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66歳, 男性。口唇のほぼ全域に有棘細胞癌および前癌性病変を認めた症例に, 初回治療として動注化学療法と放射線療法の同時併用を行い好結果を得た。動注法は左側はオトガイ下動脈経由顔面動脈順行性挿管法を, 右側は顔面動脈直接挿管法を用いて硫酸ペプロマイシンを1日に片側5mgずつ連日, 総量70mgを投与した。放射線は6MeVの電子線を1日250cGy, 週に5日間連日照射し総線量5000cGy用いた。照射終了7カ月を経た現在再発をみていない。治療後の口腔の整容と機能に問題なし。

In the past 2 years at our institution, 87 patients with hepatic metastasis from colorectal carcinoma have undergone surgical implantation of an arterial pump for the direct infusion of chemotherapeutic agents into the liver. We report six cases of cholangitis complicating the course of these patients.

One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion.

Despite almost three decades of experience, the use of intra-arterial chemotherapy for the treatment of head and neck cancer is not universally accepted [1]. Overall reported response rates are not substantially different from the therapeutic results obtained with systemic therapy. The additional complications associated with establishing and maintaining arterial access have further dampened enthusiasm for this approach. It is clear that considerable improvement in regional therapy techniques and efficacy will be necessary before widespread clinical acceptance of intra-arterial chemotherapy is attained. These improvements must be based on the anatomic and pharmacologic factors that determine the success of regional therapy, and require the development of safe and reliable delivery systems.

Malignant gliomas of the brain have a poor prognosis despite surgery and radiotherapy and/or systemic chemotherapy (10, 11). Therefore, alternative ways of administering chemotherapeutic agents have been developed, as for instance the intra-arterial (ia) route, which has been used for BCNU, ACNU, cisplatin, and other drugs (3, 6, 13). Although local complications have been reported with various chemotherapeutic agents, the retinotoxicity of these ia administered cytostatics has received relatively minor attention in the clinical literature (5, 7, 9), and experimental investigations on this subject have been performed rarely (2).

The complications of percutaneous intraarterial infusion chemotherapy of the head-and-neck-cancer patient has dampened enthusiasm for this approach. A totally implantable infusion pump system circumvents many of these complications and will in the long term enhance the opportunity to expand upon the advantanges of infusion chemotherapy for the benefit of all cancer patients.

The rationale of regional chemotherapy in malignant liver tumours is based on an increased drug uptake in the tumour tissue, while at the same time the side effects of the therapy are reduced. Although nearly 40 years ago the theoretical treatment concept was already discussed in detail by Klopp [1], great uncertainties still arise as to the practical value of this form of therapy. Experimental and clinical knowledge, but also unanswered questions, will be discussed in the present chapter.

Bronchial angiography and intraarterial infusion of mitomycin-C were successfully performed in 39 of 47 patients with bronchogenic carcinoma. More than one course was given to several patients. No neurologic complications occurred and the side effects were insignificant. The pertinent anatomy of the bronchial and spinal arteries is summarized and a comprehensive description of the angiography and infusion technique is given. It is important that the infused artery is not occluded by the catheter and that the drug is properly diluted to avoid complications. The method appears to be of therapeutic value in the treatment of pulmonary carcinoma.

The principal objective of regional chemotherapy is tumor cell kill. The rationale for regional delivery is based on the steep dose/response curve exhibited by most antineoplastic agents. Intraarterial (IA) chemotherapy has the potential advantage of increased drug concentration at the tumor site, decreased systemic drug levels, and continuous tumor cell exposure to an antineoplastic agent. Despite these advantages, the use of IA chemotherapy has not been universally accepted. This is in part due to the difficulties associated with establishing and maintaining arterial access. Considerable improvement in the techniques and efficacy of regional therapy for head and neck cancer will be necessary before there is widespread clinical acceptance. These improvements must be based on anatomic and pharmacologic factors that ensure success of regional therapy. In addition, the development of safe, reliable delivery systems will be necessary. Part 1 of this two-part article will review these factors and discuss delivery systems.

Surgery, radiation therapy, and chemotherapy each produce a distinctive response within the lesion and in the surrounding tissue that may be evaluated with diagnostic imaging techniques

Intraarterial chemotherapy of high grade gliomas has been undertaken for 13 months in our institution. This was the continuation of the work performed by one of us (9) (10) at the Montreal Neurological Hospital. However, the protocol was modified on a major point: knowing the efficacy of the BCNU on the gliomas (4) but also its toxicity on the normal brain (5), our goal was to treat, if possible with lower doses, the tumour before the post surgical recurrence can be recognized on the clinical signs and on the CT findings.

Between December 1984 and December 1986, 46 patients suffering from malignant gliomas were considered as unoperable because of tumor location or extent. These patients were treated by 4 courses of intraarterial chemotherapy followed by conventional radiotherapy (50 grays). The response rate after IAC was 49%. The responders had in almost cases good clinical improvement, a median duration of response of 15 months and a median survival of 19 months (median survival of all the patients = 8.5 months). The complication rate is low: major visual loss occurred in 3 cases and neurological complications occurred, always after radiotherapy, in 5 cases.

The development of biliary strictures simulating sclerosing cholangitis is now well-known. We report a patient undergoing intraarterial chemotherapy for metastatic colon cancer of the liver in whom segmental intrahepatic biliary strictures occurred remote from known metastases. The patient remains alive 3-4 years after documented liver metastases with severe progressive portal hypertension, hypersplenism, and fat malabsorption. A table of cases so far reported is given.

