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1.
J Perioper Pract ; 33(11): 332-341, 2023 Nov.
Article in English | MEDLINE | ID: mdl-35297287

ABSTRACT

BACKGROUND: Rectus sheath catheters are used as an analgesic alternative to thoracic epidural. The aim of this meta-analysis is to compare the analgesic effects and side effects of thoracic epidural and rectus sheath catheter in the setting of emergency or elective laparotomy. MATERIALS AND METHODS: A systematic review of the Cochrane library, Embase, PubMed and Medline was conducted. Papers that directly compared thoracic epidurals and rectus sheath catheters following laparotomy were identified. Literature published between 2001 and 2021 were included. Data were extracted on the following postoperative outcomes: additional analgesic requirements, pain scores, hypotension and ambulation. A random effects meta-analysis model was used to compare additional opioid requirements between thoracic epidural and rectus sheath catheter. RESULTS: Eight publications were included from five countries. This comprised 484 patients, with 120 patients being extracted from randomised trials. Thoracic epidural reduced the requirement for additional intravenous analgesia compared with rectus sheath catheters (p = 0.004). Despite this, both analgesic techniques were equivalent with regard to reported pain scores. Furthermore, rectus sheath catheters have a lower rate of postoperative hypotension and allow for earlier ambulation compared with thoracic epidural. CONCLUSIONS: The literature suggests that rectus sheath catheters provide similar analgesic effect to thoracic epidurals, but rectus sheath catheters have a favourable side effect profile.


Subject(s)
Hypotension , Laparotomy , Humans , Pain, Postoperative/prevention & control , Pain, Postoperative/drug therapy , Catheters , Analgesics, Opioid , Hypotension/drug therapy
3.
Colorectal Dis ; 23(1): 284-297, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33002261

ABSTRACT

AIM: Emergency colorectal surgery is associated with significant morbidity and mortality. Most general surgeons have a subspecialty, which forms the focus of their elective work, allowing development of specialist skill sets. The aim of this study was to assess the impact of consultant subspecialization on patient outcomes following emergency colorectal resections. METHODS: Data were requested for all emergency admissions under a general surgeon between 1 January 2002 and 31 December 2016 within the north of England. These were acquired from individual Trusts following Caldicott approval. Data included demographics, diagnoses and any procedures undertaken. Patients were assigned to cohorts based on the subspecialist interest of the consultant they were under the care of. The primary outcome of interest was 30-day postoperative mortality. Categorical data were compared with the chi-squared test, and continuous data with the t test or ANOVA. A logistic regression model determined factors associated with 30-day in-hospital mortality. RESULTS: Overall, 7648 emergency colorectal resections were performed with a 30-day postoperative mortality of 13.8%. This was significantly lower if the responsible consultant was a colorectal surgeon compared with other general surgery subspecialties (11.8% vs. 15.2%, P < 0.001). This was significant on univariate analysis (OR 0.75, P < 0.001); however, following multivariable adjustment, this was not statistically significant (P = 0.380). The colorectal specialists had a higher laparoscopy rate than their colleagues-9.8% versus 6.8% (P < 0.001). Stoma rates were also lower (46.9% vs. 51.0%, P = 0.001) and anastomosis rates higher (55.9% vs. 49.3%, P < 0.001) amongst colorectal surgeons. CONCLUSION: These findings add to the growing body of evidence that patient outcomes may be improved by involving subspecialists in colorectal emergencies.


Subject(s)
Colorectal Neoplasms , Colorectal Surgery , Colorectal Neoplasms/surgery , Emergencies , England , Humans , Retrospective Studies
4.
Eur J Gastroenterol Hepatol ; 33(6): 852-858, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33136721

