Phase I/II trial of docetaxel and concurrent radiation therapy in localized high risk prostate cancer (AGUSG 03-10).

PURPOSE: A Phase I/II trial was conducted to assess the radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent intensity modulated radiation therapy (72 Gy at 1.8 Gy/fraction) in high risk prostate cancer. PATIENTS AND METHODS: Patients with high risk prostate cancer (clinical stage > or = T3; Gleason score 8, 9, or 10; Gleason score 7 and PSA > 10) received IMRT (Clinac 600 CD with 6 MV photons and sliding window technique) and concurrent weekly docetaxel (20 mg/m(2)) as a continuous 30 minute infusion for 8 weeks. Patients desirous of concurrent androgen suppression were not excluded. RESULTS: Twenty men (median age: 64 years; range, 50-78 years) were enrolled in the chemoradiation protocol. Three patients experienced treatment interruptions: dehydration requiring inpatient hydration (n = 2); NSAID induced GI bleed (n = 1). An additional patient required outpatient hydration (<24 hours) with no treatment interruption. Overall, the most frequently observed toxicities were grade 2 diarrhea (40%), grade 2 fatigue (40%), grade 2 urinary frequency (35%), taste aversion (20%), grade 2 constipation (20%), and rectal bleeding (15%). No significant hematologic toxicity (grades 2-4) was encountered among the 20 patients. Although the follow-up interval was relatively short, no significant subacute gastrointestinal toxicities have been observed. At a median follow-up duration of 11.7 months, 17 patients were free of biochemical disease recurrence, and all patients are alive. CONCLUSION: The radiosensitizer docetaxel administered weekly (20 mg/m(2)) with concurrent IMRT is well tolerated with acceptable toxicity. Early oncologic outcomes in this challenging patient cohort are encouraging.

Missed diagnoses by urologists resulting in malpractice payment.

PURPOSE: Missed diagnoses are a patient safety concern and they can result in malpractice allegation. The specialist physician may be liable for missed or delayed diagnoses even if an abnormality in the physician area of expertise is ruled out. We approached this largely unstudied area of medical malpractice in an effort to increase physician awareness and identify opportunities for prevention. MATERIALS AND METHODS: Working with the Medical Liability Mutual Insurance Company of New York State, we evaluated malpractice claims in urology that were closed with indemnity payment between 1985 and 2004. We identified all such claims resulting from alleged missed or delayed diagnoses by urologists. Claims were divided into 2 main categories based on whether the missed diagnosis was primarily urological, ie testis torsion, or not urological, ie appendicitis. RESULTS: A total of 75 missed diagnosis claims were identified, representing 15% of claims overall. The total indemnity payment for missed diagnosis claims was $32,591,013, which represented 27% of all indemnity payments for the study period. They were divided into 58 missed urological diagnoses and 17 missed nonurological diagnoses. Cancer represented 71% of missed urological diagnoses and 41% of missed nonurological diagnoses. Urological cancer missed diagnosis claims were associated with the highest average indemnity payment of $526,460. The average indemnity payment for missed diagnosis claims was 92% greater than the average indemnity payment for all other claims ($434,546 vs $226,133). An increase in the frequency of missed diagnosis claims closed with indemnity payment and in the amount of payment for missed diagnosis claims were observed during the 20-year study period. CONCLUSIONS: Indemnity payments resulting from missed diagnosis claims represent a disproportionately high percent of total indemnity payments (27%) due to a high average payment for such claims. Liability for the urologist resulted from missed diagnoses not only of urological conditions, but also of nonurological conditions.

Bidirectional-barbed sutured knotless running anastomosis v classic Van Velthoven suturing in a model system.

