The treatment of clinically overt metastatic breast cancer, despite several treatment modalities (biological response modifiers, megatherapy with autologous bone marrow transplantation, growth factors, new agents, etc.) is in a static phase. In the decision-making one has to consider the patient's age, her menstrual state, the metastatic site, previous adjuvant and/or postoperative treatment modalities. Roughly there are two treatment forms, the hormonal and the cytostatic ones. Endocrine therapy should be given as follows: 1. only for low risk group, 2. gestagen or antiestrogen therapy is the choice for the first step, 3. if there is a progression in 3 months, the hormonal treatment should be changed to cytostatic combination, 4. if there is a progression beyond 3 months further hormonal therapy can be considered. The efficacy of endocrine therapy is 30%. In patients with advanced breast cancer chemotherapy provides a response rate of 30 to 60%, however total survival of the patients does not improve substantially. Doxorubicin containing regimens are more effective, however no response in total survival can be obtained. New plant alkaloids and altered treatment forms will probably influence survival. Taking all these into consideration one has to decide on the quality of life of the breast cancer patients.
One hundred ninety patients with germ cell line testicular tumours were treated according to the modified Einhorn scheme. The response rate was 67.9%. The most favourable results were found in the embryonal histologic type (RR = 76.9%) in the biological markers (beta-HCG and AFP) negative (RR = 97.4%) and in the minimal pulmonary extent group (RR = 94.1%). The authors treated 112 patients with including these VPB-resistant germ cell testicular tumour and those with recurrence after this treatment. The patients' mean age was 28.8 (limits 19 to 44) years. Patients were given Vepeside (100 mg/m in infusion for days 1-5), Adriablastin (40 mg/m in infusion on day 1) and Cisplatin (20 mg/m in infusion) for day 1-5. The treatment resulted in CR with 18 patients (16.1%) and PR with 42 (37.5%) (RR = 53.6%). The best results were obtained with the seminoma patients who were marker-negative and had small-volume metastasis. CR developed in 4 of 7 seminoma patients (57%) and in 7 of 25 marker-negative individuals (28%), and PR developed in 11 patients (44%) (RR = 72%). Out of 12 patients with small volume metastatis four (33%) showed CR and five revealed PR (41.7%), their RR turned out to be 74.6%. The average remission period was 37 (range 4-70) months in CR but merely 6.1 (range 2-38) months in PR. It can be stated that fairly good results can be achieved with second-line VpAP treatment in case of resistance developed to primary VPB therapy or subsequent relapse. The efficacy of combined chemotherapy of Vepesed+Holoxan +/- Adriablastin as third-choice was studied in advanced testicular cancer patients refractory to, or recurrent after, first- and second-line cytostatic therapy. Between September 1981 and January 1988 49 evaluable patients were treated with Vepesid (VP-16213--100 mg/m2 days 1-5), Holoxan (40 ml/kg days 1-5), hydration, urine-alkylation + Uromitexan +/- Adriablastin (40 mg/m day 1). The single dose of Uromitexan was 20% of the daily dose of Holoxan, and the patients received it i.v. just prior to Holoxan administration (h 0), the 4 and 8 h later. Two patients got into CR and 10 to PR. The rate of remission was 24.5%. The most severe side effect was leukopenia. The elevation of BUN and se. creatinine was transient and mild. In those cases where Holoxan was not included in the first- or second-line regimens, when combined with Vepesid and Adriablastin as third-choice therapy one could achieve further improvement. In case of CR the prolongation of life is also noteworthy. The first-, second- and third-line therapy plus salvage RLA and/or pulmonary metastasectomy achieved long-term survival only in one quarter of the patients.
The success of surgery performed for pulmonary carcinoma is based on the selection of the patients for operation. Cytological or histological verification of the tumour prior to surgery is important as concerns the choice of the type of surgery and the complex antitumour therapy. It is currently considered that patients with tumours in stages I, II and IIIa are suitable for surgery. Operations are also performed in cases involving solitary cerebral metastases, and centrally-lying tumours which reach the bifurcation carina or the lower portion of the trachea (T4) are similar rarely resectable. The basic operation for pulmonary carcinoma is lobectomy. In selected cases of squamous cell carcinomas in stage T1N0, atypical wedge resection too may be considered. Extended surgery is also performed, depending on the size of the tumour. For all types of tumours, it is essential to take a sample from the lymph nodes for accurate staging. Prospective randomized clinical trials on 288 patients undergoing resection for pulmonary cancer revealed that extended medistinal lymphadenectomy improved the 5-year survival rate in cases of adenocarcinomas and squamous cell carcinoma, involving lymph node metastases. Intraoperative cytological examinations or frozen sections are extremely important as concerns the indication of extended mediastinal lymphadenectomy and adjuvant antitumour treatment.
