Microbial ecosystems that inhabit the human gut form central component of our physiology and metabolism, regulating and modulating both health and disease. Changes or disturbances in the composition and activity of this gut microbiota can result in altered immunity, inflammation, and even cancer.

Across the globe, gastric cancer is a significant public health problem. This meta-analysis was conducted to investigate the association of microRNA-27a (miRNA-27a) rs895819 with gastric cancer risk.

Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach cancer. The three main subtypes have different pathogeneses, biological behaviours and clinical characteristics, so they require different management strategies. This article will provide an overview of g-NENs and highlight recent advances in the field.

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. It takes some time from chronic gastritis to develop in GC. Early detection of GC will help patients obtain timely treatment. Understanding disease evolution is crucial for the prevention and treatment of GC. Here, we present a convolutional neural network (CNN)-based system to detect abnormalities in the gastric mucosa. We identified normal mucosa, chronic gastritis, and intestinal-type GC: this is the most common route of gastric carcinogenesis. We integrated digitalizing histopathology of whole-slide images (WSIs), stain normalization, a deep CNN, and a random forest classifier. The staining variability of WSIs was reduced significantly through stain normalization, and saved the cost and time of preparing new slides. Stain normalization improved the effect of the CNN model. The accuracy rate at the patch-level reached 98.4%, and 94.5% for discriminating normal → chronic gastritis → GC. The accuracy rate at the WSIs-level for discriminating normal tissue and cancerous tissue reached 96.0%, which is a state-of-the-art result. Survival analyses indicated that the features extracted from the CNN exerted a significant impact on predicting the survival of cancer patients. Our CNN model disclosed significant potential for adjuvant diagnosis of gastric diseases, especially GC, and usefulness for predicting the prognosis.

Neuroendocrine neoplasms (NENs) are rare epithelial tumors with heterogeneous and frequently unpredictable clinical behavior. Available biomarkers are insufficient to guide individual patient prognosis or therapy selection. Peptidylglycine α-amidating monooxygenase (PAM) is an enzyme expressed by neuroendocrine cells that participates in hormone maturation. The objective of this study was to assess the distribution, clinical associations and survival implications of PAM immunoreactivity in primary NENs. Of 109 primary NENs, 7% were PAM-negative, 25% were PAM-low and 68% were PAM-high. Staining intensity was high in small bowel (p = 0.04) and low in stomach (p = 0.004) NENs. PAM staining was lower in higher grade tumors (p < 0.001) and patients who died (p < 0.001) but did not vary by tumor size or stage at surgery. In patients who died, time to death was shorter in patients with reduced PAM immunoreactivity: median times to death were 11.3 (PAM-negative), 29.4 (PAM-low) and 61.7 (PAM-high) months. Lower PAM staining was associated with increased risk of death after adjusting for disease stage [PAM negative, HR = 13.8 (CI: 4.2-45.5)]. PAM immunoreactivity in primary NENs is readily assessable and a potentially useful stage-independent predictor of survival.

Feed-forward loops (FFLs), consisting of miRNAs, transcription factors (TFs) and their common target genes, have been validated to be important for the initialization and development of complex diseases, including cancer. Esophageal Carcinoma (ESCA) and Stomach Adenocarcinoma (STAD) are two types of malignant tumors in the digestive tract. Understanding common and distinct molecular mechanisms of ESCA and STAD is extremely crucial.

MicroRNAs (miRNAs) have been applied to cancer diagnosis taking into account their role in tumorigenesis. The main purpose of our study was to confirm the possibility of using miRNAs as noninvasive biomarkers for stomach adenocarcinoma (STAD) diagnosis.

Background. Surgery remains the only curative treatment for gastrointestinal stromal tumour (GIST). Resection needs to ensure tumour-free margins while lymphadenectomy is not required. Thus, partial gastric resection is the treatment of choice for small gastric GISTs. Evidence on whether performing resection laparoscopically compromises outcome is limited. Methods. We compiled patients undergoing laparoscopic resection of suspected gastric GIST between 2003 and 2007. Follow-up was performed to obtain information on tumour recurrence. Results. Laparoscopic resection with free margins was performed in 21/22 patients. Histology confirmed GIST in 17 cases, 4 tumours were benign neoplasms. Median operation time and postoperative stay for GIST patients were 130 (range 80-201) mins and 7 (range 5-95) days. Two patients experienced stapler line leakage necessitating surgical revision. After median follow-up of 18 (range 1-53) months, no recurrence occurred. Conclusions. Laparoscopic resection of gastric GISTs yields good perioperative outcomes. Oncologic outcome needs to be assessed with longer follow-up. For posterior lesions, special precaution is needed. Laparoscopic resection could become standard for circumscribed gastric GISTs if necessary precautions for oncological procedures are observed.

Previous studies have confirmed the biglycan (BGN) as a core gene in stomach adenocarcinoma (STAD). Present study aimed at conducting further investigations to reveal the potential function of BGN in STAD.

