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In 2010, the International Society of Geriatric Oncology (SIOG) developed treatment guidelines for men with prostate cancer who are older than 70 years old. In 2013, a new multidisciplinary SIOG working group was formed to update these recommendations. The consensus of the task force is that older men with prostate cancer should be managed according to their individual health status, not according to age. On the basis of a validated rapid health status screening instrument and simple assessment, the task force recommends that patients are classed into three groups for treatment: healthy or fit patients who should have the same treatment options as younger patients; vulnerable patients with reversible impairment who should receive standard treatment after medical intervention; and frail patients with non-reversible impairment who should receive adapted treatment.

Isolation of circulating tumor cells (CTCs) from peripheral blood has the potential to provide a far easier \"liquid biopsy\" than tumor tissue biopsies, to monitor tumor cell populations during disease progression and in response to therapies. Many CTC isolation technologies have been developed. We optimized the Parsortix system, an epitope independent, size and compressibility-based platform for CTCs isolation, making it possible to harvest CTCs at the speed and sample volume comparable to standard CellSearch system. We captured more than half of cancer cells from different cancer cell lines spiked in blood samples from healthy donors using this system. Cell loss during immunostaining of cells transferred and fixed on the slides is a major problem for analyzing rare cell samples. We developed a novel cell transfer and fixation method to retain >90% of cells on the slide after the immunofluorescence process without affecting signal strength and specificity. Using this optimized method, we evaluated the Parsortix system for CTC harvest in prostate cancer patients in comparison to immunobead based CTC isolation systems IsoFlux and CellSearch. We harvested a similar number (p = 0.33) of cytokeratin (CK) positive CTCs using Parsortix and IsoFlux from 7.5 mL blood samples of 10 prostate cancer patients (an average of 33.8 and 37.6 respectively). The purity of the CTCs harvested by Parsortix at 3.1% was significantly higher than IsoFlux at 1.0% (p = 0.02). Parsortix harvested significantly more CK positive CTCs than CellSearch (p = 0.04) in seven prostate cancer patient samples, where both systems were utilized (an average of 32.1 and 10.1 respectively). We also captured CTC clusters using Parsortix. Using four-color immunofluorescence we found that 85.8% of PC3 cells expressed EpCAM, 91.7% expressed CK and 2.5% cells lacked both epithelial markers. Interestingly, 95.6% of PC3 cells expressed Vimentin, including those cells that lacked both epithelial marker expression, indicating epithelial-to-mesenchymal transition. CK-positive/Vimentin-positive/CD45-negative, and CK-negative/Vimentin-positive/CD45-negative cells were also observed in four of five prostate cancer patients but rarely in three healthy controls, indicating that Parsortix harvests CTCs with both epithelial and mesenchymal features. We also demonstrated using PC3 and DU145 spiking experiment that Parsortix harvested cells were viable for cell culture.

Background:Robot-assisted radical prostatectomy (RARP) has been rapidly adopted without robust evidence comparing its functional outcomes against laparoscopic radical prostatectomy (LRP) or open retropubic radical prostatectomy (ORP) approaches. This study compared patient-reported functional outcomes following RARP, LRP or ORP.Methods:All men diagnosed with prostate cancer in England during April - October 2014 who underwent radical prostatectomy were identified from the National Prostate Cancer Audit and mailed a questionnaire 18 months after diagnosis. Group differences in patient-reported sexual, urinary, bowel and hormonal function (EPIC-26 domain scores) and generic health-related quality of life (HRQoL; EQ-5D-5L scores), with adjustment for patient and tumour characteristics, were estimated using linear regression.Results:In all, 2219 men (77.0%) responded; 1310 (59.0%) had RARP, 487 (21.9%) LRP and 422 (19.0%) ORP. RARP was associated with slightly higher adjusted mean EPIC-26 sexual function scores compared with LRP (3·5 point difference; 95% CI: 1.1-5.9, P=0.004) or ORP (4.0 point difference; 95% CI: 1.5-6.5, P=0.002), which did not meet the threshold for a minimal clinically important difference (10-12 points). There were no significant differences in other EPIC-26 domain scores or HRQoL.Conclusions:It is unlikely that the rapid adoption of RARP in the English NHS has produced substantial improvements in functional outcomes for patients.

