A case of uterine inclusion cysts in a sow

Background Serosal inclusion cysts are thin walled-structures located on the peritoneal surface of the uterus, frequently observed as multiple cystic structures in aggregates or grape-like clusters containing a clear, non-viscous fluid. In human and veterinary medicine, they are thought to be developed under hormonal effects, or after manipulation or inflammation of the reproductive tract. However, they have not yet been described in swine. Case presentation A uterus of a 3-year-old crossbreed sow was condemned at slaughter due to the presence of multiples cystic cavities attached to the serosal surface. Microscopically, multiple cystic dilations emerging from the serosa were lined by a simple and flattened epithelium (cytokeratine positive and vimentin negative on immunohistochemistry) supported by a subepithelial layer of collagen. Grossly and histologically, they were diagnosed as serosal inclusion cysts. Conclusion To the authors’ knowledge, this report represents the first description of serosal inclusion cysts in sows. These lesions should be taken into consideration within the differential diagnostic list of cystic peritoneal lesions such as cystic neoplasms, congenital cysts, and parasitic diseases.

Histone deacetylase 7 mediates endothelin-1-induced connective tissue growth factor expression in human lung fibroblasts through p300 and activator protein-1 activation

Background Histone deacetylase (HDAC) inhibition was reported to ameliorate lung fibrosis in animal models. However, little is known about the underlying mechanism of HDAC7 in the regulation of CTGF production in lung fibroblasts. Methods The role of HDAC7 in CTGF production caused by ET-1 stimulation in WI-38 cells (human lung fibroblast) was examined. We also evaluated the expression of HDAC7 in the lung of ovalbumin-induced airway fibrosis model. Statistical data were shown as mean ± standard error. Results ET-1-stimulated CTGF and α-SMA expression was attenuated by small interfering (si)RNA interference of HDAC7. ET-1 promoted HDAC7 translocation from the cytosol to nucleus. ET-1-stimulated CTGF expression was reduced by the transfection of p300 siRNA. ET-1 induced an increase in p300 activity. Furthermore, the acetylation of c-Jun was time-dependently induced by ET-1 stimulation, which was reduced by transfection of either HDAC7 or p300 siRNA. Both transfection of HDAC7 and p300 siRNA suppressed the ET-1-increased activity of AP-1-luciferase. Moreover, the presence of HDAC7 was required for ET-1-stimulated formation of HDAC7, p300, and AP-1 complex and recruitment to the CTGF promoter region. In an ovalbumin-induced airway fibrosis model, the protein level of HDAC7 was increased in the lung tissue, and the distribution of HDAC7 was colocalized with α-SMA-positive cells in the subepithelial layer of the airway. Conclusions ET-1 activates HDAC7 to initiate AP-1 transcriptional activity by recruiting p300 and eventually promotes the production of CTGF. HDAC7 might play a vital role in airway fibrosis and have the potential to be developed as a therapeutic target.

Morphological features of experimental chronic tonsillitis

Purpose. To study the morphological features of the palatine tonsils of experimental animals in normal conditions and during the modeling of chronic tonsillitis. Material and methods. A model of experimental chronic tonsillitis was created on 15 rabbits, 5 animals were included in the control group. Chronic tonsillitis was simulated under general anesthesia. Staphylococcus aureus was injected into the palatine tonsils of animals in a dose of 3 million microbial bodies. Morphological studies of the tissues of the palatine tonsils of animals in the control group and the experimental group were carried out one month after modeling. Results. The results of a morphological study of the tonsils of the experimental group of rabbits clearly demonstrated manifestations of chronic tonsillitis (proliferation of connective tissue in the subepithelial layer, weakening of the muscle tone of the vessels with a simultaneous change in the permeability of the vascular wall, developing hyalinosis). Conclusion. Morphological studies of the tonsils have confirmed the similarity of the modeled chronic pathology with the disease of a similar human organ. Key words: palatine tonsils, rabbits, chronic tonsillitis model, morphological studies.

