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.

Mucinous Colorectal Cancer is Associated With Expression of the TIM-3 Immune Checkpoint Independently of Microsatellite Instability (MSI) Status.

BACKGROUND: Immune checkpoint inhibition has demonstrated success in overcoming tumor-mediated immune suppression in several types of cancer. However, its clinical use is limited to a small subset of colorectal cancer (CRC) patients, and response is highly variable between CRC subtypes. This study aimed to determine the profile of immune checkpoints and factors associated with immune checkpoint inhibitor response in mucinous CRC. METHODS: Gene expression data from CRC was extracted from the TCGA PanCanAtlas data-freeze release. Gene expression data were reported as batch-corrected and normalized RNA expression derived from RNA-Seq quantification. Clinical, pathologic, and transcriptomic data were compared between mucinous and non-mucinous CRC cohorts. RESULTS: The 557 cases of CRC eligible for inclusion in this study comprised 486 cases of non-mucinous CRC (87.3 %) and 71 cases of mucinous CRC (12.7 %). High correlation was observed in the expression of the included immune checkpoints. Significantly higher expression of programmed cell death protein 1 ligand (PD-L1) and T cell immunoglobulin and mucin domain 3 (TIM-3) was observed in mucinous CRC than in non-mucinous CRC. In a multiple regression model, significant contributors to the prediction of TIM-3 gene expression were microsatellite instability (MSI) (unstandardized regression coefficient [B] = 1.223; p < 0.001), stage (American Joint Committee on Cancer [AJCC] 2; B = 0.423; p < 0.05), and mucinous status (B = 0.591; p < 0.01). CONCLUSION: Expression of TIM-3, an emerging immune checkpoint inhibition target, was significantly higher in mucinous CRC, and expression was predicted by mucinous status independently of MSI. These findings should prompt investigation of immune checkpoint signaling in the mucinous tumor microenvironment to clarify the potential for immune checkpoint inhibition in mucinous CRC.

An Insight Into the Driver Mutations and Molecular Mechanisms Underlying Mucinous Adenocarcinoma of the Rectum.

