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L D Sullivan

Publications and source records attributed to L D Sullivan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Optimal duration of neoadjuvant androgen withdrawal therapy before radical prostatectomy in clinically confined prostate cancer.

Experimental studies have shown that neoadjuvant androgen therapy dramatically reduces the rate of local recurrence after tumor excision. In the clinical setting, a 3-month course of neoadjuvant therapy before radical prostatectomy has been shown to significantly reduce positive margin rates, but follow-up is too short to assess the impact of such therapy on biochemical and clinical recurrence rates. A phase II study using an ultrasensitive assay showed that 8 months of neoadjuvant therapy were required before prostate-specific antigen (PSA) levels to reach their nadir in 84% of study participants. The positive margin rate in this study was substantially lower than those reported in the literature. Importantly, restaging of specimens after prostatic acid phosphatase (PAP) immunostaining did not upstage or increase positive margin rates. In addition, prolonged neoadjuvant therapy did not appear to result in progression of androgen-independent clones. A randomized phase III trial has been initiated to determine whether an 8-month course of neoadjuvant hormonal therapy is superior to a 3-month course in reducing positive margin rates and biochemical recurrences in patients with clinically confined prostate cancer.

Adult↗
PubMed1996

[Hormone release and intermittent hormonal therapy in the LN CaP model of human prostate cancer].

Androgen-independent progression invariably occurs following castration of patients with prostate cancer. Animal model data suggest that androgen resistance may result from adaptive cell survival mechanisms activated by androgen withdrawal. If this is true, then re-exposure to, or low levels of, androgens may suppress or downregulate these mechanisms. The objective of this study is to determine whether intermittent androgen suppression (IAS) delays the onset of nonandrogen-regulated PSA production in the LNCaP prostate tumour model, when compared to continuous androgen suppression (CAS). Serum PSA levels correlate highly with LNCaP tumour volume and decrease rapidly following castration; beginning 3-4 weeks post-castration LN CaP tumours become androgen-independent with respect to PSA gene expression and produce PSA in amounts similar to precastrate state. In this study, IAS-treated mice were implanted with testosterone pellets beginning two weeks post-castration; cycles of testosterone replacement for 1 week and withdrawal for 2 weeks were repeated until serum PSA levels no longer returned to baseline. IAS therapy prolonged time to androgen-independent PSA production 3-fold, from an average of 26 days in the CAS group to 77 days in the IAS group. Serum and LNCaP tumour mRNA PSA levels remained below precastrate levels by 60 days post-castration in 75% of the IAS group, while serum PSA in all mice in the CAS group exceeded precastrate PSA by 28 days post-castration. Following castration, serum PSA levels increased 9-fold faster with CAS compared to IAS therapy. Observations using IAS in the LNCaP tumour model suggest that the onset of androgen-independent PSA gene regulation is prolonged 3-fold, perhaps due to androgen-induced differentiation and/or downregulation of androgen-suppressed gene expression.

Androgens↗
PubMed1995

Intermittent androgen suppression in the treatment of prostate cancer: a preliminary report.

OBJECTIVES: To test the feasibility of using intermittent androgen suppression in the treatment of prostate cancer by taking advantage of the reversible action of medical castration. METHODS: Observations were made on a group of 47 patients (clinical Stage D2, 14; D1, 10; C, 19; B2, 2; and A2, 2) with a mean follow-up time of 125 weeks. Treatment was initiated with combined androgen blockade and continued for at least 6 months until a serum prostate-specific antigen (PSA) nadir was observed. Medication was then withheld until the serum PSA increased to a mean value between 10 and 20 ng/mL. This cycle of treatment and no treatment was repeated until the regulation of serum PSA became androgen independent. RESULTS: The first two treatment cycles lasted 73 and 75 weeks, with a mean time off therapy of 30 and 33 weeks and an overall mean percentage time off therapy of 41% and 45%, respectively. The mean time to achieve a nadir level of serum PSA was 20 weeks in cycle 1 and 18 weeks in cycle 2. Serum testosterone returned to the normal range within 8 weeks (range, 1 to 26) of stopping treatment. The off-treatment period in both cycles was associated with an improvement in sense of well-being and the recovery of libido and potency in the men who reported normal or near-normal sexual function before the start of therapy. In 7 patients with Stage D2 disease, the cancer progressed to an androgen-independent state. The mean and median times to progression were 128 weeks and 108 weeks, respectively. Seven patients have died, 1 from a noncancer-related illness, with mean and median overall survival times of 210 weeks and 166 weeks, respectively. CONCLUSIONS: Prostate cancer is amenable to control by intermittent androgen suppression. This approach affords an improved quality of life when the patient is off therapy. It also results in reduced toxicity and cost of treatment and possibly delays tumor progression. Whether survival is affected in a beneficial or adverse way remains to be studied in a randomized, prospective study.

