RESUMEN
This study showcases a novel AI-driven approach to accurately differentiate between stage one and stage two gastric carcinoma based on pathology slide analysis. Gastric carcinoma, a significant contributor to cancer-related mortality globally, necessitates precise staging for optimal treatment planning and patient management. Leveraging a comprehensive dataset of 3540 high-resolution pathology images sourced from Kaggle.com, comprising an equal distribution of stage one and stage two tumors, the developed AI model demonstrates remarkable performance in tumor staging. Through the application of state-of-the-art deep learning techniques on Google's Collaboration platform, the model achieves outstanding accuracy and precision rates of 100%, accompanied by notable sensitivity (97.09%), specificity (100%), and F1-score (98.31%). Additionally, the model exhibits an impressive area under the receiver operating characteristic curve (AUC) of 0.999, indicating superior discriminatory power and robustness. By providing clinicians with an efficient and reliable tool for gastric carcinoma staging, this AI-driven approach has the potential to significantly enhance diagnostic accuracy, inform treatment decisions, and ultimately improve patient outcomes in the management of gastric carcinoma. This research contributes to the ongoing advancement of cancer diagnosis and underscores the transformative potential of artificial intelligence in clinical practice.
RESUMEN
OBJECTIVES: The range of histopathologic features of gastric syphilis is not well described. Here we describe the clinicopathologic findings of eight patients with syphilitic gastritis. METHODS: A search of our Pathology Data System (2003-2022) and multiple other institutions identified eight patients with syphilitic gastritis. Clinical information, pathology reports, and available slides were reviewed. RESULTS: Lesions predominated in middle-aged adults (mean age, 47.2 years; range, 23-61 years) with a propensity for men (nâ =â 7). Three patients had a documented history of human immunodeficiency virus. Clinical presentations included weight loss, abdominal pain, hematochezia, fever, dyspepsia, nausea and vomiting, hematemesis, anemia, and early satiety. Endoscopic findings included ulcerations, erosions, abnormal mucosa, and nodularity. All specimens shared an active chronic gastritis pattern with intense lymphohistiocytic infiltrates, variable plasma cells, and gland loss. Prominent lymphoid aggregates were seen in four specimens. The diagnosis was confirmed either by immunostain for Treponema pallidum (n = 7) or by direct immunofluorescence staining and real-time polymerase chain reaction (n = 1). All patients with available follow-up data showed resolution of symptoms after antibiotic therapy (n = 4). CONCLUSIONS: Recognition of the histologic pattern of syphilitic gastritis facilitates timely treatment, prevents further transmission, and avoids unnecessarily aggressive treatment.
Asunto(s)
Gastritis , Sífilis , Adulto , Masculino , Persona de Mediana Edad , Humanos , Sífilis/diagnóstico , Gastritis/diagnóstico , Gastritis/patología , Treponema pallidum , AntibacterianosRESUMEN
Besides Helicobacter pylori, a Gram-negative bacterium that may cause gastric disorders in humans, non-Helicobacter pylori helicobacters (NHPH) may also colonize the stomach of humans and animals. In pigs, H. suis can induce gastritis and may play a role in gastric ulcer disease, possibly in association with Fusobacterium gastrosuis. In the present study, gastric samples from 71 slaughtered pigs and 14 hunted free range wild boars were tested for the presence of DNA of F. gastrosuis and gastric Helicobacter species associated with pigs, dogs cats and humans, using species-specific PCR assays, followed by sequencing of the amplicon. These gastric samples were also histopathologically evaluated. Almost all the pigs presented gastritis (95.8%). Helicobacter spp. were detected in 78.9% and F. gastrosuis in 35.2% of the animals. H. suis was the most frequently identified Helicobacter species (57.7% of the animals), followed by a H. pylori-like species (50.7%) and less often H. salomonis and H. felis (each in 2.8% of the animals). H. suis was most often detected in the glandular (distal) part of the stomach (pars oesophagea 9.9%, oxyntic mucosa 35.2%, antral mucosa 40.8%), while the H. pylori-like species was mainly found in the non-glandular (proximal) part of the stomach (pars oesophagea 39.4%, oxyntic mucosa 14.1%, antral mucosa 4.2%). The great majority of wild boars were also affected with gastritis (71.4%) and Helicobacter spp. and F. gastrosuis were detected in 64.3% and 42.9% of the animals, respectively. H. bizzozeronii and H. salomonis were the most frequently detected Helicobacter species, while a H. pylori-like species and H. suis were only occasionally identified. These findings suggest that these microorganisms can colonize the stomach of both porcine species and may be associated with gastric pathology. This should, however, be confirmed through bacterial isolation. This is the first description of the presence of F. gastrosuis DNA in the stomach of wild boars and a H. pylori-like species in the pars oesophagea of the porcine stomach.
