Efficacy of adjuvant chemotherapy schedules for breast cancer according to body mass index: results from the phase III GIM2 trial.

BACKGROUND: The phase III GIM2 trial showed improved disease-free survival (DFS) and overall survival (OS) with adjuvant dose-dense (DD) as compared with standard-interval (SI) chemotherapy in women with node-positive early-stage breast cancer (BC). This exploratory analysis aimed to investigate the benefit of different schedules according to body mass index (BMI) in this trial. PATIENTS AND METHODS: This analysis explored the efficacy, in terms of DFS and OS, of different chemotherapy schedules according to BMI. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. RESULTS: Out of 2091 patients enrolled, 1925 with known baseline BMI were randomized in the DD versus SI comparison and therefore included in this analysis: 31.6% were overweight and 19.3% obese. Overweight and obesity were significantly associated with postmenopausal status, pT >2, and pN >2 tumors. After a median follow-up of 15.0 years (interquartile range 8.4-16.3 years), multivariable Cox survival models demonstrated no association of different BMI categories on DFS [adjusted hazard ratio (adjHR) 0.96, 95% confidence interval (CI) 0.80-1.15 and adjHR 1.11, 95% CI 0.91-1.35 for overweight and obese patients, respectively, compared to patients with normal BMI] or OS (adjHR 0.90, 95% CI 0.71-1.14 and adjHR 1.18, 95% CI 0.92-1.52 for overweight and obese patients, respectively). No significant interaction was found between BMI and treatment schedule in terms of DFS (Pfor interaction = 0.56) or OS (Pfor interaction = 0.19). The survival benefit of DD chemotherapy was observed irrespective of different BMI categories, with a more pronounced benefit for overweight and obese patients. CONCLUSION: In node-positive BC patients, DD schedule should be considered the preferred schedule irrespective of BMI.

Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic prostate cancer in Italy.

OBJECTIVES: Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs. METHODS: A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists. RESULTS: Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained. CONCLUSIONS: Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

Laparoscopic bilateral cutaneous ureterostomy for palliation of ureteral obstruction caused by advanced pelvic cancer.

In cases of advanced urologic malignancies with impairment of renal function secondary to tumor infiltration in high-risk patients, the possibility of performing a laparoscopic instead of an open cutaneous ureterostomy should be considered. We performed laparoscopic cutaneous ureterostomy in three male patients, two with prostate cancer and one with bladder cancer, and in one female patient with uterine cancer. Five operative ports were used. The ureters were identified, dissected, severed, and passed through two 10-mm ports; and cutaneous ureterostomies were performed in the usual manner. The mean operative time was 96 minutes. Patients were discharged after 5 to 7 (mean 6) days. The two patients with prostate cancer are now in treatment with GnRH analogues with a follow-up of 3 and 7 months. The patient with bladder cancer underwent palliative radiotherapy and is well after 6 months. The patient with uterine cancer has stable disease after 3 months. Laparoscopic urinary diversion causes less discomfort and has a low complication rate and may be the first-choice diversion in patients with advanced cancer who have a life expectancy longer than 6 months.

Heat-expansible permanent intraurethral stents for benign prostatic hyperplasia and urethral strictures.

We report our experience with the insertion of a new thermoexpansible permanent intraurethral stent, the Memotherm. We treated 49 patients, 25 with benign prostic hyperplasia (BPH), 21 with recurrent urethral strictures (2 cervicourethral and 18 bulbar and 1 of a vescicourethral anastomosis after radical prostatectomy), and 3 with sphincterotomies (2 for dyssynergia and 1 with incontinence plus stenosis). The patients' ages ranged from 24 to 84 (mean 59.7) years. In all patients, stent insertion was achieved without any operative problem. In two patients, stents were removed (one in the BPH group and one in the urethral stricture group), and at long-term follow-up, we have seen two patients with severe mucosal hyperplasia.

Evaluation of cervico-urethral obstruction with ambulatory pressure/flow studies: an alternative to conventional pressure/flow studies?

