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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-01-22)
    Abstract: A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2615211-3
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  • 2
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 107, No. 8 ( 2020-06-15), p. 1042-1052
    Abstract: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20–30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. Methods Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. Results A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal–external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). Conclusion The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 3
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 109, No. Supplement_9 ( 2022-12-07)
    Abstract: Endoluminal Vacuum Therapy (EVT) continues to gain momentum as a first line treatment for oesophageal perforations. Outside the emergency setting there is growing interest in using EVT prophylactically to protect high-risk elective oesophageal repairs. We present a case which demonstrates the benefit of prophylactic EVT in preventing extraluminal contamination, mediastinitis and sepsis following elective oesophageal surgery. Methods An 80-year-old female underwent laparoscopic Hellers Myotomy and Dor Fundoplication for Type 2 Achalasia following worsening symptoms including weight loss despite nutritional optimisation. She had multiple prior balloon dilatations without long term symptom control and remained frail, with a performance status of 0 and an ASA 2. During surgery the oesophageal myotomy was challenging due to extensive scarring. Endoscopy was performed on completion of the myotomy to confirm adequacy and a 1cm oesophageal perforation at 38cm was noted. Primary repair was performed with 5 interrupted 3/0 maxon sutures. An ad-hoc EVT device was constructed using V.A.C granufoam (KCI) sutured to the end of an 18Fr nasogastric tube, and placed intraluminally in the oesophagus across the repair. Continuous negative pressure of 75mmHg was applied. Post operatively the patient was kept nil by mouth and received parenteral nutrition. Her clinical and biochemical parameters were monitored, and the progress of her oesophageal repair was assessed endoscopically. Results The first post-operative endoscopy was performed at day 4. On visual inspection a full thickness oesophageal defect was seen at the proximal aspect of the oesophageal repair. There was no associated leak cavity or other endoscopic evidence of extraluminal contamination. A further ad-hoc EVT device was constructed and placed intraluminally in the oesophagus across the suture repair and oesophageal wall defect. A second endoscopy was performed on day 10 post-operative and the oesophageal defect had completely healed. Despite having a documented full thickness oesophageal wall defect the patient remained clinically well throughout her post-operative recovery with no clinical signs of sepsis. The highest recorded CRP was 131 and WCC was 12.7 on day 1 and day 8 respectively. At no point was a higher level of care or input required than the general surgical ward. Her total LOS was 14 days. Conclusions A leak following elective oesophageal surgery is a serious complication which may result in mediastinitis, sepsis and death. This case demonstrates the utility of prophylactic EVT in reducing the impact of an oesophageal leak in patients where breakdown of the oesophageal repair occurs. Without prophylactic EVT in this case, we are certain the breakdown of the oesophageal repair would have resulted in a significant oesophageal leak with mediastinitis and sepsis which an 80-year-old patient with limited physiological reserve may not have survived. While prophylactic EVT is not a substitute for sound surgical technique, it should be considered in high-risk patients undergoing elective oesophageal surgery to reduce or prevent the septic hit consequent to an oesophageal leak if breakdown of an oesophageal repair occurs.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 4
    In: Gastroenterology, Elsevier BV, Vol. 158, No. 6 ( 2020-05), p. 1682-1697.e1
    Type of Medium: Online Resource
    ISSN: 0016-5085
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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  • 5
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2019-07-15)
    Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2553671-0
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  • 6
    In: Gastroenterology, Elsevier BV, Vol. 155, No. 6 ( 2018-12), p. 1720-1728.e4
    Type of Medium: Online Resource
    ISSN: 0016-5085
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 7
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-09-07)
