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.

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.

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.

Efficacy of nephron-sparing surgery for renal cell carcinoma: analysis based on the new 1997 tumor-node-metastasis staging system.

PURPOSE: To analyze the experience with nephron-sparing surgery as a treatment modality for renal cell carcinoma (RCC). PATIENTS AND METHODS: Between 1980 and 1997, 146 patients underwent partial nephrectomy at the University of California-Los Angeles Medical Center. A matched group of 125 patients who underwent radical nephrectomy at the same institution between 1986 and 1997 were selected for comparison. Patients were monitored for an average period of 57 months. Patients were staged according to both the 1997 and 1987 tumor-node-metastasis (TNM) staging criteria. Survival data were calculated in terms of both staging criteria. RESULTS: When comparing cancer-specific survival rates for patients with T1 lesions under both the 1987 and 1997 TNM staging criteria, no statistically significant difference in survival was noted (P =.53), although most of the tumors in our series measured < or = 4 cm. Patients with T2 lesions (1997 TNM) demonstrated a significant decrease in survival (66%) when compared with patients with T1 lesions (100%; P <.001). No statistically significant difference in survival for patients with T1 RCC treated with either radical or partial nephrectomy was noted (P =.219). Survival rates of partial and radical nephrectomies for patients with unilateral T1 RCC and a normal contralateral kidney also were not significantly different (P =.53). In contrast, for patients with lesions greater than T1, survival rates were significantly higher with radical versus partial nephrectomy (P =.001). CONCLUSION: Partial nephrectomy has become an effective method of treating T1 RCC lesions as categorized by both the 1987 and the revised 1997 TNM staging criteria. Selected patients with localized unilateral RCC lesions less than 7 cm (ideally, < 4 cm) and a normal contralateral kidney will benefit from partial nephrectomy.

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.

A randomized study on palliative radiation therapy for inoperable non small cell carcinoma of the lung.

Between October 1981 and November 1984, 291 patients with inoperable advanced non-small cell carcinoma of the lung (NSCLC) were randomized to a two-arm study. Eighteen of 291 defaulted treatment and were excluded from the study. Twenty-seven of 273 died during treatment; they were invaluable for treatment response but were included in survival analysis. Without correction for lung attenuation 45 Gy/18 fractions/4 1/2 weeks were given in arm 1 and 31.2 Gy/4 fractions/4 weeks were given in arm 2. One hundred twenty-eight of 273 were included in arm 1 and 145/273 in arm 2. The two arms were comparable in patient age, sex, performance status and symptoms, primary tumor site, histology, stage of the disease, and distribution of metastases and radiation portal size used. Prognosis was poor with an overall median survival of 20 weeks and was similar in both arms. Radiological tumor response was also similar: 53% in arm 1 and 50% in arm 2. However arm 1 was superior than arm 2 in achieving symptom palliation, 71% vs 54%, p less than 0.02. Treatment complications were mild and included mainly radiation oesophagitis and pneumonitis and pulmonary fibrosis. Treatments in both arms were equally well tolerated.

Adjunctive chemotherapy to radical radiation therapy in the treatment of advanced nasopharyngeal carcinoma.

Sixty-eight consecutive patients with previously untreated nasopharyngeal carcinoma (NPC) with advanced cervical lymph nodal metastases were studied retrospectively for the effectiveness of combining chemotherapy with radical radiation therapy (RT). In 1981 and 1982, 36 patients were treated with radical radiation therapy alone (arm 1). In 1983, 13 patients were given 2 courses of VBMF prior to RT (arm 2). In 1984, 19 patients were given radical RT sandwiched between 2 courses of PVBMF before and 2 after (arm 3). The three arms were comparable in patient characteristics with similar stages of the disease, sex, age distribution, and rates of completion of the prescribed treatments. There was no significant difference in actuarial or disease-free survival between arm 1 and 3 or arm 2 and 3, but arm 1 compared favorably with arm 2 in actuarial survival (X2 = 9.533, p = 0.002). The distant relapses in arms 2 and 3 occurred at significantly shorter times after diagnosis than those in arm 1 (t = 4.1083, p = 0.0001). Postponement of radiation therapy by chemotherapy might have accounted for the earlier distant relapses in arm 2 and 3. Radiation therapy alone given in radical dose had been demonstrated to achieve significantly more complete responses in cervical nodal metastases than either forms of chemotherapy (VBMF or PVBMF) given just two courses prior to radiation therapy (p less than 0.00003). More controlled clinical trials must be completed before acceptance of chemotherapy as part of a standard radical treatment for advanced nasopharyngeal carcinoma with advanced cervical lymph nodal metastases. In all future trials, closer integration in time sequence between the two treatment modalities is indicated. Meanwhile cervical nodal status (CR vs, PR plus NR) at the end of any treatment was shown to be of paramount prognostic significance.

