Personalised mapping of tumour development in synchronous colorectal cancer patients

Synchronous colorectal cancers (syCRCs) are two or more primary tumours identified simultaneously in a patient. Previous studies report high inter-tumour heterogeneity between syCRCs, suggesting independent origin and different treatment response, making their management particularly challenging, with no specific guidelines currently in place. Here, we performed in-depth bioinformatic analyses of genomic and transcriptomic data of a total of eleven syCRCs and one metachronous CRC collected from three patients. We found mixed microsatellite status between and within patients. Overlap of mutations between synchronous tumours was consistently low (<0.5%) and heterogeneity of driver events across syCRCs was high in all patients. Microbial analysis revealed the presence of Fusobacterium nucleatum species in patients with MSI tumours, while quantification of tumour immune infiltration showed varying immune responses between syCRCs. Our results suggest high heterogeneity of syCRCs within patients but find clinically actionable biomarkers that help predict responses to currently available targeted therapies. Our study highlights the importance of personalised genome and transcriptome sequencing of all synchronous lesions to aid therapy decision and improve management of syCRC patients

Comparison of treatment outcomes for fluoroscopic and fluoroscopy-free endourological procedures: a systematic review on behalf of the European Association of Urology Urolithiasis Guidelines Panel

Context: Endourological procedures frequently require fluoroscopic guidance, which results in harmful radiation exposure to patients and staff. One clinician-controlled method for decreasing exposure to ionising radiation in patients with urolithiasis is to avoid the use of intraoperative fluoroscopy during stone intervention procedures. Objective: To comparatively assess the benefits and risks of "fluoroscopy-free" and fluoroscopic endourological interventions in patients with urolithiasis. Evidence acquisition: A systematic review of the literature from 1970 to 2022 was performed using the MEDLINE/PubMed, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov. Primary outcomes assessed were complications and the stone-free rate (SFR). Studies reporting data on ureteroscopy and percutaneous nephrolithotomy (PCNL) were eligible for inclusion. Secondary outcomes were operative duration, hospital length of stay, conversion from a fluoroscopy-free to a fluoroscopic procedure, and requirement for an auxiliary procedure to achieve stone clearance. Evidence synthesis: In total, 24 studies (12 randomised and 12 observational) out of 834 abstracts screened were eligible for analysis. There were 4564 patients with urolithiasis in total, of whom 2309 underwent a fluoroscopy-free procedure and 2255 underwent a comparative fluoroscopic procedure for treatment of urolithiasis. Pooled analysis of all procedures revealed no significant difference between the groups in SFR (p = 0.84), operative duration (p = 0.11), or length of stay (p = 0.13). Complication rates were significantly higher in the fluoroscopy group (p = 0.009). The incidence of conversion from a fluoroscopy-free to a fluoroscopic procedure was 2.84%. Similar results were noted in subanalyses for ureteroscopy (n = 2647) and PCNL (n = 1917). When only randomised studies were analysed (n = 12), the overall complication rate was significantly in the fluoroscopy group (p Conclusions: For carefully selected patients with urolithiasis, fluoroscopy-free and fluoroscopic endourological procedures have comparable stone-free and complication rates when performed by experienced urologists. In addition, the conversion rate from a fluoroscopy-free to a fluoroscopic endourological procedure is low at 2.84%. These findings are important for clinicians and patients, as the detrimental health effects of ionising radiation are negated with fluoroscopy-free procedures. Patient summary: We compared treatments for kidney stones with and without the use of radiation. We found that kidney stone procedures without the use of radiation can be safely performed by experienced urologists in patients with normal kidney anatomy. These findings are important, as they indicate that the harmful effects of radiation can be avoided during kidney stone surgery.</p

Characterising the prognostic potential of HLA‑DR during colorectal cancer development

HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma–adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15–3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59–4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279–10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32–19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p < 0.01) and stroma (p < 0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p < 0.001) and stroma (p < 0.01). HLA-DR expression was lower (p < 0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma–adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions