Survival chance in papillary thyroid cancer in Hungary: individual survival probability estimation using the Markov method.

PURPOSE: The typically benign, but occasionally rapidly fatal clinical course of papillary thyroid cancer has raised the need for individual survival probability estimation, to tailor the treatment strategy exclusively to a given patient. MATERIALS AND METHODS: A retrospective study was performed on 400 papillary thyroid cancer patients with a median follow-up time of 7.1 years to establish a clinical database for uni- and multivariate analysis of the prognostic factors related to survival (Kaplan-Meier product limit method and Cox regression). For a more precise prognosis estimation, the effect of the most important clinical events were then investigated on the basis of a Markov renewal model. The basic concept of this approach is that each patient has an individual disease course which (besides the initial clinical categories) is affected by special events, e.g. internal covariates (local/regional/distant relapses). On the supposition that these events and the cause-specific death are influenced by the same biological processes, the parameters of transient survival probability characterizing the speed of the course of the disease for each clinical event and their sequence were determined. The individual survival curves for each patient were calculated by using these parameters and the independent significant clinical variables selected from multivariate studies, summation of which resulted in a mean cause-specific survival function valid for the entire group. On the basis of this Markov model, prediction of the cause-specific survival probability is possible for extrastudy cases, if it is supposed that the clinical events occur within new patients in the same manner and with the similar probability as within the study population. RESULTS: The patient's age, a distant metastasis at presentation, the extent of the surgical intervention, the primary tumor size and extent (pT), the external irradiation dosage and the degree of TSH suppression proved to be statistically significant and independent prognostic factors with regard to cause-specific survival in multivariate studies. During follow-up, 14, 14, 9 and 12% of the patients underwent local/regional/distant relapses or thyroid cancer-related death, respectively. Through use of the above six independent clinical variables and the parameters relating to the four clinical events and their interrelations, mean cause-specific survival probabilities of 88, 83 and 78% were determined at 10, 20 and 30 years, respectively. The survival-predicting software (PATHYPRE) written on the basis of the biostatistical model is available through Internet connections on the home page of the National Institute of Oncology, Budapest (www.oncol.hu). CONCLUSION: Prediction of the individual survival probability for extrastudy cases affords a rationale for individualization of the treatment of papillary thyroid cancer patients.

[Survival potentials of patients with papillary carcinoma of the thyroid gland in Hungary]. / A papillaris pajzsmirigyrákos betegek túlélési esélyei Magyarországon.

The typically benign, but occasionally rapid fatal clinical course of papillary thyroid cancer has raised the need for individual survival probability estimation, to tailor the treatment strategy exclusively to the given patient. A retrospective study was performed on 400 papillary thyroid cancer patients, with a mean follow-up time of 10.3 years, to establish a clinical database for uni- and multivariate analysis of the survival probability-related prognostic factors (Kaplan-Meier product limit method and Cox regression). For a more precise prognosis estimation, in the next step the most important clinical events were investigated and survival functions for each patient were calculated on the basis of a Markov renewal model. The basic concept of this approach is as follows: each patient has an individual disease course, which (besides the initial clinical categories) is affected by special events, e.g. internal covariates (local/regional/distant relapses), that a patient experiences throughout the course of the disease. On the supposition that these events and the cause-specific death are influenced by the same biological process, the parameters of transient survival probability characterizing the speed of the course of the disease for each sequence of clinical events were determined. The individual survival curves for each patients were calculated by using the former parameters and the independent, significant clinical variables, summation of which resulted in an overall cause-specific survival function valid for the entire group. The patient's age, a distant metastasis at presentation, the extent of the surgical intervention, the primary tumour size, the dosage of the external irradiation and the degree of the TSH suppression proved to be statistically significant (in that sequence) and independent prognostic factors as concerns cause-specific survival in multivariate studies. During follow-up 14%, 14%, 9% and 12% of the patients underwent local/regional/distant relapses and thyroid cancer-related death. Through use of the above six independent clinical variables and the parameters relating to the interrelations of the four clinical events, mean cause-specific survival probabilities of 88%, 83% and 78% were determined at 10, 20 and 30 years, respectively. The 30-year individual survival probability prediction for these study cases showed that no cancer-related death occurred > or = 92% (low-risk group), while the tumour-related deaths were considerable (31%) < or = 78% (high-risk group), and there were only 6% deaths in the intermediate-risk group. The constructed survival function permits a prediction of the individual survival probability of extra-study cases under the given treatment conditions and within the given population, and thus affords a rationale for individualization of the treatment of papillary thyroid cancer patients.

[Hormonal and biochemical characterization of breast cyst fluid in gross cystic mastopathy]. / A nagycisztás mastopathia cisztafolyadékának hormonális és biokémiai jellemzése.

A total of 93 breast cyst fluids (BCF) obtained by needle aspiration of women suffering from gross cystic mastopathy was hormonally investigated. The mean age of the patients was 45 years (range 27-65). Estradiol (E2), progesterone (PROG), testosterone (TE), prolactin (PROL), estriol (E3), dehydroisoandrosterone and its sulfate (DHA, DHA-S) levels were investigated in the BCF and in the respective sera. Tumour marker beta-HCG and CA 15-3 as well as cations (K+, Na+) were determined, too. E2, E3, PROG, TE, PROL, DHA, DHA-S and K+ showed significant accumulation in the BCF compared to the serum values. The K+/Na+ ratio proved to be a useful tool to divide cysts into type I (> or = 1), type II (< 1 but > or = 0.1) and type III (< 0.1) subgroups. In case of type I BCF, higher E2, DHA, DHA-S and PROL levels could be detected, while PROG and TE contents proved to be the highest in type II cysts. These findings indicate that the type I BCF is a marker for "active" GCD of the breast and suggest that it may be associated with increased breast cancer risk. It is suggested therefore when macrocysts are aspirated, sex steroids, steroid hormone precursors and cations in the BCF should be examined routinely, and women with type I cysts should be controlled carefully.

