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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., (© 2024. The Author(s).)

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases 1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease 3 . Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn's disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner's glands. Although previously linked to mucosal healing 4 , we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases., Competing Interests: Competing interests: S.A.T. is a scientific advisory board member of ForeSite Labs, OMass Therapeutics, a co-founder and equity holder of TransitionBio and EnsoCell Therapeutics, a non-executive director of 10x Genomics and a part-time employee of GlaxoSmithKline. R.E. is an equity holder in EnsoCell. P.K. has consulted for AstraZeneca, UCB, Biomunex and Infinitopes. N.M.P reports consulting fees from Infinitopes. J.S.-R. reports funding from GSK, Pfizer and Sanofi and fees/honoraria from Travere Therapeutics, Stadapharm, Astex, Owkin, Pfizer, Moderna and Grunenthal. A.S. is the recipient of research grants from Roche-Genentech, Abbvie, GSK, Scipher Medicine, Pfizer, Alimentiv, Boehringer Ingelheim and Agomab and has received consulting fees from Genentech, GSK, Pfizer, HotSpot Therapeutics, Alimentiv, Agomab, Goodgut and Orikine. R.E. and S.A.T are inventors on the patent GB2412853.0 filed in the UK, some components of which are related to this work. All other authors declare no competing interests., (© 2024. The Author(s).)

Background: Map-like redness, pathological intestinal metaplasia, is observed in one-fourth to one-third of patients 1 year after Helicobacter pylori eradication therapy, mainly in the corpus, and is a newly identified endoscopic risk factor for gastric cancer development after eradication. However, it is unclear whether intestinal metaplasia is present before eradication at the site where the map-like redness appears. We aimed to identify endoscopic findings that predict the occurrence of map-like redness before H. pylori eradication., Materials and Methods: As a prospective multicenter trial, the characteristics of patients in whom map-like redness developed after eradication, and the association between the endoscopic severity of gastritis and the development of map-like redness in patients who underwent endoscopy before and 1-year after eradication were investigated., Results: The rate of map-like redness in all 93 patients 1-year postsuccessful eradication was 30.1% (95% confidence interval [CI]: 21.0-40.5). All patients with map-like redness were endoscopically observed to have intestinal metaplasia before eradication, in the site that subsequently developed map-like redness. Patients who developed map-like redness were older, had more severe intestinal metaplasia and nodularity and a higher total score on the Kyoto Classification of Gastritis both before and after eradication than patients who did not. On multivariate analysis, map-like redness was found to be associated with posttreatment intestinal metaplasia (odds ratio: 8.144; 95% CI: 2.811-23.592)., Conclusions: In all patients who developed map-like redness after eradication, endoscopic intestinal metaplasia was observed at the site developed map-like redness before eradication therapy. Map-like redness was especially observed in patients with more severe intestinal metaplasia at 1-year after eradication. Such patients require increased attention at surveillance endoscopy, owing to generally having a higher risk of gastric cancer development., Trial Registration: University Hospital Medical Information Network: UMIN000044707., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

Airway mucous cell metaplasia is a significant feature of many chronic airway diseases, such as chronic obstructive pulmonary disease, cystic fibrosis and asthma. However, the mechanisms underlying this process remain poorly understood. Here, we employed in vivo mouse genetic models to demonstrate that Hippo and p53 (encoded by Trp53) cooperate to modulate the differentiation of club cells into goblet cells. We revealed that ablation of Mst1 (Stk4) and Mst2 (Stk3), encoding the core components of Hippo signaling, significantly reduces mucous metaplasia in the lung airways in a lipopolysaccharide (LPS)-induced lung inflammation murine model while promoting club cell proliferation in a Yap (Yap1)-dependent manner. Additionally, we showed that deleting Mst1/2 is sufficient to suppress p53 deficiency-mediated goblet cell metaplasia. Finally, single-cell RNA-sequencing analysis revealed downregulation of YAP and p53 signaling in goblet cells in human airways. These findings underscore the important role of Hippo and p53 signaling in regulating airway mucous metaplasia., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

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., (© 2024. The Author(s).)

Metaplastic breast tumour is a rare, aggressive, mostly triple- negative, dedifferentiated malignancy, which poorly responds to chemotherapy compared to other invasive breast tumours. Since 2000, the WHO has considered it as a separate entity among breast tumours. Given the extremely poor prognosis of the tumour, more studies are needed to establish the most effective treatment strategy supported by data to increase overall survival. The objective of our research was a retrospective analysis of 77 patients with metaplastic breast cancer treated between 01.01.2012 and 28.02.2023 at our institute. Following the descriptive statistics of the patients, the pathological or clinical response was examined in cases of 15 patients treated with neoadjuvant and 14 patients with palliative chemotherapy. Finally, we compared the overall and progression-free survival of metaplastic breast cancer patients treated at our institute with those described in the international literature. The research results, both at our institute and in the literature, are limited by the small number of cases. In our research, with similar numbers of cases as many other investigations, we obtained results close to international data, thereby supporting the collection of data and further research necessary for the most effective treatment strategy for this rare tumour.

