Improving surgical therapy for oesophageal cancer

Despite advances in multimodality treatment, surgery remains the mainstay of curative treatment for oesophageal cancer. However short- and long-term mortality from oesophagectomy for oesophageal cancer still shows large variations nationally and internationally. This thesis addresses three themes concerning oesophageal cancer surgery. The first theme focuses on technical challenges, learning in surgery and the influence of surgeon age on outcomes from oesophagectomy. Study I utilised a large French multi-centre database (FREGAT), and showed in contrast to previous smaller single-centre studies, salvage oesophagectomy after definitive chemoradiotherapy can offer acceptable short- and long- term outcomes in selected patients at experienced oesophageal cancer centres. Study II used a national Swedish dataset (SESS) and demonstrated that the period during which surgeons gain proficiency in performing oesophagectomy for cancer is associated with substantial adverse effects upon short- and long-term mortality at a national level. The length of the proficiency gain period was longer for long-term mortality than for short-term mortality, implying a change in surgeon focus during the initial stages of their independent practice. Study III also used the SESS and was able to show the optimal surgeon age in performing oesophagectomy in Sweden is between 51 and 56 years. Outside of this age period, increases in short- and long-term mortality are noted, as surgeons are still gaining experience or maybe experiencing decline in their technical abilities. The second theme, sought to evaluate the effect of hospital factors, which may affect outcome from oesophagectomy for cancer. Study IV used SESS once more, and showed surgery performed in university hospitals has no improvements in long-term mortality from oesophagectomy after adjustment for surgeon volume and other confounders. The third theme of this thesis considered the effect of complications during treatment for oesophageal cancer upon long-term prognosis. Study V used FREGAT and demonstrated severe oesophageal anastomotic leak following oesophagectomy for cancer, adversely impacts cancer prognosis with a decrease in overall and disease-free survival and an increasing in overall, loco-regional and mixed cancer recurrence. In conclusion, the studies conducted within this thesis have shown the safety of new therapeutic surgical strategies for oesophageal cancer, the importance of surgeon proficiency gain and surgeon age in prognosis, the lack of significance of university hospital status, and the adverse long-term prognostic effects of severe oesophageal anastomotic leak

Novel Multi-Modal Therapies and Their Prognostic Potential in Gastric Cancer

Background: Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. Results: The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p p p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. Conclusions: Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection

Protocol for LAsting Symptoms after Oesophageal Resectional Surgery (LASORS): multicentre validation cohort study.

INTRODUCTION Surgery is the primary curative treatment for oesophageal cancer, with considerable recent improvements in long-term survival. However, surgery has a long-lasting impact on patient's health-related quality of life (HRQOL). Through a multicentre European study, our research group was able to identify key symptoms that affect patient's HRQOL. These symptoms were combined to produce a tool to identify poor HRQOL following oesophagectomy (LAsting Symptoms after Oesophageal Resection (LASOR) tool). The objective of this multicentre study is to validate a six-symptom clinical tool to identify patients with poor HRQOL for use in everyday clinical practice. METHODS AND ANALYSIS Included patients will: (1) be aged 18 years or older, (2) have undergone an oesophagectomy for cancer between 2015 and 2019, and (3) be at least 12 months after the completion of adjuvant oncological treatments. Patients will be given the previously created LASOR questionnaire. Each symptom from the LASOR questionnaire will be graded according to impact on quality of life and frequency of the symptom, with a composite score from 0 to 5. The previously developed LASOR symptom tool will be validated against HRQOL as measured by the European Organisation for Research and Treatment of Cancer QLQC30 and OG25. SAMPLE SIZE With a predicted prevalence of poor HRQOL of 45%, based on the previously generated LASOR clinical symptom tool, to validate this tool with a sensitivity and specificity of 80%, respectively, a minimum of 640 patients will need to be recruited to the study. ETHICS AND DISSEMINATION NHS Health Research Authority (North East-York Research Ethics Committee) approval was gained 8 November 2019 (REC reference 19/NE/0352). Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal

Recurrence and survival after minimally invasive and open esophagectomy for esophageal cancer: a post hoc analysis of the Ensure Study.

Objective: to determine the impact of operative approach [open (OE), hybrid minimally invasive (HMIE), and total minimally invasive (TMIE) esophagectomy] on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer.Background: the optimum oncologic surgical approach to esophageal and junctional cancer is unclear.Methods: this secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009 and 2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield, and overall survival (OS).Results: in total, 3199 patients were included. Of these, 55% underwent OE, 17% HMIE, and 29% TMIE. DFS was independently increased post-TMIE [hazard ratio (HR): 0.86 (95% CI: 0.76-0.98), P = 0.022] compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to the operative approach [HMIE vs OE, odds ratio (OR): 0.79, P = 0.257; TMIE vs OE, OR: 0.84, P = 0.243]. The probability of systemic recurrence was independently increased post-HMIE (OR: 2.07, P = 0.031), but not TMIE (OR: 0.86, P = 0.508). R0 resection rates ( P = 0.005) and nodal yield ( P &lt; 0.001) were independently increased after TMIE, but not HMIE ( P = 0.424; P = 0.512) compared with OE. OS was independently improved following both HMIE (HR: 0.79, P = 0.009) and TMIE (HR: 0.82, P = 0.003) as compared with OE.Conclusion: in this European multicenter study, TMIE was associated with improved surgical quality and DFS, whereas both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer