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BACKGROUND/AIMS: While DNA methylation and gastric microbiome are each associated with gastric cancer (GC), their combined role in predicting GC remains unclear. This study investigated the potential of a combined DNA methylation and gastric microbiome signature to predict Helicobacter pylori-negative GC. METHODS: In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of DKK3, SFRP1, EMX1, NKX6-1, MIR124-3, and TWIST1 in the gastric mucosa from 75 H. pylori-negative patients, including chronic gastritis (CG), intestinal metaplasia (IM), and GC. A combined analysis of DNA methylation and gastric microbiome, using 16S rRNA gene sequencing, was performed in 30 of 75 patients. RESULTS: The methylation levels of DKK3, SFRP1, EMX1, MIR124-3, and TWIST1 were significantly higher in patients with GC than in controls (all q

Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGF-β1 signaling inhibitor epigallocatechin gallate (EGCG) to interstitial lung disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA-Seq on spare tissue. Biopsies from untreated patients showed higher fibroblast TGF-β1 signaling compared with nondisease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGF-β1 signaling and several proinflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzled-related protein 2 (sFRP2), an unrecognized TGF-β1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision-cut lung slices (PCLSs) from nondiseased donors, we found TGF-β1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature cytokeratin 5+ (Krt5+) basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGF-β1 signaling in ILD and the therapeutic potential of EGCG in reducing idiopathic pulmonary fibrosis-related (IPF-related) transcriptional changes and identify TGF-β1/noncanonical Wnt pathway crosstalk via sFRP2 as a mechanism for dysfunctional epithelial signaling in IPF/ILD.

Ankylosaurs were a group of heavily armored non‐avian dinosaurs (Dinosauria, Ankylosauria), represented by a relatively abundant fossil record from the Cretaceous of North and South America. Their dermal skeleton was characterized by large osteoderms whose development and functional role have been largely investigated. However, interstitial small ossicles, forming between these osteoderms, have been far more overlooked and it remains unknown whether they were formed through the ossification of a preexisting fibrous matrix of connective tissue (i.e., metaplasia) or by a cell‐induced differentiation of new fiber bundles followed by mineralization (i.e., neoplasia sensu (Zeitschrift für Wissenschaftliche Zoologie, 1858, 9, 147)). Here, we propose a hypothesis on the developmental origin of these small ossicles in the ankylosaurian Antarctopelta oliveroi using light microcopy, scanning electron microscopy and three‐dimensional virtual histology through propagation phase‐contrast synchrotron radiation micro‐computed tomography (PPC‐SRμCT). Ossicles are located in the dermis. They are composed of two layers: (1) a thin external layer, and (2) a thick basal plate, composed of collagen fiber bundles, which forms the main part of the ossicle. The external layer is made of a smooth, vitreous mineralized tissue that does not look like bone. The basal plate, however, is of osseous origin. In this basal plate, the collagen fiber bundles are organized in two orthogonal systems: one horizontal—observable in cross‐sections—and one vertical—observable in the primary plane of sections sensu (Journal of Vertebrate Paleontology, 2004, 24, 874). The horizontal system is itself composed of successive layers of collagen fiber bundles arranged into an orthogonal plywood‐like structure. The bundles of the vertical system radiate from the center of the ossicle at the level of the transition between the external layer and the basal plate and run towards the periphery of the basal plate. Their thickness increases from the center of the ossicle towards its periphery. Numerous bundles of the vertical system form thin threads that interweave and penetrate within the thick bundles of the horizontal system. Our new data suggest that the ossicles were at least partially formed by metaplasia, that is, through the ossification of a preexisting fibrous matrix of connective tissue. This process was probably supplemented by a cell‐induced differentiation of new fiber bundles laid down prior to their incorporation into the fibrous system and its mineralization. This process looks more akin to neoplasia sensu (Zeitschrift für Wissenschaftliche Zoologie, 1858, 9, 147) than to metaplasia. Consequently, metaplastic and neoplastic processes may coexist in these ossicles with a possible differential expression during ontogeny. [ABSTRACT FROM AUTHOR]

Background: To present a case of conjunctival growth on the amniotic membrane and subsequent pathology revealing conjunctival squamous metaplasia in a patient with Stevens-Johnson syndrome. Case presentation: A 21-year-old female presented with painful, blurred vision in both eyes for two weeks. She was diagnosed with Stevens-Johnson syndrome 5 weeks before. Due to bilateral corneal epithelial defects, ProKera®, an amniotic membrane corneal bandage with a polycarbonate ring, was placed in both eyes. However, three weeks later, a slit-lamp examination revealed vascularized tissue growth from the palpebral conjunctiva to the amniotic membrane, along with symblepharon formation in the left eye. The patient underwent conjunctival biopsy, amniotic membrane removal, and symblepharon release. Pathology report showed the growth of squamous epithelium on the acellular amniotic membrane. Immunohistochemistry further supported the diagnosis, revealing squamous markers through p40 staining and highlighting the presence of the amniotic membrane using trichrome stain. Three months later, the patient's visual acuity had improved to 20/25 and no symblepharon was noted. Conclusions: This is the first case of conjunctival squamous metaplasia on amniotic membrane associated with Stevens-Johnson syndrome. Our case indicates that, despite the anti-inflammatory properties of amniotic membrane, conjunctival squamous metaplasia may arise after amniotic membrane grafting due to intense inflammation in Stevens-Johnson syndrome. Clinicians should conduct regular monitoring before amniotic membrane dissolution to preclude the development of conjunctival squamous metaplasia on the membrane and potential invasion into the cornea. [ABSTRACT FROM AUTHOR]

