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Article ; Online: Predictors of anastomotic leak and conduit necrosis after oesophagectomy: Results from the oesophago-gastric anastomosis audit (OGAA).

Griffiths, Ewen A

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2024 Volume 50, Issue 6, Page(s) 107983

Abstract: Background: Both anastomotic leak (AL) and conduit necrosis (CN) after oesophagectomy are associated with high morbidity and mortality. Therefore, the identification of preoperative, modifiable risk factors is desirable. The aim of this study was to ... ...

Abstract	Background: Both anastomotic leak (AL) and conduit necrosis (CN) after oesophagectomy are associated with high morbidity and mortality. Therefore, the identification of preoperative, modifiable risk factors is desirable. The aim of this study was to generate a risk scoring model for AL and CN after oesophagectomy. Methods: Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018-December 2018. Definitions for AL and CN were those set out by the Oesophageal Complications Consensus Group. Univariate and multivariate analyses were performed to identify risk factors for both AL and CN. A risk score was then produced for both AL and CN using the derivation set, then internally validated using the validation set. Results: This study included 2247 oesophagectomies across 137 hospitals in 41 countries. The AL rate was 14.2% and CN rate was 2.7%. Preoperative factors that were independent predictors of AL were cardiovascular comorbidity and chronic obstructive pulmonary disease. The risk scoring model showed insufficient predictive ability in internal validation (area under the receiver-operating-characteristic curve [AUROC] = 0.618). Preoperative factors that were independent predictors of CN were: body mass index, Eastern Cooperative Oncology Group performance status, previous myocardial infarction and smoking history. These were converted into a risk-scoring model and internally validated using the validation set with an AUROC of 0.775. Conclusion: Despite a large dataset, AL proves difficult to predict using preoperative factors. The risk-scoring model for CN provides an internally validated tool to estimate a patient's risk preoperatively.
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2024.107983
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Article ; Online: Diagnosis and treatment of junctional cancer from a global perspective.

Wijnhoven, Bas P L / Griffiths, Ewen A

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

2024

Language	English
Publishing date	2024-03-15
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/doae017
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Article ; Online: Predictors of textbook outcome following oesophagogastric cancer surgery.

Velayudham, Ganesh K / Dermanis, Alexander / Kamarajah, Sivesh K / Griffiths, Ewen A

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

2024

Abstract: Textbook outcome (TO) is a composite measure representing an ideal perioperative course, which has been utilized to assess the quality of care in oesophagogastric cancer (OGC) surgery. We aim to determine TO rates among OGC patients in a UK tertiary ... ...

Abstract	Textbook outcome (TO) is a composite measure representing an ideal perioperative course, which has been utilized to assess the quality of care in oesophagogastric cancer (OGC) surgery. We aim to determine TO rates among OGC patients in a UK tertiary center, investigate predictors of TO attainment, and evaluate the relationship between TO and survival. A retrospective analysis of a prospectively collected departmental database between 2006 and 2021 was conducted. Patients that underwent radical OGC surgery with curative intent were included. TO attainment required margin-negative resection, adequate lymphadenectomy, uncomplicated postoperative course, and no hospital readmission. Predictors of TO were investigated using multivariable logistic regression. The association between TO and survival was evaluated using Kaplan-Meier analysis and Cox regression modeling. In sum, 667 esophageal cancer and 312 gastric cancer patients were included. TO was achieved in 35.1% of esophagectomy patients and 51.3% of gastrectomy patients. Several factors were independently associated with a low likelihood of TO attainment: T3 stage (odds ratio (OR): 0.41, 95% confidence interval (CI) [0.22-0.79], p = 0.008) and T4 stage (OR:0.26, 95% CI [0.08-0.72], p = 0.013) in the esophagectomy cohort and high BMI (OR:0.93, 95% CI [0.88-0.98], p = 0.011) in the gastrectomy cohort. TO attainment was associated with greater overall survival and recurrence-free survival in esophagectomy and gastrectomy cohorts. TO is a relevant quality metric that can be utilized to compare surgical performance between centers and investigate patients at risk of TO failure. Enhancement of preoperative care measures can improve TO rates and, subsequently, long-term survival.
Language	English
Publishing date	2024-03-24
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/doae023
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Article ; Online: Comment on "Anastomotic Techniques and Associated Morbidity in Total Minimally Invasive Transthoracic Esophagectomy: Results From the EsoBenchmark Database".

