ABSTRACT
Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins [MMR]) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan-Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5-year overall survival (OS) of 58% and recurrence-free survival (RFS) of 45% was detected. Sequence variations were observed in TP53 (66%), KRAS (21%), BRAF (4%), PIK3CA (4%), FGFR1 (1%), MET (1%), NRAS (1%), and PDGFRA (1%). Gene amplifications were found in EGFR (5%), ERBB2 (2%), and MET (2%). We detected no evidence of MMR-deficiency (MMR-d)/MSI-high (MSI-h), whereas 10 of 63 cases (16%) expressed PD-L1. Therefore, anti-PD-1/PD-L1 immunotherapy approaches might be tested in UrC. Importantly, we found aberrations in intracellular signal transduction pathways (RAS/RAF/PI3K) in 31% of UrCs with potential implications for anti-EGFR therapy. Less frequent potentially actionable genetic alterations were additionally detected in ERBB2 (HER2), MET, FGFR1, and PDGFRA. The molecular profile strengthens the notion that UrC is a distinct entity on the genomic level with closer resemblance to colorectal than to bladder cancer.
Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/pathology , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Microsatellite Instability , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Adenocarcinoma, Mucinous/genetics , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Carcinoma, Signet Ring Cell/genetics , Carcinoma, Signet Ring Cell/pathology , Female , Follow-Up Studies , Gene Amplification , Gene Expression Profiling , Humans , Male , Middle Aged , Mutation , Prognosis , Young AdultABSTRACT
In Hungary and in the developed countries urinary stones occur more often due to nutritional habits, obesity and sedentary lifestyle beside the endocrine and metabolic causes. In the daily urological and family doctor practice prevention should have an important role. Prevention is based not only on body weight control, physical exercise and medical treatment, but on proper diet as well. The nutritional components can change the consistence of urine, causing supersaturation, which is essential in stone formation. Specific nutritional components can either prevent stone formation (increased fluid intake, citrate, magnesium, fruits and vegetables) or either increase stone formation (decreased fluid intake, proteins, carbohydrates, oxalate, salt, increased calcium intake, ascorbic-acid etc). We summarized evidence-based practical dietary suggestions on the primary and secondary prevention of urinary stones. Orv Hetil. 2017; 158(22): 851-855.
Subject(s)
Diet/statistics & numerical data , Drinking Water/administration & dosage , Feeding Behavior , Kidney Calculi/prevention & control , Dietary Supplements , Evidence-Based Medicine , Female , Humans , Kidney Calculi/etiology , Male , Prevalence , Risk Factors , Sodium, Dietary/adverse effects , VegetablesABSTRACT
According to the statistical data of tumor registries the incidence of cancer has increased in the last decade, however the mortality shows only a slight change due to the new and effective multimodal treatments. The aim of our overview article is to present the changes in the survival of the metastatic patients, and to demonstrate which factors influence their prognosis. The improvement of survival resulted in a more active surgical role both in metastases of the bone of the extremities and the pelvis. We present a diagnostic flow chart and current options for the reconstruction of the different regions of the bone and skeleton, and we will discuss their potential advantages, disadvantages and complications. It is evident that apart from the impending and pathological fracture surgery it is not the first choice of treatment but rather a palliative measure. The aim of surgery is to alleviate pain, to regain mobility and improve quality of life. If possible minimal invasive techniques are performed, as they are less demanding and allow fast rehabilitation for the patient, and they are solutions that last for a lifetime. In optimal conditions radical curative surgery can be performed in about 10 to 15 per cent of the cases, and better survival is encouraging. Orv Hetil. 2017; 158(40): 1563-1569.