Intestinal metaplasia (IM) is a premalignant condition that increases the risk for subsequent gastric cancer (GC). Traditional Chinese medicine generally plays a role in the treatment of IM, and the phytochemical naringenin used in Chinese herbal medicine has shown therapeutic potential for the treatment of gastric diseases. However, naringenin's specific effect on IM is not yet clearly understood. Therefore, this study identified potential gene targets for the treatment of IM through bioinformatics analysis and experiment validation. Two genes (MTTP and APOB) were selected as potential targets after a comparison of RNA-seq results of clinical samples, the GEO dataset (GSE78523), and naringenin-related genes from the GeneCards database. The results of both cell and animal experiments suggested that naringenin can improve the changes in the intestinal epithelial metaplasia model via MTTP/APOB expression. In summary, naringenin likely inhibits the MTTP/APOB axis and therefore inhibits IM progression. These results support the development of naringenin as an anti-IM agent and may contribute to the discovery of novel IM therapeutic targets., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Background and Aim: Intestinal metaplasia (IM) of the gastric mucosa is strongly associated with the risk of gastric cancer (GC). This study was performed to investigate the usefulness of endoscopic and histological risk stratification for GC using IM., Methods: This was a post-hoc analysis of a multicenter prospective study involving 10 Japanese facilities (UMINCTR000027023). The ridge/tubulovillous pattern, light blue crest (LBC), white opaque substance (WOS), endoscopic grading of gastric IM (EGGIM) score using non-magnifying image-enhanced endoscopy, and operative link on gastric IM assessment (OLGIM) were evaluated for their associations with GC risk in all patients., Results: In total, 380 patients (115 with GC and 265 without GC) were analyzed. The presence of an LBC (limited to antrum: odds ratio [OR] 2.4 [95% confidence interval 1.1-5.0], extended to corpus: OR 3.6 [2.1-6.3]), the presence of WOS (limited to antrum: OR 3.0 [1.7-5.3], extended to corpus: OR 4.2 [2.1-8.2]), and histological IM (limited to antrum: OR 3.2 [1.4-7.4], extended to corpus: OR 8.5 [4.5-16.0]) were significantly associated with GC risk. Additionally, the EGGIM score (5-8 points: OR 8.8 [4.4-16.0]) and OLGIM (stage III/IV: OR 12.5 [6.1-25.8]) were useful for stratification of GC risk. The area under the receiver operating characteristic curve value for GC risk was 0.740 for OLGIM and 0.706 for EGGIM., Conclusions: The LBC, WOS, EGGIM, and OLGIM were strongly associated with GC risk in Japanese patients. This finding can be useful for GC risk assessment in daily clinical practice., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The early mechanisms of spontaneous tumor initiation that precede malignancy are largely unknown. We show that reduced aPKC levels correlate with stem cell loss and the induction of revival and metaplastic programs in serrated- and conventional-initiated premalignant lesions, which is perpetuated in colorectal cancers (CRCs). Acute inactivation of PKCλ/ι in vivo and in mouse organoids is sufficient to stimulate JNK in non-transformed intestinal epithelial cells (IECs), which promotes cell death and the rapid loss of the intestinal stem cells (ISCs), including those that are LGR5 + . This is followed by the accumulation of revival stem cells (RSCs) at the bottom of the crypt and fetal-metaplastic cells (FMCs) at the top, creating two spatiotemporally distinct cell populations that depend on JNK-induced AP-1 and YAP. These cell lineage changes are maintained during cancer initiation and progression and determine the aggressive phenotype of human CRC, irrespective of their serrated or conventional origin., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Atmospheric pollution has been demonstrated to be associated with ocular surface diseases characterized by corneal epithelial damage, including impaired barrier function and squamous metaplasia. However, the specific mechanisms underlying the impact of atmospheric pollution on corneal damage are still unknow. To address this gap in knowledge, we conducted a study using a whole-body exposure system to investigate the detrimental effects of traffic-related air pollution, specifically diesel exhaust (DE), on corneal epithelium in C57BL/6 mice over a 28-day period. Following DE exposure, the pathological alterations in corneal epithelium, including significant increase in corneal thickness and epithelial stratification, were observed in mice. Additionally, exposure to DE was also shown to disrupt the barrier functions of corneal epithelium, leading to excessive proliferation of basal cells and even causing squamous metaplasia in corneal epithelium. Further studies have found that the activation of yes-associated protein (YAP), characterized by nuclear translocation, may play a significant role in DE-induced corneal squamous metaplasia. In vitro assays confirmed that DE exposure triggered the YAP/β-catenin pathway, resulting in squamous metaplasia and destruction of barrier functions. These findings provide the preliminary evidence that YAP activation is one of the mechanisms of the damage to corneal epithelium caused by traffic-related air pollution. These findings contribute to the knowledge base for promoting eye health in the context of atmospheric pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Cytokeratins (CKs) have been associated with precancerous and cancerous gastric lesions in patients with Helicobacter pylori-associated chronic gastritis, making them useful for diagnosing epithelial tumors., Methodology: A retrospective study was conducted utilizing 200 formalin-fixed paraffin-embedded gastric biopsy samples collected from the lesser curvature of the stomach. Samples from the control group, patients with H. pylori infection, and patients with H. pylori-associated gastritis, with complete and incomplete intestinal metaplasia (IM) were immunostained. Monoclonal antibodies were utilized to determine the expression of CK7, CK20, and Ki-67., Results: Patients infected with H. pylori had strong CK20 expression on the surface, and weak CK7 expression on the surface and deep glands; while non-specific chronic gastritis patients had weak focal CK7 expression and strong CK20 expression. The normal gastric mucosa of patients in the control group had relatively weak CK7 expression, restricted to a few cells in the neck and deep glands. CK20 showed diffuse strong reactivity on the surface. On the other hand, patients with complete IM showed a CK7 staining pattern that was either negative or weakly focal on the surface and crypts associated with diffuse surface CK20 and focal crypt staining corresponding to gastric type IM. The Ki67 proliferating index was low (≤ 15%) in H. pylori infected patients, high (> 30%) in patients with incomplete IM, and intermediate (16-30%) in patients with complete IM., Conclusions: These results indicate a significant link between the expressions of CK7/CK20 and Ki67 in patients afflicted with H. pylori and IM., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Ava T Ismael, Rafal A Abdulhameed, Jalal A Jalal, Rawaz D Tawfeeq, Aram Ommar, Aveen Jalal.)

Background: Acute exacerbation (AE) is a potentially lethal event in patients with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF). However, to date, no pathological predictors of AE have been identified. This retrospective study aimed to elucidate the pathological features that could predict AE in patients with UIP., Methods: We reviewed the pathological findings of 91 patients with UIP/IPF and correlated these findings with AE events. Thirteen histological variables related to acute lung injury were evaluated by three independent observers and classified as positive or negative. The patients' clinical data during follow-up were collected and reviewed for AE. A recursive partition using the Gini index for the prediction of AE was performed, with each pathological finding as a candidate for branching., Results: Twenty patients (22%) developed AE during the median follow-up duration of 40 months. Thirty-eight patients died (15 due to AE and 23 for other reasons). The median time interval from surgical lung biopsy to AE onset was 497 (interquartile range: 901-1657) days. Histologically, squamous metaplasia was positively associated with AE (odds ratio: 4.7, P = 0.015) and worse event-free survival in patients with UIP (P = 0.04). Leaf scoring based on the Gini index for recursive partition, including five positive findings (squamous metaplasia, neutrophilic infiltration, septal widening, Kuhn's hyaline, and fibrin), showed a sensitivity of 90% with a specificity of 74.7% (area under curve: 0.89)., Conclusions: We found that squamous metaplasia is an important histopathological finding that predicts AE events and tends to unfavorable outcome in patients with UIP/IPF., Competing Interests: Declaration of competing interest Yasuhiro Kondoh received lecture fees from YK: Boehringer Ingelheim Co., Ltd; Takeshi Johkoh received lecture fees from Nihon Bohringer Ingelheim Japan, Kyorin, and AstraZeneca; Kensuke Kataoka received manuscript fees from Nippon Boehringer Ingelheim; Yasuhiko Yamano received manuscript fees from Nippon Boehringer Ingelheim and Bristol-Myers Squibb. The other authors have no conflict of interest to disclose., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Background: Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously., Case Presentation: We report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment., Conclusions: This is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians' understanding of this disease for early detection, diagnosis and treatment., (© 2024. The Author(s).)

Goblet cell hyperplasia and increased mucus production are features of airway diseases, including asthma, and excess airway mucus often worsens these conditions. Even steroids are not uniformly effective in mucus production in severe asthma, and new therapeutic options are needed. Seihaito is a Japanese traditional medicine that is used clinically as an antitussive and expectorant. In the present study, we examined the effect of Seihaito on goblet cell differentiation and mucus production. In in vitro studies, using air-liquid interface culture of guinea-pig tracheal epithelial cells, Seihaito inhibited IL-13-induced proliferation of goblet cells and MUC5AC, a major component of mucus production. Seihaito suppressed goblet cell-specific gene expression, without changing ciliary cell-specific genes, suggesting that it inhibits goblet cell differentiation. In addition, Seihaito suppressed MUC5AC expression in cells transfected with SPDEF, a transcription factor activated by IL-13. Furthermore, Seihaito attenuated in vivo goblet cell proliferation and MUC5AC mRNA expression in IL-13-treated mouse lungs. Collectively, these findings demonstrated that Seihaito has an inhibitory effect on goblet cell differentiation and mucus production, which is at least partly due to the inhibition of SPDEF., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

