Renal tumors in young adults.

PURPOSE: The clinical and pathological features of solid or complex cystic renal masses in young adults have not been defined. We present our experience with patients 17 to 45 years old with such renal masses to define the incidence of malignant vs benign lesions, familial tendencies and clinical outcomes. MATERIALS AND METHODS: The medical records of all patients 17 to 45 years old who presented with a solid or suspicious complex cystic renal mass at 2 tertiary care hospitals between 1988 and 2002 were retrospectively reviewed. Pertinent clinical information was compiled, including age, gender, mode of presentation, renal function, year and type of surgery, pathological analysis and survival data. RESULTS: There were 114 evaluable patients who underwent a total of 119 nephrectomies. Mean patient age was 37.1 years and males comprised 56.1% of the population. Twelve patients had familial renal cell carcinoma (RCC), the von Hippel-Lindau syndrome. Mode of presentation for patients with sporadic disease was symptomatic (55.9%), incidental (35.3%) or unknown (8.8%). Radical nephrectomy, partial nephrectomy and nephroureterectomy were performed in 80 kidneys (67.2%), 37 (31.1%) and 2 (1.7%), respectively. Malignant lesions comprised 79.8% of all masses and 95.8% of these were renal cell carcinoma. Of the RCCs 75.8% were grade 1 or 2 and 89% were organ confined. Young women were much more likely than men to have a benign lesion (36.0% vs 9.5%, p <0.01) and the diversity of histologies was impressive (of the 24 total benign masses 9 were different tumor types). With an average followup of 38.3 months overall survival is 90.2%. Among patients with RCC 84.9% are alive and cancer-free, 11.6% are dead from disease and 3.5% are alive with recurrent disease. CONCLUSIONS: We report the largest known series of solid or suspicious complex renal masses in young adults. As expected, familial tumors are more common in this population. While RCC is the most common tumor, a wide variety of potential pathological outcomes are possible, particularly in women, who were much more likely to have a benign lesion. RCC in this patient population appears to have a favorable prognosis, despite symptomatic presentation in the majority of cases.

T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer.

Manipulations capable of breaking host tolerance to induce tissue-specific T cell-mediated inflammation are of central importance to tumor immunotherapy and our understanding of autoimmunity. We demonstrate that androgen ablative therapy induces profuse T cell infiltration of benign glands and tumors in human prostates. T cell infiltration is readily apparent after 7-28 days of therapy and is comprised predominantly of a response by CD4+ T cells and comparatively fewer CD8+ T cells. Also, T cells within the treated prostate exhibit restricted TCR Vbeta gene usage, consistent with a local oligoclonal response. Recruitment/activation of antigen-presenting cells in treated prostate tissues may contribute to local T cell activation. The induction of T cell infiltration in prostate tissues treated with androgen ablation may have implications for the immunotherapeutic treatment of prostate cancer as well as other hormone-sensitive malignancies, including breast carcinoma.

Assessing the effect of fatty acids on prostate carcinogenesis in humans: does self-reported dietary intake rank prostatic exposure correctly?

BACKGROUND: Dietary fatty acids may influence prostate carcinogenesis. Although the standard for assessing dietary effects in humans is the semiquantitative food-frequency questionnaire, the extent to which self-reported intake correctly ranks prostatic exposure is unknown. OBJECTIVE: The objective was to examine the correlation between reported intakes of different fatty acids and their concentrations in prostate tissue. DESIGN: This was a cross-sectional study of 52 men undergoing surgical resection of the prostate gland. Usual dietary intake of saturated, total unsaturated, oleic, and linoleic fatty acids over the previous year was estimated with use of a 122-item version of the Health Habits and History Questionnaire. Concentrations in prostate tissue were measured directly by use of gas chromatography in healthy tissue collected at the time of surgery and were expressed as a percentage of total fatty acids. Correlations with 4 measures of dietary intake [g/d, g/d adjusted for total daily energy intake, % of total fat (as g/d), and % of total energy] were evaluated by Spearman's rank-order correlation coefficients. RESULTS: Linoleic acid concentrations in prostate tissue were significantly correlated with dietary intake expressed as g/d adjusted for total energy [r = 0.29 (95% CI: 0.03, 0.49), P = 0.04], % of total fat [r = 0.36 (0.14, 0.550), P = 0.008], and % of total energy [r = 0.28 (0.04, 0.49), P = 0.042], but not as g/d. Although mean concentrations of saturated, total unsaturated, and oleic fatty acids in prostate tissue resembled mean intakes for the group, prostatic concentrations did not correlate with individual intakes. CONCLUSION: Self-reported intake of fatty acids is a satisfactory marker of prostatic exposure at the group level, but, with the exception of linoleic acid, does not correctly rank individuals with respect to intensity of exposure.

