Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary.

We have investigated the impact of BRCA1 and BRCA2 mutations that were frequently identified among Hungarian high-risk breast-ovarian cancer families (Ramus et al., 1997b, AJHG), on the development of breast and ovarian cancer in the general Hungarian population. The prevalence of 3 BRCA1 mutations (185delAG, 300T-->G and 5382insC) and 2 BRCA2 mutations (6174delT and 9326insA) was evaluated in a hospital-based consecutive series of 500 female breast cancer patients and 90 ovarian cancer patients, not selected for age at diagnosis or family history of cancer, as well as in 350 controls. Among breast cancer patients, 3.6% (18/500) carried a founder mutation: 9 BRCA1 300T-->G, 7 BRCA1 5382insC, 1 BRCA1 185delAG and 1 BRCA2 9326insA. Among ovarian cancer patients, 11% (10/90) carried a founder mutation: 5 BRCA1 185delAG, 4 BRCA1 300T-->G and 1 BRCA1 5382insC. One control carried a mutation, BRCA1 5382insC. Inherited breast cancer was more frequent among women with younger age at diagnosis: 6.1% of women younger than age 50 but 2.4% of women diagnosed at age 50 or older carried one of the founder mutations. There was no association between mutation status and age at diagnosis of ovarian cancer. Three of 23 medullary breast cancers were inherited (p = 0.038). Carrier status was also associated with a non-significant trend toward advanced tumor stage at diagnosis. These mutations could be evaluated among all ovarian cancer patients and breast cancer patients younger than age 60 and of Hungarian ancestry.

[Morphological parameters of breast cancers detected by mammography with and without organized screening; a comparative study]. / Mammográfiával felismert rákok morphologiai paramétereinek összehasonlítása a területileg szervezett szürés során és alkalomszerüen vizsgáltaknál.

Some pathological findings and prognostic indices recorded in breast cancer cases, detected, on one hand, by a provider-initiated mammography screening program (Group 1), and, opportunistically, in self-referred symptomatic women (Group 2) on the other, are compared. In 8877 symptom-free women, aged 50-65 years, individually invited to attend the screening offered for the residents of the III., XII. and XIII. districts of Budapest, 67 cancer cases were detected (7.5 in 1000 screenees), in accordance with the cancer detection rate of the first, "prevalence" round of organised screening programmes. In the other group of 1593 symptomatic, self-referred women of the same age, 113 cancer cases were diagnosed by mammography. As far as the pathological parameters are concerned, the number of cases with invasive cancer less than 15 mm in diameter, and those with axillary nodes present was found to be significantly higher in the screened group as compared to the self-referred one (p < 0.01). In "small" cancers (i.e. less than 15 mm in diameter), no significant difference was found in the proportion of histologic grade III tumours among the two groups. In screen-detected cancers both the morphometric prognostic index (as calculated by Baak et al.) and the Nottingham Prognostic Index (NPI) proved to be more favourable, as compared to those in the self-referred group. The p-value as determined by Mann-Whithey test was 0.000003 in the screened group, and 0.000015 in the other one. These findings provide convincing evidence in support of the public health importance of provider-initiated, organised mammography screening for breast cancer, therefore, the introduction on service basis of organised breast screening into the health care system in Hungary is strongly recommended by the authors.

[The observation of edema in the substantia alba during postoperative brain irradiation. The role of computed tomographic studies]. / Beobachtung von Odemen in der weissen Substanz während postopertiver Hirnbestrahlung. Die Rolle computertomographischer Untersuchungen.

