National Cancer Institute®
Last Modified: April 1, 2002
UI - 11197247
AU - Xia HH; Talley NJ
TI - Apoptosis in gastric epithelium induced by helicobacter pylori infection: implications in gastric carcinogenesis.
SO - Am J Gastroenterol 2001 Jan;96(1):16-26
AD - Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, NSW, Australia.
OBJECTIVES: Helicobacter pylori is an identified carcinogen for gastric cancer, however, the underlying mechanisms remain to be defined. In this review, we sought to elucidate the role of apoptosis in gastric carcinogenesis, to determine the influence of H. pylori infection on apoptosis, and finally to provide insights into the mechanisms by which H. pylori may lead to gastric carcinogenesis. METHODS: A broad-based MEDLINE and Current Contents literature search was performed to identify infection, apoptosis, cell proliferation, gastric carcinoma, oncogenes, and tumor suppressor genes, as well as the products of these genes. Abstracts from recent major conferences that provided adequate additional data were also included. RESULTS: Apoptotic cells are rare in the glandular neck region (the generative cell zone) of normal gastric mucosa. With progression of atrophic gastritis, the generative cell zone shifts downward and a relatively large number of apoptotic cells occur. In intestinalized glands, both apoptotic cells and proliferative cells are present in deeper portions of the glands, corresponding to the generative zone. A higher frequency of apoptosis has been observed in gastric dysplasia than in coexisting gastric carcinomas, whereas the number of proliferative cells is significantly higher in gastric carcinoma than in dysplasia. Upregulation of oncogene bcl-2 in premalignant lesions and "downregulation" of the gene after malignant change is probably a common event. Accumulation of p53 protein is first detected in dysplasia, although mutation of the pS3 gene may occur in intestinal metaplasia. H. pylori infection induces apoptosis in gastric epithelial cells, which returns to normal after eradication of the infection. Numerous molecules produced by H. pylori including cytotoxin (VacA), lipopolysaccharide, monochloramine, and nitric oxide may directly induce apoptosis. Moreover, H. pylori-stimulated host inflammatory/immune responses lead to release of a large amount of cytokines. Cytokines produced by type 1 T helper cells, such as TNF-alpha and IFN-gamma, markedly potentiate apoptosis. Gastric cell proliferation is significantly higher in patients with H. pylori infection than in normal controls, and eradication of the infection leads to a reduction in cell proliferation. Apoptosis and cell proliferation are also increased in precancerous lesions such as gastric atrophy, intestinal metaplasia, and dysplasia in the presence of H. pylori infection. However, H. pylori-induced apoptosis may no longer be cell cycle-dependent in these lesions because of the occurrence of alterations and mutations of apoptosis-regulating genes, resulting in a loss of balance between apoptosis and cell proliferation. CONCLUSIONS: It is hypothesized that H. pylori-induced apoptosis may play a key role in gastric carcinogenesis by increasing cell proliferation and/or resulting in gastric atrophy.
UI - 11686031
AU - Aiba K
TI - Upper gastrointestinal tumors.
SO - Cancer Chemother Biol Response Modif 2001;19():535-45
AD - Japanese Foundation for Cancer Research, Cancer Chemotherapy Center, Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo 170-8455, Japan.
UI - 11875724
AU - Cuschieri A; Talbot IC; Weeden S; MRC Upper GI Cancer Working Party
TI - Influence of pathological tumour variables on long-term survival in resectable gastric cancer.
SO - Br J Cancer 2002 Mar 4;86(5):674-9
AD - Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. firstname.lastname@example.org
Although tumour stage and nodal status are established prognostic factors for resectable gastric cancer, the relative importance of other pathological characteristics remains unclear. This study reports univariate and multivariate analyses of the prognostic value of various pathological and staging factors based on 324 patients entered into the MRC randomised surgical trial for gastric cancer. In the univariate analysis tumour stage, nodal status, UICC clinical stage, number of involved nodes, WHO predominant type, mixed Lauren type, Ming type, tumour differentiation, lymphocytic and tumour stromal eosinophilic infiltration were all found to have a significant impact on survival (logrank test, 5% level). In the multivariate analysis, UICC clinical stage and eosinophilic infiltration were found to have a significant influence. Risk of death increased for UICC stage II and III patients (Hazard Ratio for stage II compared to stage I=2.0, 95% Confidence Interval (CI) 1.4-2.9; Hazard Ratio for stage III compared to stage I=3.5, 95% CI 2.5-4.8). Patients with numerous eosinophils had a lower risk of death than those with none (Hazard Ratio=0.5, 95% CI 0.3-0.8). This association between survival and eosinophilic infiltration merits further study. Copyright 2002 Cancer Research UK
UI - 11875729
AU - Burgess DE; Woodman CB; Flavell KJ; Rowlands DC; Crocker J; Scott K;
TI - Biddulph JP; Young LS; Murray PG Low prevalence of Epstein-Barr virus in incident gastric adenocarcinomas from the United Kingdom.
