Peritoneal Metastasis Of Gastric Cancer Research Articles

Inhibitory effects of a specific phage-displayed peptide on high peritoneal metastasis of gastric cancer

Peritoneal dissemination in gastric cancer is the most frequent cause of the noncurative resection and recurrence after curative resection. We, therefore, evaluated the feasibility of a peptide, which was obtained by screening a random phage display library, in the treatment of peritoneal metastases of gastric cancer. In this study, a novel cell line, GC9811-P, with a high potential peritoneal metastasis of gastric cancer derived from its parental cell line, GC9811, was established. Using a phage display library, we isolated a specific peptide that selectively bound to GC9811-P cells rather than its parental GC9811cells. The isolated phage-displaying peptide, SMSIASPYIALE (named peptide PIII), was obtained after four rounds of selection, showing a tendency to preferentially bind to GC9811-P cells compared with a panel of other gastric cancer cell lines, and preferentially accumulate in peritoneal metastasis tumor tissue in comparison with control organs, peritoneum, liver, pancreas, spleen, lung, and kidney. Further study showed that synthetic peptide PIII could significantly inhibit adhesive and invasional ability of GC9811-P cells and could effectively block the corresponding phage binding to the GC9811-P cells, whereas, exposure of the cells to various concentrations of peptide PIII showed no obvious cell growth inhibition. Furthermore, a highly reproducible animal experimental model of gastric cancer with peritoneal dissemination was established in nude mice by injecting a suspension of the cell line into the gastric wall of nude mice. Animals intraperitoneally treated with peptide PIII in this model or another animal model of gastric cancer with peritoneal dissemination established using MKN45 cells showed suppressed tumor metastasis to peritoneum and significantly prolonged survival. In conclusion, the selected peptide PIII was a biologically active peptide and could effectively inhibit peritoneal dissemination of gastric cancer.

Efficacy of S-1 for Patients with Peritoneal Metastasis of Gastric Cancer

Background: This study was designed to examine the efficacy and compliance of S-1 for the patients with peritoneal metastasis of gastric cancer. Methods: Sixteen consecutive patients with peritoneal metastasis of gastric cancer were treated with S-1. Their survival was compared with that of the historical control group (25 patients). Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase and orotate phosphoribosyl transferase mRNA expression in the tumor were evaluated. Results: The median survival time of S-1-treated patients was 550 days, which was significantly longer than that of the historical control group (215 days). We elucidated some factors to prolong the survival of the patients treated with S-1 for peritoneal metastasis: peritoneal metastasis without other distant metastases, the combination of S-1 treatment and gastrectomy, and low expression of thymidine phosphorylase mRNA in primary tumors. Conclusions: S-1 showed a surprisingly long-term survival with minimum toxicity in patients with peritoneal metastasis of gastric cancer.

Identification of oligopeptides binding to peritoneal tumors of gastric cancer

This is a report of in vivo intraperitoneal biopanning, and we successfully identified a novel peptide to target the multiple peritoneal tumors of gastric cancer. A phage display library was injected directly into the abdominal cavity of mice bearing peritoneal tumors of human gastric cancer, and phages associated with the tumors were subsequently reclaimed from isolated samples. The tumor-associated phages were amplified and the biopanning cycle was repeated five times to enrich for high affinity tumor-selective binding peptides. Finally, a tri-peptide motif, KLP, which showed homology with laminin 5 (a ligand for alpha3beta1 integrin), was identified as a binding peptide for peritoneal tumors of gastric cancer. Phage clones displaying the sequence KLP showed 64-fold higher binding to peritoneal tumors than control phage and were preferentially distributed in tumors rather than in normal organs after intraperitoneal injection into mice. In addition, the KLP phages were more likely to bind to cancer cells in malignant ascites derived from a patient with recurrent gastric cancer. Synthesized peptide containing the motif KLP (SWKLPPS) also showed a strong binding activity to peritoneal tumors without cancer growth effect. Liposomes conjugated with SWKLPPS peptide appeared significantly more often in tumors than control liposomes after intraperitoneal injection into mice. Furthermore, modification of liposomes with SWKLPPS peptide enhanced the antitumor activity of adriamycin on gastric cancer cells. The peptide motif KLP seems a potential targeting ligand for the treatment of peritoneal metastasis of gastric cancer.