BACKGROUND AND PURPOSE: Robotic prostatectomy is exploding into popular utilization throughout much of the United States. It is expected that the rise in the number of these cases into 2006 will continue exponentially. A significant amount of research has begun to focus on the anastomosis, because the robot allows unprecedented illumination and dexterous control to make the quality of this repair equal to that of a microscopic approach. Here, we report our results with a circular anastomosis technique using an innovative bidirectional-barbed suture material for knotless, tension-free repair and compare it with a standard polyglecaprone single-knot technique. MATERIALS AND METHODS: Using a previously described in-vitro model of microfiber synthetic material, a running anastomosis was performed using the da Vinci Surgical System by one surgeon. Two pre-tied 3-0 polyglecaprone sutures on a tapered Rb-1 needle were compared with a bidirectional-barbed suture (3-0 PDO) designed specifically for our use (Quill Sutures, Research Triangle Park, NC). The times needed to perform the anastomosis, the accuracy in idealized phantoms, and the surgeon's security in the quality of his work (linear scale) were all recorded for 10 consecutive anastomoses. RESULTS: The PDO suture was faster to deploy (17.3 minutes v 19.2 minutes), and the security score by the surgeon was greater. The accuracy was equivalent for both types of running closure comparing the classic van Velthoven with the PDO-sutured anastomosis. CONCLUSIONS: It appears from our preliminary work that a bidirectional-barbed suture might improve the vesicourethral anastomosis during a robotic radical prostatectomy. Further investigations should be done to measure the disruptive force necessary to distract these sutures, whether the applied forces of the barbs are adequate for maintaining a watertight seal, and the reproducibility of our results by other surgeons. All of these investigations are in progress in our laboratory.

Does laparoscopy beget underuse of partial nephrectomy for T(1) renal masses? Competing treatment decision pathways may influence utilization.

BACKGROUND AND PURPOSE: It has been suggested that renal laparoscopy has resulted in an underuse of partial nephrectomy (PN) for small renal masses in the U.S. In the absence of evidence-based medicine (EBM) guide-lines, multiple-perspective reasoning is required where complete v partial nephrectomy and the laparoscopic v the open surgical approach must be considered. We report on the PN rate in a contemporary laparoscopicera series of patients with T(1) renal masses and examine the potential influence of the management decision tree on the PN rate. PATIENTS AND METHODS: An actively managed database of referred patients with T(1) renal masses was utilized retrospectively. All patients were evaluated by a single fellowship-trained urologic oncologist with formal laparoscopic training. Patients were presented with a management decision tree in which PN v total nephrectomy (TN) was the first decision node, laparoscopy v open surgery was the second decision node, and the actual PN rate was reported. We then constructed a hypothetical decision tree in which the first and second decision nodes were reversed and the criteria for performing laparoscopic nephrectomy remained constant. RESULTS: Seventy consecutive patients were entered during a 36-month period (July 2002-June 2005). The actual PN rate was 60%: 91% for lesions <2.0 cm, 68% for lesions 2.1 to 4.0 cm, and 33% for lesions 4.1 to 7.0 cm; and 62% of patients were treated laparoscopically. When the first and second decision nodes were reversed and this hypothetical model was applied to the study cohort, the projected PN rate was 23%, and 96% of the patients were treated laparoscopically. In the hypothetical model, the PN rate fell when patients who chose laparoscopy at the first decision node were excluded from PN at the second decision node if the criteria for laparoscopic PN were not met. CONCLUSION: Laparoscopy did not appear to result in underuse of PN. We explain this by suggesting that the PN rate may be influenced by variation in the decision tree itself. Such variation is inherent in complex clinical decision making where EBM guidelines are lacking.

Phase I trial of weekly docetaxel with concurrent three-dimensional conformal radiation therapy in the treatment of unfavorable localized adenocarcinoma of the prostate.