    Abstract: New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic genetic variations from MFD-1, tumour, normal oesophagus, and leucocytes were analysed with SNP6. WGS was performed in tumour and leucocytes. RNAseq was performed in MFD-1, and two classic OAC cell lines FLO1 and OE33. Transposase-accessible chromatin sequencing (ATAC-seq) was performed in MFD-1, OE33, and non-neoplastic HET1A cells. Functional studies were performed. MFD-1 had a high SNP genotype concordance with matched germline/tumour. Parental tumour and MFD-1 carried four somatically acquired mutations in three recurrent mutated genes in OAC: TP53 , ABCB1 and SEMA5A , not present in FLO-1 or OE33. MFD-1 displayed high expression of epithelial and glandular markers and a unique fingerprint of open chromatin. MFD-1 was tumorigenic in SCID mouse and proliferative and invasive in 3D cultures. The clinical utility of whole genome sequencing projects will be delivered using accurate model systems to develop molecular-phenotype therapeutics. We have described the first such system to arise from the oesophageal International Cancer Genome Consortium project.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
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  • 8
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 34, No. Supplement_1 ( 2021-09-17)
    Abstract: Esophageal leaks present a significant management challenge, especially in patients with delayed presentation and established sepsis. Endoluminal vacuum therapy (EVT) is an emerging treatment strategy which may reduce morbidity and mortality compared to traditional treatments in this patient group. We report the outcomes for patients with esophageal leaks from a range of different causes that were treated with EVT in a tertiary UK hospital over a 10-year period. Methods Between April 2011 and March 2021, 45 patients with a median age of 67 years (31–92) who had an esophageal leak were treated with EVT. All patients were treated with an ad-hoc endoluminal vacuum device (EVD) constructed using V.A.C GRANUFOAMTM (KCI) and a standard nasogastric (Ryles) tube. The median Apache II score for patients at the time of leak diagnosis was 20 (6–36). The cause of the leak was anastomotic in 16 patients (36%), iatrogenic in 14 patients (31%), spontaneous in 14 patients (31%), and traumatic in 1 patient (2%). Information related to treatment and outcome was recorded prospectively. Results Successful resolution of the leak was achieved in 39 (87%) patients. The median number of EVD changes required to heal the leak was 6 (1–17). There were no complications related to insertion of the EVD. The median length of hospital stay was 49 days (1–108). Six (13%) patients died during treatment. Six (13%) patients had complications during treatment requiring further intervention; 2 (4%) had a significant bleed requiring angiography and aortic stent placement, 1 (2%) had a stroke, 1 (2%) had a pulmonary embolism, 1 (2%) had a myocardial infarction, and 1 (2%) contracted COVID-19. Conclusion EVT is a safe and effective treatment that can be used successfully to treat esophageal leaks from a disparate range of leak causes in selected critically unwell patients. Further studies are required to develop a standardized procedure and management pathway which will enable broader adoption of EVT in this group of patients.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2004949-3
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  • 9
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 108, No. Supplement_9 ( 2021-12-15)
    Abstract: Endoluminal vacuum therapy (EVT) is an emerging treatment strategy for the management of anastomotic leaks following oesophagectomy. However, patients are often critically unwell with mediastinitis and established sepsis by the time the leak is diagnosed. This results in a protracted recovery period regardless of the effectiveness of EVT in treating the leak. Prophylactic EVT to protect the anastomosis following oesophagectomy may reduce the incidence of anastomotic leak, and/or mediastinitis and sepsis if the anastomosis does fail. We report the outcomes of two patients considered high risk for anastomotic leak who were managed with prophylactic EVT following esophagectomy for cancer. Methods Two patients received prophylactic EVT following oesophagectomy between May and July 2021. The patients were considered high risk for anastomotic leak due to technical concerns with, or complications during, the operation. In both cases the oesophagogastric anastomosis (OGA) was fashioned with a circular stapler. The endoluminal vacuum device (EVD) was constructed using an 18F nasogastric tube and a piece of open cell foam, and placed intraluminally across the anastomosis under endoscopic guidance at the time of surgery. Continuous negative pressure (125mmHg) was applied. Information relating to treatment and outcome was recorded prospectively. Results Patient-1, a 72-year-old female, ASA 2, underwent minimally invasive oesophgectomy for an