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Biomedical subjects

Larry Goldenberg

Publications and source records attributed to Larry Goldenberg.

7 recordsLinked to original sources
PubMed2006

Rh2 synergistically enhances paclitaxel or mitoxantrone in prostate cancer models.

PURPOSE: We explored the efficacy of the ginsenoside Rh2 and examined its impact on the effective dose of paclitaxel and mitoxantrone in the LNCaP prostate tumor model. MATERIALS AND METHODS: Cultured LNCaP cell viability was assessed following treatment (48 hours) with Rh2 (0 to 40 microM) alone or in combination with paclitaxel and mitoxantrone. Synergism or antagonism observed when combining treatment was calculated using CalcuSyn software (Biosoft). In addition, the inhibition of LNCaP human xenograft tumor growth was examined in vivo when Rh2 treatment was combined with chemotherapy. Harvested tumors were immunohistochemical stained with p27kip and Ki67. RESULTS: Rh2 and paclitaxel act synergistically in cultured LNCaP cells to lower ED50 and ED75 values. Rh2 and mitoxantrone are also synergistic. However, when combined as ED95, an antagonistic effect was observed in this cell line. Treatment of LNCaP tumors by Rh2 plus paclitaxel produced a significant decrease in tumor growth and serum prostate specific antigen. Immunohistochemical analysis revealed an apparent but nonsignificant effect on proliferation markers in LNCaP tumors. When Rh2 and mitoxantrone were combined in vivo, there was no significant benefit observed. CONCLUSIONS: These results indicate that the combination of Rh2 and paclitaxel has an effect on growth inhibition that is greater and synergistic, as demonstrated in a cultured LNCaP cell line. Conversely combining Rh2 with mitoxantrone appears to elicit no benefit. Therefore, combination therapy using chemotherapy and Rh2 requires further investigation.

Animals↗
PubMed2006

Does prolonging the time to prostate cancer surgery impact long-term cancer control: a systematic review of the literature.

BACKGROUND: The wait times for prostate cancer surgery in Canada has increased over the past 2 decades. Prolonged wait times have a negative impact on patient quality of life but the effect on long-term cancer control is undefined. We conducted a systematic literature review to examine the best available evidence addressing the following key questions: . What is the reported time interval for prostate cancer patients from the decision to operate until the day of cancer surgery? . Are there recommendations/guidelines in the urological cancer literature and, if so, how do the Canadian times compare? . Is there a known association between duration of wait time beyond the recommended standard and clinical outcome (i.e. recurrence free survival, overall survival)? METHODS: A structured literature search of Medline, Pubmed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, the Cochrane Database of Abstracts of Reviews of Effects, Healthstar and Google Scholar was performed from January 1980 to January 2006 for published epidemiological studies and international guidelines/consensus documents that evaluated surgical wait times for prostate cancer. Data extracted from eligible studies included median time to prostate cancer surgery from the point of patient contact and adjusted hazard ratios (HR) for wait times. All HR from the included studies were examined for the possibility of statistical pooling via meta analytic techniques. RESULTS: Thirteen studies evaluating wait times for prostate cancers were identified, six of which measured the HR for prostate specific antigen (PSA) recurrence in patients with prolonged wait times. Differences in study data availability, method of analysis and wait time definitions precluded statistical pooling of the findings. Median wait times from various points of patient contact ranged from 42 days to 244 days. In the six Canadian studies identified, wait times ranged from 42 days (consultation to operation) to 83 days (consultation to hospital admission). This was in contrast to national and international guidelines, which recommended a maximum wait time for prostatectomy between 2 to 4 weeks. The association between surgical delay and disease recurrence remained controversial where only two of six epidemiological studies reported at least a statistical trend for an increased risk of PSA recurrence free survival in patients with surgical delays of 3 months or more. CONCLUSIONS: Unlike comparable countries, surgical wait times in Canada appear to be increasing and are well beyond the threshold recommended by national and international expert bodies. Even though the association between surgical delay and disease recurrence remains unclear, there is an ongoing concern that the psychological impact of prolonged waiting could negatively impact patient outcomes. To address these important issues, the surgical wait times (SWAT) initiative is mandated to provide the necessary guidance and recommendations to the federal and provincial governments. Through a partnership of the key stakeholders, it is the vision of SWAT to ultimately improve the care and quality of life of prostate cancer patients and their families.

