Search

Background: The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. Methods: Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin–eosin staining. Only patients with negative hematoxylin–eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. Results: Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. Conclusion: In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.

Background & Aims: This review was developed to provide a thorough and effective update on models relevant to esophageal metaplasia, dysplasia, and carcinogenesis, focusing on the advantages and limitations of different models of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). Methods: This expert review was written on the basis of a thorough review of the literature combined with expert interpretation of the state of the field. We emphasized advances over the years 2012–2023 and provided detailed information related to the characterization of established human esophageal cell lines. Results: New insights have been gained into the pathogenesis of BE and EAC using patient-derived samples and single-cell approaches. Relevant animal models include genetic as well as surgical mouse models and emphasize the development of lesions at the squamocolumnar junction in the mouse stomach. Rat models are generated using surgical approaches that directly connect the small intestine and esophagus. Large animal models have the advantage of including features in human esophagus such as esophageal submucosal glands. Alternatively, cell culture approaches remain important in the field and allow for personalized approaches, and scientific rigor can be ensured by authentication of cell lines. Conclusions: Research in BE and EAC remains highly relevant given the morbidity and mortality associated with cancers of the tubular esophagus and gastroesophageal junction. Careful selection of models and inclusion of human samples whenever possible will ensure relevance to human health and disease.

Numerous recent studies using single cell RNA sequencing and spatial transcriptomics have shown the vast cell heterogeneity, including epithelial, immune, and stromal cells, present in the normal human stomach and at different stages of gastric carcinogenesis. Fibroblasts within the metaplastic and dysplastic mucosal stroma represent key contributors to the carcinogenic microenvironment in the stomach. The heterogeneity of fibroblast populations is present in the normal stomach, but plasticity within these populations underlies their alterations in association with both metaplasia and dysplasia. In this review, we summarize and discuss efforts over the past several years to study the fibroblast components in human stomach from normal to metaplasia, dysplasia, and cancer. In the stomach, myofibroblast populations increase during late phase carcinogenesis and are a source of matrix proteins. PDGFRA-expressing telocyte-like cells are present in normal stomach and expand during metaplasia and dysplasia in close proximity with epithelial lineages, likely providing support for both normal and metaplastic progenitor niches. The alterations in fibroblast transcriptional signatures across the stomach carcinogenesis process indicate that fibroblast populations are likely as plastic as epithelial populations during the evolution of carcinogenesis.

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.

Background & Aims: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into proliferative, mucin-rich spasmolytic polypeptide–expressing metaplasia (SPEM) cells. Overall, pyloric metaplastic units show increased proliferation and specific expansion of mucous lineages, both by proliferation of normal mucous neck cells and recruitment of SPEM cells. Here, we identify Sox9 as a potential gene of interest in the regulation of mucous neck and SPEM cell identity in the stomach. Methods: We used immunostaining and electron microscopy to characterize the expression pattern of SRY-box transcription factor 9 (SOX9) during murine gastric development, homeostasis, and injury in homeostasis, after genetic deletion of Sox9 and after targeted genetic misexpression of Sox9 in the gastric epithelium and chief cells. Results: SOX9 is expressed in all early gastric progenitors and strongly expressed in mature mucous neck cells with minor expression in the other principal gastric lineages during adult homeostasis. After injury, strong SOX9 expression was induced in the neck and base of corpus units in SPEM cells. Adult corpus units derived from Sox9-deficient gastric progenitors lacked normal mucous neck cells. Misexpression of Sox9 during postnatal development and adult homeostasis expanded mucous gene expression throughout corpus units including within the chief cell zone in the base. Sox9 deletion specifically in chief cells blunts their reprogramming into SPEM. Conclusions: Sox9 is a master regulator of mucous neck cell differentiation during gastric development. Sox9 also is required for chief cells to fully reprogram into SPEM after injury.

