Age and gender related differences in renal cell carcinoma in a European cohort.

PURPOSE: We evaluated the influence of age on gender related differences in the renal cell carcinoma presentation of patients operated on between 1995 and 2005 in a European country. We also assessed the trend of missing pathological data. MATERIALS AND METHODS: Data on all patients who underwent radical or partial nephrectomy for renal cell carcinoma during 1995 to 2005 in The Netherlands were retrospectively collected from the prospective PALGA (Pathological Anatomical National Automated Archive) database. Patients were divided into 5 cohorts based on age at surgery, including 40 or less, 41 to 50, 51 to 60, 61 to 70 and greater than 70 years. Variables evaluated were gender differences by age, and tumor size, subtype, stage and Fuhrman grade. RESULTS: A higher mean age in women was only observed in those older than 70 years (p <0.001). The male-to-female ratio was 2:1 at ages 41 to 60 years and 1.2:1 at greater than 70 years. Compared to men women had smaller tumors at ages 51 to 60 years (p = 0.03), stage pT3 was less common at age 41 years or greater (p = 0.02), and grade 2 was less common at age 61 years or greater (p <0.001). The incidence of tumors with missing data on stage (14.9%), subtype (52.2%) and grade (47.1%) decreased substantially during the study period (p <0.001). CONCLUSIONS: Older age in women than in men who present to surgery for RCC was only prevalent in those older than 70 years. The male-to-female ratio was almost equal in patients older than 70 years compared to a 2:1 ratio at ages 41 to 60 years. Women presented with fewer pT3 tumors than men at age 41 years or greater. Missing pathological data decreased significantly between 1995 and 2005.

Trends in epidemiology and treatment of upper urinary tract tumours in the Netherlands 1995-2005: an analysis of PALGA, the Dutch national histopathology registry.

OBJECTIVE: To evaluate changes in incidence, distribution of stage and grade as well as surgical treatment of upper urinary tract (UUT) tumours in the Netherlands from 1995 to 2005. PATIENTS AND METHODS: The PALGA registry, a nationwide network and registry of pathology encompassing all hospitals in the Netherlands, was used as primary data source. Pathology reports of all primary surgical procedures or biopsies without further surgical treatment within the next year, of cancer of the renal pelvis or ureter during the period 1995-2005, were included. The number of surgically treated UUT tumours per year, type of treatment and tumour characteristics were recorded. RESULTS: The population consisted of 2321 (67%) men and 1145 (33%) women with a mean age of 68.6 years. The distribution according to side was similar (left 44.1%, right 41.5%), bilateral tumours were rare (0.6%) and most tumours were in the renal pelvis (51.3%). Both the incidence and the incidence rate per 100 000 person-years increased during the study period (P < 0.001). Most urothelial cancers were grade 2 (40.9%) or 3 (41.2%) and stage Ta (30.6%), T1 (18.1%) or T3 (22.8%). There was an increase in grade 3 (P = 0.003) and muscle-invasive (P = 0.003) tumours in men only. Nephroureterectomy was performed in 41.3% of the cases and there was an increasing trend to endoscopic surgery (P = 0.019), although the absolute number was low. CONCLUSION: The incidence of surgically treated UUT tumours increased, with a significant trend towards more advanced disease in men. Most tumours were treated by nephroureterectomy or nephrectomy, although there was an increasing trend to endoscopic surgery.

Changes in the stage and surgical management of renal tumours during 1995-2005: an analysis of the Dutch national histopathology registry.

