J V Reynolds

St. James's Hospital, Dublin, Leinster, Ireland

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Publications (162)616.22 Total impact

  • S Croghan · O McCormack · C Muldoon · N Ravi · J V Reynolds
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    ABSTRACT: A 53-year-old man underwent neo-adjuvant chemo-radiotherapy and a 2 stage oesophagectomy for a junctional oesophageal tumour in 1996. In March 2012, a metachronous oesophageal tumour was identified, 7cm above the anastomotic margin, on a background of non-inflamed squamous mucosa. He is currently being managed with chemo-radiotherapy. Oesophageal cancer is associated with a historically poor survival rate, with primary concerns being local recurrence or death from disseminated disease. This case highlights the challenges which must be faced, as treatment strategies improve and consequently survival rates increase.
    Irish medical journal 02/2015; 108(1):22-3. · 0.51 Impact Factor
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    ABSTRACT: Background The role of CT–PET after neoadjuvant chemoradiation (nCRT) for prediction of pathological response and oncological outcome in oesophageal and junctional adenocarcinoma (OAC) is unclear. The relationship between complete metabolic response (cMR), pathological complete response (pCR) and nodal status has not been clarified.Methods Patients with locally advanced OAC selected to receive nCRT and surgery with curative intent, on the basis of staging that included CT–PET positivity, were included. Repeat scanning (PET2) with an identical protocol was performed 2–4 weeks after completion of nCRT (cisplatin and 5-fluorouracil plus 44 Gy radiation). Changes in [18F]fluorodeoxyglucose uptake, considered as either a maximum standardized uptake value (SUVmax) or a relative reduction (%ΔSUVmax), and PET-predicted nodal status following nCRT were compared with histopathological response, histological node positivity and survival.ResultsOne hundred consecutive patients with PET-positive OAC were studied. Following nCRT, PET2 identified M1 disease in 2·0 per cent of patients. There were no significant associations between PET2 SUVmax or %ΔSUVmax with respect to primary tumour stage (ypT) (P = 0.216 and P = 0·975 respectively), tumour regression grade (P = 0·109 and P = 0·232), pCR (P = 0·633 and P = 0·870) or complete resection (R0) (P = 0·440 and P = 0·235). The sensitivity of PET2 for ypN was 10 per cent. %ΔSUVmax was not associated with disease-free or overall survival (P = 0·162 and P = 0·154 respectively). Of 46 patients with a cMR on PET2, 37 (80 per cent) had histological evidence of residual tumour in the resected specimen, and cMR was not associated with overall survival benefit (P = 0·478).ConclusionCT–PET following nCRT for OAC has poor prognostic and discriminatory value for clinical application.
    British Journal of Surgery 12/2014; 101(13). DOI:10.1002/bjs.9670 · 5.54 Impact Factor
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    ABSTRACT: Contemporary clinical management of Barrett's esophagus has highlighted the lack of accurate predictive markers of disease progression to esophageal cancer. This study aims to examine alterations in mitochondrial energy metabolism profiles across the entire disease progression sequence in Barrett's esophagus. An in-vitro model was used to screen 84 genes associated with mitochondrial energy metabolism. Three energy metabolism genes (ATP12A, COX4I2, COX8C) were significantly altered across the in-vitro Barrett's disease sequence. In-vivo validations across the Barrett's sequence demonstrated differential expression of these genes. Tissue microarrays demonstrated significant alterations in both epithelial and stromal oxidative phosphorylation (ATP5B and Hsp60) and glycolytic (PKM2 and GAPDH) protein markers across the in-vivo Barrett's sequence. Levels of ATP5B in sequential follow up surveillance biopsy material segregated Barrett's non progressors and progressors to HGD and cancer. Utilizing the Seahorse XF24 flux analyzer, in-vitro Barrett's and adenocarcinoma cells exhibited altered levels of various oxidative parameters. We show for the first time that mitochondrial energy metabolism is differentially altered across the metaplasia-dysplasia-adenocarcinoma sequence and that oxidative phosphorylation profiles have predictive value in segregating Barrett's non progressors and progressors to adenocarcinoma.
    Cancer Letters 08/2014; 354(1). DOI:10.1016/j.canlet.2014.07.035 · 5.62 Impact Factor
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    ABSTRACT: Background: The MAGIC/UK Medical Research Council (MRC) trial set the standard of care for treatment of resectable gastric and junctional adenocarcinoma, demonstrating that perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (ECF) confers a survival benefit over surgery alone. The randomized ECF for advanced and locally advanced esophagogastric cancer (REAL-2) trial showed that, in the metastatic setting, the EOX regimen (epirubicin, oxaliplatin and capecitabine) is as effective as ECF, with a favourable toxicity profile. Methods: Consecutive patients with resectable gastric or junctional adenocarcinoma treated with perioperative EOX, between 2007 and 2012, were retrospectively analysed. Results: Fifty-nine patients (12 female, 47 male), commenced EOX therapy; 47 underwent surgery. A good pathological response was seen in 34%, (16/47). Disease recurrence occurred in 19 patients (19/47, 40%). Median overall survival was 22 months, with 4-year survival of 47%. Chemotoxicities were consistent with those previously reported for this regimen. Conclusion: This study in a high-volume centre demonstrates that EOX in resectable gastric and junctional adenocarcinoma is associated with a reasonable safety profile, and efficacy consistent with that reported for ECF.
    Irish Journal of Medical Science 05/2014; 184(2). DOI:10.1007/s11845-014-1135-y · 0.83 Impact Factor
  • T Moran · P Lawlor · M Brennan · N Ravi · J V Reynolds
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    ABSTRACT: Manometry is the gold standard investigation of innate or acquired motility disorders in the oesophagus. New technology in the form of high-resolution manometry (HRM) may supplant traditional water-perfused manometry and enhance standardisation of manometric interpretation and reporting. This study reports on a 10-year experience of 5,184 consecutive patients using the traditional methods, and an early experience with HRM. Of 5,184 patients assessed, 4,509 (87 %) had both pH and manometry and 675 (13 %) had manometry only. 3,523 (78 %) of the pH /manometry group had normal motility, 635 (14 %) showed ineffective motility (IM), 213 (5 %) a non-specific motility disturbance (NSMD), 42 (0.9 %) achalasia, 58 (1.3 %) nutcracker oesophagus, 22 (0.5 %) hypertensive LOS (HLOS), 8 (0.2 %) diffuse oesophageal spasm (DOS) and 8 (0.2 %) had scleroderma. For those referred solely for manometry only, 324 (48 %) had normal motility, 72 (11 %) IM, 51 (8 %) NSMD, 175 (26 %) achalasia, 16 (2 %) nutcracker oesophagus, 32 (5 %) HLOS, 1 (0.1 %) DOS and 4 (0.6 %) had scleroderma. 92 patients to date have been studied with HRM, with enhanced definition of lower oesophageal sphincter (LOS) function. For patients referred for reflux related symptoms, motility disorders are present in 22 % of the cases. Conversely, of the patients referred for dysphagia, motility disturbances are detected in 52 % of the cases sent for manometry. Our initial experience shows that HRM technology is adding a valuable dimension and clearer understanding of motility patterns in the dysphagic patient.
