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Article ; Online: Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity.

Donlon, N E / Power, R / Hayes, C / Reynolds, J V / Lysaght, J

2021 Volume 502, Page(s) 84–96

Abstract: Immune checkpoint blockade (ICB) has revolutionised the treatment of solid tumours, yet most patients do not derive a clinical benefit. Resistance to ICB is often contingent on the tumour microenvironment (TME) and modulating aspects of this ... ...

Abstract	Immune checkpoint blockade (ICB) has revolutionised the treatment of solid tumours, yet most patients do not derive a clinical benefit. Resistance to ICB is often contingent on the tumour microenvironment (TME) and modulating aspects of this immunosuppressive milieu is a goal of combination treatment approaches. Radiation has been used for over a century in the management of cancer with more than half of all cancer patients receiving radiotherapy. Here, we outline the rationale behind combining radiotherapy with ICB, a potential synergy through mutually beneficial remodelling of the TME. We discuss the pleiotropic effects radiation has on the TME including immunogenic cell death, activation of cytosolic DNA sensors, remodelling the stroma and vasculature, and paradoxical infiltration of both anti-tumour and suppressive immune cell populations. These events depend on the radiation dose and fractionation and optimising these parameters will be key to develop safe and effective combination regimens. Finally, we highlight ongoing efforts that combine radiation, immunotherapy and inhibitors of DNA damage response, which can help achieve a favourable equilibrium between the immunogenic and tolerogenic effects of radiation on the immune microenvironment.
MeSH term(s)	Combined Modality Therapy ; Drug Resistance, Neoplasm/radiation effects ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/therapy ; Radiotherapy ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/radiation effects
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2021-01-12
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2020.12.045
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Article ; Online: Gone in 60 days: our first experience with a bioconvertible IVC filter.

Lambe, Gerard / Mahony, Johnny O' / Courtney, Michael / Donlon, Noel / Donohoe, Claire / Ryan, JMark

Irish journal of medical science

2021 Volume 191, Issue 5, Page(s) 2041–2046

Abstract: The Sentry bioconvertible IVC filter (Boston Scientific, MA, USA) contains a bioabsorbable filament which hydrolyses after 60 days, allowing the arms of the filter to spring open, retract into the vessel wall and endothelialise, leaving an unobstructed ... ...

Abstract	The Sentry bioconvertible IVC filter (Boston Scientific, MA, USA) contains a bioabsorbable filament which hydrolyses after 60 days, allowing the arms of the filter to spring open, retract into the vessel wall and endothelialise, leaving an unobstructed IVC lumen.It is a novel treatment option for patients at transient risk of pulmonary emboli with a contraindication to anticoagulation. The device provides similar protection to other currently available devices against pulmonary emboli with minimal complications. It represents an effective alternative to retrievable filters, the removal of which is variously not attempted, not possible or associated with high complication rates.We review the literature which underpins the development of the bioconvertible filter. We describe our first deployment of the filter in an 85-year-old female with gastric malignancy (who subsequently underwent a subtotal gastrectomy) with a history of anaemia and previous pulmonary emboli. The availability of a bioconvertible filter constitutes a further step forward in the management of patients with potential or active thromboembolic disease.
MeSH term(s)	Aged, 80 and over ; Anticoagulants ; Device Removal ; Female ; Humans ; Pulmonary Embolism/prevention & control ; Retrospective Studies ; Thromboembolism/complications ; Treatment Outcome ; Vena Cava Filters/adverse effects ; Venous Thrombosis
Chemical Substances	Anticoagulants
Language	English
Publishing date	2021-11-02
Publishing country	Ireland
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	390895-1
ISSN	1863-4362 ; 0021-1265
ISSN (online)	1863-4362
ISSN	0021-1265
DOI	10.1007/s11845-021-02818-6
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Article ; Online: Endobronchial valve use in COVID-19 related pneumothorax and persistent air leak.

