Prognostic value of metastatic lymph node ratio in gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVES</b>To evaluate the value of the metastatic to examined lymph nodes (rN) ratio in gastric cancer patients who underwent radical resection.</p><p><b>METHODS</b>In this retrospective study, data were collected from the medical records of 710 patients who underwent radical gastrectomy (R0) for gastric cancer from 1980 to 2006 in the Department of Surgical Oncology at the First Affiliated Hospital of China Medical University. The patients were divided into 2 groups according to the number of examined lymph nodes: Group 1 consisted of 327 patients with <15 examined lymph nodes and Group 2 consisted of 383 patients with ≥15 lymph nodes. rN categories staging and pN categories were divided separately according to the metastatic lymph node ratio and the examined lymph nodes. The prognostic factors were analyzed by univariate (Log-rank) and multivariate (Cox model) analysis methods.</p><p><b>RESULTS</b>The median survival time was 74 months (95% CI:55.6-92.4 months) in Group 1 and 96 months (95% CI:77.8-119.2 months) in Group 2, and the difference was not statistically significant (P>0.05). On multivariate analysis, the N ratio remained as an independent prognostic factor in both Group 1 (P<0.01, RR=1.225, 95% CI:1.102-1.362) and Group 2 (P<0.01, RR=1.421, 95% CI:1.269-1.592). However, pN stage was an independent prognostic factor only in Group 1. When the rN ratio classification was applied, there were no significant differences between each categories (P>0.05). However, the overall survival of patients with pN1 disease in Group 1 was significantly shorter than that in Group 2 according to the pN stage classification (P<0.01).</p><p><b>CONCLUSIONS</b>The metastatic lymph node ratio is an independent prognostic factor of the prognosis of gastric cancer. The staging system based on metastatic lymph node ratio (rN) is more reliable than the system based on the number of metastatic lymph nodes in the prediction of the prognosis of gastric cancer.</p>

Lymphadenectomy adjacent to inferior mesenteric artery root during radical operation and prognosis in rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of lymphadenectomy adjacent to inferior mesenteric artery root on the prognosis of rectal cancer.</p><p><b>METHODS</b>Clinicopathological data of 260 cases with rectal cancer undergone radical operation were analyzed retrospectively. The patients were divided into two groups. Group D(2): the lymph nodes adjacent to mesenteric artery root were not excised (n=188). Group D(3): the lymph nodes adjacent to mesenteric artery root were excised (n=72). Prognosis of two groups was compared during the follow-up period.</p><p><b>RESULTS</b>In group D(2), the 1-, 3-, 5-year total survival rates (TS) were 97.3%, 87.2% and 77.1%, and tumor-free survival rates (TFS) were 93.1%, 83.0% and 76.8% respectively. In group D(3 ), the 1-, 3-, 5-year total survival rates (TS) were 94.4%, 79.2% and 73.6%, and tumor-free survival rates (TFS) were 86.1%, 76.4% and 71.0% respectively. The differences of TS and TFS between two groups were not significant according to Kaplan-Meier analysis (P>0.05). Multivariate analysis revealed that the excision of lymph nodes adjacent to mesenteric artery root was not statistically correlated with the recurrence, metastasis and survival time after radical operation of rectal cancer.</p><p><b>CONCLUSION</b>Excision of lymph nodes adjacent to inferior mesenteric artery root has no significant impact on prognosis and it is unnecessary in the radical operation of rectal cancer.</p>

Diagnosis and surgery treatment of gastric neurogenic tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics, diagnosis and treatment of gastric neurogenic tumors.</p><p><b>METHODS</b>Clinical data of 11 patients with gastric neurogenic tumors confirmed by pathology, operation and immunohistochemistry were analysed retrospectively.</p><p><b>RESULTS</b>There were 7 males and 4 females with a median age of 55.5 years. The main manifestations were gastrointestinal hemorrhage, abdominal pain, upper abdominal discomfort and anaemia. Nine patients underwent gastroscopy and only one case was confirmed by the examination. Two patients were diagnosed during operation. Eight patients were submitted to subtotal gastrectomy, three were partial gastrectomy. All patients were followed up, and perioperative death occurred in one patient because of respiratory failure, recurrence occurred in two patients. Other patients with long- term follow- up had a good prognosis.</p><p><b>CONCLUSIONS</b>Gastric neurogenic tumors have no specific clinical characteristics preoperatively, and the misdiagnosis rate is high. Once the diagnosis of gastric neurogenic tumors is made, an operation should be performed as early as possible.</p>