The conjunctiva is a non-keratinized, stratified columnar epithelium with characteristics different from the cornea and eyelid epidermis. From development to adulthood, a distinguishing feature of ocular versus epidermal epithelia is the expression of the master regulator PAX6. A conditionally immortalized conjunctival epithelial cell line (iHCjEC) devoid of stromal or immune cells established in our laboratory spontaneously manifested epidermal metaplasia and upregulated expression of the keratinization-related genes SPRR1A/B and the epidermal cytokeratins KRT1 and KRT10 at the expense of the conjunctival trait. In addition, iHCjEC indicated a significant decrease in PAX6 expression. Dry eye syndrome (DES) and severe ocular surface diseases, such as Sjögren's syndrome and Stevens-Johnson syndrome, cause the keratinization of the entire ocular surface epithelia. We used iHCjECs as a conjunctiva epidermal metaplasia model to test PAX6, serum, and glucocorticoid interventions. Reintroducing PAX6 to iHCjECs resulted in upregulating genes related to cell adhesion and tight junctions, including MIR200CHG and CLDN1. The administration of glucocorticoids or serum resulted in the downregulation of epidermal genes (DSG1, SPRR1A/B, and KRT1) and partially corrected epidermal metaplasia. Our results using an isolated conjunctival epidermal metaplasia model point toward the possibility of rationally "repurposing" clinical interventions, such as glucocorticoid, serum, or PAX6 administration, for treating epidermal metaplasia of the conjunctiva., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Ventricular tachycardia (VT) recurrence rates remain high following ablation among patients with nonischemic cardiomyopathy (NICM)., Objectives: This study sought to define the prevalence of lipomatous metaplasia (LM) in patients with NICM and VT and its association with postablation VT recurrence., Methods: From patients who had ablation of left ventricular VT, we retrospectively identified 113 consecutive NICM patients with preprocedural contrast-enhanced cardiac computed tomography (CECT), from which LM was segmented. Nested within this cohort were 62 patients that prospectively underwent CECT and cardiac magnetic resonance from which myocardial border zone and dense late gadolinium enhancement (LGE) were segmented. A control arm of 30 NICM patients without VT with CECT was identified., Results: LM was identified among 57% of control patients without VT vs 83% of patients without VT recurrence and 100% of patients with VT recurrence following ablation. In multivariable analyses, LM extent was the only independent predictor of VT recurrence, with an adjusted HR per 1-g LM increase of 1.1 (P < 0.001). Patients with LM extent ≥2.5 g had 4.9-fold higher hazard of VT recurrence than those with LM <2.5 g (P < 0.001). In the nested cohort with 32 VT recurrences, LM extent was independently associated with VT recurrence after adjustment for border zone and LGE extent (HR per 1 g increase: 1.1; P = 0.036)., Conclusions: Myocardial LM is prevalent in patients with NICM of a variety of etiologies, and its extent is associated with postablation VT recurrence independent of the degree of fibrosis., Competing Interests: Funding Support and Author Disclosures The INFINITY study is funded by National Institutes of Health grant 1R01HL142893-01. Dr Xu is an American Heart Association postdoctoral fellow (23POST909139). The University of Pennsylvania Conflict of Interest Committee manages all commercial arrangements. Dr Marchlinski has served as consultant for Abbott Medical, Biosense Webster, Biotronik, and Medtronic Inc. Dr Nazarian has served as a consultant for CardioSolv and Circle CVI; and principal investigator for research funding from Biosense Webster, ImriCor, Siemens, ADAS software, and the U.S. National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the prevalence of concomitant squamous metaplasia (SM), the initial histological change from normal urethra to urethral stricture, in bulbar urethral strictures and to investigate the associated clinical factors., Methods: A retrospective review was conducted on 165 male patients with bulbar urethral strictures who underwent excision and primary anastomosis (EPA) between 2010 and 2020, for whom complete clinical data and excised urethral specimens were available. An experienced pathologist histologically evaluated concomitant SM in paraffin sections of the proximal end of the excised urethra blinded to the clinical data. Disease duration was calculated as the period from the initial diagnosis of urethral stricture to the date of EPA. The association between concomitant SM and clinical background was investigated., Results: SM was identified in 86 (52.1%) patients. The median disease duration in patients with SM (38 months) was significantly longer than that in patients without SM (9 months, p < 0.0001). In multivariate analysis, the longer disease duration, non-traumatic stricture etiology, and failure to maintain urethral rest with urinary diversion via a suprapubic tube for more than 90 days were independent factors predicting concomitant SM. No significant difference was observed in success rates of EPA between patients with SM (93.2%) and those without SM (97.5%, p = 0.18)., Conclusions: Reconstructive urologists need to be aware that concomitant SM is frequent in patients with bulbar urethral stricture, especially in those with long disease duration and those who were voiding volitionally during the period of urethral rest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies., Method: The air-liquid interface (ALI) model was adopted for the long-term culture of GIM cells in the present work. This study conducted Immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), transcriptomic sequencing, and mucoproteomic sequencing (MS) techniques to identify the pathways for differential expressed genes (DEGs) enrichment among different groups, furthermore, to verify novel biomarkers of GIM cells., Result: Our study suggests that GIM-ALI model is analog to the innate GIM cells, which thus can be used for mucus collection and drug screening. We found genes MUC17, CDA, TRIM15, TBX3, FLVCR2, ONECUT2, ACY3, NMUR2, and MAL2 were highly expressed in GIM cells, while GLDN, SLC5A5, MAL, and MALAT1 showed down-regulated, which can be used as potential biomarkers for GIM cells. In parallel, these genes that highly expressed in GIM samples were mainly involved in cancer-related pathways, such as the MAPK signal pathway and oxidative phosphorylation signal pathway., Conclusion: The ALI model is validated for the first time for the in vitro study of GIM. GIM-ALI model is a novel in vitro model that can mimic the tissue micro-environment in GIM patients and further provide an avenue for studying the characteristics of GIM mucus. Our study identified new markers of GIM as well as pathways associated with GIM, which provides outstanding insight for exploring GIM pathogenesis and potentially other related conditions., (© 2024. The Author(s).)

Gastric cancer is the fifth most common cancer and the fourth cause of global cancer mortality. The identification of new biomarkers and drug targets is crucial to allow the better prognosis and treatment of patients. The mitotic spindle positioning (MISP) protein has the function of correcting mitotic spindle positioning and centrosome clustering and has been implicated in the cytokinesis and migration of cancer cells. The goal of this work was to evaluate the expression and clinical relevance of MISP in gastric cancer. MISP expression was evaluated by immunohistochemistry in a single hospital series (n = 286) of gastric adenocarcinomas and compared with normal gastric mucosa and intestinal metaplasia, a preneoplastic lesion. MISP was detected on the membrane in 83% of the cases, being overexpressed in gastric cancer compared to normal gastric mucosa (n = 10). Its expression was negatively associated with diffuse and poorly cohesive types. On the other hand, it was strongly expressed in intestinal metaplasia where it was associated with MUC2 and CDX2 expression. Furthermore, when we silenced MISP in vitro, a significant decrease in the viability of gastric carcinoma cells was observed. In conclusion, MISP is overexpressed in gastric cancer, being associated with an intestinal phenotype in gastric carcinogenesis and having a role in cellular proliferation.

