This aims of this study are to establish an ultra-rapid quantitative reverse transcription-PCR (RT-PCR) protocol that enables the diagnosis of i.p. cancer spread during operation, to reveal the ...mechanisms of peritoneal metastasis from non-serosa-invasive gastric carcinoma, and to evaluate the effect of the extensive intraoperative peritoneal lavage (EIPL) using the ultra-rapid quantitative RT-PCR as a prophylactic strategy for peritoneal metastasis.
Peritoneal lavage samples from 63 patients with non-serosa-invasive gastric carcinoma were obtained at laparotomy and immediately after lymph node dissection. To identify the free cancer cells in the samples, carcinoembryonic antigen- and cytokeratin 20-specific RT-PCRs were performed using the LightCycler method in combination with an automated mRNA extractor. In addition, EIPL was performed in five cases with serosa-invasive gastric carcinoma, and its efficacy was evaluated by the ultra-rapid quantitative RT-PCR protocol.
The method enabled us to complete the detection of cancer cells within approximately 70 min. Both the carcinoembryonic antigen and cytokeratin 20 mRNA in i.p. lavages after lymph node dissection were identified in three (14.3%), four (26.7%), and six (46.2%) patients with submucosal, muscularis propria, and subserosal tumors, respectively. Lymph node metastasis was the independent predictor of the existence of i.p. free cancer cells. The ultra-rapid quantitative RT-PCR demonstrated that EIPL reduced free cancer cells from 3.8 x 10(5) +/- 1.4 x 10(5) cells to 2.8 +/- 1.5 cells/100 ml lavage after six to eight washes, and they disappeared after seventh to ninth wash.
The present study proved that lymph node dissection opened lymphatic channels and spread viable cancer cells into the peritoneal cavity. It is suggested that the combination of the novel detection system with the intraoperative therapy of EIPL can be a useful prophylactic strategy for peritoneal metastasis from gastric carcinoma.
Although reports have suggested that differentiated gastric carcinomas have different phenotypes, i.e., gastric and intestinal type, this classification is complicated and can be confusing. Our ...previous studies have demonstrated a close relationship between carcinogenesis in differentiated-type gastric cancer and the expression of brain (fetal)-type glycogen phosphorylase (BGP). The purpose of this study was to investigate the relationship between the mucin phenotype of gastric carcinoma and BGP expression.
Ninety-six specimens of gastric carcinoma were studied using specific anti-BGP antibody. Correlation of BGP expression with intestinal and gastric phenotypes was determined with the anti-mucin antibodies, HGM, CD10, and MUC2.
BGP was expressed in 82.6% (38/46) of differentiated type and in 24.0% (12/50) of undifferentiated type carcinomas. The incidence of BGP positivity was significantly greater in the differentiated-type carcinoma than in the undifferentiated type (P < 0.001). The proportions of gastric, mixed and intestinal types in differentiated and undifferentiated gastric carcinomas were 13.0%, 47.8%, and 39.2%, and 56.0%, 32.0%, and 12.0%, respectively. In both differentiated and undifferentiated types, the phenotype of gastric and intestinal mucin expression corresponded very well with BGP expression, that is, more than 90% of carcinomas with gastric type did not express BGP, whereas approximately 90% of carcinomas with intestinal type did express BGP.
The classification of gastric and intestinal phenotypes of gastric carcinoma in terms of BGP expression was simpler and clearer than such classification in terms of mucin immunohistochemistry. It is suggested that BGP is a useful biomarker for the classification of intestinal and gastric type carcinoma of the human stomach, including classification from the carcinogenetic point of view.
The aim of this study was to clarify the outcomes of lung resection for lung cancer in patients with cardiac disease, especially coronary artery disease, in a large-scale multi-institutional cohort.
...We retrospectively analyzed the data on 1,254 patients who underwent major lung resection for lung cancer and had been diagnosed with coronary stenosis, atrial fibrillation, or both, in 58 institutions in Japan between January 2009 and December 2011. The primary outcome was 90-day postoperative mortality or in-hospital death.