    Irish Journal of Medical Science 05/2014; 184(2). DOI:10.1007/s11845-014-1123-2 · 0.83 Impact Factor
  • J M Howard · M C Cathcart · L Healy · P Beddy · C Muldoon · G P Pidgeon · J V Reynolds
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    ABSTRACT: Oesophageal adenocarcinoma is an exemplar model of an obesity-associated adenocarcinoma. Altered secretion of adipokines by visceral fat is believed to play a key role in tumorigenesis. This study examined leptin receptor (ObR) and adiponectin receptor (AdipoR1 and AdipoR2) expression in oesophageal cancer, and its relationship with patient obesity status, clinicopathological data and patient survival. Tissue microarrays were constructed from paraffin-embedded oesophagectomy specimens. ObR, AdipoR1 and AdipoR2 expression was quantified by immunohistochemistry. Anthropometric data were measured at the time of diagnosis, and obesity status was assessed using visceral fat area determined by computed tomography and body mass index. Receptor expression was correlated with various clinicopathological and anthropometric variables. Patient survival was estimated using the Kaplan-Meier method, and results compared between those with low versus high receptor expression. A Cox multivariable regression model was used to assess the relationship between survival and a number of co-variables. All 125 tumours analysed expressed AdipoR1 and AdipoR2, whereas 96·8 per cent expressed ObR. There was no significant difference in tumour pathological features or patient obesity status between tumours with low versus high ObR expression. A high level of AdipoR1 expression was significantly associated with increased patient age, obesity and less advanced tumour (T) category. Expression of AdipoR2 was inversely associated with T category (P = 0·043). Low AdipoR1 expression was an independent predictor of improved overall survival (hazard ratio 0·56, 95 per cent confidence interval 0·35 to 0·90; P = 0·017). The association between adiponectin receptor expression, obesity status and tumour category and survival suggests a potential mechanism linking obesity and oesophageal cancer.
    British Journal of Surgery 05/2014; 101(6). DOI:10.1002/bjs.9469 · 5.54 Impact Factor
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    ABSTRACT: Barrett's esophagus (BE) arising from chronic gastro-oesophageal reflux (GERD) is the main pathologic precursor of esophageal adenocarcinoma (EAC). The risk of progression to high-grade dysplasia (HGD) and EAC is unclear, and recent population studies from Denmark and Northern Ireland suggest that this has been overestimated in the past. No data exist from the Republic of Ireland. A detailed clinical, endoscopic, and pathologic database was established in one center as a proposed pilot for a national registry, and initial and follow-up data were abstracted by a data manager. One thousand ninety-three patients were registered, 60 patients with HGD were excluded, leaving 1033, with a median age of 59 and 2 : 1 male to female ratio, and 3599 person-years of follow-up. The overall incidence of HGD/EAC was 1.33% per year overall, 0.85% if the first year is excluded. Within the first year after index endoscopy, 18 cases of HGD or EAC were identified, and 30 following the first year. Low-grade dysplasia (LGD) on index endoscopy was associated with an incidence of progression of 6.5% per year, and 3.1% when tertiary referrals were excluded. These data provide important demographic and clinical information on the population of Irish patients with BE, with incidence rates of progression higher than recently published population-based registry series, perhaps relating to sampling and pathological assessment. Low-grade dysplasia on initial biopsy is a significant proxy marker of risk of progression.
    Diseases of the Esophagus 01/2014; 28(2). DOI:10.1111/dote.12166 · 1.78 Impact Factor
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    ABSTRACT: Maple syrup urine disease (MSUD) has an incidence of 1:125,000 newborns in Ireland. Patients, when fasting, or in a catabolic state build up toxic metabolites leading to progressive neurological dysfunction. We describe the necessary peri-operative management of a patient with MSUD who developed symptomatic gallstones requiring a laparoscopic cholecystectomy.
    Irish medical journal 10/2013; Volume 106(9). · 0.51 Impact Factor
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    ABSTRACT: Maple syrup urine disease (MSUD) has an incidence of 1:125,000 newborns in Ireland. Patients, when fasting, or in a catabolic state build up toxic metabolites leading to progressive neurological dysfunction. We describe the necessary peri-operative management of a patient with MSUD who developed symptomatic gallstones requiring a laparoscopic cholecystectomy.
