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1.
Surgeon ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38735800

RESUMO

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.

2.
Gut Microbes ; 16(1): 2350149, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709233

RESUMO

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.


Assuntos
Dano ao DNA , Perfilação da Expressão Gênica , Neoplasias Retais , Transdução de Sinais , Humanos , Neoplasias Retais/genética , Neoplasias Retais/imunologia , Neoplasias Retais/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Transcriptoma , Idoso
3.
Artigo em Inglês | MEDLINE | ID: mdl-38625823

RESUMO

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.

4.
Eur J Gastroenterol Hepatol ; 36(5): 578-583, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489595

RESUMO

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.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Humanos , Colite Ulcerativa/cirurgia , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Colectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia
5.
BJS Open ; 8(2)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426257

RESUMO

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.


Assuntos
Transferência da Responsabilidade pelo Paciente , Humanos , Hospitais
6.
BJS Open ; 7(6)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37931232

RESUMO

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.


Assuntos
Hospitais , Indicadores de Qualidade em Assistência à Saúde , Humanos , Risco Ajustado , Avaliação de Resultados em Cuidados de Saúde
8.
Antibiotics (Basel) ; 12(5)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37237811

RESUMO

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.

9.
Front Oncol ; 12: 815001, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912268

RESUMO

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.

10.
Ir J Med Sci ; 191(2): 681-686, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33977391

RESUMO

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.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos
11.
Cell Death Differ ; 29(4): 806-817, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34754079

RESUMO

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.


Assuntos
Neoplasias Colorretais , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X , Apoptose/fisiologia , Neoplasias Colorretais/metabolismo , Humanos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
12.
Ir J Med Sci ; 191(5): 2275-2282, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34822021

RESUMO

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.


Assuntos
COVID-19 , COVID-19/epidemiologia , Hospitais Públicos , Humanos , Tempo de Internação , Pandemias , Estudos Retrospectivos , SARS-CoV-2
14.
Dis Colon Rectum ; 64(6): 677-688, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33955407

RESUMO

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.


Assuntos
Adenocarcinoma Mucinoso/genética , Adenocarcinoma/genética , Reparo de Erro de Pareamento de DNA/genética , Neoplasias Retais/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico , Idoso , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Genes Supressores de Tumor , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Biologia Molecular/métodos , Mutação , Terapia Neoadjuvante/estatística & dados numéricos , Estadiamento de Neoplasias , Oncogenes/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Retais/cirurgia , Sequenciamento Completo do Genoma/métodos
15.
Ann Surg Oncol ; 28(12): 7999-8006, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33876348

RESUMO

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.


Assuntos
Neoplasias Colorretais , Receptor Celular 2 do Vírus da Hepatite A , Instabilidade de Microssatélites , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Receptor Celular 2 do Vírus da Hepatite A/genética , Humanos , Estadiamento de Neoplasias , Microambiente Tumoral/genética
16.
Cancers (Basel) ; 13(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808549

RESUMO

Mucinous colorectal cancer (CRC) is estimated to occur in approximately 10-15% of CRC cases and is characterized by abundant extracellular mucin. Mucinous CRC is frequently associated with resistance to apoptosis. Inferior prognosis is observed in mucinous CRC, particularly in rectal cancer and metastatic cases. Mucins are heavily glycosylated secretory or transmembrane proteins that participate in protection of the colonic epithelium. MUC2 overexpression is a hallmark of mucinous CRCs. Mucinous CRC is associated with KRAS and BRAF mutation, microsatellite instability and the CpG island methylator phenotype. Mutations of the APC gene and p53 mutations which are characteristic non-mucinous colorectal adenocarcinoma are less common in mucinous CRC. Both physical and anti-apoptotic properties of mucin provide mechanisms for resistance to cell death. Mucin glycoproteins are associated with decreased expression of pro-apoptotic proteins, increased expression of anti-apoptotic proteins and increased cell survival signaling. The role for BCL-2 proteins, including BCL-XL, in preventing apoptosis in mucinous CRC has been explored to a limited extent. Additional mechanisms opposing cell death include altered death receptor expression and altered mutation rates in genes responsible for chemotherapy resistance. The roles of alternate cell death programs including necroptosis and pyroptosis are not well understood in mucinous CRC. While the presence of MUC2 is associated with an immunosuppressive environment, the tumor immune environment of mucinous CRC and the role of immune-mediated tumor cell death likewise require further investigation. Improved understanding of cell death mechanisms in mucinous CRC may allow modification of currently used regimens and facilitate targeted treatment.

17.
Colorectal Dis ; 23(5): 1043-1048, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33512737

RESUMO

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.


Assuntos
Colite Ulcerativa , Neoplasias Colorretais/genética , Proteína Smad7/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Estudos de Casos e Controles , Colite Ulcerativa/complicações , Colite Ulcerativa/genética , Predisposição Genética para Doença , Humanos , Masculino , Recidiva Local de Neoplasia , Polimorfismo de Nucleotídeo Único
18.
Ir J Med Sci ; 190(1): 275-280, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32638152

RESUMO

INTRODUCTION: An ileal pouch anal anastomosis (IPAA) is the treatment of choice in selected patients to restore intestinal continuity following proctocolectomy. Data on IPAA in the Republic of Ireland is lacking, and surgery for IPAA has evolved over time. The aim of this retrospective study was to report our institutional outcomes from IPAA over a 20-year period. METHODS: Data were retrospectively collated from consecutive primary IPAA cases between 1998 and 2017 at Beaumont Hospital. Patient demographics and operative approach were examined, and pouch failure was estimated using the Kaplan-Meier method. RESULTS: Ninety-five patients underwent IPAA over the study period with a mean follow-up of 9.4 ± 5.6 years. The mean age at IPAA was 35.9 ± 10.0 years, and 58.9% were male. The majority were performed in 3 stages (78.9%), were performed to treat ulcerative colitis (66.3%), were of a J-pouch configuration (96.8%), and had a stapled anastomosis (70.5%). On follow-up, 28.4% reported experiencing at least 1 episode of pouchitis and the 10-year pouch failure rate was 14%. In the last decile of the study period, the mean number of IPAA performed per year increased to 10.5 ± 2.1 (P = 0.013), the age of IPAA formation reduced (P = 0.049), and the proportion completed in a minimally invasive manner increased (P < 0.001). CONCLUSIONS: Acceptable long-term outcomes were observed by our institution. A recent increase in institutional volume, reduction in patient age, and increase in the proportion of cases performed laparoscopically have been identified.


Assuntos
Anastomose Cirúrgica/métodos , Proctocolectomia Restauradora/métodos , Adulto , Feminino , Hospitais , Humanos , Irlanda , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
Surgeon ; 19(3): 156-161, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32444339

RESUMO

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.


Assuntos
Emergências , Cirurgia Geral , Serviço Hospitalar de Emergência , Mortalidade Hospitalar , Humanos , Laparotomia , Morbidade , Centros de Atenção Terciária
20.
J Surg Oncol ; 123(2): 614-621, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33238062

RESUMO

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.


Assuntos
Neoplasias Abdominais/mortalidade , Implementação de Plano de Saúde/métodos , Recidiva Local de Neoplasia/mortalidade , Períneo/cirurgia , Protectomia/mortalidade , Neoplasias Retais/mortalidade , Neoplasias Abdominais/patologia , Neoplasias Abdominais/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Períneo/patologia , Prognóstico , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
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