Adenoviral vector transduction of the human deoxycytidine kinase gene enhances the cytotoxic and radiosensitizing effect of gemcitabine on experimental gliomas.

The aim of this work was to improve the cytotoxic and radiosensitizing effects of gemcitabine using a gene-directed enzyme prodrug therapy approach. Murine Gl261, rat C6 and human U373 glioma cell lines were transduced with an adenoviral vector encoding the human deoxycytidine kinase gene (Ad-HudCK). Intracranial tumors were established in C57BL/6 mice and Wistar rats using either wild-type or Ad-HudCK-transduced Gl261 and C6 glioma cells. In vitro growing cells and established tumors were treated with gemcitabine and irradiation either alone or in combination. Deoxycytidine kinase overexpression substantially increased both the toxic and radiosensitizing effects of gemcitabine in each cell line, but the enhancement rate varied: it was mild in the Gl261 cells and much stronger in the C6 and U373 cells. In vivo experiments showed a mild radiosensitizing effect of dCK overexpression both in the Gl261 and C6 models. The combination of dCK overexpression, gemcitabine treatment and irradiation improved the survival rate of C6 bearing rats significantly. In conclusion, overexpression of the dCK gene can improve the cytotoxic and radiosensitizing effect of gemcitabine both in vitro and in vivo in a tumor-specific manner.

Angiography-proven liver metastases explain low efficacy of lymph node dissections in medullary thyroid cancer patients.

AIM: To report the role of liver angiography in the staging of medullary thyroid cancer (MTC) patients. MATERIAL AND METHODS: Sixty MTC patients with persistent or recurrent hypercalcitonemia (n=49), a characteristic general symptom (diarrhea, n=4) or a normal basal calcitonin level without general symptoms (n=7) were investigated by dynamic liver CT, MRI and angiography between 06/1998 and 06/2002. RESULTS: Dual-phase CT and MRI investigations identified hepatic metastases with relatively low frequency (8/58 on MRI, and 7/60 on CT). Angiography indicated liver involvement in 54/60 cases. The hepatic metastases were typically multiple, hypervascular, small foci (only 13 foci measured >/=10 mm). With one exception significant disease progression was not observed over 5 years of follow-up. CONCLUSIONS: Liver angiography is a powerful tool to reveal hepatic metastases in MTC patients. Frequent, inoperable liver metastases in hypercalcitoninemic MTC patients demonstrate that secondary lymph node dissection is an inefficient technique for restoration of a normal calcitonin level.

A novel technique with a flexible applicator for MRI-based brachytherapy of cervical cancer.

PURPOSE: To introduce a novel technique for magnetic resonance (MR)-based 3-dimensional planned high-dose rate intracervical brachytherapy (BT). MATERIALS AND METHODS: During 2002, 16 patients received external beam radiotherapy and BT as part of radiochemotherapy for cervical cancer. A special adjustable applicator device was designed and used for BT. The isodose distribution was calculated from MR images with the applicator in place. RESULTS: The planning target volume coverage was adequate and the radiation burden on the organs at risk was within acceptable limits. Complete regression was achieved in two patients (12.5%), and partial regression in ten (62.5%) patients. The overall response rate for the complex treatment was 93.75%. In three cases the disease was considered to be stable. CONCLUSION: The MR-compatible, flexible applicator allows safe and reproducible cervical radiotherapy with no added discomfort or hazard for the patient.

Characteristics of radiogenic lower motor neurone disease, a possible link with a preceding viral infection.