Subject(s)
Bone Neoplasms/surgery , Fractures, Spontaneous/prevention & control , Bone Neoplasms/complications , Bone Neoplasms/secondary , Disease Progression , Fractures, Spontaneous/etiology , Humans , Orthopedic Procedures/methods , PrognosisABSTRACT
PURPOSE: Urachal carcinoma of the bladder is a rare malignancy. Its histological phenotype is similar to that of primary bladder and colorectal adenocarcinoma. The aim of this study was to explore the expression and prognostic relevance of 6 select protein markers of urachal carcinoma of the bladder, including p53, Ki67, RHAMM, BGN, IMP3 and MMP-7, which were formerly shown to be prognostic in urothelial carcinoma and colorectal adenocarcinoma. MATERIALS AND METHODS: Clinical and followup data were obtained on a total of 26 patients with urachal carcinoma of the bladder treated at 2 university hospitals. Immunohistochemical analysis of p53, Ki67, RHAMM, BGN, IMP3 and MMP-7 expression was performed in samples from 15 patients. Clinicopathological parameters and immunohistochemical results were tested for prognostic value on univariable and multivariable analyses. RESULTS: Followup was 50 months. Five-year overall and progression-free survival was 46% and 32%, respectively. On multivariable analysis a positive resection margin was an independent predictor of poor overall survival (p = 0.025). RHAMM (p = 0.0431), IMP3 (p = 0.0052), Ki67 (p = 0.0006) and p53 (p = 0.0024) expression rates were significantly increased in urachal carcinoma of the bladder cells compared to normal urothelium. IMP3 was elevated in Sheldon tumor stage IIIA compared to IIIB or greater (p = 0.0048). None of the analyzed protein markers was associated with survival. CONCLUSIONS: The independent prognostic value of a positive resection margin underlines the importance of complete surgical removal of urachal carcinoma of the bladder combined with en bloc resection of the median umbilical ligament and umbilicus. Our results in a limited number of samples show that Ki67, p53, RHAMM and IMP3 expression is enhanced but has no prognostic significance in urachal carcinoma of the bladder.
Subject(s)
Biomarkers, Tumor/metabolism , Urinary Bladder Neoplasms/metabolism , Urinary Bladder/metabolism , Adult , Aged , Biglycan/metabolism , Extracellular Matrix Proteins/metabolism , Female , Humans , Hyaluronan Receptors/metabolism , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Matrix Metalloproteinase 7/metabolism , Middle Aged , Prognosis , RNA-Binding Proteins/metabolism , Retrospective Studies , Survival Analysis , Tumor Suppressor Protein p53/metabolism , Urinary Bladder/pathology , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: MicroRNAs (miRNAs) are regulators of gene expression in tumor development and progression. However, their influence on metastasis of clear cell renal cell carcinoma (ccRCC) is less understood. To determine the role of miRNAs in metastatic progression, miRNA expression in primary ccRCC was compared to distant metastases. METHODS: Total RNA of 53 primary ccRCCs, 35 distant metastases from lung, bone, brain, and abdomen, as well as 17 normal kidney tissues was isolated from fresh frozen tissue and formalin-fixed paraffin-embedded (FFPE) samples. The miRNA microarrays were performed based on fresh frozen tissue. Results were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on fresh frozen tissue and FFPE samples. Real-time cell analyses and transwell invasion assays were carried out after transient transfection of microRNA-30c (miR-30c) in cell line 786-O. RESULTS: There were 14 miRNAs differently expressed in metastatic primary ccRCC and distant metastases compared to non-metastatic primary tumors. A strong correlation of miRNAs to progression-free- and cancer-specific 5-year-survival was determined. Specific miRNAs were differently expressed in distant metastases compared to primary ccRCC. A miRNA signature distinguished lung metastases from other metastatic sites. Overexpression of miR-30c increased adherence and decreased migration and invasion in the ccRCC cell line. CONCLUSIONS: MiRNAs are deregulated in metastatic primary ccRCC and could be promising prognostic markers for an early prediction of metastasis. Alterations in miRNA expression characterize distant metastases of different metastatic sites. Furthermore, our study suggests a functional role of miR-30c in metastasis. The miRNAs could be a helpful tool for individual follow-up prediction and personalized therapy selection.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/genetics , MicroRNAs/genetics , Adult , Aged , Biomarkers, Tumor/metabolism , Blotting, Western , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Cell Adhesion , Cell Movement , Cell Proliferation , Female , Follow-Up Studies , Gene Expression Profiling , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Oligonucleotide Array Sequence Analysis , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate , Tumor Cells, CulturedABSTRACT
