Association between lower urinary tract symptoms and sexual dysfunction in Taiwanese men.

The study investigated the association between lower urinary tract symptoms (LUTS) and sexual dysfunction in ageing men. It was a cross-sectional study in an unselected consecutive sample of 398 men aged >40 years attending a urology clinic. LUTS and sexual function were assessed by validated symptom scales, including the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-5 (IIEF-5). Clinically the severity of total and obstructive IPSS showed no significant correlation with age, but irritative IPSS is statistically correlated with age (P < 0.05). The prevalence of moderate to severe ED (IIEF-5 < 12) was significantly associated with LUTS severity (P < 0.05) and the severity of IIEF-5 correlated significantly with age (P < 0.01). A consistent inverse correlation was found between IIEF-5 and IPSS severity across the age groups, with the strongest effect within aged 60 to 69 years (r = -0.286, P < 0.01). The irritative IPSS showed a significant correlation with IIEF-5 severity across all age groups. These results reveal a significant correlation between LUTS and the severity of ED, especially on the irritative domain.

Anti-fas activating antibody enhances trophoblast outgrowth on endometrial epithelial cells by induction of P38 MAPK/JNK-mediated apoptosis.

In species with hemochorial placentation, such as the mouse and human, trophoblast cells of the implanting blastocyst induce apoptosis and displace endometrial epithelial cells (EEC) to cross the luminal epithelium of the endometrium. Since Fas and Fas ligand (FasL) are expressed in EEC and trophoblast cells respectively and mitogen-activated protein kinases (MAPKs) mediate Fas-induced apoptosis, the roles of Fas/FasL and MAPK signaling in trophoblast-EEC interactions were studied. By co-culturing BeWo trophoblast spheroids with RL95-2 EEC monolayers to mimic blastocyst-endometrial interactions, we found that trophoblast spheroid outgrowth on EEC was significantly enhanced by anti-Fas activating antibody. Since anti-Fas activating antibody had no effect on spheroid expansion on EEC-free culture surfaces, its enhancing effect on spheroid outgrowth on EEC may be mediated by acting on EEC to facilitate trophoblast-induced EEC apoptosis and displacement. Valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (VAD-FMK) staining showed that the percentage of apoptotic EEC at the spheroid-EEC interface was markedly increased by anti-Fas activating antibody. Moreover, the pancaspase inhibitor benzyloxycarbonyl-VAD-FMK was able to suppress the enhancing effect of anti-Fas activating antibody on spheroid expansion on EEC. Upon anti-Fas activating antibody stimulation, both p38 MAPK and c-Jun NH(2)-terminal kinase (JNK) were activated. Furthermore, the anti-Fas activating antibody-enhanced EEC apoptosis and spheroid expansion on EEC were significantly inhibited by the p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125. Our results establish that anti-Fas activating antibody could activate p38 MAPK and JNK to induce EEC apoptosis, thereby promoting trophoblast outgrowth on EEC.

Urinary cell-free DNA as a potential tumor marker for bladder cancer.

The objective was to assess the possibility of measuring urine creatinine (UCr)-adjusted urinary cell-free (ucf) DNA concentration as a noninvasive screening tool for bladder cancer. Using PicoGreen-based detection, the ucf-DNA/UCr concentration was quantified in urine supernatant specimens from 46 bladder cancer patients and 98 controls and compared to 400-bp real-time PCR-based detection, which detected the amplification of 400-bp beta-actin (named 400-bp ucf-DNA/UCr). The mean concentrations for both PicoGreen and 400-bp ucf-DNA (ng/mL)/UCr (mg/dL) were significantly higher in bladder cancer patients than in controls: 15.28 vs 6.68 (p<0.001, t-test) and 14.98 vs 1.07 (p<0.001), respectively. Among different stages and grades, no significant difference was found between these two methods. The areas under the ROC curves of PicoGreen and 400-bp ucf-DNA/UCr were 0.571 (95% confidence interval, 0.451-0.692) and 0.805 (95% confidence interval, 0.713-0.896), respectively. In 400-bp ucf-DNA/UCr, the best sensitivity and specificity were 86.1% and 72.0% at the cutoff value of 0.0645. These data indicated that 400-bp ucf-DNA/UCr is more reliable for bladder cancer detection than PicoGreen. In conclusion, our results suggest that ucf-DNA/UCr can be used as a potential tumor marker for bladder cancer, especially for detecting longer DNA fragments.