The extent of biopsy involvement as an independent predictor of extraprostatic extension and surgical margin status in low risk prostate cancer: implications for treatment selection.

PURPOSE: We identify predictors of extraprostatic extension and positive surgical margins in patients with low risk prostate cancer (prostate specific antigen [PSA] 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b). MATERIALS AND METHODS: From August 1997 to January 1999, 143 previously untreated patients underwent radical retropubic prostatectomy for clinically localized prostate cancer. A total of 62 patients were low risk, with PSA 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b, and had sextant biopsy with separate pathological evaluation of each sextant cores. PSA, clinical stage, biopsy Gleason score, average percentage of cancer in the entire biopsy specimen, maximum percentage of cancer on the most involved core, number of cores involved and bilaterality were evaluated for association with extraprostatic extension, seminal vesicle involvement and positive surgical margins. RESULTS: Of the 62 patients 13 (21%) had extraprostatic extension, 6 (10%) seminal vesicle involvement and 20 (32%) positive surgical margins. Average percentage greater than 10% and maximum percentage greater than 25% were associated with extraprostatic extension (p = 0.01 and 0.004, respectively). Average percentage greater than 10%, maximum percentage greater than 25%, more than 2 cores involved and bilaterality were associated with positive surgical margins (p = 0.007, 0.01, 0.002 and 0.03, respectively). On multivariate analysis maximum percentage remained the only independent predictor of extraprostatic extension (p = 0.03), and the number of cores involved remained an independent predictor of positive surgical margins (p = 0.01). Biopsy Gleason score, PSA and clinical stage did not correlate with extraprostatic extension or positive surgical margins in this patient population. CONCLUSIONS: In low risk prostate cancer the extent of biopsy involvement significantly correlates with the risk of extraprostatic extension and positive surgical margins. Biopsy information should be considered when selecting and modifying treatment modalities.

Prostatic levels of fatty acids and the histopathology of localized prostate cancer.

PURPOSE: The consumption of various fatty acids has been associated with advanced stage and fatal prostate cancer. While numerous mechanisms have been postulated, to our knowledge there physiological data linking exposure and prognosis in humans are lacking. We examined prostatic levels of individual fatty acids in relation to the prevalence of histopathological characteristics associated with invasiveness and the risk of progression in 49 men undergoing radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS: Fatty acids were measured using capillary gas chromatography in fresh nonmalignant prostate tissue collected at surgery. Markers of invasiveness and increased risk of progression (Gleason sum 7 or greater, perineural invasion, anatomical or surgical margin involvement, extracapsular extension, seminal vesical involvement and stage T3 tumor) were evaluated separately. Each marker was dichotomized into a yes (case) and no (control) level with patients grouped accordingly. Mean concentrations were compared using the Wilcoxon rank sum test. RESULTS: The percent of total prostatic polyunsaturated fat and polyunsaturated-to-saturated fat ratios were significantly lower in the presence of perineural invasion, seminal vesical involvement and stage T3 tumor (p = 0.02 to 0.049). alpha-Linolenic acid was significantly lower when tumor extended to an anatomical or surgical margin (p = 0.008). The omega-3 and omega-3-to-omega-6 fatty acid ratios were 1.5 to 3.3-fold lower in cases than in controls, reaching borderline significance in nearly all comparisons (p = 0.052 to 0.097). Saturated and monounsaturated fatty acids were not associated with the traits examined. CONCLUSIONS: These data suggest that polyunsaturated fatty acids and perhaps essential fatty acids in particular help to regulate prostate carcinogenesis in humans.

Daily subcutaneous ultra-low-dose interleukin 2 with daily low-dose interferon-alpha in patients with advanced renal cell carcinoma.