Background and Aim: Barrett's oesophagus predisposes individuals to oesophageal adenocarcinoma (OAC), with the risk of progression to malignancy increasing with the degree of dysplasia, categorized as either low‐grade dysplasia (LGD) or high‐grade dysplasia (HGD). The reported incidence of progression to OAC in LGD ranges from 0.02% to 11.43% per annum. In patients with LGD, Australian guidelines recommend 6‐monthly endoscopic surveillance. We aimed to describe the surveillance practices within a tertiary centre, and to determine the predictive value of surveillance as well as other risk factors for progression. Methods: Endoscopy and pathology databases were searched over a 10‐year period to collate all cases of Barrett's oesophagus with LGD. Medical records were reviewed to document patient factors and endoscopic and histologic details. Because follow‐up times varied greatly, survival analysis techniques were employed. Results: Fifty‐nine patients were found to have LGD. Thirteen patients (22.0%) progressed to either HGD or OAC (10 (16.9%) and three (5.1%) respectively); the annual incidence rates of progression to HGD/OAC and OAC were 5.5% and 1.1% respectively. All patients who developed OAC had non‐guideline‐adherent surveillance. A Cox model found only two predictors of progression: (i) guideline‐adherent surveillance, performed in 16 (27.1%), detected progression to HGD/OAC four times earlier than non‐guideline‐adherent surveillance (95% confidence interval (CI) = 1.3–12.3; P = 0.016). (ii) The detection of visible lesions at exit endoscopy independently predicted progression (hazard ratio = 6.5; 95% CI = 1.9–22.8; P = 0.003). Conclusion: Barrett's oesophagus with LGD poses a significant risk of progression to HGD/OAC. Guideline‐recommended surveillance is effective, but is difficult to adhere to. Clinical predictors for those who are more likely to progress are yet to be defined. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion The implementation of computer‐aided detection (CAD) devices in esophagogastroduodenoscopy (EGD) could autonomously identify gastric precancerous lesions and neoplasms and reduce the miss rate of gastric neoplasms in prospective trials. However, there is still insufficient evidence of their use in real‐life clinical practice.A real‐world, two‐center study was conducted at Wenzhou Central Hospital (WCH) and Renmin Hospital of Wuhan University (RHWU). High biopsy rate and low biopsy rate strategies were adopted, and CAD devices were applied in 2019 and 2021 at WCH and RHWU, respectively. We compared differences in gastric precancerous and neoplasm detection of EGD before and after the use of CAD devices in the first half of the year.A total of 33 885 patients were included and 32 886 patients were ultimately analyzed. In WCH of which biopsy rate >95%, with the implementation of CAD, more the number of early gastric cancer divided by all gastric neoplasm (EGC/GN) (0.35% vs 0.59%, P = 0.028, OR [95% CI] = 1.65 [1.0–2.60]) was found, while gastric neoplasm detection rate (1.39% vs 1.36%, P = 0.897, OR [95% CI] = 0.98 [0.76–1.26]) remained stable. In RHWU of which biopsy rate <20%, the gastric neoplasm detection rate (1.78% vs 3.23%, P < 0.001, OR [95% CI] = 1.84 [1.33–2.54]) nearly doubled after the implementation of CAD, while there was no significant change in the EGC/GN.The application of CAD devices devoted to distinct increases in gastric neoplasm detection according to different biopsy strategies, which implied that CAD devices demonstrated assistance on gastric neoplasm detection while varied effectiveness according to different implementation scenarios. [ABSTRACT FROM AUTHOR]

The capacity to regenerate lost tissues varies significantly among animals. Some phyla, such as the annelids, display substantial regenerating abilities, although little is known about the cellular mechanisms underlying the process. To precisely determine the origin, plasticity and fate of the cells participating in blastema formation and posterior end regeneration after amputation in the annelid Platynereis dumerilii, we developed specific tools to track different cell populations. Using these tools, we find that regeneration is partly promoted by a population of proliferative gut cells whose regenerative potential varies as a function of their position along the antero-posterior axis of the worm. Gut progenitors from anterior differentiated tissues are lineage restricted, whereas gut progenitors from the less differentiated and more proliferative posterior tissues are much more plastic. However, they are unable to regenerate the stem cells responsible for the growth of the worms. Those stem cells are of local origin, deriving from the cells present in the segment abutting the amputation plane, as are most of the blastema cells. Our results favour a hybrid and flexible cellular model for posterior regeneration in Platynereis relying on different degrees of cell plasticity. [ABSTRACT FROM AUTHOR]

