We often experience a hypercoagulable state after esophageal cancer surgery, and it is well known that this state is related to development of postoperative complications and organ dysfunction. To investigate if preoperative infusion of methylprednisolone (MP) could modify the disorders in coagulation and fibrinolytic status, we randomized 20 thoracic esophageal cancer patients to two equal groups preoperatively. One group received an infusion of MP (10 mg/kg) 30 minutes prior to the induction of anesthesia (MP group) and the other received a placebo infusion (control group, C group). In the C group, prolongation of activated partial thrombin time (APTT) and decreases in platelet, antithrombin III (AT-III), and plasminogen (Plg) levels were observed postoperatively. In the MP group, prolongation of APTT was shorter, and the lowest levels of AT-III and Plg were higher than in the C group (p<0.05). Postoperative changes in interleukin 6, C-reactive protein and urinary N-acetyl-β-D-glucosaminidase were less in the MP group (p<0.05). The durations of intratracheal intubation and SIRS were also shortened in the MP group. These findings suggest that we could control the postoperative hypercoagula-ble state and relieve surgical stress and postoperative organ injury by preoperative infusion of MP.

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The aim of this study was to clarify the clinical and Immunohistochemical characteristics of gastric adenosquamous (ad-sq) carcinoma. All patients in this study had undergone surgery at our hospital. We examined immunohistochemically the correlation between the 11 patients with ad-sq carcinoma and the 44 patients with the common type (common) of advanced gastric carcinoma. Expression of proliferating cell nuclear antigen (PCNA), p53 and CD44, and the apoptotic index were evaluated by immunohistochemical staining. Microvessel density was assessed by immunostaining for anti-CD34 antibody in the 5 most vascularized areas. The PCNA labeling index in the ad-sq carcinomas was significantly higher than that in the common carcinomas. The apoptotic index in the ad-sq carcinomas was significantly lower than that in the common carcinomas. The p53 positive rate in the ad-sq carcinomas was significantly higher than that in the common carcinomas. The CD44 positive rate in the ad-sq carcinomas was significantly higher than that in the common carcinomas. In the ad-sq carcinomas, expression of both p53 and CD44 in the adenocarcinoma areas was similar to that squamouscarcinoma areas in the neighboring. Intratumoral microvessel density assessed by anti-CD34 staining in the ad-sq carcinomas was significantly higher than that in the common carcinomas. From these findings taken together, it could be speculated in terms of biological background in the development of the ad-sq carcinomas that the squamous elements likely originated from one of the undifferentiated epithelial carcinomas having multipotency, not from a preexisting differentiated adenocarcinoma.

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To determine whether the limited surgery is possible for the early gastric cancer invading submucosal layer (sm-cancer), a total of three hundred and seventy-eight cases with sm-cancer were investigated clinicopathologically. We divided sm-cancers into the following three subgroups according to the degree of cancerous invasion: sml group with minute submucosal invasion, sm2 group with invasion to the mid-submucosal layer, and sm3 group with deep and massive submucosal invasion near to the proper muscle. As a result, there was no lymph node metastasis in cases of sm-cancer less than 10 mm, in cases of the elevated type cancer less than 20 mm, or in cases of the differentiated sml or sm2-cancer less than 20 mm. However, the reports on the micro lymph node metastasis, which could not be detected in the conventional pathological examination, suggests that the evaluation of lymph node metastasis using conventional method is insufficient as an indicator for the plan of limited surgery. Consequently, to determine the strict indications of limited surgery, we examined lymphatic invasion of the cancerous lesion which related closely to lymph node metastasis. The examination of lymphatic invasion demonstrated that lymph node dissection can be omitted in cases of differentiated sml-cancer less than 10mm. However, the preoperative diagnosis of sml of less than 10 mm had been difficult. Thus, the lymphadenectomy should be performed for cases diagnosed as SM-cancer preoperatively at the present time.

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Early detection of a poor-functioning hepatic graft is one of the most important issues in liver transplantation and liver surgery, but neither easy or very reliable methods exist. To determine their capabilities to predict early liver function and/or liver graft quality and the resultant postoperative outcome, the hepatic oxygen consumption, hepatic venous oxygen hemoglobin saturation (Shvo₂), arterial ketone body ratio (AKBR) and adenine triphosphate (ATP) levels of hepatic tissue were investigated in warm ischemic models using adult mongrel dogs. In particular information from the Shvo₂ measurement could be derived in both real-time and continuously, if it could be a very reliable liver function test. 60 and/or 90 minutes of warm ischemia of the liver were created by temporarily blocking the hepatic artery and portal vein flow after formation of a porto-venous bypass between the splenic vein and the femoral vein for hemodynamic stability, The results of the hepatic oxygen consumption correlated well with tissue ATP levels and AKBR according to the severity of the warm ischemic damage. Shvo₂ correlated well with the total hepatic flow (hepatic arterial flow plus portal vein flow)(p= 0.011). However, Shvo₂ was not significantly reduced according to the severity of 60 and 90 minutes of warm ischemic damage. Therefore, Shvo₂ would be reliable to predict the decline of the hepatic blood flow, but it could not predict the severity of the warm ischemic parenchymal damage to the liver. The hepatic oxygen consumption, AKBR and/or tissue ATP levels would be a reliable indicator of postoperative liver dysfunction or an indicator of graft quality after liver ischemia and/or transplantation.

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We investigated serologically and immunohistochemically the correlation between positive area of immunoreactivity in NCC-ST-439 (ST-439) antigen and the degree of clinicopathological factors and examined its utility as a tumor-associated antigen of colorectal cancer. The colorectal cancer tissue was removed surgically from 200 patients with colorectal cancer in our department. For the immunohistochemical examination, the streptoavidin-biotin (SAB) method was conducted with a specific monoclonal antibody. For measuring of the positive area, we used the CAS 200 Image Analyzer. The rates of an immunohistochemical expression of ST-439 were 81.6% for the apical and intraluminal types and 18.4% for the cytoplasmic type. The expression of ST-439 and the positive area in differentiated adenocarcinoma were higher than in undifferentiated adenocarcinoma. There was a close correlation among staging, depth of invasion, tumor diameter and lymph node metastasis, liver metastasis, peritoneal dissemination and positive area and expression of ST-439 antigen. These results demonstrated that the grade of the positive area and expression of ST-439 antigen were strongly associated with malignancy and prognosis of colorectal cancer. It is suggested that ST-439 antigen is useful as a tumor marker for colorectal cancer.

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A case of congenital esophagobronchial fistula with an esophageal diverticulum is described. The patient is a 53-year-old male. Esophago-gastro-duodenogram was carried out with contrast medium as part of a complete medical chekcup. This revealed a diverticulum in the left side of the middle-third intra-thoracic esophagus. In addition, a bronchus of the left inferior lobe was seen at the base of the diverticulum. The opening of the fistula was recognized at the bottom of the esophageal diverticulum with an esophagoscope. But the opening of a fistula was not able to be identified with a bronchoscope. An outflow of the pigment medium from the left B⁶was recognized, as the medium was infused therough a tube that passed into the esophagus. An operation to resect the diverticulum and the fistula was carried out. Pathological findings showed that the lumen of the fistula was covered with stratified squamous epithelium and accompanying smooth muscle. Multi-layer ciliated epithelium was seen at a part of the periphery. One section showed migration between squamous epithelium and ciliated epithelium. 55 cases of this disease have been reported in Japan, including this case. But the case of a fistula to the left bronchus is rare. This case is the eighth report in Japan.

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Primary malignant tumors rarely arise from the duodenum. We report a case of a duodenal stromal tumor with lymph node metastases, and discuss this case in relation to the literature. A 45-year-old woman was hospitalized with complaints of anemia and fatigue. We detected a submucosal tumor (5.3× 3.5×2.5cm) in the post-bulbar portion of the duodenum. Histological findings of the biopsy specimen suggested leiomyoma or leiomyosarcoma. Local resection of the tumor and sampling of regional lymph nodes were performed. In theresected specimen, the tumor cells were immunohistochemically positive for Vimentin, α smooth muscle actin and S-100 protein, It was diagnosed as a stromal tumor (combined smooth muscle neural type). Histological examination revealed low-grade malignancy, but two of four lymph nodes examined showed metastasis. Therefore pylorus-preserving pancreaticodudenectomy (PpPD) was carried out to complete the lymph adenectomy 3 weeks later. One of the dissected lymph nodes showed metastasis. A stromal tumor with lymph node metastasis is reported to be rare and it is still controversial whether lymph adenectomy improves the prognosis. But this case suggest that concurrent regional lymph adenectomy may be beneficial for a large stromal tumor with evident lymph adenopathy.

