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J Kao

Publications and source records attributed to J Kao.

At least 19 recordsLinked to original sources
PubMed2006

Diagnosis of renal tumors on needle biopsy specimens by histological and molecular analysis.

PURPOSE: We diagnosed the subtypes of renal cell carcinoma on needle core biopsies using a combination of histopathology and a molecular diagnostic algorithm. MATERIALS AND METHODS: Core biopsies were taken of renal tumors following nephrectomy. RNA was extracted and quantitative real-time polymerase chain reaction was performed for 4 gene products to differentiate among renal cell carcinoma subtypes. Histopathological diagnosis was achieved on a second core before and after obtaining the molecular diagnostic algorithm results. RESULTS: Based on the nephrectomy diagnosis 6 of 77 renal masses were nonneoplastic and 71 were tumors, including 65 renal cell carcinoma/oncocytomas. The overall diagnostic accuracy using histology and our molecular diagnostic algorithm combined was 90.0% (70 of 77). Side by side comparison of histology vs molecular diagnostic algorithm was feasible for 60 classifiable renal cell carcinoma/oncocytomas (31 clear cell, 14 papillary renal cell carcinoma, 6 chromophobe renal cell carcinoma, 2 mucinous tubular and spindle cell carcinoma, and 7 oncocytoma). In this group histology correctly predicted the final histological subtype in 83.3% (50 of 60) of cores. Addition of the molecular diagnostic algorithm to histology improved the subtyping accuracy to 95% (57 of 60), whereas the molecular diagnostic algorithm alone was accurate in 50 of 60 cases (83.3%). Dividing these 60 specimens into clear cell and nonclear cell neoplasms, the addition of the molecular diagnostic algorithm improved the sensitivity for the diagnosis of clear cell carcinoma from 87.1% (27 of 31) to 100% and the negative predictive value from 87.5% to 100%. CONCLUSIONS: Core biopsies of renal tumors provide adequate material for diagnosing and subtyping renal cell carcinoma. The addition of our molecular diagnostic algorithm to histology improved the diagnostic accuracy of core biopsies of renal masses.

Adult↗
PubMed2006

gamma-H2AX as a therapeutic target for improving the efficacy of radiation therapy.

Exposure to ionizing radiation (IR) results in the formation of DNA double strand breaks, resulting in the activation of phosphatidylinositol 3'-kinase-like kinases ATM, ATR and DNK-PKcs. A physiologically important downstream target is the minor histone H2A variant, H2AX, which is rapidly phosphorylated on Ser 139 of the carboxyl tail after IR. Recent work suggests that phosphorylated H2AX (gamma-H2AX) plays an important role in the recruitment and/or retention of DNA repair and checkpoint proteins such as BRCA1, MRE11/RAD50/NBS1 complex, MDC1 and 53BP1. H2AX-/- mouse embryonic fibroblasts are radiation sensitive and demonstrate deficits in repairing DNA damage compared to their wildtype counterparts. Cells treated with peptide inhibitors of gamma-H2AX demonstrate increased radiosensitivity following radiation compared with untreated irradiated cells. Analysis of the kinetics of gamma-H2AX clearance after IR or other DNA damaging agents reveals a correlation between increased gamma-H2AX persistence and unrepaired DNA damage and cell death. These data highlight the potential of post-translational modifications of chromatin as a therapeutic target for enhancing the efficacy of radiotherapy. Therapies that either block gamma-H2AX foci formation by inhibiting upstream kinase activity or that directly inhibit H2AX function may interfere with DNA damage repair processes and warrant further investigation as potential radiosensitizing agents. Agents that increase persistence of gamma-H2AX after IR are likely to increase unrepaired DNA damage.

Antineoplastic Agents↗
PubMed2005

Use of canalicular membrane vesicles (CMVs) from rats, dogs, monkeys and humans to assess drug transport across the canalicular membrane.

