OBJECTIVETo evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.

METHODSTwenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study. The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2+++ by immunohistochemistry or HER-2 gene amplification-positive by FISH, and if they failed to at least one previous chemotherapy. Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.

RESULTSThe twenty patients received trastuzumab plus second- or later-line chemotherapy, consisting of nine platinum with fluoropyrimidines, five paclitaxel with fluoropyrimidines, three fluoropyrimidines monotherapy, two irinotecan monotherapy, and one docetaxel monotherapy. In these 20 cases, 3 PR (15.0%) and 10 SD (50.0%) were achieved, with a disease control rate of 65.0%. The median PFS was 6.1 months (95%CI 3.0-9.2) and median OS was 11.1 months (95%CI 8.4-13.7). The median cycle number of Trastuzumab administration was 6.5. The patients treated with Trastuzumab ≥ 6 times had a median OS of 13.8 months, significantly longer than that of 9.5 months in the patients treated <6 times (P < 0.001). The patients treated with Trastuzumab ≥ 6 times had a median PFS of 7.8 months, significantly longer than that of 3.7 months in patients treated <6 times (P = 0.029). Among the 20 cases, loss of appetite (13 cases of grade 1-2), neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events. No cardiac events including asymptomatic decreases in LVEF ≥ 10% and no treatment-related death were recorded.

CONCLUSIONSCombination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma. However, prospective studies are warranted to further confirm its efficacy and safety.

Adenocarcinoma ; drug therapy ; metabolism ; secondary ; surgery ; Adult ; Aged ; Anorexia ; chemically induced ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Cisplatin ; administration & dosage ; adverse effects ; Disease Progression ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Esophagogastric Junction ; Fatigue ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; adverse effects ; Pyrimidines ; administration & dosage ; adverse effects ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; metabolism ; secondary ; surgery ; Survival Rate ; Trastuzumab

OBJECTIVETo investigate the clinical value of the expression of glucose regulated protein 78 (GRP78) for assessment of severity, chemoresistance and prognosis in patients with gastric adenocarcinoma ( GC) .

METHODSA cohort of 237 patients with gastric cancer was included in this study. 160 patients of them were treated by D2 radical gastrectomy and adjuvant chemotherapy. The GRP78 expression was detected by immunohistochemistry and 80 patients of them were tested in vitro for cancer chemosensitivity by ATP-tumor chemosensitivity assay (ATP-TCA). In addition, the relationships were analyzed between GRP78 and age, gender, tumor differentiation, invasion, disease stage, lymph node metastasis and chemoresistance as well as disease-free survival (DFS).

RESULTSThe positive rate of GRP78 expression in the gastric adenocarcinoma was 68.8% before the initiation of chemotherapy. The positive GRP78 expression was significantly correlated with tumor invasion depth, poor differentiation, TNM stages, and lymph node metastasis (all P < 0.05), not correlated with gender and age, and high GRP78 expression was associated with the chemoresistance of the gastric cancer cells to chemotherapeutic agents. Negative GRP78 expression was associated with higher sensitivity to both drugs and regimens. The DFS of GRP78-positive group and GRP78-negative group was (53.6 ± 0.9) months and (38.3 ± 0.8) months, respectively (P = 0.041). Interestingly, subgroup analysis revealed that the DFS in GRP78-negative and-positive patients treated with taxane-containing chemotherapy was (58.6 ± 2.6) months and (49.1 ± 2.7) months, respectively, but the difference was statistically not significant (P = 0.111). In contrast, in the subset of GRP78-negative and- positive patients treated with taxane-containing regimens, the DFS was (45.5 ± 1.9) months and (35.1 ± 2.2) months, respectively, showing a significant difference (P = 0.038). In the group of patients with positive GRP78 expression, the patients treated with taxane-containing chemotherapy had a longer DFS [(49.1 ± 2.7) months] than those without that treatment [(35.1 ± 2.2) months], showing a significant difference (P = 0.017). Univariate analysis revealed that DFS was correlated with histological grade, GRP78 expression and lymph node metastasis (all P < 0.05). Multivariate analysis showed that GRP78 expression and TNM staging were independent influencing factors for gastric cancer (both P < 0.05).

CONCLUSIONSThe results of our study suggest that GRP78 may be a novel biomarker for assessment of malignant degree and prediction of chemoresistance in gastric cancer, and may be helpful to chemotherapy planning and prognosis prediction in patients with gastric cancer.

Adenocarcinoma ; drug therapy ; metabolism ; pathology ; surgery ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Bridged-Ring Compounds ; administration & dosage ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Female ; Gastrectomy ; Heat-Shock Proteins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Taxoids ; administration & dosage

OBJECTIVEThe purpose of this study was to investigate the efficacy and mechanism of oxaliplatin in combination with capecitabine (XELOX) regimen as neoadjuvant chemotherapy in the treatment of patients with advanced gastric cancer.