OBJECTIVE: To evaluate changes in the pathological characteristics, stage of primary renal tumours and their surgical management in the Netherlands during the period 1995-2005. METHODS: Extracts from the records of all patients who had surgery for primary renal tumours in the Netherlands during the period 1995-2005 were reviewed. Data were collected from PALGA, the nationwide network and archive of histocytopathology. The 2002 Tumour-Node-Metastasis and the three-tier Fuhrman grade were used for staging and grading. RESULTS: In all there were 12 471 operations for primary renal masses during the study period. The incidence of surgically removed renal cancers increased from 6.2 in 1995 to 7.5 cases per 100 000 inhabitants (P = 0.005) in 2005. The mean (sd, median) age of the patients was 63.3 (11.9, 65.0) years, with a male-to-female ratio of 3:2. The mean (sd) tumour size of malignant tumours decreased from 7.3 (3.6) to 6.9 (3.7) cm (P = 0.301). The percentage of benign removed tumours remained relatively stable (P = 0.056), with a mean of 5.4% of all resected tumours. There was an increase of grade 1 tumours; the incidence of T1 tumours increased from 36.6% to 44.2%, and advanced tumours decreased from 46.4% to 33.7%, respectively. The percentage of nephron-sparing surgery increased from 3.5% in 1995 to 10.1% (P = 0.003) in 2005, mainly in the T1a tumours. CONCLUSIONS: During the last decade there was an increase in the incidence of surgically treated renal tumours in the Netherlands. Tumours with favourable histopathological characteristics, low stage and grade, accounted for most of this increase. The percentage of surgically removed benign tumours remained stable. The use of nephron-sparing surgery increased during the last decade, especially in T1a tumours.

NADPH production by the pentose phosphate pathway in the zona fasciculata of rat adrenal gland.

Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD), the third enzyme of that pathway, malate dehydrogenase (MDH), and isocitrate dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH production in the cortex of adrenal gland has not been established. Therefore, activity of G6PD, PGD, MDH, and ICDH was localized and quantified in rat adrenocortical tissue using metabolic mapping, image analysis, and electron microscopy. The four enzymes have similar localization patterns in adrenal gland with highest activities in the zona fasciculata of the cortex. G6PD activity was strongest, PGD, MDH, and ICDH activity was approximately 60%, 15%, and 7% of G6PD activity, respectively. The K(m) value of G6PD for glucose-6-phosphate was two times higher than the K(m) value of PGD for phosphogluconate. As a consequence, virtual flux rates through G6PD and PGD are largely similar. It is concluded that G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their activity is localized in the cytoplasm associated with free ribosomes and membranes of the smooth endoplasmic reticulum, indicating that NADPH-demanding processes related to biosynthesis of steroid hormones take place at these sites. Complete inhibition of G6PD by androsterones suggests that there is feedback regulation of steroid hormone biosynthesis via G6PD.

Nephron-sparing surgery and percutaneous biopsies in renal-cell carcinoma: a global impression among endourologists.

BACKGROUND AND PURPOSE: On the one hand, nephron-sparing surgery (NSS) in small renal tumors is a safe and effective alternative to radical nephrectomy. On the other hand, the role of preoperative percutaneous needle biopsies (PNB) remains controversial. The purpose of this study was to evaluate the global current use of NSS in the treatment of renal-cell carcinoma (RCC) and the use of PNB among endourologists. MATERIALS AND METHODS: One thousand questionnaires were distributed during the 23rd World Congress of Endourology and SWL. Six questions regarding NSS and two questions regarding PNB were presented. Two hundred twenty-two questionnaires were returned. RESULTS: Of the respondents, 86.6% perform NSS for small renal tumors, whereas 13.4% perform only radical nephrectomies; 7.5% will consider NSS only in patients with a solitary kidney, and 0.5% will never consider NSS. The techniques for NSS, in descending order of preference, are partial nephrectomy, enucleation, cryoablation, radiofrequency ablation, and high-intensity focused ultrasound. The mean and maximum diameter of the tumor in patients with a normal contralateral kidney for which the urologists perform NSS is 4.0 cm. For a centrally located tumor, NSS is an option for 27.2% of the respondents. Regarding PNB in patients with suspicion of RCC, 55.9% of respondents never obtain renal biopsies in the preoperative assessment and 41.8% obtain them only in rare cases. The majority (90%) prefer histologic over cytologic biopsies. CONCLUSIONS: Nephron-sparing surgery is evolving to a global worldwide standard treatment for small renal tumors. Percutaneous needle biopsy remains a highly debated procedure.

A decade of surgically removed small renal masses in the Netherlands: characteristics and trends in type of surgery and pathologic reporting.