Aged↗
PubMed1995

The correlation of multichannel urodynamic pressure-flow studies and American Urological Association symptom index in the evaluation of benign prostatic hyperplasia.

PURPOSE: We correlated multichannel pressure-flow urodynamics and the American Urological Association (AUA) symptom index in the evaluation of benign prostatic hyperplasia. MATERIALS AND METHODS: We evaluated 121 consecutive, symptomatic patients older than 55 years with the AUA symptom score and multichannel pressure-flow urodynamic studies. Testing was performed during a single session and the data obtained from 103 patients were plotted on the Schäfer nomogram for assessment of outflow obstruction. Linear regression statistical analysis was used to determine correlations. RESULTS: There was no significant correlation between uroflowmetry and Schäfer curves (r = 0.173 to 0.326), uroflowmetry and AUA symptom scores (r = 0.134 to 0.153) and, most importantly, AUA symptom scores and Schäfer curves (r = 0.025 to 0.137). CONCLUSIONS: We conclude that these modalities measure independent variables, and should not be linked in the evaluation and treatment decision of the patient with prostatism.

Aged↗
PubMed1995

Should we reconsider the indications for ileo-obturator node dissection with localized prostate cancer?

OBJECTIVE: To evaluate the need for ileo-obturator node dissection in patients with localized prostate cancer who are undergoing radical retropubic prostatectomy. PATIENTS AND METHODS: Over a 5-year-period, 95 patients underwent bilateral pelvic lymphadenectomy. Ninety were performed in association with planned radical prostatectomy and five were staging procedures in clinical stage T3 patients prior to radiotherapy or hormonal therapy. The patients with localized prostate cancer were stage T1a (one patient), T1b (21), T2a (30), and T2b (38). Pre-operative biopsies in the patients with localized cancer were well differentiated in 44 patients, moderately well differentiated in 45 and poorly differentiated in one. In the patients with T3 tumours, pre-operative biopsies were well differentiated in one, moderately well differentiated in two and poorly differentiated in two. Prostate-specific antigen (PSA) levels ranged from 0.4 to 110.1 ng/mL (Hybritech assay). RESULTS: Two patients had positive lymph node dissections on fixed section. These two patients had well-differentiated T1b disease with a PSA level of 72.4 ng/mL and poorly differentiated T3 disease with a PSA level of 58.5 ng/mL. There was significant upstaging (P < 0.001) and upgrading (P < 0.001) on pathological examination. None of the 71 patients with a PSA < or = 10 ng/mL had positive lymph nodes compared with 8.3% of the 24 patients with a PSA > 10 ng/mL (P = 0.0618). Lymph node metastases were present in 1% of patients with well or moderately well-differentiated prostate cancer on pre-operative biopsy versus 33% with poorly differentiated disease (P = 0.0625). These P values strongly suggest an association, achieving significance only at the 10% level which might be the more appropriate level given the relative lack of power of the study due to the small number of patients with positive lymph nodes. CONCLUSION: These results suggest that routine ileo-obturator node dissection in patients with well or moderately well-differentiated, localized prostate cancer and a PSA level < 10 ng/mL may be unnecessary, especially as a separate procedure.

Aged↗
PubMed1995

Transition zone carcinoma of the prostate.

Transition zone carinoma of the prostate can present a difficult diagnostic challenge. This entity should be considered in patients who have high prostate specific antigens (PSA) in relation to prostate volume and negative transrectal ultrasounds and ultrasound-guided biopsies. A transurethral biopsy of the prostate may be necessary to obtain the diagnosis.

Journal Article↗
PubMed1995

Benign scrotal inclusion cyst of the male perineum: an unusual post-operative complication.

