Are active surveillance criteria sufficient for predicting advanced stage prostate cancer patients?

OBJECTIVES: To examine the treatment outcomes of the prostate cancer (PCa) patients treated by radical prostatectomy (RP) who could be good candidates for active surveillance (AS) and test the confidence and reliability of the AS criterias for predicting advanced stage disease (RP Gleason score≥7 or Pathological stage T3). METHODS: Between 2005 and 2012 the records of the 401 patients who underwent RP with a diagnosis of PCa were examined. Of these patients, 173 were found to be candidates of AS. The inclusion criteria were as follows; clinical stage T2a or less, PSA<10ng/ml, 2 or fewer cores involved with cancer, no single core with 50% or greater maximum involvement of cancer, and no Gleason grade greater than 3 in the specimen. RESULTS: Univariate analyzes revealed that patients with advanced stage disease have higher prostate specific antigen density (PSAD), higher maximum percent (max%) in positive cores and higher RP tumor volumes. In multivariate analyzes PSAD, max% in positive cores and RP tumor volumes were statistically significant determinants for advanced stage disease. ROC analyzes revealed that the RP tumor volume is a good test on advanced stage disease. CONCLUSIONS: Decreasing the cutoff values for PSAD and max% in positive cores should be considered for AS inclusion criteria. If we could calculate the tumor volume before RP, we can minimize the treatment failures (over or undertreatment) of PCa. Perhaps new biopsy protocols, tissue biomarkers, and molecular imaging technology may refine AS criteria.

[Prostatic calculi: silent stones]. / Litiasis prostática: cálculos silentes.

INTRODUCTION AND OBJECTIVES: Prostate stones are frequently encountered during transurethral resection of the prostate in urology practice. We aimed to demonstrate the physical and chemical properties of prostate stones. We also aimed to determine possible relationship between inflammation of prostate gland and prostate stones. METHODS: The consecutive patients (excluding subjects with PSA>or=4ng/ml and urolithiasis), who underwent TURP operation and who were observed to have prostatic calculi during TURP, were included in the study. The prostatic stones obtained from each patient during TURP were analysed for chemical composition and observed under electron microscopy (SEM) for structure and surface morphology. The pathological specimens were assessed by the uropathologist for the final diagnosis and existence and degree of inflammation. RESULTS: Five patients were included in the study. From each patient at least three (range 3-8) samples of stones (diameter varying from 1mm up to 5mm) were obtained. The stones were made of mixed composition of calcium phosphate and calcium carbonate. The stones were found to have lobular surface made up of small spheres under SEM. Histopathological examination of the TURP specimens revealed being prostatic hyperplasia accompanied with inflammation of mild to severe degree. CONCLUSIONS: Prostatic stones are concentrically precipitated calcium stones within the prostatic ductuli with granular grape like morphology. Histopathological inflammation seems to be associated with these prostatic calculi.

Adhesion of erythrocytes to endothelial cells after acute exercise: differences in red blood cells from juvenile and adult rats.

Erythrocytes (RBC) from untrained male Wistar rats and rat glomerular endothelial cells (EC) were used to investigate the effects of acute exercise (speed: 20 m/min, slope: 0, duration: 1 hour) on RBC membrane protein oxidation and adhesion to cultured EC. Experimental animals were divided into juvenile (age 10 weeks) and adult (age 30 weeks) groups for these studies. Immediately following exercise, juvenile rat RBC membrane protein oxidation was significantly enhanced. Adult rat RBC showed significantly higher basal protein oxidation than juvenile RBC; but the level of adult rat RBC membrane protein oxidation was unaffected by exercise. Prior to exercise, adult rat RBC showed significantly higher adhesion to EC than RBC of juvenile rat. There was no difference in plasma fibronectin or fibrinogen levels following exercise. Only juvenile rat RBC showed a significant decrease in sialic acid residue content following exercise. These experiments show that there are changes in RBC-EC interactions following exercise that are influenced by animal age.

Significance of heat shock protein-27 expression in patients with renal cell carcinoma.

