A different prognostic value of BRAFV600E mutation positivity in various age groups of patients with papillary thyroid cancer.

The aim of the retrospective single-center study was to assess the prognostic value of BRAFV600E mutation positivity (BRAFV600E+) on disease persistence/recurrence in patients with papillary thyroid cancer (PTC). A total of 199 patients having had initial surgery with neck dissection in our hospital between 6/2009-6/2012 were included in the cohort. Excluded were patients with unifocal microcarcinoma ≤1cm. BRAFV600E mutation was tested from formalin-fixed paraffin-embedded surgicaly removed tumors. All included patients were postoperatively treated with radioiodine. The median duration of follow-up was 43 months, quartiles range 30 - 58 months. Variables included in the final model: BRAFV600E+, categorised age, sex, and high-risk status, or alternatively lymph node status. Based on differences in persistence/recurrence rates, patients were divided into three age categories (<35, 35-60, ≥60). Multiple regression analysis showed a significant interaction between BRAFV600E+ and age, modifying the effect of BRAFV600E+ on persistence/recurrence. BRAFV600E+ in low-risk patients of any age and in high-risk middle-aged patients did not confer additional hazard compared with BRAFV600E mutation negative (BRAFV600E-) low-risk and BRAFV600E- high-risk patients, respectively. However, younger (<35 years) and older (≥60 years) high-risk BRAFV600E+ patients had 17.28 and 33.49-fold increased hazard of persistence/recurrence, respectively, compared with low-risk BRAFV600E- patients. The alternative model including lymph node status yielded similar results for the prognostic significance of BRAFV600E+ in younger and older patients. In conclusion, the prognostic value of BRAFV600E+ depends on high-risk status and likely on age-associated factors. Such additional knowledge could change clinical decision-making in treatment modality.

[History of Oncology in Slovakia]. / História onkológie na Slovensku.

The history of oncology in Slovakia is closely linked to the history of St. Elizabeth Hospital, which was set up in the mid-18th century by nuns of the St. Elizabeth Order in Bratislava. In the first half of the 20th century, a unit was set up in the hospital dedicated to diagnosis and treatment of cancer. Shortly after World War II, the unit was turned into the Institute for Cancer Research and Treatment. In 1950, St. Elizabeth Hospital was nationalized, and the Cancer Research Institute of the Slovak Academy of Science and the Institute of Clinical Oncology were located there as centers for oncological diagnosis and treatment. After the restitution of church property in the early 1990s, the hospital was returned to the Order of St. Elizabeth, which set up the St. Elisabeth Cancer Institute in the hospital premises in January of 1996. This year marks the 20th anniversary of this institute in its new premises and the 85th anniversary of the Institute of Radiumtherapy founded in Bratislava, and thus the establishment of institutional healthcare for cancer patients in Slovakia is the reason for balancing. We present a view of the consecutive changes in the organization, space and staff of the Institute and evaluate the impact of celebrities on medicine who developed oncology as a clinical, scientific and educational discipline in Bratislava and in other cities and regions of Slovakia.

Advanced detection and measurement of cells on membrane from peripheral blood by laser scanning cytometry (LSC) in early stage breast cancer patients.

BACKGROUND: The aim of our study was the potential detection of circulating tumour cells (CTCs) in early stage breast cancer patients. Our approach was cell microfiltration through polycarbonate membrane as a concentration method suitable for CTC selection in peripheral blood. The isolated cells on membrane were further analysed by laser scanning cytometry. METHODS: Sixteen patients were enrolled in the study, of which 13 had early stage breast carcinoma and 3 patients had metastatic breast carcinoma. The analyses were performed from 9 ml of peripheral blood, in one patient blood was drawn twice. Blood samples were taken after adjuvant chemotherapy but prior to adjuvant radiotherapy. The control group consisted of 12 clinically healthy subjects. CONCLUSIONS: In the control group 3 subjects out of 12 had 1 CTC, the mean CTC numbers being 0.25 +/- 0.45. In the early stage breast cancer patients 0-36 CTCs were detected (mean 13.9 +/- 12.9 CTCs. 10 patients out of 13 had more than 2 CTCs (62%). The detection and measurement of cells on membrane is a simple and reproducible method of detection of CTCs in peripheral blood. Sensitivity of the method is 88.5%. Detection of CTCs seems to be a promising method for the monitoring of adjuvant therapy in early stage breast cancer patients and for the identification of high risk patients in whom elevated numbers of CTCs are persisting following the termination of adjuvant therapy (Tab. 1, Fig. 4, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

The detection of circulating tumor cells expressing E6/E7 HR-HPV oncogenes in peripheral blood in cervical cancer patients after radical hysterectomy.

