Acknowledgements to Reviewers of World Journal of Gastroenterology

In this issue,many reviewers contribute their expertiseto peer review,a process that contributes critically tothe quality of our journal.The editors and the authors ofthe papers submitted to the journal are grateful to all thereviewers and editorial members for their uniquecontribution to World Journal of Gastroenterology inreviewing the papers (including papers published andrejected) of this issue.     

Angiographic findings of gastrointestinal stromal tumor

AIM:To discuss the angiographic features of gastrointestinalstromal tumor(GIST)and to evaluate their diagnostic role.METHODS:Twelve patients with pathologically proved GISTunderwent angiography(DSA)1 wk before operation,usingPuck and digital subtraction DSA.The origin,size,morphologyand angiographic appearance of the lesions were reviewed.RESULTS:Two tumors arose from stomach,8 from jejunum,and 2 from ileum.Seven cases were benign and 5 weremalignant.Obviously thickened supplying arteries weredetected in 8 tumors,and early-developed veins were foundin 3.Two types of angiographic changes of GIST were observed.Four cases had twisted irregular neoplastic vessels withpartially coarse and indistinct margins,which were allmalignant.Eight cases had ball-like neoplastic vessels withuniform tumor staining,of which 7 were benign and 1 wasmalignant.CONCLUSION:Angiography facilitates localization anddiagnosis of GIST,helps define their size,range and location,and is especially valuable to patients suffering from melenawith unknown reasons.     

Acknowledgements to Reviewers of World Journal of Gastroenterology

In this issue,many reviewers contribute their expertiseto peer review,a process that contributes critically tothe quality of our journal.The editors and the authors ofthe papers submitted to the journal are grateful to allthe reviewers and editorial members for their uniquecontribution to World Journal of Gastroenterology inreviewing the papers (including papers published andrejected) of this issue.     

Acknowledgements to Reviewers of World Journal of Gastroenterology

In this issue,many reviewers contribute their expertiseto peer review,a process that contributes critically tothe quality of our journal.The editors and the authors ofthe papers submitted to the journal are grateful to allthe reviewers and editorial members for their uniquecontribution to World Journal of Gastroenterology inreviewing the papers(including papers published andrejected)of this issue.     

Acknowledgements to Reviewers of World Journal of Gastroenterology

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastroenterology.The editors and     

Acknowledgments to Reviewers of World Journal of Gastroenterology

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastroenterology. The editors and authors     

Acknowledgments to Reviewers of World Journal of Gastroenterology

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastroenterology. The editors and authors     

Antiproliferative effect of octreotide on gastric cancer cells mediated by inhibition of Akt／PKB and telomerase

AIM: To investigate the antiproliferative effect of octreotide,a long-acting analogue of somatostatin, on gastric cancer cell line SGC7901 and its possible molecular mechanisms.METHODS: Gastric cancer cell line SGC7901 employed in the study was treated with 0.008, 0.04, 0.2, 1, 5 and 25μg@ml-1 of octreotide respectively for 24 h to evaluate the antiproliferative effect of somatostatin analog on the tumor cells by MTT assay method. To elucidate the underlying mechanism, the cells were exposed to 1 μg@ml-1 of octreotide for 0, 12, 24 and 48 h, when their Akt/PKB and telomerase activities were respectively determined using PCR-ELSIA and nonradioactive protein kinase assay protocols. The same experimental procedures were also performed in the control cells that were treated with corresponding vehicles instead of somatostatin analog.RESULTS: After exposed to octreotide for 24 h at the concentrations of more than 1 μg@ml-1 SGC7901 cells exhibited a dose-dependent inhibition of growth with the inhibiting rate to be as high as 34.66 % when 25 μg@ml-1 of octreotide was applied. The Akt/PKB and telomerase activity of SGC7901 cells was significantly inhibited when the cells were exposed to 1 μg@ml-1 of octreotide for 12, 24 and 48 h compared with that of their control counterparts (P＜0.01),both of which exhibited in a time-dependent manner.CONCLUSION: The antiproliferative effect of octreotide on SGC7901 cells might be mediated by the inhibition of Akt/PKB and telomerase.     

Unexpected discovery of 2 cases of hepatocyte nuclear factor 1α-mutated infracentimetric adenomatosis

We present 2 cases of hepatocyte nuclear factor 1α(HNF1α)-mutated adenomatosis,discovered for reasons unrelated to this disease,and identified using immunohistochemical methods.These new tools may further our understanding of the link between adenomas/adenornatosis subtypes and their complications,and their association with other abnormalities.     

Hepatocyte nuclear factor-1 alpha gene inactivation: cosegregation between liver adenomatosis and diabetes phenotypes in two maturity-onset diabetes of the young (MODY)3 families

Heterozygous germline mutations of the hepatocyte nuclear factor (HNF)-1 alpha are associated with maturity-onset diabetes of the young (MODY)3. Recently, the biallelic inactivation of the HNF-1 alpha gene was reported in liver adenomas. We show the occurrence of liver adenomatosis in six MODY3-affected patients from two unrelated and large families. Liver adenomatosis was characterized by the presence of numerous adenomas within a normal hepatic parenchyma. The HNF-1 alpha hot-spot germline mutation P291fs was identified in the two probands and in 16 relatives from the two families. The six patients affected by liver adenomatosis and diabetes exhibited the mutation. The analysis of liver-cell tumors from two affected patients evidenced the biallelic inactivation of HNF-1 alpha. The familial screening confirmed the clinical heterogeneity of the liver phenotype, from silent liver adenomatosis to fatal hemorrhage. These observations warrant the systematic screening for liver adenomatosis in MODY3 families to prevent its potentially deadly complications. Moreover, such screening may help to determine if a particular mutational spectrum of HNF-1 alpha is associated with liver adenomatosis and to establish its prevalence in this frequent form of diabetes in the young adult.     

