Epithelial Research Articles

Oncocytic sinonasal papilloma in the nasal and paranasal sinuses: a case report and review of the literature.

Oncocytic sinonasal papilloma (OSP) is an uncommon, benign neoplasm characterized by papillary growths arising from the Schneiderian mucosa of the nasal and paranasal sinuses. OSP accounts for about 3-6% of all sinonasal papillomas (SPs), and clinically is often confused with inverted sinonasal papilloma (incidence 73%). Although SP shares some of the clinical characteristics of OSP, the pathogenesis differs and it is very important to distinguish between them. Here we present a case of OSP in the nasal and paranasal sinuses of a 67-year-old Japanese male, who complained of persistent left-sided nasal obstruction. A benign nasal paranasal tumor was diagnosed, and endoscopic sinus surgery was performed. Histopathologically, the tumor cells exhibited an exophytic and endophytic growth pattern, composed of multilayered eosinophilic columnar epithelium with finely granular cytoplasm, and forming microcysts filled with mucin or microabscesses. The epithelium was PTAH-positive, and showed positivity for cytokeratin-7 with oncocytic features. A review of the literature revealed 166 cases of OSP in the nasal and paranasal sinuses, with an overall recurrence rate of about 15%. Here we report a case of OSP in the nasal and paranasal sinuses for which PTAH staining specific for oncocytes was useful, together with a review of the relevant literature.

Hemangioma-Like Clear Cell Renal Cell Carcinoma Exhibiting Aggressive Behavior and High Stage: A Case Report.

Clear cell renal cell carcinoma (CCRCC) displays a variety of architectural patterns, which are often intermingled. However, a predominant or purely multicystic growth with diffuse intracystic hemorrhage leading to hemangioma-like histomorphology, is extremely rare in CCRCC. In this article, we describe a CCRCC exhibiting a pure hemangioma-like architecture and aggressive behavior. The patient was a 73-year-old man with a tumor of the left kidney measuring 70 mm in the largest dimension. Histological examination of the nephrectomy specimen revealed a tumor composed entirely of blood filled spaces lined by a single layer of flattened or low cuboidal cells lacking high-grade features or voluminous clear cytoplasm. These cells showed diffuse immunohistochemical positivity for keratin AE1/AE3 and carbonic anhydrase 9 and focal positivity for PAX8, CD10, and alpha-methylacyl-CoA racemase. The tumor invaded the renal vein; no lymph nodes or extension of the tumor into the soft tissues of the hilum were detected (stage pT3a pNx). Using the Illumina TruSight Oncology 500 kit, a clinically significant c.3481dup, p.(Arg1161LysfsTer13) and c.2050del, p.(Gln684Asnfs4) mutations of the tet methylcytosine dioxygenase 2 (TET2) gene and c.296, p.(Pro99GlnfsTer60) mutation of the von Hippel-Lindau (VHL) gene were identified. The immunophenotype and molecular genetics of our tumor were consistent with CCRCC, suggesting that the unusual hemangioma-like growth pattern is most likely the result of extensive regressive changes. In contrast to all previously published reports, our study demonstrated that, despite the bland histological appearance, renal cell carcinomas with hemangioma-like features can invade the renal vein and follow an aggressive clinical course.

A New Blood-Based Epigenetic Diagnostic Biomarker Test (EpiSwitch®® NST) with High Sensitivity and Positive Predictive Value for Colorectal Cancer and Precancerous Polyps