Kamarajah, Sivesh K / Griffiths, Ewen A

Annals of surgery

2020 Volume 274, Issue 6, Page(s) e685–e686

MeSH term(s)	Anastomosis, Surgical ; Esophageal Neoplasms/surgery ; Esophagectomy/adverse effects ; Humans ; Morbidity
Language	English
Publishing date	2020-02-17
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000003842
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Article ; Online: Corrigendum to: The influence of the SARS-CoV-2 pandemic on esophagogastric cancer services: an international survey of esophagogastric surgeons.

Kamarajah, Sivesh K / Markar, Sheraz R / Singh, Pritam / Griffiths, Ewen A

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

2021 Volume 34, Issue 8

Language	English
Publishing date	2021-05-08
Publishing country	United States
Document type	Published Erratum
ZDB-ID	639470-x
ISSN	1442-2050 ; 1120-8694
ISSN (online)	1442-2050
ISSN	1120-8694
DOI	10.1093/dote/doab035
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Article ; Online: ASO Author Reflections: Challenges in the Management of Gastroesophageal Junctional Adenocarcinoma.

Kamarajah, Sivesh K / Phillips, Alexander W / Markar, Sheraz R / Griffiths, Ewen A

Annals of surgical oncology

2021 Volume 28, Issue 13, Page(s) 8495–8496

MeSH term(s)	Adenocarcinoma/therapy ; Esophageal Neoplasms/therapy ; Humans
Language	English
Publishing date	2021-08-14
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-021-10397-0
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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: 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

Cancers

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: Effect of Anastomotic Leak on Long-Term Survival After Esophagectomy: Multivariate Meta-analysis and Restricted Mean Survival Times Examination.

Aiolfi, Alberto / Griffiths, Ewen A / Sozzi, Andrea / Manara, Michele / Bonitta, Gianluca / Bonavina, Luigi / Bona, Davide

Annals of surgical oncology

2023 Volume 30, Issue 9, Page(s) 5564–5572

Abstract: Background: Anastomotic leak (AL) is a serious complication after esophagectomy. It is associated with prolonged hospital stay, increased costs, and increased risk for 90-day mortality. Controversy exists concerning the impact of AL on survival. This ... ...

Abstract	Background: Anastomotic leak (AL) is a serious complication after esophagectomy. It is associated with prolonged hospital stay, increased costs, and increased risk for 90-day mortality. Controversy exists concerning the impact of AL on survival. This study was designed to investigate the effect of AL on long-term survival after esophagectomy for esophageal cancer. Methods: PubMed, MEDLINE, Scopus, and Web of Science were searched through October 30, 2022. The included studies evaluated the effect of AL on long-term survival. Primary outcome was long-term overall survival. Restricted mean survival time difference (RMSTD), hazard ratio (HR), and 95% confidence intervals (CI) were used as pooled effect size measures. Results: Thirteen studies (7118 patients) were included. Overall, 727 (10.2%) patients experienced AL. The RMSTD analysis shows that at 12, 24, 36, 48, and 60 months, patients not experiencing AL live an average of 0.7 (95% CI 0.2-1.2; p < 0.001), 1.9 (95% CI 1.1-2.6; p < 0.001), 2.6 (95% CI 1.6-3.7; p < 0.001), 3.4 (95% CI 1.9-4.9; p < 0.001), and 4.2 (95% CI 2.1-6.4; p < 0.001) months longer compared with those with AL, respectively. The time-dependent HRs analysis for AL versus no AL shows a higher mortality hazard in patients with AL at 3 (HR 1.94, 95% CI 1.54-2.34), 6 (HR 1.56, 95% CI 1.39-1.75), 12 (HR 1.47, 95% CI 1.24-1.54), and 24 months (HR 1.19, 95% CI 1.02-1.31). Conclusions: This study seems to suggest a modest clinical impact of AL on long-term OS after esophagectomy. Patients who experience AL seem to have a higher mortality hazard during the first 2 years of follow-up.
MeSH term(s)	Humans ; Anastomotic Leak/surgery ; Esophagectomy/adverse effects ; Survival Rate ; Esophageal Neoplasms
Language	English
Publishing date	2023-05-20
Publishing country	United States
Document type	Meta-Analysis ; Journal Article ; Review
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-023-13670-6
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