PubMed Health⌕ Search

Biomedical subjects

Mark S Soloway

Publications and source records attributed to Mark S Soloway.

At least 19 recordsLinked to original sources

HAS1 expression in bladder cancer and its relation to urinary HA test.

Hyaluronic acid (HA) levels are elevated in bladder cancer tissues and regulate tumor growth and progression. Urinary HA levels measured by the HA test are an accurate marker for bladder cancer. In cells, HA is synthesized by one of the 3 HA-synthase(s) i.e., HAS1, HAS2 and HAS3. In this study, we examined HAS1 expression in bladder cancer cells and tissues. Real-time RT-PCR and northern blot analyses showed that HAS1 transcript levels are elevated 5- to 10-fold in bladder cancer tissues, when compared with normal tissues (p < 0.001). Among the 3 HAS1 splice variants, only HAS1-va was expressed in bladder tissues, but the expression was significantly lower than the wild type HAS1 transcript. Increased HAS1 expression in bladder tumor tissues correlated with increased tissue HA levels (p < 0.001). Size of the large HA species (2.0 x 10(6) D) present in bladder tissues was consistent with the size of the HA polymer synthesized by HAS1. The amount of HA produced by bladder cancer cell lines correlated with the expression of HAS1 protein. Immunohistochemical analyses of bladder tumor tissues showed that HAS1 and HA expression had 79-88% sensitivity and 83.3-100% specificity. Both HAS1 and HA expression in bladder cancer tissues correlated with a positive HA urine test (p < 0.001). HAS1 expression correlated with tumor recurrence, prior treatment (p < 0.05) and possibly disease progression (p = 0.058). Therefore, elevated HAS1 expression in bladder tumor tissues contributes to a positive HA urine test and may have some prognostic potential.

Adult↗

Metastatic adenoid cystic carcinoma to the kidney in a young woman.

The incidence of an adenoid cystic carcinoma on major salivary glands is low, constituting only about 10% to 15% of all parotid malignancies. Cases of delayed metastasis have been reported, but reports of specific renal involvement have not been extensively found. We present the case of a 21-year-old woman with a left renal metastasis from an adenoid cystic carcinoma of the parotid gland that had been surgically treated 7 years previously. The patient underwent successful left radical nephrectomy. During follow-up, the patient developed pulmonary nodules that were metastatic adenoid cystic carcinoma and were surgically excised. At last follow-up, the patient was doing well with no evidence of disease.

Adult↗

HYAL1-v1, an alternatively spliced variant of HYAL1 hyaluronidase: a negative regulator of bladder cancer.

Tumor cells express HYAL1 hyaluronidase, which degrades hyaluronic acid. HYAL1 expression in bladder cancer cells promotes tumor growth, invasion, and angiogenesis. We previously described five alternatively spliced variants of HYAL1 that encode enzymatically inactive proteins. The HYAL1-v1 variant lacks a 30-amino acid sequence that is present in HYAL1. In this study, we examined whether HYAL1-v1 expression affects bladder cancer growth and invasion by stably transfecting HT1376 bladder cancer cells with a HYAL1-v1 cDNA construct. Although HYAL1-v1 transfectants expressed equivalent levels of enzymatically active HYAL1 protein when compared with vector transfectants, their conditioned medium had 4-fold less hyaluronidase activity due to a noncovalent complex formed between HYAL1 and HYAL1-v1 proteins. HYAL1-v1 transfectants grew 3- to 4-fold slower due to cell cycle arrest in the G(2)-M phase and increased apoptosis. In HYAL1-v1 transfectants, cyclin B1, cdc2/p34, and cdc25c levels were > or =2-fold lower than those in vector transfectants. The increased apoptosis in HYAL1-v1 transfectants was due to the extrinsic pathway involving Fas and Fas-associated death domain up-regulation, caspase-8 activation, and BID cleavage, leading to caspase-9 and caspase-3 activation and poly(ADP-ribose) polymerase cleavage. When implanted in athymic mice, HYAL1-v1-expressing tumors grew 3- to 4-fold slower and tumor weights at day 35 were 3- to 6-fold less than the vector tumors (P < 0.001). Whereas vector tumors were infiltrating and had high mitoses and microvessel density, HYAL1-v1 tumors were necrotic, infiltrated with neutrophils, and showed low mitoses and microvessel density. Therefore, HYAL-v1 expression may negatively regulate bladder tumor growth, infiltration, and angiogenesis.

