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Biomedical subjects

J Breza

Publications and source records attributed to J Breza.

At least 19 recordsLinked to original sources

Cystic renal cell carcinoma--rare clinical finding. Radiographic variations of tumor/cyst appearance and further diagnostic work-up.

OBJECTIVES: To review the cases of cystic renal cell carcinoma and multilocular cystic nephroma, point out the radiographic variations and define further diagnostic work-up. MATERIALS AND METHODS: Between 2003 and 2005 5 patients with suspected cystic renal cell carcinoma were treated surgically (1 pt underwent radical nephrectomy, 1 pt laparoscopic cyst decortication, 3 pts ablation), 2 patients with multilocular cystic nephroma underwent ultrasound guided biopsy. RESULTS: Histopathologic examination confirmed cystic renal cell carcinoma (CRCC) T1aNOM0 Fuhrman grade 1 in 3 cases, T1bN0M0 Fuhrman grade 2 in one case. One patient with suspected tumor inside the cyst wall who underwent laparoscopic cyst decortication was excluded (final histology confirmed organized hematoma in the cyst wall). Biopsy in 2 patients with multilocular cystic nephroma did not confirm the presence of malignant cells. The mean tumor size was 4.2 cm (range 3.7 to 5.5) for CRCC and 4.7 cm (range 4 to 4.5 cm) for multilocular cystic nephroma. All 4 cases of CRCC were clear cell type. CONCLUSION: In conclusion according to the data described and from our study, tumor/cyst co-existence requires further surgical exploration in group 2, 3, 4. Small cystic renal cell carcinomas up to 4 cm in diameter have usually favourable pathology and prognosis, which offers the minimally invasive nephron-sparing treatment options such as excision, ablation or partial nephrectomy (Fig. 9, Ref. 18).

Aged↗

Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma.

Metastatic lesions occur in up to 36% of patients with pheochromocytoma. Currently there is no way to reliably detect or predict which patients are at risk for metastatic pheochromocytoma. Thus, the discovery of biomarkers that could distinguish patients with benign disease from those with metastatic disease would be of great clinical value. Using surface-enhanced laser desorption ionization protein chips combined with high-resolution mass spectrometry, we tested the hypothesis that pheochromocytoma pathologic states can be reflected as biomarker information within the low molecular weight (LMW) region of the serum proteome. LMW protein profiles were generated from the serum of 67 pheochromocytoma patients from four institutions and analyzed by two different bioinformatics approaches employing pattern recognition algorithms to determine if the LMW component of the circulatory proteome contains potentially useful discriminatory information. Both approaches were able to identify combinations of LMW molecules which could distinguish all metastatic from all benign pheochromocytomas in a separate blinded validation set. In conclusion, for this study set low molecular mass biomarker information correlated with pheochromocytoma pathologic state using blinded validation. If confirmed in larger validation studies, efforts to identify the underlying diagnostic molecules by sequencing would be warranted. In the future, measurement of these biomarkers could be potentially used to improve the ability to identify patients with metastatic disease.

Adolescent↗

Novel germline mutation in the transmembrane region of RET gene close to Cys634Ser mutation associated with MEN 2A syndrome.

Two mutations on the same allele of RET gene were revealed in a family with predisposition to multiple endocrine neoplasia (MEN) type 2A. The first mutation changes codon 634 from cysteine to serine. The second, a novel mutation in codon 641, changes alanine to serine in the transmembrane domain of the RET protein. Two mutations were present in close proximity in both the patients' germline and tumor DNA and were absent in DNA isolated from healthy family members and control blood donors. All MEN 2A affected family members suffered from medullary thyroid carcinoma and two of ten patients for pheochromocytoma. No parathyroid gland alterations were observed in patients with two RET gene mutations. Analysis of four genetic polymorphisms in the RET gene showed higher incidence of polymorphisms of exons 11 and 15. The observed allelic imbalance in favor of mutated allele in pheochromocytoma corresponded to higher expression of the RET gene. These observations confirm the multifactorial process leading to development of MEN 2A syndrome.