Nugent, T S / Aladaileh, M / Donlon, N E / Murphy, N / Eaton, D

Annals of the Royal College of Surgeons of England

2021 Volume 104, Issue 5, Page(s) e137–e138

Abstract: Pneumothoraces may occur rarely in coronavirus (COVID-19) patients, often resulting from a combination of fibrotic parenchymal changes and prolonged high-pressure ventilation. Very few studies have been published describing the management of pneumothorax ...

Abstract	Pneumothoraces may occur rarely in coronavirus (COVID-19) patients, often resulting from a combination of fibrotic parenchymal changes and prolonged high-pressure ventilation. Very few studies have been published describing the management of pneumothorax in the novel COVID-19 pneumonia patients. Although chest drain insertion represents the first line of treatment, a persistent pneumothorax and air leak requiring intervention could be managed by a thoracoscopic procedure or, as is the case here, by endobronchial valve insertion. Endobronchial valve insertion is a minimally invasive technique that provides a treatment option in patients with severe parenchymal COVID-19 related lung disease. As far as the authors are aware this is the first report of the use of endobronchial valves in a COVID-19 patient.
MeSH term(s)	Bronchoscopy/methods ; COVID-19/complications ; Chest Tubes ; Humans ; Pneumothorax/etiology ; Pneumothorax/surgery ; Prostheses and Implants
Language	English
Publishing date	2021-11-03
Publishing country	England
Document type	Journal Article
ZDB-ID	80044-2
ISSN	1478-7083 ; 0035-8843
ISSN (online)	1478-7083
ISSN	0035-8843
DOI	10.1308/rcsann.2021.0197
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Article ; Online: PD-1 inhibitors in esophageal cancer: a systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic paradigm.

Whooley, J / Alazzawi, M / Donlon, N E / Bolger, J C / Robb, W B

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

2021 Volume 35, Issue 5

Abstract: Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of ... ...

Abstract	Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors has emerged as exciting therapeutic options in the curative and palliative setting of other solid tumors. We assessed the efficacy and safety of PD-1 inhibitors in esophageal and GEJ cancers. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE, and Google Scholar databases was conducted up to 25 July 2021. This review identified 11 eligible studies reporting outcomes of 3451 patients treated with PD-1 blockade compared with 2286 patients treated with either a placebo or the standard regimen of chemotherapy. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic esophageal and GEJ cancer while maintaining acceptable safety profiles. Promising survival data have also recently emerged from PD-1 blockade in the adjuvant setting. PD-1 blockade in esophageal and GEJ cancer has delivered impressive survival benefit while remaining well tolerated. Its use in the adjuvant setting will further advance treatment options, and more advancements in this area of therapy are highly anticipated. However, further characterization of the PD-1/programmed death ligand-1 pathway and elucidation of biomarkers to predict response are required to optimize patient selection.
MeSH term(s)	B7-H1 Antigen/metabolism ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/pathology ; Esophagogastric Junction/pathology ; Humans ; Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor/therapeutic use ; Stomach Neoplasms/pathology
Chemical Substances	B7-H1 Antigen ; Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2021-09-22
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	639470-x
ISSN	1442-2050 ; 1120-8694
ISSN (online)	1442-2050
ISSN	1120-8694
DOI	10.1093/dote/doab063
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Article ; Online: Endoscopic vacuum therapy significantly improves clinical outcomes of anastomotic leakages after 2-stage, 3-stage, and transhiatal esophagectomies.

Maier, Jonas / Kandulski, A / Donlon, N E / Werner, J M / Mehrl, A / Müller, M / Doenecke, A / Schlitt, H J / Hornung, M / Weiss, A R R

Langenbeck's archives of surgery

2023 Volume 408, Issue 1, Page(s) 90

Abstract: Background: Anastomotic leakages after esophagectomies continue to constitute significant morbidity and mortality. Intrathoracic anastomoses pose a high risk for mediastinitis, sepsis, and death, if a leak is not addressed timely and appropriately. ... ...