Background The enhanced recovery program (ERP) aims to reduce the metabolic response to surgery, hastening recovery and shortening hospital stay. Concerns exist regarding morbidity and hospital stay in elderly patients. The present study aimed to compare the outcomes and compliance of elderly patients managed by an ERP protocol with a younger group. Methods A review was performed of a prospective database of patients undergoing colorectal resection managed under the ERP protocol between 2005 and 2010. Patients were grouped into <80 years and ≥80 years, and perioperative data were collated. The postoperative outcomes were compared with the goals set out by the ERP protocol. Results A total of 688 patients were included, 558 were <80 years (median: 66 years; range: 17–79 years) and 130 were ≥80 years (median: 83 years; range: 80–95 years). Some 96% of operations were planned laparoscopically. Median total length of hospital stay was 6 days (range: 1–108 days) for the <80 year group and 8 days (range: 1–167 days; P 0.363) for the elderly group, with a 30 day readmission rate of 8.6% for the population and no significant differences between groups. The 30 day mortality was 5%, with a significant difference between the two groups ( P  < 0.0001). Differences in protocol adherence were identified in the discontinuation of intravenous fluids, catheter removal, and early mobilization. Conclusions An enhanced recovery program is feasible for colorectal surgery patients ≥80 years of age, with similar compliance as the younger group to some aspects of the protocol and an acceptable readmission rate. Attention to improving compliance in the postoperative phase is necessary, particularly in such high-risk patients, as such improvement may reduce the morbidity and mortality.

Background Metformin is a biguanide oral hypoglycaemic agent commonly used for the treatment of type 2 diabetes mellitus. In addition to its anti-diabetic effect, metformin has also been associated with a reduced risk of cancer incidence of a number of solid tumours, including prostate cancer (PCa). However, the underlying biological mechanisms for these observations have not been fully characterised in PCa. One hypothesis is that the indirect insulin lowering effect may have an anti-neoplastic action as elevated insulin and insulin like growth factor − 1 (IGF-1) levels play a role in PCa development and progression. In addition, metformin is a potent activator of activated protein kinase (AMPK) which in turn inhibits the mammalian target of rapamycin (mTOR) and other signal transduction mechanisms. These direct effects can lead to reduced cell proliferation. Given its wide availability and tolerable side effect profile, metformin represents an attractive potential therapeutic option for men with PCa. Hence, the need for a clinical trial investigating its biological mechanisms in PCa. Methods METAL is a randomised, placebo-controlled, double-blind, window of opportunity study investigating the biological mechanism of metformin in PCa. 100 patients with newly-diagnosed, localised PCa scheduled for radical prostatectomy will be randomised 1:1 to receive metformin (1 g b.d.) or placebo for four weeks (+/− 1 week) prior to prostatectomy. Tissue will be collected from both diagnostic biopsy and prostatectomy specimens. The primary endpoint is the difference in expression levels of markers of the Fatty acid synthase (FASN)/AMPK pathway pre and post treatment between the placebo and metformin arms. Secondary endpoints include the difference in expression levels of indicators of proliferation (ki67 and TUNEL) pre and post treatment between the placebo and metformin arms. METAL is currently open to recruitment at Guy’s and St Thomas’ Hospital and the Royal Marsden Hospital, London. Discussion This randomised placebo-controlled double blinded trial of metformin vs. placebo in men with localised PCa due to undergo radical prostatectomy, aims to elucidate the mechanism of action of metformin in PCa cells, which should then enable further larger stratification trials to take place. Trial registration EudraCT number 2014–005193-11 . Registered on September 09, 2015.