The aim of this study was to establish the sensitive, specific and clinically acceptable method for detection of tumor cells (TCs) circulating in peripheral blood (PB) of cervical cancer patients without the clinically detectable risk of disease progression. The 7.5 ml of PB of healthy donor was spiked with 5 to 100 cells from SiHa or HeLa cell lines. The spiked tumor cells were collected without gradient centrifugation, by standard gradient centrifugation or by modified gradient centrifugation combined with immunomagnetic separation using EpCAM antibody with affinity for epithelial cell adhesion molecule. The number of collected TCs was determined by EpCAM-FITC-staining and their viability was detected by nested RT-PCR amplifying E6/E7 HR-HPV 16 or HR-HPV 18 oncogenes. For the technical validation of this approach the TCs separation and RT-PCRs were repeated several times. The recovery of viable TCs was reproducibly higher using modified gradient centrifugation combined with immunomagnetic separation in comparison with standard approach. The recovery of TCs in low number of spiked TCs (range from 5 - 20 TCs in 7.5 ml of PB) using modified gradient centrifugation was not reproducible. The recovery of TCs in higher number of spiked TCs (25 TCs and more in 7.5 ml of PB) was reproducible with average recovery about 50 %. The sensitivity of nested RT-PCR amplifying E6/E7 oncogenes was decisively influenced by the number of recovered TCs and the amount of cDNA introduced to RT-PCR, as well. Using this approach we were allowed to detect circulating TCs (CTCs) in cervical cancer patients without metastases, thus this procedure might become a tool to early estimation of disease progression. According to our knowledge, this is the first report describing the use of EpCAM antibody for CTCs detection in cervical cancer patients.

Genetic analysis of KRAS mutation status in metastatic colorectal cancer patients.

Colorectal carcinoma (CRC) represents a serious problem worldwide: in the Slovak republic are diagnosed about 2600 new CRC cases annually and its incidence is increasing. Colorectal cancer patients may succumb to the disease because of local recurrence or local formation of metastasis. Therefore, it is necessary to modulate therapeutic algorithm with new methods, leading to early diagnostic of CRC or changing the existing therapeutic procedures. Recent progresses have been made in understanding of EGFR pathway involved in CRC carcinogenesis, especially the role of Ras protein. Mutations in KRAS oncogene are frequently found in human cancers, particularly colorectal, pancreatic, billiary tract and lung tumors. The presence of the KRAS mutations in metastatic colorectal cancer patients correlates with lack of response to the certain epidemal growth factor receptor (EGFR) inhibitor therapies, such as Panitumumab and Cetuximab. Consequently, screening for KRAS mutations status may be used as a prognostic marker, because the CRC patients with KRAS positive tumors have a worse prognosis. The aim of our study was to establish the methods for rapid and sensitive detection of KRAS mutation status in formalin fixed paraffin embedded (FFPE) tissues DNA. We applied Real Time PCR analysis (TheraScreen KRAS Mutation Test Kit) and sequencing analysis (optimised for the analysis of FFPE tissues) to detect somatic mutations in codon 12 and 13 of KRAS gene. Both methods were used concurrently in the panel of DNA isolated from 25 colorectal FFPE tissues tumor. The positive or negative results from all 25 samples were identified by both methods independently. The KRAS mutations were presented in 8 of 25 patients (32%). Our results demonstrate that the Real Time PCR analysis can be used for detection of somatic KRAS mutations in FFPE clinical samples. However, we also recognize that the sequencing analysis of approximately 200bp amplicons may be used for mutations status screening, but with care of method sensitivity.

The spectrum and incidence of BRCA1 pathogenic mutations in Slovak breast/ovarian cancer families.

