Surgical Handover Core Outcome Measures (SH-CORE): a protocol for the development of a core outcome set for trials in surgical handover.

BACKGROUND: Surgical handover is associated with a significant risk of care failures. Existing research displays methodological deficiencies and little consensus on the outcomes that should be used to evaluate interventions in this area. This paper reports a protocol to develop a core outcome set (COS) to support standardisation, comparability, and evidence synthesis in future studies of surgical handover between doctors. METHODS: This study adheres to the Core Outcome Measures in Effectiveness Trials (COMET) initiative guidance for COS development, including the COS-Standards for Development (COS-STAD) and Reporting (COS-STAR) recommendations. It has been registered prospectively on the COMET database and will be led by an international steering group that includes surgical healthcare professionals, researchers, and patient and public partners. An initial list of reported outcomes was generated through a systematic review of interventions to improve surgical handover (PROSPERO: CRD42022363198). Findings of a qualitative evidence synthesis of patient and public perspectives on handover will augment this list, followed by a real-time Delphi survey involving all stakeholder groups. Each Delphi participant will then be invited to take part in at least one online consensus meeting to finalise the COS. ETHICS AND DISSEMINATION: This study was approved by the Royal College of Surgeons in Ireland (RCSI) Research Ethics Committee (202309015, 7th November 2023). Results will be presented at surgical scientific meetings and submitted to a peer-reviewed journal. A plain English summary will be disseminated through national websites and social media. The authors aim to integrate the COS into the handover curriculum of the Irish national surgical training body and ensure it is shared internationally with other postgraduate surgical training programmes. Collaborators will be encouraged to share the findings with relevant national health service functions and national bodies. DISCUSSION: This study will represent the first published COS for interventions to improve surgical handover, the first use of a real-time Delphi survey in a surgical context, and will support the generation of better-quality evidence to inform best practice. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials (COMET) initiative 2675.  http://www.comet-initiative.org/Studies/Details/2675 .

Spatial transcriptomic analysis reveals local effects of intratumoral fusobacterial infection on DNA damage and immune signaling in rectal cancer.

Mucinous colorectal cancer (CRC) is a common histological subtype of colorectal adenocarcinoma, associated with a poor response to chemoradiotherapy. The commensal facultative anaerobes fusobacteria, have been associated with poor prognosis specifically in mesenchymal CRC. Interestingly, fusobacterial infection is especially prevalent in mucinous CRC. The objective of this study was therefore to increase our understanding of beneficial and detrimental effects of fusobacterial infection, by contrasting host cell signaling and immune responses in areas of high vs. low infection, using mucinous rectal cancer as a clinically relevant example. We employed spatial transcriptomic profiling of 106 regions of interest from 8 mucinous rectal cancer samples to study gene expression in the epithelial and immune segments across regions of high versus low fusobacterial infection. Fusobacteria high regions were associated with increased oxidative stress, DNA damage, and P53 signaling. Meanwhile regions of low fusobacterial prevalence were characterized by elevated JAK-STAT, Il-17, Il-1, chemokine and TNF signaling. Immune masks within fusobacterial high regions were characterized by elevated proportions of cytotoxic (CD8+) T cells (p = 0.037), natural killer (NK) cells (p < 0.001), B-cells (p < 0.001), and gamma delta T cells (p = 0.003). Meanwhile, fusobacteria low regions were associated with significantly greater M2 macrophage (p < 0.001), fibroblast (p < 0.001), pericyte (p = 0.002), and endothelial (p < 0.001) counts.

Assessing current handover practices in surgery: A survey of non-consultant hospital doctors in Ireland.