A limited institution Phase II pilot study was performed using a very low-dose combination of daily s.c. interleukin (IL)-2 with IFN-alpha-2b in patients with advanced renal cancer in an attempt to duplicate or increase the response documented with higher dose schedules without the attendant toxicity profile. We selected a dose of IL-2 with documented immunological activity and combined it with clinically active low-dose IFN. Between August 1994 and September 1996, 19 patients with metastatic renal cell carcinoma, who had been judged incapable of tolerating high-dose i.v. IL-2, were treated with IL-2 (1 million units/m2/day) and IFN (1 million units/day), administered s.c. daily. All treatments were administered on an outpatient basis. Virtually all patients had bulky tumor burden with multiple sites of involvement, including five patients with bone metastases. No major objective responses were observed; however, one patient experienced a minor response lasting 13 months, with an associated improvement in performance status. Median survival was 6 months, and 1-year survival was 16%. Toxicity was generally mild and consisted almost entirely of constitutional symptoms. No serious grade 3 or 4 toxicity was observed, although two patients withdrew from treatment due to treatment-related fatigue. On therapy, mild eosinophilia but no lymphocytosis was noted; in fact, peripheral lymphocyte counts decreased, only to rebound after treatment was discontinued. No toxic deaths occurred. Despite the reasonable tolerability of this daily low-dose s.c. regimen, we conclude that this regimen is an ineffective treatment in metastatic renal cell carcinoma patients who are incapable of tolerating high-dose i.v. IL-2.

Does the choice of anesthetic technique affect the recovery of bowel function after radical prostatectomy?

OBJECTIVES: Return of bowel function after radical prostatectomy surgery may be the limiting factor in discharging these patients from the hospital. Recent studies have shown that postoperative epidural infusion of bupivacaine decreases time to return of bowel function compared with intravenous and epidural morphine in patients after abdominal surgery. This study focuses on the role of the intraoperative anesthetic technique on recovery of bowel function, intraoperative blood loss, and the incidence of postoperative deep venous thrombosis (DVT) in patients undergoing radical retropubic prostatectomy and pelvic lymphadenectomy. METHODS: Forty patients undergoing prostatectomy were randomized to either group A (general endotracheal anesthesia, including muscle relaxation and mechanical ventilation, followed by postoperative intravenous morphine patient-controlled analgesia) or group B (thoracic epidural anesthesia using bupivacaine, combined with "light" general anesthesia using a laryngeal mask airway and spontaneous ventilation, followed by epidural morphine analgesia). Intra- and postoperative data were collected on blood loss, volumes of crystalloid and colloid infused, blood transfused, duration of anesthesia and surgery, anesthetic and surgical complications, time to recovery of bowel function, quality of postoperative pain control, and time to discharge from hospital. Each patient underwent lower extremity venous ultrasonography to detect DVT. RESULTS: Twenty-one patients received general anesthesia and 19 received combined epidural and general anesthesia. Intraoperative blood loss was significantly lower in the epidural group, and times to first flatus and first bowel movement were also shorter in this group. There were no significant differences in duration of anesthesia or surgery, quality of postoperative analgesia, side effects of analgesia, or time to discharge from hospital. There was no DVT detected in any patient. CONCLUSIONS: The combined anesthetic technique of thoracic epidural anesthesia and "light" general anesthesia with spontaneous ventilation decreased intraoperative blood loss and shortened the time to return of bowel function. However, this earlier return of bowel function was not great enough to realize a difference in time to hospital discharge. There was no evidence of increased complications secondary to epidural anesthesia or of prolonged anesthetic time necessary to place epidural catheters.

Efficacy of retrograde stentograms following cystectomy and diversion.

PURPOSE: The radiological evaluation of ureteroenteric anastomoses following cystectomy and diversion is standard practice at our institution. To our knowledge there are no data that demonstrate the efficacy of retrograde "stentograms" following cystectomy. MATERIALS AND METHODS: A retrospective analysis of the retrograde stentograms of 73 patients who underwent cystectomy and diversion was reviewed. RESULTS: Of 135 ureteroenteric anastomoses 3 (2.2%) demonstrated a leak by retrograde stentogram. No patients had evidence of obstruction. CONCLUSIONS: The 2.2% incidence of ureteroenteric leak in our series does not support the routine use of retrograde stentogram following cystectomy and diversion.

Limited efficacy of preoperative computed tomographic scanning for the evaluation of lymph node metastasis in patients before radical prostatectomy.

