Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Conservative treatment of superficial transitional cell carcinoma of prostatic urethra with intravesical BCG.

We reviewed 125 male patients treated with a six-week course of intravesical bacillus Calmette-Guerin (BCG) for superficial transitional cell cancer (TCC) of the bladder that was associated with mucosal involvement of the prostatic urethra in 15 cases. In 13 of these cases, there was a sustained complete response in both the bladder and the prostate. Among the other 110 patients, in 14 TCC developed in the prostate from one to fifty-three (mean 15) months after completion of BCG. Six of these 14 had had complete response in the bladder. Recurrent TCC in the prostate was seen in only 4 percent and 6 percent of patients who had prostatic urethritis on cystoscopy and prostatic granulomas on biopsy, respectively. In contrast, recurrence was observed in 14 percent of those without urethritis and in 44 percent of those without granulomas. Transurethral resection of the prostate (TURP) prior to BCG did not appear to influence tumor recurrence in the prostate. However, after BCG, 3 patients with recurrent TCC in the prostate had complete local response after TURP alone. Further, prostatic urethritis (73%) and prostatic granulomas (60%) were more frequent among patients who had TURP prior to BCG than in those without TURP (33% and 27%, respectively). Superficial TCC of the bladder associated with mucosal involvement of the prostatic urethra can be treated successfully with intravesical BCG. In addition, our results suggest that intravesical BCG has a prophylactic effect on tumor recurrence in the prostate, and that TURP may have an important role by removing present disease and by facilitating the development of an effective biologic response to BCG in the prostate. TCC in the prostate is a significant cause of relapse, and frequent surveillance of the prostatic urethra should be performed in conservatively treated patients with superficial bladder cancer.

Mechanism of healing of the human prostatic urethra following thermal injury.

OBJECTIVES: To characterize histopathologically the healing response of the prostatic urethra after laser thermal coagulation and standard transurethral resection of the prostate (TURP). METHODS: The study included 31 patients who underwent radical prostatectomy because of malignancy. Twenty-two (first group) had laser radiation either at the time of surgery (18 patients) or from 1 to 12 weeks prior to prostatectomy (4 patients). Nine patients (second group) had TURP from 6 to 96 weeks prior to prostatectomy. RESULTS: Coagulation necrosis followed by sloughing was observed during the first 10 weeks after laser radiation. After the first 10 weeks, the healing response was otherwise stereotypical and comparable for both groups of patients. Re-epithelialization was prominent and resulted from migration of proliferating epithelial cells from the remaining acinar and ductal epithelium. Squamous metaplasia was conspicuous and present indefinitely. Development of inflammatory reaction followed by granulation tissue and well-organized fibroblastic stroma were sequentially recognized, but less prominent. Complete re-epithelialization and wound sealing was not observed before the first 12 weeks of healing. CONCLUSIONS: Our study suggests that laser thermal coagulation and TURP are partial-thickness injuries. Because of the abundant germinal epithelium in the remaining prostatic glands and ducts, the healing response of the prostatic urethra is relatively unimpeded and free of contractures, analogous to second-degree skin burns.

Optical characterization and coagulation performance of side-emitting fiber delivery systems for laser therapy of benign prostatic hyperplasia: a comparative study.

OBJECTIVES: Currently, various side-emitting optical fibers with different tip geometry are used transurethrally to deliver laser radiation for treatment of benign prostatic hyperplasia (BPH). Since fiber tip design could profoundly affect the size and profile of the emitted laser beam, and consequently the tissue response and the extent of tissue coagulation, we evaluted commercially available fibers in regard to their optical characteristics and their ability to coagulate tissue in a controlled experimental setting. METHODS: Thirteen fibers manufactured by different companies and clinically used at the present time were tested using a surgical neodymium: yttrium-aluminum-garnet laser. The profile of the laser beam delivered via each fiber was imaged on a CCD camera at various distances and evaluated by means of a laser beam analyzer. Beam divergence angle was then calculated for each tip. Tissue coagulation effects were assessed by irradiating samples of beef muscle immersed in water at 37 degrees C. The fiber tip was kept 2.5 mm away from the tissue and irrigation was maintained at flow rate of 350 to 400 cc/min during irradation. Laser powers of 20, 40, and 60 W were used for 180, 90, and 60 seconds, respectively, delivering a total energy of 3600 J. RESULTS: The results of the optical evaluation divided the fibers into two major groups: broad beam with large divergence angle and narrow beam with small divergence angle. Statistical analysis of the data (using analysis of variance) showed that volumes of coagulated tissue were significantly larger for broad beam fibers than for narrow beam fibers (1.15 +/- 0.32 versus 0.89 +/- 0.34 cm 3; P < 0.05). Also, significantly larger volumes were obtained for 20 W when compared with 60 W (1.08 +/- 0.43 versus 0.88 +/- 0.27 cm 3; P < 0.05). CONCLUSIONS: The laser power density delivered by individual fibers to the prostate tissue may vary significantly, thus greatly affecting the extent of tissue coagulation. Therefore, irradiation parameters must be optimized for each fiber type.

