E2, GnRH, FSH and LH, and the expressions of ER, HSP90 and COX-2, respectively. In addition, peritoneal macrophages of each rat were cultured in vitro and treated with (FA+LZ+THP)-medicated serum for 24h. The proliferation and phagocytosis abilities, the levels of IL-1ß and TNF-α, and the expression of IκBα were then measured for the changes of peritoneal macrophage activities. RESULTS: Combination use of FA+LZ+THP diminished the volume of the ectopic endometrial tissues (P<0.05 or P<0.01). It also decreased the E2 level, suppressed the expression of GnRH, FSH and LH, and decreased the protein expression of ER, HSP90 and COX-2 (all P<0.05 or P<0.01). The phagocytosis ability of peritoneal macrophage was enhanced by (FA+LZ+THP)-medicated serum (P<0.05) with no change of proliferation (P>0.05). Moreover, IL-1ß and TNF-α were downregulated (both P<0.05 or P<0.01) and IκBα was upregulated by the (FA+LZ+THP)-medicated serum (P<0.01). CONCLUSIONS: The combination use of FA, LZ and THP could inhibit the growth of ectopic endometrial tissue in endometriosis rats. It might be related to the down-regulation of hypothalamic-pituitary-ovarian axis, the amelioration in ERE pathway and the improvement of peritoneal macrophage activities.

Obscure bleeding colonic duplication responds to proton pump inhibitor therapy.

We report the case of a 17-year-old male admitted to our academic hospital with massive rectal bleeding. Since childhood he had reported recurrent gastrointestinal bleeding and had two exploratory laparotomies 5 and 2 years previously. An emergency abdominal computed tomography scan, gastroscopy and colonoscopy, performed after hemodynamic stabilization, were considered normal. High-dose intravenous proton pump inhibitor (PPI) therapy was initiated and bleeding stopped spontaneously. Two other massive rectal bleeds occurred 8 h after each cessation of PPI which led to a hemostatic laparotomy after negative gastroscopy and small bowel capsule endoscopy. This showed long tubular duplication of the right colon, with fresh blood in the duplicated colon. Obscure lower gastrointestinal bleeding is a difficult medical situation and potentially life-threatening. The presence of ulcerated ectopic gastric mucosa in the colonic duplication explains the partial efficacy of PPI therapy. Obscure gastrointestinal bleeding responding to empiric anti-acid therapy should probably evoke the diagnosis of bleeding ectopic gastric mucosa such as Meckel's diverticulum or gastrointestinal duplication, and gastroenterologists should be aware of this potential medical situation.

Recurrent inflammation of accessory parotid tissue associated with unilateral parotid gland aplasia: diagnostic and therapeutic implications.

Aplasia of the major salivary glands is a rare condition due to an alteration in the development of the ectodermal tissue of the oral cavity often related to other craniofacial abnormalities or alteration of structures deriving from the first or second archial branch, in particular the lacrimal glands; it can be total or partial and determine clinical states ranging from an asymptomatic condition to a severe xerostomia. The accessory parotid tissue is similar to normal parotid tissue, completely independent from the main gland and susceptible to the same pathological disorders. We describe a very unusual case of an inflammatory disorder of accessory parotid tissue in a 44-year-old male patient with concomitant, and previously unknown, aplasia of the main ipsilateral parotid gland. We also discuss the role of imaging and conservative therapeutic modalities such as botulinum toxin therapy and, in the future, minimally invasive endoscopic-assisted resection in the management of such salivary disorder.

Inlet patch: clinical presentation and outcome in children.

OBJECTIVES: An inlet patch (IP) is defined as heterotopic gastric mucosa located in the proximal esophagus. Little information is available in children. The aim of this retrospective study was to assess clinical significance, endoscopic and histological characteristics, and natural history of IP in children. PATIENTS AND METHODS: This retrospective multicenter study included all of the cases of IP recorded in 7 tertiary French pediatric gastrointestinal centers. Information about demographics, clinical symptoms, endoscopic characteristics, histology, treatment, and evolution was collected. RESULTS: Fifteen children were included (8 boys, 7 girls). The median age at diagnosis was 9.5 years (range 3.3-15 years). Five children had esophageal atresia and 9 had gastroesophageal reflux. Only 1 child was asymptomatic. Digestive symptoms (dysphagia, food impaction) were noted in 14 patients and respiratory or ear, nose, and throat symptoms in 6. At endoscopy, IP was characterized by a small, round salmon-pink lesion of the proximal esophagus. Helicobacter pylori was found in 2 patients. Proton pump inhibitor treatment was initiated in 14 children for a mean duration of 4.7 months (range 1-12 months). Two patients were lost to follow-up. Clinical symptoms disappeared in 5 patients and decreased in 3 others. One case of hematemesis was noted after a mean follow-up of 9 months. Recurrent symptoms were noted in 2 patients after treatment discontinuation. CONCLUSIONS: IP is an uncommon but almost certainly underrecognized lesion in children, and may be the cause of digestive and respiratory symptoms in some children.

Axillary breast cancer in a Nigerian woman.

Ectopic breast cancer is rare and diagnosis is commonly delayed. We report the case of a 34-year-old Nigerian woman with a locally advanced invasive ductal carcinoma in the axillary breast. She underwent an axillary mastectomy and is due to receive adjuvant chemotherapy and radiotherapy. The management of this patient is discussed in relation to existing medical literature on the subject.

Meniscal ossicle.

Meniscal ossicle, or bone within the substance of meniscus, is a rare entity and commonly confused with a loose body both clinically and radiologically. MRI is the modality that can definitely diagnose meniscal ossicle and avoid unnecessary diagnostic arthroscopy. Here we report one such case diagnosed using MRI; this patient is doing well without surgery one year after diagnosis.

Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats.

Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these beneficial effects are not fully understood. In this study, we compared the effects of dietary (n-3) LCPUFA, in the form of either fish oil (FO) or krill oil (KO) balanced for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, with a control (C) diet containing no EPA and DHA and similar contents of oleic, linoleic, and alpha-linolenic acids, on ectopic fat and inflammation in Zucker rats, a model of obesity and related metabolic dysfunction. Diets were fed for 4 wk. Given the emerging evidence for an association between elevated endocannabinoid concentrations and metabolic syndrome, we also measured tissue endocannabinoid concentrations. In (n-3) LCPUFA-supplemented rats, liver triglycerides and the peritoneal macrophage response to an inflammatory stimulus were significantly lower than in rats fed the control diet, and heart triglycerides were lower, but only in KO-fed rats. These effects were associated with a lower concentration of the endocannabinoids, anandamide and 2-arachidonoylglycerol, in the visceral adipose tissue and of anandamide in the liver and heart, which, in turn, was associated with lower levels of arachidonic acid in membrane phospholipids, but not with higher activity of endocannabinoid-degrading enzymes. Our data suggest that the beneficial effects of a diet enriched with (n-3) LCPUFA are the result of changes in membrane fatty acid composition. The reduction of substrates for inflammatory molecules and endocannabinoids may account for the dampened inflammatory response and the physiological reequilibration of body fat deposition in obese rats.