Clinical and diagnostic significance of preoperative computed tomography findings of ascites in patients with advanced gastric cancer

Background The relationship between ascites, as detected by preoperative computed tomography (CT), and peritoneal metastasis of gastric cancer requires clarification because of its likely significance for clinical outcome. Methods A retrospective analysis of 293 patients with advanced gastric cancer investigated the association between preoperative CT findings of ascites and surgical findings of peritoneal washing cytology and peritoneal metastasis. Results Forty-five of 293 patients (15%) presented with ascites on preoperative CT. Positive ascites on CT predicted the presence of free tumor cells with 40% sensitivity and 97% specificity, and peritoneal metastasis with 51% sensitivity and 97% specificity. Ascites on CT was an independent prognostic factor by univariate ( P < .001) and multivariate (relative risk, 2.03; 95% confidence interval, 1.39–2.96; P < .001) analyses. The median survival time was 6.0 months in patients with positive ascites on CT. Conclusions The presence of ascites on CT suggests the presence of peritoneal metastasis and indicates a poor prognosis. The presence of peritoneal metastasis should be confirmed by diagnostic laparoscopy in gastric cancer patients with ascites.

Inhibition of PRL-3 gene expression in gastric cancer cell line SGC7901 via microRNA suppressed reduces peritoneal metastasis

High expression of PRL-3, a protein tyrosine phosphatase, is proved to be associated with lymph node metastasis in gastric carcinoma from previous studies. In this paper, we examined the relationship between PRL-3 expression and peritoneal metastasis in gastric carcinoma. We applied the artificial miRNA (pCMV-PRL3miRNA), which is based on the murine miR-155 sequence, to efficiently silence the target gene expression of PRL-3 in SGC7901 gastric cancer cells at both mRNA and protein levels. Then we observed that, in vitro, pCMV-PRL3miRNA significantly depressed the SGC7901 cell invasion and migration independent of cellular proliferation. In vivo, PRL-3 knockdown effectively suppressed the growth of peritoneal metastases and improved the prognosis in nude mice. Therefore, we concluded that artificial miRNA can depress the expression of PRL-3, and that PRL-3 might be a potential therapeutic target for gastric cancer peritoneal metastasis.

SIADH Caused by the Synergistic Effect of S-1 and Thiazide

Hyponatremia is a dangerous electrolyte disturbance in patients on chemotherapy and may cause sudden death if not detected early. SIADH (syndrome of inappropriate antidiuretic hormone) is one of the known causes of hyponatremia in patients undergoing chemotherapy. Few chemotherapeutic agents, however, are reported to cause SIADH. The current study reports that SIADH developed in a 55 year old woman on S-1 () and cisplatin () chemotherapy for the peritoneal metastasis of gastric cancer. The patient underwent a total gastrectomy, a splenectomy, and a segmental resection of the transverse colon for gastric cancer. She had used thiazide and to treat hyperiension for 12 years. She admitted to our hospital with complaining of general weakness, dysarthria, loss of appetite, and urinary discomfort. The serum level of sodium and potassium were 94 mEq/L and 2.2 mEq/L respectively. The hyponatremia completely resolved uneventfully after 3% saline infusion, which led to normalized electrolyte balance. The patient was discharged on the 13th hospital day.

Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer

Inhibitor of DNA binding (Id) proteins are essential for cell differentiation, proliferation, migration, invasion and angiogenesis. Recently, they have been shown to correlate with less differentiated phenotypes, high malignant potential and poor clinical outcome in various kinds of tumors. In an attempt to develop new strategies for the treatment of peritoneal metastasis of gastric cancer, we prepared an Id1, 3 double-knockdown gastric cancer cell line, MKN45, by RNA interference and investigated its effects on the development of metastatic nodules in the peritoneal cavity. Both cell proliferation and migration capabilities were decreased in Id1, 3 double-knockdown cells, as was their ability to bind to laminin, which could be explained by the decreased expression of integrin alpha6. These are important steps in the metastatic process. In a mouse model, the number of peritoneal metastatic nodules formed by Id1, 3 double-knockdown cells was reduced compared to mock-transfected control cells, as was the size of individual tumors. In this study, we clearly demonstrated that Id1, 3 double-knockdown significantly impaired the ability of gastric cancer cells to form peritoneal metastasis. Id should be considered an ideal target for the treatment and prevention of gastric cancer, and RNA interference is an attractive and promising strategy to achieve it.

Possible Involvement of RUNX3 Silencing in the Peritoneal Metastases of Gastric Cancers

Our previous results suggested that a lack of RUNX3 function contributed to human gastric carcinogenesis, but the role of RUNX3 in progression and metastasis remains unclear. We examined RUNX3 expression in clinical samples of peritoneal metastases in gastric cancers. Changes in metastatic potential were assessed in animal experiments using stable RUNX3 transfectants of gastric cancer cells. Finally, global expression changes were analyzed using a cDNA microarray. Significant down-regulation of RUNX3 through methylation on the promoter region was observed in primary tumors (75%) as well as in all clinical peritoneal metastases of gastric cancers (100%) compared with normal gastric mucosa. Stable transfection of RUNX3 inhibited cell proliferation slightly, and modest transforming growth factor-beta (TGF-beta)-induced antiproliferative and apoptotic effects were observed. Interestingly, it strongly inhibited peritoneal metastases of gastric cancers in animal model (P < 0.01). Furthermore, we did globally analyzed expression profiles of approximately 21,000 genes in parent cells and stable transfectant of RUNX3 using a cDNA microarray. Microarray analysis identified approximately 28 candidate genes under the possible downstream control of RUNX3, some of these genes were considered to be possibly involved in peritoneal metastases, which were related to signal transduction (vav3, TOLL-like receptor, MAPKK, MET, S1 00A1 1, and cathepsin E), apoptosis (caspase 9), immune responses (CD55 and TLR1O), and cell adhesion (sialyltransferase 1 and galectin 4). Some of the genes are involved in the TGF-beta signaling pathway. These results indicate that silencing of RUNX3 affects expression of important genes involved in aspects of metastasis including cell adhesion, proliferation, apoptosis, and promoting the peritoneal metastasis of gastric cancer. Identification of such genes could suggest new therapeutic modalities and therapeutic targets.

Sequential chemotherapy of S-1/weekly paclitaxel in patients with peritoneal metastasis of gastric cancer

4236 Background: The aim of this study is to clarify the survival benefit of sequential chemotherapy of S-1/weekly paclitaxel in patients (pts) with peritoneal metastasis of gastric cancer. Methods: A total of 91 gastric cancer pts, including synchronous peritoneal metasitasis in 66 and metachronous one in 25 pts, were treated with S-1 (80mg/m2/day for 4 weeks with 2 weeks rest) until progression. When S-1 was failed, pts then underwent paclitaxel (80 mg/m2 at day 1, 8, 15 every 28 days) if applicable. Of 66 synchronous disease, 9 were only positive for intra-peritoneal lavage cytology. Median age was 64 years (27–85). Fifteen pts had undergone prior chemotherapy. Performance status (PS) was 0 in 22 pts, 1 in 49 pts, and 2 in 20 pts. Results: S-1 was discontinued because of toxicity in 10 pts. Paclitaxel was applicable for 47 pts including PS0–2 in 36 pts, and PS3 in 11 pts. Overall median survival time (O-MST) after the initiation of S-1 was 300 days. O-MST was 256 days in pts with prior chemotherapy and 329 days in pts without one (p=0.02), and 356 days for PS0/1 and 234 days for PS2 (p=0.00), respectively. Median time to progression of S-1 was 173 days. MST after paclitaxel (P-MST) was 155 days. P-MST was 222 days and O-MST was 507 days in pts with PS 0/1/2 when paclitaxel was started. Conclusions: Sequential chemotherapy of S-1/weekly paclitaxel may benefit pts with peritoneal metastases, especially for pts with good PS. No significant financial relationships to disclose.

Experimental radioimmunoguided surgery for peritoneal metastases of gastric cancer using anticarcinoembryonic antigen-specific T84.66 F(ab’)2

