Jose Luis F. Duque

Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer

OBJECTIVES Vascular endothelial growth factor (VEGF) is a cytokine that plays an important role in tumor angiogenesis. VEGF is overexpressed in many human cancers, including prostate cancer, but circulating levels of VEGF in patients with prostate cancer have not been reported. In this study, we analyzed plasma concentrations of VEGF in a cohort of patients with prostate cancer and compared them with a normal population. METHODS Twenty-six healthy, cancer-free individuals and 80 patients with prostate cancer (54 patients with localized prostate cancer and 26 patients with metastatic prostate cancer [bone or lymph node positive]) were analyzed in this study. Blood was drawn in the same fashion from all individuals and deposited in tubes containing ethylenediaminetetraacetic acid as anticoagulant. Plasma was extracted and VEGF concentrations were determined using a quantitative sandwich enzyme immunoassay technique. RESULTS Median plasma VEGF was 28.5 pg/mL (interquartile range 19.3 to 57.0) in patients with metastases; 7.0 pg/mL (interquartile range 0 to 26.5) in patients with localized disease, and 0 pg/mL (interquartile range 0 to 24) in controls. These differences were statistically significant (P <0.001). When compared group by group, the metastatic group had significantly higher plasma VEGF than the localized disease group and the control group (P = 0.003 and P <0.001, respectively). There was a tendency for plasma VEGF to be higher in the localized disease group than in the control group, a trend that almost reached statistical significance (P = 0.038). Using a cutoff of 18 pg/mL, the sensitivity and specificity of the test in differentiating between patients with and without metastatic disease was 81% and 71%, respectively. The odds of metastatic disease were almost 10 times greater for patients with VEGF values greater than 18 pg/mL than for those with values less than 18 pg/mL. There was no correlation between age and plasma VEGF values or between plasma VEGF and serum prostate-specific antigen (PSA). However, patients with serum PSA greater than 20 ng/mL had significantly higher plasma VEGF values than patients with serum PSA less than 20 ng/mL (P <0.001). No direct relation was found between Gleason sum and plasma VEGF, although VEGF levels were higher in patients with Gleason sums of 8 to 10 than in patients with lower Gleason sums. CONCLUSIONS Our study indicates that patients with metastatic prostate cancer have higher plasma VEGF levels than patients with localized disease or healthy controls. A larger prospective study is needed to confirm the predictive utility of VEGF.

Partial nephrectomy: alternative treatment for selected patients with renal cell carcinoma

OBJECTIVES To analyze the experience and the results of partial nephrectomy in a single institution over the last 10 years in order to optimize patient selection and minimize morbidity. METHODS This is a retrospective chart review of 64 patients (mean age 56.6 years, range 18 to 88; 43 men, 21 women) who underwent 66 partial nephrectomies at the Brigham and Womens Hospital between 1987 and 1997. Preoperatively, 62% of the patients had no symptoms, whereas 38% had pain and/or hematuria. The indications were elective in 23 patients, solitary kidney in 28 (14 with bilateral asynchronous tumor), bilateral synchronous tumor in 7, von Hippel-Lindau disease with normal contralateral kidney in 3, lymphoma in 3, and other indications in 2 patients. Surgery was performed for solid or indeterminate renal mass suspected of being renal cell carcinoma in 58 patients. RESULTS The most common final pathologic diagnosis was renal cell carcinoma in 47 procedures. One or more complications occurred after 18 procedures (15 with solitary kidney and 3 in patients with normal contralateral kidney) or 27% of the patients. The most common complication was an increased creatinine level (two times the baseline), occurring in 10 procedures (15.1%). Transfusion was necessary in 37 of 66 procedures (56%), and the mean blood loss was 836 cc (range 100 to 3200). Regarding renal function, 85% of the patients had a minimal increase in creatinine of less than 0.5 mg/dL after surgery (all patients with a normal contralateral kidney are in this group); 3 patients required either temporary (n = 1) or permanent (n = 2) dialysis. Other complications are also described. The mean length of stay among 65 patients was 6.5 days (range 3 to 14). The differences between length of stay, blood loss, and tumor size were statistically significant between the solitary kidney group and the elective indications group (P < 0.001). CONCLUSIONS Nephron sparing surgery is feasible and relatively safe in patients with a normal contralateral kidney. Awareness of potential complications should aid in the selection of appropriate patients for this procedure.

An overview of the treatment of superficial bladder cancer. Intravesical chemotherapy.

Superficial bladder cancer accounts for approximately 70% to 80% of all newly diagnosed bladder cancers. The vast majority of these cancers are transitional bladder tumors of various histologic grades (I to III). Superficial tumors include carcinoma in situ (CIS), tumors confined to the epithelium (Ta), and superficial tumors that invade the lamina propria (T1) but do not involve superficial muscle layers. The primary treatment for eradication of stage Ta and T1 bladder cancers is transurethral resection of the tumor. Many patients with superficial bladder tumors treated with endoscopic surgery alone have recurrence or tumor progression at some point in their follow-up, and, in these patients, the need for adjuvant treatment becomes a major concern.