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A case of inflammatory pseudotumor of the liver associated with hepatolithiasis is reported. A 74-year-old woman complained of fever and general malaise. Laboratory findings on admission revealed a severe inflammatory reaction and elevation of bile duct enzymes. Abdominal ultrasonography demonstrated many stones in the intra and extra bile ducts. The periphery of the lateral segment of the liver was swollen because of a low echoic area with cystic lesions. Abdonimal CT with enhancement on arterial dominant phase revealed multipleringed enhanced lesions with a multilocular cystic area at the periphery of S3. CT arteriography on the 10th day after admission revealed reduction of the swollen low echoic area. The size of each lesion was reduced in consequence of disappearance of cystic area and thelesions were disk-likely enhanced. Under the diagnosis of intra-and extrahepatic type hepatolithiasis and a liver abscess, biliary lithotomy and lateral segmentectomy were performed. Multiple yellow-white solid nodules were recognized at the periphery of S3. Pathologically solitary or gatherings of inflammatory nodules with Glisson's capsule in the center consisted mainly of lymphocytes and histiocytes and her codition was diagnosed as IPTs.

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A case of solid cystic tumor (SCT) of the pancreas with liver metastases in a 13-year-old woman is reported. The patient, who had been followed for systemic lupus erythematosus, was admitted to our hospital because of pancreatic and liver masses incidentally discovered by abdominal ultrasonography. Diagnostic imaging studies revealed a mass, 8×6×5 cm in size, consisting of solid and cystic components, in the body and tail of the pancreas, and two masses, 2 and 0.5 cm in diameter, in segment VII and IV of the liver, respectively. This led to a clinical diagnosis of pancreatic SCT with liver metastases. A distal pancreatectomy with splenectomy and partial resection of the liver was performed. The histological findings confirmed the diagnosis of pancreatic SCT with liver metastases. No capsular invasion or other metastatic lesions, other than those involving the liver, were found. Flow cytometry revealed a diploid pattern for both primary and metastatic SCTs. The patient has been followed for 4 years and 5 months since the operation with no signs of recurrence. 21 cases of pancreatic SCT with liver metastasis, including this one, have been reported in Japan. This paper presents the clinicopathological studies of these 21 cases.

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We report a case of enteroliths in duplication of the ileum. A 35-year-old woman, whose chief complaint was lower abdominal pain, underwent laparotomy under the diagnosis of torsion of a right ovarian dermoid cyst. Operative findings revealed a tumor, about 6×5cm in diameter, on the anterior wall of the ileum 5cm proximal from its end and three hard stones were palpated in the tumor. Partial resection of the ileum with the tumor was carried out. Macroscopic and microscopic findings showed duplication of the alimentary tract, which is a rare congenital disorder said to be difficult to diagnose preoperatively because of the wide variety of the abdominal symptoms and the diagnostic imagings. The enterolithsin our case consisted of calcium oxalate. There have been only nine reported cases of calcium oxalate enteroliths thus far in Japan. To the best of our knowledge, this is first case ever reported in Japan of duplication of the alimentary tract with enteroliths.

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A 71-year-old woman admitted with complaints of abdominal pain and vomiting. Abdominal findings were not remarkable except for mild tenderness. But two days later, there was severetenderness in the abdomen with peritoneal sign. Abdominal CT demonstrated a whirl-like pattern of volvulated small intestinal loops around the superior mesenteric artery. An emergency operation was performed upon the diagnosis of strangulated ileus due to volvulus of thesmall intestine. Abdominal exploration revealed a gangrenous small intestine from about 30cm from Treitz ligament to near the terminal ileum twisted by 900° clockwise rotation. After detorsion, the extensive gangrenous small bowel was resected and end to end anastomosis was performed. The postoperative course was uneventful Because of the absence of a predisposing anatomical abnormality, the patient was diagnosed as having primary volvulus of the small intestine. Reports of primary volvulus of the small intestine are very few in Japan, and care should be taken for this disease because it develops necrosis rapidly, resulting inhigh mortality. Abdominal CT may provide useful information and may be essential to an early diagnosis of this disease.

