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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., Conditional survival accounts for the time already survived after surgery and may be of additional informative value. A nomogram was constructed that predicts 5‐year survival of patients with oesophageal cancer after neoadjuvant treatment followed by surgery, based on cardiac co‐morbidity, cN category, ypTN stage, chyle leakage and pulmonary complications, taking years already survived into account. Informative for patient and doctor

Background There is scarce evidence on whether a total gastrectomy or an Ivor Lewis esophagectomy is preferred for gastroesophageal junction (GEJ) cancers regarding effects on morbidity, pathology, survival and health-related quality of life (HR-QoL). The aim of this study was to investigate the difference in long-term HR-QoL in patients undergoing total gastrectomy versus Ivor Lewis esophagectomy in a tertiary referral center. Methods Patients with a follow-up of >1 year after a total gastrectomy or an Ivor Lewis esophagectomy for GEJ/cardia carcinoma completed the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. ‘Problems with eating,’ ‘reflux,’ and ‘nausea and vomiting’ were the primary HR-QoL endpoints. The secondary endpoints were the remaining HR-QoL domains, postoperative complications and pathology results. Results Thirty patients after gastrectomy and 71 after esophagectomy were included. Mean age was 63 years. Median follow-up was 2 years (range 12–84 months). Patients after gastrectomy reported less ‘choking when swallowing’ and ‘coughing’ (β = − 5.952, 95% CI − 9.437 to − 2.466; β = − 13.084, 95% CI − 18.525 to − 7.643). More lymph nodes were resected in esophagectomy group (p = 0.008). No difference was found in number of positive lymph nodes, R0 resection or postoperative complications. Conclusions After a follow-up of >1 year ‘choking when swallowing’ and ‘coughing’ were less common after a total gastrectomy. No differences were found in postoperative complications or radicality of surgery. Based on this study, no general preference can be given to either of the procedures for GEJ cancer. These results support shared decision making when a choice between the two treatment options is possible.

Summary Curative treatment for locally advanced esophageal cancer consists of (neo)adjuvant treatment followed by esophagectomy. Both neoadjuvant chemoradiotherapy and perioperative chemotherapy improve the 5-year overall survival rate compared with surgery alone. However, it is unknown whether these treatment strategies are associated with differences in long-term health-related quality of life (HRQL). The aim of this study is to compare long-term HRQL in patients after esophagectomy treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy. Disease-free cancer patients having undergone esophagectomy and (neo)adjuvant treatment in one of the participating lasting symptoms after esophageal resection (LASER) study centers between 2010 and 2016, were identified from the LASER study dataset. Included patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), EORTC QLQ-OG25, and LASER questionnaires at least 1 year after the completion of treatment. Long-term HRQL was compared between patients treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy, using univariable and multivariable regression and presented as differences in mean score. Among the 565 included patients, 349 (61.8%) received neoadjuvant chemoradiotherapy, and 216 (38.2%) perioperative chemotherapy. Patients treated with perioperative chemotherapy reported more symptomatology for diarrhea (difference in means 5.93), reflux (difference in means 7.40), and odynophagia (difference in means 4.66). The differences did not exceed the 10 points to be of clinical relevance. No significant differences for the LASER key symptoms were observed. The observed differences in long-term HRQL are in favor of patients treated with neoadjuvant chemoradiotherapy compared with patients treated with perioperative chemotherapy; however, the differences were small. Patients need to be informed about long-term HRQL when considering allocation of (neo)adjuvant treatment.

