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The authors investigated the usefulness of W-Spiral (WS) catheters for hepatic arterial infusion (HAI) chemotherapy especially from the viewpoint of a removable catheter after cessation of chemotherapy. A WS catheter was successfully inserted into the hepatic artery without a coil fixation in 40 out of 47 patients with hepatic malignant disease. A stable position of the catheter tip was maintained throughout the period in all cases. In 20 patients, the catheter was easily and uneventfully removed after chemotherapy, which resulted in improved patients' quality of life. An electron microscope examination revealed that there was no fibrin network formation on the surface of the catheter. Stenosis of the hepatic artery was confirmed in 7 out of 12 patients with 5 Fr catheter by 3DCT angiography, whereas patency of the artery was well preserved in 7 of 8 cases with 3.3 Fr catheter. This catheter has a special shape-memory alloy in its tip, which allows a preferable fixation without coils and removal of the catheter if desired. HAI using this catheter and subsequent removal of it is a reasonable strategy especially for patients who need limited courses of chemotherapy.

The authors experienced a case with obstruction of the inferior vena cava (IVC) and the common bile duct due to a recurrent hepatocellular carcinoma. In order to improve severe edema of the lower extremities and obstructive jaundice, IVC metallic stent as well as biliary stent were applied. A Luminexx stent of 8 cm in length was placed in the bile duct via subcutaneous route after biliary drainage. A spiral zigzag stent of 8 cm in length was also inserted into the IVC through the femoral vein following balloon dilatation of the obstructed portion. Subsequently, jaundice and edema were dramatically improved in a short period of time, which resulted in patient discharge from the hospital. Although the patient died of the cancer in 2 months, the quality of life was well maintained until death.

The authors investigated the usefulness of W-Spiral Catheters for adjuvant hepatic arterial infusion (HAI) chemotherapy following curative resection of colorectal liver metastases. The catheter has a special shape-memory alloy in its tip, which allows preferable fixation without coils and removal of the catheter if desired. A W-spiral catheter was successfully placed in 13 out of 16 patients who had undergone curative hepatectomy. In the remaining 3 cases in which the hepatic artery was smaller in diameter, a catheter was placed using the conventional GDA coiling method. Removal of the W-Spiral Catheter was attempted in 10 of the 13 patients with a Spiral Catheter after termination of HAI chemotherapy. In all cases, the catheters were easily and uneventfully removed, and 3D-CT angiography revealed that the hepatic artery was well preserved in most cases. These findings suggest that a new approach to prophylactic HAI chemotherapy with W-Spiral Catheters and subsequent removal of the catheters is reasonable and desirable.

A 38-year-old man had multiple recurrence of hepatocellular carcinoma (HCC) with portal vein thrombosis after hepatectomy and postoperative transcatheter arterial chemotherapy with 5-fluorouracil (5-FU). He was treated by trans hepatic arterial embolization (TAE) with 100 mg of cisplatin (CDDP) and degrable starch microspheres (DSM). After 3 courses were administered, the recurrent lesions almost disappeared on CT, and the postoperative rise in PIVKA-II level and AFP level normalized. There were no side effects except slight fever and general fatigue. We recognized a partial response, and the patient is still alive 14 months after hepatectomy. This case suggests that TAE with CDDP and DSM might be useful for prolonging the survival of advanced HCC patients.

The authors discuss the reasonable management of implantable ports and catheters after cessation of adjuvant hepatic arterial infusion (HAI) chemotherapy following curative resection of colorectal liver metastases. Local recurrence in the residual liver was observed in only 4 patients of thirty-two patients (13%). Although heparin administration into the port was regularly performed in 17 patients to prevent its occlusion, the ports were successfully maintained in only 9 patients at a median time of 11.8 months postoperatively, and only one patient received further regional chemotherapy for recurrent disease. These findings indicate that heparin administration to maintain the port brings little benefit. In the most recent 3 cases, we used a new Piolax W Spiral catheter and removed the catheter and port after cessation of adjuvant chemotherapy. No complication related to the procedure occurred, and patients' quality of life was well preserved, suggesting that this approach for HAI is reasonable and beneficial.

A 70-year-old man underwent total gastrectomy for advanced gastric cancer in January 2000. He was treated with UFT of 300 mg/day after surgery. In December 2000, liver metastasis was detected. In January 2001, treatment was switched to oral administration of TS-1 at 100 mg/day. In April 2001, there were no extrahepatic lesions. However, the metastatic liver focus showed progression of the disease (PD). TS-1 was discontinued. In May 2001, a hepatic arterial injection reservoir was inserted. Thereafter, arterial injection chemotherapy with 5-FU was administered. However, in November, liver dysfunction was exacerbated, and computed tomography (CT) revealed PD. Therefore, in December, the above chemotherapy was switched to arterial injection of paclitaxel at 100 mg, which was administered once a week for 3 weeks and discontinued for the subsequent week. In March 2002, hepatopathy had subsided at the end of the 4th course, the performance status (PS) improved and CT revealed a minor response. In June 2002, the condition deteriorated to PD. However, there were no side effects other than alopecia. During the administration period, treatment at the outpatient clinic could be safely performed. These findings suggest that hepatic arterial injection therapy with paclitaxel for liver metastasis after surgery for gastric cancer is a useful second line for 5-FU-resistant patients.

Unlabelled: We have performed intra-hepatic arterial chemotherapy for 9 patients with liver metastasis arising from gastric cancer. We mainly used 5-FU and CDDP as antineoplastic drugs., Results: The median survival after gastrectomy was 600 days. Of 9 cases, 2 showed CR, 4 PR, 2 NC, 1 PD. The response rate was 67%. The 9 cases were classified into 2 groups. One group, the short-term survival group, concised of 5 patients that had no more than 2 years survival and the other, the long-term survival group, consisted 4 patients that had more than 2 years survival. We compared these 2 groups and found no difference in the primary lesions between the 2 groups. The patients in the long-term survival group had fewer and smaller metastatic lesions in the liver than the patients of the short-term survival group. The patients in the long-term survival group had no unresectable lesions except liver metastasis when gastrectomy was performed. However, 2 patients in the short term survival group had unresectable lymphatic involvement at the time gastrectomy was performed. Of 9 patients, 6 died from the extrahepatic lesion., Conclusion: The intra-arterial chemotherapy was effective and useful for liver metastasis arising from gastric cancer. However, the majority of patients died from extrahepatic lesions. We should therefore consider the use of systemic chemotherapy with intra-arterial chemotherapy.

We evaluated the usefulness of the following three in vitro assays in cases of resected colorectal liver metastases. Chemosensitivity by collagen gel droplet drug sensitivity test (CD-DST) was very low in all cases, suggesting this method is not predictive for this disease. In contrast, thymidylate synthetase (TS) activity and dihydropyrimidine dehydrogenase (DPD) activity in tumor tissue were high in many patients with recurrent disease. Thus, these enzyme activities are promising for assessment of clinical outcome following hepatic resection of colorectal liver metastases. Further analyses with large numbers of cases are needed to determine the significance of these in vitro studies.

A 57-year-old woman underwent distal pancreatectomy for malignant islet cell tumor of the pancreas in 1991. One year later, multiple liver metastases appeared. Although three transcatheter arterial embolizations (TAE) with spongel and nine ethanol injections were performed over seven years, the tumors were growing gradually. Therefore, TAE with degradable starch microspheres (DSM) was selected. Under angiography, TAE of the left hepatic artery was done using 900 mg of DSM following injection of Farumorubicin (20 mg), Lipiodol (3 ml) and cisplatin (90 mg). The tumors in the embolized hepatic area were remarkably decreased in size, and satisfactory local control was obtained. Thereafter, TAE with DSM was carried out twice, and she is still living with outpatient treatment. Thus, it is suggested that TAE with DSM could be a promising, alternative therapeutic modality for liver metastases from malignant islet cell tumor of the pancreas.

