Generation of antitumor immunity against large colon tumors by repeated runs of electrochemotherapy.

BACKGROUND/AIMS: Electrochemotherapy, which uses two parallel electrodes for delivery of electric pulses, may be useful for treatment of tumor nodules. However, in clinical fields, tumors that are larger than the distance between the two electrodes are frequently observed, and it would be difficult in such cases to deliver electric pulses to the tumor. This study was done to define how host antitumor immunity is generated by repeated electrochemotherapy treatments, and whether it is associated with regression of even large tumor nodules. METHODOLOGY: Balb/c mice and Balb/c nude mice were inoculated subcutaneously with colon 26. Electrochemotherapy using bleomycin and electroporation (CUY21) was administered as a treatment for tumor nodules that were larger than the distance between the electrodes. RESULTS: In Balb/c mice, growth of large tumors at the start of treatment is not inhibited by a single electrochemotherapy treatment. However, complete tumor regression was obtained through repeated electrochemotherapy treatments. No tumor cure was observed among Balb/c nude mice under the same therapeutic conditions. Inflammatory cells were accumulated in the tumor tissue seven days after the third electrochemotherapy treatment. CONCLUSIONS: Repeated electrochemotherapy is a promising treatment, even for large tumors, such as are usually encountered in clinical practice, by generating T-cell dependent, antitumor immunity.

Evaluation of Ki-67 and p53 expression in primary and repeated liver metastases of GISTs.

There has been little research evaluating changes related to tumor cell proliferation between primary and metastatic tumors of gastrointestinal tumors in the same case. We herein report the case of a 50-year-old woman with a gastric gastrointestinal stromal tumor (GIST), who developed metastatic liver tumors three times in the 7 years after proximal gastrectomy for GIST. The primary and all the metastatic liver tumors, except the second, showed fascicular/storiform architecture and the short spindle cell type. The diffuse epithelioid cell proliferation was observed in the second metastatic liver tumor. Although the immunostaining pattern with respect to GIST differentiation markers had been preserved in the primary tumor as well as in all of the metastatic tumors, the latter showed weaker positivity of both Ki-67 and p53 than the primary GIST. The primary tumor showed diffuse positive p53, and the highest value of Ki-67 labeling index (LI) among them. The metastatic liver tumors showed focal, negative or sporadic positive appearances of p53, however, Ki-67 LI were scattering among them. Immunohistochemical assessment of Ki-67 LI and p53 might be useful for evaluating changes related to tumor cell proliferation between primary and metastatic tumors of GISTs.

High en bloc resection rate achieved by endoscopic mucosal resection with IT knife for early gastric cancer.

BACKGROUND/AIMS: Circumferential endoscopic mucosal resection (EMR) around lesions performed by an insulation-tipped diathermic knife (IT knife) increases en bloc resection rates, suggesting the possibility of expanding indications for EMR. METHODOLOGY: Clinical outcome of EMR performed by IT knife under general anesthesia was evaluated for 26 patients with 29 early gastric cancer. RESULTS: Successful en bloc resection rates obtained by the IT knife were 100, 87.5, 90.0 and 100% for lesions < or =10 mm in size, 11-20 mm, 21-30 mm, and > or =31 mm, respectively. They were significantly higher with the IT knife than those obtained by the conventional method (IT knife method: 93.1% vs. conventional method: 28.5%, p<0.0001). Two lesions were lateral margin positive, and in three cases invasion of lesions was observed as deep as the submucosa. Distal, total, and proximal gastrectomy with D2 lymphadenectomy, respectively, was provided in 3 cases; however, no lymph node involvement was found in any of the resected specimens. Bleeding and perforation were observed in 3 cases, respectively, however, no additional surgical treatment was required for these patients. CONCLUSIONS: EMR by means of the IT knife under general anesthesia can be performed safely and adequately. It is a useful treatment modality for early gastric cancer.

Primary non-Hodgkin's lymphoma of the breast: report of a case with special reference to 380 cases in the Japanese literature.

