RESUMO
We are observing the largest worldwide wave of migration ever. Displaced persons usually do not have access to general health care and are faced with a lack of hygienic conditions and infection control while fleeing, which leads to an accumulation of "exotic" infectious diseases. The number of patients with tuberculosis (TB) had declined for many years in Germany; however, increasing numbers of cases have recently been observed. For urologists, of course, the manifestations of urogenital TB (UGTB) are of particular interest. Therefore, the basics regarding diagnosis and therapy of UGTB are discussed in this article and explained using case studies. The second important "exotic" infectious disease that urologists are increasingly facing is schistosomiasis. The larvae (found mostly in stagnant water) penetrate through intact human skin, mature and migrate into the liver, from where they immigrate into the venous capillaries of the intestine, the small pelvis, the bladder wall and the distal ureter, and there cause chronic inflammation. All urologists should be familiar with the diagnosis, therapy and prophylaxis of urogenital schistosomiasis and the oncogenesis of schistosomiasis-associated bladder carcinoma.
Assuntos
Refugiados , Esquistossomose Urinária , Tuberculose Urogenital , Animais , Alemanha , Humanos , Schistosoma , Esquistossomose Urinária/diagnóstico , Tuberculose Urogenital/diagnósticoRESUMO
Infection stones make up approximately 15% of urinary stone diseases and are thus an important group. These stones are composed of struvite and/or carbonate apatite. The basic precondition for the formation of infection stones is a urease positive urinary tract infection. Urease is necessary to split urea to ammonia and CO(2). As a result, ammonia ions can form and at the same time alkaline urine develops, both being preconditions for the formation of struvite and carbonate apatite crystals. When these crystals deposit themselves infection stones form. If these infections are not treated and the stones are not removed, the kidney will be damaged. For stone removal modern methods are available, e.g. ESWL and/or instrumental urinary stone removal. Here especially less invasive methods are preferable. Any treatment must be adjusted to the patient individually. Patients should be examined frequently for recurrent urinary tract infections and stone recurrences and, newly arising infections must be resolutely treated. Good therapy and prophylaxis are possible with present-day treatment modalities.
Assuntos
Cálculos Urinários/complicações , Infecções Urinárias/complicações , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Humanos , Fatores de Risco , Cálculos Urinários/tratamento farmacológico , Cálculos Urinários/microbiologia , Cálculos Urinários/cirurgia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologiaRESUMO
The circadian rhythms of melatonin and 6-sulfatoxymelatonin (aMT6s) were analyzed in serum and urine of young men (YM, n = 8), of elderly patients with benign prostatic hyperplasia (BPH, n = 7) and of patients of similar age with primary prostate cancer (PC, n = 9). The data expressed as concentration and in urine also as hourly excreted quantity were analyzed chronobiologically by the single cosinor method and, subsequently submitted to linear regression analyses. Circadian rhythms were detected in all cases except for the excreted quantity of melatonin. The circadian patterns of melatonin and aMT6s in serum were very similar in the different groups and regression analyses showed close correlations between both variables. MESOR and amplitude were significantly depressed in PC (40-60%) as compared to BPH and YM indicating that the depression of serum melatonin in PC is due to a reduced pineal activity and is not caused by an enhanced metabolic degradation in the liver. Acrophases of serum melatonin occurred between 01:34 and 03:26 h and of serum aMT6s between 03:58 and 04:35 h. Circadian rhythms similar to those of serum melatonin and aMT6s were found in urine, particularly for aMT6s excretion as well as melatonin concentration; the determination of both parameters in overnight urine samples closely correlated with the nocturnal peak of circulating melatonin. These results imply that it is feasible to estimate changes in pineal function of prostate cancer patients by means of non-invasive determination using urinary melatonin and aMT6s.
Assuntos
Ritmo Circadiano , Melatonina/análogos & derivados , Melatonina/metabolismo , Glândula Pineal/fisiopatologia , Neoplasias da Próstata/metabolismo , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The treatment of metastatic renal cell carcinoma presents major unsolved problems. All of the therapeutic options have shown only minimal success rates. In addition to partial clarification of tumour genesis, basic findings regarding the heterogeneity of tumors were made. Options for further therapeutic developments will result from increased knowledge of the pathogenesis of metastatic spread. After the growth of new tumor vessels (angiogenesis) the metastasizing cell must break away from the cell formation (loss of cadherines). By migration it reaches the vessel wall which is made permeable by proteolysis (matrix metaloproteinase). After reaching the target organ, adhesion results (adhesion molecules and integrins) within the vessel system and ex-travasation follows. With stimulation the metastatic cell will grow in the target organ. Growth is subject to the cytokine control mechanism (interleukines). Based on these individual steps, future therapeutic options can be developed. However, the treatment modalities at our disposal today must not be neglected: for example, immuno(chemo)therapy and various radiation therapies as well as metastases surgery.
Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Animais , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/secundário , Moléculas de Adesão Celular/fisiologia , Divisão Celular , Citocinas/fisiologia , Humanos , Integrinas/fisiologia , Metástase Neoplásica , Neovascularização PatológicaRESUMO
Bladder cancer is clinically characterized by a high recurrence rate for superficial tumours up to 70% and by the invasiveness of advanced bladder cancer. To learn more about the biological behaviour of an individual bladder cancer different tumour markers have been investigated. The aim of our study was to compare the potential of aggression of both superficial and invasive bladder tumours by means of the proliferation marker Ki67, the tumour suppressor gene p53, the non metastasizing protein nm23 and the evaluation of DNA ploidy. We examined 36 patients, 28 with a bladder tumour (Ta-T4) and 8 without as a control group. For immunohistochemistry (Ki67, p53, nm23) we took paraffin sections and scored semiquantitatively under a microscope. The DNA cytophotometry was done on bladder washings by evaluating the DNA ploidy of single cells. The results showed that benign tissues were negative for Ki67 and p53 but positive for nm23. The DNA diagnosis was diploid for all benign samples. The superficial bladder cancer (Ta, T1) showed, in comparison to the invasive tumours, significantly lower numbers of aneuploid cells and a higher rate of p53 mutations. On the other hand the invasive tumours (T2-4) were correlated to significantly higher proliferation rates and higher potencies for metastasizing. The combination of the investigated tumour markers allowed a graduation of the biological behavior of an individual bladder cancer. Especially a high p53 mutation rate and a non aneuploid DNA diagnosis were indicators for the recurrence of superficial bladder tumours. Invasive growth of bladder cancer was characterized by high Ki67 proliferation and low nm23 protein binding.
Assuntos
Antígeno Ki-67/análise , Proteínas Monoméricas de Ligação ao GTP/análise , Núcleosídeo-Difosfato Quinase , Fatores de Transcrição/análise , Proteína Supressora de Tumor p53/análise , Neoplasias da Bexiga Urinária/química , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA de Neoplasias/análise , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Nucleosídeo NM23 Difosfato Quinases , Invasividade Neoplásica , Ploidias , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Treosulfan is a bifunctional alkylating cytostatic agent that has mainly been used in the therapy of advanced ovarian cancer. Lately, a growth inhibiting effect could be detected in human renal cell carcinoma-cell lines as well. In vitro, Treosulfan showed an even higher growth inhibition than Vinblastine. MATERIALS AND METHODS: We performed a