Background/Objectives: Colorectal cancer (CRC) arises from the epithelial lining of the colon or rectum, often following a progression from benign adenomatous polyps to malignant carcinoma. Screening modalities such as colonoscopy, faecal immunochemical tests (FIT), and FIT-DNA are critical for early detection and prevention, but non-invasive methods lack sensitivity to polyps and early CRC. Chromosome conformations (CCs) are potent epigenetic regulators of gene expression. We have previously developed an epigenetic assay, EpiSwitch®®, that employs an algorithmic-based CCs analysis. Using EpiSwitch®® technology, we have shown the presence of cancer-specific CCs in peripheral blood mononuclear cells (PBMCs) and primary tumours of patients with melanoma and prostate cancer. EpiSwitch®®-based commercial tests are now available to diagnose prostate cancer with 94% accuracy (PSE test) and response to immune checkpoint inhibitors across 14 cancers with 85% accuracy (CiRT test). Methods/Results/Conclusions: Using blood samples collected from n = 171 patients with CRC, n = 44 patients with colorectal polyps and n = 110 patients with a ‘clear’ colonoscopy we performed whole Genome DNA screening for CCs correlating to CRC diagnosis. Our findings suggest the presence of two eight-marker CC signatures (EpiSwitch®® NST) in whole blood that allow diagnosis of CRC and precancerous polyps, respectively. Independent validation cohort testing demonstrated high accuracy in identifying colorectal polyps and early versus late stages of CRC with an exceptionally high sensitivity of 79–90% and a high positive prediction value of 60–84%. Linking the top diagnostic CCs to nearby genes, we have built pathways maps that likely underline processes contributing to the pathology of polyp and CRC progression, including TGFβ, cMYC, Rho GTPase, ROS, TNFa/NFκB, and APC.

Claudin 18.2 Immunohistochemistry Expression in Gastric Cancer: A Systematic Review.

Claudin 18.2 is a transmembrane protein, part of the tight-junction complex, selectively expressed in gastric epithelium. It is showing promising results as a target in advanced gastric cancer in phase 3 clinical trials using a monoclonal antibody against claudin 18.2. A systematic review on expression of claudin 18.2 in gastric cancer was performed using the PubMed database. The following search expression was used: ("Stomach Neoplasms" [Mesh]) AND (("claudin-18[TIAB]") OR ("CLDN18[TIAB]")). A total of n=99 articles were retrieved. Of those, 17 preclinical studies about claudin 18.2 expression by immunohistochemistry were selected. The results of those studies showed great variability in the criteria used for defining the thresholds for positivity of the stain. The proportion of claudin 18.2 positive cases varied between 24% and 83%. In works using a positivity threshold set at >40% or >70% of cells with membranous/cytoplasmic staining at 2+/3+ intensity, the average rate of positive cases was 50% or 30%, respectively (similar with clones 43-14A and EPR19202). Positivity of claudin 18.2 was associated with advanced stage, diffuse phenotype and PD-L1 and EBV positivity in some of the studies. Variability in criteria used to define claudin 18.2 positivity, as well as methodological differences, could explain the variation in the proportion of positive cases described, as well as the inconsistency of the association with clinical, molecular, and survival variables. The upcoming anticlaudin 18.2 therapy in advanced gastric cancer should prompt pathology laboratories to adjust their staining protocols and evaluation criteria in their series of patients, to further establish the association of claudin expression with clinical and molecular variables.

P-1220. Humanizing Plasma and Pulmonary Epithelial Lining Fluid (ELF) Exposures of Cefiderocol in Standardized Murine Lung Infection Model

Abstract Background The clinical translation of preclinical in vivo murine infection models can be enhanced by humanizing exposures. However, humanizing plasma exposures does not ensure equivalent exposures at other target sites, such as the ELF, due to interspecies differences in penetration. We developed both plasma and ELF human simulated regimens (HSRs) of cefiderocol in a standardized murine lung infection model.Table 1.Cefiderocol %free time>MIC plasma profiles of mouse and man Methods In accordance with the collaboration for prevention and treatment of MDR bacterial infections (COMBINE) murine lung infection model, specific pathogen-free, 6-8 week old female CD-1 mice were rendered neutropenic and received a single 5 mg/kg IP injection of uranyl nitrate 3 days prior to inoculation. Under isoflurane anesthesia, mice were inoculated with 0.05 mL of a ∼108 CFU/mL bacterial suspension of Klebsiella pneumoniae via intranasal route. A historic cefiderocol plasma HSR from a murine thigh model was used as a baseline regimen. Two hours after inoculation, cefiderocol HSRs were administered. Groups of 6 mice were euthanized at predefined timepoints throughout the dosing interval for plasma and bronchoalveolar fluid collection. Samples were assayed by LC-MS/MS and urea correction was used to determine ELF concentrations. Murine plasma protein binding (32%) was determined previously and used to calculate free drug. Pharmacokinetic models for both plasma and ELF were fitted to the data in Phoenix WinNonlin and HSRs were mathematically altered and subsequently confirmed in the model.Figure 1.Free cefiderocol plasma concentration-time profiles in humans receiving 2g q8h as 3h infusion and mice receiving a human-simulated regimen. Results Cefiderocol 2g q8h 3h infusion plasma exposures were recapitulated in the murine model with 5, 7.5, 10, 3.5, and 1 mg/kg at 0, 1, 2, 4, and 6h, administered every 8h, as presented in Table/Figure 1. ELF penetration for cefiderocol was greater in infected mice relative to man, necessitating a dosage reduction to 3.75, 5, 6.25, 1.75, and 1 mg/kg at 0, 1, 2, 4, and 6h, administered every 8h, to humanize ELF exposures (Figure 2).Figure 2.Cefiderocol pulmonary epithelial lining fluid concentration-time profiles in humans receiving 2g q8h as 3h infusion and mice receiving a human-simulated regimen. Conclusion Plasma and ELF HSRs for cefiderocol were developed and validated in the COMBINE murine neutropenic lung infection model. Cefiderocol ELF penetration was greater in mice than man, underscoring the importance of understanding interspecies differences in target site penetration for bench-to-bedside translation. Disclosures Andrew J. Fratoni, PharmD, InsightRX: Grant/Research Support Erin Duffy, PhD, CARB-X: Employee David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Grant/Research Support|Innoviva: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Venatorx: Grant/Research Support