Summary Introduction The prognostic value of histomorphologic regression in primary esophageal cancer has been previously established, however the impact of lymph node (LN) response on survival still remains unclear. The aim of this review was to assess the prognostic significance of LN regression or downstaging following neoadjuvant therapy for esophageal cancer. Methods An electronic search was performed to identify articles evaluating LN regression or downstaging after neoadjuvant therapy. Random effects meta-analyses were performed to assess the influence of regression in the LNs and nodal downstaging on overall survival. Histomorphologic tumor regression in LNs was defined by the absence of viable cells or degree of fibrosis on histopathologic examination. Downstaged LNs were defined as pN0 nodes by the tumor, node, and metastasis classification, which were positive prior to treatment neoadjuvant. Results Eight articles were included, three of which assessed tumor regression (number of patients = 292) and five assessed downstaging (number of patients = 1368). Complete tumor regression (average rate of 29.1%) in the LNs was associated with improved survival, although not statistically significant (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.26–1.06; P = 0.17). LNs downstaging (average rate of 32.2%) was associated with improved survival compared to node positivity after neoadjuvant treatment (HR = 0.41, 95%CI = 0.22–0.77; P = 0.005). Discussion The findings of this meta-analysis have shown a survival benefit in patients with LN downstaging and are suggestive for considering LN downstaging to ypN0 as an additional prognostic marker in staging and in the comparative evaluation of differing neoadjuvant regimens in clinical trials. No statistically significant effect of histopathologic regression in the LNs on long-term survival was seen.

Lymph node status in patients with esophageal carcinoma is one of the most important prognostic parameters in esophageal carcinoma. The distribution pattern of lymph node metastases and the optimal extent of lymphadenectomy remains unclear. Therefore the extent of high mediastinal lymphadenectomy, including removal of the paratracheal lymph node stations, in esophageal surgery is a subject of debate. The aim of this study is to investigate the impact of paratracheal lymphadenectomy on survival. Methods For this nation-wide population-based cohort study, patients with an esophageal or gastro-esophageal junction carcinoma treated by elective transthoracic esophagectomy with two-field lymphadenectomy between 2011 and 2017 were included from the national Dutch Upper Gastro-intestinal Cancer Audit (DUCA) registry. Patients who died within 30 days after surgery or where lymphadenectomy data was missing were excluded from analyses. After propensity score matching patients with adenocarcinoma and squamous cell separately, overall survival was compared between patients who underwent paratracheal lymphadenectomy versus patients who did not. Subgroup analysis was performed in patients with cN0 disease. Results 3143 patients were included in the DUCA. A total of 512 patients with adenocarcinoma (n = 256 vs. n = 256) and 157 patients with squamous cell carcinoma (n = 62 vs. n = 62) were matched. For both patients with adenocarcinoma and squamous cell carcinoma a paratracheal lymphadenectomy was not significantly associated with longer overall survival (11 versus 10 months, p = 0.209 and 12 versus 11 months, p = 0.206, figure 1). In subgroup analysis, including patients with a squamous cell carcinoma and cN0 disease, paratracheal lymphadenectomy was associated with longer survival (13 versus 9 months, p = 0.011). This was not seen in patients with adenocarcinoma (11 versus 9 months p = 0.263). Conclusion In both patients with an esophageal adenocarcinoma as squamous cell carcinoma, the addition of paratracheal lymphadenectomy during transthoracic esophagectomy was not significantly associated with longer survival. However, a significantly longer survival was seen in cN0 patients who underwent an additional paratracheal lymphadenectomy, therefore routine removal of paratracheal lymph nodes might still be beneficial. Further studies are warranted with larger subgroups to investigate the impact of an additional (routine) paratracheal lymphadenectomy on survival.