Background and Aims: Loss of bone morphogenetic protein (BMP) signaling in the stomach, achieved by transgenic expression of the BMP inhibitor noggin (H+/K+-Nog mice), causes parietal cell (PC) loss, spasmolytic polypeptide-expressing metaplasia, a marker of preneoplasia, and activation of cell proliferation. We examined if specific inhibition of BMP signaling in PCs leads to aberrations in epithelial homeostasis. Methods: Mice with floxed alleles of BMP receptor 1a (Bmpr1aflox/flox mice) were crossed to H+/K+-Cre mice to generate H+/K+-Cre;Bmpr1aflox/flox mice. Morphology of the mucosa was analyzed by hematoxylin and eosin staining. Distribution of H+/K+-ATPase-, IF-, and Ki-67-positive cells was analyzed by immunostaining. Expression of pit and neck cell mucins was determined by staining with the lectins Ulex Europaeus Agglutinin 1 and Griffonia (Bandeiraea) simplicifolia lectin II, respectively. Isolation of PCs from control and Nog-expressing mice was achieved by crossing H+/K+-Nog mice to Rosa26-tdTomato (Tom) mice to generate H+/K+-Nog;Rosa26-tdTom mice. H+/K+-Cre mice were then crossed to H+/K+-Nog;Rosa26-tdTom mice to generate H+/K+-Cre;H+/K+-Nog;Rosa26-tdTom mice. Tom-labeled PCs were purified by flow cytometry. Changes in PC transcripts were measured by RNA-Seq. Results: Six-month-old H+/K+-Cre;Bmpr1aflox/flox mice exhibited increased epithelial cell proliferation, presence of transitional cells showing colocalization of IF with both Griffonia (Bandeiraea) simplicifolia lectin II-binding mucins and the H+/K+-ATPase, and expansion of Ulex Europaeus Agglutinin 1-positive cells. PC transcripts from Nog-expressing mice demonstrated induction of markers of Spasmolytic Polypeptide-Expressing Metaplasia. Conclusion: PC-specific loss of BMP signaling alters the homeostasis of the gastric epithelium leading to the development of metaplasia.

Primary synovial osteochondromatosis of the ankle is a rare and benign disease of the young adult. It is characterized by the formation of multiple nodules of hyaline cartilage under the synovium. It is usually asymptomatic but can sometimes be revealed by pain or joint mobility disorders. X-rays and CT scans can easily diagnose calcified osteochondromas, but ultrasound and MRI can provide a quicker diagnosis by visualizing non-calcified foreign bodies. Surgery under arthroscopy remains the best therapeutic choice, however, this pathology still causes recurrence in less than 1/3 of cases.

We described a breast papillary lesion related to silicone breast implant exposure. The case report is in accordance with our initial publication, where we proposed that silicone particles may trigger a process of reverse morphogenesis in pericapsular tissue resulting in metaplasia of the epithelial cells. The relationship between breast metaplasia and silicone implants is still little discussed in the literature. Our current study is based on evidence obtained from the files of a patient with a six-year-old history of silicone breast implant, which resulted in a diagnosis of a papillary lesion after a percutaneous breast biopsy. Currently, the main complications related to implants reported in the literature are intra- and extra-capsular ruptures, capsular contracture, and the most severe, breast implant-associated anaplastic large cell lymphoma. However, another complication not yet widely accepted in the literature is breast implant illness, resulting from silicone induced granuloma of breast implant capsule. Many medical specialists are skeptical about silicone disease potential and argue the lack of scientific evidence to support its existence. We believe that presenting these findings and the appropriate discussion of the results should contribute to a better understanding of the pathologies related to breast implants. It is worth mentioning that the safety of breast implants must be questioned.

