RESUMEN
OBJECTIVE: To determine the presence of microplastics in the stomach, and the relationship between pathological changes in stomach tissue and microplastics. STUDY DESIGN: An analytical study. Place and Duration of the Study: Department of Internal Medicine, Sorgun State Hospital, Yozgat, Turkiye, from December 2022 to November 2023. METHODOLOGY: Fasting gastric fluid sampling and endoscopic sampling including mucosal and submucosal layers from the antrum were performed. The pH values of the gastric fluids were recorded. Samples were analysed gradually by adding iron solution, hydrogen peroxide, and sodium chloride (NaCl) in a beaker at 75 degrees for 30 minutes. Biopsy materials obtained from antrum were examined histopathologically and reported according to the Sydney classification. The relationship between gastric biopsy results and the presence of microplastic was evaluated using Chi-square test. The significance level was taken as p <0.005. RESULTS: The study included 61 individuals. The presence of microplastics was detected in 17 (27.86%) gastric fluid samples obtained from the individuals. A significant correlation was found between increased activity and inflammation in antrum biopsy and the presence of microplastic (χ2 = 8.55 p = 0.014; χ2 = 25.75, p = 0.001). The relationship between atrophy, metaplasia, and Helicobacter pylori in gastric tissue and the presence of microplastic was statistically insignificant (p >0.05). CONCLUSION: Microplastics were detected in gastric fasting fluid. These materials can cause histopathologic changes and inflammation in the gastric antrum. KEY WORDS: H. pylori, Intestinal metaplasia, Inflammation, Microplastic, Plastic, Sydney classification.
Asunto(s)
Ayuno , Microplásticos , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Microplásticos/análisis , Jugo Gástrico/química , Mucosa Gástrica/patología , Biopsia , Estómago/patología , Helicobacter pylori/aislamiento & purificación , Antro Pilórico/patología , Metaplasia/patología , Turquía , AncianoRESUMEN
Gastric cancer (GC) is the fifth most common cause of cancer-related death worldwide. Early detection is crucial for improving survival rates and treatment outcomes. However, accurate GC-specific biomarkers remain unknown. This study aimed to identify the metabolic differences between intestinal metaplasia (IM) and GC to determine the pathways involved in GC. A metabolic analysis of IM and tissue samples from 37 patients with GC was conducted using ultra-performance liquid chromatography with tandem mass spectrometry. Overall, 665 and 278 significant features were identified in the aqueous and 278 organic phases, respectively, using false discovery rate analysis, which controls the expected proportion of false positives among the significant results. sPLS-DA revealed a clear separation between IM and GC samples. Steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and arginine and proline metabolism were the most significantly altered pathways. The intensity of 11 metabolites, including N1, N2-diacetylspermine, creatine riboside, and N-formylkynurenine, showed significant elevation in more advanced GC. Based on pathway enrichment analysis and cancer stage-specific alterations, we identified six potential candidates as diagnostic biomarkers: aldosterone, N-formylkynurenine, guanosine triphosphate, arginine, S-adenosylmethioninamine, and creatine riboside. These metabolic differences between IM and GC provide valuable insights into gastric carcinogenesis. Further validation is needed to develop noninvasive diagnostic tools and targeted therapies to improve the outcomes of patients with GC.
Asunto(s)
Biomarcadores de Tumor , Metaplasia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Metaplasia/metabolismo , Metaplasia/patología , Masculino , Femenino , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Anciano , Metaboloma , Metabolómica/métodos , Redes y Vías Metabólicas , Espectrometría de Masas en Tándem/métodosRESUMEN
OBJECTIVE: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research. DESIGN: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM. RESULTS: From 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence. CONCLUSION: Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist.
Asunto(s)
Metaplasia , Guías de Práctica Clínica como Asunto , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Metaplasia/patología , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Lesiones Precancerosas/diagnóstico , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/diagnóstico , Gastroscopía/métodos , Helicobacter pyloriRESUMEN
The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided into five groups: Helicobacter pylori (H. pylori)-associated gastritis with gastric intestinal metaplasia (GIM) (n = 12), chronic atrophic gastritis (CAG) with GIM (n = 13), H. pylori-associated gastritis without GIM (n = 19), GC (n = 6) and controls (n = 5). TRPV1 expression was determined with immunohistochemistry and was significantly higher in patients with H. pylori-associated gastritis compared with controls (p = 0.002). TRPV1 expression was even higher in the presence of GIM compared with patients without GIM and controls (p < 0.001). There was a complete loss of TRPV1 expression in patients with GC. TRPV1 expression seems to contribute to gastric-mucosal inflammation and precursors of GC, which significantly increases in cancer precursor lesions but is completely lost in GC. These findings suggest TRPV1 expression to be a potential marker for precancerous conditions and a target for individualized treatment. Longitudinal studies are necessary to further address the role of TRPV1 in gastric carcinogenesis.
