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BACKGROUND: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a cancer stem cell (CSC) marker of colorectal cancer and may be a CSC marker of other cancer types. Few studies have been conducted on LGR5 expression in extrahepatic cholangiocarcinoma (ECC). METHODS: We analyzed LGR5 expression using RNAscope, a highly sensitive RNA in situ hybridization technique. Fifty-three ECCs were selected from the medical archives at Shinshu University Hospital and analyzed using a tissue microarray. LGR5 expression levels were divided into expression and no expression groups. LGR5 expression and clinicopathological characteristics were analyzed. RESULTS: Among 25 cases, no LGR5-positive dots were identified. Among 28 cases, some LGR5-positive dots were observed in carcinoma cells, together with a wide range of LGR5-positive cells. LGR5 expression was conspicuous in glandular duct formations. Well- to moderately differentiated types showed significantly higher LGR5 expression than the poorly differentiated type (p = 0.0268). LGR5 expression was associated with good overall survival (p = 0.0219) and good disease-free survival (DFS) (p = 0.0228). High LGR5 expression was associated with well- to moderately-differentiated types, indicating a favorable prognosis. In terms of DFS, multivariate analysis showed that high LGR5 expression was an independent favorable prognostic factor (p = 0.0397). CONCLUSIONS: These findings suggest that LGR5 is a promising, novel prognostic marker.
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Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Colangiocarcinoma , Receptores Acoplados a Proteínas G , Humanos , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Colangiocarcinoma/metabolismo , Colangiocarcinoma/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/análisis , Receptores Acoplados a Proteínas G/genética , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/genética , Masculino , Biomarcadores de Tumor/análisis , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Supervivencia sin Enfermedad , Anciano de 80 o más Años , AdultoRESUMEN
AIMS: Inflammatory bowel disease-associated colorectal carcinomas are known to have different morphology, immunoprofile, and genetic findings from sporadic colorectal carcinomas; however, little is known for Crohn's disease-associated small bowel neoplasms (CD-SBNs). Cadherin 17 is a useful biomarker of adenocarcinomas with intestinal phenotype and recently reported as an ideal target for chimeric antigen receptor T-cells (CAR-T) therapy for gastrointestinal carcinoma. Claudin 18 is a cell adhesion protein, and Claudin18 isoform 2 (CLDN18.2) is frequently expressed at high levels in gastric-type adenocarcinoma. Zolbetuximab, a targeted monoclonal antibody, has been developed for CLDN18.2-positive gastroesophageal adenocarcinoma. We examined a series of CD-SBNs for both Cadherin 17 and Claudin 18, and also hypothesized that expression of Claudin 18 was associated with gastric phenotype. METHODS AND RESULTS: We performed histological and immunohistochemical examinations on 25 CD-SBNs. Most of adenocarcinomas showed tubular morphology as seen in gastric carcinomas, whereas a subset of dysplasia was morphologically similar to that of the large bowel. Cadherin17 and Claudin 18 expression was identified in 93% and 57% CD-associated adenocarcinomas respectively. In Cadherin 17-positive CD-SBNs, frequent MUC5AC, MUC6, and Claudin18 expression was identified (61%, 57%, and 57%, respectively). Claudin 18-positive CD-SBNs showed significantly more MUC5AC and MUC6 expression than Claudin 18-negative CD-SBNs (P = 0.005, < 0.001 respectively). CONCLUSION: In CD-associated small bowel adenocarcinomas, Cadherin 17 expression was frequently retained and Claudin 18 was frequently co-expressed. Claudin 18 had a positive correlation with the expression of gastric mucins. These results suggest that CD-associated small bowel adenocarcinomas may be candidates for Cadherin 17- and Claudin 18-targeted immunotherapies.