Objectives To investigate optical coherence microscopy (OCM) imaging features and the application value of these high-resolution images for identifying endocervical canal lesions (ECLs), which is a clinical dilemma in cervical cancer screening programs. Methods In total, 520 OCM images were obtained by scanning the cervical canal lesions with an ultra-high-resolution OCM system (204 specimens from 73 patients). The OCM morphologic characteristics of ECLs were observed and summarized, and then 3 researchers performed a diagnostic test of OCM images of cervical canal lesions. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, 95% confidence interval of each parameter, and interinvestigator agreement (κ) were calculated. Results Normal endocervix, cysts, squamous metaplasia, high-grade squamous intraepithelial lesions involving glands, and invasive carcinoma had distinct OCM characteristics, which correlated well with corresponding H&E histologic sections. The accuracy, sensitivity, and specificity of the 3 researchers were 90.6%, 89.3% (95% CI, 86.5%-91.7%) and 91.6% (95% CI, 89.2%-93.5%), respectively. The positive predictive value was 90.1% (95% CI, 87.3%-92.4%), and the negative predictive value was 90.9% (95% CI, 88.5%-92.9%), with almost perfect agreement (κ = 0.874). Conclusions The application of the OCM system in cervical canal lesions is feasible and could help improve detection of occult ECLs in cervical cancer screening programs. This study lays the foundation for further research on OCM in cervical canal lesions in vivo, which also has a potential impact on projecting pathologic evaluation beyond what is currently possible, perhaps globally. [ABSTRACT FROM AUTHOR]

Transglutaminase 2 (Tgm2) plays an essential role in hepatic repair following prolonged toxic injury. During cholestatic liver injury, the intrahepatic cholangiocytes undergo dynamic tissue expansion and remodelling, referred to as ductular reaction (DR), which is crucial for liver regeneration. However, the molecular mechanisms governing the dynamics of active cells in DR are still largely unclear. Here, we generated Tgm2‐knockout mice (Tgm2−/−) and Tgm2‐CreERT2‐Rosa26‐mTmG flox/flox (Tgm2CreERT2‐R26T/Gf/f) mice and performed a three‐dimensional (3D) collagen gel culture of mouse hepatocytes to demonstrate how Tgm2 signalling is involved in DR to remodel intrahepatic cholangiocytes. Our results showed that the deletion of Tgm2 adversely affected the functionality and maturity of the proliferative cholangiocytes in DR, thus leading to more severe cholestasis during DDC‐induced liver injury. Additionally, Tgm2 hepatocytes played a crucial role in the regulation of DR through metaplasia. We unveiled that Tgm2 regulated H3K4me3Q5ser via serotonin to promote BMP signalling activation to participate in DR. Besides, we revealed that the activation or inhibition of BMP signalling could promote or suppress the development and maturation of cholangiocytes in DDC‐induced DR. Furthermore, our 3D collagen gel culture assay indicated that Tgm2 was vital for the development of cholangiocytes in vitro. Our results uncovered a considerable role of BMP signalling in controlling metaplasia of Tgm2 hepatocytes in DR and revealed the phenotypic plasticity of mature hepatocytes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy for Barrett's esophagus (BE) frequently demonstrate columnar-lined epithelium, with forceps biopsies (FBs) failing to yield intestinal metaplasia (IM). Repeat endoscopy is then often necessary to confirm a BE diagnosis. The aim of this study was to assess the yield of IM leading to a diagnosis of BE by the addition of wide-area transepithelial sampling (WATS-3D) to FB in the screening of patients with GERD. METHODS: We performed a prospective registry study of patients with GERD undergoing screening upper endoscopy. Patients had both WATS-3D and FB. Patients were classified by their Z line appearance: regular, irregular (<1 cm columnar-lined epithelium), possible short-segment BE (1 to <3 cm), and possible long-segment BE (≥3 cm). Demographics, IM yield, and dysplasia yield were calculated. Adjunctive yield was defined as cases identified by WATS-3D not detected by FB, divided by cases detected by FB. Clinicians were asked if WATS-3D results affected patient management. RESULTS: Of 23,933 patients, 6,829 (28.5%) met endoscopic criteria for BE. Of these, 2,878 (42.1%) had IM identified by either FB or WATS-3D. Among patients fulfilling endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and absolute yield was 18.1%. One thousand three hundred seventeen patients (19.3%) who fulfilled endoscopic BE criteria had IM detected solely by WATS-3D. Of 240 patients with dysplasia, 107 (44.6%) were found solely by WATS-3D. Among patients with positive WATS-3D but negative FB, the care plan changed in 90.7%. DISCUSSION: The addition of WATS-3D to FB in patients with GERD being screened for BE resulted in confirmation of BE in an additional one-fifth of patients. Furthermore, dysplasia diagnoses approximately doubled. [ABSTRACT FROM AUTHOR]

We present a unique case of metastatic metaplastic breast carcinoma responding dramatically to immunochemotherapy. A 46‐year‐old Japanese woman with primary metaplastic carcinoma of the breast, which was immunohistochemically confirmed to be triple‐negative breast cancer, underwent radical surgery, followed by adjuvant chemotherapy with an anthracycline and a taxane. Since multiple lung metastases were detected two months post‐chemotherapy and the primary site was shown to be PD‐L1‐positive, the immune checkpoint inhibitor (ICI) pembrolizumab plus gemcitabine/carboplatin was initiated. While the treatment was discontinued after 15 days due to suspected drug‐induced pneumonitis, the lung metastases significantly shrank with no development of new lesions for three months. The patient remained alive as of approximately 15 months after the recurrence date. This case highlights the potential of immunochemotherapy in treating metaplastic breast carcinomas. [ABSTRACT FROM AUTHOR]