Randomized clinical trial comparing low power-slow heating versus high power-rapid heating noncontact neodymium:yttrium-aluminum-garnet laser regimens for the treatment of benign prostatic hyperplasia.

OBJECTIVES: To evaluate and compare the safety and effectiveness of two noncontact laser regimens for the treatment of human benign prostatic hyperplasia (BPH), and to assess the impact of the spatial distribution of the laser-induced lesions on treatment outcome. METHODS: This was a prospective, double-blind, randomized study that included 29 patients with BPH (both the patients and the study physician assistant in charge of the follow-up evaluation were blinded to the treatment rendered). The patients were randomized to receive either a 15 W for 180 s (15 patients) or 50 W for 60 s (14 patients) laser regimen (powers measured at the fiber tip). There were two study phases for each treatment group: the irradiated sites were not overlapping during the first phase (lesions 1.5 cm apart), and were overlapping during the second phase (lesion less than 1.0 cm apart). RESULTS: Morbidity was minimal in both groups. At 1 year of follow-up, there was significant improvement of the American Urological Association-7 symptom score, the peak urinary flow rate, and the postvoid residual in both treatment groups. These improvements were not statistically significantly different regardless of time or the phase of the study for the two treatment groups. There were 3 treatment failures, 2 of whom were later successfully re-treated with larger amounts of laser energy. Furthermore, the peak flows in the second phase of the study were statistically significantly higher than those in the first phase of the study, regardless of the treatment group. CONCLUSIONS: Our results suggest that both the 15 W for 180 s and the 50 W for 60 s are equally safe and effective treatments for BPH. Perhaps more importantly, they also suggest that the spatial distribution of lesions and overlapping of treated (irradiated) sites has significant impact on treatment outcome.

Thermocoagulation effect of diode laser radiation in the human prostate: acute and chronic study.

OBJECTIVES: To evaluate the safety and efficacy of low-power slow-heating diode laser-induced photocoagulation of prostatic tissue for treatment of benign prostatic hyperplasia, we conducted a series of acute and chronic studies using a diode laser (810 nm) to irradiate human prostate. METHODS: The study included 6 patients undergoing radical prostatectomy because of malignancy. Laser radiation to the prostate was given transurethrally, in a noncontact mode, at the time of the procedure in 2 patients (acute group): 10 W for 300 seconds on the right side of the prostate and 15 W for 180 seconds on the left. In the remaining 4 patients (chronic group), laser radiation was given at 1, 7, 10, and 12 weeks prior to the prostatectomy. RESULTS: In the acute group the average depth of coagulation was 8.5 and 9.0 mm for the laser regimens of 15 W for 180 seconds and the 10 W for 300 seconds, respectively. In the chronic group, the average depth of coagulation was 8.9 mm for both laser regimens studied. In the acute group, there was an ill-defined hemorrhagic ring at the periphery of the lesion. At 1 week, an intact necrotic coagulum was present. At 7 weeks, some of the coagulated tissue had already sloughed off. Longer follow-up at 10 and 12 weeks demonstrated formation of a well-defined cavity with mostly re-epithelialized surface. CONCLUSIONS: Our findings suggest that noncontact diode laser (810 nm) irradiation can induce in the human prostate significant coagulation necrosis followed by sloughing of tissue and cavitation of the prostatic urethra.

Are we overlooking stage a prostate cancer in patients treated for benign prostatic hyperplasia with medical or minimally invasive modalities?

Our objective was to assess the likelihood of overlooking the diagnosis of prostate cancer (PCA), using current screening methods, in patients treated for benign prostatic hyperplasia (BPH) with medical or minimally invasive treatment modalities, which do not produce tissue specimens for histologic review. To appraise this, we examined the impact of the preoperative use of prostatic specific antigen (PSA) in combination with transrectal ultrasound (TRUS) and systematic sextant prostate needle biopsy (PNbx) on the subsequent incidence of stage A PCA in patients undergoing transurethral resection of the prostate (TURP). After excluding all patients found to have PCA during pretreatment screening, 485 patients who underwent TURP for presumed BPH from 1976 to 1994 were reviewed. From 1976 to 1989, PSA was not used for pretreatment screening, and stage A PCA was diagnosed in 11.4% of 317 patients. In 1990 and 1991, pretreatment screening included PNbx obtained under ultrasound guidance for PSA of 15.0 ng/ml or greater. Stage A PCA was diagnosed in 14.2% of 63 patients. From 1992 to 1994, pretreatment screening included systematic sextant PNbx performed for PSA greater than 4.0 ng/ml, and stage A PCA was diagnosed in 2.8% of 105 patients. The difference in incidence of stage A PCA between the first two groups and group three was significant (p = 0.021), as it was the difference in incidence of stage A(2) (P = 0.037). For stage A(1), the difference did not reach statistical significance (p = 0.089). Our findings suggest that systematic sextant PNbx for PSA greater than 4.0 ng/ml significantly reduces the risk of overlooking prostate cancer in patients undergoing treatment of BPH with modalities that do not provide tissue specimens.