Asunto(s)
Enfermedades de los Perros , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Helicobacter , Enfermedades de los Porcinos , Animales , Enfermedades de los Perros/microbiología , Perros , Fusobacterium , Mucosa Gástrica , Gastritis/microbiología , Gastritis/veterinaria , Helicobacter/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/veterinaria , Helicobacter pylori/genética , Humanos , Sus scrofa , Porcinos , Enfermedades de los Porcinos/microbiologíaRESUMEN
The Zuojin Pill consists of Coptidis Rhizoma (CR) and Euodiae Fructus (EF). It has been a classic prescription for the treatment of gastrointestinal diseases in China since ancient times. Alkaloids are considered to be its main pharmacologically active substances. The authors of the present study investigated the feasibility of preparing high purity total alkaloids (TAs) from CR and EF extracts separately and evaluated the effect for the treatment of bile reflux gastritis (BRG). Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. were used in the study. An optimized method for the enrichment and purification of TAs with macroporous resin was established. Furthermore, qualitative analysis by using ultra-high performance liquid chromatography coupled with electrospray ionization and quadrupole-time of flight mass spectrometry (UHPLC-ESI-QTOF-MS) was explored to identify the components of purified TAs. Thirty-one compounds, thirty alkaloids and one phenolic compound, were identified or tentatively assigned by comparison with reference standards or literature data. A method of ultra-high performance liquid chromatography coupled with diode array detector (UHPLC-DAD) for quantitative analysis was also developed. The contents of nine alkaloids were determined. Moreover, a rat model of BRG was used to investigate the therapeutic effect of the combination of purified TAs from CR and EF. Gastric pathologic examination suggested that the alkaloids' combination could markedly attenuate the pathological changes of gastric mucosa.
Asunto(s)
Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Reflujo Biliar/tratamiento farmacológico , Coptis/química , Evodia/química , Gastritis/tratamiento farmacológico , Resinas de Plantas/química , Alcaloides/química , Animales , Reflujo Biliar/metabolismo , Reflujo Biliar/patología , Gastritis/metabolismo , Gastritis/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Gastrointestinal (GI) tract perforation is a surgical emergency. The epidemiology and etiology of perforation vary considerably across geography. Lower GI tract perforations in the elderly predominate in the West compared to upper GI perforations in the younger population in the tropics. Fungi and viruses have been reported to cause GI perforations in immuno-compromised individuals but it is rare in immuno-competent individuals. We report a very rare case of gastric perforation secondary to fungal gastritis in an immuno-competent 35-year-old female who presented with features of peritonitis. At emergency laparotomy, gastric perforation was found which was repaired by the Cellan-Jones method. Perforation edge biopsy findings were consistent with fungal etiology. She responded well to Antifungal therapy. We conclude that fungal etiology can be considered in patients with gastric perforation without any history of peptic ulcer disease (PUD) or use of oral non-steroidal anti-inflammatory drugs.