INTRODUCTION: A novel application of a Ultrafree filter cartridge/centrifugation method was evaluated to determine uptake in canalicular membrane vesicles (CMVs) from SD rats, beagle dogs, cynomolgus monkeys (common safety species in the pharmaceutical industry) and humans to assess biliary transport. METHODS: CMVs prepared from fresh livers of rats, dogs, monkeys and humans (four donors) were characterized for enrichment, basolateral and Golgi contamination and orientation. The presence of MRP2 and p-glycoprotein (P-gp) were confirmed by Western blots. Uptake of [3H]-leukotriene C4 (LTC4) and [3H]-estradiol-17beta-d-glucuronide (E2-Gluc) was determined at a low substrate concentration and/or by kinetic measurements (K(m) and V(max)). Correlation of in vitro data with in vivo findings was achieved by determining the biliary clearance of E2-Gluc in rats after a single i.v. dose and with literature in vivo data for LTC4. RESULTS: CMVs were highly enriched and minimally contaminated based on marker enzyme activities. Uptake clearance among different species varied by approximately ten-fold (rat > dog = human > monkey) for LTC4 and less than two-fold for E2-Gluc. The lower uptake of LTC4 by human than rat CMVs may be attributed to a higher Km value for human than rat CMVs. Uptake of LTC4 or E2-Gluc by human CMVs showed little inter-subject variability (2-5-fold). Differences in in vitro uptake clearance (10-fold) between LTC4 and E2-Gluc in rat CMVs seemed to correlate with differences in their biliary clearance (4-fold) in rats, consistent with LTC4 and E2-Gluc being a high and a low clearance substrate, respectively. DISCUSSION: A novel application of a Ultrafree filter cartridge/centrifugation method was developed to determine uptake in CMVs from different preclinical animal safety species and humans, and may represent a useful approach to study the mechanism of biliary excretion during drug discovery and development.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Sparing of the penile bulb and proximal penile structures with intensity-modulated radiation therapy for prostate cancer.

Quality of life is an important consideration in the treatment of early prostate cancer. Laboratory and clinical data suggest that higher radiation doses delivered to the bulb of penis and proximal penile structures correlates with higher rates of post-radiation impotence. The goal of this investigation was to determine if intensity-modulated radiation therapy (IMRT) spares dose to the penile bulb while maintaining coverage of the prostate. 10 consecutive patients with clinically organ confined prostate cancer were planned with 3D conformal radiation therapy (3D-CRT) or IMRT to give a dose of 74 Gy without specifically constraining the plans to spare the penile bulb. All 10 patients were ultimately treated with IMRT. Dose-volume histograms were evaluated and the doses to prostate, rectum, bladder and penile bulb were compared. IMRT reduced the mean penile bulb doses compared with 3D-CRT (33.2 Gy vs 48.9 Gy, p<0.001), the percentage of penile bulb receiving over 40 Gy (37.7% vs 67.2%, p<0.001) and the dose received by >95% of penile bulb (5.3 Gy vs 11.7 Gy, p=0.003). Maximum penile bulb doses were higher with IMRT (81.2 Gy vs 73.1 Gy, p<0.001) although the volume of this high dose region was small. Both methods resulted in similar coverage of the prostate. The volume of rectum receiving 70 Gy was significantly reduced with IMRT (18.4% vs 21.9%, p=0.003) but the volumes of bladder receiving 70 Gy were similar (p=0.3). IMRT may potentially reduce long term sexual morbidity by reducing the dose to the majority of the penile bulb.

Dose-Response Relationship, Radiation↗
PubMed2003

Clinical management of prostatic intraepithelial neoplasia as diagnosed by extended needle biopsies.