ABSTRACT

BACKGROUND: Endoscopic full-thickness resection (eFTR) of the colon using the full-thickness resection device (FTRD) is a novel method for removing lesions involving, or tethered to, deeper layers of the colonic wall. The UK FTRD Registry collected data from multiple centres performing this procedure. We describe the technical feasibility, safety and early outcomes of this technique in the UK. METHODS: Data were collected and analysed on 68 patients who underwent eFTR at 11 UK centres from April 2015 to June 2019. Outcome measures were technical success, procedural time, specimen size, R0 resection, endoscopic clearance, and adverse events. Reported technical difficulties were collated. RESULTS: Indications for eFTR included non-lifting polyps (29 cases), T1 tumour resection (13), subepithelial tumour (9), and polyps at the appendix base or diverticulum (17). Target lesion resection was achieved in 60/68 (88.2%). Median specimen size was 21.7 mm (10-35 mm). Histologically confirmed R0 resection was achieved in 43/56 (76.8%) with full-thickness resection in 52/56 (92.9%). Technical difficulties occurred in 17/68 (25%) and complications in 3/68 (5.9%) patients. CONCLUSION: eFTR is a useful technique with a high success rate in treating lesions not previously amenable to endoscopic therapy. Whilst technical difficulties may arise, complication rates are low and outcomes are acceptable, making eFTR a viable alternative to surgery for some specific lesions.


Subject(s)
Adenoma , Rectum , Colon , Humans , Registries , Retrospective Studies , Treatment Outcome , United Kingdom/epidemiology
5.
J Epidemiol Community Health ; 75(1): 1-9, 2021 01.
Article in English | MEDLINE | ID: mdl-33055178

ABSTRACT

BACKGROUND: Poorer colorectal cancer survival in the UK than in similar countries may be partly due to delays in the care pathway. To address this, cancer waiting time targets were established. We investigated if socio-demographic inequalities exist in meeting cancer waiting times for colorectal cancer. METHODS: We identified primary colorectal cancers (International Classification of Diseases, Tenth Revision C18-C20; n=35 142) diagnosed in the period 2001-2010 in the Northern and Yorkshire Cancer Registry area. Using multivariable logistic regression, we calculated likelihood of referral and treatment within target by age group and deprivation quintile. RESULTS: 48% of the patients were referred to hospital within target (≤14 days from general practitioner (GP) referral to first hospital appointment); 52% started treatment within 31 days of diagnosis; and 44% started treatment within 62 days of GP referral. Individuals aged 60-69, 70-79 and 80+ years were significantly more likely to attend a first hospital appointment within 14 days than those aged <60 years (adjusted OR=1.23, 95% CI 1.12 to 1.34; adjusted OR=1.19, 95% CI 1.09 to 1.29; adjusted OR=1.30, 95% CI 1.18 to 1.42, respectively). Older age was significantly associated with lower likelihood of starting treatment within 31 days of diagnosis and 62 days of referral. Deprivation was not related to referral within target but was associated with lower likelihood of starting treatment within 31 days of diagnosis or 62 days of referral (most vs least: adjusted OR=0.82, 95% CI 0.74 to 0.91). CONCLUSIONS: Older patients with colorectal cancer were less likely to experience referral delays but more likely to experience treatment delays. More deprived patients were more likely to experience treatment delays. Investigation of patient pathways, treatment decision-making and treatment planning would improve understanding of these inequalities.


Subject(s)
Colorectal Neoplasms , Referral and Consultation , Aged , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapy , Humans , Registries , Socioeconomic Factors
6.
Cancer Prev Res (Phila) ; 14(3): 337-346, 2021 03.
Article in English | MEDLINE | ID: mdl-33115783

ABSTRACT

Inflammation drives colorectal cancer development, and colorectal cancer risk is influenced by dietary factors, including dietary fiber. Hyperactive WNT signaling occurs in colorectal cancer and may regulate inflammation. This study investigated (i) relationships between the inflammatory potential of diet, assessed using the Energy-adjusted Dietary Inflammatory Index (E-DII), and markers of WNT signaling, and (ii) whether DII status modulated the response to supplementation with two types of dietary fiber. Seventy-five healthy participants were supplemented with resistant starch and/or polydextrose (PD) or placebo for 50 days. Rectal biopsies were collected before and after intervention and used to assess WNT pathway gene expression and crypt cell proliferation. E-DII scores were calculated from food frequency questionnaire data. High-sensitivity C-reactive protein (hsCRP) and fecal calprotectin concentrations were quantified. hsCRP concentration was significantly greater in participants with higher E-DII scores [least square means (LSM) 4.7 vs. 2.4 mg/L, P = 0.03]. Baseline E-DII score correlated with FOSL1 (ß = 0.503, P = 0.003) and WNT11 (ß = 0.472, P = 0.006) expression, after adjusting for age, gender, body mass index, endoscopy procedure, and smoking status. WNT11 expression was more than 2-fold greater in individuals with higher E-DII scores (LSM 0.131 vs. 0.059, P = 0.002). Baseline E-DII modulated the effects of PD supplementation on FOSL1 expression (P = 0.04). More proinflammatory diets were associated with altered WNT signaling and appeared to modulate the effects of PD supplementation on expression of FOSL1 This is the first study to investigate relationships between the E-DII and molecular markers of WNT signaling in rectal tissue of healthy individuals.Prevention Relevance: Our finding that more inflammatory dietary components may impact large bowel health through effects on a well-recognized pathway involved in cancer development will strengthen the evidence base for dietary advice to help prevent bowel cancer.