In gastric cancer, peritoneal dissemination is the most frequent cause of the noncurative resection and recurrence after curative resection. We therefore evaluated the feasibility of radioimmunoguided surgery (RIGS) in the treatment of peritoneal metastases of gastric cancer and the use of anti-CEA-specific T84.66 F(ab')2 as an efficient immune agent. Two human gastric cancer cell lines, MKN45 and RF48, were intraperitoneally xenografted into nude mice, which were later injected with 125I-labeled T84.66 F(ab')2. Peritoneal tumors were localized by RIGS 5 days after antibody injection. The minimum number of cells detected by a gamma probe was assayed by in vitro tumor cell localization. We observed 37 peritoneal metastases: 8 invisible (long diameter, <1 mm), 6 small (1- < 5 mm), and 23 large (> or =5 mm) tumors. The accuracy, sensitivity and specificity of RIGS in detecting peritoneal metastasis were 82% (69/84), 76% (28/37), and 87% (41/47), respectively. RIGS accuracy did not differ with respect to tumor diameter. Mean labeling indices over minimal and maximal normal counts were 6.1+/-1.2 (mean +/- SEM) and 4.7+/-1, respectively. Mean scores of CEA immunostaining and silver grains in tumors were significantly higher than those in the nontumor-bearing peritoneum (P < 0.001). There was a close correlation among radioactivity, immunostaining and microautoradiography (P < 0.001-0.005). We observed six false-positive and nine false-negatives which may have been due to high blood background and negative radioimmune reactivity, respectively. 125I-labeled T84.66 F(ab')2 efficiently targeted peritoneally disseminated gastric cancer cells, suggesting that RIGS using this immune agent may accurately detect occult peritoneal metastases in patients with gastric cancer.

Study on association between the expression of galectin- 3 and the peritoneal metastasis in gastric cancer

To investigate the association between the expression of galectin- 3 protein and peritoneal metastasis in gastric cancer. The expressions of galectin- 3 was detected in matching- samples including primary gastric cancer lesions,lymph node metastases,peritoneal metastases and paratumor normal tissues by immunohistochemistry. All specimens were gained from 35 patients who had synchronous peritoneal metastasis from gastric cancer. The over- expression of galectin- 3 was observed in 97% (34/35) of the gastric cancer lesions, the peritoneal metastases and the lymph node metastases,whereas in 14% (5/35) of paratumor normal tissues. There were significant differences in the expression of galectin- 3 between paratumor normal tissues and the gastric carcinoma lesions,peritoneal metastases and lymph node metastases (P< 0.05),but there were no significant differences among the gastric cancer lesions,the peritoneal metastases,and the lymph node metastases (P> 0.05). The expression of galectin- 3 in gastric cancer lesions can be used as a biological marker of peritoneal metastasis from gastric cancer before operation and as a prognostic factor of gastric cancer.

Adenoviral-mediated Gene transduction of the hepatocyte growth factor (HGF) antagonist, NK4, suppresses peritoneal metastases of gastric cancer in nude mice

The competitive inhibitory effects of NK4 (a specific hepatocyte growth factor (HGF)-antagonist) on the interaction between HGF and the c-Met/HGF receptor has been shown in HGF-mediated invasion of some distinct types of human cancer cells. Furthermore, NK4 has inhibitory effects on the angiogenic pathways driven by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), as well as by HGF. In this study, to evaluate the therapeutic efficacy of adenoviral-mediated NK4 gene treatment, we employed animal models of peritoneal metastasis using two gastric cancer cell lines, the strongly c-Met expressing MKN45 cell line and the weakly c-Met-expressing cell line, TMK1. In both models, the total number and weight of peritoneal tumours per mouse and ascites treated early with AxCANK4 (administered 3 times 2, 7 and 12 days after the tumour inoculation) were significantly reduced compared with those treated with phosphate-buffered solution (PBS) and AxCALacZ ( P<0.05). In Factor-VIII-related-antigen-stained sections from peritoneal metastatic tumours, the inhibition of intratumour vessels was observed in tissues from tumours of MKN45 and TMK1 treated with AxCANK4. We also compared the therapeutic effect of early AxCANK4 treatment with that of late treatment (at 7, 12 and 17 days). Peritoneal metastases and ascites treated late with AxCANK4 showed less of an improvement than those treated early with AxCANK4 in both models. In addition, the inhibitory effect of cisplatin (CDDP) on peritoneal metastasis was significantly enhanced by AxCANK4, suggesting that the combination of intraperitoneal (i.p.) chemotherapy with NK4 gene therapy might be effective, even in cases of advanced peritoneal metastasis from gastric cancer. To conclude, these results show clearly that NK4 gene therapy inhibits peritoneal metastases from gastric cancer, regardless of the level of c-Met/HGF receptor expression in the tumour cells, and especially in the early stages of peritoneal metastasis.