Rational approach to the management of IV stage gastric carcinoma with hepatic metastasis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the benefit of surgical resection on the prognosis of patients with advanced gastric carcinoma and liver metastasis.</p><p><b>METHODS</b>Data of 102 cases of advanced gastric carcinoma with liver metastases from 1993 to 2004 were studied retrospectively.</p><p><b>RESULTS</b>The half-, one- and two-year postoperative survival rates of gastric carcinoma patients with H(1) metastasis undergone palliative resections were 69%, 44% and 6% respectively, which were significantly better than those of patients not undergone resection(accepted by-pass procedure or exploratory laparotomy) (P=0.009). The half-, one- and two-year postoperative survival rates of gastric carcinoma patients with H(2) metastasis undergone palliative resections were 56%,13% and 6% respectively, which were not significantly different compared with those of patients not undergone resection(P=0.068). The half-, one- and two-year postoperative survival rates of gastric carcinoma patients with H(3) metastasis undergone palliative resections were 25%, 13% and 0, which were not significantly different compared with those of cases not undergone resection (P=0.157). Regardless of peritoneal metastases, there were no significant differences between the survival rate of resection group and that of non-resection group.</p><p><b>CONCLUSIONS</b>Gastric carcinoma patients with H(1) metastasis would benefit from palliative resection regardless of peritoneal metastasis. Gastric carcinoma patients with H(2) or H(3) metastasis are not benefit from surgical resection.</p>

Retrospective analysis of extended gastrectomy and lymphadenectomy in early gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To objectively evaluate the practical significance of different extended surgeries in early gastric cancer(EGC) patients, and to choose reasonable gastrectomies and lymphadenectomies.</p><p><b>METHODS</b>A total of 217 EGC patients were investigated undergone normalized D2 or above extended surgery and their clinicopathological data were recorded in detail. The efficiency of the extended lymphadenectomies, complications and operation causes were analyzed, and the correlation between the group 2 lymph node metastasis (LNM) and clinicopathological factors were assessed, too.</p><p><b>RESULTS</b>There was no nodal involvement in the No.5 and No.6 lymph nodes among the total gastrectomy in the upper third of the stomach, neither was in the No.10, 11p and 11d lymph nodes among the combined splenectomy, and neither was in the No.15 lymph nodes among the combined transverse mesocolon resection in the lower third of the stomach. There was no distant nodal involvement in the EGC. Above all, most of them were mistaken for advanced gastric cancer preoperatively and intraoperatively, the operation time was longer and the blood loss was more during operation. Among the resected nodes of group 2 in the lower third of the stomach, metastasis was not found in the No.11p, 12a and 14v lymph nodes. The rate of the No.7 and 8a nodal involvement in the submucosa cancer was higher than that in the mucosa cancer(P<0.05) and so did the No.7 in the lymphatic penetration positive(P<0.001). The No.1 and No.13 nodal involvement were only seen in the high risk cases, such as submucosa cancer, the lesion diameter more than 3.0 cm, depressed type and lymphatic involvement.</p><p><b>CONCLUSION</b>It is not necessary to execute total gastrectomy in the upper third of the stomach, combined organ resection (such as splenectomy, transverse mesocolon resection), and distant lymph node dissection in the EGC. In the lower third of the stomach, the No.11p 12a and 14v lymph nodes shouldn't be dissected. With respect to the high risk nodal involvement cases in the lower third of the stomach, the No.1 lymph nodes should be dissected and so does the No.13 lymph nodes if it's tumefied. It is the key point of reasonable operation to exactly diagnose the EGC before and during the surgery.</p>

