Table of Contents
CancerMail from the National Cancer Institute
UI - 21200156
AU - D'Elia F; Zingarelli A; Palli D; Grani M
TI - Hydro-dynamic CT preoperative staging of gastric cancer: correlation with pathological findings. A prospective study of 107 cases.
SO - Eur Radiol 2000;10(12):1877-85
AD - Department of Radiology, S. Donato Hospital, Arezzo, Italy.
The aim of this study was to evaluate the accuracy of dynamic CT in the preoperative staging of gastric cancer. One hundred seven patients affected by gastric cancer diagnosed by endoscopic biopsy were prospectively staged by dynamic CT prior to tumor resection. After an oral intake of 400-600 ml of tap water and an intravenous infusion of a hypotonic agent, 200 ml of non-ionic contrast agent were administered by power injector using a biphasic technique. The CT findings were prospectively analyzed and correlated with the pathological findings at surgery. The accuracy of dynamic CT for tumor detection was 80 and 99% in early and advanced gastric cancer, respectively, with overall detection rate of 96% (103 of 107). Three early (pT1) and one advanced (pT2) cancers were undetected. Tumor stage as determined by dynamic CT agreed with pathological findings in 83 of 107 patients with an overall accuracy of 78%. The accuracy of CT in detecting increasing degrees of depth of tumor invasion when compared with pathological TNM staging was 20% (3 of 15) and 87% (80 of 92) in early and advanced cancer, respectively. The sensitivity, specificity, and accuracy of CT in the preoperative staging (pT3-pT4 vs pT1-pT2) was 93, 90, and 91.6%, respectively. The sensitivity, specificity, and accuracy of CT in assessing metastasis to regional lymph nodes was 97.2, 65.7, and 87%, respectively. Computed tomography correctly staged liver metastases in 105 of 107 patients with an overall sensitivity of 87.5% and specificity of 99 %. The sensitivity of peritoneal involvement was 30% when ascites or peritoneal nodules were absent. Our findings show that dynamic CTcan play a role in the preoperative definition of gastric cancer stage. The results can be used to optimize the therapeutic strategy for each individual patient prior to surgery, thus avoiding unnecessary intervention and allowing careful planning of extended surgery in eligible patients.
UI - 21092572
AU - Chen D; Shou C
TI - Molecular cloning of a tumor-associated antigen recognized by monoclonal antibody 3H11.
SO - Biochem Biophys Res Commun 2001 Jan 12;280(1):99-103
AD - Beijing Institute for Cancer Research, Beijing 100034, People's Republic of China.
Monoclonal antibody (MAb) 3H11 can bind specifically to different cancer cells from different tissues. MAb 3H11 labeled with radioactive isotopes has been used clinically to detect primary cancer and metastatic cancer. Molecular cloning of the antigen recognized by MAb 3H11 is important in studying tumor occurrence and in developing new biotherapy for cancer. Using MAb 3H11, we screened cDNA library made from the human gastric cancer cell line MGC 803, which reacts with MAb 3H11, and isolated one positive clone specifically recognized by the antibody. The insert cDNA fragment was 0.5 kb. After recombining with glutathione-S-transferase expression vector pGEX-4T, the cDNA fragment could be expressed into a fusion protein that specifically reacted with MAb 3H11. Moreover, the fusion protein could competitively inhibit MAb 3H11 binding to MGC 803 cells. Based on the nucleotide sequence of the cDNA fragment, the full length of the cDNA (2156 bp) was obtained by Rapid-Amplification-cDNA-End (RACE) and nested PCR. Its reading frame was 1767 bp encoding a protein of 589 amino acids. Sequence analysis indicated that there is no highly homologous gene in the GenBank. Northern blot and RT-PCR showed that the mRNA of MAb 3H11 antigen was extensively distributed in embryonic tissue and in different cancerous tissues, but not in corresponding normal tissues. Moreover, in producing antibodies to the antigen expressed prokaryotically, we found that the immunogenicity of the antigen was low in mammalian. Thus we believe that this novel antigen acts as an expression regulator in embryo cells and regains expression in tumor cells. In addition, this antigen is characterized by low differentiation and high proliferation. Molecular function of the antigen needs to be investigated. Copyright 2001 Academic Press.
UI - 21236548
AU - Sun CF; Hsieh YY; Ngan KW; Wang WT
TI - Search for immunomodulatory effects of blood transfusion in gastric cancer patients: flow cytometry of Th1/Th2 cells in peripheral blood.
SO - Ann Clin Lab Sci 2001 Apr;31(2):171-8
AD - Department of Clinical Pathology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Tao-Yuan, Taiwan.
