UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) with oxaliplatin for colorectal cancer peritoneal metastases (NCT03868228).

Objectives: This is the first UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for colorectal cancer peritoneal metastases. This trial aimed to assess the impact of PIPAC in combination with standard of care systemic treatment on: progression free survival (PFS); quality of life (QoL); and short-term complications. In addition, this trial set out to demonstrate that PIPAC can be performed safely in operating theatres within a National Health Service (NHS) setting. Methods: Single-centre clinical trial with prospective data collection for patients undergoing 8-weekly PIPAC with oxaliplatin at 92 mg/m2 from January 2019 till January 2022. Progression free survival was assessed using peritoneal carcinomatosis index (PCI) by CT scans and laparoscopy. Quality of life was assessed by EORTC QLQ-C30 questionnaire. Adverse events were recorded using CTCAE. Results: Five patients underwent a total of ten PIPAC administrations (median 2, range 1-4). Median PFS was 6.0 months. QoL was maintained across repeat PIPAC procedures but a decrease in social functioning and increased fatigue were evident. Three incidences of grade 3 adverse events occurred but PIPAC was well tolerated. Conclusions: The presented data demonstrates that PIPAC is feasible and can be safely delivered within the NHS for patients with colorectal cancer peritoneal metastases, but caution must also be exercised given a risk of adverse events. Systemic chemotherapy can be safely administered at a different unit to the PIPAC procedure if both groups have clear lines of communication and timely data sharing.

Development and Evaluation of Machine Learning in Whole-Body Magnetic Resonance Imaging for Detecting Metastases in Patients With Lung or Colon Cancer: A Diagnostic Test Accuracy Study.

OBJECTIVES: Whole-body magnetic resonance imaging (WB-MRI) has been demonstrated to be efficient and cost-effective for cancer staging. The study aim was to develop a machine learning (ML) algorithm to improve radiologists' sensitivity and specificity for metastasis detection and reduce reading times. MATERIALS AND METHODS: A retrospective analysis of 438 prospectively collected WB-MRI scans from multicenter Streamline studies (February 2013-September 2016) was undertaken. Disease sites were manually labeled using Streamline reference standard. Whole-body MRI scans were randomly allocated to training and testing sets. A model for malignant lesion detection was developed based on convolutional neural networks and a 2-stage training strategy. The final algorithm generated lesion probability heat maps. Using a concurrent reader paradigm, 25 radiologists (18 experienced, 7 inexperienced in WB-/MRI) were randomly allocated WB-MRI scans with or without ML support to detect malignant lesions over 2 or 3 reading rounds. Reads were undertaken in the setting of a diagnostic radiology reading room between November 2019 and March 2020. Reading times were recorded by a scribe. Prespecified analysis included sensitivity, specificity, interobserver agreement, and reading time of radiology readers to detect metastases with or without ML support. Reader performance for detection of the primary tumor was also evaluated. RESULTS: Four hundred thirty-three evaluable WB-MRI scans were allocated to algorithm training (245) or radiology testing (50 patients with metastases, from primary 117 colon [n = 117] or lung [n = 71] cancer). Among a total 562 reads by experienced radiologists over 2 reading rounds, per-patient specificity was 86.2% (ML) and 87.7% (non-ML) (-1.5% difference; 95% confidence interval [CI], -6.4%, 3.5%; P = 0.39). Sensitivity was 66.0% (ML) and 70.0% (non-ML) (-4.0% difference; 95% CI, -13.5%, 5.5%; P = 0.344). Among 161 reads by inexperienced readers, per-patient specificity in both groups was 76.3% (0% difference; 95% CI, -15.0%, 15.0%; P = 0.613), with sensitivity of 73.3% (ML) and 60.0% (non-ML) (13.3% difference; 95% CI, -7.9%, 34.5%; P = 0.313). Per-site specificity was high (>90%) for all metastatic sites and experience levels. There was high sensitivity for the detection of primary tumors (lung cancer detection rate of 98.6% with and without ML [0.0% difference; 95% CI, -2.0%, 2.0%; P = 1.00], colon cancer detection rate of 89.0% with and 90.6% without ML [-1.7% difference; 95% CI, -5.6%, 2.2%; P = 0.65]). When combining all reads from rounds 1 and 2, reading times fell by 6.2% (95% CI, -22.8%, 10.0%) when using ML. Round 2 read-times fell by 32% (95% CI, 20.8%, 42.8%) compared with round 1. Within round 2, there was a significant decrease in read-time when using ML support, estimated as 286 seconds (or 11%) quicker ( P = 0.0281), using regression analysis to account for reader experience, read round, and tumor type. Interobserver variance suggests moderate agreement, Cohen κ = 0.64; 95% CI, 0.47, 0.81 (with ML), and Cohen κ = 0.66; 95% CI, 0.47, 0.81 (without ML). CONCLUSIONS: There was no evidence of a significant difference in per-patient sensitivity and specificity for detecting metastases or the primary tumor using concurrent ML compared with standard WB-MRI. Radiology read-times with or without ML support fell for round 2 reads compared with round 1, suggesting that readers familiarized themselves with the study reading method. During the second reading round, there was a significant reduction in reading time when using ML support.