Curative treatment for patients with esophageal cancer consists of neoadjuvant treatment and radical surgical resection. Two different strategies exist; patients can either be treated with perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT). Both strategies improve 5-year survival rates, it is however not known if these treatments affect long-term Health-Related Quality of Life (HR-QoL) differently. The aim of this study was to compare HR-QoL between patients following CT and CRT followed by esophagectomy for esophageal cancer. Methods The LASER study database comprises data of a multicenter European study, with focus on HR-QoL among disease-free patients at least one year following an esophagectomy for esophageal or junctional cancer. Included patients completed the LASER, EORTC-QLQ-C30 and EORTC-QLQ-OG25 questionnaires. From this database we extracted patients either treated with CT or CRT for analysis. The primary endpoint was the mean difference in all long-term HR-QoL domains and LASER key symptom scores, using univariable and multivariable logistic regression analysis. The secondary endpoint was to compare the reported HR-QoL domain scores in the study population to the reference values of the general population. Results Among the 565 included patients, 349 (61.8%) received CRT, and 216 (38.2%) were treated with CT. The mean age was 63.7 years (±SD 8.6), and mean time since surgery was 4.3 years (±SD 1.7). After multivariable analysis, patients treated with CT reported worse outcomes on ‘Social Functioning’ (∆means 4.56, p-value Conclusion Significant differences in favor of CRT were observed in several long-term HR-QoL domains for patients following esophagectomy for cancer. However, none of the observed differences in the reported long-term HR-QoL domains between patients treated with CT or with CRT, were clinically relevant (∆means≠ ≥ 10 points). Selection of neoadjuvant therapy should therefore be based on patient characteristics.

To compare complications following totally minimally invasive (TMIE), laparoscopically assisted (hybrid) and open Ivor Lewis esophagectomy in patients with esophageal cancer. Three randomized trials have reported benefits for minimally invasive esophagectomy. Two studies compared TMIE versus open esophagectomy and another compared hybrid versus open Ivor Lewis esophagectomy. Only small retrospective studies compared TMIE with hybrid Ivor Lewis esophagectomy. Methods Data were used from the International Esodata Study Group assessing patients undergoing TMIE, hybrid or open Ivor Lewis esophagectomy. Primary outcome was pneumonia, secondary outcomes included incidence and severity of anastomotic leakage, (major) complications, length of stay, escalation of care and 90-day mortality. Data were analyzed using multivariate multilevel models. Results In total, 4733 patients were included in this study (TMIE:1472, hybrid:1364 and open:1897). Patients undergoing TMIE had lower incidence of pneumonia compared to hybrid (10.9% vs 16.3%, Odds Ratio (OR):0.56, 95%CI: 0.40–0.80) and open esophagectomy (10.9% vs 17.4%, OR:0.60, 95%CI: 0.42–0.84) and had shorter length of stay (median 10 days (IQR 8–16)) compared to hybrid (14 (11–19), p = 0.041) and open esophagectomy (11 (9–16), p = 0.027). Patients undergoing TMIE had higher rate of anastomotic leakage compared to hybrid (15.1% vs 10.7%, OR:1.47, 95%CI: 1.01–2.13) and open esophagectomy (7.3%, OR:1.73, 95%CI: 1.26–2.38). No differences were reported between hybrid and open esophagectomy. Conclusion Compared to hybrid and open Ivor Lewis esophagectomy, TMIE resulted in a lower pneumonia rate, a shorter hospital length of stay but a higher anastomotic leakage rate. The impact of these individual complications on survival and long-term quality of life should be further investigated.

Numerous prediction models have been proposed to estimate the risk of complications after esophagectomy. However, these models are not commonly used in practice and surgeons generally trust on their own clinical judgment. The aim of this study is to compare the clinical judgment of the surgeons with the existing risk stratification models with regard to predicting complications after esophageal surgery. Methods Patients with resectable esophageal cancer who underwent an esophagectomy between March 2019 and January 2020 were included in this prospective study. Literature was searched to identify prediction models predicting the incidence of postoperative complications after esophagectomy. Clinical judgment of three surgeons was assessed using a standardized form where surgeons could indicate their estimated risk for postoperative complications. The best performing prediction model was compared with the judgment of the surgeons, using the Net Reclassification Improvement (NRI). A higher NRI correlates with better estimation by the surgeon and a negative NRI indicates a better prediction by the prediction model. Results Fifty-three patients were included, 36 patients (68%) developed a complication. Two risk classification models were identified in literature: Model 1 (Lagarde et al, Annals of thoracic surgery, 2008) and model 2 (Reeh et al, Medicine, 2016). Model 1 had a better discriminative ability than model 2 (Area Under the Receiver Operator Curve 0.738 versus 0.609). The NRI for the surgeons combined was −2%, meaning that model 1 outperforms the combined judgment of the surgeons. However, there was a large difference in clinical judgment between surgeons. Figure 1 shows the NRI for all three surgeons separately. Conclusion Surgeons‘assessment does not outperform prediction models in predicting the incidence of postoperative complications after esophageal surgery. However, there is a poor agreement between surgeons regarding their risk assessment based on their clinical judgment. Some surgeons might individually outperform existing risk stratification models. Surgeon’s assessment can therefore still be important when counseling patients about the risks of esophageal surgery in addition to risk stratification models.