Evaluation of a decision-support system for preoperative staging of prostate cancer.

The usefulness and effectiveness of a decision-support system for preoperative staging of prostate cancers (PCES) were evaluated. The study population consisted of 43 consecutive patients with the preoperative diagnosis of prostate cancer who underwent surgical operation. Results obtained using the PCES were compared with staging by four urology attending physicians and five urology residents. The effect of PCES consultation on the physicians' staging of prostate cancer was also evaluated. To confirm the usefulness of the clinical findings of prostate-specific antigen, prostate-specific antigen density, prostate volume, and abnormal Gleason score in the PCES, their receiver operating characteristic (ROC) curves for diagnosis of advanced prostate cancer were plotted. The values of the areas under the curves were 0.772, 0.800, 0.531, and 0.752. The stage of prostate cancer was correctly determined by the PCES for 38 of the 43 patients, yielding 88.4% preoperative diagnostic accuracy. The PCES was significantly more accurate than two of the attending physicians and all residents. PCES consultation improved the residents' staging accuracy to approximately that of the attending physicians. The effect of PCES consultation on the residents' staging was significantly (p < 0.001) greater than the effect on the physicians' staging. The PCES may be useful in the preoperative staging of prostate cancers, especially during residency. The system's accuracy in determining the stage of advanced prostate cancer may make it possible to avoid unneccesary surgical operations.

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.

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.

Diagnosis of prostate cancer: comparison of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography.

BACKGROUND: While prostate specific antigen (PSA) is useful as a tumor marker for monitoring patients with prostate cancer after definitive therapy, limitations have been noted when it is used for early detection of prostate cancer. METHODS: We reviewed the charts of 121 patients who had undergone prostate needle biopsies, documented digital rectal examination (DRE) and serum PSA determination before biopsy from January 1993 to October 1994. Indications for biopsy included abnormal DRE. PSA level greater than 4.0 ng/ml or abnormal lesions on transrectal ultrasonography (TRUS). RESULTS: Seventeen patients (14%) had stage A carcinoma with normal DRE and PSA levels from 0.1 to 34.9 ng/ml (mean 9.0 ng/ml). Four patients (3%) had stage B carcinoma with an average PSA level of 32.3 ng/ml and less than one lobe indurated on DRE. Six patients (5%) had stage C carcinoma and had an average PSA level of 48.5 ng/ml and less than one lobe indurated on DRE. Ninety-four (78%) patients had stage D carcinoma with an average PSA level of 120 ng/ml and more than one lobe indurated on DRE. While hypoechoic sectors were more than twice as likely as isoechoic sectors of the prostate to contain malignancy on biopsy, nearly 20% of cancers were found in isoechoic sectors. CONCLUSION: Serum PSA is the most accurate of the three diagnostic tests evaluated. The addition of DRE or TRUS improves the detection rate of prostate cancer over PSA alone.

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.

Nephron-sparing surgery for renal cell carcinoma.

Nephron-sparing surgery has become an established surgical treatment for patients with renal cell carcinoma (RCC), particularly in situations in which preservation of renal parenchyma is critical. However, due to the fear of local renal fossa recurrence with nephron-sparing surgery, radical nephrectomy has historically been the treatment of choice for patients with unilateral RCC and a normal contralateral kidney. Recently, increased incidence of low-stage, localized, solitary RCC has led to renewed interest in partial nephrectomy. With excellent disease-specific survival and recurrence rates comparable to that achieved with radical nephrectomy, nephron-sparing surgery can be confidently utilized in treating patients with stage T1 RCC lesions (<7 cm) and a normal contralateral kidney. The utility of nephron-sparing surgery in the context of adjunctive systemic immunotherapy remains to be explored.

Septicemia caused by cysteine-dependent Escherichia coli.

A case of septicemia and urinary tract infection caused by cysteine-dependent Escherichia coli in a 70-year-old woman with bilateral staghorn calculi is described. This is the second report of a cysteine-dependent E. coli bacteremia. The bacterium was falsely susceptible to ampicillin and co-trimoxazole when tested on a medium without cysteine supplement.

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.

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.

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.

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.

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.