SO - Br J Cancer 2002 Mar 4;86(5):702-4
AD - Department of Pathology, Division of Cancer Studies, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Epstein-Barr virus has been associated with a proportion of typical gastric adenocarcinomas. Here we report that the prevalence of Epstein-Barr virus in gastric adenocarcinomas from the United Kingdom is one of the lowest in the World. Gastric adenocarcinoma is another tumour whose association with Epstein-Barr virus varies with the population studied. Copyright 2002 Cancer Research UK
UI - 11875736
AU - Krieg A; Mahotka C; Krieg T; Grabsch H; Muller W; Takeno S; Suschek CV;
TI - Heydthausen M; Gabbert HE; Gerharz CD Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression.
SO - Br J Cancer 2002 Mar 4;86(5):737-43
AD - Institute of Pathology, Heinrich Heine-University, Moorenstr 5, D-40225, Duesseldorf, Germany.
Survivin is a novel member of the inhibitor of apoptosis family and determines the susceptibility of tumour cells to pro-apoptotic stimuli. Recently, we identified two novel alternative splice variants of survivin, differing in their anti-apoptotic properties: whereas the anti-apoptotic potential of survivin-DeltaEx3 is preserved, survivin-2B has lost its anti-apoptotic potential and may act as a naturally occurring antagonist of survivin. Because the in vivo expression of these alternative splice variants has not been explored so far, we analysed gastric carcinomas of different histological subtypes, grades and stages. Since no antibodies are currently available to determine the novel splice variants, quantitative reverse transcriptase polymerase chain reaction was performed, using RNA samples obtained from 30 different gastric carcinomas. Polymerase chain reactions products were quantified by densitometric evaluation. We found that all gastric carcinomas, irrespective of their histological types, grades or stages, express survivin-DeltaEx3, survivin-2B and survivin, the latter being the dominant transcript. Comparing the disease stages I+II with III+IV, expression of survivin and survivin-DeltaEx3 remained unchanged. In contrast, a significant (P=0.033) stage-dependent decrease in the expression of survivin-2B became evident. Our study demonstrates for the first time the expression of alternative splice variants in gastric carcinomas and provides a first clue to a role of survivin-2B in tumour progression. Copyright 2002 Cancer Research UK
UI - 11891177
AU - Kang GH; Lee S; Kim WH; Lee HW; Kim JC; Rhyu MG; Ro JY
TI - Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma.
SO - Am J Pathol 2002 Mar;160(3):787-94
AD - Department of Pathology, Seoul NationalUniversity College of Medicine and Cancer Research Institute, Seoul, Korea. email@example.com
CpG island methylation is an important mechanism for inactivating the genes involved in tumorigenesis. Gastric carcinoma (GC) is one of the tumors that exhibits a high frequency of aberrant CpG island methylation. There have been many reports suggesting a close link between Epstein-Barr virus (EBV) and the development of GC. However, little is known about the oncogenic mechanism of EBV in gastric carcinogenesis. Twenty-one cases of EBV-positive GC and 56 cases of EBV-negative GC were examined for aberrant DNA methylation of the CpG islands of 19 genes or loci and the differences in the methylation frequency between EBV-positive and -negative GCs were investigated to determine a role of aberrant methylation in EBV-related gastric carcinogenesis. The average number of methylated genes or loci was higher in EBV-positive GCs than in EBV-negative GCs (13.4 versus 7.8, respectively, P < 0.001). EBV-positive GCs showed methylation in at least 10 CpG islands (52.6% of the tested genes), whereas 62.5% of EBV-negative GCs showed methylation in <10 CpG islands. THBS1, APC, p16, 14-3-3 sigma, MINT1, and MINT25 were methylated at a frequency >90% in EBV-positive GCs. The methylation frequency difference in the respective CpG islands between EBV-positive and -negative GCs was statistically significant (P < 0.05). Among these genes or loci, the methylation frequency of p16 in the EBV-positive GCs was more than three times higher than in the EBV-negative GCs. The PTEN, RASSF1A, GSTP1, MGMT, and MINT2 were methylated in EBV-positive GCs at a frequency of more than three times that of the EBV-negative GCs. These results demonstrate a relationship between EBV and aberrant methylation in GC and suggest that aberrant methylation may be an important mechanism of EBV-related gastric carcinogenesis.