Background: Identifying predictors of anastomotic leakage can contribute to prevention of this common complication after esophagectomy. This study identified predictors for anastomotic leakage and assessed the influence of anastomotic leakage on short-term outcomes and long-term survival. Methods: A retrospective cohort study was conducted of consecutive patients who underwent esophagectomy in the Amsterdam University Medical Centers, location Amsterdam Medical Center, between 1993 and 2019. Multilevel logistic and Cox regression models were used to assess predictors for anastomotic leakage and survival, and an operation year-level random effects was considered for the unmeasured characteristics at year of operation. Results: Included were 1539 patients, and anastomotic leakage developed in 288 (19%). Predictors for developing anastomotic leakage after a transthoracic esophagectomy were a higher body mass index and a cervical anastomosis. Diabetes mellitus type 2 and chronic obstructive pulmonary disease were predictors for anastomotic leakage after a transhiatal esophagectomy. Median intensive care unit and hospital stay was longer for patients with anastomotic leakage than for patients without anastomotic leakage (both P < .001 for transthoracic esophagectomy, P = .010 and P < .001, respectively, for transhiatal esophagectomy). A higher percentage of patients with anastomotic leakage died within 30 days (3.8% vs 1.9%, P = .050). However, anastomotic leakage did not significantly influence long-term survival (hazard ratio, 0.994; 95% CI, 0.849-1.176; P = .994). Conclusions: Higher body mass index, cervical anastomosis, diabetes mellitus, and chronic obstructive pulmonary disease are predictors for anastomotic leakage after esophagectomy. Anastomotic leakage is associated with worse short-term outcomes, but long-term survival was not influenced. Future studies should focus on patient optimization, accurate patient selection, and development of tools in risk assessment.

Background The impact of transthoracic (TTE) and transhiatal esophagectomy (THE) on long-term health-related quality of life (HR-QoL) in patients with distal esophageal or gastro-esophageal junction (GEJ) cancer has been studied with variable results. This study investigates long-term HR-QoL in patients having undergone TTE or THE. Methods Disease-free patients after TTE or THE for distal esophageal or GEJ cancer with a follow-up > 2 years were included. Patients who visited the outpatient clinic of a tertiary referral center between 2014 and 2018 were asked to complete EORTC-QLQ-C30 and EORTC-QLQ-OG25 questionnaires. Uni- and multivariable linear regression analysis of HR-QoL was performed in all patients and in subgroups of minimally invasive esophagectomy and neoadjuvant therapy. Results A total of 132 patients after TTE and 56 after THE were included. When compared with the general population, all patients reported worse HR-QoL in ‘role functioning’ and ‘social functioning’ and in a range of disease- and/or treatment-specific symptoms. The only significant difference between TTE and THE was a better HR-QoL score for “hair loss” following TTE (ß = 29.4,95%CI = -49.108 – −9.671, p = 0.016). Subgroup analysis of minimally invasively operated patients showed better scores in “physical functioning” following TTE (ß = 13.8,95%CI = 2.755–24.933, p = 0.030). No significant differences in HR-QoL were found between TTE and THE after neoadjuvant therapy. Conclusion Long-term HR-QoL is largely comparable in disease-free patients following TTE or THE for distal esophageal or GEJ cancer. If there were differences between the surgical groups, they were in favor of TTE. These findings may aid in preoperative counseling of patients with esophageal or GEJ cancer.

