Gastric neuroendocrine tumors in a BRCA2 germline mutation carrier:A case report

BACKGROUND The molecular changes present in gastric neuroendocrine tumors(NETs)include a loss of heterozygosity or mutation of MEN1,CDKN1B gene mutation,P27 heterozygous mutation,and ATP4A gene missense mutation.We identified and are the first to report a case of type 1 histamine-producing enterochromaffin-like cell NETs(ECL-cell NETs)with a BRCA2 gene germline mutation.CASE SUMMARY The patient had a history of iron-deficient anemia for 5 years,and gastroscopic examination indicated multiple gastric tumors.Then,the patient underwent distal gastrectomy.Microscopically,multifocal tumor cells were found in the mucosa and submucosa;tumor cells were organoid and arranged in nests and cords,and the stroma was rich in sinusoids.The surrounding gastric mucosa showed atrophy with mild intestinal metaplasia or pseudopyloric gland metaplasia.Neuroendocrine cells could be seen with diffuse linear,nodular,and adenomatous hyperplasia.Immunohistochemically,the tumor cells diffusely expressed cytokeratin,chromogranin,synaptophysin,and CD56.Whole-genome highthroughput molecular sequencing revealed a pathogenic germline mutation in the BRCA2 gene,a heterozygous germline frameshift mutation in exon 11,c.6443_6444del(p.S2148Yfs*2).The final diagnosis was gastric type 1 ECL-cell NETs with a BRCA2 gene germline mutation,accompanied by autoimmune gastritis.CONCLUSION This is the first report of a case of type 1 gastric ECL-cell NETs with a pathogenic germline mutation of the BRCA2 gene.The findings of this report will expand the germline mutation spectrum of gastric NETs and increase the understanding of the molecular changes present in these tumors for their improved diagnosis in the future.

Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion

A bibliometric analysis of studies dedicated to autoimmune gastritis(AIG)recently published demonstrated a noteworthy surge in publications over the last three years.This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition.Follow-up studies and retrospective analyses showed that the risk of gastric cancer(GC)in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori(H.pylori)were excluded.The low prevalence of precancerous lesions,such as the incomplete type of intestinal metaplasia,may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion.However,changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric microbiome,stimulating the growth of bacterial species such as streptococci,which may promote the development of precancerous lesions and GC.Thus,Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice,reproducing the wellestablished process for carcinogenesis associated with H.pylori.Prospective studies in H.pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts,which has been reported in economically developed countries.

The expression of p27^(Kip1) and β-catenin in multiple endocrine neoplasia type 1-related parathyroid tumors

Objective To explore tissue expression of cyclin-dependent kinase inhibitor p27Kip1 andβ-catenin in multiple endocrine neoplasia type1（MEN1）-related parathyroid tumors（MHPT）.Methods Immunohistochemistry was performed to analyze the expression of p27Kip1 andβ-catenin in parathyroid glands from 31 subjects

Increased risk of hyperglycemia associated with the use of everolimus in patients with cancer: a systematic review and meta-analysis

Everolimus is an orally administered rapamycin analogue that has been approved to treat several types of solid tumors. However, some patients develop hyperglycemia after being treated with everolimus. In this meta-analysis, we aimed to evaluate the incidence and risk of hyperglycemia in patients with cancer who received everolimus. We searched the medical literature, as index in the Cochrane Library, PubMed, EMBASE, and abstracts from the top scientific meetings （AACR, ASCO, and ESMO）. Our meta-analysis included the randomly controlled trials published before November 2014. We calculated overall incidence, relative risk （RR） and 95% confidence intervals （CI） using fixed-effects or random-effects models, depending on the heterogene- ity among the trials. A total of 3377 patients （everolimus： 1971; control： 1406） from 8 randomized clinical trials were included in the meta-analysis. In the everolimus groups, the incidence of all grades of hyperglycemia was 20.0% （95% CI： 11.0%-29.0%）, while the incidence of high-grade hyperglycemia was 6.0% （95% CI： 3.0%-8.0%）. Patients treated with everolimus had an in- creased risk of hyperglycemia as compared with that of controls （all-grade RR： 2.94, 95% CI： 2.34-3.70; high-grade RR： 4.66, 95% CI： 2.75-7.89）. Everolimus significantly increased the risk of hyperglycemia. This risk may depend on the tumor type and the everolimus dosage.

Effect of Acupuncture-moxibustion on TNF-α,sTNFR-Ⅰ and sTNFR-Ⅱ of Rats with Crohn's Disease

Objective： To observe the effect of acupuncture-moxibustion on TNF-α, sTNFR-Ⅰ and sTNFR-Ⅱ in rats with Crohn＇s disease （CD）. Method： The models of CD rats induced by TNBS were randomized into model group, herbal cake-partitioned moxibustion group and electroacupuncture group as well as a normal control group. The histopathological changes of colon mucus membrane were observed with HE staining and the contents of TNF-α, sTNFR-Ⅰ and sTNFR-Ⅱ were detected with ELISA method. Results： When compared with the normal group, the TNF-α level in CD rats was substantially elevated and the sTNFR-Ⅰ and sTNFR-Ⅱ showed no marked changes. After herbal cake-partitioned moxibustion and electroacupuncture treatment, the TNF-α level in CD rats was substantially reduced and sTNFR-Ⅰ and sTNFR-Ⅱ showed no marked changes. The inflammatory lesions and abnormal structures of CD rats were significantly improved after herbal cake-partitioned moxibustion and electric stimulation. Conclusion： Herbal cake-partitioned moxibustion and electroacupuncture can both remarkably reduce the TNF-α level in blood serum, and this might be one of the action mechanisms in the treatment of CD.