BACKGROUND: Mucinous adenocarcinoma of the rectum accounts for 10% of all rectal cancers and has an impaired response to neoadjuvant chemoradiotherapy and worse overall survival. To date, insufficient genomic research has been performed on this histological subtype. OBJECTIVE: This study aims to define the mismatch repair deficiency rate and the driver mutations underpinning mucinous adenocarcinoma of the rectum and to compare it with rectal adenocarcinoma not otherwise specified. DESIGN: Immunohistochemistry and sequencing were performed on tumor samples from our tumor biobank. SETTINGS: This study was conducted across 2 tertiary referral centers. PATIENTS: Patients with mucinous adenocarcinoma and rectal adenocarcinoma not otherwise specified who underwent rectal resection between 2008 and 2018 were included. MAIN OUTCOME MEASURES: Mismatch repair status was performed by immunohistochemical staining. Mutations in the panel of oncogenes and tumor suppressor genes were determined by sequencing on the MiSeq V3 platform. RESULTS: The study included 33 patients with mucinous adenocarcinoma of the rectum and 100 patients with rectal adenocarcinoma not otherwise specified. Those with mucinous adenocarcinoma had a mismatch repair deficiency rate of 12.1% compared to 2.0% in the adenocarcinoma not otherwise specified cohort (p = 0.04). Mucinous adenocarcinoma and adenocarcinoma not otherwise specified rectal tumors had similar mutation frequencies in most oncogenes and tumor suppressor genes. No difference was found in the KRAS mutation rate (50.0% vs 37.1%, p = 0.29) or BRAF mutation rate (6.7% vs 3.1%, p = 0.34) between the cohorts. No difference was found between the cohorts regarding recurrence-free (p = 0.29) or overall survival (p = 0.14). LIMITATIONS: The major limitations of this study were the use of formalin-fixed, paraffin-embedded tissue over fresh-frozen tissue and the small number of patients included, in particular, in the mucinous rectal cohort. CONCLUSIONS: Most mucinous rectal tumors develop and progress along the chromosomal instability pathway. Further research in the form of transcriptomics, proteomics, and analysis of the effects of the mucin barrier may yield valuable insights into the mechanisms of resistance to chemoradiotherapy in this cohort. See Video Abstract at http://links.lww.com/DCR/B464. UNA PERCEPCIN SOBRE MUTACIONES IMPULSORAS Y MECANISMOS MOLECULARES SUBYACENTES AL ADENOCARCINOMA MUCINOSO DEL RECTO: ANTECEDENTES:El adenocarcinoma mucinoso del recto, representa el 10% de todos los cánceres rectales y tiene una respuesta deficiente a la quimioradioterapia neoadyuvante y una peor supervivencia en general. A la fecha, se han realizado muy pocas investigaciones genómicas sobre este subtipo histológico.OBJETIVO:Definir la tasa de deficiencia en la reparación de desajustes y mutaciones impulsoras, que sustentan el adenocarcinoma mucinoso del recto y compararlo con el adenocarcinoma rectal no especificado de otra manera.DISEÑO:Se realizaron inmunohistoquímica y secuenciación en muestras tumorales de nuestro biobanco de tumores.AJUSTE:El estudio se realizó en dos centros de referencia terciarios.PACIENTES:Se incluyeron pacientes con adenocarcinoma mucinoso y adenocarcinoma no especificado de otra manera, sometidos a resección rectal entre 2008 y 2018.PRINCIPALES MEDIDAS DE RESULTADO:El estado de reparación de desajustes se realizó mediante tinción inmunohistoquímica. Las mutaciones en el panel de oncogenes y genes supresores de tumores, se determinaron mediante secuenciación en la plataforma MiSeq V3.RESULTADOS:El estudio incluyó a 33 pacientes con adenocarcinoma mucinoso del recto y 100 pacientes con adenocarcinoma del recto no especificado de otra manera. Aquellos con adenocarcinoma mucinoso, tenían una tasa de deficiencia de reparación de desajustes del 12,1% en comparación con el 2,0% en la cohorte de adenocarcinoma no especificado de otra manera (p = 0,04). El adenocarcinoma mucinoso y el adenocarcinoma no especificado de otra manera, tuvieron frecuencias de mutación similares en la mayoría de los oncogenes y genes supresores de tumores. No se encontraron diferencias en la tasa de mutación de KRAS (50,0% frente a 37,1%, p = 0,29) o la tasa de mutación de BRAF (6,7% frente a 3,1%, p = 0,34) entre las cohortes. No se encontraron diferencias entre las cohortes con respecto a la supervivencia libre de recurrencia (p = 0,29) o la supervivencia global (p = 0,14).LIMITACIONES:Las mayores limitaciones de este estudio, fueron el uso de tejido embebido en parafina y fijado con formalina, sobre el tejido fresco congelado y el pequeño número de pacientes incluidos, particularmente en la cohorte mucinoso rectal.CONCLUSIONES:La mayoría de los tumores rectales mucinosos se desarrollan y progresan a lo largo de la vía de inestabilidad cromosómica. La investigación adicional en forma transcriptómica, proteómica y análisis de los efectos de la barrera de la mucina, puede proporcionar información valiosa sobre los mecanismos de resistencia a la quimioradioterapia, en esta cohorte. Consulte Video Resumen en http://links.lww.com/DCR/B464.

A comparison of oncological outcomes after abdominoperineal excision before and after the implementation of a selective perineal flap closure program.

BACKGROUND AND OBJECTIVES: Abdominoperineal excision (APE) is the operation chosen when a patient has low rectal cancer unamenable to sphincter preserving surgery. Perineal flap reconstruction is associated with less wound morbidity but little is known about oncological outcomes. The objective was to compare outcomes in patients undergoing APE before and after the introduction of a program that utilized flap reconstruction of the perineum. METHODS: A retrospective review of a prospectively maintained database was performed. Patients who underwent APE followed by primary closure or flap reconstruction between 1998 and 2018 were selected. The cohorts were divided according to the implementation of the flap reconstruction program in July 2009. Clinicopathological data, recurrence and survival were compared between the cohorts. RESULTS: One hundred and forty nine patients underwent APE for rectal adenocarcinoma between 1998 and 2018. There were 57 patients in the pre-flap era and 92 in the post-flap era. Forty-six patients underwent flap reconstruction in the latter cohort (50%). More patients in the post-flap era underwent neoadjuvant chemoradiotherapy (85.9% vs. 63.2%; p < .01). Margin positivity rates decreased from 21.1% in the pre-flap era to 10.9% in the post-flap era (p = .10) and there was an associated improvement in incidence and time to local recurrence (p = .03). CONCLUSION: The use of perineal flap reconstruction is associated with a longer median time to local recurrence. Perineal flap reconstruction may contribute to reduced margin positivity.