OBJECTIVE: To examine the results of the clinical management of patients with high-grade prostatic intraepithelial neoplasia (PIN), as diagnosed by extended needle biopsies. PATIENTS AND METHODS: The clinical data were reviewed from a cohort of 387 men who underwent > or = 10 core prostate needle biopsies between 1 January 1996 and 31 December 1997 by one urologist (W.C.D.). Two study groups were identified; the first comprised 47 patients with only high-grade PIN and the second was a control group of 137 patients with only benign findings on their biopsies. Those patients with cancer, atypia or a prostatic biopsy with fewer than 10 cores were excluded. The clinical and histological data were evaluated. The criteria for re-biopsy were two successive increases in prostate specific antigen (PSA) level or any change in the findings on digital rectal examination (DRE). All patients were monitored at 6-12 month intervals. RESULTS: Of the 387 patients, 46% had normal findings, 5.2% had atypia, 12.6% had PIN alone, 15 (3.9%) had PIN plus atypia, 6.7% had PIN plus cancer and 32.3% had cancer. There was no significant difference between the PIN and control groups in age, DRE, PSA level, prostate size (by ultrasonography), free testosterone level, number of the cores and time of follow-up (median 34.8 and 36.6 months for the PIN and control groups, respectively). Of the PIN and control groups, 21 (45%) and 43 (31%) respectively had at least one re-biopsy. Five patients (24%) in the PIN and one (2.3%) in the control group developed cancer (P = 0.0124). All these patients had organ-confined disease and were found to have either Gleason scores 3 + 3 or 3 + 4 on surgical specimens. There was no correlation between the original location of PIN and the location of subsequent malignancy. CONCLUSIONS: Patients with one set of extended needle biopsies with high-grade PIN should be followed clinically every 6-12 months, and it may be safe to reserve repeat biopsy for those with changes in PSA level and/or in the DRE.

Aged↗
PubMed2002

X-ray crystallographic structure of ABT-378 (lopinavir) bound to HIV-1 protease.

The crystal structure of ABT-378 (lopinavir), bound to the active site of HIV-1 protease is described. A comparison with crystal structures of ritonavir, A-78791, and BILA-2450 shows some analogous features with previous reported compounds. A cyclic urea unit in the P(2) position of ABT-378 is novel and makes two bidentate hydrogen bonds with Asp 29 of HIV-1 protease. In addition, a previously unreported shift in the Gly 48 carbonyl position is observed. A discussion of the structural features responsible for its high potency against wild-type HIV protease is given along with an analysis of the effect of active site mutations on potency in in vitro assays.

Binding Sites↗
PubMed2002

Use of a quantitative real-time reverse transcription-polymerase chain reaction method to study the induction of CYP1A, CYP2B and CYP4A forms in precision-cut rat liver slices.

1. The aim was to employ real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) technology (TaqMan to examine the induction of some selected cytochrome P450 (CYP) forms in precision-cut rat liver slices. 2. Taqman primers and probe sets were developed for rat CYP1A1, CYP1A2, CYP2B1 and CYP4A1 forms. 3. Rat liver slices were cultured in control medium or medium containing either 10 micro g ml(-1) Aroclor 1254 (ARO), 500 micro M sodium phenobarbitone (NaPB) or 50 micro M Wy-14643 (WY) for 3, 6 and 24 h. 4. Compared with control liver slices, treatment with ARO for 3 and 6 h produced 24- and 184-fold increases, respectively, in CYP1A1 mRNA levels, and after 24h produced an 85-fold increase in CYP1A2 mRNA levels. Levels of CYP1A1 and CYP1A2 mRNA were not markedly affected by NaPB and WY. 5. Treatment with ARO and PB for 24 h produced 10.6- and 23.8-fold increases, respectively, in CYP2B1 mRNA. Levels of CYP2B1 mRNA were not markedly affected by WY. 6. Treatment with WY, but not ARO and NaPB, for 24h produced a 20.4-fold increase in levels of CYP4A1 mRNA. 7. These results demonstrate that cultured liver slices may be used to evaluate the effect of xenobiotics on CYP form mRNA levels.

Animals↗
PubMed2002

Inhibition of zaleplon metabolism by cimetidine in the human liver: in vitro studies with subcellular fractions and precision-cut liver slices.

1. The effect of cimetidine on the metabolism of zaleplon (ZAL) in human liver subcellular fractions and precision-cut liver slices was investigated. 2. ZAL was metabolized to a number of products including 5-oxo-ZAL (M2), which is known to be formed by aldehyde oxidase, N-desethyl-ZAL (DZAL), which is known to be formed by CYP3A forms, and N-desethyl-5-oxo-ZAL (M1). 3. Human liver microsomes catalysed the NADPH-dependent metabolism of ZAL to DZAL. Kinetic analysis of three microsomal preparations revealed mean (+/-SEM) S(50) and V(max) of 310 +/- 24 micro M and 920 +/- 274 pmol/min/mg protein, respectively. 4. Human liver cytosol preparations catalysed the metabolism of ZAL to M2. Kinetic analysis of three cytosol preparations revealed mean (+/-SEM), K(m) and V(max) of 124 +/- 14 micro M and 564 +/- 143 pmol/min/mg protein, respectively. 5. Cimetidine inhibited ZAL metabolism to DZAL in liver microsomes and to M2 in the liver cytosol. With a ZAL substrate concentration of 62 micro M, the calculated mean (+/-SEM, n = 3) IC50 were 596 +/- 103 and 231 +/- 23 micro M for DZAL and M2 formation, respectively. Kinetic analysis revealed that cimetidine was a competitive inhibitor of M2 formation in liver cytosol with a mean (+/-SEM, n = 3) K(i) of 155 +/- 16 micro M. 6. Freshly cut human liver slices metabolized ZAL to a number of products including 1, M2 and DZAL. 7. Cimetidine inhibited ZAL metabolism in liver slices to M1 and M2, but not to DZAL. Kinetic analysis revealed that cimetidine was a competitive inhibitor of M2 formation in liver slices with an average (n = 2 preparations) K(i) of 506 micro M. 8. The results demonstrate that cimetidine can inhibit both the CYP3A and aldehyde oxidase pathways of ZAL metabolism in the human liver. Cimetidine appears to be a more potent inhibitor of aldehyde oxidase than of CYP3A forms and hence in vivo is likely to have a more marked effect on ZAL metabolism to M2 than on DZAL formation. 9. The results also demonstrate that precision-cut liver slices may be a useful model system for in vitro drug-interaction studies.

Acetamides↗
PubMed2002

Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidase.

1. The metabolism of Zaleplon (CL-284,846; ZAL) has been studied in precision-cut human liver slices and liver cytosol preparations. 2. Human liver slices metabolized ZAL to a number of products including 5-oxo-ZAL (M2), N-desethyl-5-oxo-ZAL (M1) and N-desethyl-ZAL (DZAL), the latter metabolite being known to be formed by CYP3A forms. 3. Human liver cytosol preparations catalysed the metabolism of ZAL to M2. Kinetic analysis of three cytosol preparations revealed mean (+/- SEM) K(m) and V(max) of 93 +/- 18 mm and 317 +/- 241 pmol/min/mg protein, respectively. 4. Using 16 individual human liver cytosol preparations a 33-fold variability in the metabolism of 80 micro M ZAL to M2 was observed. Correlations were observed between M2 formation and the metabolism of the aldehyde oxidase substrates phenanthridine (r(2) = 0.774) and phthalazine (r(2) = 0.460). 5. The metabolism of 80 micro M ZAL to M2 in liver cytosol preparations was markedly inhibited by the aldehyde oxidase inhibitors chlorpromazine, promethazine, hydralazine and menadione. Additional kinetic analysis suggested that chlorpromazine and promethazine were non-competitive inhibitors of M2 formation with K(i) of 2.3 and 1.9 micro M, respectively. ZAL metabolism to M2 was also inhibited by cimetidine. 6. Incubations conducted with human liver cytosol and H(2)(18)O demonstrated that the oxygen atom incorporated into ZAL and DZAL to form M2 and M1, respectively, was derived from water and not from molecular oxygen. 7. In summary, by correlation analysis, chemical inhibition and H(2)(18)O incorporation studies, ZAL metabolism to M2 in human liver appears to be catalysed by aldehyde oxidase. With human liver slices, ZAL was metabolized to products dependent on both aldehyde oxidase and CYP3A forms.

