Effect of balloon occluded arterial infusion of anticancer drugs on the prognosis of cervical cancer treated with radiation therapy.

PURPOSE: The effect of local injection of anticancer drugs by balloon catheter, i.e., balloon occluded arterial infusion (BOAI), on the prognosis of cervical cancer treated with radiotherapy were retrospectively estimated. METHODS AND MATERIALS: Sixty-five patients with cervical cancer (Stage I-IV) treated by irradiation were included in the study. Among the 65 cases, 2 were in Stage I, 13 in Stage II, 40 in Stage III, and 10 in Stage IV. Patients who received surgical resection were excluded. Thirty-nine patients received BOAI and 44 received brachytherapy. Twenty-six patients were not indicated for BOAI because of insufficient renal function, hepatic complications, hematological complications, and refusal from the patients. Cisplatin (0.9-1.7 mg/kg), Adriamycin (0.7-0.9 mg/kg), and Pepleomycin (0.4-0.6 mg/kg) were administered simultaneously into the bilateral internal iliac arteries by BOAI. External irradiation was given by 10 MV x-ray. Total dose administered to the regional lymph nodes by the external irradiation was 48.3 +/- 8.7 Gy. Radium was used at brachytherapy. The dose delivered by the brachytherapy at point A was 45.3 +/- 14.9 Gy. Patients without brachytherapy received 26.1 +/- 19.1 Gy of boost irradiation by the external photon beam. The survival probabilities of the patients were calculated by Kaplan-Meier method. RESULTS: The 5-year survival rates of the Stage III patients with and without BOAI were 53 +/- 13% and 24 +/- 18%, respectively (p = 0.036). By multivariate analyses using Cox's proportional hazard model, stage and BOAI were selected as significant predictors of the prognosis. Transient bone marrow suppression was observed in about half of the patients with BOAI. No significant increase of the incidence of the late radiation damage by BOAI in rectum or in urinary bladder was observed. CONCLUSION: Balloon occluded arterial infusion of anticancer drugs may improve the prognosis of the patients with cervical cancer without increasing the incidence of the late radiation damage. A larger scale prospective randomized study is desired.

[Self-expandable metallic stent therapy for inferior vena cava obstruction secondary to malignancy: clinical observations].

To evaluate the self-expandable metallic stent therapy for inferior vena caval obstruction (IVCO) secondary to malignant liver tumors, changes in caval pressure, the symptoms and hemobiochemical values were observed. Among 16 IVCO cases with higher caval pressure than 20 cmH2O at the peripheral caval lumen to the stenosis, nine cases consisting of five extracaval compression cases and four intravenous tumor thrombi cases subjected the stent therapy. Other three subjected radiotherapy and the other four cases inactive supportive care. Immediately after the Z-stent implantation, the averaged caval pressure distal to the stenosis decreased from 27.7 +/- 3.5 cmH2O to 14.7 +/- 2.6 cmH2O. One case developed 8 cmH2O increase of right atrial pressure but no lung edema. The urine excretion volume increased after stent. The decrease in caval pressure correlated with the urine volume of the day after the stenting (gamma = 0.83), symptomatic improvements of leg edema (gamma = 0.68), ascites (gamma v 0.51) and scrotal edema (gamma = 0.70). Five cases showed gradual increase in platelet number. All elevated LDH and elevated fibrinogen value decreased. These changes would suggest physiologic benefits of the IVC stent therapy. Compression cases showed better improvements and courses than the thrombi cases. Two thrombi cases endured severe conditions suspected of triggered by the procedure. Conclusively, the stent therapy to the IVC obstruction was thought to effect hemodynamically and hematobiochemically.

Self-expandable metallic stent therapy for superior vena cava syndrome: clinical observations.

