Torrence M. Wilson

Clinical stage Bo or T1c prostate cancer: Nonpalpable disease identified by elevated serum prostate-specific antigen concentration

A retrospective study was performed to evaluate the clinical and pathologic characteristics of 60 patients with a palpably benign prostate gland, but with biopsy-proved prostate cancer. All patients underwent prostate biopsy because of elevated serum prostate-specific antigen (PSA) concentration, and subsequently underwent radical retropubic prostatectomy (RRP). Similar analysis was performed for a randomly selected group of 60 clinical Stage B1 prostate cancers from the same period (control cohort). Patients with nonpalpable prostate cancers had a higher preoperative PSA level as compared with the clinical Stage B1 group (median value: 12.3 ng/mL versus 4.6 ng/mL, p < 0.001). There was no significant difference between the two groups with regard to clinical parameters (voiding symptoms, hematuria, age). The nonpalpable prostate cancers exhibited a significant tumor volume (mean: 7.4 cc; range: 0.3-56 cc), and 18 (30%) demonstrated capsular perforation to involve the periprostatic tissues. Of these, three (5%) had seminal vesicle invasion, and one (2%) had pelvic lymph node involvement. There was no difference between these pathologic characteristics and those of the clinical Stage B1 prostate cancers. These findings suggest that nonpalpable prostate cancers identified by an elevated serum PSA level can be of clinical significance and warrant therapeutic consideration. Although nonpalpable, these cancers are peripherally located and were clinically suspected prior to biopsy. Therefore, we propose that these cancers be classified as clinical Stage B0 in the Whitmore-Jewett staging system; in the new TNM staging system, they are designated as clinical Stage T1c.

PROSTATE BRACHYTHERAPY SEED MIGRATION TO THE RIGHT VENTRICLE FOUND AT AUTOPSY FOLLOWING ACUTE CARDIAC DYSRHYTHMIA

A 66-year-old man with coronary artery disease and a history of myocardial infarction underwent transperineal interstitial permanent prostate brachytherapy for localized prostatic adenocarcinoma in 1999. The 124 iodine loose radioactive seeds were implanted in the prostate and periprostatic tissues. On the day of brachytherapy a routine post-implant pelvic computerized tomography showed 46 seeds placed in extraprostatic locations immediately adjacent to the prostate. Two months following brachytherapy a chest x-ray revealed that 2 seeds had migrated to the mid right ventricle and 1 to the upper lobe of the right lung. Nine months after brachytherapy the patient died of acute cardiac dysrhythmia, which was unrelated to the presence of seeds in the heart. At postmortem examination the heart was dissected first by making several transverse slices through both ventricles. At the mid ventricular level 1 seed was discovered free in the lateral right ventricular cavity and 1 seed was next to it but adherent to the endocardium and encapsulated in a thin fibrous sheath (see figure). No gross or microscopic injury to the adjacent myocardium was present.

Prostate brachytherapy seed migration to a coronary artery found during angiography

Vascular migration of radioactive seeds to the lungs following permanent prostate brachytherapy is a recognized phenomenon. We report a case in which a seed became lodged in a coronary artery. CASE REPORT A 77-year-old man with a long-standing history of coronary artery disease underwent transperineal interstitial permanent prostate brachytherapy elsewhere in mid 2000 for treatment of early stage prostate cancer. More than 80 103 palladium loose radioactive seeds (TheraSeed Model 200, Theragenics Corp., Buford, Georgia) were implanted in the prostate and periprostatic tissues. Nine months after brachytherapy, the patient experienced increasing intermittent chest pain and underwent coronary angiography at our institution. This study demonstrated multiple vessel coronary artery disease and the presence of a metallic object in the septal perforator branch of the left anterior descending coronary artery. X-ray of the pelvis revealed the presence of multiple brachytherapy seeds in the prostate with radiopaque markers of the same size (approximately 1.1 mm. 0.5 mm.) as that of the metallic object in the coronary artery. Symptoms were deemed unrelated to the presence of the brachytherapy seed in the coronary artery according to the attending cardiologists (J. F. B., B. L. K.). Examination of the cine angiogram and pelvic x-ray by all coauthors confirmed that the metallic object in the coronary artery was a brachytherapy seed that had migrated (see figure). DISCUSSION We report a case of radioactive seed migration to a coronary artery. We previously described a case of seed migration to the right ventricle and noted that the presence of a right to left cardiac shunt might allow seed migration to a coronary artery or other locations.1 Seeds used in transperineal interstitial permanent prostate brachytherapy are 4.5 mm. in length and 800 m. in diameter and, thus, are small enough to migrate through the venous system to the right ventricle and become lodged in small pulmonary arterioles.2, 3 It is noteworthy that 25% of adults are found to have a probe patent foramen ovale at autopsy and, therefore, may have a right to left shunt. Such shunts are usually clinically insignificant, but they could nevertheless allow passage of a brachytherapy seed from the right to the left ventricle and into a coronary artery without traversing the pulmonary vasculature. Prior reports indicate that the percentage of patients who have at least 1 seed migrate to the chest following transperineal interstitial permanent prostate brachytherapy varies widely from 0.7% to 55%, whereas the total percentage of seeds that eventually migrate is less than 1%.2, 3 Thus, seed