UI - 11906123
AU - Kim H; Takashima S; Kaminou T; Hayashi S; Nishida N; Matsuoka T;
TI - Nakamura K; Yamada R Clinical studies on the visualization of gastric lesions using virtual CT endoscopy.
SO - Osaka City Med J 2001 Dec;47(2):115-26
AD - Department of Radiology, Osaka City University Medical School, Osaka, Japan.
OBJECTIVE: We evaluated the clinical usefulness of virtual CT gastroendoscopy (VCTGE). METHODS: The subjects were 124 patients with endoscopically identified gastric lesions. VCTGE images were obtained using a GE-Navigator. We evaluated VCTGE in the visualization of gastric lesions for their presence and morphology. RESULTS: The detection rate of all gastric lesions by VCTGE was 76% (94 of 124 patients). The smallest detectable early gastric cancer was II c measuring 10 x 8 mm. The detection rates of each gastric lesion by VCTGE were 73% in early gastric cancer, and 90% in advanced gastric cancer. VCTGE imaging in the advanced gastric cancer was good in 12 (30%), fair in 25 (60%) and poor in 4 (10%). VCTGE imaging in early gastric cancer was good in 20 (46%), fair in 12 (27%) and poor in 12 (27%). The significance P level was 0.005 between the evaluation of the imaging of advanced and early gastric cancer. CONCLUSIONS: VCTGE visualized the characteristics of diverse gastric lesions and was considered useful for the detection and the diagnosis of these lesions.
UI - 10049413
AU - Kolve M; Fischbach W; Greiner A; Wilms K
TI - Differences in endoscopic and clinicopathological features of primary and secondary gastric non-Hodgkin's lymphoma. German Gastrointestinal Lymphoma Study Group.
SO - Gastrointest Endosc 1999 Mar;49(3 Pt 1):307-15
AD - Medizinische Poliklinik, University of Wurzburg, Germany.
BACKGROUND: Lymphomatous neoplasia of the stomach is initially seen either as primary gastric B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) or as nodal non-Hodgkin s lymphoma (NHL) secondarily involving the GI tract. One hundred seventy-six patients with primary gastric NHL (low grade, n = 65; high grade, n = 111) and 29 with secondary gastric NHL (low grade, n = 19; high grade, n = 10) were studied to evaluate whether differences in pathogenesis are associated with distinct clinical and endoscopic features. METHODS: Clinical features, tumor size, localization, and growth pattern were analyzed by means of esophagogastroduodenoscopy; grading was determined with histologic examination. RESULTS: The analysis of various clinical symptoms and endoscopic findings revealed a relationship between the occurrence of abdominal pain, vomiting, and unifocal growth pattern with an affiliation to the group with primary gastric NHL (p < 0.001), whereas tumor localization in the gastric fundus was predominantly found in secondary gastric NHL (p < 0.001). An equation has been generated that may help to predict affiliation to primary or secondary gastric NHL with an accuracy of 96%. CONCLUSIONS: Our results indicate that careful pretreatment analysis of clinical and endoscopic findings may be helpful in the diagnosis of primary or secondary gastric involvement by NHL, although reliable discrimination still requires histologic verification.
UI - 11484286
AU - Belchev B
TI - [Esophagojejunostomy after Roux following gastrectomy for cancer of the stomach]
SO - Khirurgiia (Sofiia) 2000;56(2):36-7
Not big number of cases (17) operated for cardia cancer are subject of retrospective analyzing. Ezophagoejunoanastomosis by termino-lateral plastic, type of Roux is realized in more of cases (9). Termino-terminal junction and this after proximal gastric resection performed on hand, are subject of discussion.
UI - 11852408
AU - Huntsman D; Carneiro F; Lewis F; MacLeod P; Hayashi A; Monaghan K; Maung
TI - R; Seruca R; Jackson C; Caldas C [Prophylactic gastrectomy in patients with deleterious E-cadherin gene mutation]
SO - Gastroenterol Clin Biol 2001 Oct;25(10):931-2
AD - Hopital Europeen Georges-Pompidou, Paris, France.
UI - 11902529
AU - Du MQ; Isaccson PG
TI - Gastric MALT lymphoma: from aetiology to treatment.