BACKGROUND: Transitional cell carcinoma (TCC) may mimic renal cell carcinoma (RCC) when it develops in a similar location, therefore, differentiation with imaging techniques might be challenging. Preoperative differentiation may have a significant role indicating the type of surgical treatment (nephrectomy vs. ureteronephrectomy). PURPOSE: To retrospectively analyze the differences in the contrast enhancement of TCC and RCC. MATERIAL AND METHODS: Images of 20 RCC and 12 TCC (mean ages, 62.3 ± 14.1 and 67.4 ± 12.0 years, respectively) were analyzed from patients who underwent multiphase computed tomography (CT) examinations following 1.5 mL/kg non-ionic contrast agent administration. Unenhanced corticomedullary (30-45 s), nephrographic (70-90 s), and excretory (300-480 s) phases were imaged. The attenuation characteristics of RCC and TCC were compared to the attenuation of the normal renal cortex. RESULTS: Significant differences were found in the attenuation ratios between RCC or TCC in the corticomedullary (P = 0.040) and nephrographic (P = 0.004) phases using three regions of interest (ROIs) of 10 mm(2) size. If measuring ROIs comprising the complete tumor lesion instead of three small ROIs, no significant difference was observed in the attenuation ratios between RCC in TCC in any phases. CONCLUSION: Our study reports significant attenuation differences between RCC and TCC in the corticomedullary and nephrographic phases by multiphase CT. The findings underscore the importance of multiphase CT in the differentiation of these two different entities. Using multiple small (three) ROIs is more accurate than measuring the whole tumor attenuation.
Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Transitional Cell/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Aged , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Contrast Media , Female , Humans , Iohexol/analogs & derivatives , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed/methods , Triiodobenzoic AcidsABSTRACT
AIM: To retrospectively analyze patients treated by renal tumor and venous tumor thrombus (VVT) removal and to introduce a less stressful and safer surgical method without thoracotomy in Neves level 3 cases. METHODS: From 2002 to 2011, 33 patients underwent surgery for renal cell cancer combined with tumor thrombus of the inferior vena cava. Preoperative symptoms, tumor-node-metastasis classification of tumors, thrombus extension classified by Neves and Zincke system, types of surgical interventions, complications, postoperative management, and survival results were analyzed. RESULTS: Ten patients had level 1, 17 had level 2, and 6 had level 3 thrombi according to Neves and Zincke. In 5 patients with level 3 thrombi, the liver was mobilized without thoracotomy and in 1 patient endoluminal occlusion was utilized. There was no intraoperative mortality. The median survival time of 10 patients who died during follow-up period was 36.6 months (range, 0-121 months). CONCLUSION: Renal cell cancer complicated with tumor thrombus without metastasis can be curable by performing a complete resection. The thrombus level determines the surgical approach and method. Our results confirm that level 3 caval vein tumor thrombus can be safely surgically treated by laparotomy with liver mobilization. Thoracotomy, use of cardiopulmonal bypass, and hypothermic circulatory arrest can be avoided with adequate liver- and vascular surgery methods.
Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Neoplastic Cells, Circulating , Vena Cava, Inferior/surgery , Venous Thromboembolism/surgery , Adult , Aged , Carcinoma, Renal Cell/pathology , Female , Humans , Kidney Neoplasms/pathology , Laparotomy/methods , Male , Middle Aged , Nephrectomy/methods , Retrospective Studies , Thoracotomy , Venous Thromboembolism/etiologyABSTRACT
BACKGROUND: Complex indeterminate Bosniak category III renal cystic masses are traditionally considered to be malignant in 50%. Our aim was to retrospectively evaluate the attenuation characteristics in multiphase computed tomography (CT) and to determinate the incidence of malignancy based on histological findings on all Bosniak category III renal cystic masses investigated in our department between April 3, 2007 and November 21, 2013. MATERIALS AND METHODS: QUADRIPHASIC MULTIDETECTOR CT IMAGES OF NINETEEN PATIENTS (MEAN AGE: 56.5 ± 16.5 years) with radiologically detected Bosniak category III lesions were reviewed retrospectively. All lesions were surgically removed, and the incidence of malignancy, based on pathological results was determined. RESULTS: Calcification was present in four lesions (21%). The mean largest diameter was 48.7 ± 28.8 mm. All lesions were multilobulated and septated. Of the 19 removed lesions, 16 (84%) were malignant, and 3 (16%) were benign (one inflammatory cyst including a nephrolith, one cystic nephroma and one atypical angiomyolipoma). CT and histological findings of 19 Bosniak III cysts were correlated. CONCLUSION: Our study demonstrated much higher prevalence of malignancy (84%) in radiologically detected Bosniak category III cysts than it has been described before. It may due to the era of modern multidetector CT technology and multiphase protocol.