OBJECTIVES: To investigate heat shock protein (HSP)-27 expression in patients with renal cell carcinoma (RCC) and examine its biologic significance. HSPs were first defined as proteins induced by heat shock and other environmental and pathophysiologic stresses. They are implicated in protein-protein interactions and are thought to play an important role in cancer. The expression of HSP-27 has been demonstrated in some human tumors. METHODS: The expression of HSP-27 was studied in tumor and normal parenchyma tissue specimens from 76 patients with RCC by immunohistochemistry. The findings were correlated with clinical stage, lymph node metastasis, histologic grade, and survival. RESULTS: Of the 76 RCC tissue specimens studied, the presence of HSP-27 was demonstrated in 73 (96%). The expression was low in 10 patients (14%), intermediate in 38 (50%), and high in 25 (33%). HSP-27 expression was greater in RCC tissue compared with adjacent noncancerous renal tissue (P <0.001). An inverse relationship was found between tumor stage and HSP-27 expression (r = -0.281, P = 0.016). However, no statistically significant difference was observed in progression-free survival with respect to HSP-27 expression. No relationship was found between HSP-27 expression and tumor grade, lymph node metastasis, distant metastasis, or cause-specific survival. CONCLUSIONS: Our data suggest that HSP-27 expression is not a powerful and statistically significant prognostic indicator for disease-free survival for patients with RCC.

Prognostic significance of nuclear morphometry in renal cell carcinoma.

OBJECTIVE: To assess nuclear morphometry as a predictor of prognosis in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: The study included 65 consecutive patients with RCC who underwent radical nephrectomy and were followed up for a median (range) of 80 (27-138) months. Nuclear morphometry was assessed using a computer-assisted image analysis system on histological sections and characterized by five nuclear variables (area, perimeter, major and minor diameter, and form factor). From the patients' records and pathology specimens, the clinicopathological prognostic variables (histological type, Fuhrman grade and pathological stage) were recorded. The proliferative activity was assessed using immunohistochemical staining with Ki-67 antibody. RESULTS: Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher nuclear grade, proliferative activity and advanced tumour stage. They were significant predictors of disease progression and survival, together with grade, stage, sarcomatoid histology and proliferative activity. Of all significant prognostic factors predicting progression-free survival, only stage was independent (T4 vs T1, hazard ratio 6.55, 95% CI 1.63-26.13, P=0.008). CONCLUSION: Although the significance of these preliminary results must not be overstated, nuclear morphometry might provide significant prognostic information in predicting survival and tumours at high risk of progression in RCC.

Osteonecrosis of the accessory navicular bone.

A case of osteonecrosis of the accessory navicular bone is reported. This entity should be kept in mind in the differential diagnosis of painful accessory navicular.

Prognostic significance of nuclear morphometry in superficial bladder cancer.

OBJECTIVE: To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer. STUDY DESIGN: The study included 73 patients with superficial transitional cell carcinoma of the bladder who were followed for a median of 21 months (range, 1-90). Nuclear morphometry was performed by a computer-assisted image analyzer system on hematoxylineosin-stained histologic sections and characterized by five nuclear variables: area, perimeter, major and minor diameter, and form factor. Patient charts and microscopic slides were reviewed to record tumor stage, grade and size. Tumor proliferative activity was assessed by immunohistochemical staining with Ki-67 antibody. RESULTS: None of the morphometric variables showed a significant relation to tumor progression and recurrence. Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher grade and proliferative activity. Mean nuclear area and minor diameter were associated with advanced stage. Of established prognostic factors, only histologic grade was significant in predicting progression. CONCLUSION: The results suggest that nuclear morphometry may be valuable in determining proliferative activity and may be well correlated with histologic grade in superficial bladder cancer. However, like many other potential prognostic factors, it seems to be unreliable in predicting clinical behavior.

Dissection of the ascending aorta due to metastatic carcinoma.

The association of aortic dissection with a malignancy is a rare finding and previous reports are usually those of primary aortic sarcomas. In this report we present a case with typical ascending aorta dissection associated with metastatic carcinoma originating from the lungs. The metastatic infiltration of the vasovasorum of the aorta by carcinoma cells may have caused aortic dissection by decreasing medial strength and integrity. This is a mechanism of aortic dissection that we have not encountered in previous reports.