Histological changes in the human esophagus following triamcinolone injection to prevent esophageal stricture after endoscopic submucosal dissection

Background Locoregional steroid injection prevents post-endoscopic submucosal dissection (ESD) esophageal stricture, but histological changes that occur following steroid injection in the human esophagus are unclear. This study investigated the histopathological characteristics caused by locoregional triamcinolone acetonide (TA) injection using human esophagectomy specimens. Methods From January 2014 to December 2019, among 297 patients (373 lesions) who underwent esophageal ESD, 13 patients who underwent additional esophagectomy after ESD were examined. Seven patients (TA group) with wide excisions were injected with TA after ESD and another six patients (Non-TA group) with smaller tumors were not injected with TA. The clinical background of these patients and histopathological features of ESD ulcer scar obtained from esophagectomy specimens were retrospectively investigated. Results The circumferential rate of ESD excision was more than three-quarters in all cases in the TA group, whereas it was less than three-quarters in the Non-TA group. No other statistical difference in the clinical background was found between the two groups. The subepithelial fibrous tissue of the ESD ulcer scar in the TA group was significantly thinner than that in the Non-TA group (P < 0.05). There was no significant difference in the thickness of the regenerated epithelium and muscularis propria layer of the ESD ulcer scar. Conclusions Histological finding of thinning of the subepithelial fibrous tissue of ESD ulcer scar in the human esophagus after TA injection was obtained. This suggests that TA suppresses the proliferation of the fibrous tissue of the subepithelial layer to help prevent esophageal stricture after widespread ESD in the human esophagus.

The Efficacy of Rituximab in the Treatment of Membranous Nephropathy

Rituximab is a chimeric monoclonal antibody directed against the CD20 expressed on B cells, originally used to treat lymphoma but is increasingly used for the treatment of autoimmune diseases. Membranous nephropathy is an autoimmune disease resulting from the deposition of IgG and complements components onto the subepithelial layer of the glomerular capillary wall and remains the leading cause of nephrotic syndrome in adults. Several prospective and retrospective studies showed rituximab induces remission and may decrease proteinuria in patients with membranous nephropathy. Considerable evidence supports the use of B-cell depletion as initial therapy in nephrotic patients with membranous nephropathy. This review focuses on the efficacy and safety of rituximab in the treatment of membranous nephropathy.Keywords: Membranous nephropathy; rituximab; treatment

Case report – Acute Corneal Subepithelial Hydrops (ACSH) during Micropulse Transscleral Cyclophotocoagulation (MPTSC)

Background To present an unusual intra-operative complication of micropulse transscleral cyclophotocoagulation (MPTSC). Case presentation A 72-year old Chinese gentleman, who had primary angle closure glaucoma and had received bilateral laser iridotomy, presented with progressive left eye blurred vision (visual acuity of 20/40 OD and 20/200 OS). Examination reviewed left eye central retinal venous occlusion. The intraocular pressure (IOP) was 19 mmHg OS and was on maximally tolerated topical medications. Four weeks later, the left eye was complication by neovascular glaucoma; the IOP was raised to 26 mmHg despite additional oral acetazolamide and remained elevated after pan-retinal photocoagulation as well as cataract extraction by phacoemulsification. MPTSC was performed 8 days after the phacoemulsification. During the procedure, a sudden protrusion was formed on the corneal surface. On-table examination with operating microscope and portable slit-lamp reviewed an intact corneal epithelium with a globular-shaped collection of fluid at the subepithelial layer – acute corneal subepithelial hydrops (ACSH). The anterior chamber was formed and the globe was intact. After approximately 10–15 minutes, the swelling spontaneously ruptured and became a corneal epithelial defect. The defect healed on the tenth day after the event with conservative management. There was no irreversible corneal damage and the patient subsequently underwent a successful second MPTSC of the left eye because of poorly controlled IOP. Conclusion ACSH is a possible intra-operative complication of MPTSC. We have proposed the possible mechanisms of ACSH. It is best to exercise caution when using MPTSC shortly after any incisional intraocular surgery.