Allogeneic transfusion seems to drive the immune system toward a Th2 response and away from a Th1 response, providing a hypothetical mechanism for transfusion-induced immunomodulation. By means of an intracytoplasmic cytokine detection technique with flow cytometry, it is possible to measure Th1 and Th2 cells derived from peripheral blood mononuclear cells. This study evaluated the presence of transfusion-induced immunomodulation in 11 gastric cancer patients after gastrectomy with perioperative blood transfusion, compared to 11 gastric cancer patients who were treated by gastrectomy without transfusion. Lymphocytes subsets, including CD4 T cells, CD8 T cells, CD4/CD8 Ratio, CD2(+) T cells, CD3(+) T cells, and CD19(+) B cells, were measured in these patients, as well as variables that might suggest transfusion-induced immunomodulation, such as duration of antibiotic use, duration of hospital stay, and total hospital charges. This study also measured changes in the Th1/Th2 ratio. Th1 and Th2 lymphocytes were characterized by measuring intracellular expression of cytokines with flow cytometry. Cells were stimulated with phorbol myristate acetate and ionomycin in the presence of brefeldin-A. The results showed no significant differences in lymphocyte subsets, Th1/Th2 ratio, total hospital charges, or duration of antibiotic utilization between the groups of transfused and non-transfused gastric cancer patients after gastrectomy. The only significant difference was a longer hospital stay for transfused patients (mean 20.5 da) compared to non-transfused patients (mean 16.2 da). The anticipated finding of a Th2 response after blood transfusion was not observed. A larger group of patients may be needed to document such an effect, since many confounding variables affect the morbidity and outcome of surgery in these patients.
UI - 21317183
AU - Jung HY; Jung KC; Shim YH; Ro JY; Kang GH
TI - Methylation of the hMLH1 promoter in multiple gastric carcinomas with microsatellite instability.
SO - Pathol Int 2001 Jun;51(6):445-51
AD - Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Hypermethylation of the hMLH1 promoter is observed in the majority of sporadic gastric carcinomas with high frequency microsatellite instability (MSI), and it contributes to the genesis of MSI-positive gastric carcinoma. Multiple gastric carcinoma is known to have a higher frequency of MSI positivity than single gastric carcinoma. However, the molecular basis of MSI in these tumors remains obscure. We investigated the role of hMLH1 promoter hypermethylation in the genesis of multiple gastric carcinoma with MSI. We analyzed 33 tumors from 15 patients with multiple gastric carcinoma (12 double tumors and three triple tumors) for MSI, expression of hMLH1 and hMSH2, and hypermethylation of hMLH1 and hMSH2 promoters. High frequency MSI was found in seven out of 33 tumors (21%) in five out of 15 patients (33%). All of the tumors with high frequency MSI had a lack of hMLH1 expression, with the presence of hMSH2 expression, while all the tumors with no MSI or low frequency MSI were positive for both hMLH1 and hMSH2. All of the tumors with no expression of hMLH1 had hMLH1 hypermethylation, whereas hMLH1 hypermethylation was observed in two out of 26 (8%) tumors with no or low frequency MSI. None of the tumors showed hMSH2 hypermethylation. These results suggest that epigenetic changes in the hMLH1 promoter account for the genesis of multiple gastric carcinoma with high frequency MSI.
UI - 21317187
AU - Jin Z; Tamura G; Satoh M; Meguro T; Miura T; Hayashi M; Osakabe M; Ohmura K; Ogata S; Endoh Y; Motoyama T
TI - Absence of BAT-26 instability in gastric intestinal metaplasia.
SO - Pathol Int 2001 Jun;51(6):473-5
AD - Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.
BAT-26 instability, a sensitive marker for the high-frequency microsatellite instability (MSI-H) phenotype, was analyzed in samples of gastric cancer and in adjacent intestinal metaplastic mucosae. Although all MSI-H gastric cancer samples showed BAT-26 instability, as assessed using 12 dinucleotide microsatellite markers, BAT-26 instability was not found in the adjacent intestinal metaplastic mucosa in any of the samples.
UI - 21385069
AU - Grabsch H; Takeno S; Noguchi T; Hommel G; Gabbert HE; Mueller W
TI - Different patterns of beta-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome.
SO - Histopathology 2001 Aug;39(2):141-9
AD - Institute of Pathology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Dusseldorf, Germany.
AIMS: The cadherin-catenin complex is known to play a critical role in maintenance of cell adhesion. Additionally beta-catenin (beta-ct) can also take part in signal transduction and nuclear beta-ct expression could be correlated with poor prognosis in several malignancies. Since, in gastric cancer, this role of beta-ct is still uncertain, we investigated the expression pattern of beta-ct as well as the possible prognostic role. METHODS AND RESULTS: beta-catenin expression was immunohistochemically investigated in a retrospective series of 401 R0-resected gastric carcinomas. Out of these cases, 54 tumours (13.5%) revealed a preserved membranous beta-ct expression similar to that in normal gastric mucosa. In 80 tumours beta-ct expression was moderately reduced and in 117 tumours highly reduced. In 150 tumours (37.4%), no or only a weak membranous beta-ct expression was found. Additionally, in 53 tumours, a strong beta-ct expression could be observed in the cytoplasm with a simultaneous nuclear beta-ct immunoreactivity in 17 of these 53 tumours, while nine tumours only showed nuclear immunoreactivity without cytoplasmic staining. There were no significant correlations between the degree of membranous beta-ct expression or the different staining pattern (membranous vs. cytoplasmic/nuclear) and the grade of tumour differentiation, the histological tumour type according to Lauren, as well as with the prognostic parameters pT, pN category and vascular invasion. No associations could be found with tumour cell proliferation and the expression of E-cadherin, irrespectively of the different beta-ct staining pattern. Univariate analysis revealed no influence on survival, either for membranous or for cytoplasmic/nuclear beta-ct expression. CONCLUSION: Our data on 401 tumours suggest that activation of the Wnt/beta-catenin signalling does also occur in a subset of gastric carcinomas. However, in gastric cancer, neither the presence of cytoplasmic/nuclear beta-ct expression nor the reduction or loss of membranous beta-ct expression is correlated with a specific histological tumour type, tumour progression or prognosis.
