Interstitial laser prostatectomy.

In an attempt to minimize the need for hospitalization and the associated perioperative and postoperative morbidity, alternatives to transurethral resection of the prostate (the standard treatment modality for benign prostatic hyperplasia) have been sought. Various types of laser prostatectomy have been proposed. Interstitial laser coagulation is performed by placing laser-diffusing fibers directly in the hyperplastic prostatic adenoma. The goal is to achieve coagulation necrosis within the adenoma, which causes the prostatic lobes to regress and thereby relieves the bladder outlet obstruction. Either the transurethral cystoscopic approach or the perineal approach can be used for laser application. Numerous published studies have shown that this laser procedure safely and effectively decreases symptoms of prostatism, increases the urinary flow rate, and reduces the volume of the prostate. Because of substantial tissue edema after treatment, catheter drainage may be necessary for 7 to 21 days. Although retrograde ejaculation has occurred occasionally (affecting from 0 to 11.9% of patients in reported studies) and uncomplicated urinary tract infections are common after interstitial laser coagulation, no cases of impotence or sustained incontinence have been described. Because interstitial laser coagulation is not associated with blood loss or intravascular fluid shifts and, if necessary, can be performed with a combination of local anesthesia and intravenous sedation, even high-risk patients are candidates for this procedure.

The optimization of laser prostatectomy. Part I: Free beam side fire coagulation.

OBJECTIVES: To study laser-tissue interaction and develop unifying principles for the optimization of free beam side fire neodymium:yttrium-aluminum-garnet (Nd:YAG) laser coagulation prostatectomy. METHODS: The heating patterns and coagulation volumes created by different right angle deflecting fibers were studied at different wattages and times in potato and canine models. RESULTS: In the potato, higher wattage resulted in deeper and more rapid heating. The high power density fibers created lesions of smaller volume which increased less with rising wattage than those fibers of lower power density. In the canine model, carbonization decreased heat penetration, and "popcorn" decreased superficial temperature without altering lesion size as long as it occurred without carbonization. As lasing progressed, smaller incremental increases in coagulation depth were achieved. CONCLUSIONS: To optimize coagulation laser prostatectomy, the surgeon should operate at the highest wattage which does not cause carbonization. The visualized intraoperative laser-tissue interaction allows the adjustment of laser power during the case as needed.

The optimization of laser prostatectomy. Part II: Other lasing techniques.

OBJECTIVES: To evaluate the laser-tissue interaction during neodymium:yttrium-aluminum-garnet (Nd:YAG) irradiation using right angle firing fibers in motion, contact vaporization applicators, and interstitial lightguides. METHODS: The heating patterns and coagulation volumes created during right angle firing fiber pulling and painting, contact tip vaporization, and interstitial thermotherapy were studied in potato and canine models. RESULTS: High power density right angle firing fibers can be used in motion to create coagulation lesions at 40 and 60 watts (W). The depth of such lesions was less than that obtained during fixed free beam side fire coagulation. Contact vaporization applicators caused tissue vaporization without creating concurrent coagulation lesions. Interstitial lightguide thermotherapy created coagulation lesions without carbonization using A step power reduction approach during irradiation. CONCLUSIONS: Each of the investigated methods had the ability to destroy prostate tissue, and therefore may have a role in the evolution of laser prostatectomy.

Electrosurgical vaporization of the prostate in the canine model.

OBJECTIVES: To investigate the histopathologic changes and heating patterns caused by electrosurgical vaporization of the prostate in the living canine model. METHODS: Prostate electrosurgical vaporization was undertaken in the canine model. Temperatures within and near the prostate and of the irrigation fluid were measured during a single pass and during the creation of a vaporized cavity. The prostate and adjacent tissues were examined by gross and microscopic pathology. RESULTS: Coagulation occurred deep to the vaporization zone for 1.38 to 1.44 mm for a single pass of the rolling cylinder and up to 2.52 mm for multiple passes. Thermometry revealed temperature increases of only 4 degrees C 5 mm away from the vaporization site. The largest temperature increases were found in the irrigation fluid as it passed through the prostatic fossa. Microscopic pathology revealed no damage to adjacent tissues. CONCLUSIONS: Electrosurgical vaporization creates minimal deep heating and coagulation beyond the vaporized cavity. The majority of the heat is removed by the irrigation fluid.

The influence of prostate size on cancer detection.