Introduction Esophagectomy and lymphadenectomy are essential parts of the multimodal treatment of esophageal carcinoma with curative intent. Treatment regimens vary globally and are subject to debate. A global survey was designed to gain insight into current practice. Methods Fifty-seven international expert upper gastrointestinal surgeons received a personal invitation to participate in the survey, which focused on demographics and experience; extent of lymphadenectomy in adeno and squamous cell carcinoma; use of classification systems; neoadjuvant therapy; surgical approach; and specimen handling. Results The response rate was 88% (50/57 surgeons), with a mean age of 51.6 years and a median number of 15 years of experience in esophageal surgery. The variety in the extent of lymphadenectomy in proximal, middle and distal squamous cell carcinoma, and Siewert I, II and III adenocarcinoma, was considerable. The number of different combinations of lymph node (LN) stations that were resected in the same tumor was high, while the number of surgeons who removed the exact same combination of LN stations was low. Illustrative is Siewert I adenocarcinoma, in which 27 unique combinations of LN stations were resected, with a maximum of two surgeons performing the exact same dissection. Use of neoadjuvant therapy, surgical approach, and specimen handling also show great variety among participants. Conclusion There is no uniform, worldwide strategy for surgical treatment of esophageal cancer. The extent of lymphadenectomy shows great variation for both histologic types. An international observational study is needed to provide evidence on the distribution pattern of lymph node metastases in esophageal cancer and the necessary extent of lymphadenectomy. Electronic supplementary material The online version of this article (10.1245/s10434-019-07316-9) contains supplementary material, which is available to authorized users.

Summary The 11th edition of the “Japanese Classification of Esophageal Cancer” by the Japan Esophageal Society (JES) and the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) “Cancer Staging Manual” are two separate classification systems both widely used for the clinical and pathological staging of esophageal cancer. Furthermore, the lymph node stations from these classification systems are combined for research purposes in the multinational TIGER study, which investigates the distribution pattern of lymph node metastases. The existing classification systems greatly differ with regard to number, location and anatomical boundaries of locoregional lymph node stations. The differences in these classifications cause significant heterogeneity in studies on lymph node metastases in esophageal cancer. This makes data interpretation difficult and comparison of studies challenging. In this article, we propose a match for these two commonly used classification systems and additionally for the TIGER study classification, in order to be able to compare results of studies and exchange knowledge and to make steps towards one global uniform classification system for all patients with esophageal cancer.

Background: The distribution of lymph node metastases in esophageal adenocarcinoma following neoadjuvant chemoradiation (nCRTx) is unclear, but may have consequences for radiotherapy and surgery. The aim of this study was to define the distribution of lymph node metastases and relation to the radiation field in patients following nCRTx and esophagectomy. Methods: Between April 2014 and August 2015 esophageal adenocarcinoma patients undergoing transthoracic esophagectomy with 2-field lymphadenectomy following nCRTx were included in this prospective observational study. Lymph node stations according to AJCC 7 were separately investigated. The location of lymph node metastases in relation to the radiation field was determined. The primary endpoint was the distribution of lymph node metastases and relation to the radiation field, the secondary endpoints were high-risk stations and risk factors for lymph node metastases and relation to survival. Results: Fifty consecutive patients were included. Lymph node metastases were found in 60% of patients and most frequently observed in paraesophageal (28%), left gastric artery (24%), and celiac trunk (18%) stations. Fifty-two percent had lymph node metastases within the radiation field. The incidence of lymph node metastases correlated significantly with ypT-stage (p = 0.002), cT-stage (p = 0.005), lymph angioinvasion (p = 0.004), and Mandard (p = 0.002). The number of lymph node metastases was associated with survival in univariable analysis (HR 1.12, 95% CI 1.068–1.173, p ' 0.001). Conclusions: Esophageal adenocarcinoma frequently metastasizes to both the mediastinal and abdominal lymph node stations. In this study, more than half of the patients had lymph node metastases within the radiation field. nCRTx is therefore not a reason to minimize lymphadenectomy in patients with esophageal adenocarcinoma.

