Cryosurgery of prostate cancer. Use of adjuvant hormonal therapy and temperature monitoring--A one year follow-up.

OBJECTIVE: To determine the clinical outcomes at one year of Stages T2-T3 prostate cancer by cryosurgery utilizing pretreatment with total androgen ablation therapy and temperature monitoring to control the freezing process. Study Group To date, 347 patients have had 356 cryosurgical procedures, 280 have reached one year post treatment. Of these 131 had re-evaluation with prostatic biopsy and serum PSA. METHODS: Transrectal ultrasound (TRUS) measurement of tumor size and biopsy of extraprostatic space was used to stage patients into two main groups: confined (66.6%) versus nonconfined (19.3%). Radiation failures (14.1%) formed a separate group. Failure rates for the 131 men include all cancer diagnosed during the one year period following cryosurgery. RESULTS: The one year failure rate for the study group was 19.8% (26/131). For stages T2a, T2h C, T3 and radiation failures, the rates of positive biopsies were 13.9%, 12.9%, 33.3% and 35%, respectively. For those with local control of cancer (negative biopsy), 80% had prostate specific antigen (PSA) levels of < 0.5 ng/ml. The statistical variables for persistent cancer with prostate specific antigen > 0.5 ng/ml were: sensitivity of 66.7%, PPV of 16.7%, NPV of 98% and specificity of 83.7%. A statistically significant difference exist between stages T2 vs T3 and radiation failures (p = < 0.5). Major complications of rectal fistula and total incontinence for previously non-treated cancer versus radiation failures were 0.33% and 8.7% respectively, a 26 times greater risk. CONCLUSION: Results of cryosurgery for all stages of prostate cancer at one year are encouraging, being 80% free of disease (biopsy and prostate specific antigen). The morbidity of the previously non-treated cancers from this procedure for us was minimal with high patient acceptance. For radiation failures a local control rate of 65% was achieved. However, early in our experience significant morbidity did occur and our enthusiasm for attempted salvage was initially tempered.

Differential pulmonary responses in rats inhaling crystalline, colloidal or amorphous silica dusts.

Pulmonary responses in rats were compared after short-term inhalation exposure to polymorphs of silica dust. Groups of CD rats were exposed 6 h a day for 3 d to crystalline silica or amorphous silica. Another group was exposed to Ludox colloidal silica for 6 h a day, 5 d a week for two or four weeks. Thereafter the groups were killed, and the lungs washed at several postexposure times. The crystalline silica produced persistent pulmonary inflammatory responses characterized by neutrophil recruitment and consistently elevated biomarkers of cytotoxicity in bronchoalveolar lavage fluids, and progressive histopathological lesions were observed within one month of the exposure. Amorphous silica produced a transient pulmonary inflammatory response, and Ludox elicited transient pulmonary inflammatory responses at 50 or 150 mg center dot m-3 but not at 10 mg center dot m-3. After three months most of the biochemical values of the Ludox-exposed animals had returned to the control level. These results demonstrate that crystalline silica dust is more potent in producing pulmonary toxicity when compared with amorphous or colloidal silica particles.

Biopersistence of inhaled organic and inorganic fibers in the lungs of rats.

Fiber dimension and durability are recognized as important features in influencing the development of pulmonary carcinogenic and fibrogenic effects. Using a short-term inhalation bioassay, we have studied pulmonary deposition and clearance patterns and evaluated and compared the pulmonary toxicity of two previously tested reference materials, an inhaled organic fiber, Kevlar para-aramid fibrils, and an inorganic fiber, wollastonite. Rats were exposed for 5 days to aerosols of Kevlar fibrils (900-1344 f/cc; 9-11 mg/m3) or wollastonite fibers (800 f/cc; 115 mg/m3). The lungs of exposed rats were digested to quantify dose, fiber dimensional changes over time, and clearance kinetics. The results showed that inhaled wollastonite fibers were cleared rapidly with a retention half-time of < 1 week. Mean fiber lengths decreased from 11 microns to 6 microns over a 1-month period, and fiber diameters increased from 0.5 micron to 1.0 micron in the same time. Fiber clearance studies with Kevlar showed a transient increase in the numbers of retained fibrils at 1 week postexposure, with rapid clearance of fibers thereafter, and retention half-time of 30 days. A progressive decrease in the mean lengths from 12.5 microns to 7.5 microns and mean diameters from 0.33 micron to 0.23 micron was recorded 6 months after exposure to inhaled Kevlar fibrils. The percentages of fibers > 15 microns in length decreased from 30% immediately after exposure to 5% after 6 months; the percentages of fibers in the 4 to 7 microns range increased from 25 to 55% in the same period.(ABSTRACT TRUNCATED AT 250 WORDS)

US-guided percutaneous cryoablation of prostate cancer.