OBJECTIVES: To evaluate the efficacy of preoperative computed tomographic (CT) scanning in patients with presumed localized prostatectomy prior to radical retropubic prostatectomy. METHODS: A retrospective study of 173 consecutive patients believed to be candidates for radical retropubic prostatectomy who underwent preoperative CT scanning regardless of preoperative prostate-specific antigen (PSA) value, clinical stage, or Gleason grade was undertaken. All patients underwent radical retropubic prostatectomy with bilateral pelvic lymph node dissection or aspiration needle biopsy of abnormal nodes on CT scanning. RESULTS: One hundred sixty-five of 173 patients (95.4%) were believed to have normal CT scans preoperatively. Of these 165 patients, 156 (94.5%) were found to have negative lymph nodes confirmed histologically at the time of lymphadenectomy. Nine patients (5.5%) were found to have lymph node metastases confirmed histologically, despite a negative CT scan. Computed tomographic scanning understaged 9 of 12 (75%) patients with proven metastases. Incidental abdominal pathology of clinical significance was documented in 4 patients (2.3%), including 2 with renal cell cancers, 1 with colon cancer, and 1 with a large (8 cm) abdominal aortic aneurysm. Prostate-specific antigen levels in patients with metastatic lymph nodes ranged from 0.7 to 130 ng/mL (Hybritech Tandem assay), with a mean level of 42 ng/mL. Although 9 of 33 patients (27.3%) with PSA levels greater than 25 ng/mL had node metastases, only 3 of these 33 patients (9.1%) were correctly diagnosed by CT scanning. CONCLUSIONS: Although additional numbers of patients with high PSA levels need to be evaluated, we could not find any justification for routine preoperative CT scanning in patients with a PSA of less than 25 ng/mL. These results suggest that significant savings can be realized by abandoning the practice of routine CT scanning for lymph node metastasis in all patients with newly diagnosed prostate cancer.

Primary leiomyosarcoma of the ureter.

We report the thirteenth case of primary leiomyosarcoma of the ureter, as well as a summary of previous cases. It is the first case reported to be studied by computer tomography and immunohistochemical procedure. Further evaluation included intravenous pyelogram, cystoscopy with retrograde pyelogram, cell block for cytology, and electron microscopy. Leiomyosarcoma is a very rare disease that is difficult to diagnose. It has a very poor 5-year disease-specific survival.

Transrectal ultrasound of the prostate bed after collagen injection.

OBJECTIVE: Transurethral injection of collagen (TCI) may be used to treat urinary incontinence following radical prostatectomy for prostate cancer. The transrectal ultrasound (TRUS) findings after TCI are described in this report. MATERIALS AND METHODS: TRUS exams of four postprostatectomy patients who had undergone TCI were reviewed. Findings were correlated with pathologic specimens obtained at TRUS-guided core biopsy. These histologic specimens were compared with others from postprostatectomy patients who had not undergone TCI. RESULTS: Well defined bladder apex masses of uniform echogenicity, hypoechoic to adjacent fat and muscle, were identified sonographically in all TCI patients. Masses from which positive biopsies were obtained were similar in appearance to those with no malignancy. Hypocellular fibrous tissue and foci of acellular loose connective tissue were identified in the biopsies of those patients who had undergone TCI. No acellular areas were identified in specimens from patients who had not had TCI. CONCLUSION: Sequelae of TCI should be included in the differential diagnosis of perianastomotic masses in postprostatectomy patients. However, the need for biopsy is not obviated as residual or recurrent prostate carcinoma may coexist.

Directed and random biopsies of the prostate: indications based on combined results of transrectal sonography and prostate-specific antigen density determinations.

OBJECTIVE: We studied the usefulness of transrectal sonography, prostate-specific antigen levels, and prostate-specific antigen density as indications for directed and random biopsies of the prostate in patients with possible prostatic cancer. MATERIALS AND METHODS: A total of 141 patients with increased levels of prostate-specific antigen or abnormal findings on digital rectal examination had transrectal sonography of the prostate and determination of prostate-specific antigen density. Through sonographic visualization, all patients had biopsies of possible cancerous lesions and random biopsies of regions of the prostate that appeared normal. Histologic results were correlated with sonographic findings and determinations of prostate-specific antigen levels and prostate-specific antigen density. RESULTS: Adenocarcinoma was detected in 40 (28%) of the 141 patients. Transrectal sonography showed an abnormality that was determined by directed biopsy to be a carcinoma in 27 (68%) of the 40 patients. Transrectal sonography showed no carcinoma in 13 patients (32%) for whom random biopsy revealed a tumor. The sensitivity of sonography was 68%, and the specificity was 49%. The combination of sonographic findings suggestive of cancer and increased prostate-specific antigen density had a sensitivity of 75% and a specificity of 75%; we calculated a sensitivity of 72% and a specificity of 56% for the combination of sonographic findings suggestive of tumor and increased levels of prostate-specific antigen. Thirty-nine (97%) of 40 patients with cancer had either sonographic findings suggestive of tumor or increased prostate-specific antigen density, and one (3%) had no evidence of tumor on sonography and a normal prostate-specific antigen density. CONCLUSION: Directed and random sonographic biopsies of the prostate are indicated in patients with sonographic findings suggestive of tumor and increased prostate-specific antigen density and in patients with abnormal sonographic findings and normal prostate-specific antigen density. Random biopsies are indicated in patients with normal sonographic findings and increased prostate-specific antigen density. In our series, random biopsies were not indicated in 25 of 26 patients with normal sonographic findings and normal prostate-specific antigen density. Further research on the need for random biopsies when there are no sonographic abnormalities and when prostate-specific antigen densities are not elevated is warranted.

