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Article: Current and Future Immunotherapy-Based Treatments for Oesophageal Cancers.

To, Natalie / Evans, Richard P T / Pearce, Hayden / Kamarajah, Sivesh K / Moss, Paul / Griffiths, Ewen A

2022 Volume 14, Issue 13

Abstract: Oesophageal cancer is a disease that causes significant morbidity and mortality worldwide, and the prognosis of this condition has hardly improved in the past few years. Standard treatment includes a combination of chemotherapy, radiotherapy and surgery; ...

Abstract	Oesophageal cancer is a disease that causes significant morbidity and mortality worldwide, and the prognosis of this condition has hardly improved in the past few years. Standard treatment includes a combination of chemotherapy, radiotherapy and surgery; however, only a proportion of patients go on to treatment intended to cure the disease due to the late presentation of this disease. New treatment options are of utmost importance, and immunotherapy is a new option that has the potential to transform the landscape of this disease. This treatment is developed to act on the changes within the immune system caused by cancer, including checkpoint inhibitors, which have recently shown great promise in the treatment of this disease and have recently been included in the adjuvant treatment of oesophageal cancer in many countries worldwide. This review will outline the mechanisms by which cancer evades the immune system in those diagnosed with oesophageal cancer and will summarize current and ongoing trials that focus on the use of our own immune system to combat disease.
Language	English
Publishing date	2022-06-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14133104
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Article ; Online: Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by radical surgery for locally advanced oesophageal squamous cell carcinoma: meta-analysis.

Kamarajah, Sivesh K / Evans, Richard P T / Griffiths, Ewen A / Gossage, James A / Pucher, Philip H

BJS open

2022 Volume 6, Issue 6

Abstract: Background: The literature lacks robust evidence comparing definitive chemoradiotherapy (dCRT) with neoadjuvant chemoradiotherapy and surgery (nCRS) for oesophageal squamous cell carcinoma (ESCC). This study aimed to compare long-term survival of these ... ...

Abstract	Background: The literature lacks robust evidence comparing definitive chemoradiotherapy (dCRT) with neoadjuvant chemoradiotherapy and surgery (nCRS) for oesophageal squamous cell carcinoma (ESCC). This study aimed to compare long-term survival of these approaches in patients with ESCC. Methods: A systematic review performed according to PRISMA guidelines included studies identified from PubMed, Scopus, and Cochrane CENTRAL databases up to July 2021 comparing outcomes between dCRT and nCRS for ESCC. The main outcome measure was overall survival (OS), secondary outcome was disease-free survival (DFS). A meta-analysis was conducted using random-effects modelling to determine pooled adjusted multivariable hazard ratios (HRs). Results: Ten studies including 14 092 patients were included, of which 30 per cent received nCRS. Three studies were randomized clinical trials (RCTs) and the remainder were retrospective cohort studies. dCRT and nCRS regimens were reported in six studies and surgical quality control was reported in two studies. Outcomes for OS and DFS were reported in eight and three studies respectively. Following meta-analysis, nCRS demonstrated significantly longer OS (HR 0.68, 95 per cent c.i. 0.54 to 0.87, P < 0.001) and DFS (HR 0.50, 95 per cent c.i. 0.36 to 0.70, P < 0.001) compared with dCRT. Conclusion: Neoadjuvant chemoradiotherapy followed by oesophagectomy correlated with improved survival compared with definitive chemoradiation in the treatment of ESCC; however, there is a lack of literature on RCTs.
MeSH term(s)	Humans ; Esophageal Squamous Cell Carcinoma/therapy ; Esophageal Neoplasms/therapy
Language	English
Publishing date	2022-12-07
Publishing country	England
Document type	Systematic Review ; Meta-Analysis ; Journal Article
ISSN	2474-9842
ISSN (online)	2474-9842
DOI	10.1093/bjsopen/zrac125
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Article ; Online: The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy.

Croft, Wayne / Evans, Richard P T / Pearce, Hayden / Elshafie, Mona / Griffiths, Ewen A / Moss, Paul

Molecular cancer

2022 Volume 21, Issue 1, Page(s) 200

Abstract: Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients ...