OBJECTIVES: To determine if cancer detection rates vary with prostate size using a sextant core biopsy pattern. METHODS: We reviewed 1021 transrectal ultrasound (TRUS)-guided sextant pattern prostate biopsies to determine if cancer detection varied based on prostate size. Prostate size was determined using a computer generated elliptical estimation method. Sextant core biopsies were taken, and the patients divided into groups based on estimated size of the prostate and biopsy outcome. Large prostates were those that were estimated by TRUS as 50 cc or more. Prostates were considered small if they were less than 50 cc. Groups were compared based on size and biopsy outcome. RESULTS: Adenocarcinoma was detected in 33% (334 of 1021) of the patients. Large prostates were noted in 34% (346 of 1021), of which 23% (80 of 346) had cancer detected by sextant biopsy. Small prostates were noted in 66% (675 of 1021), of which 38% (254 of 675) had cancer detected. The difference in cancer detection in large and small glands using a sextant pattern was statistically significant (P < 0.01). Patients with positive biopsies had significantly smaller prostate sizes (40 cc +/- 26) when compared with those with negative biopsies (51 cc +/- 33) (P < 0.01). Only 14% (8 of 58) of patients with gland sizes 100 cc or greater had positive sextant biopsies while 49% (118 of 239) with prostates 25 cc or less had cancer detected. Multivariate statistical analysis was used to control for differences in age, prostate-specific antigen (PSA), PSA density, TRUS findings, and digital rectal examination between the large and small prostate groups. The difference in cancer detection persisted (P < 0.05) CONCLUSIONS: Currently no evidence exists to support differing cancer rates based on gland size alone. Our cancer detection rate using a sextant pattern was higher in men with prostates less than 50 cc, and patients diagnosed with cancer had significantly smaller prostates than those with a negative sextant biopsy. Our data suggest that significant sampling error may occur in men with large glands, and more biopsies may be needed under these circumstances. The effects of tumor volume, focality, and specimen size in relation to overall gland size may contribute to these findings.

Gold-tip laser sleeve for a bare fiber.

A gold-tip laser sleeve for a bare laser fiber has been used for Nd:YAG laser irradiation of the prostate in both the canine model and a pilot clinical series. In the animal model, irradiation was undertaken using the Ablaser catheter through an open suprapubic cystotomy, and the procedure was monitored by video endoscopy via a perineal urethrostomy. Intraprostatic heating profiles were determined using real-time interstitial thermometry. As long as no carbonization occurred, irradiation with higher wattage resulted in higher intraprostatic temperatures. The "popcorn effect" caused a superficial temperature reduction but did not alter the ability of thermal conduction to heat deeper in the prostate. A small series of patients has been treated, with good results.

The "Wedge" resection device for electrosurgical transurethral prostatectomy.

The "Wedge" (Microvasive, Natick MA) is a new electroresection device for transurethral prostatectomy (TURP) using the standard resectoscope. The design, which is broader than the standard loop and thickens from front to back, results in better hemostasis when used at 275 to 300 W because of its ability to cut and coagulate tissue simultaneously. In the canine model, histologic examination demonstrated a 2-mm zone of coagulation around the chips and in the resection bed; this response was not observed in the specimens resected by the standard tungsten loop. No adjacent tissue damage was found with either the Wedge or the loop, and the temperatures recorded at the capsule rose only 4 degrees C regardless of the device used. In the 65 patients treated, the average hematocrit drop on postoperative Day 1 was 3.0%, and serum sodium was unchanged. One year postoperatively, the peak flow rate had increased by 101%, and the AUA Symptom Score was 6.1. The only surgical complication was urethral strictures (3%) necessitating incision. Most striking was the increased case of resection attributable to improved intraoperative vision. The data suggest that Wedge TURP is as safe and efficacious as standard loop TURP. The surgical field is markedly improved and clear because of intraoperative hemostasis. A TURP can be performed with a view toward minimizing patient morbidity and increasing surgical ease.

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.

Thick loop transurethral resection of the prostate.

OBJECTIVES: To evaluate the safety and efficacy of the new resection loops for transurethral resection of the prostate (TURP). These loops, which are both thicker and have a modified shape, allow simultaneous resection, increased tissue vaporization, and improved hemostasis. METHODS: Two open studies have been performed with the thick resection loop. In one series, 91 patients underwent TURP with the Vapor Cut (G. Vallancien, Paris), and in another series, 65 patients underwent Wedge (Microvasive, Natick, Mass., USA) resection (A. Perlmutter, New York). RESULTS: At 1 year follow-up, patients who underwent thick loop resection enjoyed the same clinical benefit of thin loop TURP without additional morbidity. Peak urinary flow rate improved to 18.4 and 16.3 cm3/s at 1 year with the Vapor Cut and Wedge, respectively. IPSS fell to 7.2 (Vapor Cut) and 6.2 (Wedge). Postoperative bleeding, meatal stenosis, and urethral stricture were noted, but no impotence or incontinence was observed. CONCLUSIONS: Thick loop resection offers the advantage of improved surgical vision during resection, thus allowing a more accurate and safer resection. This can be performed with only minor modifications of the standard TURP technique.