The lectin TFF2 belongs to the trefoil factor family (TFF). This polypeptide is typically co-secreted with the mucin MUC6 from gastric mucous neck cells, antral gland cells, and duodenal Brunner glands. Here, TFF2 fulfills a protective function by forming a high-molecular-mass complex with the MUC6, physically stabilizing the mucus barrier. In pigs and mice, and slightly in humans, TFF2 is also synthesized in the pancreas. Here, we investigated the murine stomach, pancreas, and duodenum by fast protein liquid chromatography (FPLC) and proteomics and identified different forms of Tff2. In both the stomach and duodenum, the predominant form is a high-molecular-mass complex with Muc6, whereas, in the pancreas, only low-molecular-mass monomeric Tff2 was detectable. We also investigated the expression of Tff2 and other selected genes in the stomach, pancreas, and the proximal, medial, and distal duodenum (RT-PCR analysis). The absence of the Tff2/Muc6 complex in the pancreas is due to a lack of Muc6. Based on its known motogenic, anti-apoptotic, and anti-inflammatory effects, we propose a protective receptor-mediated function of monomeric Tff2 for the pancreatic ductal epithelium. This view is supported by a report that a loss of Tff2 promotes the formation of pancreatic intraductal mucinous neoplasms.

Early postoperative intraperitoneal chemotherapy (EPIC) can be used in combination with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat patients with peritoneal carcinomatosis (PC) of multiple origins. The present study is a systematic review to evaluate the role of EPIC after CRS + HIPEC for appendiceal and colorectal cancers with PC.

Decomposing somatic mutation spectra into mutational signatures and their corresponding etiologies provides a powerful approach for investigating the mechanism of DNA damage and repair. Assessing microsatellite (in)stability (MSI/MSS) status and interpreting their clinical relevance in different malignancies offers significant diagnostic and prognostic value. However, little is known about microsatellite (in)stability and its interactions with other DNA repair mechanisms such as homologous recombination (HR) in different cancer types. Based on whole-genome/exome mutational signature analysis, we showed HR deficiency (HRd) and mismatch repair deficiency (MMRd) occur in a significantly mutually exclusive manner in stomach and colorectal adenocarcinomas. ID11 signature with currently unknown etiology was prevalent in MSS tumors, co-occurred with HRd and was mutually exclusive with MMRd. Apolipoprotein B mRNA editing enzyme, Catalytic polypeptide-like (APOBEC) signature co-occurred with HRd and was mutually exclusive with MMRd in stomach tumors. The HRd signature in MSS tumors and the MMRd signature in MSI tumors were the first or second dominant signatures wherever detected. HRd may drive a distinct subgroup of MSS tumors and lead to poor clinical outcome. These analyses offer insight into mutational signatures in MSI and MMS tumors and reveal opportunities for improved clinical diagnosis and personalized treatment of MSS tumors.

Gastrointestinal schwannomas are slow-growing benign mesenchymal neoplasms that originate from Schwann cells of the nerve sheath of Auerbach´s plexus or less frequently from Meissner´s plexus. The main differential diagnosis of gastric schwannomas are the gastrointestinal stromal tumors (GISTs), which are classified by their immunohistochemistry. The treatment of choice for gastric schwannomas is surgery where laparoscopy plays an important role. Wedge resection, subtotal or total gastrectomy can be done. In its counterpart, esophageal schwannomas are benign tumors of the esophagus that are very uncommon since they comprise less than 2% of all esophageal tumors. The main differential diagnosis is the leiomyoma which corresponds to the most common benign esophageal tumor, followed by GIST. The treatment consists on tumoral enucleation or esophagectomy.

Background: Anti-bacterial drugs are thought to be associated with several malignancies. Objective: We conducted a systematic review and meta-analysis to assess the association between antibacterial drug exposure and the risk of digestive system neoplasms. Methods: Relevant publications reporting a relationship between antibiotic use and the risk of cancer were identified in PubMed, EMBASE, and Cochrane Central Register through June 2018. The random-effects model was selected to pool the risk ratios (RRs) and determine 95% confidence intervals (95% CIs). We performed subgroup analyses by tumor organ site, individual antibacterial drug class, and drug dose accumulation. Results: A total of 17 eligible studies (four randomized trials and 13 observational studies) involving 77,284 cancer patients were included in our analyses. Anti-bacterial drug exposure slightly increased the risk of overall digestive system cancer (RR, 1.12; 95% CI, 1.10-1.14), stomach and small intestine (RR, 1.12; 95% CI, 1.07-1.17), anorectocolonic (RR, 1.08; 95% CI, 1.05-1.12), and hepatobiliary and pancreatic cancers (RR, 1.18; 95% CI, 1.14-1.22). For different anti-bacterial drugs classes, nitroimidazoles (RR, 1.17; 95% CI, 1.09-1.26) and quinolones (RR, 1.18; 95% CI, 1.11-1.26) showed a modest association with the risk of cancers incidence. The risks of digestive system cancers increased with the rise of drug dose accumulation: low (RR, 1.08; 95% CI, 1.05-1.11), intermediate (RR, 1.15; 95% CI, 1.12-1.18), and high (RR, 1.22; 95% CI, 1.18-1.26). Conclusions: Anti-bacterial drug exposure was associated with the risks of digestive system cancer occurrence in our analysis.