Background & Aims: It is well established that chronic inflammation promotes gastric cancer–associated metaplasia, but little is known regarding the mechanisms by which immune cells and cytokines regulate metaplastic cellular changes. The goals of this study were to identify interleukin 13 (IL13)-producing immune cells, determine the gastric epithelial cell response(s) to IL13, and establish the role(s) of IL13 in metaplasia development. Methods: Experiments used an established mouse model of autoimmune gastritis (TxA23), TxA23×Il4ra-/- mice, which develop gastritis but do not express the IL4/IL13-receptor subunit IL4Rα, and TxA23×Il13-Yfp mice, which express yellow fluorescent protein in IL13-producing cells. Flow cytometry was used to measure IL13 secretion and identify IL13-producing immune cells. Mouse and human gastric organoids were cultured with IL13 to determine epithelial cell response(s) to IL13. Single-cell RNA sequencing was performed on gastric epithelial cells from healthy and inflamed mouse stomachs. Mice with gastritis were administered IL13-neutralizing antibodies and stomachs were analyzed by histopathology and immunofluorescence. Results: We identified 6 unique subsets of IL13-producing immune cells in the inflamed stomach. Organoid cultures showed that IL13 acts directly on gastric epithelium to induce a metaplastic phenotype. IL4Rα-deficient mice did not progress to metaplasia. Single-cell RNA sequencing determined that gastric epithelial cells from IL4Rα-deficient mice up-regulated inflammatory genes but failed to up-regulate metaplasia-associated transcripts. Neutralization of IL13 significantly reduced and reversed metaplasia development in mice with gastritis. Conclusions: IL13 is made by a variety of immune cell subsets during chronic gastritis and promotes gastric cancer–associated metaplastic epithelial cell changes. Neutralization of IL13 reduces metaplasia severity during chronic gastritis.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating type of cancer. While many studies have shed light into the pathobiology of PDAC, the nature of PDAC’s cell of origin remains under debate. Studies in adult pancreatic tissue have unveiled a remarkable exocrine cell plasticity including transitional states, mostly exemplified by acinar to ductal cell metaplasia, but also with recent evidence hinting at duct to basal cell transitions. Single-cell RNA sequencing has further revealed intrapopulation heterogeneity among acinar and duct cells. Transcriptomic and epigenomic relationships between these exocrine cell differentiation states and PDAC molecular subtypes have started to emerge, suggesting different ontogenies for different tumor subtypes. This review sheds light on these diverse aspects with particular focus on studies with human cells. Understanding the “masked ball” of exocrine cells at origin of PDAC and leaving behind the binary acinar vs duct cell classification may significantly advance our insights in PDAC biology.

There is no doubt that chronic gastroesophageal reflux disease increases the risk of esophageal adenocarcinoma (EAC) by several fold (odds ratio, 6.4; 95% CI, 4.6–9.1), and some relationships between reflux disease–mediated inflammation and oncogenic processes have been explored; however, the precise interconnections between the immune response and genomic instabilities underlying these pathologic processes only now are emerging. Furthermore, the precise cell of origin of the precancerous stages associated with EAC development, Barrett’s esophagus, be it cardia resident or embryonic remnant, may shape our interpretation of the likely immune drivers. This review integrates the current collective knowledge of the immunology underlying EAC development and outlines a framework connecting proinflammatory pathways, such as those mediated by interleukin 1β, tumor necrosis factor α, leukemia inhibitory factor, interleukin 6, signal transduction and activator of transcription 3, nuclear factor-κB, cyclooxygenase-2, and transforming growth factor β, with oncogenic pathways in the gastroesophageal reflux disease–Barrett’s esophagus–EAC cancer sequence. Further defining these immune and molecular railroads may show a map of the routes taken by gastroesophageal cells on their journey toward EAC tumor phylogeny. The selective pressures applied by this immune-induced journey likely impact the phenotype and genotype of the resulting oncogenic destination and further exploration of lesser-defined immune drivers may be useful in future individualized therapies or enhanced selective application of recent immune-driven therapeutics.

Olfactory neuroblastoma is a rare neuroendocrine tumor derived from the olfactory epithelium. We report a case that showed peculiar histology in a late lymph node metastasis. The patient was a 78-year-old Japanese male, who had headache, epistaxis, and nasal obstruction following bloody sputum that was untreated for ten years. The initial biopsy was interpreted as anaplastic carcinoma, and after being referred to a regional university hospital, a total of 60 Gy of radiation therapy was performed prior to the excision of the residual tumor. Neck metastasis was found on the left side two years later, and the patient died of other disease with no recurrence five years after successful neck dissection.Retrospective examination of the biopsy specimen revealed a neurofibrillary matrix besides nesting growth of basophilic naked cells. The neck metastases exhibited similar histology, and a large number of rosette structures containing mucus and extensive squamous metaplasia were observed. Immunohistochemically, naked cells and neurofibrillary matrix were positive for synaptophysin and chromogranin A, and rosette structures and some naked cells were positive for AE1/AE3 and CAM5.2. While epithelial differentiation of olfactory neuroblastoma is a unique feature absent in neuroblastomas in other regions, it was clearly and prominently manifested in the present case.

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.)