A case-control study examining the association of smad7 and TLR single nucleotide polymorphisms on the risk of colorectal cancer in ulcerative colitis.

AIM: Ulcerative colitis (UC) is characterized by chronic mucosal inflammation and an increased risk of colorectal cancer. smad7, TLR2 and TLR4 modulate intestinal inflammation and their polymorphisms affect the risk of development of sporadic colorectal cancer. The aim of the current study was to examine the association between single nucleotide polymorphisms (SNPs) in smad7, TLR2 and TLR4 and the development of colorectal cancer in patients with UC. METHOD: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 90 patients with UC who had undergone panproctocolectomy between 1985 and 2013 (30 with UC-associated colorectal cancer and 60 control UC patients). Control cases were matched 2:1 for age at diagnosis of colitis, duration of disease and gender. Genotyping was performed for the smad7 rs4464148, rs11874392, rs12953717 and rs4939827 SNPs, the TLR2 rs5743704 and rs5743708 SNPs and the TLR4 rs4986790 and rs4986791 SNPs. RESULTS: Sixty three of the 90 patients (70%) were men and the mean age at diagnosis of UC was 38.6 ± 1.6 years. The mean time to the diagnosis of UC-associated colorectal cancer was 13.5 ± 1.9 years. The 5-year recurrence-free and cancer-specific survival rates were 76% and 88%, respectively. All eight SNPs were in Hardy-Weinberg equilibrium. None of the eight SNPs assessed in smad7, TLR2 or TLR4 were associated with the development of UC-associated colorectal cancer at an allelic or genotypic level. CONCLUSIONS: These data do not support an association between polymorphisms in smad7, TLR2 or TLR4 and the development of UC-associated colorectal cancer.

Impact of service delivery factors on patient outcomes in emergency general surgery.

BACKGROUND: Emergency general surgery (EGS) is a high-risk process and is associated with poor outcomes and high mortality. This study aimed to evaluate the service delivery factors in a tertiary referral centre which may influence patient outcomes in emergency general surgery. METHODS: Data on consecutive patients undergoing emergency laparotomy in a tertiary referral centre were prospectively collected from July 2017-July 2018. An extensive review of patient charts and IT systems was performed to extract demographic, clinical and care pathway data. Transfers for surgery from within the institution or within the centralised hospital network were recorded. RESULTS: The unadjusted 30-day mortality rate in 163 patients undergoing emergency laparotomy was 13%. On multivariate analysis, 30-day mortality was significantly associated with p-POSSUM predicted mortality (p = 0.003), p-POSSUM predicted morbidity (p = 0.01), SORT mortality (p = 0.004), ICU admission (p = 0.02), ASA grade (p < 0.001) and transfer from non-surgical services (p < 0.001). 19.2% of patients were transferred from a referring hospital for emergency laparotomy. There was no association between inter-hospital transfer and 30-day mortality while increased mortality was observed in patients admitted to non-surgical services who required laparotomy (p < 0.001). CONCLUSION: Inter-hospital transfer for emergency laparotomy was not associated with increased mortality. Increased mortality was observed in patients admitted to non-surgical services who subsequently required emergency laparotomy. Configuration of emergency general surgery services must accommodate safe and effective transfer of patients, both between and within hospitals.