METHODSEighty-five patients with advanced gastric cancer (stage IIB and IIIC) were randomly divided into two groups: neoadjuvant chemotherapy group (40 cases) and surgery alone group (45 cases). In the neoadjuvant chemotherapy group, patients received oral administration of Xeloda 1000 mg/m(2) twice a day on days 1-14 and intravenous infusion of oxaliplatin 130 mg/m(2) on day 1 (XELOX regimen). The regimen was repeated every 21 days. In the surgery alone group, patients directly received radical resection of gastric cancer. The R0 resection rate, overall survival and disease free survival (DFS) were observed in all cases. The cycles and apoptosis rate of the gastric cancer cells were detected by flow cytometry. The expression of proliferating cell nuclear antigen (PCNA), p21, p53 and survivin was detected by Western blot.

RESULTSIn the neoadjuvant chemotherapy group, the total effective rate was 32.5% (13/40), and the tumor control rate was 90% (36/40), with few side effects. Compared with the surgery alone group, R0 resection rate was significantly higher in the neoadjuvant chemotherapy group (P < 0.05). The survival analysis indicated that both the overall survival and DFS were longer in the neoadjuvant chemotherapy group in comparison with those in the surgery alone group, but no significant differences were found (P > 0.05). In the neoadjuvant chemotherapy group, both the apoptosis rate and the ratio of cells in stage G0 and G1 were significantly higher than those in the surgery alone group (P < 0.05). The expression of PCNA and survivin was lower in the neoadjuvant chemotherapy group, while the expression of p21 and p53 was higher.

CONCLUSIONSXELOX regimen as neoadjuvant chemotherapy in the treatment of patients with advanced gastric cancer can effectively improve the R0 resection rate and prolong the survival time of the patients. Its mechanism is probably that the neoadjuvant chemotherapy can markedly enhance apoptosis in gastric cancer cells and inhibit their proliferation.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Chemotherapy, Adjuvant ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Gastrectomy ; methods ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins p21(ras) ; metabolism ; Remission Induction ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo explore an ideal method of digestive tract reconstruction and tolerance to adjuvant chemotherapy after radical proximal gastrectomy.

METHODSThirty patients in the reconstruction group were treated by jejunal interposition, and other 30 patients received gastroesophagostomy (control group). The operation time, operation risk, occurrence of reflux esophagitis and postoperative 1-, 3-, 6-month nutrition statuses were evaluated. Forty-three patients received postoperative adjuvant chemotherapy with mFOLFOX-6 and tolerance to the chemotherapy was assessed.

RESULTSThe operation time of the reconstructional group was (162.2 ± 14.0)min and that of the control group was (137.6 ± 18.9)mi, with a statistically significant difference. (t = -5.7, P<0.01). There were no significant differences of operation risk, postoperative 2-, 4-, and 6-day C-reactive protein, 2-, 4- and 6-day systemic inflammatory response syndrome between the two groups. The differences of the occurrence of postoperative 1-, 3- and 6-month reflux esophagitis and 3- and 6-month nutritional status between the two groups were statistically significant. 18 of 19 (94.7%) patients in the reconstruction group completed all six cycles of chemotherapy, 24 patients in the control group received chemotherapy, and 12 (50.0%) of them completed 6 cycles of chemotherapy. There was a significant difference in the completion rate of chemotherapy of the two groups (P<0.05).

CONCLUSIONSThe postoperative complications of jejunal interposition are not inceased, the symptoms of reflux esophagitis are alleviated, the quality of life can be improved, and there is a better tolerance to adjuvant chemotherapy. Therefore, jejunal interposition after radical proximal gastrectomy is a rational method of digestive tract reconstruction.

Aged ; Anastomosis, Surgical ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; C-Reactive Protein ; metabolism ; Chemotherapy, Adjuvant ; Female ; Fluorouracil ; therapeutic use ; Follow-Up Studies ; Gastrectomy ; adverse effects ; methods ; Gastroesophageal Reflux ; etiology ; Humans ; Jejunum ; surgery ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Operative Time ; Organoplatinum Compounds ; therapeutic use ; Quality of Life ; Reconstructive Surgical Procedures ; adverse effects ; methods ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; metabolism ; surgery ; Systemic Inflammatory Response Syndrome ; etiology