Both a transthoracic (TTE) and a transhiatal (THE) esophagectomy may be possible in patients with a distal esophageal or gastroesophageal junction (GEJ) cancer. A number of studies report conflicting results in long-term health-related quality of life (HR-QoL) following these operations. This study investigates long-term HR-QoL in TTE and THE in a tertiary referral center. Methods Disease-free patients after a TTE or THE for distal esophageal or GEJ carcinoma with a follow-up >2 years were included. Patients who visited the outpatient clinic of a tertiary referral center in the Netherlands between 2014–2018 were asked to complete the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. Outcome measures were all 31 HR-QoL domains. Results During the study period, 132 patients underwent a TTE and 56 a THE. A better HR-QoL score was found for “problems with hair loss” (mean score 85.0 vs 114.4, p = 0.016) following TTE. Patients after minimally invasive TTE had better scores in ´physical functioning´ compared to minimally invasive THE (mean score 103.2 vs 88.6, p = 0.020). Patients following neoadjuvant therapy and TTE reported better “social functioning” compared to patients after neoadjuvant therapy and THE (mean scores 76.1 vs 59.9, p = 0.040). Conclusion Long-term HR-QoL results are largely comparable in disease-free patients following TTE or THE for distal esophageal or GEJ carcinoma. Some domains in the whole cohort and in subgroups differed at the advantage of a TTE. These findings may aid in providing information to esophageal or GEJ cancer patients on what can be expected following treatment.

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.

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.

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.

Summary Introduction Both cervical (McKeown) and intrathoracic (Ivor Lewis) anastomosis of transthoracic esophagectomy are surgical procedures that can be performed for distal esophageal or gastro-esophageal junction (GEJ) cancer. The purpose of this study was to investigate the long-term health-related quality of life (HR-QoL) after McKeown and Ivor Lewis esophagectomy in a tertiary referral center. Methods Disease-free patients >1 year following a McKeown or an Ivor Lewis esophagectomy with a two-field lymphadenectomy for a distal or GEJ carcinoma visiting the outpatient clinic between 2014 and 2018 were asked to complete the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. HR-QoL was investigated in both groups. Results A total of 89 patients were included after McKeown and 115 after Ivor Lewis esophagectomy. Median follow-up was 2.4 years (IQR 1.7–3.6). Patients after McKeown esophagectomy reported more problems with ‘eating with others’ compared to patients after Ivor Lewis esophagectomy (mean scores: 49.9 vs. 38.8). This difference was both clinically relevant and significant after correction for multiple testing (β = 11.1, 95% CI 3.105–19.127, P = 0.042). Patients in both groups reported a poorer HR-QoL (≥10 points) than the general population with respect to nausea and vomiting, dyspnea, appetite loss, financial difficulties, problems with eating, reflux, eating with others, choked when swallowing, trouble with coughing, and weight loss. Conclusion Long-term HR-QoL of disease-free patients following a McKeown or Ivor Lewis esophagectomy for a distal or GEJ carcinoma is largely comparable. Irrespective of the surgical technique, patients’ HR-QoL following esophagectomy is compromised. When given the choice, patients should be informed that after a McKeown esophagectomy more problems while eating with others can occur.

