RESUMEN
Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.
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Suplementos Dietéticos , Ácidos Grasos Omega-3 , Aceites de Pescado , Peces , Humanos , Aceites de Pescado/administración & dosificación , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-3/administración & dosificación , Reino Unido , Masculino , Femenino , Persona de Mediana Edad , Anciano , Dieta , Adulto , Bancos de Muestras Biológicas , Alimentos Marinos , Animales , Biobanco del Reino UnidoRESUMEN
Data from experimental studies have demonstrated that marine omega-3 polyunsaturated fatty acids (O3FAs) have anti-inflammatory and anticancer properties. In the last decade, large-scale randomised controlled trials of pharmacological delivery of O3FAs and prospective cohort studies of dietary O3FA intake have continued to investigate the relationship between O3FA intake and colorectal cancer (CRC) risk and mortality. Clinical data suggest that O3FAs have differential anti-CRC activity depending on several host factors (including pretreatment blood O3FA level, ethnicity and systemic inflammatory response) and tumour characteristics (including location in the colorectum, histological phenotype (eg, conventional adenoma or serrated polyp) and molecular features (eg, microsatellite instability, cyclooxygenase expression)). Recent data also highlight the need for further investigation of the effect of O3FAs on the gut microbiota as a possible anti-CRC mechanism, when used either alone or in combination with other anti-CRC therapies. Overall, these data point towards a precision approach to using O3FAs for optimal prevention and treatment of CRC based on mechanistic understanding of host, tumour and gut microbiota factors that predict anticancer activity of O3FAs.
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Adenoma , Neoplasias Colorrectales , Ácidos Grasos Omega-3 , Adenoma/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/prevención & control , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Inestabilidad de Microsatélites , Estudios ProspectivosRESUMEN
BACKGROUND: PuraStat® is a non-bioactive haemostatic agent that has demonstrated efficacy in a number of different surgical procedures. We performed a prospective multi-centre post-market study to evaluate the efficacy and safety of PuraStat® in liver resections performed for metastatic tumors. METHODS: This was a prospective cohort study. Patients undergoing liver resection for metastatic tumor were screened for eligibility, and included if they were ≥18 years old, undergoing open liver resection, had normal liver function, and required application of PuraStat® for haemostasis where standard haemostatic techniques were either insufficient or impractical. The primary endpoint was "time to haemostasis" (TTH). Secondary endpoints included blood loss, total postoperative drainage volume, transfusion of blood products, and ease of use. RESULTS: Eighty patients were included for analysis in the intention to treat population. 207 bleeding sites were treated with PuraStat. Of these, 190 (91.7%) bleeding sites reached haemostasis after PuraStat® application. Mean TTH (mm:ss) was 1:01 (SD 1:06, range 0:09-6:55). Ease of use of the product was described as either "excellent" or "good" in 78 (98.8%) patients. No serious adverse events were identified. CONCLUSION: This study confirms the safety, efficacy and ease of use of PuraStat® in the management of bleeding in liver surgery.
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Hemostáticos , Adolescente , Hemorragia/etiología , Hemostáticos/efectos adversos , Hepatectomía/efectos adversos , Humanos , Hígado , Estudios ProspectivosRESUMEN
BACKGROUND: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut. OBJECTIVES: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum. METHODS: Ileostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC-tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing. RESULTS: There was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05). CONCLUSIONS: Oral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy. This study is registered on the ISRCTN registry as ISRCTN14530452.