Pathogenic germline mutations in BRCA1 and BRCA2 account for the majority of hereditary breast/ovarian cancer cases. The analysis of BRCA1 gene was carried out in 156 breast/ovarian cancer families: 82 families with strong family history and 59 families with medium family history. Generally, 31 families and 71 cases with BRCA1 pathologic mutations (14 different types) were identified in this study by combination of SSCP and direct sequencing techniques. Using approved systematic nomenclature numbering, c.5266dupC (8 families, 21 cases), c.181T>G (5 families, 11 cases), c.68_69delAG (3 families, 5 samples) and c.843_846del4 (3 families, 4 samples) were the most frequently found mutations in BRCA1 gene. Altogether these 4 mutations accounted for 61.3% of all detected pathogenic mutations in BRCA1. One novel mutation c.1166delG was detected in one family (4 cases). Frame-shift mutations were found in 21 families (46 cases), nonsense mutations in 4 families (8 cases) and missense mutations in 6 families (17 cases). Even though the 4 most frequent mutations account for 61.3% of all detected pathogenic mutations, screening of the whole BRCA1 coding region is necessary, due to the large scale of low frequency disease causing mutations in breast/ovarian cancer families in Slovakia.

New approach to human high-risk papillomavirus (HR-HPV) genotyping.

Human high-risk papillomaviruses (HR-HPVs) are involved in the induction of invasive cervical cancer. The aim of this study was to introduce a simple, semi-automated and reproducible approach suitable for HR-HPV detection in clinical practice. The procedure is based on DNA isolation, nested polymerase chain reaction, single strand conformational polymorphism and evaluation of HR-HPV genotypes with Gel-Pro software. The clinical performance of the new approach was assessed in two different patient materials: 1) cervical smears with cytological classification Pap2-3 or Pap3 lacking nuclear atypia (anisonucleosis and polychromasia) or koilocytotic atypia and without any previous therapy 2) formalin-fixed, paraffin-embedded cervical carcinoma and lymph node sections. Using the new approach we detected HR-HPV DNA in 64% patient samples cytologically classified as Pap2-3 or Pap3 respectively and in 80% formalin-fixed, paraffin-embedded lymph node sections histologically classified as lymph nodes without carcinoma cell infiltration. The combination of methods described in this study results in increased sensitivity of HR-HPV identification allowing detection of HPV DNA in a very small amount of target DNA so that it can be widely used in distinguishing the pre- malignant lesions and in determination of invading carcinoma cells to lymph nodes in patients with advanced cervical cancer. The new approach is useful in unambiguous HR-HPV genotyping even in double-HPV infection.

Further studies of blood levels of some tumor markers in the area polluted by polychlorinated biphenyls and control population.

The levels of beta2-microglobulin (beta2-m), alpha-fetoprotein (AFP) and thyroglobulin (TG) were measured in the serum of 245 employees of chemical factory formerly producing polychlorinated biphenyls (PCB) consisting of 54 males (age range 24-65 years, median 45) and 191 females (age range 20-69 years, median 45). The control population consisted of 636 adults from control areas of northwest and east Slovakia. The frequency of beta2-microglobulin levels lower than 1.6 microg/ml in 242 employees of chemical factory was 76.8% (186/242) which was three times higher (P<0.001) than 24.4% (155/635) in 636 controls. Still more remarkable difference was obtained when using the cut/off level of 1.2 microg/ml, the frequency of such values in the employees being 45.4% (110/242) vs. 4.4% (28/635) in the controls. In contrast, no difference in alpha-fetoprotein levels was observed between the employees and the controls, the respective frequency of these < 5.0 ng/ml being 87.6% (212/242) vs. 86.2% (389/451) and these < 10.0 ng/ml being 100.0% (242/242) vs. 97.8% (441/451). Similarly, the frequency of normal thyroglobulin levels < 50.0 ng/ml) did not differ, being 95.6% (174/182) in the employees and 87.9% (87/99) in the controls. Most of a total of 20 cases with thyroglobulin level > 50.0 ng/ml showed sonographicaly enlarged and multinodular thyroid with focal or diffuse hypoechogenicity, three of them showed solitary nodule with a diameter > 10 mm. Although the decreased levels of beta2-microglobulin might be somehow related to the modulation of immune system, more plausible explanation appears to be the possible impairment of renal tubules by PCB similar to that caused by heavy metals resulting in increased urinary excretion of beta2-microglobulin and decrease of its blood level.

Delayed orchiectomy after chemotherapy in patients with advanced testicular cancer.