SO - Lancet Oncol 2002 Feb;3(2):97-104
AD - Department of Histopathology, Royal Free and University College Medical School, University College London, UK. firstname.lastname@example.org
The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is dependent on Helicobacter pylori infection. Bacterial colonisation of the gastric mucosa triggers lymphoid infiltration and the formation of acquired MALT. The bacterial infection induces and sustains an actively proliferating B-cell population through direct (autoantigen) and indirect (intratumoral T cells specific for H. pylori) immunological stimulation. Moreover, the bacterial infection provokes a neutrophilic response, which causes the release of oxygen free radicals. These reactive species may promote the acquisition of genetic abnormalities and malignant transformation of reactive B cells. A transformed clone carrying the translocation t(1;18)(q21;q21) forms a MALT lymphoma, the growth of which is independent of H. pylori and will not respond to bacterial eradication. Malignant clones without t(11;18)(q21;q21), but with other genetic abnormalities, such as trisomy 3 or microsatellite instability, depend critically on immune stimulation mediated by H. pylori for their clonal expansion. In the early stages, the tumour can be successfully treated by eradication of the bacterium, whereas at later stages the tumour may escape its growth dependency through acquisition of additional genetic abnormalities such as t(1;14)(p22;q32) and t(1;2)(p22,p12) involving the BCL-10 gene. Finally, further genetic abnormalities, such as inactivation of the tumour suppressor genes, p53 and p16, can lead to high-grade transformation. Detection of these abnormalities may help with the clinical management of patients with gastric MALT lymphoma.
UI - 11896205
AU - Laghi L; Ranzani GN; Bianchi P; Mori A; Heinimann K; Orbetegli O; Spaudo
TI - MR; Luinetti O; Francisconi S; Roncalli M; Solcia E; Malesci A Frameshift mutations of human gastrin receptor gene (hGARE) in gastrointestinal cancers with microsatellite instability.
SO - Lab Invest 2002 Mar;82(3):265-71
AD - Division of Gastroenterology, Istituto Clinico Humanitas, Rozzano-Milan, Italy.
Gastrointestinal tumors with DNA mismatch repair (MMR) defects show microsatellite instability (MSI) and harbor frameshift mutations in coding mononucleotide repeats of cancer-related genes (targets). We assessed MSI status in 233 sporadic gastrointestinal tumors. We classified as MSI-H (high-frequency microsatellite instability) 15 (10%) of 150 colorectal cancers and 13 (16%) of 83 gastric cancers. We searched for frameshift mutations in a coding poly(T)(8) tract within the gastrin receptor gene (hGARE), which has a potential role in gastrointestinal carcinogenesis. To this purpose, we screened 43 unstable tumors (including 15 hereditary nonpolyposis colorectal cancer cases previously classified as MSI-H), 98 stable tumors, as well as 3 MMR-deficient and 4 MMR-proficient gastrointestinal cancer cell lines. We found mutations in 8 (19%) of the 43 MSI-H tumors but in none of the 98 stable cancers. hGARE mutation frequency was similar in gastric (23%) and colorectal cancers, including sporadic (13%) and hereditary (20%) cases. All mutated tumors proved to harbor frameshift mutations in other cancer-related genes that are considered as targets in MSI tumorigenesis. The MMR-deficient and gastrin-sensitive LoVo colorectal cancer cells also showed a hGARE heterozygous frameshift mutation, but expressed only the mutated allele. All detected mutations can be predicted to generate a truncated protein carrying amino acid changes. On the basis of genetic findings, we propose hGARE as a new candidate target gene in MSI tumorigenesis. Functional studies are warranted to elucidate the mechanism by which the hGARE mutation might contribute to gastrointestinal carcinogenesis.
UI - 11896207
AU - Kang YH; Lee HS; Kim WH
TI - Promoter methylation and silencing of PTEN in gastric carcinoma.
SO - Lab Invest 2002 Mar;82(3):285-91
AD - Cancer Research Institute, Seoul National University College of Medicine and BK21 Project for Medicine, Dentistry and Pharmacy, Seoul, Korea.