UI - 21255262
AU - Rembacken B; Fujii T; Kondo H
TI - The recognition and endoscopic treatment of early gastric and colonic cancer.
SO - Best Pract Res Clin Gastroenterol 2001 Apr;15(2):317-36
AD - Department of Gastroenterology, Centre for Digestive Diseases, The General Infirmary at Leeds, Great George Street, Leeds, LS16 8LT, UK.
As the prognosis of both gastric and colonic cancer remains poor, the challenge is to detect lesions at an early and treatable stage. The benefit of early detection is not only improved survival, but also that patients may be treated with endoscopic mucosal resection, a low-cost, low-morbidity and low-mortality alternative to surgery. In spite of the increasing use of endoscopy in the West, we are not detecting as many early cancers as in Japan. This chapter will discuss the possible reasons for this discrepancy and give a practical guide to 'Japanese endoscopy techniques'. Finally, we have compiled a comprehensive review of the indications, techniques and complications of endoscopic mucosal resection. Throughout the chapter, controversies have been highlighted to give an insight into the limits of our knowledge and stimulate future research. Copyright 2001 Harcourt Publishers Ltd.
UI - 21241494
AU - Chan JK; Wong CS
TI - Loss of E-cadherin is the fundamental defect in diffuse-type gastric carcinoma and infiltrating lobular carcinoma of the breast.
SO - Adv Anat Pathol 2001 May;8(3):165-72
AD - Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
UI - 21354117
AU - Medrado-Faria MA; Rodrigues de Almeida JW; Zanetta DM
TI - Gastric and colorectal cancer mortality in an urban and industrialized area of Brazil.
SO - Rev Hosp Clin Fac Med Sao Paulo 2001 Mar-Apr;56(2):47-52
AD - Discipline of Labor and Social Medicine, Oscar Freire Institute, Faculty of Medicine, University of Sao Paulo.
PURPOSE: To study the gastric and colorectal cancer mortalities and their relation to the urban-industrialization in Baixada Santista, located in the southeastern region of Brazil. METHODS: Selected from the registries of the State System of Data Analysis Foundation (SEADE) were 1105 deaths due to gastric cancer (ICD 153 - 154) and 690 due to colorectal cancer (ICD 151) that occurred from 1980 to 1993 in males, above 10 years of age, residing in Baixada Santista. For each of these types of cancer, the standardized mortality rates, age-adjusted by world population in the 1960s, for 4 industrialized and 4 non-industrialized urban communities in that region were calculated. The ratios among those rates were calculated in order to compare the mortality in the periods 1980 - 93, 1980 - 1986, and 1987 - 1993. RESULTS: Standardized mortality rates for colorectal cancer were significantly higher in industrialized area, with ratios of 1.6 [95% CI 1.22 - 2.29], 1.6 [95% CI 1.2 - 2.0], and 1.6 [95% CI 1.3 - 2.0] in the periods 1980 - 86, 1987 - 1993 and 1980 - 93, respectively. Gastric cancer did not show any statistical difference between the industrialized and non-industrialized areas, but there was a significant decrease in BS from the period 1980 - 1986 to 1987 - 1993. CONCLUSIONS: The significant elevation of colorectal cancer mortality in the industrialized area could be related to exposure to numerous carcinogens such as aromatic hydrocarbon, organic-chloride, metals, and industrial-port dust present in the region. Alternatively, the non-significant difference in gastric cancer between industrialized and non-industrialized areas and significant decrease in the last few years could be predominately reflecting the advances in the quality of life in urban areas. These results require further case-control studies that could help with the analysis of the associations among cancer and environmental factors (occupational, urban-industrial, habit, and life condition) and genetic susceptibility.
UI - 21181657
AU - Humphries TJ
TI - On gastric polyps, proton pump inhibitors and long-term risks.
SO - Aliment Pharmacol Ther 2001 Apr;15(4):559-60
UI - 20181099
AU - Elias D
TI - Reflections and proposals for the standardization of lymphadenectomy for gastric carcinoma.
SO - Eur J Surg Oncol 2000 Feb;26(1):6-10
AD - Department of Surgical Oncology, Institut Gustave Roussy, Comprehensive Cancer Center, Villejuif, France. email@example.com
In this paper, I consider: the value of various histological procedures; the feasibility and reproducibility of lymphadenectomies according to the Japanese Research Society for Gastric Cancer; the minimal number of lymph nodes (LNs) which should be resected for each type of lymphadenectomy; and the best way to present the results concerning the LN status. A reproducible lymphadenectomy is proposed for simplified anatomical level I (anterior plane, along the gastric curves) and level II (intermediate plane, along the gastric arteries), without spleno-pancreatectomy for the majority of cases. The LN status must be based on the total number of involved nodes, as recommended by the 1997 UICC classification. These simple, reproducible guidelines offer a basis for the standardization of procedures used for the treatment and classification of gastric carcinomas.
UI - 21111286
AU - Weston AP; Tran TN; Zoubine MN; Banerjee S; Banerjee SK
TI - Identification of genomic imbalances in gastric MALT lymphoma using arbitrarily primed PCR DNA fingerprinting.
