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1.
Surgeon ; 22(3): 166-173, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38521683

ABSTRACT

BACKGROUND: Long-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6-8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. METHODS: PubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. RESULTS: Four RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI â€‹= â€‹0.39-0.95, p â€‹= â€‹0.03), and more TD (OR 0.60, 95%CI â€‹= â€‹0.37-0.97, p â€‹= â€‹0.04) compared to SI. However, there was no difference in rates of R0 resection (p â€‹= â€‹0.87), +CRM (p â€‹= â€‹0.66), sphincter preservation (p â€‹= â€‹0.26), incomplete TME (p â€‹= â€‹0.49), LNY (p â€‹= â€‹0.55), SSI (p â€‹= â€‹0.33), AL (p â€‹= â€‹0.20), operative duration (p â€‹= â€‹0.07), mortality (p â€‹= â€‹0.89) or any surgical complication (p â€‹= â€‹0.91). CONCLUSIONS: A LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.


Subject(s)
Neoadjuvant Therapy , Randomized Controlled Trials as Topic , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/mortality , Time-to-Treatment , Chemoradiotherapy
2.
BMC Gastroenterol ; 22(1): 31, 2022 Jan 24.
Article in English | MEDLINE | ID: mdl-35073873

ABSTRACT

BACKGROUND: Colon Capsule Endoscopy (CCE) has proven efficacy in a variety of gastrointestinal diseases. Few studies have assessed patient-reported outcomes and preference between colonoscopy and CCE. METHODS: Patients from our centre who had both a CCE and colonoscopy within a 12-month period were identified. We performed over-the-phone interviews focused on satisfaction, comfort, and overall preference with a 10-point Likert scale. Electronic records were reviewed; reported Modified-Gloucester-Comfort-Scale (GCS) score, sedation, bowel preparation and endoscopist grade were documented. Data was compared between procedures. A Fishers exact test was used to compare proportions and a Student t-test was used to compare means, a p < 0.05 was considered significant. RESULTS: In all, 40 patients were identified, 57.5% (23/40) were female and the mean age was 48 years (24-78). All patients were referred for investigation of lower gastrointestinal symptoms as part of an ongoing study [Endosc Int Open. 2021;09(06):E965-70]. There was a significance difference in mean comfort (9.2 vs 6.7, p < 0.0001, 95% CI - 3.51 to - 1.44) but not satisfaction (8.3 vs 7.7, p = 0.2, 95% CI - 1.48 to 0.33) between CCE and colonoscopy. Main cause of dissatisfaction with CCE was bowel preparation and for colonoscopy was discomfort. Age and gender were not found to be variables. The correlation between GCS and patient reported values was weak (R = - 0.28). Overall, 77.5% (31/40) of patients would prefer a CCE if they required further bowel investigation. Of these, 77.4% (24/31) preferred a CCE despite the potential need for follow-up colonoscopy. CONCLUSIONS: CCE has a high satisfaction rating (8.3 vs 7.7) and has a higher patient reported comfort rating (9.2 vs 6.7) than colonoscopy. Studies have confirmed CCE and colonoscopy have equivalent diagnostic yields. The majority of patients in our cohort prefer CCE to colonoscopy. CCE should be considered as an alternative to colonoscopy in selected individuals.


Subject(s)
Capsule Endoscopy , Colorectal Neoplasms , Cohort Studies , Colonoscopy , Colorectal Neoplasms/diagnosis , Female , Humans , Middle Aged
3.
Eur J Surg Oncol ; 48(4): 890-895, 2022 04.
Article in English | MEDLINE | ID: mdl-34774395