OBJECTIVE: To investigate the pathogenesis of the rare radiogenic lower motor neurone disease (LMND) on the basis of a meta-analysis of the published case histories. MATERIALS AND METHODS: The authors reviewed 47 well-documented radiogenic LMND cases from the English literature. RESULTS: The disease typically occurs following the irradiation of radiosensitive cancers situated near the spinal cord. It arises predominantly (46 cases) in the lower extremities; only one case involved the upper extremities. There is a male predominance (male:female ratio 7.8:1), and the patients are characteristically young (13-40 years, with four exceptions). An overdose does not seem to be a particular risk factor for the development of the disease, as total dose, fraction size and biologically effective dose are typically below 50 Gy, 2 Gy and 128 Gy2, respectively, which are regarded as safe doses. Other risk factors (chemotherapy, operations, etc) have been identified only rarely. Radiogenic LMND is manifested in an apparently random manner, 4-312 (mean 48.7) months after the completion of radiotherapy. DISCUSSION: The complete lack of a dose-effect relationship argues strongly against a pure radiogenic nature of the pathological process. The latency period is typically several years and it varies extremely, which excludes a direct and complete causal relationship between radiotherapy and LMND. As the interaction of ionizing radiation with living tissues is highly unspecific, thus a selective motor injury due to irradiation alone, without comparable effects on the sensory and vegetative fibers, seems improbable. CONCLUSIONS: On analogy with the viral motor neurone diseases, we suppose that radiogenic LMND may be preceded by viral (enterovirus/poliovirus) infection. Based on the meta-analysis, it is suggested that irradiation may be only a single component of the set of factors jointly resulting in the clinical state regarded as radiogenic LMND.

FDG PET imaging in hereditary thyroid cancer.

AIM: To report the role of different imaging methods in staging individuals with multiple endocrine neoplasia 2A (MEN2A) or familial medullary thyroid carcinoma (FMTC). MATERIAL AND METHODS: Fourteen newly diagnosed gene carriers underwent cervical ultrasound scanning (US), cervical and mediastinal CT, MRI and whole-body meta-[131I]iodobenzylguanidine (MIBG) scintigraphy and [18F]fluorodeoxyglucose (FDG) PET scanning. RESULTS: US identified seven true primary cancer. CT and MRI located only tumors > or =5 mm in diameter. MIBG scintigraphy and FDG PET could not identify MTC foci within the thyroid. Whole-body FDG PET identified two true-positive and one false-positive lymph node metastases. MIBG scintigraphy did not identify lymph node metastases. Total thyroidectomy was performed in 12 cases, and subtotal thyroidectomy in two subjects. CONCLUSIONS: Whole-body FDG PET and cervical US help stage individuals carrying mutant genes verifying MEN2A or FMTC.

Autopsy verifies demyelination and lack of vascular damage in partially reversible radiation myelopathy.

STUDY DESIGN: Case report of recovering radiation myelopathy. OBJECTIVE: To present autopsy and functional imaging findings on a unique case of slowly recovering radiation myelopathy with the aim of the clarification of the underlying mechanism. PATIENT: The cervical spinal cord and the distal part of the medulla oblongata of a 36-year-old thyroid cancer patient had been incorrectly irradiated with a total dose of 61 Gy and a fraction size of 3.4 Gy (J Neurol Sci 1999; 163:39-43), resulting in incomplete cervical transection with a 5-month latency period following the termination of radiotherapy. This was followed by a 9.5-year spontaneous improvement until her demise, during which the check-ups were supplemented by positron emission tomography (PET) investigations; these indicated increased [18F]deoxyglucose and [15O]butanol uptakes, but a diminished [11C]methionine accumulation by the irradiated spinal cord segment. RESULTS: Autopsy revealed demyelination (with axonal loss) and neuronal damage in the cervical spinal cord and the distal part of the medulla oblongata. In the same region, only minimal vascular injury (thickening of some of the capillary walls) was detected, but not cell proliferation or chronic inflammation. Bilateral, secondary pyramidal tract degeneration caudal to the irradiated segment was observed. The PET and autopsy findings, although separated by 2 years, are consistent. CONCLUSIONS: The pathological state of the spinal cord revealed by the autopsy is concordant with the incomplete cervical transection, implying that the functional recovery is supported by a process that probably differs from the restoration of the mechanism destroyed by the radiotherapy. For the restoration of the function, we suggest an altered conduction mechanism of the action potential, involving an increased number of sodium channels along the demyelinated segments of the injured axons, which is fully congruent with the PET findings.

A PET study on the characterization of partially reversible radiogenic lower motor neurone disease.