ABSTRACT
OBJECTIVE: Administration of targeted therapies provides a promising treatment strategy for urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC); however, the selection of appropriate drugs remains difficult. Here, we aimed to establish a routine compatible methodological pipeline for the identification of the most important therapeutic targets and potentially effective drugs for UrC and PBAC. METHODS: Next-generation sequencing, using a 161 cancer driver gene panel, was performed on 41 UrC and 13 PBAC samples. Clinically relevant alterations were filtered, and therapeutic interpretation was performed by in silico evaluation of drug-gene interactions. RESULTS: After data processing, 45/54 samples passed the quality control. Sequencing analysis revealed 191 pathogenic mutations in 68 genes. The most frequent gain-of-function mutations in UrC were found in KRAS (33%), and MYC (15%), while in PBAC KRAS (25%), MYC (25%), FLT3 (17%) and TERT (17%) were recurrently affected. The most frequently affected pathways were the cell cycle regulation, and the DNA damage control pathway. Actionable mutations with at least one available approved drug were identified in 31/33 (94%) UrC and 8/12 (67%) PBAC patients. CONCLUSIONS: In this study, we developed a data-processing pipeline for the detection and therapeutic interpretation of genetic alterations in two rare cancers. Our analyses revealed actionable mutations in a high rate of cases, suggesting that this approach is a potentially feasible strategy for both UrC and PBAC treatments.
Subject(s)
Adenocarcinoma , Urinary Bladder Neoplasms , Humans , Urinary Bladder/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Mutation , Urinary Bladder Neoplasms/pathology , High-Throughput Nucleotide SequencingABSTRACT
Endostatin, the proteolytic fragment of collagen XVIII, is an inhibitor of angiogenesis and tumor growth. Interestingly, elevated circulating endostatin levels have been found to correlate with poor patients' prognosis in several cancers. The aim of this study was to assess the prognostic value of endostatin in bladder cancer (BC) and to gain insight into the mechanisms involved in its production. This retrospective study included a total of 337 patients with BC and 103 controls. Collagen XVIII gene expression was analyzed using real-time PCR (n = 82). Endostatin tissue localization was assessed by immunohistochemistry (n = 27). Endostatin serum (n = 87) and urine (n = 153) levels were determined by ELISA. In 12 cases, both serum and paraffinized tissue samples from the same patients were available. We found decreased collagen XVIII tissue expression and increased endostatin urine and serum concentration in samples of patients with BC compared to controls. High serum endostatin levels correlated with the presence of lymph node metastases and MMP-7 concentrations and were independently associated with poor metastasis-free and disease-specific survival. Immunohistochemical analysis revealed a strong endostatin staining in the wall of tumor associated blood vessels in superficial but not in muscle-invasive BCs. Based on these, we concluded that elevated endostatin levels in patients with BC are the consequence of enhanced extracellular matrix degradation and are independent from collagen XVIII expression. Furthermore, serum endostatin levels may provide prognostic information independent from histopathological parameters and may therefore help to optimize therapy decisions. Loss of endostatin expression in tumor associated blood vessels might represent an important step supporting tumor-induced angiogenesis.