We evaluated the significance of hepatectomy following hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. The prognosis of 4 cases with initially resectable tumors was discouraging, indicating no benefit of preoperative HAI for resectable tumors. The 2- and 3-year survival of patients who underwent hepatectomy after downstaging by HAI of originally unresectable metastases were 100% and 67%, respectively, suggesting that hepatectomy combined with HAI is a promising modality for those patients. However, it seems that the control of extrahepatic disease and decision making for the timing for surgical therapy are issues requiring improvement.

Between 1986 and 1997, we treated 55 patients with liver metastases of breast cancer. In this study, the clinical features and effects of systemic or intra-arterial chemo-endocrine therapy for these patients were reviewed to clarify the characteristics of liver metastases and establish the optimum therapy. One of the 55 patients underwent hepatectomy, 25 were treated with systemic chemo-endocrine therapy [A] and 10 were treated with one-shot intra-arterial chemoembolization through hepatic artery [B] while the other 19 were given hepatic arterial infusion chemotherapy [C]. The response rate in the group [B] and [C] were better than in group [A], whereas there was no significant difference in survival time among the three groups. There were 14 cases (25.5%) among them showing metastasis in the thoracico-abdominal lymph nodes. In these patients, liver metastases seemed to have occurred through the lymphogenic route. In the intra-arterial chemotherapy ([B] + [C]) group, the survival time of patients with metastasis in the thoracico-abdominal lymph nodes was significantly shorter than that of patients without metastasis (p = 0.01). This study suggests that intra-arterial chemotherapy combined with MPA should be effective and useful for advanced breast cancer patients with liver metastases. And for lymphogenic liver metastases, it should be necessary to be combined with more intensive systemic chemo-endocrine therapy.

A total of 91 breast cancer patients died of advanced and recurrent breast cancer at the Osaka Teishin Hospital from 1986 to 1996. There were 18 cases (19.8%) among them showing hypercalcemia (serum corrected Ca > or = 11.0 mg/dl). These 18 cases were analyzed to determine the incidence of hypercalcemia and to find a more effective treatment. All these patients had multiple bone metastases during their clinical course, and six patients (33.3%) had pathologic bone fracture just before the occurrence of hypercalcemia. Their common symptoms were general fatigue, gastrointestinal symptoms, renal dysfunction or neurological symptoms. There was no definitive correlation between clinical signs and serum calcium values. Among various therapies, the use of pamidronate disodium (Aredia) in combination with hydration, steroid and calcitonin was found to be the most effective treatment for hypercalcemia. The survival time from the diagnosis of hypercalcemia in the patients undergoing treatment with Aredia was significantly better than without it (p < 0.01). This suggests that Aredia should be effective and useful for advanced breast cancer patients with hypercalcemia.

Excessive enterogastric reflux following partial gastrectomy is believed to be responsible for the cause of inflammation in the gastric remnant. We examined the effect of FUT-187, a synthetic serine protease inhibitor, on symptoms and endoscopic findings in 33 patients who were diagnosed endoscopically as postgastrectomy gastritis. Patients took 50 mg FUT-187 orally after each meal and at bedtime for 8 weeks. Before treatment, 30 patients (91%) suffered from several symptoms including regurgitation and/or bitter taste in the mouth (49%), epigastric pain (42%) and nausea (36%). From endoscopic observation, erythema was detected in 32 patients, edema in 23 patients and erosion and/or ulcer in 9 patients. After treatment the global improvement rating for subjective symptoms was 76.7% (23/30) and the improvement of endoscopic findings was 63.6% (21/33). Diarrhea was observed in one patient but could be easily controlled by discontinuation of the drug. Our results suggest that FUT-187 can be a useful drug for the treatment of postgastrectomy gastritis with its efficacy and safety.