adenocarcinoma at the gastro-oesophageal junction. After creating the stapled OGA, inspection revealed the proximal (oesophageal) tissue doughnut was complete but attenuated. Patient 2, a 67-year-old male, ASA 3, underwent a hybrid Ivor Lewis oesophgectomy for a lower 1/3 oesophageal adenocarcinoma. Surgery was complicated by significant intra-abdominal bleeding requiring blood transfusion and pressor support. In both cases, endoscopic assessment of the anastomosis following removal of the prophylactic EVD was performed day seven post-operatively. The anastomoses were healthy with no evidence of a leak, dehiscence, or early stricture formation. Conclusions In this limited case series, prophylactic EVT of the OGA following oesophagectomy was delivered safely with no complications related to insertion of the EVD or delivery of EVT. This intervention should be considered in cases where the risk of anastomotic leak is high. An intraluminal EVD situated across the OGA may minimise the extent of extraluminal contamination, and the systemic consequences of sepsis associated with this, should an anastomotic breakdown occur. Further studies are required to determine the safety of prophylactic EVT following oesophagectomy, and whether this improves surgical outcomes by reducing the incidence and impact of anastomotic leaks.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 10
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 109, No. Supplement_9 ( 2022-12-07)
    Abstract: A leak following oesophago-gastric surgery remains a life-threatening complication associated with a long intensive care stay and high mortality and morbidity. We hypothesised that Endoluminal Vacuum Therapy (EVT) could be used prophylactically to provide source control, prevent mediastinitis and minimise sepsis related morbidity if breakdown of an oesophageal or gastric anastomosis or repair occurred. In the first instance, this could be a particularly attractive adjunct in cases where technical and/or patient factors deem an anastomosis or repair as high risk. Methods We collected data prospectively from all patients where a prophylactic EVT device was placed during elective oesophago-gastric surgery. Primary outcome measures included length of stay (LOS) and post-operative leak rate. Prophylactic EVT was provided using an ad-hoc EVT device constructed by suturing a piece of V.A.C granufoam (KCI) to the end of an 18Fr NG tube and positioning this intraluminally across the anastomosis or area of repair at the time of surgery using endoscopic guidance. Continuous negative pressure of between 75 and 125mmHg was applied. Following removal of the EVT device, assessment of the integrity of the anastomosis or repair was made using one, or a combination of endoscopic assessment, CT with oral contrast, and clinical assessment. Results Prophylactic EVT was utilised in 9 patients; M:F ratio=7:2, median age 72 years (range 50–80). 8 patients had ASA 3, and 1 had ASA 2. The index surgery was resection of an epithelial cancer in 7 patients (3 partial/total gastrectomies, 4 oesophagectomies), resection of a gastric GIST in 1 patient, and a Hellers myotomy in 1 patient. All anastomosis/repairs were deemed high risk due to technical(n=3), patient(n=4) or combined (n=2) factors. Prophylactic EVT was placed for a median of 6 days (range 4–10). The integrity of the anastomosis/repair was assessed using both CT and gastroscopy (n=3), CT alone (n=3), gastroscopy alone (n=2), and clinical grounds (n=1). One patient was found to have a full thickness oesophageal defect at their first endoscopic assessment. This was managed with a further period of intraluminal EVT until the oesophageal defect healed. The patient remained clinically well throughout and was managed entirely with ward-based care. The median LOS was 11 days (range 7–96). The two longest stays were secondary to a prolonged chyle leak and longer term sequelae of a life threatening on-table bleed. In all cases the site of repair remained healthy with no evidence of early stricturing. Conclusions Prophylactic EVT therapy was safe and did not result in any short-term adverse events in this small cohort of patients. Although it may not prevent breakdown at the site of oesophageal anastomosis/repair and is not an alternative to sound surgical technique, the use of prophylactic EVT in high risk anastomosis could be beneficial in preventing life threatening sepsis and associated systemic effects resulting from inadequate source control. Current studies are under way to look at longer term outcomes in the form of prospective cohort studies and randomised controlled trials. This provides the oesophago-gastric community the unique opportunity to collectively eliminate life threatening leak related morbidity and mortality for once and for all.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2006309-X
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