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This report describes a case of severe typhoid fever (TF) requiring surgical management, which is very rare in Japan. A 63-year-old man had been admitted elsewhere with fever of unknown origin. He was transferred to our facility ten days later, in shock with massive melena. Angiography revealed extravasation of contrast medium from a branch of the ileal artery. At an emergency laparotomy, active bleeding and penetration were found in the ileum. The ileum and mesentery, with palpable indurated lesions, were resected. Salmonella typhi was isolated by blood culture. Angiography for massive typhoid hemorrhage has been recommended in a few reports. The classical approach to the management of intestinal hemorrhage and perforation due to TF has been conservative, but emergency surgical intervention has recently been recommended. Although several operative procedures have been reported, it seemsto be important to resect thoroughly the intestine and mesentery which include typhoid lesions. In the diagnosis and treatment of lower intestinal hemorrhage and/or perforation, TFshould not be forgotten as a possible cause, and it is important to have a thorough knowledge of the intestinal characteristics of TF.

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A 33-year-old woman was admitted to our hospital because of rectal cancer with multiple liver metastases (H₃). Almost the whole liver was occupied by multiple huge metastatic tumors except for the segments 1, 2, 4 (part) and 6 (part). The hepatic volume was calculated by computer imaging. The remnant hepatic volume (segment 1, 2, 4 [part]) was estimated to be 337ml after right extended hepatectomy. This volume was tnought to be enough for this patient because it was greater than half of the total normal liver and than theminimal essential liver volume of this patient. Based on this estimation, simultaneous S3 excision+extended right hepatectomy and low anterior resection with lymph node dissction (D₂) were carried out with no difficulty. No postoperative complications like hepatic failure and anastomotic insufficiency were observed. The patient is alive with lung metastases 2 years and 6 months postoper-atively without evidence of liver recurrence. This case showed that extensive hepatectomy for patients with H₃prolonged their survival and that simultaneous aggressive hepatectomy and intestinal resection based on preoperative detailed estimation of the liver function and volume were effective because of the low burden for the patients and the reduction of tumor bearing time compared with a metachronous operation.

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We clarified the characteristics of the treatment of gastric cancer in Miyagi Prefecture, Japan, in relation to mass-screening, investigated differences in gastric cancer surgery among 7 main hospitals in Miyagi Prefecture, and investigated the reasons for improved outcome of patients with stage II and III cancer who were treated from 1977 to 1991 compared to those who were treated from 1967 to 1976 in Miyagi Cancer Center (MCC). Although the incidence of gastric cancer has increased annually, the age-adjusted incidence rate has steadily decreased over the past 30 years. These findings resulted from a marked increase in the aged population im Miyagi Prefecture. The rate of detection by mass-screening was the highest in MCC among the 7 main hospitals, and the rate in the 7 hospitals was higher than among patients enrolled in the gastric cancer registry of the Japanese Research Society forGastric Cancer. A decreased fatality rate as a result of mass-screening and recent progress in treatment of gastric cancer occupied the 71% of decrease of mortality rate in males and 37% in females. The surgical outcome in patients whose cancer was detected by mass-screening was significantly better than that of patients diagnosed by hospital examination, because those operations were performed in the early stage. Adjutant chemotherapy appeared to contribute partly to the improved survival of patients with gastric cancer treated from 1977 to 1991.

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Gastric cancer occurs frequently in Niigata prefecture. Niigata Cancer Center Hospital isone of the central hospitals in Niigata and about 10% of gastric cancer patients in Niigata are operated on there. Rational surgery (RS) was used for early gastric cancer, and long-term survival and quality of life (QOL) were evaluated according to the method of surgery. RS included 112 surgical local resections (SLRs), 5l aparoscopic wedge resections (LAPs), 51 pylorus-preserving gastrectomies (PPGs), 38 proximal gastrectomies (PXGs), and 377 omentum-preserving modified radical gastrectomies (OPGs). Results:(1) There were few postoperative complaints after SLR, and 6 re-treatments (2 under-treatments and 4 metachronous cancers). The 5-year survival was 81/9%, and there was only one gastric cancer death.(2) All LAP patients are alive and healthy.(3) Remnant gastritis and esophagitis were rare after PPG, and the recovery of weight loss was good and rapid. Tc^99m scintiscans, however, revealed bile juice regurgitation in 24%. Two re-operations were performed for recurrence, but all patients are alive and cancer-free. The 5-year survival for PXG was 84.2%, and there have been no gastric cancer deaths.(5) Ileus occurred less frequently after OPG than after gastrectomy with omentectomy. The 5-year survival after OPG was 79.4%, and there were no gastric cancer deaths. The postoperative survival of the treated patients was almost the same as for standard gastrectomy, and their postoperative QOL was found to be better than after radical surgery. In conclusion, these methods of rational surgery appear to be appropriate for improving postoperative QOL without loss of survival benefit.

