Saturday, September 28, 2013

Small-incision access retroperitoneoscopic technique (SMART) pyeloplasty in adult patients: comparison of cosmetic and post-operative pain outcomes in a matched-pair analysis with standard retroperitoneoscopy: preliminary report.

Department of Urology, SLK Kliniken Heilbronn, University of Heidelberg, Am Gesundbrunnen 20-24, 74078 Heilbronn, Germany.
To present small-incision access retroperitoneoscopic technique pyeloplasty (SMARTp), a novel mini-laparoscopic approach for management of uretero-pelvic junction obstruction (UPJO) in adults including comparison with the standard retroperitoneoscopic technique (SRTp).
In a non-randomised study, we matched 12 adult patients treated from August to November 2010 by SMARTp with 12 patients treated with SRTp from January to November 2010. Mini-laparoscopic retroperitoneal space was created with a home-made 6-mm balloon trocar. One 6-mm (for 5-mm 30° telescope) and two 3.5-mm trocars (for 3-mm working instrument) were used. SRTp was performed with 11- and 6-mm trocar. Primary endpoints included evaluation of cosmetic appearance and post-operative pain evaluated respectively by the patient and observer scar assessment scale (POSAS) and analogue visual scale (VAS). Secondary endpoints were comparison between operative and functional parameters.
Cosmetic cumulative results were statistically significant in favour of SMARTp (POSAS: 37.9 vs. 52.4; P = 0.002). A better trend has been shown by post-operative pain (first to fourth day VAS), although not statistically significant (4.2 vs. 4.9, P = 0.891). No differences were recorded in terms of operative time, pre- and post-operative Hb difference, DJ-stent removal and resistive index (RI) improvement. The SMARTp group showed a faster drain removal (2.4 vs. 3.4 day, P = 0.004) and discharge (4.5 vs. 5.4 day P = 0.017).

Preliminary data support SMARTp as safe procedures in experienced hands, providing better cosmetic results compared to SRTp. Further studies and clinical randomised trial performed in a larger population sample are requested.

Thursday, September 26, 2013

Current therapeutic options for Peyronie's disease

Published on 10 September 2013
Peyronie's disease is a heterogeneous disorder with typical symptoms of plaque formation, penile pain, deviation, penile shortening and erectile dysfunction.
The etiology is unknown. Repetitive micro-traumatic lesions with the formation of inelastic scar tissue at the level of the tunica albuginea are discussed as a trigger mechanism for a questionable genetic disposition. A non-surgical therapy based on a clear pathophysiology does not exist although several conservative treatment regimes are practiced.
 In the stable stage of the disease surgical therapy of penile angulation is the most frequent operation. Depending on the deviation angle, penile length and erectile dysfunction, different types of straightening surgery can be offered. This article provides an overview of conservative management and commonly used surgical techniques.
Written by:
Hauptmann A, Diemer T, Weidner W.

Wednesday, September 25, 2013

FDA OKs New Device to Treat BPH Mark Crane Disclosures Sep 13, 2013

The US Food and Drug Administration (FDA) today authorized the marketing of the UroLift system, the first permanent implant to relieve low or blocked urine flow in men aged 50 years and older with an enlarged prostate.

EU Okays Novel Drugs for Breast and Prostate Cancer Zosia Chustecka Disclosures Sep 20, 2013

In the European Union, the Committee for Medicinal Products for Human Use (CHMP) has recommended 2 novel cancer drugs for approval — trastuzumab emtansine (Kadcyla, Roche) for the treatment of metastatic breast cancer, and radium-223 chloride (Xofigo, Bayer) for the treatment of castration-resistant prostate cancer. Both have been shown to prolong survival.

Abstract Submission Deadline: 4 November 2013

The 5th Congress of the Asia Pacific Regional Initiative on Reproduction (ASPIRE 2014) is an important opportunity for you to contribute to the advancement of reproductive medicine, both its science and practice.
Guided by the theme, “The Future of Reproductive Medicine in the Asian Century”, ASPIRE 2014 will attract acclaimed professionals from the fields of fertility preservation, embryology, andrology, clinical trials, PCOS, PGS, IVM, as well as other specialties.

By submitting an abstract online to ASPIRE 2014, you will be sharing your research and analysis with leading clinicians, researchers, academics, nurses and other allied health professionals from across the Asia Pacific and around the world who are united by an interest in reproductive medicine and fertility.
Topics to be debated and discussed at ASPIRE 2014 include the most controversial issues of the day including:
  • ART, Laboratory
  • Contraception
  • Endocrinology, Clinical
  • And much more..

