Summary: Anastomotic leakage is one of the most severe complications after esophagectomy and is associated with increased postoperative morbidity and mortality. Several projects ranging from small retrospective studies to large collaborations have aimed to identify potential pre- and perioperative risk factors and to improve the diagnostic processes and management. Despite the increase in available literature, many aspects of anastomotic leakage are still debated, without the existence of widely accepted guidelines. The purpose of this review is to provide a cutting edge overview of the recent literature regarding the definition and classification of anastomotic leakage, risk factors, novel diagnostic modalities, and emerging therapeutic options for treatment and prevention of anastomotic leakage following esophagectomy.

An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. NCT03222895 , date of registration: July 19th, 2017.

Metastatic lymphatic mapping in esophageal cancer is important to determine the optimal extent of the radiation field in case of neoadjuvant chemoradiotherapy and lymphadenectomy when esophagectomy is indicated. The objective of this review is to identify the distribution pattern of metastatic lymphatic spread in relation to histology, tumor location, and T-stage in patients with esophageal cancer. Embase and Medline databases were searched by two independent researchers. Studies were included if published before July 2019 and if a transthoracic esophagectomy with a complete 2- or 3-field lymphadenectomy was performed without neoadjuvant therapy. The prevalence of lymph node metastases was described per histologic subtype and primary tumor location. Fourteen studies were included in this review with a total of 8952 patients. We found that both squamous cell carcinoma and adenocarcinoma metastasize to cervical, thoracic, and abdominal lymph node stations, regardless of the primary tumor location. In patients with an upper, middle, and lower thoracic squamous cell carcinoma, the lymph nodes along the right recurrent nerve are often affected (34%, 24% and 10%, respectively). Few studies describe the metastatic pattern of adenocarcinoma. The current literature is heterogeneous in the classification and reporting of lymph node metastases. This complicates evidence-based strategies in neoadjuvant and surgical treatment.

Background: Influence of sarcopenia in combination with other body composition parameters and muscle strength on outcomes after oesophageal surgery for oesophageal cancer remains unclear. The objectives were (i) to describe the incidence of sarcopenia in relation to adipose tissue quantity and distribution and muscle strength; (ii) to evaluate if neoadjuvant chemoradiation (nCRTx) influences body composition and muscle strength; and (iii) to evaluate the influence of body composition and muscle strength on post‐operative morbidity and long‐term survival.Methods: This retrospective study included patients with oesophageal cancer who received nCRTx followed by surgery between January 2011 and 2016. Skeletal muscle, visceral, and subcutaneous adipose tissue cross‐sectional areas were calculated based on computed tomography scans, and muscle strength was measured using hand grip tests, 30 seconds chair stand tests, and maximal inspiratory and expiratory pressure tests prior to nCRTx and after nCRTx.Results: A total of 322 patients were included in this study. Sarcopenia was present in 55.6% of the patients prior to nCRTx and in 58.2% after nCRTx (P = 0.082). Patients with sarcopenia had a significantly lower muscle strength and higher fat percentage. The muscle strength and incidence of sarcopenia increased while the mean body mass index and fat percentage decreased during nCRTx. A body mass index above 25 kg/m² was associated with anastomotic leakage (P = 0.032). Other body composition parameters were not associated with post‐operative morbidity. A lower handgrip strength prior to nCRTx was associated with pulmonary and cardiac complications (P = 0.023 and P = 0.009, respectively). In multivariable analysis, a lower number of stands during the 30 seconds chair stand test prior to nCRTx (hazard ratio 0.93, 95% confidence interval 0.87–0.99, P = 0.017) and visceral adipose tissue of >128 cm² after nCRTx (hazard ratio 1.81, 95% confidence interval 1.30–2.53, P = 0.001) were associated with worse overall survival.Conclusions: Sarcopenia occurs frequently in patients with oesophageal cancer and is associated with less muscle strength and a higher fat percentage. Body composition changes during nCRTx did not influence survival. Impaired muscle strength and a high amount of visceral adipose tissue are associated with worse survival. Therefore, patients with poor fitness might benefit from preoperative nutritional and muscle strengthening guidance, aiming to increase muscle strength and decrease visceral adipose tissue. However, this should be confirmed in a large prospective study.

Background Conditional survival accounts for the time already survived after surgery and may be of additional informative value. The aim was to assess conditional survival in patients with oesophageal cancer and to create a nomogram predicting the conditional probability of survival after oesophagectomy. Methods This retrospective study included consecutive patients with oesophageal cancer who received neoadjuvant chemoradiation followed by oesophagectomy between January 2004 and 2019. Conditional survival was defined as the probability of surviving y years after already surviving for x years. The formula used for conditional survival (CS) was: CS_(x|y) = S_(x + y)/S_(x), where S_(x) represents overall survival at x years. Cox proportional hazards models were used to evaluate predictors of overall survival. A nomogram was constructed to predict 5‐year survival directly after surgery and given survival for 1, 2, 3 and 4 years after surgery. Results Some 660 patients were included. Median overall survival was 44·4 (95 per cent c.i. 37·0 to 51·8) months. The probability of achieving 5‐year overall survival after resection increased from 45 per cent directly after surgery to 54, 65, 79 and 88 per cent given 1, 2, 3 and 4 years already survived respectively. Cardiac co‐morbidity, cN category, ypT category, ypN category, chyle leakage and pulmonary complications were independent predictors of survival. The nomogram predicted 5‐year survival using these predictors and number of years already survived. Conclusion The probability of achieving 5‐year overall survival after oesophagectomy for cancer increases with each additional year survived. The proposed nomogram predicts survival in patients after oesophagectomy, taking the years already survived into account.

Large studies comparing totally minimally invasive oesophagectomy (TMIE) with laparoscopically assisted (hybrid) oesophagectomy are lacking. Although randomized trials have compared TMIE invasive with open oesophagectomy, daily clinical practice does not always resemble the results reported in such trials. The aim of the present study was to compare complications after totally minimally invasive, hybrid and open Ivor Lewis oesophagectomy in patients with oesophageal cancer. The study was performed using data from the International Esodata Study Group registered between February 2015 and December 2019. The primary outcome was pneumonia, and secondary outcomes included the incidence and severity of anastomotic leakage, (major) complications, duration of hospital stay, escalation of care, and 90-day mortality. Data were analysed using multivariable multilevel models. Some 8640 patients were included between 2015 and 2019. Patients undergoing TMIE had a lower incidence of pneumonia than those having hybrid (10.9 versus 16.3 per cent; odds ratio (OR) 0.56, 95 per cent c.i. 0.40 to 0.80) or open (10.9 versus 17.4 per cent; OR 0.60, 0.42 to 0.84) oesophagectomy, and had a shorter hospital stay (median 10 (i.q.r. 8–16) days versus 14 (11–19) days (P = 0.041) and 11 (9–16) days (P = 0.027) respectively). The rate of anastomotic leakage was higher after TMIE than hybrid (15.1 versus 10.7 per cent; OR 1.47, 1.01 to 2.13) or open (15.1 versus 7.3 per cent; OR 1.73, 1.26 to 2.38) procedures. Compared with hybrid and open Ivor Lewis oesophagectomy, TMIE resulted in a lower pneumonia rate, a shorter duration of hospital stay, but higher anastomotic leakage rates. Therefore, no clear advantage was seen for either TMIE, hybrid or open Ivor Lewis oesophagectomy when performed in daily clinical practice.