Subject(s)
Body Mass Index , Diet/adverse effects , Dietary Fiber/therapeutic use , Dietary Supplements , Inflammation/diet therapy , Rectum/metabolism , Wnt Signaling Pathway , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Case-Control Studies , Female , Humans , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Male , Middle Aged , Risk Factors
7.
Nat Cancer ; 1(10): 976-989, 2020 10.
Article in English | MEDLINE | ID: mdl-33073241

ABSTRACT

Oxidative phosphorylation (OXPHOS) defects caused by somatic mitochondrial DNA (mtDNA) mutations increase with age in human colorectal epithelium and are prevalent in colorectal tumours, but whether they actively contribute to tumorigenesis remains unknown. Here we demonstrate that mtDNA mutations causing OXPHOS defects are enriched during the human adenoma/carcinoma sequence, suggesting they may confer a metabolic advantage. To test this we deleted the tumour suppressor Apc in OXPHOS deficient intestinal stem cells in mice. The resulting tumours were larger than in control mice due to accelerated cell proliferation and reduced apoptosis. We show that both normal crypts and tumours undergo metabolic remodelling in response to OXPHOS deficiency by upregulating the de novo serine synthesis pathway (SSP). Moreover, normal human colonic crypts upregulate the SSP in response to OXPHOS deficiency prior to tumorigenesis. Our data show that age-associated OXPHOS deficiency causes metabolic remodelling that can functionally contribute to accelerated intestinal cancer development.


Subject(s)
Intestinal Neoplasms , Mitochondrial Diseases , Animals , Cell Transformation, Neoplastic/genetics , DNA, Mitochondrial/genetics , Intestinal Neoplasms/genetics , Mice , Mitochondria/genetics , Mutation
8.
Br J Nutr ; 124(4): 374-385, 2020 08 28.
Article in English | MEDLINE | ID: mdl-32279690

ABSTRACT

There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.


Subject(s)
Cell Proliferation/drug effects , Dietary Supplements , Glucans/pharmacology , Intestinal Mucosa/cytology , Rectum/cytology , Starch/pharmacology , Aberrant Crypt Foci/metabolism , Adult , Aged , Aged, 80 and over , Colonic Neoplasms/metabolism , Double-Blind Method , Feces/chemistry , Female , Healthy Volunteers , Humans , Male , Middle Aged
9.
Int J Surg ; 77: 154-162, 2020 May.
Article in English | MEDLINE | ID: mdl-32234579

