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Biomedical subjects

J H Lynch

Publications and source records attributed to J H Lynch.

At least 19 recordsLinked to original sources
PubMed2002

Investigating the distribution of prostate cancer using three-dimensional computer simulation.

The objective of this work was to investigate the distribution of prostate cancer using three-dimensional (3-D) computer simulation. Two hundred and eighty-one 3-D computer prostate models were constructed from radical prostatectomy specimens. An algorithm was developed which divided each model into 24 symmetrical regions, and it then detected the presence of tumor within an individual region. The distribution rate of prostate cancer was assessed within each region of all 281 prostate models, and the difference between the rates was statistically analyzed using Mantel-Haenszel methodology. There was a statistically significant higher distribution rate of cancer in the posterior half (57.2%) compared to the anterior half ( 40.5%; P=0.001). The base regions (36.8%) had a statistically significant lower distribution rate than either the mid regions (56.3%; P=0.001) or the apical regions (53.5%; P=0.001). The mid regions did have a statistically significant higher distribution rate compared to the apical regions (P=0.032). There was no statistically significant difference between the distribution rate on the left half (48.5%) compared to that on the right half (49.2%; P=0.494). The spatial distribution of prostate cancer can be analyzed using 3-D computer prostate models. The results illustrate that prostate cancer is least commonly located in the anterior half and base regions of the prostate. Through an analysis of the spatial distribution of prostate cancer, we believe that new optimal biopsy strategies and techniques can be developed.

Biopsy↗
PubMed2000

Limitations of reduced-field irradiated volume and technique in conventional radiation therapy of prostate cancer: implications for conformal 3-D treatment.

In order to define technical limitations of conventional external beam irradiation for clinically localized prostate cancer, we evaluated the impact of several reduced-field treatment factors, such as reduced-field (RF) irradiated volume, RF technique, photon energy of treatment, and dose on survival endpoints and local control in a retrospective series. Several survival endpoints, such as disease-specific survival, freedom from relapse survival, biochemical no-evidence of disease (bNED) survival, and local control were associated with several treatment variables using univariate and multivariate analyses in 329 patients. Reduced-field technique appeared to predict survival outcome, with patients treated by bilateral 120 degrees arcs faring less well than those treated by full 360 degrees rotational fields. The irradiated volume of the reduced-field was also significantly associated with survival outcome, with patients treated with smaller volumes faring less well. Local failure rates also appeared increased, although not statistically, in patients treated with smaller RF sizes. In an attempt to explain these detected deficiencies, dose-volume histograms for prostate coverage were created for a small sample of patients. The deficiencies related to small reduced-field volume appeared to be largely attributable to poor dosimetric coverage of the prostate. These results underscore the limitations of conventional external beam treatment for prostate carcinoma when conventional techniques are employed, particularly if small reduced fields are used, and further supports the development of improved treatment techniques, such as conformal irradiation, as alternatives.

Adenocarcinoma↗
PubMed1999

A new temporary catheter (ContiCath) for the treatment of temporary, reversible, postoperative urinary retention.

OBJECTIVES: To describe the initial experience of a newly designed temporary urethral catheter, ContiCath, as an aid in the management of postoperative or temporary outflow obstruction. In patients with normal detrusor and sphincter function, this catheter allows volitional voiding while maintaining an open prostatic urethra. METHODS: In a pilot study, 64 nonconsecutive patients with postoperative or temporary urinary retention, at eight clinical trial sites, were enrolled for the placement of this temporary catheter. Three patients did not have the catheter placed because of placement failure because of either a large median lobe or a urethral stricture. The remaining 61 patients were divided into three groups: those with non-neuropathic causes of retention and retention for 1 week or less (37 patients), those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), and those with neuropathic causes of retention and retention for longer than 1 week (5 patients). The ContiCath is placed in the office setting, in the same fashion as a Foley catheter. A blue prolene tether extends from the bulbar urethra to the meatus to assist in the removal of the device. Patients were then reassessed at 3 hours, and at 7, 14, 21, and 28 days, at which point the device was removed. RESULTS: In patients with a neuropathic cause for their retention (5 patients) and those with non-neuropathic causes of retention and retention for longer than 1 week (19 patients), only 3 patients were able to void after the catheter was placed. Of the 37 patients with a non-neuropathic cause and retention 1 week or less, controlled voiding was seen in 33 patients (89%). Controlled voiding was defined as the patient's volitional ability to initiate and stop his urinary stream. There were no complications with catheter placement; however, 8 patients (24.2%) had minor adverse experiences of frequency/urgency (n = 3), incontinence (n = 3), migration of the catheter (n = 1), and pain (n = 1). CONCLUSIONS: ContiCath offers an alternative to an indwelling Foley catheter in men with temporary bladder outlet obstruction and urinary retention.