Osseous metaplasia of the endometrium is a rare entity in which there is presence of mature or immature bone tissue in the endometrium. It is a rare disorder that usually leads to secondary infertility and is frequently associated with recurrent miscarriages and can be rarely asymptomatic. We present the case of a patient with endometrial ossification associated with secondary infertility. The patient presented with excessive vaginal discharge and was undergoing evaluation for secondary infertility. Transvaginal sonography showed a hyperechoic elongated lesion in the endometrium suggestive of endometrial calcification with posterior acoustic shadowing. Diagnostic hysteroscopy was done and the endometrial cavity showed multiple white‐colored, solid, fan‐shaped structures and bony spicules all over the endometrium, which were removed with a hysteroscopic grasper and sent for histopathological examination (HPE). The HPE confirmed the presence of bony trabeculae along with secretory endometrial glands. There have only been a few cases of endometrial osseous metaplasia reported in India and it is usually an overlooked cause of infertility. Although rare, we should consider this as a probable cause of secondary infertility when the characteristic ultrasound features are visualized and that hysteroscopic resection is the gold standard treatment. Synopsis: We present a case report of osseous metaplasia of the endometrium; the patient presented with secondary infertility and successful diagnosis and resection were done by hysteroscopy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Empty nose syndrome (ENS) is a debilitating condition that often results from traumatic or iatrogenic causes, such as nasal surgery. There are various conservative and surgical treatments for ENS, but their effectiveness remains uncertain. Therefore, the development of animal models that accurately mimic human ENS is essential for advancing effective treatment strategies. Materials and Methods: To investigate ENS development, turbinoplasty was performed in the nasal cavity of swine, entailing partial removal of the ventral turbinate using turbinectomy scissors followed by electrocauterization. After 56 days, samples were obtained for histological and morphological analyses. Results: A significant reduction in the volume of the ventral turbinate in the ENS model led to an expansion of the nasal cavity. Histological analysis revealed mucosal epithelial changes similar to those observed in ENS patients, including squamous cell metaplasia, goblet cell metaplasia, submucosal fibrosis, and glandular atrophy. Biomarkers related to these histopathological features were identified, and signals potentially contributing to squamous cell metaplasia were elucidated. Conclusions: The swine ENS model is anticipated to be instrumental in unraveling the pathogenesis of ENS and may also be useful for evaluating the effectiveness of various treatments for ENS. [ABSTRACT FROM AUTHOR]

Background: Gastric intestinal metaplasia (GIM) is a precancerous lesion that increases the risk of gastric cancer. Several preliminary studies have examined the prevalence of GIM. The present systematic review and meta-analysis were conducted aimed estimating the global prevalence of GIM. Methods: The present systematic review and meta-analysis was conducted based on the PRISMA reporting guidelines in the range of 1988–2022. Articles related to the purpose of the study were obtained from Embase, PubMed, Scopus, Web of Science (WOS), MagIran, SID databases, and Google Scholar search engine using relevant and validated keywords in MeSH/Emtree. Inclusion criteria were observational articles, access to the full text of the article, and articles that reported prevalence. Heterogeneity among studies was examined using the I2 index. The random effects model was used in this review due to the high heterogeneity between the results of the studies. Data were statistically analyzed using the Comprehensive Meta-Analysis (CMA) software. Results: In the initial search, 4946 studies were found, of which 20 articles with a sample size of 57,263 met all the criteria for inclusion in the study. The global prevalence of GIM was 17.5% (95% confidence interval: 14.6–20.8%). The highest percentage of prevalence of GIM belonged to American continent with 18.6% (95% confidence interval: 13.8–24.6%) and patients with gastroesophageal reflux with 22.9% (95% confidence interval: 9.9–44.6%). Conclusion: The results of this study showed that the prevalence of GIM in the world is high and needs further investigation. Therefore, it is recommended to be given more attention by experts, officials, and health policymakers. [ABSTRACT FROM AUTHOR]

A number of studies have demonstrated that it is possible to directly convert one cell type to another by factor-mediated transdifferentiation, but in the vast majority of cases, the resulting reprogrammed cells are unable to maintain their new cell identity for prolonged culture times and have a phenotype only partially similar to their endogenous counterparts. To better understand this phenomenon, we developed an analytical approach for better characterizing trans-differentiation-associated changes in DNA methylation, a major determinant of long-term cell identity. By examining various models of transdifferentiation both in vitro and in vivo, our studies indicate that despite convincing expression changes, transdifferentiated cells seem unable to alter their original developmentally mandated methylation patterns. We propose that this blockage is due to basic developmental limitations built into the regulatory sequences that govern epigenetic programming of cell identity. These results shed light on the molecular rules necessary to achieve complete somatic cell reprogramming. [ABSTRACT FROM AUTHOR]

Purpose: The anatomical location of inflammation in and around the ileal pouch affects the pouch survival rate, and diffuse inflammation has poor pouch survival rates. We aimed to clarify the symptoms and histological findings of diffuse inflammation of the pouch. Methods: We evaluated the symptoms, treatment, and histological findings according to the endoscopic phenotypes of diffuse inflammation, focal inflammation, and normal as the pouch body phenotype and afferent limb involvement, inlet involvement, cuffitis, and fistula as the peripheral findings. Results: Of the 318 pouchoscopies, 47 had diffuse inflammation, 201 had focal inflammation, and 70 were normal. Symptomatic patients had diffuse inflammation more frequently (46.8%) than focal inflammation (13.4%) and normal (14.2%), with no difference between focal inflammation and normal. Antibiotics and steroids were higher rate administered in cases of diffuse inflammation, but not in cases of focal inflammation or in normal cases. Histological inflammation, inflammatory bowel disease (IBD)–specific finding, and colonic metaplasia showed severity in the order of diffuse inflammation > focal inflammation > normal. The number of peripheral inflammatory findings overlapped in the following order: diffuse inflammation > focal inflammation > normal. The number of symptomatic patients increased as the number of peripheral inflammatory findings increased. Conclusion: Pouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and have more severe histological inflammation, IBD-specific finding, and colonic metaplasia accompanying peripheral inflammatory findings than the other groups. The higher the overlap of inflammatory findings in the surrounding tissues, the more symptomatic the patients will appear. [ABSTRACT FROM AUTHOR]

Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGF-β1 signaling inhibitor epigallocatechin gallate (EGCG) to interstitial lung disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA-Seq on spare tissue. Biopsies from untreated patients showed higher fibroblast TGF-β1 signaling compared with nondisease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGF-β1 signaling and several proinflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzledrelated protein 2 (sFRP2), an unrecognized TGF-β1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision-cut lung slices (PCLSs) from nondiseased donors, we found TGF-β1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature cytokeratin 5+ (Krt5+ ) basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGF-β1 signaling in ILD and the therapeutic potential of EGCG in reducing idiopathic pulmonary fibrosis–related (IPF-related) transcriptional changes and identify TGF-β1/noncanonical Wnt pathway crosstalk via sFRP2 as a mechanism for dysfunctional epithelial signaling in IPF/ILD. [ABSTRACT FROM AUTHOR]

An approximately 26‐year‐old, suspected female, red‐tailed hawk (Buteo jamaicensis) was presented with a history of chronic ocular changes of the left eye likely secondary to blunt trauma resulting in blindness and phthisis bulbi. Ophthalmic evaluation of OS revealed a large intraocular mass, 3+ aqueous flare indicating anterior uveitis, and severely decreased intraocular pressure measuring 5 mmHg. Ocular ultrasound revealed an abnormal, spherical shaped and hyperechoic lens, as well as hyperechoic material or a mass lesion in the posterior segment. An enucleation procedure was performed, and histopathology of the eye revealed no signs of neoplasia but instead intraocular osseous metaplasia with bone marrow and adipose tissue replacing the lens. Similar mass lesions were found in the retina and choroid. Multiple fractures in the scleral ossicle and cartilage correlated the intraocular lesions with a blunt traumatic event. A bioresorbable disk of porcine small intestine submucosa (BioSIS Vetrix®) was incorporated to relieve tension during closure. The graft sloughed during healing process, revealing a healed wound underneath. The BioSIS was not incorporated into the wound as designed but may have facilitated healing. This is the first report of intraocular osseous metaplasia in a raptor and the use of BioSIS Vetrix® with enucleation in an avian species. [ABSTRACT FROM AUTHOR]

Introduction. Barret’s esophagus (BE), is a common state, concerning roughly about 15% of GERD patients. The pathomechanism of BE is replacement of typical squamous-cell mucosa by a layer of intestinal-type glandular mucosa (intestinal metaplasia). In a number of cases the glands are prone to dysplasia which may lead to the occurrence of esophageal adenocarcinoma. The golden standard in diagnosis of BE is endoscopy combined with histopathological examination of biopsy material of the altered Z line. Unfortunately, many guidelines do not recommend endoscopic treatment in most cases of BE in favor of long-term screening, reserving the need for treatment for dysplastic BE. Material and methods. 53 patients suspected of BE (study group) and 45 patients without any macroscopic signs of BE (control group) underwent upper GI endoscopy during which several biopsies were taken from the elevated Z line. The study group was divided into 2 subgroups: I — without histopathological evidence of BE (n = 11); II — hi-stopathologically confirmed BE (n = 42). In addition to the standard histopathological examination, the material was screened for levels of CDX2 and p53 expression. Results. In the control group, none of the patients presented elevated CDX2 or p53 expression (0%). In the study group, 24 patients were CDX2 positive (45.28%) and 27 were p53 positive (50.94%). Both markers were positive in 21 cases (39.62%). Conclusions. Standard histopathological examination combined with immunohistochemical examination can prove to be a useful tool in confirming the diagnosis of BE, diagnosing early glandular displasia and, in some cases, eliminating false negative results. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. METHODS: Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. RESULTS: A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. DISCUSSION: Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: Cryoablation therapy is an emerging modality in the treatment of Barrett's esophagus. Our systematic review collected data on this technique to provide evidence of its efficacy and safety and to compare it with the established RFA. The results from twenty-three studies revealed that the complete eradication of dysplasia and intestinal metaplasia was comparable between RFA and cryoablation. More specifically, cryoablation achieved a complete eradication of dysplasia and intestinal metaplasia at rates of 84.2% (95%CI: 79.1–89.3) and 64.1% (95%CI: 49.2–79.0), respectively, whereas 8.3% (95%CI: 4.7–11.9) of cases presented with recurrence. Studies on cryoballoons seem to be more homogenous in terms of dysplasia treatment, complications, and, especially, strictures. Background: The mainstay approach in endoscopic eradication therapy (EET) for dysplastic Barrett's esophagus (BE) includes the endoscopic resection of visible lesions, accompanied by ablation of the residual metaplastic epithelium. Cryoablation therapy is one such emerging ablation technique in this field. This systematic review with a meta-analysis aims to accumulate pooled data on cryoablation performance in the treatment of patients with BE and to compare this technique to the standard of care radiofrequency ablation (RFA). Methods: The MEDLINE, Cochrane, and Scopus databases were searched until June 2024 for studies evaluating BE management using cryoablation for cumulative results. The primary outcome was the complete eradication of dysplasia (CED) and intestinal metaplasia (CEIM) in BE compared to RFA, while secondary outcomes included the respective pooled rates using cryoablation, recurrence, and adverse events, with a separate analysis for strictures. The meta-analyses were based on a random-effects model, and the results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses by type of cryoablation were also performed. Results: Twenty-three studies (1604 patients) were finally included, four of which were comparative. CED and CEIM did not differ significantly between cryoablation and RFA [OR= 0.95 (95%CI: 0.50–1.81) and OR = 0.57 (95%CI: 0.20–1.63), respectively)]. The pooled rates of CED, CEIM, and recurrence after cryoablation were 84.2% (95%CI: 79.1–89.3), 64.1% (95%CI: 49.2–79.0), and 8.3% (95%CI: 4.7–11.9), accompanied by high rates of heterogeneity. Adverse events were noted in 14.5% (95%CI: 9.9–19.2) of cases, and 6.5% (95%CI: 4.1–9.0) developed strictures. In the subgroup analysis, the cryoballoon achieved a reduction in heterogeneity in CED, adverse events, and stricture formation, whereas spray catheters provided homogenous results in terms of recurrence. Conclusions: Cryoablation provides equal outcomes compared to RFA in the treatment of patients with BE, with the cryoballoon achieving relatively homogenous rates of CED and adverse events. [ABSTRACT FROM AUTHOR]