ABSTRACT

BACKGROUND: Centralisation of rectal cancer surgery to designated centres was a key objective of the Irish national cancer control program. A national audit of rectal cancer surgery indicated centralisation was associated with improved early surgical outcomes. This study aimed to determine the impact of implementation of the national cancer strategy on survival from rectal cancer. MATERIALS AND METHODS: Data were collected from the National Cancer Registry of Ireland to include all patients with Stage I-III rectal cancer undergoing rectal cancer surgery with curative intent between 2003 and 2012. Five-year overall survival and cancer-specific survival was compared between patients in the pre-centralisation (2003-2007) and post-centralisation period (2008-2012) and between patients receiving surgery in designated cancer centres and non-cancer centres. RESULTS: The proportion of rectal cancer surgery performed in a designated cancer centre increased from 42% during 2003-2007 to 58% during 2008-2012. Five-year overall survival increased from 66.1% in 2003-2007 to 73.5% in 2008-2012 (p < 0.001). Five-year cancer-specific survival increased from 75.3% in 2003-2007 to 81.9% in 2008-2012 (p < 0.001). Surgery in a cancer centre and surgery post-centralisation were significantly associated with overall and cancer specific survival using Cox proportional hazards regression. CONCLUSION: Survival following resection of rectal cancer was significantly improved following implementation of a national cancer strategy incorporating centralisation of rectal cancer surgery.


Subject(s)
Rectal Neoplasms , Humans , Ireland/epidemiology , Rectal Neoplasms/surgery , Rectum , Registries , Retrospective Studies
4.
Pharmacogenomics J ; 21(4): 510-519, 2021 08.
Article in English | MEDLINE | ID: mdl-33731881

ABSTRACT

Previous research has identified differences in mutation frequency in genes implicated in chemotherapy resistance between mucinous and non-mucinous colorectal cancers (CRC). We hypothesized that outcomes in mucinous and non-mucinous CRC may be influenced by expression of genes responsible for chemotherapy resistance. Gene expression data from primary tumor samples were extracted from The Cancer Genome Atlas PanCancer Atlas. The distribution of clinical, pathological, and gene expression variables was compared between 74 mucinous and 521 non-mucinous CRCs. Predictors of overall survival (OS) were assessed in a multivariate analysis. Kaplan-Meier curves were constructed to compare survival according to gene expression using the log rank test. The median expression of 5-FU-related genes TYMS, TYMP, and DYPD was significantly higher in mucinous CRC compared to non-mucinous CRC (p < 0.001, p = 0.003, p < 0.001, respectively). The median expression of oxaliplatin-related genes ATP7B and SRPK1 was significantly reduced in mucinous versus non-mucinous CRC (p = 0.004, p = 0.007, respectively). At multivariate analysis, age (odds ratio (OR) = 0.96, p < 0.001), node positive disease (OR = 0.49, p = 0.005), and metastatic disease (OR = 0.32, p < 0.001) remained significant negative predictors of OS, while high SRPK1 remained a significant positive predictor of OS (OR = 1.59, p = 0.037). Subgroup analysis of rectal cancers demonstrated high SRPK1 expression was associated with significantly longer OS compared to low SRPK1 expression (p = 0.011). This study highlights that the molecular differences in mucinous CRC and non-mucinous CRC extend to chemotherapy resistance gene expression. SRPK1 gene expression was associated with OS, with a prognostic role identified in rectal cancers.


Subject(s)
Colorectal Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Inactivation, Metabolic/genetics , Aged , Copper-Transporting ATPases/genetics , Female , Gene Expression/genetics , Humans , Male , Prognosis , Protein Serine-Threonine Kinases/genetics
5.
Clin Res Hepatol Gastroenterol ; 45(6): 101637, 2021 11.
Article in English | MEDLINE | ID: mdl-33662785

ABSTRACT

BACKGROUND AND AIM: Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. MATERIALS AND METHODS: Sixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2-5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (-2) / unlikely (-1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤-0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively. RESULTS: 8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple. CONCLUSION: This study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.


