[A case of postoperative multiple hepatic metastasis from esophageal cancer successfully treated by surgical resection and hepatic arterial infusion chemotherapy].

A 66-year-old male who underwent radical resection for esophageal cancer (stage IV) was diagnosed with multiple hepatic metastasis 1 year and 3 months after the surgery. He underwent hepatic resection and received systemic chemotherapy (FAP: 5-FU, ADR, CDDP), as the post-operative adjuvant therapy. One year and 3 months later, there was a huge recurrence in the residual liver and hepatic arterial infusion chemotherapy (FAP) was performed. The recurrent lesion disappeared completely after 3 sessions of arterial infusion chemotherapy. The arterial infusion chemotherapy was continued in the outpatient clinic and the recurrent lesion is well controlled. At present, this patient has returned to social life, 2 years and 3 months after the hepatic resection. The utility of hepatic arterial infusion chemotherapy and hepatectomy for postoperative multiple hepatic metastasis from esophageal cancer was shown in the present case.

Proline accumulation by mutation or disruption of the proline oxidase gene improves resistance to freezing and desiccation stresses in Saccharomyces cerevisiae.

We examined the role of intracellular proline under freezing and desiccation stress conditions in Saccharomyces cerevisiae. When cultured in liquid minimal medium, the proline-nonutilizing mutant containing the put1 mutation (proline oxidase-deficient) produced more intracellular proline, and increased the cell survival rate as compared to the wild-type strain after freezing and desiccation. We also constructed two PUT1 gene disruptants. PUT1-disrupted mutants in minimal medium supplemented with external proline at 0.1% accumulated higher proline levels than those of the control strains (17-22-fold). These disruptants also had a 2-5-fold increase in cell viability compared to the control strains after freezing and desiccation stresses. These results indicate that proline has a stress-protective function in yeast.

Regional chemotherapy to prevent hepatic metastasis after resection of pancreatic cancer.

BACKGROUND/AIMS: Liver metastasis is one of the major causes of cancer death after resection of pancreatic cancer. To deal with this problem, we developed a liver perfusion chemotherapy via the hepatic artery and portal vein. The present paper is designed to introduce the technique of this method and report on the promising results. METHODOLOGY: Between 1987 and 1995, 98 consecutive patients with adenocarcinoma of the pancreas received an extended pancreatectomy, in which a wide range of lymphatic and connective tissue clearance was performed in addition to the conventional pancreatectomy, at Osaka Medical Center for Cancer and Cardiovascular Diseases. All patients were followed-up to determine whether and where cancer recurrence developed. RESULTS: Excluding 4 patients who died of postoperative complications, our liver perfusion chemotherapy was performed on 27 patients. The other 67 patients did not receive this treatment. In the group that underwent liver perfusion chemotherapy, no patients experienced complications such as leucocytopenia (< 3000/mm3), thrombocytopenia (< 50,000/mm3), or liver disfunction. The cumulative survival rate differed remarkably between the two groups: 92% vs 62% at one year (p < 0.05); 51% vs 35% at three years (p < 0.05); and 41% vs 25% at five years (ns). CONCLUSIONS: When this method was performed after an extended pancreatectomy for adenocarcinoma of the pancreas, our preliminary report (Am J Surg. 1994; 168:361-364) indicated that it was useful not only for preventing hepatic metastasis, but also for improving patients' survival rate. Since then, further positive and supportive results have been obtained in an additional investigation.

[A case of successful management of advanced cholangiocellular carcinoma by repeated hepatic resection].

A 50-year-old woman with advanced cholangiocellular carcinoma (CCC) underwent extended left hepatectomy and catheterization into the hepatic artery. Following the procedure, intra-arterial infusion chemotherapy of the fluorouracil (5-FU) was performed. This chemotherapy was given 13 times at 2,500 mg for 10 months, so the total dose of 5-FU was 32.5 g. About two years after the operation, the patient underwent hepatic resection again for solitary recurrence of CCC. The prognosis of CCC is very poor. Aggressive surgical resection may be the only method to assure a good outcome. However, the survival rate after curative resection has been low. Adjuvant hepatic arterial infusion chemotherapy after surgery may be effective for a good prognosis.

[Adjuvant chemotherapy for advanced gastric cancer].