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Cadherin 17 (CDH17) and claudin 18.2 (CLDN18.2) are highly selective markers of intestinal and gastric lineages and are expressed in adenocarcinomas of various organs. They have also been identified as potential targets for immunotherapy. Expression of CDH17 and CLDN18.2 has been observed in a subset of pancreatic neuroendocrine tumours (PanNETs). This study investigates the immunohistochemical expression of CDH17 and CLDN18 in PanNETs in comparison with hormonal expression profiles to provide baseline data for determining candidate indications for targeted therapy with CDH17 and CLDN18.2 in PanNETs, including insulinomas (n = 22), glucagonomas (n = 13), gastrinomas (n = 3), serotoninomas (n = 2) and PanNETs not otherwise specified (NOS) (n = 17). In the normal pancreas, CDH17 was expressed in the lateral membrane of ducts and some islet cells, whereas CLDN18 was occasionally expressed in the intercalated ducts and centroacinar cells. In PanNETs, CDH17 and CLDN18 was detected by membranous staining. CDH17 expression was observed in 9 to 17 (58.8â¯%) PanNETs NOS, 3 of 13 (23.1â¯%) glucagonomas, 1 of 3 (33.3â¯%,) gastrinomas, 1 of 2 (50â¯%) serotoninomas, and none of the insulinomas. According to predefined criteria, 7 of 17 (41.2â¯%) PanNETs NOS, 1 of 3 (33.3â¯%) gastrinomas, and 1 of 2 (50â¯%) serotoninomas were classified as CDH17-positive. There were no significant differences in clinicopathological features between CDH17-positive and CDH17-negative PanNETs, except for a higher tumour grade in the former (p<0.05). For CLDN18, expression was noted in 2 out of 3 (66.7â¯%) gastrinomas, one with focal staining and the other with diffuse staining. One of three (33.3â¯%) gastrinomas was classified as CLDN18-positive using predefined criteria. These findings suggest that a particular subset of PanNETs, including PanNET NOS, gastrinoma, and serotoninoma, may be potential candidates for CDH17-targeted immunotherapy. Additionally, gastrinoma may be a potential candidate for immunotherapy targeting CLDN18.2.
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Introduction: Gastric cancer has been reported to occur with mild to moderate mucosal atrophy, particularly after the eradication of Helicobacter pylori (HP) more than 10 years previously. However, no conclusion has been reached on how many years of esophagogastroduodenoscopy should be performed after HP eradication. Presentation of case: This was a case of gastric carcinoma of the fundic gland type (GCFGT) 32 years after the eradication of HP, which is the longest posteradication period reported. A 62-year-old male patient was diagnosed with GCFGT after HP eradication and regular esophagogastroduodenoscopy, which revealed a white raised lesion on the anterior wall of the upper part of the body. Endoscopic submucosal dissection was performed for GCFGT, and the vertical and horizontal margins were negative. Clinical discussion: In this case, HP was eradicated in 1990, and GCFGT developed 32 years later. To the best of our knowledge, this is the longest case in which gastric cancer appeared after HP eradication. HP eradication therapy for a duodenal ulcer was first reported in 1990, supporting that this is the longest case. Conclusions: This is the first case of gastric cancer more than 20 years after the eradication of HP. The endoscopic findings of this case are typical of GCFGT and may be useful when encountering such cases in the future. Therefore, the risk of gastric cancer should be considered for an extended period even after the eradication of HP, and regular esophagogastroduodenoscopy is recommended even after the eradication of HP.
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Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a significant cancer stem cell marker in colorectal cancer (CRC), lacks lymph node (LN) expression studies. In this study, we identified LGR5 expression by RNAscope, a highly sensitive RNA in situ method, and analyzed its association with clinicopathological characteristics. Tissue microarrays were generated from primary tumors (PTs) and LN metastases in paraffin-embedded blocks of 38 CRC surgical resection materials. LGR5 expression by RNAscope was evaluated by dividing the expression levels into negative and positive expression. In all but two cases of LN metastasis, LGR5-positive dots were detected in tumor cells, and there was a wide range of LGR5-positive cells. More LGR5-positive dots were identified in the gland-forming region. Twenty-three cases were classified into a high LGR5-expression group, and 15 cases were classified into a low LGR5-expression group. In the high LGR5-expression group, the histological grade was lower than in the low LGR5-expression group (p = 0.0159), while necrosis was significantly more prevalent (p = 0.0326), and the tumor, node, metastasis stage was significantly lower (p = 0.0302). There was no association between LGR5 expression levels in LN metastases and LGR5 expression levels in PT tissue. LGR5 expression in LN metastases may influence prognosis. Further analysis may lead to new therapeutic strategies.
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Biomarcadores de Tumor , Neoplasias Colorrectales , Metástasis Linfática , Receptores Acoplados a Proteínas G , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Masculino , Femenino , Metástasis Linfática/patología , Persona de Mediana Edad , Anciano , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Anciano de 80 o más Años , Adulto , Ganglios Linfáticos/patología , Ganglios Linfáticos/metabolismoRESUMEN
BACKGROUND: At present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH. METHODS: Subjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient. RESULTS: PCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases. CONCLUSIONS: In NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI's acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated. STUDY REGISTRATION: This study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).