The PTEN/MMAC1/TEP1 gene (phosphatase and tensin homolog deleted on chromosome 10/mutated in multiple advanced cancers/TGF-beta regulated and epithelial cell enriched phosphatase 1), which regulates the signaling pathways of Akt, is a novel tumor suppressor gene implicated in multiple cancers. Because a number of tumor suppressor genes are known to be silenced by aberrant promoter methylation, we examined the methylation status of the 5' CpG islands of PTEN using methylation-specific PCR. The altered expression of PTEN in 310 gastric carcinomas was analyzed by immunohistochemical staining using tissue-array and clinicopathologic profiles related to PTEN expression were characterized. Of 310 consecutive gastric carcinomas, 62 cases (20%) showed expression loss of PTEN. Altered PTEN expression was significantly associated with tumor depth and size, lymphatic invasion, advanced stage, pTNM stage, and patient survival (p < 0.001). The promoter methylation frequency of PTEN was found to be present in 26 (39%) of 66 cases examined, and 19 (73%) of 26 gastric cancer tissues showing promoter methylation exhibited the loss of PTEN expression. Abnormalities in the expression of PTEN significantly correlated with promoter methylation (p < 0.001). In conclusion, silencing of the PTEN gene occurs frequently in gastric carcinoma and aberrant promoter methylation is a major mechanism of silencing of the PTEN gene. The abnormalities of the PTEN gene are associated with tumor progression, metastasis, and survival.
UI - 11695220
AU - Kikuchi S; Matsuzaki H; Kurita A; Kobayashi N; Shimao H; Sakakibara Y;
TI - Sato K; Kakita A Tumor volume as an indicator of nodal status in advanced gastric carcinoma.
SO - In Vivo 2001 Jul-Aug;15(4):295-8
AD - Department of Surgery, School of Medicine, Kitasato University, 1-15-1, Kitasato, Sagamihara-shi, Kanagawa 228, Japan.
BACKGROUND: The significance of tumor volume as an indicator of lymph node metastasis in advanced gastric cancer remains to be clarified. MATERIALS AND METHODS: Tumor volume was measured from continuous tissue sections taken from 60 patients with advanced gastric cancer (34 males and 26 females, aged 35 to 81 years; average 57.3 years) using a computer generated surface rendering method. The tumor volume and conventional clinicopathological factors were then analyzed with respect to the prevalence of lymph node metastasis. RESULTS: Lymph node metastasis was detected in 26 patients (43%). Of 28 patients with a tumor > or = 2000 mm3, lymph node metastasis was observed in 17 patients (61%): n1, 12 patients; n2, 3 patients; n3, 2 patients. Of 32 patients with a tumor < 2000 mm3, lymph node metastasis was observed in 9 patients (28%): n1, 6 patients; n2, 3 patients. A significant difference was found in the prevalence of lymph node metastasis between the two groups (p = 0.011). Furthermore, only tumor volume was an independent variable associated with lymph node metastasis according to logistic regression analysis (p = 0.013, odds ratio: 0.253, 95% confidence interval: 0.086-0.747). CONCLUSION: Tumor volume appears to be an important indicator of lymph node metastasis in advanced gastric cancer. However, this factor cannot be used to introduce the option of limited lymphadenectomy for such patients.
UI - 11788899
AU - Saitoh T; Mine T; Katoh M
TI - Up-regulation of WNT8B mRNA in human gastric cancer.
SO - Int J Oncol 2002 Feb;20(2):343-8
AD - Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
WNT - beta-catenin - TCF signaling pathway is activated by Xenopus wnt-8 (Xwnt-8) during Xenopus early development, and dysregulated activation of beta-catenin - TCF signaling pathway in mammalian cells leads to carcinogenesis. We have previously cloned and characterized human WNT8A, one of human orthologues of Xwnt-8. Here, we cloned and characterized human WNT8B by using bioinformatics, cDNA-PCR, and RACE. WNT8B gene of about 23-kb in size consisted of six exons, and encoded a 351-amino-acid polypeptide with the N-terminal signal peptide and two N-linked glycosylation sites. C-terminal region of WNT8B, WNT8A, WNT2, and WNT2B were longer than that of other human WNTs. Thirty-five nucleotide changes between WNT8B isolated by us and WNT8B isolated by another group resulted in Gly230Ala and Arg284Leu amino-acid substitutions. Gly230 and Arg284 of WNT8B were conserved in WNT8A. Gly230-Arg284 WNT8B allele was also identified in human genome draft sequences AL133352.10, AL359759.18, and human EST BF732616. These results indicate that the Gly230-Arg284 WNT8B cDNA isolated in this study is derived from the more common WNT8B allele. WNT8B mRNAs of 4.4- and 3.5-kb in size were weakly detected in a colorectal cancer cell line SW480, but were undetectable in any normal human tissues by using Northern blot analyses. WNT8B was significantly up-regulated in gastric cancer cell lines KATO-III (signet-ring cell carcinoma) and MKN45 (poorly differentiated adenocarcinoma), and also in 5 out of 10 cases of primary gastric cancer. WNT8B might play key roles in gastric cancer through activation of the beta-catenin - TCF signaling pathway.