A 52-year-old Japanese woman presented with a mass in the left breast. A tumor 2.9 cm in diameter was found in the D area on ultrasonography. An ipsilateral swollen axillary lymph node was detected. Invasion of the tumor to the pectoralis major muscle was seen. Based on a diagnosis of malignant lymphoma by fine needle aspiration cytology, radical mastectomy with ipsilateral axillary lymph node dissection was performed. Malignant diffuse large B-cell type lymphoma was diagnosed histologically according to the World Health Organization classification, and the clinical stage was II E by the Ann Arbor staging system. Four courses of adjuvant chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were subsequently performed. The patient is free of recurrence 7 years after surgery. Up to 2002, 380 cases of primary breast non-Hodgkin's lymphoma had been documented in the Japanese literature. When the tumor size was bigger than 4.5 cm, the outcome was poor. Regarding treatment methods, we showed that only enucleation of the tumor is necessary and axillary dissection is not necessary. In our case, we thought that the prognosis was good despite the large tumor and axillary lymph node metastasis, and that we could omit axillary dissection.

Inhibitory remnant stomach motility by duodenal distention after B-I gastrectomy.

BACKGROUND/AIMS: Although control of gastric motility is a highly regulated process, B-I gastrectomy causes accelerated gastric emptying. We found few reports so far concerned with the mechanical effect of balloon distention of the duodenum on the remnant stomach in B-I dogs. METHODOLOGY: Four weeks after conventional distal gastrectomy with B-I reconstruction procedure, a balloon was inserted into the duodenum, and strain gauge force transducers (SGTs) were sutured onto the wall of the gastric remnant and duodenal serosa in beagles. After a two-week postoperative recovery period, gastro-duodenal motility was measured with SGTs prior to distention, during distention, and after evacuation of the balloon. The motility index (MI) was calculated every 30 minutes. RESULTS: Upon duodenal distention with 4 mL of water, motility of gastric remnant was significantly inhibited, however, no reduction in duodenal MI was observed. The response was maintained for as long as duodenal distension continued. Ninety minutes after evacuation of the balloon, MI returned to predistension levels. Increased plasma levels of cholecystokinin (CCK) were observed upon distention of the duodenal balloon. CONCLUSIONS: Motility of the remnant stomach in B-I dogs was inhibited by duodenal distension. Increased levels of plasma CCK during distention might play a role in this feedback mechanism.

[A case of the 5-year survivor of ascending colon cancer associated with synchronous multiple liver metastasis and peritoneal dissemination successfully treated with combination therapy of systemic and hepatic arterial infusion chemotherapy].

A 67-year-old woman was diagnosed by a series of examinations as having ascending colon cancer with synchronous multiple liver metastasis. She underwent an operation after the PTPE (percutaneous transhepatic portal vein embolization) to the right lobe of the liver, as we considered that the metastatic liver tumors were all resectable. In the surgery, we identified seven peritoneal tumors and a lymph node swelling. We then pathologically diagnosed them as being peritoneal dissemination (p3) and lymph node metastasis (n2(+)). Therefore, hepatectomy was not performed, but the right hemicolectomy (D2) and insertion of an arterial infusion catheter into the hepatic artery were performed. In addition, all seven peritoneal tumors were resected. After being discharged from hospital, she was treated as an outpatient with the combination chemotherapy of systemic intravenous administration (5-fluorouracil or 5-FU, 2,500 mg/month) and hepatic arterial infusion (5-FU, 1,500 mg/week) for 16 months. Then, she continued to take tegafur uracil (300 mg/day) by mouth for 39 months. The metastatic liver tumors were gradually reduced and resulted in complete response (CR) for 20 months after the operation. She has been in remission for the past 5 years without recurrence. During the treatment, we noticed a complete atrophy that was sustained in the right lobe of the liver to which PTPE was performed. As far as hepatic arterial infusion chemotherapy is concerned, our case study was interesting and effective.

Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation.

Antiangiogenic factors are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vitro and tumor growth in mice. We have demonstrated the synergistic antitumor effect of antiangiogenic genes (mouse angiostatin: pBLAST-mAngio; and mouse endostatin: p-BLAST42-mEndo XV) delivered to tumors by low-voltage electroporation in mouse colon 26 models. A synergistic antitumor effect was strongly suggested by in vivo tumor growth kinetics, as well as in survival studies with the mice. RT-PCR confirmed that the fragments of each gene were transferred by low-voltage electroporation in the tumor. Decreased microvessel density measurements in tumors also confirmed the efficacy of the synergistic antitumor effect of both genes. Significant growth inhibition was observed in mice treated with a 1:1 proportion of angiostatin and endostatin genes, and the order of the both genes transferred (first the endostatin gene, followed 1 week later by the angiostatin gene) had a profound inhibitory effect on tumor growth. These data suggest that in vivo delivery of antiangiogenic genes with low-voltage electroporation could be a possible therapeutic strategy for established solid tumors when both genes were applied in combination.