P-1221. Benchmark Efficacy for Humanized Cefiderocol Plasma and Pulmonary Epithelial Lining Fluid (ELF) Exposures Against Gram Negative Isolates in Standardized Murine Lung Infection Model

Abstract Background The collaboration for prevention and treatment of MDR bacterial infections (COMBINE) consortium have developed a standardized murine neutropenic lung infection model to align fundamental model elements to reduce inter-laboratory variability. We developed human simulated regimens (HSRs) based on both plasma and ELF exposures for cefiderocol in the COMBINE murine model and herein provide benchmark efficacy against a collection of Klebsiella pneumoniae and Pseudomonas aeruginosa isolates.Table 1.Phenotypic and genotypic information of Klebsiella pneumoniae and Pseudomonas aeruginosa isolates Methods Following the COMBINE protocol for the preclinical murine lung model, neutropenic mice that received uranyl nitrate on day -3 to provide predictable renal impairment were administered 0.05 mL intranasal inoculums of K. pneumoniae (n=9) or P. aeruginosa (n=4) under isoflurane anesthesia. Isolate MICs were determined via BMD. Six mice per isolate were sacrificed 2h after inoculation to determine baseline bacterial burden, and 4-6 received saline control for 24h. Humanized exposures of cefiderocol 2g q8h as 3h infusion in plasma (5, 7.5, 10, 3.5, and 1 mg/kg at 0, 1, 2, 4, and 6h, every 8h) and ELF (3.75, 5, 6.25, 1.75, and 1 mg/kg at 0, 1, 2, 4, and 6h, every 8h) were administered to groups of 6 mice. Efficacy was measured in log10 CFU/lung at 24h compared with baseline bacterial burden.Figure 1.CFU/Lung data in Klebsiella pneumoniae isolates following administration of humanized cefiderocol (2g q8h 3h infusion) plasma and ELF exposures in the COMBINE murine neutropenic lung infection model. Outlier mice determined by Tukey’s Test and displayed as individual dots. Results Cefiderocol MICs and genotypic information are presented in Table 1. The CFU/lung data for K. pneumoniae and P. aeruginosa isolates are displayed in Figures 1 and 2, respectively. The K. pneumoniae isolates required higher log10 CFU/lung starting bacterial burden (mean ± SD, 7.23 ± 0.18) compared with P. aeruginosa (5.68 ± 0.24) to achieve adequate (≥ 1 log10 CFU/lung) growth in 24h controls. With the exception of PSA INT 4-99, the FDC plasma HSR, which over-exposes murine ELF relative to human, achieved greater average CFU reduction than the ELF HSR. Differences in CFU reduction between the matrix HSRs were most pronounced in the 2 isolates with MIC of 16 mg/L at the resistance breakpoint.Figure 2.CFU/Lung data in Pseudomonas aeruginosa isolates following administration of humanized cefiderocol (2g q8h 3h infusion) plasma and ELF exposures in the COMBINE murine neutropenic lung infection model. Conclusion These data provide a comparative benchmark for expected efficacy with humanized cefiderocol exposures of both plasma and ELF when using the COMBINE protocol. Humanizing exposures at the target site of infection may provide better clinical translation when interspecies differences in penetration from plasma exist. Disclosures Andrew J. Fratoni, PharmD, InsightRX: Grant/Research Support Erin Duffy, PhD, CARB-X: Employee David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Grant/Research Support|Innoviva: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Venatorx: Grant/Research Support

Retinoic acid antagonizes estrogen signaling to maintain adult uterine cell fate

Classical tissue recombination experiments demonstrate that cell-fate determination along the anterior-posterior axis of the Müllerian duct occurs prior to postnatal day 7 in mice. However, little is known about how these cell types are maintained in adults. In this study, we provide genetic evidence that a balance between antagonistic retinoic acid (RA) and estrogen signaling activity is required to maintain simple columnar cell fate in adult uterine epithelium. Transdifferentiation of simple columnar uterine epithelium into stratified cervicovaginal-like epithelium was observed in three related mouse genetic models, in which RA signaling was perturbed in the postnatal uterus. Single-cell RNA sequencing analysis identified the transformed epithelial cell populations and revealed extensive immune cell infiltration resulting from loss of RA signaling. Surprisingly, disruption of RA signaling led to dysregulated expression of a substantial number of estrogen target genes, suggesting that these two pathways may functionally oppose each other in determining and maintaining uterine epithelial cell fate. Consistent with this model, neonatal exposure to the strong synthetic estrogen, diethylstilbestrol, downregulated expression of a group of RA target genes and led to epithelial stratification and immune cell infiltration in wild-type uterus. Treating RA receptor triple conditional knockout pups with fulvestrant, an estrogen antagonist, reestablished the balance between the two signaling pathways, and effectively prevented the transformation of mutant simple columnar epithelia to metaplastic stratified epithelia. These findings implicate an essential role for RA signaling in maintaining uterine cytodifferentiation by antagonizing estrogen signaling in the postnatal uterus.

Role of Cryotherapy in the Management of Cervical Ectropion: A Comprehensive Review

Cervical ectropion, also known as columnar epithelium on the vaginal portion of the cervix, is one of the common benign conditions that occur in women of reproductive age. Although generally asymptomatic, symptomatic CE can cause painful symptoms such as vaginal discharge, itching, dyspareunia, and post-coital bleeding, and could potentially increase the risk of infection with HPV and cervical dysplasia. Cryotherapy is inexpensive and minimally invasive, and widely used for symptomatic CE. Double-freeze cycle of liquid nitrogen at extremely low temperatures in liquid nitrogen freezes the affected tissue and destroys ectopic epithelium. Cryotherapy is easy, well-tolerated, and may be performed without anesthesia and on an outpatient basis. There are published studies that show a high efficacy rate of up to 98% for resolution of ectropion with symptom relief of 95% in the treated patients. General side effects include cramping and copious vaginal discharge and, in general, resolve spontaneously over weeks. Other complications that include cervical stenosis and infection are unusual but can occur with more significant outcomes. Cryotherapy remains a treatment of choice because of high success rates and minimum side effects and it is very inexpensive, therefore highly advantageous in low-resource settings, where the accessibility of more advanced treatments may be limited. More advanced cases or lesions far in the cervical canal of cases may not be adequate enough to be treated through cryotherapy; however, it is usually effective for most women who experience symptomatic cervical ectropion. Key words: Cervical ectropion, Cryotherapy, Cervical dysplasia, Liquid nitrogen, Vaginal discharge, post-coital bleeding, Minimal invasive treatment.

Human organotypic colon in vitro microtissue: unveiling a new window into colonic drug disposition.