Adrenal Gland Neoplasms↗

Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer.

BACKGROUND: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. PATIENTS AND METHODS: Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat analyses. All progressions and responses were reviewed by an independent panel. RESULTS: PFS was significantly prolonged in the VRL plus HT arm compared with the HT alone arm, according to the statistical hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre-specified significance level of 10%). The 6-month PFS rates were 33.2% versus 22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the multivariate Cox analysis, which included age, Karnofsky performance status (PS), haemoglobin, alkaline phosphatase at study entry and number of prior hormonal treatments, the P value was decreased to 0.005. The prostate-specific antigen (PSA) response rate (> or =50% decline sustained for at least 6 weeks) was significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%; P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least stable assessment in the other two, was also more frequently observed in patients who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no statistical difference in overall survival. Forty-three per cent of patients in the HT arm received at least one line of further chemotherapy after progression, compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not seem to result in better efficacy for either arm. VRL plus HT was well tolerated, with a median administered relative dose intensity of 90%; grade 4 neutropenia occurred in 6.5% of patients and non-haematological toxicity was rare. CONCLUSIONS: The combination of VRL and hydrocortisone compared with hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response rate. This therapeutic gain is similar to that previously reported with mitoxantrone in combination with low-dose corticosteroids. There was no gain in survival; however, the combination is well tolerated in this elderly group of patients, who often present cardiac co-morbidities, and therefore offers an active and safe therapeutic option for patients with hormone-refractory prostate cancer.

Aged↗

Retrospective analysis of patients clinical manifestations before and after pheochromocytoma surgery.

MAIN PURPOSE: A retrospective analysis of presurgical clinical picture and blood pressures of 34 patients with histologically verified pheochromocytoma. Assessment of clinical state, blood pressure and prognosis in the course of patients control hospitalizations from 2001 to 2002. PATIENTS AND METHODS: The study was designed as a synoptic one, based on a retrospective analysis of 34 patients records with histologically verified pheochromocytoma (26 women and 8 men). Our assessments of clinical symptomatology, maximum paroxysmal hypertension values, average blood pressure values in patients with persistent arterial hypertension, arterial hypertension grade and circadian index were based on patients records. Patients epinephrectomies were followed during their control hospitalizations to assess their clinical state. Their blood pressures were evaluated by means of their circadian monitoring. RESULTS: From the 34 patients, 21 were diagnosed with solitary pheochromocytomas. The circadian index persistence analysis prior to the surgery was associated with circadian blood pressure monitoring in 21 patients. It was lost in 57% of patients. During their control hospitalization as many as 82% of patients preserved their circadian blood pressure variability with a more than 10% decrease in the night time, 5 patients did not preserve their circadian blood pressure variability. Seven from the original 34 patients died: Three of them died from their primary disease, one 63-year old man died from shock following tumour extirpation. The death of other 3 patients was not associated with their primary disease. CONCLUSION: Long-lasting survival of patients with pheochromocytoma after surgical treatment--except for those with malignant disease--was demonstrated. Although our assessment of the resulting treatment effects was positive, a long-term follow-up is inevitable because of a difficult pathologic-anatomical verification of the malignant nature of the disease as well as of the risk of tumour relapse assessment. (Tab. 1, Fig. 5, Ref 36.)

Adrenal Gland Neoplasms↗

[Use of RT-PCR in the detection of circulating micrometastases].

During assessment of the progression of several types of carcinomas, such as cancer of the breast, lungs, prostate or urinary bladder world-wide the presence of circulating cells (micrometastases) in the circulation is followed up. These methods are gradually introduced also in Slovakia. First we tried in the Institute of Medical Biology and Genetics Medical Faculty Comenius University in collaboration with the Urological Clinic of Dérers the Faculty Hospital with policlinic to apply this method in carcinoma of the prostate (CaP). We detected the presence of epithelial prostate cells in the peripheral blood stream of patients with advanced prostate cancer where before secondaries were not detected.