Among the 1,254 patients, 902 (71.9%) and 452 patients (36.0%) were preoperatively diagnosed with coronary stenosis and atrial fibrillation, respectively, and 951 patients (75.8%) received antiplatelet therapy. Among the patients with coronary stents (n = 532; 42.4%), 204 (16.3%) received drug-eluting stents. The 90-mortality or in-hospital death rate was 2.6% (n = 32), including stent thrombosis (n = 1), thromboembolic events without stent thrombosis (n = 2), and bleeding events (n = 2). In the multivariate analyses, blood transfusion, history of cerebrovascular disease, amount of bleeding, and history of congestive heart failure were associated with a higher independent risk of 90-day mortality or in-hospital death (odds ratio, 9.400, 3.574, 2.827, and 2.945, respectively). Preoperative discontinuation of antiplatelet therapy was not associated with an independent risk of 90-day mortality or in-hospital death on univariate analysis.
Major lung resection for lung cancer in patients with coronary artery disease is feasible. Our study suggests that discontinuation of antiplatelet therapy may not increase postoperative complications in patients with coronary artery disease.
Background and Aims. The optimal protocol of the treatment for early gastric cancer has not been fully established. The current study was designed to elucidate the relationship between the depth of ...tumors with or without an ulcer and the presence of lymph node metastasis and to establish the optimal and practical therapeutic strategy for patients with early gastric cancer. Patients and Methods. A retrospective analysis of 1051 patients with early gastric cancer treated by gastrectomy with D1 or D2 lymph node dissection was performed. The patients were divided into those with mucosal (M) tumors and those with submucosal (SM) tumors. These 2 groups were subclassified, depending on the coexistence of ulcer or the degree of submucosal invasion, and were characterized in relation to clinicopathologic factors and 5-year prognosis. Results. The incidence of lymph node metastases from SM tumors (19.8%, 85 of 430) was more frequent than that from M tumors (2.3%, 14 of 621) (P <.001). All M tumors with lymph node involvement, including tumors smaller than 1.5 cm in diameter, had ulceration or ulceration scar in the lesions. SM tumors that had invaded less than 200 μm in depth (SM1a) had significantly less lymph node involvement than those with deeper invasion. The node metastases were confined to epigastric lymph nodes (N1) in both M tumors with ulceration or ulceration scar and SM1a tumors. Conclusions. All macroscopic M tumors without ulceration or ulceration scar should be considered for endoscopic mucosal resection. The need for reoperation for a formal gastrectomy with lymphadenectomy or a limited surgical operation will vary depending on the pathologic analysis of endoscopic mucosal resection specimens (depth of invasion, presence of ulceration).(Surgery 2001;129:714-9.)
'De novo' carcinogenesis has been advocated besides 'adenoma carcinoma sequence' as another dominant pathway leading to the colorectal carcinoma. Our previous study demonstrated that brain ...(fetal)-type glycogen phosphorylase (BGP) positive foci in the transitional mucosa (BGP foci) have frequent p53 mutations and that the distribution of BGP foci has a close relationship with the location of 'de novo' carcinoma. The aims of the present study were to investigate further genetic alterations in the BGP foci and to clarify the mechanism of 'de novo' carcinogenesis. Twenty-eight colorectal carcinomas with invasion into submucosa or superficial muscularis propria without any adenoma component expressing immunoreactive p53 protein were selected from 168 resected specimens. Investigations of the p53, K-ras and APC mutations was performed in the BGP foci, BGP negative colorectal mucosa and 'de novo' carcinoma using PCR-SSCP and DNA squencing. In all 28 cases, immunoreactive BGP was positive in the carcinomas and the BGP foci were observed sporadically in the mucosa adjacent to the carcinoma. No K-ras mutation was observed in either carcinoma or BGP foci in any of the cases. Mutations of p53 and APC were 14 (50.0%) and 9 (32.1%) in 'de novo' carcinomas, and 11 (39.3%) and 1 (3.6%) in BGP foci, respectively. Both p53 and APC mutations were detected in 8 and 1, p53 mutation alone in 6 and 10, APC mutation alone in 1 and 0 out of 28 carcinomas and BGP positive foci, respectively. These results suggest that the BGP foci may play a very important role in the 'de novo' colorectal carcinogenesis from the frequent genetic alterations of p53, and that there may be two major pathways, i.e., the p53-APC pathway and the p53 alone pathway, from the chain of genetic alterations between BGP foci and 'de novo' carcinoma.