OBJECTIVE: To investigate the pathomechanism of the rare radiogenic lower motor neurone disease (LMND) on the basis of a case history involving a partial functional recovery. PATIENT: A 31-year-old seminoma patient received postoperative para-aortic and para-iliac telecobalt irradiation with a biologically effective dose of 88 Gy(2) (44 Gy in 2 Gy fractions/day, with an estimated alpha/beta of 2 Gy) delivered to the spinal cord following a single cycle of chemotherapy. LMND developed 4 months after the completion of radiotherapy. The patient exhibited flaccid paraparesis of the lower extremities (without sensory or vegetative signs), followed by a worsening after further chemotherapy, due to pulmonary metastatization. A gradual spontaneous functional improvement commenced and led several years later to a stabilized state involving moderately severe symptoms. METHODS: In the 15th year of the clinical course, magnetic resonance imaging (MRI) and positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) and [(11)C] methionine were conducted. Four lines of experiments (clonogenic assay using fibroblasts isolated from a skin biopsy sample of the patient, comet assay, micronucleus assay, and the testing of chromosome aberrations after in vitro irradiation of peripheral blood samples) were performed in a search for an increased individual radiosensitivity. RESULTS: MRI investigations failed to reveal any pathological change. PET demonstrated an increased FDG accumulation, but a negligible [(11)C] methionine uptake in the irradiated spinal cord segments. The radiobiological investigations did not indicate any sign of an increased individual radiosensitivity. CONCLUSIONS: We suggest that the observed partial functional recovery and stabilization of the symptoms of radiogenic LMND may be explained by the higher than normal density of sodium channels expressed along the demyelinated axons of the restored conduction. The increased energy demands of this type of conduction are proved by a higher metabolic rate (increased FDG uptake) of the irradiated spinal cord segments without a substantial regenerative process (lack of detectable protein synthesis).

Ovarian steroid cell tumor and a contralateral ovarian thecoma in a postmenopausal woman with severe hyperandrogenism.

A 49-year-old woman presented with rapidly progressing hirsutism, receding hairline, male-pattern baldness and deepening of voice, which had developed over the past 2 years. Hormonal evaluation showed a markedly elevated serum testosterone level (418 ng/dl) and no evidence of increased production of cortisol, dehydroepiandrosterone, dehydroepiadrosterone-sulfate, androstenedione, or 17-hydroxyprogesterone. Transvaginal ultrasound examination suggested the presence of a small mass within the left ovary, but all other radiological studies, including adrenal and ovarian computed tomography, magnetic resonance imaging, radio-labelled cholesterol scintigraphy and positron emission tomography, were negative. Subsequently, bilateral selective venous sampling showed a marked testosterone gradient in the right ovarian vein. Bilateral salpingo-oophorectomy was performed (the patient had had a previous vaginal hysterectomy), and histopathological examination revealed a 10-mm steroid cell tumor within the right ovary and a 15-mm thecal cell tumor within the left ovary. The postoperative serum testosterone level returned to normal and the patient showed a slow regression of clinical symptoms. The simultaneous occurrence of a virilizing ovarian steroid cell tumor and an apparently non-functioning thecoma within the contralateral ovary emphasizes the potential pitfalls that may exist in the preoperative evaluation of patients with markedly increased testosterone production.

Molecular genetic diagnostic program of multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma syndromes in Hungary.