SO - Int J Mol Med 2001 Mar;7(3):317-20
AD - Cancer Research Unit, Research Division, V.A. Medical Center, Kansas City, Missouri 64128, USA. firstname.lastname@example.org
Arbitrarily primed PCR (AP-PCR) is a unique method to identify the cancer cell specific losses and gains of chromosomal regions by targeting specific genes or chromosomal segments. In the present study, introducing the AP-PCR technique with a single primer, we have ascertained the gains and losses of DNA fingerprints in 15 MALT lymphoma samples. Out of 15 prominent DNA fingerprints, the signal intensity of two fingerprints, labeled bands G and I, were significantly lower in 40 and 50% of tumors as compared to adjacent normal DNA fingerprints, respectively. Similarly, gains of signal intensity of DNA fingerprints (bands A and C) were detected in 13% of tumor samples studied. Variations in signal intensities were also found in other bands within a few samples. Although, the functional importance of these bands is unknown, this study indicates that the AP-PCR generated under or over amplified DNA fingerprints may participate during the progression of MALT lymphoma in human stomach. Moreover, these studies also suggest that the AP-PCR technique, with different primers, can be utilized for the determination of new chromosomal segments in MALT lymphoma samples that can be used for the identification of these diseases.
UI - 21303173
AU - Vecchione A; Ishii H; Shiao YH; Trapasso F; Rugge M; Tamburrino JF; Murakumo Y; Alder H; Croce CM; Baffa R
TI - Fez1/lzts1 alterations in gastric carcinoma.
SO - Clin Cancer Res 2001 Jun;7(6):1546-52
AD - Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
PURPOSE: Loss of heterozygosity (LOH) involving the short arm of chromosome 8 (8p) is a common feature of the malignant progression of human tumors, including gastric cancer. We have cloned and mapped a candidate tumor suppressor gene, FEZ1/LZTS1, to 8p22. Here we have analyzed whether FEZ1/LZTS1 alterations play a role in the development and progression of gastric carcinoma. Experimental Design: We examined Fez1/Lzts1 expression in 8 gastric carcinoma cell lines by Western blot, and in 88 primary gastric carcinomas by immunohistochemistry. Twenty-six of these 88 primary gastric carcinomas were also microdissected and tested for LOH at the FEZ1/LZTS1 locus and for mutation of the FEZ1/LZTS1 gene. Furthermore, we studied the FEZ1/LZTS1 gene regulation and transcriptional control and the methylation status of the 5' region of the gene in all 8 gastric carcinoma cell lines. RESULTS: Fez1/Lzts1 protein was barely detectable in all of the gastric cancer cell lines tested and was absent or significantly reduced in 39 of the 88 (44.3%) gastric carcinomas analyzed by immunohistochemistry, with a significant correlation (P < 0.001) to diffuse histotype. DNA allelotyping analysis showed allelic loss in 3 of 17 (18%) and microsatellite instability in 4 of 17 (23.5%) cases informative for D8S261 at the FEZ1/LZTS1 locus. When we compared the presence of LOH with Fez1/Lzts1 expression, we found loss of protein expression in all three of the tumors with allelic imbalance at D8S261. A missense mutation was detected in one case that did not express Fez1/Lzts1. Hypermethylation of the CpG island flanking the Fez1/Lzts1 promoter was evident in six of the eight cell lines examined as well as in the normal control. CONCLUSIONS: Our findings support FEZ1/LZTS1 as a candidate tumor suppressor gene at 8p in a subtype of gastric cancer and suggest that its inactivation is attributable to several factors including genomic deletion and methylation.
UI - 21303186
AU - Yonemura Y; Fujimura T; Ninomiya I; Kim BS; Bandou E; Sawa T; Kinoshita K; Endo Y; Sugiyama K; Sasaki T
TI - Prediction of peritoneal micrometastasis by peritoneal lavaged cytology and reverse transcriptase-polymerase chain reaction for matrix metalloproteinase-7 mRNA.
SO - Clin Cancer Res 2001 Jun;7(6):1647-53
AD - Second Department of Surgery, School of Medicine, Kanazawa University, Kanazawa 920-8640, Japan. email@example.com
PURPOSE: Peritoneal dissemination is the most common cause of death associated with gastric cancer. In this study, we report the significance of molecular diagnosis of peritoneal dissemination by means of matrix metalloproteinase-7 (MMP-7) reverse transcriptase-PCR (RT-PCR) assay using preoperative peritoneal wash fluid. EXPERIMENTAL DESIGN: Preoperative peritoneal lavage by paracentesis was performed on 152 patients with gastric cancer. The peritoneal lavaged fluid was subjected to RT-PCR analysis with primers specific for MMP-7 and conventional cytological Papanicolaou examination. RESULTS: The MMP-7 RT-PCR assay was able to detect cancer cells at densities even lower than 10 cells/sample. There was no signal of MMP-7 mRNA from mesothelial cells, fibroblasts, peripheral blood, and lavaged fluid from patients with benign disease. Cytological examination and MMP-7 RT-PCR assay results were positive for 27 (18%) and 28 (18%) samples, respectively. The sensitivity for the prediction of peritoneal dissemination by cytology and MMP-7 RT-PCR assay were 46% and 33%, but the combination analysis using both parameters improved the sensitivity rate with 62%. Logistic regression analysis revealed that the cytological examination and MMP-7 RT-PCR assay are independent predictors of peritoneal dissemination. CONCLUSION: The combination of cytological examination and RT-PCR assay of preoperative peritoneal lavaged fluid is a highly efficient and reliable method for the selection of patients for adjuvant i.p. chemotherapy.
UI - 21416113
AU - McCulloch P
TI - Gastric cancer.
