OBJECTIVE: Gastric cancer (GC) is one of the most prevalent malignancies worldwide, and early detection is crucial for improving patient survival rates. We aimed to identify immune infiltrating cell-related biomarkers in early gastric cancer (EGC) progression.
METHODS: The GSE55696 and GSE130823 datasets with low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and EGC samples were downloaded from the Gene Expression Omnibus database to perform an observational study. Immune infiltration analysis was performed by single sample gene set enrichment analysis and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data. Weighted gene co-expression network analysis was used to explore the co-expression modules and genes, and further enrichment analysis was performed on these genes. A protein-protein interaction (PPI) network of these genes was constructed to identify biomarkers associated with EGC progression. Screened hub genes were validated by the rank sum test and reverse transcription quantitative polymerase chain reaction.
RESULTS: Immune scores were significantly elevated in EGC samples compared to LGIN and HGIN samples. The green-yellow module exhibited the strongest correlation with both immune score and disease progression. The 87 genes within this module were associated with the chemokine signaling pathways, the PI3K-Akt signaling pathways, leukocyte transendothelial migration, and Ras signaling pathways. Through PPI network analysis, the hub genes identified were protein tyrosine phosphatase receptor-type C (PTPRC), pleckstrin, CD53, CD48, lymphocyte cytosolic protein 1 (LCP1), hematopoietic cell-specific Lyn substrate 1, IKAROS Family Zinc Finger 1, Bruton tyrosine kinase, and Vav guanine nucleotide exchange factor 1. Notably, CD48, LCP1, and PTPRC showed high expression levels in EGC samples, with the remaining hub genes demonstrating a similar expression trend.
CONCLUSIONS: This study identified 9 immune cell-related biomarkers that may be actively involved in the progression of EGC and serve as potential targets for GC diagnosis and treatment.

UNASSIGNED: Early diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for effective treatment and optimal prognosis; however, less study on serum biomarkers for the early ESCC detection has been reported. The aim of this study was to identify and evaluate several serum autoantibody biomarkers in early ESCC.
UNASSIGNED: We initially screened candidate tumor-associated autoantibodies (TAAbs) associated with ESCC by serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (nano-LC-Q-TOF-MS/MS), and the TAAbs were further subjected to analysis by Enzyme-linked immunosorbent assay (ELISA) in a clinical cohort (386 participants, including 161 patients with ESCC, 49 patients with high-grade intraepithelial neoplasia [HGIN] and 176 healthy controls [HC]). Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance.
UNASSIGNED: The serum levels of CETN2 and POFUT1 autoantibodies which were identified by SERPA were statistically different between ESCC or HGIN patients and HC in ELISA analysis with the area under the curve (AUC) values of 0.709 (95%CI: 0.654-0.764) and 0.741 (95%CI: 0.689-0.793), 0.717 (95%CI: 0.634-0.800) and 0.703 (95%CI: 0.627-0.779) for detection of ESCC and HGIN, respectively. Combining these two markers, the AUCs were 0.781 (95%CI: 0.733-0.829), 0.754 (95%CI: 0.694-0.814) and 0.756 (95%CI: 0.686-0.827) when distinguishing ESCC, early ESCC and HGIN from HC, respectively. Meanwhile, the expression of CETN2 and POFUT1 was found to be correlated with ESCC progression.
UNASSIGNED: Our data suggest that CETN2 and POFUT1 autoantibodies have potential diagnostic value for ESCC and HGIN, which may provide novel insights for early ESCC and precancerous lesions detection.

