To determine the optimal surgical management of resectable distal gastric cancer, we evaluated the long-term prognoses of 516 consecutive patients who underwent total or distal gastrectomy with D2 lymph node dissection between August 1974 and May 1997. We focused on the relationships among the extent of gastric resection, the consequent duodenal passage reconstruction and the type of postoperative adjuvant therapy. For patients with stage 2 or 3A gastric cancer, survival rates were significantly higher among those who received subtotal rather than total gastrectomy, and among those who received duodenal food passage reconstruction versus those who did not. Multivariate analysis revealed that the extent of the gastric resection and the reconstruction of the duodenal food passage were the significant independent prognostic variables, which also included residual tumor, age at operation, depth of tumor and lymph node metastasis. In patients who received gastrectomy alone, the extent of the gastric resection and the reconstruction of the duodenal food passage were not independent prognostic variables. On the other hand, in patients who underwent gastrectomy with postoperative adjuvant therapy, the extent of the gastric resection and the condition of the duodenal food passage were significant independent prognostic factors. In conclusion, gastric surgeons must ensure that their surgical resection procedures follow more physiological DFPR and postoperative adjuvant therapy when they treat distal gastric adenocarcinoma.
A consecutive series of 570 patients with middle gastric cancer were evaluated in order to assess their prognosis, focusing on the relationship among the extent of gastric resection, consequent duodenal passage reconstruction, and postoperative adjuvant therapy. These patients underwent total, subtotal (distal or proximal) gastrectomy between Aug. 1974 and May 1997. Patients receiving subtotal gastrectomy had significantly better survival than those receiving total gastrectomy in stage 1A and 3A gastric cancer. On the other hand, patients with duodenal food passage (DFP) reconstruction had better survival than those without DFP reconstruction, though the difference between these groups was not significant. Multivariate analysis revealed that the duodenal food passage and the extent of the gastric resection were independent prognostic variables; in patients who underwent only gastrectomy, the extent of resection and DFP were independent prognostic variables, whereas in patients who underwent gastrectomy with postoperative adjuvant therapy, these two factors were not independent prognostic variables. Though the actual mechanism behind this difference is unclear, our findings indicate that gastric surgeons must carefully consider among the surgical resection procedures when treating adenocarcinoma of the middle gastric cancer.
The optimal extent of resection for proximal gastric adenocarcinoma is controversial. We evaluated a consecutive series of 214 patients to identify the best principal method of surgical therapy for resectable proximal gastric cancer and its longterm outcome. We focused on the relationships among the extent of gastric resection, the consequent duodenal passage (DFP) reconstruction and the type of postoperative adjuvant therapy. The patients underwent total or proximal gastrectomy between August 1974 and May 1997. They ranged in age from 28 to 80 years (median: 60 years), and 75.2% were men. Among the patients at stage 1A or stage 4 gastric cancer, those who received subtotal rather than total gastrectomy had significantly better survival rates. Patients at stage 1A who received duodenal passage reconstruction also had significantly higher survival rates than those who did not receive it. Multivariate analysis revealed that DFP reconstruction and the extent of the gastric resection were significant independent prognostic factors for patients at all stages. In patients who underwent gastrectomy alone without postoperative therapy the extent of the gastric resection was an independent prognostic. On the other hand, in patients who underwent either proximal or total gastrectomy followed by postoperative adjuvant therapy, DFP reconstruction was an independent prognostic factor. Though the actual mechanism underlying this is unclear, our findings indicate that surgeons dealing with proximal gastric cancer must take into consideration the relationships among the extent of gastric resection, DFPR and the type of postoperative adjuvant therapy.
Reported differences in clinicopathological patterns of early gastric carcinoma (GC) between the West and Japan suggest the presence of changes in cancer biology. The aim of this study was to analyze clinopathological-changing patterns of early gastric cancer (GC) biology in a large series of patients from Japan, where mortality rates for GC are high. Using the collected data of 1005 early GC patients treated surgically between 1975 and 2000, we analyzed differences in clinicopathological patterns for five consecutive periods: 1975-80 (group I), 1981-1985 (group II), 1986-1990 (group III), 1991-1995 (group IV), and 1996-2000 (group V). The mean age of the patients was 58 years (range, 21-88), which increased from 57 years (range 32-78), 55 years (21-78), 57 years (range 28-86), 58 years (range 24-87), and 60 years (range 32-84) in groups I, II, III, IV, and V, respectively (group II vs. IV, p<0.05). Analysis revealed differences in histological type (differentiated vs. undifferentiated adenocarcinoma in male and female) between groups; no tendency to decrease or increase was observed in either histological type in men, whereas a significant trend toward increasing of undifferentiated type and decreasing incidence of differentiated type was observed in women (p<0.05). The number of female patients with poorly differentiated adenocarcinoma increased from 50% to 69.7% over the period of the study. The patterns of GC location, macroscopic type, condition of lymph node metastasis and gender have no changed during the analyzed period of time, while those of GC histology, aging changed.
PSK (Krestin), a protein-bound polysaccharide, is known to be an immunomodulating agent. In addition, PSK was reported to have an anti-angiogenic effect in vivo, but the mechanism was unknown. In this study, we investigated the mechanism by which PSK affects angiogenesis. PSK inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) in the absence of basic fibroblast growth factor (bFGF) but inhibited more effectively in its presence. PSK at a high concentration slightly suppressed tube formation of HUVECs and their adhesion to extracellular matrix proteins. PSK also suppressed the bFGF-dependent MAP kinase phosphorylation. A gel filtration experiment demonstrated direct binding of PSK to 125I-bFGF. PSK (5mg/kg, i. v.) injection reduced the bFGF-induced angiogenesis in an in vivo rat cornea assay. These data suggest that PSK binds to bFGF and interferes with its signal transduction to inhibit the proliferation of HUVECs, resulting in the suppression of angiogenesis.
Aim: Two sequential studies were performed to examine the effect of combination chemotherapy for patients with preoperative TNM stage III/IV advanced pancreatic cancer. Methods: In the first study, a randomized Phase II trial, comparing intraoperative radiation therapy (IORT) to IORT plus combination chemotherapy of methotrexate (MTX) and 5-fuluorouracil (5-FU) was performed. Based on the results of the first trial, a second randomized trial combination therapy comparing MTX plus 5-FU to that of cisplatin (CDDP) plus 5-FU was performed. Results: Thirty-three patients were entered into the first study. The second study was conducted sequentially and enrolled 27 patients. In the first study, overall survival and hospital-free survival were significantly better in the IORT plus MTX/5-FU group compared to the IORT alone group. In the second study, comparison of the overall survival and HFS between MTX/5FU group and CDDP/5FU group did not show any significant difference between the two groups. However, MTX/5-FU group showed better treatment compliance and less toxicity compared to the CDDP/5-FU group. Conclusions: The results of these two sequential studies of combination chemotherapies for advanced pancreatic cancer suggested that the treatment with IORT plus MTX/5FU was superior to the treatment without chemotherapy in the first study. In the second study, IORT plus MTX/5-FU was also shown to have less toxicity and better compliance compared to the IORT plus CDDP/5-FU.