UI - 11865368
AU - Ichikura T; Morita D; Uchida T; Okura E; Majima T; Ogawa T; Mochizuki H
TI - Sentinel node concept in gastric carcinoma.
SO - World J Surg 2002 Mar;26(3):318-22
AD - Department of Surgery I, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa 359-8513, Japan.
To assess the applicability of the sentinel node concept to gastric carcinoma. The location of metastatic lymph nodes was analyzed retrospectively in 119 patients with gastric carcinoma in whom metastasis was limited to one or two nodes. Intraoperative lymphatic mapping was attempted in 62 patients using indocyanine green injected endoscopically into the gastric submucosa adjacent to the tumor. Metastatic lymph nodes were distributed beyond the perigastric area in 4% of patients with a single node involved. The positive node was located along the greater curvature in 21% of the patients with a tumor on the lesser curvature. Two patients had a metastatic node totally occupied by cancer tissue. In 16% of patients with two nodes involved, a positive node was located on both the lesser and greater curvatures. Lymphatic mapping was successful in all subjects. A larger number and wider distribution of green-stained nodes were observed in patients injected with 8 ml of indocyanine green solution than in those injected with 4 ml. No metastasis was observed in any nodes in 47 (96%) of the 49 patients who had no metastasis in green nodes. In one patient showing metastasis in non-green nodes without metastasis in green nodes, the positive nodes were totally occupied by cancer tissue. Our results showed the complexity of lymphatic streams within and from the stomach. Lymphatic mapping using indocyanine green can be a tool for identifying sentinel nodes in gastric carcinoma although lymph nodes occupied by cancer tissue may not be detected by this technique.
UI - 11865369
AU - Hyung WJ; Noh SH; Yoo CH; Huh JH; Shin DW; Lah KH; Lee JH; Choi SH; Min
TI - JS Prognostic significance of metastatic lymph node ratio in T3 gastric cancer.
SO - World J Surg 2002 Mar;26(3):323-9
AD - Department of Surgery, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-ku, 120-752 Seoul, Korea.
The fifth International Union Against Cancer tumor node metastasis (UICC TNM) classification, based on the number of metastatic lymph nodes (LN), has proved to be a reliable and objective method for predicting the prognosis of patients with gastric cancer. However, the prognosis of patients with T3 gastric cancer is still heterogeneous. This study was carried out to investigate the validity of metastatic LN ratio as a prognostic factor in T3 gastric cancer. A retrospective analysis was performed on a total of 833 patients that had either T3N1M0 (n = 504) or T3N2M0 (n = 329) gastric cancer by the fifth UICC classification. A preliminary analysis revealed the cutoff values for T3N1M0 to be 10% and for T3N2M0 to be 25%. The mean metastatic LN ratio was 9.0% for T3N1M0 cancer and 26.9% for T3N2M0 cancer. For the T3N1M0 stage, the patients who showed less than 10% of the metastatic LN ratio were grouped as N1-low with the others grouped as N1-high. For the T3N2M0 stage group, those who had less than 25% of the metastatic LN ratio were grouped as N2-low, the remainder as N2-high. The metastatic LN ratio decreased in proportion to the extent of lymphadenectomy and it increased in relation to the increasing scale of the fourth N classification. The rates of recurrence were significantly different according to the metastatic LN ratio in N1 and N2 classification of the fifth UICC classification (p < 0.05). The 5-year survival rates after gastrectomy decreased significantly by increasing the metastatic LN ratio in both T3N1M0 cancers (p =0.0026) and T3N2M0 cancers (p = 0.0057). The metastatic LN ratio was an independent risk factor for recurrence and poor prognosis. Our data suggest that the metastatic LN ratio is a significant prognostic factor for T3 gastric cancer. Furthermore, the application of the metastatic LN ratio can provide information not only about the extent of LN metastasis but also about the extent of lymphadenectomy in T3 gastric cancer.
UI - 11865370
AU - Nogueira C; Silva AS; Santos JN; Silva AG; Ferreira J; Matos E; Vilaca H
TI - Early gastric cancer: ten years of experience.