Double-mutant dihydrofolate reductase gene transfection into bone marrow cells protects mice from chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the feasibility of transfecting DHFR (human double-mutant dihydrofolate reductase) gene into mouse bone marrow cells and the effect of resistance to high dose MTX chemotherapy.</p><p><b>METHODS</b>After DHFR gene was transfected into mouse bone marrow cells with retroviral vector, the cells were treated with methotrexate (MTX) and then CFU-GM (granulocyte-macrophage colony-forming unit) assay was performed. Peripheral blood leucocytes and platelets, body weight and survival rate were observed. After treatment with high dose MTX, the expression of drug resistance gene was checked by RT-PCR in the transfected bone marrow cells.</p><p><b>RESULTS</b>SFG-F/S-NeoR gene-transfected mice bone marrow cells yielded drug-resistance colonies to MTX (donor mice: 15.8%, recipient mice: 18.0%, control: 0) The peripheral blood leucocytes and platelets, body weight recovered gradually and the survival rate was 83.3% at the 40th day, while 0 in controls in gene transfected mice after large dose MTX treatment. RT-PCR of transgenic mouse marrow cells showed the band of F/S gene (400 bp).</p><p><b>CONCLUSION</b>DHFR gene can not only be integrated and expressed in bone marrow cells but also improve their drug-resistence to MTX.</p>

Expression and significance of interleukin-8 cyclooxygenase-2 and trefoil family factor 1 in the remnant stomach mucosa / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression and significance of interleukin-8 (IL-8), cyclooxygenase-2 (COX-2) and trefoil family factor 1 (TFF1) in the remnant stomach mucosa.</p><p><b>METHODS</b>Patients after gastrectomy were examined by upper gastrointestinal endoscopy. Biopsy specimens were obtained from stoma and the greater curvature of the upper corpus to be assessed for Hp (by H.E. and Giemsa staining) and conduct real-time semi-quantitative PCR. mRNA was extracted from the biopsy specimens to determine the IL-8, COX-2 and TFF1 gene mRNA levels by real-time PCR method.</p><p><b>RESULTS</b>In the stoma, COX-2 level in Hp-positive patients was significantly higher than that in Hp-negative patients, but the difference of IL-8 levels between them was not significant. In the corpus, IL-8 and COX-2 levels in Hp-positive patients were significantly higher than those in Hp-negative patients. In Hp-negative patients, IL-8 and COX-2 levels in the stoma were significantly higher in B II anastomosis than in B I anastomosis cases; COX-2 level in the stoma was significantly higher in B II anastomosis than in B I anastomosis cases, but the difference of IL-8 levels between them was not significant. TFF1 level in the remnant stomach mucosa showed no significant difference between Hp-positive and Hp-negative patients.</p><p><b>CONCLUSION</b>Hp infection and bile reflux are important risk factors for the secondary stomach carcinogenesis. Expression of IL-8 and COX-2 in the remnant stomach mucosa is related to the risk of secondary stomach carcinogenesis. The relationship between the TFF1 expression and secondary stomach carcinogenesis in the remnant stomach mucosa is still unclear and should further be studied.</p>

Evaluation of the correlations of cell proliferation activity with lymphatic and vascular invasion and prognosis in gastric carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate bromodeoxyuridine/DNA (BrdUrd/DNA) double-parametric flow cytometric analysis in detection of gastric carcinoma and to study the correlations of cellular BrdUrd labeling index (LI), G(2)/M phase fraction (G(2)/MPF) and DNA content, with lymphatic and vascular invasion and prognosis.</p><p><b>METHODS</b>Sixty cases of fresh tumor samples were examined by BrdUrd/DNA double-parametric flow cytometry.</p><p><b>RESULTS</b>BrdUrd LI and G(2)/MPF values were both significantly higher in patients with lymphatic invasion than those without invasion (P < 0.01). There was statistically significant difference between the 5-year survival rates in cases with and without lymphatic invasion (P < 0.01). Both BrdUrd LI and G(2)/MPF values were significantly higher in patients with lymph node metastasis than those in cases without metastasis (P < 0.01). There was a significant difference in 5-year survival rates between patients with and without lymph node metastases. The incidence of lymph node metastasis was significantly higher in aneuploid carcinoma (P < 0.05), and the patients with aneuploidy had significantly poor prognosis. BrdUrd LI was significantly higher in patients with more than 5 metastatic lymph nodes than those with 1-4 metastatic lymph nodes (P < 0.05) and no metastasis (P < 0.01). G(2)/MPF values in cases with more than 5 and 1-4 metastatic lymph nodes were higher than that in cases with no metastasis (P < 0.01 and P < 0.05, respectively). There were significant differences in 5-year survival rates among patients with no lymph node metastasis, 1-4 nodes metastasis and more than 5 nodes metastasis. G(2)/MPF values were significantly higher in patients with and without vascular invasion (P < 0.01).</p><p><b>CONCLUSION</b>Correlations exist among cellular BrdUrd LI, G(2)/MPF, DNA content and lymphatic involvement, vascular invasions and prognosis in gastric carcinoma.</p>