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Microbioma Gastrointestinal , Ileostomía , Disponibilidad Biológica , Humanos , Íleon , Persona de Mediana Edad , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: There is a dearth of information about operative outcomes in patients ≥80 years for hepatocellular carcinoma (HCC) from Western institutions. We compare the result of HCC resections in patients <80 years vs. patients ≥80 years from our institution in the UK. METHODS: We conducted a retrospective review of all patients undergoing liver resections for HCC between 2005 and 2015. Demographics, comorbidities, morbidity, mortality and survival were compared between the two age groups. RESULTS: 200 patients underwent resection for HCC in this time period. Nineteen patients were ≥80 years and 181 were <80 years. Comorbidities measured by the Charlson Comorbidity Index were significantly higher in the ≥80 group (p < 0.0001). There was no significant difference in the extent of resection in the two groups. Morbidity and mortality between the <80 years and the ≥80 years group were not significantly different (morbidity 27% vs.16%; p = 0.29) (mortality 7% vs. 0%; p = 0.11). The one-year (83.4% vs. 88.2%; p = 0.83), five-year (56.3% vs. 55.8%; p = 0.83) and the overall survival rate rates (887 days vs. 1035 days; p = 0.66) were not significantly different between the groups. DISCUSSION: Liver resection should not be precluded based on age alone; with good outcomes in patients ≥80 years justifying surgery.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Anciano de 80 o más Años , Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Humanos , Neoplasias Hepáticas/cirugía , Estudios RetrospectivosRESUMEN
AIM: To compare outcomes following open liver resection (OLR) between patients receiving thoracic epidural (EP) versus abdominal wound catheters plus patient-controlled analgesia (AWC-PCA). METHOD: Patients were randomized 1:1 to either EP or AWC-PCA within an enhanced recovery protocol. Primary outcome was length of stay (LOS), other variables included functional recovery, pain scores, peak flow, vasopressor and fluid requirements, and postoperative complications. RESULTS: Between April 2015 and November 2017, 83 patients were randomized to EP (n = 41) or AWC-PCA (n = 42). Baseline demographics were comparable. No difference was noted in LOS (EP 6 d (3-27) vs AWC-PCA 6 d (3-66), P = 0.886). Treatment failure was 20% in the EP group versus 7% in the AWC-PCA (P = 0.09). Preoperative anesthetic time was shorter in the AWC-PCA group, 49âminutes versus 62âminutes (P = 0.003). EP patients required more vasopressor support immediately postoperatively on day 0 (14% vs 54%, Pâ=â<0.001) and day 1 (5% vs 23%, P = 0.021). Pain scores were greater on day 0, afternoon of day 1 and morning of day 2 in the AWC-PCA group however were regarded as low at all time points. No other significant differences were noted in IV fluid requirements, nausea/sedation scores, days to open bowels, length of HDU, and postoperative complications. CONCLUSION: AWC-PCA was associated with reduced treatment failure and a reduced vasopressor requirement than EP up to 2 days postoperatively. While the use of AWC-PCA did not translate into a shorter LOS in this study, it simplified patient management after OLR. EP cannot be routinely recommended following open liver resections.
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Analgesia Epidural , Analgesia Controlada por el Paciente , Anestesia Local , Recuperación Mejorada Después de la Cirugía , Hepatectomía , Dolor Postoperatorio/prevención & control , Abdomen , Adulto , Anciano , Anciano de 80 o más Años , Analgesia Controlada por el Paciente/métodos , Anestesia Local/métodos , Cateterismo/métodos , Femenino , Estudios de Seguimiento , Hepatectomía/métodos , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/epidemiología , Estudios Prospectivos , Recuperación de la Función , Herida Quirúrgica , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to investigate variation in the frequency of resections for colorectal cancer liver metastases across the English NHS. BACKGROUND: Previous research has shown significant variation in access to liver resection surgery across the English NHS. This study uses more recent data to identify whether inequalities in access to liver resection still persist. METHODS: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2012 were identified in the COloRECTal cancer data Repository (CORECT-R). All episodes of care, occurring within 3 years of the initial bowel operation, corresponding to liver resection were identified. RESULT: During the study period 157,383 patients were identified as undergoing major resection for a colorectal tumor, of whom 7423 (4.7%) underwent ≥1 liver resections. The resection rate increased from 4.1% in 2005, reaching a plateau around 5% by 2012. There was significant variation in the rate of liver resection across hospitals (2.1%-12.2%). Patients with synchronous metastases who have their primary colorectal resection in a hospital with an onsite specialist hepatobiliary team were more likely to receive a liver resection (odds ratio 1.22; 95% confidence interval, 1.10-1.35) than those treated in one without. This effect was absent in resection for metachronous metastases. CONCLUSIONS: This study presents the largest reported population-based analysis of liver resection rates in colorectal cancer patients. Significant variation has been observed in patient and hospital characteristics and the likelihood of patients receiving a liver resection, with the data showing that proximity to a liver resection service is as important a factor as deprivation.
