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gastroenterostoma after Billroth antrectomy as a premalignant condition

World Journal of gastroenterology 2012年第25期18卷 3201-3206页

作者： Robert Sitarz Ryszard Maciejewski Wojciech P Polkowski g johan.a offerhaus Department of Pathology University Medical CentreUtrecht3584 CX UtrechtThe Netherlands Department of Human Anatomy Medical University of Lublin20-950 LublinPoland Department of Surgical Oncology Medical University of Lublin20-081 LublinPoland Department of Pathology Academic Medical Centre 1105 AZ Amsterdam The Netherlands

gastric stump carcinoma （gSC） following remote gastric surgery is widely recognized as a separate entity within the group of various types of gastric cancer. gastrecto- my is a well established risk factor for the development of gSC at a long time after the initial surgery. Both exo- as well as endogenous factors appear to be involved in the etiopathogenesis of gSC, such as achlorhydria, hypergastrinemia and biliary reflux, Epstein-Barr virus and Helicobacter pylori infection, atrophic gastritis, and also some polymorphisms in interleukin-l~ and maybe cyclo-oxygenase-2. This review summarizes the litera- ture of gSC, with special reference to reliable early di- agnostics. In particular, dysplasia can be considered as a dependable morphological marker. Therefore, close endoscopic surveillance with multiple biopsies of the gastroenterostomy is recommended. Screening start- ing at 15 years after the initial ulcer surgery can detect tumors at a curable stage. This approach can be ofspecial interest in Eastern European countries, where surgery for benign gastroduodenal ulcers has remained a practice for a much longer time than in Western Eu- rope, and therefore gSC is found with higher frequency.

关键词： gastric stump cancer gastrectomy Riskfactors Endoscopic surveillance

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Early-onset gastric cancer:Learning lessons from the young

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World Journal of gastrointestinal Oncology 2010年第2期2卷 59-64页

作者： Anya N Milne g johan.a offerhaus Department of Pathology University Medical Centre Utrecht Department of Pathology Academic Medical CentreUniversity of Amsterdam

There is by no means a clear-cut pattern of mutations contributing to gastric cancers,and gastric cancer research can be hampered by the diversity of factors that can induce gastric cancer,such as Helicobacter pylori infection,diet,ageing and other environmental *** are unquestionably riddled with genetic changes yet we are faced with an unsolvable puzzle with respect to a temporal *** is postulated that inherited genetic factors may be more important in early-onset gastric cancer (EOgC) than in gastric cancers found in older patients as they have less exposure to environmental ***,therefore,could provide a key to unravelling the genetic changes in gastric *** cancers occurring in young patients provide an ideal background on which to try and uncover the initiating stages of gastric *** review summarizes the literature regarding EOgC and also presents evidence that these cancers have a unique molecular-genetic phenotype,distinct from conventional gastric cancer.

关键词： gastric cancer Early-onset gastric cancer Helicobacter pylori

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Juvenile polyposis syndrome

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World Journal of gastroenterology 2011年第44期17卷 4839-4844页

作者： Lodewijk AA Brosens Danielle Langeveld W Arnout van Hattem Francis M giardiello g johan.a offerhaus Department of Pathology University Medical Centre Utrecht Department of Pathology Academic Medical Centre Division of gastroenterology Department of Medicine The Johns Hopkins University School of Medicine

Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal *** cumulative life-time risk of colorectal cancer is 39% and the relative risk is *** polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive ***,juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum,juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile *** about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is *** genes play a role in the BMP/TgF-beta signalling *** has been suggested that cancer in juvenile polyposis may develop through the socalled "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive *** of this rare disorder is important for patients and their families with regard to treatment,follow-up and screening of at risk *** clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis *** addition,juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of *** review discusses clinical manifestations,genetics,pathogenesis and management of juvenile polyposis syndrome.

关键词： Juvenile polyposis syndrome Hamartoma Colorectal cancer SMAD4 BMPR1A

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Molecular alterations in gastric cancer with special reference to the early-onset subtype

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World Journal of gastroenterology 2016年第8期22卷 2460-2474页

作者： Malgorzata Skierucha Anya NA Milne g johan.a offerhaus Wojciech P Polkowski Ryszard Maciejewski Robert Sitarz Department of Human Anatomy Medical University of Lublin 20-950 Lublin Poland Department of Pathology Diakonessenhuis 3582 KE Utrecht The Netherlands Department of Pathology H04-312 University Medical Centre Utrecht Post box 85500 3508 GA Utrecht The Netherlands Department of Surgical Oncology Medical University of Lublin 20-081 Lublin Poland Department of Pathology H04-312 University Medical Centre Utrecht Post box 85500 3508 GA Utrecht The Netherlands

Currently, gastric cancer(gC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the procarcinogenic activity of important genes. These factors include genetic susceptibility expressed in a singlenucleotide polymorphism, various acquired mutations(chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances(e.g., helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for gC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma(EOgC) and hereditary gC may contribute towards unravelling some part of the mystery of the gC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOgCs and conventional gCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesisare modifiable, discover specific gC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of gC and highlights the outstanding features of EOgC.

关键词： gastric cancer Early-onset gastric cancer Molecular alterations Chromosomal instability Single-nucleotide polymorphism Microsatellite instability Epigenetic alterations Loss of heterozygosity

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