Despite almost 3 decades of experience, the use of intraarterial (IA) chemotherapy for the treatment of head and neck cancer is not universally accepted. The overall reported response rates are not substantially different from the therapeutic results obtained with systemic therapy. The additional complications associated with establishing and maintaining arterial access have further dampened enthusiasm for this approach. It is clear that considerable improvement in the techniques and efficacy of IA chemotherapy is necessary. This second and last part of this article considers the past and present clinical experience with IA therapy in the treatment of head and neck cancer and explores future developments.

Surgery and radiotherapy are standard therapy for malignant gliomas and have proved efficacity in increasing survival (Walker et al 1980). Other therapeutic approaches have been investigated but their influence on tumor growth remains uncertain; in particular, chemotherapy is judged controversially among clinicians, although some increase in median survival time and in the proportion of longterm survivors has been reported (Kornblith & Walker 1988). Chemotherapy of malignant gliomas may be administered by a locoregional approach via the internal carotid artery (ICA), and this might have a positive influence on the therapeutic efficacity, both on theoretical grounds (Eckman et al 1974) as well as suggested by clinical reports (Greenberg et al 1984; Tyler et al 1986). The hydrophilic nitrosourea ACNU has been shown to achieve high blood and tumor tissue levels after intra-arterial (i.a. ) administration (Hori et al 1987) and a preliminary report on i.a. infusion of ACNU (iaACNU) demonstrated a good tumor response with minor side effects (Yamashita et al 1983). Therefore, we initiated a clinical study of adjuvant iaACNU chemotherapy in addition to surgery and irradiation, and present some of our results in patients with WHO grade IV cerebral gliomas.

Intraarterial therapy was performed in 17 women with various gynecologic tumors in order to facilitate surgery (13 patients) and for palliation (4 patients). In the non-surgery group intraarterial chemotherapy was supplemented by occlusion in 2 patients. In the surgery group 5 women received intraarterial chemotherapy before the occlusion procedure. In the palliation group the result was poor, but 9 of 13 patients in the surgery group had radical surgery. They had all previously been found to be non-resectable at laparotomy (11 patients) or clinically (2 patients). No severe complications of using the intraarterial technique were encountered, though such are frequently reported.

The prognosis of malignant gliomas remains grave despite surgery, radiotherapy and various kinds of adjuvant therapy, including chemotherapy. At our institution these tumors are treated with a combination of postoperative radiotherapy and intra-arterial (i.a.) chemotherapy with ACNU (iaACNU) as is reported elsewhere in the Proceedings of the XVth Congress of the European Society of Neuroradiology, Wurzburg 1988. Because only some of these neoplasms respond to chemotherapy, a number of patients are treated unnecessarily with i.a. chemotherapy, which may have serious side effects. The measurement of early metabolic effects of iaACNU may provide important information to distinguish responders from non-responders. Previously published reports concerning the metabolic effects of chemotherapy in malignant gliomas dealt with longterm changes observed after completion of chemotherapy or after at least several cycles of radiochemotherapy. The present study reports on early effects of iaACNU in patients with malignant gliomas as mea sured with the use of positron emission tomography (PET).

Intraarterial administration of chemotherapy results in augmentation of both local peak plasma concentration of the drug and local area under the concentration - times - time curve (AUC) during the drug infusion (1–4). It can be particularly advantageous to administer drugs with a rapid total body clearance intraarterially since if clearance is rapid, the usual AUC will be relatively small, and the local increase in AUC resulting from intraarterial administration will be proportionally quite large (3, 4). For some drugs, intraarterial administration would be expected to result in increased therapeutic efficacy, while for other drugs, there would be relatively little advantage (1–4). Augmentation of local tissue concentrations by intraarterial administration has been documented for some drugs (5–9), but not for others (10).

We report one retinoblastoma patient with dual ophthalmic arteries (also known as double ophthalmic arteries) arising from the internal carotid artery which fuse with each other inside the orbit. The caudal ophthalmic artery with larger caliber originated from the cavernous segment of internal carotid artery and passed through the superior orbital fissure. The cranial and tiny one arose more cranially from the supraclinoid internal carotid artery and passed through the optic canal. After superselective catheterization, frank anastomosis was shown between two ophthalmic arteries and the central retinal artery arose from the cranial one. To the best of our knowledge, this case is the first observation of a dual ophthalmic artery with cavernous/supracavernous origins fusing with each other proven by superselective ophthalmic angiography. Whether there is an anastomosis between two ophthalmic arteries is important for deciding which artery to be selected for intraarterial treatment. In cases of retinoblastoma, detailed angiographic analysis may be essential to examine the orbital arterial system and to avoid unexpected complications during intraarterial chemotherapy.

The successful application of radiolabeled antibodies in diagnosis and therapy of human diseases is the final result of a long and intimate cooperation and collaboration between at least four scientific branches: immunology, radiochemistry/biology, oncology, and nuclear medicine (Table 1/ Figure 1).

To the Editor:— Tindel's communication (200:913, 1967) reports his experience with 28 intra-arterial infusions in 25 patients with recurrent regional neoplastic diseases, and Creech's editorial (200:983) in reference to this article also conveys the general impression that intraarterial chemotherapy is a dangerous procedure of doubtful benefit. (Other authors have reported similar experiences in larger series, particularly in reference to complications.) I totally disagree that intra-arterial chemotherapy is a dangerous procedure of doubtful benefit. To condemn an effective modality of chemotherapy on the basis of one investigator's results, and in only 25 cases, is not justified and compromises scientific judgment. I personally have performed over 3,600 intra-arterial infusions on more than 1,200 patients from 1960 to the present time, infusing all regional areas of the body from the head to the foot. Thirty percent of the first 900 patients treated had an objective response rate of six months' to