Increasing knowledge of fragile bone has been gained by non-invasive mineral assessments. Its future importance seems to be twofold. First by, it seems likely that patients with low bone mineral will be treated to try to increase this bone mineral or at least to keep it steady. Secondly, in the presence of osteoporosis special strategies must be taken into consideration. In many locations osteoporotic fractures may need special solutions. It seems that osteosynthesis with plates and screws which have their definite indications in younger patients may be replaced by alternatives, such as cerclage wiring and intramedullary implants. Polymethylmethacrylate has been a good adjunct to strengthen screw fixation and to fill defects after compression of fragile cancellous bone.
A tumour and its environment constitute a three-dimensional (3D) phenomenon. Consequently, adequate management of the target volume (tumour + safety zone) is feasible only with a 30 treatment planning and irradiating system. The more precise planning and dose delivery involved in such a 30 treatment lead to an improved therapeutic effectiveness.
The magnitude of brachytherapy doses depends on the applied dose rates: high-dose-rate or low-dose-rate techniques. Brachytherapy is usually performed as a complementary modality with megavoltage external beam therapy, but it is also used preoperatively for cancers of the uterine cervix and corpus. The most common localization is reviewed in this paper with special regard to the indications, treatment methods and prognosis of curing for rectal and breast cancer.
Experience with more than 500 tumour cases operated in one year in the National Institute of Neurosurgery and the relevant oncological literature point to an important role of neurosurgery in the treatment of cerebral tumours. After reviewing the dramatic advances of neuroimaging and neurosurgical methods the main problems of neuro-oncology will be brought to light and the new directions of brain tumour research will be shown.
Those research trends which are currently in the focus of interest of various research groups are summarized. The main tendency is to look for new molecular targets and to synthesize new antitumour drugs. Moreover, new research concepts emerge out of which differentiation induction, inhibition of MDR and study of apoptosis seem to be promising. Among clinical approaches megachemotherapy, neoadjuvant treatment and progress in supportive therapy are the main research directions. Last but not least, quality of life issues of the cancer patient are of particular importance.
Treatment modalities of head and neck tumours such as cancers of the skin, lips, oral cavity, sinuses, epi-, meso- and hypopharynx, larynx and cervical soft tissues are discussed. Cervical cysts, thyroid tumours and salivary gland alterations are also examined from the therapeutic point of view. Therapeutic advices are given for the treatment of regional metastases.
Extended lymph node dissection is an important part of the surgical treatment for cancer of the esophagus, stomach, colon and rectum. With an appropriate lymphadenectomy a more precise tumour-staging, an increase in resectability, a rise of the rate of R0-resections, further a decrease in local tumour recurrences and an improvement of prognosis can be achieved.
The advantages of and the information given by CT examinations in the proper and valid treatment planning of radiotherapy of malignant tumours are discussed. Without individual and thoughtful application of CT before and during radiotherapy the chances of cure are significantly reduced. Radiotherapists must be familiar with this imaging method.
Cytokines are pleiotropic peptides produced by lymphoid cells that play important roles in cellular proliferation and multiplication. Diminished or enhanced production or constitutive secretion of cytokines contributes to the aetiology and pathogenesis of several diseases. They are soluble mediators eliciting specific responses of different target cells of paracrine, autocrine and cascade systems of the organism. Their secretion is regulated at the molecular genetic level. Gene rearrangements of cytokines and their receptors have been demonstrated in several diseases. As means of specific or supportive therapy, cytokine treatment has been used both in neoplastic and other proliferative diseases. Lymphokines and interferons comprise the first, whereas colony stimulating factors and growth factors yield the second group of cytokines. Most scientific experience is with interferon-alpha. Its anti-viral mechanism of action has been extensively studied and clarified, whereas its antitumour effect is more obscure and is a result of many simultaneous biologic events.
The author gives a survey of literature on bone tumours in childhood and a comparison with his own work. Introducing four cases he concluded, that the survival rate of malignant bone tumours are increasing, the autologous bone transplantation seems to take priority against prosthesis in childhood, and the autologous bone transplantation is more reliable method, than the homologous one.
Operative treatment of gynaecological tumours includes exploration, staging and removal of tumour for both therapeutic and diagnostic purposes for advanced processes the optimum conditions of postoperative supplementary treatment are to be developed. In contrast with the earlier view suggesting that a malignant tumour of a given organ is always the same in every case, nowadays tumour heterogeneity is emphasized. Multicentrical co-operative surgical research should widen our knowledge. Well-designed and well-equipped centres should be made available for our patients suffering from gynaecological malignancies; gynaecological oncology needs well-planned functioning special clinics/wards.
The author reports on the progress made in the treatment of bone tumours in the last two decades. There is a short description of new entities like the solid form of aneurysmal bone cyst; dedifferentiated and clear-cell chrondrosarcoma; low malignant central osteosarcoma; periosteal and high-grade surface osteosarcoma, which have recently been reported in the literature. The response to the chemotherapy in osteosarcoma and the problems of limb-saving surgery in bone tumours are discussed.