Most of the urodynamic studies are conducted in the laboratory during a brief recording time and under nonphysiological conditions and, thus, may fail to unfold the nature of existing pathological conditions of the lower urinary tract; false positives and false negatives are possible. To overcome some of the difficulties associated with conventional P/F studies we have developed, with the cooperation of Medical Measurement System company, Entschede, The Netherlands, a portable system (UDS 2000) for ambulatory monitoring of intravesical pressure, abdominal pressure and EMG connectable with a weight-transducer flowmeter that allows to perform Holter P/F measurements. We compared the results obtained with conventional P/F studies and with Holter P/F studies in 58 BPH patients. During the filling phase we observed a slightly increased number of stable detrusors with Holter P/F recording (46 vs 42); conversely, the number of patients suffering from urge incontinence was the same (7 pts). During the voiding phase, out of 45 patients considered obstructed at conventional P/F study, only 42 were really urodynamically obstructed (93.3%), while other 3 patients had bordeline obstruction. 4 patients with bordeline obstruction at conventional P/F study were considered non-obstructed after Holter P/F. In conclusion, Holter P/F proved to be reliable in the assessment of bladder function during storage and emptying in BPH patients and to be more specific in defining outlet obstruction than the conventional study because of the physiologic filling, the reduction of urethral irritation, the lack of a urethral catheter either during filling or voiding, and the reduction of emotional stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Laparoscopic pelvic lymphnodes dissection for prostate and bladder cancer: indication, techniques and results.

Laparoscopic pelvic lymphadenectomy has been proposed for staging of prostate cancer and it might be used, in selected cases, also in bladder cancer. On a total of 31 laparoscopic lymphadenectomies (LPND), 18 for prostate cancer and 13 for bladder cancer, we found positive nodes in 8 cases (26.1%), 4 in prostate and 4 in bladder cancer group. We had no intraoperative complications and negligible postoperative complications (in 10% of cases shoulder-tip pain and in 24% subcutaneous emphysema); all these spontaneously disappeared after 24-36 hours. Patients with negative nodes underwent radical surgery except two prostate cancer patients who underwent radiotherapy, and patients with positive nodes underwent hormonal therapy (for prostate cancer) or chemoradiotherapy protocol (for bladder cancer). In conclusion, laparoscopic lymphadenectomy proved to be a feasible and safe method for staging urological malignancies, being less invasive, with shorter hospitalization and postoperative convalescence than open lymphadenectomy. It should be mainly indicated in high risk prostate cancer patients (elevated PSA and/or Gleason score). In bladder cancer patients, it could be proposed in bladder sparing investigational protocols, as the percentage of pelvic nodes metastases in T2/T3 bladder cancer is sufficiently high to justify an additional staging procedure.

Clinical stage, prostate-specific antigen and Gleason grade to predict extracapsular disease or nodal metastasis in men with newly diagnosed, previously untreated prostate cancer. A multicenter study. A. Ur. O. Cooperative Group.

OBJECTIVE: To draw nomograms for preoperative predictions of extracapsular and of nodal disease based upon preoperative prostate-specific antigen, Gleason grade and clinical stage. METHODS: The complete charts of 1,738 patients submitted to radical retropubic prostatectomy in 34 Italian urological departments have been reviewed. The correlation between preoperative variables and pathological examination was tested by both univariate and multivariate techniques. Logistic regression analysis with the likelihood ratio chi 2 test was used to predict the pathological features (T > = 3; N+) of a patient for various combinations of preoperative variables. RESULTS: Probability plots were constructed for the prediction of either extracapsular disease or lymph node involvement by the above-mentioned combination of preoperative variables. CONCLUSIONS: The obtained probability curves could be useful for patient counselling, for planning a staging laparoscopic lymphadenectomy in high-risk patients and for deciding whether to perform a nerve-sparing prostatectomy.

Evaluation of cervico-urethral obstruction with ambulatory pressure/flow studies: an alternative to conventional pressure/flow studies?

Most of the urodynamic studies are conducted in the laboratory during a brief recording time and under nonphysiological conditions and, thus, may fail to unfold the nature of existing pathological conditions of the lower urinary tract; false positives and false negatives are possible. To overcome some of the difficulties associated with conventional P/F studies we have developed, with the cooperation of Medical Measurement System company, Entschede, The Netherlands, a portable system (UDS 2000) for ambulatory monitoring of intravesical pressure, abdominal pressure and EMG connectable with a weight transducer flowmeter that permits performing Holter P/F measurements. We compared the results obtained with conventional P/F studies and with the Holter P/F studies in 58 BPH patients. During the filling phase we observed a slightly increased number of stable detrusors with Holter P/F recording (46 vs 42); conversely, the number of patients suffering from urge incontinence was the same (7 pts). During the voiding phase, out of 45 patients considered obstructed at conventional P/F study, only 42 were really urodynamically obstructed (93.3%), while 3 other patients had borderline obstruction. Four patients with borderline obstruction at conventional P/F study were considered nonobstructed after Holter P/F.

Mechanism of microwave thermotherapy.