small clinical phase II study using Treosulfan as a monotherapy in the treatment of metastatic renal cell carcinoma. Treosulfan was given to 15 patients with bidimensionally measurable metastases. RESULTS: 10 patients were evaluable. Side effects were negligeable. A complete or even partial remission was not seen. 4 patients showed no change, whereas 6 were progressive. The average time to progress was short (4 months, range 1 to 12 months). CONCLUSIONS: Since Treosulfan did not lead to a measurable tumor remission in the given dose regimen, it does not seem to be suitable for the therapy of metastatic renal cell carcinoma.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Bussulfano/análogos & derivados , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Bussulfano/efeitos adversos , Bussulfano/uso terapêutico , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Humanos , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Fatores de TempoRESUMO
Development and progression of tumours is generally driven by an accumulation of genetic alterations. In this study we correlated chromosome 17 aneuploidy to invasiveness of bladder cancer by the method of fluorescence in situ hybridisation (FISH) in urinary cytospins. We investigated the value of FISH compared to DNA cytophotometry in the diagnosis of bladder cancer. 39 patients with or suspicious for bladder tumour were analyzed. 19 patients had a bladder tumor at the time of diagnosis, 14 superficial (Ta-T1) and 5 invasive (T2-3). The remaining 20 patients had no tumour at the time of diagnosis, however 9 of them had one in prehistory (Ta-T2). For FISH we used the DNA probe of HER-2/neu located on chromosome 17. DNA image cytometry was performed according to single cell interpretation of Böcking. Our results showed a correlation between HER-2/neu CEP 17 alterations and invasive bladder cancer to the extent of 10-70% aberrant cells for patients with current invasive bladder tumour as well as for patients who had been cured but with as invasive bladder cancer in prehistory. On the other hand, the percentage of aneuploid cells for negative biopsy and superficial tumour was 0-2%. The DNA cytophotometry brought an uniform aneuploidy only for present invasive tumours: negative biopsies, superficial cancer and invasive tumour just in prehistory, showed mixed diploid-aneuploid DNA patterns. Our results showed that for the detection of aberrant tumour cells the method of FISH is more sensitive than DNA cytometry. FISH could provide important information in the prognosis of bladder cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células de Transição/diagnóstico , Receptor ErbB-2/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/secundário , DNA de Neoplasias/análise , Feminino , Citometria de Fluxo , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
A new possibility for improved differentiation between malignant and benign prostatic disease is the determination of free-PSA in the indifferent grey area of total PSA between 2 and 30 ng/ml. In a retrospective study of 106 men with a total PSA between 2 and 30 ng/ml we studied the ratio of free to total PSA. The differentiation between prostatic carcinoma (PCa) and benign prostatic hyperplasia (BPH) was verified by randomised biopsies. PSA was measured with Tandem-E, Hybritech, USA and free-PSA with Tandem-R, Hybritech, USA and Immunite-R, DPC-Biermann, USA. Patients (pts.) with an untreated, virgin PCa releaved a highest quotient free-PSA/PSA lower than 0.25. The highest quotient in pts. with treated PCa was 0.51 and in pts with BPH was 0.52. Therapy of PCa with LHRH-analogues changed free-PSA toward a BPH-profile. Both kits used for free-PSA gave similar results. Our study suggests, that every free-PSA higher than 25% of PSA should not be a valuable, supplementary parameter for pts. with unclear diagnosis.
Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: The evaluate a potential tumor marker for RCC. Tumor formation is generally linked to an expansion of glycolytic phosphometabolite pools and aerobic glycolyticflux rates. To achieve this, tumor cells generally overexpress a special glycolytic isoenzyme, termed pyruvate kinase type M2. To establish the expansion of phosphometabolite pools pyruvate kinase switches between a tetrameric form with high phosphoenol-pyruvate (PEP) affinity and a dimeric form with a lower PEP affinity. The dimeric form is predominant in all tumors that have been investigated and has been termed TuM2Pk. MATERIALS AND METHODS: We studied: a) the expression of TuM2Pk in RCC by immunohistochemistry using a monoclonal antibody recognizing only the mono- or dimeric form of pyruvate kinase, b) the stability of TuM2Pk in serum by measuring TuM2Pk in 3 patients at different times after taking blood with a two-site immunometric assay, c) the a circadiane rhythm of TuM2Pk in blood by measuring levels every 4 hours in 5 patients, d) TuM2Pk- expression in serum (see 2.) in 5 patients by taking blood from tumor-side vena renalis compared to peripherally blood, e) TuM2Pk (see point 2.) in 40 RCC-patients comparing the results with 39 healthy persons and clinical data of RCC, f) the influence of wound healing to TuM2Pk by measuring serum-levels during a period of more than 12 weeks in 6 patients, g) the individual follow up of 4 patients with RCC stage Robson III for more than 2 years. Comparing TuM2Pk-levels to findings of staging by computed tomography. RESULTS: The isoenzyme TuM2Pk could be demonstrated in RCC and their metastases by immunohistochemistry with a monoclonal antibody specific for pyruvate kinase type M2. In normal kidney cells pyruvate kinase type M2 is not detectable. The stability of TuM2Pk was studied in the serum within 30 minutes. No circadian rhythm was found. Most serum TuM2Pk comes from tumor. Serum evaluation in 39 healthy persons was used to determine normal values, with an upper concentration of 28 U/ml of TuM2Pk (95% percentile of normal healthy persons). Serum evaluation in 40 RCC showed a significant difference to healthy persons and a positive correlation with Robson stage and grading No correlation of TuM2Pk was found with histopathological cell type of tumor diameter. After radical nephrectomy normalization of TuM2Pk level was found within 11 weeks in all localized RCC. Continuously elevated serum levels were seen in metastatic RCC. Individual follow-up seems to be possible. CONCLUSION: Initial discrimination is not possible between localized and metastasized RCC using TuM2PK; however, it is possible to differentiate between benign and malignant renal processes; the specificity under these circumstances is 75%. After successful surgery of localized RCC, an elevated TuM2Pk will be normalized within 11 weeks, and will be remain elevated or will increase again in case of RCC-relapse or metastasis. Thus TuM2Pk would appear to be a useful marker for RCC detection and follow-up.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Piruvato Quinase/análise , Anticorpos Monoclonais , Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/patologia , Ritmo Circadiano , Dimerização , Humanos , Imuno-Histoquímica , Isoenzimas/análise , Isoenzimas/sangue , Rim/enzimologia , Neoplasias Renais/sangue , Neoplasias Renais/enzimologia , Neoplasias Renais/patologia , Piruvato Quinase/sangue , Valores de ReferênciaRESUMO
CEA is discussed as a potential tumour marker for carcinomas of the urothelium. However, investigations by means of polyclonal antibodies have shown various cross reactions which are not to be expected with monoclonal antibodies (MAb). Immunohistochemistry was done with the MAb anti-CEA BW 431/26 (Behring), N 1522 (Dako), and C 7292 (Sigma) on 37 carcinomas of the urothelium (grades 1-3). The MAb BW 431/26 showed the best results concerning specificity and sensitivity. In general, immunohistological investigations demonstrated negative or moderate staining reactions. Positive reactions were seen in 32% (12/37) of the carcinomas. Staining intensity for CEA correlated with differentiation grade. On the whole, a maximum of 5% of the tumour cells were CEA positive. Our results indicate that monoclonal anti-CEA antibodies are not usefull as a tumour marker for urothelial carcinomas. For the suitability of CEA for in vitro and for in vivo diagnosis a threshold of CEA positive tumour cells has to be defined.
