Cardiorespiratory comorbidity and postoperative complications following esophagectomy: a European multicenter cohort study

BACKGROUND: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. PATIENTS AND METHODS: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. RESULTS: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. CONCLUSIONS: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk

Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis.

Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P < 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women

Cardiorespiratory Comorbidity and Postoperative Complications following Esophagectomy: a European Multicenter Cohort Study

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Outcome of neoadjuvant therapies for cancer of the oesophagus or gastro-oesophageal junction based on a national data registry

Background: Randomized trials have shown that neoadjuvant treatment improves survival in the curative treatment of oesophageal and gastro-oesophageal junction cancer. Results from population-based observational studies are, however, sparse and ambiguous. Methods: This prospective population-based cohort study included all patients who had oesophagectomy for cancer in Sweden, excluding clinical T1 N0, recorded in the National Register for Oesophageal and Gastric Cancer, 2006–2014. Patients were stratified into three groups: surgery alone, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy. Results: Neoadjuvant treatment was given to 521 patients (51·1 per cent) and 499 (48·9 per cent) received surgery alone. Neoadjuvant chemotherapy increased the risk of postoperative surgical complications compared with surgery alone (adjusted odds ratio 2·01, 95 per cent c.i. 1·24 to 3·25; P = 0·005). Postoperative mortality was significantly increased after neoadjuvant chemoradiotherapy compared with surgery alone (odds ratio 2·37, 1·06 to 5·29; P = 0·035). Survival improved in patients with squamous cell carcinoma after neoadjuvant chemotherapy, whereas after neoadjuvant chemoradiotherapy survival was significantly improved only in the subgroup with the highest performance status and without known co-morbidity. In adenocarcinoma there was a trend towards improved overall survival after neoadjuvant chemotherapy, but neoadjuvant chemoradiotherapy did not offer a survival benefit. Stratified analysis including only patients with adenocarcinoma in the highest performance category without known co-morbidity showed a strong trend towards improved survival after neoadjuvant chemotherapy compared with surgery alone (adjusted hazard ratio 0·47, 0·21 to 1·04; P = 0·061). Conclusion: For patients with squamous cell carcinoma of the oesophagus or gastro-oesophageal junction, neoadjuvant treatments seemed to increase long-term survival, but also the risk of postoperative morbidity and mortality, compared with surgery alone. Neither neoadjuvant treatment option seemed to improve survival significantly among patients with adenocarcinoma, compared with surgery alone

Burden of in-hospital care in oesophageal cancer : national population-based study

Background: Oesophageal cancer management requires extensive in-hospital care. This cohort study aimed to quantify in-hospital care for patients with oesophageal cancer in relation to intended treatment, and to analyse factors associated with risk of spending a large proportion of survival time in hospital. Methods: All patients with oesophageal cancer in three nationwide registers over a 10-year period were included. In-hospital care during the first year after diagnosis was evaluated, and the proportion of survival time spent in hospital, stratified by intended treatment (curative, palliative or best supportive care), was calculated. Associations between relevant factors and a greater proportion of survival time in hospital were analysed by multivariable logistic regression. Results: In-hospital care was provided for a median of 39, 26, and 15 days in the first year after diagnosis of oesophageal cancer in curative, palliative, and best supportive care groups respectively. Patients receiving curatively intended treatment spent a median of 12 per cent of their survival time in hospital during the first year after diagnosis, whereas those receiving palliative or best supportive care spent 19 and 23 per cent respectively. Factors associated with more in-hospital care included older age, female sex, being unmarried, and chronic obstructive pulmonary disease. Conclusion: The burden of in-hospital care during the first year after diagnosis of oesophageal cancer was substantial. Important clinical and socioeconomic factors were identified that predisposed to a greater proportion of survival time spent in hospital

Health-related quality of life following total minimally invasive, hybrid minimally invasive or open oesophagectomy:a population-based cohort study

Abstract Background: Minimally invasive oesophagectomy has been shown to reduce the risk of pulmonary complications compared with open oesophagectomy, but the effects on health-related quality of life (HRQoL) and oesophageal cancer survivorship remain unclear. The aim of this study was to assess the longitudinal effects of minimally invasive compared with open oesophagectomy for cancer on HRQoL. Methods: All patients who had surgery for oesophageal cancer in Sweden from January 2013 to April 2018 were identified. The exposure was total or hybrid minimally invasive oesophagectomy, compared with open surgery. The study outcome was HRQoL, evaluated by means of the European Organisation for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-OG25 at 1 and 2 years after surgery. Mean differences and 95 per cent confidence intervals were adjusted for confounders. Results: Of the 246 patients recruited, 153 underwent minimally invasive oesophagectomy, of which 75 were hybrid minimally invasive and 78 were total minimally invasive procedures. After adjustment for age, sex, Charlson Co-morbidity Index score, pathological tumour stage and neoadjuvant therapy, there were no clinically and statistically significant differences in overall or disease-specific HRQoL after oesophagectomy between hybrid minimally invasive and total minimally invasive surgical technique versus open surgery. Conclusions: In this population-based nationwide Swedish study, longitudinal HRQoL after minimally invasive oesophagectomy was similar to that of the open surgical approach

Open left thoracoabdominal esophagectomy a viable option in the era of minimally invasive esophagectomy