Aged↗
PubMed1999

Transurethral microwave thermotherapy.

OBJECTIVES AND METHODS: The present status of transurethral microwave thermotherapy (TUMT) in the low (LE) and high energy (HE) version is given as an overview. RESULTS: With LE software, approximately 75% of patients will note significant improvement with 65% reduction in symptom scores and a 35-40% improvement in peak flow rate. Sham studies have shown statistically significant improvement in treated patients compared to sham. Randomized studies between TUMT and TURP show similar improvements in symptom scores with TURP producing higher flow rates, as expected. Long-term studies have been reported to 5 years showing durability, although 10-20% of patients subsequently undergo TURP. The clinical efficacy of HE-TUMT 2.5 has been documented in recently completed studies. Approximately 37% of patients develop cavitation with HE-TUMT. The symptomatic improvement is similar between low and high energy while the flow rates with high energy improve by approximately 65%. Pressure flow studies have documented relief of obstruction in most of those patients who had obstruction prior to treatment. The morbidity of HE-TUMT in terms of retrograde ejaculation and posttreatment retention is higher compared to the LE version. CONCLUSIONS: TUMT is a 1-hour out-patient, local anesthetic procedure, minimally invasive treatment option for benign prostatic hyperplasia that encompasses microwave radiative heating and water conductive cooling. TUMT has been proven both safe and efficacious for relieving benign prostatic hyperplasia symptoms in several large-scale controlled studies. The existence of low and high energy versions offers the opportunity to select patients according to obstruction grade.

Diathermy↗
PubMed1997

Renal angiosarcoma: a rare primary genitourinary malignancy.

Sarcomatous lesions of the kidney comprise less than 2% of all primary renal malignancies. Angiosarcomas are an exquisitely infrequent histologic type in this setting and are associated with a universally poor prognosis. We report the eighth known case of primary renal angiosarcoma and review the available literature on this rare entity.

Aged↗
PubMed1997

Treatment of female urethral carcinoma in medically inoperable patients using external beam irradiation and high dose rate intracavitary brachytherapy.

PURPOSE: We developed and present our experience with high dose rate brachytherapy for treatment of carcinoma of the urethra in medically inoperable women. MATERIALS AND METHODS: Since 1991, 4 women with localized urethral cancer, medically unable to undergo resection or interstitial implantation, were treated with external beam and high dose rate intracavitary implantation rather than external beam irradiation alone. The fractionated implants were delivered with a high dose rate remote afterloader using a shielded vaginal applicator and modified urethral catheter. The urethral catheter was inserted through the lumen of a 20F Foley tube to improve depth dose. Homogeneous dose distribution was achieved and customized to the individual patient. RESULTS: All high dose rate brachytherapy treatments were given at the clinic without use of sedation or anesthesia. Treatment was well tolerated, and all patients maintained voluntary urinary function and local control at 12 to 55 months after therapy. Chronic morbidity due to urethral, bladder, vaginal or rectal injury, including urethral stenosis, necrosis or fistula, was not noted. Isodose distributions were compared among this technique, interstitial implantation and external beam radiotherapy alone. CONCLUSIONS: Although we prefer interstitial implantation as the boost technique for women with urethral cancer, high dose rate brachytherapy is a reasonable option for medically inoperable patients. This outpatient treatment is well tolerated, preserves voluntary urinary function and enhances quality of life.

Aged↗
PubMed1997

The radiographic diagnosis of pelvic lipomatosis.

We describe a patient who initially presented with asymptomatic hydronephrosis. He underwent extensive radiologic evaluation which led to the diagnosis of pelvic lipomatosis. The possible etiology, workup, and treatment options of this unusual entity are discussed.

Diagnosis, Differential↗
PubMed1996

Management of locally advanced prostate cancer.

The staging and treatment of prostate cancer are complex, particularly in patients with clinical disease that has advanced locally beyond the confines of the gland. Management choices are made more difficult by a paucity of quality randomized and controlled studies. Staging has traditionally relied on digital rectal examination, which is now being augmented by improved noninvasive radiologic studies. Radiation is the most common form of treatment today, and newer techniques are being examined and compared to external-beam therapy. Surgical intervention as monotherapy has failed to show a survival advantage. Current approaches treatment appear to be evolving toward combination therapies, potentially incorporating hormonal manipulation. Patients with locally advanced disease should be encouraged to enter prospective clinical trials.

Combined Modality Therapy↗
PubMed1993

Chemotaxis and chemokinesis of human prostate tumor cell lines in response to human prostate stromal cell secretory proteins containing a nerve growth factor-like protein.