OBJECTIVE: Gastric precancerous conditions such as atrophic gastritis (AG) and intestinal metaplasia (IM) are considered independent risk factors for gastric cancer (GC). The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development. This study investigated the appropriate monitoring interval for AG/IM patients.
METHODS: Totally, 957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study. Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia (HGIN)/GC in AG/IM patients, and to determine an appropriate endoscopic monitoring scheme.
RESULTS: During follow-up, 28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia (LGIN) (0.7%), HGIN (0.9%), and GC (1.3%). Multivariate analysis identified H. pylori infection (P=0.022) and extensive AG/IM lesions (P=0.002) as risk factors for HGIN/GC progression (P=0.025).
CONCLUSIONS: In our study, HGIN/GC was present in 2.2% of AG/IM patients. In AG/IM patients with extensive lesions, a 1-2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Little is known about esophageal high-grade intraepithelial neoplasia dominated by cytological atypia (HGINc). We aimed to elucidate the endoscopic features of HGINc compared with esophageal high-grade intraepithelial neoplasia dominated by architectural atypia (HGINa). All patients pathologically diagnosed as esophageal high-grade intraepithelial neoplasia after endoscopic submucosal dissection at our center between January 2018 and December 2019 were included in this study. According to the pathological diagnosis, the patients were divided into two groups: HGINa group and HGINc group. Basic characteristics and endoscopic information were collected in detail. Data were analyzed statistically. Binary logistic regression was performed and a predictive model for HGINc was established. Then we evaluated its predictive value and built a nomogram for clinical application. A total of 175 patients were included in this study (126 with HGINa and 49 with HGINc). Among 228 lesions found in all patients, there were 148 HGINa and 80 HGINc. The independent relevant factors for HGINc were tobacco and alcohol usage, color, and gross type. To predict risk of HGINc, a three-factor model (TFM) was established with a highest area under curve (AUC) as 0.869 (95% CI, 0.852, 0.939). When the cut-off value was set as 0.3569184, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for HGINc was 81.14%, 88.75%, 77.03%, 67.62%, and 92.68%, respectively. HGINc differs greatly in endoscopic features from HGINa in our study. It\'s important to reduce misdiagnosis that our model was established with good predictive value for clinical application.

Long non-coding (lnc) RNAs in circulating exosomes are a new class of promising cancer biomarkers; however, their expression in exosomes derived from gastric high-grade intraepithelial neoplasia (GHGIN) has not been reported. In the present study, differentially expressed (DE) lncRNAs were analyzed in the peripheral blood collected from 5 patients with GHGIN and 5 healthy donors using high-throughput sequencing. Reverse transcription-quantitative PCR analysis was performed on 6 randomly selected DE lncRNAs to validate the reliability of the sequencing results. The potential roles of the DE lncRNAs in GHGIN were investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses. A total of 25,145 lncRNAs were identified in all the samples and 83 DE lncRNAs were further screened, including 76 upregulated and 7 downregulated DE lncRNAs. GO and KEGG analyses predicted that the DE lncRNAs played notable roles in \'protein/macromolecule glycosylation\', \'regulation of protein ubiquitination\', \'renin-angiotensin system\' and \'MAPK signaling pathways\'. A lncRNA-micro (mi)RNA-mRNA interaction network was constructed and used to perform association analyses. It was found that 83 lncRNAs were abnormally expressed in GHGIN, with some potential functions associated with gastric cancer. Furthermore, the lncRNA-miRNA-mRNA interaction network indicated that 7 DE lncRNAs may play a notable role in the occurrence and development of GHGIN. The results of the present study showed the expression profiles of lncRNAs in human GHGIN, elucidated some of the molecular changes associated with GHGIN and improved the understanding of the molecular mechanisms underlying GHGIN and gastric cancer.

OBJECTIVE: To analyse the current predictive value of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) for clinically significant prostate cancer (csPCa) detection in repeat biopsies.
METHODS: A cohort of 293 men with isolated HGPIN detected in previous biopsies performed without multiparametric magnetic resonance imaging (mpMRI), and who underwent repeat biopsy within 1 to 3 years, was analysed. Pre-repeat biopsy mpMRI and guided biopsies to suspicious lesions (Prostate Imaging - Reporting and Data System [PI-RADS] ≥3) and/or and systematic biopsies were performed. Persistent prostate cancer (PCa) suspicion, defined as sustained serum prostate-specific antigen level >4 ng/mL and/or abnormal digital rectal examination, was present in 248 men (84.6%), and was absent in 45 men (15.4%). A control group of 190 men who had no previous HGPIN, atypical small acinar proliferation or HGPIN with atypia who were scheduled to undergo repeat biopsy due to persistent PCa suspicion were also analysed. csPCa was defined as tumours of Grade Group ≥2.
RESULTS: In the subset of 45 men with isolated HGPIN, in whom PCa suspicion disappeared, only one csPCa (2.2%) and one insignificant PCa (iPCa) were detected. csPCa was detected in 34.7% of men with persistent PCa suspicion and previous HGPIN, and in 28.4% of those without previous HGPIN (P =0.180). iPCa was detected in 12.1% and 6.3%, respectively (P =0.039). Logistic regression analysis showed that the risk of csPCa detection was not predicted by previous HGPIN: odds ratio (OR) 1.369 (95% confidence interval [CI] 0.894-2.095; P =0.149); however, previous HGPIN increased the risk of iPCa detection: OR 2.043 (95% CI 1.016-4.109; P =0.006).
CONCLUSIONS: The risk of csPCa in men with isolated HGPIN, in whom PCa suspicion disappears, is extremely low. Moreover, in those men in whom PCa suspicion persists, the risk of csPCa is not influenced by the previous finding of HGPIN. However, previous HGPIN increases the risk of iPCa detection. Therefore, repeat prostate biopsy should not be recommended solely because of a previous HGPIN.