Background: Asthma is a common obstructive airway disease with an inflammatory etiology. The main unmet need in the management of asthma is inadequate adherence to pharmacotherapy, leading to a poorly-controlled disease state, necessitating the development of novel therapies. Bronchom is a calcio-herbal formulation, which is purported to treat chronic asthma. The objective of the current study was to examine the in-vivo efficacy of Bronchom in mouse model of allergic asthma., Methods: Ultra high performance liquid chromatography was utilized to analyze the phytocompounds in Bronchom. Further, the in-vivo efficacy of Bronchom was evaluated in House dust mite (HDM)-induced allergic asthma in mice. Mice were challenged with aerosolized methacholine to assess airway hyperresponsiveness. Subsequently, inflammatory cell influx was evaluated in bronchoalveolar lavage fluid (BALF) followed by lung histology, wherein airway remodeling features were studied. Simultaneously, the levels of Th2 cytokines and chemokines in the BALF was also evaluated. Additionally, the mRNA expression of pro-inflammatory and Th2 cytokines was also assessed in the lung along with the oxidative stress markers., Results: Phytocompounds present in Bronchom included, gallic acid, protocatechuic acid, methyl gallate, rosmarinic acid, glycyrrhizin, eugenol, 6-gingerol and piperine. Bronchom effectively suppressed HDM-induced airway hyperresponsiveness along with the influx of leukocytes in the BALF. Additionally, Bronchom reduced the infiltration of inflammatory cells in the lung and it also ameliorated goblet cell metaplasia, sub-epithelial fibrosis and increase in α-smooth muscle actin. Bronchom decreased Th2 cytokines (IL-4 and IL-5) and chemokines (Eotaxin and IP-10) in the BALF. Likewise, it could also suppress the mRNA expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6 and IL-33), and IL-13. Moreover, Bronchom restored the HDM-induced diminution of endogenous anti-oxidants (GSH and SOD) and the increase in pro-oxidants (GSSG and MDA). Furthermore, Bronchom could also decrease the nitrosative stress by lowering the observed increase in nitrite levels., Conclusion: Taken together, the results of the present study data convincingly demonstrate that Bronchom exhibits pharmacological effects in an animal model of allergic asthma. Bronchom mitigated airway hyperresponsiveness, inflammation and airway remodeling evoked by a clinically relevant allergen and accordingly it possesses therapeutic potential for the treatment of asthma., Competing Interests: The test formulation, Bronchom was sourced from Divya Pharmacy, Haridwar, Uttarakhand, India. Bronchom is a marketed medicinal product of Divya Pharmacy, Haridwar, India. AB is an honorary trustee in Divya Yog Mandir Trust, which governs Divya Pharmacy, Haridwar. In addition, he holds an honorary managerial position in Patanjali Ayurved Ltd, Haridwar, India. Divya Pharmacy, Haridwar and Patanjali Ayurved Ltd. Haridwar manufacture and sell many herbal medicinal products. Other than providing the test formulation, Divya Pharmacy was not involved in any aspect of the research reported in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Balkrishna, Sinha, Karumuri, Maity, Dev and Varshney.)

Background and Aim: Gastric intestinal metaplasia (GIM) is a high-risk factor for the development of gastric cancer. Narrow-band imaging (NBI) enables endoscopic grading of GIM (EGGIM). In the era of climate change, gastrointestinal endoscopists are expected to reduce greenhouse gas emissions and medical waste. Based on the diagnostic performance of NBI endoscopy, this study measured the environmental impact and reduced cost of implementing EGGIM during gastroscopy., Methods: Using NBI endoscopy in 242 patients, EGGIM classification and operative link on GIM (OLGIM) staging were prospectively performed in five different areas (lesser and greater curvatures of the corpus and antrum, and the incisura angularis). We estimated the environmental impact and cost reduction of the biopsy procedures and pathological processing if EGGIM were used instead of OLGIM., Results: The diagnostic accuracy of NBI endoscopy for GIM was 93.0-97.1% depending on the gastric area. When a high EGGIM score ≥ 5 was the cut-off value for predicting OLGIM stages III-IV, the area under the curve was 0.862, sensitivity was 81.9%, and specificity was 90.4%. The reduction in the carbon footprint by EGGIM was -0.4059 kg carbon dioxide equivalents per patient, equivalent to 1 mile driven by a gasoline-powered car. The cost savings were calculated to be $47.36 per patient., Conclusions: EGGIM is a reliable method for identifying high-risk gastric cancer patients, thereby reducing the carbon footprint and medical costs in endoscopy practice., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.

Background & Aims: Gastric carcinogenesis develops within a sequential carcinogenic cascade from precancerous metaplasia to dysplasia and adenocarcinoma, and oncogenic gene activation can drive the process. Metabolic reprogramming is considered a key mechanism for cancer cell growth and proliferation. However, how metabolic changes contribute to the progression of metaplasia to dysplasia remains unclear. We have examined metabolic dynamics during gastric carcinogenesis using a novel mouse model that induces Kras activation in zymogen-secreting chief cells., Methods: We generated a Gif-rtTA;TetO-Cre;Kras G12D (GCK) mouse model that continuously induces active Kras expression in chief cells after doxycycline treatment. Histologic examination and imaging mass spectrometry were performed in the GCK mouse stomachs at 2 to 14 weeks after doxycycline treatment. Mouse and human gastric organoids were used for metabolic enzyme inhibitor treatment. The GCK mice were treated with a stearoyl- coenzyme A desaturase (SCD) inhibitor to inhibit the fatty acid desaturation. Tissue microarrays were used to assess the SCD expression in human gastrointestinal cancers., Results: The GCK mice developed metaplasia and high-grade dysplasia within 4 months. Metabolic reprogramming from glycolysis to fatty acid metabolism occurred during metaplasia progression to dysplasia. Altered fatty acid desaturation through SCD produces a novel eicosenoic acid, which fuels dysplastic cell hyperproliferation and survival. The SCD inhibitor killed both mouse and human dysplastic organoids and selectively targeted dysplastic cells in vivo. SCD was up-regulated during carcinogenesis in human gastrointestinal cancers., Conclusions: Active Kras expression only in gastric chief cells drives the full spectrum of gastric carcinogenesis. Also, oncogenic metabolic rewiring is an essential adaptation for high-energy demand in dysplastic cells., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

