High power potassium-titanyl-phosphate laser vaporization prostatectomy.

PURPOSE: We prospectively studied a cumulative cohort of men with obstructive benign prostatic hyperplasia who underwent potassium-titanyl-phosphate (KTP) laser vaporization prostatectomy to determine the safety and efficacy of this procedure. MATERIALS AND METHODS: A total of 55 men with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia were treated with a 60 W. KTP laser produced by a prototype Laserscopedagger generator and delivered through a side-deflecting fiber with a 22Fr continuous flow cystoscope. Sterile water was used for irrigation. The prostatic lobes were vaporized to within capsular fibers. Mean lasing time plus or minus standard deviation was 44 +/- 19 minutes. RESULTS: Mean prostate volume plus or minus standard deviation was 43 +/- 14 ml. No patient had any significant blood loss or fluid absorption, or required blood transfusion. Foley catheters did not require irrigation and were removed less than 24 hours postoperatively. All patients remained satisfied with voiding outcome, which changed significantly (p <0.0001). Mean improvement in American Urological Association symptom score at 3, 6, 12 and 24-month intervals was 75%, 79%, 82% and 82%, respectively. Mean increase in peak flow rate at the same intervals was 250%, 242%, 255% and 278%, respectively. Complications included mild transient dysuria in 7%, bladder neck contracture in 2% and delayed hematuria in 4% of patients. None of the patients required re-catheterization or reoperation, or had incontinence or newly developed impotence. Of the sexually active patients 15% and 9% had retrograde ejaculation at 1 and 2 years, respectively. CONCLUSIONS: Our observation in a 2-year period indicates that 60 W. KTP laser vaporization prostatectomy is safe and effective for quickly relieving bladder outlet obstruction with minimal postoperative complications, a high rate of patient satisfaction and, to date, a generally good outcome.

High-power potassium titanyl phosphate laser vaporization prostatectomy.

In a search for potential therapeutic strategies for benign prostatic hyperplasia (BPH) that would be associated with less morbidity than transurethral resection of the prostate, various types of laser prostatectomy have been used. Although the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser allows performance of prostatectomy in an almost bloodless field and without absorption of irrigant, the remaining necrotic tissue causes bladder outlet obstruction and related symptoms for 5 to 7 days after treatment. In contrast, the potassium titanyl phosphate (KTP) laser has been found to vaporize tissue with minimal coagulation of the underlying structures. With use of the KTP laser, heat is concentrated into a small volume, the tissue is ablated by rapid vaporization of cellular water, and a 2-mm rim of coagulated tissue is left. After favorable results were obtained in studies of canine prostates and human cadavers, we implemented clinical use of 60-W KTP laser prostatectomy in selected patients. In 10 patients with symptomatic BPH who ranged in age from 52 to 80 years, outpatient KTP laser prostatectomy yielded significantly increased mean peak urinary flow rates (from 8.0 mL/s preoperatively to 19.4 mL/s within 24 hours after the procedure). No patient had hematuria, dysuria, or incontinence after removal of the catheter, and no patient required recatheterization. One patient, however, had urgency, and two other patients became febrile during the 24-hour observation period. Overall, KTP laser vaporization prostatectomy can provide immediate relief from obstructive symptoms of BPH and is not associated with dysuria.

High-power potassium-titanyl-phosphate (KTP/532) laser vaporization prostatectomy: 24 hours later.

OBJECTIVES: To study the feasibility and immediate postoperative outcome of vaporization prostatectomy by high-power potassium-titanyl-phosphate (KTP/532) laser in 10 men with bladder outlet obstruction due to benign prostatic hyperplasia (BPH) and to evaluate their clinical and voiding outcome 24 hours postoperatively. METHODS: The KTP/532 laser at 60 W was produced by a prototype Laserscope generator and delivered through a side-deflecting fiber with a 22F continuous-flow cystoscope. Sterile water was used for irrigation. The prostatic lobes were readily vaporized to within capsular fibers. The mean lasing time was 29 +/- 8 minutes, during which a mean of 104.6 +/- 30 kJ of energy was delivered. RESULTS: The prostate volumes ranged from 22 to 60 mL (mean 38.4 +/- 9.7). None of the 10 patients had any significant blood loss or any fluid absorption. Foley catheters were removed in less than 24 hours postoperatively. All patients were satisfied with their voiding outcome. The mean peak urine flow rate increased from 8 +/- 1.3 mL/s preoperatively to 19.4 +/- 8.4 mL/s (142%, P = 0.003266) 24 hours postoperatively. Postvoid residual volumes remained essentially unchanged from their preoperative levels, as expected (P = 0.767423). One patient had urgency, but none had dysuria, hematuria, or incontinence or required recatheterization. Three patients have returned for 3-month follow-up; all 3 patients have had excellent results and are very satisfied with the outcome. CONCLUSIONS: Our very early and limited experience indicates that high-power KTP/532 laser vaporization prostatectomy is feasible and appears to be safe and effective for quickly relieving bladder outlet obstruction due to BPH. Larger randomized clinical trials to compare this technique with standard transurethral resection of the prostate and more follow-up data are needed to determine its long-term efficacy and durability.