Alternative Splicing↗

Cyclooxygenase-2 (COX-2) expression is an independent predictor of prostate cancer recurrence.

Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty-three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high- or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at > or = 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process.

Aged↗

A pelvic drain can often be avoided after radical retropubic prostatectomy--an update in 552 cases.

OBJECTIVES: The routine placement of a pelvic drain following radical retropubic prostatectomy (RRP) may not be required. We describe our experience in 552 consecutive RRPs to emphasise the safety of this approach and explain our rationale for avoiding a drain when possible. METHODS: RRP was performed in 552 consecutive patients with clinically localised adenocarcinoma of the prostate between January 2002 and June 2005. Clinical and pathologic information was documented for each patient. After the prostate was removed and the anastomotic sutures tied, the bladder was gently filled with approximately 50 ml of saline through the urethral catheter. If there was no leak, a drain was not placed. RESULTS: A drain was not placed in 419 (76%) of the 552 patients. We compared the postoperative complication rates in those with (D+) and without (D-) a drain. There were 27 (5%) immediate postoperative complications and no significant difference between the two groups (D+, 6%; D-, 5%; p=0.629): three (1%) patients who did not have a drain had a urinoma, one (1%) who had a drain had a lymphocele, and two (2%) who had a drain had a small pelvic haematoma. CONCLUSIONS: If the bladder neck is preserved or meticulously reconstructed, there may be little extravasation and, thus, routine drainage is unnecessary. Our 4-year experience indicates that morbidity is not increased by omitting a drain from the pelvic cavity after RRP in properly selected cases.

Adenocarcinoma↗

Radical cystectomy after bacillus Calmette-Guérin for high-risk Ta, T1, and carcinoma in situ: defining the risk of initial bladder preservation.

OBJECTIVES: To critically evaluate the survival of patients with high-grade Ta or T1 urothelial cancer (UC) or carcinoma in situ of the bladder who have received bacillus Calmette-Guérin (BCG) and who have undergone radical cystectomy. METHODS: We retrospectively reviewed our single-surgeon database of those patients who underwent cystectomy and previously received BCG. We evaluated the baseline characteristics, pathologic outcomes, and survival data. RESULTS: Of 313 patients who underwent cystectomy between January 1992 and March 2004, 90 (29%) received BCG before bladder removal. The mean time from the first BCG course to the date of cystectomy was 27.9 months. The mean duration of follow-up from cystectomy was 32.1 months. The risk of progression to muscle invasion for those who underwent cystectomy less than or more than 1 year from the time of their first BCG dose was 59% and 36%, respectively (P = 0.05). The disease-specific survival rate was 81% versus 80% for those who underwent early versus delayed cystectomy (P = 0.9). CONCLUSIONS: Patients with high-grade UC are at risk of dying from this cancer, even if they ultimately undergo cystectomy. Patients who receive BCG should be appropriately counseled that they remain at risk for disease progression and death from UC. It is difficult to ascertain the proper time to proceed with cystectomy if an initial bladder conservation approach is used.

Adjuvants, Immunologic↗

The diagnosis and staging of bladder cancer: from RBCs to TURs.

Timely and accurate diagnosis and staging of bladder cancer is critical for the successful management of patients with this disease. We review the literature on screening, signs and symptoms, cystoscopic evaluation, diagnostic tests, transurethral resection, and imaging. We highlight emerging areas, such as markers and fluorescence cystoscopy. Suspicion, accuracy, and technologic advances are key factors in ensuring the best outcomes for patients with bladder cancer.

Cystectomy↗

Prostate specific antigen recurrence rates are low after radical retropubic prostatectomy and positive margins.

