Outcomes of Autologous Fascia Pubovaginal Sling for Patients with Transvaginal Mesh Related Complications Requiring Mesh Removal.

PURPOSE: We reviewed the outcomes of the autologous fascial pubovaginal sling as a salvage procedure for recurrent stress incontinence after intervention for polypropylene mesh erosion/exposure and/or bladder outlet obstruction in patients treated with prior transvaginal synthetic mesh for stress urinary incontinence. MATERIALS AND METHODS: In a review of surgical databases at 2 institutions between January 2007 and June 2013 we identified 46 patients who underwent autologous fascial pubovaginal sling following removal of transvaginal synthetic mesh in simultaneous or staged fashion. This cohort of patients was evaluated for outcomes, including subjective and objective success, change in quality of life and complications between those who underwent staged vs concomitant synthetic mesh removal with autologous fascial pubovaginal sling placement. RESULTS: All 46 patients had received at least 1 prior mesh sling for incontinence and 8 (17%) had received prior transvaginal polypropylene mesh for pelvic organ prolapse repair. A total of 30 patients underwent concomitant mesh incision with or without partial excision and autologous sling placement while 16 underwent staged autologous sling placement. Mean followup was 16 months. Of the patients 22% required a mean of 1.8 subsequent interventions an average of 6.5 months after autologous sling placement with no difference in median quality of life at final followup. At last followup 42 of 46 patients (91%) and 35 of 46 (76%) had achieved objective and subjective success, respectively. There was no difference in subjective success between patients treated with a staged vs a concomitant approach (69% vs 80%, p = 0.48). CONCLUSIONS: Autologous fascial pubovaginal sling placement after synthetic mesh removal can be performed successfully in patients with stress urinary incontinence as a single or staged procedure.

Patient perception of transvaginal mesh and the media.

OBJECTIVE: To assess the penetration of media-based information on transvaginal mesh (TVM) in our patient population and to determine whether exposure affects patient opinion. Since the 2011 Federal Drug Administration communication on TVM, many advertisements from legal practices have been directed toward patients. MATERIALS AND METHODS: An 18-item survey was administered to female patients at 2 sites from August 2012 to April 2013. Patients presenting with new diagnoses of pelvic organ prolapse or stress urinary incontinence or patients who reported prior mesh surgery were excluded. RESULTS: Ninety-nine questionnaires were completed. Sixty-six of the patients (67%) were aware of TVM; and of these, 38 (58%) cited advertisements as the initial source of information. Only 12% were aware of the Food and Drug Administration's communication. Regarding opinion of TVM, 9% chose "it is a safe product," 9% "safety depends on factors related to patient," 4.5% "not a safe product," 1.5% "safety depends on the doctor," 68% "I don't know," and 4.5% marked 2 selections. Only 12% indicated knowing the difference in the use of TVM for pelvic organ prolapse vs stress urinary incontinence. When asked what influenced their opinion of TVM the most; responses were as follows: advertisement (33.3%), medical professional (22.7%), friends or family who underwent TVM procedure (12.1%), media article (6.1%), and "not sure" (25.8%). CONCLUSION: Advertisements of TVM lawsuits had a high penetration into our patient population but did not produce an overtly negative response in our sample. Clinicians should be aware of the impact of these advertisements on patient opinion and counsel patients accordingly with unbiased and scientifically accurate information.

Emerging biomarkers of prostate cancer (Review).

Prostate cancer progression involves activation of signaling pathways controlling cell proliferation, apoptosis, anoikis, angiogenesis and metastasis. The current PSA-based test for the diagnosis of prostate cancer lacks sensitivity and specificity, resulting in missed diagnoses and unnecessary biopsies. Intense research efforts to identify serum and tissue biomarkers will expand the opportunities to understand the functional activation of cancer-related pathways and consequently lead to molecular therapeutic targeting towards inhibition of tumor growth. Current literature describes multiple biomarkers that indicate the properties of prostate cancer including its presence, stage, metastatic potential and prognosis. Used singly, assays detecting these biomarkers have their respective shortcomings. Several recent studies evaluating the clinical utilization of multiple markers show promising results in improving prostate cancer profiling. This review discusses the current understanding of biomarker signature cluster-based approaches for the diagnosis and therapeutic response of prostate cancer derived from panels of biomarker tests that provide a selective molecular signature characteristic of the tumor. As these signatures are robustly defined and their pathways are exhaustively dissected, prostate cancer can be more accurately diagnosed, characterized, staged and targeted with inhibitory antitumor agents. The growing promise surrounding the recent evidence in identifying and utilizing such biomarker panels, will lead to improvement in cancer prognosis and management of the therapeutic response of prostate cancer patients.

Apoptosis induction by doxazosin and other quinazoline alpha1-adrenoceptor antagonists: a new mechanism for cancer treatment?

Doxazosin and related, quinazoline-based alpha(1)-adrenoceptor antagonists can induce apoptosis in prostate and various other normal, benign, smooth muscle, endothelial and malignant cells. Such apoptosis-inducing effects occur independently of alpha(1)-adrenoceptor antagonism and typically require much high concentrations than those required for receptor occupancy. Several studies have invested efforts towards the elucidation of the molecular mechanisms underlying doxazosin-induced apoptosis. These include various tumor cells, cardiomyocytes, endothelial cells and bladder smooth muscle cells. While the high concentrations of doxazosin required to induce apoptosis challenge the use of this and related drugs for clinical optimization of apoptosis induction, such quinazoline structure may represent chemical starting points to develop more potent apoptosis-inducing agents free of alpha(1)-adrenoceptor antagonistic action and suitable for cancer treatment with minimal and well-tolerated side effects.

Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical-site infection, pneumonia, and sepsis in general surgery patients.

BACKGROUND: Transfusion of packed red blood cells (PRBCs) increases morbidity and mortality in select surgical specialty patients. The impact of low-volume, leukoreduced RBC transfusion on general surgery patients is less well understood. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Program participant use file was queried for general surgery patients recorded in 2005 to 2006 (n = 125,223). Thirty-day morbidity (21 uniformly defined complications) and mortality, demographic, preoperative, and intraoperative risk variables were obtained. Infectious complications and composite morbidity and mortality were stratified across intraoperative PRBCs units received. Multivariable logistic regression was used to assess influence of transfusion on outcomes, while adjusting for transfusion propensity, procedure type, wound class, operative duration, and 30+ patient risk factors. RESULTS: After adjustment for transfusion propensity, procedure group, wound class, operative duration, and all other important risk variables, 1 U PRBCs significantly (p < 0.05) increased risk of 30-day mortality (odds ratio [OR] = 1.32), composite morbidity (OR = 1.23), pneumonia (OR = 1.24), and sepsis/shock (OR = 1.29). Transfusion of 2 U additionally increased risk for these outcomes (OR = 1.38, 1.40, 1.25, 1.53, respectively; p