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Antibacterianos , Quimioterapia Combinada , Gastritis , Infecciones por Helicobacter , Helicobacter heilmannii , Inhibidores de la Bomba de Protones , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Gastritis/tratamiento farmacológico , Gastritis/microbiología , Adulto , Anciano , Helicobacter heilmannii/aislamiento & purificación , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Claritromicina/administración & dosificación , Claritromicina/uso terapéutico , Helicobacter/aislamiento & purificación , Helicobacter/efectos de los fármacos , Resultado del Tratamiento , Mucosa Gástrica/microbiología , Mucosa Gástrica/patologíaRESUMEN
Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival ( P = 0.007) and recurrence-free survival ( P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.
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Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Proteínas de Unión al Calcio , Colangiocarcinoma , Inmunohistoquímica , Osteopontina , Humanos , Colangiocarcinoma/patología , Colangiocarcinoma/clasificación , Colangiocarcinoma/mortalidad , Colangiocarcinoma/química , Colangiocarcinoma/diagnóstico , Osteopontina/análisis , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/clasificación , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/química , Neoplasias de los Conductos Biliares/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores de Tumor/análisis , Anciano , Estudios Retrospectivos , Proteínas de Unión al Calcio/análisis , Adulto , Anciano de 80 o más Años , Proteínas de Neoplasias/análisis , Valor Predictivo de las Pruebas , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/químicaRESUMEN
BACKGROUND: Non-Helicobacter pylori Helicobacter (NHPH) is rarely detected in duodenal mucosa due to its preference for slightly acidic environments. Here, we report four cases of NHPH-infected gastritis with duodenal spiral bacilli, potentially NHPH, indicating the possibility of duodenal mucosal infection. CASE PRESENTATION: In every case, gastric mucosa showed endoscopic findings characteristic of NHPH-infected gastritis, and a mucosal biopsy was taken from the duodenal bulb; spiral bacilli were identified under microscopy using Giemsa staining. Case 1, a 46-year-old man, had diffuse spotty redness, mucosal edema, and multiple tiny erosions in the duodenal bulb, along with larger erosions in the second portion of the duodenum upon endoscopic examination. Histopathologically, moderate infiltration of mononuclear cells and neutrophils in the lamina propria and gastric epithelial metaplasia were observed. Case 2, a 54-year-old man, showed an elevated lesion, 1 cm in diameter, with multiple red spots and a few tiny erosions in the duodenal bulb. Histopathologically, mild inflammatory cell infiltration and gastric epithelial metaplasia were observed. In Case 3, a 52-year-old man, endoscopy revealed a flat elevated lesion, 7 mm in diameter, with multiple red spots and a few tiny erosions in the anterior wall of the duodenal bulb. Histopathologically, we observed moderate inflammatory cell infiltration in the gastric antrum and gastric epithelial metaplasia in the duodenal bulb. Case 4, a 40-year-old man, showed mild spotty redness in the duodenal bulb. Histopathologically, mild mononucleocyte infiltration and gastric epithelial metaplasia were observed. A single spiral bacillus was observed in Case 4 by microscopy. In all but Case 2, Helicobacter suis was identified in the gastric juice by polymerase chain reaction analysis. CONCLUSIONS: Spiral bacilli resembling NHPH may infect the duodenal mucosa, particularly the bulb, causing inflammation. Gastric contents entering the duodenum may reduce the intraduodenal pH, promoting NHPH survival and proliferation.