Radical prostatectomy: transrectal sonographic evaluation to assess for local recurrence.

PURPOSE: To determine sonographic features associated with locally recurrent or residual tumor. MATERIALS AND METHODS: Twenty-three transcretal ultrasound (TRUS) studies were performed in 21 patients with suspected recurrent prostatic carcinoma after prostatectomy. The original prospective TRUS reports were reviewed, followed by blinded review, and the findings were compared with biopsy results. RESULTS: A discrete perianastomotic mass was identified prospectively in eight (73%) of 11 patients with positive biopsy results and in two (17%) of 12 with negative results; no mass was identified in the remaining patients. At preliminary retrospective review, the echogenic retroanastomotic fat plane was not intact in 10 (91%) of 11 patients with positive biopsy results and in two (17%) of 12 with negative results; it was intact in the remaining patients. CONCLUSION: Sonographic visualization of a mass in the prostate bed or loss of integrity of the retroanastomotic fat plane is strongly correlated with finding recurrent or residual tumor in this location. TRUS in evaluation of the source of postoperative evaluation of prostate-specific antigen levels warrants further investigation.

Treatment of persistent lymphatic drainage after laparoscopic pelvic lymph node dissection and radical retropubic prostatectomy.

A patient with a lymphocele after laparoscopic pelvic lymphadenectomy and radical retropubic prostatectomy was treated successfully with a single instillation of diatrizoate meglumine through a Jackson-Pratt drain. The authors review the origin of lymphoceles and various methods for treating them.

Prostatic cystic epithelial-stromal tumors: a report of 2 new cases.

The case records of 2 patients recently treated at our medical centers with prostatic cystic epithelial-stromal tumor (ages 22 and 62 years), as well as 14 cases previously reported in the literature were reviewed to obtain a consensus as to the therapy for this uncommon malignancy. Patients with prostatic cystic epithelial-stromal tumor often present with obstructive voiding symptoms and a palpable suprapubic mass. Computerized tomography typically reveals a huge, complex retrovesical mass with displacement of surrounding pelvic and abdominal structures, which may invade locally into the bladder, ureters or rectal wall. Our experience with immunohistochemical staining of these tumors suggests an epithelial component that is positive for prostate specific antigen, prostatic acid phosphatase, epithelial membrane antigen, chorioembryonic antigen and cytokeratin, and a stromal component that is positive for vimentin, desmin, cytokeratin and myosin. Rapid recurrences are the rule in patients in whom the tumor is incompletely resected. Histological evidence of malignant transformation and distant metastases has been reported in these neoplasms. An aggressive surgical approach aimed at total removal of this pelvic tumor will be discussed.

Penile carcinoma: a twenty-five-year experience.

The treatment of 34 patients with carcinoma of the penis was reviewed during a twenty-five-year period (1958-1983). There were 26 patients with Stage I disease, 7 patients with Stage II, and 1 patient with Stage III disease. Among the Stage I group, 12 patients underwent partial/total penectomy and immediate ilioinguinal lymphadenectomy; 14 patients were treated with partial/total penectomy and observation of clinically nonpalpable nodes. Within the observation period, 10 of the 26 patients died, with a mean survival time of one hundred thirty-three months (standard error = 20.4), and a median of one hundred twenty months. Both the Mantel-Cox and Breslow test statistics showed the survival distribution of these groups of patients not to be significantly different from each other. All 7 patients with Stage II penile cancer died, with a mean survival time of 10.6 months (standard error = 2.1) which is significantly different from the Stage I group and the reported survival of 30-60 percent in the literature. A plan of management for the primary lesion and the role of ilioinguinal lymphadenectomy are presented.