Common complications after cystourethrectomy include wound infection, pneumonia, pyelonephritis and ureteral obstruction. No perineal cysts have been reported. We describe a perineal cystiic mass excised 14 years after cystourethrectomy. The cyst was lined by keratinizing stratified squamous epithelium with prominent rete ridges and basal pigmentation. A subjacent, concentric layer of smooth muscle was evident. An eccrine sweat gland was present in the cyst wall. Taken together, the features strongly suggest a scrotal inclusion cyst, a hitherto undescribed entity. Although rare, this lesion could masquerade as a local recurrence of carcinoma.

Journal Article↗
PubMed1995

Venovenous bypass in renal cell carcinoma with caval tumor thrombus.

We describe two patients with a T3bN2M0 renal cell carcinoma with caval extension to the hepatic veins in which we successfully utilized extracorporeal femoralaxillary venovenous bypass for tumor thrombus resection. The inherent advantage of this modified venovenous bypass are discussed with a current review of the literature.

Journal Article↗
PubMed1995

A prospective trial comparing the efficacy and complications of the modified Dornier HM3 and MFL 5000 lithotriptors for solitary renal calculi.

A prospective randomized study of 198 patients was conducted to compare the efficacy of the modified Dornier HM3 lithotriptor to the MFL 5000 lithotriptor. Entrance criteria included solitary stones at any location within the upper collecting system that had not previously been treated with lithotripsy. Following lithotripsy the patients were evaluated by a blinded radiologist with a plain abdominal film, tomograms and renal ultrasound at 1, 4 and 12 weeks. Patients were classified at 12 weeks after lithotripsy as failing treatment if any stone fragments were imaged. Of the patients 170 were available for complete 3-month followup. No statistical or clinical difference in stone-free rates was apparent for calculi in the ureter or renal pelvis in either group. Of patients with lower caliceal stones 80% had no residual fragments visualized at 12 weeks when treated with the modified HM3 device versus 56% with the MFL 5000 lithotriptor (p = 0.05). Treatment time on the MFL 5000 unit was significantly prolonged compared with the modified HM3 device (0.7 hours versus 0.4 hours, respectively) resulting in fewer patients being treated in a given day (p < 0.001). No statistical difference in complication rates could be found between the 2 machines. Steinstrasse were noted in 10% of the patients treated with the modified HM3 device and 6% of the MFL 5000 group. Subcapsular hematomas were noted in 4% of the MFL 5000 treatment arm compared to 1% in the modified HM3 group. Overall, the MFL 5000 lithotriptor was believed to offer no significant clinical advantage over the modified HM3 device in terms of lithotripsy efficacy, although the multifunctional table did offer more versatility for stone treatment. For a busy lithotripsy center, the modified HM3 lithotriptor is still the most efficacious.

Adult↗
PubMed1994

Controversies in the management of clinical T3 carcinoma of the prostate.

The therapy of all stages of prostate cancer remains controversial. Perhaps the management of T3 disease is most difficult to evaluate. By definition, T3 disease is: 1) outside the capsule of the prostate (with invasion of the pericapsular tissue, the apex, the bladder neck and/or the seminal vesicles); 2) mobile; and 3) localized to the pelvis. Pelvic fixation is described as T4 disease in the TNM system and will not be included in this review. Comparisons of various treatment methods are difficult to achieve due to the lack of knowledge regarding the natural history of this disease and the variations in staging methods. The number of patients diagnosed with clinical T3 cancer of the prostate in Canada and the US is unknown. It is estimated that approximately 145 000 cases of prostate cancer will be diagnosed in the two countries in 1994; furthermore, it is estimated that 12-15% or 15 000-18 000 of these cases will have T3 disease. The percentage of cases diagnosed as T3 is expected to drop with the increase use of methods of early detection.

Journal Article↗
PubMed1993

Effects of intermittent androgen suppression on androgen-dependent tumors. Apoptosis and serum prostate-specific antigen.

