losartan-potassium and Stomach-Neoplasms

We conducted a retrospective analysis of publicly available preclinical toxicology studies with erythropoiesis-stimulating agents (ESAs) to examine common adverse events in rats, Beagle dogs, and cynomolgus monkeys. Mortality and/or thrombotic events were reported sporadically in a subset of studies and attributed to the high hematocrit (HCT) achieved in the animals. However, similarly high HCT was achieved in both high-dose and low-dose groups, but there were no reported adverse events in the low-dose group suggesting HCT was not the sole contributing factor leading to toxicity. Our analysis indicated that increased dose, dose frequency, and dosing duration in addition to high HCT contributed to mortality and thrombosis. To further evaluate this relationship, the incidence of toxicities was compared in rats administered an experimental hyperglycosylated analog of recombinant human erythropoietin (AMG 114) at varying dosing schedules in 1-month toxicity studies. The incidence of mortality and thrombotic events increased in higher dose groups and when dosed more frequently, despite a similarly high HCT in all animals. The results from the investigative study and retrospective analysis demonstrate that ESA-related toxicities in preclinical species are associated with dose level, dose frequency, and dosing duration, and not solely dependent upon a high HCT.

Topics: Animals; Biomedical Research; Dogs; Erythropoiesis; Erythropoietin; Heart Valve Diseases; Hematinics; Hematocrit; Humans; Macaca fascicularis; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Retrospective Studies; Stomach Neoplasms; Thrombosis

The impact of erythropoiesis-stimulating agents in chemotherapy-induced anemia has been a constant topic of debate over recent years. We prospectively assessed the efficacy of epoetin beta (Epo-b) in improving hemoglobin (Hb) levels and outcome in patients within an open label, randomized clinical phase II trial with advanced or metastatic gastric/esophagogastric cancer.. Previously untreated patients were randomized to receive 3-weekly cycles of capecitabine (1000 mg/m(2) bid) for 14 days plus on day 1 either irinotecan 250 mg/m(2) or cisplatin 80 mg/m(2). Epo-b (30000 IU once weekly) was initiated in patients with Hb <11 g/dl and continued until Hb ≥12 g/dl was reached. If after 4 weeks the Hb increase was <0.5 g/dl, Epo-b was increased to 30000 IU, twice weekly.. Of 118 patients enrolled, 32 received Epo-b treatment; of these, 65 % achieved an increase in Hb levels of at least 2 g/dl, with 74 % achieving the target Hb of ≥12 g/dl. Within the study population, patients receiving Epo-b showed better overall survival (median 14.5 vs. 8.0 months, P = 0.056) as well as a significantly improved disease control rate (78 vs. 55 %, P = 0.025). Patients in the irinotecan group profited significantly (P < 0.05) in terms of progression-free survival and overall survival under Epo-b treatment (median 6.5 vs 4.1 months and median 15.4 vs 8.4 months, respectively).. Epo-b was effective in raising Hb levels in patients with advanced esophagogastric cancer. Patients receiving Epo-b had a significantly increased response to chemotherapy and a clear trend to improved survival.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Esophagogastric Junction; Female; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Stomach Neoplasms

A phase II trial was performed to determine the efficacy and tolerance of docetaxel plus oxaliplatin with hematopoietic growth factor support in previously untreated patients with advanced gastroesophageal adenocarcinoma. Thirty-five patients were entered in this trial. Treatment consisted of 3-weekly docetaxel 80 mg/m2 and oxaliplatin 100 mg/m2 both infused on day 1. A prophylactic 5-day course of human granulocyte colony-stimulating factor 5 microg/kg/day was given subcutaneously, and erythropoietin (10,000 IU subcutaneously three times per week) was administered if hemoglobin was less than 12.0 mg/dl. The confirmed overall response rate was 34%, including two complete responses (6%) and 10 partial responses (28%). Fifteen patients (43%) had stable disease. The median time to response was 2.5 months (1-3.5), the median time to progression was 8.9 (4-42.5) months and the median overall survival time was 11.6 (2.5-51) months. Hematologic toxicity was common, though World Health Organization grade 3 or 4 neutropenia occurred only in six (17%) patients and anemia in six (17%) patients, respectively. Nonhematologic adverse reactions were usually mild-to-moderate. Our data suggest that the combination of docetaxel and oxaliplatin with granulocyte colony-stimulating factor and erythropoietin has a promising therapeutic index in patients with advanced gastroesophageal adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Erythropoietin; Esophageal Neoplasms; Female; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Rate; Taxoids