Abstract	Background: Anastomotic leakages after esophagectomies continue to constitute significant morbidity and mortality. Intrathoracic anastomoses pose a high risk for mediastinitis, sepsis, and death, if a leak is not addressed timely and appropriately. However, there are no standardized treatment recommendations or algorithms as for how to treat these leakages. Methods: The study included all patients at the University Hospital Regensburg, who developed an anastomotic leakage after esophagectomy with gastric pull-up reconstruction from 2007 to 2022. Patients receiving conventional treatment options for an anastomotic leakage (stents, drainage tubes, clips, etc.) were compared to patients receiving endoscopic vacuum-assisted closure (eVAC) therapy as their mainstay of treatment. Treatment failure was defined as cervical esophagostomy formation or death. Results: In total, 37 patients developed an anastomotic leakage after esophagectomy with a gastric pull-up reconstruction. Twenty patients were included into the non-eVAC cohort, whereas 17 patients were treated with eVAC. Treatment failure was observed in 50% of patients (n = 10) in the non-eVAC cohort and in 6% of patients (n = 1) in the eVAC cohort (p < 0.05). The 90-day mortality in the non-eVAC cohort was 15% (n = 3) compared to 6% (n = 1) in the eVAC cohort. Cervical esophagostomy formation was required in 40% of cases (n = 8) in the non-eVAC cohort, whereas no patient in the eVAC cohort underwent cervical esophagostomy formation. Conclusion: eVAC therapy for leaking esophagogastric anastomoses appears to be superior to other treatment strategies as it significantly reduces morbidity and mortality. Therefore, we suggest eVAC as an essential component in the treatment algorithm for anastomotic leakages following esophagectomies, especially in patients with intrathoracic anastomoses.
MeSH term(s)	Humans ; Anastomotic Leak/etiology ; Anastomotic Leak/surgery ; Esophagectomy/adverse effects ; Negative-Pressure Wound Therapy ; Anastomosis, Surgical/adverse effects ; Endoscopy ; Esophageal Neoplasms/surgery ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2023-02-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1423681-3
ISSN	1435-2451 ; 1435-2443
ISSN (online)	1435-2451
ISSN	1435-2443
DOI	10.1007/s00423-023-02826-3
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Article ; Online: Non-bariatric Surgeons' Perspectives on Perioperative Care for Patients Living with Obesity: Results of an International Survey.

Cullinane, Carolyn / Edwards-Murphy, Amy / Fullard, Anna / Kennedy, Czara / Donlon, Noel / Clements, Joshua / Bolger, Jarlath / Croghan, Stefanie / Elliott, Jessie A / Fleming, Christina A

Obesity surgery

2023 Volume 33, Issue 11, Page(s) 3696–3698

MeSH term(s)	Humans ; Obesity, Morbid/surgery ; Obesity ; Surgeons ; Surveys and Questionnaires ; Perioperative Care ; Bariatric Surgery/methods
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-023-06852-4
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Zs.A 3381: Show issues

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Article: Total hip arthroplasty in patients with haemophilia - What are the risks of bleeding in the immediate peri-operative period?

Colgan, Grainne / Baker, Joseph F / Donlon, N / Hogan, N / McCarthy, T

Journal of orthopaedics

2016 Volume 13, Issue 4, Page(s) 389–393

Abstract: Background: Undergoing a major surgical intervention such as total hip arthroplasty (THA) with an underlying clotting disorder like haemophilia poses its own unique challenges. Despite the advances in factor replacement and medical management, the ... ...