High-power (60-watt) potassium-titanyl-phosphate laser vaporization prostatectomy in living canines and in human and canine cadavers.

OBJECTIVES: We studied the safety and efficacy of 60-W potassium-titanyl-phosphate (KTP) laser prostatectomy in living dogs and compared the efficacy with that in fresh human and dog cadavers. METHODS: Ten dogs underwent 60-W KTP laser prostatectomy and were sacrificed 3 hours (n = 5) or 7 weeks (n = 5) after operation. Two thawed fresh-frozen human cadaver prostates and two thawed fresh-frozen canine prostates were also vaporized with the 60-W KTP laser. All prostates were weighed, measured, serially sectioned, and whole mounted for histologic analysis. RESULTS: In dogs, the in vivo procedure was hemostatic, and no irrigant absorption was detected. Prostatic defects with a mean diameter of 3.0 and 2.5 cm at 3 hours and 7 weeks postoperatively, respectively, were produced. With experience, resection time was reduced to 14 minutes. Of the 5 dogs that were studied for 7 weeks, 4 voided immediately after removal of the urethral catheter on the morning after operation, and 1 dog required recatheterization but voided with a strong stream when the urethral catheter was removed 4 days later. All 5 dogs were continent and had normal erectile function postoperatively. Defects of 2.0 and 2.5 cm were produced in the two human cadaver prostates (weight, 29.5 and 55 g) with resection times of 26 and 54 minutes, respectively. Human and canine cadaver prostates required similar energies for tissue vaporization (15.2 and 13.7 kJ/cm3 cavity created, respectively, P > 0.6), whereas living canine prostates required only 7.0 kJ/cm3 cavity created (P < 0.01 compared with cadaver tissue). CONCLUSIONS: The 60-W KTP laser allows technically easy, safe, rapid, and hemostatic removal of canine prostatic tissue in vivo. Furthermore, there is no difference in the efficacy of KTP laser vaporization between human and canine cadaver prostates. These findings suggest that KTP laser vaporization may be as effective in living human prostates as it is in living dogs, and thus it may be a useful technique in the surgical treatment of human benign prostatic hyperplasia.

Potassium-titanyl-phosphate laser vaporization of the prostate: a comparative functional and pathologic study in canines.

OBJECTIVE: We compared the functional and pathologic results of potassium-titanyl-phosphate (KTP) laser vaporization prostatectomy with those of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser vaporization and coagulation prostatectomy in dogs. METHODS: The prostates of 41 dogs were treated with KTP laser vaporization (n = 21), Nd:YAG laser vaporization (n = 10), or Nd:YAG laser coagulation (n = 10). Dogs were sacrificed 2 days or 8 weeks after treatment. Prostates were weighed, measured, serially sectioned, and whole-mounted for histologic analysis. RESULTS: All techniques were hemostatic, and no irrigant absorption was detected. KTP laser vaporization produced a prostatic defect with a mean diameter of 3.0 and 2.4 cm at 2 days and 8 weeks postoperatively, respectively. Smaller defects (P < 0.0005 at 2 days and P < 0.02 at 8 weeks) were produced by Nd:YAG laser vaporization (2.0 and 1.4 cm, respectively) and coagulation (0.5 and 0.9 cm, respectively). No dog treated with KTP laser vaporization was incontinent or developed urinary retention, including 5 dogs whose urethral catheters were removed within 24 hours of surgery. CONCLUSIONS: KTP laser vaporization prostatectomy not only provides hemostasis similar to that obtained with Nd:YAG laser coagulation, but also removes tissue at the time of operation, allowing dogs to void without straining within 24 hours of treatment. In addition, the procedure is technically simple, and the operator has excellent control over exactly which tissue is removed and which is left intact. These findings suggest that KTP laser vaporization may be useful in the treatment of human benign prostatic hyperplasia.

Stimulatory effect of phenobarbital on the metabolism of the oral contraceptive 17 alpha-ethynylestradiol-3-methyl ether (mestranol) by rat liver microsomes.

Pretreatment of rats with phenobarbital for 4 days stimulates the activity of liver microsomal enzymes that metabolize 17 alpha-ethynylestradiol-3-methyl ether (mestranol). This effect provides an explanation for the decreased uterotropic action of mestranol in rats pretreated with phenobarbital and may provide an explanation for unwanted pregnancies in women taking oral contraceptives in combination with phenobarbital or other enzyme-inducing drugs.

Phenacetin metabolism: effect of hydrocarbons and cigarette smoking.

The effects of cigarette smoking on phenacetin metabolism in the rat and in man have been investigated. Exposure of rats to cigarette smoke or pretreatment with the polycyclic hydrocarbon, 3,4-benzpyrene (benzo[a]pyrene), resulted in a more rapid disappearance of phenacetin in vivo. Additional studies demonstrated that hydrocarbon and smoking pretreatment of rats enhanced the 0-dealkylation of phenacetin to N-acetyl-p-aminophenol (APAP) by the intestinal mucosa. Cigarette smoking also increased the metabolism of phenacetin in man. The plasma concentration of phenacetin in cigarette smokers was lower than that in nonsmokers, whereas the ratio of the concentration of APAP to that of phenacetin was increased severalfold in the smokers. No difference in plasma half-life of elimination of phenacetin or in the amount of APAP excreted was found between smokers and nonsmokers. The lower blood levels of phenacetin in cigarette smokers could be the result of increased intestinal metabolism of the drug and/or first-pass metabolism in the liver.

Regulation of drug metabolism in man by environmental chemicals and diet.

Studies in animals have shown that many environmental pollutants induce the synthesis or inhibit the activity of microsomal mixed-function oxygenases that metabolize drugs, carcinogens and normal body constituents such as steroid hormones. These effects on microsomal enzyme activity alter the duration and intensity of action of foreign and endogenous chemicals in animals, and such effects on metabolism may influence the carcinogenicity of some pollutants in man. Studies on the effects of environmental chemicals on drug metabolism in man are sparse. Exposure of humans to DDT or lindane in a pesticide factory results in an enhanced rate of metabolism of antipyrine and phenylbutazone and an increased urinary excretion of 6-beta-hydroxycortisol. Polycyclic aromatic hydrocarbons present in cigarette smoke, in charcoal-broiled meats, and in polluted city air are potent inducers of drug-metabolizing enzymes in animals. In humans, cigarette smoking stimulates the activity of placental enzymes that metabolize several drugs and carcinogens. In addition, cigarette smokers metabolize phenacetin, theophylline, and other drugs more rapidly in vivo than nonsmokers. Dietary factors are important in the regulation of drug metabolism in animals and man. Feeding rats brussels sprouts or cabbage stimulates the intestinal and hepatic metabolism of drugs in animals. This effect is caused, at least in part, by certain indoles normally present in these vegetables. The feeding of a charcoal-broiled beef diet to rats stimulates the metabolism of phenacetin in vitro, and a similar diet stimulates the in vivo metabolism of phenacetin in man. It is likely that polycyclic aromatic hydrocarbons are the major inducers in charcoal-broiled beef.

Inhibition by CO of hepatic benzo[a]pyrene hydroxylation and its reversal by monochromatic light.

Inhibition by CO of benzo[a]pyrene hydroxylation was studied in hepatic microsomes from rats pretreated with phenobarbital, 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin, from animals treated with vehicle (saline or corn oil, respectively), and in a reconstituted microsomal cytochrome P-448 system prepared from rats treated with 3-methylcholanthrene. In all preparations the hydroxylation was inhibited by CO, and this inhibition was most effectively reversed by irradiation with monochromatic light of 450 nm wavelength. These observations provide direct evidence that the oxygen-activating component of all the examined benzo[a]pyrene hydroxylase systems is a P-450-type heme protein. The only striking difference observed in these systems was the low CO sensitivity of the benzo[a]pyrene hydroxylase reaction in microsomes from animals treated with 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Half-maximal inhibition occurred at CO/O2 ratios of 9--12, rather than at 1--2, which is the usual range for P-450-linked mixed-function oxidase reactions. In contrast, the reconstituted benzo[a]pyrene hydroxylase system, with purified cytochrome P-448 from 3-methylcholanthrene-induced rats, exhibited a considerably higher sensitivity towards CO (CO/O2 ratio approximately 1), well within the range for mixed-function oxidase reactions. It is concluded that the observed diminished CO sensitivity of microsomal benzo[a]pyrene hydroxylase in 3-methylcholanthrene- or 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats results from alterations in the composition and/or structural organization of the microenvironment of cytochrome P-448 in the endoplasmic reticulum in response to the inducing action of polycyclic aromatic hydrocarbons and related agents, and is not related to changes in the heme protein P-448 per se. The detailed nature of these changes is the subject of ongoing studies.