The purpose of this study was to evaluate EpiColon, a novel human organotypic 3D colon microtissue prototype, developed to assess colonic drug disposition, with a particular focus on permeability ranking, and compare its performance to Caco-2 monolayers. EpiColon was characterized for barrier function using transepithelial electrical resistance (TEER), morphology via histology and immunohistochemistry, and functionality through drug transport studies measuring apparent permeability (Papp). Cutoff thresholds for the permeability of FITC-dextran 4 kDa (FD4), FITC-dextran 10 kDa (FD10S), and [14C]mannitol were established to monitor microtissue integrity. Permeability of EpiColon for 20 benchmark drugs was compared with Caco-2 data, and the activity of pivotal efflux transporters, including multidrug resistance protein 1/P-glycoprotein (MDR1/P-gp), along with multidrug resistance protein 2 (MRP2) and breast cancer resistance protein (BCRP), was evaluated using selective substrates. EpiColon exhibited a physiological barrier function (272.0 ± 53.05 Ω x cm2) and effectively discriminated between high (e.g., budesonide and [3H]metoprolol) and low permeable compounds (e.g., [3H]atenolol and [14C]mannitol). The model demonstrated functional activity for key efflux transporters, with efflux ratios of 2.32 for [3H]digoxin (MDR1/P-gp) and 3.34 for sulfasalazine (MRP2 and BCRP). Notably, EpiColon showed an enhanced dynamic range in the low permeability range, differentiating Papp between FD4 and FD10S, in contrast to Caco-2 monolayers. Significant positive correlations were observed between human fraction absorbed (fabs) and logarithmically transformed Papp [AP-BL] values for both EpiColon (rs = 0.68) and Caco-2 (rs = 0.68). Furthermore, EpiColon recapitulates some essential phenotypic and cellular features of the human colon, including the expression of critical marker genes (Pan-Cytokeratin+: epithelial/colonocytes, Vimentin+: mesenchymal/fibroblast, and Alcian Blue+: goblet cell/mucus). In conclusion, EpiColon is a promising platform that offers a valuable complement to conventional Caco-2 monolayers for studying colonic drug disposition. However, the presence of flat and some cuboidal cells, along with low throughput, must be addressed to improve its applicability in both academic research and pharmaceutical industry.

Invasive stratified mucin-producing carcinoma of the cervix: A case report and review of the literature

ABSTRACT Invasive stratified mucin-producing carcinoma (ISMC) is a rare, recently described subtype of HPV-associated cervical adenocarcinoma. It shows varied morphological patterns, making it difficult to diagnose, especially the mixed forms. A 57-year-old female, P7L7, presented with postmenopausal bleeding for the past five months. On per-vaginal examination, a friable cervical growth was noted. Microscopic examination of the cervical biopsy showed an invasive tumor composed of nests of stratified columnar cells with peripheral palisading and a variable amount of (alcian blue-positive) intracytoplasmic mucin. Another component of the tumor showed sheets and nests of undifferentiated tumor cells. IHC on both components showed diffuse positivity for P16, PAX8, and keratin 7. Based on these findings, a diagnosis of ISMC was made. Awareness of the morphological features and ancillary stain results of ISMC can aid in picking up the diagnosis in a small biopsy. These findings have prognostic value, as most cases of ISMC behave aggressively.

Development of Ideas About the Nature of the Prechordal Plate in the Research of Russian Scientists of the XX century. Facts and Discussion Aspects

The purpose of the review was to analyze the results of domestic research of the twentieth century on the formation and differentiation of the prechordal plate in vertebrate embryogenesis. The prechordal plate is a kind of embryonic germ that passed from the outer germ leaf through the middle to the inner one during gastrulation. Since its discovery in amphibians, the prechordal plate has been a subject of debate. The main issues of discussion are the sources of the prechordal plate and the differentiation of its derivatives. A significant part of Russian researchers share the view of ectoderm as a source of formation of the prechordal plate. A number of authors name the endoderm as the source of the formation of the prechordal plate. There is also a point of view according to which neither the ectoderm nor the endoderm are the source of the formation of the prechordal plate. The prechordal plate is a rudiment with complex developmental potentials. Thus, its lateral parts are not part of the intestinal tube, but go to the formation of the first two pairs of mesodermal somites, giving rise to a number of structures of the face and skull, for example, the external eye muscles. The medial area, growing, forms the epithelial lining of the anterior part of the intestinal tube. The characteristics of the epithelium developing their prechordal plate have been studied in the most detail. The epithelium formed from the material of the prechordal.