The presence of ectopic prostatic tissue (EPT) in the female reproductive system has rarely been reported. To date, only a little more than 10 cases have been documented. Herein, we report a case of EPT detected in the uterine cervix of a 72-year-old woman who experienced two episodes of light vaginal bleeding more than 20 years after attaining menopause. Physical, radiological, and laboratory examinations indicated the presence of uterine leiomyoma and endometrial polyps; hence, a transabdominal hysterectomy was performed. EPT (diameter, 3 mm) was found incidentally at a random section of the uterine cervix. On account of its rare occurrence in women, this paper examines the clinicopathological characteristics of cervical EPT, with a review of the literature. We hope that this report will improve pathologists’ understanding of this condition and reduce the possibility of clinical misdiagnosis.

Background: Melanotic oncocytic metaplasia is a rare non-neoplastic lesion. It has been described as a phenomenon in which cells change their morphology to adapt to various stimuli. The incidence of melanotic oncocytic metaplasia is higher in middle-aged Asian males and smokers. The nasopharynx is the most common site of occurrence. Clinically, it is necessary to distinguish this lesion from malignant melanoma. Case: The patient was a man in his sixties and a heavy smoker. Brownish lesions were observed at bilateral pharyngeal openings of the eustachian tube through nasopharyngoscopy. Histopathologically, oncocytic cells without atypia having abundant granular cytoplasm and brownish pigmented granules were observed in the biopsy specimen obtained from the lesion. Immunohistochemically, most of these cells showed positive reaction for anti-mitochondria, S100, and Melan A, but not for HMB45. Discussion: The characteristic histological finding of this lesion was the presence of abundant mitochondria and melanin pigments in the cytoplasm. The former may be the result of a mitochondrial response to various stimuli, while the latter may be transported from dendritic cells mixed in the surrounding mucosal epithelium. Conclusion: It is important that otolaryngologists understand the features of this lesion, perform thorough observations, and reach a diagnosis through biopsy.

Pleomorphic adenoma is the most common benign tumour of the salivary glands. It accounts for up to 76% of all salivary gland neoplasms and most commonly affects the parotid gland. Extensive squamous metaplasia in such tumours can cause histological misinterpretation, leading to misdiagnosis in some circumstances. We present a patient who had a pleomorphic adenoma misdiagnosed as metastatic oral squamous cell carcinoma. This case highlights the potential difficulties and diagnostic pitfalls, which may arise when diagnosing pleomorphic adenomas.

Ozone is a common air pollutant associated with various human diseases. The human ocular surface is frequently exposed to ozone in the troposphere, but the mechanisms by which ozone affects the ocular surface health remain unclear. This study aimed to establish a mouse model to investigate the effects of ozone exposure on the ocular surface and the corneal epithelium. The findings revealed that ozone exposure disrupted corneal epithelial homeostasis and differentiation, resulting in corneal squamous metaplasia. Further, ozone exposure induced oxidative damage and cytoplasmic leakage of mitochondrial DNA (mtDNA), thereby activating the cGAS/STING signaling pathway. The activation of the cGAS/STING signaling pathway triggered the activation of downstream NF-κB and TRAF6 signaling pathways, causing corneal inflammation, thereby promoting corneal inflammation and squamous metaplasia. Finally, C-176, a selective STING inhibitor, effectively prevented and treated corneal inflammation and squamous metaplasia caused by ozone exposure. This study revealed the role of mtDNA leakage-mediated cGAS/STING activation in corneal squamous epithelial metaplasia caused by ozone exposure. It also depicted the abnormal expression pattern of corneal epithelial keratin using three-dimensional images, providing new targets and strategies for preventing and treating corneal squamous metaplasia and other ocular surface diseases., Competing Interests: Declaration of Competing Interest None of the content of the present manuscript has been published or submitted to any other journal. All the listed authors reviewed and approved the content prior to submission. None of the authors have any ethical conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Osteolipoma is a very rare type of lipoma, originating from the mature lamellar bone within the tumor. In this case report, we describe the clinical, radiographic, and histopathological features of a case of osteolipoma in the oral cavity. Our patient was a 58-year-old Iranian female presenting to the Oral and Maxillofacial Clinic of Al-Zahra Hospital, in Isfahan, complaining of a mandibular swelling in the right side. The patient had a history of breast cancer 4 years earlier, which had been treated. She also had been diagnosed with osteoma in the mandibular region 2 years earlier, for which, she had undergone a surgical procedure. Microscopic examination of biopsy specimen revealed mesenchymal tissue composed of mature adipose cells with a lobular pattern, which led to a diagnosis of lipoma with central osseous metaplasia. The patient recovered after surgery. Intraoral lipoma is extremely rare. However, it should be included in the list of differential diagnosis when encountering a lesion composed of adipose tissue in combination with osseous tissue. The prognosis of osteolipoma is similar to that of lipoma, and its management includes complete surgical resection of the tumor. Recurrence has not been reported.