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Duodeno , Gastritis , Infecciones por Helicobacter , Humanos , Masculino , Persona de Mediana Edad , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/complicaciones , Duodeno/patología , Duodeno/microbiología , Biopsia , Helicobacter/aislamiento & purificación , Helicobacter/fisiología , Helicobacter/genética , Adulto , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Mucosa Gástrica/microbiología , Mucosa Gástrica/patologíaRESUMEN
BACKGROUND: The characteristic endoscopic findings of non-Helicobacter pylori Helicobacter (NHPH) gastritis, including white marbled appearance and crack-like mucosa, have been reported. However, these findings can also manifest in H. pylori (HP)-infected gastritis. This study compared NHPH gastritis and mild atrophic HP gastritis to identify features that may enhance NHPH diagnosis. MATERIALS AND METHODS: A total of 2087 patients underwent upper gastrointestinal endoscopy and were histologically evaluated by multiple gastric mucosal biopsies according to the updated Sydney System (USS) at Shinshu University Hospital between 2005 and 2023. Among them, nine patients were classified into the NHPH group and 134 patients with HP infection and mild atrophy were classified into the HP group for retrospective comparisons of endoscopic findings and clinicopathological characteristics. RESULTS: All nine patients in the NHPH group (eight males [89%], median ± standard deviation [SD] age: 49 ± 13.0 years) were infected with H. suis. The 134 patients in the HP group contained 70 men (52%) and had a median ± SD age of 35 ± 19.9 years. Endoscopic findings were statistically comparable for white marbled appearance (three patients [33%] in the NHPH group and 37 patients [31%] in the HP group) and crack-like mucosa (three patients [33%] and 27 patients [20%], respectively). Diffuse redness was significantly less frequent in the NHPH group (one patient [14%] vs. 97 patients [72%], p < 0.001). White marbled appearance or crack-like mucosa without diffuse redness was significantly more common in the NHPH group (56% vs. 13%, p = 0.004), with a sensitivity and specificity of 56% and 87%, respectively. Mean USS neutrophil infiltration and Helicobacter density scores were significantly higher in the HP group (both p < 0.01), which might have influenced the endoscopic findings of diffuse redness. CONCLUSIONS: When endoscopic findings of white marbled appearance or cracked-like mucosa are present, evaluation for diffuse redness may contribute to a more accurate diagnosis of NHPH gastritis.
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Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Helicobacter , Masculino , Humanos , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/patología , Estudios Retrospectivos , Gastritis/diagnóstico , Gastritis/patología , Mucosa Gástrica/patologíaRESUMEN
Background. Tumor budding is a poor prognostic factor in colorectal adenocarcinoma, but the underlying mechanism remains unclear. Interleukin-6 (IL6) is one of the main cytokines produced by cancer-associated fibroblasts. IL6 is linked with cancer progression and poor prognosis by activating cancer cells and modifying the cancer microenvironment. However, little is known about the expression of IL6 in tumor budding and its association with tumor budding in colorectal adenocarcinoma. Methods. The clinicopathological and prognostic significance of IL6 in tumor budding was examined using a tissue microarray consisting of 36 patient samples of tumor budding in colorectal adenocarcinoma. IL6 mRNA was detected by RNAscope. Patients were stratified into negative and positive IL6 expression groups. Results. IL6 expression was overwhelmingly observed in cancer stroma but was negligible in cancer cells. Tumor budding grade was higher in the IL6-positive group in cancer stroma than in the IL6-negative group (P = .0161), while the IL6-positive group significantly exhibited the epithelial-mesenchymal transition phenotype compared with the IL6-negative group in cancer stroma (P = .0301). There was no significant difference in overall survival between colorectal adenocarcinoma patients in the IL6-positive and -negative groups in cancer stroma. Conclusion. Tumor budding may be affected by IL6 expression, and IL6 expression in cancer stroma at tumor budding may be an important prognostic marker.
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Adenocarcinoma , Neoplasias Colorrectales , Humanos , Adenocarcinoma/diagnóstico , Transición Epitelial-Mesenquimal , Interleucina-6 , Fenotipo , Microambiente TumoralRESUMEN
BACKGROUND: The frequency of gallbladder carcinoma is high in pancreaticobiliary maljunction (PBM), and the mechanism of carcinogenesis is not well understood. METHODS: The expression of γH2AX, the most sensitive marker for detecting DNA damage, was analyzed using immunohistochemistry in patients with PBM, in which the gallbladder and bile duct were simultaneously resected. Gallbladder and bile ducts were evaluated in non-neoplastic regions in 13 cases of PBM without cancer in the gallbladder and bile ducts. RESULTS: The median frequencies of γH2AX expression in the bile duct and gallbladder within the same case were 5.9% (range 1.7-12.05%) and 9.9% (range 2.8-25%), respectively, and were significantly higher in the gallbladder mucosa (P < 0.0004). γH2AX expression strongly correlated in the bile duct and gallbladder (r = 0.9436, P < 0.0001). PBM caused marked mucosal damage to the gallbladder. CONCLUSIONS: Mucosal damage may be involved in carcinogenesis, which may be useful for predicting malignant transformation.