A tailored approach to cryosurgery of prostate cancer is presented. The authors have performed 214 cryoprocedures to date with use of this protocol. The technique requires pretreatment with androgen ablation therapy, preoperative diagnosis and staging with ultrasound (US)-guided biopsies, and detailed knowledge of prostate and rectal anatomy. Five cryoprobes are placed in the prostate under US guidance in a configuration that depends on tumor location, sites of extracapsular extension, the size of the tumor, and gland geometry. Freezing starts anteriorly to keep from obstructing the ultrasound beam. Two freezes are performed at the known cancer site, and additional freezes are performed, if necessary, to include the remainder of the gland. Thermosensors enable monitoring of the cryosurgical ice ball and determination of the number of freezes. Cryosurgery is always performed by a urologist and a radiologist working together.

The role of transrectal ultrasound-guided staging biopsy and androgen ablation therapy prior to radical prostatectomy.

Radical prostatectomy is the most common therapy for localized prostate cancer. Unfortunately, resection is associated with positive surgical margins in 35-50% of cases. We report the use of ultrasound-guided staging biopsies to stage tumors preoperatively with greater accuracy. We also report the use of androgen ablation therapy (AAT) as an adjunct to radical prostatectomy in an attempt to downstage tumors preoperatively and decrease the incidence of positive margins. Between 1 June 1991 and 31 July 1992, 131 patients underwent radical prostatectomies, 119 of whom underwent AAT before surgery and 12 of whom did not. Specimens were examined for the presence of positive surgical margins, extracapsular extension, and perineural invasion. Cases pretreated with AAT had a 9.2% positive surgical margin rate compared with 33% in untreated subjects. Extracapsular extension was seen in 22 of 119 (18.5%) of AAT, and 5 of 12 (41.7%) of non-AAT, cases. Perineural invasion was nearly 3 times less likely in AAT patients. Moreover, perineural invasion was significantly less marked in AAT patients. We present a subset of 11 patients who were definitively proven as pathologic stage C cancer by transrectal ultrasound (TRUS)-guided needle biopsy. These cases had prostate cancer intermixed with fatty tissue and pigmented seminal vesicle epithelium, elements not found in the prostate. In this selected stage C subset, gland shrinkage, evidence of downstaging, and tumor obliteration were seen after AAT. We conclude that TRUS-guided staging biopsy can definitively stage prostate cancer as stage C when tumor is intermixed with extraprostatic elements, and AAT appears to decrease the incidence of positive surgical margins by tumoral necrosis and selective perineural kill. We believe that these findings demonstrate the antitumor effects of AAT and deserve further scrutiny in a large randomized clinical trial.

Hormone ablation therapy as neoadjuvant treatment to radical prostatectomy.

Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone (n = 119) or were treated for an average period of 3 months with combination therapy using the antiandrogen flutamide and one luteinizing hormone-releasing hormone (LHRH) agonist (Lupron or Zoladex). The positive margins decreased from 35.3% in the group undergoing prostatectomy alone to 11.5% in the group of men who received combination therapy before radical prostatectomy. In 41 apical tumors, the incidence of positive margins decreased from 50% in the control group to 18.6% in the combination therapy group. In stage C disease, the incidence of positive tumor showed a tendency to decrease with the extended duration of endocrine treatment with a rate of 37.5% after 3 months and 16.7% after 6 months. Whether the decreased incidence of positive surgical margins will all translate into prolonged survival remains to be verified by long-term follow-up of these patients. However, the initial results obtained in the present study are very encouraging.