SO - World J Surg 2002 Mar;26(3):330-4
AD - Surgery Department, Surgery 1, Hospital Geral de Santo Antonio, Largo Prof. Abel Salazar, 4000 Oporto, Portugal. email@example.com
Gastric cancer is a disease in which the main treatment is surgical extirpation. The modifications introduced in the surgical treatment over the last decades were accompanied by a clear increase of survival, which reaches global values of 61% at 5 years in Japan. One of the reasons that contribute to this improvement is early diagnosis of the lesions. In the period between January 1, 1990 and December 31, 1999 662 patients with gastric adenocarcinoma were treated in the Service of Surgery 1 of our hospital; 110 were refused surgical treatment. Of the resected patients, 91 (21.4%) were classified as early gastric cancer according to the definition of the Japanese Society of Digestive Endoscopy. There were 30 women and 61 men, with a median age of 60.2 +/- 15 years; 3 patients had a preoperative diagnosis of gastric ulcer; 2 others were operated without recent histology; and 1 patient was urgently resected for a bleeding ulcer. In all the remaining patients biopsy confirmed the presence of cancer (89%) or serious dysplasia (4.6%). The lesions had been distributed essentially in the medium 1/3 (48.3%) and distal 1/3 of the stomach. Subtotal gastrectomy was accomplished in 48 patients, total gastrectomy in 40, total desgastrogastrectomy in 3, and in 9 patients the surgery involved the spleen (8 patients) and the spleen and tail of the pancreas in 1 patient. Lymphadenectomy was not performed in 5 patients, lymph nodes by the first lymph node barrier were removed in 25 patients and by the second barrier in 61 patients (67%). Median tumor size was 26 +/- 1.8 mm. The lesion reached the mucosa in 46 patients and the mucosa and submucosa in 45. In 6 patients the removed lymph nodes were microscopically invaded (6.7%). Five patients died (5.7%). The median follow-up of the patients is 41 +/- 26 months; 7 patients died (8.1%) during this period; 4 died unequivocally of disease progression. The median survival of patients was 85% at 5 years and 80% at 10 years. In our series, survival was affected by the presence of invaded lymph nodes, not by the penetration in depth of the lesion or the size of the tumor.
UI - 11911346
AU - Sato Y; Iwafuchi M; Ueki J; Yoshimura A; Mochizuki T; Motoyama H;
TI - Sugimura K; Honma T; Narisawa R; Ichida T; Asakura H; Van T Gastric carcinoid tumors without autoimmune gastritis in Japan: a relationship with Helicobacter pylori infection.
SO - Dig Dis Sci 2002 Mar;47(3):579-85
AD - Third Department of Internal Medicine, Faculty of Health Science, Niigata University School of Medicine, Japan.
In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.
UI - 11565793
AU - Sinha P; Poland J; Schnolzer M; Celis JE; Lage H
TI - Characterization of the differential protein expression associated with thermoresistance in human gastric carcinoma cell lines.
SO - Electrophoresis 2001 Aug;22(14):2990-3000
AD - Institut fur Laboratoriumsmedizin und Pathobiochemie, Universitatsklinikum Charite, Berlin, Germany. firstname.lastname@example.org
Resistance to chemotherapeutic agents is one of the major problems faced during palliative therapy of tumor cells. Thus, chemotherapy is frequently combined with other modes of therapy such as radiation therapy and/or hyperthermia. Tumor cells respond to heat stress with development of thermotolerance and the interactions between chemo- and thermoresistance phenomena are not clearly understood. In this paper, we analyze the differential protein expression in vitro in human stomach cancer cells, their chemoresistant and thermoresistant counterparts using proteomics. The immediate aim was to identify sets of proteins that may lead to the development of thermoresistance. Based on these results, we aim to develop functional tests and methods for the modulation of thermoresistance and chemoresistance phenomena that may assist the therapy of inoperable cancers.
UI - 11869324
AU - Flett ME; Lim MN; Bruce D; Campbell SH; Park KG
TI - Prognostic value of laparoscopic ultrasound in patients with gastro-esophageal cancer.
SO - Dis Esophagus 2001;14(3-4):223-6
AD - Department of Surgery, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK.