Assuntos
Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/análise , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Adenocarcinoma/patologia , Anticorpos Monoclonais , Carcinoma de Células de Transição/cirurgia , Neoplasias do Colo/patologia , Humanos , Imuno-Histoquímica , Prognóstico , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/cirurgia , Urotélio/citologia , Urotélio/patologiaRESUMO
Renal Cell Carcinoma (RCC) is characterized by high intratumoral microvascular density (iMVD) and significantly elevated serologic titers of angiogenesis factors, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (vEGF) and angiogenin (Ag). The goal of the present study was to find whether a correlation exists between any of these factors and intratumoral microvascular density (iMVD). Serologic angiogenesis factors were determined directly before nephrectomy of a tumorous kidney in 12 patients (average age: 67.6 years [49-78] with localized clear-cell RCC (Robson I-II) (Quantikine', R&D Systems Europe, Abington, UK). Sections were taken in each case from the microscopically most aggressive area of the tumorous kidney preparations. Staining was carried out with a primary antibody against CD31 (DAKO M 0823, Hamburg, Germany). iMVD was counted at 160x magnification at five "hot spots" 200 x 200 microns in size, and the individual factors were then correlated with the areas of maximum and average iMVD (iMVDmax, iMVD-d). Average concentrations of 38 pg/ml +/- 68 were found for bFGF, 712 pg/ml +/- 791 for vEGF, and 358 ng/ml +/- 97 for Ag. iMVDmax was 20 +/- 11 per area, iMVD-d was 410/mm2 +/- 243. No correlation was found between microvascular density and serologic angiogenesis factors for any parameter. Actual tumor vascularization, expressed as iMVD, was not correlated with the 3 angiogenesis parameters which were studied. On the one hand, this raises the question whether angiogenesis can be measured at all with these parameters; on the other, it remains nuclear whether the continuous process of angiogenesis can be registered at all by chronologic, specific factor analysis.
Assuntos
Indutores da Angiogênese/sangue , Carcinoma de Células Renais/sangue , Neoplasias Renais/sangue , Idoso , Carcinoma de Células Renais/irrigação sanguínea , Fatores de Crescimento Endotelial/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Humanos , Neoplasias Renais/irrigação sanguínea , Linfocinas/sangue , Microcirculação , Pessoa de Meia-Idade , Estatística como Assunto , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
alpha v beta 3 Integrin has been shown in various tumor entities to promote binding to superficial structures of the basement membrane during metastasis. The goal of the present paper was a structural demonstration of this Integrin in renal cell carcinoma (RCC). After removal of paraffin from formalin-fixed tissue, the cells were labelled with the antibody (VNR 147, H. Biermann, Bad Nauheim) using the peroxidase-antiperoxidase method (DAKO Diagnostical GmbH, Hamburg). Evaluation was carried out microscopically and semiquantitatively from missing (-) through moderate (+) to strong (+2) staining. A total of n = 79 RCCs and n = 53 healthy areas were examined. Semiquantitative staining results: there was a grading-dependent increase (+2) of stainability and thus alpha v beta 3 expression. Two of 53 benign specimens showed strong staining, 11 of 53, only weak staining. Four of 18 G1 RCCs showed strong staining, 11 of 18 only weak staining. Results for G2-RCCs: 11 with strong staining, 21 of 40 with weak staining. G3-RCCs: 4 with strong staining, 2 of 7 with weak staining. Of the metastases, on the other hand, 2 of 14 showed strong staining, another 8 of 14 only weak staining. There were no deviations within the histologic (clear-cell, chromophil, or chromophobe) subpopulations. This grading-dependent expression permits the conclusion that the probability of binding to the human basement membrane mediated by alpha v beta 3 Integrin rises with increasing grading, but the already metastatic cell exhibited this Integrin less strongly, since a basement membrane adhesion is no longer necessary for this cell group.
Assuntos
Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Receptores de Vitronectina/análise , Carcinoma de Células Renais/cirurgia , Humanos , Imuno-Histoquímica/métodos , Neoplasias Renais/cirurgia , Metástase Neoplásica , Estadiamento de NeoplasiasRESUMO
Angiogenesis is essential for tumour growth. Mostly hypervasculariced renal cell carcinoma (RCC) usually express angiogenic factors, e.g. basic fibroblast factor (bFGF), vascular endothelial growth factor, and angiogenin (ag). This study was designed to evaluate the improvement of serological angiogenesis-factors, their prognostic relevance and correlation to tumour-grade, -stage and -volume. Measurement of bFGF, vEGF and ag was done with ELISA (Quantikine), R and D-Systems Europe Abbington, United Kingdom. The control group comprised 39 healthy blood donors, RCC-group were 35 patients with different RCC. Survival dates were presented with Kaplan-Meyer-curves, significance was tested with students-t-test. For all angiogenic factors a highly significant difference between the healthy and RCC-group was found. A strong correlation between angiogenic factors and tumor grade, -stage and -volume, was not found, but a trend for each of the angiogenic factors to correlate with grade was seen. No survival benefit was seen between patients with normal angiogenic factor over those with elevated angiogenic levels.