Iron uptake from transferrin and asialotransferrin by hepatocytes from chronically alcohol-fed rats.

Chronic alcohol intake is often associated with alterations to iron homeostasis and an increase in the serum levels of carbohydrate-deficient transferrin. As the liver is a major iron storage site and also synthesizes transferrin, the normal serum iron transport protein, the aim of this study was to test the hypothesis that these disturbances in iron homeostasis were caused by altered hepatocyte iron uptake from the abnormal transferrin. To achieve this, we have investigated iron uptake from both transferrin and asialotransferrin by hepatocytes from male Sprague-Dawley rats fed the De Carli and Lieber alcohol diet. Iron uptake from transferrin by hepatocytes from alcoholic rats was less than 60% that of control values, and in the presence of 50 mM ethanol decreased still further to 35% of the uptake by the corresponding control cells. Iron uptake from rat asialotransferrin was reduced in both groups when compared to that observed from normal transferrin; 13% by control cells and 39% by hepatocytes from alcohol-fed rats. Alcohol, however, had no further effect on asialotransferrin uptake by either hepatocytes from alcohol-fed rats, or their pair-fed controls. Transferrin binding to hepatocytes was also influenced by the alcohol diet. Although there was no difference in binding at 37 degrees C, cells from alcohol-fed rats bound 85% of this total at 4 degrees C, compared to 44% by control hepatocytes. Similar values were also obtained for hepatocyte binding of asialotransferrin; alcohol feeding resulted in an increase in binding at 4 degrees C to 73% from 58% with control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Predicted prostate specific antigen results using transrectal ultrasound gland volume. Differentiation of benign prostatic hyperplasia and prostate cancer.

METHODS: The diagnostic performance of transrectal ultrasound (TRUS) gland volume and prostate specific antigen (PSA) results were evaluated in 204 men consecutively scheduled to undergo transurethral prostatic resection (TUR). RESULTS: Nonpalpable prostate cancer was detected by TRUS alone in 18% (29 of 161) and by TUR alone in 9% (14/161), for an overall cancer incidence of 27%. A predicted PSA value (TRUS gland volume x 0.20 ng/ml/g = polyclonal PSA) was used for comparison with serum PSA for each patient. TRUS positive predictive value improved from 52% to 86% when serum PSA exceeded the predicted value. The specificity and positive predictive value of PSA at 2.5 ng/ml were 23% and 37%, respectively, which increased to 88% and 72%, respectively, when serum PSA exceeded the predicted value. CONCLUSIONS: Predicted PSA values produce decision levels near the 95th percentile for each patient and assist individual biopsy decisions better than grouped gland volume ranges. Wider application of TRUS and PSA in any clinical setting or early detection program is now possible.

Social support and treatment outcome in behavioral family therapy for child conduct problems.

This study assessed the role of social support in the outcome of child management training (CMT) for single parents of conduct problem children and assessed the impact of adjunctive ally support training (AST) on treatment outcome. Single parents (N = 22) with a child diagnosed as oppositional or conduct-disordered received CMT or CMT plus AST. Each group received the same 6-week parent training program and the AST group received an extra social support intervention. Measures of parent behavior, child deviance, social support (SS), and parental depression were obtained at pre- and posttreatment and at 6-month follow-up. Both groups improved, and changes maintained at follow-up. AST produced no extra gains. Responders from either group were more likely than nonresponders to report high levels of SS from friends. Results emphasize the importance of SS and the difficulty of incorporating changes in SS into treatment programs.

Role dissatisfaction and the decline in marital quality across the transition to parenthood.