Twelve patients with liver metastases of breast cancer were treated with hepatic arterial infusion chemotherapy using 20-30 mg/body of epi-adriamycin (epi-ADM) every 2 weeks and continuous infusion of 250 mg/body/day of 5-fluorouracil (5-FU). All patients were followed by systemic chemo-endocrine therapy with oral administration of 600-1,200 mg/day of me droxyprogesterone acetate (MPA) alone or with 600-800 mg/day of 5'-deoxy-5-flurouridine (5'-DFUR). The response rate was 41.7% (5/12 cases). Duration of response was 2-28 months (mean 10 months). At one year, the survival rate was 46.8% (Kaplan-Meier method). As for side effects, gastrointestinal disturbance, bone marrow depression and alopecia were mild. These results suggest that hepatic arterial infusion therapy in combination with MPA is safe and effective for controlling liver metastases of breast cancer.

Seventeen patients with liver metastases of breast cancer were treated with a combination of intra-arterial chemotherapy and endocrine therapy at our hospital from 1986 to 1994. Of 17 patients, 9 were treated with transarterial chemoembolization through hepatic artery using 40-50 mg/body of 4'epi-adriamycin (epi-ADM) and lipiodol, and the other 8 were treated with hepatic infusion chemotherapy using 20-30 mg/body of epi-ADM every 2 weeks. All patients were followed by endocrine therapy with oral administration of 800-1,200 mg/day of medroxyprogesterone acetate (MPA). The results were as follows: 1) The comparison of response rate between the two groups was not substantially changed (44.4% x 4/9 in TAE group and 50.0% x 4/8 in Reservoir group). 2) Duration of response was 4-45 months (mean 25 months) in TAE group and 3-15+ alpha months (mean 8.7 months) in Reservoir group. But in the latter group, 3 patients are now under treatment. 3) At one year, the survival rates were 44.4 percent in TAE group and 50.0 percent in Reservoir group. We conclude that combination of intra-arterial chemotherapy and endocrine therapy is a useful treatment modality for controlling liver metastases of breast cancer.

Detection of non-palpable (T0) breast cancer by pathological nipple discharge is possible 3 years or more earlier than tumorous breast cancer. However, the definite diagnosis of T0 breast cancer has been considered to be very difficult because the standard diagnostic method such as exfoliative cytology and ductography were not totally reliable. In 1985 we first demonstrated the significance of CEA measurement in nipple discharge for diagnosis of T0 breast cancer. Since then CEA activity in nipple discharge was estimated in 60 patients with breast diseases by means of enzyme immunoassay using monoclonal anti CEA antibody. They include 17 with T0 breast cancer, 9 with borderline lesion, 20 with intraductal papilloma and 14 with fibrocystic diseases. When the cut off value of CEA concentration was set at 600 ng/ml, the sensitivity, specificity and accuracy were 76.5%, 100% and 92.2%, respectively. These levels were higher than those for mammography or cytology. In the past 7 years, 13 cases of T0 breast cancer were detected in our hospital. They accounted for 2.5% of total breast cancer cases. In conclusion, CEA measurement in nipple discharge is a useful method for the diagnosis of non-palpable breast cancer.

We studied and analysed the effects of combination therapy with TAE and PEIT for unresectable HCC. The subjects were 28 patients (21 males, 7 females) with 31 tumors treated in the Department of Surgery, Osaka Teishin Hospital. The patients were divided into four groups on the basis of the tumor size (< 3 cm, 3-5 cm, 5-8 cm, > 8 cm). The therapeutic effect on the tumors was evaluated on the basis of the maximum reduction rate within 3 months after TAE and PEIT. The response rates after treatment were 87.5%, 60.0%, 25.0% and 0% for < 3 cm, 3-5 cm, 5-8 cm, and > 8 cm tumor size, respectively. The 50% survival period was 50.9 months. The 1-, 2-, 3- and 5-year survival rates were 92%, 76%, 52% and 32%, respectively. In the cases of over 8 cm, this combination therapy had no effects on the survival period. The findings of the present study suggest that the combination therapy was useful for the unresectable HCC of under 5 cm in diameter.