Assuntos
Carcinoma de Células Renais/sangue , Fatores de Crescimento Endotelial/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Neoplasias Renais/sangue , Linfocinas/sangue , Proteínas/análise , Ribonuclease Pancreático , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Metástase Neoplásica , Proteínas de Neoplasias/sangue , Estadiamento de Neoplasias , Prognóstico , Valores de Referência , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
RCC can go hand-in-hand with an elevation of various hepatic proteins. An interrelationship between the IL-6 titer, C-reactive protein (CRP) and the blood sedimentation rate (BSR) has already been proven. The aim of the present study was to study 1) the possibility of differentiating between healthy and RCC patients via IL-6 in the serum and 2) the relationship of IL-6 to hepatic parameters {alkaline phosphatase (AP), gamma-glutamyltransferase (gGT), serum proteins (E'p)} and the usual clinical prognostic parameters (tumor grading, staging). Serum analysis of 38 healthy patients via ELISA (DPC-Biermann, Germany) showed normal values of 1.2 ng/ml for IL-6, with a standards deviation of +/- 1.7 and a peak concentration of 3 ng/ml (specificity: 95%). In 20 RCCs there were IL-6 titers of 10.7 ng/ml +/- 6.56 in the pre-operative serum. The sensitivity of IL-6 was about 90%. The difference was statistically significant (p < 0.0001, Wilcoxon test). For IL-6 there was a positive correlation with the BSR (1-hour value: r = 0.7; 2-hour value: r = 0.6), CRP (r = 0.85), E'p (r = 0.6), and gGT (r = 0.6). No correlation was found between AP, the Robson stage, grading, and IL-6. IL-6 is potentially suitable for differentiating between healthy and RCC patients but is not tumor specific. IL-6 has a strong correlation with all laboratory values which were analyzed except AP thus there is considerable evidence for a cytokine (IL-6) control of the hepatic changes. Since some of the above-named laboratory parameters have prognostic relevance, IL-6 can be regarded as a cumulative prognostic parameter.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/sangue , Interleucina-6/sangue , Neoplasias Renais/sangue , Testes de Função Hepática , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Sedimentação Sanguínea , Proteína C-Reativa/análise , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Estadiamento de Neoplasias , Valores de Referência , Análise de Regressão , gama-Glutamiltransferase/sangueRESUMO
We report on a prospective DNA cytophotometric study of 66 patients with renal tumors, 61 of whom had renal cell carcinoma (RCC) (pT1-pT4, G1-G3). 16 of the patients had a metastasis at the time of diagnosis. Cell material from 1-5 specimens of each tumor was analyzed for intratumoral heterogeneity. The aim of the study was to evaluate the prognostic value of the following DNA parameters: DNA ploidy, DNA grade of malignancy (DNA MG), mean DNA, DNA index, 2c deviation index (2cDI), and 5c exceeding rate (5cER). In this study 21% of the tumors were non-aneuploid, 79% were aneuploid; however, it proved possible to diagnose 38% of the total collective as aneuploid only by analyzing several tumor areas. In five of 61 RCC patients who died during an observation period of 42 months, at least one area of the primary tumor was aneuploid. Aneuploid primary tumors also accompanied the development of metastases and recurrent tumors in four of the 61 RCC patients. Only DNA 2cDI was found to have a significantly positive clinical correlation with metastasis (r = 0.261) during the clinical course. This was not true, however, for the histopathologic parameters. Significantly positive correlations were found between the tumor stages and the following DNA parameters: mean DNA, DNA index, and 5cER. Histopathologic tumor grading showed a significantly positive correlation with DNA MG, mean DNA, and 5cER. Statistically, the mean values of all evaluated parameters were significantly higher in metastasizing and recurrent RCCs than in non-metastasizing carcinomas (p < 0.05; t-test). DNA cytophotometry cannot substitute histopathologic prognosis. However, the analysis of various DNA parameters helps considerably in evaluating both the malignant potential of kidney tumors and the benign parenchyma of tumor-bearing kidneys.
Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , DNA de Neoplasias/análise , Neoplasias Renais/genética , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Feminino , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Chromosome studies were done on six renal cell carcinomas (RCC) and on the corresponding renal parenchymas of the tumor bearing kidneys. Histopathologically, all tumors belonged to the clear cell subtype. All examined parenchymas were pathologically benign. None of the tumor cells showed the typical chromosomal aberrations described for (nonpapillary) RCC, i.e. deletions in the short arm of chromosome #3, or gains in the long arm of chromosome #5. In our series both the tumor and the benign kidney tissues were characterized by loss of chromosomes, especially of the chromosomes #6, #9, #16, #20, and of the Y chromosome. Trisomy of chromosome #7 was found frequently in benign parenchyma cells. The identical chromosomal changes in the tumor and in the parenchyma tissues might reflect rather in vivo mosaics rather than primary chromosomal aberrations in the oncogenetic process of clear cell RCC.
Assuntos
Adenocarcinoma de Células Claras/genética , Carcinoma de Células Renais/genética , Deleção Cromossômica , Neoplasias Renais/genética , Rim/patologia , Perda de Heterozigosidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Idoso , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Mapeamento Cromossômico , Feminino , Humanos , Cariotipagem , Rim/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Cromossomo YRESUMO
Cystinuria is a frequent autosomal recessive transport disorder characterized by defective renal resorption of cystine and other dibasic amino acids. Biochemically, three types of cystinuria can be defined. Here we present our results of screening for mutations in the SLC3A1 gene, which codes for a dibasic amino acid transporter protein and appears to be involved in the pathogenesis of cystinuria type I. Our study population consists of 5 Italian cystinuria type I patients and 10 cystinuric patients as yet unclassified as to clinical type. The latter were of different ethnic origin. In total, we found 13 point mutations and 8 genomic rearrangements in 15 cystinuric patients, i.e., our detection rate was 70% (23/30 chromosomes). Remarkably, in patients known to be suffering from cystinuria type I, the mutation detection rate was only 50%, whereas in patients unselected as to cystinuria type, we found 80% of mutations. Additionally, our results, as with those published in the literature, indicate a possible population specific distribution of mutations: Each of the 4 Greek patients analyzed here showed homozygosity for mutation T216M in exon 3. Analysis of a Yugoslavian patient showed homozygosity for a novel mutation, R365L, in exon 6 (nt1094G > T). Findings from molecular genetic studies, as well as physiological investigations, suggest that there are further genes that play a role in the etiology of cystinuria. Nevertheless, our results show that screening for mutations in the SLC3A1 gene can be a meaningful step toward molecular genetic diagnosis of cystinuria in patients without biochemical classification. As with cystic fibrosis, the finding of specific mutations in particular ethnic populations, suggest that the diagnostic approach should take into consideration a patient's ethnic origins.
Assuntos
Sistemas de Transporte de Aminoácidos Básicos , Proteínas de Transporte/genética , Cistinúria/genética , Glicoproteínas de Membrana/genética , Mutação , Sequência de Bases , Cistinúria/classificação , DNA/genética , Análise Mutacional de DNA , Etnicidade/genética , Frequência do Gene , Rearranjo Gênico , Genes Recessivos , Testes Genéticos , Humanos , Mutação PuntualRESUMO
Male Fü-albino rats were weaned at the age of four weeks and maintained on a vitamin A-deficient diet. When they were 14-18 and 21-26 weeks old, the concentration of uromucoid, calcium and other substances possibly important for the pathogenesis of urinary calculi were determined. Reduced uromucoid excretion with hypercalciuria and reduced phosphate levels were observed. Subsequent examination of the kidneys did not demonstrate the presence of nephrocalcinosis or lithiasis. The relation between vitamin A, the synthesis of uromucoid and AMPS and calcium metabolism in the renal tubules is discussed.