SO - Surg Oncol 2000 Jul;9(1):1-3
UI - 21416115
AU - Steele RJ; Lane DP
TI - Gene therapy for gastric cancer: problems and prospects.
SO - Surg Oncol 2000 Jul;9(1):13-6
AD - Department of Surgery and Molecular Oncology, University of Dundee, Scotland, UK.
UI - 21416116
AU - Sano T; Katai H; Sasako M; Maruyama K
TI - The management of early gastric cancer.
SO - Surg Oncol 2000 Jul;9(1):17-22
AD - Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan.
UI - 21416117
AU - Tschmelitsch J; Weiser MR; Karpeh MS
TI - Modern staging in gastric cancer.
SO - Surg Oncol 2000 Jul;9(1):23-30
AD - Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
UI - 21416119
AU - Stein HJ; Feith M; Siewert JR
TI - Cancer of the esophagogastric junction.
SO - Surg Oncol 2000 Jul;9(1):35-41
AD - Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universitat Munchen, Munich, Germany. firstname.lastname@example.org
In the Western world, there has been an alarming rise in the incidence and prevalence of adenocarcinoma arising at the esophagogastric junction during recent decades. Epidemiological, clinical and pathological data support a sub-classification of adenocarcinomas arising in the vicinity of the esophagogastric junction (AEG) into adenocarcinoma of the distal esophagus (Type I), true carcinoma of the cardia (Type II) and subcardial carcinoma (Type III). While most, if not all, adenocarcinomas of the distal esophagus arise from areas with specialized intestinal metaplasia, which develop as a consequence of chronic gastroesophageal reflux, the etiology and pathogenesis of true carcinoma of the gastric cardia and subcardial gastric cancer is not clear at present. Although a subgroup of true carcinomas of the gastric cardia may also develop within short segments of intestinal metaplasia at the esophagogastric junction, a causal relation between these tumors and gastroesophageal reflux has been difficult to establish. Irrespective of the etiology, a complete removal of the primary tumor and its lymphatic drainage has to be the primary goal of any surgical approach to adenocarcinoma of the esophagogastric junction. Our experience in the management of more than 1000 such patients during the past 18 years suggests that an individualized therapeutic strategy oriented by tumor type and stage results in survival rates superior to those reported with a more indiscriminate approach. This individualized strategy prescribes a transmediastinal esophagectomy with lymphadenectomy in the lower posterior mediastinum and along the celiac axis for Type I tumors, extended total gastrectomy with transhiatal resection of the distal esophagus and D2 lymphadenectomy for Type II and Type III tumors, a limited resection of the esophagogastric junction and distal esophagus with interposition of a pedicled jejunal segment for uT1N0 tumors, and neoadjuvant chemotherapy followed by resection for uT3/T4 tumors. Extensive preoperative staging is essential to allow correct selection of the appropriate therapeutic strategy using this tailored approach.
UI - 21416114
AU - Becker KF; Keller G; Hoefler H
TI - The use of molecular biology in diagnosis and prognosis of gastric cancer.
SO - Surg Oncol 2000 Jul;9(1):5-11
AD - Technische Universitaet Muenchen, Klinikum rechts der Isar, Institut fuer Pathologie, Munich, Germany. email@example.com
The investigation of molecular and genetic changes in gastric cancer has brought new insights into the pathogenesis of the disease. Knowledge of the genetic abnormalities and altered molecules could be used for differential diagnosis in case of an unknown primary tumor, allows their evaluation as prognostic factors, and could open novel avenues for more specific clinical interventions. Clinically relevant molecules whose expression or structure is altered include the plasminogen activator and its inhibitor plasminogen activator inhibitor type 1, the cell cycle regulator cyclin E, epidermal growth factor, the apoptosis inhibitor bcl-2, the cell adhesion molecule E-cadherin, and the multifunctional protein beta-Catenin. In addition, genetic instability is commonly seen. Gene amplification and protein overexpression of the growth factor receptors c-erbB2 and K-sam may be prognostic factors for intestinal- and diffuse-type gastric cancer, respectively. There has long been evidence for a genetic predisposition to gastric cancer by epidemiological studies and case reports. Very recently, germ line mutations of E-cadherin have been identified that are responsible for a dominantly inherited from of diffuse-type gastric cancer and could be used to identify individuals that are at high risk. The clinical implications of the recent findings for diagnosis, prognosis, therapy, and risk assessment are discussed.
UI - 21358742
AU - Guarner J; Mohar A
TI - [The association between Helicobacter pylori and gastric neoplasia. Epidemiologic evidence]
SO - Rev Gastroenterol Mex 2000 Oct-Dec;65(4 Suppl 2):20-4
AD - Division of Viral Rickettsial Diseases, Centers for Disease Control and Prevention, Mailstop G32 1600 Clifton Rd, NE. Atlanta, GA 30333, USA.
Helicobacter pylori (HP) causes chronic gastritis and, together with non-steroidal anti-inflammatory drugs, is considered the most frequent etiologic agent of peptic ulcer. Since there are numerous epidemiologic and pathogenesis studies that demonstrate an association between infection by HP and gastric neoplasias, the World Health Organization declared, in 1994, HP infection a Group 1 carcinogen (a definitive cause of human neoplasias, similar to tobacco). This article reviews the epidemiological evidence supporting the association between HP infection and two gastric neoplasias: adenocarcinoma and B cell lymphoma associated to mucosas (MALT). This article also presents preliminary results of a project performed in the mountainous region of Chiapas, Mexico, in which the decrease of precancerous gastric lesions were studied one year after treatment for HP infection.