Expression of pS2 protein and its relation with the Ki-67 proliferative indices and tumor recurrence in superficial bladder carcinomas.

OBJECTIVE: To investigate the expression and possible role of pS2 protein as a predictor of tumor recurrence in superficial transitional cell carcinoma of the bladder and to determine its relation with tumor stage, grade, size, number, recurrence and proliferative activity. METHODS: Paraffin sections of transurethral resection material from 80 patients with superficial transitional cell bladder carcinoma were stained with pS2 and Ki-67 antibodies using the standard streptavidin biotin immunoperoxidase method. Cytoplasmic pS2 staining was scored on a scale of 1-3 and the Ki-67-labelling index was determined as a percentage of positively staining tumor cells. RESULTS: An inverse relationship was found between pS2 expression and Ki-67 index (p<0.001). pS2 expression showed no relation with any clinicopathological prognostic parameters as well as the recurrence rate. The recurrence rate was only associated with increased tumor number (p = 0.05), while the time to first recurrence was significantly related to tumor size, proliferative activity and tumor grade (p = 0.04, p<0.001, and p = 0.03, respectively). On the other hand, higher tumor grade was correlated with increased tumor number, Ki-67 index and tumor stage (p = 0.016, p = 0.006, and p<0.001, respectively). CONCLUSION: pS2 expression is associated with a low proliferative potential of superficial transitional cell carcinoma of the bladder, while it does not seem to be related to the recurrence rate of the tumor and other prognostic factors. Tumor size and proliferative activity may aid in the estimation of the time to the first recurrence.

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder?

OBJECTIVES: To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. METHODS: The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. RESULTS: VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. CONCLUSIONS: Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Metallothionein expression in renal cell carcinoma: subcellular localization and prognostic significance.

PURPOSE: We investigated the immunohistochemical localization of metallothionein (MT) in renal cell carcinoma and determined the potential role of MT expression as a possible prognostic variable for tumor proliferation and progression. MATERIALS AND METHODS: Tumor tissue blocks from 70 patients with renal cell carcinoma who underwent radical or partial nephrectomy were investigated. Mean followup plus or minus standard error was 36 +/- 3 months. Immunohistochemical testing was performed by the avidin-streptavidin method using a monoclonal mouse antiMT antibody. MT staining intensity in samples was evaluated semiquantitatively. The subcellular distribution of MT was also determined. Staining characteristics were compared with the clinicopathological results. RESULTS: MT immunostaining was found in 39 of 70 tumors (55.7%) and subcellulary MT was localized in the cytoplasm, nucleus and cell membrane. The survival of patients with MT immunostaining was significantly worse than that of those with MT negative results (p = 0.02). A significant relationship of higher tumor grade and MT staining intensity was observed in grades I and III (p = 0.01), and grades II and III (p = 0.02) tumors. No association was found of MT expression and pathological stage. Sarcomatoid tumors showed significantly higher MT expression than clear cell, papillary, granular or chromophobe tumors (p = 0.02, 0.001, 0.01 and 0.01, respectively). MT expression was not an independent prognostic variable. CONCLUSIONS: MT over expression seems to be associated with malignant behavior and poor prognosis in renal cell carcinoma. Therefore, MT expression may be considered a useful marker of less differentiated and more aggressive renal cell carcinoma.

Quantification of tumor cellularity and mitotic index in invasive ductal carcinoma of the breast.