    Irish medical journal 10/2013; 106(9):277-8. · 0.51 Impact Factor
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    ABSTRACT: Esophageal adenocarcinoma (EAC) is the eighth most common cancer worldwide, and approximately 15% of patients survive 5 years. Reflux disease (GERD) and Barrett's esophagus (BE) are major risk factors for the development of EAC, and epidemiologic studies highlight a strong association with obesity. The immune, inflammatory and intracellular signaling changes resulting from chronic inflammation of the esophageal squamous epithelium are increasingly well characterized. In GERD and Barrett's, an essential role for T-cells in the initiation of inflammation in the esophagus has been identified, and a balance between T-cell responses and phenotype may play an important role in disease progression. Obesity is a chronic low-grade inflammatory state, fuelled by adipose tissue derived- inflammatory mediators such as IL-6, TNF-α and leptin, representing a novel area for targeted research. Additionally, reactive oxygen species (ROS) and receptor tyrosine kinase (RTK) activation may drive progression from esophagitis to EAC, and downstream signaling pathways employed by these molecules may be important. This review will explain the diverse range of mechanisms potentially driving and maintaining inflammation within the esophagus and explore both existing and future therapeutic strategies targeting the process.
    Cancer letters 08/2013; 345(2). DOI:10.1016/j.canlet.2013.08.017 · 5.62 Impact Factor
  • A M Mongan · V Malik · S Rowley · Z Claxton · C Muldoon · D O'Toole · N Ravi · J V Reynolds
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    ABSTRACT: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal tumour of the gastrointestinal tract. The aim of this study was to present the experience of a single centre. A prospective GIST database from 1997 to 2011 in a tertiary referral centre wa reviewed. 78 patients (36 male/42 female) with a median age of 66 (range 10-93) were diagnosed with GIST during this period. Surgery was the primary treatment for 70 patients (90%); 19 (24%) resections were laparoscopic. Nineteen patients (24%) received Imatinib therapy. At a median follow up of 3 years, 10 patients (15%) had recurrence. Five-year survival was 89%. Surgery remains the mainstay of treatment. Minimally invasive approaches may be carried out with high cure rates. This study highlights the changing presentation and treatment approach, as well as the excellent outcomes achievable for GIST tumours.
    Irish medical journal 08/2013; 106(6):176-9. · 0.51 Impact Factor
  • F N Awan · M S Zulkifli · O McCormack · T Manzoor · N Ravi · B Mehigan · J V Reynolds
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    ABSTRACT: The aim in this audit study was to identify the rate of and the reasons for unanticipated admissions in general day surgery. All day ward procedures performed during the one year period from January 2011 to January 2012 were reviewed. Of 560 procedures performed, 25 (4.4%) patients were admitted. The age range of the patients admitted was from 26 to 83 years. The average BMI of the admitted patient was 28.9 (range 24-39).The average stay in hospital was 1.7 days (range 1-3 days). The reason for admission was potentially preventable in ten (40%) patients. This included eight (80%) out of ten admissions for control of postoperative pain, nausea and vomiting. Two (20%) were admitted for surgical observation due to high risk of bleeding. Fifteen (60%) of admissions were due to a non-preventable source, including 5 with a drain inserted at a perceived difficult laparoscopic cholecystectomy, 5 for urinary retention post open inguinal hernia repair, 2 for a cardiology review and 2 for further urgent investigations because of an unexpected intraoperative finding of malignancy. The rate of un-planned admission can be reduced by controlling potentially preventable causes, however a small contribution from unexpected scenarios is inevitable.
    Irish medical journal 05/2013; 106(5):153-4. · 0.51 Impact Factor
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  • K E O'Sullivan · A R Moriarty · J O Larkin · J V Reynolds
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    ABSTRACT: Adrenal metastases of oesophageal adenocarcinoma are rarely detected in the clinical setting, more frequently being found as an incidental postmortem finding in the presence of widespread metastases. With improvements in the sensitivity of radiological diagnostic modalities, the incidence of adrenal tumour detection is on the rise. We report herein a particularly rare case of primary operative management by adrenalectomy for an isolated right-sided adrenal metastasis secondary to oesophageal adenocarcinoma, with a long-term survival.