Complications following combined transrectal ultrasound-guided prostate needle biopsies and transurethral resection of the prostate.

In order to evaluate safety and morbidity aspects of additional systematic prostate biopsies, we have conducted a retrospective review of patients who had undergone transurethral resection of the prostate (TUR-P) combined with additional systemic prostate needle biopsies at the Chang Gung Memorial Hospital. To this end, the records of 80 men presenting consecutively at our institution between February 2001 and January 2004 inclusively were examined. These 80 individuals included patients experiencing obstructive voiding symptoms and those featuring suspicious screening parameters, all of whom were to undergo transurethral resection of the prostate for symptomatic benign prostatic hyperplasia (BPH), all procedures being performed by a single surgeon. A total of 20 (25%) specimens were found to be positive for prostate cancer. Cancer was detected in the transrectal prostate biopsy specimen of 16 of 57 men (28%) who had not undergone a previous prostate biopsy, and for four of 23 (17%) who had undergone at least one previous (benign) biopsy. Mild complications associated with transurethral prostrate resection, such as hematuria and hemospermia, were reported frequently, featuring rates of 10% and 2.5%, respectively; more severe complications being noted far less frequently. Fever, usually of a low grade, was observed post-operatively for six (7.5%) patients, but a prompt return to normal temperature following antibiotic treatment for one day was revealed. Four (5%) patients remained admitted to the hospital for a prolonged period following surgery. A review of the literature concerning transrectal biopsies and TUR-P has shown that surgery-associated complication rates are slightly lower than was the case for our study. Additional systematic prostate biopsies for patients undergoing TUR-P would appear to be a relatively safe treatment procedure. Identification of risk factors for post-surgery complications might further improve the safety of the screening procedure.

Malignant phyllodes tumor of the prostate.

This is a report of a 70-year-old man with malignant phyllodes tumor of prostate. The retropubic prostatectomy was done. The stroma of the tumor was cellular and composed of elongated cells with spindle shaped nuclei and fragmented bizarre giant cells. After recovery from surgery, prophylatic radiotherapy was given over 2 months. A case report of a patient treated at our medical center and a review of the literature was done.

Probability based diagnostic biopsy specimens as predictors of tumor grade and stage found.

The Gleason score of prostatic adenocarcinoma in biopsy specimens was compared with the Gleason score of corresponding radical prostatectomy specimens from 78 patients with localized prostate cancer. Grading errors were found to be significant for well-differentiated (Gleason score 2-4) tumors. The accuracy was 6 (23%) for Gleason scores of 2-4 on needle biopsy. All of the Gleason scores of 8-10 on needle biopsy were graded correctly. When the preoperative Gleason score was <7, 20 (37%) patients had organ-confined lesions, while when preoperative Gleason score > or = 7, 5 (21%) patients were confined to the prostate. Discrepancies between the Gleason score of the biopsy material and prostatectomy specimens were larger for biopsy specimens with low Gleason scores than for biopsy specimens with high Gleason scores. Large differences existed between the Gleason histologic scores of the biopsy and prostatectomy specimens when only a single microscopic focus of the tumor in the biopsy specimen is low grade. Consequently, when tumor grade influences the clinical management of prostate cancer, patients with limited biopsy material, provided this material is not poorly differentiated, should probably undergo repeated biopsy to reduce the likihood of tumor sampling error. This awareness influences treatment policy, particularly for the watchful waiting criteria of prostate cancer.

Testosterone modulates mitochondrial aconitase in the full-length human androgen receptor-transfected PC-3 prostatic carcinoma cells.

In vitro studies indicated that dihydrotestosterone (DHT) stimulates the enzymatic activity of the mitochondrial aconitase (mACON) in androgen-sensitive prostatic carcinoma cells, LNCaP. Cell proliferation assay determined that DHT doubles the optimal proliferation response of LNCaP cells. The androgen-insensitive human prostatic carcinoma cells, PC-3, were overexpressed in the human androgen receptor to assess the involvement of the native androgen receptor in the regulation by DHT of mACON gene expression. A stable-transfected clone that expresses the full-length androgen receptor was selected and termed PCAR9. The results revealed that DHT-treated PCAR9 cells paradoxically not only reduced the enzymatic activity of mACON but also blocked the biosynthesis of intracellular ATP attenuating cell proliferation. Transient gene expression assay indicated that DHT divergently regulates the promoter activity of the mACON gene in LNCaP and PCAR9 cells. This study suggested that DHT regulates mACON gene expression and the proliferation of cells in a receptor-dependent model through modulation by unidentified non-receptor factors.