UI - 21402260
AU - Matsushita M; Takakuwa H; Nishio A
TI - Characteristic endosonographic features of gastric inflammatory fibroid polyps.
SO - Endoscopy 2001 Aug;33(8):729-30
UI - 21404075
AU - Delchier JC; Lamarque D; Levy M; Tkoub EM; Copie-Bergman C; Deforges L; Chaumette MT; Haioun C
TI - Helicobacter pylori and gastric lymphoma: high seroprevalence of CagA in diffuse large B-cell lymphoma but not in low-grade lymphoma of mucosa-associated lymphoid tissue type.
SO - Am J Gastroenterol 2001 Aug;96(8):2324-8
AD - Services d'Hepatologie, Hjpital Henri Mondor, Creteil, France.
OBJECTIVE: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is closely related to Helicobacter pylori (H. pylori) infection. In vitro studies have demonstrated H. pylori-induced B cell proliferation to be strain dependent. High prevalences of CagA protein and FldA protein have been reported in strains obtained from patients with gastric lymphoma of MALT type. The aims of the present study were to evaluate the prevalence of H. pylori infection and to search for antigenic particularities in 53 patients with primary gastric lymphoma in comparison with a group of infected patients with benign disease. METHODS: Of the 53 patients, 37 presented with low-grade lymphoma of MALT type (LGLM) and 16 with diffuse large B-cell lymphoma (DLBCL). They were compared to a group of 162 H. pylori-infected subjects comprising the control group: 111 had gastric or duodenal ulcer (GDU) and 51 nonulcer dyspepsia (NUD). Diagnosis of gastric lymphoma was established on histological examination of endoscopic specimens. Anti-H. pylori antibodies were assayed by third-generation ELISA. Western blot assay was used to detect antibodies against nine antigens (including CagA protein), which were recognized on the basis of their molecular weight. RESULTS: Of the 53 patients with gastric lymphoma, 45 were H. pylori-positive (85%): of these, 25 (56.5%) had anti-CagA antibodies. The prevalence of H. pylori seropositivity was 78% (29/37) in LGLM and 100% (16/16) in DLBCL. The prevalence of CagA seropositivity in H. pylori-positive patients was 44.8% (13/29) and 75% (12/16), respectively (p < 0.05). In comparison, the seroprevalence of CagA was 77.4% (86/111) in GDU patients and 43.1% (22/53) in NUD patients. The prevalence of antibodies to other antigenic proteins detected with Helicoblot 2.0 (19.5kd, 30kd, 35kd, VacA, HSPb, Urease A, and Urease B) did not differ among the groups except for 35kd protein, which was significantly higher (p < 0.01) in GDU than in NUD and in LGLM (76.6% vs 49% and 46.7%). CONCLUSION: These findings suggest that in patients who develop gastric lymphomas in response to H. pylori, virulent strains expressing CagA protein are preferentially associated with DLBCL.
UI - 21404116
AU - Testino G
TI - Helicobacter pylori, cell proliferation, and carcinogenesis.
SO - Am J Gastroenterol 2001 Aug;96(8):2514
UI - 21402606
AU - Yamaji Y; Mitsushima T; Ikuma H; Okamoto M; Yoshida H; Kawabe T; Shiratori Y; Saito K; Yokouchi K; Omata M
TI - Inverse background of Helicobacter pylori antibody and pepsinogen in reflux oesophagitis compared with gastric cancer: analysis of 5732 Japanese subjects.
SO - Gut 2001 Sep;49(3):335-40
AD - Division of Gastroenterology, Department of Internal Medicine, University of Tokyo, Tokyo, Japan. firstname.lastname@example.org
BACKGROUND: The relationship between Helicobacter pylori and reflux oesophagitis remains controversial. AIMS: To evaluate the relationship between H pylori and reflux oesophagitis in a large number of Japanese subjects. SUBJECTS: A total of 5732 consecutive Japanese subjects during a health screening were enrolled. METHODS: Gastrointestinal endoscopy was performed on all subjects. We simultaneously measured serum anti-H pylori antibody and pepsinogen as markers of H pylori infection together with gastric atrophy. The risk of reflux oesophagitis was evaluated in relation to these markers, and the results were compared with those of gastric cancer. RESULTS: Reflux oesophagitis was found in 108 subjects. Both positivity for H pylori antibody (adjusted odds ratio (OR) 0.67 (95% confidence interval 0.45-1.0)) and "low" pepsinogen indicating gastric atrophy (OR 0.35 (0.18-0.68)) were negatively associated with reflux oesophagitis. After subjects were classified into four groups based on positivity or negativity for H pylori antibody and "low" pepsinogen, the prevalence of reflux oesophagitis showed a decreasing trend as H pylori induced gastric atrophy became more severe. The risk of gastric cancer showed an increasing trend, exactly the opposite to that of reflux oesophagitis. CONCLUSIONS: Analysis of a large series of Japanese subjects revealed a decreasing prevalence of reflux oesophagitis in conjunction with progress of gastric atrophy induced by H pylori infection. This pattern was completely opposite to that of gastric cancer cases. A protective role of H pylori for reflux oesophagitis through the development of gastric atrophy has been suggested.