BACKGROUND: Handovers of care are potentially hazardous moments in the patient journey and can lead to harm if conducted poorly. Through a national survey of surgical doctors in Ireland, this paper assesses contemporary surgical handover practices and evaluates barriers and facilitators of effective handover. METHODS: After ethical approval and pre-testing with a representative sample, a cross-sectional, online survey was distributed to non-consultant hospital doctors (NCHDs) working in the Republic of Ireland. A mixed-methods approach was used, combining data using triangulation design. MAIN FINDINGS: A total of 201 responses were received (18.5%). Most participants were senior house officers or senior registrars (49.7% and 37.3%). Most people (85.1%) reported that information received during handover was missing or incorrect at least some of the time. One-third of respondents reported that a near-miss had occurred as a result of handover within the past three months, and handover-related errors resulted in minor (16.9%), moderate (4.9%), or major (1.5%) harm. Only 11.4% had received any formal training. Reported barriers to handover included negative attitudes, a lack of institutional support, and competing clinical activities. Facilitators included process standardisation, improved access to resources, and staff engagement. CONCLUSIONS: Surgical NCHDs working in Irish hospitals reported poor compliance with international best practice for handover and identified potential harms. Process standardisation, appropriate staff training, and the provision of necessary handover-related resources is required at a national level to address this significant patient safety concern.

The effect of implementing a transanal minimally invasive surgical programme for the local excision of early rectal neoplasia on outcomes in a tertiary referral rectal cancer centre.

Transanal minimally invasive surgery (TAMIS) is a surgical alternative to proctectomy in the management of complex rectal polyps and early rectal cancers. In 2016, our institution introduced a TAMIS programme. The purpose of this study was to evaluate changes in practice and outcomes in our institution in the 3 years before and after the implementation of TAMIS. We conducted a retrospective analysis of a prospective database of patients who underwent proctectomy or TAMIS for the management of complex rectal polyps or early rectal cancers at our institution between 2013 and 2018. 96 patients were included in this study (41 proctectomy vs 55 TAMIS). A significant reduction was noted in the number of proctectomies performed in the 3 years after the implementation of TAMIS as compared to the 3 years before (13 vs 28) ( P  < 0.001); 43% of patients ( n  = 12) who underwent proctectomy in the period prior to implementation of TAMIS were American Society of Anaesthesiologists grade III, as compared to only 15% ( n  = 2) of patients during the period following TAMIS implementation ( P  = 0.02). TAMIS was associated with a significant reduction in length of inpatient stay ( P  < 0.001). Oncological outcomes were comparable between groups (log rank P  = 0.83). Our findings support TAMIS as a safe and effective alternative to radical resection. The availability of TAMIS has resulted in a significant reduction in the number of comorbid patients undergoing proctectomy at our institution. Consequently, we have observed a significant reduction in postoperative complications over this time period.

Daily handover in surgery: systematic review and a novel taxonomy of interventions and outcomes.

BACKGROUND: Poor-quality handovers lead to adverse outcomes for patients; however, there is a lack of evidence to support safe surgical handovers. This systematic review aims to summarize the interventions available to improve end-of-shift surgical handover. A novel taxonomy of interventions and outcomes and a modified quality assessment tool are also described. METHODS: Ovid MEDLINE®, PubMed, Embase, and Cochrane databases were searched for articles up to April 2023. Comparative studies describing interventions for daily in-hospital surgical handovers between doctors were included. Studies were grouped according to their interventions and outcomes. RESULTS: In total, 6139 citations were retrieved, and 41 studies met the inclusion criteria. The total patient sample sizes in the control and intervention groups were 11 946 and 11 563 patients, respectively. Most studies were pre-/post-intervention cohort studies (92.7%), and most (73.2%) represented level V evidence. The mean quality assessment score was 53.4% (17.1). A taxonomy of handover interventions and outcomes was developed, with interventions including handover tools, process standardization measures, staff education, and the use of mnemonics. More than 25% of studies used a document as the only intervention. Overall, 55 discrete outcomes were assessed in four categories including process (n = 27), staff (n = 14), patient (n = 12) and system-level (n = 2) outcomes. Significant improvements were seen in 51.8%, 78.5%, 58.3% (n = 9761 versus 9312 patients) and 100% of these outcomes, respectively. CONCLUSIONS: Most publications demonstrate that good-quality surgical handover improves outcomes and many interventions appear to be effective; however, studies are methodologically heterogeneous. These novel taxonomies and quality assessment tool will help standardize future studies.