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Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Sistema de Registros , Adulto , Anciano , Estudios de Cohortes , Colectomía/métodos , Supervivencia sin Enfermedad , Femenino , Hepatectomía/estadística & datos numéricos , Humanos , Incidencia , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Reino UnidoRESUMEN
OBJECTIVE: Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). DESIGN: A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. RESULTS: Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or ß diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. CONCLUSION: Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. TRIAL REGISTRATION NUMBER: ISRCTN18662143.
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Ácidos Grasos Omega-3/uso terapéutico , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Anciano , Cromatografía Liquida , Estudios Cruzados , Suplementos Dietéticos , Ácidos Grasos/sangre , Femenino , Voluntarios Sanos , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Liver transplantation (LT) is a transformative, life-saving procedure with life-long sequale for patients and their caregivers. The impact of LT on the patient's main caregiver can be underestimated. We carried out a systematic review of the impact of LT on the Health-Related Quality of Life (HRQL) of LT patients' main caregivers. We searched 13 medical databases from 1996 to 2015. We included studies with HRQL data on caregivers of patients following LT then quality assessed and narratively synthesized the findings from these studies. Of 7076 initial hits, only five studies fell within the scope of this study. In general, they showed caregiver burden persisted in the early period following LT. One study showed improvements, however, the other four showed caregiver's levels of stress, anxiety and depression, remained similar or got worse post-LT and remained above that of the normal population. It was suggested that HRQL of the patient impacted on the caregiver and vice versa and may be linked to patient outcomes. No data were available investigating which groups were at particular risk of low HRQL following LT or if any interventions could improve this. The current information about LT caregivers' needs and factors that impact on their HRQL are not adequately defined. Large studies are needed to examine the effects of LT on the patients' family and caregivers to understand the importance of caregiver support to maximize outcomes of LT for the patient and their caregivers.
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Cuidadores/psicología , Trasplante de Hígado , Calidad de Vida , Estrés Psicológico/epidemiología , Adaptación Psicológica , Ansiedad/epidemiología , Depresión/epidemiología , HumanosRESUMEN
BACKGROUND: Oral administration of the omega-3 fatty acid eicosapentaenoic acid (EPA), as the free fatty acid (FFA), leads to EPA incorporation into, and reduced growth of, experimental colorectal cancer liver metastases (CRCLM). DESIGN: We performed a Phase II double-blind, randomised, placebo-controlled trial of EPA-FFA 2â g daily in patients undergoing liver resection surgery for CRCLM. The patients took EPA-FFA (n=43) or placebo (n=45) prior to surgery. The primary end-point was the CRCLM Ki67 proliferation index (PI). Secondary end-points included safety and tolerability of EPA-FFA, tumour fatty acid content and CD31-positive vascularity. We also analysed overall survival (OS) and disease-free survival (DFS). RESULTS: The median (range) duration of EPA-FFA treatment was 30 (12-65) days. Treatment groups were well matched with no significant difference in disease burden at surgery or preoperative chemotherapy. EPA-FFA treatment was well tolerated with no excess of postoperative complications. Tumour tissue from EPA-FFA-treated patients demonstrated a 40% increase in EPA content (p=0.0008), no difference in Ki67 PI, but reduced vascularity in 'EPA-naïve' individuals (p=0.075). EPA-FFA also demonstrated antiangiogenic activity in vitro. In the first 18â months after CRCLM resection, EPA-FFA-treated individuals obtained OS benefit compared with placebo, although early CRC recurrence rates were similar. CONCLUSIONS: EPA-FFA therapy is safe and well tolerated in patients with advanced CRC undergoing liver surgery. EPA-FFA may have antiangiogenic properties. Remarkably, limited preoperative treatment may provide postoperative OS benefit. Phase III clinical evaluation of prolonged EPA-FFA treatment in CRCLM patients is warranted. TRIAL IDENTIFIER: ClinicalTrials.gov NCT01070355.