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We report the history of the gastric cancer surgery and recent treatment a the Cancer Institute Hospital. Use of the gross classification developed by Kajitani is the most characteristics of our institu-tion. The most important aim in our institution is to cure patients with adequate, both conservative and aggressive, surgical approach. A typical example of minimally invasive surgery is transeverse gas-trectomy and a typical example of aggressive is left upper abdominal evisceration. Many problems in gastric cancer surgery remain, unresolved, such as type of resection, extent of lymph node dissection, reconstruction, and approach. We at the Cancer Institute, bear responsibility for resolving these oroblems.

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There is no consensus regarding the surgical approach to gastric caner that had invaded the esophagus. Fifty-eight cases treated before 1998 at NCCH were analyzed. A high incidence of mediastinal nodal metastasis (30% when esophageal invasion was longer than 1 cm) was seen, and patients with mediastinal nodal metastasis frequently had extensive nodal metastasis in the abdominal cavity. Based on these findings, between 1988 and 94, we principally used a left thoraco-abdominal oblique incision to treat these patients. Thirty-seven patients underwent this surgery; morbidity was acceptable and only one patient died in the hospital. All 5 patients who had mediastinal node metastasis died within two years. Mediastinal node metastasis was found to be a clear indicator of poor prognosis, and the effects of treating it are very limited, although the reported survival for surgery with thoracotomy is almost always better than without it. This superiority is probably due to better local control or simply to selectin bias. Recently, resection of the lower esophagus up to 10 cm without thoracotomy has become safe to perform by using staplers for esophagojejunostomy, thereby enabling adequate resection of the proximal extension of cardia cancer. Based on this finding, we started a controlled trial comparing two operative methods: left thoraco-abdominal oblique incision with thorough mediastinal dissection and transabdominal resec-tion with limited mediastinal dissection. This trial has been carried out in 16 Japanese hospitals since 1995. The most remarkable characteristics of NCCH is to decide on treatment strategy based on evidence, as is shown by the example of gastric cancer invading the esophagus.

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1) During the 30 years since the establishment of Aichi Cancer Center, there has been a marked increase in the proportion of early gastric carcinomas (especially of mucosal cancers) and a corresponding decrease in non-resectable cases. Operation was performed on 4, 839 patients during the 25 years between 1965 and 1989. These 25 years were divided into 5-year groups numbered I to V, and treatment outcome was compared according to period. An increase of 20% between groups I and V was observed in the 5-year survival rate of patients rated as curability A or B (n=3, 600). No stet difference was observed in patients rated either curability C or not resectable. The improvement in survival rate was especially prominent in 395 patients with t₂ n (+) status. The improvement in outcome after surgery in patients in groups III to IV was so great that no survival benefit of adjuvant chemotherapy was observed in these groups.
2) Highly sensitive detection of intraperitoneal free cells by polymerase chain reaction-mediated amplification of carcinoembryonic antigen mRNA was performed in 150 patients. Five of the 16 patients who were positive for carcinoembryonic antigen mRNA but negative by the conventional cytology examination, have been found to have peritoneal metastases thus far.
3) Intra-arterial chemotherapy, consisting of 5-fluorouracil, mitomycin C, and adriamycin, through indwelling catheters was performed in 40 patients with hepatic metastases. The response rate was 72%, including 6 cases with a complete response, resulting in 50% survival of 15 months.

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Background: The prognosis after surgery for scirrhous gastric cancer is quite poor. An extended operation, left upper abdominal exenteration plus Appleby's operation (LUAE), has been performed for scirrhous gastric cancer to improve their survival. Patients and Methods: Since 1983, LUAE has been performed in 54 patients with scirrhous gastric cancer (Group A). The results of LUAE were evaluated and compared with findings in patients with scirrhous cancer who underwent total gastrectomy with pancreatosplenectomy between 1973 and 1983 (Group B). Results: There was no difference in the incidence of postoperative complications between the two groups. In stage III, the 5-year survival rate in Group A was 40%, and better than in Group B (20%: p<0.05). In stage IV, there was no difference in the survival rate between the two groups. Conclusion: LUAE improved the survival of patients with scirrhous gastric cancer in stage III, but failed to improve the survival of patients with stage IV disease.