The relationship between the expressions of interleukin-8 and cyclooxygenase-2 and the type of anastomosis in the remnant stomach / 中华外科杂志

<p><b>OBJECTIVE</b>To study the expressions and the significance of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in the remnant stomach.</p><p><b>METHODS</b>Fifty-eight patients with gastrectomy were examined by upper gastrointestinal endoscopy. Two biopsy specimens were obtained from the stoma and the upper corpus gastric mucosa in the remnant stomach. mRNA was extracted from biopsy specimens to measure the IL-8 and COX-2 gene mRNA levels by real-time PCR method.</p><p><b>RESULTS</b>IL-8 and COX-2 levels were higher in stoma than in corpus, IL-8 levels in BI anastomosis were significantly higher in stoma than in corpus (P< 0.05). In Hp-negative patients, IL-8 and COX-2 levels in stoma were significantly higher in BII anastomosis than in BI anastomosis (P < 0.05). In Hp-positive patients, IL-8 and COX-2 levels in stoma showed no significant differences between BII anastomosis and BI anastomosis. In corpus, IL-8 and COX-2 levels in Hp-positive patients were significantly higher than those in Hp-negative patients, (P < 0.05), including in BI anastomosis and in BII anastomosis.</p><p><b>CONCLUSIONS</b>The risk of the secondary stomach carcinogenesis in stoma after distal gastrectomy is higher than that in corpus; The types of anastomosis may influence the risk for the secondary stomach carcinogenesis in the remnant stomach mucosa.</p>

Mice transduced with double-mutant dihydrofolate reductase-cytidine deaminase fusion gene attained protection from high dose chemotherapy / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility of transferring fusion gene of dihydrofolate reductase (DHFR) gene and cytidine deaminase (CD) gene into mouse bone marrow cells in order to observe the drug resistance of high dose methotrexate (MTX) and cytosine arabinoside (Ara-C) in the bone marrow cells and to improve the tolerance of myelosuppression following combination chemotherapy.</p><p><b>METHODS</b>Human double-mutant dihydrofolate reductase-cytidine deaminase fusion gene was transferred into two mice bone marrow cells by retroviral vector. Resistant colony-forming unit granulocyte-macrophage (CFU-GM) assays were performed in mouse bone marrow cells by retroviral infection and after treatment by drugs (Ara-C, MTX, and Ara-C + MTX). DNA was extracted from mouse bone marrow cells. The expression of drug resistant genes in mouse bone marrow cells after transferring by retroviral vector was checked by polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Bone marrow cells after coculture with the retroviral producer cells transduced with the genes (SFG-F/S-CD) showed the drug resistance colonies yield (Colony formation after exposure to Ara-C, MTX and Ara-C + MTX were 56%, 22% and 14%, respectively) and the increase in drug resistant to both MTX and Ara-C (P < 0.005). Expression of DHFR and CD gene in extracted DNA of transfected mice were demonstrated by PCR.</p><p><b>CONCLUSIONS</b>Double drug resistant gene can not only integrate and co-express in mice bone marrow cells but also increase the drug resistance to MTX and Ara-C.</p>