Abstract	Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy.
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics ; Endothelial Cells/pathology ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/genetics ; Humans ; Immune Checkpoint Inhibitors ; Neoadjuvant Therapy ; Tumor Microenvironment/genetics
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2022-10-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2091373-4
ISSN	1476-4598 ; 1476-4598
ISSN (online)	1476-4598
ISSN	1476-4598
DOI	10.1186/s12943-022-01666-x
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Article ; Online: Peri-operative Outcomes and Survival Following Palliative Gastrectomy for Gastric Cancer: a Systematic Review and Meta-analysis.

Cowling, Joseph / Gorman, Bethany / Riaz, Afrah / Bundred, James R / Kamarajah, Sivesh K / Evans, Richard P T / Singh, Pritam / Griffiths, Ewen A

Journal of gastrointestinal cancer

2020 Volume 52, Issue 1, Page(s) 41–56

Abstract: Background: Many patients with gastric cancer present with late stage disease. Palliative gastrectomy remains a contentious intervention aiming to debulk tumour and prevent or treat complications such as gastric outlet obstruction, perforation and ... ...

Abstract	Background: Many patients with gastric cancer present with late stage disease. Palliative gastrectomy remains a contentious intervention aiming to debulk tumour and prevent or treat complications such as gastric outlet obstruction, perforation and bleeding. Methods: We conducted a systematic review of the literature for all papers describing palliative resections for gastric cancer and reporting peri-operative or survival outcomes. Data from peri-operative and survival outcomes were meta-analysed using random effects modelling. Survival data from patients undergoing palliative resections, non-resective surgery and palliative chemotherapy were also combined. This study was registered with the PROSPERO database (CRD42019159136). Results: One hundred and twenty-eight papers which included 58,675 patients contributed data. At 1 year, there was a significantly improved survival in patients who underwent palliative gastrectomy when compared to non-resectional surgery and no treatment. At 2 years following treatment, palliative gastrectomy was associated with significantly improved survival compared to chemotherapy only; however, there was no significant improvement in survival compared to patients who underwent non-resectional surgery after 1 year. Palliative resections were associated with higher rates of overall complications versus non-resectional surgery (OR 2.14; 95% CI, 1.34, 3.46; p < 0.001). However, palliative resections were associated with similar peri-operative mortality rates to non-resectional surgery. Conclusion: Palliative gastrectomy is associated with a small improvement in survival at 1 year when compared to non-resectional surgery and chemotherapy. However, at 2 and 3 years following treatment, survival benefits are less clear. Any survival benefits come at the expense of increased major and overall complications.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Chemotherapy, Adjuvant/methods ; Chemotherapy, Adjuvant/statistics & numerical data ; Cytoreduction Surgical Procedures/adverse effects ; Cytoreduction Surgical Procedures/methods ; Cytoreduction Surgical Procedures/statistics & numerical data ; Disease-Free Survival ; Gastrectomy/adverse effects ; Gastrectomy/methods ; Gastrectomy/statistics & numerical data ; Gastric Outlet Obstruction/etiology ; Gastric Outlet Obstruction/surgery ; Gastrointestinal Hemorrhage/etiology ; Gastrointestinal Hemorrhage/surgery ; Humans ; Neoadjuvant Therapy/methods ; Neoadjuvant Therapy/statistics & numerical data ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Recurrence, Local/prevention & control ; Palliative Care/methods ; Palliative Care/statistics & numerical data ; Perioperative Period ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Quality of Life ; Spontaneous Perforation/etiology ; Spontaneous Perforation/surgery ; Stomach Neoplasms/complications ; Stomach Neoplasms/mortality ; Stomach Neoplasms/therapy ; Survival Rate
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2020-09-22
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	2452514-5
ISSN	1941-6636 ; 1559-0739 ; 1941-6628 ; 1537-3649
ISSN (online)	1941-6636 ; 1559-0739
ISSN	1941-6628 ; 1537-3649
DOI	10.1007/s12029-020-00519-4
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Article: Hepatic and Intra-abdominal Tuberculosis: 2016 Update.