Minilaparotomy radical retropubic prostatectomy for prostate cancer.

Radical prostatectomy is still the gold standard for treating patients with clinically localized cancer. A total of 33 consecutive patients underwent minilaparotomy radical prostatectomy by a single surgeon. The minilaparotomy radical retropubic prostatectomy was performed via an eight-centimeter lower midline incision and a Book Walter retractor for surgical assistance. Mean patient age was 65 years (range 47 to 74). Tumor stages were observed as 12.1% of total for T1c, 21.2% for T2a, 45.5% for T2b, 6% for T3a and 15.2% for T3b. Satisfactory continence was achieved in 80% of the patients. 85% of patients revealed a prostate-specific antigen at a serum concentration of less than 0.2 ng/ml. Minilaparotomy radical retropubic prostatectomy compares favorably with standard radical retropubic prostatectomy.

Hematuria from left internal pudendal and obturator arterial bleeding following sexual intercourse.

Bladder tamponade is an uncommon clinical symptom among men who experience suffering related to sexual intercourse. The authors report on a 46-year-old man with this symptom 4-5 years before hospitalization. Angiography confirmed the presence of left pudendal and obturator arterial bleeding, and embolotherapy of the internal pudendal and obturator arteries was performed. There was no mortality, or limb loss or loss of sexual potency at follow-up.

Intractable bladder tamponade due to left internal pudendal and obturator arterial bleeding induced by erection: a superselective arteriography followed by transcatheter arterial embolization.

Bladder tamponade is an uncommon clinical symptom among men suffering during sexual intercourse. The authors report on a 46-year-old man for whom this symptom appeared 4-5 years prior to hospitalization. Angiography confirmed the presence of left pudendal and obturator arterial bleeding, and embolotherapy of the internal pudendal and obturator arteries was performed. There was no mortality, or limb loss or sexual potency loss at follow-up.

The 99mTc-DMSA renal scan and 99mTc-DTPA diuretic renogram in children and adolescents with incidental diagnosis of horseshoe kidney.

A prospective study was conducted to determine the possibility of obstructive hydronephrosis in horseshoe kidney found incidentally in school children and adolescents by using a radionuclide diuretic renogram. In a 2-year period, 22 school children and adolescents with horseshoe kidney were found in a mass renal sonography survey. They each underwent a 99mTc dimercaptosuccinic acid renal cortical scan to confirm the horseshoe kidney. Each diuretic renogram was performed with the patient in the supine position to rule out obstructive hydronephrosis. The patients were advised to empty their bladders before the intravenous injection of furosemide (1 mg x kg(-1)). The half-time for the clearance of radioactivity from the renal pelvis were calculated. Of the 22 patients, asymmetrical renal cortical function between the two kidneys was found in 14 (63.6%). Eleven kidneys (11/44, 25%) showed stasis of radioactive urine in the renal pelvic region prior to injection of furosemide. There was no incidence of bilateral hydronephrosis in these 22 patients. Only one kidney (1/44, 2.3%) showed obstructive hydronephrosis and five showed clearance of radioactive urine stasis from the renal pelvis immediately after standing up for voiding. There is a low percentage of obstructive hydronephrosis in these cases of horseshoe kidney found incidentally in children and adolescents. A follow-up cohort study on these patients would be valuable for monitoring the development of complications.

Improvement of practice performance in urological surgery via clinical pathway implementation.

The purpose of this study was to compare performance measurements to evaluate the effects of clinical pathway implementation on improving practice performances in urology. Since April 1997, a total of 18 clinical pathways have been created in the urology department. Of these clinical pathways, six were implemented for endoscopic surgery, and four and eight were for minor and major surgery, respectively. Eight prominent performance measurements, which were identified as representative indicators of the practice performances, were selected in endoscopic surgery, five in minor surgery, and 11 in major surgery. Between April 1997 and March 1999, 2,883 consecutive patients, who underwent endoscopic surgery, minor surgery, and major surgery, were evaluated herein. The treatment results for patients in the first and second years of clinical pathway implementation were compared to those from the year preceding the implementation. In endoscopic surgery, five of the eight performance measurements improved significantly in the first year of implementation. Notably, three of the five improved performances continued to improve in the second year. Similarly, in minor surgery, four of the five performance measurements improved significantly following 2 years. Finally, in major urological surgery, six of the 11 performance measurements also improved significantly after 1 year; four of which continued to improve during the second year. Therefore, we conclude that patient care, which is based on the implementation of clinical pathways, can improve practice performances and facilitate medical care.