Antibodies of the secondary response can be expressed without switch recombination in normal mouse B cells.

A few percent of mouse splenocytes express isotypes characteristic of the secondary response together with IgM, and some cells express these isotypes alone. We isolated populations of small memory cells that express (i) IgM but not IgG1, (ii) IgM but not IgA, (iii) IgM and IgG1, (iv) IgM and IgA, and (v) IgG1 but not IgM. We have analyzed their DNA to show that there has been no switch recombination or deletion in the Ig constant region (C) genes. Using sandwich RNA hybridizations, we have found that cells expressing IgG1 contain nuclear RNAs that have both C mu and C gamma 1 sequences, and that cells expressing IgA contain nuclear RNAs that have both C mu and C alpha sequences. We propose that the expression of an isotype characteristic of the secondary response in memory cells is accomplished by alternative RNA processing of large (up to 180 kilobases) nuclear RNA transcripts that span the heavy chain gene locus.

Prostatic heat treatments for urinary outflow obstruction.

A nonrandomized pilot study was done of 139 patients with symptomatic benign prostatic hyperplasia treated with 3 prostatic heating devices. Of the patients 19 underwent transrectal hyperthermia with the Biodan Prostathermer and in 15 the Primus Prostate Machine was used. At 2 1/2 years 7 of 19 patients (37%) patients in the Prostathermer group and 6 of 15 (40%) in the Primus group had adequate sustained improvement and had not undergone further treatment. At 1 year 55 of 100 patients (55%) treated with the Thermex-II section transurethral thermotherapy unit had a satisfactory result, with 40 (40%) having undergone transurethral resection of the prostate. The number of patients who failed therapy increased with each followup. Analysis of pretreatment parameters, including patient age, prostate size, peak urinary flow rate, post-void residual urine volume and symptom score, did not predict a successful outcome. Although these devices have minimal effect on peak urinary flow rate, a subset of patients enjoy symptomatic improvement.

The effect of popcorn and carbonization on neodymium: YAG laser dosimetry in the canine model.

Neodymium:YAG laser irradiation of the canine prostate provides an experimental model for the study of the laser-tissue interaction in laser prostatectomy. Prostate irradiation was undertaken using right-angle-firing laser fibers through an open suprapubic cystotomy, and the procedure was monitored by video endoscopy via a perineal urethrostomy. The effects of popcorn and surface carbonization on intraprostatic heating profiles were determined by interstitial thermometry. We found that popcorn reduced intraprostatic temperatures but that continued irradiation resulted in the restoration of heating. Carbonization resulted in the loss of heating ability deep in the prostate. These observations allow the urologist to understand the thermal implications of observed surface change and to modify lasing parameters during surgery to obtain the desired laser-tissue interaction.

Creation of a volume lesion in the dog prostate using neodymium:YAG laser coagulation: concepts for clinical treatment.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine the geometrical development of a coagulated zone in the canine prostate during free beam side fire Nd:YAG laser coagulation. STUDY DESIGN/MATERIALS AND METHODS: A series of 10 male dogs underwent endoscopic prostatic Nd:YAG fixed position laser coagulation through a suprapubic cystotomy using a right-angle deflecting delivery catheter (Microvasive, Boston, MA) at times varying from 10 to 120 seconds at 30 watts. In addition, two dogs underwent lasing by pulling the catheter at 1 mm/s in four quadrants. Acute gross and microscopic pathology specimens were prepared and the lesion shape and volume determined. RESULTS: Analysis of the coagulated volume showed that during the initial 15 seconds of lasing, the zone of coagulation approximates a sphere centered on the urothelium opposite the laser fiber. However, as lasing progressed, the lesion changed from a sphere to an expanding ellipse. This changing geometry can be explained by the absorption and scatter characteristics of the laser and the temperature equilibrium that is established within the prostate. CONCLUSION: An understanding of this time-dependent geometrical shift from a sphere to an ellipse allows the surgeon to supplement the fixed protocols for lasing at certain positions for given amounts of time. Specific plans can then be established for tissue at the bladder neck, apex, anterior stroma, floor, and irregular prostatic regrowth.

Monoclonal AKR/J thymic leukemias contain multiple JH immunoglobulin gene rearrangements.

We have examined the patterns of heavy-chain immunoglobulin gene rearrangement and provirus integration in seven murine leukemia virus-induced thymic leukemias from AKR/J mice. In five of the seven tumors examined, there were between two and five rearrangements of the heavy-chain immunoglobulin J (JH) segment. Except for one case, the rearranged JH segments are present in less than one copy per cell, indicating that these tumors contain subpopulations of thymocytes with differing JH rearrangements. Nevertheless, each tumor is probably of monoclonal origin because the cells in a given tumor contain a common set of randomly integrated murine leukemia proviruses. Our results indicate that the JH segments rearranged within a few cell divisions after tumor cell proliferation began and may, therefore, identify a specific stage in T-cell differentiation when tumorigenesis occurs.