Evans, Richard P T / Mourad, Moustafa Mabrouk / Dvorkin, Lee / Bramhall, Simon R

Current infectious disease reports

2016 Volume 18, Issue 12, Page(s) 45

Abstract: Mycobacterium tuberculosis (TB) infection affects nearly 10 million people a year and causes 1.5 million deaths. TB is common in the immunosuppressed population with 12 % of all new diagnoses occurring in human immune deficiency virus (HIV)-positive ... ...

Abstract	Mycobacterium tuberculosis (TB) infection affects nearly 10 million people a year and causes 1.5 million deaths. TB is common in the immunosuppressed population with 12 % of all new diagnoses occurring in human immune deficiency virus (HIV)-positive patients. Extra-pulmonary TB occurs in 12 % of patients with active TB infection of which 3.5 % is hepatobiliary and 6-38 % is intra-abdominal. Hepatobiliary and intra-abdominal TB can present with a myriad of non-specific symptoms, and therefore, diagnosis requires a high level of suspicion. Accurate and rapid diagnosis requires a multidisciplinary team (MDT) approach using radiology, interventional radiology, surgery and pathology services. Treatment of TB is predominantly medical, yet surgery plays an important role in managing the complications of hepatobiliary and intra-abdominal TB.
Language	English
Publishing date	2016-10-28
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2019948-X
ISSN	1534-3146 ; 1523-3847
ISSN (online)	1534-3146
ISSN	1523-3847
DOI	10.1007/s11908-016-0546-5
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Article: Colonic Perforation: A Medical Complication.

Parsons, Christopher / Chan, Elizabeth / Evans, Richard P T / Mourad, Moustafa Mabrouk / Leung, Edmund

Prague medical report

2017 Volume 118, Issue 2-3, Page(s) 100–104

Abstract: Hypothyroidism is a common comorbidity that on acute presentation is often overlooked. It can be an easily managed condition; however non-compliance can have severe consequences. In the presented case it was requirement for emergency surgery that ... ...

Abstract	Hypothyroidism is a common comorbidity that on acute presentation is often overlooked. It can be an easily managed condition; however non-compliance can have severe consequences. In the presented case it was requirement for emergency surgery that resulted in stoma formation. This case is a first example of the need to include patient's decision making process with regards to medication adherence in the setting of chronic disease.
Language	English
Publishing date	2017
Publishing country	Czech Republic
Document type	Journal Article
ZDB-ID	2148569-0
ISSN	1214-6994
ISSN	1214-6994
DOI	10.14712/23362936.2017.10
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Article ; Online: Evolving management of metaplasia and dysplasia in Barrett's epithelium.

Evans, Richard P T / Mourad, Moustafa Mabrouk / Fisher, Simon G / Bramhall, Simon R

World journal of gastroenterology

2016 Volume 22, Issue 47, Page(s) 10316–10324

Abstract: Oesophageal cancer affects more than 450000 people worldwide and despite continued medical advancements the incidence of oesophageal cancer is increasing. Oesophageal cancer has a 5 year survival of 15%-25% and now globally attempts are made to more ... ...

Abstract	Oesophageal cancer affects more than 450000 people worldwide and despite continued medical advancements the incidence of oesophageal cancer is increasing. Oesophageal cancer has a 5 year survival of 15%-25% and now globally attempts are made to more aggressively diagnose and treat Barrett's oesophagus the known precursor to invasive disease. Currently diagnosis the of Barrett's oesophagus is predominantly made after endoscopic visualisation and histopathological confirmation. Minimally invasive techniques are being developed to improve the viability of screening programs. The management of Barrett's oesophagus can vary greatly dependent on the presence and severity of dysplasia. There is no consensus between the major international medical societies to determine and agreed surveillance and intervention pathway. In this review we analysed the current literature to demonstrate the evolving management of metaplasia and dysplasia in Barrett's epithelium.
MeSH term(s)	Adenocarcinoma/diagnosis ; Adenocarcinoma/epidemiology ; Adenocarcinoma/surgery ; Barrett Esophagus/diagnosis ; Barrett Esophagus/epidemiology ; Barrett Esophagus/therapy ; Disease Progression ; Esophageal Neoplasms/diagnosis ; Esophageal Neoplasms/epidemiology ; Esophageal Neoplasms/surgery ; Esophagectomy/adverse effects ; Esophagectomy/methods ; Esophagoscopy/adverse effects ; Esophagus/drug effects ; Esophagus/pathology ; Esophagus/surgery ; Humans ; Metaplasia ; Predictive Value of Tests ; Proton Pump Inhibitors/adverse effects ; Proton Pump Inhibitors/therapeutic use ; Risk Factors ; Severity of Illness Index ; Treatment Outcome ; Watchful Waiting
Chemical Substances	Proton Pump Inhibitors
Language	English
Publishing date	2016-12-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v22.i47.10316
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Article ; Online: Meta-analysis of prognostic factors of overall survival in patients undergoing oesophagectomy for oesophageal cancer.