Saraca asoca (Fabaceae) is a prime ingredient in Asokarishta, a well-known Ayurvedic preparation for gynecological ailments. Due to scarcity, adulteration or substitution of related raw drugs is a common practice in its preparation. The bark of Kingiodendron pinnatum (Roxb. ex DC.) Harms, morphologically similar to S. asoca (Asoka) is a widely used substitute. The present study aimed to evaluate the pharmacological effectiveness of K. pinnatum as an alternative for S. asoca in Asokarishta by determining the inhibitory effect of estrogen induced uterus endometrial thickening in immature female rats. Arishta was prepared using S. asoca and with the substitute, K. pinnatum as per Ayurvedic Pharmacopeia. Uterus endometrial thickening was induced by the administration of estradiol (20 μg/kg b. wt, i.p) to 8-day-old rats for 5 alternate days. On day 16, following estradiol administration, the serum estrogen level was found elevated to 156.5 ± 8 pg/ml from the normal value 32.4 ± 5 pg/ml and consequently increased the thickness of uterus endometrium from 16.7 ± 1.4 to 75.2 ± 15.3 μm. Upon oral administration of 400 μl/kg b. wt Asokarishta (ASA) and Arishta made with K. pinnatum (AKP), the thickening was reduced to 42.5 ± 12.7 and 47.1 ± 10.5 μm and the estrogen level diminished to 102.6 ± 10 and 97.3 ± 8 pg/ml, respectively. Arishta also reduced the chronic/acute inflammations in mice and improved the antioxidant status of rats. No toxic symptom was observed in the animals by the treatment of Arishta. The study supports the use of K. pinnatum as an alternative to S. asoca in Asokarishta and gives a scientific validation for Asokarishta in gynecological ailments.

The contributions of the innate immune system to the development of pancreatic cancer are still ill defined. Inflammatory macrophages can initiate metaplasia of pancreatic acinar cells to a duct-like phenotype (acinar-to-ductal metaplasia [ADM]), which then gives rise to pancreatic intraepithelial neoplasia (PanIN) when oncogenic KRas is present. However, it remains unclear when and how this inflammatory macrophage population is replaced by tumor-promoting macrophages. Here, we demonstrate the presence of interleukin-13 (IL-13), which can convert inflammatory into Ym1+ alternatively activated macrophages, at ADM/PanIN lesions. We further show that Ym1+ macrophages release factors, such as IL-1ra and CCL2, to drive pancreatic fibrogenesis and tumorigenesis. Treatment of mice expressing oncogenic KRas under an acinar cell-specific promoter with a neutralizing antibody for IL-13 significantly decreased the accumulation of alternatively activated macrophages at these lesions, resulting in decreased fibrosis and lesion growth.

Background & Aims: Barrett's esophagus (BE) might recur after complete eradication of intestinal metaplasia (CEIM). We investigated  factors associated with recurrence of BE after successful Radiofrequency ablation (RFA)., Methods: A longitudinal study of BE patients with dysplasia treated with RFA from 2014 to 2021 in two large referral centers. Recurrence was identified in histologic specimens. Factors associated with post-RFA recurrence were analyzed using Cox regression analysis., Results: A total of 728 patients with BE were identified, 118 had underwent RFA, and 113 had sufficient follow up time. Mean age was 63.7 (±11.7) years, 73.5% were males, 59.3% had long segment of BE, and 30.1% had multifocal dysplasia. During 340.8 patient-years of follow-up, 15 patients (13.3%) had recurrence of BE, which represent an incidence rate of 4.41% per patient-year. Incidence rate of recurrence with dysplasia was 1.17% per patient-year. Multifocal dysplasia, number of RFA sessions, and endoscopic resection before RFA were associated with risk of recurrence in univariate analysis. However, in cox regression analysis only multifocal dysplasia (HR 10.99; 95% CI 2.83-22.62, p = 0.001) was associated with post-RFA recurrence., Conclusion: Total recurrence rates after CEIM are low, and multifocal dysplasia before the ablative therapy is significantly associated with BE recurrence after CEIM. Patients with multifocal dysplasia should be monitored rigorously after successful ablation., Competing Interests: Conflict of interest For all authors there are no conflict of interest to declare., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