INTRODUCTION: The therapeutic procedures in the management of testicular cancer are determined by histological findings in the removed testis and by the extent of the disease at the time of diagnosis. However, all advanced tumors could be treated by primary chemotherapy regardless of the histological findings. The current imaging techniques (ultrasound of the testis, abdominal and chest CT examination) and laboratory tests (determination of serum tumor markers AFP and hCG) provide sufficient evidence for the presence of cancer. When the diagnosis of advanced tumor is evident, it is possible to start the treatment without orchiectomy. The aim of this study was to evaluate the advantages of neo-adjuvant chemotherapy with delayed orchiectomy in the management of advanced testicular cancer. MATERIAL AND METHODS: A total of 36 patients with advanced germ cell testicular cancer underwent primary PVB or BEP chemotherapy without previous orchiectomy. Mean age of patients was 32 years. Detailed medical, surgical and urological examination showed pulmonary metastases and/or extensive abdominal tumorous masses imitating acute abdominal crisis and impaired drainage of the kidney due to ureteral obstruction. Searching for the origin, testicular tumor was detected. Eleven patients had a bulky disease in the retroperitoneum (Stage IIC), two had enlarged retroperitoneal lymph nodes (Stage IIB), two had enlarged mediastinal lymph nodes (Stage III) and other 16 patients had also pulmonary metastases, and 5 pts had pulmonary metastases only. The patients were treated with cisplatin-containing combination chemotherapy. Following completion of chemotherapy, orchiectomy was performed alone or simultaneously with retroperitoneal lymph node dissection (RPLND) and/or lung metastasectomy in cases with persistent residual mass. Following orchiectomy the patients were regularly checked and in cases with viable malignant tumor found in the testis sequential chemotherapy was administered. Similarly when the relapse of the disease was detected, the patients were treated with sequential chemotherapy. RESULTS: Complete disappearance of metastases was observed in 12 patients following chemotherapy alone. The residual mass persisted in 24 patients (in 22 out of them in the retroperitoneum and in two patients also in the lungs) and was removed surgically. The viable tumor in the removed tissue was found in one patient. Delayed orchiectomy was performed simultaneously with surgical removal of residual mass in the retroperitoneum in 24 patients and as a separate procedure in 12 patients who have been considered to be complete responders following chemotherapy alone. Residual viable tumor in testicular specimen was found in three patients, necrotic or fibrotic tissue in 18, and mature teratoma in 15 patients. Overall survival of the patients was 26/36 (72.7%) at mean of 56.9 months (range 7-145 months, median 50 months) since the start of the treatment. CONCLUSIONS: In patients with advanced germ cell testicular cancer preference must be given to the early beginning of intensive chemotherapy without the need of tissue diagnosis of primary tumor that should be obtained by orchiectomy. Benefit of this therapeutic approach is the timely management of acute abdominal and/or pulmonary symptoms of life-threatening distant metastases.

[Diagnosis of thyreopatic diseases by laboratory examinations--possibility for rational economy]. / Laboratórne vysetrovacie metódy v diagnostike tyreopatií--moznosti racionálnej ekonomizácie.

This paper is oriented on the possibility of racional economy of laboratory diagnostical process of thyreopathies. The study was based on analysis of 29,683 examinations made at biochemical department in hospital Trencín. The overuse--mostly of antibodies and also, but less of thyreoidal hormones was discovered, mostly in the group of physicians in general practise and less in hospital and internal practise. The absence of initial algoritmus in thyreoidology is documented. The followed approach was formulated as new proposal: the first step is the examination of TSH (by ultrasensitive method) with possibility for all groups of physicians. Clinical and biochemical department should have responsibility to add fT4 in the case of pathological TSH. The endokerinologist should have responsibility for all other thyreoidal examinations, but in reasonable case also the internists in ambulatory and hospital care, and other relevant hospital physicians could order these examinations. Probability of cost saving was about 34% of expanditures on thyreoidology. To make the recount for Slovak republic the saving cost could be about 42,500,000 Sk.

[Serum neopterin levels in oncology patients in intensive care]. / Hladiny sérového neopterínu u onkologických pacientov v intenzívnej starostlivosti.