Kamarajah, Sivesh K / Marson, Ella J / Zhou, Dengyi / Wyn-Griffiths, Freddie / Lin, Aaron / Evans, Richard P T / Bundred, James R / Singh, Pritam / Griffiths, Ewen A

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

2020 Volume 33, Issue 11

Abstract: Introduction: Currently, the American Joint Commission on Cancer (AJCC) staging system is used for prognostication for oesophageal cancer. However, several prognostically important factors have been reported but not incorporated. This meta-analysis ... ...

Abstract	Introduction: Currently, the American Joint Commission on Cancer (AJCC) staging system is used for prognostication for oesophageal cancer. However, several prognostically important factors have been reported but not incorporated. This meta-analysis aimed to characterize the impact of preoperative, operative, and oncological factors on the prognosis of patients undergoing curative resection for oesophageal cancer. Methods: This systematic review was performed according to PRISMA guidelines and eligible studies were identified through a search of PubMed, Scopus, and Cochrane CENTRAL databases up to 31 December 2018. A meta-analysis was conducted with the use of random-effects modeling to determine pooled univariable hazard ratios (HRs). The study was prospectively registered with the PROSPERO database (Registration: CRD42018157966). Results: One-hundred and seventy-one articles including 73,629 patients were assessed quantitatively. Of the 122 factors associated with survival, 39 were significant on pooled analysis. Of these. the strongly associated prognostic factors were 'pathological' T stage (HR: 2.07, CI95%: 1.77-2.43, P < 0.001), 'pathological' N stage (HR: 2.24, CI95%: 1.95-2.59, P < 0.001), perineural invasion (HR: 1.54, CI95%: 1.36-1.74, P < 0.001), circumferential resection margin (HR: 2.17, CI95%: 1.82-2.59, P < 0.001), poor tumor grade (HR: 1.53, CI95%: 1.34-1.74, P < 0.001), and high neutrophil:lymphocyte ratio (HR: 1.47, CI95%: 1.30-1.66, P < 0.001). Conclusion: Several tumor biological variables not included in the AJCC 8th edition classification can impact on overall survival. Incorporation and validation of these factors into prognostic models and next edition of the AJCC system will enable personalized approach to prognostication and treatment.
MeSH term(s)	Esophageal Neoplasms/pathology ; Esophageal Neoplasms/surgery ; Esophagectomy ; Humans ; Margins of Excision ; Neoplasm Staging ; Prognosis
Language	English
Publishing date	2020-05-16
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	639470-x
ISSN	1442-2050 ; 1120-8694
ISSN (online)	1442-2050
ISSN	1120-8694
DOI	10.1093/dote/doaa038
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Article ; Online: Risk factors and outcomes associated with anastomotic leaks following esophagectomy: a systematic review and meta-analysis.

Kamarajah, Sivesh K / Lin, Aaron / Tharmaraja, Thahesh / Bharwada, Yashvi / Bundred, James R / Nepogodiev, Dmitri / Evans, Richard P T / Singh, Pritam / Griffiths, Ewen A

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

2020 Volume 33, Issue 3

Abstract: Anastomotic leaks (AL) are a major complication after esophagectomy. This meta-analysis aimed to determine identify risks factors for AL (preoperative, intra-operative, and post-operative factors) and assess the consequences to outcome on patients who ... ...