Possible mechanisms by which transurethral microwave thermotherapy creates an improvement in vodiing parameters are reviewed. The therapy creates coagulation necrosis in the hyperplastic adenoma, and thus has the potential to create volume reduction, change in the periurethral tissue, and changes in efferent neuromuscular elements and sensory neural elements. Evidence is presented that suggests that several of these mechanisms are likely important, and there is not a singular mechanism of action.

Malignant priapism due to a huge renal carcinoma.

Metastases to the penis from renal cell carcinoma producing priapism are very rare, as only 18 cases have been described since 1964. We present an additional case of priapism due to massive metastatic involvement of the corpora cavernosa in a patient with huge renal cell carcinoma, 28 cm in diameter, discussing the possible pathogenetic mechanism of such a rare condition.

Procollagen type I carboxyterminal extension peptide in serum: a reliable marker of bone metastatic disease in newly diagnosed prostate cancer?

OBJECTIVE: This study evaluates the accuracy of type I procollagen, a bone matrix glycoprotein, and prostate-specific antigen (PSA) as markers for predicting the results of radionuclide bone scan in newly diagnosed, previously untreated patients with prostate cancer. METHODS: 74 patients underwent serum PSA and procollagen determination using specific antibodies. A staging radionuclide bone scan was then performed; patients with positive bone scan were submitted to x-rays of the suspicious zones. Then, we calculated sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of procollagen and PSA in the detection of bone metastases. RESULTS: Procollagen alone had 83.3% sensitivity, 96% specificity, 90.9% positive predictive value, 92.3% negative predictive value and 91.9% overall accuracy. PSA alone had 70.1% sensitivity, 86% specificity, 70.8% positive predictive value, 86% negative predictive value and 81.1% overall accuracy. CONCLUSIONS: According to our data, we no longer perform a staging radionuclide bone scan in patients with PSA < 20 ng/ml and normal procollagen level, diminishing the number of radionuclide bone scans and increasing the overall net savings for the health care system.

Transurethral ultrasound-guided laser-induced prostatectomy. Objective and subjective assessment of its efficacy for treating benign prostatic hyperplasia.

We describe our experience with transurethral ultrasound-guided laser-induced prostatectomy (TULIP), a new procedure to relieve bladder outlet obstruction caused by benign prostatic hyperplasia. This device is composed of a real-time 7.5 MHz ultrasound transducer coupled to a Nd:YAG laser that fires through an intraprostatic balloon. To date, we performed 16 TULIP procedures; all patients were evaluated from a subjective point of view by a questionnaire based on the Boyarsky scale. They all underwent complete urodynamic studies, including flowmetry with measurement of the residual volume (by catheter) and pressure/flow studies. Preoperative symptom score ranged between 7 and 14 (mean 11.4). Preoperative peak flow rates ranged between 0 and 13 ml/s (mean 6.8). Suprapubic drainage was kept for a mean of 11.6 days after the procedure (7-20 days). Postoperative acute retention was observed in 4 patients (25%) 5-7 days after the procedure. In 13 out of 16 patients, urodynamic obstruction was corrected by the procedure. Two patients kept a borderline obstruction. In 1 case transurethral resection of the prostate (TURP) was performed for persisting obstruction and in another case TURP was performed for persisting untreatable irritative symptoms. At 3 months after the operation, the Boyarsky symptom score (11 patients) ranged between 3 and 12 (mean 7.7) and peak flow rates ranged between 11 and 30 ml/s (mean 16.3). One patient is managed with a suprapubic tube. Retrograde ejaculation was observed in 2 out of 9 patients (22.2%). With a mean follow-up of 6.7 months, we did not observe any late complication.

Prostate cancer detection in BPH patients.

The first problem to be solved in the evaluation of BPH patients is surely the differential diagnosis with prostate carcinoma. We evaluated the impact of a combined approach for prostate cancer detection using DRE, PSA, TRUS and ultrasound-guided biopsy, determining the sensitivity and specificity of different tools, in order to obtain a diagnostic algorithm to be used for pretreatment differential diagnosis between prostate cancer and BPH.

Laparoscopic tumorectomy for renal cell carcinoma in a HIV-positive patient.

We report on a HIV-positive patient in whom laparoscopic nephron-sparing surgery has been performed. A 47-year-old white male referred for evaluation and treatment of an asymptomatic, serendipitously discovered renal mass. The patient underwent a laparoscopic tumorectomy; indications, surgical technique and rationale are described in detail.

Retroperitoneoscopic treatment of ureteropelvic junction obstruction.