Forty-four patients with gastro-esophageal tumors regarded as resectable by conventional staging underwent laparoscopic ultrasonography (LUS). Following LUS, seven were found to be irresectable and were managed by palliative therapies. Thirty-seven patients proceeded to surgical exploration and 36 were resected (R0 80%, R1 11%, and R2 9%). All patients were reviewed until death or for a minimum of 24 months. Patients undergoing resection had a 62% 1-year survival (median 17 months; confidence intervals, CI 6-28). LUS defined nodal status indicated a trend toward prolonged survival in the node-negative group, median 22 months (CI 5-39), compared with 13 months (CI 6-20) in the node-positive group. Disease-free survival was greater in LUS node-negative patients at 29 months (CI 23-35) compared with node-positive patients at 13 months (CI 5-21) P=0.0083. LUS staging allows prediction of the likelihood of recurrence of gastro-esophageal malignancies. This may prove useful for the appropriate allocation of patients to primary and adjuvant therapies.
UI - 11054376
AU - Fischbach W; Dragosics B; Kolve-Goebeler ME; Ohmann C; Greiner A; Yang
TI - Q; Bohm S; Verreet P; Horstmann O; Busch M; Duhmke E; Muller-Hermelink HK; Wilms K; Allinger S; Bauer P; Bauer S; Bender A; Brandstatter G; Chott A; Dittrich C; Erhart K; Eysselt D; Ellersdorfer H; Ferlitsch A; Fridrik MA; Gartner A; Hausmaninger M; Hinterberger W; Hugel K; Ilsinger P; Jonaus K; Judmaier G; Karner J; Kerstan E; Knoflach P; Lenz K; Kandutsch A; Lobmeyer M; Michlmeier H; Mach H; Marosi C; Ohlinger W; Oprean H; Pointer H; Pont J; Salabon H; Samec HJ; Ulsperger A; Wimmer A; Wewalka F Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.
SO - Gastroenterology 2000 Nov;119(5):1191-202
AD - Medizinische Klinik II, Klinikum Aschaffenburg, Aschaffenburg, Germany.
BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.
UI - 11885923
AU - Jedrychowski W; Popiela T; Steindorf K; Tobiasz-Adamczyk B; Kulig J;
TI - Penar A; Wahrendorf J Nutrient intake patterns in gastric and colorectal cancers.
SO - Int J Occup Med Environ Health 2001;14(4):391-5
AD - Collegium Medicum, Jagiellonian University, Cracow, Poland. email@example.com
The purpose of the study was to present the dietary risk pattern in gastric and colorectal cancers, using the same methodological approach in a parallel hospital-based case-control study. In all, 180 cases of colorectal cancer and 80 cases of stomach cancer, confirmed histopathologically, were enrolled from the University Hospital in Cracow. A high intake of carbohydrates was associated with an increased risk of colorectal cancer (OR = 2.45). For stomach cancer, a moderate consumption of carbohydrates markedly increased relative risk (OR = 4.29), while a high intake of carbohydrates increased the risk by 8.73. The patterns of dietary risk factors related to intake of fats were definitively different in both cancer sites. The higher fat consumption was not associated with the higher risk of stomach cancer. A medium intake of fats increased the risk of colorectal cancer by 1.96 and that above 83 g/day by 2.20. In colorectal cancer, the significant protective effect of retinol, carotene and vitamin C has been evidenced, however, only carotene and vitamin E were inversely correlated with stomach cancer.
UI - 11888878
AU - Yasuda K; Inomata M; Fujii K; Shiraishi N; Adachi Y; Kitano S
TI - Superficially spreading cancer of the stomach.
SO - Ann Surg Oncol 2002 Mar;9(2):192-6
AD - Department of Surgery I, Oita Medical University, Oita, Japan. firstname.lastname@example.org
BACKGROUND: Superficially spreading cancer (SSC) of the stomach is rare and extends widely along the mucosa or submucosa of the stomach. This study was conducted to clarify the clinicopathologic characteristics and prognosis of patients with SSC. METHODS: SSC was defined as a tumor invading the mucosa or submucosa and measuring > or =5 cm in size. The clinicopathologic findings and outcomes of 36 patients with SSC were compared with those of 300 patients with early gastric cancer (EGC) measuring < or =5 cm and 271 with advanced gastric cancer measuring > or =5 cm. RESULTS: SSC was significantly different from ordinary EGC in tumor size, frequency of lymph node metastasis, lymphatic invasion, venous invasion, and stage II, III, and IV disease. The frequency of serosal invasion, lymph node metastasis, and lymphatic and venous invasions in cases of SSC was significantly lower than with advanced gastric cancer. Although tumor size of SSC evaluated before operation was smaller than that on the resected specimen, the 10-year survival rate was not different between SSC and ordinary EGC. CONCLUSIONS: SSC was characterized by high frequency of lymp