USE OF HIGH FIDELITY OPERATING ROOM SIMULATION TO ASSESS AND TEACH COMMUNICATION, TEAMWORK AND LAPAROSCOPIC SKILLS: INITIAL EXPERIENCE

PURPOSE Structured opportunities for learning communication, teamwork and laparoscopic principles are limited for urology residents. We evaluated and taught teamwork, communication and laparoscopic skills to urology residents in a simulated operating room. MATERIALS AND METHODS Scenarios related to laparoscopy (insufflator failure, carbon dioxide embolism) were developed using mannequins, urology residents and nurses. These scenarios were developed based on Accreditation Council for Graduate Medical Education core competencies and performed in a simulation center. Between the pretest scenario (insufflation failure) and the posttest scenario (carbon dioxide embolism) instruction was given on teamwork, communication and laparoscopic skills. A total of 19 urology residents participated in the training that involved participation in at least 2 scenarios. Performance was evaluated using validated teamwork instruments, questionnaires and videotape analysis. RESULTS Significant improvement was noted on validated teamwork instruments between scenarios based on resident (pretest 24, posttest 27, p = 0.01) and expert (pretest 16, posttest 25, p = 0.008) evaluation. Increased teamwork and team performance were also noted between scenarios on videotape analysis with significant improvement for adherence to best practice (p = 0.01) and maintenance of positive rapport among team members (p = 0.02). Significant improvement in the setup of the laparoscopic procedure was observed (p = 0.01). Favorable face and content validity was noted for both scenarios. CONCLUSIONS Teamwork, intraoperative communication and laparoscopic skills of urology residents improved during the high fidelity simulation course. Face and content validity of the individual sessions was favorable. In this study high fidelity simulation was effective for assessing and teaching Accreditation Council for Graduate Medical Education core competencies related to intraoperative communication, teamwork and laparoscopic skills.

Pathogenesis of Bladder Calculi in the Presence of Urinary Stasis

PURPOSE Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. MATERIALS AND METHODS Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. RESULTS Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). CONCLUSIONS In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis.

Prostate Cryotherapy Monitoring Using Vibroacoustography: Preliminary Results of an Ex Vivo Study and Technical Feasibility

The objective of this research is to prospectively evaluate the feasibility of vibroacoustography (VA) imaging in monitoring prostate cryotherapy in an ex vivo model. Baseline scanning of an excised human prostate is accomplished by a VA system apparatus in a tank of degassed water. Alcohol and dry ice mixture are used to freeze two prostate tissue samples. The frozen prostates are subsequently placed within the water tank at 27degC and rescanned. VA images were acquired at prescribed time intervals to characterize the acoustic properties of the partially frozen tissue. The frozen prostate tissue appears in the images as hypoemitting signal. Once the tissue thaws, previously frozen regions show coarser texture than prior to freezing. The margin of the frozen tissue is delineated with a well-defined rim. The thawed cryolesions show a different contrast compared with normal unfrozen prostate. In conclusion, this pilot study shows that VA produces clear images of a frozen prostate at different temperature stages. The frozen tissue appears as a uniform region with well-defined borders that are readily identified. These characteristic images should allow safer and more efficient application of prostatic cryosurgery. These results provide substantial motivation to further investigate VA as a potential modality to monitor prostate cryotherapy intraoperatively.

Vibro-acoustography imaging of permanent prostate brachytherapy seeds in an excised human prostate--preliminary results and technical feasibility.

