The incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy. To systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy. Medline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included. A total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2-100%, 29-40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting. Our systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required.

The use of buccal mucosa graft onlay urethroplasty represents the most widespread method of bulbar urethral stricture repair. The graft may be placed on the ventral or dorsal urethral surface according to surgeon experience and preference. We investigated whether the results are affected by the surgical technique by comparing the outcome of 3 types of bulbar urethroplasty using buccal mucosa graft. We repaired 50 bulbar urethral strictures with buccal mucosa grafts from 1997 to 2002. Mean patient age was 42 years. The etiology of stricture was ischemia in 12 cases, trauma in 6, instrumentation in 4 and unknown in 28. Patients with lichen sclerosus, failed hypospadias or urethroplasty and stricture extending into the penile urethra were not included. A total of 47 patients (94%) had undergone previous urethrotomy or dilation. The buccal mucosa graft was always harvested from the cheek using a 2 team approach. Mean graft length was 4.2 cm. The graft was placed on the ventral, dorsal and lateral bulbar urethral surface in 17, 27 and 6 cases, respectively. Clinical outcome was considered a success or failure at the time that any postoperative procedure was needed, including dilation. Mean followup was 42 months (range 12 to 76). Of 50 cases 42 (84%) were successful and 8 (16%) failed. The 17 ventral grafts provided success in 14 cases (83%) and failure in 3 (17%). The 27 dorsal grafts provided success in 23 cases (85%) and failure in 4 (15%). The 6 lateral grafts provided success in 5 cases (83%) and failure in 1 (17%). No surgical complications were observed. Failures involved the anastomotic site (distal in 2 and proximal in 3) and the whole grafted area in 3 cases. They were treated with urethrotomy in 5 cases and 2-stage urethroplasty in 3. In our experience the placement of buccal mucosa grafts into the ventral, dorsal or lateral surface of the bulbar urethra showed the same success rates (83% to 85%) and the outcome was not affected by the surgical technique. Moreover, stricture recurrence was uniformly distributed in all patients.

Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis of this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used to profile the transcriptional landscape of TAMs in human PCa, leading to identification of a subset of macrophages characterized by dysregulation in transcriptional pathways associated with lipid metabolism. This subset of TAMs correlates positively with PCa progression and shorter disease-free survival and is characterized by an accumulation of lipids that is dependent on Marco. Mechanistically, cancer cell–derived IL-1β enhances Marco expression on macrophages, and reciprocally, cancer cell migration is promoted by CCL6 released by lipid-loaded TAMs. Moreover, administration of a high-fat diet to tumor-bearing mice raises the abundance of lipid-loaded TAMs. Finally, targeting lipid accumulation by Marco blockade hinders tumor growth and invasiveness and improves the efficacy of chemotherapy in models of PCa, pointing to combinatorial strategies that may influence patient outcomes.