• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2703-2706
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• 2013

Purpose: This study was to determine the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic gastric cancer who failed to respond to first and (or) second line chemotherapy. Patients and Methods: Metastatic gastric cancer patients who failed first and (or) second line chemotherapy, were enrolled. All patients were recruited from Jiangsu Cancer Hospital & Research Institute, and were treated with pemetrexed $500mg/m2$ (intravenous; on day 1), and a platinum (or irinotecan) every 3 weeks until disease progression, or intolerable toxicity. Evaluation on efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: From Jun 2011 to May 2013, 23 patients were enrolled. All eligible 23 patients completed at least 2 cycles of chemotherapy with pemetrexed based chemotherapy, and were evaluable. Their median age was 55 years (range 40 to 78 years). Seventeen patients were male and 6 female. Three patients (13%) achieved partial response, five patients (22%) stable, 15 patients (65%) with disease progression, and none with complete response. Grade 2 neutrophil suppression occurred in 4.3%, grade 3 in 13% of patients, and no grade 4 was reported. Thrombocytopenia was encountered as follows: 4.3% grade 2, 4.3% grade 3 and 4.3% grade 4. Incidence of anemia was 34.8% in grade 2, 8.7% grade 3 and 0% grade 4. Only 4.3% of patients required packed red blood cell infusion. Elevated transaminase were 4.3% in grade 2 and 0% in grade 3 or 4. Other toxicity included oral mucositis. Conclusions: Pemetrexed based chemotherapy is mildly effective in treating patients with metastatic gastric cancer with tolerable toxicity.

• Journal of Gastric Cancer
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• 제14권2호
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• pp.67-86
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• 2014

Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field.

• Journal of Gastric Cancer
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• 제3권3호
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• pp.134-138
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• 2003

Purpose: The lymph node (N) classification in the International Union Against Cancer (UICC) TNM staging system for gastric adenocarcinomas has been revised from the anatomic sites of metastatic lymph nodes to the number of metastatic lymph nodes. The purpose of this study was to investigate the proper number of retrieved lymph nodes for applying the new TNM staging system. Materials and Methods: We retrospectively studied 267 patients who had undergone a curative resection performed by one surgeon for gastric adenocarcinomas from March 1993 to December 1996 at Korea University Guro Hospital. We compared the old staging system to the new one and analyzed the number of retrieved and metastatic lymph nodes. We also analyzed the number of retrieved and metastatic lymph nodes according to the operative procedure and the extent of the lymphadenectomy, as well as the correlation of lymph-node metastasis to the number of retrieved lymph nodes. Results: The mean number of retrieved lymph nodes was $34.27\pm14.18$, of those $6.85\pm6.24$ were metastatic. According to the extent of the lymphadenectomy, these numbers were $17.8\pm9.3\;and\;7.0\pm5.3$ in D1, $33.1\pm14.6\;and\;3.0\pm3.0$ in $D1+\alpha$, $33.9\pm13.8\;and\;7.5\pm6.2$ in D2, and $40.6\pm13.3\;and\;7.9\pm7.5$ in $D2+\alpha$. There was no correlation between the percentage of the specimen with positive lymph nodes and the number of retrieved lymph nodes, but a logistic regres sion analysis showed that the probability of lymph-node metastasis increased as the number of retrieved lymph nodes increased. Conclusion: The mean number of retrieved lymph nodes was about 34. Although by logistic regression analysis, the probability of lymph-node metastasis increased as the number of retrieved lymph nodes increased, we failed to determine the minimum number of nodes retrieved during a lymphadenectomy needed for accurate staging in a gastric adenocarcinoma. Further study is required to identify the optimum number of lymph nodes that need to be retrieved.