Contemporary perioperative outcomes after total abdominal colectomy for ulcerative colitis in a tertiary referral centre.

OBJECTIVE: Colectomy for ulcerative colitis (UC) is common despite therapeutic advances. Post-operative morbidity and mortality demonstrate an association between hospital volumes and outcomes. This single-centre retrospective study examines outcomes after emergency colectomy for UC. METHODS: Patient demographics, perioperative variables and outcomes were collected in Beaumont Hospital between 2010 and 2023. Univariant analysis was used to assess relationships between perioperative variables and morbidity and length of stay (LOS). RESULTS: A total of 115 patients underwent total abdominal colectomy with end ileostomy for UC, 8.7 (±3.8) per annum. Indications were refractory acute severe colitis (88.7%), toxic megacolon (6.1%), perforation (4.3%), or obstruction (0.9%). Over 80% of cases were performed laparoscopically. Pre-operative steroid (93%) and biologic (77.4%) use was common. Median post-operative LOS was 8 days (interquartile range 6-12). There were no 30-day mortalities, and 30-day post-operative morbidity was 38.3%. There was no association between time to colectomy ( P  = 0.85) or biologic use ( P  = 0.24) and morbidity. Increasing age was associated with prolonged LOS ( P  = 0.01). Laparoscopic approach (7 vs. 12 days P  =0.01, 36.8% vs. 45% P  = 0.66) was associated with reduced LOS and morbidity. CONCLUSION: This study highlights contemporary outcomes after emergency colectomy for UC at a specialist high-volume, tertiary referral centre, and superior outcomes after laparoscopic surgery in the biologic era.

Composite quality measures of abdominal surgery at a population level: systematic review.

BACKGROUND: Measurement of surgical quality at a population level is challenging. Composite quality measures derived from administrative and clinical information systems could support system-wide surgical quality improvement by providing a simple metric that can be evaluated over time. The aim of this systematic review was to identify published studies of composite measures used to assess the overall quality of abdominal surgical services at a hospital or population level. METHODS: A search was conducted in PubMed and MEDLINE for references describing measurement instruments evaluating the overall quality of abdominal surgery. Instruments combining multiple process and quality indicators into a single composite quality score were included. The identified instruments were described in terms of transparency, justification, handling of missing data, case-mix adjustment, scale branding and choice of weight and uncertainty to assess their relative strengths and weaknesses (PROSPERO registration: CRD42022345074). RESULTS: Of 5234 manuscripts screened, 13 were included. Ten unique composite quality measures were identified, mostly developed within the past decade. Outcome measures such as mortality rate (40 per cent), length of stay (40 per cent), complication rate (60 per cent) and morbidity rate (70 per cent) were consistently included. A major challenge for all instruments is the reliance of valid administrative data and the challenges of assigning appropriate weights to the underlying instrument components. A conceptual framework for composite measures of surgical quality was developed. CONCLUSION: None of the composite quality measures identified demonstrated marked superiority over others. The degree to which administrative and clinical data influences each composite measure differs in important ways. There is a need for further testing and development of these measures.

A systematic review of patient risk factors for complications following stoma formation among adults undergoing colorectal surgery.

BACKGROUND: Stoma formation is a commonly performed procedure both during and following colorectal surgery. When designed correctly, stomas can dramatically improve patients' quality of life, but the reverse may occur when complications arise. Given the significant negative impact of complications following stoma formation, understanding risk factors that may be mitigated pre-operatively is important. METHOD: A systematic search of publications using MEDLINE, CINAHL, and Cochrane databases was conducted in May 2022. Data was extracted and a narrative synthesis undertaken. The evidence-based librarianship (EBL) checklist assessed the methodological quality of the included studies. The systematic review includes various research designs such as randomised controlled trials (RCT), case-control studies, and observational cohort studies written in English. Reviews, conference papers, opinion papers, and those including participants < 18 years old were excluded. No restrictions on the date of publication and study setting were applied. RESULTS: This review included 17 studies, conducted between 2001 and 2020. The study designs were prospective audit, prospective analysis, retrospective analysis, longitudinal analysis and multivariate analysis of self-reported questionaires/surveys. Twenty-two possible risk factors for the development of stoma complications following stoma formation were identified. These include demographical risk factors, underlying medical condition, type of surgery, elective vs emergency surgery, stoma factors, surgical factors, indications for surgery and factors which may impact healing. Furthermore, high BMI, emergency surgery, and stoma type were identified as the most frequently occurring risk factors. CONCLUSION: Given the large number of risk factors identified, the implementation of a risk stratification tool may decrease the incidence and prevalence of stoma complication development. This, in turn, would decrease the associated healthcare-related costs, and negative impact on mortality, length of stay and quality of life.