A comparative randomized study of intra-arterial infusion chemotherapy (IA) and systemic chemotherapy (IV) was carried out on 41 patients with locally advanced breast cancer, and the following results were obtained. 1) The response rate of primary lesions to IA (63.2%) was better than that of IV (40.9%). 2) In the patients treated with IA, grade of leukopenia, as well as the percentage of gastro-intestinal disorders, was low. 3) More prolonged follow-up studies are required on the therapeutic effects on micrometastasis. The author confirmed that IA was an efficacious neoadjuvant therapy in terms of down staging of locally advanced breast cancer.

Thirty-two patients with locally advanced or disseminated breast cancer were treated with preoperative intra-arterial infusion chemotherapy with epirubicin (30 mg/m2, day 1, 4, 7). The results were as follows: 1) the response rate (CR + PR) was as high as 71.9% (23/32) in the primary lesions. Marked degenerative changes were, also, histologically observed in 22 cases (68.8%). 2) As for side effects, mild grade of leukopenia and hair loss were frequently encountered in 75.0% and 62.5%, respectively. Gastrointestinal disorders, however, was extremely rare (6.3%). 3) Follow-up time was not long enough, but considerable survival advantages were suggested. The author confirmed that intra-arterial infusion chemotherapy with epirubicin was an efficacious modality for the treatment of advanced breast cancer.

A group study was conducted to investigate the effect of intra-hepatic arterial administration of epirubicin in the treatment of non-resectable hepatocellular carcinoma(HCC). Sixty-four patients were entered into the study. There were 51 males and 13 females, with an age range from 32 to 79 years, the average being 59.1 years. Fifty-four patients had associated cirrhosis of the liver. Epirubicin at a dose of 60-90 mg/m2 was infused as a bolus into the hepatic artery 1 to 4 times (average 1.8) at an interval of 3 weeks to 3 months. Tumor size was properly evaluated in 53 patients. There were 1 CR, 7 PR, 7 MR, 27 NC, and 11 PD. Thus, the response rate (CR + PR) was 15.1%. Seventeen patients are still alive 305 to 720 days (mean 505 days) after the initial treatment. The most common side effects of this drug were bone marrow suppression, gastrointestinal complaints, and alopecia. Cardiac toxicity was negligible at the doses used in this study. A retrospective comparison of the present results with those for patients treated by intra-arterial administration of doxorubicin demonstrated that epirubicin is more effective than doxorubicin in terms of survival rate. The current study indicates that epirubicin may be a promising alternative in the treatment of HCC. The appropriate dosage of the drug and the interval for infusion are to be elucidated. Also, the combination of epirubicin with other cytostatic drugs is open for study.

A 63-year-old female, who had undergone sigmoidectomy for sigmoid carcinoma one year before, was admitted for multiple liver metastases. A urokinase-immobilized catheter was introduced into the proper hepatic artery via the gastroepiploic artery operatively. A daily arterial infusion of 5-FU (250 mg) was combined with a weekly arterial infusion of adriamycin (30 mg) or MMC (10 mg). After discharge, 5-FU (200 mg/day) was given orally and MMC (10 mg) was infused intraarterially every other week at an outpatient clinic. ADR or MMC was infused with angiotensin II, known to increase arterial blood supply to a malignant lesion. Ultrasonography demonstrated 35 to 50% reduction in tumor diameter. The density of metastases seen in computerized tomography became low indicating tumor necrosis. Plasma CEA level, which had initially been as high as 864 ng/ml, decreased rapidly and has remained within normal limits up to the present time. Arterial infusion chemotherapy using 5-FU, ADR or MMC in combination with angiotensin II seems to be effective in the treatment of multiple hepatic metastases from colorectal carcinoma.