ABSTRACT

BACKGROUND: Emergency laparotomy is associated with high morbidity and mortality. Current trends suggest improvements have been made in recent years, with increased survival and shorter lengths of stay in hospital. The National Emergency Laparotomy Audit (NELA) has evaluated participating hospitals in England and Wales and their individual outcomes since 2013. This study aims to establish temporal trends for patients undergoing emergency laparotomy and evaluate the influence of NELA. METHODS: Data for emergency laparotomies admitted to NHS hospitals in the Northern Deanery between 2001 and 2016 were collected, including demographics, co-morbidities, diagnoses, operations undertaken and outcomes. The primary outcome of interest was in-hospital death within 30 days of admission. Cox-regression analysis was undertaken with adjustment for covariates. RESULTS: There were 2828 in-hospital deaths from 24,291 laparotomies within 30 days of admission (11.6%). Overall 30-day mortality significantly reduced during the 15-year period studied from 16.3% (2001-04), to 8.1% during 2013-16 (p < 0.001). After multivariate adjustment, laparotomies undertaken in more recent years were associated with a lower mortality risk compared to earlier years (2013-16: HR 0.73, p < 0.001). There was a significant improvement in 30-day postoperative mortality year-on-year during the NELA period (from 9.1 to 7.1%, p = 0.039). However, there was no difference in postoperative mortality for patients who underwent laparotomy during NELA (2013-16) compared with the preceding three years (both 8.1%, p = 0.526). DISCUSSION: 30 day postoperative mortality for emergency laparotomy has improved over the past 15-years, with significantly reduced mortality risk in recent years. However, it is unclear if NELA has yet had a measurable effect on 30-day post-operative mortality.


Subject(s)
Emergencies , Laparotomy/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Medical Audit , Middle Aged , Retrospective Studies , Young Adult
11.
Int J Surg ; 64: 24-32, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30872174

ABSTRACT

BACKGROUND: The management of perforated peptic ulcers has evolved over time and includes laparoscopic or open repair, and conservative management. The utilisation of, and outcomes from these strategies are not clear. Trends in epidemiology, management and outcomes for perforated peptic ulcer across the North of England over a 15-year period were analyzed. PATIENTS AND METHODS: Emergency General Surgical admissions data from nine NHS trusts in the North of England from 2002 to 2016 were collected and analyzed, including demographics, interventions and outcomes. Cases were identified using ICD-10 codes K25, K26 and K27 0.1, 0.2, 0.5, 0.6. RESULTS: Peptic ulcer perforation accounted for 2373 of 491141 admissions (0.48%), with a decreased incidence over time (0.62% in 2002-2006 to 0.36% in 2012-2016). Over the 15 years studied, an increasing proportion of cases were managed laparoscopically (4.5%-18.4%, p < 0.001) and under upper-gastrointestinal consultants (15.4%-28.6%, p < 0.001). Thirty-day inpatient mortality improved significantly over time (20.0%-10.8%, p < 0.001) as did mean length of stay (17.3-13.0 days, p = 0.001). Independent predictors of increased 30-day mortality were increasing age, Charlson co-morbidity score, clinical and operative risk, earlier year of admission, winter admission, weekend/bank holiday procedure and management strategy, with laparotomy and conservative management increasing risk. CONCLUSION: Outcomes (30-day mortality and LOS) improved significantly over the study period. Laparoscopic approach was increasingly utilised and was an independently significant factor associated with improved mortality. Management by upper-gastrointestinal specialists increased rates of laparoscopy, with fewer conversions to open.


Subject(s)
Laparoscopy/methods , Peptic Ulcer Perforation/surgery , Adolescent , Adult , Aged , Aged, 80 and over , England/epidemiology , Female , Humans , Laparotomy/methods , Length of Stay , Male , Middle Aged , Peptic Ulcer Perforation/epidemiology , Peptic Ulcer Perforation/mortality , Retrospective Studies , Seasons , Young Adult
12.
Int J Surg ; 62: 67-73, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30673595

ABSTRACT

BACKGROUND: General surgeons have become increasingly subspecialised in their elective practice. Emergency laparotomies, however, are performed by a range of subspecialists who may or may not have an interest in the affected area of gastrointestinal tract. This retrospective cohort study evaluates the impact of surgical subspecialisation on patient outcomes following emergency laparotomy. METHODS: Data was collected for patients who underwent an emergency abdominal procedure on the gastrointestinal tract in the North of England from 2001 to 2016. This included demographics, co-morbidities, diagnoses and procedures undertaken. Patients were grouped according to consultants' subspecialist interest. The primary outcome of interest was 30-day postoperative mortality. RESULTS: 24,291 emergency laparotomies were performed with an associated 30-day postoperative mortality of 11.7%. Laparotomies undertaken by upper gastrointestinal (UGI) or colorectal surgeons have significantly lower mortality (10.1%) when compared with other subspecialities (13.5%). More specifically, mortality was decreased for UGI (7.9% vs. 12.9%) and colorectal procedures (10.9% vs. 14.2%) when performed by surgeons with a specialist interest in the relevant area of the gastrointestinal tract (both p < 0.001). The utilisation of laparoscopic surgery is higher, in both UGI (21.8% vs. 9.0%) and colorectal procedures (7.2% vs. 3.5%), when the causative pathology is relevant to the surgeon's subspeciality (both p < 0.001). CONCLUSION: Mortality following emergency laparotomy is improved when performed under the care of gastrointestinal surgeons. Both UGI and colorectal emergency procedures have improved outcomes, with lower mortality and higher rates of laparoscopy, when under the care of a surgeon with a subspecialist interest in the affected area of the gastrointestinal tract.