PURPOSE: To assess nationwide the pathologic characteristics and trends in type of surgery and pathologic reporting in surgically managed renal tumors ≤ 4 cm. MATERIALS AND METHODS: A review of all pathologic reports of primary small renal masses operated on in the Netherlands during the period 1995 to 2005 was performed. The data source was a nationwide central archive of histocytopathology (Patologisch Anatomisch Landelijk Geautomatiseerde Archief). Tumors were stratified into three groups: ≤ 2, 2.1 to 3.0, and 3.1 to 4.0 cm. Age, sex, type of operation, and tumor pathology were analyzed. For renal-cell carcinomas, grade (3-tiers Fuhrman) and stage (2002 Tumor, Node, Metastasis) were assessed. Trends in type of surgery (radical or partial nephrectomy [PN]) and pathologic reporting during the study period were analyzed. RESULTS: Of all operated primary kidney tumors, 25.3% were ≤ 4.0 cm. The mean age of the patients was 63.1 years (standard deviation 11.7), and the male/female ratio was 3:2. Only 7.5% were benign tumors, and 9.8% were locally advanced (≥ T3). Tumors ≤ 3.0 cm were more likely to be benign (P = 0.006) and of lower stage (P ≤ 0.001) than tumors of 3.1 to 4 cm. PN was performed in 16.5% of the cases. Grade and subtype were reported in 55% of the cases. The rate of PNs performed increased during the decade. There was a trend in increased reporting of grade and subtype. CONCLUSIONS: A quarter of all the operated primary kidney tumors were ≤ 4 cm. Smaller tumors were more likely to be benign and of lower stage. A cutoff size regarding biologic aggressiveness can be settled at the 3 cm size. The PN rate increased along the decade. Grade and subtype reporting rates remained suboptimal, although a positive trend was noted.

Cytological punctures in the diagnosis of renal tumours: a study on accuracy and reproducibility.

BACKGROUND: Fine needle aspiration (FNA) cytology is under consideration as an auxiliary preoperative diagnostic technique in the diagnosis of renal masses. However, reports for FNA are contradictory with regard to diagnostic accuracy and applicability. OBJECTIVE: To evaluate the diagnostic accuracy and reproducibility of FNA from renal masses. DESIGN: FNAs performed in-bench (hematoxylin and eosin [H&E] stains) from 66 consecutive renal tumours (58 malignant and 8 benign tumours) were presented twice with a 6-mo interval to five pathologists with little experience in renal cytology. Pathologists were blinded for the results of the first round as well for the surgical specimen. The FNAs were stained for Papanicolaou and Giemsa. MEASUREMENTS: Diagnostic accuracy, concordance between smears and surgical specimens, and the generalized kappa for interobserver/intraobserver agreement were calculated. RESULTS AND LIMITATIONS: The number of nondiagnostic and nonconclusive cases ranged from 5-14% in the first and 3-8% in the second round. Overall accuracy varied between 73-89% and 71-91% for the first and second round, respectively. Sensitivity (72-97%) and positive predictive value (PPV) (93-100%) to classify a malignant tumour in both rounds was high. Sensitivity (25-100%) and PPV (28-100%) to classify a benign tumour was lower with a wide confidence interval. Overall concordance in subtyping ranged from 39-70% in the first, and from 52-74% in the second round. Interobserver agreement ranged from fair (kappa=0.039) to substantial (kappa=0.540) for the different subtypes. The intraobserver agreement (mean kappa=0.357, CI 95%=0.304-0.411) was moderate for all pathologists. The low number of benign tumours in this study precludes sound statements regarding the diagnostic accuracy of FNA to classify benignity. CONCLUSION: Despite the lack of experience in renal cytology, all pathologists showed a high diagnostic yield and good overall accuracy in distinguishing between malignant and benign tumours. Concordance in subtyping varied widely among pathologists and was reliable only for clear cell renal cell carcinoma (ccRCC). These results suggest that FNA may have a potential role in the diagnosis of renal tumours although its value in subtyping was limited in our setting.