Subject(s)
Endostatins/blood , Extracellular Matrix/pathology , Urinary Bladder Neoplasms/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Collagen/biosynthesis , Disease-Free Survival , Endostatins/urine , Extracellular Matrix/metabolism , Female , Humans , Lymphatic Metastasis , Male , Matrix Metalloproteinase 7/blood , Middle Aged , Neovascularization, Pathologic , Prognosis , Retrospective Studies , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/mortalityABSTRACT
Even during normal pregnancy, significant morphological, functional and hemodynamic changes take place in the kidneys, resulting in a slightly increased proteinuria. However, an abnormal increase, especially if accompanied by hypertension or impaired renal function, requires close maternal and fetal follow-up, as it may predict severe perina-tal complications. Differential diagnosis of proteinuria is diverse, and the primary consideration in clarifying the etiol-ogy is to differentiate between preeclampsia and other possible primary kidney disease. We list all the diseases on the etiological palette that may even mimic the symptoms of preeclampsia, making it difficult to make an accurate diag-nosis. In the case of a 31-year-old gravida, we review the differential diagnosis of progressive proteinuria observed during pregnancy. In addition to the diagnosis of postpartum preeclampsia, renal malignancy was confirmed. We are also looking for the answer whether malignant kidney cancer can be blamed for the clinical presentation that includes hypertension, progressive proteinuria.
Subject(s)
Hypertension , Pre-Eclampsia , Adult , Female , Fetus , Humans , Kidney , Pregnancy , Proteinuria/etiologyABSTRACT
Introduction: This study aimed to construct a radiomics-based machine learning (ML) model for differentiation between non-clear cell and clear cell renal cell carcinomas (ccRCC) that is robust against institutional imaging protocols and scanners. Materials and methods: Preoperative unenhanced (UN), corticomedullary (CM), and excretory (EX) phase CT scans from 209 patients diagnosed with RCCs were retrospectively collected. After the three-dimensional segmentation, 107 radiomics features (RFs) were extracted from the tumor volumes in each contrast phase. For the ML analysis, the cases were randomly split into training and test sets with a 3:1 ratio. Highly correlated RFs were filtered out based on Pearson's correlation coefficient (r > 0.95). Intraclass correlation coefficient analysis was used to select RFs with excellent reproducibility (ICC ≥ 0.90). The most predictive RFs were selected by the least absolute shrinkage and selection operator (LASSO). A support vector machine algorithm-based binary classifier (SVC) was constructed to predict tumor types and its performance was evaluated based-on receiver operating characteristic curve (ROC) analysis. The "Kidney Tumor Segmentation 2019" (KiTS19) publicly available dataset was used during external validation of the model. The performance of the SVC was also compared with an expert radiologist's. Results: The training set consisted of 121 ccRCCs and 38 non-ccRCCs, while the independent internal test set contained 40 ccRCCs and 13 non-ccRCCs. For external validation, 50 ccRCCs and 23 non-ccRCCs were identified from the KiTS19 dataset with the available UN, CM, and EX phase CTs. After filtering out the highly correlated and poorly reproducible features, the LASSO algorithm selected 10 CM phase RFs that were then used for model construction. During external validation, the SVC achieved an area under the ROC curve (AUC) value, accuracy, sensitivity, and specificity of 0.83, 0.78, 0.80, and 0.74, respectively. UN and/or EX phase RFs did not further increase the model's performance. Meanwhile, in the same comparison, the expert radiologist achieved similar performance with an AUC of 0.77, an accuracy of 0.79, a sensitivity of 0.84, and a specificity of 0.69. Conclusion: Radiomics analysis of CM phase CT scans combined with ML can achieve comparable performance with an expert radiologist in differentiating ccRCCs from non-ccRCCs.