We look forward to seeing you in Brisbane!

Pan Arab Continence Society

Friday, September 20, 2013

New radiation treatment for prostate cancer reduces bone pain, extends survival rates Published on 27 August 2013

The treatment, recently approved by the Food and Drug Administration, is called Xofigo®. A radioactive substance, radium-223, is injected into the patient. Because it is similar to calcium, radium-223 binds to the bone. Radium-223 delivers high-energy radiation over a short distance, providing a targeted treatment that is less damaging to other structures or tissues, said Robert Wagner, MD, medical director of Nuclear Medicine in Loyola’s Department of Radiology.
Radium-223 is rapidly cleared from the bloodstream. Fifteen minutes after injection, about 20 percent of the injected radioactivity remains in the blood. By 24 hours, less than 1 percent of radioactivity remains.
Xofigo is recommended for prostate cancer patients in which:
§  The cancer has spread to the bones but not to other organs
§  The cancer is not responding to hormone therapy or surgery that blocks production of testosterone
§  The cancer that has spread to the bones is causing other serious symptoms
Radium-223 is injected into an IV line in a patient’s vein in a procedure that takes less than five minutes. The patient receives a series of six injections, given once every four to six weeks.
Side effects can include upset stomach, diarrhea, swelling in the hands and feet and decreased counts of red blood cells, white blood cells and platelets.
“While the treatment is not a cure, it can enable patients to live longer, with significantly improved quality of life,” Wagner said.
Loyola University Health System (LUHS) is a member of Trinity Health. Based in the western suburbs of Chicago, LUHS is a quaternary care system with a 61-acre main medical center campus, the 36-acre Gottlieb Memorial Hospital campus and more than 30 primary and specialty care facilities in Cook, Will and DuPage counties. The medical center campus is conveniently located in Maywood, 13 miles west of the Chicago Loop and 8 miles east of Oak Brook, Ill. The heart of the medical center campus is a 559-licensed-bed hospital that houses a Level 1 Trauma Center, a Burn Center and the Ronald McDonald® Children's Hospital of Loyola University Medical Center. Also on campus are the Cardinal Bernardin Cancer Center, Loyola Outpatient Center, Center for Heart & Vascular Medicine and Loyola Oral Health Center as well as the LUC Stritch School of Medicine, the LUC Marcella Niehoff School of Nursing and the Loyola Center for Fitness. Loyola's Gottlieb campus in Melrose Park includes the 255-licensed-bed community hospital, the Professional Office Building housing 150 private practice clinics, the Adult Day Care, the Gottlieb Center for Fitness, Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park.

New treatment option: 223Ra chloride, the first approved unsealed α-emitting radiopharmaceutical Published on 29 August 2013

A 66-year-old man with prostate cancer presented with intractable pain associated with multifocal bone metastases.

After receiving 180 µCi (1.35 µCi/kg) of 223Ra chloride, radiation survey measured 0.2 mR/h at 1 m, and the patient was discharged to home. He will return monthly for the next 5 months for repeat 223Ra chloride administrations. 223Ra chloride is the first Food and Drug Administration-approved unsealed α-emitting radiopharmaceutical.

Wednesday, September 18, 2013

Hepatitis C

Tuesday, September 17, 2013

Current, New and Novel Therapy for Castration-Resistant Prostate Cancer part 7

Other Targets

Drugs Targeting Src Kinase. Src family kinases are overexpressed in prostate cancer, and Src inhibition reduces cancer cell proliferation, adhesion, invasion and migration.[63]
Dasatinib is an oral Bcr/Abl inhibitor that also inhibits the Src family of kinases. Although preliminary studies provided a rationale for use of dasatinib in mCRPC[64]and early clinical trials suggested that the combination of dasatinib plus docetaxel had acceptable safety and activity,[65] the Phase III results suggest that this combination will not be pursued further. READY is one of a string of trials that fail to show an advantage for the addition of newer agents to docetaxel. The addition of dasatinib to standard therapy with docetaxel failed to improve survival and most other clinical end points in men with metastatic castration-resistant prostate cancer (mCRPC) in the Phase III READY trial, Araujo et al. reported at the 2013 Genitourinary (GU) Cancers Symposium.[66]

Drugs Targeting Prostate-specific Membrane Antigen (PSMA). PSMA, a highly specific antigen of prostate epithelial cell membrane, is eventually overexpressed in all prostate cancers.[67] The mAb J591 features high affinity binding to the PSMA. Two Phase I studies defined the maximum tolerated dose and showed preliminary evidence of antineoplastic activity.[68]

Current, New and Novel Therapy for Castration-Resistant Prostate Cancer part 6

Novel Targets & Trials

Several agents attenuating new biological targets are in clinical trials. Each drug targets different pathways, with effects ranging from immune modulation, cytotoxicity, hormonal manipulation and bone turnover.