Medullary thyroid carcinoma (MTC) occurs usually in sporadic form, but about a quarter of the cases are hereditary and appear as part of one of the multiple endocrine neoplasia type 2 (MEN2) syndromes. Mutations in the RET protooncogene are known to be the cause of the MEN2A and familial medullary thyroid carcinoma (FMTC) syndromes in the majority of the families. Direct DNA testing allows prophylactic thyroidectomy to be offered to individuals carrying a mutation in the above codons, and in mutation-negative cases it reduces the yearly screening-related burden on family members at risk of the disease. By DNA sequencing and PCR-restriction fragment length polymorphisms, 65 MTC probands were examined for mutations in residues 609, 611, 618, 620 of exon 10, and in residues 634, 768, 804 of exons 11, 13, and 14 respectively of the RET protooncogene. In our study, mutations in the above codons were detected in all of the 14 clinically MEN2A and FMTC families. One of these mutations, TGC609 TCC has not been reported previously. Of the 14 probands with the mutation, 25 relatives also had the identified mutation and 18 relatives proved to be non-carriers. Among the 51 probands with clinically sporadic MTC, none was found to carry a mutation in the above positions even if indirect signs of MTC, pheochromocytoma or hyperparathyroidism could be detected in some families. The frequency of the TGC634AGC mutation is unexpectedly high in our samples, which can probably be attributed to a founder effect. We conclude that screening for mutations in these codons is effective in families fulfilling the strict clinical criteria of MEN2A or FMTC.

Angiography effectively supports the diagnosis of hepatic metastases in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) belongs in the group of neuroendocrine tumors with early lymphatic and hepatic dissemination. A high rate of undetectable metastases is hypothesized to be responsible for the frequent mismatch between the apparent relatively small tumor burden and the elevated plasma tumor marker level. METHODS: Thirty-six MTC patients with residual/recurrent biochemical signs (elevated basal calcitonin level) and/or characteristic general symptoms (diarrhea and/or flushing) were systematically examined by conventional radiology, whole-body 18F-deoxyglucose positron emission tomography (PET), dynamic liver computed tomography and magnetic resonance imaging, and hepatic angiography. RESULTS: Conventional diagnostic imaging revealed lymph node (LN) involvement in the cervical, mediastinal, supraclavicular, and axillary regions (16 cases), and multiple pulmonary (3 cases), bony (1 solitary and 1 multiple case), and breast (1 case) metastases. (18)F-deoxyglucose PET identified all these extralymphatic metastatic lesions (except 2 cases with multiple pulmonary metastases), and also supradiaphragmatic LN involvement in 34 (94%) patients. In 32 (89%) cases, multiple small (generally < or = 1 cm) hypervascular, hepatic metastases undetectable by other imaging methods were localized angiographically. Of the 23 original pathologic specimens investigated, 18 (78%) exhibited LN involvement. The smallest primary tumor in patients with hepatic metastases was 1 cm. CONCLUSIONS: Hepatic angiography is recommended for primary staging in MTC patients with a primary tumor measuring 1 cm or larger, and/or pathologically proven LN involvement, and also during restaging for suspected recurrences to avoid unnecessary extensive surgical LN dissection in the neck and mediastinum.

Hypoglycemia activates compensatory mechanism of glucose metabolism of brain.

The effect of plasma glucose concentration on the cerebral uptake of [18F]-fluorodeoxy-D-glucose (FDG) was studied in a broad concentration range in a rabbit brain model using dynamic FDG PET measurements. Hypoglycemic and hyperglycemic conditions were maintained by manipulating plasma glucose applying i.v. glucose or insulin load. FDG utilization (K) and cerebral glucose metabolic rate (CGMR) were evaluated in a plasma glucose concentration range between 0.5 mM and 26 mM from the kinetic constant k1, k2, k3 obtained by the Sokoloff model of FDG accumulation. A decreasing set of standard FDG uptake values found with increasing blood glucose concentration was explained by competition between the plasma glucose and the radiopharmacon FDG. A similar trend was observed for the forward kinetic constants k1, and k3 in the entire concentration range studied. The same decreasing tendency of k2 was of a smaller magnitude and was reverted at the lowest glucose concentrations where a pronounced decrease of this backward transport rate constant was detected. Our kinetic data indicate a modulation of the kinetics of carbohydrate metabolism by the blood glucose concentration and report on a special mechanism compensating for the low glucose supply under conditions of extremely low blood glucose level.

Second malignancies after treatment for Hodgkin's disease.