For recent 40 years, many authors reported the results of adjuvant chemotherapy for advanced gastric cancer including 5-fluorouracil, uracil and tegafur, mitomycin C, cytosine arabinoside. OK-432 adriamycin, methotrexate, and cis-pltatin in solitary use of combinations. It is difficult to find a standard effective adjuvant chemotherapy for advanced gastric cancer in these reports. The reasons of this unclearness were as follows; (1) In phase III studies, surgery alone was not a control group in some reports. (2) The number of patients was too small to evaluate statistically. (3) Inter-institutional differences had important roles in the results of multicenter study in the other studies. For the future plans on adjuvant chemotherapy, it is important to make a simple designed protocol, and perform it as a multicenter study including institutions with minimum inter-institutional differences.

[Effects of adjuvant surgical therapy for continuous regional therapy for advanced hepatocellular carcinoma].

In order to repeat the effective transarterial embolization (TAE) or regional chemotherapy, adjuvant surgical therapies were performed for 25 patients with advanced hepatocellular carcinomas (HCC) having collateral feeders. The procedures involved the reduction of tumors with collateral feeders, permanent decollateralization using silicone rubber sheeting of the liver (WRAP therapy), and combination therapies. The 1-, 3- and 5-year survival rates of the patients after the adjuvant surgery were 67%, 18% and 5%, respectively. The 3- and 5-year survival rates of the patients after the initial TAE or arterial chemotherapy were 57% and 12%, respectively. On the other hand, the 3- and 5-year survival rates of patients who had TAE alone (n = 443) were 29% and 14%, respectively. Consequently, this adjuvant surgical therapy may be a useful palliative treatment for HCC.

[Preoperative neoadjuvant chemotherapy with a combination of 5-fluorouracil, adriamycin and cisplatin (FAP) for advanced esophageal cancer invading trachea or main bronchus].

Conventional irradiation and systemic chemotherapy is scarcely effective for advanced esophageal cancer invading trachea or main bronchus. Therefore, to reduce the area of invasion and suppress distant metastasis, we have preoperatively treated 4 patients suffering from advanced esophageal cancer invading the trachea or main bronchus by neoadjuvant chemotherapy (FAP) as follows: 2 times every 4 weeks, CDDP 100 mg and ADR 50 mg on day 1 and continuous infusion of 5-FU 1,000 mg/day for 7 days. The response rate (PR) was 75% (3/4). In 2 of 4 patients (50%), no cancer cells except broad fibrosis were detected histologically in the region of the trachea or main bronchus suspected to be invaded. There was no severe complication. This FAP regimen is suspected to be useful chemotherapy for advanced esophageal cancer.

Liver perfusion chemotherapy via both the hepatic artery and portal vein to prevent hepatic metastasis after extended pancreatectomy for adenocarcinoma of the pancreas.

Since hepatic metastasis is a common cause of treatment failure after curative pancreatectomy for adenocarcinoma of the pancreas, we developed a new method of postoperative hepatic perfusion chemotherapy via both the hepatic artery and portal vein. The present study was conducted to determine if this method decreases the hepatic recurrence and improves the survival rate. Following extended pancreatectomy with wide lymphatic and connective tissue clearance for pancreatic cancer, one catheter was placed in the hepatic artery and one in the portal vein. Immediately after surgery, 5-fluorouracil (125 mg/d) was continuously infused via these two routes simultaneously for 28 to 35 days. There were no treatment-related complications in the 20 patients who survived surgery. The 3-year survival rate was 54%, and the cumulative rate of death from hepatic metastasis was 8%. These figures were significantly better than those of our historical control groups. We conclude that this method should be evaluated in a prospective, randomized controlled study.

[Pharmacokinetics following intraperitoneal sequential administration of cisplatin and fluorouracil for gastric cancer].