Acetamides↗
PubMed2001

Anodic cyclization reactions: reversing the polarity of ketene dithioacetal groups.

Intramolecular coupling reactions of ketene dithioacetal groups with enol ether and alcohol nucleophiles have been studied. The reactions were initiated by an anodic oxidation of the ketene dithioacetal and proved to be compatible with the formation of five- or six-member rings, as well as the stereoselective generation of quaternary carbons.

Cyclization↗
PubMed2001

NMR identification of heavy metal-binding sites in a synthetic zinc finger peptide: toxicological implications for the interactions of xenobiotic metals with zinc finger proteins.

Lead (Pb), mercury (Hg), and cadmium (Cd) are toxic and interfere with protein metal-binding sites. The Cys(2)/His(2) zinc finger is a structural motif required for sequence-specific DNA binding and is present in zinc finger transcription factors (ZFP): Sp1, Egr-1, and TFIIIA. Neurotoxic studies have shown that heavy metals directly inhibit the DNA binding of ZFP and result in adverse cellular effects. Recently, we demonstrated the ability of heavy metals to alter the DNA binding of a synthetic Cys(2)/His(2) finger peptide (Razmiafshari and Zawia, Toxicol. Appl. Pharmacol. 166, 1-12, 2000). To determine the precise site of interactions between heavy metals and this protein domain, Pb, Hg, Cd, and Ca were reconstituted with the synthetic apopeptide and studied by one- and two-dimensional NMR spectroscopy. In the presence of Zn, Cd, Hg, and Pb, but not Ca, distinct peptide NMR signal changes in the aliphatic region were observed and attributed to metal-cystiene interactions. However, chemical shifts indicative of metal-histidine binding were elicited by all the metals in the peptide's aromatic region. Chemical shift assignments and sequential connectivity were established in the presence and absence of Zn, Pb, and Ca through TOCSY and NOESY spectra. Cysteine and histidine residues showed a distinct change in their amide and beta resonances in the presence of Zn and Pb, suggesting the metal-ligand binding sites were near these residues. However, Ca led to no significant spectral changes in these regions, suggesting that it is not actively involved in the binding site. These studies reveal this structure as a mediator of metal-induced alterations in protein function.

Binding, Competitive↗
PubMed2001

Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity.

There is evidence that the "acid mantle" of the stratum corneum is important for both permeability barrier formation and cutaneous antimicrobial defense. The origin of the acidic pH of the stratum corneum remains conjectural, however. Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed. We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to stratum corneum acidification and function. Topical applications of two chemically unrelated secretory phospholipase sPLA2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered stratum corneum integrity (number of strippings required to break the barrier) and decreased stratum corneum cohesion (protein weight removed per stripping). Not only stratum corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors. Moreover, exposure of intact murine stratum corneum to a neutral pH for as little as 3 h produced comparable abnormalities in stratum corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations. Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in stratum corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels. Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the stratum corneum (shown by immunofluorescence staining and visualized by confocal microscopy). Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal stratum corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of stratum corneum integrity and cohesion.

Acetophenones↗
PubMed2001

Penile erectile function after permanent radioactive seed implantation for treatment of prostate cancer.