Asunto(s)
Infecciones por Helicobacter , Neoplasias Gástricas , Canales Catiónicos TRPV , Humanos , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/patología , Carcinogénesis/metabolismo , Carcinogénesis/patología , Estudios Retrospectivos , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Helicobacter pylori/patogenicidad , Metaplasia/metabolismo , Metaplasia/patología , Gastritis/metabolismo , Gastritis/patología , Gastritis/microbiología , Adulto , Inmunohistoquímica , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Gastritis Atrófica/metabolismo , Gastritis Atrófica/patologíaRESUMEN
ABSTRACT: Melanocytic nevi can show a great number of morphological, cytoarchitectural, and stromal variations. Some of these histopathological patterns, infrequent or unusual, can occasionally produce diagnostic doubts or problems. A 22-year-old female patient presented a poorly pigmented cutaneous polypoid lesion of the scalp. Histopathological examination showed an intradermal melanocytic nevus composed of aggregates, nests, and cords of benign melanocytes, with collagenous stroma and large lipomatous areas. In the lipidized portion of the lesion, nevus cells, arranged in clusters, nests, and cords, were intimately associated with mature-appearing adipocytes, CD34-positive spindle cells, Alcian Blue-positive fibromyxoid stroma, and eosinophilic collagen bundles, findings resembling those typically seen in spindle cell lipoma. Spindle cell lipomatous metaplasia, rarely observed in some benign nonmelanocytic skin lesions, can be considered an additional unusual, not previously described, stromal variation occurring in melanocytic nevi.
Asunto(s)
Metaplasia , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Femenino , Metaplasia/patología , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Adulto Joven , Lipoma/patología , Cuero Cabelludo/patología , InmunohistoquímicaRESUMEN
BACKGROUND AND PURPOSE: Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp. MATERIALS AND METHODS: In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered. RESULTS: Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis. INTERPRETATION: Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , Pronóstico , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Anciano de 80 o más Años , Resultado del Tratamiento , Supervivencia sin Enfermedad , Metaplasia/patología , Metaplasia/terapia , Mastectomía , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/mortalidadRESUMEN
BACKGROUND: Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM. METHOD: The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes. RESULTS: A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM. CONCLUSION: We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM.
Asunto(s)
Ferroptosis , Aprendizaje Automático , Metaplasia , Ferroptosis/genética , Humanos , Metaplasia/genética , Metaplasia/patología , Metaplasia/diagnóstico , Perfilación de la Expresión Génica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Biomarcadores de Tumor/genética , Curva ROC , Transcriptoma , Biología Computacional/métodos , Máquina de Vectores de Soporte , Regulación Neoplásica de la Expresión Génica , Mapas de Interacción de ProteínasRESUMEN
OBJECTIVES: We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: From EGC patients who underwent ESD, bulk RNA sequencing was performed on non-cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially-expressed genes were identified, from which biomarkers were selected using real-time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis. RESULTS: From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85-0.97) for MGC prediction. CONCLUSION: Assessing biomarkers in non-cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance.
