Lars Lund

Can low-intensity extracorporeal shockwave therapy improve erectile dysfunction? A prospective, randomized, double-blind, placebo-controlled study

Abstract Objective. The aim of this study was to investigate whether low-intensity extracorporeal shockwave therapy (LI-ESWT) can be used as a treatment for men with erectile dysfunction of organic origin. Materials and methods. This prospective, randomized, blinded, placebo-controlled study included 112 men unable to have intercourse either with or without medication. Erectile dysfunction was assessed at screening and 5, 12 and 24 weeks after treatment. Assessment was performed by interview and using the Erection Hardness Scale (EHS) and the International Index of Erectile Function (IIEF-15) questionnaire. The men were randomly assigned either to LI-ESWT (n = 51, active group) or placebo (n = 54, placebo group). They received five treatments over 5 weeks. Both the participants and the doctors were blinded to the treatment. After 10 weeks, the placebo group received active treatment (active placebo group). Results. Twenty-nine men (57%, active group) were able to obtain an erection after treatment and to have sexual intercourse without the use of medication. In the placebo group, only five men (9%) showed similar results (p = 0.0001). The EHS after 5 weeks showed that men in the active group experienced a significant improvement in their erectile dysfunction, but no significant result was found with the use of the IIEF – Erectile Function domain. Conclusions. This placebo-controlled study over 5 weeks shows that 57% of the men who suffered from erectile dysfunction had an effect from LI-ESWT. After 24 weeks, seven (19%, active group) and nine (23%, active placebo group) men were still able to have intercourse without medication. This study shows a possible cure in some patients, but more research, longer follow-up in the placebo group and an international multicentre randomized study are needed.

Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial

Background Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction. Methods Seventeen men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5–18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed for the presence of stem cell surface markers, viability and ability to differentiate. Primary endpoint was the safety and tolerance of the cell therapy while the secondary outcome was improvement of erectile function. Any adverse events were reported and erectile function was assessed by IIEF-5 scores. The study is registered with ClinicalTrials.gov, NCT02240823. Findings Intracavernous injection of ADRCs was well-tolerated and only minor events related to the liposuction and cell injections were reported at the one-month evaluation, but none at later time points. Overall during the study period, 8 of 17 men recovered their erectile function and were able to accomplish sexual intercourse. Post-hoc stratification according to urinary continence status was performed. Accordingly, for continent men (median IIEFinclusion = 7 (95% CI 5–12), 8 out of 11 men recovered erectile function (IIEF6months = 17 (6–23)), corresponding to a mean difference of 0.57 (0.38–0.85; p = 0.0069), versus inclusion. In contrast, incontinent men did not regain erectile function (median IIEF1/3/6 months = 5 (95% CI 5–6); mean difference 1 (95% CI 0.85–1.18), p > 0.9999). Interpretation In this phase I trial a single intracavernosal injection of freshly isolated autologous ADRCs was a safe procedure. A potential efficacy is suggested by a significant improvement in IIEF-5 scores and erectile function. We suggest that ADRCs represent a promising interventional therapy of ED following prostatectomy. Funding Danish Medical Research Council, Odense University Hospital and the Danish Cancer Society.

Bone Scan Index predicts outcome in patients with metastatic hormone-sensitive prostate cancer.

To evaluate the Bone Scan Index (BSI) for prediction of castration resistance and prostate cancer‐specific survival (PCSS). In this retrospective study, we used novel computer‐assisted software for automated detection/quantification of bone metastases by BSI. Patients with prostate cancer are M‐staged by whole‐body bone scintigraphy (WBS) and categorised as M0 or M1. Within the M1 group, there is a wide range of clinical outcomes. The BSI was introduced a decade ago providing quantification of bone metastases by estimating the percentage of bone involvement. Being too time consuming, it never gained widespread clinical use.

Trends in cancer in the elderly population in Denmark, 1980-2012.