Diagnosis and treatment of pyogenic psoas abscess in diabetic patients: usefulness of computed tomography and gallium-67 scanning.

OBJECTIVES: To examine retrospectively the clinical presentations, microbiologic characteristics, and treatment outcomes of psoas abscess in patients with diabetes mellitus (DM) and to assess the usefulness of computed tomography and gallium-67 scanning in its early diagnosis. METHODS: During a 9-year period, psoas abscesses in patients with DM were collected at a medical center. The clinical history and associated etiologic factors, microbiologic results, clinical outcomes, and hospitalization days were recorded. The use of imaging in the diagnosis of psoas abscess and other concomitant infectious lesions was also studied. RESULTS: Fifteen patients with DM and psoas abscess (13 women and 2 men; mean age 58.7 +/- 9.0 years) were found. The most frequent symptom was fever (12 of 15). Of the six different microorganisms that grew in the blood and/or abscess cultures, Staphylococcus aureus was the most frequent (7 of 15). The most commonly associated pathologic finding was vertebral osteomyelitis (5 of 15). Computed tomography and/or magnetic resonance imaging confirmed the diagnosis of psoas abscesses in all 15 patients. The gallium-67 scan especially aided in the diagnosis of the patients who had initially been diagnosed as having fever of unknown origin (4 of 5) and in the diagnosis of concomitant lesions (9 of 12). Debridement or surgical drainage of the abscess was done in 12 patients. All the patients received adequate antibiotic treatment. However, the mortality rate was 20%. The average hospitalization stay was 42.7 +/- 20.7 days. CONCLUSIONS: Psoas abscess in patients with DM is a disease with both diagnostic and therapeutic challenges. We found the infecting microorganisms to be variable and the mortality rate high.

Androgen deprivation induces selective outgrowth of aggressive hormone-refractory prostate cancer clones expressing distinct cellular and molecular properties not present in parental androgen-dependent cancer cells.

PURPOSE: The mechanism of progression of human prostate cancer (CaP) cells under androgen ablation therapy remains unclear. To study the alternative pathways of CaP cell growth under conditions of androgen deprivation, androgen-independent CaP variants were selected and expanded from an androgen-dependent CaP line via an in vitro androgen deprivation treatment. Cellular and molecular properties of these androgen-independent variants were characterized both in vitro and in vivo and compared with those of their parental androgen-dependent cells. METHODS: Androgen deprivation treatment of an androgen-dependent CaP cell line, LNCaP, was carried out by replacing culture medium with RPMI 1640 medium plus 10% charcoal-stripped serum. Cells that survived through the androgen deprivation treatment were harvested and expanded in the androgen-deficient culture medium and were designated CL-1. The CL-1 cells were also recultured in androgen-containing medium and designated CL-2. The growth (cell cycle analysis, 3H-thymidine incorporation assay, growth expansion, and colonization efficiency), expression of CaP-associated markers (semiquantitative reverse transcriptase polymerase chain reaction), interaction with endothelial and bone marrow stromal cells, sensitivity to anticancer agents and radiation (growth inhibition), and tumorigenicity of CL-1 and CL-2 cells were determined and compared with these characteristics in parental LNCaP cells. RESULTS: CL-1 and CL-2 cells are fast-growing cells when compared with parental LNCaP cells. They were capable of potentiating the growth of endothelial and bone marrow stromal cells in co-culture experiments and acquired significant resistance to radiation and to anticancer cytotoxic agents (Taxol paclitaxel, vinblastine, and etoposide). In contrast to the poorly tumorigenic parental LNCaP cells, CL-1 and CL-2 lines proved highly tumorigenic, exhibiting invasive and metastatic characteristics in intact and castrated mice or in female mice within a short period of 3 to 4 weeks. No growth supplements (e.g., Matrigel) were needed. When transfected with the green fluorescence protein (GFP) gene and transplanted orthotopically in the accessory sex gland, extensive metastatic disease from the primary CL tumor could be identified in bone, lymph nodes, lung, liver, spleen, kidney, and brain. Semiquantitative reverse transcriptase polymerase chain reaction analysis revealed a markedly distinct molecular expression profile in the CL lines: overexpression of basic fibroblast growth factor, interleukin-6, interleukin-8, vascular endothelial growth factor, transforming growth factor-beta, epidermal growth factor receptor, caveolin, and bcl-2 messenger RNAs and marked down-regulation of E-cadherin, p-53, and pentaerythritol tetranitrate. CONCLUSIONS: Early administration of hormonal therapy after failure of first-line treatment is associated with a profound clonal selection of aggressive AI variants, such as CL-1 and CL-2 lines. These tumor lines, with their parental counterparts, can serve as valuable tools for studying the cellular and molecular mechanisms of CaP progression and metastasis under hormonal therapy. CL-1 and CL-2 offer a unique and reproducible model for the evaluation of drug sensitivity and for other therapeutic modalities for advanced prostate cancer.

