A substantial proportion of patients with colorectal cancer present with or ultimately develop metastatic disease confined to the liver. The management of colorectal liver metastases remains one of the most complex and debated areas in oncological practice, with curative resection feasible in only a minority of cases. However, emerging evidence, most notably from the TransMet study, has reshaped the therapeutic landscape. The demonstration of a clear survival advantage in carefully selected patients with unresectable hepatic disease undergoing liver transplantation represents a transformative advance and challenges longstanding treatment paradigms. This narrative review critically appraises the epidemiological burden of colorectal liver metastases and delineates the key biological and clinical determinants underpinning their development. We synthesise the pivotal clinical trial data establishing the rationale for liver transplantation in this population and define the parameters for appropriate patient selection. The evolving perioperative integration of systemic therapies and the optimisation of postoperative surveillance strategies are examined in detail. Finally, we evaluate the emerging role of liquid biopsy as a precision tool to refine risk stratification and guide management, while addressing the ethical, logistical, and immunological considerations inherent to expanding transplant indications in this setting.

Patients with unresectable Gastrointestinal cancers (GI) including advanced colorectal cancer (CRC) and gall bladder cancer (GBC) have limited treatment options. Treatment with chemotherapy is associated with limited success resulting from therapeutic resistance. Immune checkpoint inhibitors are effective for a subset of metastatic CRC (5% with MSI-H status) and up to 30% of patients with GBC. Therefore, there is an urgent unmet need to discover new predictive biomarkers to aid patient selection for ICIs with a demonstrated clinical value in a challenging patient population. We highlight the utility of a liquid biopsy approach to aid selection of GI cancer patients harbouring rare POLE mutations for immunotherapy, leading to complete metabolic response in addition to radiologic responses and extended survival in all three patients. This study advocates for specialised multi-disciplinary teams performing shared clinical decision making to advance personalised care and improve outcomes of a subset of GI cancer patients with a poor prognosis.

Objectives:Peritoneal metastases (PM) represent a significant unmet need requiring urgent development of treatment options to improve patient prognosis and quality of life (QoL). A novel anti-cancer technology is Pressurised IntraPeritoneal Aerosolised Chemotherapy (PIPAC). PIPAC aims to improve target specificity of anti-cancer therapies by delivering medication as an aerosol directly to the peritoneum at laparoscopy. Early phase I/II studies suggest that PIPAC has the potential to improve treatment efficacy and cancer outcomes whilst maintaining or improving QoL through less systemic drug absorption. PICCOS aims to determine whether PIPAC can improve peritoneal progression free survival (pPFS) in patients with PM from, compared to SACT alone. Methods:PICCOS is a phase II, multi-centre, superiority, randomised controlled trial (ISRCTN 17575409). It aims to determine whether PIPAC (given alone or in combination with systemic anti-cancer therapy (SACT)) can improve peritoneal progression free survival (pPFS) as per RECIST (V1.1) in patients with PM, compared to SACT alone. Key secondary outcome measures include quality of life, safety, overall survival and progression free survival. 216 patients with non-resectable PM from colorectal cancer, platinum resistant ovarian cancer and gastric cancer will be recruited. Patients will be randomised to receive either standard of care SACT alone or PIPAC in combination with (colorectal, gastric groups) or without (ovarian group) standard of care SACT. Median pPFS will be estimated using the Kaplan-Meier method. The log-rank test, stratified by prognostic factors, will be used to compare PFS distributions. Results:PIPAC is expected to achieve improved peritoneal progression free survival for patients in comparison to those treated with standard care. Conclusions:PICCOS aims to provide much needed, high-quality evidence on the efficacy of PIPAC in treating PM.

AIM:Instrumental delivery typically describes the use of ventouse or forceps to aid vaginal delivery. They are used in 10%-15% of all vaginal deliveries and in almost a third of all primiparous deliveries. They are associated with an increased risk of maternal and neonatal injury. Such maternal injuries may lead to significant functional problems such as faecal incontinence and these conditions can be life changing. Informed consent should be obtained before any medical procedure. This should be taken well before the procedure, documented clearly, and alternatives should be discussed. The aim of this study was to assess the information provided to pregnant women and the quality of consent obtained prior to instrumental vaginal delivery. METHOD:Patients were approached at 36 weeks' gestation, prior to a planned vaginal delivery. The study was undertaken in the Obstetric Department of a busy District General Hospital in the UK. The patients' understanding of labour, vaginal delivery and the use of instrumentation was assessed. Clinical notes of women who had an assisted vaginal delivery were reviewed to ascertain time of consent for use of instrumentation and amount of analgesia received at that point. RESULTS:A total of 138 patients were included for prospective assessment. Only 4% were able to describe all stages of labour, 17% could describe some of the stages of labour and 78% were unable to describe any of the stages of labour. Eighty per cent of the participants were unaware that instrumentation may be used during delivery, 21% were aware that it may be used if necessary and only 2% were aware of the risk of maternal injury. Fifty-nine case notes were reviewed. All had undergone either forceps or ventouse instrumentation. Eighteen per cent showed no record of informed consent. Sixty-one per cent showed evidence of verbal consent and 20% had a signed consent in the clinical notes. All had been consented for use of instrumentation during the second stage of labour, often when opioid analgesia had been administered prior to consent. CONCLUSION:Knowledge about labour and the use of instrumentation during delivery appeared to be poor. The quality of consent taken for instrumental delivery appeared to be sub-standard. Larger studies, done post the COVID-19 epidemic, are needed to confirm that similar practices still occur in other hospitals and, if this is the case, urgent measures need to be taken to correct this.