Measurement of plasma levels of vascular endothelial growth factor in prostate cancer patients: relationship with clinical stage, Gleason score, prostate volume, and serum prostate-specific antigen

PURPOSE This study focused on circulating levels of vascular endothelial growth factor in patients with prostate cancer compared to a normal population. METHODS We analyzed 26 normal individuals and 80 patients with prostate cancer. Blood was drawn from all subjects, and plasma was extracted to determine the concentration of vascular endothelial growth factor using a quantitative immunoassay technique (ELISA-enzyme-linked immunosorbent assay). RESULTS The median plasma level of vascular endothelial growth factor was significantly elevated in patients with metastatic disease compared to patients with localized disease and with healthy controls. Patients with serum prostate-specific antigen > 20 ng/mL had significantly higher levels of plasma vascular endothelial growth factor than patients with serum prostate-specific antigen < 20 ng/mL. There was a trend for patients with a Gleason score of 8 to 10 to have higher levels of plasma vascular endothelial growth factor when compared to patients with lower Gleason scores. No relationship was found between plasma vascular endothelial growth factor and clinical staging, or between plasma vascular endothelial growth factor and prostate volume, in patients with localized prostate cancer. CONCLUSION This study indicates that patients with metastatic prostate cancer have higher plasma vascular endothelial growth factor levels than patients with localized disease or in healthy controls.

Morbidity of flank incision for renal donors

OBJECTIVES To analyze the short and long-term morbidity of flank incision in renal donors. The flank incision has been widely used by urologists for decades, and its morbidity has always been an issue. METHODS A questionnaire assessing the morbidity and quality of life was sent to the last 100 living donors at our institution. All operations had been performed through the flank approach. Fifty-two questionnaires were returned. The mean age was 45 years. The mean follow-up was 29.5 months (range 7 to 58). The questionnaire was composed of questions regarding pain, cosmesis of the incision, and quality-of-life issues after surgery. RESULTS No patients had any major postoperative complications. Pain was described in the first postoperative day as severe, moderate, or mild by 36 (69.3%), 6 (11.5%), and 10 (19.2%) patients, respectively. On the day of discharge (mean 4 days), 17 patients (32.7%) reported severe pain. Pain was completely or somewhat controlled with analgesics after surgery in all but 3 patients. Most (81%) discontinued pain medication by the end of fourth postoperative week (54% by the end of second week). Only 3 patients (5.8%) related being very bothered by the incision at the time of the questionnaire. Bother relates to pain, location, length, and unsightliness of scar. In 43 patients (83%), the incision did not impact negatively on their self-esteem and quality of life, and 93% of patients in retrospect would undergo the same procedure without any reservation. CONCLUSIONS The short and long-term morbidity of the flank incision for living donor nephrectomy is acceptable. Most patients are content after the kidney donation, and all would undergo the same procedure all over again, the vast majority without any reservation.

HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR IS AN AUTOCRINE MEDIATOR OF HUMAN PROSTATE STROMAL CELL GROWTH IN VITRO

PURPOSE The physiological mechanisms by which soluble mediators of cell proliferation and survival alter expansion of the prostatic stroma in benign prostatic hyperplasia are poorly understood. We recently identified heparin-binding epidermal growth factor like growth factor (HB-EGF) as a product predominantly of the smooth muscle cell compartments of the adult human prostate. We assess the potential role of this growth factor as a stromal cell regulator. MATERIALS AND METHODS Primary cultures of desmin and alpha-actin positive human prostate stromal cells were shown to express several cell associated HB-EGF isoforms as well as the primary cognate HB-EGF receptor, ErbB1/HER1, suggesting the existence of an autocrine or juxtacrine regulatory loop. The related receptor tyrosine kinase, ErbB2/HER2, was also expressed as assessed by reverse transcriptase (RT) polymerase chain reaction (PCR). HB-EGF messenger RNA levels in human prostate stromal cells increased modestly (70%) in response to a repetitive mechanical stimulus, a lower response than has been reported for neonatal rat bladder smooth muscle cells, in which HB-EGF was originally identified as a mechanically responsive gene. RESULTS HB-EGF, epidermal growth factor and basic fibroblast growth factor stimulated human prostate stromal cell growth, while a specific antagonist of HB-EGF, [Glu52]-diphtheria toxin/CRM197, inhibited human prostate stromal growth in serum-free medium by a mechanism that did not involve increased apoptosis. A function blocking antibody against CD9/DRAP27/MRP-1, a cell surface binding partner of the membrane form of HB-EGF, also stimulated human prostate stromal cell proliferation. CONCLUSIONS HB-EGF is an endogenously produced human prostate stromal cell growth factor and, thus, may have a role as a physiologically relevant autocrine or juxtacrine mediator of stromal expansion in benign prostatic hyperplasia.

Short and long-term morbidity of thoracoabdominal incision for nephrectomy : A comparison with the flank approach

PURPOSE A thoracoabdominal incision provides optimal exposure for radical nephrectomy, especially for large tumors. Intuitively it is perceived that the morbidity of a thoracoabdominal incision far exceeds that of a flank incision. We compare the morbidity of thoracoabdominal and flank incisions, which to our knowledge has not been reported previously. MATERIALS AND METHODS A questionnaire assessing postoperative pain, use of pain medications and return to activities was sent to the last 100 renal donors who underwent nephrectomy at our institution through the 11th rib (flank incision, group 1) and the last 100 patients who underwent radical nephrectomy through the 8th to 10th rib (thoracoabdominal incision, group 2). A total of 52 group 1 and 42 group 2 questionnaires were returned. Pain was assessed at 4 periods using a visual analog scale. RESULTS Length of stay was the same in both groups. There were no differences between groups in terms of pain severity on postoperative day 1, on day of discharge home, 1 month postoperatively and at the time of study (p >0.05). There were no significant differences between groups in times following surgery when pain completely disappeared, when pain medications were discontinued, and when the patient returned to daily activities and work (p >0.05). CONCLUSIONS Morbidity was comparable for thoracoabdominal and flank incisions in terms of incisional pain, analgesic requirements after discharge home and return to normal activities.