PIP: In the examination of role dissatisfaction and decline in marital quality across the transition to parenthood, it is postulated that 1) there would be a decline in the mean level of marital quality particularly among females, and 2) that the level of perceived inequity in postpartum allocation of marital roles would moderate the effects of the transition. A background review of pertinent literature pertaining to role dissatisfaction is presented, and found to be complex. Role inequity was measured as the level of dissatisfaction with a partner's contribution to a range of different role activities postpartum. The Australian sample was comprised of 59 primiparous couples who reported levels of marital satisfaction during the last trimester of pregnancy (Time 1) and then 3 months after the birth of the baby (Time 2). Couples were recruited from a variety of sources: private physicians, childbirth classes, and public hospitals. Average marriage duration was 3.5 years. Mean female age was 23.85 years and mean male age was 26.71 years. Most had completed at least 12 years of formal education. Marital quality was measured by a 32 item Dyadic Adjustment Scale (DAS) comprised of units on dyadic satisfaction, consensus, cohesion, and affectional expression. Time 1 mean correlation of subscales was .43, and Time 2, .36. Dissatisfaction with partner's role performance was measured with an instrument of 18 items developed by Noller and Callan. Alpha coefficients were .69 and .71 for males and females respectively. Multivariate analysis of variance was used to assess marital quality scores by sex and time period and changes in marital quality due to level of postnatal role dissatisfaction by sex and time period. The Bonferronni procedure was used to control the Type 1 error rate for all analyses after the initial analysis of variance. The results revealed that the decline in marital quality reported in the literature may be a reflection of a decline in affectional expression. There was no support for the expectation that females experienced greater declines in marital quality than males, although it is possible that those experiencing greater dissatisfaction may not have provided followup data. There was support for the notion that females' levels of role dissatisfaction account for declines in marital quality; i.e., there was a decline in scores of affectional expression of women only who were also dissatisfied with a partner's role performance. When females perceived partner's performing a fair share in household tasks, marital quality increased. Future research on causation should explore the inequity model and use an objective measure of 1 or both variables. The link between role relations to the extent of change in new mothers' levels of marital quality suggests prenatal counseling on marital roles. Role inequity had no effect on male levels of decline in marital quality. Independent processes may account for these results, but there is a promising direction.^ieng

Prostate cancer: transrectal ultrasound and pathology comparison. A preliminary study of outer gland (peripheral and central zones) and inner gland (transition zone) cancer.

A study was conducted to compare results of transrectal ultrasound with pathologic findings on 116 patients who underwent radical prostatectomy for treatment of prostate cancer. In 96% (111 of 116), transrectal ultrasound guided biopsies of a hypoechoic lesion proved cancer; seven patients had known Stage A cancer; one patient had cancer detected by palpation and not detected by ultrasound. Cancers in the outer gland (peripheral and central zones) were compared with cancers in the inner gland (transition zone) by both ultrasound and pathology. Forty-eight percent (52 of 108) of cancers originating in the outer gland showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the outer gland were the prostatic capsule (38%), anterior fibromuscular stroma (5%), seminal vesicle (18%), the base of the gland at the neurovascular bundle (21%), and the apex (31%). Twenty-two percent (17 of 54) of cancers originating in the inner gland (transition zone) showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the inner gland were the anterior fibromuscular stroma (6%) and apex (11%). Both histologic and biologic differences between outer and inner gland cancers were found when tumor size was controlled. Gleason scores were significantly different for inner and outer gland cancers, with mean scores of 6.2 +/- 1.6 and 7.4 +/- 0.9, respectively. An odds ratio of 8.6 confirmed the increased risk of extraprostatic extension for outer gland cancer. Outer gland cancers showed increased aggressive behavior of both histologic and biologic nature. The difference in biologic aggressiveness of outer and inner gland cancers has definite implications for treatment options. Use of other diagnostic parameters, such as DNA ploidy, may help to determine which cancers to treat and when to treat them; this may have more relevance for cancers originating in the inner gland. Strategic transrectal ultrasound guided biopsy affords accurate tumor mapping and staging when modes of internal spread and escape of cancer from both outer and inner gland are known. Thus, transrectal ultrasound may be our "window of observation" through which additional research may explain the histologic and biologic discrepancies between outer and inner gland cancers.

Nonpalpable cancer of the prostate: assessment with transrectal US.

Palpable cancer of the prostate is widely believed to be clinically significant. The authors compared the clinical significance of palpable prostate cancer with nonpalpable prostate cancer discovered with transrectal ultrasound (US). A strong association between lesion volume measured with preoperative transrectal US and volumetric measurements in 60 radical prostatectomy specimens permitted the use of tumor size measured with transrectal US as a reasonable estimation of gross tumor volume. In a subsequent clinical series, 147 biopsy-proved cancers were grouped according to size measured at US, the findings at digital rectal examination (DRE), and the Gleason score. For the 147 patients with known prostate cancer, a statistically significant difference between Gleason scores of palpable and nonpalpable cancers could not be demonstrated when the size of the tumor and its location within the prostate were held constant. Assuming that the Gleason score is a reliable indication of malignant potential and clinical significance, the authors conclude that nonpalpable prostatic cancer detected with transrectal US alone may be just as clinically significant as prostatic cancer discovered with DRE.