PURPOSE: A phase I trial was conducted to determine the maximally tolerated dose (MTD) of concurrent weekly docetaxel and three-dimensional conformal radiation therapy (3-D CRT) in unfavorable localized adenocarcinoma of the prostate. PATIENTS AND METHODS: Patients with unfavorable localized adenocarcinoma of the prostate underwent daily 3-D CRT to a total dose of 70.2 Gy at 1.8 Gy/fraction and concurrent docetaxel given once a week for 8 to 9 weeks. The initial weekly docetaxel dose level was 5 mg/m(2) and the docetaxel doses were escalated as follows: 8, 12, 16, 20, and 25 mg/m(2). RESULTS: Between January 2000 and August 2002, 22 men completed the chemoradiation therapy protocol. The dose-limiting toxicity was grade 3 diarrhea, which occurred in the first two patients treated at the 25 mg/m(2) docetaxel dose level. The MTD of weekly docetaxel was determined to be 20 mg/m(2). The overall incidence of grade 2 diarrhea and grade 2 dysuria was 36% and 23%, respectively. Seven (32%) and 15 (68%) patients did not experience any diarrhea or dysuria, respectively. No neutropenia or thrombocytopenia was observed. One patient required intermittent urinary catheterization 10 months postcompletion of therapy, which resolved without any surgical intervention. Seventeen patients remain in prostate-specific antigen remission. At a median follow-up interval of 8 months (range, 2 to 27 months), all patients are alive. CONCLUSION: Concurrent weekly docetaxel in conjunction with 3-D CRT is well tolerated with acceptable toxicity. The MTD of weekly docetaxel was determined to be 20 mg/m(2) with concurrent 3-D CRT.

Robotic prostatectomy outcomes.

The triad of cancer cure, rapid recovery of complete urinary continence, and preservation of sexual function are desirable in the contemporary surgical treatment of the young potent male with prostate cancer. Robotic prostatectomy is a Food and Drug Administration approved approach to radical prostatectomy, and is performed at our institution and elsewhere. We present a critical assessment of reported outcomes using this minimally invasive technique.

Prospective metastatic risk assignment in clinical stage I nonseminomatous germ cell testis cancer: a single institution pilot study.

OBJECTIVE: To gain initial experience with a histopathologic model to assign metastatic risk in patients with clinical stage I nonseminomatous germ cell testis cancer (CSI NSGCTC). MATERIALS AND METHODS: Histopathologic factors were recorded prospectively, and metastatic risk assigned according to the proposed model. In the model tested, percentage of embryonal carcinoma (%EMB) > or = 80% and/or vascular invasion (+VI) denoted high (> 50%) occult disease risk, while %EMB < 80% plus absence of VI denoted low (< or = 10%) risk. Risk stratification was correlated with outcome and assessed statistically. RESULTS: There were 54 patients with CSI testis cancer evaluated during the study period. Patients with pure seminoma (n = 30), Sertoli cell tumor (n = 1), and Leydig cell tumor (n = 1) were excluded from analysis. Twenty-two patients had CSI NSGCTC and comprise the pilot study cohort. The median follow-up duration from the time of study entry is 31 months (range, 20-61 months). Utilizing the model tested, a statistically significant higher likelihood of occult disease in the high risk cohort compared to the low risk cohort was observed (67% vs. 0%; Fisher's exact test, P = 0.005). CONCLUSIONS: The results of the present pilot study are encouraging, particularly in the potential of identifying a cohort at low metastatic risk. In the appropriate setting, such a patient might be considered for surveillance alone following orchiectomy. High risk assignment was associated with a positive predictive value (PPV) of 67%. This level of risk is superior to single factor PPV, and if confirmed, could influence clinical decision making. Further experience with this model in an expanded setting is required to establish its reproducibility and predictive value.

Laparoscopic bilateral adrenalectomy with the use of a single midline hand-assist port.

Indications for bilateral adrenalectomy are rarely present in patients with Cushing's syndrome. The laparoscopic approach to adrenalectomy provides a postoperative course that compares favorably with that of open adrenalectomy, and the hand-assisted technique may provide an additional alternative to the open approach in performing bilateral adrenalectomy.

Dutasteride monotherapy in men with serologic relapse following radical therapy for adenocarcinoma of the prostate: a pilot study.