OBJECTIVE: To evaluate the use of stereologically estimated tumor cell counts in the mitotic index as well as to investigate its correlation with the currently used method and test the reproducibility of the method. STUDY DESIGN: The stereologic method described by Simpson et al was used to estimate tumor cellularity in 50 invasive ductal carcinomas. Mitotic counts were also performed, and the mitotic index was calculated by the use of estimated tumor cell counts. Estimated cell counts and the mitotic index calculated were compared statistically with the actual cell counts and the traditional mitotic grades, respectively. Interobserver reproducibility of the method was also tested. RESULTS: Stereologically estimated tumor cell counts had a good correlation with actual cell counts (r = .891, P < .001). Besides, the mitotic indices calculated with tumor cell counts (calculated with both estimated and actual cell counts) in the denominator of the fraction of the mitotic index were in agreement with the currently used method (P < .01 for both). There was no statistically significant difference between the counts of two observers (P = .068). CONCLUSION: The suggested method, considering tumor cellularity as an influencing factor, was practical, reproducible and in agreement with the traditional method. This method should be studied in a large group of patients with follow-up data to determine the threshold values for different grades and determine its prognostic value during the disease course.

Tumor volume estimation by the percentage carcinoma method in uterine cervix carcinoma.

OBJECTIVE: To assess the capacity of the percentage carcinoma method to predict tumor volume in cervical carcinoma and generate a mathematical equation for calculation of tumor volume. STUDY DESIGN: Thirteen radical hysterectomy specimens were studied. The actual tumor volume was assessed by stereology. A factor was generated by the formula tumor volume = factor x percentage carcinoma x number of blocks. The percentage carcinoma was calculated by the grid method. Then tumor volume was estimated by the same formula. The relationship between actual and estimated tumor volumes was analyzed by Spearman's correlation. RESULTS: Correlation of the tumor volumes assessed by the two methods was excellent (r = .945) and statistically significant (P = .01). CONCLUSION: Percentage carcinoma assessed by the grid ratio method is highly predictive of tumor volume, but care must be taken not to overstate the importance of our results due to the small number of patients. The prediction of outcome in cervical carcinoma by means of percentage carcinoma should be evaluated in large clinical studies.

Erythropoietin exerts neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/BL mice via increasing nitric oxide production.

Erythropoietin (EPO), produced by the kidney and fetal liver, is a cytokine-hormone that stimulates erythropoiesis under hypoxic conditions. It has been shown that EPO is produced in the central nervous system and its receptor is expressed on neurons. Since EPO has neuroprotective effects in vitro and in vivo against brain injury, we investigated the effect of EPO treatment on locomotor activities of animals, survival of nigral dopaminergic neurons and nitrate levels in substantia nigra and striatum in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of Parkinsonism in C57/BL mice. Our findings suggest that EPO has protective and treating effect in MPTP-induced neurotoxicity in this mouse model of Parkinson's Disease via increasing nitric oxide production.

Proliferative activity, angiogenesis and nuclear morphometry in renal cell carcinoma.

BACKGROUND: Prognostic parameters other than tumor stage and grade are essential for renal cell carcinoma (RCC) patients. This study was undertaken to determine the usefulness of cellular proliferation, angiogenesis and nuclear morphometry in predicting the biological aggressiveness of RCC. METHODS: Surgical specimens of 70 patients with RCC were investigated by conventional histology, Ki-67 immunostaining and stereological assessment of angiogenesis and mean nuclear volume. RESULTS: There was no difference in disease-specific survival with respect to sex, age and histopathological type (except sarcomatoid and other types). The survival was significantly lower and the chance of metastases was higher in the group with higher proliferative activity (P=0.007). There was no relation between angiogenesis, mean nuclear volume, stage and survival. There was a significant relation between both Fuhrman and WHO grades, tumor stage and survival. Histopathological type, grade, angiogenesis and mean nuclear volume failed to predict recurrences and/or metastases. In multivariate analysis, only TNM stage and proliferative activity were found to be independent prognostic factors. CONCLUSIONS: In addition to tumor grade and stage, proliferative activity of a given RCC may have the potential to identify patients with an impaired prognosis.

Premalignant lesions in the kidney.

Renal cell carcinoma (RCC) is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN) is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1) morphological similarity; (2) spatial association; (3) development of microinvasive carcinoma; (4) higher frequency, severity, and extent then invasive carcinoma; (5) progression to invasive cancer; and (6) similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

Prognostic significance of microvascular invasion in localized renal cell carcinoma.