Assuntos
Mucoproteínas/urina , Deficiência de Vitamina A/urina , Albuminúria/urina , Animais , Cálcio/urina , Glicosaminoglicanos/urina , Cálculos Renais/etiologia , Masculino , Fosfatos/urina , Ratos , Ratos Endogâmicos WF , Microglobulina beta-2/urinaRESUMO
Benign prostatic hyperplasia (BPH) is a very common condition affecting over 800,000 American males each year. A standard, effective, and well-proven therapy is prostatectomy. This surgical procedure is used to treat, in the United States, approximately 400,000 BPH patients annually. Major treatment benefit is expected in 70% to 80% of patients. Complications are seen in 20% of the surgically treated patients. Due to the advanced age of BPH patients and the presence of other serious coexisting medical problems, surgical therapy may be difficult to utilize. These patients, who present a high risk for surgery, are in need of alternative treatments. Alternative therapy in BPH patients with clinically important symptoms and signs of urinary outflow obstruction include treatment with pharmacological agents, balloon dilatation, laser beam therapy, transurethral thermal therapy, transrectal microwave hyperthermia, and transurethral microwave hyperthermia. These alternative treatment modalities are currently under intensive study. These new treatment modalities ultimately must be compared with the standard treatment, which is prostatectomy. Due to the unpredictable natural history of BPH, it is desirable that each Phase III study should contain a no-treatment observation-only arm. Adenocarcinoma of the prostate (CaP) has become a tumor, which first in frequency, and second in importance in cancer mortality statistics of American males. Local tumor control rates and long-term survivals, with radical prostatectomy or radiation therapy, have been excellent. There was, however, recent concern regarding a high incidence of microscopic local tumor recurrence following a definitive course of irradiation. Deep regional or intracavitary hyperthermia (HT) with phase steering may be of value as an adjuvant treatment to radiotherapy. This HT may increase the incidence of local tumor control obtained with radiotherapy. Phase I-II clinical studies are currently underway.
Assuntos
Hiperplasia Prostática/terapia , Neoplasias da Próstata/terapia , Antagonistas Adrenérgicos alfa/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Cateterismo/métodos , Ensaios Clínicos como Assunto , Diatermia/métodos , Humanos , Hipertermia Induzida/métodos , Terapia a Laser/métodos , Masculino , Micro-Ondas , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Prostatectomia/normas , Hiperplasia Prostática/classificação , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/fisiopatologiaRESUMO
Previous investigations on Madin Darby Canine Kidney (MDCK) cells demonstrated the protective effect of verapamil against shockwave-induced tubular dysfunction. In the present study, we investigated whether verapamil is also protective against shockwave-induced damage in vivo. Male rates were randomly assigned to three groups: verapamil (N = 18) (Group I), control (N = 18) (Group II), or sham treatment (N = 4) (Group III). Groups I and II were treated with 500 shockwaves to each kidney with the Dornier MFL 5000 at 18 kV. Animals assigned to Group III received only anesthesics. Verapamil was given to the animals in Group I for 5 days starting 1 day before shockwave exposure. Urine was collected for 8 hours the day before and immediately, 1.7, and 28 days after shockwave exposure (SWE) for measurement of volume, osmolality, hemoglobin, protein, N-acetyl-beta-glucosaminidase (NAG), beta 2-microglobulin (beta 2M), sodium, and creatinine. Kidneys were perfused and removed for histologic study 1, 7, and 28 days after SWE in six animals of Groups I and II. Blood was taken in these rats (Day 1 after SWE) for the determination of creatinine and sodium and the calculation of the creatinine clearance (CCr) and the fractional excretion of sodium (FENa). After SWE, there was strong diuresis and significantly increased excretion of NAG and beta 2M in the controls, while urine osmolality decreased. These changes were significantly less pronounced in the verapamil-treated rats. The CCr was higher and FENa lower than in the latter group.(ABSTRACT TRUNCATED AT 250 WORDS)