BACKGROUND: Elevated neopterin serum levels are associated with diseases that stimulate the cellular immune response. This includes viral infections, autoimmune diseases, transplant rejection and dissemination of certain types of cancer. T-helper lymphocytes and macrophages play a key role in neopterin synthesis. The degree of activation of Th1-lymphocytes is responsible for the production of interferon-gamma and interleukin-2, which stimulate neopterin production in human macrophages. DESIGN AND METHODS: We have designed a prospective observational study to assess the dynamics of serum neopterin levels in 75 oncological patients during post-surgery period. We measured serum neopterin by means of RIA method (radioimmunoassay) in 50 uncomplicated surgery patients (group A), in 15 complicated surgery patients (group B--abdominal sepsis, peritonitis, ileus) and 10 medical ICU patients (group C). Serum levels of neopterin were measured in 5 consecutive periods: before surgery, after surgery, and on the 1st, 2nd, 3rd postoperative days. RESULTS: In all groups, we observed gradual elevation of serum neopterin. The lowest values of neopterin were measured in group A in patients with uncomplicated course following surgery: 6.75 nmol/l, 7.67 nmol/l, 8.9 nmol/l, 10.82 nmol/l and 13.66 nmol/l. A significant increase in serum neopterin levels was measured in group B in patients with septic complications during perioperative period: 18.9; 23.2; 26.82; 29.53 and 27.32 nmol/l. High values of neopterin were also measured in medical ICU patients with disseminated cancer and sepsis during ICU stay: 26.1; 58.1; 28.7 and 22.5 nmol/l. We concluded that serum neopterin levels were increased during the post-surgery period. We observed a significant increase in serum neopterin in patients with severe systemic infection or sepsis or in patients with cancer progression or dissemination (more than 15-20 nmol/l). Neopterin is a simple, reliable and sensitive parameter of cell-mediated immunity, suitable for early diagnosis of viral, autoimmune and transplantant rejection diseases. Neopterin can be used also for non-specific laboratory monitoring of cancer progression and/or dissemination. (Tab. 3, Fig. 4, Ref. 7.)

Prognostic factors in clinical stage I nonseminomatous germ cell testicular tumors: rationale for different risk-adapted treatment.

OBJECTIVE: Surveillance after orchiectomy alone becomes popular for the management of clinical stage I nonseminomatous germ cell testicular tumours (CS I NSGCTT). Effort to identify patients at high risk of relapse leads to searching prognostic factors of CS I NSGCTT. The aim of this study was to identify those patients in whom a surveillance policy is less likely to be successful. PATIENTS AND RESULTS: Seventy-two CS I NSGCTT patients were stratified to different risk-adapted therapeutic approaches according to histopathologic findings of primary tumor removed by inguinal orchiectomy. Eighteen patients (group A) with vascular invasion and majority of embryonal carcinoma component in the primary tumor were treated with adjuvant BEP chemotherapy. None of them experienced disease progression after a median follow-up period of 36 months after orchiectomy. Five patients (group B) with vascular invasion and the majority of teratomatous elements in the primary tumor have been followed up 56 months after orchiectomy. They were treated with primary retroperitoneal lymph node dissection (RPLND). Two of them (40%) had pathologic stage II after RPLND and underwent subsequent chemotherapy. One of them died due to disease progression 29 months following orchiectomy. Another one lives with no evidence of disease (NED). Three patients in pathologic stage I are alive with NED. Forth-nine patients (group C) without vascular invasion have been followed up for a median duration of 37 months after orchiectomy. They were kept under close surveillance, consisted of regular follow-up with tumor markers, chest x-ray and CT of the retroperitoneum. Disease progression was observed in 7 (14.3%) patients after a median duration of 8 months after orchiectomy. They were treated with BEP chemotherapy and live with disease-free median survival of 22 months after completion of therapy. The overall survival rate of all 72 patients was 98.6%. The median survival for all patients was 37 months (range 7-73). CONCLUSIONS: The authors will continue to use surveillance policy only in patients without vascular invasion in the primary tumor.

Decreased blood level of beta 2-microglobulin in the employees of a factory which produced polychlorinated biphenyls.

Under the project of evaluating the health status of the employees of CHEMKO factory (East Slovakia) which produced PCBs between 1955 and 1985, the level of beta 2-microglobulin (beta 2-m) was measured in the serum of 242 subjects from CHEMKO (Group A) and two control groups from much less polluted areas: 1,277 females from a small mountainous village (Group B), 2,179 adults from the area of a large city of Kosice (Group C). The level of thymidine kinase (TK) was measured in the groups A and B only. In addition, age-matched groups of 155 women each from all areas were evaluated. In both the whole group and the age-matched group from CHEMKO the level of beta 2-m was significantly lower (P < 0.001) than that in the respective control groups, while no difference was found in the level of TK. In conclusion, it is suggested that the decrease of beta 2-m in CHEMKO employees might be related to the immunotoxic effects of organochlorines.