Asunto(s)
Biomarcadores de Tumor , Neoplasias Primarias Secundarias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Masculino , Femenino , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Anciano , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/patología , Resección Endoscópica de la Mucosa , Proteína Quinasa CDC2/genética , Proteína Quinasa CDC2/metabolismo , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Mucosa Gástrica/microbiología , Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Gastroscopía , Regulación Neoplásica de la Expresión Génica , Metaplasia/genética , Metaplasia/patología , Helicobacter pylori/aislamiento & purificación , Estudios de Casos y ControlesRESUMEN
Recurrence within one or two years is common after Crohn's disease (CD) resection. In this study, we seek to identify histologic features in CD resections that may predict earlier (≤18 months) recurrence to potentially guide post-operative management. A single-institution, retrospective review was performed on patients with first-time CD bowel resection specimens (2002-2007). Patient demographics and CD course were also documented. Slides were reviewed for inflammatory distribution and composition, small bowel (SB) pyloric metaplasia (PM), and presence and characteristics of submucosal fibrosis and granulomas. In our cohort, 14 of 41 patients experienced earlier clinical or endoscopic recurrence after initial resection. In the 38 patients who underwent SB resection (3 were colon only), PM was less common in those with earlier recurrence (6/12 [50%]) compared to those with later (>18 months) or no known recurrence (22/26 [85%]) (P = 0.045). PM was present even in patients with <1 year of known CD. Additionally, therapy with anti-tumor necrosis factor (TNF) prior to surgery was more common in earlier recurrence patients (7/14 [50%]) than later or no recurrence patients (4/27 [15%]) (P = 0.026). There was no significant difference in age, sex, smoking status, duration of CD, post-operative CD medication, distribution or features of inflammation, granulomas, or fibrosis. Overall, our results indicate that SB PM and pre-surgical anti-TNF therapy are possible helpful clinicopathologic features to evaluate for recurrence risk.
Asunto(s)
Enfermedad de Crohn , Intestino Delgado , Metaplasia , Recurrencia , Humanos , Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Masculino , Femenino , Estudios Retrospectivos , Metaplasia/patología , Adulto , Persona de Mediana Edad , Intestino Delgado/patología , Intestino Delgado/cirugía , Adulto Joven , Factores de Riesgo , Adolescente , Factores de Tiempo , Fibrosis/patología , AncianoRESUMEN
Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGF-ß1 signaling inhibitor epigallocatechin gallate (EGCG) to interstitial lung disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA-Seq on spare tissue. Biopsies from untreated patients showed higher fibroblast TGF-ß1 signaling compared with nondisease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGF-ß1 signaling and several proinflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzled-related protein 2 (sFRP2), an unrecognized TGF-ß1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision-cut lung slices (PCLSs) from nondiseased donors, we found TGF-ß1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature cytokeratin 5+ (Krt5+) basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGF-ß1 signaling in ILD and the therapeutic potential of EGCG in reducing idiopathic pulmonary fibrosis-related (IPF-related) transcriptional changes and identify TGF-ß1/noncanonical Wnt pathway crosstalk via sFRP2 as a mechanism for dysfunctional epithelial signaling in IPF/ILD.
Asunto(s)
Fibroblastos , Fibrosis Pulmonar Idiopática , Metaplasia , Factor de Crecimiento Transformador beta1 , Vía de Señalización Wnt , Humanos , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/genética , Fibroblastos/metabolismo , Fibroblastos/patología , Metaplasia/metabolismo , Metaplasia/patología , Masculino , Femenino , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Animales , Ratones , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Persona de Mediana EdadRESUMEN
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.
Asunto(s)
Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Queratina-20 , Queratina-7 , Antígeno Ki-67 , Metaplasia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biopsia , Mucosa Gástrica/patología , Mucosa Gástrica/microbiología , Mucosa Gástrica/metabolismo , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/microbiología , Inmunohistoquímica , Queratina-20/metabolismo , Queratina-7/metabolismo , Antígeno Ki-67/metabolismo , Metaplasia/patología , Metaplasia/microbiología , Estudios RetrospectivosRESUMEN
ABSTRACT: Metaplastic breast cancer is a rare and heterogeneous breast cancer group that encompasses both malign epithelial and mesenchymal tissue components. Squamous cell breast cancer (SCC) is one of the types of metaplastic breast cancer, and diagnosis is established when more than 90% of the malignant cells are of squamous cell origin. Squamous cell metaplastic breast carcinoma is considered an aggressive tumor because of the risk of distant metastases, and there are limited data on treatment patterns. In this study, we report patient characteristics and treatment results of one patient with bilateral metaplastic squamous cell breast cancer.