Systematic review and meta-analysis of factors which reduce the length of stay associated with elective laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy is a safe ambulatory procedure in appropriately selected patients; however, day case rates remain low. The objective of this systematic review and meta-analysis was to identify interventions which are effective in reducing the length of stay (LOS) or improving the day case rate for elective laparoscopic cholecystectomy. METHODS: Comparative English-language studies describing perioperative interventions applicable to elective laparoscopic cholecystectomy in adult patients and their impact on LOS or day case rate were included. RESULTS: Quantitative data were available for meta-analysis from 80 studies of 10,615 patients. There were an additional 17 studies included for systematic review. The included studies evaluated 14 peri-operative interventions. Implementation of a formal day case care pathway was associated with a significantly shorter LOS (MD = 24.9 h, 95% CI, 18.7-31.2, p < 0.001) and an improved day case rate (OR = 3.5; 95% CI, 1.5-8.1, p = 0.005). Use of non-steroidal anti-inflammatories, dexamethasone and prophylactic antibiotics were associated with smaller reductions in LOS. CONCLUSION: Care pathway implementation demonstrated a significant impact on LOS and day case rates. A limited effect was noted for smaller independent interventions. In order to achieve optimal day case targets, a greater understanding of the effective elements of a care pathway and local barriers to implementation is required.

Mucin glycoproteins block apoptosis; promote invasion, proliferation, and migration; and cause chemoresistance through diverse pathways in epithelial cancers.

Overexpression of mucin glycoproteins has been demonstrated in many epithelial-derived cancers. The significance of this overexpression remains uncertain. The aim of this paper was to define the association of mucin glycoproteins with apoptosis, cell growth, invasion, migration, adhesion, and clonogenicity in vitro as well as tumor growth, tumorigenicity, and metastasis in vivo in epithelial-derived cancers by performing a systematic review of all published data. A systematic review of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify all papers that evaluated the association between mucin glycoproteins with apoptosis, cell growth, invasion, migration, adhesion, and clonogenicity in vitro as well as tumor growth, tumorigenicity, and metastasis in vivo in epithelial-derived cancers. PRISMA guidelines were adhered to. Results of individual studies were extracted and pooled together based on the organ in which the cancer was derived from. The initial search revealed 2031 papers, of which 90 were deemed eligible for inclusion in the study. The studies included details on MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC13, and MUC16. The majority of studies evaluated MUC1. MUC1 overexpression was consistently associated with resistance to apoptosis and resistance to chemotherapy. There was also evidence that overexpression of MUC2, MUC4, MUC5AC, MUC5B, MUC13, and MUC16 conferred resistance to apoptosis in epithelial-derived cancers. The overexpression of mucin glycoproteins is associated with resistance to apoptosis in numerous epithelial cancers. They cause resistance through diverse signaling pathways. Targeting the expression of mucin glycoproteins represents a potential therapeutic target in the treatment of epithelial-derived cancers.

Mucinous adenocarcinoma is a pharmacogenomically distinct subtype of colorectal cancer.

Mucinous colorectal cancer is a unique histological subtype that is known to respond poorly to cytotoxic chemotherapy and radiotherapy. There are a number of genes known to be associated with resistance to 5-fluorouracil (5-FU), oxaliplatin, and irinotecan. The aim of this study was to compare the somatic mutation frequency and copy number variation (CNV) in these genes between mucinous and non-mucinous colorectal cancer. A systematic search of PubMed was performed to identify papers investigating drug resistance in colorectal cancer. From this review, a list of 26 drug-resistance-associated genes was compiled. Using patient data from The Cancer Genome Atlas (TCGA), the somatic mutation rate and CNV was compared between patients with mucinous and non-mucinous colorectal cancer. Statistical analysis was carried out using GraphPad PRISM® version 5.00. Data were available on 531 patients (464 non-mucinous, 67 mucinous). A statistically significant difference in the somatic mutation rate between the two cohorts was identified in the TYMP (p = 0.0179), ATP7B (p = 0.0465), SRPK1 (p = 0.0135), ABCB1 (p = 0.0423), and ABCG2 (p = 0.0102) genes. A statistically significant difference in CNV was identified between the two cohorts in the GSTP1 (p = 0.0405), CCS (p = 0.0063), and TOP1 (p = 0.0048) genes. Differences in somatic mutation rate and CNV in genes associated with resistance to 5-FU, oxaliplatin, and irinotecan may partly account for the pattern of resistance observed in mucinous colorectal cancers. These genetic alterations may prove useful when deciding on a personalized approach to chemotherapy and may also represent potential therapeutic targets going forward.