UI - 21402608
AU - Helicobacter and Cancer Collaborative Group
TI - Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts.
SO - Gut 2001 Sep;49(3):347-53
BACKGROUND: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classification of cases as H pylori negative when they were infected in the past. AIMS: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection. To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. METHODS: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer. RESULTS: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to non-cardia cancers (OR 3.0; 95% CI 2.3-3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4-10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7-1.4). CONCLUSIONS: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated.
UI - 21409930
AU - Oue N; Shigeishi H; Kuniyasu H; Yokozaki H; Kuraoka K; Ito R; Yasui W
TI - Promoter hypermethylation of MGMT is associated with protein loss in gastric carcinoma.
SO - Int J Cancer 2001 Sep15;93(6):805-9
AD - First Department of Pathology, Hiroshima University School of Medicine, Hiroshima, Japan.
Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumor suppressor genes in neoplasms. Recently, O(6)-methylguanine-DNA methyltransferase, MGMT, was shown to be hypermethylated in certain carcinomas, resulting in loss of MGMT protein. We studied DNA methylation of CpG islands of the MGMT gene by methylation specific PCR in 26 gastric carcinoma tissues and 8 gastric carcinoma cell lines for comparison with levels of MGMT protein expression. In addition, we examined p53 mutation status in the same tissues by PCR-SSCP analysis for comparison with MGMT protein expression levels. In total, promoter hypermethylation of the MGMT gene was found in 8 (31%) of the 26 gastric carcinomas with reduced expression of MGMT protein, whereas the hypermethylation was not detected in the 18 carcinomas with non-reduced MGMT expression. MGMT protein expression levels were associated with promoter hypermethylation of MGMT (p = 0.0001; Mann-Whitney test); however, MGMT expression was not associated with p53 mutation status (p = 0.461; Mann-Whitney test). Among in gastric carcinoma cell lines, the TMK-1 cell line showed loss of the MGMT protein association with promoter hypermethylation and this loss was rectified by treatment with a demethylating agent, 5-Aza-2'-deoxycytidine. Our results suggest that transcriptional inactivation of MGMT by aberrant methylation of the promoter region may participate in carcinogenesis in the stomach. Copyright 2001 Wiley-Liss, Inc.
UI - 21413769
AU - zur Hausen A; van Grieken NC; Meijer GA; Hermsen MA; Bloemena E; Meuwissen SG; Baak JP; Meijer CJ; Kuipers EJ; van den Brule AJ
TI - Distinct chromosomal aberrations in Epstein-Barr virus-carrying gastric carcinomas tested by comparative genomic hybridization.
SO - Gastroenterology 2001 Sep;121(3):612-8
AD - Department of Pathology, Section Molecular Pathology, University Hospital Vrije Universiteit, Amsterdam, the Netherlands.
BACKGROUND & AIMS: Approximately 10% of gastric adenocarcinomas carry the human pathogenic Epstein-Barr virus (EBV). The role of EBV in the pathogenesis of these carcinomas remains to be established. METHODS: To obtain a comprehensive overview of chromosomal aberrations in EBV-carrying and EBV-negative gastric carcinomas we performed comparative genomic hybridization (CGH) on 44 gastric carcinomas, 10 EBV-positive, and 34 EBV-negative. Additionally, DNA flow cytometry was done. RESULTS: Loss of chromosome 4p (P < 0.001) and of 11p (P < 0.02) was exclusively restricted to EBV-carrying gastric carcinomas. In addition, loss of 18q (P < 0.02) was significantly more frequent in EBV-carrying gastric carcinomas. The latter involves loci, which have already been linked to gastric carcinogenesis such as the DCC and SMAD4 gene. In contrast, the losses on chromosome 4 and 11 do not yet harbor a gene related to gastric carcinogenesis. No significant correlation was found between DNA-ploidy and the EBV-status. A number of chromosomal aberrations were found at comparable frequencies in both groups, i.e., losses of chromosome 17, 12q, and loss of 1p. Interestingly, gains of 13q (10/34) and 3q (5/34) and loss of 1q (5/34) were solely observed in EBV-negative gastric carcinomas. CONCLUSIONS: These data indicate that EBV-carrying and EBV-negative gastric carcinomas have different pathogenetic pathways in which EBV might play a crucial role.
UI - 21413781
AU - Meltzer SJ
TI - Tumor genomics vs. tumor genetics: a paradigm shift?
SO - Gastroenterology 2001 Sep;121(3):726-9
UI - 21418114
AU - Uemura N; Okamoto S; Yamamoto S; Matsumura N; Yamaguchi S; Yamakido M; Taniyama K; Sasaki N; Schlemper RJ
TI - Helicobacter pylori infection and the development of gastric cancer.
SO - N Engl J Med 2001 Sep 13;345(11):784-9
AD - Department of Gastroenterology, Kure Kyosai Hospital, Kure City, Japan. email@example.com
BACKGROUND: Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. METHODS: We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. RESULTS: Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia were at significantly higher risk for gastric cancer. We detected gastric cancers in 21 (4.7 percent) of the 445 patients with nonulcer dyspepsia, 10 (3.4 percent) of the 297 with gastric ulcers, 5 (2.2 percent) of the 229 with gastric hyperplastic polyps, and none of the 275 with duodenal ulcers. CONCLUSIONS: Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpus-predominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.
UI - 21418123
AU - Fox JG; Wang TC
TI - Helicobacter pylori--not a good bug after all!