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Neoplasias de la Vesícula Biliar , Mala Unión Pancreaticobiliar , Humanos , Mala Unión Pancreaticobiliar/metabolismo , Conductos Pancreáticos/patología , Conductos Biliares , Neoplasias de la Vesícula Biliar/patología , Membrana Mucosa/patología , Carcinogénesis/metabolismoRESUMEN
BACKGROUND AND AIMS: Gastric cancer (GC) is associated with chronic gastritis. To evaluate the risk, the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) system was constructed and showed a higher GC risk in stage III or IV patients, determined by the degree of intestinal metaplasia (IM). Although the OLGIM system is useful, evaluating the degree of IM requires substantial experience to produce precise scoring. Whole-slide imaging is becoming routine, but most artificial intelligence (AI) systems in pathology are focused on neoplastic lesions. METHODS: Hematoxylin and eosin-stained slides were scanned. Images were divided into each gastric biopsy tissue sample and labeled with an IM score. IM was scored as follows: 0 (no IM), 1 (mild IM), 2 (moderate IM), and 3 (severe IM). Overall, 5753 images were prepared. A deep convolutional neural network (DCNN) model, ResNet50, was used for classification. RESULTS: ResNet50 classified images with and without IM with a sensitivity of 97.7% and specificity of 94.6%. IM scores 2 and 3, involved as criteria of stage III or IV in the OLGIM system, were classified by ResNet50 in 18%. The respective sensitivity and specificity values of classifying IM between scores 0 and 1 and 2 and 3 were 98.5% and 94.9%, respectively. The IM scores classified by pathologists and the AI system were different in only 438 images (7.6%), and we found that ResNet50 tended to miss small foci of IM but successfully identified minimal IM areas that pathologists missed during the review. CONCLUSIONS: Our findings suggested that this AI system would contribute to evaluating the risk of GC accuracy, reliability, and repeatability with worldwide standardization.
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Aprendizaje Profundo , Infecciones por Helicobacter , Intestinos , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Inteligencia Artificial , Metaplasia , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Reproducibilidad de los Resultados , Factores de Riesgo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Intestinos/patologíaRESUMEN
BACKGROUND/AIMS: This study examined changes in the esophageal-gastric junction and gastric mucosa in young Japanese adults undergoing endoscopy in the last 15 years. MATERIALS AND METHODS: This was a retrospective study of young Japanese adults (aged 19-30 years) who underwent esophagogastrod uodenoscopy between 2006 and 2020. The indications were upper gastrointestinal symptoms and anemia. Changes in the appearance of the esophago-gastric junction (i.e., the Z line and distal esophagitis) and gastric mucosa were examined. Endoscopic Barrett's esophagus was defined using the Japanese criteria. RESULTS: One thousand eight hundred forty-five patients were examined: 848 from 2006 to 2012 [400 males, mean age 26.5 years (range 19-30)] and 997 from 2013 to 2020 [433 males, mean age 26.2 years (range 19-30)]. The proportion showing endoscopic Barrett's esophagus and gastric fundic gland polyps increased significantly between the 2 periods (12.5% vs. 22.4%, P < .001; 3.4% vs. 7.2%, P < .001) with a significant correlation between the prevalence trends for endoscopic Barrett's esophagus and gastric fundic gland polyps (r = 0.789, P = .0008). Pathological examination showed that the prevalence of traditional fundic gland polyps unrelated to the use of proton pump inhibitors significantly increased from 40% (4/10) to 81% (25/31) between the 2 periods (P = .04). CONCLUSION: The prevalence of both endoscopic Barrett's esophagus and gastric fundic gland polyps among young Japanese adults significantly increased in the last 15 years. The trend in endoscopic Barrett's esophagus was significantly correlated with that of nonproton pump inhibitor-related gastric fundic gland polyps.