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.

[Follow up of thyroglobulin levels in patients with surgically treated, highly differentiated thyroid cancer]. / Magasan differenciált pajzsmirigyrák miatt mütött betegek követése thyreoglobulin szint meghatározással.

The highly differentiated thyroid tumours account for 0.80 percent of all human malignancies. The papillary and follicular tumour tissues of this tumour type are relatively benign, hormone dependent and beside their treatment specificity they secrete the tumour specific thyreoglobulin. Thus it becomes possible to follow the development of metastases, the effectiveness of therapy applied as well as the history of the disease. The authors studied the change of thyreoglobulin level in 153 patients with highly differentiated thyroid cancer. In 29 of 32 metastatic patients pathologically elevated (70 to 100 ng/ml) thyreoglobulin level was observed. This proves the 91 percent specificity of the method in verified metastatic tumours. Compared to the total body scintigraphy 3 false negative cases were found. The authors establish that, irrespective of the site of metastasis, the thyreoglobulin level is higher in the follicular than in the papillary subtype. It is concluded that the measurement of the serum thyreoglobulin level is a suitable marker of the highly differentiated thyroid cancer since it represents the local recurrence of distant metastases with a significant increase while the therapy-resultant tumour diminution with a marked decrease, respectively.

Postoperative thyroglobulin level determination to follow up patients with highly differentiated thyroid cancer.

The highly differentiated thyroid tumours account for 0.80% of all human malignancies. The papillary and follicular tumour tissues of this tumour type are relatively benign, hormone-dependent and beside their treatment specificity they secrete the tumour-specific thyroglobulin. This it becomes possible to follow the development of metastases, the effectiveness of therapy applied as well as the history of the disease. The authors studied the change of thyroglobulin level in 153 patients with highly differentiated thyroid cancer. In 29 of 32 metastatic patients a pathologically elevated (70-100 ng/ml) thyroglobulin level was observed. This proves the 91% specificity of the method in verified metastatic tumours. Compared to the total body scintigraphy 3 false-negative and 6 false-positive cases were found. The authors establish that, irrespective of the site of metastasis, the thyroglobulin level is higher in the follicular than in the papillary subtype. It is concluded that the measurement of the serum thyroglobulin level is a suitable marker of the highly differentiated thyroid cancer since it indicates local recurrence or distant metastases by a significant increase while therapy-resultant tumour diminution is accompanied by a marked decrease.

Anorectal sarcomas.

The authors report on their observations of nine patients with anorectal sarcoma. They agree with others that best results can be expected from radical surgery. Even in operable patients anorectal sarcomas have a worse prognosis than other malignant lesions in the same region.

Elective Hartmann's Operation.

Hartmann's operation has been performed as an elective intervention. In the case of tumours of the sigmoid and the upper two-thirds of the rectum this operation involves less risk and less stress than Dixon's anterior resection or extirpation of the abdominoperineal rectum. Hartmann's operation is being performed on, and is recommended for, elderly patient and for those suffering from some serious intercurrent disease having therefore a reduced resistance to operational strain. The authors removed under these conditions 16 sigmoidorectal tumours. In 12 cases the operation consisted of radical extirpation.

Fine-needle biopsy of thyroid gland.

Critical analysis is provided by the authors on cytologic examination combined with histology of 131 patients with thyroid alterations. Cytologic examination yielded seven false-negative and four false-positive findings. Sensitivity of the procedure was 0.78 and the specificity 0.97. Aspiration cytology of the thyroid gland combined with other methods of examination can be considered an advance in the diagnostics of thyroid diseases.

Indication and clinical evaluation of radical and semiradical neck dissection on the basis of 271 operations.

Between the period of 1956 and 1973, 271 radical and semiradical neck dissections were performed. The 'en bloc' method was used in 75 patients with cancer of the larynx and in 47 thyroid cancer patients. Analysis of the patient material revealed the operative mortality of 1.5%. 5-year survival was observed in 34.8% of the patients. The incidence of local recurrence amounted to 21%.

[Aspiration cytodiagnosis of breast tumors]. / Aspiratsionnaia tsitodiagnostika opukholei molochnoi zhelezy.

Aspiration biopsy cytology was employed by the authors in 250 cases for pathological changes in the mammary gland, in 183 cases the cytological investigation was followed by the histological one. The method proved to be of diagnostic value in 86% (sensitivity). Together with other methods of clinical diagnostics (palpation, mammography, xeromammography, thermography) the method concerned may widen the diagnostic opportunities and allows getting the information on the morphological nature of the tumor. Due to this, the practical application of this prompt, economic and devoid of any complications method seems to be rational. It is suggested to employ it routinely in the clinical practice.

Diagnosis of carcinoma of the breast by aspiration biopsy cytology.

The authors performed fine needle aspiration biopsy in 174 patients with mammary lesions. In 124 cases the cytologic examination was followed by surgery combined with histologic examination. The cytologic findings can be considered to be satisfactory in regard to literary data. In principles, however, it cannot substitute the histologic examination. In combination with the other diagnostic methods aspiration cytology may yield useful diagnostic information. In case of recurrences, inoperable tumors and contralateral metastases the fine needle aspiration biopsy cytology is of diagnostic value.

[Operability and prognosis of rectosigmoid cancer]. / Angaben zur Operabilität und Prognose der rektosigmoidalen Krebse.

The data of 571 rectosigmoidal cancer patients treated between 1959 and 1972 analysed to establish the factors hindering operability. The most important factor was a belated diagnosis. Suggestions are made for early diagnosis to improve the rate of early operations and thereby the prognosis.