After the publication of the original article, the authors noticed an error in the departmental affiliation of one of the contributors, Don MASCARENHAS. The corrected version of the department is provided below, and the original article has been updated accordingly. Archana BHAT < sup > 1 < /sup > , Manjunath J < sup > 1 < /sup > , Don MASCARENHAS < sup > 2 < /sup > < br / > Department of < sup > 1 < /sup > Pathology and < sup > 2 < /sup > Pulmonology, Father Muller Medical College, MANGALORE, INDIA.

Background & Aims: Type 2 innate lymphoid cells (ILC2s) and interleukin-13 (IL-13) promote the onset of spasmolytic polypeptide-expressing metaplasia (SPEM) cells. However, little is known about molecular effects of IL-13 in SPEM cells. We now sought to establish a reliable organoid model, Meta1 gastroids, to model SPEM cells in vitro. We evaluated cellular and molecular effects of ILC2s and IL-13 on maturation and proliferation of SPEM cells., Methods: We performed single-cell RNA sequencing to characterize Meta1 gastroids, which were derived from stomachs of Mist1-Kras transgenic mice that displayed pyloric metaplasia. Cell sorting was used to isolate activated ILC2s from stomachs of IL-13-tdTomato reporter mice treated with L635. Three-dimensional co-culture was used to determine the effects of ILC2s on Meta1 gastroids. Mouse normal or metaplastic (Meta1) and human metaplastic gastroids were cultured with IL-13 to evaluate cell responses. Air-Liquid Interface culture was performed to test long-term culture effects of IL-13. In silico analysis determined possible STAT6-binding sites in gene promoter regions. STAT6 inhibition was performed to corroborate STAT6 role in SPEM cells maturation., Results: Meta1 gastroids showed the characteristics of SPEM cell lineages in vitro even after several passages. We demonstrated that co-culture with ILC2s or IL-13 treatment can induce phosphorylation of STAT6 in Meta1 and normal gastroids and promote the maturation and proliferation of SPEM cell lineages. IL-13 up-regulated expression of mucin-related proteins in human metaplastic gastroids. Inhibition of STAT6 blocked SPEM-related gene expression in Meta1 gastroids and maturation of SPEM in both normal and Meta1 gastroids., Conclusions: IL-13 promotes the maturation and proliferation of SPEM cells consistent with gastric mucosal regeneration., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aim: Telocytes, a recently identified type of subepithelial interstitial cell, have garnered attention for their potential roles in tissue homeostasis and repair. However, their contribution to gastric metaplasia remains unexplored. This study elucidates the role of telocytes in the development of metaplasia within the gastric environment., Methods: To investigate the presence and behavior of telocytes during metaplastic transitions, we used drug-induced acute injury models (using DMP-777 or L635) and a genetically engineered mouse model (Mist1-Kras). Lineage tracing via the Foxl1-CreERT2;R26R-tdTomato mouse model was used to track telocyte migratory dynamics. Immunofluorescence staining was used to identify telocyte markers and evaluate their correlation with metaplasia-related changes., Results: We confirmed the existence of FOXL1+/PDGFRα+ double-positive telocytes in the stomach's isthmus region. As metaplasia developed, we observed a marked increase in the telocyte population. The distribution of telocytes expanded beyond the isthmus to encompass the entire gland and closely reflected the expansion of the proliferative cell zone. Rather than a general response to mucosal damage, the shift in telocyte distribution was associated with the establishment of a metaplastic cell niche at the gland base. Furthermore, lineage-tracing experiments highlighted the active recruitment of telocytes to the emerging metaplastic cell niche, and we observed expression of Wnt5a, Bmp4, and Bmp7 in PDGFRα+ telocytes., Conclusions: These results suggest that telocytes contribute to the evolution of a gastric metaplasia niche. The dynamic behavior of these stromal cells, their responsiveness to metaplastic changes, and potential association with Wnt5a, Bmp4, and Bmp7 signaling emphasize the significance of telocytes in tissue adaptation and repair., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Distal airway metaplasia may precede honeycombing in progressive fibrosing interstitial lung disease (ILD). The SCGB1A1 + bronchiolar-specific club cell may play a role in this aberrant regenerative process. Objective: To assess the presence of club cells in the small airways of patients suffering from ILD. Methods: Small airways (internal diameter <2 mm) in lung samples [surgical lung biopsy (SLB) and/or transbronchial lung cryobiopsy (TBLC)] from 14 patients suffering from ILD and 10 controls were morphologically assessed and stained for SCGB1A1. SCGB1A1 was weighted by epithelial height as a marker of airway generation (SCGB1A1/EH). Correlations between clinical, functional, and high-resolution CT (HRCT) prognostic factors and histomorphometry were assessed. Results: Small airways from samples with ILD patterns were significantly less dense in terms of SCGB1A1 + cells [0.064 (0.020-0.172)] as compared to controls' sample's small airways [0.393 (0.082-0.698), p < 0.0001]. Usual interstitial pneumonia (UIP) patterns most frequently contained small airways with limited or absent SCGB1A1 expression (SCGB1A1/EH <0.025): UIP (18/33; 55%) as compared with non-UIP patterns (4/31; 13%) or controls (0/29; 0%): p < 0.0001. In addition, correlations with HRCT indicated a significant negative relationship between SCGB1A1 and bronchiectasis as a feature of bronchiolization (Rho -0.63, p < 0.001) and a positive relationship with both forced vital capacity (FVC) and Hounsfield unit (HU)-distribution pattern in kurtosis (Rho 0.38 and 0.50, respectively, both p < 0.001) as markers of fibrotic changes. Conclusion: Compared with controls, the small airways of patients with ILD more often lack SCGB1A1, especially so in UIP. Low densities of SCGB1A1-marked cells correlate with bronchiectasis and fibrotic changes. Further research investigating SCGB1A1 staining as a pathological feature of the bronchiolization process is merited., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Reynaud, Ahmed, Serre, Knabe, Bommart, Suehs, Vachier, Berthet, Romagnoli, Vernisse, Mallet, Gamez and Bourdin.)