Colloid goiter is the most common type of non-neoplastic thyroid condition. They may present with secondary degenerative changes like hyalinization, cystic changes, hemorrhages, fibrosis with rarely presenting with calcification and eventual ossification. Herein we present a case of colloid goiter with fibro-osseous metaplasia in a 55 year male patient who underwent total thyroidectomy due to the clinical suspicion of malignancy. [ABSTRACT FROM AUTHOR]

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Simple Summary: Tendon injuries lead to poor healing with scarring and occasionally calcification. In these metaplastic drifts, mice with injured Achilles tendons (ATs) represent a good preclinical model since about one-third of tissues show calcium deposits (i.e., non-calcified vs. calcified tendons) at 28 days post-injury (p.i.). No information has been collected to date about the role exerted in metaplasia by neuromarkers, which, on the contrary, modulate tendon healing in diverse animal models. In particular, it remains to be clarified whether specific patterns in non-calcified/calcified tendons could be predictive of the tissue healing fate. The present results show that neuromarkers such as neurofilament-200 (NF200), nerve growth factor (NGF), neuropeptide Y (NPY), galanin (GAL), and calcitonin gene-related protein (CGRP) had a dynamic (7 vs. 28 days p.i.) and differentiative expression during early tendon healing. In detail, in non-calcified tendons, NF200 values were similar to pre-injury, whereas, in calcified tendons, NF200 persisted at high levels. Notably, a high CGRP/NPY (vasodilatory/vasoconstrictive) neuromediator ratio characterised tendon healing towards calcification. A novel finding was the contribution of tendon cells in the synthesis of neuromarkers, suggesting a connection between the cells and the nervous system. This research offers novel insights into neurobiological mechanisms during early tendon healing in mice and identifies a neuromarker pattern predictive of tendon metaplastic repair. Unsuccessful tendon healing leads to fibrosis and occasionally calcification. In these metaplastic drifts, the mouse AT preclinical injury model represents a robust experimental setting for studying tendon calcifications. Previously, calcium deposits were found in about 30% of tendons after 28 days post-injury. Although a neuromediated healing process has previously been documented, the expression patterns of NF200, NGF, NPY, GAL, and CGRP in mouse AT and their roles in metaplastic calcific repair remain to be explored. This study included a spatiotemporal analysis of these neuromarkers during the inflammatory phase (7 days p.i.) and the proliferative/early-remodelling phase (28 days p.i.). While the inflammatory phase is characterised by NF200 and CGRP upregulation, in the 28 days p.i., the non-calcified tendons (n = 16/24) showed overall NGF, NPY, GAL, and CGRP upregulation (compared to 7 days post-injury) and a return of NF200 expression to values similar to pre-injury. Presenting a different picture, in calcified tendons (n = 8), NF200 persisted at high levels, while NGF and NPY significantly increased, resulting in a higher NPY/CGRP ratio. Therefore, high levels of NF200 and imbalance between vasoconstrictive (NPY) and vasodilatory (CGRP) neuromarkers may be indicative of calcification. Tendon cells contributed to the synthesis of neuromarkers, suggesting that their neuro-autocrine/paracrine role is exerted by coordinating growth factors, cytokines, and neuropeptides. These findings offer insights into the neurobiological mechanisms of early tendon healing and identify new neuromarker profiles predictive of tendon healing outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Inflammatory mammary carcinoma (IMC) is the most aggressive and malignant type of mammary tumour, described in humans, dogs, and rarely in cats. This entity may clinically resemble an inflammation but is characterized by a fulminant clinical course, recurrence after surgery, with poor prognosis and survival rates. Cytology is rarely applied for the preliminary diagnosis of mammary tumours, given their complex or mixed morphology in dogs, and especially for IMC, where the diagnosis derives from the association of histopathology and clinical features. Therefore, the aim of this study was to describe cytological features of canine IMC and find possible cytological aspects allowing IMC specific diagnosis and differentiation from other mammary tumour types. Distinctive features of IMC included low cellular cohesiveness, ballooning aspect of some neoplastic cells, marked multinucleation, specific chromatin pattern, and occurrence of squamous metaplasia in some individualised cells or in cells in small groups. Thus, even without clinical information, IMC cytological features allow to suspect and/or to perform a diagnosis of IMC. The study highlights a relevant utility of cytological examination, from which both pathologists and clinicians could benefit, avoiding unnecessary treatments as IMC surgery is not curative. Background: Inflammatory mammary carcinoma (IMC) is the most aggressive and malignant type of mammary carcinoma. As in humans, canine IMC resembles mastitis clinically. However, IMC is highly aggressive with high incidence of metastases and common recurrence after surgery, leading to guarded prognosis and low survival rate. Given the complex morphology of canine mammary tumours, cytological examination is not performed routinely, and IMC diagnosis relies on the association of clinical features and histopathology. The purpose of this study is to describe the characteristics of canine IMC cytology, in an attempt to find possible cytological features that allow differentiation of IMC from other mammary tumour types. Methods: We analysed preoperative cytological samples from 25 dogs with IMC, later confirmed by corroborating clinical and histopathological examinations. Results: Distinct cytological features of canine IMC included scarce cellular cohesiveness, ballooning aspect of neoplastic cells, frequent multinucleation, irregularly dispersed and ropy chromatin pattern, and squamous metaplasia in some individualised cells or those in small groups. Conclusions: Our results indicate that cytological examination can contribute to the diagnosis of IMC and might help differentiate it from other mammary carcinomas, even when clinical data is not available, which is common in cytological routine. [ABSTRACT FROM AUTHOR]