Suppression of peritoneal metastasis in human gastric carcinoma by enhanced immunogenicity of B7-1 transfection

B7-1, a co-stimulatory factor, has been reported to induce cytotoxic T lymphocytes (CTL). In the present study, we transfected B7-1 genes into a gastric cancer cell line (2MD3) and analyzed the effects of B7-1 transduction on peritoneal metastasis in vitro and in vivo. We revealed that mononuclear lymphocytes show significantly stronger adherence and cytotoxicity to B7-1 transfected cells (2MD3/B7) than to their parent 2MD3 cells. We also demonstrated that mice inoculated with 2MD3/B7 cells in the peritoneal cavity have a significantly better survival rate than those inoculated with 2MD3 cells (log-rank test, p<0.01). Histologic findings showed that leukocytes intensively infiltrate the 2MD3/B7 metastatic nodules, but can scarcely be observed in the nodules associated with 2MD3 cells. These findings indicate that the B7-1 may play an important role in suppressing peritoneal metastasis by the mechanism of enhanced immunogenicity, and that B7-1 gene transduction might be effective against peritoneal metastases of gastric cancer.

Predictive value of preoperative serum CEA, CA19-9 and CA125 levels for peritoneal metastasis in patients with gastric carcinoma.

Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. This study analyzed the usefulness of diagnostic imaging and various tumor markers in the detection of peritoneal metastasis in gastric cancer. The sera from 768 patients with gastric cancer were measured for CEA, CA19-9 and CA125 levels using a commercial immunoradiometric assay. All the patients underwent diagnostic imaging with computed tomography (CT) and ultrasound (US) before laparotomy. Preoperative levels of CEA, CA19-9 and CA125 were above the cut-off levels in 15.4%, 8.7% and 5.7% of all cases, respectively. Eighty-eight patients were diagnosed with peritoneal metastasis by laparotomy. CT and US revealed peritoneal dissemination in 15 of 88 patients (17%). Among the three tumor markers, CA19-9 and CA125 showed similar detection rates of peritoneal metastasis (37.5% and 38.6%, respectively). In particular, the serum CA125 levels showed the best sensitivity (38.6%), specificity (98.4%), and diagnostic accuracy (91.5%), and the highest odd ratio (24.46, 95% CI: 11.17 approximately 53.57) for predicting peritoneal metastasis among the markers tested. CEA did not add significant predictive information (p=0.471). Preoperative serum CA19-9 and CA125 levels may provide a predictable value in determining peritoneal metastasis in patients with gastric cancer.

A new scoring system for peritoneal metastasis in gastric cancer.

The degree of peritoneal metastasis (PM) of gastric cancer has been classified into four grades (P0, P1, P2, and P3) in the Japanese Classification of Gastric Carcinoma, First English Edition. However, the PM category in this version was so ambiguous in terms of volumetry that it was unlikely to estimate PM status correctly. We have developed a new volume scoring system for PM, modifying Sugarbaker's classification. Eighty-five patients with gastric cancer with PM underwent surgery and/or laparoscopy at our hospital at Kanazawa University between January 1990 and December 2000. The grading (Gr) by the volume scoring system was decided according to the sum of scores for nine (in male) or ten (in female) abdominopelvic regions. These regions included left subphrenics, right subphrenics, left flank, right flank, pelvis, omenta, mesentery, small and large bowels, ovaries (only for females), and other intraabdominal organs. Volumetry for each region was carried out using the following categories: VS0, indicating the absence of cancer in a particular abdominopelvic region; VS1, indicating that tumor nodules are less than 10 mm in diameter; VS2, indicating tumors between 1 and 5 cm in diameter; and VS3, indicating that tumor is more than 5 cm in diameter or that an organ is coated by a mat of tumor (confluent disease). The scores for VS0, VS1, VS2, and VS3 were 0, 1, 2, and 3 points, respectively. Total scores of 1 to 3 were the equivalent of Gr I, total scores of 4 to 6 were equivalent to Gr II, total scores of 7 to 9 were equivalent to Gr III, and total scores of more than 9 were equivalent to Gr IV. There was no significant difference between P1 and P2, or between P1 and P3 in survival curves. But the 50% survival times of Gr I, Gr II, Gr III, and Gr IV were 1.23, 0.66, 0.67, and 0.32 years, respectively. The prognosis of Gr I was significantly better than that of any other grades. Eight of the 28 patients (29%) assessed as Gr I survived more than 2 years, whereas only 2 of the 57 (4%) assessed as Gr II, Gr III, or Gr IV did so. Multivariate analysis by Cox's proportional hazard model revealed that the volume scoring, resection of primary tumor, and resection of peritoneal tumor were independent factors to predict prognosis. These results showed that the volume scoring system was strongly related to the prognosis, and the patients assessed as Gr I had a great probability of cure by surgery.

Diagnostic laparoscopy, serum CA125, and peritoneal metastasis in gastric cancer.

Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. We report on the utility of laparoscopy and its indications in the detection of peritoneal metastasis in gastric cancer. A total of 39 patients with gastric cancer underwent laparoscopy and peritoneal cytology investigation in our department, between April 1992 and April 2000. Laparoscopic diagnosis for peritoneal metastasis (LP-P) was determined through macroscopic, pathological and cytological diagnoses. All the patients underwent diagnostic imaging with computed tomography (CT) and ultrasound before laparoscopy. Carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, and CA125 levels in serum and peritoneal fluid were measured using enzyme immunoassay. Laparoscopic diagnosis for peritoneal metastasis gave negative results in 21 patients and positive results in 18. All the patients with negative LP-P findings underwent surgery; 18 of the 21 patients showed no peritoneal metastasis, but three were diagnosed as having peritoneal metastasis, one at the pouch of Douglas and two at the mesentery. The diagnosis of all the patients with positive LP-P findings was finally confirmed as correct. The specificity, sensitivity, and accuracy of laparoscopy for peritoneal metastasis were 100 % (18/18, 95 % CI 0.82 - 1), 86 % (18/21, 95 % CI 0.64 - 0.97), and 92 % (36/39, 95 % CI 0.79 - 0.98), respectively. The specificity, sensitivity, and accuracy of diagnostic imaging for peritoneal metastasis were 100 % (18/18, 95 % CI 0.82 - 1), 38 % (8/21, 95 % CI 0.18 - 0.62), and 67 % (26/39, 95 % CI 0.50 - 0.81), respectively. All of the 11 patients showing high levels of serum CA125 (equal to or more than 35 U/ml) had peritoneal metastasis whereas 17 of the 26 patients with low levels of serum CA125 (less than 35 U/ml) did not ( P < 0.001). The sensitivity of laparoscopy for peritoneal metastasis was much higher than that of diagnostic imaging. Laparoscopy and serum CA125 level both predicted peritoneal metastasis, but the degree, volume, or distribution of peritoneal metastasis was disclosed only by laparoscopy. Laparoscopy is a useful way of detecting peritoneal metastasis in gastric cancer, and patients with an elevated level of serum CA125 are the best candidates for laparoscopy.

Peritoneal metastasis in gastric cancer with particular reference to lymphatic advancement; extranodal invasion is a significant risk factor for peritoneal metastasis.

We investigated the relationship between peritoneal metastasis and lymphatic involvement in gastric cancer by examining resected specimens. Twenty-seven consecutive gastric cancer patients who had synchronous peritoneal metastasis and 29 who developed metachronous peritoneal metastasis after surgery between 1985 and 1997 were included in this study. They were compared with 61 advanced gastric cancer (pT2 or more deeply into the gastric wall in the UICC-TNM) patients who had neither synchronous nor subsequent peritoneal metastasis, and who lived a disease-free course during 3 years. We compared the patients' clinico-pathological features and in particular, the patterns of extranodal invasion in the resected lymph nodes. Extranodal invasion with peritoneal metastasis was more common than extranodal invasion without peritoneal metastasis (P < 0.0001). Multivariate analysis revealed that the correlation between extranodal invasion and peritoneal metastasis was highly significant (P < 0.0001); the odds ratio was 18.894. Metastasis to the lymph nodes was the next most significant risk for peritoneal metastasis (P = 0.0043). We believe that the lymphatic system correlates closely with the establishment of peritoneal metastasis.

胃癌腹膜播種によるイレウス症例の検討

胃癌腹膜播種によるイレウス症例の検討

Matrix metalloproteinase-1 expression is a prognostic factor for patients with advanced gastric cancer.

Proteolytic activity of cancer cells is an important factor in metastasis. This study examined the relationship between MMP-1 expression of gastric cancer cells and peritoneal metastasis. MMP-1 expression was found in 76/103 (75.2%) cases examined and was significantly associated with both peritoneal metastasis and lymph node metastasis (p<0.05, respectively). The prognosis of patients with MMP-1 positive tumor was significantly worse than that of patients with MMP-1 negative tumor (p<0.05). These findings suggested that MMP-1 might be a prognostic factor in case of advanced gastric cancer and might be useful in determining whether or not adjuvant therapy was indicated for patients at high risk of peritoneal recurrence.

胃癌の腹膜播種性転移によるイレウスに対する手術術式の選択

胃癌の腹膜播種性転移によるイレウスに対する手術術式の選択