Corrigendum: Mucinous adenocarcinoma of the rectum: a whole genome sequencing study.

[This corrects the article DOI: 10.3389/fonc.2020.01682.].

Six Long-Standing Questions about Antibiotic Prophylaxis in Surgery.

Surgical site infections (SSIs) are the most common adverse event occurring in surgical patients. Optimal prevention of SSIs requires the bundled integration of a variety of measures before, during, and after surgery. Surgical antibiotic prophylaxis (SAP) is an effective measure for preventing SSIs. It aims to counteract the inevitable introduction of bacteria that colonize skin or mucosa into the surgical site during the intervention. This document aims to guide surgeons in appropriate administration of SAP by addressing six key questions. The expert panel identifies a list of principles in response to these questions that every surgeon around the world should always respect in administering SAP.

A systematic review of the association between parastomal hernia and sarcopenia.

BACKGROUND: Sarcopenia is a multifactorial loss of muscle mass that can complicate surgical outcomes and increase morbidity and mortality. Parastomal hernias can occur after any surgery requiring stoma formation and is an area of concern as a complication as it can require a second surgery or emergency surgical intervention. AIM: To assess the impact of sarcopenia on parastomal hernia formation in the postoperative period. METHOD: A systematic search of publications using MEDLINE, CINAHL, and Cochrane databases was conducted in June 2022. Data were extracted, and a narrative synthesis was undertaken. The Crowe Critical Appraisal Tool (CCAT) assessed the quality of the included studies. The systematic review included original research studies, prospective and retrospective designs, and human studies written in English. Reviews, conference papers, opinion papers, and those including participants < 18 years old were excluded. No restrictions on the date of publication and study setting were applied. RESULTS: Nine studies met the inclusion criteria, and these were conducted between 2016 and 2021; 56% (n = 5) used a retrospective study design. The mean sample size was 242.5 participants (SD = ±358.6). No consistent or standardized way of defining sarcopenia or measuring muscle mass was seen between the studies reviewed. However, 45% (n = 4) of the studies reported a significant relationship between sarcopenia and wound healing complications, including an increased incidence of parastomal and incisional hernias. The average CCAT score was 27.56 (SD = ±4.39). CONCLUSION: There is no definitive relationship between sarcopenia and hernia development; however, four studies found a significant relationship between sarcopenia and hernia formation. It must also be considered that different disease processes can cause sarcopenia either through the disease process itself, or the treatment and management. More research and consistent measurements are needed before comparable and consistent outcomes can be compiled.

A meta-analysis of laparoscopic versus ultrasound-guided transversus abdominis plane block in laparoscopic colorectal surgery.