El Esófago de Barrett (EB) es una patología adquirida producto del reflujo gastroesofágico crónico que provoca la lesión de la mucosa esofágica normal y su reemplazo por mucosa metaplásica. La importancia clínica del EB radica en que constituye un factor de riesgo para el desarrollo de adenocarcinoma esofágico. La incidencia del adenocarcinoma esofágico se encuentra en aumento y su diagnóstico se realiza generalmente en etapas avanzadas, teniendo un pronóstico sombrío. Actualmente el objetivo es detectar el cáncer en etapas iniciales y eventualmente tratables, para lo cual se han planteado distintos protocolos de vigilancia y numerosas alternativas de tratamiento del epitelio metaplásico del esófago de Barrett. En el siguiente artículo se revisan los conceptos más recientes de manejo.

Barrett's oesophagus (BO) is a pathological condition in which the squamous epithelium of the distal oesophagus is replaced by an intestinal-like columnar epithelium originating from the gastric cardia. Several somatic mutations contribute to the intestinal-like metaplasia. Once these have occurred in a single cell, it will be unable to expand further unless the altered cell can colonise the surrounding squamous epithelium of the oesophagus. The mechanisms by which this happens are still unknown. Here we have established an in vitro system for examining the competitive behaviour of two epithelia. We find that when an oesophageal epithelium model (Het1A cells) is confronted by an intestinal epithelium model (Caco-2 cells), the intestinal cells expand into the oesophageal domain. In this case the boundary involves overgrowth by the Caco-2 cells and the formation of isolated colonies. Two key transcription factors, normally involved in intestinal development, HNF4α and CDX2, are both expressed in BO. We examined the competitive ability of Het1A cells stably expressing HNF4α or CDX2 and placed in confrontation with unmodified Het1A cells. The key result is that stable expression of HNF4α, but not CDX2, increased the ability of the cells to migrate and push into the unmodified Het1A domain. In this situation the boundary between the cell types is a sharp one, as is normally seen in BO. The experiments were conducted using a variety of extracellular substrates, which all tended to increase the cell migration compared to uncoated plastic. These data provide evidence that HNF4α expression could have a potential role in the competitive spread of BO into the oesophagus as HNF4α increases the ability of cells to invade into the adjacent stratified squamous epithelium, thus enabling a single mutant cell eventually to generate a macroscopic patch of metaplasia., Competing Interests: Declarations of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Study Aims: Helicobacter pylori (H. pylori) infection has been clearly shown to be a cause of gastric cancer, and the incidence of gastric cancer has been shown to decrease with eradication. However, few reports have described the utility of eradication therapy in elderly people. Thus, an investigation focusing on how much actual histological improvement is obtained with eradication therapy in elderly people was conducted., Patients and Methods: This was a retrospective study conducted using medical information of patients diagnosed with H. pylori-associated gastritis and who underwent eradication therapy. The histological improvement was assessed based on changes in the atrophy and intestinal metaplasia scores of the Updated Sydney system from before to after eradication. We investigated the rates of histological improvement in atrophy and intestinal metaplasia one year after and long term more than five years after H. pylori eradication in an elderly group and a younger group., Results: This study included 221 patients (elderly group 123, younger group 98). In histological atrophy, higher rates of improvement were seen in the corpus than in the antrum, and the rates of cure in the antrum were lower in elderly group than in younger group (p = 0.0282). With regard to intestinal metaplasia, the rates of improvement in the antrum were lower in elderly group than in younger. In long term observation, although the rates of cure in the antrum were lower in elderly, improvements were seen in atrophy scores in most of the patients and intestinal metaplasia scores in about half of patients., Conclusion: Though there is more obvious improvement in the gastric mucosa when H. pylori eradication therapy is performed at a young age, some mucosal improvement can be expected in about half of patients after eradication, even in elderly people., Competing Interests: Declaration of competing interests 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