    Case Reports 04/2013; 2013. DOI:10.1136/bcr-2013-009657
  • K E O'Sullivan · J O Larkin · M Guiney · J V Reynolds
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    ABSTRACT: Acute pancreatitis is typically associated with classical clinical and radiological features. The sensitivity of CT to diagnose acute pancreatitis depends on the severity of the attack and ranges from 77% to 92% with a specificity approaching 100%. Despite the fact this is a common disease, there are myriad clinical presentations of acute pancreatitis. We report herein an especially rare presentation where severe acute necrotising pancreatitis presented with a tender inguinoscrotal swelling with a normal pancreas on CT imaging.
    Case Reports 04/2013; 2013. DOI:10.1136/bcr-2013-008726
  • J D Martin-Smith · J O Larkin · N Ravi · J V Reynolds
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    ABSTRACT: Epigastric pain is a very common symptom which can be caused by a wide range of clinical conditions. A 28 year old male presented to our clinic with new onset severe epigastric pain. As part of the routine work up for pain of this nature, we proceeded to upper gastrointestinal endoscopy. A toothpick was found lodged in the antral gastric wall with a resulting inflammatory mass abutting the free edge. It was removed successfully with full resolution of symptoms, however a review of the literature shows that ingested toothpicks can cause major morbidity.
    Irish medical journal 03/2013; 106(1):23. · 0.51 Impact Factor
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    ABSTRACT: BACKGROUND: For rectal cancer, an involved circumferential resection margin (CRM), defined as tumor cells within 1 mm of the CRM, is of established prognostic significance. This definition for the esophagus, however, is controversial, with the UK Royal College of Pathologists (RCP) recommending the 1 mm definition, while the College of American Pathologists (CAP) advises that only tumor cells at the cut margin (0 mm) define an incomplete (R1) resection. The aim of this study was to compare the clinical significance of both definitions in patients with pT3 tumors. METHODS: CAP- and RCP-defined CRM status in patients treated by surgery only or by multimodal therapy was recorded prospectively in a comprehensive database from May 2003 to May 2011. Kaplan-Meier survival curves were generated, and factors affecting survival were assessed by univariate and multivariate analysis. RESULTS: A total of 157 of 340 patients had pT3 esophageal tumors, with RCP-positive CRM in 60 %, and 18 % by CAP. There were no significant differences between RCP-positive CRM and negative margins for node-positive disease, local recurrence, and survival. CAP-positive CRM was associated with positive nodes (P = 0.036) and poorer survival (P = 0.023). Multivariate analysis revealed nodal invasion to be the only independent prognostic variable (P = 0.004). CONCLUSIONS: A CRM margin of <1 mm is common in pT3 esophageal tumors, a finding consistent with other reports. The <1 mm definition was not associated with node positivity, local recurrence, or survival, in contrast to actual involvement at the margin, suggesting lack of independent prognostic significance of the RCP definition and possible superiority of the CAP criteria for prospective registration of CRM.