Abstract	Background: Undergoing a major surgical intervention such as total hip arthroplasty (THA) with an underlying clotting disorder like haemophilia poses its own unique challenges. Despite the advances in factor replacement and medical management, the potential for excessive and uncontrolled haemorrhage still exists. The aim of this study was to quantify blood loss, peri-operative transfusion requirements and risk of haematoma formation in a cohort of patients with haemophilia undergoing THA. Methods: All patients with haemophilia types A or B who had undergone THA in the previous 10 years were identified from the Hospital In-Patient Enquiry system and theatre logs. A comprehensive review of operative records, laboratory parameters and peri-operative haematological management was conducted. Results: Eleven male patients (12 THA) were identified. The mean age was 56 years (range 28-76). The mean intra-operative blood loss was 502 ml (100-1250 ml) compared to an established normal blood loss of 400 ml. The mean drop in haemoglobin was 3.25 g/dl in 48 h. Only one patient required a post-operative transfusion of two units of red cell concentrate. There were no complications of haematoma formation. Conclusion: The results in our institution compare favourably with the established blood loss reported in the literature and by assessment with International Guidelines. Average blood loss in patients with haemophilia was higher than the established normal, but there was no increased transfusion requirement.
Language	English
Publishing date	2016-07-27
Publishing country	India
Document type	Journal Article
ZDB-ID	2240839-3
ISSN	0972-978X
ISSN	0972-978X
DOI	10.1016/j.jor.2016.06.022
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Article: Life-Threatening Intraparenchymal Hemorrhage of Steroid-Induced Hepatic Adenomas in a Healthy Man.

Nugent, Timothy S / Donlon, Noel / Kelly, Michael / Iqbal, Masood / Murphy, Noelle / Ryan, Mark / Maguire, Donal

ACG case reports journal

2021 Volume 8, Issue 5, Page(s) e00601

Abstract: Hepatocellular adenomas are uncommon benign epithelial tumors of the liver that are associated with several risk factors such as anabolic androgens and oral contraceptive pills. They may present as incidental findings, with abdominal pain or hemorrhage. ... ...

Abstract	Hepatocellular adenomas are uncommon benign epithelial tumors of the liver that are associated with several risk factors such as anabolic androgens and oral contraceptive pills. They may present as incidental findings, with abdominal pain or hemorrhage. This case report details the presentation and management of a life-threatening hepatocellular adenomas hemorrhage in a seemingly healthy 28-year-old man. After initial conservative management, a clinical deterioration prompted urgent reevaluation and successful embolization of the liver through transarterial embolization. As oral contraceptive pills use and anabolic steroid abuse have become more prevalent in recent decades, we may begin to see more of these presentations.
Language	English
Publishing date	2021-05-24
Publishing country	United States
Document type	Case Reports
ZDB-ID	2814825-3
ISSN	2326-3253
ISSN	2326-3253
DOI	10.14309/crj.0000000000000601
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Article ; Online: Management options for chronic anal fissure: a systematic review of randomised controlled trials.

Boland, P A / Kelly, M E / Donlon, N E / Bolger, J C / Larkin, J O / Mehigan, B J / McCormick, P H

International journal of colorectal disease

2020 Volume 35, Issue 10, Page(s) 1807–1815

Abstract: Introduction: Anal fissure is the most common cause of severe anorectal pain in adults, contributing significantly to coloproctology workloads. There are a wide variety of management options available, including topical nitrites, calcium channel ... ...