The value of prognostic factors in the management of stage I nonseminomatous germ cell testicular tumors (NSGCTT).

The prospective study, carried out from February 1992 to January 1996, included 49 patients in clinical Stage I nonseminomatous germ cell testicular tumors (NSGCTT). They were aged 16-40 years (mean, 25 years). Patients were stratified to different risk-adapted therapeutic approaches according to histopathologic findings of primary tumor removed by inguinal orchiectomy. Eleven patients of the 1st group with vascular invasion and majority of embryonal carcinoma components in the primary tumor were treated with adjuvant chemotherapy (2 cycles of BEP). None of them had disease progression after the follow-up of 4-43+ months (mean, 20.9 months) after orchiectomy. Five patients of the 2nd group with vascular invasion and majority of teratoma elements in the primary tumor were treated with primary retroperitoneal lymph node dissection (RPLND). They were followed-up 29-45+ months (mean, 33.4 months) after orchiectomy. Two of them (40%) had pathologic Stage II after RPLND and underwent subsequent BEP chemotherapy. One of them died due to disease progression in disseminated stage 29 months after orchiectomy. The second one lives with no evidence of the disease (NED). Thirty three patients in the 3rd group without vascular invasion were kept under surveillance. They were followed-up 3-48+ months (mean, 22.3 months) after orchiectomy. Disease progression was observed in 5 of them (15.1%), 7-10 months (mean, 8.8 months) following orchiectomy. These patients were treated with BEP chemotherapy and live with NED 1-16+ months (mean, 9.2 months) after completion of the therapy. The overall survival rate in clinical Stage 1 patients was 97.9%. The authors recommend the surveillance policy only in clinical Stage I NSGCTT patients without vascular invasion in the primary tumor.

Management of germ cell testicular cancer with pulmonary metastases.

Twenty eight patients with germ cell testicular cancer pulmonary metastases received primary chemotherapy including bleomycin, etoposide, and cisplatin (BEP). Complete response was achieved in 21 (75%) patients, in 11 of them CR was achieved following chemotherapy alone. Postchemotherapy surgery of residual mass was performed in 12 (42.9%) patients with normalized serum tumor markers. Retroperitoneal lymph node dissection was performed in one patient, pulmonary surgery in four, and both postchemotherapy treatments in 7 patients. Overall cure rate was 89.3%, 26 (92.9%) patients are still alive at a mean follow-up of 19.7+ months (range, 3-34+ months) after the treatment start. Two (7.1%) patients died: one of them due to disease progression during chemotherapy, and the second one due to postoperative complication (acute respiratory failure). Relapse of disease was observed in one patient 21 months following CR achievement, and sequential chemotherapy was introduced. Authors recommend surgical remove of all radiologically detected residual deposits, because the available imaging methods are not adequate for determining the histologic composition of residual mass, which is decisive for further therapy and has prognostic value.

[Prostate-specific antigen in patients with benign prostatic hyperplasia]. / Prostatický specifický antigén u pacientov s benígnou prostatickou hyperpláziou.

The authors examined 119 patients with the histological finding of benign prostatic hyperplasia (BPH). Before the planned operation of the prostate (transurethral resection or open prostatectomy) the authors examined in all patients the level of the prostate specific antigen (PSA) and the prostate volume by sonography. Of 119 patients 70 (58.8%) had elevated serum levels of PSA and in 35 (29.4%) the PSA level was higher than 10 ng/ml. The authors demonstrated a highly significant (p < 0.0001) linear relationship of the PSA serum level and volume of prostate in patients with BPH. Based on the results of simple regression analysis they elaborate an equation for the prostate volume: PSA ng/ml = (3.26 + 0.12 x volume of prostate (ml) +/- 8.44). By adding the value of the standard deviation of PSA the authors created an interval in which are most of the patients with BPH. The authors recommend supplementary examinations (transrectal sonography and biopsy of the prostate) in patients where there is a disproportion between the PSA level and the prostate volume.

Correlation of cytosolic concentrations of ER, PS2, Cath-D, TPS, TK and cAMP in primary breast carcinomas.