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Anticarcinógenos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Ácido Eicosapentaenoico/farmacología , Neoplasias Hepáticas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Cromatografía Liquida , Método Doble Ciego , Ácido Eicosapentaenoico/metabolismo , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Espectrometría de Masas en TándemRESUMEN
OBJECTIVE: To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases. BACKGROUND: There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing. METHODS: Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias. RESULTS: A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062). CONCLUSION: One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.
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Neoplasias Colorrectales/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Reino Unido/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Xanthogranulomatous cholecystitis (XGC) is often mistaken for, and may predispose to, gallbladder carcinoma (GB Ca). This study reviews the worldwide variation of the incidence, investigations, management and outcome of patients with XGC. METHODS: Data from 29 studies, cumulatively containing 1599 patients, were reviewed and results summarized by geographical region (Europe, India, Far East and Americas) with 95% confidence intervals (CIs) to present variability within regions. The main study outcomes were incidence, association with GB Ca and treatment of patients with XGC. RESULTS: Overall, the incidence of XGC was 1.3-1.9%, with the exception of India where it was 8.8%. The incidence of GB Ca associated with XGC was lowest in European studies (3.3%) varying from 5.1-5.9% in the remaining regions. Confusion with or undiagnosed GB Ca led to 10.2% of patients receiving over or under treatment. CONCLUSIONS: XGC is a global disease and is associated with GB Ca. Characteristic pathological, radiological and clinical features are shared with GB Ca and contribute to considerable treatment inaccuracy. Tissue sampling by pre-operative endoscopic ultrasound or intra-operative frozen section is required to accurately diagnose gallbladder pathology and should be performed before any extensive resection is performed.
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Colecistitis/epidemiología , Neoplasias de la Vesícula Biliar/epidemiología , Granuloma/epidemiología , Xantomatosis/epidemiología , Américas/epidemiología , Asia/epidemiología , Colecistitis/diagnóstico , Colecistitis/terapia , Errores Diagnósticos , Endosonografía , Europa (Continente)/epidemiología , Femenino , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/terapia , Granuloma/diagnóstico , Granuloma/terapia , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Xantomatosis/diagnóstico , Xantomatosis/terapiaRESUMEN
OBJECTIVE: A right and left hepatic trisectionectomy and an extended trisectionectomy are the largest liver resections performed for malignancy. This report analyses a series of 23 patients who had at least one repeat resection after a hepatic trisectionectomy for colorectal liver metastasis (CRLM). METHODS: A retrospective analysis of a single-centre prospective liver resection database from May 1996 to April 2009 was used for patient identification. Full notes, radiology and patient reviews were analysed for a variety of factors with respect to survival. RESULTS: Twenty-three patients underwent up to 3 repeat hepatic resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year survival rates after a repeat resection were 100%, 46% and 32%, respectively. No factors predictive for survival were identified. CONCLUSION: A repeat resection after a hepatic trisectionectomy for CRLM can offer extended survival and should be considered where appropriate.