S100A11 gene identified by in-house cDNA microarray as an accurate predictor of lymph node metastases of gastric cancer.

Gastric cancer is one of the most common malignancies in the world, and in Asian countries its incidence and mortality rates are very high. Worldwide, Japan ranks first in the incidence of this type of cancer for both sexes. To shed light on the mechanisms underlying the development and/or progression of gastric cancer, we compared the expression profiles in gastric cancer cells obtained from surgical dissection of 20 gastric adenocarcinoma specimens with those in the corresponding non-cancerous mucosa, by cDNA microarray analysis. In total, 8,000 cDNA clones were randomly picked up and their 5'-end nucleotide sequences were determined. On the basis of sequence information, 4,608 independent clones were selected and used to produce the cDNA microarray. We identified 26 genes that were commonly up-regulated and 44 genes that were commonly down-regulated in cancerous tissues. To validate the cDNA microarray analysis, real-time PCR was performed. We found that gene S100A11 expression was associated with the development of lymph node metastases. S100A11 gene expression was clearly up-regulated in specimens from patients with lymph node metastases relative to those from patients without lymph node metastases. S100A11 gene expression status was useful to distinguish gastric cancers with lymph node metastases from those without lymph node metastasis. This genome-wide information contributes to an improved understanding of molecular changes during the development of gastric cancers. It may also help clinicians predict the development of lymph node metastases and assist researchers in identifying novel therapeutic targets for patients with gastric cancer.

Effect of the anastomosis-site after Billroth I gastrectomy on the motility of the remnant stomach.

BACKGROUND/AIMS: Gastric emptying, in healthy individuals, is a highly regulated process, and plasma cholecystokinin plays a major role in its feedback regulation. However, the hormonal regulation of postprandial gastric emptying of the remnant stomach after distal gastrectomy with Billroth I reconstruction procedure has not been well described. The aim of this study is to characterize the gastroduodenal motility and gastric emptying of the two anastomosis-methods after Billroth I gastrectomy, while assessing the effect of cholecystokinin on the motility of the remnant stomach. METHODOLOGY: Two types of anastomosis (end-to-end, side (posterior wall)-to-end) after Billroth I gastrectomy were measured with strain gauge force transducers, and evaluated as to gastroduodenal motility, gastric emptying, gastrointestinal hormones (cholecystokinin, gastrin), and blood glucose associated with food administration. RESULTS: Remnant stomachs with side-to-end anastomosis showed superior motility as compared to those with end-to-end anastomosis. Plasma cholecystokinin was higher in the end-to-end anastomosis group. No differences as to gastric emptying, levels of plasma gastrin, or blood glucose were observed between the two groups. CONCLUSIONS: Plasma cholecystokinin may explain the difference in motility index between the two groups.

Thrombocytosis associated with poor prognosis in patients with esophageal carcinoma.

BACKGROUND: Thrombocytosis in patients with cancer has been reported to be associated with increased expression of angiogenic factors and with a poor prognosis in some types of cancer. The aim of this study is to analyze the clinicopathologic significance and prognostic value of platelet counts in patients with esophageal cancer. STUDY DESIGN: Platelet counts were measured before surgery in 374 patients diagnosed between 1987 and 1999 with primary esophageal squamous cell carcinoma. We used the cut-off level of 293 x 10(9)/L (mean of 80 healthy controls +/- standard deviation) to define thrombocytosis. We analyzed the relationship between platelet counts, TNM factors, and white blood cell counts. Among 374 patients, the levels of C-reactive protein were analyzed in 170 patients and serum thymidine phosphorylase concentration was analyzed in 91 patients. The multivariate prognostic value of platelet counts, tumor size, and TNM factors were determined using Cox's proportional hazards model. RESULTS: Platelet counts were significantly increased in patients with large tumors (p < 0.001), deep tumors, nodal involvement, and distant metastasis in univariate analysis. C-reactive protein level, white blood cell count, and serum thymidine phosphorylase concentration were also significantly increased in patients analyzed with thrombocytosis in univariate analysis. Adjusting for tumor size and TNM factors, multivariate analysis indicated that thrombocytosis as defined in this study was an independent prognostic factor (hazard ratio = 1.52, 95% CI = 1.11 to 2.08, p = 0.009). CONCLUSIONS: A high platelet count is associated with tumor progression and poor survival in patients with esophageal carcinoma.

A prospective randomized trial of hand-sutured versus mechanically stapled anastomoses for gastroduodenostomy after distal gastrectomy.