BACKGROUND: Since postcastration progression of tumors to an androgen-independent state appears to be linked to the cessation of androgen-induced differentiation of tumorigenic stem cells, the authors hypothesized that the replacement of androgens at the end of a period of apoptotic regression might result in the regeneration of differentiated tumor cells with further apoptotic potential. METHODS AND RESULTS: To determine the effect of intermittent exposure of androgens on the androgen-dependent Shionogi carcinoma, the tumor was transplanted into a succession of male mice, each of which was castrated when the estimated tumor weight became about 3 g. After the tumor had regressed to 30% of the original weight, it was transplanted into the next noncastrated male. This cycle of transplantation and castration-induced apoptosis was repeated successfully four times before growth became androgen-independent during the fifth cycle. In four of Stage C and three of Stage D patients with prostate cancer, androgen withdrawal was initiated with cyproterone acetate (100 mg/d) and diethylstilbestrol (0.1 mg/d) and then maintained with cyproterone acetate in combination with the luteinizing hormone-releasing hormone agonist, goserelin acetate (3.6 mg/month). After 6 or more months of suppression of serum prostate-specific antigen (PSA) into the normal range, treatment was interrupted for 2 to 11 months. After recovery of testicular function, androgen-withdrawal therapy was resumed when serum PSA increased to a level of about 20 micrograms/l. This cycle was repeated sequentially to a total of two to four times over treatment periods of 21 to 47 months with no loss of androgen dependence. CONCLUSIONS: These results demonstrate that intermittent androgen suppression can be used to induce multiple apoptotic regressions of a tumor; they also suggest that the cyclic effects of such treatment on prostate cancer can be followed by the sequential measurement of serum PSA levels.

Adenocarcinoma↗
PubMed1992

Major vessel excision in retroperitoneal lymph node dissection.

Retroperitoneal malignant tumours, both primary and metastatic, may involve surrounding structures such as the aorta and vena cava, making complete tumour excision difficult. En bloc resection of major blood vessels should be considered in such cases. The authors describe three patients who underwent excision of major blood vessels with retroperitoneal lymph node dissection. Two patients had aortic resection with placement of a Dacron tube graft, and one had excision of the vena cava from above the renal vessels to the level of the common iliac veins with distal venous ligation. The low complication rate confirms the feasibility of excising major blood vessels to accomplish complete retroperitoneal lymphadenectomy.

Adolescent↗
PubMed1987

A routine method for cytogenetic analysis of small urinary bladder tumor biopsies.

A method that allows routine cytogenetic analysis of small cystoscopic biopsies from urothelial tumors is described. This method is based on prolonged mild collagenase disaggregation, a 12-16 hour culture, and harvesting procedures adapted to give maximal metaphase recovery. In addition to providing a means for cytogenetic studies of small biopsies from urinary bladder tumors, this method provides the advantages of direct preparations, with chromosome morphology and banding sufficient for karyotypic analysis. Conventional cell synchronization techniques, applied to this system, should enable high-resolution banding and optimize analysis.

Carcinoma, Transitional Cell↗
PubMed1985

Sonography and CT in staging nonseminomatous testicular tumors.

The usefulness of sonography and computed tomography (CT) in the clinical staging of nonseminomatous testes tumors was examined by retrospectively reviewing the clinical staging of 57 patients. Twenty-five patients had sonographic examinations; two were considered inadequate and there were no false-positive results. Understaging occurred in 13% (3/23), while the negative predictive value for sonography was 73% (8/11). CT was performed on 29 patients; no patients were overstaged and only one examination was inadequate due to technical reasons. Understaging occurred in 18% (5/28), and CT had a negative predictive value of 67% (8/12). A subgroup of 18 patients having both sonography and CT was examined, and each staging procedure had a 22% false-negative and a 0 false-positive rate. Twenty-seven lymphangiograms, 28 excretory urograms, and 49 tumor marker determinations were also performed on this patient population, and their false-negative rates were 35%, 78%, and 61%, respectively. False-positive rates of 30% for lymphangiograms, 6% for tumor markers, and 0 for excretory urograms were also obtained. On the basis of these results, sonography and CT are equivalent and superior examinations that have a high degree of accuracy (90%) in predicting bulky metastatic disease, either stage B3 or C disease. All patients would have received appropriate therapy if both examinations were carried out. However, this same goal could have been achieved with greater cost efficiency by initial sonographic screening, followed by CT in only those patients with negative or inadequate sonographic examinations.

Adolescent↗
PubMed1984

Intraoperative balloon catheter control of renal arteriovenous fistula.

Renal arteriovenous fistulas have been managed with embolic therapy or surgical excision. In the case of a large, hemodynamically significant shunt sudden occlusion of the renal artery may result in profound circulatory decompensation. We managed such a case with a combined approach. An intra-arterial balloon catheter was inserted into the renal artery under fluoroscopic guidance, with constant monitoring of the central cardiac indexes via a Swan-Ganz line. The balloon was inflated and then released as circulatory changes were corrected. Once the patient was stable we performed a simple nephrectomy. We recommend this combined, controlled approach for the management of large arteriovenous fistulas.

Aged↗