A new technique for intestinal isoperistaltic anastomosis utilizing a linear stapler for enlargement after anastomosis performed with a circular stapler.

BACKGROUND: The high incidence of anastomotic stenosis after gastrointestinal surgery using circular staplers is a major problem. In response, we have developed a new technique that uses a linear stapler to enlarge an anastomotic opening made using a circular stapler. METHODS: Anastomoses were created by the new technique or by the conventional approach using a circular stapler in pig small intestine. The method was also applied in treatment of a colon cancer patient. RESULTS: The area of the anastomotic opening obtained with the new technique was more than 3 times that in the control (p < 0.001), with no significant difference between the methods in a leak test. Follow-up of the patient undergoing surgery with this approach revealed an uneventful course with a widely patent anastomosis confirmed after 3 months. CONCLUSIONS: This procedure provides a larger anastomotic opening than conventional anastomosis with circular staplers, without impairing the integrity of the anastomosis.

[Efficacy of intraperitoneal chemotherapy for peritoneal recurrence of gastric carcinoma].

We report a patient in whom intraperitoneal chemotherapy was effective against peritoneal recurrence of gastric carcinoma. A 74-year-old woman underwent total gastrectomy with splenectomy and transverse colectomy for Borrmann type IV gastric carcinoma (curability B) in January 2000. The diagnosis was Stage IV gastric carcinoma (T4, N2, P1, H0, M0 and CY0). In July 2000, peritoneal recurrence occurred along with slight elevation of CEA. In September, two ports were inserted into the upper and lower peritoneal cavity for intraperitoneal chemotherapy with low-dose CDDP and 5-FU plus MMC. She was followed-up for four months as an outpatient and received intraperitoneal chemotherapy biweekly with good control of peritoneal metastasis. However, she died of bone and lung metastases in January 2001. Intraperitoneal chemotherapy was effective in this patient for peritoneal recurrence of gastric carcinoma and could be delivered on an outpatient basis while maintaining the patient's quality of life.

Alteration of integrins by interleukin-1alpha in human pancreatic cancer cells.

INTRODUCTION: Adhesion of tumor cells to extracellular matrix (ECM) proteins plays an important role in tumor invasion and metastasis. AIMS: To investigate the expression of integrins in human pancreatic cancer cell lines and its alteration by interleukin (IL)-1alpha to examine the mechanism of adhesion of metastatic human pancreatic cancer cells to ECM proteins. METHODOLOGY: The expression of integrin subunits and their alteration by IL-1alpha were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in three metastatic human pancreatic cancer cell lines (AsPC-1, BxPC-3, and SW1990) and two nonmetastatic cancer cell lines (PaCa-2 and PANC-1). In addition, assays of cancer cell adhesion to ECM proteins were performed to investigate if increased integrin expression actually affected the adhesive interaction between cancer cells and the putative integrin ECM ligands. RESULTS: The alpha(6) subunit expressed in metastatic cancer cells was enhanced by IL-1alpha. Metastatic cancer cells also showed preferential adherence to laminin compared with nonmetastatic cancer cells, and this was enhanced by IL-1alpha. CONCLUSION: In pancreatic cancer, the enhancement of alpha(6)beta(1) integrin by IL-1alpha through IL-1 receptor type I, as well as the expression of alpha(6)beta(1) integrin, plays an important role in metastasis formation.

[A case of advanced gastric cancer that was resectable after asctic fluid had disappeared following administration of TS-1].

A 60-year-old man who had suffered from epigastic pain and general malaise from November 1999 was admitted to our hospital due to Borrmann type 3 gastric cancer with ascites on December 7, 1999. We considered a radical B operation impossible, and placed the patient on neoadjuvant TS-1 chemotherapy consisting of 1 M tegafur, 0.4 M gimestat, and 1 M otastat potassium. There were no side effects other than Grade 1 nausea and mild loss of appetite throughout the chemotherapy. After 8 weeks of administration, the primary lesion was reduced in size, and ascitic fluid had disappeared on abdominal computed tomography images. Therefore, a total gastrectomy with splenectomy and D2 lymph node dissection was performed on March 31, 2000. This was a radical B operation that was not possible earlier. The pathological diagnosis was tub2, SE, N1, CY0, H0, P0, M0, INF gamma, ly1, v1, PM (-), DM (-) and the antitumor efficacy of TS-1 was Grade 2 histologically. The patient remains alive and in good condition with no relapse of the gastric cancer 8 months after surgery.

[An effective case of intraperitoneal and intra-arterial combined chemotherapy for unresectably advanced Borrmann type IV gastric carcinoma].

We report an effective case of intraperitoneal and intra-arterial combined chemotherapy for unresectably advanced Borrmann type IV gastric carcinoma. A 59-year-old man was admitted with advanced Borrmann type IV gastric carcinoma in June 1999. With informed consent, the patient underwent laparotomy, which revealed far advanced Stage IV gastric carcinoma of T4, N3, P1, H0, M1, CY1 for resection. Three ports to both subphrenic pouches and Douglas' pouch were placed for intraperitoneal infusion chemotherapy. Pathological findings of omental lesions were metastatic gastric carcinomas of por 2-histological type. Intraperitoneal and intravenous infusion combined chemotherapy with a modified low-dose CDDP and 5-FU regimen were started. The artery-side port was placed in the aorta at the Th. 9/10 levels for arterial infusion chemotherapy in September 1999. The patient was followed-up as an outpatient and continued to receive the intraperitoneal and intra-arterial combined chemotherapy. We report an effective case of intraperitoneal and intra-arterial combined chemotherapy for unresectably advanced Borrmann type IV gastric carcinoma, who could be followed-up as an outpatient while maintaining his quality of life.

[Intraperitoneal and intrathoracic administration of hydroxyapatite-carboplatin (HAp-CBDCA)].

We have investigated the efficacy of intraperitoneal or intrathoracic administration of hydroxyapatite particles (HAp) loaded carboplatin (CBDCA). HAp-CBDCA (HAp; 200 mg, CBDCA; 4 mg) was administered intraperitoneally to rats with peritoneal carcinomatosis. The area under the curve of the ascitic platinum (Pt) increased significantly with rats given HAp-CBDCA, and the omental Pt levels in the HAp-CBDCA group remained higher and longer. Additionally, the HAp-CBDCA group showed a trend toward longer survival when compared with the CBDCA alone group. In clinical use, HAp-CBDCA (HAp; 5 g, CBDCA; 150 mg) was administered intrathoracically to a patient who had undergone esophagectomy. The Pt in serum was detected until 7 days after administration of HAp-CBDCA.

[An effective case of arterial infusion therapy of low-dose CDDP and continuous 5-FU for isolated hepatic recurrence of gastric carcinoma].

We report an effective case of arterial infusion therapy of low-dose CDDP and continuous 5-FU for isolated hepatic recurrence of gastric carcinoma. An 83-year-old man was admitted for epigastric pain and vomiting due to a huge liver metastasis of gastric carcinoma in May, 1997. Nineteen months earlier, in October of 1995, he had undergone distal gastrectomy and D2 lymph node dissection with Billroth I reconstruction. His conclusive stage and pathological findings were as follows. The conclusive stage was stage II: t3, n0, P0, H0. Histological typing was tub 2. Lymph node involvement was not detected, but venous invasion was found in the surrounding regional lymph nodes. CEA had been getting elevated from November, 1996. But he had been well until March, 1997, when CT scans revealed huge hepatic recurrence. The artery-side port was placed for hepatic arterial infusion therapy for liver metastasis. Intra-arterial bolus injection of low-dose CDDP (5 mg) and continuous intra-arterial infusion of 5-FU (250 mg/day for 7 days) were started. Through 4 courses of this arterial infusion therapy, the patient improved. CT scans revealed shrinking of liver metastasis after 3 months of this therapy. The patient was followed in an outpatient clinic and continued to receive this arterial infusion therapy once every 4 weeks. New lung metastasis was detected 9 months after the start, but liver metastasis continued to be responded. The patient died from bleeding into the bile duct from the liver metastasis 16 months after the start of arterial infusion therapy, when metastatic lesions of liver continued to shrink. Arterial infusion therapy of low-dose CDDP and continuous 5-FU may be effective for isolated hepatic recurrence of gastric carcinoma.