BACKGROUND: The aim of our study was to determine on CT whether a relation exists between a radiation-induced brain edema, treated with diuretics and its corresponding Houndsfield Units (HU). PATIENTS AND METHODS: Seventy-five patients (age 20 to 65 years, suffering from headaches but without hypertension brain tumors or cerebral arteriosclerosis were examined as a reference group. Three slices with 8 mm thickness, 24 mm apart in the upper, middle and lower third of the brain were obtained to measure the HU of the white matter. The second group consisted of 20 patients with brain tumors, which underwent brain surgery. HU of the white matter were measured before radiation and after 10, 20, 30, 40 and 50 Gy. If a reduction in density was detected, diuretic therapy with 40 mg furosemide per o.s. was initiated. If no increase in density was found on follow-up additional therapy with glycerine (4.5 g/kg body weight) was started. In this cases follow-up was on day 4 after initiation of diuretics. If clinical symptoms suggested an increasing in intracranial pressure, CT-examination was performed immediately. Therapy was started according to measurement results. The third group consisted of 64 patients with brain tumors, that underwent postsurgical radiation therapy. Prior to radiation therapy 40 mg furosemide per o.s. were given. CT-examinations, intensified diuretic therapy and follow-up examinations were performed as in group 2. If, despite therapy, the HU decreased, infusion of mannites was added. The second and third group of patients received radiation therapy with telecobalt and/or a linear accelerator (6 and 9 MeV X-ray). RESULTS: In the first group white matter density was > 30 HU. In the second group white matter density was between 25 and 29 HU prior to diuretic therapy. Under 25 HU a continuous headache, vertigo and confusion ensued. Diuretic therapy was intensified until the measured values reached 25 to 29 HU. Forty-seven of 64 patients in the third group had 25 to 29 HU prior to radiation therapy. Despite prophylactic diuretic therapy in 28 cases density decreased to 20 to 24 HU. Improvement was achieved with an additional glycerine per o.s. The measured values reached again 25 to 29 HU. In 1 case the values dropped under 20 HU. Additional mannite infusion was necessary. In 17 of 64 patients white matter density was > 30 HU prior to radiation therapy, dropping to 25 to 29 HU during radiation. Prophylactic diuretic administration kept the values in this range. A correlation between age of the patient, radiation source, total dose, tumor histology and degree of change in HU was not found. CONCLUSION: Measurements of HU can serve as a good indicator for spontaneous or diuretic induced changes of a white matter edema during radiation therapy.

[Volume changes to the neck lymph node metastases in head-neck tumors. The evaluation of radiotherapeutic treatment success]. / Volumenveränderung der Halslymphknotenmetastasen bei Kopf-Hals-Tumoren. Bewertung des strahlentherapeutischen Behandlungserfolges.

AIM: This work is engaged with the volume change of neck lymph node metastasis of malignant tumors in the head-neck region during radiotherapy. PATIENTS AND METHOD: In 54 patients with head and neck tumors, the volume of neck lymph nodes before and after radiation was measured. The volumetry was done with CT planimetry. The total dose was 66 Gy (2 Gy/d) telecobalt from 2 lateral opponated fields. The time of volume change could be defined with measuring of the half-time and the doubling-time by the help of Schwartz formula. RESULTS: After 10 Gy the volume diminution was about 20% and half-time 24 to 26 days. Afterwards the time of volume diminution picked up speed and finally achieved 60 to 72%. Meanwhile the half-time decreased to the half value. The result was independent of the site of primary tumor, the patient's sex and age. CONCLUSION: In our opinion the effectivity of radiotherapy can best be judged with defining of the volume change of lymph nodes of the neck.

[Cancer screening in Hungary: World Bank supported model programs]. / Rákszúrés magyarországon: modellprogramok világbanki támogatással.

Since 1995, a model cancer screening program has been in operation in Hungary, the overall purpose of which is to promote the establishment of effective and efficient screening programs by means of adapting the internationally agreed principles of organized screening to the needs and opportunities in Hungary. The establishment and operation of a national population-based cancer registration system is an other aim of the Program. The model program--financed partly from a loan from the World Bank, partly from local funds provided by the Government of Hungary--is to develop standard procedure for cervical, breast and colorectal screening and to end up with tested recommendations for introduction of organized screening of proved effectiveness, integrated into the health care system, on country-wide service bases in Hungary.

[The current evaluation of radiotherapy treatment results]. / Die aktuelle Bewertung strahlentherapeutischer Behandlungsergebnisse.