PURPOSE: Treatment in patients with a positive surgical margin after radical retropubic prostatectomy is controversial. Options are observation, radiation therapy and early hormone therapy. Making the appropriate choice should be based on an understanding of the risk of recurrence without treatment. MATERIALS AND METHODS: We reviewed the records of 1,383 patients after radical retropubic prostatectomy was performed by a single surgeon. All specimens were analyzed by a single pathologist. Of the patients 936 met criteria for analysis. RESULTS: Mean followup in these 936 patients was 45.8 months (minimum 12). The overall PSA biochemical recurrence rate was 11.5% (108 of 936 cases). Of the 936 patients 350 (37%) had tumor at an inked margin. These patients had a recurrence rate of 19% (67 of 350), while patients with negative margins had a recurrence rate of 7% (41 of 586). This difference was statistically significant (p <0.01). Multivariate HR analysis revealed that significant risk factors for recurrence in the 936 patients were PSA greater than 20 ng/ml, clinical stage T2 or greater, Gleason 7 or greater, seminal vesicle involvement, extraprostatic extension, a visual estimate of prostate cancer volume of greater than 9.1% and positive surgical margins. Statistically significant risk factors for recurrence in patients with a positive margin on multivariate HR analysis were PSA greater than 20 ng/ml, Gleason score 7 or greater and seminal vesicle involvement. CONCLUSIONS: Although the positive margin rate in this series was 37%, the recurrence rate in these patients was only 19%. It is important to consider other factors, such as PSA, Gleason score, seminal vesicle involvement and extraprostatic extension, when making treatment decisions.

Humans↗

Complications of intravesical therapy for urothelial cancer of the bladder.

PURPOSE: Intravesical therapy is an integral part of treatment in patients with superficial urothelial carcinoma of the bladder. The American Urological Association and European Association of Urology guidelines on bladder cancer incorporate it for the treatment of superficial bladder cancer. Given the extensive use of intravesical immunotherapy and chemotherapy, it is essential for the practicing urologist to be aware of the local and systemic side effects of these therapies. MATERIALS AND METHODS: We reviewed the literature on intravesical immunotherapy and chemotherapy with particular emphasis on side effects, complications and their management. A Medline search of the English language literature for the last 25 years was done on Entrez PubMed and all relevant articles were studied in full. All side effects and complications were studied and their management was reviewed. RESULTS: Intravesical therapy for transitional cell carcinoma of the bladder is generally safe. There is a high incidence of local, usually self-limiting, relatively minor side effects and infrequent, potentially severe local and systemic side effects. Most side effects are avoidable. CONCLUSIONS: Although intravesical therapy is generally safe, local and systemic side effects occur and it is important to be aware of them. Identifying complications early, preventing them when possible and managing them efficiently are critical. Most complications are preventable. Knowing the risks and benefits of chemotherapeutic and immunotherapeutic agents may decrease the short-term and long-term toxicity of these agents. Adherence to guidelines may prevent inappropriate use, which can lead to unnecessary complications, resulting in bladder dysfunction and even cystectomy.

Adjuvants, Immunologic↗

En bloc mobilization of the inferior vena cava and large hypervascular right renal tumors with or without inferior vena cava thrombus: Posterior ligation of the renal artery.

We describe our approach of posterior ligation of the renal artery during resection of large hypervascular right renal tumors. This technique uses en bloc mobilization of the inferior vena cava and renal tumor to ligate the renal artery at its origin from the aorta. In our experience, the use of this posterior approach for renal artery ligation is safe and effective, even with large renal tumors with multiple collaterals and/or lymph nodes making the identification of the renal artery difficult.

Aged↗

Concurrent radical retropubic prostatectomy and Lichtenstein inguinal hernia repair through a single modified Pfannenstiel incision: a 3-year experience.