RESUMEN
BACKGROUND: The purpose of this study was to assess the prevalence of Helicobacter pylori infection in Algerian patients with peptic disorders and evaluate the impact of different epidemiological factors (age, sex, sampling site, presence or absence of H. pylori, and type of pathology related to this bacterium). METHODS: We undertook a retrospective and descriptive study on a series of 735 symptomatic patients identified in the laboratory of pathological anatomy at Hassani Abdelkader University Hospital Center of Sidi Bel Abbes, Algeria, over a period of 16 years from January 2002 to December 2017. All patients had benefited from a high gastroscopic fibroscopy and the diagnosis was made by histological examination (hematoxylin-eosin staining). The epidemiological factors, as well as the main gastric diseases related to this bacterium, were studied. RESULTS: The prevalence of H. pylori infection was 66.12%. The infection was more important in the age group 60-69 years (71.43%). The prevalence of H. pylori infection was statistically higher in women than in men (69.3% vs. 60.7%, p < 0.01).The antral region was most colonized by H. pylori (71.73%). In addition, the infection was associated mainly with atrophic gastritis (69.65%). CONCLUSION: In this context, the identification of epidemiological data would be of great value in guiding strategies to control the spread of this bacterium.
Asunto(s)
Enfermedades del Sistema Digestivo , Infecciones por Helicobacter , Helicobacter pylori , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Argelia/epidemiología , Niño , Preescolar , Enfermedades del Sistema Digestivo/epidemiología , Enfermedades del Sistema Digestivo/microbiología , Femenino , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/aislamiento & purificación , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Bariatric surgical procedures are employed when there is a failure of lifestyle modification in arresting obesity. Laparoscopic sleeve gastrectomy (LSG) is quickly becoming the bariatric surgical procedure of choice. LSG results in a gastric remnant that is subject to pathological examination. The objective of this paper is to review the literature in regard to histological findings identified in gastric remnants post-LSG and identify the most pertinent histological findings. MATERIALS AND METHODS: A literature search was performed to identify relevant case series. Data gathered from relevant case series then underwent statistical analysis. RESULTS: The most common histological findings in an LSG specimen were clinically indolent findings such as no pathological abnormalities identified followed by non-specific gastritis. A minority of cases demonstrated clinically actionable findings for which Helicobacter pylori represented the majority of these findings. CONCLUSION: There is a broad spectrum of pathological findings in LSG specimens, ranging from clinically indolent to clinically actionable. The most common histological findings are clinically indolent and only a small portion are of clinical significance and, hence, actionable.
Asunto(s)
Obesidad Mórbida/patología , Obesidad Mórbida/cirugía , Estómago/patología , Adulto , Cirugía Bariátrica , Femenino , Gastrectomía , Humanos , Laparoscopía , Masculino , Persona de Mediana EdadAsunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Gastritis/inducido químicamente , Neutrófilos/metabolismo , Nivolumab/efectos adversos , Biomarcadores/metabolismo , Femenino , Gastritis/diagnóstico , Gastritis/inmunología , Gastritis/patología , Gastroscopía , Humanos , Persona de Mediana EdadRESUMEN
AIM: Tissue microarray (TMA) is a powerful and effective tool for in situ tissue analysis. However, manual TMA construction methods showed varied qualities. This study aimed to raise a standardised TMA preparation technique that can be easily operated and is economical. METHODS: A sampling needle was used to punch the tissue rods from the donor block and holes in the recipient block. To indicate the dots' positions and ensure vertical punching, a novel auxiliary device made using commercial three-dimensional printing technology was attached. The TMA block was made up of tissue rods and a recipient block. RESULTS: A 77-rod (7×11) TMA block was constructed. The rows and columns were fixed in straight lines. There was no specimen loss during the process of embedding. CONCLUSIONS: An alternative method for the construction of TMA blocks that met the basic requirement of many laboratories and can be effortlessly performed was presented.