Relations of proliferative activities of gastric carcinoma cells to lymphatic involvement, venous invasion and prognosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This study was to evaluate bivariate bromodeoxyuridine (BrdUrd)/DNA flow cytometric analysis in detection of gastric carcinoma and to study the relations of cellular BrdUrd labeling indices (LI), G2/M-phase fraction (G2/MPF) and DNA ploidy pattern to lymphatic involvement, venous invasion and prognosis.</p><p><b>METHODS</b>Fresh tumor samples from 60 patients with gastric carcinoma were analyzed by bivariate BrdUrd/DNA flow cytometry. The results were correlated with lymphatic vessel invasion, lymphatic node metastasis, the number of metastatic lymphatic nodes, and venous invasion. Propidium iodide (PI) was used as a fluorescent probe for total cellular DNA, and a monoclonal antibody against BrdUrd was used as a probe for BrdUrd incorporated into DNA. Fluorescent-labeled goat anti-mouse antibody was used as a second antibody. S-phase fractions were measured by in vitro BrdUrd labeling, and DNA ploidy and G2/MPF were also measured. Comparison of survival was performed with the log-rank test, the Chi-square test for qualitative data, and Student's t test for quantu data.</p><p><b>RESULTS</b>BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic vessel invasion than in those without invasion respectively (P < 0.01); the patients who had tumors with lymphatic vessel invasion showed a significantly poor prognosis (P < 0.01). Both BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic node metastasis than in those without metastasis (P < 0.01). A statistical significant difference was noted in the 5-year survival rates between the patients with lymph node metastasis and those without metastasis. Compared with diploid carcinoma, the incidence of lymph node metastasis was significantly higher in aneuploid carcinoma (P < 0.05), and the patients with aneuploid carcinoma showed a significantly poor prognosis (P < 0.05). BrdUrd LI was significantly higher in patients with more than 5 metastatic lymph nodes than those with 1 - 4 metastatic lymph nodes (P < 0.05) and those without metastasis (P < 0.01). G2/MPF values in those patients either with more than 5 metastatic lymph nodes or 1 - 4 metastatic lymph nodes were higher than those without metastasis (P < 0.01 and P < 0.05). A statistical significance was seen in the 5-year survival rates among the patients with no metastatic lymph node, 1 - 4 metastatic nodes and more than 5 metastatic nodes (P < 0.01). G2/MPF values were significantly higher in patients with venous invasion than in those without invasion (P < 0.01).</p><p><b>CONCLUSIONS</b>Positive correlations exist between cellular BrdUrd LI, G2/MPF with lymphatic involvement and prognosis, and DNA aneuploid with lymphatic involvement and prognosis. The same was true between G2/MPF value and venous invasion in gastric carcinoma.</p>

Effect of activated greater omental milky spots and peritoneal macrophages on tumoricidal activity against gastric carcinoma SGC-7901 in mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of activated greater omental milky spots and peritoneal macrophages in mice on tumoricidal activity against gastric carcinoma SGC-7901, following intraperitoneal (i.p.) injection of INF-gamma, staphylococcin aureus or NDV-L.</p><p><b>METHODS</b>The quantitative changes of milky spots were determined by activated carbon, the number of the macrophage in milky spots was assessed by nonspecific esterase stain and the number of peritoneal macrophages was counted by trypan blue exclusion. The morphology of peritoneal macrophages was observed by scanning electron microscope, the amount of TNF-alpha and iNOS mRNA expressed by peritoneal macrophages was measured by fluorescence quantitative PCR and the cytotoxicity of peritoneal macrophages supernatant against SGC-7901 was evaluated by MTT assay.</p><p><b>RESULTS</b>It was found in the treated groups that: 1. The amount of greater omental milky spots and the macrophages in milky spots increased, 2. The number of peritoneal macrophages increased. The peritoneal macrophages were in activated status. The effect TNF-alpha and iNOS mRNA expression increased and 3. The cytotoxicity against in vitro SGC-7901 increased.</p><p><b>CONCLUSION</b>Intraperitoneal injection of IFN-gamma, staphylococcin aureus or NDV-L could activate the milky spots of the greater omentum and the macrophages in peritoneal cavity in mice, with IFN-gamma being the best. The supernatant of activated peritoneal macrophages has cytotoxicity against SGC-7901. Administration of LPS to macrophages cultured in vitro could amplify the activation and enhance the cytotoxicity of the supernatant against SGC-7901.</p>