Humans↗

[Acute conditions after kidney transplantation in patients with autosomal dominant polycystic kidney disease].

There is a high risk of severe complications after kidney transplantation. In patients with autosomal dominant polycystic kidney disease (AD-PKD) the incidence of complications like ischaemic cardiac disease, acute myocardial infarction, pulmonary embolism, perforation of colonic diverticulosis is especially higher. The authors want to indicate another specific complication, rupture of the cyst of own polycystic kidney with retroperitoneal haemorrhage. Within the group of 658 patients who underwent kidney transplantation between January 1981 and January 2000 there were 54 (8.2%) patients with AD-PKD. Four patients with severe retroperitoneal haemorrhage due to rupture of the cyst of own polycystic kidney we present in a short case reports. All cases were fatal. Expect morphologic and functional follow up of the graft it is necessary to follow up polycystic kidney and indicate urgent nephrectomy in the case of any change.

Adult↗

Modern methods of oral treatment of erectile dysfunction.

Erectile dysfunction (ED) is defined as a temporary or permanent inability to obtain or maintain erection sufficient for satisfactory sexual intercourse. ED is not considered to be a genuine disease, it is rather a symptom accompanying other systemic diseases. Almost 52 per cent of men claim erectile dysfunction of different degree, however, only 5-10 per cent of them would confirm their handicap.

Erectile Dysfunction↗

Phase II study of vinorelbine in patients with androgen-independent prostate cancer.

PURPOSE: To evaluate the efficacy and toxicity of vinorelbine in a phase II study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Forty-seven men with progressive metastatic prostate cancer refractory to first-line or second-line hormonal therapy were treated with vinorelbine, a semisynthetic vinca-alkaloid. Vinorelbine was given, on an outpatient schedule, at 25 mg/m2 weekly for at least eight weeks or until progression or excessive toxicity. RESULTS: Forty-seven patients were included in the study, 33 being evaluable for tumour response, 36 for response to PSA, 21 for clinical benefit and 45 for toxicity. Median actual weekly dose was 19 mg/m2 (range 12.0-26.2 mg/m2). Six of thirty-six patients (17%) demonstrated a biologic response with a 50% or more decline in serum PSA on two consecutive measurements taken at least two weeks apart. The median duration of biologic response was 2.7 months. Two of three patients with measurable disease obtained an objective response but remained unconfirmed. No change disease was reported in 23 patients (49%). On entry into the study, 30 patients had symptomatic bone pain and required narcotic or non-narcotic analgesics. Clinical benefit from vinorelbine was achieved in 15 patients out of 21 (32% of the intent to treat analysis population and 71% of the assessable patients). Due to the low number of questionnaires (QLQ-C30) filled in, it was insufficient to allow any statistical analysis. The median survival was 10.2 months. Toxicity was mainly haematologic with 51% of patients experiencing grade 3 or 4 granulocytopenia. Three patients developed deep vein thrombosis. Non-haematologic toxicity, mainly nausea and neurotoxicity, was mild. CONCLUSION: The administration of weekly vinorelbine appears to be a safe treatment for those patients with androgen-independent prostate cancer and poor prognosis features who require chemotherapy. These results provide data for future investigation of vinorelbine in combination regimens.

Adenocarcinoma↗

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.

Adult↗

[Laparoscopic fenestration of lymphoceles after kidney transplantation].