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Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Neoplasias Colorrectales/patología , Hepatectomía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Metastasectomía , Adenocarcinoma/mortalidad , Adulto , Anciano , Quimioterapia Adyuvante , Neoplasias Colorrectales/mortalidad , Inglaterra , Femenino , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Imagen por Resonancia Magnética , Masculino , Metastasectomía/efectos adversos , Metastasectomía/mortalidad , Persona de Mediana Edad , Terapia Neoadyuvante , Reoperación , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Obesity levels in the United Kingdom have risen over the years. Studies from the United States and elsewhere have reported variable outcomes for obese liver transplant recipients in terms of post-liver transplant morbidity, mortality, and graft survival. This study was designed to analyze the impact of the body mass index (BMI) on outcomes following adult liver transplantation. Data from 1994 to 2009 were retrieved from a prospectively maintained database. Patients were stratified into 5 World Health Organization BMI categories: underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), obese (30.0-34.9 kg/m(2)), and morbidly obese (≥35.0 kg/m(2)). The primary outcome was an evaluation of graft and patient survival, and the secondary outcome was an assessment of postoperative morbidity. Bonferroni correction was applied with statistical significance set at P < 0.012. Kaplan-Meier curves were used to study the effects of BMI on graft and patient survival. A total of 1325 patients were included in the study: underweight (n = 47 or 3.5%), normal-weight (n = 643 or 48.5%), overweight (n = 417 or 31.5%), obese (n = 145 or 10.9%), and morbidly obese patients (n = 73 or 5.5%). The rate of postoperative infective complications was significantly higher in the overweight (60.7%, P < 0.01) and obese recipients (65.5%, P < 0.01) versus the normal-weight recipients (50.4%). The morbidly obese patients had a longer mean intensive care unit (ICU) stay than the normal-weight patients (4.7 versus 3.2 days, P = 0.03). The mean hospital stay was longer for the overweight (22.4 days, P < 0.001), obese (21.3 days, P = 0.04), and morbidly obese recipients (22.4 days, P = 0.047) versus the normal-weight recipients (18.0 days). There was no difference in death-censored graft survival or patient survival between the groups. In conclusion, this is the largest and only reported UK series on BMI and outcomes following liver transplantation. Overweight and obese patients have significantly increased morbidity in terms of infective complications after liver transplantation and, consequently, longer ICU and hospital stays.
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Trasplante de Hígado , Obesidad/complicaciones , Sobrepeso/complicaciones , Adulto , Índice de Masa Corporal , Femenino , Supervivencia de Injerto , Humanos , Tiempo de Internación , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Morbilidad , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Prospectivos , Reino UnidoRESUMEN
BACKGROUND: Prostaglandin (PG) E2 plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE2 catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE2 content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGE2 in human CRC cells in vitro. METHODS: Tissue from the periphery and centre of 20 human CRCLM was analysed for PGE2 levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) ß. RESULTS: PGE2 levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGE2. Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo. CONCLUSIONS: There is significant intra-tumoral heterogeneity in PGE2 content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGE2 metabolism should be targeted for novel treatment of advanced CRC.
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Neoplasias Colorrectales/patología , Dinoprostona/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Proteínas de Neoplasias/metabolismo , Hipoxia de la Célula , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Hidroxiprostaglandina Deshidrogenasas/metabolismo , Inmunohistoquímica , Análisis por Micromatrices , Factor de Crecimiento Transformador beta/farmacología , Células Tumorales Cultivadas , Microambiente TumoralRESUMEN
INTRODUCTION: There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis. METHODS AND ANALYSIS: The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6 monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%. ETHICS AND DISSEMINATION: Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently. TRIAL REGISTRATION NUMBER: NCT03428477.
Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Ácido Eicosapentaenoico/uso terapéutico , Calidad de Vida , Resultado del Tratamiento , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Colorrectales/patología , Método Doble Ciego , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/secundario , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
OBJECTIVES: The increase in the routine use of abdominal imaging has led to a parallel surge in the identification of polypoid lesions in the gallbladder. True gallbladder polyps (GBP) have malignant potential and surgery can prevent or treat early gallbladder cancer. In an era of constraint on health care resources, it is important to ensure that surgery is offered only to patients who have appropriate indications. The aim of this study was to assess treatment and surveillance policies for GBP among hepatobiliary and upper gastrointestinal tract surgeons in the UK in the light of published evidence. METHODS: A questionnaire on the management of GBP was devised and sent to consultant surgeon members of the Association of Upper Gastrointestinal Surgeons (AUGIS) of Great Britain and Ireland with the approval of the AUGIS Committee. It included eight questions on indications for laparoscopic cholecystectomy and surveillance based on GBP (size, number, growth rate) and patient (age, comorbidities, ethnicity) characteristics. RESULTS: A total of 79 completed questionnaires were returned. The vast majority of surgeons (>75%) stated that they would perform surgery when a single GBP reached 10 mm in size. However, there was a lack of uniformity in the management of multiple polyps and polyp growth rate, with different surveillance protocols for patients treated conservatively. CONCLUSIONS: Gallbladder polyps are a relatively common finding on abdominal ultrasound scans. The survey showed considerable heterogeneity among surgeons regarding treatment and surveillance protocols. Although no randomized controlled trials exist, national guidelines would facilitate standardization, the formulation of an appropriate algorithm and appropriate use of resources.