The occurrence of treatment-related second malignancy following Hodgkin's disease (HD) has now been recognized as a major problem. The purpose of this study was to review our experience with second malignancies in patients treated for Hodgkin's disease, comparing the results with the international literature data. Six hundred and sixty five patients with HD were treated in our department, between 1978 and 1996. Second neoplasm developed in 32 cases (4.8%). Seven secondary hematological malignancies were observed: four acute nonlymphocytic leukemias, two non-Hodgkin's lymphomas and one chronic myeloid leukemia. Among patients with second hematological malignancies, the mean age at diagnosis of HD was 44 years and the mean interval until the development of second malignancy was 6.1 years. Five patients received chemo- and radiotherapy and in two cases chemotherapy was used. Three of the seven patients are alive. Twenty-five patients have had solid tumors, affecting lung (5), breast (3), colon (3), stomach (2), urinary bladder (2), head-and-neck (1), thyroid gland (1), esophagus (1), liver (1), pancreas (1), furthermore, three sarcomas and two malignant melanomas were observed. Their mean age at the diagnosis of HD was 46 years and the mean period of latency was 8.3 years. Chemotherapy was applied to nine patients, 16 patients received both chemo- and radiotherapy. Eleven patients had solid tumors in the region irradiated earlier. Ten out of the 25 patients are alive, three patients' present state is unknown. Since alkylating agents increase the risk of leukemia and irradiation contributes mainly to other malignancies, future treatment protocols should attempt to reduce the most serious consequence of therapy without compromising the survival. It is necessary to investigate the impact of additional risk factors. Careful, lifelong observation is indicated for patients with HD, with special attention given to new clinical signs and symptoms.

[PET scanning in head and neck cancer] / Pozitronemissziós tomográfia a fej-nyaki tumorok diagnosztikájában.

INTRODUCTION: FDG (fluorine-labeled deoxy-glucose) and 11C-methionine positron emission tomography was evaluated in the diagnostics of head and neck cancer. PET scans were applied for identifying/staging relapse after oncotherapy or searching unknown primary tumor with metastatic lymph nodes of the neck. METHODS: Retrospective analysis of 22 patients examined by 17 (18)FDG and 15 (11)C-methionine PET scan. In 9 cases indication was unknown primary tumor with positive neck, in 13 cases previously treated head and neck cancer patients were examined for recurrence/restaging. RESULTS: In searching for unknown primary tumor not detectable with conventional methods, PET was effective in 22%, however, false positivity and uncertain results were found as well. In restaging PET proved to be very effective (85%) to discover recurrences and to differentiate them from post-treatment (mainly irradiation) effects. In two cases silent distant metastase were detected. CONCLUSION: PET can provide valuable information about unknown primary tumors, recurrences after oncotherapy and distant metastases as well. Simultaneous use of FDG/methionine scans does not improve the results.

[Current diagnostic method, prognosis estimation and therapy of papillary thyroid cancer: recommendations of the medical universities and the National Oncologic Institute of Budapest]. / A papillaris pajzsmirigy-carcinoma korszerü kivizsgálása, prognózisbecslése és kezelése: az orvostudományi egyetemek és az Országos Onkológiai Intézet ajánlása.

Physical examination, cervical ultrasonography (US) and aspiration cytology are the mainstays of the preoperative diagnostics of papillary thyroid carcinoma. For the staging of suspected malignant cases, cervical and mediastinal CT (MRI for inconclusive results) is indicated before any surgery. The end-result of primary treatment is assessed by total-body iodine scintigraphy and the serum human thyroglobulin (hTG) level. For long-term follow-up, physical examination and the serum hTG level are the most reliable tools (6-monthly), supplemented by cervical US and chest X-ray (yearly), and total-body iodine scintigraphy (2-yearly). If these furnish positive results, further examinations may be indicated. In suspected relapses of hTG non-producing and iodine non-accumulating papillary carcinomas, 201thallium chloride or 99mTc-sesta-MIBI (methoxy-isobutyl-isonitrile) scintigraphy, and positron emission tomography with 18fluoro-deoxyglucose or 11C-methionine may be of help. For estimation of the prognosis (cause-specific survival) of the patients, the MACIS score system of the Mayo Clinic is widely accepted, the patients being divided into low-risk and intermediate/high-risk categories. The recommended standard surgical intervention is near-total thyroidectomy (2-4 g residual glandular tissue left at the upper pole of the less-involved lobe), with a central cervical lymph node dissection for diagnostic purposes. In cases of lymph node dissemination, dissection (radical, modified radical, selective or microdissection) of any of the involved compartments (central, right or left cervical, or upper mediastinal) is indicated for therapeutic reasons, the method of which is depending on the extent of the metastatic involvement. Following adequate surgical intervention, no adjuvant radioiodine therapy is indicated for low-risk cases with a tumour of less than 1 cm diameter. For other low-risk or intermediate/high-risk patients, radioiodine ablation (R0N0M0) or a therapeutic radioiodine dosage (R2N1M1) is indicated. In cases at high-risk of local/regional relapse and in radioiodine non-accumulating tumorous cases, external radiotherapy may be applied. Thyroid hormone medication in a TSH suppressive dose is indicated during the first 5 postsurgical years: the goal is to achieve a TSH level below 0.1 (determined by a 3rd generation assay). If no relapse occurs or the case is a low-risk one, following the 5 years, it is enough to maintain the TSH level in a subnormal range (0.1-0.3).