Abstract Background Age is the strongest risk factor for developing cancer. The aim of the present analysis is to give an overview of the trends in cancer incidence, mortality, prevalence, and relative survival in Denmark from 1980 to 2012 focusing on age, comparing persons aged 70 years or more with those aged less than 70 years. Material and methods Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries. The Danish data originate from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. Results Incidence and mortality rates of all sites, but non-melanoma skin cancer, were higher and relative survival was lower among persons aged 70 years or more than those aged less than 70 years. The age distribution (age group-specific percentages of total number of incident cases) remained constant over time while the percentage of persons dying from cancer decreased with time up to the age of 79 years but increased for those aged 80 years or more, in whom about a third of all cancer deaths occurred in 2012. In 2003–2007, the five-year relative survival was 48% for men aged 70–79 years, 38% for men aged 80–89 years, and 29% for men aged 90 years or more and the corresponding figures for women were 46%, 39%, and 36%, respectively. There was a substantial increase in the number of prevalent cancer cases aged 70 years or older, especially among those aged 90 years or more. Conclusion An increase in elderly cancer patients is expected over the coming 20 years due to an increasing elderly population. Healthcare providers need to focus on developing specific strategies for treatment of elderly cancer patients in the future.

Prostate cancer: a review of active surveillance

The objective of this paper is to review the current recommendations for active surveillance in prostate cancer from the present prospective studies. Worldwide, there are increasing numbers of men with prostate cancer. It is now accepted as standard care that a number of men with favorable-risk disease can be followed with active surveillance. In 1995, the first prospective studies were initiated to assess the feasibility of active surveillance, in which the decision to intervene was determined by prostate-specific antigen and/or histological progression. The strategy was to provide therapy individualized to the biological behavior of the cancer. Clinical trials assessing active surveillance have usually included patients younger than 70 years of age, although the guidelines have changed over time for Gleason score and prostate-specific antigen, eg, doubling time, thereby changing the indication for active treatment. The present review focuses on patient selection, prospective studies reported in the literature, and future directions.

The Long-Term Efficacy of Hydrocele Treatment with Aspiration and Sclerotherapy with Polidocanol Compared to Placebo: a Prospective, Double-Blind, Randomized Study

PURPOSE We evaluate whether aspiration and sclerosing of hydrocele testis is an effective treatment. MATERIALS AND METHODS Men with symptomatic hydrocele testis were included in this prospective, double-blind, randomized study with polidocanol and placebo. Patients were randomized to active treatment or placebo at the first treatment. Depending on hydrocele testis size (less than 100, 100 to 200 and greater than 200 ml), the patients were treated with 1, 3 or 4 ml polidocanol after aspiration. Patients with recurrence at the 5-week followup received active treatment. RESULTS A total of 77 patients were included in the study. In group 1 (active treatment) there were 36 patients with a median age of 63 years (range 34 to 92). In group 2, comprised of 41 patients, the median age was 59 years (range 26 to 82). Median followup was 72 months. A significant difference between the groups was observed after the first and second treatments. Recurrence after the first treatment was seen in 16 (44%) patients from group 1 and in 32 (78%) from group 2 (p <0.05). Recurrence after re-treatment with the active drug in both groups was seen in 4 (25%) patients in group 1 and in 14 (44%) in the former placebo group (p <0.05). The overall success rate of treatment in the active group was 89%. There was no difference between the 2 groups in terms of volume of fluid aspirated, symptoms or complications. CONCLUSIONS This long-term efficacy randomized study with placebo showed that polidocanol is effective for the treatment of hydrocele testis with a low recurrence rate.

Small renal masses in the era of personalized medicine: Tumor heterogeneity, growth kinetics, and risk of metastasis

Small renal masses (SRMs) represent a heterogeneous group showing a variety of clinical and biological behaviors. The best treatment for SRMs has been the focus of much debate over the past decades. Present strategies include surgery (partial or radical nephrectomy), local treatments (radiofrequency and cryoablation), or active surveillance. The choice among these therapeutic options is based on patient clinical features such as age or comorbidities rather than on tumor characteristics. Several studies have recently focused on the molecular behavior of SRMs. They showed that SRMs present histotype and nuclear grading heterogeneity, together with not unvarying growth kinetics and risk of recurrence or metastasis, suggesting that personalized approaches should be designed to optimize the management of these patients. At present, several studies are in course to identify predictive biomarkers to guide the decision-making process in this subpopulation. In this review, we summarized the data on growth kinetics, tumor heterogeneity, and risk of metastasis in patients with SRMs, with focus on the current role of biopsies and imaging in the management of these patients.

Predicting Prostate Biopsy Results Using a Panel of Plasma and Urine Biomarkers Combined in a Scoring System.

Background: Determining the need for prostate biopsy is frequently difficult and more objective criteria are needed to predict the presence of high grade prostate cancer (PCa). To reduce the rate of unnecessary biopsies, we explored the potential of using biomarkers in urine and plasma to develop a scoring system to predict prostate biopsy results and the presence of high grade PCa. Methods: Urine and plasma specimens were collected from 319 patients recommended for prostate biopsies. We measured the gene expression levels of UAP1, PDLIM5, IMPDH2, HSPD1, PCA3, PSA, TMPRSS2, ERG, GAPDH, B2M, AR, and PTEN in plasma and urine. Patient age, serum prostate-specific antigen (sPSA) level, and biomarkers data were used to develop two independent algorithms, one for predicting the presence of PCa and the other for predicting high-grade PCa (Gleason score [GS] ≥7). Results: Using training and validation data sets, a model for predicting the outcome of PCa biopsy was developed with an area under receiver operating characteristic curve (AUROC) of 0.87. The positive and negative predictive values (PPV and NPV) were 87% and 63%, respectively. We then developed a second algorithm to identify patients with high-grade PCa (GS ≥7). This algorithms AUROC was 0.80, and had a PPV and NPV of 56% and 77%, respectively. Patients who demonstrated concordant results using both algorithms showed a sensitivity of 84% and specificity of 93% for predicting high-grade aggressive PCa. Thus, the use of both algorithms resulted in a PPV of 90% and NPV of 89% for predicting high-grade PCa with toleration of some low-grade PCa (GS <7) being detected. Conclusions: This model of a biomarker panel with algorithmic interpretation can be used as a “liquid biopsy” to reduce the need for unnecessary tissue biopsies, and help to guide appropriate treatment decisions.

Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model.

Background A large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. Methods 10 pigs (group A) underwent infrarenal aortic dissection, balloon dilatation, infusion of elastase into the lumen and placement of a stenosing cuff around the aorta. 10 control pigs (group B) underwent a sham procedure. The subsequent 28 days the AP-diameters of the aneurysms were measured using ultrasound, hereafter the pigs were euthanized for inspection and AAA wall sampling for histological analysis. Results In group A, all pigs developed continuous expanding AAAs with a mean increase in AP-diameter to 16.26 ± 0.93 mm equivalent to a 57% increase. In group B the AP-diameters increased to 11.33 ± 0.13 mm equivalent to 9.3% which was significantly less than in group A (p < 0.001). In group A, a significant negative association between the preoperative weight and the resulting AP-diameters was found. Histology shoved more or less complete resolution of the elastic tissue in the tunica media in group A. The most frequent complication was a neurological deficit in the lower limbs. Conclusion In pigs its possible to induce continuous expanding AAAs based upon proteolytic degradation and pathological flow, resembling the real life dynamics of human aneurysms. Because the lumbars are preserved, its also a potential model for further studies of novel endovascular devices and their complications.

Oncological outcomes and complication rates after laparoscopic-assisted cryoablation: a European Registry for Renal Cryoablation (EuRECA) multi-institutional study

To assess complication rates and intermediate oncological outcomes of laparoscopic‐assisted cryoablation (LCA) in patients with small renal masses (SRMs).