Sleeve gastrectomy reveals the plasticity of the human gastric epithelium

Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epithelium in 12 women, we observed that SG is associated with an increase in a sub-population of acid-secreting parietal cells that overexpress respiratory enzymes and an increase in histamine-secreting enterochromaffin-like cells (ECLs). ECLs of SG-operated patients overexpressed genes coding for biosynthesis of neuropeptides and serotonin. Mathematical modeling showed that pH homeostasis by gastrin is analogous to non-linear proportional and integral control, that drives adaptation of the epithelium to acid-secretion demand. Quantitative model predictions were validated in patients. The results demonstrate human gastric epithelium remodeling following SG at the molecular and cellular levels, and more generally how trophic hormones enable robust adaptation of tissue function to meet physiological demand.

Frank Invasion in Tall Cell Carcinoma with Reversed Polarity of the Breast: Report of Two Cases.

Tall cell carcinoma with reversed polarity (TCCRP) is a rare neoplasm of the breast composed of columnar tumor cells arranged in solid and solid papillary nests with evidence of apical nuclear polarity. No frank invasion is evident despite the lack of a myoepithelial cell layer throughout the tumor. TCCRP has a triple negative or hormone receptor-low immunophenotype. Recurrent IDH2 R172 hotspot mutation coexisting with genetic alterations in the PI3K pathway characterize this tumor. Here, we report on two postmenopausal patients with TCCRPs with frank stromal invasion. IDH2 R172 mutations were detected in both tumors by immunohistochemistry. Targeted sequencing of case 2 demonstrated the presence of IDH2 R172T and RTEL1 E839K mutations. Both patients underwent breast conservation surgery, radiation therapy and adjuvant endocrine therapy with anastrozole and show no evidence of disease at 65 and 25 months, respectively. This study suggests that tall cell carcinoma with reversed polarity may give rise to frank invasive carcinoma, the prognostic significance of which is yet unknown.

Morphology and Immunoexpression of Selenoproteins in Term Placenta of Alpaca (Vicugna pacos) from the Peruvian Andes.

South American camelids inhabit high-altitude environments characterized by hypoxia, influencing embryonic, fetal, and placental development. This study examined the term placenta morphology of alpacas (Vicugna pacos, N = 12) and the immunoexpression of antioxidant selenoproteins (SP). We hypothesize that the placenta of alpacas, adapted to high altitudes, has characteristics with other species also adapted to altitude. Placentas were paraffin-embedded, sectioned (3-5 µm), stained with hematoxylin-eosin (H&E), Masson's trichrome, and picrosirius red, and analyzed via light and polarized light microscopy. The chorion showed simple cuboidal epithelium with binucleated cells, a subepithelial mesenchyme rich in blood capillaries (area: 124.90 ± 9.82 µm2), and type III collagen fibers. The chorionic villi measured 2740.22 ± 132.75 µm. The allantois contained a simple columnar epithelium and mesenchyme with type I collagen fibers. Immunohistochemistry localized SP-N, SP-P, Dio-3, and GPx-3 in the blood capillaries and mesenchymal tissue of the chorion but not in the allantois. These findings were compared to human and sheep placentas from different altitudes due to a lack of camelid data at low levels. The morphological features resembled adaptations to hypoxia observed in other species. This preliminary study suggests a potential role for selenoproteins in hypoxia adaptation, providing a basis for future functional studies.

Incidentally Diagnosed Endolymphatic Sac Tumor on 68Ga-DOTA-TATE PET/CT in a Suspected Case of Pheochromocytoma.

Endolymphatic sac tumors (ELSTs) are rare, slow-growing, and locally aggressive neoplasms that originate from the epithelial lining of the endolymphatic duct and sac. These are characterized by their infiltrative growth pattern and the potential for local destruction of surrounding structures, including the inner ear and temporal bone. We report a case of an incidentally diagnosed sporadic ELST. The article provides an overview of the relevant literature on this topic and discusses the clinical, radiological, and surgical findings pertaining to this particular ELST case. Given their indolent growth pattern and lack of significant changes on interval imaging, surgical intervention is often deferred for these lesions.

Laparoscopic peritoneal mucinous cystadenoma debulking: A case report.