In a previous study we showed that many patients with esophagogastric adenocarcinoma experience anemia during neoadjuvant chemotherapy. We now investigated the role of erythropoietin in managing anemia during neoadjuvant chemotherapy.. Patients with esophagogastric adenocarcinoma who experienced anemia (hemoglobin < 12 g/dL) during neoadjuvant treatment received erythropoietin 10,000 IE subcutaneously three times a week. Primary outcomes were the response to erythropoietin, safety, the need for allogeneic red blood cell transfusion, and the rate of postoperative complications.. Between April 2003 and December 2004, 24 patients (median age, 62 years) were enrolled. The mean hemoglobin level before chemotherapy was 12.5 g/dL and the mean hemoglobin level before patients received erythropoietin was 11.5 g/dL. One year after involvement in the trial, 4 of 17 analyzable patients were still anemic (hemoglobin level < 12 mg/dL). Twenty-two patients received erythropoietin, and 16 (73%) responded. We could observe a significant increase in hemoglobin concentrations under therapy with erythropoietin to 12.6 g/dL (p < 0.001). Two patients (8%) received allogeneic transfusions; the rate of postoperative complications was 16%. There were no erythropoietin-related adverse events.. Treatment with erythropoietin is effective and well tolerated in patients with esophagogastric adenocarcinoma who experience anemia during neoadjuvant chemotherapy.

Topics: Adenocarcinoma; Aged; Anastomosis, Surgical; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Hemoglobins; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Postoperative Complications; Prospective Studies; Recombinant Proteins; Stomach Neoplasms; Survival Analysis

A phase II trial was performed to determine the antitumor efficacy and tolerance of combined docetaxel and cisplatin with or without hematopoietic growth factor support in patients with advanced gastroesophageal cancer.. Thirty-seven patients with histologically confirmed metastatic gastroesophageal cancer were entered in this trial. Treatment consisted of 4-weekly courses of docetaxel 50 mg/m(2) and cisplatin 50 mg/m(2) both given on day 1 and 15. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1,000-2,000/microl), a 5-day course of human granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/day was given subcutaneously; in addition, if hemoglobin was <12.0 mg/dl, erythropoietin 10,000 IU was administered subcutaneously 3 times per week.. The confirmed overall response rate (intent-to-treat) was 46%, including 4 complete responses (11%) and 13 partial responses (35%). Eleven patients (30%) had stable disease and 9 (24%) progressed while on treatment. The median time to response was 3 months, the median time to progression was 7 months and the median overall survival time was 11.5 months with 16 (43%) patients currently alive. Hematologic toxicity was common, though WHO grade 4 neutropenia occurred only in 3 patients. Nonhematologic adverse reaction were usually mild to moderate; grade 3 toxicities included alopecia in 5 patients (14%), infection in 1 (3%), neutrotoxicity in 2 (5%) and anaphylaxis in 1 patient.. Our data suggest that the combination of docetaxel and cisplatin with or without G-CSF and/or erythropoietin has a promising therapeutic index in patients with advanced gastroesophageal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Therapy, Combination; Erythropoietin; Esophageal Neoplasms; Esophagogastric Junction; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Maximum Tolerated Dose; Middle Aged; Stomach Neoplasms; Survival Rate; Taxoids; Treatment Outcome

A phase II trial was performed to determine the antitumour efficacy and tolerance of combined paclitaxel and cisplatin with or without hematopoetic growth factor support in patients with advanced gastric cancer. Forty-five patients with histologically confirmed metastatic gastric cancer were entered in this trial. Treatment consisted of 2-weekly courses of paclitaxel 160 mg per m2 and cisplatin 60 mg per m2 both given on day 1. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1000-2000 per microl), a 5-day course of human granulocyte colony-stimulating factor 5 microg x kg(-1) per day was given subcutaneously; in addition, if haemoglobin was <12.0 mg dl(-1), erythropoietin 10 000 IU was administered subcutaneously three times per week. The confirmed overall response rate (intent-to-treat) was 44%, including five complete (11%) and 15 partial remissions (33%). Twelve patients had stable disease (27%), 11 (24%) progressed while on chemotherapy, and two patients were not evaluable. The median time to response was 3 months, the median time to progression 7.0 months, and the median survival time was 11.2 months with 12 patients currently alive. Haematologic toxicity was common, though WHO grade 4 neutropenia occurred in only five patients (11%). Apart from total alopecia in 16 patients (36%), severe non-haematologic adverse reactions included grade 3 peripheral neuropathy in six (13%) and anaphylaxis in two patients. In addition, there was one patient each who experienced grade 3 emesis, diarrhea, and infection, respectively. Our data suggest that the combination of paclitaxel and cisplatin with or without G-CSF and/or erythropoietin has promising therapeutic activity in patients with advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Male; Middle Aged; Paclitaxel; Stomach Neoplasms; Survival Rate; Treatment Outcome