Blood loss and the need for transfusion in patients who undergo partial or radical nephrectomy for renal cell carcinoma.

PURPOSE: We assessed blood loss and subsequent transfusion associated with nephrectomy performed for suspected renal cell carcinoma to establish guidelines for preoperative autologous blood donation and identify a subgroup of patients that may benefit from erythropoietin administration. MATERIALS AND METHODS: We retrospectively reviewed the charts of 211 patients who underwent partial (73%) or radical (23%) nephrectomy for presumed renal cell carcinoma at our institution between 1990 and 1999. Patients were divided into groups 1-44.5% treated with radical nephrectomy for localized disease, 2-21.3% radical nephrectomy for metastatic lesions invading the renal vasculature or inferior vena cava, 3-8% radical nephrectomy for metastatic disease with locally extensive lesions and 4-26.5% partial nephrectomy for localized lesions. Patient charts were evaluated for preoperative and postoperative hematocrit, estimated blood loss, transfusions received, surgical complications and underlying disease. RESULTS: Median estimated blood loss was 200, 400, 250 and 555 cc in groups 1 to 4, respectively. However, patients in groups 2 and 3 had a substantially greater range of blood loss than those in groups 1 and 4, respectively. The incidence of those with a blood loss of greater than 1 l. was 7%, 36%, 24% and 11% in groups 1, to 4, respectively. The incidence of those requiring transfusion was significantly lower in group 1 than in groups 2 to 4 (18% versus 44%, 24% and 30%, respectively, p <0.009). Mean transfusion requirement plus or minus standard deviation was significantly greater in groups 2 and 3 than in 1 and 4 (2.3 +/- 1.08, 5.5 +/- 4.4, 11.3 +/- 9.6 and 2.3 +/- 1.7 units, respectively, p <0.05). No significant difference was noted in the change in hematocrit as a result of surgery in the 4 groups (p >0.05). Similarly underlying disease and operative complications did not have a significant effect on blood loss or transfusion (p >0. 05). CONCLUSIONS: Radical or partial nephrectomy for localized renal cell carcinoma leads to consistent and well tolerated operative blood loss that rarely results in the need for substantial transfusion. In contrast, nephrectomy for advanced disease may cause a risk of greater blood loss and subsequent need for the transfusion of multiple units of blood. While preoperative autologous blood donation may have limited value in this regard due to the high cost and number of units needed, preoperative erythropoietin administration may be a viable option. Prospective randomized studies are currently planned.

CL1-GFP: an androgen independent metastatic tumor model for prostate cancer.