Abstract Background Gastric intestinal metaplasia (GIM) is a precancerous lesion that increases the risk of gastric cancer. Several preliminary studies have examined the prevalence of GIM. The present systematic review and meta-analysis were conducted aimed estimating the global prevalence of GIM. Methods The present systematic review and meta-analysis was conducted based on the PRISMA reporting guidelines in the range of 1988–2022. Articles related to the purpose of the study were obtained from Embase, PubMed, Scopus, Web of Science (WOS), MagIran, SID databases, and Google Scholar search engine using relevant and validated keywords in MeSH/Emtree. Inclusion criteria were observational articles, access to the full text of the article, and articles that reported prevalence. Heterogeneity among studies was examined using the I 2 index. The random effects model was used in this review due to the high heterogeneity between the results of the studies. Data were statistically analyzed using the Comprehensive Meta-Analysis (CMA) software. Results In the initial search, 4946 studies were found, of which 20 articles with a sample size of 57,263 met all the criteria for inclusion in the study. The global prevalence of GIM was 17.5% (95% confidence interval: 14.6–20.8%). The highest percentage of prevalence of GIM belonged to American continent with 18.6% (95% confidence interval: 13.8–24.6%) and patients with gastroesophageal reflux with 22.9% (95% confidence interval: 9.9–44.6%). Conclusion The results of this study showed that the prevalence of GIM in the world is high and needs further investigation. Therefore, it is recommended to be given more attention by experts, officials, and health policymakers.

The histological similarities between pleomorphic adenomas (PAs) and cutaneous mixed tumors (CMTs) found in certain facial regions can create a diagnostic challenge. Molecular findings reveal common genetic profiles, particularly PLAG1 rearrangements in both PA and CMT. Although molecular distinctions have received limited attention, our observations indicate multiple cases of CMTs carrying the TRPS1::PLAG1 fusion. This clinical experience has driven our investigation into the potential diagnostic utility of TRPS1::PLAG1 fusions for determining tumor origin. Two cohorts consisting of 46 cases of CMT and 45 cases of PA of the salivary glands were obtained from French institutions and reviewed by specialists in each subspecialty. RNA sequencing analysis was conducted to identify the molecular features of cases harboring PLAG1. Clinical, pathological, and molecular data were collected. In this study, cases of CMT exhibited recurrent gene fusions, primarily TRPS1::PLAG1 (74%). These tumors shared characteristic histological features, including tubuloductal differentiation in 55% of cases and squamous metaplasia in varying proportions. In contrast, cases of PA had gene fusions involving PLAG1 with various gene partners, with only one case in which TRPS1::PLAG1 was identified. This disparity was also observed at the transcriptomic level between TRPS1::PLAG1 CMTs and other tumors. However, TRPS1 immunostaining did not correlate with TRPS1::PLAG1 fusion. In conclusion, we report that recurrent TRPS1::PLAG1 fusion CMTs exhibit similar characteristic histological features, including tubuloductal differentiation that is associated with squamous metaplasia in around half of cases. Detection of this fusion could be valuable in correctly identifying the origin of these tumors. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Purpose: The authors evaluated a cohort of 37 patients with histologically verified synovial chondromatosis (SC) between 2013 and 2022. Methods: The cohort consisted of 37 patients (26 women, 11 men). 36 patients had unilateral involvement, while one patient had bilateral involvement. The average age of the patients was 54.77 years. The authors used the Milgram histopathological classification. They evaluated SC localisation, clinical symptoms, diagnostics and treatment (including recurrence incidence) in this cohort. Results: In 31 patients (83.7%) SC affected only the upper joint space in one patient (2.7%) the lower space, and in five patients (13.6%) both spaces. 12 patients (32%) were Milgram Stage 1 (presence of synovial metaplasia without loose bodies), eight patients (22%) were Stage 2 (presence of synovial changes, loose bodies), and 17 patients (46%) were Stage 3 (presence of loose bodies, no synovial changes). Pain was the dominant clinical symptom (32 patients, 86.4%). Treatment consisted of arthroscopy and open surgery. Two patients underwent primary reconstruction and total TMJ replacement. Treatment was successful in 89.2% of cases (33 patients), with four (10.8%) patients suffering recurrence. Conclusion: As this patient cohort shows, pain was the dominant symptom in patients with SC. Magnetic resonance imaging is fundamental in the diagnosis of SC, demonstrating pathological findings even in patients for whom an initial X-ray was negative. These were mainly patients with Milgram Stages 1 and 2 without calcification, loose bodies or pathological changes of the bone structures. This is why the authors recommend MRI for any patient experiencing pain for more than three months, and if this reveals an effusion, joint distension or intraarticular soft tissue mass, they will always indicate arthroscopy. Thorough follow-up of patients is recommended, although SC recurrence is not very frequent. The authors recommend follow-up one, three and six months after surgery, and then annually for the first five years after surgery. They recommend follow-up MRI one, two and five years after surgery. [ABSTRACT FROM AUTHOR]