Atypical small acinar proliferation (ASAP) and high grade intraepithelial neoplasia (HGPIN) patterns identified at prostate biopsy yield an important clinical significance, their presence signaling an increased likelihood of future oncological development or underdiagnosed PCa. MRI and MRI-TRUS fusion prostate biopsy have recently become the standard for the diagnosis of prostate cancer. Thus, we aimed to assess the role of ASAP/HGPIN pattern in the context of these recent developments as compared with the standard systematic biopsy. The present study included 400 patients who underwent MRI-TRUS fusion prostate biopsy. A subgroup of these patients had a history of prior systematic biopsy and their results were also included in the analysis. We observed that ASAP/HGPIN pattern diagnosed at systematic biopsy is suggestive of a high-volume clinically-significant disease, most probably located outside the standard sampling area. On the contrary, ASAP/HGPIN at MRI-TRUS fusion biopsy has clinical features more similar to benign prostate hyperplasia, thus suggesting a more incipient disease, if present. No relation between concurrent ASAP/HGPIN and PCa was observed in our study.

UNASSIGNED: The emergence of endoscopic submucosal dissection (ESD) made possible en bloc resection of neoplastic gastric lesions, regardless of lesion size, with reduced rates of complications and recurrence. This technique has become the preferred method for curative resection, instead of conventional endoscopic mucosal resection and surgery, when distant metastases have negligible risk. In Western countries experience with this technique has evolved quickly, with an increasing number of case series reported in the literature. This study aims to report the short- and long-term outcomes of ESD in gastric epithelial neoplastic lesions by a single operator in a Portuguese centre.
UNASSIGNED: A retrospective analysis of all gastric ESDs in a tertiary specialised unit during a 5-year period, between May 2012 and September 2017, was performed.
UNASSIGNED: A total of 114 ESDs of gastric epithelial lesions were performed during this period; 96.5% of them were removed en bloc and 87.6% with R0 resection. A curative treatment was achieved in 83.2% of the cases. Complications occurred in 13.2% of the procedures, including early and delayed bleeding in 12 patients (10.5%) and one perforation (0.9%). With a median follow-up period of 12 months (interquartile range [IQR] = 18), 6 cases of recurrence at the previous ESD site were diagnosed: 4 residual lesions and 2 local recurrences in previous R0 resections. Residual lesions occurred more often in patients with larger lesions (median = 40.0 mm, IQR = 26 vs. median = 20.0 mm, IQR = 15, p = 0.008) and with positive horizontal margins (HMs) after resection (50.0 vs. 0.0%, Fisher exact test, p < 0.001). The cumulative incidence of metachronous gastric lesions at 34 months was 16.1%. All new lesions were effectively treated using an endoscopic technique. The disease-specific survival at 12 months was 100%.
UNASSIGNED: This study showed that ESD is an effective resection technique for gastric lesions with a good safety profile, confirming other European series. Regardless, high en bloc resection positive HM is still a problem in some specimens resected by ESD. Endoscopic surveillance can detect local recurrence and new lesions during early stages, potentially treatable by endoscopy.
UNASSIGNED: O aparecimento da dissecção endoscópica da submucosa (ESD) tornou possível a resseção em bloco de lesões neoplásicas superficiais do estômago, independentemente da sua dimensão, com reduzidas taxas de complicações e recorrência. Esta técnica tem evoluído como método preferencial face á mucosectomia convencional e cirurgia, quando a metastização á distância tem risco negligenciável. No mundo ocidental a experiência nesta técnica tem evoluído de forma rápida surgindo um número crescente de séries na literatura. Este estudo tem como objetivo reportar os resultados a curto e longo prazo da ESD de lesões epiteliais gástricas realizadas por um único operador num centro Português.
UNASSIGNED: Análise retrospetiva unicêntrica dos casos de ESD de lesões epiteliais gástricas, realizadas durante um período de 5 anos, entre maio de 2012 e setembro de 2017.
UNASSIGNED: Foram realizadas 114 ESDs de neoplasias epiteliais gástricas durante o período em estudo, com uma taxa de resseção em bloco de 96.5% e R0 de 87.6%. A resseção curativa confirmou-se em 83.2% dos casos. Ocorreram complicações em 13.2% dos procedimentos, incluindo hemorragia em 12 doentes (10.5%) e 1 perfuração (0.9%). Com uma mediana de follow-up de 12 meses (variação interquartil [IQR] 18), verificaram-se 6 casos de recorrência local: 4 lesões residuais e 2 recorrências em resseções R0 prévias. Observaram-se mais frequentemente lesões residuais de ESD de lesões de maiores dimensões (mediana = 40.0 mm, IQR = 26 vs. mediana = 20.0 mm, IQR = 15, p = 0.008) e com margens horizontais (HM) positivas após a resseção (50.0% vs. 0.0%, Teste exato de Fisher, p < 0.001). A incidência cumulativa de lesões gástricas metácronas aos 34 meses foi de 16.1%. Todas as novas lesões foram eficazmente tratadas por endoscopia. A sobrevivência específica aos 12 meses de follow-up foi de 100%. Conclusão: Este estudo mostra que a ESD gástrica é uma técnica eficaz e segura para o tratamento de lesões neoplásicas precoces confirmando a maioria das séries europeias. Embora a ESD permita geralmente uma resseção em bloco as HM positivas continuam a ser um problema em alguns doentes. A vigilância endoscópica pode detetar recorrência local e novas lesões, em estádios precoces, potencialmente tratáveis por endoscopia.