PURPOSE: The mechanisms responsible for tumor progression to androgen independence in prostate cancer (CaP) remain unknown. To characterize these changes and provide a basis for rational therapeutic strategies for advanced CaP, an in vivo model from a highly aggressive androgen independent CaP cell line with distinct cellular and molecular properties was developed. MATERIALS AND METHODS: An aggressive androgen-independent cell line designated CL1 was derived from a slow-growing, and androgen-dependent, parental LNCaP cell line through in-vitro androgen-deprivation and selection. CL1 was stably transfected with a green fluorescence protein gene (CL1-GFP) and orthotopically injected into SCID mice. The pathologic behavior, histology, and molecular determinants of CL1 tumor and metastases were determined and characterized by standard light and fluorescent microscopy, and quantitative RT-PCR analysis. RESULTS: CL1 is an anaplastic prostate cancer cell line which demonstrates extensive local invasion and metastases to various organs that can be visualized via GFP expression. When compared with parental LNCaP cells, RT-PCR analysis of the tumor revealed an over-expression of EGFR, b-FGF, VEGF, TGF-beta, IL-8, IL-6, and bcl-2 and a down regulated expression of the p53, E-cadherin and PTEN. In contrast to LNCaP cells, CL1 tumors express lower levels of androgen receptor and barely detectable PSA mRNA. CONCLUSIONS: CL1-GFP represents an aggressive androgen-independent CaP tumor model derived through androgen deprivation whose pathologic development and molecular properties in animals resembles the clinical characteristics of hormone refractory prostate cancer (HRPC). Metastatic sites of CL1-GFP can be visualized with fluorescence microscopy offering a unique therapeutic model for the evaluation of drug sensitivity and other therapeutic modalities.

Prognostic indicators for renal cell carcinoma: a multivariate analysis of 643 patients using the revised 1997 TNM staging criteria.

PURPOSE: We determine independent prognostic indicators for renal cell carcinoma using the revised 1997 TNM staging criteria. MATERIALS AND METHODS: The records of 643 consecutive patients undergoing partial or radical nephrectomy at our institution between 1987 and 1998 were reviewed. Preoperative evaluation of functional status using the Eastern Cooperative Oncology Group (ECOG) criteria was performed in all cases. Renal cell carcinoma grade and stage were evaluated using the 1997 American Joint Committee on Cancer grading and TNM staging criteria, respectively. Patients were followed for a mean plus or minus standard deviation of 47+/-40 months (median 87). Kaplan-Meier survival curves were used to determine 5-year cancer specific survival for all patient groups. Univariate analysis using log rank sum tests was performed to evaluate the prognostic significance of overall TNM stage, tumor stage, disease grade and ECOG status. Multivariate analysis was performed to determine which factors had an independent impact on survival of patients with renal cell carcinoma. RESULTS: The 5-year cancer specific survival rate was 91%, 74%, 67% and 32% for TNM stages I, II, III and IV lesions, respectively (p<0.001). Analysis demonstrated a survival rate of 83% for stage T1, 57% for stage T2, 42% for stage T3 and 28% for stage T4 disease (p<0.001), and 89% for grade 1, 65% for grade 2, and 46% for grades 3 and 4 (p<0.001). Multivariate analysis revealed that overall TNM stage and grade of disease were the most important prognostic indicators for renal cell carcinoma (p<0.001). ECOG classification was a less significant predictor (p = 0.031) and tumor stage was not shown to have any independent impact on patient survival (p = 0.138). CONCLUSIONS: Better survival rates of patients with localized and advanced renal cell carcinoma can be demonstrated with recent advances in diagnosis and treatment. The revised 1997 TNM criteria manifest an appropriate adjustment in staging renal cell carcinoma based on these improvements, with overall stage correlating with cancer specific survival. In contrast, while effectively predicting survival, tumor stage did not demonstrate an independent impact on renal cell carcinoma prognosis under multivariate analysis. Instead, other factors, such as ECOG status and more importantly grade of disease, appeared to affect survival significantly as independent elements. Based on our recent experience with patients treated for renal cell carcinoma in the era of enhanced technology and improved survival, tumor grade and molecular markers may serve as useful adjuncts to TNM staging in guiding treatment and predicting survival outcomes.

Renal cell carcinoma: prognostic significance of incidentally detected tumors.