Transrectal ultrasound, digital rectal examination, and prostate-specific antigen: preliminary results of an early detection program for prostate cancer.

Three hundred and ninety eight self-referred men with no histories of prostate problems were followed once each year for up to four years to determine the feasibility of early prostate cancer detection by digital rectal examination, transrectal ultrasound, and prostate-specific antigen. Evaluation of prostate-specific antigen was based on a polyclonal level of normal of 2.6 nanograms per milliliter by the Yang assay. Biopsies were performed when indicated by either transrectal ultrasound or digital rectal examination. The overall cancer detection rate for the four year period was 6.3 percent. A 3:1 cancer detection advantage of transrectal ultrasound over digital rectal examination was shown. Transrectal ultrasound and prostate-specific antigen each detected 92 percent of the proven cancers, and were complementary when either test was normal, together detecting 100 percent of the cancers. Thirty two percent (8/25) of all cancers were detected by digital examination, with digital exam having no predictive power after two study years. Prostate-specific antigen as an initial screening test for early prostate cancer may identify a suspicious group, whom may further be evaluated by transrectal ultrasound and digital exam. Results of this study lend credibility to the large scale randomized screening study proposed by the U.S. National Institutes of Health in which prostate-specific antigen and digital rectal examination are to be used as initial tests for prostate cancer detection.

Dose-related effects of phenobarbital on hepatic glutathione-S-transferase activity and ligandin levels in the rat.

To determine which individual parameters contribute to the increased bilirubin clearance which follows phenobarbital administration in the rat, dose response studies are being conducted relating changes in various aspects of bilirubin transport to the dose of phenobarbital administered. The relationships between phenobarbital dose, immunoreactive ligandin concentrations, and cytosolic glutathione-S-transferase (GSHT) enzymatic activities were determined in the 100,000g liver cytosol obtained from non-fasted male Sprague-Dawley rats, treated for 6 days (ip) with either phenobarbital at various doses ranging from 1 to 125 mg/kg/day or distilled water. Ligandin levels were measured by radioimmunoassay employing an antiserum which reacts with both GSHT-1 (Ya) and -2 (Yc) subunits. Ligandin concentration increased in a dose-dependent fashion, achieving a maximal observed value of 278% of control at the highest administered phenobarbital dose. Values were significantly elevated compared to controls at doses as low as 3 mg/kg/day. GSH-dependent delta 5-3-ketosteroid isomerase (KSI) activity, which reflects predominantly GSH transferase subunit 1, and GSHT activity against 1-chloro-2,4-dinitrobenzene (CDNB) also increased over the entire range of phenobarbital doses administered. Both of these enzymatic activities were highly correlated with immunoreactive ligandin levels (KSI: r = 0.89, p less than 0.005; GSHT (CDNB): r = 0.92, p less than 0.001). By contrast, GSHT activity against 1,2-dichloro-4-nitrobenzene (DCNB), which resides principally on GSHT subunits not present in ligandin, did not correlate significantly with measured ligandin concentrations. These studies indicate that phenobarbital is capable of inducing immunoreactive ligandin concentrations and related enzymatic activities at doses as small as 5% of those commonly employed to demonstrate this effect.

Effects of endotoxin on iron uptake by the hepatocyte.