BACKGROUND: Enhanced recovery programmes in laparoscopic colorectal surgery (LCS) employ combined approaches to achieve postoperative analgesia. Transversus abdominis plane (TAP) block is a locoregional anaesthetic technique that may reduce postoperative pain. AIMS: To perform a systematic review and meta-analysis to compare the effectiveness of laparoscopic- versus ultrasound-guided TAP block in LCS. METHODS: Databases were searched for relevant articles from inception until March 2022. All randomised controlled trials (RCTs) that compared laparoscopic (LTB) versus ultrasound-guided (UTB) TAP blocks in LCS were included. The primary outcome was narcotic consumption at 24 h postoperatively, whilst secondary outcomes included pain scores at 24 h postoperatively, operative time, postoperative nausea and vomiting (PONV) and complication rates. Random effects models were used to calculate pooled effect size estimates. RESULTS: Three RCTs were included capturing 219 patients. Studies were clinically heterogenous. On random effects analysis, LTB was associated with significantly lower narcotic consumption (SMD - 0.30 mg, 95% CI = - 0.57 to - 0.03, p = 0.03) and pain scores (SMD - 0.29, 95% CI = - 0.56 to - 0.03, p = 0.03) at 24 h. However, there were no differences in operative time (SMD - 0.09 min, 95% CI = - 0.40 to 0.22, p = 0.56), PONV (OR = 0.97, 95% CI = 0.36 to 2.65, p = 0.96) or complication (OR = 1.30, 95% CI = 0.64 to 2.64, p = 0.47) rates. CONCLUSIONS: LTB is associated with significantly less narcotic usage and pain at 24 h postoperatively but similar PONV, operative time and complication rates, compared to UTB. However, the data were inconsistent, and our findings require further investigation. LTB obviates the need for ultrasound devices whilst also decreasing procedure logistical complexity.

Multiplexed Immunofluorescence Imaging Reveals an Immune-Rich Tumor Microenvironment in Mucinous Rectal Cancer Characterized by Increased Lymphocyte Infiltration and Enhanced Programmed Cell Death Protein 1 Expression.

BACKGROUND: Mucinous rectal cancer is associated with a higher incidence of microsatellite instability and a poorer response to neoadjuvant chemoradiotherapy compared to other subtypes of rectal adenocarcinoma. Immune checkpoint inhibitors are an emerging family of anticancer therapeutics associated with highly variable outcomes in colorectal cancer. Although the immune landscape of mucinous rectal cancer has not been fully explored, the presence of mucin is thought to act as a barrier preventing immune-cell infiltration. OBJECTIVE: The aim of this study was to determine the immune properties of mucinous rectal cancer and investigate the degree of lymphocyte infiltration in this cohort. DESIGN: This is a retrospective cohort study that involved multiplexed immunofluorescence staining of tumor microarrays. SETTINGS: Samples originated from a single university teaching hospital. PATIENTS: Our cohort included 15 cases of mucinous and 43 cases of nonmucinous rectal cancer. MAIN OUTCOME MEASURES: Immune cells were classified and quantified. Immune-cell counts were compared between mucinous and nonmucinous cohorts. Immune marker expression within tumor epithelial tissue was evaluated to determine the degree of lymphocyte infiltration. RESULTS: Cytotoxic ( p = 0.022) and regulatory T cells ( p = 0.010) were found to be overrepresented in the mucinous cohort compared to the nonmucinous group. Programmed cell death protein 1 expression was also found to be significantly greater in the mucinous group ( p = 0.001). CD3 ( p = 0.001) and CD8 ( p = 0.054) expressions within the tumor epithelium were also higher in the mucinous group, suggesting adequate immune infiltration despite the presence of mucin. In our analysis, microsatellite instability status was not a predictor of immune marker expression. LIMITATIONS: The relatively small size of the cohort. CONCLUSIONS: Mucinous rectal cancer is associated with an immune-rich tumor microenvironment, which was not associated with microsatellite instability status. See Video Abstract at http://links.lww.com/DCR/C65 . IMGENES DE INMUNOFLUORESCENCIA MULTIPLEXADAS REVELAN UN MICROAMBIENTE TUMORAL RICO EN INMUNIDAD EN EL CNCER RECTAL MUCINOSO CARACTERIZADO POR UNA MAYOR INFILTRACIN DE LINFOCITOS Y UNA EXPRESIN MEJORADA DE PD: ANTECEDENTES:El cáncer rectal mucinoso se asocia con una mayor incidencia de inestabilidad de microsatélites y una peor respuesta a la quimiorradioterapia neoadyuvante en comparación con otros subtipos de adenocarcinoma rectal. Los inhibidores de puntos de control inmunitarios son una familia emergente de tratamientos contra el cáncer asociados con resultados muy variables en el cáncer colorrectal. Aunque el panorama inmunitario del cáncer rectal mucinoso no se ha explorado completamente, se cree que la presencia de mucina actúa como una barrera que previene la infiltración de células inmunitarias.OBJETIVO:El objetivo de este estudio fue determinar las propiedades inmunes del cáncer de recto mucinoso e investigar el grado de infiltración de linfocitos en esta cohorte.DISEÑO:Este es un estudio de cohorte retrospectivo que involucró la tinción de inmunofluorescencia multiplexada de micromatrices tumorales.AJUSTES:Las muestras se originaron en un solo hospital docente universitario.PACIENTES:Nuestra cohorte incluyó 15 casos de cáncer de recto mucinoso y 43 casos de cáncer de recto no mucinosoPRINCIPALES MEDIDAS DE RESULTADO:Las células inmunitarias se clasificaron y cuantificaron. Se compararon los recuentos de células inmunitarias entre cohortes mucinosas y no mucinosas. Se evaluó la expresión del marcador inmunitario dentro del tejido epitelial tumoral para determinar el grado de infiltración de linfocitos.RESULTADOS:Se encontró que las células T citotóxicas ( p = 0,022) y reguladoras ( p = 0,010) estaban sobrerrepresentadas en la cohorte mucinosa en comparación con el grupo no mucinoso. También se encontró que la expresión de PD-1 era significativamente mayor en el grupo mucinoso ( p = 0,001). La expresión de CD3 ( p = 0,001) y CD8 ( p = 0,054) dentro del epitelio tumoral también fue mayor en el grupo mucinoso, lo que sugiere una infiltración inmunitaria adecuada a pesar de la presencia de mucina. En nuestro análisis, no se encontró que el estado de inestabilidad de los microsatélites sea un predictor de la expresión del marcador inmunitario.LIMITACIONES:El tamaño relativamente pequeño de la cohorte.CONCLUSIONES:El cáncer rectal mucinoso se asocia con un microambiente tumoral rico en inmunidad, que no se asoció con el estado de inestabilidad de microsatélites. Consulte el Video del Resumen en http://links.lww.com/DCR/C65 . (Traducción- Dr. Yesenia Rojas-Khalil ).