Asunto(s)
Neoplasias de la Mama , Carcinoma de Células Escamosas , Metaplasia , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Metaplasia/patología , Persona de Mediana EdadRESUMEN
BACKGROUND: The requirement for routine biopsy sampling in esophagogastroduodenoscopy (EGD) with normal endoscopic findings is a subject of debate. In this study, patients who had normal endoscopic findings in EGD and underwent biopsy sampling were retrospectively analyzed. METHODS: This single-center retrospective cohort study included 671 patients who underwent EGD between 2021 and 2023 in the Sisli Hamidiye Etfal Training and Research Hospital Surgical Endoscopy Unit. All patients had normal endoscopic findings and a sampling biopsy was performed on all patients included. Patients were evaluated based on demographic and clinicopathologic findings. This study was registered to ClinicalTrials.gov (NCT06269380). RESULTS: Two hundred sixty patients (38.7%) have abnormal histopathologic findings. Helicobacter pylori positivity was detected in 200 (29.8%) patients. Intestinal metaplasia (IM) was present in 80 of 260 patients (30.8%). The frequency of IM was higher in older age groups and cases with mild gastritis ( P <0.001). The frequency and severity of gastritis were associated with increased H. pylori positivity and density ( P <0.001). CONCLUSIONS: The biopsy sampling may contribute to the diagnosis and treatment process in cases where normal endoscopic findings are observed during EGD.
Asunto(s)
Endoscopía del Sistema Digestivo , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Biopsia/métodos , Endoscopía del Sistema Digestivo/métodos , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Adulto , Gastritis/patología , Gastritis/microbiología , Gastritis/diagnóstico , Anciano , Antro Pilórico/patología , Antro Pilórico/microbiología , Metaplasia/patología , Adulto JovenRESUMEN
Metabolic reprogramming is a hallmark of cancer and is crucial for cancer progression, making it an attractive therapeutic target. Understanding the role of metabolic reprogramming in cancer initiation could help identify prevention strategies. To address this, we investigated metabolism during acinar-to-ductal metaplasia (ADM), the first step of pancreatic carcinogenesis. Glycolytic markers were elevated in ADM lesions compared with normal tissue from human samples. Comprehensive metabolic assessment in three mouse models with pancreas-specific activation of KRAS, PI3K, or MEK1 using Seahorse measurements, nuclear magnetic resonance metabolome analysis, mass spectrometry, isotope tracing, and RNA sequencing analysis revealed a switch from oxidative phosphorylation to glycolysis in ADM. Blocking the metabolic switch attenuated ADM formation. Furthermore, mitochondrial metabolism was required for de novo synthesis of serine and glutathione (GSH) but not for ATP production. MYC mediated the increase in GSH intermediates in ADM, and inhibition of GSH synthesis suppressed ADM development. This study thus identifies metabolic changes and vulnerabilities in the early stages of pancreatic carcinogenesis. Significance: Metabolic reprogramming from oxidative phosphorylation to glycolysis mediated by MYC plays a crucial role in the development of pancreatic cancer, revealing a mechanism driving tumorigenesis and potential therapeutic targets. See related commentary by Storz, p. 2225.
Asunto(s)
Metaplasia , Neoplasias Pancreáticas , Animales , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Ratones , Metaplasia/metabolismo , Metaplasia/patología , Glucólisis , Carcinogénesis/metabolismo , Células Acinares/metabolismo , Células Acinares/patología , Fosforilación Oxidativa , Glutatión/metabolismo , Reprogramación Celular , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Masculino , Mitocondrias/metabolismo , Mitocondrias/patología , Reprogramación MetabólicaRESUMEN
Squamous cell lung cancer (SCLC) occurs as a result of dysregenerative changes in the bronchial epithelium: basal cell hyperplasia (BCH), squamous cell metaplasia (SM), and dysplasia. We previously suggested that combinations of precancerous changes detected in the small bronchi of patients with SCLC may reflect various "scenarios" of the precancerous process: isolated BCHâstopping at the stage of hyperplasia, BCH+SMâprogression of hyperplasia into metaplasia, SM+dysplasiaâprogression of metaplasia into dysplasia. In this study, DNA methylome of various forms of precancerous changes in the bronchial epithelium of SCLC patients was analyzed using the genome-wide bisulfite sequencing. In BCH combined with SM, in contrast to isolated BCH, differentially methylated regions were identified in genes of the pathogenetically significant MET signaling pathway (RNMT, HPN). Differentially methylated regions affecting genes involved in inflammation regulation (IL-23, IL-23R, IL12B, IL12RB1, and FIS1) were detected in SM combined with dysplasia in comparison with SM combined with BCH. The revealed changes in DNA methylation may underlie various "scenarios" of the precancerous process in the bronchial epithelium.