OBJECTIVES: The treatment of localized and even advanced renal cell carcinoma (RCC) is radical nephrectomy. However, 30% of these patients progress after radical nephrectomy. Prognostic factors are needed in order to determine the course of disease in patients undergoing radical nephrectomy. The aim of this study is to study the prognostic significance of microvascular invasion (MVI) in patients who had undergone radical nephrectomy for localized RCC. METHODS: Between June 1989 and February 1999, pathologic sections of the specimens from 41 patients without metastases, nodal involvement or macroscopic venous involvement were investigated for MVI. RESULTS: MVI was observed in 17% of the patients. MVI was related to the grade of the tumor and tumor size (p = 0.032, p = 0.017). In sarcomatoid-type RCC, MVI was more common than in other histologic types (p = 0.003). After a median follow-up of 48 months, the progression rate was 29% in patients with MVI and 17% without MVI (p = 0.001). Median progression time was 3 months in those with MVI and 41 months with no MVI (p = 0.01). The survival rate decreased from 85 to 70% in patients with MVI during a median follow-up of 48 months (p = 0.031). In multivariate analysis, MVI was not found to be an independent prognostic factor. CONCLUSION: Although MVI is closely related to progression and prognosis, in multivariate analysis it was not found to be an independent prognostic factor in localized RCC. We conclude that MVI should also be evaluated together with tumor grade in predicting the prognosis of patients with localized RCC.

Primary non-Hodgkin's T-cell lymphoma of the thyroid gland complicating Hashimoto's thyroiditis: case report.

This case report presents an extremely rare case of primary non-Hodgkin's T-cell lymphoma of the thyroid gland complicating Hashimoto's thyroiditis and discusses the clinical history, findings, treatment, and prognosis. Although the place of surgery in the treatment of thyroid lymphoma is controversial, in this case, surgery followed by three rounds of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone, and radiation therapy to neck and mediastinum were a very effective treatment for the disease so that no relapse has been detected during 3-year follow-up.

Various radiological appearances of angiomyolipomas in the same kidney.

A 21-year-old woman with tuberous sclerosis presented with abdominal distension and flank pain. Imaging studies, including CT and MR imaging, revealed bilateral renal mass lesions, containing fat and suggesting the diagnosis of tuberous sclerosis. However the imaging characteristics of one of these lesions differed from the others with no radiologically detectable fat tissue in this solid lesion suggesting renal cell carcinoma. Histopathological examination of this lesion in the left kidney revealed an angiomyolipoma within minimal fat tissue. The radiological diagnosis of angiomyolipomas with minimal fat tissue remains difficult and the differential diagnosis is discussed.

Ganglion cells in the human prostate.

Prostate carcinoma infiltrating around ganglion cells is claimed to be diagnostic of extracapsular extension because ganglion cells are only found in periprostatic soft tissue. However, the presence of autonomic ganglion cells in the fibrous capsule of the prostate has been reported. In this study, we aimed to define the exact localization of the ganglion cells in radical prostatectomy specimens. Slides of 64 totally embedded radical prostatectomies were reviewed. The ganglion cells were noted as outside the gland if no relation could be defined with prostate capsule or prostatic glands. They were noted as in the capsule when ganglion cells were observed inside the capsule, which was easily and definitely discerned. Ganglion cells were noted as in the prostate when ganglion cells were observed beneath the capsule and in close proximity to the prostatic glands. Also, the ganglion cells were noted as in the capsule if they were observed inside the capsule but not adjacent to the prostatic glands, and as outside the prostate when the capsule could not be easily defined and distant from the prostatic glands. Ganglion cells were observed in the prostate in 12 cases (18.75%). There was no relationship of these ganglion cells with the tumor in the prostatectomy specimens. Ganglion cells were located in the capsule in 14 cases (21.9%). The ganglion cells were observed outside the prostate in the other 38 cases (59.4%). These results show that there may be ganglion cells in the prostate. Therefore, defining ganglion cell invasion by the tumor as extracapsular invasion may lead to staging error and cause erroneous management of the disease. Presence of carcinoma in ganglion cells should be recorded by defining whether these structures are within or outside the prostate gland. Prostate Cancer and Prostatic diseases (2000) 3, 34-36