Lymphocele is a relatively frequent complication after kidney transplantation, which impair the passage of urine from the kidney, cause emptying of bladder lymphoedemas of the lower limbs, etc. Percutaneous drainage of lymphocele is associated with a risk of infection and a high percentage of recurrence. Until recently, standard surgical treatment of this complication was open fenestration of the lymphocele into the peritoneal cavity. In their paper, the authors describe their first experience with laparoscopic fenestration of the lymphocele. From May 1998 till April 1999 the authors performed laparoscopic fenestration in 5 patients. In four patients the intervention was successful, in one female patient recurrence of lymphocele was observed, which was later resolved by an open operation. In none of the patients early or late surgical complications occurred, the use of analgetics during the postoperative period was minimal, the length of hospitalisation ranged from 2 to 4 days. The authors consider the discussed method a suitable alternative for treating lymphocele after renal transplantation thanks to its minimal invasivity. It involves practically no load of the sick patients after kidney transplantation.

Adolescent↗

Germline mutation of the RET proto-oncogene in members of Slovak families with multiple endocrine neoplasia 2.

Detection of mutations in RET proto-oncogene in Slovak families from different localities and of different ethnic origin with MEN 2 syndrome is reported. Despite the fact that the same mutation of RET oncogene was found in different family members, the latency period of tumor appearance and their pathogenicity differed substantially. In addition, also different phenotypes of the disease were expressed in various family members having the same RET gene mutation. The data indicate that the mechanism of MEN2 syndrome is not only due to the RET gene mutation, and strongly support the conclusion that additional genetic events are involved in the disease formation.

Adolescent↗

Ultrastructure of the normal adult human female prostate gland (Skene's gland).

The predominant cells of female prostatic glands lining their lumen were found to be tall cylindrical secretory cells with short stubby microvilli, protuberances of the apical cytoplasm, and with bleb formation. Abundant secretory vacuoles and granules, rough endoplasmic reticulum, developed Golgi complexes and numerous mitochondria are characteristic of their active secretory configuration with apocrine (apical blebs) and merocrine (secretory vacuoles and granules) type of secretion. Basal (reserve) cells were seen to be located between the secretory (luminal) cells and the basement membrane. Their ground cytoplasm is dense with rough endoplasmic reticulum and mitochondria. Their nuclei, unlike those of secretory cells, possess more peripheral condensed chromatin, denser dispersed chromatin and sporadic nucleoli. Besides the two basic types of mature prostatic cells intermediary cells were also seen, located between the basal and secretory cells or in their close vicinity. Their cytoplasm exhibits numerous profiles of rough endoplasmic reticulum and free ribosomes. Secretory vacuoles and granules were mostly practically absent (type 1 intermediary cells) so that they resembled basal (reserve) cells. In some of them, however, as in secretory cells, such secretory elements do gradually appear (type 2 intermediary cells). The finding of intermediary cells in the lining of prostatic glands supports the role of basal (reserve) cells in the renewal of cells in glands of the female prostate. The first ultrastructural analysis of the normal female prostate performed by transmission electron microscopy showed that, as in the postpubertal male, the prostatic glands in the adult female display mature secretory and basal cells. The results of the presented study further corroborate the contemporary concept of the female prostate as a functional genitourinary organ.

Adult↗

The incidence of tumours in renal transplant recipients with long-term immunosuppressive therapy.