• Journal of Gastric Cancer
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• 제15권2호
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• pp.87-104
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• 2015

Purpose: To assess real-world treatment patterns, health care utilization, costs, and survival among Medicare enrollees with locally advanced/unresectable or metastatic gastric cancer receiving standard first-line chemotherapy. Materials and Methods: This was a retrospective analysis of the Surveillance, Epidemiology, and End Results-Medicare linked database (2000~2009). The inclusion criteria were as follows: (1) first diagnosed with locally advanced/unresectable or metastatic gastric cancer between July 1, 2000 and December 31, 2007 (first diagnosis defined the index date); (2) ${\geq}65$ years of age at index; (3) continuously enrolled in Medicare Part A and B from 6 months before index through the end of follow-up, defined by death or the database end date (December 31, 2009), whichever occurred first; and (4) received first-line treatment with fluoropyrimidine and/or a platinum chemotherapy agent. Results: In total, 2,583 patients met the inclusion criteria. The mean age at index was $74.8{\pm}6.0years$. Over 90% of patients died during follow-up, with a median survival of 361 days for the overall post-index period and 167 days for the period after the completion of first-line chemotherapy. The mean total gastric cancer-related cost per patient over the entire post-index follow-up period was United States dollar (USD) $70,808{\pm}56,620$. Following the completion of first-line chemotherapy, patients receiving further cancer-directed treatment had USD 25,216 additional disease-related costs versus patients receiving supportive care only (P<0.001). Conclusions: The economic burden of advanced gastric cancer is substantial. Extrapolating based on published incidence estimates and staging distributions, the estimated total disease-related lifetime cost to Medicare for the roughly 22,200 patients expected to be diagnosed with this disease in 2014 approaches USD 300 millions.

• Journal of Gastric Cancer
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• 제13권3호
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• pp.129-135
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• 2013

Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathways have reinforced the discovery of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discoveries to practical clinical benefits. Although there is a flood of biomarkers and target agents, only a minority of patients are tested and treated accordingly. Numerous molecular target agents have been under investigation for gastric cancer. Currently, targets for gastric cancer include the epidermal growth factor receptor family, mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways. Deeper insights of molecular characteristics for gastric cancer has enabled the molecular classification of gastric cancer, the diagnosis of gastric cancer, the prediction of prognosis, the recognition of gastric cancer driver genes, and the discovery of potential therapeutic targets. Not only have we deeper insights for the molecular diversity of gastric cancer, but we have also prospected both affirmative potentials and hurdles to molecular diagnostics. New paradigm of transdisciplinary team science, which is composed of innovative explorations and clinical investigations of oncologists, geneticists, pathologists, biologists, and bio-informaticians, is mandatory to recognize personalized target therapy.

• Journal of Gastric Cancer
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• 제21권3호
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• pp.236-245
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• 2021

Purpose: The numeric N stage has replaced the topographic N stage in the current tumor node metastasis (TNM) staging in gastric carcinoma. However, the usefulness of the topographic N stage in the current TNM staging system is uncertain. We aimed to investigate the prognostic value of the topographic N stage in the current TNM staging system. Materials and Methods: We reviewed the data of 3350 patients with gastric cancer who underwent curative gastrectomy. The anatomic regions of the metastatic lymph nodes (MLNs) were classified into 2 groups: perigastric and extra-perigastric. The prognostic value of the anatomic region was analyzed using a multivariate prognostic model with adjustments for the TNM stage. Results: In patients with lymph node metastasis, extra-perigastric metastasis demonstrated significantly worse survival than perigastric metastasis alone (5-year survival rate, 39.6% vs. 73.1%, respectively, P<0.001). Extra-perigastric metastasis demonstrated significantly worse survival within the same pN stage; the multivariate analysis indicated that extra-perigastric metastasis was an independent poor prognostic factor (hazard ratio=1.33; 95% confidence interval=1.01-1.75). The anatomic region of the MLNs improved the goodness-of-fit (likelihood ratio statistics, 4.57; P=0.033) of the prognostic model using the TNM stage. Conclusions: The anatomic region of MLNs has an independent prognostic value in the numeric N stage in the current TNM staging of gastric carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5433-5438
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• 2015