Peritoneal mucinous cystadenoma is rare in the clinic, lacks specific clinical manifestations, tumor markers, and imaging features, and is easily misdiagnosed and missed. Clinical practitioners should maintain a high level of vigilance. Here, we report a case of laparoscopic peritoneal mucinous cystadenoma stripping to improve our understanding of the disease. A 34-year-old woman was admitted to our hospital with a history of epigastric pain over the past year that had worsened over the previous 4 months. The patient had no history of trauma or surgery. A computed tomography scan of the whole abdomen, as well as hepatobiliary and pancreatic scans and magnetic resonance cholangiopancreatography examinations, showed a low-density mass of approximately 5.8 × 4.8 cm between the right lobe of the liver and the right kidney. The lesion showed no significant enhancement on the enhanced scan, and analysis of tumor markers was normal. The preoperative diagnosis was cholelithiasis with cholecystitis and hepatic cysts. It was proposed to perform "laparoscopic cholecystectomy + hepatic cyst decapitation and decompression" under general anesthesia; however, intraoperative exploration revealed that the abdominal cyst had originated from the right side of the peritoneum and was located between the liver and kidney. The surgical procedure was thus changed to "laparoscopic abdominal cyst removal + cholecystectomy." The patient recovered well and was discharged on the fourth postoperative day. Postoperative pathological examination (abdominal cyst) showed mostly serous cells partially covered with high columnar mucus cells, which was consistent with mucinous cystadenoma. The postoperative diagnosis was peritoneal mucinous cystadenoma and cholecystolithiasis with cholecystitis. Clinical diagnosis of mucinous cystadenoma of the abdominal wall is difficult. The possibility of the disease should be considered when a cystic space is found in the abdominal cavity. Diagnosis depends on postoperative pathological examination, and surgery is the preferred treatment option. During the operation, attention should be paid to avoid rupture of the cyst wall and overflow of cyst fluid, and to avoid blind fenestration and drainage or puncture and aspiration sclerotherapy when the diagnosis is unclear.

Toxicity and histological architecture of <i>Semecarpus anacardium </i>kernel extract on the foregut of <i>Heliothis armigera </i>

The efficacy of Semecarpus anacardium Linn. kernel extract in chloroform as an antifeedant and stomach poison agent was assessed against Heliothis armigera (Hubner) early fourth instars. Larvae that were fed with food containing different doses of extract showed antifeedant, toxic effects and decreased consumption. The foregut histopathological architecture of larvae fed with S. anacardium kernel extract in chloroform at concentration equal to LD50 value and after 24 and 96 hours of treatment, demonstrates substantial injury to the epithelium layer, including vacuolization in some areas, gut tissue shrinkage, and peritrophic membrane disruption, which leads to the degeneration of goblet, regenerative, and epithelial cells. The height of the columnar epithelium and diameter of lumen were also reduced after 24 hours of exposure. These alterations in the gut had a detrimental effect on the larvae’s ability to digest and absorb food, resulting to a nutritional deficit that may have stunted their development. The findings of this study indicate that S. anacardium kernel extracts in chloroform have a significant stomach poisoning capability against H. armigera larvae, suggesting that this approach could be investigated as an environmentally safe method of integrated pest management.

Alterations in the uterine echotexture, hemodynamics, and histological findings in relation to metabolomic profiles in goats with different ovarian activities (active versus inactive ovaries).