[A case of gastric cancer with decreased dihydropyrimidine dehydrogenase activity].

We analyzed the pyrimidine metabolite in the urine of a patient with severe mucositis and hand and foot syndrome, who was administered 5-fluorouracil for recurrence of gastric cancer. From our analysis, it was suggested that the patient had decreased dihydropyrimidine dehydrogenase activity. Dihydropyrimidine dehydrogenase activity is usually measured in peripheral blood mononuclear cells, but this time it was estimated from the analysis of uracil, dihydrouracil, thymine, and dihydrothymine in the urine. We concluded that urinary analysis of the pyrimidine metabolism is effective as screening for the prediction and prevention of 5-fluorouracil toxicity.

[Chemotherapy targeting regional lymph nodes by gastric submucosal injection of liposomal adriamycin in patients with gastric cancer].

We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F-ADR) in 18 patients, then followed these patients for a minimum of 5 years or until death. Prior to radical gastrectomy. Lipo-ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle-tipped catheter. After Lipo-ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to the involvement of metastasis showed higher levels of ADR. In contrast, the intravenous administration of F-ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 mg of Lipo-ADR (n = 19) was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of Lipo-ADR. The ADR levels (microgram/g) after gastric submucosal injection were 15.1 +/- 8.30 on day 1 (n = 4) and 11.9 +/- 4.80 on day 4 (n = 6), whereas, the ADR levels after intravenous administration were 0.29 +/- 0.10 on day 1 (n = 4) and 0.36 +/- 0.0 on day 4 (n = 2). The differences between the two groups were significant (p < 0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo-ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Disease-free survival of the stage III a-b patients (n = 7) with this regional lymph nodes-targeted chemotherapy was 71.4% in 5 years, while that with intravenous F-ADR administration (n = 5) was 60.0%. This preoperative adjuvant chemotherapy targeting the regional lymph nodes may be effective in preventing the recurrence of gastric carcinoma.

[Possibility of alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier for treatment of abdominal carcinomatosis].

It is reported that cancer foci are unevenly distributed in abdominal carcinomatosis after intraperitoneal inoculation of cancer cells in rats. The organs may be briefly classified into two groups in terms of the deposit of cancer cells: one that shows an affinity to the cells includes the greater omentum, mesenterium, and gonadal fat and etc., and the other having lesser affinity the stomach, intestine, and spleen and etc. Such uneven distributions are likely to occur in clinical cases of abdominal carcinomatosis resulting from progressive digestive cancers. We have explored the possibility of alpha-Tricalcium Phosphate (alpha-TCP) particles as a drug carrier in which carboplatin (CBDCA) was incorporated. alpha-TCP, which has chemically similar properties to hydroxyapatite, is known to have an excellent biocompatibility with human tissues and is biodegradable. The present study focused on the localization and the forms of alpha-TCP particles, and the morphological changes of the surrounding tissues after intraperitoneal administration using normal and cancer-bearing rats. The following results were obtained: (1) alpha-TCP particles were taken up to a large extent in the "milky spot" of the greater omentum, followed by the "stomata" of the mesenterium, gonadal fat, diaphragm, peritoneum, and liver in normal rats. No alpha-TCP particles were caught up in the tissues of the stomach, small intestine, colon, and spleen. The margination and emigration of lymphocytes were slightly observed around those organs. (2) alpha-TCP particles were predominantly detected on the cancer mass of the greater omentum in abdominal carcinomatosis-bearing rats. It should be noted that the particles collected in the same place where cancer cells were caught, suggesting that the localization of the drug-containing particles result in higher drug concentrations in the cells possibly for extended times. The alpha-TCP particles system is expected to be a good candidate for targeting chemotherapy and specially for abdominal carcinomatosis.

[Intraperitoneal administration of carboplatin loaded alpha-tricalcium phosphate (alpha-TCP) particles in rats bearing abdominal carcinomatosis].