Asunto(s)
Neoplasias Colorrectales/diagnóstico , Neoplasias Gástricas/diagnóstico , Análisis de Matrices Tisulares/métodos , Costos y Análisis de Costo , Humanos , Inmunohistoquímica , Agujas , Adhesión en Parafina , Manejo de Especímenes , Análisis de Matrices Tisulares/economía , Análisis de Matrices Tisulares/instrumentaciónRESUMEN
AIM: The aim of this study was to evaluate the risk factors for proximal resection margin involvement and its impact on survival outcome in patients with proximal gastric cancer. METHODS: A total of 488 patients who underwent potentially curative resection for proximal gastric cancer were retrospectively reviewed. Clinicopathological characteristics and survival differences between patients with positive and negative resection margins were compared and prognostic factors were determined by Cox multivariate analysis. RESULTS: In this study, 7.6% (37/488) of patients with proximal gastric cancer had a positive proximal resection margin after postoperative histopathological examination. Positive resection margins were significantly associated with advanced tumour stage and more aggressive biological features including larger tumour size, serosal invasion and lymphovascular invasion. Serosal invasion (OR 4.543, 95% CI 2.201 to 9.380, p<0.001) and lymphovascular invasion (OR 2.279, 95% CI 1.129 to 4.600, p<0.05) were independent risk factors for positive proximal resection margins. In terms of survival outcome, positive resection margins had an adverse impact on the prognosis of patients with proximal gastric cancer (median DFS: 20.7 vs 30.2 months, p<0.001). The multivariate analysis indicated that positive resection margins (HR 1.494, 95% CI 1.042 to 2.142, p=0.029), T stage (T3-T4, HR 2.264, 95% CI 1.484 to 3.454, p<0.001) and N stage (N1-N2 stage, HR 1.696, 95% CI 1.279 to 2.248, p<0.001; N3 stage, HR 2.691, 95% CI 1.967 to 3.681, p<0.001) were independent prognostic factors for patients with proximal gastric cancer. CONCLUSION: Proximal resection margin involvement was an indicator of more aggressive tumours and an independent prognostic factor for patients with proximal gastric cancer. Aggressive efforts should be made to achieve a negative resection margin if gastric cancer was deemed to be potentially resectable.
Asunto(s)
Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis en-Y de Roux/métodos , Anastomosis en-Y de Roux/mortalidad , China/epidemiología , Femenino , Gastrectomía/mortalidad , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The E3 ubiquitin ligase ring finger protein 43 (RNF43) is frequently mutated in gastric tumors and loss of RNF43 expression was suggested to be one of the key events during the transition from adenoma to gastric carcinoma. Functional studies on RNF43 have shown that it acts as a tumor suppressor by negatively regulating Wnt signaling. Interestingly, we observed that RNF43H292R/H295R mice bearing two point mutations in the ring domain displayed thickening of the mucosa at early age but did not develop neoplasia. In this study, we infected these mice for 6 months with Helicobacter pylori, which has been described as one of the major risk factors for gastric cancer. Mice bearing mutant RNF43H292R/H295R showed higher gastritis scores upon H. pylori infection compared to wild-type mice, accompanied by increased lymphocyte infiltration and Ifng levels. Furthermore, infected Rnf43 mutant mice developed atrophy, hyperplasia and MUC2 expressing metaplasia and displayed higher levels of the gastric stem cell marker CD44 and canonical NF-κB signaling. In summary, our results show that transactivating mutations in the tumor suppressor Rnf43 can worsen H. pylori induced pathology.