PURPOSE: Efficacy of treatment is expressed in terms of postradiotherapeutic tumor volume decrease and halving time indicating regression rate. Tumors of the same histology and TNM stage were compared after different treatments. Prior to this comparative study tumor volume changes and halving time were tested for judging the efficacy of chemotherapeutic treatment of 765 patients with lung metastasis. PATIENTS AND METHODS: Tumor volume was determined by CT planimetry before and after radiotherapy in 56 tumor patients (42 lung tumors, 14 thyroid tumors). The rate of regression, i.e., the halving time was calculated on the basis of exponential curve. Fourteen thyroid tumor patients given telecobalt and photon irradiation for post-operative recurrence formed a separate group of patients. Halving time was determined at 30-day intervals, the values were qualified as "fast", "moderately fast", "moderately slow" and "slow". RESULTS: Partial remission rate of patients treated by telecobalt irradiation was not higher than 60%, accompanied by fast halving time. With those receiving photon irradiation, however, partial remission reached even 70%, also with a fast halving time. In both groups minimal remission was associated with moderately fast halving time. The partial remission of recurring thyroid tumor patients receiving telecobalt irradiation was partly fast, partly moderately fast. Their minimal remission data developed with a moderately fast halving time, although chemotherapy subsequent to radiotherapy did not result in regression. CONCLUSION: Appraisal of radiotherapeutic efficacy is based on the simultaneous monitoring of decrease in tumor volume (%) and halving time. It is to be stressed that neither the planimetric volume determination nor the halving time data can be taken as absolute values, since they are subject to other factors. In authors opinion, the most effective methods of the following of the tumor regression is the planimetric volume measurement calculated by CT, in the clinical praxis in recent time.

Cisplatin containing combination chemotherapy of advanced germ cell line testicular tumours.

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.

[Value of computer tomography in the diagnosis of lung hamartomas]. / A computer tomographia jelentösége a tüdö hamartomák diagnosztikájában.

Detailed radiological examinations were undertaken in six cases of hamartochondromas verified by histopathology on surgical samples. It has been shown that examination of lung hamartochondromas by computer tomography provides a good approach for separation of different tissues constructing hamartochondromas. Thus cartilage, lose and dense and mixed forms of connective tissue, and adipose tissue can be well separated. The growth rate of hamartochondromas is very slow, characterized by doubling times of several hundred to several thousand hours.

Examination and evaluation of surgical margins in bone tumours. Comparative pre- and postoperative CT and MR imaging.

An objective method of evaluating surgical margins and the extent of limb-preserving surgery is described in a study of 10 malignant bone tumours. The resected specimen was imaged by computerised tomography and magnetic resonance, and the appearances compared with the preoperative images of the tumour. CT was better than MR for detecting bony changes, but MR was more satisfactory for showing the extraosseous and intramedullary outline of the tumour. These two methods should therefore be combined. Intralesional excision is an absolute indication; marginal excision a relative indication for reoperation.

Calcitonin therapy of aneurysmal bone cysts.

Seven aneurysmal bone cysts (ABC) were treated with the hormone calcitonin. Six of the cysts, which were hypovascular responded well to the calcitonin administered directly into the cyst. Ossification and rebuilding of the ABC occurred after some months in every case. One hypervascularized ABC, however, failed to respond either to embolo-therapy or to the calcitonin hormone treatment. The authors recommend calcitonin administration as a useful non-invasive method for the treatment of hypovascular ABC.

Response to Coss-86 neoadjuvant therapy assessed by computed tomography and histology.

Authors state that in osteosarcoma the measure of mineralization of the tumorous osteoid can be precisely assessed with CT. Hounsfield Units (H.U.) values < 300 demonstrate tumorous osteoids not yet mineralized. Over this limit, however, there is a linear correlation between H.U. values and the extent of mineralization. Since CT detects only tumorous osteoids and demonstrates its measure of mineralization, it does not provide information about the tumour cell components. Consequently, it is not a suitable tool for the assessment of tumour response to neoadjuvant chemotherapy. CT has, however, some advantages over conventional radiographic estimation of tumour extent and detection of tumorous osteoid before mineralization. Because of this diagnostic power, CT is indispensable in limb salving surgeries when the level of amputation is to be determined.

Follicular cancer of the thyroid gland.

Between 1965 and 1987 the authors studied the survival of 169 patients (130 females, 39 males) suffering from follicular thyroid cancer. It is established that the factors favorably influencing the course of the disease are as follows: age below 40 years, female sex, tumor location inside the thyroid capsule. Radical surgery does not affect the survival, though it prolongs the time to the onset of metastases. In women below 40 years of age, iodine treatment performed within 1.5 months following surgery does not increase the effectiveness; therefore, its routine application is not recommended. In case of local metastases associated with hindered swallowing or respiration, external beam radiotherapy is indicated. Hormone substitution ensuring TSH restriction results in improved prognosis.