Preoperative treatment with 600 U/kg of recombinant human erythropoietin (r-HuEPO) effectively increases erythropoiesis in cancer patients. The aim of this study was to evaluate the erythropoietic response after different doses of r-HuEPO in order to find the minimum effective dose.. Twenty anemic sideropenic patients (hemoglobin

Topics: Adenocarcinoma; Aged; Anemia; Colorectal Neoplasms; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Preoperative Care; Prospective Studies; Recombinant Proteins; Stomach Neoplasms

To evaluate the role of recombinant human erythropoietin in reducing the need for homologous blood transfusion during operations by studying its effect on the recovery of postoperative anaemia.. Randomised controlled trial.. University hospital, Japan.. 10 patients with gastric cancer undergoing distal gastrectomy.. 5 Patients were given erythropoietin 200 IU/kg/day together with ferric pyrophosphate 40 mg/day intravenously for seven days before operation and 14 days afterwards, and 5 were given ferric pyrophosphate 40 mg/day alone (control group).. Packed cell volume, haemoglobin concentration, and white and red cell counts.. There was no significant change in packed cell volume after the operation in the erythropoietin group, but in the control group it dropped from a mean (SD) of 0.378 (0.074) before operation to 0.329 (0.068) on day 1 (p < 0.05). Haemoglobin concentrations were significantly higher in the erythropoietin group than the control group on day 7 (mean (SD) 137 (14) compared with 110 (19) p < 0.05), and on day 10 (140 (9) compared with 108 (15) p < 0.01) after operation.. Erythropoietin prevented postoperative anaemia after gastrectomy as judged by packed cell volume, haemoglobin concentration, and red cell count. Erythropoietin given before and after operation therefore has the potential to reduce the need for homologous blood transfusion during and after major operations.

Topics: Adult; Aged; Anemia; Blood Cell Count; Diphosphates; Erythropoietin; Female; Gastrectomy; Hematocrit; Hemoglobins; Humans; Iron; Male; Middle Aged; Pilot Projects; Postoperative Care; Postoperative Complications; Preoperative Care; Recombinant Proteins; Stomach Neoplasms; Time Factors

The aim of this study was to determine whether the preoperative administration of recombinant human erythropoietin (rHuEPO) could increase the rate of autologous blood donation and reduce the perioperative need for homologous blood in anaemic patients with cancer. Twenty-two anaemic (haematocrit less than 34 per cent), iron-deficient (iron less than 700 micrograms/l) patients, with gastric or colorectal cancer scheduled for elective surgery, were allocated randomly to two groups. The first (n = 11) received iron saccharate 200 mg/day intravenously for 12 consecutive days. The second (n = 11) received rHuEPO subcutaneously (300 units/kg as first administration, and 100 units/kg 4, 8 and 12 days later) with supplemental iron. On days 4, 8 and 12, if the haematocrit was greater than 34 per cent, patients donated one unit (350 ml) of autologous blood. In the iron group the mean haematocrit did not change from admission (31 per cent) to day 12 of treatment (31 per cent), and no patient could donate autologous blood. In the rHuEPO group, eight patients donated two units of autologous blood and three donated one unit. Four patients in the iron group received perioperative transfusion of homologous blood compared with none in the rHuEPO group. Administration of rHuEPO facilitated the donation of autologous blood and reduced perioperative homologous blood transfusion in anaemic patients with cancer.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Blood Transfusion, Autologous; Colonic Neoplasms; Erythropoietin; Female; Humans; Male; Middle Aged; Preoperative Care; Prospective Studies; Recombinant Proteins; Rectal Neoplasms; Stomach Neoplasms