OBJECTIVE: The objective of this study was to assess the effect of dutasteride on serum prostate specific antigen (PSA) levels in men with serologic relapse following radical prostatectomy and/or radiation therapy for clinically localized adenocarcinoma of the prostate. METHODS: A prospective, single institution, IRB approved trial was conducted. Entry criteria required that all participants have serologic disease relapse only with serum PSA levels between 0.4 and 10.0 ng/ml. Enrolled participants were treated with 0.5 mg dutasteride daily. The primary endpoints were serum PSA level and clinical recurrence. The rate of durable decline in PSA was assessed according to the recommendations of the Prostate-Specific Antigen Working Group. RESULTS: Thirty-five patients provided informed consent and participated in the present study. At a median follow-up duration of 27 months (range, 4-42 months), 46% of enrolled men had a serum PSA decrease of greater than 10%, and 25% had a serum PSA decrease of greater than 50% (P < 0.001). Pre-study PSA doubling time (PSADT) (≥12 months vs. <12 months), and Gleason score (≤6 vs. ≥7) were associated with a better response to dutasteride, but only PSADT was statistically significant (P < 0.001). Thirty percent of patients experienced PSA progression (increase in serum PSA of greater than 50%). Two (6%) patients developed bone metastasis. No patient was removed from the study for drug-related toxicity. CONCLUSIONS: In the present pilot study, treatment with dutasteride resulted in a significant decrease in serum PSA in men with serologic relapse following radical treatment for adenocarcinoma of the prostate. These data appear to suggest that dutasteride may delay or prevent progression of prostate cancer in some men with biochemical relapse after radical therapy. These findings require confirmation in the setting of a larger, longer trial.

Fast track open partial nephrectomy: reduced postoperative length of stay with a goal-directed pathway does not compromise outcome.

Introduction. The aim of this study is to examine the feasibility of reducing postoperative hospital stay following open partial nephrectomy through the implementation of a goal directed clinical management pathway. Materials and Methods. A fast track clinical pathway for open partial nephrectomy was introduced in July 2006 at our institution. The pathway has daily goals and targets discharge for all patients on the 3rd postoperative day (POD). Defined goals are (1) ambulation and liquid diet on the evening of the operative day; (2) out of bed (OOB) at least 4 times on POD 1; (3) removal of Foley catheter on the morning of POD 2; (4) removal of Jackson Pratt drain on the afternoon of POD 2; (4) discharge to home on POD 3. Patients and family are instructed in the fast track protocol preoperatively. Demographic data, tumor size, length of stay, and complications were captured in a prospective database, and compared to a control group managed consecutively immediately preceding the institution of the fast track clinical pathway. Results. Data on 33 consecutive patients managed on the fast track clinical pathway was compared to that of 25 control patients. Twenty two (61%) out of 36 fast track patients and 4 (16%) out of 25 control patients achieved discharge on POD 3. Overall, fast track patients had a shorter hospital stay than controls (median, 3 versus 4 days; P = .012). Age (median, 55 versus 57 years), tumor size (median, 2.5 versus 2.5 cm), readmission within 30 days (5.5% versus 5.1%), and complications (10.2% versus 13.8%) were similar in the fast track patients and control, respectively. Conclusions. In the present series, a fast track clinical pathway after open partial nephrectomy reduced the postoperative length of hospital stay and did not appear to increase the postoperative complication rate.

Medical malpractice in urology, 1985 to 2004: 469 consecutive cases closed with indemnity payment.

PURPOSE: Malpractice premiums have increased by up to 57% for urologists in the last 3 years, for which the reasons are not clearly reported. We sought to better understand factors contributing to the current medical malpractice crisis in urology. MATERIALS AND METHODS: Working with the Medical Liability Mutual Insurance Company of New York State we evaluated malpractice claims in urology that were closed with indemnity payment between 1985 and 2004. Individual claims were assessed for the purported negligent act, the procedure when applicable and the expense incurred. We also evaluated the impact of new technologies, eg laparoscopic nephrectomy, on reported claims. RESULTS: A total of 469 urology malpractice claims were closed with indemnity payment during the period evaluated for a total loss indemnity of Dollars 99,335,431. The number of files closed with indemnity payment yearly remained relatively constant at an average of 22 claims. The average indemnity payment increased each year and after correcting for inflation a 191% increase was observed for the period evaluated. The greatest number of claims was related to postoperative events (total of 101), followed by intraoperative events (96), failure to diagnose a given condition (60), medication administration error (21) and a foreign body left following surgery (20). In the area of new technologies laparoscopic surgery accounted for 4 claims and transurethral needle ablation accounted for 1. Vasectomy accounted for 8 claims. CONCLUSIONS: In the current study surgical procedures were the greatest generator of claims with the most common being oncological. Emerging and new technologies, eg laparoscopy and robotics, did not account for the increase in indemnity payments observed to date. Only further investigation will determine whether this is secondary to a lag time in the closure of suits related to these emerging technologies or to a lack of such suits. The actual number of claims closed with indemnity payment yearly remained relatively constant. However, the indemnity payment per claim far outpaced that expected for inflation. The observed increase in indemnity payment per claim would appear to be a significant contributing factor to the current malpractice crisis in urology.