ABSTRACT
OBJECTIVE: ⢠To assess the presence of matrix metalloproteinase (MMP)-7 in urine samples of patients with bladder cancer and to investigate the correlation between MMP-7 urine concentration and clinicopathological variables. PATIENTS AND METHODS: ⢠The presence of MMP-7 in the urine of patients with bladder cancer was tested in 32 representative cases using immunoprecipitation followed by western blot analysis. ⢠Urinary MMP-7 concentration levels were analyzed in 132 patients with bladder cancer and 96 controls using an enzyme-linked immunosorbent assay. RESULTS: ⢠MMP-7 levels did not differ significantly between patients with localized bladder cancer and controls (P= 0.174). On the other hand, we detected a fourfold, significantly elevated MMP-7 concentration in urine samples of patients with bladder cancer with regional or distant metastasis (P= 0.003). ⢠Using a threshold value of 6.88 ng/ml, determined by receiver-operating characteristic curve analysis, a specificity of 82% and a sensitivity of 78% were observed. ⢠Western blot analysis revealed that the 55-kDa tissue inhibitor of metalloproteinase 1 complexed MMP-7 is the dominant form of urinary matrilysin. CONCLUSIONS: ⢠MMP-7 is present in detectable amounts in the urine of patients with bladder cancer. Its concentrations are significantly elevated in patients with metastatic disease. ⢠Determination of urinary matrilysin level could help to detect bladder cancer metastasis, and may therefore provide a more reliable prognosis and influence therapy decisions.
Subject(s)
Biomarkers, Tumor/urine , Matrix Metalloproteinase 7/urine , Urinary Bladder Neoplasms/enzymology , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Matrix Metalloproteinase 7/blood , Middle Aged , Prognosis , Sensitivity and Specificity , Urinary Bladder Neoplasms/urineABSTRACT
INTRODUCTION: Prostate cancer is the second leading cause of cancer death among men in developed countries. Estrogen receptor-alpha (ER-α), vitamin D receptor (VDR), and the calcium-sensing receptor (CaSR), partly through their effects on calcium levels are implicated in the proliferation and carcinogenesis in the prostate gland. VDR, ER-α and CaSR genes show polymorphisms in humans that appear to have clinical significance in many pathological conditions, such as prostate cancer. Our aim was to evaluate the role of ER-α (PvuII, XbaI), VDR (BsmI) and CaSR (A986S) gene polymorphisms and serum calcium levels in the pathogenesis of prostate cancer. MATERIAL AND METHODS: Two hundred four patients with prostate cancer and 102 healthy controls were recruited into a hospital-based case control study. After genotyping, the relationship between the individual genotypes and prostate cancer was investigated. RESULTS: Both the ER-α XbaI and the VDR BsmI polymorphisms were significantly related to the risk of prostate cancer. An age adjusted logistic regression limited to controls and patients not receiving bisphosphonate therapy showed that higher corrected serum calcium and the VDR Bb/BB genotypes independently increased the risk of prostate cancer. CONCLUSIONS: ER-α XbaI and VDR BsmI genetic polymorphisms had a significant association with the risk of prostate cancer. Both VDR BsmI genotypes and serum calcium levels were independently related to the risk of prostate cancer, suggesting an influence of VDR on the development of this malignancy.
Subject(s)
Calcium/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/genetics , Receptors, Calcitriol/genetics , Receptors, Calcium-Sensing/genetics , Receptors, Estrogen/genetics , Aged , Aged, 80 and over , Case-Control Studies , Genetic Predisposition to Disease/genetics , Genotype , Humans , Logistic Models , Male , Middle Aged , Polymorphism, Genetic/genetics , Prostatic Neoplasms/physiopathology , Risk FactorsABSTRACT
AIM: Follow-up and review of patients who underwent surgery for renal cell cancer combined with tumor thrombus of the inferior vena cava at the Department of Urology Semmelweis University, Budapest, Hungary. MATERIAL AND METHODS: From l998 to 2010 twenty one patients underwent surgery for renal cell cancer combined with tumor thrombus of the inferior caval vein. Preoperative symptoms, TNM classification of the tumors, types of surgical interventions, complications, postoperative management and survival results were involved in the analysis. Mean follow-up period was 39 months, ranging from 3 to 101 months. RESULTS: In five cases of level 3 thrombi the liver was mobilized without thoracotomy, and endoluminar occlusion was applied in one case. Intraoperative mortality was 9,5%. Survival time of patients with distant metastases was 12.1 months (3-9). Three patients without metastases died in the follow up period, their survival time was 26.7 months ranging from 22 to 31 months. Eight patients (73%) were alive at the time of the last follow-up. The mean survival time was 5.6 years ranging from 39 to 101 months. CONCLUSION: Our results support that level 3 caval vein tumor thrombus can be removed by less aggressive surgical approach and underline the benefit of the surgical intervention without thoracotomy.
Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Nephrectomy , Thrombectomy , Vena Cava, Inferior/surgery , Venous Thromboembolism/etiology , Venous Thromboembolism/surgery , Adult , Aged , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Female , Follow-Up Studies , Humans , Intraoperative Complications/etiology , Kidney Neoplasms/complications , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Lymph Node Excision , Male , Middle Aged , Neoplasm Staging , Neoplastic Cells, Circulating , Nephrectomy/methods , Reoperation , Survival Analysis , Thoracotomy , Thrombectomy/adverse effects , Thrombectomy/mortality , Tomography, X-Ray Computed , Treatment Outcome , Venous Thromboembolism/mortalityABSTRACT
OBJECTIVE: To investigate the patterns of expression of the junctional proteins beta-catenin and claudins in different prognostic groups of patients with prostatic cancer, to determine their value as prognostic markers. PATIENTS AND METHODS: We evaluated the samples of 30 patients who had a radical prostatectomy for organ-confined cancer (pT2N0M0), men with clinically advanced cancer, and a control group with benign prostatic hyperplasia. Using immunohistochemistry applied to tissue microarrays, each group was evaluated for claudin-1, -2, -3, -4, -5, -7, -8 and -10, and beta-catenin expression. RESULTS: There were differences among the three groups in the expression of claudin-1 (P = 0.001), -2 (P = 0.014), -3 (P = 0.027), -4 (P = 0.001), -8 (P = 0.001) and beta-catenin (P = 0.002), regardless of Gleason score. By contrast, claudin-5, -7 and -10 patterns were not significantly different among the groups. Furthermore, claudin-1 (P = 0.014) and -4 (P = 0.004) could be used to distinguish between those patients who had metastases and those who did not. CONCLUSIONS: The pattern of claudin expression could be a novel diagnostic marker in re-classifying adenocarcinomas, and an additional sensitive predictive factor for a clinically poor prognosis. Our results suggest that patients with organ-confined and advanced cancer are subsets with distinct claudin expression profiles, and that claudin-4 is related to cellular differentiation in prostate cancer, which is not only the receptor molecule for the Clostridium perfringens enterotoxin, and thus a theoretical future therapeutic target for prostate cancer, but also a marker of progression.
Subject(s)
Biomarkers, Tumor/metabolism , Claudins/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , beta Catenin/metabolism , Aged , Case-Control Studies , Disease Progression , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Prostatectomy , Prostatic Neoplasms/surgery , Tissue Array AnalysisABSTRACT
CASE REPORT: A renal cell cancer patient with late onset of multiorgan metastases showed an unusually long survival following surgical resection. Femoral metastasis appeared 11 years, and contra lateral kidney and adrenal gland metastasis 19 years after the primary nephrectomy, respectively. Following the resection of the femur and implantation of endoprosthesis and removal of adrenal gland and partial nephrectomy, the patient was disease-free 20 years after the first diagnosis of cancer. CONCLUSION: The long survival and successful treatment underline the importance and efficiency of radical metastasectomy even in the case of late onset multiorgan metastases of renal cell cancer. The life expectancies are better in the late onset of bone metastasis following the nephrectomy. The very late onset of metastases in this case shows however the importance of lifelong follow up.