Prostate cancer in transgender women: what does a urologist need to know?

OBJECTIVE: To review of the existing literature, current guidelines and standard of practice related to prostate cancer in transgender women, as the transgender population share many of the same healthcare needs as their cisgender counterparts, but may have additional specialist needs. MATERIALS AND METHODS: We performed a non-systematic review of the literature, current guidelines and standard of practice related to prostate cancer in transgender women. RESULTS: Our search revealed 10 case reports of prostate cancer in transgender women, four specialist opinion papers, six cohort studies, and four systematic reviews. The information in these publications were assimilated to produce a review of prostate cancer in transgender women. CONCLUSION: The risk of prostate cancer in transgender women who are not on gender-affirming hormone therapy (GAHT) or who have not had gender-affirming surgery (GAS) and gender non-conforming individuals (who may never commence GAHT or have GAS) is the same as that in the cis male population. In these patients, healthcare professionals need to be able to discuss screening, diagnostic and treatment options considering future wishes for gender-affirming treatment. Prostate cancer incidence in transgender women on GAHT or following GAS is lower than age-matched cis-male counterparts, but diagnosis and treatment is more nuanced. The present review discusses the existing literature about development and incidence of prostate cancer in this population, and makes recommendations about screening, the usefulness of diagnostic tools e.g. prostate-specific antigen and magnetic resonance imaging, and considerations when formulating treatment. Potential directions for future research are discussed, which will hopefully lead to development of robust evidence-based guidelines for the diagnosis and management of prostate cancer in transgender women.

A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans.

Introduction: A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. Methods: We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an in vitro continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. Registration: ISRCTN11327221.

Volume assessment magnetic resonance imaging technique for monitoring perianal Crohn's fistulas.

BACKGROUND: Perianal Crohn's fistula and their response to anti-tumour necrosis factor (TNF) therapies are best assessed with magnetic resonance imaging (MRI), but radiologist reporting is subjective and variable. This study investigates whether segmentation software could provide precise and reproducible objective measurements of fistula volume. METHODS: Retrospective analysis of patients with perianal Crohn's fistula at our institution between 2007 and 2013. Pre- and post-biologic MRI scans were used with varying time intervals. A total of two radiologists recorded fistula volumes, mean signal intensity and time taken to measure fistula volumes using validated Open Source segmentation software. A total of three radiologists assessed fistula response to treatment (improved, worse or unchanged) by comparing MRI scans. RESULTS: A total of 18 cases were reviewed for this pilot study. Inter-observer variability was very good for volume and mean signal intensity; intra-class correlation (ICC) 0.95 [95% confidence interval (CI) 0.91-0.98] and 0.95 (95% CI 0.90-0.97) respectively. Intra-observer variability was very good for volume and mean signal intensity; ICC 0.99 (95% CI 0.97-0.99) and 0.98 (95% CI 0.95-0.99) respectively. Average time taken to measure fistula volume was 202 s and 250 s for readers 1 and 2. Agreement between three specialist radiologists was good [kappa 0.69 (95% CI 0.49-0.90)] for the subjective assessment of fistula response. Significant association was found between objective percentage volume change and subjective consensus agreement of response (p = 0.001). Median volume change for improved, stable or worsening fistula response was -67% [interquartile range (IQR): -78, -47], 0% (IQR: -16, +17), and +487% (IQR: +217, +559) respectively. CONCLUSION: Quantification of fistula volumes and signal intensities is feasible and reliable, providing an objective measure of perianal Crohn's fistula and response to treatment.

Oblique upper tibial opening wedge osteotomy for genu varum.

OBJECTIVE: Restoration of mechanical axis of the leg. INDICATIONS: Osteoarthritis of medial knee compartment. Overload of medial compartment. Genu varum. CONTRAINDICATIONS: Smoker. Vascular impairment. Poor soft-tissue envelope. SURGICAL TECHNIQUE: Straight 12-cm midline incision starting distal to the tibial tubercle medially and continuing parallel to the tibial crest. Oblique osteotomy at 60 degrees distal-medial to proximal-lateral preserving the lateral cortex. Osteotomy wedged open and alignment checked with diathermy cord. Two tricortical bone blocks harvested from ipsilateral iliac crest or bone substitute wedges placed in osteotomy. Stabilization with contoured T-plate. Closure over drain. RESULTS: 44 patients (32 men, twelve women, average age 48 years) with 45 osteotomies. Follow-up 30 months (7-74 months). All osteotomies consolidated. 90% patients had excellent results according to the HSS (Hospital for Special Surgery) Knee Score. In 77% the femorotibial angle was corrected to 5-12 degrees . Patients regained their preoperative range of motion. There were no major complications.