It is difficult to treat abdominal carcinomatosis with conventional chemotherapy, and many kinds of localized chemotherapy have been attempted. We used alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier in this study. alpha-TCP, which has chemically similar properties to human bone, has an excellent biocompatibility with human tissues and is biodegradable. The particles measured 50 to 100 microns in diameter, were round in shape and very porous. These particles have many open micro-pores of about 1 to 3 microns, which are beneficial for containing drugs. The compatibility and biodegradation of alpha-TCP particles were studied following intraperitoneal (ip) administration in normal rats. The following results were obtained: (1) alpha-TCP particles were intaken in the great omentum, and dissolved gradually. (2) The efficacy of ip administration of carboplatin-loaded alpha-TCP (alpha-TCP-CBDCA) was examined using a Donryu rat model with AH130 abdominal carcinomatosis. The alpha-TCP-CBDCA contained 200 mg alpha-TCP and 4 mg CBDCA. The pharmacokinetics of CBDCA following ip administration of alpha-TCP-CBDCA were studied. Pt levels in ascites and great omentum were higher in the alpha-TCP-CBDCA ip from 0.5 to 168 hours than those in the free-CBDCA ip and iv groups. These results suggest that the efficacy of CBDCA may be enhanced by utilizing alpha-TCP particles as a drug delivery carrier.

[Antitumor effects of liposome-entrapped carboplatin (Lipo-CBDCA) after intraperitoneal administration in rats bearing carcinomatous peritonitis].

We examined the distribution of Lipo-CBDCA after intraperitoneal administration and antitumor effects in rats. The serum levels of platinum in Lipo-CBDCA were lower than in free-CBDCA intraperitoneal or intravenous administration at 15 and 30 min. after administration. After 3 hours, Lipo-CBDCA showed higher levels of serum platinum than free-CBDCA. These data showed the slow release of Lipo-CBDCA. The antitumor effects of Lipo-CBDCA were studied in rats with peritoneal dissemination due to AH 130 tumors. Intraperitoneal treatment with Lipo-CBDCA prolonged the life span significantly compared with Lipo-CBDCA. No side effects of chemotherapy were found in the liver, kidney, spleen or small intestine. A gastric cancer patient suffering from carcinomatous peritonitis with remarkable ascites was treated with Lipo-CBDCA intraperitoneally. After several injections of Lipo-CBDCA, the ascites disappeared completely and the CEA level of ascites decreased dramatically. These results indicate that intraperitoneal chemotherapy with Lipo-CBDCA may be more effective than free-CBDCA to manage carcinomatous peritonitis, and may be therapeutically useful without toxic side effects.

Perforated acute appendicitis in a patient with AIDS/HIV infection: report of a case.

We report herein the case of a 40-year-old man with AIDS who was admitted to hospital with severe abdominal pain, fever, and chills. He underwent an emergency laparotomy which revealed a perforated appendix with suppurative peritonitis. An appendectomy with peritoneal drainage was carried out, but the postoperative course was complicated by fever without leukocytosis; however, he gradually improved following treatment with intravenous antibiotics, granulocyte colony-stimulating factor (G-CSF) and immunoglobulins, and made a complete recovery. His postoperative course demonstrates the effectiveness of this treatment regimen for patients with AIDS complicated by infection without an increase in the white blood cell count (WBC).

Chemotherapy targeting regional lymph nodes by gastric submucosal injection of liposomal adriamycin in patients with gastric carcinoma.

We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F-ADR) in another 18 patients. Prior to radical gastrectomy, Lipo-ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle-tipped catheter. After Lipo-ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to metastasis showed higher levels of ADR. In contrast, the intravenous administration of F-ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 ml of Lipo-ADR was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of F-ADR. The ADR levels (micrograms/g) after gastric submucosal injection were 15.1 +/- 8.30 on day 1 (n = 4); and 11.9 +/- 4.80 on day 4 (n = 6). Those after intravenous administration were 0.29 +/- 0.10 on day 1 (n = 4); and 0.36 +/- 0.0 on day 4 (n = 2). The differences between the two groups were significant (P < 0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo-ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Such preoperative adjuvant chemotherapy targeting the regional lymph nodes may be useful for preventing the lymph node recurrence of gastric carcinoma.