Appointments and Schedules↗
PubMed2005

Technology review: high-intensity focused ultrasound for prostate cancer.

INTRODUCTION AND OBJECTIVE: High-Intensity Focused Ultrasound (HIFU) is a technology that has moved from being used for benign prostate disease to the treatment of prostate cancer. A technology review was undertaken to guide patients and physicians as to its suitability. METHOD: An evidence-based review of published papers in the English language, with additional material from internet and other sources. RESULTS AND CONCLUSIONS: Only case series have been published; there are no randomized studies. The quality of evidence is poor, with no reports having longer follow-up than a mean of 2 years, with median follow-ups substantially shorter. Efficacy outcomes are thus premature and preclude assessment. Toxicity varies substantially with impotence rates 44%-61%, grade 2-3 incontinence 0%-14%, and rectal fistulae 0.7%-3.2%. There is limited data on the use of HIFU for the salvage therapy after radiation failure. There are no data on the toxicity of subsequent standard curative therapies after HIFU. In view of the lack of efficacy outcomes, and in the presence of significant toxicity, HIFU should only be offered within a research setting.

Evidence-Based Medicine↗
PubMed2005

Canadian guidelines for the management of benign prostatic hyperplasia.

OBJECTIVE: To develop the first Canadian guidelines for the management of lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH). METHODS: These guidelines, developed under a mandate provided by the Canadian Urological Association (CUA), were a collaborative effort between the CUA guidelines committee and the Canadian Prostate Health Council. BPH guidelines developed by the American Urological Association, the European Association of Urology, the World Health Organization International Consultation on BPH, and similar committees from Germany, Sweden and Australia were reviewed. The committee further reviewed a systematic literature search, updated to May 2004, and systematically derived Canadian urological opinion data. RESULTS: The subsequent Canadian BPH guidelines were developed as an evidence based consensus among the committee members. Mandatory evaluation includes history, physical examination and urinalysis, while a symptom inventory and PSA in selected patients are recommended. Serum creatinine, uroflow, voiding diary, post void residual and sexual function questionnaire are optional. Unless there is an indication, other related tests are not recommended. Treatment choices should be governed by the severity of the symptoms, bother and patient preference. Guidelines for medical, surgical and minimally invasive treatment as well as special considerations are described in terms of guideline, option and recommendation. CONCLUSIONS: Diagnostic and treatment guidelines for BPH reflect the Canadian social priorities, economics, socialized medical practice, manpower issues, and medicolegal considerations.

Canada↗
PubMed2003

Prostate specific antigen: an updated review.

Since its discovery in 1979, serum PSA has revolutionized how physicians manage men with prostate cancer. PSA screening, although currently under much debate, has been recommended by most North American medical bodies, including the Canadian Urological Association, to be performed as a shared-decision making process after discussing with patients the pros and cons of treatment. Although most commonly thought of as a screening tool, serum PSA has also been used to predict tumor volume, stage and prognosis in patients before and after treatment. In this review, we examine PSA testing and its effectiveness in the diagnosis and management of prostate cancer. Further, we also evaluate recent literature regarding the use of PSA derivatives and other prostate cancer markers, such as proPSA, bPSA, and hk2

Humans↗
PubMed1997

Hypertension and nephritic urine sediment following retroperitoneal lymph node dissection.

Retroperitonela lymph node dissection (RPLND), cisplatin-based chemotherapy, and tumor surveillance has dramatically improved survival of patients with non-seminomatous germ cell tumors. Complications, including renal vascular injuries, have been encountered with post-chemotherapy RPLND. We report on a patient with delayed renovascular hypertension and nephritic sediment following RPLND. A thirty year old man presented with well-controlled hypertension following treatment of a left testicular non-seminomatous germ cell tumor 11 years earlier. Post-orchiectomy investigation revealed retroperitoneal lymphadenopathy which was treated with cispaltin-based chemotherapy. A residual mass was managed surgically and during perihilar dissection, the left renal vein was injured and repaired. Current investigation revealed hypertension and a nephritic urine sediment, both of which resolved with left simple nephrectomy. We believe that inadvertent renal artery injury was responsible for this late complication.

Journal Article↗