Subject(s)
Digestive System Surgical Procedures/standards , Specialization/standards , Adult , Aged , Clinical Competence , Digestive System Surgical Procedures/methods , Digestive System Surgical Procedures/mortality , Emergencies , England/epidemiology , Female , Humans , Laparoscopy/methods , Laparotomy/methods , Laparotomy/mortality , Laparotomy/standards , Male , Middle Aged , Postoperative Complications/mortality , Retrospective Studies , Specialization/statistics & numerical data , Specialties, Surgical/standards , Specialties, Surgical/statistics & numerical data , Surgeons/standards , Treatment Outcome
13.
Br J Nutr ; 122(5): 509-517, 2019 09 14.
Article in English | MEDLINE | ID: mdl-30255827

ABSTRACT

Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman's rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P=0·039) and WNT11 (P=0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P=0·042), WNT11 (P=0·012) and c-MYC (P=0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3ß), catenin ß1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.


Subject(s)
Biomarkers, Tumor/metabolism , Colonic Neoplasms/prevention & control , Guideline Adherence , Wnt Signaling Pathway , Adult , Aged , Aged, 80 and over , Colonic Neoplasms/metabolism , Female , Humans , Male , Middle Aged , Proto-Oncogene Mas
14.
Mol Carcinog ; 56(9): 2104-2111, 2017 09.
Article in English | MEDLINE | ID: mdl-28418082

ABSTRACT

Colorectal cancer (CRC) risk is modulated by diet and there is convincing evidence of reduced risk with higher non-digestible carbohydrates (NDCs) consumption. Resistant starch (RS), a NDC, positively modulates the expression of oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs protect against CRC. The present study aimed to investigate the effects of supplementation with two NDCs, RS, and polydextrose (PD), on microRNA expression in the macroscopically-normal human rectal epithelium using samples from the DISC Study, a randomized, double-blind, placebo-controlled dietary intervention. We screened 1008 miRNAs in pooled post-intervention rectal mucosal samples from participants allocated to the double placebo group and those supplemented with both RS and PD. A total of 111 miRNAs were up- or down-regulated by at least twofold in the RS + PD group compared with the control group. From these, eight were selected for quantification in individual participant samples by qPCR, and fold-change direction was consistent with the array for seven miRNAs. The inconsistency for miR-133b and the lower fold-change values observed for the seven miRNAs is probably because qPCR of individual participant samples is a more robust and sensitive method of quantification than the array. miR-32 expression was increased by approximately threefold (P = 0.033) in the rectal mucosa of participants supplemented with RS + PD compared with placebo. miR-32 is involved in the regulation of processes such as cell proliferation that are dysregulated in CRC. Furthermore, miR-32 may affect non-canonical NF-κB signaling via regulation of TRAF3 expression and consequently NIK stabilization.


Subject(s)
Colon/drug effects , Dietary Supplements , Glucans/pharmacology , Intestinal Mucosa/drug effects , MicroRNAs/biosynthesis , Rectum/drug effects , Starch/pharmacology , Adult , Aged , Colon/metabolism , Digestion , Double-Blind Method , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction/methods , Rectum/metabolism
15.
Am J Clin Nutr ; 105(2): 400-410, 2017 02.
Article in English | MEDLINE | ID: mdl-28077379