Background: Systemic chemotherapy for patients with metastatic gastric cancer (MGC) is generally palliative, although some patients experience long-term survival after treatment. Thus, we identified clinical characteristics that are associated with long-term survival of patients with MGC after palliative chemotherapy. Materials and Methods: We retrospectively reviewed 514 MGC patients who received systemic chemotherapy at our institution from 2001 to 2008. To identify clinical predictors of survival beyond 2 years, multivariate logistic regression analyses were performed, and 5-year survival rates were estimated among MGC patients following chemotherapy. Results: Among 514 patients, 96 (19%) and 16 (3%) survived beyond 2 and 5 years, respectively, and performance status of 0 or 1 (odds ratio [OR]=3.39; p=0.01), previous gastrectomy (OR=1.86; p=0.01), single metastatic site (OR=1.80; p=0.03), and normal alkaline phosphatase levels (OR=2.81; p<0.01) were identified as independent predictors of long-term survival. Of the 16 5-year survivors, six were alive at the end of the study and showed no evidence of disease despite cessation of chemotherapy. Conclusions: The present data demonstrate distinct clinical characteristics that are associated with long-term survival of MGC patients, and indicated that palliative chemotherapy can be curative in highly selected patients.

• Journal of Gastric Cancer
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• 제15권3호
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• pp.209-213
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• 2015

A 78-year-old man underwent laparoscopy-assisted total gastrectomy for gastric cancer (pT3N0M0). Multiple port sites were used, including a 10 mm port for a videoscope at the umbilical point and three other working ports. During the six-month follow-up evaluation, a 2 cm enhancing mass confined to the muscle layer was found 12 mm from the right lower quadrant port site, suggesting a metastatic or desmoid tumor. Follow-up computed tomography imaging two months later showed that the mass had increased in size to 3.5 cm. We confirmed that there was no intra-abdominal metastasis by diagnostic laparoscopy and then performed a wide resection of the recurrent mass. The histologic findings revealed poorly differentiated adenocarcinoma, suggesting a metastatic mass from the stomach cancer. The postoperative course was uneventful, and the patient completed adjuvant chemotherapy with TS-1 (tegafur, gimeracil, and oteracil potassium). There was no evidence of tumor recurrence during the 50-month follow-up period.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.985-989
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• 2015

Background: Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliative regimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluate the efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancer patients. Materials and Methods: 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG (Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least two cycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocol included $25mg/m^2$ docetaxel, $25mg/m^2$ cisplatin, and 24 hours infusion of $750mg/m^2$ 5-fluorouracil, repeated every week. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related to treatment, progression free survival (PFS) and overall survival (OS) were evaluated. Results: Of the patients, 41 were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23 were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observed in 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was noted in 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survival was 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9% had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renal toxicity (7.8%) and thrombosis (1.6%). Conclusions: In patients with locally advanced or metastatic gastric cancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstrated modest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment option for such patients.

• Journal of Gastric Cancer
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• 제12권3호
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• pp.140-148
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• 2012

Purpose: Among cell adhesion molecules, serum levels of intercellular adhesion molecule-1 and E-selectin are known to be correlated with the metastatic potential of gastric cancer. In the present study, the authors investigated the expression of intercellular adhesion molecule-1 and E-selectin in gastric cancer tissues and cultured gastric cancer cells, and examined their clinical value in gastric cancer. Materials and Methods: The protein was extracted from gastric cancer tissues and cultured gastric cancer cells (MKN-28 and Kato-III) and the expression of intercellular adhesion molecule-1 and E-selectin was examined by western blotting. The clinical significance of intercellular adhesion molecule-1 and E-selectin was explored, using immunohistochemical staining of specimens from 157 gastric cancer patients. Results: In western blot analysis, the expressions of intercellular adhesion molecule-1 in gastric cancer tissues and cultured gastric cancer cells were increased, however, E-selectin in gastric cancer tissues and cells were not increased. Among 157 gastric cancer patients, 79 patients (50%) were intercellular adhesion molecule-1 positive and had larger tumor size, an increased depth of tumor invasion, lymph node metastasis and perineural invasion. The intercellular adhesion molecule-1 positive group showed a higher incidence of tumor recurrence (40.5%), and a poorer 3-year survival than the negative group (54.9 vs. 85.9%, respectively). Conclusions: Intercellular adhesion molecule-1 is overexpressed in gastric cancer tissues and cultured gastric cancer cells, whereas E-selectin is not overexpressed. Increased expression of intercellular adhesion molecule-1 in gastric cancer could be related to the aggressive nature of the tumor, and has a poor prognostic effect on gastric cancer.