Regional adjuvant chemotherapy after partial hepatectomy for metastatic colorectal carcinoma.

The prognostic factors after hepatic resection for metastases from colorectal carcinoma were examined, and the results of adjuvant hepatic arterial chemotherapy are presented. Hepatic resection was undertaken in 57 patients with metastatic liver tumor from colorectal cancer. Adjuvant hepatic arterial chemotherapy using 5-fluorouracil, doxorubicin or epirubicin, and mitomycin C was administered to 31 patients. The 3- and 5-year survival rates for the 57 patients were 53% and 23%, respectively. The significant prognostic factors were solitary liver tumor and metachronous liver tumor. However, type of hepatectomy, surgical margin, site of the primary tumor, and histologic differentiation of the carcinoma did not relate to the prognosis. The 3- and 5-year survival rates for the patients given adjuvant arterial chemotherapy were 57% and 57%, respectively, indicating a significantly better survival rate than in the nontreated patients. These results suggest that hepatic arterial chemotherapy is effective treatment in patients with hepatic resection for metastases from colorectal carcinoma. However, recurrence in the lung is relatively high. Further improvement might be achieved by administering hepatic arterial chemotherapy as well as effective systemic chemotherapy.

Advances in hepatic resection and results for hepatocellular carcinoma.

The mortality and morbidity of hepatic resection for hepatocellular carcinoma (HCC) have decreased in recent years because of the various advances in hepatic resection. Various improvements are evident in dissecting apparatus, liver hepatic inflow clamp, cold hepatic perfusion technique, intraoperative ultrasonography, accurate assessment of hepatic function, autologous blood transfusion, and so on. Five-year survival after hepatic resection for HCC was reported at 26-59% in Eastern as well as Western series. The prognostic factors were portal invasion, multiplicity, serum alpha-fetoprotein level, tumor size, associated cirrhosis, age, alcohol abuse, histologic classification, DNA ploidy, and surgical margin. Segmental or lobar hepatic resection brought about better survival, especially in stage I and II patients. Effective adjuvant therapy should improve the diagnosis.

High-resolution and analytical electron microscopic studies of new crystals induced by a bioactive ceramic (diopside).

Diopside has been developed for use in dental root implants and for the filling of bone defects. In previous studies, diopside developed hydroxyapatite (HA) on its surface and achieved a direct bond with bone. The purpose of this study was to investigate the mechanism of crystal formation on the diopside surface. We ultrastructurally evaluated the interface between new diopside-induced crystals and diopside. Specimens were prepared in three experiments: (1) Granular diopside was immersed in simulated body fluid (SBF); (2) granular diopside was implanted into a cavity in rabbit bone; and (3) a diopside dental root implant was implanted into a Japanese monkey. The specimens were examined by contact microradiography, high-resolution transmission electron microscopy, and analytical electron microscopy. In the experiment with SBF, many platelet-like crystals formed in the diopside surface layer. The lattice of diopside and that of the new crystals were very close, but no clear continuation of the lattice was observed. In the experiments which used a rabbit and a monkey, contact microradiography showed close contact between bone and diopside. High-resolution transmission electron microscopy revealed crystal growth from the diopside surface layer, and continuity between the diopside lattice and that of the new crystals. The morphological characteristics of the new crystals and the results of these analyses suggest that these new crystals are HA. With regard to the mechanism by which crystals are formed on the diopside surface layer, it is possible that epitaxial crystal growth could originate as a nucleus on the surface. In this case, epitaxial crystal growth of primarily octacalcium phosphate (OCP) may have occurred, and this may have changed to HA by a phase transition. However, epitaxial growth of OCP on the diopside surface is still highly speculative, since there is no direct supporting evidence.

Autologous blood transfusion for hepatectomy in patients with cirrhosis and hepatocellular carcinoma: use of recombinant human erythropoietin.

BACKGROUND: We evaluated the benefit of autologous blood transfusion and the effect of recombinant human erythropoietin (rh-EPO) on preoperative autologous blood donation for hepatectomy in patients with cirrhosis. METHODS: Forty-two patients with cirrhosis and hepatocellular carcinoma underwent hepatectomy, 21 of whom (group A) donated autologous blood before operation. Eleven of these patients (group A1) were administered rh-EPO before operation, and ten patients (group A2) were untreated. Twenty-one patients (group B) did not donate autologous blood. RESULTS: The frequency of homologous blood transfusion was 24% in group A and 62% in group B (p < 0.05). Preoperative erythropoiesis increased markedly in group A1, and postoperative erythropoietin production was not suppressed in this group. Postoperative hematocrits recovered significantly more rapidly in patients transfused with only autologous blood. Postoperative serum total bilirubin concentrations were significantly higher in patients with transfused homologous blood. CONCLUSIONS: Autologous blood transfusion yields clinically superior results for hepatectomy in patients with cirrhosis when compared with homologous transfusion. Preoperative rh-EPO administration minimizes presurgical decreases in hematocrit caused by autologous blood donation.

Effects of hepatic arterial infusion chemotherapy on unresectable or recurrent hepatocellular carcinoma.