ABSTRACT

BACKGROUND: Hyperactive Wnt signaling is frequently observed in colorectal cancer. Higher intakes of dietary fiber [nondigestible carbohydrates (NDCs)] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway. OBJECTIVES: We investigated the effects of supplementing healthy individuals with 2 NDCs [resistant starch (RS) and polydextrose] on fecal calprotectin concentrations and Wnt pathway-related gene expression. In addition, we determined whether effects on secreted frizzled-related protein 1 (SFRP1) expression are mediated via the epigenetic mechanisms DNA methylation and microRNA expression. DESIGN: In a randomized, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study), 75 healthy participants were supplemented with RS and/or polydextrose or placebo for 50 d in a 2 × 2 factorial design. Pre- and postintervention stool samples and rectal mucosal biopsies were collected and used to quantify calprotectin and expression of 12 Wnt-related genes, respectively. The expression of 10 microRNAs predicted to target SFRP1 was also quantified by quantitative reverse transcriptase-polymerase chain reaction, and DNA methylation was quantified at 7 CpG sites within the SFRP1 promoter region by pyrosequencing. RESULTS: NDC supplementation did not affect fecal calprotectin concentration. SFRP1 mRNA expression was reduced by both RS (P = 0.005) and polydextrose (P = 0.053). RS and polydextrose did not affect SFRP1 methylation or alter the expression of 10 microRNAs predicted to target SFRP1. There were no significant interactions between RS and polydextrose. CONCLUSIONS: RS and polydextrose supplementation did not affect fecal calprotectin concentrations. Downregulation of SFRP1 with RS and polydextrose could result in increased Wnt pathway activity. However, effects on Wnt pathway activity and downstream functional effects in the healthy large-bowel mucosa remain to be investigated. The DISC Study was registered at clinicaltrials.gov as NCT01214681.


Subject(s)
Dietary Carbohydrates/administration & dosage , Epigenesis, Genetic , Feces/chemistry , Intercellular Signaling Peptides and Proteins/metabolism , Intestinal Mucosa/metabolism , Leukocyte L1 Antigen Complex/chemistry , Membrane Proteins/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , DNA Methylation , Dietary Carbohydrates/pharmacokinetics , Double-Blind Method , Down-Regulation , Female , Glucans/chemistry , Humans , Intercellular Signaling Peptides and Proteins/genetics , Male , Membrane Proteins/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Middle Aged , Promoter Regions, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , Starch/chemistry , Wnt Signaling Pathway , Young Adult
16.
BMJ Open ; 6(9): e008810, 2016 09 06.
Article in English | MEDLINE | ID: mdl-27601484

ABSTRACT

INTRODUCTION: Laparoscopic surgery combined with enhanced recovery programmes has become the gold standard in the elective management of colorectal disease. However, there is no consensus with regard to the optimal perioperative analgesic regime in this cohort of patients, with a number of options available, including thoracic epidural spinal analgesia, patient-controlled analgesia, subcutaneous and/or intraperitoneal local anaesthetics, local anaesthetic wound infiltration catheters and transversus abdominis plane blocks. This study aims to explore any differences in analgesic strategies employed across the North East of England and to assess whether any variation in practice has an impact on clinical outcomes. METHODS AND ANALYSIS: All North East Colorectal units will be recruited for participation by the Northern Surgical Trainees Research Association (NoSTRA). Data will be collected over a consecutive 2-month period. Outcome measures will include postoperative pain score, postoperative opioid analgesic use and side effects, length of stay, 30-day complication rates, 30-day reoperative rates and 30-day readmission rates. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the National Research Ethics Service. The protocol will be disseminated through NoSTRA. Individual unit data will be presented at local meetings. Overall collective data will be published in peer-reviewed journals and presented at relevant surgical meetings.


Subject(s)
Anesthesia, Conduction/methods , Laparoscopy/adverse effects , Pain Management/methods , Perioperative Care/methods , Reoperation/statistics & numerical data , Adolescent , Adult , Aged , Analgesics, Opioid/therapeutic use , Colon/surgery , Elective Surgical Procedures/adverse effects , England , Female , Humans , Laparoscopy/methods , Length of Stay/statistics & numerical data , Male , Middle Aged , Pain Measurement , Pain, Postoperative/etiology , Patient Readmission/statistics & numerical data , Prospective Studies , Rectum/surgery , Research Design , Treatment Outcome , Young Adult
17.
Int J Surg ; 28: 13-21, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26892599