Background: Gastrointestinal masses in cats are of clinical relevance, but pathological studies with larger case numbers are lacking. Biomarkers such as miRNA have not yet been investigated in feline intestinal neoplasms. Methods: A retrospective analysis of pathology reports included 860 feline gastrointestinal masses. Immunohistochemistry was performed on 91 lymphomas, 10 sarcomas and 7 mast cell tumours (MCT). Analyses of miRNA-20b and miRNA-192 were performed on 11 lymphomas, 5 carcinomas and 5 control tissues by ddPCR. Results: The pathological diagnosis identified 679 lymphomas, 122 carcinomas, 28 sarcomas, 23 polyps, 7 MCT and 1 leiomyoma. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCT only occurred in the small intestine. Besides the well-described small-cell, mitotic count <2 T-cell lymphomas and the large-cell B-cell lymphomas with a high mitotic count, several variants of lymphomas were identified. The values of miRNA-20b were found to be up-regulated in samples of all types of cancer, whereas miRNA-192 was only up-regulated in carcinomas and B-cell lymphomas. Conclusions: The histopathological and immunohistochemical (sub-)classification of feline intestinal masses confirmed the occurrence of different tumour types, with lymphoma being the most frequent neoplasm. Novel biomarkers such as miRNA-20b and miRNA-192 might have diagnostic potential in feline intestinal neoplasms and should be further investigated.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a group of rare tumors with limited research currently available. This study aimed to analyze the incidence, survival, and prognostic factors of gastrointestinal MiNENs.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) that histologically resembles hepatocellular carcinoma (HCC). Despite its low incidence, HAS had a poor 5-year survival rate. Currently, the linkages between clinicopathological and genomic features of HAS and its therapeutic targets remain largely unknown. Herein, we enrolled 90 HAS patients and 270 stage-matched non-HAS patients from our institution for comparing clinicopathological features. We found that HAS had worse overall survival and were more prone to develop liver metastasis than non-HAS in our cohort, which was validated via meta-analysis. By comparing whole-exome sequencing data of HAS (n=30), non-HAS (n=63), and HCC (n=355, The Cancer Genome Atlas), we identified a genomic landscape associated with unfavorable clinical features in HAS, which contained frequent somatic mutations and widespread copy number variations. Notably, signaling pathways regulating pluripotency of stem cells affected by frequent genomic alterations might contribute to liver metastasis and poor prognosis in HAS patients. Furthermore, HAS developed abundant multiclonal architecture associated with liver metastasis. Encouragingly, target analysis suggested that HAS patients might potentially benefit from anti-ERBB2 or anti-PD-1 therapy. Taken together, this study systematically demonstrated a high risk of liver metastasis and poor prognosis in HAS, provided a clinicogenomic landscape underlying these unfavorable clinical features, and identified potential therapeutic targets, laying the foundations for developing precise diagnosis and therapy in this rare but lethal disease.

To evaluate through meta-analysis whether long-term use of proton pump inhibitor (PPI) increases the risk of precancerous lesions in the stomach.

Children receiving radiotherapy face the probability of a subsequent malignant neoplasm (SMN). In some cases, the predicted SMN risk can be reduced by proton therapy. The purpose of this study was to apply the most comprehensive dose assessment methods to estimate the reduction in SMN risk after proton therapy vs. photon therapy for a 13-year-old girl requiring craniospinal irradiation (CSI). We reconstructed the equivalent dose throughout the patient's body from therapeutic and stray radiation and applied SMN incidence and mortality risk models for each modality. Excluding skin cancer, the risk of incidence after proton CSI was a third of that of photon CSI. The predicted absolute SMN risks were high. For photon CSI, the SMN incidence rates greater than 10% were for thyroid, non-melanoma skin, lung, colon, stomach, and other solid cancers, and for proton CSI they were non-melanoma skin, lung, and other solid cancers. In each setting, lung cancer accounted for half the risk of mortality. In conclusion, the predicted SMN risk for a 13-year-old girl undergoing proton CSI was reduced vs. photon CSI. This study demonstrates the feasibility of inter-institutional whole-body dose and risk assessments and also serves as a model for including risk estimation in personalized cancer care.

Enteral immunonutrition is a nutritional intervention that has been studied in postoperative patients with gastric cancer, but its effectiveness is controversial. This study aimed to investigate the effects of enteral immunonutrition and enteral nutrition on immune function in patients who undergo gastric cancer surgery.