[Surgical treatment of pulmonary metastases of colorectal tumors]. / A colo-rectális daganatok pulmonális áttéteinek sebészi kezelése.

In 22 cases of the 510 patients underwent surgery and followed up because of colorectal cancer, only pulmonary metastases were found. General problems in the surgery of pulmonary metastases are discussed and the possibilities and the expected results of the surgical therapy of pulmonary metastases in colorectal patients are analysed in details on the base of the data of their 8 patients underwent surgery and according to the literature. In carefully selected cases the surgical therapy of the metastases can be recommended.

Vinblastine, cisplatin and bleomycin treatment of advanced nonseminomatous testicular tumors.

Between December 1979 and July 1986, 190 patients with nonseminomatous germ-cell testicular tumors were treated according to the modified Einhorn scheme. The response rate was 67.89%. The most favorable results were found in the embryonal histologic type (RR = 76.9%), in the biological marker (AFP, HCG) negative (RR = 97.43%) and in the minimal pulmonary extent group (RR = 94.12%).

"Second-look" operations in patients with colorectal tumour.

The diagnostic problems of metastases and recurrences in colorectal tumour patients are reviewed. The question and indications of relaparotomies are discussed in detail. The results of relaparotomies made for tumorous and nontumorous indications at the Department of Surgery of the National Cancer Institute are reported.

Pulmonary metastasis of colorectal tumours.

A total of 21 metastases manifesting only in the lungs were observed during the follow-up of 510 colorectal tumour patients. The general aspects of the surgical solution of pulmonary metastases are reviewed and, based on the data of the patients operated by the authors and that of the literature, the possibilities and expected results of the surgical treatment of pulmonary metastases of colorectal tumours patients are discussed in detail. The surgical solution of metastases is suggested in carefully selected cases.

[Esophago-bronchial fistula originating in an esophageal diverticulum]. / Nyelöcsö diverticulumból kiinduló oesophago-bronchialis sipoly.

In connection with an esophageal diverticulum the case of an infrequent acquired esophago-bronchial fistula appearing in symptom-poor form is described. The fistula persisted over a long period however owing to the poor symptoms and absence of pulmonary complications operation was left out of consideration. In the course of the regular control the complaints of the patient ceased and the endoscopy showed shrinking of the fistula. No similar observation was found in the Hungarian literature.

[CT examination of diverticular sigmoiditis]. / A sigmoiditis diverticularis CT-vizsgálata.

The authors deal with the incidence of sigmoid diverticulosis in Hungary. The pathomorphological types of the inflammatory complications (pericolic inflammation, abscess, abscess-phlegmon, chronic phlegmonic diverticulitis) are discussed in details. It is pointed out that besides the examinations available so far (irrigoscopy, colonoscopy), the clinical picture decided the question of whether or not the inflammatory complication required surgical treatment. CT examination offers a new possibility as well as an examination free of complication which furnishes more exact information as compared to every method used so far to the determination of the inflammation and thus to the decision of using surgical or conservative therapy.

Diagnostic value of infrared thermography in breast cancer, and in proliferative and non proliferative mastopathies.

The authors present the results of breast examinations in 201 female patients controlled by cytology and histology. Based on their results obtained by an AGA 680 type infrared thermography, their conclusion was that the method is primarily suitable for the examination of biological thermogenesis, one of the functional characteristics of tumours. Some T1 breast cancer of the same histological type are thermographically "silent", i.e. display no pathological alterations. Thermographical signs characteristic of carcinomas are to be found only in 60-70% of the cases. It is explained by the biological heterogeneity of tumours, i.e. the amount of heat generated by the metabolic processes of the different carcinomas is not equal, as well as they are different in vascularization and as a consequence of it in their heat conduction parameters. Similar reasons explain the appearance of different thermographic patterns--negative or characteristic of cancerous alterations--in proliferative mastopathies.

[Tuberculosis of the female breast]. / Die Tuberkulose der weiblichen Brustdrüse.

The authors briefly summarize the most important characteristics of the female breast tuberculosis. They base their data on 7 histologically verified cases as well as on 2 other cases which, in view of the course of disease, were suspected to be breast tuberculosis. The various courses of disease as well as the difficulties in its differential diagnostic are described.