Gastric cancer patients with peritoneal dissemination underwent a palliative resection of the stomach and received an intraperitoneal administration of CDDP (70 mg/m2) and 5-FU (700 mg/m2), immediately after the surgery. The levels of CDDP and 5-FU in serum and peritoneal cavity were serially monitored in order to study the pharmacokinetics of these drugs. group A (n = 9): CDDP dissolved in 500 ml saline was infused intraperitoneally at 200 ml/min, and one hour later, 5-FU dissolved in 500 ml saline was infused at the same speed. The infusion catheter was clamped for two hours after completion of 5-FU infusion. Group B (n = 3): CDDP in 500 ml saline were infused at 10 ml/min and then 5-FU in 500 ml were infused at 5 ml/min. Group C (n = 2): CDDP in 1,000 ml saline was infused at 200 ml/min. Group D (n = 2): 5-FU in 1,000 ml saline was infused at 200 ml/min. The free CDDP levels in the peritoneal cavity were 22 micrograms/ml in group A, 57 micrograms/ml in group B, and 13 micrograms/ml in group C at one hour after completion of the infusion. The 5-FU levels in the peritoneal cavity measured two hours after completion of the infusion were significantly higher in the group B (349 micrograms/ml) than in group A (132 micrograms/ml) and C (71 micrograms/ml). The Cmax of 5-FU in serum was lowest in group B. The AUCs in the peritoneal cavity of free CDDP and 5-FU were 63.6 micrograms.hr/ml and 925 micrograms.hr/ml, respectively. These values were above the 10th percentile of IC90 for gastric cancer. No serious complications were encountered in group A and B where both CDDP and 5-FU were administered as compared with group C and D, where either CDDP or 5-FU was administered.

[Evaluation of intra-arterial infusion chemotherapy and radical pancreatectomy in patients with locally advanced pancreatic cancer].

This is a retrospective study to evaluate arterial infusion chemotherapy and resection for locally advanced pancreatic cancer involving retro-peritoneal organs or large vessels such as superior mesenteric artery or celiac trunks. Intra-arterial chemotherapy was performed for 19 patients, and 15 underwent pancreatectomy. Patients in the intra-arterial chemotherapy group could live 11 months out of the hospital, against 4 months in the resected cases (p < 0.05). The period of over 2nd degree in performance status was 11 months in the arterial chemotherapy group and 3 months in resected groups (p < 0.05). The survival rates were 53, 18 and 9% at 1, 2 and 3 years in the patients with arterial chemotherapy, respectively, against 22, 15 and 15% in the resected patients (p < 0.05). These results suggested that intra-arterial chemotherapy was significantly effective in prolonging the survival period with a better quality of life.

[A case report of malignant pseudomyxoma peritonei treated by a new modality of intraperitoneal chemo-hyperthermia].

A patient with malignant pseudomyxoma peritonei underwent a palliative surgical resection and intraperitoneal lavage with 5% dextrose. One hundred and twenty-five mg of cisplatin resolved in 1,500 ml saline was infused into the peritoneal cavity through the reservoir, and the patient was treated with hyperthermia (Thermotron RH 8). As a result the tumor markers (CEA, CA 19-9, and CA-125) markedly decreased after two courses of chemo-hyperthermia. These results suggest that intraperitoneal chemo-hyperthermia is an effective treatment for non-resectable malignant pseudomyxoma peritonei.

Delayed washout of intratumor blood flow is associated with good response to intraarterial chemoembolization for liver metastasis of colorectal cancer.

BACKGROUND: We studied stagnation of the blood in hepatic metastatic lesions of colorectal cancer. METHODS: Twenty-two hepatic tumors in 11 patients with liver metastases of colorectal cancers were investigated in this study. With a catheter inserted into the roots of the proper hepatic artery, 5 to 10 mCi 133Xe was injected. The half-time (t1/2) was calculated for the tumor region based on the washout curve by the compartmental method and expressed as the intratumor retention time of the blood. RESULTS: Transcatheter arterial chemoembolization with iodized oil (Lipiodol) and cisplatin was effective in eight (50%) of 16 tumors that were hypervascular but in only one (17%) of six tumors that were hypovascular (p < 0.05). Regardless of the hypervascular tumor, transcatheter arterial chemoembolization was not effective in tumors that had shown a t1/2 of less than 80 seconds. Seven of eight good-responding lesions that were hypervascular and had a long t1/2 (187 +/- 74.6 seconds) revealed characteristic fireworks-shaped accumulation of Lipiodol. CONCLUSIONS: Transarterial infusion chemotherapy for liver metastasis of colorectal cancer was considered effective for hypervascular hepatic tumors with a long t1/2.