Subject(s)
Adrenal Gland Neoplasms/secondary , Bone Neoplasms/secondary , Bone Neoplasms/surgery , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/secondary , Adrenal Gland Neoplasms/surgery , Carcinoma, Renal Cell/surgery , Critical Pathways , Femur/pathology , Femur/surgery , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm MetastasisABSTRACT
UNLABELLED: Inverted papilloma of the urinary bladder is a rare entity. According to literature data, this disease is not malignant, and has low recurrence rate. Authors studied cases detected at the Urology Department and Urooncological Centrum at Semmelweis University in the last 11 years. They aimed to find out the rate of inverted papilloma recurrences, and transformations into malignant bladder cancer. MATERIALS AND METHODS: Thirty patients with histologically proven inverted papilloma were followed after transurethral resection of bladder, which meant urine tests every three months, abdominal ultrasound and cystoscopy. After a year, these examinations were done in every six months. RESULTS: Three patients presented transitiocellular carcinoma (17, 60, 92 months later) during this period. In one case, inverted papilloma and transitiocellular tumor (pTa G1) were detected. In one patient, inverted papilloma was found by control cystoscopy after transurethral resection of bladder (pT1 G2) and local chemotherapy 15 months later. CONCLUSIONS: Based on authors' experience, inverted papilloma of the urinary bladder is a benign lesion, but malignant changes or concomitant transitiocellular tumor may occur, thus follow-up is needed. Although references are not standardized, authors suggest following patients with inverted papilloma as a primary (pTa G1) bladder cancer.
Subject(s)
Neoplasm Recurrence, Local/pathology , Papilloma, Inverted/pathology , Papilloma, Inverted/surgery , Precancerous Conditions/pathology , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Cystoscopy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Precancerous Conditions/surgery , Prognosis , Prospective Studies , UrethraABSTRACT
OBJECTIVES: Our aim was to predict progression of non-muscle-invasive bladder urothelial carcinomas (NMIUCs) into muscle-invasive disease by assessing cytogenetic abnormality of tumors with a new UroVysion scoring system. METHODS: Seventy-five bladder cancer cases (including 57 NMIUCs) were classified according to the quantitatively assessed degree of UroVysion-detected chromosomal abnormalities into urine fluorescence in situ hybridization score (UFS) groups: UFS I, II, and III. Cox time-to-event, Kaplan-Meier, and C-statistics analyses were performed. RESULTS: UFS proved to be an independent prognostic factor of progression-free survival (PFS) and time to progression (TTP). NMIUCs with UFS III had a 34.05-fold increased hazard for progression to muscle-invasive cancer (TTP; 95% confidence interval, 5.841-198.5; P < .001) in comparison with UFS I to II cases. The addition of UFS to conventional risk scores increased the C-index for PFS and TTP. CONCLUSIONS: UFS can indicate an increased risk for progression into muscle-invasive disease in patients with NMIUC and improves prognostic accuracy of the current clinical risk assessment systems.
Subject(s)
In Situ Hybridization, Fluorescence/methods , Urinary Bladder Neoplasms/genetics , Disease Progression , Humans , Prognosis , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/mortalityABSTRACT
Cisplatin-containing chemotherapy represents the first-line treatment for patients with locally advanced or metastatic muscle-invasive bladder cancer. Recently, novel therapies have become available for cisplatin-ineligible or -resistant patients. Therefore, prediction of cisplatin response is required to optimize therapy decisions. Syndecan-1 (SDC1) tissue expression and serum concentration may be associated with cisplatin resistance. Thus, pre-treatment serum levels of SDC1 and its expression in chemo-naïve tissues were assessed in 121 muscle-invasive bladder cancer patients who underwent postoperative platinum-based chemotherapy. SDC1 concentrations were evaluated by ELISA in 52 baseline and 90 follow-up serum samples and tissue expressions were analyzed by immunohistochemistry in an independent cohort of 69 formalin-fixed paraffin-embedded tumor samples. Pre-treatment SDC1 serum levels were significantly higher in lymph node metastatic (p = 0.009) and female patients (p = 0.026). SDC1 tissue expression did not correlate with clinicopathological parameters. High pre-treatment SDC1 serum level and the presence of distant metastasis were independent risk factors for overall survival (Hazard ratio (HR): 1.439, 95% Confidence interval (CI): 1.003-2.065, p = 0.048; HR: 2.269, 95%CI: 1.053-4.887, p = 0.036). Our results demonstrate an independent association between high baseline serum SDC1 concentration and poor survival in platinum-treated patients. Analyzing baseline serum SDC1 levels may help to predict platinum-containing chemotherapy and could help to optimize therapeutic decision-making.