Routine pouchograms are not necessary after continent urinary diversion.

OBJECTIVES: Pouchograms are routinely performed before catheter removal after continent urinary diversion at our institution. Our aim was to determine the necessity of pouchograms based on a review of our experience. METHODS: A retrospective review of patient records and radiographic studies was done for patients undergoing radical cystectomy and continent urinary diversions between 1991 and 2001. RESULTS: Seventy-two patients underwent continent urinary diversion (orthotopic, n = 59; cutaneous, n = 13) during the study period. All underwent pouchogram postoperatively (median 22 days; range 20 to 27). Six patients (8.3%) had a demonstrable radiographic leak; in 5 of the 6 patients, the urine leak was suspected on clinical grounds. Three patients (4.7%) developed urosepsis after pouchogram. CONCLUSIONS: Our findings indicate that routine pouchograms before pouch activation after continent urinary diversion may not be necessary.

Implications of radioactive seed migration to the lungs after prostate brachytherapy.

OBJECTIVES: To review the incidence and the impact of pulmonary seed migration after prostate brachytherapy on lung function. Isolated reports of seed migration to the lungs after prostate brachytherapy have been published; however, the clinical consequences of this pulmonary migration have not been adequately evaluated. METHODS: We performed a retrospective review of patients undergoing prostate brachytherapy from 1998 to 2000. Pulmonary imaging with chest x-ray was performed 15 to 90 days (median 45) after the procedure. The chest radiographs were reviewed by a single radiologist (V.S.D.), and patients with seed migration to the lungs were evaluated by a single pulmonologist (A.M.H.) using a questionnaire, chest radiography, and pulmonary function tests. Computed tomography of the prostate after seed implantation was performed to check seed position and dosimetry. Odds ratio, confidence intervals, chi-square tests, and logistic regression analysis were performed to evaluate the relationship between the type and number of seeds used, the incidence of pulmonary migration, and the effects on pulmonary function. RESULTS: A total of 83 patients underwent prostate brachytherapy during the study period and 58 patients underwent chest radiography. Seed migration occurred in 21 (36.2%) of 58 patients (95% confidence interval 23.8% to 48.6%). Thirty-four (0.71%) of 4755 seeds used migrated to the lungs. Nine patients had single seed migration to the right lung and three to the left lung. Nine patients had multiple (maximum of 4) and bilateral seed migration. No consistent relationship was found between seed migration and the type of seeds used (P = 0.24). Borderline statistical significance suggested an increased incidence of seed migration with an increasing number of implanted seeds (P = 0.054). Repeat chest radiography in 21 patients revealed no delayed migration at a median follow-up of 16 months. Clinical and pulmonary function testing revealed no consistent abnormality attributable to seed migration. CONCLUSIONS: Radioactive seed migration occurred in 36.2% of brachytherapy patients who had chest radiographs done in our series. Pulmonary seed migration may be influenced by the number of implanted seeds and does not appear to be influenced by the seed type. Additional study of this observed phenomenon is required. A thorough pulmonary workup failed to reveal any short-term harmful side effects; however, long-term follow-up is needed. Healthcare providers should discuss the possibility of pulmonary seed migration with patients with prostate cancer considering prostate brachytherapy.