ABSTRACT

INTRODUCTION: Life expectancies in the UK are increasing and with this there is an increasing elderly population with more complex co-morbidity. Emergency surgery in the elderly is challenging in terms of decision making, managing co-morbidity and post-operative rehabilitation with high morbidity and mortality. To optimise service design and development, it is important to understand the changing pattern of emergency surgical care for this group. METHODS: After obtaining necessary approvals, we approached each hospital trust in the North of England for details of every emergency admission under a general surgeon from 2000 to 2014. Data for each admission included demographics, co-morbidities, diagnoses, procedures undertaken and outcomes. RESULTS: There were 105 002 elderly (≥70 years) emergency general surgical admissions, and mean age and co-morbidity (defined by Charlson index scores) increased (both p < 0.001). Operative intervention was undertaken in a similar proportion of patients in all age groups (13%), with more patients undergoing operations over time (p < 0.001), of which 50% were within 48 h of admission. Overall in-hospital mortality decreased significantly as did length of hospital stay (both p < 0.001). Factors associated with increased 30 day in-hospital mortality were increasing age and Charlson score, admissions directly from clinic, operations undertaken at the weekend and patients admitted earlier in the study period. CONCLUSION: The workload of emergency general surgery in the elderly is becoming more complex. This challenge is already being addressed with improvements in outcomes. The data presented here reinforces the need for new models of care with increased multidisciplinary geriatric care input into elderly surgical patient care in the perioperative period.


Subject(s)
Hospitalization/statistics & numerical data , Surgical Procedures, Operative/statistics & numerical data , Age Factors , Aged , Aged, 80 and over , Comorbidity , Emergency Treatment , England/epidemiology , Female , Geriatric Assessment , Hospital Mortality/trends , Hospitalization/trends , Humans , Length of Stay/statistics & numerical data , Length of Stay/trends , Male , Patient Readmission/statistics & numerical data , Patient Readmission/trends , Retrospective Studies , Risk Factors , Surgical Procedures, Operative/mortality , Surgical Procedures, Operative/trends , Treatment Outcome , Workload/statistics & numerical data
18.
Int J Surg ; 23(Pt A): 108-14, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26408949

ABSTRACT

AIM: We propose long-term -ostomy rate following laparoscopic rectal cancer resection must be included as an overall quality indicator of treatment in conjunction with frequently reported and readily available end points. METHOD: A database was collated prospectively of consecutive rectal cancer resections over a 6-year period. Recorded data included pre-operative MRI (tumour stage and height from the anal-verge), as well as demographics, treatment, local recurrence rate, survival and -ostomy rate as the primary outcome measure. RESULTS: 65 patients were identified and classified as low-rectal cancer if the tumour on MRI was < 6 cm from the anal verge or middle/upper-rectal cancer if between 6 and 15 cm from the anal-verge and below the peritoneal reflection. Permanent stoma rates including colostomies and non-reversed ileostomies were 31.7% for middle/upper rectal cancer; 62.5% for low-rectal cancer and an overall rate of 42.1% for all rectal cancers. For upper-rectal cancer the rates of local recurrence, predicted mortality, R0 resection and conversion were: 0%, 1.9%, 97.6% and 0% respectively. Corresponding figures for low-rectal cancer were: 4.2%, 2.7%, 95.8% and 0%. There were no significant differences for age, sex, predicted morbidity/mortality, survival, recurrence or leak rates between the groups. CONCLUSION: Laparoscopic rectal cancer surgery has a comparable permanent -ostomy rate to open rectal cancer surgery. We benchmark 31.7% as the permanent -ostomy rate for upper-rectal cancer and 62.5% for low-rectal cancer following laparoscopic resection, in the context of 96.9% R0 resection and 0% conversion rate in a consecutive series of patients.