Percutaneous treatment of transitional cell carcinoma of the upper urinary tract.

Fourteen selected patients with renal pelvic transitional cell carcinoma were managed percutaneously in our institution between March 1984 and April 1987. With a mean follow-up of 19 months, and excluding those patients who underwent immediate nephroureterectomy, six patients remain free of recurrent disease, which is similar to the results obtained with open parenchyma-sparing conservative operations. Our results suggest that percutaneous operations can provide cure in selected patients, including those with a normal contralateral kidney and with small (no more than 2-cm), single, low-grade, papillary tumors that are confined to the mucosa who, in addition, have negative cytology, negative random biopsies of contiguous mucosa, and no history of or concurrent transitional cell carcinoma elsewhere in the urinary tract. Further, our results suggest that second-look procedures with resection of suspicious residual disease, Nd:YAG laser irradiation of the tumor bed, and intracavitary administration of BCG all appear to help prevent recurrences.

Laser treatment of transitional cell cancer of the bladder and upper urinary tract.

Nd:YAG laser therapy now has a well-defined role in the treatment of superficial bladder cancer, that is, it is indicated only when one needs to destroy present tumors. Available results suggest that tumor recurrence is reduced, but definitive evidence of this is lacking. The laser's main advantage is that the procedure is carried out without anesthesia on an outpatient basis, because it is a noncontact technique that is associated with minimal morbidity and reduced pain and bleeding. Nd:YAG laser use in invasive bladder cancer would appear to be adequate for palliation only. For this indication, its benefits must be compared with conventional palliative TUR and/or radiation therapy. Laser therapy of tumors in the upper urinary tract is still in its infancy. Urothelial cancer is a multifocal disease, and the critical caveat, as in the case of bladder cancer, is tumor recurrence. Routine access to the upper tract and accurate assessment of the grade and stage of the tumor and the multifocality of the disease are of paramount importance and are not yet perfected. Photodynamic therapy is an intriguing modality. It has much potential for future development, but at present, because of its reduced ability to control superficial cancer, particularly when compared with other available forms of treatment such as intravesical BCG, and because of its significant associated morbidity, its use remains investigational.

Failure of the polymerase chain reaction (PCR) to detect human papilloma virus (HPV) in transitional cell carcinoma of the bladder.

In contrast to cervical and penile carcinoma, in situ hybridization techniques have not been able to demonstrate an association of HPV with transitional cell carcinoma (TCC) of the bladder. The introduction of the polymerase chain reaction (PCR) in the mid 1980s has significantly increased the ability to detect small quantities of viral DNA over conventional methods. Thus, we designed a study to determine if the PCR technique was able to demonstrate the presence of HPV DNA in TCC specimens. The study involved both consensus primers directed toward the E1 and L1 open reading frames of the HPV viral DNA, specific for HPV 6, 11, 16, 18, 31, 33. Thirty-three TCC specimens were studied (Fresh: 8, paraffin embedded: 25). Seven were Grade I, nine Grade II, seventeen Grade III; thirteen were superficial (Stages 0 and A) and twenty were invasive or metastatic (Stages B or Higher). None of the patients had known evidence of clinical HPV infection. In each experiment, the CaSki cell line was used for a positive control. In addition, the results of the PCR reactions were confirmed by Southern blot hybridization. Neither the PCR by direct ethidium bromide viewing, nor the Southern blot technique detected HPV DNA in any of the TCC specimens. This was in contrast to our controls, which were positive by both techniques. Although it is possible that there is a link between HPV and TCC, our results suggest that there is no such association among the HPV types tested.

Response of renal intrahilar retroperitoneal fibrosis to immunosuppressive therapy.

We report the case of a 37-year-old woman who developed renal failure secondary to obstruction by renal intrahilar retroperitoneal fibrosis. Her disease proved to be sensitive only to high-dose immunosuppression. Our case illustrates an unusual course of this disease and the role of immunosuppression in its management.

Effect of temperature and flow rate of irrigant on coagulation necrosis in canine prostate treated with neodymium:YAG laser.