RESUMEN
The probiotic Lactobacillus rhamnosus GG (LGG) can play a role in establishing a harmless relationship with Helicobacter pylori and reduce gastric pathology in East African populations. H. pylori has the ability to inhabit the surface of the mucous layer of the human stomach and duodenum. In the developing world, an estimated 51% of the population is carrier of H. pylori, while in some Western countries these numbers dropped below 20%, which is probably associated with improved sanitation and smaller family sizes. Colonization by H. pylori can be followed by inflammation of the gastric mucus layer, and is a risk factor in the development of atrophic gastritis, peptic ulcers and gastric cancer. Notwithstanding the higher prevalence of H. pylori carriers in developing countries, no equal overall increase in gastric pathology is found. This has been attributed to a less pro-inflammatory immune response to H. pylori in African compared to Caucasian populations. In addition, a relatively low exposure to other risk factors in certain African populations may play a role, including the use of non-steroidal anti-inflammatory drugs, smoking, and diets without certain protective factors. A novel approach to the reduction of H. pylori associated gastric pathology is found in the administration of the probiotic bacterium Lactobacillus rhamnosus yoba 2012 (LRY), the generic variant of LGG. This gastro-intestinal isolate inhibits H. pylori by competition for substrate and binding sites as well as production of antimicrobial compounds such as lactic acid. In addition, it attenuates the host's H. pylori-induced apoptosis and inflammation responses and stimulates angiogenesis in the gastric and duodenal epithelium. The probiotic LRY is not able to eradicate H. pylori completely, but its co-supplementation in antibiotic eradication therapy has been shown to relieve side effects of this therapy. In Uganda, unlike other African countries, gastric pathology is relatively common, presumably resulting from the lack of dietary protective factors in the traditional diet. Supplementation with LRY through local production of probiotic yogurt, could be a solution to establish a harmless relationship with H. pylori and reduce gastric pathology and subsequent eradication therapy treatment.
RESUMEN
AIMS: α-Fetoprotein (AFP)-producing gastric carcinoma (AFPGC) is one of the most aggressive GC subtypes. Frequent expression of human epidermal growth factor receptor 2 (HER2) has previously been reported in hepatoid adenocarcinoma (HAC), a major histological subtype of AFPGC originating from common-type GC (CGC). However, HER2 expression levels in other AFPGC histological subtypes are unknown. In this study, we analysed HER2 expression in GCs with primitive phenotypes in addition to HAC. METHODS: HER2 expression was evaluated in representative complete sections from 16 HACs, 19 GCs with enteroblastic differentiation (GCEDs) and 334 GCs of other histological types as controls. The Ruschoff/Hofmann method was used to score HER2 immunohistochemistry. Samples with a HER2 score of 2+ were further assessed using fluorescence in situ hybridisation. Oncofetal protein (OFP) expression in HAC and GCED was tested via immunohistochemical staining for AFP, glypican 3 and Sal-like protein 4. RESULTS: Thirty of 35 HAC/GCED cases comprised more than two histological patterns. The HER2 positivity rates of each histological component in the HACs/GCEDs were 25.0% for HAC (n=16), 34.6% for GCED (n=26) and 48.1% for CGC (n=27), which were higher than those of the control group (13.8%). Additionally, the majority of CGC components in HACs/GCEDs were positive for OFP (88.9%). CONCLUSIONS: HER2 is frequently overexpressed not only in HAC but also in GCED and CGC components of HACs/GCEDs, which suggests an association between HER2 and OFP expression. Moreover, our findings suggest that HER2-positive CGC has a higher risk of progression to HAC/GCED than HER2-negative GC.