PURPOSE: We assess erectile function after prostate brachytherapy and analyze those factors affecting potency preservation. MATERIALS AND METHODS: A total of 416 patients treated from October 1990 to September 1998 with permanent radioactive seed implantation for T1 to T2 prostate cancer had erectile function assessed before and after treatment. Erectile function was assessed using the scoring system of 0-complete inability to have erections, 1-able to have erections but insufficient for intercourse, 2-can have erections sufficient for intercourse but considered suboptimal and 3-has normal erectile function. Implant dose was defined as the D90, which was the dose delivered to 90% of the gland on a dose volume histogram from the 1-month computerized tomography based dosimetric analysis. RESULTS: Pretreatment erectile function assessment revealed scores of 0 in 57 (14%), 1 in 46 (11%), 2 in 77 (18%) and 3 in 236 (57%) patients. In 313 patients who were potent with a score 2 or greater before therapy the actuarial freedom from any decrease in erectile function score was 64% and 30% at 3 and 6 years, respectively. The actuarial preservation of potency, with a score 2 or greater, was 79% and 59% at 3 and 6 years, respectively. The 2 factors found to have a significant negative effect on potency in univariate and multivariate analyses were high implant dose (D90 greater than 160 Gy. for I-125 and D90 greater than 100 Gy. for Pd-103) and a pretreatment erectile function score of 2 versus 3. CONCLUSIONS: The rate of potency preservation after brachytherapy is high, although a decrease occurs from 3 to 6 years. Pretreatment erectile dysfunction as well as higher implant dose are associated with greater impotency.

Adult↗
PubMed2000

The effect of disease and treatment-related factors on biopsy results after prostate brachytherapy: implications for treatment optimization.

BACKGROUND: Posttreatment prostate biopsy is a method of assessing local control after irradiation for prostate carcinoma. An analysis of the effect of disease- and treatment-related factors on biopsy results after prostate brachytherapy was performed to aid in patient selection and treatment optimization. METHODS: Two hundred sixty-eight patients underwent posttreatment prostate biopsy (6-8 cores) 2 years after brachytherapy alone without external beam irradiation. Follow-up ranged from 24 to 111 months (median, 43 months). Implants were performed using a real-time ultrasound guided technique with the isotopes (125)I in 186 and (103)Pd in 82 patients. Ninety-eight patients underwent hormonal therapy (HT) 3 months before and 2-3 months after implant. Implant dose was defined as the D90 (dose delivered to 90% of the gland from the dose volume histogram generated using 1-month computed tomography-based dosimetry). RESULTS: Overall, 89% of patients (238 of 268) had negative biopsies. A positive biopsy was a predictor of biochemical failure. Patients with a positive biopsy had a 5-year freedom from biochemical failure of 40% versus 76% for patients with a negative biopsy (P = 0.0003). Univariate and multivariate analysis found that risk group, HT, and implant dose significantly affected biopsy outcome. Patients with low risk features (prostate specific antigen [PSA] </= 10 ng/mL; Gleason score </= 6; and classification T2a or lower) (n = 104) had a negative biopsy rate of 95% versus 85% for those with high risk features (PSA > 10 ng/mL or Gleason score >/= 7 or classification T2b or higher) (n = 164) (P = 0.008). Hormonal therapy was associated with a negative biopsy rate of 98% versus 84% for implant alone (P = 0.003). Patients receiving a high implant dose (D90 >/= 140 grays [Gy] for (125)I or >/= 100 Gy for (103)Pd) (n = 174) had a negative biopsy rate of 95% versus 77% for those receiving a low dose (D90 < 140 Gy for (125)I or < 100 Gy for (103)Pd) (n = 87; P < 0.001). CONCLUSIONS: Biopsy results support the use of brachytherapy without external beam irradiation for patients with low risk features and highlight the importance of achieving an adequate implant dose.

Biopsy, Needle↗
PubMed2000

Postimplant dosimetry for (125)I prostate implants: definitions and factors affecting outcome.