Previous studies suggested that polymorphisms of proinflammatory cytokine genes are important host genetic factors in Helicobacter pylori infection. The present study evaluated whether IL-8-251 polymorphism affected H. pylori eradication rate and to investigate the effect of H. pylori eradication on angiogenesis and the inflammatory process according to the IL-8-251 polymorphism. A total of 250 H. pylori-positive patients treated by endoscopic resection of the gastric neoplasm were classified into 3 groups (134 H. pylori-eradicated group, 19 H. pylori-eradication failure group, and 97 H. pylori-infected group). H. pylori status, histology, and angiogenic factor levels were evaluated at baseline, 6 months, and 18 months. H. pylori eradication rate was 92.9% in AA genotype, 85.7% in AT genotype and 88.4% in TT genotype (P value = 0.731). Elevated IL-8 and matrix metalloproteinase-9 concentrations in H. pylori-infected gastric mucosa were reversible by successful eradication of H. pylori, independent of the IL-8-251 polymorphism. It is suggested that elevated IL-8 and MMP-9 concentrations in H. pylori-infected gastric mucosa are altered significantly after successful eradication and these conditions continue for 18 months. However, IL-8-251 polymorphism does not affect H. pylori eradication rate and the sequential changes of related angiogenic factors after H. pylori eradication in Koreans.
Aged ; Alleles ; Angiopoietin-1/analysis ; Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Asian Continental Ancestry Group/*genetics ; Female ; Gastric Mucosa/metabolism/pathology ; Genotype ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Interleukin-8/analysis/*genetics ; Male ; Matrix Metalloproteinase 9/analysis ; Middle Aged ; *Polymorphism, Single Nucleotide ; Proton Pump Inhibitors/therapeutic use ; Republic of Korea ; Retrospective Studies ; Stomach Neoplasms/pathology/surgery ; Time Factors ; Vascular Endothelial Growth Factor A/analysis

PURPOSE: The purpose of this study was to identify the effects of a home based exercise program for patients with stomach cancer who were undergoing oral chemotherapy. METHODS: The home-based exercise program was developed from the study findings of Winningham (1990) and data from the Korea Athletic Promotion Association (2007). The home-based exercise program consisted of 8 weeks of individual exercise education and exercise adherence strategy. Participants were 24 patients with stomach cancer who were undergoing oral chemotherapy following surgery in 2007 or 2008 at a university hospital in Seoul. Patients were randomly assigned to either the experimental group (11) or control group (13). The effects of the home-based exercise program were measured by level of cancer related fatigue, NK cell ratio, anxiety, and quality of life. Data were analyzed using SPSS/WIN 13.0 version. RESULTS: The degree of cancer related fatigue and anxiety in the experimental group decreased compared to the control group. The NK cell ratio and the degree of quality of life of experimental group increased while that of the control group decreased. CONCLUSION: This study result indicate the importance of exercise and provide empirical evidence for continuation of safe exercise for patients with cancer during their chemotherapy.
Administration, Oral ; Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Anxiety ; *Exercise Therapy ; Fatigue ; Female ; Humans ; Killer Cells, Natural/immunology/metabolism ; Male ; Middle Aged ; Program Evaluation ; Quality of Life ; Stomach Neoplasms/*drug therapy/surgery ; Treatment Outcome

Adolescent ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Burkitt Lymphoma ; drug therapy ; metabolism ; pathology ; surgery ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; DNA-Binding Proteins ; metabolism ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Genes, myc ; Humans ; Hyaluronan Receptors ; metabolism ; Ki-67 Antigen ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Male ; Neoplasm Staging ; Neprilysin ; metabolism ; Peritoneal Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; Stomach Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Translocation, Genetic ; Vincristine ; therapeutic use

OBJECTIVETo study the immunophenotype and prognostic significance of primary gastrointestinal diffuse large B-cell lymphoma, with reference to Hans, Choi and Tally algorithms.

METHODSThe clinicopathologic features and follow-up data in 90 cases of primary gastrointestinal diffuse large B-cell lymphoma were analyzed by Kaplan-Meier method, Log-rank test and Cox regression model. Immunohistochemistry was carried out using EliVision and EnVision methods for CD20, CD3ε, CD10, bcl-6, MUM-1, CD5, bcl-2, GCET1, FOXP1, LMO2, BLIMP1 and Ki-67.

RESULTSThe age of patients ranged from 27 to 83 years (mean = 58 years). The male-to-female ratio was 1.31:1. Amongst the 90 cases studied, 64.4% (58/90) involved the stomach and 35.6% (32/90) involved the intestine. The immunohistochemical findings were as follows: 100% positivity for CD20, 0% for CD3ε and CD5, 17.8% (16/90) for CD10, 75.6% (68/90) for bcl-6, 52.2% (47/90) for MUM-1 (cut off was 30%), 43.3% (39/90) for MUM-1 (cut off was 80%), 50.0% (45/90) for GCET1, 45.6% (41/90) for FOXP1, 23.3% (21/90) for LMO2, 42.2% (38/90) for bcl-2 and 8.9% (8/90) for BLIMP1. The Ki-67 index ranged from 20% to 95% (median = 80%). According to Hans algorithm, 51.1% of the cases belonged to germinal center B-cell (GCB) subtype and 48.9% belonged to non-GCB subtype. In contrast, Choi algorithm classified 55.6% cases as GCB subtype and 44.4% as activated B-cell (ABC) subtype. According to Tally algorithm, 34.4% were of GCB subtype and 65.6% of non-GCB subtype. Most of the patients (67.8%, 61/90) received chemotherapy and 68.9% (62/90) underwent surgical resection. The overall 2, 3 and 5-year survival rates were 58.5%, 52.8% and 49.8%, respectively. The overall 2, 3 and 5-year survival rates in the CHOP therapy group were 68.5%, 61.2% and 52.9%, respectively.