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Esófago de Barrett , Adulto , Humanos , Masculino , Adulto Joven , Esófago de Barrett/patología , Pueblos del Este de Asia , Endoscopía Gastrointestinal , Estudios Retrospectivos , Estómago/patología , FemeninoRESUMEN
Helicobacter suis, hosted by hogs, is the most prevalent gastric non-Helicobacter pylori Helicobacter species found in humans. Recent studies have suggested that H. suis infection has caused many cases of gastric disease, but the transmission route from hogs remains unclear. Diagnostic methods based on H. suis urease activity often yield negative results, and there is no reliable method for diagnosing H. suis infection in clinical practice without gastric biopsy specimens. This study presents the world's first use of whole-bacterial cell ELISA to simultaneously assess H. suis and H. pylori infections. The ELISAs showed high accuracy, with an area under the ROC curve of 0.96, 100% sensitivity, 92.6% specificity, 76.9% positive predictive value, and 100% negative predictive value for the H. suis test, and an area under the ROC curve of 0.92, 88.2% sensitivity, 87.5% specificity, 65.2% positive predictive value, and 96.6% negative predictive value for the H. pylori test.
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BACKGROUND: ADP-ribosylation factor-like protein 4 C (ARL4C) is a member of the ARF small GTP-binding protein subfamily. The ARL4C gene is highly expressed in colorectal cancer (CRC). ARL4C protein promotes cell motility, invasion, and proliferation. METHODS: We investigated the characteristics of ARL4C by comparing its expression at the invasion front and relationships with clinicopathological data using RNAscope, a highly sensitive RNA in situ method. RESULTS: In all cases, ARL4C expression was observed in cancer stromal cells and cancer cells. ARL4C expression in cancer cells was localized at the invasion front. In cancer stromal cells, ARL4C expression was significantly stronger in cases with high-grade tumor budding than in cases with low-grade tumor budding (P = 0.0002). Additionally, ARL4C expression was significantly increased in patients with high histological grade compared with those with low histological grade (P = 0.0227). Furthermore, ARL4C expression was significantly stronger in lesions with the epithelial-to-mesenchymal transition (EMT) phenotype compared with the non-EMT phenotype (P = 0.0289). In CRC cells, ARL4C expression was significantly stronger in cells that had the EMT phenotype compared with those with a non-EMT phenotype (P = 0.0366). ARL4C expression was significantly higher in cancer stromal cells than in CRC cells (P < 0.0001). CONCLUSION: Our analysis reinforces the possibility that ARL4C expression worsens the prognosis of patients with CRC. Further elucidation of the function of ARL4C is desired.
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Transformación Celular Neoplásica , Neoplasias Colorrectales , Humanos , Pronóstico , Fenotipo , Transformación Celular Neoplásica/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Proliferación Celular/genética , Línea Celular Tumoral , Factores de Ribosilacion-ADP/genética , Factores de Ribosilacion-ADP/metabolismoAsunto(s)
Neoplasias de los Conductos Biliares , Conductos Biliares Extrahepáticos , Tumores Neuroendocrinos , Humanos , Estudios de Seguimiento , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Conductos Biliares Extrahepáticos/cirugía , Conductos Biliares Extrahepáticos/patología , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patologíaRESUMEN
IgG4-positive plasma cells are reportedly increased in the tumour microenvironment, and a high number of these cells in tumours is a poor prognostic factor in several cancers. However, there are no reported analyses of IgG4 expression in intrahepatic cholangiocarcinoma (ICC). This study aimed to analyse the correlations between prognosis-related clinicopathological features of patients with ICC and IgG4 expression. We identified 37 ICC patients who underwent surgical resection between January 2010 and December 2020. The number of IgG-positive and IgG4-positive plasma cells in the tumour, invasion front, and stroma near the tumour was analysed by immunostaining. Furthermore, we examined the association of prognosis-related clinicopathological data with the number of IgG4-positive plasma cells and IgG4/IgG ratio in ICC patients. The IgG4-positive plasma cell percentages for the intra-tumour area, invasion front, and non-cancerous area (NCA) near the tumour were 91.9%, 56.8%, and 81.1%, respectively. IgG-positive plasma cells were observed in each region for all cases, except for NCA tissue in one case. A high IgG4 expression level and IgG4/IgG ratio in the invasion front were significantly associated with poor overall survival (OS) (log-rank test p=0.0438 and p=0.0338, respectively). Multivariate analysis for OS revealed that high IgG4 expression (p=0.0140), lymph node metastasis (p=0.0205), and positive surgical margin (p=0.0009) or a high IgG4/IgG ratio (p=0.0051), lymph node metastasis (p=0.0280), and positive surgical margin (p=0.0009) were independent poor prognostic factors. In conclusion, a high IgG4 expression level and IgG4/IgG ratio in the invasion front are independent poor prognostic factors for ICC. Targeted therapy for IgG4 may improve the prognosis for patients with ICC.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Metástasis Linfática/patología , Inmunoglobulina G , Márgenes de Escisión , Pronóstico , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/cirugía , Estudios Retrospectivos , Microambiente TumoralRESUMEN