PURPOSE: To study clinical and physiologic aspects of Z-stent therapy for superior vena cava (SVC) syndrome secondary to malignant disease. MATERIALS AND METHODS: Signs and symptoms of SVC syndrome were classified, graded, and scored in 11 cases. Six patients with caval pressure higher than 22 mm Hg peripheral to the stenosis underwent stent therapy. RESULTS: Immediately after Z-stent implantation into the stenotic lesion, the diameter of the constriction increased from 3.3 mm +/- 2.0 (mean +/- standard deviation) to 14.0 mm +/- 3.2, the mean caval pressure peripheral to the stenosis decreased from 26.6 mm Hg +/- 2.5 to 8.9 mm Hg +/- 0.7, and the symptom score decreased from 6.7 +/- 1.8 to 1.3 +/- 1.4. The caval pressure, lesion diameter, and symptom score correlated highly with each other. One complication--transient pulmonary edema attributable to volume overload caused by reperfusion--was observed. Mean survival exceeded 7.1 months. CONCLUSION: Stent placement could be a useful treatment for refractory SVC syndrome.

Dacron-covered stent therapy for portal vein tumor thrombus in hepatocellular carcinoma.

A tumor thrombus of the portal vein is refractory to therapy and constitutes a serious prognostic factor in hepatocellular carcinoma. For the purpose of treating portal vein tumor thrombus by restoring the blood flow and preventing recurrent ingrowth of tumor, we devised a metallic stent partially covered with a Dacron mesh sheet, and a coaxial percutaneous delivery system. One half of the wall of a Gianturco Z-stent was covered with a sheet of 0.25-mm-thick Dacron mesh, fixed to the stent wall with nylon threads. The covered stent was implanted in a patient with severe main portal vein stenosis due to tumor thrombus protruding from the left portal vein branch. Immediately after stent placement the tumor stenosis was effectively dilated, the portal blood flow restored, and the portal hypertension relieved. CT and angiography after 8 months still showed complete portal vein patency. Intrahepatic tumor dissemination or other complications were not observed. Intraportal placement of a covered metallic stent appears to be an efficacious therapy of major portal tumor thrombi.

[Expandable metallic stent therapy for SVC syndrome--effects on local venous pressure, vascular diameter, symptoms, and these correlations].

To evaluate the efficacy of Z-stent therapy for SVC syndrome, we studied changes in the pressure, the diameter of stenotic lumen and the symptoms in the cases of SVC syndrome with higher pressure than 30 cmH2O at distal to the stenosis. The symptoms were classified and graded to be scored up. Immediately after the Z-stent placement into the stenotic lesions, the venous pressure distal to the stenosis decreased from 36.0 +/- 3.4 cmH2O to 12.0 +/- 12.0 cmH2O (p < 0.001), the diameter of stenotic lumen increased from 3.3 +/- 3.4 mm to 14.0 +/- 3.4 mm (p < 0.01). According to the remarkable symptomatic improvements the averaged score decreased from 6.7 to 1.3 (p < 0.01). The pressure, the diameter and the symptom scores were highly correlated each other (magnitude of gamma not equal to 0.9). Among two cases with the right atrial pressure increase by 2 cmH2O after the placement one suffered transient cardiac in compensation due to overload by reperfusion. Conclusively, the Z-stent therapy was very effective on the SVC syndrome in reducing abnormally elevated venous pressure due to the stenosis, and relieving the symptoms, while the pressure monitor was necessary.

Time courses of PIVKA-II and AFP levels after hepatic artery embolization and hepatic artery infusion against hepatocellular carcinoma: relation between the time course and tumor necrosis.

We examined 35 untreated patients with unresectable hepatocellular carcinoma who exhibited positivity for both plasma PIVKA-II and serum AFP, and studied the weekly course of these markers from the pre-TAE or -HAI period to the third week of treatment. We correlated changes in these markers with the tumor necrosis rate and the time course on X-ray CT images. One week after TAE, the tumor necrosis rate and the time course of PIVKA-II showed a significant correlation (r = 0.7), while the correlation was between the time course of AFP and the tumor necrosis rate was insignificant (r = 0.2). At two and three weeks after TAE, both the time course of AFP and PIVKA-II showed significant correlations with the tumor necrosis rate. In 16 patients with tumor necrosis rates of not less than 90%, the mean of the actual half-life (AHL) of PIVKA-II was 3.2 days, the shortest was 1.83 days, and 75% of all AHLs clustered from two days to four days, while the mean and shortest AHLs of AFP were six days and 2.98 days, respectively, exhibiting a broader distribution. On the other hand, in three out of the nine cases of hepatocellular carcinoma complicated with portal tumor thrombi, PIVKA-II increased after HAI in spite of a reduction in tumor size. It was suggested that the PIVKA-II level requires careful interpretation in cases of portal vein obstruction after intensive hepatic arterial infusion of anticancer agents.