Stimulatory effect of vegetables on intestinal drug metabolism in the rat.

The intestinal metabolism of hexobarbital, phenacetin, 7-ethoxycoumarin and benzo [a] pyrene in vitro was increased in rats fed either dried Brussels sprouts or dried cabbage in a nutritionally complete semisynthetic diet as compared to rats fed only the semisynthetic diet. Pretreatment of rats with several indoles present in Brussels sprouts and cabbage also stimulated intestinal drug metabolism, but the effect was smaller than when dried Brussels sprouts or dried cabbage was fed. The results obtained suggest a need for studies in man to determine whether vegetables and other dietary constituents can stimulate the intestinal metabolism of drugs and thereby alter their biological effects.

Inhibition of the acute toxicity and adrenocorticolytic effect of 7,12-dimethylbenz(a)anthracene by isopropylvaleramide and allylisopropylacetamide in the rat.

Isopropylvaleramide (IVA) and allylisopropylacetamide (AIA) inhibit hemorrhagic adrenocortical necrosis and mortality caused by 7,12-dimethylbenz(a)anthracene (DMBA) in female Sprague-Dawley rats. Unlike their effect on hepatic microsomal cytochrome P-450, the anti-DMBA action of these compounds does not depend on the presence of the reactive allyl group in the molecule. Similarly, related barbiturates, regardless of whether they contain, like AIA, an allyl group and consequently destroy cytochrome P-450 (secobarbital and aprobarbital) or have, like IVA, saturated side chains and therefore do not effect the microsomal hemoprotein (pentobarbital and phenobarbital), proved ineffective in preventing both adrenal damage and death caused by DMBA. Hence, the protective action of IVA and AIA cannot be attributed to the destruction of the microsomal enzyme system responsible for the activation of DMBA. The toxicity of another carcinogen, dimethylnitrosamine, which also requires metabolic activation by microsomal enzymes, is not influenced by either IVA or AIA. IVA, which counteracts the adrenocorticolytic action of DMBA when given prior to, simultaneously with, or even after this carcinogen, has no discernible effect on hydrocarbon metabolism in vivo or in vitro. IVA is one of the most powerful inhibitors of the acute toxicity of DMBA. It has the simplest aliphatic structure and the smallest molecule among protectors of the adrenals against hydrocarbon-induced damage; its mechanism of action awaits further elucidation.

Intestinal metabolism of phenacetin in the rat: effect of charcoal-broiled beef and rat chow.

The intestinal metabolism of phenacetin in vitro was increased 1100 percent in rats fed charcoal-broiled ground beef in a semisynthetic diet. The intestinal metabolism of phenacetin was increased 200 percent in rats fed a chow diet, as compared to rats fed the semisynthetic diet. The results obtained suggest a need for studies in man to determine whether charcoal-broiled meat and other dietary constituents can stimulate the intestinal metabolism of phenacetin or other drugs and thereby decrease their absorption and bioavailability.

Partial purification and separation of multiple forms of cytochrome. P-450 and cytochrome P-448 from rat liver microsomes.

1. Partial purification of liver microsomal cytochrome p-450 results in the separation of two forms of cytochrome p-450 from phenobarbital-treated rats and two forms of cytochrome p-44, from 3-methylcholanthrene-treated rats. 2. Each of the four cytochrome fractions had different spectral properties (absolute spectra, CO differences spectra, and ethylisocyanide difference spectra). 3. The hemeprotein in fractions which elute from a DEAE-cellulose column at 100 mKM KCl fraction IV B) are more highly purified than the hemeproteins (fraction IV A) that elute in the column volume. 4. The more highly purified cytochrome fractions (IV B) contain 9-11 moles of cytochrome P-450 or P-448 per mg protein (an approximately 5-7 fold purification over microsomes) and are enzymatically active in the metabolism of a variety of substrates when combined with lipid and NADPH-cytochrome c reductase. These hemeprotein fractions are free of cytochrome b5 and NADPH-cytochrome c reductase, and the hemeproteins are purified approximately 100-fold with respect to phospholipid. The cytochrome P-450 and P-448 are virtually free of epoxide hydrase.