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Colecistectomía Laparoscópica , Enfermedades de la Vesícula Biliar/diagnóstico , Enfermedades de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/cirugía , Pólipos/diagnóstico , Pólipos/cirugía , Pautas de la Práctica en Medicina , Pólipos Adenomatosos/diagnóstico , Pólipos Adenomatosos/cirugía , Factores de Edad , Anciano , Anciano de 80 o más Años , Colecistectomía Laparoscópica/estadística & datos numéricos , Consenso , Enfermedades de la Vesícula Biliar/etnología , Enfermedades de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/etnología , Neoplasias de la Vesícula Biliar/patología , Encuestas de Atención de la Salud , Humanos , Persona de Mediana Edad , Selección de Paciente , Pólipos/etnología , Pólipos/patología , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pronóstico , Encuestas y Cuestionarios , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: Single-incision laparoscopic cholecystectomy (SILC) may be associated with less pain, shorter hospital stay and better cosmetic results than multiport laparoscopic cholecystectomy (MLC). Advocates suggest that patients prefer SILC, although research directly addressing the question of patient preferences is limited. This study aimed to assess patient preferences using currently available evidence. METHODS: Patients awaiting elective cholecystectomy were shown a series of postoperative images taken after SILC or MLC and asked which procedure this led them to prefer. This was repeated after patients had completed a questionnaire constructed using published objective data comparing patient-reported outcomes of SILC and MLC. RESULTS: The study was completed by 113 consecutive patients. After their initial viewing of the images, 16% of subjects preferred MLC. Younger age, lower body mass index and female sex were associated with choosing SILC. After completing the questionnaire, 88% of patients preferred MLC (P < 0.001). Patients ranked the level of risk for complications and postoperative pain above cosmetic results in determining their choice of procedure. CONCLUSIONS: Patients' initial preference when presented with cosmetic appearance was for SILC. When contemporary outcome data were included, the majority chose MLC. This underlines the need to fully inform patients during the consent process and indicates that patient views of SILC may differ from the views of those introducing the technology.
Asunto(s)
Conducta de Elección , Colecistectomía Laparoscópica/métodos , Colecistectomía Laparoscópica/psicología , Conocimientos, Actitudes y Práctica en Salud , Prioridad del Paciente , Pacientes/psicología , Acceso a la Información , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Índice de Masa Corporal , Distribución de Chi-Cuadrado , Colecistectomía Laparoscópica/efectos adversos , Cicatriz/etiología , Procedimientos Quirúrgicos Electivos , Inglaterra , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/etiología , Estudios Prospectivos , Recuperación de la Función , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: Accurate prediction of safe remnant liver volume to minimize complications following liver resection remains challenging. The aim of this study was to assess whether quantification of steatosis improved the predictive value of preoperative volumetric analysis. METHODS: Thirty patients undergoing planned right or extended right hemi-hepatectomy for colorectal metastases were recruited prospectively. Magnetic resonance imaging was used to assess the level of hepatic steatosis and future remnant liver volume. These data were correlated with data on postoperative hepatic insufficiency, complications and hospital stay. Correlations of remnant percentage, remnant mass to patient mass and remnant mass to body surface area with and without steatosis measurements were assessed. RESULTS: In 10 of the 30 patients the planned liver resection was altered. Moderate-severe postoperative hepatic dysfunction was seen in 17 patients. Complications arose in 14 patients. The median level of steatosis was 3.8% (range: 1.2-17.6%), but was higher in patients (n= 10) who received preoperative chemotherapy (P= 0.124), in whom the median level was 4.8% (range: 1.5-17.6%). The strongest correlation was that of remnant liver mass to patient mass (r= 0.77, P < 0.001). However, the addition of steatosis quantification did not improve this correlation (r= 0.76, P < 0.001). CONCLUSIONS: This is the first study to combine volumetric with steatosis quantifications. No significant benefit was seen in this small pilot. However, these techniques may be useful in operative planning, particularly in patients receiving preoperative chemotherapy.