The authors studied the distribution of the paracetamol conjugation in a Hungarian population (53 adult Caucasian persons). The data indicated that the excretion of paracetamol glucuronide and sulphate were not normally distributed. Bimodality were apparent in both conjugation pathways: 15.1% of subjects was relatively extensive glucuronidators, and the 24.5% of subjects was extensive sulphatators. Monitoring the ratios of various urinary paracetamol conjugates/paracetamol may be useful as a tool for determining the glucuronide and sulphate conjugation capacity in humans.
The study was aimed to investigate the electrophysiological properties of long QT syndrome associated with permanent bradycardia. The investigations were performed in 26 patients suffering from long QT duration (QTC-frequency adapted QT-:484 +/- 34 ms) with permanent, marked bradycardia (heart rate: 42 +/- 7 min-1). Adams Stokes syncopal attack appeared in 12 patients, while in 14 cases ventricular tachycardia attack with syncope could be observed (study group). As control served the data of 30 patients suffering from long lasting marked bradycardia (heart rate: 44 +/- 7 min-1) with normal QT (QTC:420 +/- 28 ms). Each patient was candidate for pacemaker implantation. The following questions were studied: 1. The effect of heart rate on QT duration. The experiments were performed by electrical ventricular stimulation. 2. The effect of sympathetic and parasympathetic-pharmacologic-blockade on QT time. The study was performed under electrical ventricular stimulation by administration of propranolol and atropine. 3. The dispersion of QT time was studied by using electrical heart stimulation and 12 lead ECG recording. Electrophysiological investigations were performed in 14 patients with long QT and permanent bradycardia. On augmentation of the cycle length (bradycardia) the increase in the QT duration was more-out of all proportion-expressed in long QT. On pharmacologic sympathetic blockade in long QT syndrome the QT duration significantly diminished. The QT dispersion was more expressed in patients with prolonged QT interval and on bradycardia the QT dispersion further increased significantly. The irritability of the ventricle was markedly augmented in patients with long QT and bradycardia. Appearance of polymorphous ventricular tachycardia could frequently be observed and could be regularly induced by early ventricular extrastimuli and bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitotic delay (MD) often occurs in cells of donors exposed in vivo to genotoxic agents. To investigate individual sensitivity with genetic background, author measured the 3-methyl-cholanthrene (MC)-induced MD in cultured human skin fibroblasts (FBs) and in peripheral blood lymphocytes (PBLs) obtained from a 4-year-old patient with Down's disease. Samples from a 10-year-old healthy subject served as controls. Skin samples were obtained during surgical intervention. The induced MD was calculated from the mitotic index (MI) which was expressed in per cent of the control; at various times up to 18 h after treatment. Cells were treated with 10(-7), 10(-6) and 10(-5) M MC (with S-9 liver homogenate). At passage 10, the average MI (+/- SE) was 8.32 +/- 0.43%, and 7.85 +/- 0.64% for the healthy and for the Down's FBs, respectively; and it was 4.89 +/- 0.59%, and 4.92 +/- 0.72% for the healthy and for the Down's PBLs, respectively. MD was characterized as 50% MI of control (MD50). The MD50 values were the most expressed when cells were treated with 10(-5) M MC. No difference was found in MD of healthy and Down's fibroblasts. For Down's lymphocytes, on the other hand, MD was approximately 30% longer than for healthy cells. This result agrees well the reported increased SCE and decreased DNA-repair data obtained in PBL of Down patients.
One hundred male insulin-dependent diabetic patients, aged 16 to 85 (mean 51.9) years, with albumin excretion ranging from normal to gross excess were examined for glomerular and tubular functional alterations by estimating urinary levels of albumin and indicator proteins of tubular damage. Urine protein 1 (UP1), a newly-discovered low-molecular weight alpha-2 glycomicroglobulin, together with alpha 1-microglobulin was used to assess tubular function. 19% of the patients showed increased albumin excretion with normal levels of tubular proteins (glomerular proteinuria), 11% excreted only tubular proteins in excess (tubular proteinuria), while 40% had a mixed pattern of both increased albumin and tubular proteins (glomerulotubular or mixed proteinuria). 30% had normal albumin and tubular protein excretion in urine. UP1 was found to be a more sensitive indicator of tubular abnormality than alpha 1-microglobulin. It is concluded that, although glomerular changes may be responsible for the proteinuria seen in most diabetics (mixed proteinuria), in a small but significant proportion of diabetics, tubular functional alteration may occur before, or in the absence of, glomerular dysfunction, and may warn of subclinical tubular abnormality. This finding may have a direct bearing on the development and course of progression of diabetic nephropathy, and may question the reliability of the present prognostic interpretation of microalbuminuria.