Asunto(s)
Adenocarcinoma/química , Biomarcadores de Tumor/análisis , Diferenciación Celular , Receptor ErbB-2/análisis , Neoplasias Gástricas/química , Adenocarcinoma/clasificación , Adenocarcinoma/genética , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Diferenciación Celular/genética , Femenino , Glipicanos/análisis , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Fenotipo , Receptor ErbB-2/genética , Estudios Retrospectivos , Neoplasias Gástricas/clasificación , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Factores de Transcripción/análisis , Regulación hacia Arriba , alfa-Fetoproteínas/análisisAsunto(s)
Hemorragia Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/diagnóstico , Enfermedades del Íleon/diagnóstico , Inmunoglobulina M/sangre , Paraproteinemias/complicaciones , Macroglobulinemia de Waldenström/diagnóstico , Antineoplásicos/uso terapéutico , Biopsia , Quimioterapia Adyuvante , Diagnóstico Diferencial , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/complicaciones , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/patología , Humanos , Enfermedades del Íleon/complicaciones , Enfermedades del Íleon/tratamiento farmacológico , Enfermedades del Íleon/patología , Mesilato de Imatinib/uso terapéutico , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Paraproteinemias/sangre , Paraproteinemias/patología , Proteínas Proto-Oncogénicas c-kit/análisis , Recurrencia , Resultado del Tratamiento , Macroglobulinemia de Waldenström/complicaciones , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/patologíaRESUMEN
AIMS: Although expressed in tumour cells of various malignancies, cadherin 5 (CDH5), also known as vascular endothelial cadherin, plays an important role in homotypic cell-cell adhesion among epithelial cells. However, the clinical significance of CDH5 expression in gastric cancer has not been sufficiently demonstrated. In this study, CDH5 expression in gastric cancer was evaluated and the correlations between CDH5 expression and the clinicopathological features and outcomes of the disease were examined. METHODS: Differentiated-type gastric adenocarcinomas obtained from 102 patients who underwent gastrectomy were analysed. CDH5 expression was assessed by immunohistochemical staining of the membranes of the cancer cells. RESULTS: High CDH5 expression was significantly associated with the following clinicopathological variables related to tumour progression: depth of invasion (p=0.012), venous invasion (p=0.013), lymphatic invasion (p=0.001), metastatic lymph nodes (p=0.009), pathological stage (p=0.008) and distant metastasis or recurrent disease (p=0.009). Patients with high CDH5 expression had significantly poorer disease-specific survival (p=0.021), although CDH5 was not determined to be an independent prognostic factor by multivariate analysis. CONCLUSIONS: CDH5 may play a key role in the progression or metastasis of differentiated-type gastric cancer and serve as a target for its treatment.
Asunto(s)
Adenocarcinoma/patología , Antígenos CD/biosíntesis , Cadherinas/biosíntesis , Neoplasias Gástricas/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Antígenos CD/análisis , Biomarcadores de Tumor/análisis , Cadherinas/análisis , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidadRESUMEN
AIM: To evaluate possible colon involvement in the 'gastric adenocarcinoma and proximal polyposis of the stomach' (GAPPS) gastrointestinal polyposis syndrome. METHODS: Prospective clinicopathological evaluation of two GAPPS families and expression of nuclear ß-catenin, p53 and Ki67 measured by immunohistochemistry on endoscopic and surgical specimens from patients with GAPPS. RESULTS: Patients with the GAPPS phenotype were more frequently affected by colonic polyps than patients at risk within the same families (p<0.01). Colonic polyps shared immunohistochemical features of fundic gland polyps and gastric cancers including increased expression of nuclear ß-catenin, Ki67 and p53. Both gastric and colonic lesions harboured activating somatic variants of ß-catenin signalling. CONCLUSIONS: Similarities in expression markers in fundic gland and colonic polyps, together with an enrichment of colonic adenomas in family members affected by GAPPS phenotype compared with family members at risk, support mild colonic involvement of this rare cancer syndrome. Colonoscopic screening might be warranted. CLINICAL TRIAL REGISTRATION NUMBER: #09-C-0079; Results.
Asunto(s)
Adenocarcinoma/metabolismo , Pólipos Adenomatosos/metabolismo , Pólipos del Colon/metabolismo , Neoplasias Gástricas/metabolismo , beta Catenina/metabolismo , Adenocarcinoma/patología , Pólipos Adenomatosos/patología , Adulto , Pólipos del Colon/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Estudios Prospectivos , Neoplasias Gástricas/patología , Adulto JovenRESUMEN
AIMS: Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. Here we aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well it predicts gastric pathology. METHODS: Gastric biopsies were donated by 39 patients with H. pylori infection attending for endoscopy at Queen's Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative PCR. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. RESULTS: vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (p<0.02), neutrophil infiltration (p<0.005) and the presence of atrophy (p<0.01). A polymorphism at nucleotide +28 near the base of a potential stem-loop structure within the 5' untranslated region was significantly associated with vacA transcript level and inflammation. CONCLUSIONS: Increased gastric vacA expression during H. pylori infection is associated with inflammation and premalignant pathology. The +28 nucleotide within the vacA 5' stem-loop stratifies disease risk among toxic vacA i1-type strains.