OBJECTIVE The objective in this work is to investigate the feasibility of using a new imaging tool called vibro-acoustography (VA) as a means of permanent prostate brachytherapy (PPB) seed localization to facilitate post-implant dosimetry (PID). METHODS AND MATERIALS Twelve OncoSeed (standard) and eleven EchoSeed (echogenic) dummy seeds were implanted in a human cadaver prostate. Seventeen seeds remained after radical retropubic prostatectomy. VA imaging was conducted on the prostate that was cast in a gel phantom and placed in a tank of degassed water. 2-D magnitude and phase VA image slices were obtained at different depths within the prostate showing location and orientation of the seeds. RESULTS VA demonstrates that twelve of seventeen (71%) seeds implanted were visible in the VA image, and the remainder were obscured by intra-prostatic calcifications. Moreover, it is shown here that VA is capable of imaging and locating PPB seeds within the prostate independent of seed orientation, and the resulting images are speckle free. CONCLUSION The results presented in this research show that VA allows seed detection within a human prostate regardless of their orientation, as well as imaging intra-prostatic calcifications.

Progress in Gene Therapy for Prostate Cancer

Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies.

Prostate volume before and after permanent prostate brachytherapy in patients receiving neoadjuvant androgen suppression

PURPOSELimited duration neoadjuvant cytoreductive hormonal therapy (NHT) is used before the definitive radiotherapeutic management of prostate cancer to decrease target volume size and/or to decrease urinary obstructive symptoms. The purpose of this study is to examine the effect of NHT on prostate volume before permanent prostate brachytherapy (PPB) and on prostatic edema after PPB. METHODS AND MATERIALSBetween May 1998 and February 2004, 408 patients underwent PPB at our institution and provided research authorization for the use of their records. Of these, 122 (30%) underwent NHT. Of the 122, 78 (64%) underwent transrectal ultrasound before the start of NHT. Patients undergoing PPB who received NHT were compared with a similar non-NHT group (N = 286). Detailed measurements of prostate volume were performed by transrectal ultrasound before and after NHT, if applicable. In addition, intraoperative preim plantation transrectal ultrasound and postimplantation transrectal ultrasound were also performed. Postimplantation computed tomography was performed within 1 day of PPB. RESULTSThe mean duration of NHT was 4.0 ± 1.1 months (range, 1–8 months). The mean prostate volume before NHT was 63.3 ± 22.8 cc (range, 19–138 cc), and after NHT (before PPB), it was 41.6 ± 16.4 cc (18–98 cc). The median prostate volume decrease after NHT was 22.7 cc or 34.9%. There was no significant difference in the degree of postimplantation prostate edema, as measured by the postimplantation to preimplantation ratio (1.18 ± 0.05 [range, 0.8–1.9]} for the NHT group and 1.21 ± 0.03 (range, 0.8–1.9} for the non-NHT group (P = 0.5). CONCLUSIONSProstate volume decreased by approximately one third after 4 months of NHT. NHT did not affect the degree of post-PPB prostatic edema.

BIOPSY-PROVED PROSTATE CANCER IN 100 CONSECUTIVE MEN WITH BENIGN DIGITAL RECTAL EXAMINATION AND ELEVATED SERUM PROSTATE-SPECIFIC ANTIGEN LEVEL Prevalence and Pathologic Characteristics

To determine whether a significant percentage of patients with a benign digital rectal examination (DRE) and an elevated serum prostate-specific antigen (PSA) level harbor a prostatic malignancy, 100 consecutive patients underwent transrectal ultrasound (TRUS)-guided biopsy of the prostate. The biopsy results were correlated with the pre-biopsy serum PSA level and ultrasound findings. Overall, the cancer detection rate was 35 percent (S.E. 4.8%). When the biopsy results were analyzed according to the PSA level, the rate of cancer detection increased with advancing PSA levels, irrespective of ultrasound findings. In the 60 patients with ultrasound abnormalities, the cancer detection rate was 47 percent compared with 18 percent for those without ultrasound abnormalities. Comparison of TRUS-negative and TRUS-positive biopsy results revealed a more than two-fold increase in cancer detection for the TRUS-positive group in each PSA range. Cancer detection in the TRUS-positive, PSA 4.1-10, 10.1-20.0, and > 20 ng/mL groups was 40 percent, 56 percent, and 67 percent, respectively; in the TRUS-negative group, cancer detection was 12 percent, 27 percent, and 33 percent, respectively. Twenty (57%) of the patients with prostate cancer underwent radical retropubic prostatectomy. The mean tumor volume was 4.7 cc. Seventy percent had organ-confined disease, 30 percent demonstrated capsular penetration only, and no patients had seminal vesicle or pelvic lymph node invasion. These data indicate that a significant percentage of patients with a benign DRE and an elevated serum PSA value harbor a clinically significant, but potentially curable prostatic malignancy.