Competing Interests: None

Purpose: Main study: undertake a histological study of odontogenic cysts (OC) to determine the prevalence of dystrophic calcification and metaplasia to respiratory epithelium on a Brazilian population., Literature Review: to review the literature for studies that investigated the prevalence of respiratory metaplasia and dystrophic calcification on OC., Methods: Main study: a retrospective histopathological evaluation was made of the archives from a pathology laboratory. A total of 362 cases diagnosed as OC were identified; they were analyzed by two expert observers to determine the presence of dystrophic calcification and respiratory metaplasia. The association with sex, age and anatomic location was performed through statistical analysis., Literature Review: a critical literature review was undertaken. Two main electronic databases (PubMed and LILACS) were searched. Retrospective studies of histological evaluation that determined the prevalence of epithelial metaplasia and dystrophic calcification on OC, with at least 10 cases, were included; their findings were summarized and discussed., Results: Main study: the histological evaluation of OC revealed the presence of respiratory epithelium in 25 cases (6.9%) and dystrophic calcification in 24 cases (6.6%). Positive association was found to dystrophic calcification on residual cyst and age; respiratory metaplasia on OC and sex; respiratory metaplasia on residual cyst and gnatic bone; respiratory metaplasia in OC and gnatic bone; dystrophic calcification in OC and anatomic site of mandible., Literature Review: eleven studies were included in the literature review, and respiratory metaplasia ranged from 0.0% to 19.2% while dystrophic calcification ranged from 2.5% to 40.5%., Conclusions: the histological evaluation of this study found 6.9% of prevalence of respiratory metaplasia and 6.6% of dystrophic calcification, which is in accordance with the literature reviewed. Therefore, these phenomena must be taken into account in routine diagnosis services., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Spinal psammomatous meningioma with calcification is commonly observed, but distinctive osseous differentiation rarely occurs., Case Presentation: Here, we described a 52-year-old female complaining of chronic back pain for 5 years. CT and MRI examinations revealed an intradural extramedullary mass at the T4 level. The tumor was meticulously excised en bloc. Under the microscope, the tumor was found to be composed of conspicuous calcified psammoma bodies with remarkable immature bone formation. A primary diagnosis of psammomatous meningioma was made based on the recent WHO classification of tumors of the CNS, whereas other pathologists focused on the osseous components and preferred metaplastic meningioma as the proper subtype. A literature review was conducted, and only five cases have been reported with the same histopathological condition. Experts finally reached a consensus based on the acknowledged notion of the preferential diagnosis of psammomatous meningioma, as well as the current evidence and popular opinion that ossification is generated from osteogenic differentiation of pluripotent cells rather than the accumulation of psammoma bodies., Conclusions: A final diagnosis of psammomatous meningioma with osseous metaplasia was made. The rigid and adherent features complicate total resection of the tumor and increase the risk of neurologic deficits.

Gastric cancer (GC) is the first cancer-related cause of death in Chile; however, no plan for GC early detection has been implemented in this country. The OLGA system characterizes gastritis from stages 0 to IV according to the risk of developing GC based on H. pylori infection, atrophy, metaplasia and GC. In this study, the performance of the OLGA system was evaluated in 485 Chilean patients receiving routine endoscopy to improve the detection of early GC or preneoplastic lesions. The results showed that OLGA scores, atrophy, metaplasia and GC increased significantly with age (p < 0.001). Conversely, H. pylori infection was higher in younger groups (p < 0.05). All gastric lesions were more frequent in men than women. The majority of patients with atrophy also had metaplasia (99%, p < 0.0001). Patients with H. pylori infection had more gastric atrophy and metaplasia than those without infection (p < 0.05). Of the 485 patients, 21 (4.3%) had GC, being 2.3 times more frequent among men than women and about 2/3 (14) were in OLGA stage ≥2. In addition, 19 (90%) GC patients had atrophy and 18 (85%) had metaplasia (p < 0.001). In conclusion, the OLGA system facilitated the evaluation of GC precursor lesions particularly in patients with an OLGA score > 2 between 45 and 56 years old, because this group showed atrophy and intestinal metaplasia more frequently. Therefore, biennial endoscopic surveillance of patients with an OLGA >2 can be an important health policy in Chile for diagnosing GC in its early stages and reducing mortality over the next two decades.

