Transperitoneal Robotic-Assisted Laparoscopic Prostatectomy After Prosthetic Mesh Herniorrhaphy

BACKGROUND AND OBJECTIVES: We report our institutional experience performing transperitoneal robotic-assisted laparoscopic prostatectomy (RALP) in patients with prior prosthetic mesh herniorrhaphy to assess the feasibility of this procedure in this patient population. METHODS: From October 2005 to January 2008, transperitoneal robotic-assisted laparoscopic prostatectomies were performed and prospectively recorded. We retrospectively reviewed 309 patients. RESULTS: Twenty-seven patients (8.7%) were found to have a history of prior hernia repair with prosthetic mesh placement. The mean age was 55.7, estimated blood loss (EBL) was 228 mL, operative (console) time was 197 minutes, and length of hospital stay (LOS) was 1.62 days. In contrast, patients undergoing RALP with no history of mesh herniorrhaphy had a mean age of 59.3, EBL of 302 mL, console time of 193 minutes, and LOS of 2.2 days. These differences were not statistically significant. The mesh herniorrhaphy cohort had a lower percentage of organ-confined disease, but no difference was seen in margin status, continence, or potency rates after one year. CONCLUSIONS: Transperitoneal RALP is a feasible option for previously operated on patients with prosthetic mesh herniorrhaphy. Two areas that we identified as critical were the initial step of gaining access for pneumoperitoneum and port placement, and meticulous dissection to expose the mesh, which can be subsequently avoided and left intact. As RALP continues to gain popularity, urologists will continue to exploit the advantages of robotic surgery to perform increasingly challenging cases

Costs of Early Adjuvant Radiation Therapy After Radical Prostatectomy: A Decision Analysis

Purpose/Objective(s): Prospective, randomized trials support adjuvant radiation therapy (RT) for adverse pathologic features after radical prostatectomy (RP). However, adjuvant RT is not universally delivered in this setting. Criticisms of adjuvant RT include toxicity, financial costs, potential overtreatment, and effectiveness of salvage RT. The objective of this study was to construct a decision analytic model to estimate real world cost of RT vs. no RT within the context of the effectiveness of early adjuvant RT for prostate patients based on published clinical results of the Southwest Oncology Group prospective trial of adjuvant RT (SWOG 8794). American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy

Preventing Prostate Biopsy Complications: to Augment or to Swab?

Aims for Improvement The aim of this study was to determine the antibiotic prophylaxis associated with the fewest infectious complications following prostate biopsy Determining the safest method allows the Jefferson Department of Urology to modify its biopsy protocol and improve the rate of post-biopsy complication

Awareness of prostate cancer among patients and the general public: results of an international survey

The objective of this study was to assess the level of awareness of prostate cancer (PCa) among the general public and PCa patients in Europe and North America. A survey was undertaken across four European countries (UK, Germany, Italy and Spain), and across the United States and Canada in late 2007. In total, 1008 men with PCa and their partners (the ‘prostate sample'), and 911 men without PCa and their partners (the ‘well sample') participated in the survey, all aged ⩾50 years. Interviews were conducted through telephone, pen and paper, and online. Many people surveyed (53%) thought that breast cancer is more common than PCa. Moreover, 1 in 10 people from the well sample (10%) thought that PCa affects both men and women. When the prostate sample was asked about their perceived level of risk of PCa before diagnosis, 50% believed that they/their husband or partner were previously at low or very low risk, before they were diagnosed. Awareness of the major risk factors for PCa (age and family history) was generally good, but respondents were less clear about the role of other potential factors, such as smoking and drinking alcohol. This international survey, thought to be largest of its type, shows that although patient and public awareness of PCa is generally satisfactory, there is still a considerable lack of clarity about PCa risk factors, and a danger for people to underestimate their own/their partner's perceived risk for PCa. Programmes to responsibly educate and inform men and their partners about risk factors, prevalence and screening tools for PCa are required

DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis.

Emerging evidence demonstrates that the DNA repair kinase DNA-PKcs exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PKcs functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PKcs inhibits tumor metastases. Clinical assessment revealed that DNA-PKcs is significantly elevated in advanced disease and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PKcs in advanced tumors is highly activated, independent of DNA damage indicators. Combined, these findings reveal unexpected DNA-PKcs functions, identify DNA-PKcs as a potent driver of tumor progression and metastases, and nominate DNA-PKcs as a therapeutic target for advanced malignancies

Collecting duct carcinoma of the kidney: an immunohistochemical study of 11 cases