Delivery of lymph node-targeted adriamycin by gastric submucosal liposomal injection in rabbits.

We investigated the feasibility of specifically delivering adriamycin (ADR) to the regional lymph nodes via gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in a rabbit model. We determined the tissue distribution of ADR for up to 7 days after the gastric submucosal injection of Lipo-ADR (0.4 mg/kg of ADR potency) and i.v. administration of an equal dose of free adriamycin (F-ADR). The area under the ADR concentration-time curve (AUC) of the regional lymph nodes was 85.4 micrograms.day/g after gastric submucosal injection of Lipo-ADR and 8.44 micrograms.day/g after i.v. administration of F-ADR. The targeting index of the regional lymph nodes, defined as the ratio of the AUC after gastric submucosal injection of Lipo-ADR to the AUC after i.v. administration of F-ADR, was 10.1. Gastric submucosal injection of Lipo-ADR enhanced lymph node-specific delivery of ADR compared with i.v. administration of F-ADR. The targeting index was 0.47 for the heart, 0.25 for the bone marrow, and 0.41 for the spleen, indicating that gastric submucosal injection of Lipo-ADR reduced delivery of ADR to these organs, as compared with i.v. administration of F-ADR. These data demonstrate that gastric submucosal injection of Lipo-ADR is well suited for specific delivery of ADR to the regional lymph nodes, suggesting that this method of administration may be useful in delivering preoperative adjuvant chemotherapy for preventing gastric cancer recurrence.

Comparison of prostanoids and their precursor fatty acids in human hepatocellular carcinoma and noncancerous reference tissues.

Eicosanoid production and the compositions of precursor fatty acids were determined in human cancerous and reference liver tissues. Seventeen hepatectomized cases (12 cases of hepatocellular carcinoma (HCC) and 5 cases of metastatic liver cancer) were evaluated. The cancerous tissues and the noncancerous reference tissues were separated, lipids were extracted, and the fatty acids were determined as methyl esters by gas chromatography. Prostanoids (6-keto PGF1 alpha and TXB2) were measured by radioimmunoassay. In HCC, the levels of alpha-linolenic acid (omega-3) (0.41 +/- 0.38 x 100 micrograms/g) and docosahexaenoic acid (10.41 +/- 4.96 x 100 micrograms/g) in liver cancer tissue were significantly less than those in the reference tissues. In HCC, the levels of TXB2 reference (1.86 +/- 2.77 pg/mg wet weight) and 6-keto PGF1 alpha were 10-fold higher than those in reference tissues. We speculate that in HCC higher prostanoid levels in the liver are related in part to tumor metabolism.

[Antitumor effect of liposome-entrapped carboplatin after intraperitoneal administration in rats].

We examined the distribution in tissue and antitumor effects of freeze-dried liposome-entrapped carboplatin (Lipo-CBDCA) after intraperitoneal administration to rats bearing AH 130 tumors. Liposomes composed of egg lecithin and cholesterol were used as drug carriers. The serum concentration of platinum was decreased for a short time after the intraperitoneal administration of Lipo-CBDCA. After at least 3 hours, the serum concentration of platinum was higher with free CBDCA intraperitoneal or intravenous administration. The antitumor effects of Lipo-CBDCA were determined in rats with peritoneal dissemination due to AH 130 tumors. Intraperitoneal Lipo-CBDCA prolonged the life span of the tumor-bearing rats. No side effects of the chemotherapy were demonstrated in biochemical and histological studies in the liver, kidney, spleen and small intestine. These results indicate that intraperitoneal chemotherapy with Lipo-CBDCA may be more effective than that with free CBDCA managing in peritoneal dissemination, and may be therapeutically useful without toxic side effects.

[Efficacy of preoperative adjuvant chemotherapy using adriamycin targeting the regional lymph nodes for gastric cancer--lymph node-targeting delivery of adriamycin in rabbits].