PURPOSE: We determined the prognostic significance of incidentally discovered renal cell carcinoma in the era of increased incidental detection. MATERIALS AND METHODS: We reviewed the records of 633 consecutive patients who underwent radical or partial nephrectomy for renal cell carcinoma at our institution between 1987 and 1998. Patients were divided into those who were asymptomatic and tumor was diagnosed incidentally and those diagnosed after presenting with any of the classic symptoms of renal cell carcinoma or subsequent metastasis. All renal cell carcinoma lesions were assigned a stage and grade according to 1997 TNM criteria. All patients were followed postoperatively to assess survival rates, and monitor recurrence and metastasis. RESULTS: Of the 633 patients 95 (15%) were treated for incidentally discovered renal cell carcinoma and 538 (85%) presented with symptoms secondary to renal cell carcinoma at diagnosis. Patient age and sex distribution were similar in the 2 groups. Stage I lesions were observed in 62.1% of patients with incidental renal cell carcinoma and in 23% with symptomatic renal cell carcinoma. In contrast, stage IV lesions were present in 27.4% of patients with incidental versus 54% with symptomatic renal cell carcinoma. Thus, incidental lesions were of significantly lower stage than those causing symptoms (p <0.001). Similarly 15.8% of incidental but 42.4% of symptomatic lesions were grade 3 or 4 (p = 0.006). Patients were followed postoperatively for a mean of 47 months plus or minus 40 months. The 5-year cancer specific survival rate was significantly higher for incidental than for symptomatic tumors (85.3% versus 62.5%). Likewise, the local and distal recurrence rates were higher for symptomatic lesions. When adjusted for stage, no difference in survival was noted in the 2 groups for stages I to III disease and a minimally significant difference was noted for stage IV cancer. Multivariate analysis of stage and grade attributed the survival difference in stage IV disease to the significantly higher grade of symptomatic lesions. CONCLUSIONS: At presentation incidental tumors are of significantly lower stage and grade than tumors producing symptoms. Subsequently these clinically and histologically less aggressive lesions lead to better patient survival and decreased recurrence. Thus, the detection of renal cell carcinoma before symptom onset enables treatment of less aggressive tumors and provides a better prognosis for patients. Given these data efforts should be directed toward the development of a screening protocol to detect these lesions early, so that they may be prevented from progressing to the point when symptoms are apparent and prognosis becomes worse. In addition, the significant correlation of tumor grade with survival in our study further demonstrates the prognostic value of tumor grade and molecular markers for the future evaluation and treatment of renal cell carcinoma.

Is adrenalectomy a necessary component of radical nephrectomy? UCLA experience with 511 radical nephrectomies.

PURPOSE: We determine the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluate the role of adrenalectomy as part of radical nephrectomy. MATERIALS AND METHODS: The records of 511 patients undergoing radical nephrectomy with ipsilateral adrenalectomy for renal cell carcinoma at our medical center between 1986 and 1998 were reviewed. Mean patient age was 63.2 years (range 38 to 85), and 78% of the subjects were males and 22% were females. Patients were divided into subgroups of 164 with localized (stage T1-2 tumor, group 1) and 347 with advanced (stage T3-4N01M01, group 2) renal cell carcinoma. Staging of tumors was performed according to the 1997 TNM guidelines. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared to postoperative histopathological findings to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. RESULTS: Of the 511 patients 29 (5.7%) had adrenal involvement. Average size of the adrenal tumor was 3.86 cm. (standard deviation 1.89). Tumor stage correlated with probability of adrenal spread, with T4, T3 and T1-2 tumors accounting for 40%, 7.8% and 0.6% of cases, respectively. Upper pole intrarenal renal cell carcinoma most likely to spread was local extension to the adrenal glands, representing 58.6% of adrenal involvement. In contrast, multifocal, lower pole and mid region renal cell carcinoma tumors metastasized hematogenously, representing 32%, 7% and 4% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 8.9 cm., range 3 to 17) and adrenal involvement (independent of stage) was not statistically significant. Renal vein thrombus involvement was demonstrated in 8 of 12 cases (67%) with left and 2 of 9 (22%) with right adrenal involvement. Preoperative CT demonstrated 99.6% specificity, 99.4% negative predictive value, 89.6% sensitivity and 92.8% positive predictive value for adrenal involvement by renal cell carcinoma. CONCLUSIONS: With a low incidence of 0.6%, adrenal involvement is not likely in patients with localized, early stage renal cell carcinoma and adrenalectomy is unnecessary, particularly when CT is negative. In contrast, the 8.1% incidence of adrenal involvement with advanced renal cell carcinoma supports the need for adrenalectomy. Careful review of preoperative imaging is required to determine the need for adrenalectomy in patients at increased risk with high stage lesions, renal vein thrombus and upper pole or multifocal intrarenal tumors. With a negative predictive value of 99.4%, negative CT should decrease the need for adrenalectomy. In contrast, positive findings are less reliable given the relatively lower positive predictive value of this imaging modality. Although such positive findings may raise suspicion of adrenal involvement, they may not necessarily indicate adrenalectomy given the low incidence, unless renal cell carcinoma with risk factors, such as high stage, upper pole location, multifocality and renal vein thrombus, is present.