Precise location of two promoters for the beta-lactamase gene of pBR322. S1 mapping of ribonucleic acid isolated from Escherichia coli or synthesized in vitro.

We identified two promoters for the beta-lactamase gene of plasmid pBR322. RNA isolated from bacteria containing pBR322 or RNA transcribed in vitro on pBR322 templates was hybridized to 5' end-labeled single-stranded plasmid probes (Berk, A. J., and Sharp, P. A. (1977) Cell 12, 721-732). Electrophoretic analysis of the nuclease S1 digestion products next to Maxam-Gilbert sequencing ladders closely defines the transcriptional initiation points. The natural promoter lies near the coding sequence of the beta-lactamase gene, initiating transcription at -35 bases before the ATG initiation codon, while a second promoter initiates at positions -244 and/or -245 (on the opposite side of the Eco RI site). This promoter overlaps the promoter transcribing in the opposite direction toward the tetracycline gene(s) and starts in the -10 region of that promoter. S1 mapping of procaryotic mRNA, transcribed in vivo, allows both an accurate identification of promoters and the analysis of their transcriptional regulation.

Alteration of laser-tissue interaction with the 805 nm diode laser using indocyanine green in the canine prostate.

BACKGROUND AND OBJECTIVE: Research interests in laser prostatectomy continue to evaluate a variety of wavelengths and treatment parameters in an effort to optimize treatment. Recently, a semiconductor diode laser with a wavelength of 805 nm has become available for clinical use; however, free-beam noncontact applications were limited by the low power output (25 W). In this study in the canine prostate, the possible potentiating effects of intravenously administered indocyanine green (ICG) were evaluated with the 805 nm diode laser. STUDY DESIGN/MATERIALS AND METHODS: A total of 16 fixed position, free-beam lasings were performed at 25 W for 60 sec in four dogs with eight lasings before and eight lasings after ICG administration. Endoscopic observations and measurements of lesion volumes were used to evaluate the laser-tissue interactions. RESULTS: Prior to ICG administration, we observed that side fire irradiation produced primarily small coagulative lesions. Following ICG administration, however, immediate and more noticeable tissue vaporization occurred, although total lesion size was not increased. Pathologic review demonstrated less coagulation and hyperemia, but a larger vaporized cavity in the ICG treated tissue. CONCLUSION: These findings suggest intravenous ICG alters laser-tissue interaction with the 805 nm diode laser in the canine prostate. The use of the 805 nm diode laser with enhancing chromophores deserves further investigation.

Acute and chronic interstitial cryotherapy of the adrenal as a treatment modality.

Adrenalectomy is indicated for patients with large adrenal lesions or functional tumors. Cryoablation is currently used as a surgical alternative for the treatment of prostate, lung, brain, pharynx, and liver tumors. The purpose of this study was to determine if cryosurgery could be delivered to small areas in the adrenal gland in a controllable and reproducible manner such that tissue could heal in a nonpathologic way. A total of 14 female mongrel dogs underwent acute (n = 8) or chronic (4 weeks, n = 6) cryoablation using the Cryounit. In the acute study using an open transabdominal approach a 2-mm cryoprobe was placed interstitially into the adrenal tissue, whereas 0.032-inch thermocouples were cannulated into the ipsilateral adrenal artery and vein. Adrenal parenchymal temperature changes were measured using 0.032-inch thermocouples placed at 0.4- and 0.8-cm intervals from the cryoprobe. In the chronic study, cryoablation was achieved by transperitoneal laparoscopic access using a standard laparoscopic technique. Interstitial cryoprobe temperatures decreased from 33.1 +/- 1.9 degrees C to -148 +/- 1.2 degrees C following 15 min of freezing in the acute study. Cryoablation of adrenal tissue achieved temperatures of -41.8 +/- 5.7 degrees C and -21.8 +/- 1 degrees C at distances of 0.4 and 0.8 cm from the cryoprobe, respectively. There was no significant change in adrenazl artery or vein temperatures during cryoablation. Histologically there is a clear demarcation between viable and nonviable tissue characterized by areas of multifocal hemorrhage and pyknosis. After 4 weeks of healing a well-defined line of necrotic and viable tissue is visible. Cryoablation of the adrenal can be delivered in an effective, controllable, and reproducible manner. This controllable energy form may provide a new treatment modality for tissue destruction where adrenal gland preservation is necessary and can be performed by the laparoscopic approach. Understanding the effect of adrenal cryoablation may allow us to treat selected patients with small tumors where organ preservation is necessary.