Alpha-fetoprotein (AFP)-producing gastric carcinoma generally causes multiple liver metastases and has an extremely poor prognosis. There is no standard chemotherapy for this disease. Two recent ...consecutive patients who had AFP-producing gastric carcinoma were treated with a novel chemotherapy regimen: irinotecan hydrochloride (100 mg/body over 90 min) plus low-dose cisplatin (10 mg/body) by intravenous infusion. Treatment was done weekly during admission and once every 2 weeks on an outpatient basis. Both patients had multiple liver metastases with high serum levels of AFP, and one demonstrated resistance to 5-fluorouracil. In both patients, liver metastases showed a dramatic complete response to chemotherapy, and the serum AFP levels returned to normal. No significant toxicities were observed. These preliminary results suggest that the present regimen may cause fewer side effects while retaining its synergistic antitumor activity. This regimen may therefore be worth trying as first-line chemotherapy for patients with metastatic AFP-producing gastric carcinoma.
Percutaneous microwave coagulation therapy (PMCT) has been widely used as an effective minimal invasive therapy for small liver tumors. The occurrence of a sonographic masked space due to the ...presence of the lung, however, has become a major obstacle to visualizing the whole tumor in the hepatic dome. To facilitate the use of PMCT for liver tumors in the hepatic dome, we developed PMCT in combination with the artificial hydrothorax method (percutaneous transdiaphragmatic MCT: PTD-MCT). Our new approach for PMCT to the hepatic tumors located in Couinaud's segments VIII or VII just under the diaphragm resulted in a successful treatment. The separation of the lung from the diaphragm by the infusion of saline into the pleural cavity enabled us not only to visualize the whole tumor in the hepatic dome to accurately target the tumor, but also helped us to avoid injuring the lung. PTD-MCT is therefore strongly recommended for the treatment of liver tumors in the hepatic dome.
The established ultra-rapid quantitative RT-PCR system for intraoperative detection of intraperitoneal free cancer cells, the elucidated cause of peritoneal recurrence after curative operation for ...patients with non-serosa-invasive gastric cancer, and the extensive intraperitoneal lavage (EIPL) therapy for the prophylaxis of peritoneal recurrence from the results of evaluation using the ultra-rapid quantitative RT-PCR system were reviewed. We established ultra-rapid RT-PCR protocol that enables diagnosis of intraperitoneal cancer spread about 70 min, using LightCycler method in combination with automated mRNA extractor. Both the carcinoembryonic antigen (CEA) and cytokeratin (CK)20 messenger RNA (mRNA) in intraperitoneal lavages after lymph node dissection were identified in three (14.2%) and four (26.7%) patients with submucosal (SM) and muscularis propria (MP) tumors, respectively. Although peritoneal metastasis occurs in some patients with early gastric carcinoma, the reasons have not been fully established. These results clarified that peritoneal metastasis after operation for non-serosal-invasive gastric cancer was caused by opening lymphatic channels during lymph node dissection allowing the spread of viable cancer cells into the peritoneal cavity. Furthermore, EIPL method was performed in five cases with serosa-invasive (SE) gastric carcinoma, and its efficacy was evaluated by the quantitative RT-PCR. The quantitative RT-PCR demonstrated that EIPL reduced free cancer cells from 3.8×10
5±1.4×10
5 to 2.8±1.5 cells/100 ml of lavage by from six to eight washes, and they disappeared after the seventh to ninth wash. In conclusion, an ultra-rapid quantitative RT-PCR system for intraoperative detection of intraperitoneal free cancer cells was established for clinical use. It is suggested that the combination with the novel rapid detection system with the intraoperative therapy of EIPL can be a useful prophylactic strategy for peritoneal metastasis from gastric carcinoma.
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