Administration of endotoxins is often followed within 12-24 h by marked hypoferremia. Because the hepatocyte is the major site of both iron storage and transferrin synthesis, we have investigated the effects of an Escherichia coli endotoxin (lipopolysaccharide, LPS) on these parameters on isolated hepatocytes from normal Wistar rats (ND), rats previously treated intraperitoneally with 2.5 mg/kg (LD) or 25 mg/kg (HD) LPS, and control rats injected intraperitoneally with sterile saline (CD). No effects were observed on iron uptake from transferrin by ND cells incubated in vitro with up to 350 micrograms LPS/10(7) hepatocytes. There was also no significant difference in iron uptake between CD, HD, and LD hepatocytes 1 h after LPS injection. However, hepatocytes isolated 24 h after LPS administration took up iron significantly faster than controls. The uptake of non-transferrin-bound iron was also increased in HD and LD hepatocytes at 24 h but only in HD cells at 1 h. Transferrin binding was not altered in LPS-treated cells from ND rats but was depressed in cells from LPS-treated rats both at 1 h and at 24 h after injection. Transferrin receptor recycling was significantly increased at 24 h in cells from both LD and HD rats. Transferrin and total protein synthesis were also depressed at 1 h in LPS-treated rats, returning to normal values at 24 h. Direct preincubation of ND cells, however, failed to increase synthesis except at the highest concentrations of LPS. We conclude that LPS has an immediate (although indirect) effect on protein synthesis by the hepatocyte but not on iron uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoechoic lesions of the prostate: clinical relevance of tumor size, digital rectal examination, and prostate-specific antigen.

Two hundred fifty-six patients with hypoechoic lesions of the prostate found at transrectal ultrasound (US) were evaluated with prostate-specific antigen (PSA) study, digital rectal examination (DRE), and US-guided transrectal biopsy. Positive predictive values for cancer were calculated for transrectal US alone and in combination with DRE, PSA study, or both. Results were correlated with lesion size. The positive predictive value for transrectal US alone was 41%; this value increased to 61% if the patient had positive results from DRE, 52% if the PSA level was elevated, and 71% if both the DRE results and PSA level were abnormal. The positive predictive value for transrectal US fell to 24% if results of the DRE were normal, 12% if the PSA level was normal, and 5% if both DRE results and PSA level were normal. No cancers were detected in lesions 1.0 cm or smaller if DRE results and PSA level were normal. DRE and PSA study are valuable complements to abnormal transrectal US examinations. Biopsy of small suspicious lesions may not be indicated if results of both of the studies are normal.

Prostate cancer: comparison of transrectal US and digital rectal examination for screening.

The authors examined 784 self-referred men over age 60 years to compare clinical usefulness of transrectal ultrasound (US) and digital rectal examination in a screening program for prostate cancer. Biopsy was performed in 77 cases, 83% (64 of 77) for abnormalities detected with transrectal US and 38% (29 of 77) because of findings at digital examination. Twenty-two cancers were detected, 20 with transrectal US and ten at digital examination. Overall detection rate for prostate cancer with transrectal US was two times higher than that with digital examination (2.6% vs 1.3%). Sensitivity, specificity, and negative predictive value for transrectal US and digital examination were calculated for a range of prevalences (0.028-0.1543). Sensitivity was two times higher for transrectal US than for digital examination. Transrectal US demonstrated 100% (17 of 17) of tumors with the most favorable prognosis (less than or equal to 1.5 cm in diameter) compared with 41% (seven of 17) for digital examination. The authors conclude that transrectal US is more sensitive than digital examination in the detection of prostate cancer, and they advocate broader implementation and evaluation of transrectal US as a tool for early detection.

Needle aspiration and core biopsy of prostate cancer: comparative evaluation with biplanar transrectal US guidance.

Biplanar, transrectal ultrasound (US) guidance of needles was used in the transperineal biopsy of possibly malignant prostatic lesions in 80 patients (83 biopsies). A 22-gauge cytologic needle was used to locate and fixate the lesion, and aspiration specimens for cytologic and histologic evaluation were obtained (with 22- and 14-gauge needles, respectively). Twenty-one 19-gauge needle core biopsies were also performed. Forty-nine patients (61%) had histologically prove adenocarcinoma. The rate of cancer diagnosis was 53% with cytologic evaluation and 54% with histologic evaluation (combined yield, 61%). This included 34% of cancers less than 1.0 cm in diameter and 56% of those 1.0-1.5 cm. Thirteen of 23 (57%) of these lesions were nonpalpable or equivocal on digital rectal examination. These results suggest that transrectal US guidance of thin-needle biopsies is useful in diagnosing early prostate cancer.