A case of bilateral testicular lymphoma.

Authors report on a 75-year-old man with bilateral testicular lymphoma. He complained of painless right testicular enlargement. Orchidectomy was indicated by ultrasound examination and the diagnosis (large cell, non-Hodgkin lymphoma B-cell origin) was established by histology and immunohistochemistry. Two months later, the left testis enlarged, orchidectomy was performed, and a lymphoma with identical histology was found. PET revealed retroperitoneal spread of the tumor. Irradiation (18 Gy) was applied. Three months later, because of gastric metastases of the lymphoma the patient underwent CVP and CAVP (Cyclophosphamide, Adriablastin, Vincristin, Prednisolone) chemotherapy. Despite of the repeated courses, eleven months after the primary diagnosis the patient died due to of multiple metastases.

External audit on the clinical practice and medical decision-making at the departments of radiotherapy in Budapest and Vienna.

PURPOSE: To present an example of how to study and analyze the clinical practice and the quality of medical decision-making under daily routine working conditions in a radiotherapy department, with the aims of detecting deficiencies and improving the quality of patient care. METHODS: Two departments, each with a divisional organization structure and an established internal audit system, the University Clinic of Radiotherapy and Radiobiology in Vienna (Austria), and the Department of Radiotherapy at the National Institute of Oncology in Budapest (Hungary), conducted common external audits. The descriptive parameters of the external audit provided information on the auditing (auditor and serial number of the audit), the cohorts (diagnosis, referring institution, serial number and intention of radiotherapy) and the staff responsible for the treatment (division and physician). During the ongoing external audits, the qualifying parameters were (1) the sound foundation of the indication of radiotherapy, (2) conformity to the institution protocol (3), the adequacy of the choice of radiation equipment, (4) the appropriateness of the treatment plan, and the correspondence of the latter with (5) the simulation and (6) verification films. Various degrees of deviation from the treatment principles were defined and scored on the basis of the concept of Horiot et al. (Horiot JC, Schueren van der E. Johansson KA, Bernier J, Bartelink H. The program of quality assurance of the EORTC radiotherapy group. A historical overview. Radiother. Oncol. 1993,29:81-84), with some modifications. The action was regarded as adequate (score 1) in the event of no deviation or only a small deviation with presumably no alteration of the desired end-result of the treatment. A deviation adversely influencing the result of the therapy was considered a major deviation (score 3). Cases involving a minor deviation (score 2) were those only slightly affecting the therapeutic end-results, with effects between those of cases with scores 1 and 3. Non-performance of the necessary radiotherapeutic procedures was penalized by the highest score of 4. Statistical evaluation was performed with the BMDP software package, using variance analysis. RESULTS: Bimonthly audits (six with a duration of 4-6 h in each institution) were carried out by three auditors from the evaluating departments; they reviewed a total of 452 cases in Department A, and 265 cases in Department B. Despite the comparable staffing and instrumental conditions, a markedly higher number (1.5 times) of new cases were treated in Department A, but with a lower quality of radiotherapy, as adequate values of qualifying parameters (1-6) were more frequent for the cases treated in Department B (85.3%, 94%, 83.4%, 28.3%, 41.9% and 81.1%) than for those in Department A (67%, 83.4%, 87.8%, 26.1%, 33.2% and 17.7%). The responsible division (including staff and instrumentation), the responsible physician and the type of the disease each exerted a highly significant effect on the quality level of the treatment. Statistical analysis revealed a positive influence of the curative (relative to the palliative/symptomatic) intention of the treatment on the level of quality, but the effect of the first radiotherapy (relative to the second or further one) was statistically significant in only one department. At the same time, the quality parameters did not vary with the referring institution, the auditing person or the serial number of the audit. CONCLUSION: The external audit relating to the provision of radiotherapeutic care proved feasible with the basic conformity and compliance of the staff and resulted in valuable information to take correction measures.