RESUMEN
AIM: To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection. METHODS: Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology. RESULTS: Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively). CONCLUSIONS: H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis.
Asunto(s)
Enfermedades Autoinmunes/patología , Mucosa Gástrica/patología , Gastritis/patología , Infecciones por Helicobacter/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atrofia/sangre , Atrofia/inmunología , Atrofia/patología , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Femenino , Mucosa Gástrica/inmunología , Gastrinas/sangre , Gastritis/sangre , Gastritis/inmunología , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pepsinógeno A/sangre , Estudios Prospectivos , Adulto JovenRESUMEN
Genomically stable gastric cancers (GCs) are enriched for the diffuse phenotype and hotspot mutations of RHOA. Here we aimed to validate the occurrence, phenotype and clinicopathological characteristics of RHOA mutant GCs in an independent Central European GC cohort consisting of 415 patients. The RHOA genotype (exon 2 and 3) was correlated with various genotypic, phenotypic and clinicopathological patient characteristics. Sixteen (3.9%) tumours had a RHOA mutation including four hitherto unreported mutations, that is, p.G17Efs*24, p.V24F, p.T37A and p.L69R. RHOA mutation was more prevalent in women (5.4% vs 2.8%), distal GCs (4.5% vs 2.4%), in poorly differentiated GCs (G3/G4; 4.8% vs 1.1%), T1/T2 tumours (6.2% vs 3.1%) and lacked distant metastases. Nine RHOA mutant GCs had a diffuse, four an intestinal, two an unclassified and one a mixed Laurén phenotype. KRAS and RHOA mutations were mutually exclusive. A single case showed both a RHOA and a PIK3CA mutation. No significant difference was found in the overall survival between RHOA mutant and wildtype GCs. Our study confirms the occurrence and clinicopathological characteristics of RHOA hotspot mutations in an independent patient cohort. However, we found no evidence for a prognostic or growth advantageous effect of RHOA mutations in GC.
Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Mutación , Neoplasias Gástricas/genética , Población Blanca/genética , Proteína de Unión al GTP rhoA/genética , Adenocarcinoma/enzimología , Adenocarcinoma/etnología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Fosfatidilinositol 3-Quinasa Clase I , Análisis Mutacional de ADN , Femenino , Gastrectomía , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Alemania/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Fenotipo , Fosfatidilinositol 3-Quinasas/genética , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas p21(ras)/genética , Reproducibilidad de los Resultados , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/etnología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: p-21 activated kinase (PAK) 4, part of the six PAK families, plays an important role in growth factor signalling, cytoskeletal remodelling, gene transcription, cell proliferation and oncogenic transformation. However, the clinical significance of PAK4 in gastric cancer has yet to be fully elucidated. PAK4 expression was evaluated, and the correlations of PAK4 expression with clinicopathological features and outcomes in gastric cancer were examined. METHODS: Gastric adenocarcinomas obtained from 217 patients who underwent gastrectomy were analysed. PAK4 expression was evaluated using immunohistochemical staining. RESULTS: PAK4 overexpression was found in 95 (43.8%) of 217 tumours . High PAK4 expression was significantly correlated with clinicopathological variables related to tumour progression, including depth of invasion, metastatic lymph nodes, pathological stage, distant metastasis or recurrent disease. High PAK4 expression was significantly associated with poorer disease-specific survival (DSS) (p<0.001) and relapse-free survival (RFS) (p<0.001). On multivariable analysis, PAK4 was an independent prognostic factor for DSS (HR 2.5 (95% CI 1.4 to 4.7), p=0.003) and RFS (HR 2.8 (95% CI 1.4 to 5.6), p=0.004). Even in stage II and III disease, PAK4 was an independent prognostic factor for RFS (HR 2.2 (95% CI 1.1 to 4.5), p=0.029). CONCLUSIONS: PAK4 may become a new prognostic factor in patients with gastric cancer.