Drugs With Antiangiogenic Activity

Angiogenesis is the most important target of the novel treatment, measures of microvessel density and VEGF levels correlate with metastatic disease, Gleason grade and clinical outcome.[6] However, antiangiogenic agents have yet to prove an OS benefit for men with prostate cancer.
VEGF Receptor Inhibitors. Recently, bevacizumab and sunitinib both showed improvements in PFS, but not OS.[53,54]Sunitinib is a multitargeted tyrosine kinase inhibitor with known selectivity for VEGF receptors (VEGFR). In a Phase II trial of men with CRPC who had progressed after chemotherapy, 12.1% of the patients had more than 50% decline in PSA, with 11% showing a 30% decline in measurable disease by RECIST criteria.[55]
Aflibercept is a VEGF-Trap fusion protein that has both the VEGFR-1 and VEGFR-2 domains fused to the Fc domain of IgG1. The Phase III VENICE trial randomized 1200 patients to either docetaxel, prednisone and aflibercept or docetaxel and prednisone with results expected in 2013 ( identifier: NCT00532155).[101]
Cabozantinib is a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2, and has been shown to reduce tumor growth, metastasis and angiogenesis. Cabozantinib was approved by the FDA in November 2012 for the treatment of medullary thyroid cancer. A Phase II trial of cabozantinib (XL184) in patients with CRPC metastatic to bone ( identifier: NCT01428219) enrolled 171 patients who were randomly assigned to cabozantinib or placebo. Cabozantinib showed clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans and reductions in bone turnover markers, pain and narcotic use.[56]
Finally, tasquinimod is a quinoline-3-carboxamide derivative that has antiangiogenic effects and direct antitumor activity. PFS was prolonged in a Phase II randomized trial, leading to a 2:1 Phase III randomized trial for patients with asymptomatic or minimally symptomatic metastatic CRPC with radiographic PFS as the primary end point.[57]
Endothelin-receptor Antagonists. Endothelins are involved in proliferation, vasomotor tone and angiogenesis. The interactions between endothelins and their receptors (endothelin-A and endothelin-B) have been shown to be implicated in tumor growth, proliferation, apoptosis, angiogenesis and bone metastasis. Elevated levels of endothelins are found in patients with CRPC.[58] Atrasentan, an endothelin-A receptor antagonist, was evaluated in a Phase III trial showing that atrasentan did not reduce the risk of disease progression, but was associated with lower bone alkaline phosphatase and PSA levels.[59]
Zibotentan (ZD4054) is a highly selective endothelin-A receptor antagonist. A Phase II study of ZD4054 compared with placebo in 312 patients showed an OS benefit of 6 months.[60] However, three Phase III studies with this drug have not shown any survival benefit in an initial report.

Drugs With Antiapoptotic Activity (Bcl-2 Inhibitors)

Cytoplasmic clusterin is associated with antiapoptotic functions through mechanisms which include inhibition of the proapoptotic Bcl-2. Forced overexpression of clusterin in cancer models confers resistance to radiation, hormone and chemotherapy whereas inhibition enhances apoptotic death of tumor cells.[57]

Custirsen is a novel intravenously administered antisense oligonucleotide that inhibits clusterin at the mRNA level, increasing sensitivity to androgen deprivation as well as chemotherapy in prostate cancer cell lines and xenograft models. In a randomized Phase II study (OGX-011) of docetaxel+prednisone with or without custirsen in 82 patients with metastatic CRPC, PSA responses (58 vs 54%) and PFS (7.3 vs 6.1 months) were similar in both arms. However, OS trended in favor of the combination arm (23.8 vs 16.9 months; p = 0.06).[62] A randomized, open-label, two-arm (custirsen vs cabazitaxel) Phase III study in 630 patients with CRPC who have documented disease progression after prior first-line docetaxel treatment was recently launched, with OS being the primary end point.

Current, New and Novel Therapy for Castration-Resistant Prostate Cancer part 5


PROSTVAC is a therapeutic cancer vaccine, comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1 and LFA-3). In a Phase II controlled-randomized trial, 82 patients received PROSTVAC-VF and 40 received control vectors. The primary end point was PFS, which was similar in the two groups (p = 0.6). However, at 3 years poststudy, PROSTVAC-VF patients had a better OS with 25 (30%) out of 82 patients alive versus seven (17%) out of 40 controls, longer median survival by 8.5 months (25.1 vs 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI: 0.37–0.85) and stratified log-rank p = 0.006.[52] These provocative data provide preliminary evidence of clinically meaningful benefit to undergo PROSTVAC Phase III clinical trials. The PROSPECT study is currently recruting patients ( identifier: NCT01322490). The purpose of this study is to determine whether PROSTVAC alone or in combination with granulocyte–macrophage colony-stimulating factor is effective in prolonging overall survival in men with few or no symptoms from mCrPC.