Radiation myelopathy with partial functional recovery: PET evidence of long-term increased metabolic activity of the spinal cord.

Postoperative telecobalt irradiation was performed with a biologically effective extrapolated response dose of 165 Gy2 delivered to the spinal cord of a papillary thyroid cancer patient. Incomplete cervical transection developed, followed by a gradual functional improvement, which is still continuing 8 years after radiotherapy. Between the 6th and 8th years of the clinical course, positron emission tomography investigations demonstrated an increased 18F-deoxyglucose accumulation and (15)O-butanol perfusion, but negligible 11C-methionine uptake in the irradiated spinal cord segment. We suggest that the increased metabolism and perfusion, and the lack of detectable protein synthesis may be related to the increased energy demands of action potential conduction, due to the higher than normal density of sodium channels along demyelinated axons displaying restored conduction.

[Evaluation of the effectiveness of radiotherapy in an Austrian-Hungarian collaboration]. / A sugárterápiás tevékenység eredményességének külsö minöségi felülvizsgálata osztrák-magyar együttmüködésben.

To present an example of how to study and analyse the clinical practice and the quality of medical decision-making under daily routine working conditions in a radiotherapy department, with the aims of detecting deficiencies and improving the quality of patient care. Bimonthly audits (6 with a duration of 4-6 hours in each institution) were carried out by 3 auditors from the evaluating departments; they reviewed a total of 452 cases in Department A, and 265 cases in Department B. During the ongoing external audits, the qualifying parameters were (1) the sound foundation of the indication of radiotherapy, (2) the conformity to the institution protocol (3), the adequacy of the choice of radiation equipment, (4) the appropriateness of the treatment plan, and the correspondence of the latter with (5) the simulation and (6) verification films. Various degrees of deviation from the treatment principles were defined and scored on the basis of the concept of Horiot et al. (10), with some modifications. The action was regarded as adequate (score 1) in the event of no deviation or only a small deviation with presumably no alteration of the desired end-result of the treatment. A deviation adversely influencing the result of the therapy was considered a major deviation (score 3). Cases involving a minor deviation (score 2) were those only slightly affecting the therapeutic end-results, with effects between those of cases with scores 1 and 3. Non-performance of the necessary radiotherapeutic procedures was penalized by the highest score of 4. Statistical evaluation was performed with the BMDP software package, using variance analysis. Despite the comparable staffing and instrumental conditions, a markedly higher number (1.5 times) of new cases were treated in Department A, but with a lower quality of radiotherapy, as adequate values of qualifying parameters (1)-(6) were more frequent for the cases treated in Department B (85, 94%, 83%, 28%, 42% and 81%) than for those in Department A (67%, 83%, 88%, 26%, 33% and 18%). The responsible division (including staff and instrumentation), the responsible physician and the type of the disease each exerted a highly significant effect on the quality level of the treatment. Statistical analysis revealed a positive influence of the curative (relative to the palliative/symptomatic) intention of the treatment on the level of quality, but the effect of the first radiotherapy (relative to the second or further one) was statistically significant in only one department. The external audit related to the provision of radiotherapeutic care proved feasible with real valuation of the staff's activity.