Subject(s)
Laparoscopy/standards , Quality Indicators, Health Care , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Anal Canal/pathology , Colostomy/statistics & numerical data , England , Female , Humans , Ileostomy/statistics & numerical data , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Prospective Studies , Rectal Neoplasms/diagnosis , Rectal Neoplasms/pathology , Treatment Outcome
19.
Clin Teach ; 10(1): 38-41, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23294742

ABSTRACT

BACKGROUND: Newly qualified doctors frequently feel unprepared for clinical practice. 'Performing under stress' has been cited as a particular barrier in this transitional period. Conventional views on training using simulation state that it must take place in a controlled environment to benefit learning; however, we attempted to create a high realism 'high-stress' simulated scenario to try and prepare students for stressful situations in future practice. METHODOLOGY: Simulation stations were designed for final-year students. High realism was incorporated, as were factors designed to generate increased stress for students. Examples of this were that tutors did not prompt students during simulations, all bloods had to be taken to a 'lab', incomplete or incorrect requests were rejected and results were received in real time. All requests for senior help had to be made properly by telephone to a 'registrar'.Students completed a questionnaire rating knowledge and confidence of various session outcomes before and after the session, and rated the overall session out of 10. They also provided free-text comments. Before and after scores were compared with a Mann-Whitney U-test. RESULTS: Forty students completed the session. Overall, the session was evaluated highly by students (with a mean score of 9.6 out of 10). There was no significant difference between the pre- and post-session scores. The free-text comments reflected the utility of the enhanced realism and stress. DISCUSSION: From the students' comments we appear to have successfully created the 'stress' we set out to achieve. We were concerned that incorporating significant stress may have a negative impact on learning; however, students did not report a decrease in confidence following the session.


Subject(s)
Clinical Competence , Education, Medical, Undergraduate/methods , Health Knowledge, Attitudes, Practice , Stress, Psychological/etiology , Students, Medical/psychology , Communication , Humans , Manikins , Program Evaluation , Quality of Health Care
20.
Cochrane Database Syst Rev ; 10: CD007847, 2012 Oct 17.
Article in English | MEDLINE | ID: mdl-23076938

ABSTRACT

BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive carcinoma of the breast. The incidence of DCIS has increased substantially over the last twenty years, largely as a result of the introduction of population-based mammographic screening. The treatment of DCIS tumours involves surgery with or without radiotherapy to prevent recurrent DCIS and invasive carcinoma. However, there is clinical uncertainty as to whether postoperative hormonal treatment (tamoxifen) after surgery confers benefit in overall survival and incidence of recurrent carcinoma. OBJECTIVES: To assess the effects of postoperative tamoxifen in women having local surgical resection of DCIS. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), the Cochrane Breast Cancer Group's Specialised Register, and the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) on 16 August 2011. SELECTION CRITERIA: Published and unpublished randomised controlled trials (RCTs) and quasi-randomised controlled trials comparing tamoxifen after surgery for DCIS (regardless of oestrogen receptor status), with or without adjuvant radiotherapy. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the fixed-effect model and the results were expressed as relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs). MAIN RESULTS: We included two RCTs involving 3375 women. Tamoxifen after surgery for DCIS reduced recurrence of both ipsilateral (same side) DCIS (HR 0.75; 95% CI 0.61 to 0.92) and contralateral (opposite side) DCIS (RR 0.50; 95% CI 0.28 to 0.87). There was a trend towards decreased ipsilateral invasive cancer (HR 0.79; 95% CI 0.62 to 1.01) and reduced contralateral invasive cancer (RR 0.57; 95% CI 0.39 to 0.83). The number needed to treat in order for tamoxifen to have a protective effect against all breast events is 15. There was no evidence of a difference detected in all cause mortality (RR 1.11; 95% CI 0.89 to 1.39). Only one study, involving 1799 participants followed-up for 163 months (median) reported on adverse events (i.e. toxicity, mood changes, deep vein thrombosis, pulmonary embolism, endometrial cancer) with no significant difference between tamoxifen and placebo groups, but there was a non-significant trend towards more endometrial cancer in the tamoxifen group. AUTHORS' CONCLUSIONS: While tamoxifen after local excision for DCIS (with or without adjuvant radiotherapy) reduced the risk of recurrent DCIS (in the ipsi- and contralateral breast), it did not reduce the risk of overall mortality.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Tamoxifen/therapeutic use , Breast Neoplasms/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Female , Humans , Neoplasm Recurrence, Local/prevention & control , Postoperative Care , Randomized Controlled Trials as Topic
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