OBJECTIVE: An analysis of CT-based dosimetry was performed to assess the efficacy of the real time method of prostate implantation, explore the relationship of various dose descriptions and determine implant factors affecting outcome. METHODS AND MATERIALS: Between 7/95 and 8/99, 297 patients underwent (125)I implants for T1-T2 prostate cancer and had CT-based dosimetry performed (TG43 formalism). Dosimetry was performed 1 month postimplant. Using a dose-volume histogram, doses delivered to 100%, 95%, 90%, and 80% of the prostate (D100, D95, D90, D80, respectively) as well as percentages of the gland receiving 240 Gy, 160 Gy, 140 Gy (V240, V160, V140, respectively) were reported. Correlations between the various dose parameters and D90 were generated. The effect of the number of seeds implanted, seeds/volume, prostate volume, experience as assessed by time (8/01/99-date of implant), ultrasound probe (mechanical sector vs. dual phased electronic), and the ratio of the CT dosimetry prostate volume/ultrasound implant volume (CT/US vol) were analyzed. RESULTS: The median D100, D95, D90, and D80 values were 10,200 cGy, 15,655 cGy, 17,578 cGy, and 19,873 cGy, respectively. The median V240, V160, and V140 were 56%, 94%, and 98%, respectively. Correlations of dose descriptions found a close relationship of D95, D80, V240, V160, and V140 with D90 with r values of 0.928, 0.973, 0.911, 0.816, and 0.733, respectively. D100 correlated poorly with D90 (r = 0.099). Using a stepwise regression analysis, CT/US vol ratio, prostate volume, and seed number were the only significant factors affecting D90 with CT/US vol ratio having the greatest effect. The dual-phased electronic probe was associated with fewer D90 values of less than 140 Gy (2%) compared to the mechanical sector probe (14%) (p = 0.02). CONCLUSION: CT-based dosimetry results reveal the real-time implant technique to be an effective method of prostate implantation. Factors associated with more precise implantation, such as decreased postimplant edema, new technology, and increased number of seeds will lead to higher D90 values.

Brachytherapy↗
PubMed2000

Biopsy results after real-time ultrasound-guided transperineal implants for stage T1-T2 prostate cancer.

PURPOSE: To analyze the results of ultrasound-guided brachytherapy for stage T1-T2 prostate cancer, as shown by biopsy results. PATIENTS AND METHODS: The 268 patients (mean age 66 years; range 41-83 years) underwent real-time ultrasound-guided implantation of either iodine-125 (N = 186) or palladium-103 (N = 82) seeds. Of these patients, 96 (36%) received total androgen suppression for 3 months prior to and 3 months after implantation. Prostate biopsy was performed 24 months later, with the six to eight cores all being interpreted by the same pathologist. Each specimen was rated either positive or negative for cancer. RESULTS: Of the 268 patients, 238 (89%) had a negative biopsy at 24 months. Among the patients receiving androgen suppression, 2% were found to have positive biopsies compared with 16% of those not given hormones (P = 0.004). Of the 155 patients with stage T1-T(2a) cancer, 6% had a positive biopsy compared with 19% of patients with stage T(2b) or T(2c) cancer (P = 0.001). In the entire series, the pretreatment serum concentration of prostate specific antigen, Gleason score, and isotope (I v Pd) were not significant predictors of a positive biopsy. However, among the 172 patients who did not receive androgen suppression, all three factors were predictive: 42% for Gleason score of 7 to 10 v 13% for Gleason score < or =6 (P = 0.001): 25% for pretreatment PSA concentration >10 ng/mL v 13% for PSA < or = 10 ng/mL (P = 0.05); and 27% for stage T(2b) or T(2c) v 9% for stage T1 or T(2a) (P = 0.001). The isotope used and the last PSA value were not significant predictors. CONCLUSION: Brachytherapy provides excellent local control of prostate cancer, with 89% of patients having negative biopsies 2 years after treatment. High-risk patients may benefit from the addition of androgen suppression.

Adult↗