INTRODUCTION: The incidence of cancers after renal transplantation is significantly higher than in population that have not undergone transplantation. It is increased by a long-term survival of functional graft requiring long-term immunosuppressive therapy. MATERIAL AND METHODS: Since 1972, 620 renal transplantations have been performed for different causes of end stage renal disease. The authors report a group of 18 renal transplant patients (2.9%) who had cancer. Patients with malignancies are reviewed according to their age, sex, type of immunosuppression, interval between transplantation and the diagnosis of cancer, method of treatment and survival. RESULTS: All patients received cadaver kidneys, and secondary transplantation was performed in two patients. Five patients received conventional immunosuppression--azathioprine with prednisone, another 13 patients received cyclosporine with prednisone and/or azathioprine. In 13 males and 5 females (mean age 46.1 years) the malignant disease developed about 62.4 months after renal transplantation. Six patients had epithelial skin cancers (four of them had squamous cell carcinomas and two basal cell carcinomas). Two patients had breast cancer, colorectal carcinoma, renal cell carcinoma and bladder cancer, respectively, one patient had gastric cancer, thyroid carcinoma, carcinoma of tonsilla, and monocytic leukaemia with blastic transformation, respectively. The average survival of patients with malignancies was 20.3 months. Of 17 patients with cancer, 13 underwent surgical treatment, four patients with advanced disease received radiotherapy, hormonal treatment or only symptomatic therapy. In one patient the malignant disease was only discovered at autopsy. Five patients died of progressive malignant disease, four of intercurrent disease. Nine (50%) patients are alive, with no evidence of disease (NED), 31.9 months in average following the diagnosis of malignancy. Three patients returned to dialysis treatment, other 6 patients live with well functioning graft. CONCLUSIONS: In patients surviving long time after kidney transplantation the possibility of development of malignant disease should be considered. Preventive evaluation should guarantee early detection of cancer. Appropriate treatment, without cessation of immunosuppressive therapy, is indicated with the intention to prolong the patients' life with a functional graft and without dialysis treatment.

Drug Therapy, Combination↗

Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe.

Pygeum africanum extract is available as Tadenan in many countries, including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. The present open three-centre efficacy and safety study was conducted according to common protocol at urology clinics in the Czech and Slovak Republics and in Poland, in order to confirm the therapeutic profile of Pygeum africanum in conditions of daily practice, using International Prostate Symptom Score (IPSS) and flowmetry assessments. Men aged 50-75 years and in compliance with the selection criteria (including IPSS > or = 12, quality of life (QoL) score > or = 3, and maximum urinary flow < or = 15 ml/s) were first examined then recalled after two weeks during which no treatment was provided (washout and check of stability). If still compliant, they were entered at this point into a two-month period of treatment with Pygeum africanum extract 50 mg twice daily. There followed a further one-month period without treatment, the objective being to evaluate the persistence of any effects observed during the previous two months of Pygeum africanum administration. The primary efficacy parameter investigated was IPSS; the other efficacy parameters were QoL, nocturnal frequency, maximum urinary flow, average urinary flow, post-voiding residual volume and prostatic volume, after one and two months of Pygeum africanum treatment and one month after stopping treatment. A total of 85 patients were evenly distributed between the three centres and completed the entire study. At inclusion their mean IPSS was 16.17, QoL was 3.60 and nocturia was 2.6 times per night. The changes in subjective scores, IPSS and QoL after the two-month treatment period were highly statistically significant with mean improvements of 40% and 31%, respectively. Nocturnal frequency was reduced by 32% and the mean reduction was again highly statistically significant. Mean maximum urinary flow, average urinary flow and urine volume were also statistically significantly improved, but the modest improvement in post-voiding volume did not reach statistical significance. The improvements, which exceeded those observed with placebo in earlier studies, were maintained after one month without treatment indicating an interesting persistence of clinically useful activity. Prostatic volume and quality of sexual life remained unchanged throughout. No treatment-related adverse effects were observed. In conclusion, under conditions of daily practice, Pygeum africanum extract induces significant improvement in IPSS and uroflowmetry parameters. These positive effects are accompanied by a very satisfactory safety profile with the overall result of a substantial improvement in QoL.

Aged↗

[Problems posed by asymptomatic pheochromocytoma and malignant tumors of the adrenal medulla].

The authors analyse a group of 38 patients with a diagnosis of pheochromocytoma, in particular the topics of atypical symptomatology and malignancy. Three patients did not suffer from any subjective symptoms or other signs of pheochromocytoma ("incidentalomas"). Another three patients, although having giant tumours, only complained of atypical symptoms. Signs suspicious of malignancy were detected in 6 out of 38 patients. The authors recommend a practical approach to modern diagnostic and imaging tools for early primary diagnosis and for the early diagnosis of local recurrence and distant metastases.

Adolescent↗