Subject(s)
Capsule Endoscopy , Constriction, Pathologic , Gastrointestinal Hemorrhage/diagnosis , Humans , Intestine, Small/diagnostic imaging , Retrospective Studies , Surveys and Questionnaires
6.
Surg Oncol ; 34: 57-62, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32891354

ABSTRACT

BACKGROUND: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is variable. Identification of biomarkers to predict response is desirable in order to provide prognostic information and targeted therapy. Several studies have investigated microsatellite instability (MSI) as a predictor of response to CRT with contradictory results. This study aims to clarify the effect of MSI status on response to CRT in locally advanced rectal cancer through systematic review and meta-analysis. METHODS: A systematic search of PubMed, Embase and Cochrane databases was performed for all studies relating to MSI and response to CRT in rectal cancer using the search algorithm (Microsatellite Instability) AND (Chemoradiotherapy) AND (Rectal Cancer). From each included study the number of patients with MSI tumors and Microsatellite Stable (MSS) tumors and the numbers achieving pathological complete response (pCR) were recorded. Pooled outcome measures were determined using a random effects model and the odds ratio estimated with variance and 95% confidence interval. RESULTS: Nine published studies were identified reporting data on MSI and its effect on outcome after CRT for locally advanced rectal cancer. Five studies describing 5,877 patients included data on MSI and the number of patients achieving pCR. There was no significant association between MSI and pCR (MSI Vs MSS: 10.1% Vs 6.6%, OR 1.38, 95% CI: 0.7-2.72, p = 0.35). CONCLUSION: This meta-analysis concludes that there appears to be no significant difference in pCR rate following CRT in patients with MSI versus MSS rectal tumors.


Subject(s)
Chemoradiotherapy, Adjuvant/methods , Microsatellite Instability , Neoadjuvant Therapy/methods , Rectal Neoplasms/pathology , Humans , Prognosis , Rectal Neoplasms/genetics , Rectal Neoplasms/therapy
8.
Colorectal Dis ; 22(9): 1076-1084, 2020 09.
Article in English | MEDLINE | ID: mdl-32052545

ABSTRACT

AIM: The diagnostic role for preoperative imaging of clinically benign rectal adenomas is unclear. The objective of this systematic review and meta-analysis was to examine the diagnostic accuracy of preoperative imaging in distinguishing benign adenomas from rectal cancer. METHOD: A systematic search was performed for all studies published that correlated staging of clinically benign rectal adenomas with endorectal ultrasound (ERUS) or MRI and histology. Imaging was compared with postoperative histology and data on the numbers of true positives, false positives, true negatives and false negatives were extracted. Summary estimates of sensitivity and specificity with 95% CIs were calculated using a bivariate random effects model. The QUADAS2 tool was used to determine the methodological quality of included studies. RESULTS: Eleven studies describing 1511 patients were retrieved. A total of 1134 patients underwent local excision and 377 had a formal proctectomy. A benign rectal adenoma was diagnosed in 840 and 214 had a T1 rectal cancer. For confirming benign adenomas, the pooled sensitivity of ERUS was 0.81 (95% CI 0.69-0.89) and specificity was 0.85 (95% CI 0.68-0.93). For detecting occult T1 tumours, the pooled sensitivity of ERUS was 0.50 (95% CI 0.33-0.66) and specificity was 0.89 (95% CI 0.82-0.94). Quantitative analysis of MRI could not be performed due to insufficient studies. CONCLUSION: This study demonstrates the limited accuracy of preoperative ERUS in distinguishing benign adenomas from T1 rectal cancer. Preoperative imaging must be interpreted with caution to prevent over-staging and unnecessary proctectomy. We propose that clinically benign lesions may undergo local excision, with subsequent management based on final histology.