Transcatheter chemo-embolization is a technique for achieving a marked antitumor effect by embolizing the hepatic artery with a gelatin sponge immediately after infusion of adriamycin 60 mg into the same artery. Chemo-embolization was performed in 212 cases of hepatocellular carcinoma and 23 cases of metastatic liver cancer, a total of 235 patients. Of this population, 19 patients with hepatocellular carcinoma underwent hepatectomy, and in 7 of them, complete necrosis of tumors having thick capsules and less than 4 cm in diameter was confirmed. The cumulative survival rate of patients with unresected hepatocellular carcinoma was 75.6% at 6 months, 52.6% at 1 year, and 20.3% at 2 years. The longest survival time was 3 years and a half, and this patient is now living. As regards metastatic liver cancer, complete necrosis could be achieved in 1 of 2 patients undergoing resection, whereas the cumulative survival rate of unresected cases was 55% at 6 months and 44% at 1 year: only two patients survived for more than 1 year. Technically, the use of a balloon catheter (7F) resulted in the virtual elimination of unsuccessful cases and the prevention of adverse effects due to migration of the gelatin sponge.

Factors determining the prognosis of patients with hepatocellular carcinoma (HCC) were analyzed. Small HCC was compared to large HCC. Small HCC is less encapsulated, but has less frequent vascular invasion with favorable prognosis if resectable. Liver transplantation would be indicated in small HCC, unresectable because of far-advanced liver cirrhosis.

Intra-arterial infusion chemotherapy of adriamycin (ADM) was performed in 31 cases with locally advanced breast cancer. The overall response rate for ADM was as high as 71% (22/31) in the primary lesions and histological response rate was obtained in 54.8% (17/31). Five-year survival rates for patients with stage IIIa, IIIb and IV breast cancer were 100%, 37.5% and 40.0%, respectively, compared with 63.8%, 35.7% and 12.5%, respectively, for 80 cases of control group. Although there was no correlation between local response rate and longer survival time, a more favorable prognosis seems possible with this treatment compared with other forms of therapy.

When a large amount of iodized oil (LPD) is selectively administered to targeted segments of the liver, the tumor vessels and sinusoids around the tumor are filled with LPD, subsequently regurgitating excessive LPD via the hepatic arterioportal communication into the portal branches surrounding the tumor. Segmental arterioportal chemoembolization in HCC with Doxorubicin-in-oil emulsion (DOE), which we named cement therapy, was performed in 18 patients with HCC. DOE was administered selectively into one segment division of Couinaud in ten patients, two segments in seven and three segments in one. Computed tomography and ultrasonography following the cement therapy revealed an overall response rate of 39%. The one-year cumulative survival rate was 80%, and that for three-years was 33%. Three cases underwent segmental hepatectomy and these specimens revealed total necrosis of the main tumor and whole daughter nodules, followed by various degrees of hepatic parenchymal infarction. This cement therapy realizes the simultaneous chemoembolization via the artery and portal vein, and was considered an effective treatment for extra-capsular infiltration and daughter nodules of HCC nourished by the portal vein blood flow. Limited administration of DOE to the targeted segments enables transarterial oily chemoembolization (TOCE) without any serious side effects.

A multidisciplinary treatment for hepatocellular carcinoma including preoperative chemo-embolization with resection treatment was introduced. Recent attempts at combining lipiodol with chemo-embolization have been quite promising. An ideal multidisciplinary treatment should include an effective device using the transportal approach.

1. A multidisciplinary treatment for hepatic malignancies, using transcatheter chemoembolization followed by surgical resection, was done in 13 patients. An acturial survival rate of one year of the present series was 89%, whereas that of TCE was 53% and that of surgical resection was 36%. 2. Complete tumor necrosis was noted in 8 cases and necrosis of capsular invasion was observed in 5 of 8 cases. 3. There were 3 cases of viable daughter nodes with or without viable portal emboli. 4. The effect of TCE on tumor necrosis could be initiated firstly by arterial embolization followed by obstruction of drainage vein which was caused by granulation tissue. Subsequently, a tumor capsule might be thicker, resulting the necrosis of capsular invasion. 5. Surgical indication for hepatic malignancies is, therefore, cases with low surgical risks regardless of TCE effect or with moderate surgical risks with incomplete TCE effect.