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We describe our strategy for the treatment for gastric carcinoma in situ at National Shikoku Cancer Center. We have performed endoscopic mucosal resection (EMR) for depressed-type carcinomas less than 20mm in diameter without ulcer scars. However, depressed-type carcinomas less than 20mm in diameter and unassociated with macroscopic or microscopic regional lymph nodes metastasis have been treated by partial gastric resection with or without video-assisted approach. In cases of depressed-type carcinomas larger than 20mm in diameter but not containing poorly differentiated adenocarcinoma, partial gastrectomy without regional lymph node dissection (DO level) has been performed. In poorly differentiated adenocarcinoma, regardless of tumor size, partial gastrectomy with regional lymph nodal dissection (D2 level) which is our standard surgical treatment for gastric cancer, has been carried out. For the elevated type of m carcinomas, tumor less than 20 mm have been resected by EMR, and tumors larger than 20mm have been treated by partial gastric resection or gastrectomy. When gastric stenosis has been found after gastric partial resection, we have sometimes performed additional gastrectomy without regional lymph node dissection. We histopathologically reviewed our patients treated by the above-described strategy for m carcinomas. We performed 149 EMRs for patients with m carcinomas, and 119 carcinomas were completely removed by EMR, but 7 carcinomas were not completely removed by EMR. In addition, 30 patients were initially treated by multiple resection. Five of the 149 patients treated by EMR were found to have residual cancer or recurrence in their stomach. Two of these recurrent cancer patients initially underwent incomplete EMR, and 3 patients were initially resected with multiple resection by EMR. Seventeen patients were treated by partial gastric resection with laparotomy. Five of the 17 carcinomas were sm carcinomas histologically, i.e., invasive carcinomas. Thirty-five patients were treated by partial gastrectomy associated with a video-assisted approach. Seven, 3, and 1 carcinomas were sml, sm2 and sm3, respectively, histologically. At the present time, overall survival of the patients, treated by our strategy for m carcinoma has not been confirmed, and long-term follow-up will be needed to identify the optimal surgical treatment for these early gastric cancer patients.

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Five-year suvivals of 2146 cases who underwent gastrectomy for primary gastric cancer at the National Kyushu Cancer Center in Fukuoka between 1972 and 1991 were analyzed. Our treatment strategy and research works for gastric cancer and our cases with gastric malignant lymphoma were also described. The 5-year survival rate was 59.6% in overall cases with gradual periodical improvement; 49.9% in period I (1972-76), 55.2% in period II (1977-81), 63.1% in period III (1982-86) and 66.3% in period IV (1987-91). The same tendency was also observed in cases with curability A+ B and those with curability C. The 5-year survival was 89.1% in stage I, 68.8% in stage II, 36.1% in stage III and 9.8% in stage IV. Periodical improvement of survials was similarly observed in all stages but stages II and III in period IV where the survival rate decreased because of partial increase in the number of patients who died of cancer in other organs or tissues. Clinical data and analysis of micrometastasis using anticytikeratin protein antibody suggested that prophylactic lymph node dissection prolonges the survivals of patients with node-negative early gastric cancer.

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We investigated the clinical significance and regulation of lymphatic involvement and venous involvement in gastric carcinomas. The incidence of both lymphatic involvement andvenous involvement in 2, 404 patients with gastric carcinoma increased in tandem with tumor progression, such as depth of invasion, size, and lymph node metastasis. Lymphatic and venous involvement was often observed in tumors located in the upper third part of the stomach. Lymphatic involvement was common in solid-type, poorly differentiated carcinomas. Venous involvement was frequent in both solid- and non-solid-type, poorly differentiated carcinoma, and in mucinous carcinoma. Both lymphatic and venous involvement corelated with survival in stage III gastric carcinoma. The expression of vascularendothelial growth factor (VEGF), a potent angiogenesis-promoting factor related to tumor progression, correlated with the incidence of lymphatic and venous involvemen. Infiltration by dendritic cells (DCs), the most potent antigen-presenting cells, was inversely correlated with lymphatic and venous involvement. Serum levels of soluble interleukin 2 receptor (sIL-2R), which is released from activated T lymphocytes into the circulation, also correlated with lymphatic and venous involvement. However, neither VEGF, DCs nor sIL-2R affected the incidence of lymphoid or venous involvement in patients with stage III gastric carcinoma. These results suggest that VEGF, DCs and sIL-2R, in addition to the findings of depth of invasion, size, histologic type, and location of the tumor, may help predict lymphatic and venous involvement in gastric carcinoma.