Cleveland Clinic London Hospital, London, England Funding/Support: None reported. Financial Disclosures: None reported. Correspondence: James Murphy, Ph.D., F.R.C.S., Cleveland Clinic London Hospital, 33 Grosvenor Place, London, SW1X 7HY United Kingdom. Email: [email protected]

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.

Introduction/Background In 2021 the National Institute for Clinical Excellence (NICE) published interventional procedures guidance stipulating that in the UK, Pressurised IntraPeritoneal Aerosolised Chemotherapy (PIPAC) should only be used within the context of a randomised control trial to demonstrate efficacy against standard of care. The UK PIPAC collaborative would like to present its first randomised controlled trial assessing the efficacy of PIPAC in the management of peritoneal metastases (PM) in patients with cancer of the colon, ovary and stomach. The PICCOS trial aims to not only assess efficacy compared to standard of care in terms of progression free survival (PFS), but also quality of life. Methodology This is a basket, phase II trial with a master protocol covering the overarching research methodology, and embedded individual cancer site specific protocols, sample sizes and analysis plans. 78 patients with PM from colon cancer, 62 patients with PM from ovarian cancer and 72 patients with PM from stomach cancer will be randomised to systemic chemotherapy or alternating PIPAC and systemic chemotherapy every 2 or 3 weeks for 18 weeks in total. The primary outcome measure is PFS. CT scans undertaken every 8 weeks following treatment will be assessed against the RECIST criteria to assess disease burden and determine PFS. Quality of life will be assessed using the EORTC QLQ C30 tool. Results The PICCOS Trial has now secured funding with a National Institute of Health Research Efficacy and mechanism Evaluation (NIHR EME) grant and is due to commence in November 2022 with a four year running period. Publication and dissemination of results is anticipated in 2027. Conclusion This is the first UK randomised controlled trial assessing the efficacy and impact of quality of life of PIPAC in the treatment of peritoneal metastases aiming to provide high quality evidence to guide clinical practice and further research in the future. Disclosures None

BACKGROUND Anal inserts and percutaneous tibial nerve stimulation may be offered to those with fecal incontinence who have failed other conservative treatments. OBJECTIVE We aimed to compare anal inserts and percutaneous tibial nerve stimulation. DESIGN This was an investigator blinded randomized pilot study. SETTINGS The study was conducted at a large tertiary care hospital. PATIENTS Adult patients with passive or mixed fecal incontinence were recruited. INTERVENTIONS Patients were randomized to receive either the anal inserts or weekly percutaneous tibial nerve stimulation for a period of three months. MAIN OUTCOME MEASURES The primary endpoint was a 50% reduction of episodes of fecal incontinence per week as calculated by a prospectively completed two-week bowel diary. Secondary endpoints were St Mark's incontinence score, International Consultation on Incontinence Questionnaire-Bowel (ICIQ-B) scores (for bowel pattern, bowel control and quality of life) use of antidiarrheal agents, estimates of comfort and acceptability. RESULTS Fifty patients were recruited: 25 were randomized to anal inserts and 25 to percutaneous tibial nerve stimulation. All completed treatment. A significant improvement of scores in the two-week bowel diary, the St Mark's score and the ICIQ-B scores was seen in both groups after 3 months of treatment. A reduction of ≥ 50% fecal incontinence episodes was reached by 76% (n = 19/25) by the anal insert group, compared to 48% (n = 12/25) of those in the percutaneous tibial nerve stimulation group (p = 0.04). The St Mark's Fecal incontinence scores, ICIQ-B scores for bowel pattern, bowel control and quality of life (p = 0.01) suggest similar improvement for each group. LIMITATIONS A realistic sample size calculation could not be performed due to paucity of objective prospective studies assessing the effect of the insert device and percutaneous tibial nerve stimulation. CONCLUSIONS Both anal insert and percutaneous tibial nerve stimulation improved the symptoms of fecal incontinence after 3 months of treatment. The insert device appeared to be more effective than percutaneous tibial nerve stimulation. Larger studies are needed to investigate this further. See Video Abstract at http://links.lww.com/DCR/B460 .