Nasolacrimal Duct Obstruction: An Unusual Presentation of Sarcoidosis

Lacrimal drainage system disorders leading to epiphora are a common ophthalmologic complaint. When such a patient is identified, the ophthalmologist frequently collaborates with the otolaryngologist to perform a dacryocystorhinostomy (DCR). In rare cases, sinonasal sarcoidosis may lead to nasolacrimal duct obstruction (NLD) and dacryocystitis. A 48-year-old Caucasian female was referred to the Otolaryngology clinic for evaluation of a 6-month history of persistent right-sided nasal obstruction and epiphora. After physical examination and computerized tomography (CT) scan, she was diagnosed with right NLD with dacryocystitis. The patient underwent right endoscopic DCR. Pathology from the lacrimal bone and nasal tissue demonstrated noncaseating granulomas suggestive of sarcoidosis. Postoperative evaluation including lung CT scan confirmed systemic sarcoidosis. Nasolacrimal duct obstruction very rarely is the presenting symptom in patients with sarcoidosis. Imaging is necessary to rule out other causes of NLD, and histopathology is essential for diagnosis. Noncaseating granulomas are found along the nasal tissue and lacrimal sac, specifically in the subepithelial layer. Treatment consists of DCR, either endoscopic or external. Both approaches achieve long-lasting resolution of symptoms but may require revision from inflammation and scarring. There is no consensus on the use of intraoperative or postoperative steroids.

A111 SEVERE FAT MALABSORPTION IN A PATIENT POST ILEAL POUCH ANAL ANASTAMOSIS: A RARE PRESENTATION OF MICROSCOPIC ENTERITIS

Background Microscopic enteritis (ME) is a rare enteropathy characterized by malabsorptive diarrhea and lymphocytic infiltration +/- collagen deposition in the subepithelial layer of the small bowel. Its etiology is unclear. Aims To elucidate a rare cause of fat malabsorption and vitamin deficiency in a patient with ulcerative colitis and an ileoanal pouch. Methods A 74 yo male with a prior IPAA was referred to Internal Medicine in August 2018 for a 36 kg weight loss over 18 months and &gt;16 bowel movements (BM) per day (baseline 6, no history of pouchitis). Celiac serology and infectious workup were negative. Medical management and nutritional supplements did not result in weight gain or improvement of diarrhea. He was admitted in June 2019 with ongoing weight loss, AKI, and signs of fat-soluble vitamin deficiency. A 72-hour fecal fat analysis showed an average fecal weight of 2100 g/d (ref &lt;250 g/d), and excretion of 70% of daily fat intake (ref &lt;7%). His fecal elastase (FE) was 147 µg/g, consistent with moderate pancreatic insufficiency (PI) with mild atrophy on CT. EGD and pouch endoscopy were macroscopically normal, with histological findings of intraepithelial lymphocytosis and mild villous blunting in the duodenum and afferent limb. CT enterography excluded small bowel abnormalities. He was started on pancreatic enzyme replacement and discharged. He returned with worsening diarrhea and AKI. He was treated with supportive care and sent home. In the ensuing 3 weeks, he had up to 24 BM per day and 4 kg of weight loss. He returned in August 2019 with AKI, lack of PO intake and worsened nutritional status. Re-examination of duodenal biopsies from June 2019 revealed an added finding of focal subepithelial collagen thickening. Budesonide was started. Results On budesonide, his symptoms improved within days. BMs decreased to baseline, and his ability to sustain PO intake improved. At his 4-week follow-up visit, BMs were stable with a 6 kg weight gain and no ensuing laboratory abnormalities. Conclusions ME is a rare enteropathy that presents with malabsorption. Fat-soluble vitamin deficiencies can develop with widespread physiological disruption of the mucosal surface. This patient was a diagnostic challenge. His steatorrhea and reduced FE levels led clinicians down a diagnostic pathway of PI. FE is the most common test used in the diagnosis of PI. Levels &lt;200 µg/g are abnormal. Specificity is highest in chronic pancreatitis; however, this decreases in the presence of mucosal atrophy (i.e. IBD and diffuse small bowel disease). Thus, FE could not delineate the cause of steatorrhea in our patient. We can surmise that he likely has diffuse disease that was underestimated on duodenal biopsy. This is supported by his response to budesonide. This case highlights the heterogeneity of clinical presentations of ME. Awareness can reduce patient morbidity. Funding Agencies None

Optical coherence tomography imaging of oral mucosa bullous diseases: a preliminary study

Objectives: Optical coherence tomography (OCT) is a non-invasive technique based on optical imaging with a micrometre resolution. The purpose of this study is to investigate the potential role of OCT in evaluating oral mucosa bullous diseases. Methods: two patients with bullous pemphigoid (BP) and one patient with pemphigus vulgaris (PV) were examined and images of their oral lesions were performed using OCT. Results: In OCT images, the BP blister has a clearly different morphology from the PV one compared to the blistering level. Conclusion: This exploratory study suggests that the OCT is able to distinguish epithelial and subepithelial layer in vivo images of healthy oral mucosa from those with bullous diseases, assisting the clinicians in differential diagnosis.The presented data are in accordance with the scientific literature, although a wider pool of cases is needed to increase statistical power. Histological examination and immunofluorescence methods remain the gold standard for the diagnosis of oral bullous diseases. In this context, the OCT can provide the clinician with a valuable aid both as an additional diagnostic tool and in the follow up of the disease.

P140 3D BIOENGINEERED TISSUE MODEL OF THE LARGE INTESTINE TO STUDY INFLAMMATORY BOWEL DISEASE

An in vitro model of intestine epithelium with an immune compartment was bioengineered to mimic immunologic responses seen in inflammatory bowel disease [1]. While aspects of intestinal immunity can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelium comprised of non-transformed human colon organoid cells and a subepithelial layer laden with monocyte-derived macrophages was bioengineered to mimic native intestinal mucosa cell organization using spongy silk scaffolds. Confluent epithelial monolayers with microvilli, a mucus layer, and infiltration of macrophages to the basal side of the epithelium were observed. Inflammation, induced by E. coli O111:B4 lipopolysaccharide and interferon γ resulted in morphology changes to the epithelium, resulting in ball-like structures, decreased epithelial coverage, and migration of macrophages to the epithelium. Analysis of cytokines present in the inflamed tissue model demonstrated significantly upregulated secretion of pro-inflammatory cytokines associated with active inflammatory bowel disease, including CXCL10, IL-1β, IL-6, MCP-2, and MIP-1β. The macrophage layer enhanced epithelial and biochemical responses to inflammatory stimuli, and this new tissue system may be useful to study and develop potential therapies for inflammatory bowel disease. References: 6 Roh, T.T., et al., 3D bioengineered tissue model of the large intestine to study inflammatory bowel disease. Biomaterials, 2019: p. 119517. 7 In, J., et al., Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. Cellular and molecular gastroenterology and hepatology, 2015. 2(1): p. 48–62.e3. 8 Chen, Y., et al., In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses. PLoS ONE, 2017. 12(11): p. e0187880. Colonoid and macrophage cultivation scheme in the 3D bilayer system. (A) Human monocytes were isolated from whole blood and human colonoids from large intestine biopsies were cultured according to established protocols [2]. (B) Cell suspensions of colonoids were seeded on the film surface on the inner silk scaffold and monocyte-derived macrophages were seeded throughout the porous outer silk scaffold using established protocols [3]. (C) The model is cultured for 3 weeks total with 2 weeks in High WNT media and 1 week in differentiation media based on established protocol. Colonoids are present in the model throughout the 3 week culture time. 2 sets of macrophages are added with the first set added after the first week of culture and the second set replacing the first set after the second week.