Introduction A prospective cohort study comparing peri‐ and postoperative outcomes for patients with predominantly anterior prostate cancer (APC) identified preoperatively against non‐anterior prostate cancer (NAPC) treated via robotic‐assisted radical prostatectomy (RARP). Patients and Methods Of the 757 RARP's completed between January 2016 and April 2018, two comparative cohorts for anterior and an equivalent group of non‐anterior prostate tumours each consisting of 152 patients were compared against each other. Data were collected on the following variables: patient age; operating consultant; preoperative PSA, ISUP grade, degree of nerve sparing; tumour staging; presence and location of positive surgical margins; PSA density, postoperative ISUP grade; treatment paradigm and postoperative PSA, erectile function, and continence outcomes with 2‐year follow‐up. Results APCs were found to have significantly lower ISUP grading postoperatively; increased diagnosis via active surveillance over new diagnosis; more frequently undertaken bilateral nerve‐sparing and long‐term poorer continence outcomes at 18 and 24 months postoperatively (p < 0.05). Pre‐ and post‐op PSA levels, erectile function, PSA density, positive surgical margins (PSM), age and tumour staging showed no significant differences between the APC and NAPC cohorts (p > 0.05). Conclusion The lower ISUP grading could indicate APC as overall being less aggressive than NAPC, whereas the poorer long‐term continence outcomes require further investigating. The non‐significant differences amongst tumour staging, PSA density, preoperative PSA levels and PSM rates suggest that APC may not be as significant as predicted in diagnostic evaluation. Overall, this study provides useful information on the growing literature of anterior prostate cancer. Being the largest comparative cohort study to date on APC post‐RARP, these results indicate the true characteristics of anterior tumours and their functional outcomes to help improve education, patient expectations and management.

Objectives To test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing. Patients and Methods Newly‐diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi‐centre randomised, double‐blind, placebo‐controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12‐month disease re‐assessment (imaging/biochemical/histological), and 12‐month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging‐Reporting and Data System (PI‐RADS) 4/5 lesion(s) on multi‐parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length. Results Of 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve‐month disease progression rate was 43.3%. Assessable 12‐month treatment adherence in non‐progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug‐attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms. Conclusion Recruitment of AS PCa patients into a multi‐centre multi‐arm placebo‐controlled RCT of minimally‐toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome‐associated biomarkers.

Synopsis: This Article surveys questions regarding the allocation of GST exemption to GRAT property. Official guidance on these questions is at best unsatisfying, and there is little consensus, or in some cases even engagement, among commentators. Confidence in one's answers can be atypically important because legal \"finality\" is often many years away. The Article concludes with tactical suggestions for increasing certainty.

Other groups found that aloe vera mouthwash compared with conventionally prescribed mouthwash for radiation-induced oral mucositis (mouth inflammation) in head and neck cancer treatment was equally as effective in treating the symptoms. [...]aloe vera mouthwash could be used as an alternative if conventional mouthwash is poorly tolerated. [...]in vitro potency often fails to translate to the clinic because of several factors, including the rarity of compounds that can both adequately distribute to the tumour and reach minimum effective concentrations for sufficient periods of time.

Objective To report on the outcomes of urological cancer patients undergoing radical surgery between March–September 2020 (compared with 2019) in the European Institute of Oncology (IEO) in Milan and the South East London Cancer Alliance (SELCA). Materials and Methods Since March 2020, both institutions implemented a COVID‐19 minimal ‘green’ pathway, whereby patients were required to isolate for 14 days prior to admission and report a negative COVID‐19 polymerase chain reaction (PCR) test within 3 days of surgery. COVID‐19 positive patients had surgery deferred until a negative swab. Surgical outcomes assessed were: American Society of Anaesthesiologists (ASA) grade; surgery time; theatre time; intensive care unit (ICU) stay >24 h; pneumonia; length of stay (LOS); re‐admission. Postoperative COVID‐19 infection rates and associated mortality were also recorded. Results At IEO, uro‐oncological surgery increased by 4%, as compared with the same period in 2019 (n = 515 vs. 534). The main increase was observed for renal (16%, n = 98 vs. 114), bladder (24%, n = 45 vs. 56) and testicular (27%, n = 26 vs. 33). Patient demographics were all comparable between 2019 and 2020. Only one bladder cancer patient developed COVID‐19, reporting mild/moderate disease. There was no COVID‐19 associated mortality. In the SELCA cohort, uro‐oncological surgery declined by 23% (n = 403 vs. 312) compared with the previous year. The biggest decrease was seen for prostate (−42%, n = 156 vs. 91), penile (−100%, n = 4 vs. 0) and testicular cancers (−46%, n = 35 vs. 24). Various patient demographic characteristics were notably different when comparing 2020 versus 2019. This likely reflects the clinical decision of deferring COVID‐19 vulnerable patients. One patient developed COVID‐19, with no COVID‐19 related mortality. Conclusion The COVID‐19 minimal ‘green’ pathways that were put in place have shown to be safe for uro‐oncological patients requiring radical surgery. There were limited complications, almost no peri‐operative COVID‐19 infection and no COVID‐19‐related mortality in either cohort.