Introduction: Various types of metaplastic changes, such as gastric metaplasia (foveolar type or antral type) and intestinal metaplasia, are observed in chronic cholecystitis but not in normal mucosa. Helicobacter species can be detected in the bile and gallbladder tissue of patients with benign gallbladder disease. Objective: The present study aimed to observe the correlation between chronic cholecystitis and the presence of Helicobacter pylori as well as the different types of metaplastic changes in gallbladder mucosa. Materials and Methods: This descriptive, observational study was conducted at the Departments of Pathology and Surgery at a tertiary care medical college and hospital from April 2021 to March 2022, using a cross-sectional design. All confirmed cases of chronic cholecystitis, with or without cholelithiasis, were included in the study. Results: Intestinal metaplasia was the most common type of metaplastic change in the gallbladder epithelium in chronic cholecystitis in this region. PAS and Alcian Blue positivity were significantly higher in cases with metaplasia compared to those without metaplasia. H. pylori was detected in 3 cases (1.55%) of chronic cholecystitis in this study population. Conclusion: Mucin histochemistry may help identify early metaplastic changes in gallbladder epithelium. The use of a combination of methods for the detection of H. pylori in gallbladder tissue may increase the detection of positive cases.

PurposeMaterials and methodsParameters measuredResultsConclusionsMetaplasia, chronic inflammation and subconjunctival fibrosis favor failure of bleb-dependent glaucoma surgery. The aim of the study is to identify the patients at a higher risk of post-surgical failure.Prospective, open study, performed in the Glaucoma Unit of the Hospital Universitario Virgen Macarena, from April to November 2021, with a minimum follow-up of one year. 38 eyes with ocular hypertension or chronic open-angle glaucoma were included. All patients underwent preoperative conjunctival sampling in the operating room, under topical or locoregional anesthesia.Sex, age, and laterality; number, type and mean time of preoperative drugs use; type of surgery performed; cytology results and degree of metaplasia; percentage of patients in whom the bleb was closed. Evaluation of potential correlation between bleb closure and any of the other variables.20 women and 18 men participated, with a mean age of 67 years. The mean number of preoperative hypotensive drugs was 2.7. The mean time of use was 90,97 +/- 48,97 months. Most patients had normal cytology, 8% had inflammatory infiltrate and 21% had squamous metaplasia. When relating bleb failure and cytology, we saw that in those who failed surgery, more than half had cytological alterations. A multiple logistic regression was performed, in which we observed that there was statistically significant association (p = .02) between surgical closure and altered cytology.According to these results, preoperative conjunctival cytology can help predict those cases with a lower probability of surgical success. [ABSTRACT FROM AUTHOR]

Background: Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM. Method: The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes. Results: A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM. Conclusion: We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer with a dismal overall prognosis. NSD2 is an H3K36‐specific di‐methyltransferase that has been reported to play a crucial role in promoting tumorigenesis. Here, the study demonstrates that NSD2 acts as a putative tumor suppressor in Kras‐driven pancreatic tumorigenesis. NSD2 restrains the mice from inflammation and Kras‐induced ductal metaplasia, while NSD2 loss facilitates pancreatic tumorigenesis. Mechanistically, NSD2‐mediated H3K36me2 promotes the expression of IκBα, which inhibits the phosphorylation of p65 and NF‐κB nuclear translocation. More importantly, NSD2 interacts with the DNA binding domain of p65, attenuating NF‐κB transcriptional activity. Furthermore, inhibition of NF‐κB signaling relieves the symptoms of Nsd2‐deficient mice and sensitizes Nsd2‐null PDAC to gemcitabine. Clinically, NSD2 expression decreased in PDAC patients and negatively correlated to nuclear p65 expression. Together, the study reveals the important tumor suppressor role of NSD2 and multiple mechanisms by which NSD2 suppresses both p65 phosphorylation and downstream transcriptional activity during pancreatic tumorigenesis. This study opens therapeutic opportunities for PDAC patients with NSD2 low/loss by combined treatment with gemcitabine and NF‐κBi. [ABSTRACT FROM AUTHOR]