BACKGROUND: Although mechanical stapling is now an established alternative to conventional hand suturing for the construction of gastrointestinal anastomoses, its role in gastroduodenostomy remains to be defined. We compared the clinical outcome after mechanical stapling with that after hand suturing in patients who underwent gastroduodenostomy after distal gastrectomy. METHODS: From April 2000 through August 2001, a total of 187 patients with gastric cancer who received distal gastrectomy were randomly assigned to reconstruction by mechanically stapled or by hand-sutured gastroduodenal anastomoses. RESULTS: The baseline clinical characteristics were similar in the patients with mechanically stapled and those with hand-sutured anastomoses. There was no in-hospital mortality in either group. One patient (1.1%) in the mechanically stapled group ( n = 92) and 2 (2.1%) in the hand-sutured group ( n = 95) had anastomotic leakage. Anastomotic stenosis developed in 4 patients (4.3%) who underwent mechanical stapling, as compared with 6 (6.3%) who underwent hand suturing. Anastomotic bleeding occurred in 1 patient (1.1%) who under-went mechanical stapling and 1 patient in the hand-sutured group (1.1%). Mechanical stapling of the anastomoses was significantly quicker than hand-suturing of the anastomoses (median time, 14 vs 25 min; p = 0.02). The two groups were comparable with respect to other outcome measures, including incidence of general complications, recovery of gastrointestinal function, duration of postoperative hospital stay, and radiological diameter of the anastomosis. CONCLUSION: In patients with gastric cancer who undergo gastroduodenostomy after distal gastrectomy, mechanical stapling is quicker than hand suturing. These procedures are similar with respect to anastomotic complications and other outcome measures.

Evaluation of D3/D4 lymph node dissection for patients with grossly N2 positive advanced gastric cancer.

BACKGROUND/AIMS: Extended lymphadenectomy (D2) with complete resection of gastric cancer has been generally accepted as a standard treatment modality in Japan. However, the clinical evaluation of the superextended lymphadenectomy (D3/D4) for advanced type of gastric cancer has not been established. METHODOLOGY: Eight hundred and twenty primary gastric cancer patients underwent gastric resection in our institute (1987-1997). Of those patients, 436 patients with more than t2 depth of cancer invasion underwent curative gastrectomy either with D2 (337 cases) or D3/D4 (99 cases). D3/D4 was performed for the cases in which metastasis was recognized in N2 lymph nodes with gross inspection at the time of operation. RESULTS: There was no statistically significant survival advantage to the D3/D4 when comparing between the D2 and D3/D4 groups. However, the relative risk of death due to postoperative relapse in the D3/D4 showed a significantly lower hazard ratio than in the D2, in the Cox proportional-hazard model (0.67; 95% CI: 0.47-0.94). Patients receiving D3/D4 lymphadenectomy showed a better 5-year survival rate in stage IIIb than those with D2 (18.4% vs. 48.9%, p = 0.039). No statistically significant differences were found between the two groups as regards postoperative morbidity and mortality. CONCLUSIONS: D3/D4 lymphadenectomy might be of therapeutic value for limited patients with advanced gastric cancer.

Complete recovery from fulminant hepatic failure with severe coma by living donor liver transplantation.

In Japan, living donor liver transplantation has been established as a therapeutic strategy for the rescue of terminal liver disease, including fulminant hepatic failure that shows no signs of recovery. We performed living donor liver transplantation for a subacute type fulminant hepatic failure patient, who had developed a hepatic coma of grade V (no right reflex, no response to pain stimuli). The electroencephalogram indicated almost flat waves. However, cranial computed tomography revealed that brain edema was not severe in this case. The recipient did not have hepatitis virus and had not taken medication that had been determined to cause hepatitis. The recipient was a 12-year-old boy, 165.5 cm in height and 45.5 kg in weight. The donor was his mother, who was 42 years old; her blood type, type B, was identical to that of the boy. The mother's right hepatic lobe was transplanted to her son (the recipient). The post-transplantation condition of recipient was quite excellent. He recovered consciousness 3 days after liver transplantation, and rapidly attained normal hepatic function. The donor was discharged on the 20th postoperative day without any problems. The recipient was discharged on the 79th postoperative day without any neurological deficits. This case suggests that deep coma without electroencephalogram waves may not be a contraindication for living donor liver transplantation in fulminant hepatic failure patients, if the brain edema is not severe.

Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma.