Epstein-Barr virus (EBV) is a human tumor-associated virus that encodes various microRNAs. EBV infection causes a variety of malignant tumors, including nasopharyngeal carcinoma and gastric cancer, etc. EBV-associated gastric cancer (EBVaGC) has unique molecular characteristics from other gastric cancers, but its pathogenic mechanism remains unclear. In recent years, erythropoietin-producing human hepatocellular 2 (EphA2) has been reported to be highly expressed in various cancers and promote tumor growth and metastasis. As an important cancer oncogene, EphA2 is a potential therapeutic target. However, whether EBV is involved in the regulation of EphA2 and thus affects the progression of EBVaGC remains unclear. In this study, we found that the expression of EphA2 in EBVaGC cells was significantly lower than that in EBV-negative gastric cancer (EBVnGC) cells. Additionally, overexpression of EphA2 in EBVaGC cells promoted migration and proliferation, and inhibited autophagy. EBV-miR-BART1-3p and BART18-5p were found to target the 3'-UTR of EphA2 and down-regulate its expression. Our results suggest that EBV may be involved in gastric cancer progression by targeting EphA2 through BART1-3p and BART18-5p.

Topics: Autophagy; Carcinoma, Hepatocellular; Cell Movement; Cell Proliferation; Epstein-Barr Virus Infections; Erythropoietin; Herpesvirus 4, Human; Humans; Liver Neoplasms; MicroRNAs; Stomach Neoplasms

Myelodysplastic syndrome (MDS) is a heterogeneous malignant hematologic disease with median overall survival ranging from six months to more than ten years. Solid tumor rarely occurs in combination with MDS and the underlying pathogenesis and prognostic significance still remain controversial.. Here we report a relative low risk myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) patient, with a rare t(1; 19)chromosome translocation. This patient also suffered from gastric carcinoma.. Gastric carcinoma, Myelodysplastic syndrome with t (1; 19) chromosome translocation.. This patient received radical operation for gastric carcinoma and erythropoietin infusion.. The patient took follow up visits every 2 to 3 months in past years and now he is in stable disease without further treatment.. We reviewed the mechanism of MDS complicated by solid tumor and concluded the potential mechanisms of this patient. The interactions between potential factors may play a role in oncogenesis which, however, need an in-depth study of its operating mechanism.

Topics: Anemia, Refractory; Bone Marrow; Carcinoma; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Cytogenetic Analysis; Erythropoietin; Gastrectomy; Hematinics; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Stomach Neoplasms; Translocation, Genetic; Treatment Outcome

Erythropoietin (EPO), binding with its receptor (EPOR), plays an important role in erythropoiesis. EPOR is reported to be expressed in various non-hematopoietic cancers, including gastric cancer. Although recombinant human EPO (rhEPO) has been widely used clinically in anemia patients, it remains controversial whether it would promote tumor progression. In this study, we used siRNA interference method to downregulate EPOR expression to investigate the function of EPO/EPOR pathway in human gastric cancer cells. We found EPOR expressed significantly higher in gastric cancer tissues, and also in most gastric cancer cell lines. RhEPO promoted gastric cancer cell proliferation, migration in AGS cells, and promoted cells from G0/G1 stage to G2/M stage, but had no regulation on AGS cell apoptosis. Downregulation of EPOR expression by siRNA interference in AGS cells resulted in no significant effects on proliferation and invasiveness of the cells, but induced apoptosis (p < 0.05). Xenografted gastric tumor model was used to explore the effect of EPOR-overexpression on gastric cancer cells in vivo. Our result showed that overexpression of EPOR enhanced tumor formation in nude mice (p < 0.01). Our results suggest that EPO/EPOR pathway promotes gastric cancer formation, proliferation, migration, and decreases apoptosis.

Topics: Adult; Aged; Animals; Apoptosis; Blotting, Western; Erythropoietin; Female; Flow Cytometry; Gene Knockdown Techniques; Heterografts; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Real-Time Polymerase Chain Reaction; Receptors, Erythropoietin; Signal Transduction; Stomach Neoplasms