Abstract	Introduction: Anal fissure is the most common cause of severe anorectal pain in adults, contributing significantly to coloproctology workloads. There are a wide variety of management options available, including topical nitrites, calcium channel blockers, botulinum toxin injection and sphincterotomy. The aim of this study was to review current options for the treatment of chronic anal fissure. Methods: A comprehensive search identifying randomized controlled trials comparing treatment options for anal fissure published between January 2000 and February 2020 was performed. The primary outcome assessed was healing at 8 weeks post commencing treatment. Secondary outcomes included recurrence, intolerance of treatment and complications. Results: A total of 2822 studies were identified. After removal of duplicates and non-relevant studies, we identified nine randomized controlled trials which met pre-defined criteria. There was a total of 775 patients. At 8 weeks, healing rates were 95.13% in those treated with sphincterotomy, 66.7% in the botulinum toxin group, 63.8% in the nitrate group, 52.3% for topical diltiazem and 50% for topical minoxidil. Recurrence was highest amongst those treated with botulinum toxin injection (41.7%) and lowest for sphincterotomy (6.9%). Although the absolute number is low, there was a risk of permanent incontinence with sphincterotomy. Conclusion: This review of the randomized control data demonstrates that healing was significantly higher amongst those treated with sphincterotomy versus more conservative modalities. Topical nitrites had similar outcomes to botulinum toxin injection but were poorly tolerated in comparison to other treatments. The benefit of sphincterotomy was at a cost of increased complications, notably permanent incontinence.
MeSH term(s)	Adult ; Anal Canal/surgery ; Botulinum Toxins, Type A/therapeutic use ; Chronic Disease ; Fissure in Ano/drug therapy ; Humans ; Neoplasm Recurrence, Local ; Randomized Controlled Trials as Topic ; Treatment Outcome
Chemical Substances	Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2020-07-25
Publishing country	Germany
Document type	Journal Article ; Systematic Review
ZDB-ID	84975-3
ISSN	1432-1262 ; 0179-1958
ISSN (online)	1432-1262
ISSN	0179-1958
DOI	10.1007/s00384-020-03699-4
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Article ; Online: Comparison of Esophagectomy outcomes between a National Center, a National Audit Collaborative, and an International database using the Esophageal Complications Consensus Group (ECCG) standardized definitions.

Reynolds, John V / Donlon, Noel / Elliott, Jessie A / Donohoe, Claire / Ravi, Narayanasamy / Kuppusamy, Madhan Kumar / Low, Donald E

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

2020 Volume 34, Issue 1

Abstract: The ECCG developed a standardized platform for reporting operative complications, with consensus definitions. The Dutch Upper Gastrointestinal Cancer Audit (DUCA) published a national comparison against these benchmarks. This study compares ECCG data ... ...

Abstract	The ECCG developed a standardized platform for reporting operative complications, with consensus definitions. The Dutch Upper Gastrointestinal Cancer Audit (DUCA) published a national comparison against these benchmarks. This study compares ECCG data from the Irish National Center (INC) with both published benchmark studies. All patients undergoing multimodal therapy or surgery with curative intent from 2014 to 2018 inclusive were studied, with data recorded prospectively and entered onto a secure online database (Esodata.org). 219 patients (mean age 67; 77% male) underwent open resection, 66.6% via transthoracic en bloc resection. 30-day and 90-day mortality were 0.0 and 0.9%,nrespectively. Anastomotic leak rate was 5.4%, pneumonia 18.2%, respiratory failure 10%, ARDS 2.7%, atrial dysrhythmia 22.8%, recurrent nerve injury 3%, and delirium in 5% of patients. Compared with both ECCG and DUCA, where MIE constituted 47 and 86% of surgical approaches, respectively, overall complications were similar, as were severity of complications; however, anastomotic leak rate was several-fold less, and mortality was significantly lower (P < 0.001). In this consecutive series and comparative audit with benchmark averages from the ECCG and DUCA publications, a low mortality and anastomotic leak rate were the key differential findings. Although not risk stratified, the severity of complications from this 'open' series is consistent with series containing large numbers of total or hybrid MIE, highlighting a need to adhere to these strictly defined definitions in further prospective research and randomized studies.
MeSH term(s)	Aged ; Anastomotic Leak/epidemiology ; Anastomotic Leak/etiology ; Consensus ; Esophageal Neoplasms/surgery ; Esophagectomy/adverse effects ; Female ; Humans ; Male ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Retrospective Studies
Language	English
Publishing date	2020-06-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	639470-x
ISSN	1442-2050 ; 1120-8694
ISSN (online)	1442-2050
ISSN	1120-8694
DOI	10.1093/dote/doaa060
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