[A stent therapy for portal tumor thrombi. Use of Dacron sheet covered self expandable metallic stent].

We developed a method of intraportal placement of a covered stent against portal tumor thrombi. Half around a z-stent was covered with a Dacron mesh sheet. In one case with portal tumor thrombi protruding into the main portal branch, the stent was placed percutaneously-transhepatically, through a coaxial introducer. Immediately after the placement, portal vein was dilated and, which was still patent after six months. No complication has been observed.

[Balloon-occluded arterial infusion as chemotherapy in bladder cancer--long-term results].

One hundred three patients with bladder cancer underwent balloon-occluded arterial infusion. In 66 patients whose therapeutic effects could be evaluated by endoscope, CT and angiography, the anti-tumor effective rate (CR + PR) was 78.8%. In 15 patients who were not treated by trans-urethral resection or total cystectomy but BOAI, one-year cumulative survival rate was 46.7% and the two-year rate 13.3%. The longest survival period after BOAI was 7 years and 8 months. 133Xe activity of bladder tumor area in BOAI was 6.60 times higher than in simple arterial infusion. BOAI was thought to be a promising conservative treatment in advanced bladder cancer.

Short-term intrathrombotic injection of ultrahigh-dose urokinase for treatment of iliac and femoropopliteal artery occlusions.

Thirty-two patients with iliac and femoropopliteal artery occlusions were treated with direct intrathrombotic injection of ultrahigh-dose urokinase (10,000 IU/min). Occlusions ranged from 3 to 25 cm (average 13.3 cm) in length and the total urokinase dose from 120,000 to 1,410,000 IU (average 688,000 IU). The procedure was usually followed by balloon angioplasty to dilate the underlying stenoses. The initial recanalization rate was 96.9%, the two week patency rate 81.3%, and the cumulative one-year patency rate 66.3%. Complications associated with this procedure included three episodes of minimal bleeding, two distal embolisms, one local hematoma, and one low-grade fever. All were well controlled by palliative treatment. Results indicate that this procedure can provide rapid recanalization at a higher success rate and with fewer complications than previously reported.

An attempt of hyperthermia with balloon catheter and immunochemotherapeutic agent.

The following studies were performed to develop a new technique of hyperthermia by vascular catheterization for the treatment of malignant neoplasm. A balloon catheter was inserted into the artery of a cancer-affected organ and inflation of the balloon temporarily occluded the artery, after which an anticancer drug solution warmed to 45 degrees C was infused. The purpose of this technique was to enable the solution to arrive at the affected area undiluted by blood. It would then remain in the organ and act on the lesion. When OK-432 was intravenously administered to induce pyrexia of 40 degrees C, followed by the above-mentioned arterial infusion, it was expected that the effects of hyperthermia and chemotherapy would be synergistic. In cases of liver cancer and urinary bladder cancer subjected to the arterial infusion of warmed anticancer drugs, however, the temperature in the hepatic vein increased by only 0.5 degree C while that in urethra near the tumor increased by only 1 degree C. In the future, further improvement needs to be made to obtain effective local heating with this technique.

[Balloon occluded arterial infusion therapy for malignant hepatic tumors].

A number of reports of regional intraarterial infusion chemotherapy for malignant tumors have been published. Balloon occluded arterial infusion was newly developed by us. Balloon catheter is used for temporal occlusion of the hepatic artery during intraarterial infusion of anticancer drugs. Interruption of the arterial blood flow keeps the drugs at high concentration for a long time in the distal artery to the occluded portion. This procedure has been performed in 87 cases of hepatomas and metastatic liver cancers with the sufficiently good results.