To investigate the expression of Erythropoietin (Epo) and its receptor (EpoR) in gastric adenocarcinoma (GAC) and the correlation with angiogenesis and clinicopathological features.. The expressions of Epo, EpoR and vascular endothelial growth factor (VEGF), as well as microvessel density were evaluated in 172 GAC biopsies by immunohistochemical staining. The correlations between these parameters and patient's clinicopathological features were analyzed statistically.. The proportion of Epo and EpoR alterations in GAC was higher than that in adjacent normal mucosa (P = 0.035 and 0.030). Epo high-expression was associated with EpoR high-expression, Lauren type, extensive lymph node metastasis and advanced stage of GAC (P = 0.018, 0.018, 0.004 and 0), while EpoR expression was linked with older age, World Health Organization type, extensive lymph node metastasis and advanced stage (P = 0.001, 0.013, 0.008 and 0.001). VEGF high expression was significantly correlated with EpoR low-expression, Lauren type, extensive lymph node metastasis and advanced stage (P = 0.001, 0.001, 0.001 and 0.007). The expression of Epo or EpoR was associated with microvessel density (P = 0.004 and 0.046). On multivariate analysis, only lymph node metastasis, abnormal Epo expression and tumor nodes metastases stage were independently associated with survival. In addition, a strong association with the immunohistochemical expression of EpoR and the angiogenic protein, VEGF, was noted.. Increased expression of Epo and EpoR may play a significant role in the carcinogenesis, angiogenesis and progression of GAC. Epo may be an independent prognostic factor.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Disease Progression; Erythropoietin; Female; Humans; Male; Middle Aged; Neovascularization, Pathologic; Prognosis; Receptors, Erythropoietin; Stomach Neoplasms; Survival Rate; Vascular Endothelial Growth Factor A; Young Adult

Topics: Adenocarcinoma; Adult; Antibiotics, Antineoplastic; Antigens, CD34; Biomarkers; Burkitt Lymphoma; Calcineurin; Endothelium, Vascular; Erythropoietin; Female; Hemolytic-Uremic Syndrome; Humans; Male; Mitomycin; Renal Dialysis; Stomach Neoplasms

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Carcinoma, Signet Ring Cell; Erythropoietin; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Lymphatic Metastasis; Microvessels; Middle Aged; Stomach; Stomach Neoplasms; Tissue Array Analysis

Topics: Anemia; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cyclophosphamide; Doxorubicin; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Neutropenia; Polyethylene Glycols; Positron-Emission Tomography; Prednisone; Recombinant Proteins; Rituximab; Stomach Neoplasms; Vincristine

Previous studies have shown that increased vascularity is associated with haematogenous metastasis and poor prognosis in gastric cancer. The role of erythropoietin (Epo) in angiogenesis has not been completely clarified, although its involvement has been reported. In this study we correlated microvascular density and Epo receptor (Epo-R) expression in endothelial and tumour cells with histopathological type in gastric cancer.. Specimens of primary gastric adenocarcinomas obtained from 40 patients who had undergone curative gastrectomy were investigated immunohistochemically by using anti-CD31 and anti-Epo-R antibodies. Stage IV gastric carcinoma had a higher degree of vascularization than other stages, and Epo-R expression in both endothelial and tumour cells increased in parallel with malignancy grade and was highly correlated with the extent of angiogenesis.. Epo-R level correlates with angiogenesis and progression of patients with gastric carcinoma and we suggest that Epo might have a trophic effect on the vasculature of the gastrointestinal tract. Understanding mechanisms of gastric cancer angiogenesis provides a basis for a rational approach to the development of an anti-angiogenic therapy in patients with gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Endothelium, Vascular; Erythropoietin; Female; Humans; Immunohistochemistry; Male; Microcirculation; Middle Aged; Neoplasm Staging; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Erythropoietin; Stomach Neoplasms

A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy. Serum erythropoietin level was 181 mU/mL (181 IU/L). Gastroscopy results showed rough mucosa with hemorrhaging caused by gastric cancer. The patient underwent distal gastrectomy, and serum erythropoietin level decreased to 27.1 mU/mL (27.1 IU/L) by postoperative day 8. Existence of erythropoietin in the tumor tissue was confirmed immunohistochemically. The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis.

Topics: Adenocarcinoma; Aged; Diabetic Nephropathies; Erythropoietin; Gastrectomy; Gastrointestinal Hemorrhage; Hormones, Ectopic; Humans; Male; Paraneoplastic Endocrine Syndromes; Polycythemia; Renal Dialysis; Stomach Neoplasms

Topics: Adenoma; Adult; Erythropoietin; Female; Humans; Kidney Neoplasms; Leiomyoma; Male; Meningioma; Middle Aged; Neoplasms; Polycythemia; Stomach Neoplasms; Uterine Neoplasms

Topics: Androgens; Anemia; Diagnosis, Differential; Erythropoietin; Humans; Iron; Kidney; Lymphoma; Male; Middle Aged; Radiation Injuries; Stomach Neoplasms