Chemotherapy targeting the regional lymph nodes for gastric cancer may be more effective preoperatively than postoperatively since anticancer drugs can be transported to the regional lymph nodes via the lymphatic flow through the stomach. Distribution of Adriamycin (ADR) among the various organs was assessed following its intravenous injection in rabbits. The delivery index of the drug to each organ was assessed by the ratio of the area under the concentration-time curve (AUC) of each organ to the AUC of the regional lymph nodes following the intravenous administration. The delivery index was 0.14 for the stomach, 0.11 for the heart, 0.53 for bone marrow, 0.74 for the spleen, and 0.14 for the liver. These data suggest that preoperative adjuvant chemotherapy by intravenous administration of ADR may be effective in targeting ADR at the regional lymph nodes. Tissue ADR concentrations in the regional lymph nodes were assessed following gastric submucosal administration of ADR in rabbits. The targeting index for the regional lymph nodes was 8.20, measured by the ratio of AUC following a gastric submucosal injection to AUC after the intravenous injection of ADR. This suggests that it may be possible to selectively target chemotherapy to regional lymph nodes by employing a gastric submucosal administration of ADR.

[Endoscopic injection of liposomal adriamycin targeting lymph node metastasis of gastric cancer].

Gastric submucosal injection of 5 mg liposomal adriamycin (L-ADM) close to the main gastric cancer tumor was done in 15 patients by endoscopy. This approach was based on the idea that preoperative adjuvant chemotherapy targeting lymph node metastasis in patients with gastric cancer may be effective for prevention of lymph node recurrence. ADM concentrations in the regional lymph nodes were assessed and compared with those in patients who were administered 5 mg of free adriamycin (F-ADM) i.v. preoperatively. ADM concentrations in Group 7 lymph nodes (according to the General Rules for Gastric Cancer Study) were: After 2 days; 7.21 +/- 5.98 micrograms/g (n = 2) in the L-ADM group and 0.59 +/- 0.23 micrograms/g (n = 3) in the F-ADM group. After 4 days; 4.93 +/- 3.93 micrograms/g (n = 2) in the L-ADM group and 0.36 +/- 0.0 micrograms/g (n = 2) in the F-ADM group. After 6 days; 2.08 +/- 0.49 micrograms/g (n = 2) in the L-ADM group and 0.05 +/- 0.05 micrograms/g (n = 3) in the F-ADM group. L-ADM group: those who had L-ADM injected into the side of the lesser curvature of the stomach. F-ADM group: those who had F-ADM administered i.v. These data demonstrate that gastric submucosal injection of L-ADM is well suited for specific delivery to the regional lymph nodes, suggesting that this type of administration may prevent lymph node recurrence of gastric cancer by targeting lymph node metastasis.

[Clinical application of chemotherapy via the portal vein with liposome-encapsulated adriamycin in inoperable metastatic liver cancer].

We studied the effects of liposome-entrapped adriamycin (L-ADM) administered via the portal vein and the clinical application of this treatment in the therapy and inhibition of liver metastasis, experimentally and clinically. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. We examined the distribution in tissues and antitumor effect of freeze-dried L-ADM administered via the portal vein to rabbits bearing VX2 tumors. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The life span was prolonged by L-ADM treatment compared with the control group and the free ADM group. This L-ADM administration was confirmed to be safe and revealed a decrease in the heart toxicities compared with free adriamycin. Nineteen cases were studied from Jan. 1986 to May 1991 via the portal vein and the clinical effects were evaluated. From Mar. 1988 to date, 10 cases were treated with L-ADM (20-30 mg every 2 weeks/body) in patients with inoperable cases using subcutaneously implanted reservoir. The median survival was 450 days; 275 days for colon cancer, 492 days for gastric cancer, and 1,052 days for uterine cancer (range: 136-1,152 days), compared with 141 days (range: 52-253 days) in 9 cases of historical control treated with free-ADM via the portal vein. These results suggest that chemotherapy via the portal vein with L-ADM for metastatic liver cancer may increase survival time.