PURPOSE: To demonstrate feasibility and safety of retroperitoneoscopic treatment of ureteropelvic junction obstruction. MATERIALS AND METHODS: 11 patients with symptomatic ureteropelvic junction obstruction were selected for retroperitoneoscopic pyeloplasty. Operative time ranged between 2 h 30 min and 4 h (mean 3 h 10 min); in 5 cases we had to convert to open surgery and an open pyeloplasty was performed through a minimal (6 cm) lombotomic incision. RESULTS: Follow-up IVPs were performed in all patients approximately 2-3 weeks after stent removal. In all patients, a reduction in the grade of hydronephrosis was observed. Significant improvement was noticed in 9 patients; in 2 patients a moderate improvement was observed. CONCLUSIONS: Our experience with retroperitoneoscopic treatment of ureteropelvic junction obstruction demonstrates that also with this approach it is possible to perform reconstructive procedures, with minimal complications. Technical refinements will progressively reduce the conversion rate to open surgery, even if done through minilaparotomy.

Ureteroarterial fistula: a case report.

Ureteroarterial fistulas are rare, with less than 20 well documented cases reported. We report a case of a fistula between the left external iliac artery and the left ureter in a patient who underwent a previous operation for bladder cancer. The diagnostic and therapeutic approaches in these rare but high risk patients are discussed.

Laparoscopically assisted transvaginal radical cystectomy.

Herein we describe 5 cases of anterior pelvic exenteration in females through a combined transvaginal and laparoscopic approach for bladder cancer. In 4 cases hysterectomy and bilateral ovariectomy were performed. As far as urinary diversion is concerned, a bilateral cutaneous ureterostomy was performed in the 1st case, and in the remaining 4 an ileal conduit was accomplished through a minilaparotomy at the stoma site. The surgical specimen was withdrawn 'en bloc' transvaginally in all cases except 1, in whom vaginal atrophy forced us to perform a midline minilaparotomy. Total operative time ranged between 6 and 9 h, and 4 patients were discharged after 7-11 days with no complications. One patient was discharged only after 18 days due to obesity and diabetic problems. A larger series is needed to confirm the advantages of the combined transvaginal and videolaparoscopic approach for anterior pelvic exenteration as compared to the conventional procedure, with special regard given to the oncological outcome. Our initial experience is surely encouraging.

Does transurethral thermotherapy induce a long-term alpha blockade? An immunohistochemical study.

10 patients underwent transurethral thermotherapy and after few days were submitted to open prostatectomy. The surgical specimens were compared to those of 2 other patients used as controls. Pathological specimens were evaluated using histological and immunohistochemical stains. Microscopic examination showed a well-preserved urethra and microabscesses, epithelial necrosis and vasculitis in the prostatic tissue at a depth of 0.5-2 cm from the urethral lumen. Immunohistochemical stains showed the damage and disappearance of nervous fibers.

Videoendoscopic retroperitoneal cutaneous ureterostomy.

Since January 1993, 10 patients with bilateral ureteral obstruction due to advanced pelvic cancers underwent videoendosurgical cutaneous ureterostomy. Five patients had prostate cancer, three had uterine cancer, and only two had bladder cancer. In five cases a bilateral laparoscopic transperitoneal procedure (LCU) was performed. In five cases a retroperitoneal laparoscopic technique (RLCU) was adopted, and only in one out of these five cases was the procedure done bilaterally. All the procedures were done under general anesthesia. The procedure was accomplished in all the cases without any intraoperative complication. Monolateral retroperitoneal laparoscopic cutaneous ureterostomy (RLCU) required 35-42 min, including the dilation time. Bilateral RLCU required extra time for changing the position of the patient. Postoperative pain was rather insignificant and did not require additional medication. Postdiversion hospital stay was 3-6 days depending on the general condition of the patient. The mean follow-up was 14.4 months.

[Exploration of the intra-renal collecting system using flexible fibroscopy]. / Exploración del sistema colector intrarrenal a través de fibroscopia flexible.

23 cases of flexible retrograde nephroscopy system for undiagnosed hematuria or filling defect are reviewed. The introduction was carried out by combining hydraulic dilation, rigid ureterorenoscopy and a working sheath. The indications were merely diagnostic (filling defects and/or haematuria). The success rate was very high (22 of 23). 9 cases of papillary tumors, 4 cases of small radiolucent stones and 1 case of papillary necrosis were diagnosed. In 8 cases no pathology was found. The complication rate was extremely low and the postoperative course was uneventful. Flexible instruments offer a very good chance to explore the intrarenal collecting system and transureteral nephroscopy through a 10.8 F flexible scope is a feasible and effective procedure.