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Lymphatic involvement (ly) and lymph node metastasis (n) were predicted by immunohistochemical evaluation of the expression of E-cadherin (ECD), a representative cell adhesion molecule, and autocrine motility factor receptor (AMFR) in gastric cancer patients. Soluble fragments of E-cadherin (SECD) in the peripheral blood were simultaneously measured by the ELISA method. In the differentiated type of gastric cancers (tub, pap), ECD expression was negatively correlated with ly and n, but there was no such correlation in the undifferentiated type (por, sig). AMFR expression was carrelated with depth of invasion and tumor differentiation, but not with ly nor n. Interestingly, expression of ECD and AMFR was negatively correlated, and the ECD (-)/AMFR (+) tumors showed the highest incidence of ly and n. There was inconsistency in the evaluation of n and ly in 21% patients, and predictions could not be made on the basis of either ECD or AMFR expression. However, elevation of SECD levels was more sensitively associated with the presence of either ly or n than ECD or AMFR expression. Thus, the immunohistochemical expression of ECD and AMFR can partly predict the presence of ly and n. SECD were easily measured preoperatively, and the measurements were reproducible, objective, and more sensitive in predicting ly nad n. Thus, clinical application of SECD is expected in the future.

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We determined the level of expression several genes that regulate different steps in the process of gastric cancer metastasis (growth [epidermal growth factor receptor: EGF-R], angiogenesis [basic fibroblast growth factor: bFGF] and vascular endothelial growth factor: VEGF), invasion (type IV collagenase), and cell adhesion/cohesion (E-cadherin) in biopsy specimens of primary human gastric carcinomas by using the in situ hybridization (ISH) method to predict lymphatic invasion and vascular invasion. Our results showed that higher expression of type IV collagenase and lower expression of E-cadherin significantly related to lymphatic invasion, and higher expression of type IV collagenase and VEGF were significantly correlated with vascular invasion, These results suggest that our ISH method for gastric biopsy specimens will be useful to predict lymphatic invasion and vascular invasion followed by metastasis and recurrence of gastric cancer.

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Preoperative estimation of lymphatic invasion by gastric carcinoma was attempted by using clinicopathological or cell and molecular biological methods. In 1129 cases of gastric carcinoma, the size of cancers with lymphatic invasion (71mm) was significantly (p<0.001) greater than that of cancers without lymphatic invasion (43mm). Stainability of nm23 was relatively low in cases of positive for lymphatic invasion. Simultaneous attempts to detect of proliferating cell nuclear antigen (PCNA) and numerical chromosomal aberrations were also performed in 100 cases of gastric carcinoma. PCNA was detected by the immunofluorescence method using anti-PCNA antibody (PC-10) after acetone-ethanol fixatin. Numerical chromosomal aberrations were detected by fluorescence in situ hybridization (FISH) using the probe for chromosome 17 centromere. The frequency of the cells with positive PCNA staining that had numerical aberration of chromosome 17 was significantly (p=0.0001) higher in the cases with lymphatic invasion (15.3%), compared to the cases without lymphatic invasion (9.0). The percentage of the cells that were PCNA-negative with numerical chromosomal aberrations was unrelated to lymphatic invasion. These results revealed that lymphatic vessel invasion is not induced by chromosome aberration or the cell cycle alone, but by a combination of both of them. This method can be performed preoperativeiy. The results also indicated that tumor size and tha rate of PCNA positivity with numerical aberration of chromosome 17 could be a marker for lymphatic invasion of gastric carcinoma.

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We investigated the clinical significance of lymphovascular invasion in gastric cancer with regard to the correlation between lymphovascular invasion and clinicopathologic factors, recurrence, and prognosis. We also examined the effect of postoperative chemotherapy on recurrence of gastric cancer. Factors related to lymphovascular invasion of gasric cancer were tumor size, tumor location, macroscopic appearance, histologic type, depth of invasion, INF, lymph node metastasi, peritoneal dissemination, and hepatic metastasis. Lymphovascular invasion was extensive in patients with postoperative recurrence, regardless of the site of recurrence. Postoperative chemotherapy including mitomycin C and 5-FU and its analog was found to be significantly effective in cases with vascular invasion. We conclude that extensive lymphadenectomy must be employed in patients with gastric cancers with larger size, deep invasion, and location in the upper third of the stomach. Postoperative chemotherapy may reduce postoperative recurence in patients with gastric cancer that has invaded the blood vessels.

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