SO - N Engl J Med 2001 Sep 13;345(11):829-32
UI - 21433632
AU - Fukagawa T; Sasako M; Mann GB; Sano T; Katai H; Maruyama K; Nakanishi Y; Shimoda T
TI - Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma.
SO - Cancer 2001 Aug 15;92(4):753-60
AD - Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
BACKGROUND: Lymph node status is a major determinant of disease recurrence after patients undergo curative resection for gastric carcinoma. A proportion of patients without lymph node metastasis develop systemic recurrences. Recent studies in a range of solid tumors have found a high incidence of micrometastases in the regional lymph nodes of patients with apparently negative lymph nodes. In patients with breast and colorectal carcinoma, the presence of micrometastases has been associated with a poorer prognosis. In patients with gastric carcinoma, the significance of micrometastases in lymph nodes remains controversial. Most published reports on this subject suffer from the problems of small sample size and selection bias. METHODS: One hundred seven patients with pathologic T2N0M0 (tumor invades muscularis propria or subserosa [T2], no regional lymph node metastasis [N0], and no distant metastasis [M0]; pT2N0M0) gastric carcinoma who underwent gastric resection between 1984 and 1990 at the National Cancer Center Hospital were studied. Two consecutive sections were newly prepared from each lymph node for hematoxylin and eosin staining and immunohistochemical staining (IHC) with antibody against cytokeratin. Associations between clinicopathologic factors and the presence of micrometastases as well as micrometastases and survival were sought. RESULTS: Micrometastases were identified in 38 of 107 patients (35.5%) and in 87 of 4484 lymph nodes (1.94%) by IHC. The incidence of micrometastases was significantly higher in patients with infiltrative tumors than in patients with expansive, growing tumors (P = 0.02). Other clinicopathologic findings had no statistically significant correlation with the incidence of micrometastases. The 5-year survival rates of patients with and without micrometastases were 94% and 89%, respectively. Similarly, the 10-year survival rates were 79% and 74%, respectively. The survival curves of patients with or without micrometastasis were nearly superimposed (P = 0.86). CONCLUSIONS: The presence of immunohistochemically detected micrometastases in the regional lymph nodes did not affect the survival of Japanese patients with pT2N0M0 gastric carcinoma who had undergone gastrectomy with D2 lymph node dissection. Copyright 2001 American Cancer Society.
UI - 21423161
AU - Kocher HM; Linklater K; Patel S; Ellul JP
TI - Epidemiological study of oesophageal and gastric cancer in south-east England.
SO - Br J Surg 2001 Sep;88(9):1249-57
AD - Department of Surgery, Bromley Hospital NHS Trust, Bromley, UK. firstname.lastname@example.org
BACKGROUND: This epidemiological study was carried out to establish the magnitude of the changing incidence of gastric and oesophageal cancer. METHODS: Time-trend analyses of subsite-specific cancers of the oesophagus and stomach were performed using data from the Thames Cancer Registry database (1960-1996) for the South Thames Region. The changes in sex ratio and peak age of incidence are reported. RESULTS: In the upper two-thirds of the oesophagus there was no significant change in the incidence rate, but the lower third of the oesophagus showed a marked rise for both sexes (average annual change + 0.05 for men, + 0.009 for women). For the gastric cardia, the incidence in males increased (average annual change + 0.025), while in females it remained unchanged. Cancers of the oesophagogastric junction showed a clear increase for both sexes (average annual change + 0.07 for men, + 0.009 for women). There were changes in the sex ratio and peak age of incidence for all subsite cancers for both sexes. CONCLUSION: Over a 37-year period the incidence of cancer of the oesophagogastric junction increased threefold, while the incidence of cancers of the other subsites of the stomach decreased. Further studies are needed to investigate the aetiology of these changes.
UI - 21424081
AU - El-Zimaity HM; Ramchatesingh J; Saeed MA; Graham DY
TI - Gastric intestinal metaplasia: subtypes and natural history.
SO - J Clin Pathol 2001 Sep;54(9):679-83
AD - Gastrointestinal Mucosa Pathology Laboratory, VA Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA. email@example.com
BACKGROUND: It has been suggested that the subtyping of intestinal metaplasia in the stomach is useful in stratifying patients with regard to risk of developing gastric cancer. AIM: To determine whether subtyping intestinal metaplasia provided useful information regarding the natural history of intestinal metaplasia. METHODS: The study used large cup gastric biopsy specimens from predetermined locations (gastric mapping). Follow up biopsies were obtained at one, two, and/or nine years. Biopsies with intestinal metaplasia were stained with high iron diamine/Alcian blue (HID/AB) to determine whether they expressed neutral mucins, sialomucins, or sulphomucins. RESULTS: Seventy nine patients with intestinal metaplasia were studied and characterised with regard to the most advanced subtype of intestinal metaplasia. The most severe type of intestinal metaplasia was type II in 33 patients and type III in 34 patients. Helicobacter pylori was cured in 67 patients. Follow up showed that changes in type of metaplasia (apparent regression or progression) occurred in both directions and were independent of H pylori status. For example, biopsy sites with "loss" of metaplasia at a follow up visit might have it "reappear" at a subsequent visit. During follow up, no patient developed gastric dysplasia or died from gastric cancer. CONCLUSION: HID subtyping did not provide useful information to the clinician or the pathologist. The data are consistent with the notion that the pattern, extent, and severity of atrophy with/without intestinal metaplasia is a far