Discharge outcomes among elderly patients undergoing emergency abdominal surgery: registry study of discharge data from Irish public hospitals.

BACKGROUND: Intra-abdominal emergency surgery is associated with high mortality risk and long length of hospital stay. The objective of this study was to explore variations in surgery rates, the relationship between admission source and discharge destination, and whether the postoperative length of stay was related to nursing home capacity in Irish counties. METHODS: Data on emergency hospital episodes for 2014-18 for patients aged over 65 years with a primary abdominal procedure code were obtained from the National Quality Assurance Improvement System. Data on population and nursing home capacity were obtained from the Central Statistics Office and the Health Information and Quality Authority. Episode rates per 100,000 were estimated for sex and age groups and compared between 26 Irish counties. The association between admission source and discharge destination was explored in terms episode numbers, length of stay and mortality. A negative binomial regression model estimated casemix adjusted excess post-operative length of stay. The correlation between excess post-operative length of stay and nursing home capacity was explored by linear regression. RESULTS: Overall, 4951 hospital episodes were included. The annual surgery rate ranged from 100 episodes per 100,000 65-69 years old to 250 per 100,000 85-89 year old men. 90% of the episodes were admitted from patients' home. Four in five of these patients returned to their home while 12.7% died at hospital. The proportion of episodes where patients returned to their home reduced to two in five for those aged 85-89 years. The post-operative length of stay was 13.6 days longer (p < 0.01) for episodes admitted from home and discharged to nursing home in comparison with episodes discharged home. A negative association (p = 0.08) was found between excess post-operative length of stay and county-level nursing home capacity. CONCLUSIONS: This study provides relevant information to support informed consent to surgery for patients and clinicians and to improve the provision of care to older patients presenting with intra-abdominal emergencies.

Gender and Specialty Influences on Personal and Professional Life Among Trainees.

OBJECTIVE: This study aimed to determine the impact of surgical training on lifestyle and parenthood, and to assess for gender-based workplace issues. BACKGROUND: The effects of a surgical career on lifestyle are difficult to quantify and may vary between male and female doctors. A gender gap is present in the highest tiers of the profession, and reasons why women do not attain senior positions are complex but likely relate to factors beyond merit alone. METHODS: An anonymous Web-based survey was distributed to Irish surgical and nonsurgical trainees. They were asked questions regarding family planning, pregnancy outcomes, parenthood, and gender issues in the workplace, with results analyzed by sex and specialty. RESULTS: Four hundred sixty trainees responded with a response rate of 53.0%; almost two thirds were female. Female trainee surgeons were less likely to have children than their male counterparts (22.5% vs 40.0%, P = 0.0215). Pregnant surgical trainees were more likely to have adverse pregnancy events than the partners of their male contemporaries (65.0% vs 11.5%, P = 0.0002), or than their female nonsurgical colleagues (P = 0.0329). Women were more likely to feel that they had missed out on a job opportunity (P < 0.001) and that their fellowship choice was influenced by their gender (P < 0.001). CONCLUSIONS: The current study highlights some areas of difficulty encountered by female surgical trainees. Surmounting the barriers to progression for female surgeons, by addressing the perceived negative impacts of surgery on lifestyle, will likely encourage trainee retention of both genders.

Predictors of Readmission Following Proctectomy for Rectal Cancer.