The migration of three human prostate tumor epithelial cell lines (TSU-pr1, PC-3, DU-145) in response to secreted protein from a human prostate stromal cell line was investigated by using the modified blind-well Boyden chamber assay. Migrated cells were quantified by spectrophotometrically measuring the concentration of crystal violet stain extracted from their nuclei. Cell number was correlated linearly with the concentration of extracted crystal violet stain. All three tumor cell lines showed intrinsic migratory ability in the absence of chemoattractants, such that approximately 1-7% of plated cells migrated across the filter of the Boyden chambers during a 5-h incubation period. Prostate tumor cell migration was significantly enhanced (3-13-fold) in response to stromal cell secretory protein in a dose-dependent manner, whereas bovine serum albumin had no effect on stimulating tumor cell migration. Immunoprecipitation of the stromal cell secreted protein with a nerve growth factor antibody partially and significantly reduced its stimulatory activity for tumor cell migration. A Zigmond-Hirsch matrix assay of tumor cell migration in response to various concentration gradients of stromal cell secreted protein demonstrated both chemotaxis and chemokinesis by all three cell lines. These results are consistent with the stromal cell secretory protein stimulation of chemokinetic tumor cell migration through the capsule of the prostate. Outside of the prostate gland metastasis of tumor cells may occur by chemotaxis to preferential sites containing chemoattractants similar to or related to maintenance factors that can substitute for components of stromal cell secretory protein.

Carrier Proteins↗
PubMed1993

Transurethral microwave thermotherapy for management of benign prostatic hyperplasia: results of the United States Prostatron Cooperative Study.

The primary objective of the study was to determine the safety and efficacy of transurethral microwave thermotherapy for the treatment of symptomatic benign prostatic hyperplasia. From March to August 1991, 150 patients were entered into a multi-site study and treated with transurethral microwave thermotherapy under a Food and Drug Administration approved protocol. Only patients with symmetrical trilobar or bilobar prostatic hypertrophy, peak flow rate of less than 15 cc per second (on 2 voided volumes of 150 cc or greater) and a total Madsen symptom score of more than 8 were treated. Transurethral microwave thermotherapy was performed with a 20F catheter and 1,296 MHz. microwave antenna for 60 minutes. The mean power achieved for this single session was 32.1 watts, with a mean power at maximum urethral temperature of 41.1 watts. Mean urethral temperature was 44.3C and the mean rectal temperature was 42.2C. The rectal and urethral temperatures were continuously monitored. Mean peak urinary flow rates, Madsen symptom score, post-void residual volume and improvement in motivating symptom to seek treatment were measured at 6 weeks, and 3, 6 and 12 months. Mean peak urinary flow rates improved 33% at 12 months (p < 0.0001). Overall, the mean Madsen symptom score improved 61% (p < 0.0001). The obstructive score and the irritative score improved 67% and 43%, respectively. Of 17 patients 12 (71%) reported improvement in weak stream when that was the motivating symptom to seek treatment. Of 28 men 18 (64%) reported improvement in nocturia, while 11 of 30 (37%) reported improvement in daytime frequency and 12 of 17 (71%) reported improvement in urgency. There was no statistically significant difference in post-void residual volume at 12 months from baseline. The treatment was well tolerated by all patients, and side effects were considered mild and transitory. Our study demonstrates the safety, effectiveness, patient tolerability and durability of transurethral microwave thermotherapy.

Adult↗
PubMed1993

Treatment of advanced prostate cancer.

Many patients with prostate cancer present with advanced disease (stage C or D). For these patients, treatment is palliative and is aimed at reducing serum testosterone levels. Since the growth of prostate cancer is testosterone-dependent (approximately 95% of testosterone is produced by the testes, with the remainder coming from the adrenals), hormonal manipulation has been the mainstay of palliative treatment. Bilateral orchiectomy has been the traditional approach, but most patients prefer equally effective drug therapies that include the administration of estrogens, luteinizing hormone-releasing hormone (LHRH) agonists, and anti-androgens.

Androgen Antagonists↗
PubMed1992

Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue and loss of expression in four human metastatic prostate tumor cell lines.