Abstract	Anastomotic leaks (AL) are a major complication after esophagectomy. This meta-analysis aimed to determine identify risks factors for AL (preoperative, intra-operative, and post-operative factors) and assess the consequences to outcome on patients who developed an AL. This systematic review was performed according to PRISMA guidelines, and eligible studies were identified through a search of PubMed, Scopus, and Cochrane CENTRAL databases up to 31 December 2018. A meta-analysis was conducted with the use of random-effects modeling and prospectively registered with the PROSPERO database (Registration CRD42018130732). This review identified 174 studies reporting outcomes of 74,226 patients undergoing esophagectomy. The overall pooled AL rates were 11%, ranging from 0 to 49% in individual studies. Majority of studies were from Asia (n = 79). In pooled analyses, 23 factors were associated with AL (17 preoperative and six intraoperative). AL were associated with adverse outcomes including pulmonary (OR: 4.54, CI95%: 2.99-6.89, P < 0.001) and cardiac complications (OR: 2.44, CI95%: 1.77-3.37, P < 0.001), prolonged hospital stay (mean difference: 15 days, CI95%: 10-21 days, P < 0.001), and in-hospital mortality (OR: 5.91, CI95%: 1.41-24.79, P = 0.015). AL are a major complication following esophagectomy accounting for major morbidity and mortality. This meta-analysis identified modifiable risk factors for AL, which can be a target for interventions to reduce AL rates. Furthermore, identification of both modifiable and non-modifiable risk factors will facilitate risk stratification and prediction of AL enabling better perioperative planning, patient counseling, and informed consent.
MeSH term(s)	Anastomotic Leak/diagnosis ; Anastomotic Leak/epidemiology ; Anastomotic Leak/etiology ; Esophageal Neoplasms/surgery ; Esophagectomy/adverse effects ; Esophagectomy/methods ; Humans ; Risk Adjustment/methods
Language	English
Publishing date	2020-01-19
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	639470-x
ISSN	1442-2050 ; 1120-8694
ISSN (online)	1442-2050
ISSN	1120-8694
DOI	10.1093/dote/doz089
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Article ; Online: Perioperative outcomes after laparoscopic cholecystectomy in elderly patients: a systematic review and meta-analysis.

Kamarajah, Sivesh K / Karri, Santhosh / Bundred, James R / Evans, Richard P T / Lin, Aaron / Kew, Tania / Ekeozor, Chinenye / Powell, Susan L / Singh, Pritam / Griffiths, Ewen A

Surgical endoscopy

2020 Volume 34, Issue 11, Page(s) 4727–4740

Abstract: Background: Laparoscopic cholecystectomy is increasingly performed in an ever ageing population; however, the risks are poorly quantified. The study aims to review the current evidence to quantify further the postoperative risk of cholecystectomy in the ...

Abstract	Background: Laparoscopic cholecystectomy is increasingly performed in an ever ageing population; however, the risks are poorly quantified. The study aims to review the current evidence to quantify further the postoperative risk of cholecystectomy in the elderly population compared to younger patients. Method: A systematic literature search of PubMed, EMBASE and the Cochrane Library databases were conducted including studies reporting laparoscopic cholecystectomy in the elderly population. A meta-analysis was reported in accordance with the recommendations of the Cochrane Library and PRISMA guidelines. Primary outcome was overall complications and secondary outcomes were conversion to open surgery, bile leaks, postoperative mortality and length of stay. Results: This review identified 99 studies incorporating 326,517 patients. Increasing age was significantly associated with increased rates of overall complications (OR 2.37, CI Conclusion: Postoperative outcomes such as overall and major complications appear to be significantly higher in all age cut-offs in this meta-analysis. This study demonstrated there is a sevenfold increase in perioperative mortality which increases by tenfold in patients > 80 years old. This study appears to confirm preconceived suspicions of higher risks in elderly patients undergoing cholecystectomy and may aid treatment planning and informed consent.
MeSH term(s)	Age Factors ; Aged ; Cholecystectomy, Laparoscopic/methods ; Conversion to Open Surgery/methods ; Gallbladder Diseases/surgery ; Global Health ; Humans ; Incidence ; Postoperative Complications/epidemiology ; Risk Factors
Language	English
Publishing date	2020-07-13
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	639039-0
ISSN	1432-2218 ; 0930-2794
ISSN (online)	1432-2218
ISSN	0930-2794
DOI	10.1007/s00464-020-07805-z
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