To analyze the consistency of endoscopic biopsy of colorectal high-grade intraepithelial neoplasia (HGIN) and pathological diagnosis and to explore the value of preoperative examination in differentiating HGIN from invasive carcinoma.
Clinicopathological data of 79 patients with colorectal HGIN undergoing preoperative endoscopic biopsy from January 2012 to December 2017 were retrospectively analyzed.
Pathologically, 57 cases (72.8%) were diagnosed as invasive carcinoma and 22 (27.8%) as HGIN. Tumor size ≥3 cm, ulcer on the surface of the lesion, HGIN without adenoma, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, lymph node enlargement, and spiculation of the peri-intestinal fat on computed tomography were associated with postoperative invasive carcinoma. Multivariate analysis showed that a longest diameter ≥3 cm, preoperative diagnosis of HGIN without adenoma, and spiculation of the peri-intestinal fat were independent factors for a postoperative diagnosis of invasive carcinoma. Depending on the weight of these three independent factors in binary logistic regression analysis, a comprehensive scoring model was established. When the score was ≥1.5, the sensitivity and specificity for the diagnosis of invasive carcinoma were 86.0% and 81.8%, respectively. Utilizing the prediction index, the area under the receiver operating characteristic curve was 0.869.
A diagnosis of colorectal HGIN by colonoscopy is poorly consistent with the postoperative pathological diagnosis. The scoring model established in this study for identifying colorectal infiltrating carcinoma is simple and feasible. When the comprehensive score is ≥ 1.5, an aggressive approach of surgical treatment is recommended.

Laterally spreading tumours (LSTs) are superficial neoplasms that usually extend laterally along the intra-luminal wall of the gastrointestinal tract. Recently, the incidence of LSTs in the colorectal mucosa has greatly increased. However, LSTs in the stomach are exceedingly rare and have never been previously reported.
Here, we report a 69-year-old male with epigastric pain and a gastric LST 6 cm in diameter located in the distal stomach and grossly extended into the duodenal bulb. The stomach lesion was initially diagnosed as high-grade intraepithelial neoplasia, while the duodenal lesion was diagnosed as a tubulovillous adenoma. A therapeutic strategy of endoscopic submucosal dissection and distal gastrectomy was applied. The surgeries and postoperative course were uneventful, and the patient remained asymptomatic 1 year after surgery.
This is a clinically significant case, as it provides detailed information regarding laterally spreading early gastric cancer and emphasizes the diagnostic and therapeutic approaches for early gastric cancerous lesions.