Current, New and Novel Therapy for Castration-Resistant Prostate Cancer part 4


Ipilimumab is a human monoclonal antibody that blocks CTLA-4, which inhibits the interaction between the T-cell receptor CD28 and B7 costimulatory molecules on APCs that leads to activation of T cells.[51]An ongoing randomized multicenter Phase III study is comparing ipilimumab with placebo in asymptomatic or minimally symptomatic patients with metastatic, chemotherapy-naive CRPC ( identifier: NCT01057810).[101] A similarly designed Phase III trial is comparing ipilimumab with placebo in postdocetaxel setting after radiation. Results from both studies are still forthcoming, but this drug has previously showed good activity in terms of PSA decline, as well as radiological response ( identifier: NCT00861614).[101]

Current, New and Novel Therapy for Castration-Resistant Prostate Cancer part 3

Radioisotope Radium-223 (RA-223)

Radium-223 RA-223; Alpharadin is an α-emitting radiopharmaceutical that delivers high energy, short range irradiation that induces dsDNA breaks with lower penetration to surrounding tissues compared with the β-emitting (strontium-89 and samarium-153). In the study (ALSYMPCA), a Phase III trial tested radium in symptomatic patients who had previously received docetaxel or were otherwise unsuitable to receive chemotherapy. Patients were randomized 2:1 in favor of RA-223. The study treatment consisted of up to six intravenous administrations of RA-223 or placebo, each separated by an interval of 4 weeks. The primary end point of the study was overall survival. Secondary end points included time to occurrence of SREs and changes and time to progression in key bone markers associated with disease status (including serum levels of PSA and total alkaline phosphatase. At an updated analysis presented at the 2012 ASCO annual meeting the median OS benefit for RA-223 increased from 2.8 to 3.6 months, with a hazard ratio of 0.695 (i.e., 30.5% reduction in risk of death). RA-223 is an effective therapy that improves OS and time to first SRE with a highly favorable safety profile, and may provide a new standard of care for CRPC patients with bone metastasis.[50]

Current, New and Novel Therapy for Castration-Resistant Prostate Cancer part 2

New Emerging Treatments

Despite these advances, the median survival in the first-line setting of mCRPC is approximately 20 months, and in the postdocetaxel setting is about 15 months. The modest benefits conferred to these recently approved agents, means new tolerable drugs are necessary to make future gains. Promising new therapies include hormonal agents, as well as other immunotherapeutics and antiprostate-specific membrane antigen therapies are in advanced stages of clinical development.
Some of these trials incorporating molecular analyses are ongoing better understand tumor biology, and to identify and evaluate new biomarkers. Nowadays, OS is the only accepted end point for regulatory purposes in Phase III trials. To compensate, several ongoing Phase III trials have incorporated biomarkers as circulating tumor cells (CTCs) into their trial design in order to prospectively evaluate CTCs as surrogate of response and survival. Isolation of CTCs based on epithelial surface markers and quantification using the Cell Search platform was cleared through the FDA in 2008. This was based in a study which demonstrated that patients with a CTC count >5 detected in 7.5 ml blood had a significantly lower OS compared to patients with CTC <5.
There are concerns that ongoing Phase III trials may be contaminated if patients go off study treatment to start one of the newly approved agents or take the agent subsequently. These realities make clinical trial design more challenging than ever. We have summarized the most promising and encouraging new drugs in Phase III studies below.

TAK-700 (Orteronel)

TAK-700 is a reversible CYP17 inhibitor with preferential inhibition of 17,20-lyase over 17-hydroxylase activity. This selective inhibition may in theory reduce the need for corticosteroid supplementation. However, early data suggest that TAK-700 has similar response profiles as abiraterone and steroid support is needed to avoid tocixicity.[49] The most common adverse events were fatigue, nausea and constipation. Two randomized Phase III studies of TAK-700 and prednisone versus placebo and prednisone are underway that include patients with chemotherapy-naive and docetaxel-refractory mCRPC, respectively ( identifiers: NCT01193244 and NCT01193257).[101] However, to date, we have no data from either of these Phase III trials by which to judge its efficacy. Recently, the Southwest Oncology Group has initiated a new, randomized, double-blind, multicenter, Phase III trial designed to compare androgen deprivation therapy (ADT) + bicalutamide (Casodex) to ADT + the investigational drug TAK-700 in men newly diagnosed with metastatic, hormone-sensitive prostate cancer ( identifier: NCT01809691).[101]