In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has been shown to participate in paracrine mediated growth of a human tumor epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues, and four metastatic tumor cell lines of the human prostate. In primary epithelial cell cultures of normal human prostate the p75 NGF-R was localized by immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis of the NGF-R in subcellular fractions of normal prostate tissue identified an M(r) 75,000 immunoreactive protein in the microsomal fraction under nonreducing conditions of sodium dodecyl sulfatepolyacrylamide gel electrophoresis. However, microsomal preparations of five prostatic adenocarcinoma and five benign prostatic hyperplasia specimens showed varying immunoreactivity among samples, all of which expressed less of the p75 NGF-R than the normal tissue. Interestingly, microsomal preparations of the human prostatic epithelial cell lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate tissue, partial loss of NGF-R expression in benign and malignant prostate tissue, and complete loss of NGF-R expression in the four metastatic tumor cell lines, suggests an inverse association of p75 NGF-R expression with the neoplastic progression of the human prostate.

Adenocarcinoma↗
PubMed1992

Density dependent polarized secretion of a prostatic epithelial cell line.

The polarized secretions (apical/basal) of newly synthesized total protein and proteases from prostatic epithelial sheets of PA-III cells grown in dual compartment chambers were investigated at various cell densities and culture conditions. PA-III cells grown in a serum free defined medium (SFDM) form morphologically polarized monolayers of epithelial cells. These cells secreted their 35S-methionine labeled total protein in a predominantly apical direction (apical/basal ratio, 4-8 fold), with a lesser proportion of protein secreted apically at lower cell densities of the PA-III cell monolayer. PA-III cells grown in 5% fetal calf serum (FCS) are morphologically squamous, comparable to the anaplastic phenotype, and exhibited an inversion of polarized total protein secretion (apical/basal ratio, 0.4-0.9 fold), with an increased proportion of total protein secreted in a basal direction at lower cell densities. Since the culture of PA-III cells in FCS may approximate the anaplastic phenotype we investigated the polarized secretion of proteases from these cells at various cell densities, and compared them with the secretory pattern of protease secretion from polarized PA-III cells cultured in SFDM. At lower cell densities of the PA-III cells grown in FCS the polarity of protease secretion was inverted such that metalloproteinases, tissue type plasminogen activator, and a 72 kD gelatinase were secreted in a predominantly basal direction, as well as urokinase and a gelatinase of 26 kD that were secreted more or less equally into the apical and basal compartments of the chambers. On the other hand, for cultures of PA-III cells grown in SFDM the aforementioned proteases exhibited predominantly an apically directed polarity of secretion. These results suggest that the anaplastic phenotype characterized by a loss of polarized structure may also be characterized by a functional loss or inversion of polarized secretion. The consequences of such a loss or inversion of polarized secretion would be to increase the localized concentrations of proteases along the basal domain of cells thereby facilitating degradation of the basement membrane and interstitial tissue in vivo.

Adenocarcinoma↗
PubMed1992

The effect of pH on the in vitro colony forming ability of transitional cell carcinoma cells treated with various chemotherapeutic agents: implications for in vivo therapy.

Extracellular pH may affect the sensitivity of cancer cells to chemotherapy agents. In an attempt to maximize the conditions for chemotherapy treatment of transitional cell carcinoma we tested the effect of pH on sensitivity of MGH-U3 transitional cell carcinoma cell line to thiotepa, doxorubicin, and mitomycin c in vitro. The toxicity of each agent tested varied with pH. There was no variation in cell growth in response to pH alone. The cytotoxic activity of thiotepa was markedly enhanced when cells were treated with a diluent pH of 5.5. Significant differences were also observed after treatment with doxorubicin and mitomycin c with a diluent pH of 7.0. This in vitro assay may be useful for clinical application of pH modulation during intravesical chemotherapy.

Adult↗
PubMed1992

Distribution of nerve growth factor-like protein and nerve growth factor receptor in human benign prostatic hyperplasia and prostatic adenocarcinoma.

Recent observations from our laboratory have identified a nerve growth factor (NGF)-like protein in conditioned media of stromal cells and neoplastic epithelial cells of the human prostate which mediates paracrine interactive growth of both cell types in vitro. In order to investigate the location of this NGF-like protein in the human prostate in vivo, and whether a nerve growth factor receptor (NGF-R) could be identified, we have carried out immunocytochemical studies on frozen tissue sections of human benign prostatic hyperplasia (BPH), prostatic adenocarcinoma and normal prostatic tissue. The NGF-like protein localized predominantly to the stromal component of BPH, adenocarcinoma and normal (non-cancerous) prostatic tissue. Conversely, the NGF-R localized predominantly to the epithelial cells of these tissues. Renal tissue provided negative controls for both the NGF-like protein and the NGF-R. The testis provided positive controls for both the NGF-like protein and the NGF-R. These results provide corroborative evidence for a NGF-like protein produced by stromal cells which interacts with a NGF-R on the adjacent epithelial cells thereby mediating paracrine interactive growth regulation of the human prostate.

Adenocarcinoma↗