Background: Metaplastic breast carcinoma (MBC) is a rare disease with incidence of less than 1%. MBC present with a larger tumor size, less number of nodes involved, mostly undifferentiated triple negative tumors. We aimed to determine progression-free and overall survival and reported hospital-based incidence of MBC., Material and Methods: A retrospective closed Cohort study elicited data of 42 patients with MBC from January 2008 to December 2013; followed till August 2016. Kaplan-Meier method was applied to compute overall and progression-free survival analysis. Cox Proportional hazard ratios were computed to assess associations between survival and independent variables., Results: Hospital-based incidence of MBC was 1.92% (42/2187), 95% CI [1.41-2.56]. The median age at tumor diagnosis was 54 years (range, 25-81 years). Thirty-nine (92.9%) patients had Grade III tumor. The most common histopathology was squamous (69%). The median tumor size was 4.5 cm (range, 0.8-17 cm). Nineteen (45.2%) patients had nodal involvement at diagnosis. Four patients (9.5%) had metastatic disease at presentation. Hormone receptors were positive in 19 (45.2%) patients. Her-2 neu receptor was positive in 9 (19%) patients. Sixteen (38.1%) patients had triple negative disease. Neoadjuvant and adjuvant chemotherapy was received by 10 (31.25%) and 19 (45.2%) patients respectively. Both median progression-free and overall survival was 38 months., Conclusion: Five-year progression-free and overall survival was 79.5% and 76.3%, respectively. We report better survival outcomes when compared to series described earlier despite our patient population presenting mostly with high grade, large tumors, and half of them exhibiting nodal and hormonal involvement., Competing Interests: None

Purpose of Review: The cellular origins of Barrett's esophagus remain elusive. In this review, we discuss the potential cellular mechanisms behind squamous to columnar metaplasia as well as the limitations of these proposed mechanisms., Recent Findings: Several theories have been proposed, including the reprogramming of native squamous cells, repopulation from submucosal glands, contributions from circulating bone marrow-derived cells, and direct extension of gastric cells. Most recent data support an innate progenitor cell unique to the squamocolumnar junction that can expand into metaplastic glands. Active investigation to clarify each of these potential cells of origin is being pursued, but ultimately each could contribute to the pathogenesis of Barrett's esophagus depending on the clinical context. Nonetheless, identifying cells of origin is critical to understand the molecular mechanisms behind Barrett's esophagus and developing strategies to better treat (and possibly prevent) this increasingly significant premalignant disease.

Background: Gastric carcinoma (GC) is a rather rare pathological finding in dogs, with the exception of some breeds which seem predisposed. The etiopathogenesis is largely unknown in dogs, whereas in humans GC often develops from gastric mucosal metaplasia and dysplasia. This study investigates whether dogs of certain breeds are more often subject to gastroduodenoscopy (GDS), and diagnosed with GC, mucosal metaplasia or dysplasia. A retrospective clinical database search was performed at the Veterinary Teaching Hospital at the University of Helsinki, Finland. The following inclusion criteria were applied to estimate relative risk for metaplasia/dysplasia and GC: dogs from pure breeds with at least five individuals subject to GDS with histopathology of gastric biopsies., Results: Between 2006 and 2016, from a total of 54945 canine patients presented, 423 dogs underwent GDS. Inclusion criteria were met in 180 dogs of 20 different pure breeds. Eight dogs had GCs (mean age = 9.8 ± 1.7 years): Belgian Tervuren (n = 4), Collie (n = 2), Golden Retriever (n = 1) and Jack Russel Terrier (n = 1). Fourteen dogs of eight breeds had gastric mucosal metaplasia or dysplasia. A log-binomial statistical model revealed that dogs in the following breeds had a significantly higher probability to undergo GDS than the others in the study population: Australian Terrier, Belgian Tervuren, Cairn Terrier, Collie and Siberian Husky. Belgian Tervuren was found at higher risk to be diagnosed with GC [RR = 19 (5.7-63.9; P < 0.0001)], as well as mucosal metaplasia/dysplasia [RR (7.6; 2.95-19.58; P < 0.0001)], as compared to the other breeds included. Shetland Sheepdog had an increased RR (5.83; 1.75-19.45; P = 0.0041) for metaplasia., Conclusions: The results indicate a very low incidence of GC in dogs. The Belgian Tervuren, however, appears as predisposed. The histopathologic descriptions of mucosal changes such as metaplasia and dysplasia were also rare, but were more frequent in the Belgian Tervuren. Previous reports of these changes in dogs are very scarce, but they might be presumably related to GC in dogs, as they are in humans. Future research should investigate the possible role of metaplasia and dysplasia in the development of GC in dogs, especially those of predisposed breeds.

In this issue of Cancer Cell, Huang et al. describe comprehensive genetic and epigenetic profiling of gastric intestinal metaplasia lesions from a longitudinal cohort in which outcome data allowed for identification of potential markers of gastric neoplastic progression., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background/aims: Chronic atrophic gastritis (AG) and intestinal metaplasia (IM) of the stomach are premalignant lesions. The present study aimed to examine the associations between obesity and these lesions., Methods: A total of 2,997 patients, who underwent gastroscopy, participated in this study, excluding those who had been diagnosed with gastric cancer. Participants were divided into four groups based on their body mass index (BMI). The risk of AG and IM with increasing BMI was analyzed in men and women, separately., Results: The association between BMI and AG was not significant. After adjusting for age, smoking, alcohol, and AG, the odds ratios for IM in the overweight, obesity, and severe obesity groups were 2.25 (95% confidence interval [CI], 1.50-3.37), 2.32 (95% CI, 1.58-3.42), and 4.86 (95% CI, 2.04-11.5) in men, and 2.66 (95% CI, 1.29-5.47), 4.46 (95% CI, 2.28-8.75), and 9.57 (95% CI, 3.26-28.12) in women, compared with the normal BMI group., Conclusions: Gastric IM was significantly associated with increased BMI.