Current, New and Novel Therapy for Castration-Resistant Prostate Cancer part 1

Key Issues

  • Although hormonal therapy is highly effective for the control of cancer-related symptoms, all men who live long enough will eventually experience disease progression and develop castration-resistant prostate cancer (CRPC).
  • CRPC remains an extremely heterogeneous disease with few surrogate end points other than overall survival upon which drug development has been based.
  • Androgen signaling continues to play a critical role in prostate cancer progression following castration.
  • Advances in the understanding of the molecular mechanisms underlying CRPC has translated into a variety of treatment approaches.
  • The number of treatment options for men with metastatic CRPC has increased over the last 2 years with US FDA approval of sipuleucel-T, cabazitaxel, abiraterone and MD-3100.
  • New agents as TAK-700 and ipilimumab with early promising results are in advanced clinical trials and have the potential to provide novel treatments options for CRPC in the near future.
  • Denosumab was approved by FDA in July 2011 for patients with bone metastases from solid tumors after demonstrating its superiority against zoledronic acid to prevent skeletal-related events.
  • Standardization of clinical parameters (quality-of-life changes, pain responses), new imaging test (functional imaging) and finding of biomarkers are necessary to compare and evaluate response to the different drugs.
  • New data supporting the role of novel molecular targets is promoting new clinical trials with new drugs.

Definition of castration-resistant prostate cancer

Definition of castration-resistant prostate cancer.
  • Castrate serum levels of testosterone (testosterone <50 ng/dl or <1.7 nmol/l).
  • Three consecutive rises of prostate-specific antigen (PSA), 1 week apart, resulting in 2.5% increases over the nadir, with a PSA >2.
  • PSA progression either antiandrogen withdrawal for at least 4 weeks for flutamide and 6 weeks for bicalutamide or secondary hormonal manipulation.
  • Progression or appearance of two or more lesions on bone scan or soft tissue lesions using Response Evaluation Criteria in Solid Tumors (RECIST) and with nodes >2 cm in diameter.
  • RECIST criteria are inadequate for measuring response in PCa, while bone scans, in particular, are suboptimal in distinguishing response to therapy and tumor progression. For this reason, The Prostate Cancer Clinical Trials Working Group has defined radiological progression as the development of two or more lesions on bone scan compared with prior scan and requires additional confirmation on a subsequent scan [17].

Tuesday, September 10, 2013

Men With STD during Increased Risk of Prostate Cancer: Study

A Clever Organisation Between A Common Intimately Transmitted Infection, Trichomonas Vaginalis, And Risk Of Modernized And Fatal Prostate Cancer In Group Has Been Found By Researchers From Harvard School Of Public Health (HSPH) And Brigham And Women’s Hospital.
The Investigate Appears Online On Sep 9, 2009, On A Journal Of A National Cancer Institute Website And Will Seem In A After Imitation Edition.
“Prostate Cancer Is A Many Common Cancer Among Group In Western Countries, And A Second Heading Means Of Cancer-Specific Mortality. Identifying Modifiable Risk Factors For A Fatal Form Of Prostate Cancer Offers A Biggest Event To Revoke Pang From This Disease,” Pronounced Jennifer Stark, An HSPH Researcher And Lead Author Of A Study.
One Intensity Risk Cause Is Inflammation, That Appears To Play An Critical Purpose In A Growth And Course Of Prostate Cancer, Though A Source Of Inflammation Of A Prostate Is Not Clear.
Trichomonas Vaginalis Is A Many Common Non-Viral Intimately Transmitted Infection, And Can Taint A Prostate And Could Be A Source Of Inflammation.
In A Study, Researchers Analyzed Blood Samples From 673 Group With Prostate Cancer Who Were Participants In A Physicians’ Health Study And Compared Infection Standing Formed On Antibody Levels To 673 Control Subjects Who Were Not Diagnosed With Prostate Cancer. The Blood Samples Were Collected In 1982, On Normal A Decade Before Cancer Diagnosis.

The Formula Showed That Trichomonas Vaginalis Infection Was Compared With A Some-More Than Two-Fold Boost In A Risk Of Prostate Cancer That Was Modernized Theatre During Diagnosis, And A Scarcely Three-Fold Boost In Prostate Cancer That Would Outcome In Death.

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