Apoptotic and Necroptotic Mediators are Differentially Expressed in Mucinous and Non-Mucinous Colorectal Cancer.

Background: Mucinous colorectal cancer (CRC) represents 10% of all CRC and is associated with chemotherapy resistance. This study aimed to determine expression of apoptosis and necroptosis mediators in mucinous CRC. Methods: RNA gene expression data were extracted from TCGA. Protein levels in 14 mucinous and 39 non-mucinous tumors were measured by multiplexed immunofluorescence. Levels of apoptosis and necroptosis signalling proteins were analysed in SW1463 (mucinous rectal), SW837 (non-mucinous rectal), LS174T (mucinous colon) and HCT116 (non-mucinous colon) cell lines by western blot. Cell death was investigated by flow cytometry measurement of propidium iodide stained cells. Results: High cleaved-Caspase 3 expression was noted in resected mucinous tumors. Western blot identified alterations in apoptosis proteins in mucinous CRC, most prominently downregulation of Bcl-xL protein levels (p=0.029) which was also observed at the mRNA level in patients by analysis of TCGA gene expression data (p<0.001). Treatment with 5-FU did not significantly elevate cell death in mucinous cells, while non-mucinous cells showed robust cell death responses. However, 5-FU-induced phosphorylation of MLKL in mucinous cancer cells, suggestive of a switch to necroptotic cell death signaling. Conclusion: Apoptotic and necroptotic mediators are differentially expressed in mucinous and non-mucinous colorectal cancers and represent targets for investigation of cell death mechanisms in the mucinous subtype.

Complex surgery and optimal consent: A variety of opinions exist among healthcare professionals.

