Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study

Background: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. Methods/design: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. Discussion: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Tectonic model for development of the Byrd Glacier discontinuity and surrounding regions of the Transantarctic Mountains during Neoproterozoic-Early Paleozoic

The Byrd Glacier discontinuity us a major boundary crossing the Ross Orogen, with crystalline rocks to the north and primarily sedimentary rocks to the south. Most models for the tectonic development of the Ross Orogen in the central Transantarctic Mountains consits of two-dimensional transects across the belt, but do not adress the major longitudinal contrast at Byrd Glacier. This paper presents a tectonic model centering on the Byrd Glacier discontinuity. Rifting in the Neoproterozoic producede a crustal promontory in the craton margin to the north of Byrd Glacier. Oblique convergence of the terrane (Beardmore microcontinent) during the latest Neroproterozoic and Early Cambrian was accompanied by subduction along the craton margin of East Antarctica. New data presented herein in the support of this hypothesis are U-Pb dates of 545.7 ± 6.8 Ma and 531.0 ± 7.5 Ma on plutonic rocks from the Britannia Range, subduction stepped out, and Byrd Glacier. After docking of the terrane, subduction stepped out, and Byrd Group was deposited during the Atdabanian-Botomian across the inner margin of the terrane. Beginning in the upper Botomian, reactivation of the sutured boundaries of the terrane resulted in an outpouring of clastic sediment and folding and faulting of the Byrd Group