Subject(s)
Endosonography , Rectal Neoplasms , Humans , Magnetic Resonance Imaging , Neoplasm Staging , Preoperative Care , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Sensitivity and Specificity
9.
Dig Dis Sci ; 64(10): 2923-2932, 2019 10.
Article in English | MEDLINE | ID: mdl-31190204

ABSTRACT

BACKGROUND: Few studies have assessed factors associated with angiodysplasias during endoscopy or factors associated with symptomatic disease. AIMS: To evaluate risk factors for the presence of and contribution to symptomatic disease in patients with angiodysplasias. METHODS: We performed a systematic MEDLINE, EMBASE and Cochrane Library search according to the PRISMA guidelines for studies assessing risk factors involved in angiodysplasias detected during endoscopy and factors that lead to anemia or overt bleeding. Study quality was assessed with the Newcastle-Ottawa scale. A risk assessment was performed by selecting risk factors identified by two independent studies and/or by a large effect size. RESULTS: Twenty-three studies involving 92,634 participants were included. The overall quality of the evidence was moderate. Risk factors for the diagnosis of angiodysplasias during endoscopy confirmed by at least two studies were increasing age (OR 1.09 per year, 95% CI 1.04-1.1), chronic kidney disease (OR 4.5, 95% CI 1.9-10.5) and cardiovascular disease (2.9, 95% CI 1.4-6.2). The risk of rebleeds was higher in the presence of multiple lesions (OR 4.2, 95% CI 1.1-16.2 and 3.8, 95% CI 1.3-11.3 and 8.6, 95% CI 1.4-52.6), liver cirrhosis (OR 4.0, 95% 1.1-15.0) and prothrombin time < 30% (OR 4.2, 95% 1.1-15.4) with a moderate effect size. Multiple comorbidities were associated with an increased in-hospital mortality (OR 2.29, 95% CI 1.2-4.3). CONCLUSIONS: This systematic review identified age, chronic kidney disease and cardiovascular disease as the most important risk factors for the diagnosis of angiodysplasias during endoscopy. Multiple lesions increase the risk of recurrent bleeding.


Subject(s)
Angiodysplasia , Endoscopy, Digestive System/methods , Gastrointestinal Hemorrhage , Risk Assessment/methods , Angiodysplasia/complications , Angiodysplasia/diagnosis , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Humans , Prognosis
10.
Br J Surg ; 106(6): 682-691, 2019 05.
Article in English | MEDLINE | ID: mdl-30945755

ABSTRACT

BACKGROUND: Mucinous differentiation occurs in 5-15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta-analytical techniques to clarify the molecular associations of mucinous colorectal cancer. METHODS: This study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non-mucinous colorectal adenocarcinoma. A random-effects model was used for analysis. RESULTS: Data from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1·46, 95 per cent c.i. 1·08 to 2·00, P = 0·014) and BRAF (OR 3·49, 2·50 to 4·87; P < 0·001) mutation, MSI (OR 3·98, 3·30 to 4·79; P < 0·001) and CIMP (OR 3·56, 2·85 to 4·43; P < 0·001), and negatively with altered p53 expression (OR 0·46, 0·31 to 0·67; P < 0·001). CONCLUSION: The genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.


Subject(s)
Adenocarcinoma, Mucinous/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Adenocarcinoma, Mucinous/pathology , Colorectal Neoplasms/pathology , CpG Islands/genetics , DNA Methylation , Humans , Microsatellite Instability , Models, Statistical , Mutation , Phenotype , Proliferating Cell Nuclear Antigen/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Tumor Suppressor Protein p53/genetics
11.
Transplant Proc ; 50(10): 3434-3439, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30577217

ABSTRACT

BACKGROUND: Renal transplantation is associated with an increased risk of neoplasia, including colorectal cancer (CRC). Advances in surgical techniques and immunosuppressive medications have resulted in increased survival rates of both patients and grafts, but the incidence of CRC in the Irish renal transplant population is currently unknown. The aim of this study is to review the incidence of CRC in the Irish renal transplant population and compare it to the general population. METHODS: A retrospective review of a prospectively maintained database of all renal transplant recipients in Ireland between January 1980 and July 2017 was performed. RESULTS: Thirty-three out of 4230 transplant recipients (men = 20, women = 13) developed CRC subsequent to transplantation and were eligible for inclusion in the series. The mean age at transplantation was 51.5 years, with patients developing CRC on average 10.9 years post-transplantation; 6.1% (n = 2/33) had stage IV disease at diagnosis. The majority of patients (87.8%) had a pathologic T stage of T3/T4 and 45.5% had involvement of locoregional lymph nodes (N1/N2); 42.4% also had a mucinous component at histopathologic assessment. The incidence of CRC was higher in the transplant population compared to the general population. CONCLUSION: This is the first population-based assessment of CRC development in the Irish renal transplant population. Our data suggest that Irish transplant recipients have an increased risk of being diagnosed with a more advanced tumor than the general population, with most being diagnosed almost a decade after transplantation. This highlights the need for increased awareness among patients and clinicians and the potential need for coordinated lifelong surveillance of this patient population to ensure early detection and treatment.