    Annals of Surgical Oncology 03/2013; 20(8). DOI:10.1245/s10434-013-2899-4 · 3.93 Impact Factor
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    ABSTRACT: Objectives: Series from high volume oesophageal centres highlight an increasing prevalence of early malignant (EM) lesions. The advent of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) offer alternatives to traditional surgery. The evolution of this pattern of care in a high volume centre is analysed. Methods: Data were collected from a prospectively maintained database. 96 patients were treated with an EM lesion from 2000 to 2011. Surgery was the standard approach during the initial period (2000-2006). In 2007, with the introduction of EMR±RFA to our Centre, a rising trend toward definitive endoscopic treatment was seen. This study details the selection of cases into treatment groups and their outcomes. Results: From 2000 to 2006, 23 patients were treated with EM lesions, 96% by surgery. Seventy-three were treated from 2007 to 2011, 55% surgically and 45% by EMR±RFA. In the entire experience, there was one death from surgery and morbidity was higher in the surgery group compared with EMR±RFA (p<0.001). Three surgical patients (4.8%) relapsed with HGD or cancer, and one patient with T1N1 disease died of disease recurrence. At a median of 13 months, EMR±RFA offered 100% disease control, 72% had no endoscopic or histological evidence of Barrett's oesophagus and one patient represented with low grade dysplasia. Conclusions: This study highlights the changing pattern of care in the management of early oesophageal cancer. EMR±RFA appears an acceptable alternative to surgery in carefully selected cases. However, long-term outcome analysis using these methods is required and close interdisciplinary collaboration of specialists in gastroenterology, surgery, pathology and radiology is mandatory to achieve optimum outcomes.
    Irish Journal of Medical Science 12/2012; 182(3). DOI:10.1007/s11845-012-0890-x · 0.83 Impact Factor
  • Picardo SL · Maher SG · O'Sillivan JN · Reynolds JV
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    ABSTRACT: Cancer-related inflammation is considered the 'seventh hallmark of cancer'; many studies show that tumours develop and progress within inflammatory diseases. This review focuses on Barrett's oesophagus, a common condition in which chronic inflammation and resulting alterations in the stroma can lead to carcinogenesis, specifically oesophageal adenocarcinoma. Changes that occur in the tissue microenvironment during development of this disease are discussed. Infiltration of immune cells facilitates tumour development through production of factors that promote carcinogenesis and by enabling tumours to evade the host immune response. Small molecules including cytokines, chemokines and growth factors play key roles in both inflammation and cancer by promoting proliferation, angiogenesis and carcinogenesis and by recruiting immune cells. The extracellular matrix is altered in inflammation, and provides structural support to developing tumours. Hypoxia is a common state in cancers and inflamed tissues which causes DNA damage and induces tumourigenic factors. Finally, tissue vasculature is a vital part of its microenvironment, supplying oxygen, nutrients and growth factors to rapidly dividing cells, and providing a mechanism for metastatic spread. The cells and molecules outlined here represent potential targets for treatment of this cancer, especially in its pre-cancerous, inflammatory stage
    Digestive Surgery 08/2012; 29(3):251-260. · 2.16 Impact Factor
  • J Costelloe · O Mc Cormack · J V Reynolds
    Diseases of the Esophagus 05/2012; 26(3). DOI:10.1111/j.1442-2050.2012.01371.x · 1.78 Impact Factor

Publication Stats

3k Citations
616.22 Total Impact Points


  • 1998–2014
    • St. James's Hospital
      • Department of Vascular and Endovascular Surgery
      Dublin, Leinster, Ireland
    • Dublin Dental University Hospital
      Dublin, Leinster, Ireland
  • 1993–2014
    • Trinity College Dublin
      • • Department of Surgery
      • • Centre for Health Sciences
      Dublin, Leinster, Ireland
  • 2001–2011
    • Saint James School Of Medicine
      Παρκ Ριτζ, Illinois, United States
  • 2010
    • Dublin City University
      Dublin, Leinster, Ireland
  • 1992–1998
    • The Adelaide and Meath Hospital Ireland
      Dublin, Leinster, Ireland
    • St. Vincent’s Hospital, Fairview
      Dublin, Leinster, Ireland
  • 1995–1997
    • St. Vincent's Private Hospital
      Dublin, Leinster, Ireland
    • St. James University
      Сент-Джеймс, New York, United States
    • Royal College of Surgeons in Ireland
      Dublin, Leinster, Ireland
  • 1992–1993
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 1989
    • Hospital of the University of Pennsylvania
      • Department of Surgery
      Philadelphia, Pennsylvania, United States