BACKGROUND: Unplanned readmission after surgery negatively impacts surgical recovery. Few studies have sought to define predictors of readmission in a rectal cancer cohort alone. Readmission following rectal cancer surgery may be reduced by the identification and modification of factors associated with readmission. OBJECTIVES: This study seeks to characterize the predictors of 30-day readmission following proctectomy for rectal cancer. DESIGN: This study is a retrospective analysis of prospectively gathered cohort data. Outcomes were compared between readmitted and nonreadmitted patients. Multivariate analysis of factors association with readmission was performed by using binary logistic regression. SETTINGS: This study was conducted at Beaumont Hospital, a nationally designated, publicly funded cancer center. PATIENTS: Two hundred forty-six consecutive patients who underwent proctectomy for rectal cancer between January 2012 and December 2015 were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were readmission within 30 days of discharge and the variables associated with readmission, categorized into patient factors, perioperative factors, and postoperative factors. RESULTS: Thirty-one (12.6%) patients were readmitted within 30 days of discharge following index rectal resection. The occurrence of anastomotic leaks, high-output stoma, and surgical site infections was significantly associated with readmission within 30 days (anastomotic leak OR 3.60, p = 0.02; high-output stoma OR 11.04, p = 0.003; surgical site infections OR 13.39, p = 0.01). Surgical site infections and high-output stoma maintained significant association on multivariate analysis (surgical site infections OR 10.02, p = 0.001; high-output stoma OR 9.40, p = 0.02). No significant difference was noted in the median length of stay or frequency of prolonged admissions (greater than 24 days) between readmitted and nonreadmitted patients. LIMITATIONS: The institutional database omits a number of socioeconomic factors and comorbidities that may influence readmission, limiting our capacity to analyze the relative contribution of these factors to our findings. CONCLUSIONS: An early postoperative care bundle to detect postoperative complications could prevent some unnecessary inpatient admissions following proctectomy. Key constituents should include early identification and management of stoma-related complications and surgical site infection. See Video Abstract at http://links.lww.com/DCR/A912.

Mucinous adenocarcinoma of the colon and rectum: A genomic analysis.

BACKGROUND AND OBJECTIVES: Mucinous adenocarcinoma is a distinct subtype of colorectal cancer (CRC) with a worse prognosis when compared with non-mucinous adenocarcinoma. The aim of this study was to compare somatic mutations and copy number alteration (CNA) between mucinous and non-mucinous CRC. METHODS: Data from The Cancer Genome Atlas-colon adenocarcinoma and rectum adenocarcinoma projects were utilized. Mucinous and non-mucinous CRC were compared with regard to microsatellite status, overall mutation rate, the most frequently mutated genes, mutations in genes coding for mismatch repair (MMR) proteins and genes coding for mucin glycoproteins. CNA analysis and pathway analysis was undertaken. RESULTS: Mucinous CRC was more likely to be microsatellite instability-high (MSI-H) and hypermutated. When corrected for microsatellite status the single-nucleotide variation and insertion-deletion rate was similar between the two cohorts. Mucinous adenocarcinoma was more likely to have mutations in genes coding for MMR proteins and mucin glycoproteins. Pathway analysis revealed further differences between the two histological subtypes in the cell cycle, RTK-RAS, transforming growth factor-ß, and TP53 pathways. CONCLUSIONS: Mucinous CRC has some distinct genomic aberrations when compared with non-mucinous adenocarcinoma, many of which are driven by the increased frequency of MSI-H tumors. These genomic aberrations may play an important part in the difference seen in response to treatment and prognosis in mucinous adenocarcinoma.

Efficacy of physician associate delivered virtual outpatient clinic.

PURPOSE: The capacity available to deliver outpatient surgical services is outweighed by the demand. Although additional investment is sometimes needed, better aligning resources, increasing operational efficiency and considering new processes all have a role in improving delivering these services. The purpose of this paper is to evaluate the safety of a physician associate (PA) delivered virtual outpatient department (VOPD) consultation service that was established in a General and Colorectal Surgery Department at an Irish teaching hospital. DESIGN/METHODOLOGY/APPROACH: A series of low-risk surgical patients were referred by senior surgeons to a PA delivered virtual clinic (VOPD). Medical records belonging to half the included patients were randomly selected for review by two doctors three months following discharge back to primary care to confirm appropriate standards of care and documentation and to audit any recorded adverse incidents or outcomes. FINDINGS: In total, 191 patients had been reviewed by the PA in the VOPD with 159 discharged directly back to primary care. Among the 95 medical records that were reviewed by the NCHDs, there were no recorded adverse incidents after discharge. Medical record keeping was deficient in 1 out of 95 reviewed cases. PRACTICAL IMPLICATIONS: Using a PA delivered VOPD consultation appears to have a role in following up patients who have undergone low-risk procedures irrespective of age or co-morbidity when selected appropriately. This may assist in reducing the demand on outpatient services by reducing unnecessary return visits, thereby increasing the capacity for new referrals. ORIGINALITY/VALUE: While there are reported examples to date of virtual clinics, these relate to services delivered by registered medical practitioners. Here, the authors demonstrate the acceptability of this model of care in an Irish population as delivered by a PA.