BACKGROUND: Increased preoperative serum squamous cell carcinoma antigen (SCC-Ag) concentrations have been found to be associated with advanced stage and poor prognosis in lung and cervical cancers. Because little was known about the significance of SCC-Ag concentration in patients with esophageal cancer, the aim of this study was to analyze the clinicopathologic significance of SCC-Ag in patients with esophageal SCC. PATIENTS AND METHODS. Preoperative SCC-Ag concentration was measured with enzyme-linked immunosorbent assay in 309 patients with primary esophageal SCC. All patients underwent curative radical surgery without any preoperative therapy. In 215 of 309 patients, carcinoembryonic antigen (CEA) was also measured to compare clinical significance of CEA with that of SCC-Ag. The prognostic significance for survival of SCC-Ag concentrations was studied with multivariate analysis with Cox proportional hazards model. RESULTS: The SCC-Ag concentration and the positivity rate of SCC-Ag were significantly elevated in patients associated with tumor progression. Statistically significant differences in SCC-Ag concentrations and SCC-Ag positivity rates were observed depending on tumor size, tumor depth, lymph node status, and distant metastasis. Although CEA was not a prognostic factor (P =.21), a high SCC-Ag concentration was a significant prognostic factor (P <.01). Multivariate analyses indicated that T factor had the best predictive power, but SCC-Ag concentration contained additional, independent prognostic information. CONCLUSION: Our findings suggest that preoperative serum SCC-Ag concentrations might provide a predictive information for tumor progression and survival in patients with esophageal SCC.

Prognostic significance of CYFRA 21-1 in patients with esophageal squamous cell carcinoma.

BACKGROUND: CYFRA 21-1 has been reported as a useful tumor marker for esophageal carcinoma, but little information was reported about the clinicopathologic importance of CYFRA 21-1. The aim of this study was to analyze the clinicopathologic and prognostic significance of preoperative CYFRA 21-1 in patients with esophageal squamous cell carcinoma. STUDY DESIGN: The CYFRA 21-1 levels were measured before surgery by enzyme-linked immunosorbent assays in 157 patients with primary esophageal squamous cell carcinomas using 3.5 ng/mL as the upper limit of normal. All patients underwent radical surgical procedures without any preoperative therapy. The association between the clinicopathologic factors assessed and the CYFRA 21-1 level was determined. The CYFRA 21-1 values were monitored after surgery in 45 available patients. The prognostic values were determined by multivariate analysis using Cox's proportional hazards model. RESULTS: Thirty-one of the 157 patients (19.7%) had high CYFRA 21-1 levels (> or =3.5 ng/mL). CYFRA 21-1 levels were significantly increased in patients with large tumors (> or =40 mm, p = 0.009), deep tumors (T2-T4, p = 0.003), and node-positive tumors (p = 0.003). CYFRA 21-1 levels significantly decreased after surgery (p < 0.001). A high CYFRA 21-1 level before surgery was an independent prognostic factor for survival (p = 0.043). CONCLUSIONS: A high CYFRA 21-1 level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Possible involvement of antitumor immunity in the eradication of colon 26 induced by low-voltage electrochemotherapy with bleomycin.

PURPOSE: The antitumor efficiency of electrochemotherapy using chemotherapeutic agents and high-voltage electric pulse has been reported. This study was done to define the precise nature of the involvement of antitumor immunity in the regression of tumor nodules in electrochemotherapy, and to evaluate the effectiveness of using low-voltage electroporation. METHODS: Balb/c mice and Balb/c nu/nu nude mice were inoculated subcutaneously with Colon 26 cells or Meth A cells. Electrochemotherapy using bleomycin and low-voltage electroporation (CUY21) was performed as a treatment against tumor nodules. RESULTS: Colon 26 tumors were eradicated in the mice given an intratumor (i.t.) injection of 500 microg bleomycin followed by treatment with electric fields ranging from 50 to 150 V/cm, with complete response rates ranging from 80% to 100%. The mice rejected inoculations of rechallenged Colon 26 cells, but not Meth A cells. In the Balb/c nu/nu nude mice, complete regression of the tumor was not seen after electrochemotherapy under the same therapeutic conditions that resulted in almost complete cure in the Balb/c mice. CONCLUSION: Our results suggest that the generation of T-cell-dependent, tumor-specific protective immunity might be involved in the process of tumor nodule regression in low-voltage electrochemotherapy.

Sentinel lymph node mapping for gastric cancer using a dual procedure with dye- and gamma probe-guided techniques.