BACKGROUND: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes involved in the development of renal cancer (FEZ1/LZTS1, FHIT, TP53, P27(kip1), and BCL2). METHODS: We studied eleven patients who underwent radical nephrectomy for primary CDC. All patients had an adequate clinical follow-up and none of them received any systemic therapy before surgery. The expression of the five markers for tumor initiation and/or progression were assessed by immunohistochemistry and correlated to the clinicopathological parameters, and survival by univariate analysis. RESULTS: Results showed that Fez1 protein expression was undetectable or substantially reduced in 7 of the 11 (64%) cases. Fhit protein was absent in three cases (27%). The overexpression of p53 protein was predominantly nuclear and detected in 4 of 11 cases (36%). Immunostaining for p27 was absent in 5 of 11 cases (45.5%). Five of the six remaining cases (90%) showed exclusively cytoplasmic protein expression, where, in the last case, p27 protein was detected in both nucleus and cytoplasm. Bcl2 expression with 100% of the tumor cells positive was observed in 4 of 11 (36%) cases. Statistical analysis showed a statistical trend (P = 0.06) between loss and reduction of Fez1 and presence of lymph node metastases. CONCLUSIONS: These findings suggest that Fez1 may represent not only a molecular diagnostic marker but also a prognostic marker in CDC

Local therapy of cancer with free IL-2

This is a position paper about the therapeutic effects of locally applied free IL-2 in the treatment of cancer. Local therapy: IL-2 therapy of cancer was originally introduced as a systemic therapy. This therapy led to about 20% objective responses. Systemic therapy however was very toxic due to the vascular leakage syndrome. Nevertheless, this treatment was a break-through in cancer immunotherapy and stimulated some interesting questions: Supposing that the mechanism of IL-2 treatment is both proliferation and tumoricidal activity of the tumor infiltrating cells, then locally applied IL-2 should result in a much higher local IL-2 concentration than systemic IL-2 application. Consequently a greater beneficial effect could be expected after local IL-2 application (peritumoral = juxtatumoral, intratumoral, intra-arterial, intracavitary, or intratracheal = inhalation). Free IL-2: Many groups have tried to prepare a more effective IL-2 formulation than free IL-2. Examples are slow release systems, insertion of the IL-2 gene into a tumor cell causing prolonged IL-2 release. However, logistically free IL-2 is much easier to apply; hence we concentrated in this review and in most of our experiments on the use of free IL-2. Local therapy with free IL-2 may be effective against transplanted tumors in experimental animals, and against various spontaneous carcinomas, sarcomas, and melanoma in veterinary and human cancer patients. It may induce rejection of very large, metastasized tumor loads, for instance advanced clinical tumors. The effects of even a single IL-2 application may be impressive. Not each tumor or tumor type is sensitive to local IL-2 application. For instance transplanted EL4 lymphoma or TLX9 lymphoma were not sensitive in our hands. Also the extent of sensitivity differs: In Bovine Ocular Squamous Cell Carcinoma (BOSCC) often a complete regression is obtained, whereas with the Bovine Vulval Papilloma and Carcinoma Complex (BVPCC) mainly stable disease is attained. Analysis of the results of local IL-2 therapy in 288 cases of cancer in human patients shows that there were 27% Complete Regressions (CR), 23% Partial Regressions (PR), 18% Stable Disease (SD), and 32% Progressive Disease (PD). In all tumors analyzed, local IL-2 therapy was more effective than systemic IL-2 treatment. Intratumoral IL-2 applications are more effective than peritumoral application or application at a distant site. Tumor regression induced by intratumoral IL-2 application may be a fast process (requiring about a week) in the case of a highly vascular tumor since IL-2 induces vascular leakage/edema and consequently massive tumor necrosis. The latter then stimulates an immune response. In less vascular tumors or less vascular tumor sites, regression may require 9–20 months; this regression is mainly caused by a cytotoxic leukocyte reaction. Hence the disadvantageous vascular leakage syndrome complicating systemic treatment is however advantageous in local treatment, since local edema may initiate tumor necrosis. Thus the therapeutic effect of local IL-2 treatment is not primarily based on tumor immunity, but tumor immunity seems to be useful as a secondary component of the IL-2 induced local processes. If local IL-2 is combined with surgery, radiotherapy or local chemotherapy the therapeutic effect is usually greater than with either therapy alone. Hence local free IL-2 application can be recommended as an addition to standard treatment protocols. Local treatment with free IL-2 is straightforward and can readily be applied even during surgical interventions. Local IL-2 treatment is usually without serious side effects and besides minor complaints it is generally well supported. Only small quantities of IL-2 are required. Hence the therapy is relatively cheap. A single IL-2 application of 4.5 million U IL-2 costs about 70 Euros. Thus combined local treatment may offer an alternative in those circumstances when more expensive forms of treatment are not available, for instance in resource poor countries

A patient-derived explant (PDE) model of hormone-dependent cancer.

Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.Cancer Research UK and ERC