BACKGROUND: Leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) promotes carcinogenesis and progression in some cancer types. However, there are few reports of LGR6 expression in esophageal squamous cell carcinoma (ESCC). LGR6 expression and clinicopathological features in ESCC were investigated by RNAscope, a highly sensitive RNA in situ hybridization method. METHODS: Appropriate tumors were selected from 41 cases of ESCC from which tissue microarrays were generated, and LGR6 expression was identified by RNAscope. RESULTS: Thirty-seven patients had LGR6 expression. High LGR6 expression was observed in 17 cases and low LGR6 expression in 24 cases. LGR6 expression was significantly higher in high histological grade ESCC than in low histological grade ESCC (P = 0.0023). ESCC patients who received neoadjuvant chemotherapy had significantly higher LGR6 expression than those without neoadjuvant chemotherapy (P = 0.0109). Furthermore, high LGR6 expression showed a poorer prognosis than low LGR6 expression (log-rank test, P = 0.0365). CONCLUSIONS: LGR6 may be a prognostic factor and a potential new therapeutic target in ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas/patología , Pronóstico , Biomarcadores de Tumor/genética , Receptores Acoplados a Proteínas GRESUMEN
BACKGROUND: Primary eosinophilic gastrointestinal disorders (EGIDs) constitute chronic allergic inflammation. The number of eosinophils is one of the diagnostic criteria; more than 20 eosinophils per high-power field (HPF) in the gastrointestinal (GI) tract are considered abnormal in Japan. However, the quantity of eosinophils considered normal varies according to anatomical location and geographical region; such values have not been reported in Japanese pediatric patients, nor have the numbers of lymphocytes in the normal pediatric stomach. To establish a reference for defining diagnostic criteria for EGIDs, we evaluated the number of eosinophils in the normal Japanese pediatric GI tract. METHODS: We examined 131 biopsy cases without significant clinical history, endoscopic abnormality, or histological abnormality. Immunohistochemical analysis of CD3 and CD20 was performed. RESULTS: The mean eosinophil density was highest in the cecum (49.5 ± 22.4 per HPF). Counts of more than 20 eosinophils per HPF were observed in the duodenum [bulb (20.0 ± 9.6) and second portion (30.0 ± 15.8)], terminal ileum (38.3 ± 22.7), cecum (49.5 ± 22.4), ascending colon (42.3 ± 25.3), transverse colon (29.4 ± 17.0), and descending colon (32.2 ± 17.9). Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum; a count of fewer than one eosinophil per HPF was observed in the esophagus. More than 100 CD3-positive T cells per HPF were observed in the stomach. CONCLUSIONS: The mean numbers of eosinophils in the bowel were greater than 20 per HPF. For Japanese pediatrics, the current threshold eosinophil count should be revised.
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Eosinofilia , Eosinófilos , Humanos , Niño , Eosinófilos/patología , Pueblos del Este de Asia , Tracto Gastrointestinal/patología , Eosinofilia/diagnóstico , Biopsia , Linfocitos/patologíaRESUMEN
BACKGROUND: Tumor budding (TB) is an important prognostic factor in colorectal carcinoma (CRC). Osteopontin (OPN) functions in various processes such as immune response, migration and invasion, angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis. However, the involvement of OPN and CD44v6, which is a receptor for OPN, in TB has not been clarified. Therefore, we examined the relationship of OPN with TB in CRC and compared the clinicopathological features. METHODS: We investigated the expression of OPN and CD44v6 in 83 cases of CRC by immunostaining and analyzed the clinicopathological features. RESULTS: OPN expression was observed mostly in the cytoplasm of stromal cells such as macrophages and fibroblasts, and rarely in cancer cells. There was a significant correlation between OPN positivity and the degree of differentiation at the invasive front and TB grade. CD44v6 was positive in cancer cells in 72 cases (86.7 %) and negative in 11 cases (13.3 %). A statistically significant effect on overall survival (OS) was identified between the OPN-positive group [median OS: 1586 (range, 30-2749) days] and the OPN-negative group [median OS: 1901 (range, 8-2665) days] (log-rank test, p = 0.011). CONCLUSIONS: OPN analysis in CRC stromal cells may have prognostic implications.