BACKGROUND: Increasing evidence supports the sentinel lymph node (SN) concept for melanoma and breast cancers. SN biopsy may replace routine lymph node dissection in the treatment of these cancers. But there are little data evaluating this concept in patients with gastric cancer. The objective of this study was to test the feasibility of SN mapping in gastric cancers by using the dual-mapping procedure with dye and radioactive colloid. STUDY DESIGN: Thirty-one consecutive patients preoperatively diagnosed as T1-2 and N0 underwent SN biopsy using the dual-mapping procedure. Distributions of SNs identified by the dye-guided technique (blue nodes; BNs) were compared with those identified by the gamma probe guided technique (hot nodes; HNs). RESULTS: Among the 31 patients, 7 were found to have lymph node metastases. All positive nodes were detected by SN biopsy using the dual method. So, an accuracy rate of 100% was achieved in predicting the status of regional lymph nodes. Both BNs and HNs were identified in 28 of 31 patients (90%), but significant discrepancy of distribution was noted between BNs and HNs. Among the 28 patients with identified BNs, there was one metastasis in a non-BN. So the accuracy rate was 96% for the dye-guided technique. In contrast, among the 28 patients with identified HNs, 2 patients had metastasis in non-HNs, making the accuracy rate 93% for the gamma probe-guided technique. CONCLUSIONS: SN mapping is feasible in gastric cancer, but the dye-guided and gamma probe-guided techniques are complementary. So we recommend the dual-mapping procedure.

[Treatment of colorectal cancer--hepatic metastases].

The aim of this study was to evaluate the effect of the local therapy for colorectal liver metastases on overall survival. Seventy-two patients who had resected liver metastases from colorectal cancer during the period from 1982 to 2001 were evaluated for survival. There was no significant difference in overall survival by either surgical method for colorectal liver metastases or postoperative arterial infusion chemotherapy. However, the 5-year survival rate of resected metachronous liver metastases with postoperative arterial infusion chemotherapy was 44.9%, and that for patients with no extra hepatic metastases was 57.4%. Patients who have metachronous liver metastases from colorectal cancer should therefore be considered for postoperative arterial infusion chemotherapy. It is necessary to improve the outcome for cases that have extra hepatic metastases.

Acutely exaggerated hepatitis B induced by the withdrawal of immunosuppressants in a seroconverted renal transplant recipient: report of a case.

The long-term reciprocal impact of renal transplantation on infection by hepatitis B virus (HBV) is still a matter of intense debate, and the topic remains controversial. We herein report the case of a 50-year-old male asymptomatic HBV carrier who had seroconverted to positive anti-HBe antibody (Ab) and received a kidney transplantation from a cadaver donor (HB surface(s) antigen (Ag)-negative). Nine months later, his kidney function deteriorated due to chronic rejection, and hemodialysis was temporarily required. Triple drug therapy (cyclosporine, prednisolone, azathioprine) for immunosuppression was changed to two-drug therapy (cyclosporine and prednisolone) at a reduced dosage because of this episode. After that episode, severe hepatitis with HBV antigenemia developed without any change in the serological state. The levels of DNA polymerase in a potential recipient from a cadaveric donor should be checked before transplantation to predict the occurrence of hepatitis when the recipient is an asymptomatic carrier of HBV, especially in cases of serologically HBeAg-negative, and anti-HBeAb-positive carriers.

Analysis of experimental liver metastasis from tumors inoculated in the mouse stomach cavity.

PURPOSE: This study was conducted to develop a patient-like hematogenous metastatic model of gastric-cancer in order to gain an understanding of the tumor biology and to search for new methods of treatment. METHODS: We established a natural and easily reproducible liver metastasis model by orthotopic gastric inoculation in Balb/c mice, using the syngeneic tumor, colon 26. RESULTS: This model allowed us to evaluate the effect of partial gastric resection with excision of tumor nodules on the formation of experimental liver metastases from the stomach cavity. Mice given partial gastrectomy showed less metastatic ability than control mice. In these experimental groups, liver metastasis was observed in the only group of mice that died of local tumor regrowth due to incomplete resection of the primary tumor. It is suggested that a period of at least 10 days is required for the formation of liver metastases after tumor inoculation into the stomach cavity. There was no significant increase in the number of liver metastases following splenectomy, or after the administration of anti-asialo GM1 antibody or silica. CONCLUSION: This experimental model of liver metastases will provide a useful means of understanding tumor biology and the regulation of liver metastases by host immunocompetent cells, and for assessing new therapeutic agents.