The significance of mucin pools following neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

BACKGROUND: Neoadjuvant chemo-radiotherapy is utilized for locally advanced rectal cancer to optimize local control. A subset of patients form mucin pools following radiotherapy but the association between mucin pools and pathological and oncological outcomes following curative proctectomy for rectal cancer remains unknown. OBJECTIVE: The aim of this study was to determine the significance of mucin pool formation after neoadjuvant chemoradiotherapy for rectal cancer. METHODS: This is a retrospective analysis of a prospectively maintained rectal cancer database. Patients who underwent curative proctectomy for rectal cancer following long course chemoradiotherapy between January 2007 and December 2016 were eligible for inclusion. RESULTS: A total of 297 patients were eligible for inclusion; of these 36 (12.1%) had mucin pools on final histopathology. Tumors with mucin pools were less likely to be ypT3/T4 (25.0 vs 51.0%, P = 0.003), were more likely to have a good response (83.3 vs 53.6%, P < 0.001) and more likely to have a pathologic complete response (41.7 vs 19.2%, P = 0.006) to radiotherapy. The presence of mucin pools was associated with less distant recurrence ( P < 0.05) and improved overall survival ( P = 0.02). CONCLUSIONS: The presence of mucin pools following neoadjuvant chemoradiotherapy for rectal cancer represents a surrogate marker of response to treatment and downstaging and is associated with improved survival.

An interdisciplinary approach to improve surgical antimicrobial prophylaxis.

Purpose The purpose of this paper is to improve surgical antimicrobial prophylaxis (SAP) prescribing in orthopaedic surgery using the model for improvement framework. Design/methodology/approach Orthopaedic patients receiving joint replacements, hip fracture repairs or open-reduction internal-fixation procedures were included. Antimicrobial(s); dose, time of administration and duration of SAP were evaluated for appropriateness based on the local SAP guidelines. After baseline data collection, a driver diagram was constructed with interventions devised for plan-do-study-act cycles. Data were fed back weekly using a point prevalence design (PPD). Interventions included SAP guideline changes, reminders and tools to support key messages. Findings SAP in 168 orthopaedic surgeries from 15 June 2016 to 31 January 2017 was studied. Prescribing appropriateness improved from 20 to 78 per cent. Junior doctor changeover necessitated additional education and reminders. Practical implications Due to constant staff changeover; continuous data collection, communication, education and reminders are essential to ensure continuous compliance with clinical guidance. Patients with hip fractures are difficult to weigh, requiring weight estimation for weight-based antimicrobial dosing. Unintended consequences of interventions included the necessity to change pre-operative workflow to accommodate reconstitution time of additional antimicrobials and inadvertent continuation of new antimicrobials post-operatively. Originality/value Rather than perform the traditional retrospective focused audit, we established a prospective, continuous, interventional quality improvement (QI) project focusing on internal processes within the control of the project team with rapid cyclical changes and interventions. The weekly PPD was pragmatic and enabled the QI project to be sustained with no additional resources.

BCL-2 system analysis identifies high-risk colorectal cancer patients.

OBJECTIVE: The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). DESIGN: Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project. RESULTS: High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling. CONCLUSIONS: DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors.

A meta-analysis of the clinicopathological characteristics and survival outcomes of inflammatory bowel disease associated colorectal cancer.