Subject(s)
Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/immunology , Immunocompromised Host , Kidney Transplantation/adverse effects , Transplant Recipients/statistics & numerical data , Adult , Aged , Colorectal Neoplasms/pathology , Female , Humans , Incidence , Ireland/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors
12.
Int J Colorectal Dis ; 33(4): 459-465, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29502314

ABSTRACT

PURPOSE: Rectal prolapse is a common condition, with conflicting opinions on optimal surgical management. Existing literature is predominantly composed of case series, with a dearth of evidence demonstrating current, real-world practice. This study investigated recent national trends in management of rectal prolapse in the Republic of Ireland (ROI). METHODS: This population analysis used a national database to identify patients admitted in the ROI primarily for the management of rectal prolapse, as defined by the International Classification of Diseases, 10th Revision (ICD-10). Demographics, procedures, comorbidities, and outcomes were obtained for patients admitted from 2005 to 2015 inclusive. RESULTS: There were 2648 admissions with a primary diagnosis of rectal prolapse; 39.3% underwent surgical correction. The majority were treated with either a perineal resection (47.2%) or an abdominal rectopexy ± resection (45.1%). The population-adjusted rate of operative intervention increased over the study period, from 25 to 42 per million (p < 0.001), with no change in the mean age of patients over time (p = 0.229). The application of a laparoscopic approach increased over time (p = 0.001). Patients undergoing an abdominal rectopexy were younger than those undergoing a perineal procedure (64.1 ± 17.3 versus 75.2 ± 15.5 years, p < 0.001) despite having a similar Charlson Comorbidity Index (p = 0.097). The mortality rate for elective repair was 0.2%. CONCLUSIONS: Despite the popularization of ventral mesh rectopexy over the study period, perineal resection Delorme's procedure remains the most common procedure employed for the correction of rectal prolapse in the ROI, with specific approach determined by age.


Subject(s)
Rectal Prolapse/surgery , Aged , Aged, 80 and over , Comorbidity , Demography , Female , Humans , International Classification of Diseases , Length of Stay , Male , Middle Aged , Patient Admission , Time Factors
13.
Ir J Med Sci ; 187(2): 453-459, 2018 May.
Article in English | MEDLINE | ID: mdl-28852981

ABSTRACT

Last year, the centenary of the 1916 Easter rising in Ireland was marked by a commemorative programme organised by the Irish government including both historical and cultural events. The main themes of these events were remembering the past, celebrating Irish achievements and imagining our future. Reviewing the medical literature offers an insight into a century of achievement and change in Irish medicine, captured from the unique perspective of Ireland's oldest medical journal. This manuscript examines papers published during the last 100 years of the Irish Journal of Medical Science, specifically examining the most cited paper from each year. The majority of top cited papers originate in Ireland (77%) with Trinity College Dublin the commonest institution (n = 12) and obstetrics the most common specialty (n = 9). The average number of citations per article was 20.56 (SD ± 22.36; range 1-118) and the article with most citations was 'Coagulative properties of cancers' published in 1958 by O'Meara et al. The mean number of citations for the top cited publication each year has increased over time. The journal continued to publish even amidst backgrounds of war and civil unrest and represents an important cultural artefact that deserves our ongoing support.


Subject(s)
Publications/history , History, 20th Century , History, 21st Century , Humans
14.
Ir Med J ; 110(7): 618, 2017 Aug 12.
Article in English | MEDLINE | ID: mdl-29169000

ABSTRACT

Hidradenitis Suppurativa (HS) is characterized by chronic recurrent abscesses, nodules and draining sinus tracts with scar formation. Cutaneous Crohn's Disease (CD) may also present similarly. We wished to identify and describe an Irish cohort with combined HS and CD, with a view to a better recognition of clinical manifestations and understanding of the pathophysiology underlying these two overlapping conditions. Cases were identified using the HIPE Code at Tallaght Hospital from 1990-2014 and retrospective review was performed. Seven patients with both HS and CD were identified, 5(71%) female. The median age of diagnosis with both conditions was 37 years. In all cases, CD had preceded the diagnosis of HS. All patients smoked. Six had an increased BMI and 43% had additional autoimmune conditions. All patients required treatment with a TNF-alpha inhibitor for HS with 5 of 6 subjects having reduced frequency of flare ups and clinically less active HS on follow up.


Subject(s)
Crohn Disease/complications , Hidradenitis Suppurativa/complications , Adult , Cohort Studies , Female , Hidradenitis Suppurativa/drug therapy , Humans , Male , Research Design , Retrospective Studies
15.
Dig Dis Sci ; 62(12): 3385-3390, 2017 12.
Article in English | MEDLINE | ID: mdl-28932959

ABSTRACT

INTRODUCTION: Glucocorticoids are known to modulate a number of immunological responses including counteracting inflammation. Within tissues expressing the glucocorticoid and mineralocorticoid receptors including the colon, glucocorticoid metabolism is regulated by the isoenzymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). 11ß-HSD1 acts as an oxidoreductase converting inactive cortisone into active cortisol, while 11ß-HSD2 acts as a dehydrogenase converting active cortisol to inactive cortisone. Hexose-6 phosphate dehydrogenase (H6PDH) is a key regulator of 11ß-HSD1 activity via its generation of NADPH. Variations in the 11ß-HSD enzyme system in relation to levels of expression and regulation may have a role in IBD. The aim of this study was to investigate possible abnormalities of 11ß-HSD enzyme system in the colon of patients with IBD. METHODS: By using quantitative real-time PCR, we investigated the transcription levels of 11ß-HSD1 and 2 in colonic tissue from IBD patients and healthy controls undergoing a colonoscopy for disease assessment. Disease activity was recorded using clinical (Mayo Score/Harvey-Bradshaw Index), Biochemical (C-reactive protein), histological, and endoscopic parameters. In addition, transcription levels of H6PDH and the glucocorticoid receptor alpha (GR-α) as well as key pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, Rela (subunit for NF Kappa B)) were later examined among this group, and results were correlated with 11ß-HSD2 gene expression. Results and patient demographics were expressed as a mean (and SD), and differences between IBD patients and control groups were analyzed using a Student's t test or Mann-Whitney U test as appropriate, with a p value of ≤0.05 considered significant. Results were controlled for disease activity as outlined above. RESULTS: Results have demonstrated a significant downregulation in 11ß-HSD2 expression in IBD patients compared with controls (13.8 ± 17.1 au vs. 318.4 ± 521.1 au, p = 0.01), whereas levels of 11ß-HSD1 did not appear to vary across the two groups. Among IBD patients, there was a trend toward higher 11ß-HSD1 expression in inflamed tissue compared with matched non-inflamed tissue (422.1 ± 944 au vs. 102.2 ± 103.9, P = 0.09). Levels of H6PDH and the GR-α expression did not appear to vary among active inflamed IBD tissue and controls. As a result, we examined the association between pro-inflammatory cytokines and levels of 11ß-HSD2 expression. Results showed an upregulation of key pro-inflammatory cytokine mRNA expression (TNF-α, IL-1ß, IL-6) during inflammation with an associated downregulation of 11ß-HSD2 mRNA expression when compared to controls. Dysregulation in this pathway could have a potential role in IBD pathogenesis and may account for exogenous glucocorticoid resistance in IBD. Further work assessing the role of the 11ß-HSD enzyme system in steroid-resistant subjects is warranted.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , 11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism , Colon/enzymology , Inflammatory Bowel Diseases/enzymology , Adolescent , Adult , Aged , Aged, 80 and over , Carbohydrate Dehydrogenases/metabolism , Cytokines/metabolism , Female , Humans , Male , Middle Aged , Prospective Studies , Receptors, Glucocorticoid/metabolism , Young Adult
17.
Colorectal Dis ; 19(9): 812-818, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28273409

ABSTRACT

AIM: Anastomotic leak (AL) after anterior resection results in increased morbidity, mortality and local recurrence. The aim of this study was to assess the ability of C-reactive protein (CRP) to predict AL in the first week after anterior resection for rectal cancer. METHOD: A retrospective review of a prospectively maintained database that included all patients undergoing anterior resection between January 2008 and December 2013 was performed. The ability of CRP to predict AL was assessed using area under the receiver-operating characteristics (AUC) curves. The severity of AL was defined using the International Study Group of Rectal Cancer (ISREC) grading system. RESULTS: Two-hundred and eleven patients were included in the study. Statistically significant differences in mean CRP values were found between those with and without an AL on postoperative days 5, 6 and 7. A CRP value of 132 mg/l on postoperative day 5 had an AUC of 0.75, corresponding to a sensitivity of 70%, a specificity of 76.6%, a positive predictive value of 16.3% and a negative predictive value of 97.5%. Multivariable analysis found that a CRP of > 132 mg/l on postoperative day 5 was the only statistically significant patient factor that was linked to an increased risk of AL (HR = 8.023, 95% CI: 1.936-33.238, P = 0.004). CONCLUSION: Early detection of AL may minimize postoperative complications. CRP is a useful negative predictive test for the development of AL following anterior resection.


Subject(s)
Anastomotic Leak/etiology , C-Reactive Protein/analysis , Colectomy/adverse effects , Rectal Neoplasms/blood , Aged , Biomarkers/blood , Databases, Factual , Female , Humans , Male , Middle Aged , Postoperative Period , Predictive Value of Tests , Preoperative Period , Prospective Studies , ROC Curve , Rectal Neoplasms/surgery , Retrospective Studies , Risk Factors , Sensitivity and Specificity
18.
QJM ; 110(6): 379-382, 2017 Jun 01.
Article in English | MEDLINE | ID: mdl-28069913

ABSTRACT

AIM: To determine the prevalence of psoriasis in an IBD cohort with reference to clinical characteristics and anti-TNFα use. METHODS: Patients with psoriasis and IBD were retrospectively identified from the IBD database at Tallaght Hospital from 2000 to 2015. Pertinent clinical data were obtained from patients notes including anti-TNFα exposure. Prevalence rates of genuine and reactive psoriasis were calculated and compared using Student's T -test. A P values of <0.05 was considered significant. RESULTS: In total, 1384 IBD patients were identified. The overall prevalence rate of IBD and psoriasis was 2.4% ( n = 33), with 1.8% ( n = 25) in the Crohn's disease group and 0.6% ( n = 8) in the ulcerative colitis group. Within the psoriasis group, 24% ( n = 8 of 33) had reactive psoriasis. The prevalence rates of psoriasis in the non-biological and biological cohorts were similar 2.5% (25 of 981) and 2% (8 of 403), respectively. There was no significant association with reactive psoriasis and disease type. There was a trend towards higher rates of reactive psoriasis Adalimumab users, 3.6% (6 of 166) vs. 0.8% (2 of 237), OR = 4.283, P = 0.077, 95% CI 0.854-21.483 in infliximab users. In addition, in our cohort, smoking was not associated with any form of psoriasis in IBD, OR = 1.377, 95% CI 0.061-3.087, P = 0.437. CONCLUSION: In our large study, the prevalence rate of reactive psoriasis was similar to the background rate of psoriasis in the overall IBD cohort (2.0 vs. 2.4%). A 2% prevalence rate represents a common adverse event that clinicians should be aware of.