青少年的成人起病型糖尿病2型和3型混合家系一例临床分析并文献复习

目的探究葡萄糖激酶基因(GCK)及肝细胞核因子1α基因(HNF-1α)同时突变致青少年的成人起病型糖尿病(MODY)的临床和遗传学特点。方法对北京协和医院2017年9月诊断的一例MODY患者及其家系的临床特征、实验室资料进行分析;对家系成员进行MODY相关致病基因检测。结果该家系的5名成员检测到GCK基因(NM_000162)c.686C>T(p.Thr229Met)杂合突变。其中3名成员同时检测到HNF-1α基因(NM_001306179)c.1531C>G(p.Gln511Glu)杂合突变。结论MODY混合家系GCK及HNF-1α基因突变导致同一家系出现不同的MODY类型。诊断时需考虑混合家系的可能性,以准确诊断。     

Hepatocellular adenoma displaying a HNF1alpha inactivation in a patient with familial adenomatous polyposis coli

Patients with familial adenomatous polyposis coli (FAP) may rarely develop hepatocellular adenoma. Here we report the case of a 37-year-old FAP woman presenting a hepatocellular adenoma after oestroprogestative oral contraception use. In this steatotic adenoma, we identified an inactivating biallelic mutation of HNF1alpha. In addition to the known germline APC mutation Q1062fs, we did not find an inactivation of the second APC allele nor an activation of the beta-catenin target genes GLUL and GPR49. Our findings contrast with two hepatocellular adenoma cases related to FAP, for which a biallelic inactivation of the APC gene was previously described. Altogether, these results suggest that benign hepatocellular carcinogenesis may be dependent on or independent of the Wnt/beta-catenin pathway in patients with FAP.     

Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation

Background & Aims:

Germline mutations in hepatocyte nuclear factor 1α (TCF1/HNF-1α) are associated with maturity-onset diabetes of the young type 3 (MODY3), and somatic biallelic inactivations of the gene are found in hepatocellular adenomas and liver adenomatosis. This study investigated cosegregation of HNF-1α germline mutations with diabetes and liver adenomatosis in 2 families.

Methods:

Two unrelated patients with liver adenomatosis and harboring HNF-1α germline and somatic mutations were studied. Subsequently, we screened 9 relatives in the 2 independent families for diabetes, hepatocellular adenomas, and HNF-1α germline mutations.

Results:

In family A, a father and his son presented with an intraperitoneal hemorrhagic rupture of a liver adenomatosis without diabetes. A heterozygous R229X germline mutation was identified in HNF-1α in the father and his son and also in his second 27-year-old son without hepatocellular adenomas. In family B, a diagnosis of liver adenomatosis was made fortuitously in a 14-year-old girl. A heterozygous G55fsX57 germline mutation in HNF-1α was identified in this patient, her diabetic father, and her 2 sisters. Systematic exploration showed liver adenomatosis in the 2 sisters. Somatic inactivation of the second HNF-1α allele was found in liver tumors in both families.

Conclusions:

This study describes familial liver adenomatosis and shows the association with germline HNF-1α mutations in adults and children. It also highlights the importance of screening for hepatocellular adenomas, diabetes, and HNF-1α germline mutations in relatives of patients with liver adenomatosis. Finally, prevalence of liver adenomatosis remains to be evaluated in MODY3 subjects.     

Genotype phenotype classification of hepatocellular adenoma

Studies that compare tumor genotype with phenotype have provided the basis of a new histological/molecular classification of hepatocellular adenomas. Based on two molecular criteria (presence of a TCF1/HNF1α or β-catenin mutation), and an additional histological criterion (presence or absence of an inflammatory infiltrate), subgroups of hepatocellular adenoma can be defined and distinguished from focal nodular hyperplasia. Analysis of 96 hepatocellular adenomas performed by a French collaborative network showed that they can be divided into four broad subgroups: the fi rst one is defi ned by the presence of mutations in TCF1 gene inactivating the hepatocyte nuclear factor 1 (HNF1α); the second by the presence of β-catenin activating mutations; the category without mutations of HNF1α or β-catenin is further divided into 2 subgroups depending on the presence or absence of in? ammation. Therefore, the approach to the diagnosis of problematic benign hepatocytic nodules may be entering a new era directed by new molecular information. It is hoped that immunohistological tools will improve significantly diagnosis of liver biopsy in our ability to distinguish hepatocellular adenoma from focal nodular hyperplasia (FNH), and to delineate clinically meaningful entities within each group to define the best clinical management. The optimal care of patients with a liver nodule will benefit from the recent knowledge coming from molecular biology and the combined expertise of hepatologists, pathologists, radiologists, and surgeons.     

新型降糖药物在三种常见青少年的成年起病型糖尿病亚型上的应用

青少年的成年起病型糖尿病(maturity-onset diabetes of the young, MODY)是一种异质性的单基因糖尿病,其中MODY1、MODY2和MODY3是常见的MODY亚型。近年来胰升糖素样肽1受体激动剂(GLP-1RA)、二肽基肽酶4抑制剂(DPP-4i)、钠-葡萄糖共转运蛋白2抑制剂(SG...