Asunto(s)
Bronquios , Metilación de ADN , Hiperplasia , Neoplasias Pulmonares , Metaplasia , Lesiones Precancerosas , Humanos , Hiperplasia/patología , Hiperplasia/genética , Metaplasia/genética , Metaplasia/patología , Metaplasia/metabolismo , Bronquios/patología , Bronquios/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Lesiones Precancerosas/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Epigenoma/genética , Mucosa Respiratoria/patología , Mucosa Respiratoria/metabolismo , Anciano , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismoRESUMEN
RATIONALE: Uterine adenomyomas (UAs) are common benign tumors, usually not exceeding 280 g or the weight of the uterus at 12 weeks gestation. Postmenopausal giant UAs of diameter larger than 20 cm are rare, as well as steatosis, but curable by surgical excision. Few cases of postmenopausal giant UAs have been reported. PATIENT CONCERNS: Herein, we report a case of a 70-year-old female patient who presented with a giant pelvic tumor of about 20 cmâ ×â 18 cmâ ×â 20 cm with postmenopausal vaginal bleeding, and whose radiographic manifestations did not exclude the possibility of uterine malignancy. DIAGNOSES: Histopathology confirms an adenomyoma with partial adipose metaplasia. INTERVENTIONS: We did an open laparotomy of hysterectomy, bi-adnexectomy, and pelvic adhesion release for the patient. OUTCOMES: Pathology revealed adenomyoma with adipose metaplasia. The patient recovered well and was discharged on postoperative day 7 with satisfactory follow-up.
Asunto(s)
Adenomioma , Metaplasia , Posmenopausia , Neoplasias Uterinas , Humanos , Femenino , Anciano , Adenomioma/patología , Adenomioma/cirugía , Adenomioma/diagnóstico por imagen , Metaplasia/patología , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Tejido Adiposo/patología , HisterectomíaRESUMEN
Objective: To investigate the clinical and pathological characteristics of primary mucinous gland lesions of the fallopian tubes. Methods: The clinical data, pathomorphological characteristics and immunophenotype of 14 cases of primary mucinous gland lesions of the fallopian tube diagnosed at Obstetrics and Gynecology Hospital of Fudan University from 2015 to 2023 were analyzed retrospectively. In addition, a comprehensive review of relevant literature was conducted. Results: The age of 14 patients ranged from 53 to 83 years, with an average of 65 years. Among them, 13 cases exhibited unilateral involvement while one case showed bilateral presentation. Nine cases were mucinous metaplasia of the fallopian tube, four cases were invasive mucinous adenocarcinoma and one case was mucinous carcinoma in situ. Morphologically, mucinous metaplasia of the fallopian tube was focal, with or without inflammation. The cells of mucinous adenocarcinoma or mucinous carcinoma in situ exhibited characteristics indicative of gastrointestinal differentiation. Immunohistochemical analysis revealed diffuse positive expression of CK7, and negative expression of SATB2. CDX2 demonstrated positive staining in two cases. One case exhibited diffuse and strongly positive mutant expression of p53, whereas the remaining cases displayed wild-type expression. MUC6 showed diffuse or focally positive staining in mucinous gland lesions characterized by gastric differentiation. Some cases of mucinous adenocarcinoma of fallopian tube were subject to AB-PAS staining, resulting in red to purple cytoplasmic staining. Conclusions: Primary mucinous lesions of the fallopian tube are exceedingly uncommon. All cases of mucinous adenocarcinoma of fallopian tubes in this study exhibit the morphology and immunohistochemical characteristics of gastrointestinal differentiation. Mucinous metaplasia of the fallopian tube is a benign lesion of incidental finding, which is closely related to inflammation or gastric differentiation. Mucinous lesions of cervix, ovary and digestive tract are excluded in all patients, confirming the independent existence of mucinous lesions within fallopian tubes.
Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias de las Trompas Uterinas , Trompas Uterinas , Metaplasia , Proteína p53 Supresora de Tumor , Humanos , Femenino , Neoplasias de las Trompas Uterinas/patología , Neoplasias de las Trompas Uterinas/metabolismo , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/metabolismo , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Trompas Uterinas/patología , Anciano de 80 o más Años , Proteína p53 Supresora de Tumor/metabolismo , Metaplasia/patología , Queratina-7/metabolismo , Factor de Transcripción CDX2/metabolismo , Factor de Transcripción CDX2/genética , Mucina 6/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Carcinoma in Situ/patología , InmunohistoquímicaRESUMEN
BACKGROUND: Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. METHODS: In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. RESULTS: Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3ß and resulted in increased ß-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. CONCLUSIONS: OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.