OBJECTIVE: To present the results of a 3-year experience of radical retropubic prostatectomy (RRP) through a modified Pfannenstiel incision and concomitant repair of an inguinal hernia at the time of RRP, using a tension-free technique with a mesh, as described by Lichtenstein, with no additional incision(s), as 5-10% of patients with clinically localized prostate cancer have a detectable inguinal hernia. PATIENTS AND METHODS: Patients who had RRP between October 2002 and July 2005 were included; we used a standard open RRP, in all cases using a modified Pfannenstiel incision. If the patient had an inguinal hernia, we approached the inguinal canal through the same incision and performed a Lichtenstein mesh repair, through the inguinal canal and avoiding placing mesh within the pelvis. Patients were followed at 1 and 6 weeks, 3-monthly for 1 year and 6-monthly thereafter. All clinical variables were entered into a database and analysed. RESULTS: In all, 450 men underwent RRP; 44 (10%) had inguinal hernia and in all, 56 hernias were repaired (32 unilateral and 12 bilateral; 16 indirect, 22 direct, six both) The mean (sd) age of the patients was 60 (7) years. Most patients were discharged within 36 h. The mean (sd) follow-up was 9 (8) months. Two patients had a superficial inguinal haematoma and one had a scrotal haematoma. They were treated conservatively with no sequelae. There were no wound infections. One patient developed a recurrent inguinal hernia. None had any clinical evidence of testicular atrophy or chronic pain. CONCLUSION: Concurrent formal mesh repair of the inguinal hernia and RRP through a single modified Pfannenstiel incision is safe and effective. The complications were minimal and recurrence rates were low. This procedure eliminates the risks involved with the preperitoneal mesh repair and avoids multiple incisions.

Hernia, Inguinal↗

Optimal management of the T1G3 bladder cancer.

TIG3 transitional cell carcinoma of the bladder represents a highly malignant tumor with a variable and unpredictable biologic potential. The most critical aspect of management requires a detailed discussion with the patient regarding the treatment options. Both the physician and the patient should be willing to reconsider the treatment options as the disease continues to evolve. In most cases initial management involves complete resection of the tumor, accurate staging of the disease, and intravesical immunotherapy or chemotherapy. Rigorous surveillance with long-term follow-up is crucial for managing these cases. In selected cases with adverse prognostic factors immediate cystectomy should be considered. The choice and timing of the decision to abandon bladder preservation and proceed with cystectomy should be continuously reconsidered on an individual patient basis, in concordance with the evolution of the disease (Fig. 1). The goal is to spare the bladder when possible but not at the risk of death from metastatic disease. Radical cystectomy in high-grade stage T1 transitional cell carcinoma offers excellent results in regard to the prevention of recurrence and progression and survival. Improvements in urinary diversion and nerve-sparing techniques have decreased the magnitude of social implications related to cystectomy in most patients regardless of gender. The discovery of reliable markers may contribute to better selection of patients for bladder sparing. Until then, the optimal treatment for the T1G3 tumor remains controversial.

Administration, Intravesical↗

Evaluation of analgesic requirements and postoperative recovery after radical retropubic prostatectomy using long-acting spinal anesthesia.

OBJECTIVES: To analyze the postoperative pain, analgesic requirements, and convalescence of patients undergoing radical retropubic prostatectomy (RRP) under spinal anesthesia using long-acting morphine sulfate as preemptive analgesia. METHODS: A total of 103 consecutive men underwent RRP by a single surgeon. The time to tolerate oral fluids, time to unassisted ambulation, postoperative pain levels (visual analog pain score of 0 to 10), and analgesic requirements expressed in morphine equivalents were evaluated. Baseline patient characteristics and intraoperative factors (operating room time, blood loss) were also evaluated. RESULTS: The mean time to tolerate oral fluids and unassisted ambulation was 11.3 +/- 7.6 hours and 20 +/- 6 hours, respectively. The mean narcotic requirements were 7.4 +/- 6.1 morphine equivalents before discharge and 28.5 +/- 25.9 morphine equivalents in the first week after discharge. The mean visual analog pain score was 4.5 +/- 2.1 at discharge and fell significantly to 1.5 +/- 1.0 by the time of Foley catheter removal on postoperative day 7 or 8. The analgesic requirements after discharge correlated with the pain score at discharge (P = 0.016). The mean time to resumption of normal preoperative activities was 19.4 +/- 9.4 days. Two patients developed postspinal anesthesia headache. No other complications attributable to the anesthetic occurred. CONCLUSIONS: RRP may be performed through a small modified Pfannenstiel incision under spinal anesthesia containing long-acting morphine with little postoperative pain, low narcotic requirements, and a short convalescence. A prospective, randomized study is needed to compare the early postoperative outcomes of RRP performed using general versus spinal anesthesia.

Analgesia↗