PURPOSE: The current study aims to use meta-analytical techniques to compare the clinicopathological characteristics and survival outcomes of inflammatory bowel disease (IBD) associated and sporadic colorectal carcinoma (CRC). Patients with IBD have an established increased risk of developing CRC. There is no consensus, however, on the clinicopathological characteristics and survival outcomes of IBD associated CRC when compared to sporadic CRC. METHODS: A comprehensive search for published studies comparing IBD associated and sporadic CRC was performed. Random effect methods were used to combine data. This study adhered to the recommendations of the MOOSE guidelines. RESULTS: Data were retrieved from 20 studies describing 571,278 patients. IBD associated CRC had an increased rate of synchronous tumors (OR 4.403, 95% CI 2.320-8.359; p < 0.001), poor differentiation (OR 1.875, 95% CI 1.425-2.466; p < 0.001), and a reduced rate of rectal cancer (OR 0.827, 95% CI 0.735-0.930; p = 0.002). IBD associated CRC however did not affect the frequency of T3/T4 tumors (OR 0.931, 95% CI 0.782-1.108; p = 0.421), lymph node positivity (OR 1.061, 95% CI 0.929-1.213; p = 0.381), metastasis at presentation (OR 0.970, 95% CI 0.776-1.211; p = 0.786), sex distribution (OR 0.978, 95% CI 0.890-1.074; p = 0.640), or 5-year overall survival (OR 1.105, 95% CI 0.414-2.949; p = 0.842). CONCLUSIONS: In this large analysis of available data, IBD associated CRC was characterized by less rectal tumors and more synchronous and poorly differentiated tumors compared with sporadic cancers, but no discernable difference in sex distribution, stage at presentation, or survival could be identified.

Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance. METHODS: The expression levels of ER stress proteins calnexin, calreticulin, GRP78 and GRP94 were determined in n = 23 Stage II and III colon cancer fresh frozen tumour and matched normal tissue samples. Data were validated in a cohort of n = 11 rectal cancer patients treated with radiochemotherapy in the neoadjuvant setting. The calnexin gene was silenced using siRNA in HCT116 cells. RESULTS: There were no increased levels of ER stress proteins in tumour compared to matched normal tissue samples in Stage II or III CRC. However, increased calnexin protein levels were predictive of poor clinical outcome in the patient cohort. Data were validated in the rectal cancer cohort treated in the neoadjuvant setting. Calnexin gene-silencing significantly reduced cell survival and increased cancer cell susceptibility to 5FU chemotherapy. CONCLUSION: Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies.

Mucinous Rectal Adenocarcinoma Is Associated with a Poor Response to Neoadjuvant Chemoradiotherapy: A Systematic Review and Meta-analysis.

BACKGROUND: Mucinous adenocarcinoma represents a potentially poor prognostic subgroup of rectal cancer. A consensus on the effect of mucinous cancer on outcomes following neoadjuvant chemoradiotherapy and curative resection for rectal cancer has not been reached. OBJECTIVE: The aim of the current study is to use meta-analytical techniques to assess the association between mucinous histology and response to neoadjuvant chemoradiotherapy in rectal cancer. DATA SOURCES: A comprehensive literature search of PubMed, Embase, and The Cochrane Library was performed. STUDY SELECTION: All studies examining the effect of mucinous histology on chemotherapeutic response in rectal cancer were included. INTERVENTIONS: No direct interventions were performed. MAIN OUTCOME MEASURES: Outcomes of mucinous rectal adenocarcinoma were compared with nonmucinous tumors by using random-effects methods to analyze data. Data are presented as ORs with 95% CIs. The main outcomes measured were the rates of pathological complete response, tumor and nodal downstaging, positive resection margin rate, local recurrence, and overall mortality. RESULTS: Eight comparative series describing outcomes in 1724 patients were identified, 241 had mucinous tumors (14%). Mucinous tumors had a reduced rate of pathological complete response (OR, 0.078; 95% CI, 0.015-0.397; p = 0.002) and tumor downstaging (OR, 0.318; 95% CI, 0.185-0.547; p < 0.001) following neoadjuvant chemoradiotherapy with an increased rate of positive resection margin (OR, 5.018; 95% CI, 3.224-7.810; p < 0.001) and poorer overall survival (OR, 1.526; 95% CI, 1.060-2.198; p = 0.023) following resection. Mucin expression did not significantly affect nodal downstaging (OR, 0.706; 95% CI, 0.295-1.693; p = 0.435) or local recurrence (OR, 1.856; 95% CI, 0.933-3.693; p = 0.078). There was no across-study heterogeneity for any end point. LIMITATIONS: Most studies were retrospectively designed, and there were variations in patient populations and duration of follow-up. CONCLUSIONS: Mucinous rectal adenocarcinoma represents a biomarker for poor response to preoperative chemoradiotherapy and is an adverse prognostic indicator.