Minimally invasive surgical technique has become standard at many institutions in esophageal cancer surgery. In some situations, however other surgical approaches are required. Left thoracoabdominal esophagectomy (LTE) facilitates complete resection of esophageal cancer particularly for bulky distal esophageal tumors, but there are concerns that this approach is associated with significant morbidity. Prospectively entered esophagectomy databases from three high-volume centers were reviewed for patients undergoing LTE or MIE 2009–2019. Patient demographics, tumor characteristics, operative outcomes, postoperative outcomes, and pathologic surrogates of oncologic efficacy (R0 resection rate, and number of resected lymph nodes) were compared. In total 915 patients were included in the study, LTE was applied in 684 (74.8%) patients, and MIE in 231 (25.2%) patients. LTE patients had more locally advanced tumor stage and received more neoadjuvant treatment. Patients treated with MIE had more comorbidities. The results showed no difference in overall postoperative complications (LTE = 61.7%, MIE = 65.7%, P = 0.289), severe complications (Clavien–Dindo ≥IIIa (LTE = 25.9%, MIE 26.8%, P = 0.806)), pneumonia (LTE = 29.0%, MIE = 24.7%, P = 0.211), anastomotic leak (LTE = 7.8%, MIE = 11.3%, P = 0.101), or in-hospital mortality (LTE = 2.6%, MIE = 3.5%, P = 0.511). Median number of resected lymph nodes was 24 for LTE and 25 for MIE (P = 0.491). LTE was used for more advanced tumors in patients that were more likely to have received neoadjuvant treatment compared with MIE, however postoperative morbidity, mortality, and oncologic outcomes were equivalent to that of MIE in this cohort. In conclusion open resection with left thoracoabdominal approach is a valid option in selected patients when performed at high-volume esophagectomy centers

Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer : a national cohort study

The optimal time interval from neoadjuvant therapy to surgery in the treatment of esophageal cancer is not known. The aim of this study was to investigate if a prolonged interval between completed neoadjuvant chemoradiotherapy and surgery was associated with improved histological response rates and survival in a population-based national register cohort. The population-based cohort study included patients treated with neoadjuvant chemoradiotherapy and esophagectomy due to cancer in the esophagus or gastroesophageal junction. Patients were divided into two groups based on the median time from completed neoadjuvant treatment to surgery. The primary outcome was complete histological response. Secondary outcomes were lymph node tumor response, postoperative complications, R0 resection rate, 90-day mortality, and overall survival. In total, 643 patients were included, 344 (54%) patients underwent surgery within 49 days, and 299 (47%) after 50 days or longer. The groups were similar concerning baseline characteristics except for a higher clinical tumor stage (P = 0.009) in the prolonged time to surgery group. There were no significant differences in complete histological response, R0 resection rate, postoperative complications, 90-day mortality, or overall survival. Adjusted odds ratio for ypT0 in the prolonged time to surgery group was 0.99 (95% confidence interval: 0.64-1.53). Complete histological response in the primary tumor (ypT0) was associated with significantly higher overall survival: adjusted hazard ratio: 0.55 (95% CI 0.41-0.76). If lymph node metastases were present in these patients, the survival was, however, significantly lower: adjusted hazard ratio for ypT0N1: 2.30 (95% CI 1.21-4.35). In this prospectively collected, nationwide cohort study of esophageal and junctional type 1 and 2 cancer patients, there were no associations between time to surgery and histological complete response, postoperative outcomes, or overall survival. The results suggest that it is safe for patients to postpone surgery at least 7 to 10 weeks after completed chemoradiotherapy, but no evidence was seen in favor of recommending a prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. A definitive answer to this question requires a randomized controlled trial of standard vs. prolonged time to surgery

Open left thoracoabdominal esophagectomy a viable option in the era of minimally invasive esophagectomy

Minimally invasive surgical technique has become standard at many institutions in esophageal cancer surgery. In some situations, however other surgical approaches are required. Left thoracoabdominal esophagectomy (LTE) facilitates complete resection of esophageal cancer particularly for bulky distal esophageal tumors, but there are concerns that this approach is associated with significant morbidity. Prospectively entered esophagectomy databases from three high-volume centers were reviewed for patients undergoing LTE or MIE 2009–2019. Patient demographics, tumor characteristics, operative outcomes, postoperative outcomes, and pathologic surrogates of oncologic efficacy (R0 resection rate, and number of resected lymph nodes) were compared. In total 915 patients were included in the study, LTE was applied in 684 (74.8%) patients, and MIE in 231 (25.2%) patients. LTE patients had more locally advanced tumor stage and received more neoadjuvant treatment. Patients treated with MIE had more comorbidities. The results showed no difference in overall postoperative complications (LTE = 61.7%, MIE = 65.7%, P = 0.289), severe complications (Clavien–Dindo ≥IIIa (LTE = 25.9%, MIE 26.8%, P = 0.806)), pneumonia (LTE = 29.0%, MIE = 24.7%, P = 0.211), anastomotic leak (LTE = 7.8%, MIE = 11.3%, P = 0.101), or in-hospital mortality (LTE = 2.6%, MIE = 3.5%, P = 0.511). Median number of resected lymph nodes was 24 for LTE and 25 for MIE (P = 0.491). LTE was used for more advanced tumors in patients that were more likely to have received neoadjuvant treatment compared with MIE, however postoperative morbidity, mortality, and oncologic outcomes were equivalent to that of MIE in this cohort. In conclusion open resection with left thoracoabdominal approach is a valid option in selected patients when performed at high-volume esophagectomy centers