CONCLUSIONSThere is no significant difference in ratio between the GCB and non-GCB/ABC subtypes by Hans and Choi algorithms. The non-GCB subtype seems to be more prevalent according to Tally algorithm. Although there is no significant difference in survival between GCB and non-GCB/ABC subtypes by the 3 algorithms, GCB subtype tends to show a better survival. In univariate analysis, LDH level, international prognostic index, chemotherapy, surgical resection, B symptoms, number of involved sites and clinical stage are found to have prognostic significance. In multivariate analysis, Choi algorithm, Tally algorithm, chemotherapy, surgical resection, LDH level and clinical stage are independent prognostic factors.

Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; DNA-Binding Proteins ; metabolism ; Doxorubicin ; therapeutic use ; Female ; Forkhead Transcription Factors ; metabolism ; Germinal Center ; pathology ; Humans ; Immunophenotyping ; Interferon Regulatory Factors ; metabolism ; Intestinal Neoplasms ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Kaplan-Meier Estimate ; LIM Domain Proteins ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Metalloproteins ; metabolism ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Repressor Proteins ; metabolism ; Serpins ; metabolism ; Stomach Neoplasms ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Survival Rate ; Vincristine ; therapeutic use

OBJECTIVETo investigate the inhibitory effect of somatostatin (SST) analogue octreotide on human gastric cancer.

METHODSFifty gastric cancer patients were randomly assigned into 2 equal groups. The patients in the control group received no medication before surgical resection of gastric cancer, and those in octreotide group were given daily subcutaneous injection of 100 µg octreotide for 7 days before the surgery. The resected specimens were examined histologically and the expressions of p53 and Ras protein were detected by immunohistochemistry.

RESULTSCompared with the control group, gastric cancer tissue in octreotide group showed significantly increased necrosis (P<0.05) and enhanced proliferation of fibrous tissues (P<0.05) with lowered expressions of p53 and Ras protein (P<0.05).

CONCLUSIONOctreotide can inhibit the expressions of p53 and Ras and suppress the growth of the human gastric cancer.

Adenocarcinoma ; drug therapy ; metabolism ; surgery ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Octreotide ; therapeutic use ; Proto-Oncogene Proteins p21(ras) ; genetics ; metabolism ; Somatostatin ; analogs & derivatives ; Stomach Neoplasms ; drug therapy ; metabolism ; surgery ; Tumor Suppressor Protein p53 ; genetics ; metabolism

OBJECTIVETo assess the expression of HER-2 and leptin in gastric cancer and evaluate their relationship with VEGF expression and clinicopathological features, and their prognostic value for gastric cancer patients.

METHODSOne hundred and ten gastric cancer specimens and the corresponding metastatic lymph nodes were detected for HER-2 by immunohistochemistry (IHC). All primary cancer tissues were detected for leptin, OB-Rb and VEGF. Ninty-six specimens of normal gastric mucosa served as the control.

RESULTSThe expression level of HER-2, leptin and OB-Rb in gastric cancer tissues were significantly higher than those in normal tissues (19.1% vs. 8.0%, 49.1% vs. 34.0%, and 60.9% vs. 46.0%, P < 0.05). HER-2 overexpression was moderately homogenous in primary gastric cancer and matastatic lymph nodes (P = 0.607, Kappa = 0.581). There was a correlation between the expression of HER-2 and leptin, both of which were significantly correlated with tumor invasion depth, metastatic lymph nodes ratio (NR), distal metastasis, TNM stage and VEGF expression. However, there was no significant correlation between OB-Rb expression and the clinicopathological features evaluated. Cox regression multivariate analysis showed that tumor size, histological grade, NR, stage, chemotherapy and HER-2 expression were independent prognostic factors.

CONCLUSIONSHER-2 is stably expressed in primary gastric cancer and metastatic lymph nodes. HER-2 and leptin play an important role in the progression and angiogenesis of gastric cancer. High expression of HER-2 is a prognostic factor for poor outcome.

Adenocarcinoma ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gastrectomy ; Humans ; Leptin ; metabolism ; Lymph Nodes ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2 ; metabolism ; Receptors, Leptin ; metabolism ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Survival Rate ; Tumor Burden ; Vascular Endothelial Growth Factor A ; metabolism