In a group of 391 patients with primary breast cancer the cytosolic concentrations of ER, PS2, Cath-D, TPS, TK and cAMP were determined. PS2 production was found to be significantly dependent not only on ER but also on cAMP. A similar dependence on ER and cAMP production was found also in Cath-D. When the production of these prognostic factors was correlated with the occurrence of metastases to axillary lymph nodes, three prognostically unfavorable groups of primary breast carcinomas were revealed. The first group was represented by tumors with negative PS2 values (< or = 2.5 ng/mg) and elevated TPS values (> or = 4.0 kU/mg). The second group comprised prognostically very unfavorable tumors with moderately to highly elevated PS2 values and positive Cath-D values (> or = 35 pmol/mg), or positive TPS values (> or = 8.0 kU/mg). The third group was constituted by tumors with elevated TK (> or = 5.0 U/mg) and ER values (> or = 40 fmol/mg). The possible role of PS2 in the metastasizing of primary breast carcinomas is discussed.

[Use of the CA 19-9 tumor marker in the diagnosis of pancreatic carcinoma]. / Vyuzitie nádorového markera CA 19-9 pri diagnostike karcinómov pankreasu.

The contribution of the tumor marker CA 19-9 to differential diagnosis between malignant and nonmalignant diseases of the pancreas was assessed in a group of 120 patients. On using border values of CA 19-9 80 U/ml, its sensitivity was found to be 84.4% and its specificity 84.8% for carcinomas of the pancreas. Correlation of CA 19-9 values with results of computer tomography and endogenous retrograde cholangiopancreatography in the patients studied yielded an over 80% accordance. In the light of the obtained results, the authors consider determination of CA 19-9 levels to be a suitable method supplementing the imaging examination methods in suspect carcinoma of the pancreas.

Chemotherapy of testicular cancer: 10-year experience.

A total of 250 patients with germ cell testicular tumors were treated by PVB chemotherapy between 1982 and 1992. Mean age of patients was 28.9 years (range 15-52). Thirty-four patients in clinical Stage II (11 patients IIA, 13 patients IIB, and 10 patients IIC) underwent primary retroperitoneal lymphadenectomy (RPL) with subsequent chemotherapy. They were followed-up for a mean of 106.3 months (range 85-125). CR was achieved in 30 patients (88.2%). Three patients relapsed. Twenty-seven patients (79.4%) are alive with no evidence of disease (NED) after a minimum of 5 years since the start of therapy. One hundred and twenty-two patients underwent primary chemotherapy for clinical Stages IM (15 patients), IIA (31 patients, IIB (48 patients) and IIC (28 patients) with RPL in cases with residual mass in the retroperitoneum. They were followed-up for a mean of 47.7 months (range 6-122). CR was achieved in 115 patients (92.7%) (75 of them received chemotherapy alone, 40 patients achieved CR following combined cytostatic-surgical treatment). Eleven patients relapsed. One hundred and nine patients (89.3%) are alive with NED. Ninety-four patients in Stages III and IV (8 patients III, 86 patients IV) underwent primary chemotherapy with additional surgical removal of residual metastases. They were followed-up for a mean of 50.5 months (range 6-125). CR was achieved in 65 patients (69.1%) (32 of them received chemotherapy alone, 33 patients achieved CR following combined cytostatic-surgical treatment). Eleven patients relapsed. Fifty-seven patients (60.6%) are alive NED. There were 11 patients with advanced germ cell testicular cancer (Stages IIC and IV) who underwent initial PVB chemotherapy without previous orchiectomy. Delayed orchiectomy was done simultaneously with surgical removal of residual mass in the retroperitoneum or in the lungs or at completion of chemotherapy alone. The toxicity of chemotherapy was moderate. There were drug-related deaths in ten patients (4%).

Monitoring of patients with non-seminomatous germ cell tumors of the testis by determination of alpha-fetoprotein and beta-human chorionic gonadotropin levels and by computed tomography.

The results of a 7-year monitoring of 230 patients with non-seminomatous testicular tumors are reported with respect to the employment of radioimmunoanalysis of alpha-fetoprotein and beta-human chorionic gonadotropin levels and CT examinations of retroperitoneum and lungs. Prior to orchiectomy, elevated levels of at least one of these markers were found in 79% of patients. After orchiectomy, tumor marker levels were in 70.4% of patients in agreement with the results of CT examinations. After the completion of chemotherapy, in more than a half of patients normal tumor marker levels and positive CT findings were observed. These results were most often due to the presence of mature teratoma. In Stage I patients the advantages of tumor marker determinations and CT examinations in the early detection of tumor progression have fully been confirmed.