This study investigated, for the first time, the alterations in the uterine echotexture and blood flow in cyclic and acyclic (inactive ovary) goats using ultrasonography. The study aimed also to evaluate the metabolomic changes in the plasma of cyclic and acyclic goats. Furthermore, the histopathological approach was applied to the specimens of the uterus to validate the findings of this study. Based on monitoring the estrous cyclicity, goats were assigned into either a cyclic group or an acyclic one (n = 7, each). Ovarian morphometry and hemodynamics were assessed to confirm group assignment. Full ultrasonographic examinations were performed to assess the uterine echotexture by B-mode ultrasonography and uterine hemodynamics by color Doppler ultrasonography in the cyclic group (at days 10-12) and acyclic group. Additionally, blood samples were withdrawn for measuring hormonal concentrations and for metabolomics analysis. Specimens of the uterus were executed for histopathological evaluation in both groups. Results revealed alterations in the uterine hemodynamics and endometrial echotexture. Goats in the cyclic group attained a significantly higher color pixel area of the endometrium compared to those in the acyclic one (P< 0.001). However, the pixel intensity of the endometrium echotexture was significantly (P< 0.05) lower in the cyclic group than in the smooth inactive ovary one. There were significant (P< 0.05) increases in the concentrations of FSH, LH, and inhibin in the cyclic group compared to their concentrations in the acyclic one. Goats in the acyclic group attained noticeable (P< 0.001) lower concentrations of E2 and P4 than in the cyclic goats. The metabolomic results revealed the existence of several up- and down-regulated metabolites among the studied groups. In this investigation, untargeted metabolomic analysis revealed the existence of 5 up-regulated metabolites (ketoleucine, L-fucose, D-glucurono-6,3-lactone, melatonin, and 5-methoxy tryptamine) and 5 down-regulated ones (p-octopamine, 3-hydroxyisovaleric acid, methylmalonic acid, 4-hydroxyphenylpyruvic acid, and cadaverine) in the cyclic group compared to the acyclic one. The enrichment analysis of the significant metabolites showed top pathways that may be involved in these changes, such as fructose and mannose metabolism, valine. Leucine, and isoleucine biosynthesis, linoleic acid metabolism, arginine biosynthesis, and vitamin B6 metabolism based on the KEGG enriched pathway. Altogether, the histopathological assessment showed noticeable changes in the columnar epithelial lining of the endometrial epithelium, endometrial vascularity, and endometrial glands among the studied groups. In conclusion, this study extrapolated the differences between cyclic goats (during the mid-luteal phase) and acyclic ones in terms of hormonal, hemodynamics, echotexture of the uterus, and circulating metabolomics. These findings are very crucial to fully assess the fertility potential in goats.

Epithelial and mesenchymal compartments of the developing bladder and urethra display spatially distinct gene expression patterns.

The lower urinary tract is comprised of the bladder and urethra and develops from the cloaca, a transient endoderm-derived structure formed from the caudal hindgut. After cloacal septation to form the urogenital sinus and anorectal tract, the bladder gradually develops from the anterior portion of urogenital sinus while the urethra elongates distally into the genital tubercle. The bladder is a target for regenerative and reconstructive therapies but engineering an impermeable bladder epithelial lining has proven challenging. Urethral epithelial function, including its role as an active immune barrier, is poorly studied and neglected in regenerative therapy. A deeper understanding of epithelial patterning of the urogenital sinus by the surrounding mesenchyme, also accounting for sex-specific differences, can inform regenerative therapies. In this study, we identified spatially distinct genes in the epithelial and mesenchymal compartments of the developing mouse bladder and urethra that could be potential drivers of patterning in the lower urinary tract. Our data revealed spatially restricted domains of transcription factor expression in the epithelium that corresponded with bladder or urethra-specific differentiation. Additionally, we identified the genes Wnt2, Klf4 and Pitx2 that localize to the mesenchyme of the developing bladder and could be potential drivers of bladder differentiation. Our data revealed an increase in the expression of several chemokine genes including Cx3cl1 and Cxcl14 in the developing urethral epithelium that correlated with an increase in epithelial-associated macrophages in the urethra. A survey of sex-specific differences in epithelial and mesenchymal compartments revealed several differentially expressed genes between the male and female urethra but few sex-specific differences in bladder. By comparing spatially distinct gene expression in the developing lower urinary tract, our study provides insights into the divergent differentiation trajectories of the fetal bladder and urethra that establish their adult functions.

HISTOLOGICAL, HISTOCHEMICAL, AND IMMUNOHISTOCHEMICAL CHARACTERIZATION OF THE EFFERENT DUCTULES OF THE DOVE

This research examines the structural features of the efferent ductules (EDs) in healthy doves (Spilopelia senegalensis) collected from local hunters in Assiut, Egypt. After slaughter, the efferent ductules were promptly dissected and preserved in Bouin's fluid. Utilizing a combination of histological, histochemical, and immunohistochemical techniques, we explored the architecture of EDs, focusing on the stroma and parenchyma. The lining epithelium was made up of a simple columnar to the pseudostratified columnar epithelium, ciliated, secretory, and basal cells. However, this study is the first to identify telocytes within the peritubular region of the dove’s efferent ductules, highlighting their potential role in tissue communication and regeneration. Additionally, androgen receptor expression was detected in the epithelial cells and spermatozoa within the lumen, suggesting a significant role in the male reproductive system.