We performed hepatic arterial infusion chemotherapy (HAI) on 86 patients with unresectable hepatocellular carcinoma (HCC, 61 patients) or unresectable recurrent HCC after hepatectomy (25 patients). As drug therapy, 250 mg of 5-fluorouracil was injected daily for 14 days using a reservoir embedded in the subcutaneous layer. During this period, 0.4 mg/kg of doxorubicin and 0.12 mg/kg of mitomycin C suspended in Lipiodol Ultra-Fluide were also injected twice intra-arterially. This was defined as one course of HAI, and it was repeated every 3 months. In the patients with unresectable HCC, the 1-, 2-, and 3-year survival rates were 31.5%, 22.4%, and 10.7%, respectively, and the numbers of cases showing a complete response (CR), a partial response (PR), a minor response (MR), no change (NC), and progressive disease (PD) according to the Criteria for the Evaluation of the Clinical Effects of Solid Cancer Chemotherapy established by the Japan Society for Cancer Therapy were 1 (1.6%), 20 (32.8%), 5 (8.2%), 28 (45.9%), and 7 (11.5%), respectively. On the other hand, the 1-, 2-, and 3-year survival rates of the patients with unresectable recurrent HCC were 69.6%, 34.8%, and 14.9%, respectively. The rate of catheter patency after 1 year was 64.1%, and the mean catheter-patency period was 311.9 days. Patients in group A (CR+PR, n = 21) survived significantly longer than those in group B (MR+NC+PD, n = 40; P < 0.05). In conclusion, since responders to HAI achieve longer survival than nonresponders, the selection of effective drugs is important for this therapy.

[Two cases of esophageal varices complication after hepatic arterial infusion chemotherapy (HAI) for metastatic liver tumor].

Mild liver dysfunction is a well-known complication of HAI, but it has been thought to be transient and reversible in most cases. In the case, of metastatic liver disease, in particular, HAI has been performed safely because liver function is normal for the most part. We encountered 2 cases of irreversible severe liver dysfunction and esophageal varices after hepatectomy for metastatic liver tumor from colorectal cancer. They were treated with postoperative adjuvant HAI. Biliary enzyme as alkaline phosphatase elevated, and dilated intrahepatic bile ducts were observed in both patients. Fibrosis of Glissonean sheath, dilatation of intrahepatic bile ducts and intrahepatic biliary stones were observed at autopsy in both patients. One of the patients had obstruction of portal trunk. It must not be forgotten that such complications can occur even in a case with non-cirrhotic liver.

[Studies on the effectiveness of adjuvant hepatic arterial chemotherapy after hepatectomy for primary or metastatic liver cancer].

From January 1980 to March 1990, 399 cases of primary liver cancer (hepatocellular carcinoma 357, cholangiocellular carcinoma 42) and 148 cases of metastatic liver cancer were treated in our hospital. Some 222 of H.C.C (hepatocellular carcinoma), 20 of C.C. (cholangiocellular carcinoma) and 42 of metastatic liver cancer were resected; 24 of H.C.C, 2 of C.C and 22 of metastatic cancer received adjuvant hepatic arterial chemotherapy, in which anti-cancer drugs were administered with oily contrast medium Lipiodol in hepatic artery. The relationship between operative findings and postoperative prognosis was studied in 168 resected H.C.C cases and risk factors for recurrence were determined. Risk factors are TW(+), which means that the cancer remains macroscopically within 1 cm of surgical margin; IM(+), which means intrahepatic metastasis exists; more than Vp2, which means tumor embolus exists in the second or more proximal branch of the portal vein; and Fc(-), which means lack of capsule formation. In 132 cases with the risk factors, the survival rate of 19 cases with adjuvant arterial chemotherapy was significantly higher than that of 113 cases without it. In the cases of liver metastasis of colon cancer, resection of metastases and adjuvant hepatic arterial chemotherapy improved the prognosis.

[Studies on drug release from anti-cancer drug suspended Lipiodol].

In case of an arterial infusion chemoembolization therapy for primary or metastatic liver cancer, gradual release of the anti-cancer drug from lipiodol is a very important factor for a higher drug concentration in the tumor and for longer contact. We studied basic points about what kind of drug form has a gradual drug release. We prepared 3 forms of drugs. (1) Powder form: Powder of ADM, MMC and CDDP was suspended in lipiodol with ultrasonic suspender. (2) URO form: ADM and MMC were dissolved with Urografin and mixed with lipiodol. (3) Surfactant form: ADM and MMC were dissolved with water and then mixed with lipiodol using surfactant. We put lipiodol suspension into physiological saline and then stirred water at 100 rpm with the paddle method, measuring drug release from the suspension or emulsion. Powder form had a lowest drug release. In clinical trials, we administered intra-arterially (1) ADM, MMC dissolved with physiological saline water as usually used (physiological saline water form) (2) Powder form; (3) URO from; (1) CDDP solution as usually used was administered; (2) Powder form. Then we studied the changes of serum concentration of ADM, MMC and CDDP. The results indicated that powder form had the lowest drug release. Thus, the water-soluble anti-cancer drugs ADM, MMC and CDDP should be used in powder form.

[Arterial infusion of anticancer agent and lipiodol using a totally implanted drug delivery system].

We attempted arterial infusion of anticancer agent using a totally implanted drug delivery system in 52 patients who had inoperable liver cancer or the scheduled adjuvant chemotherapy after hepatic resection. The response rate of the cases using lipiodol was 38%, while that of the cases using only ADM and MMC was 0%. We studied changes in serum concentration of ADM and MMC. The results indicated that using 60% Urographin to make ADM, MMC-lipiodol emulsion was effective for targetting and control release.