We studied the effect of the irrigant temperature (5 degrees-38 degrees C) and flow rate (100-500 mL/min) on the extent of coagulation necrosis induced during Nd:YAG laser irradiation in the canine prostate model. The tissue response was quantified based on histopathologic evaluation of the lesions. Changing the irrigant temperature or the flow rate within the ranges studied did not significantly affect the size of the thermal lesions. The intraprostatic temperature distribution during laser irradiation is mainly governed by blood perfusion rather than by irrigant variables.

Low-power laser radiation for the treatment of benign prostatic hyperplasia: initial clinical experience.

Fifteen patients with significant bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH) were entered in a Phase II open pilot study designed to evaluate the effectiveness of a low-power-slow-heating (15 W x 180 seconds) laser regimen. Laser prostatectomies were performed with a right-angle firing neodymium:YAG laser fiber. Perioperative morbidity was minimal. Nine patients (60%) were able to void on their own within 72 hours after the procedure. The mean postoperative need for catheter drainage was 3.8 days (range 1 to 12). With a mean follow-up of 5 months (range 3-15 months), the improvement of the mean peak urinary flow rate was from 12.8 to 29 mL/sec, the mean postvoiding residual volume was reduced from 100 to 35 mL, and the AUA Symptom Score improved from 28.5 to 6. None of the patients required retreatment, and all the patients were pleased with the outcome. These results suggest that the laser regimen used in our study is safe and effective for the treatment of BPH.

Conservative management for transitional cell carcinoma of the upper urinary tract.

Transitional cell carcinoma of the upper urinary tract most frequently occurs in the sixth and seventh decades of life. Standard care for these tumors involves a nephroureterectomy with removal of a cuff of bladder. Many investigators now recommend parenchymal-sparing operations in selected patients to avert the previous inevitability of dialysis. Recently, advancements in endoscopic technology have afforded two new, less invasive complementary techniques for the diagnosis and treatment of these lesions: ureteroscopy and nephroscopy. Ureteroscopy, due to its less invasive nature, is generally used as a first line approach to diagnosis and treatment. Those tumors which are not accessible from a ureteroscopic approach or are simply too large for adequate resection may be excised by nephroscopic means. Early results of endoscopic intervention appear to be comparable to open parenchymal-sparing procedures.

Laser irradiation for the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most common medical problems encountered in the United States. For many years, transurethral resection of the prostate (TURP) has been the mainstay of treatment for symptomatic BPH. In recent times, newer modalities of treatment in the form of drugs (a- blockers, LHRH-agonist, anti-androgens, 5 a-reductase inhibitors), microwave hyperthermia, prostatic stents, balloon urethroplasty, laser prostatectomy, and most recently High Intensity Focal Ultrasound (HIFU) and Trans Urethral Needle Ablation (TUNA) are challenging TURP as the gold standard therapy for BPH. Today, laser prostatectomy holds a special place in therapy of BPH, as it is easy to perform, safe to apply with a vastly improved patient compliance, and is the first choice in certain special circumstances, e.g., patients on anticoagulants. In this chapter we discuss the present status of laser prostatectomy for BPH.

Influence of blood group type on the natural history of superficial bladder cancer.

The blood group was correlated with the grade and stage at diagnosis, and with the subsequent clinical course in 494 patients with bladder cancer treated at our institution from 1977 to 1986 who were followed for a mean of 5.5 years (range 2 to 9 years). The distribution of blood groups was similar to that reported for the general population and to that of 100 consecutive patients with urolithiasis used as controls, and the distribution was not different among patients with superficial cancer (stages O and A) than in those with advanced disease (stage B or higher). However, among patients with superficial disease high grade (III or IV) lesions were more frequent in those with blood group O (36 per cent) than in those with other blood groups (13 to 18 per cent) (p less than 0.001). In addition, in patients with superficial cancer of all grades progression to advanced disease was significantly greater among those with blood group O (37 per cent) than in those with other groups (12 to 16 per cent) (p less than 0.05). More importantly, in patients with low grade (I or II) superficial cancer development of advanced disease was significantly more frequent among those with blood group O (24 per cent) than in those with other blood groups (0 to 7 per cent) (p less than 0.004). Our findings suggest that individual genetic factors influence the natural history of superficial bladder cancer. The molecular basis of this phenomenon remains to be elucidated.

Breast masses associated with adenocarcinoma of the prostate.

A breast mass in a man with carcinoma of the prostate may represent metastatic disease or, less often, a primary carcinoma of the breast. Advances in the differentiation of these lesions and a comparison of treatment regimes are discussed.

Leiomyosarcoma of the penis.

The third case of leiomyosarcoma of the foreskin is reported. A review of the literature indicates that this lesion, which is similar to cutaneous leiomyosarcoma that is seen elsewhere in the body, has a low grade of malignancy. This finding is in contrast to leiomyosarcoma of the penis, which arises in deep structures and tends to metastasize. Circumcision appears to be the most effective treatment for leiomyosarcoma of the foreskin.