A mielofibrose idiopática é uma doença mieloproliferativa crônica, que pode evoluir com hepatoesplenomegalia, também denominada metaplasia, e acometer vários órgãos. Ocasionalmente, o baço alcança proporções gigantescas e precisa ser retirado. Entretanto, esse procedimento é seguido de elevada morbidade e mortalidade. As esplenectomias parciais, que preservam o pedículo esplênico, foram propostas para reduzir complicações pós-operatórias. Após melhora transitória do quadro clínico, surge a recorrência da esplenomegalia e da sintomatologia. A presente comunicação relata duas alternativas para tratamento de esplenomegalia: a esplenectomia subtotal, com preservação do pólo esplênico superior suprido apenas pelos vasos esplenogástricos, e a esplenectomia total, com auto-implantes de tecido esplênico. Realizamos a esplenectomia subtotal em cinco pacientes. O acompanhamento por até dez anos e a melhora clínica dos doentes sugerem que essa operação deva ser considerada para o tratamento de baços gigantes devido à esplenomegalia decorrente de mielofibrose. Um outro paciente foi submetido a esplenectomia total e auto-implante esplênico no omento maior. No seguimento de três anos deste último paciente, não foram registradas complicações relacionadas ao remanescente esplênico. Entretanto, o paciente necessitou de controle hematológico intensivo por causa da gravidade de sua doença de base. Concluindo, se for indicada operação para complementar a terapêutica hematológica da esplenomegalia, deve-se realizar um procedimento conservador do baço. A esplenectomia subtotal ou a esplenectomia total com auto-implantes de tecido esplênico são duas boas escolhas em tais situações.

Background: Special histological types (SHT) of triple-negative breast cancer (TNBC) are a heterogeneous group of rare poorly understood diseases. We aimed to evaluate the clinical features, treatment, and outcomes of patients with SHT of TNBC., Methods: We evaluated patients with a SHT of TNBC treated in a cancer center between 2009 and 2020. The endpoints were characterization of clinical and pathological features, pathologic complete response (PCR) rate after neoadjuvant chemotherapy, disease-free survival (DFS), progression-free survival, and overall survival (OS)., Results: The 132 patients included had the following histologies: metaplastic (n=71), medullary pattern (n=14), lobular (n=12), adenoid cystic (n=12), apocrine (n=10), and others (n=13). Metaplastic, lobular, and medullary pattern tumors had higher grade (66.6-85.7% grade 3); adenoid cystic and apocrine had mainly grade 1-2 (70-83.3%). Metaplastic and lobular carcinomas had higher disease stages (47.8% and 58.2% stages III-IV). PCR rates were 10.3% for metaplastic and 33.3% for lobular carcinomas, with 5-year DFS rates of 56% and 51.4%. Medullary pattern carcinomas had a great response to treatment, with PCR rate of 100%, and 5-year DFS rate of 92.8%. Apocrine carcinomas also had favorable prognosis, with no recurrence after early disease treatment, and 5-year DFS rate of 83.3%. Adenoid cystic carcinomas had intermediate prognosis, with 5-year DFS rate of 66.6%., Conclusion: SHT of TNBC encompasses heterogeneous malignancies with distinct behaviors. Lobular and metaplastic carcinomas showed high aggressiveness and poor treatment response, while medullary pattern and apocrine carcinomas had favorable outcomes. Treatment strategies focus on molecular features of each of these diseases are warranted., (Copyright © 2022. Published by Elsevier Inc.)

The epithelium of the airway has considerable capacity to undergo repair. These repair processes are responsible for maintaining and restoring function after injury of the airways, which likely occurs often as a result of infectious, toxic or other exposures. However, repair processes need not be fully effective. Inadequate repair can take a number of forms and may result in metaplasia, hyperplasia or fibrotic scarring. It is likely that repair processes that lead to tissue disruption play an important role in the chronic airways diseases, such as asthma and bronchitis. Through delineation of these processes, it may become feasible to target therapeutic interventions in order to achieve more effective maintenance of tissue structure.

We present a patient with extensive keratinizing squamous metaplasia that progressed to squamous papilloma over the course of follow-up. To our knowledge, this is the first published case of keratinizing squamous metaplasia with melanotic deposits of an unknown material with synchronous development of squamous papilloma.