BACKGROUND: Establishing healthcare professional's views on optimal consent in complex surgery could guide tailored consent policy, improving the process in challenging scenarios. To date, no studies have established if professionals of differing specialities agree on major aspects of consent in areas such as emergency surgery and cancer surgery. METHODS: An anonymous web based survey was distributed to a variety of disciplines in a tertiary referral centre. Questions regarding optimal methods and timing of consent in emergency and cancer surgery were posed. Comparative analyses of quantitative data were performed using chi-squared test. RESULTS: 57 responses were received from doctors and nurses of varying disciplines. Differences were found between doctors of separate specialities and nurses in opinion of optimal timing of consent (p = 0.02), consent validity over time (p < 0.001) and the utility of introducing more specific consent policy (p = 0.01). Almost all respondents agreed that healthcare professionals have differing ideas of what consent is. CONCLUSIONS: This study demonstrates differences in opinion regarding optimal consent for cancer and emergency surgery. Consideration should be given to developing consensus among healthcare professionals regarding what consent for complex surgery constitutes.

Anal squamous cell carcinoma: a retrospective case series.

BACKGROUND: Anal cancer is a relatively rare cancer with 660 cases diagnosed in 2000-2015 in Ireland (1). The current standard treatment is radical chemoradiotherapy (CRT). The aim of our study was to review the treatment and outcomes of patients with localised anal squamous cell carcinoma (SCC), who received radical treatment in our radiation oncology network between 2008 and 2014 inclusive. METHODS: Data were collected retrospectively from ARIA® oncology information system and patient charts. Statistical analyses were performed using IBM® SPSS® statistical software version 25.0. RESULTS: Seventy-nine cases of anal SCC were identified. Mean age of patients at commencement of radiotherapy (RT) was 60.2 years (standard deviation: 13.1 years). The most common total RT dose was 50.4 Gy in 28 fractions (N = 58; 73.4%). Median follow-up was 5.6 years. Two (2.6%) patients had persistent disease, seventeen (21.8%) patients developed loco-regional recurrence and nine (11.5%) patients developed solid organ metastases, four of whom had complete treatment response at the primary site. Eight patients underwent salvage anal surgery following completion of RT. Median overall survival was 10.5 years (95% confidence interval (CI) 5.1-15.8 years), median loco-regional relapse-free survival was 10.4 years (95% CI 4.4-16.3 years) and median disease-free survival was 9.3 years (95% CI 6.3-12.2 years). CONCLUSION: Our study demonstrates that treatment for anal SCC and outcomes following definitive CRT in Ireland during the study period were comparable to international standards.

An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution.

Cancer cells' ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity.

Impact of the COVID-19 pandemic on provision and outcomes of emergency abdominal surgery in Irish public hospitals.

BACKGROUND: The SARS-CoV-2 pandemic caused severe disruption to scheduled surgery in Ireland but its impact on emergency abdominal surgery (EAS) is unknown. AIMS: The primary objective was to identify changes in volume, length of stay (LOS), and survival outcomes following EAS during the pandemic. A secondary objective was to evaluate differences in EAS patient flow including admission source, ITU utilisation, discharge destination, and readmission rates. METHODS: Using a national administrative dataset, demographic, comorbidity, and patient flow data on 5611 patients admitted for EAS between 2018 and 2020 were extracted. Pre-pandemic and pandemic timeframes were compared using graphic and regression analyses, and bivariate logistic regression, adjusting for demographics and case-mix. RESULTS: There was a 19.9% decrease in EAS during the 2020 COVID-19 pandemic with no difference in comorbidity, nor in the commonest procedures. Most patients (92.4%) were admitted from home. In-hospital post-operative mortality was unchanged (7.6%). Patients over 80 comprised 16.3% of EAS pre-COVID, but 17.9% during COVID. Average total LOS reduced significantly by 4.9 days and 3.5 days during COVID-19 waves 1 (29 Feb 2020-30 June 2020) and 2 (1 July 2020-30 Nov 2020), respectively. During wave 1, pre-operative LOS reduced (1 day) and ICU LOS was significantly shorter (0.8 days), but similar change was not observed during wave 2. CONCLUSIONS: Significant improvements in patient flow following admission for EAS during the pandemic were observed. These changes were not associated with greater mortality nor increased readmission rates and offer important insights into optimal delivery of EAS services.