Subject(s)
Drug Eruptions/etiology , Gastrointestinal Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Psoriasis/chemically induced , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab/adverse effects , Adalimumab/therapeutic use , Adolescent , Adult , Aged , Databases, Factual , Drug Eruptions/epidemiology , Female , Gastrointestinal Agents/therapeutic use , Humans , Inflammatory Bowel Diseases/epidemiology , Infliximab/adverse effects , Infliximab/therapeutic use , Ireland/epidemiology , Male , Middle Aged , Prevalence , Psoriasis/epidemiology , Retrospective Studies , Smoking/adverse effects , Smoking/epidemiology , Young Adult
19.
Ir J Med Sci ; 186(1): 75-80, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27645221

ABSTRACT

BACKGROUND/AIMS: An increasing number of colon and rectal tumours are being resected using laparoscopic techniques. Identifying these tumours intraoperatively can be difficult. The use of tattooing can facilitate an easier resection; however, the lack of standardised guidelines can potentially lead to errors intraoperatively and potentially result in worse outcomes for patients. The aim of this study was to identify the most reliable method of preoperative tumour localisation from the available literature to date. METHODS: A literature review was undertaken to identify any articles related to endoscopic tattooing and tumour localisation during colorectal surgery. RESULTS: To date there is still mixed evidence regarding tattooing techniques and the choice of ink that should be used. There are numerous studies demonstrating safe tattooing techniques and highlighting the risks and benefits of different types of ink available. CONCLUSION: Based on the available studies we have recommended a standardised approach to endoscopic tattooing of colorectal tumours prior to laparoscopic resection.


Subject(s)
Colorectal Neoplasms/surgery , Laparoscopy/methods , Tattooing/standards , Colonoscopy/methods , Colorectal Neoplasms/pathology , Humans
20.
Ann R Coll Surg Engl ; 99(2): 113-116, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27659363

ABSTRACT

INTRODUCTION Recent studies have advocated the use of perioperative fluid restriction in patients undergoing major abdominal surgery as part of an enhanced recovery protocol. Series reported to date include a heterogenous group of high- and low-risk procedures but few studies have focused on rectal cancer surgery alone. The aim of this study was to assess the effects of perioperative fluid volumes on outcomes in patients undergoing elective rectal cancer resection. METHODS A prospectively maintained database of patients with rectal cancer who underwent elective surgery over a 2-year period was reviewed. Total volume of fluid received intraoperatively was calculated, as well as blood products required in the perioperative period. The primary outcome was postoperative morbidity (Clavien-Dindo grade I-IV) and the secondary outcomes were length of stay and major morbidity (Clavien-Dindo grade III-IV). RESULTS Over a 2-year period (2012-2013), 120 patients underwent elective surgery with curative intent for rectal cancer. Median total intraoperative fluid volume received was 3680ml (range 1200-9670ml); 65/120 (54.1%) had any complications, with 20/120 (16.6%) classified as major (Clavien-Dindo grade III-IV). Intraoperative volume >3500ml was an independent risk factor for the development of postoperative all-cause morbidity (P=0.02) and was associated with major morbidity (P=0.09). Intraoperative fluid volumes also correlated with length of hospital stay (Pearson's correlation coefficient 0.33; P<0.01). CONCLUSIONS Intraoperative fluid infusion volumes in excess of 3500ml are associated with increased morbidity and length of stay in patients undergoing elective surgery for rectal cancer.


Subject(s)
Digestive System Surgical Procedures/statistics & numerical data , Fluid Therapy/adverse effects , Fluid Therapy/statistics & numerical data , Rectal Neoplasms/surgery , Aged , Female , Humans , Male , Middle Aged , Perioperative Period , Prospective Studies , Rectal Neoplasms/epidemiology , Rectum/surgery , Retrospective Studies , Risk Factors
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