Esophageal surgery for esophageal cancer has been performed for over a century now. Minimally invasive esophagectomy (MIE) was first described in 1992, and it is now a standard approach in many countries. However, MIE is technically difficult and requires a long learning curve. It takes >100 cases to train for MIE with gastric tube reconstruction with an intrathoracic anastomosis. A possible option to overcome several challenges of MIE might be the use of a robotic system. A robot-assisted MIE was first described in 2005, and long-term results have shown its feasibility and safety. Over the years, different approaches for esophagectomy have been established. Our review discusses these developments and recent literature on open, minimally invasive and robotic esophageal surgery.

Aim To assess conditional survival and design a nomogram predicting the conditional probability of survival for esophageal cancer patients after surgery. Background and methods Conditional survival accounts for the time already survived after surgery and may be informative in addition to conventional static survival estimates during follow-up. Consecutive patients with esophageal cancer who received neoadjuvant chemoradiation followed by an esophagectomy between January 2004 and 2019 in the Amsterdam UMC, The Netherlands were included. Conditional survival was defined as the probability of surviving “y” years after already surviving for “x” years. Cox proportional hazard models were used to evaluate predictors for overall survival. A nomogram was constructed to predict 5-year survival correcting for time already survived. Results 660 patients were included in this study. The median overall survival was 46.4 months (95%CI 39.1–53.8). The probability to achieve 5-year overall survival after resection increased from 46% directly after surgery to 55%, 67%, 79% and 88% per additional year survived. ypN-stage was the strongest predictor for overall survival (HR6.50, p Conclusion The proposed nomogram showed an accurate prediction of survival in patients after esophageal cancer surgery, taking the years already survived after surgery into account. This nomogram can be helpful in counselling patients in the follow-up after esophageal cancer surgery.

Aim The aim of this study was to investigate the difference in long-term health-related quality of life in patients undergoing total gastrectomy versus Ivor Lewis esophagectomy in a tertiary referral center. Background & Methods Surgical treatment for gastroesophageal junction (GEJ) cancers is challenging. Both a total gastrectomy and an esophagectomy can be performed. Which of the two should be preferred is unknown given the scarce evidence regarding effects on surgical morbidity, pathology, long-term survival and health-related quality of life (HR-QoL). From 2014 to 2018, patients with a follow-up of > 1 year after either a total gastrectomy or an Ivor Lewis esophagectomy for GEJ or cardia carcinoma completed the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. Problems with eating, reflux and nausea and vomiting were chosen as the primary HR-QoL endpoints. The secondary endpoints were the remaining HR-QoL domains, postoperative complications and pathology results. Multivariable linear regression was applied taking confounders age, gender, ASA classification and neoadjuvant therapy into account. Results 30 patients after gastrectomy and 71 after Ivor Lewis esophagectomy with a mean age of 63 years were included. Median follow-up was two years (range 12-84 months). Patients after total gastrectomy reported significantly less choking when swallowing and coughing (β=-5.952, 95% CI -9.437 – -2.466; β=-13.084, 95% CI -18.525 – -7.643). Problems with eating, reflux and nausea and vomiting were not significantly different between the two groups. No significant difference was found in postoperative complications or Clavien-Dindo grade. Significantly more lymph nodes were resected in esophagectomy group (p=0.008). No difference in number of positive lymph nodes or R0 resection was found. Conclusion After a follow-up of > 1 year choking when swallowing and coughing were less common after total gastrectomy. No significant difference was found in problems with eating, reflux or nausea and vomiting nor in postoperative complications or radicality of surgery. Based on this study no general preference can be given to either of the procedures for GEJ cancer. Patients may be informed about the HR-QoL domains that are likely to be affected by the different surgical procedures, which in turn may support shared decision making when a choice between the two treatment options is possible.

Aim The aim of this study was to evaluate long-term HR-QoL in patients undergoing transhiatal versus transthoracic esophagectomy in a tertiary referral center. Background & Methods Treatment of esophageal cancers is challenging. Besides (neo)adjuvant chemo(radio)therapy different surgical approaches are possible such as transhiatal (THE) or transthoracic esophagectomy (TTE) with a cervical or intrathoracic anastomosis. Studies have been performed to establish evidence which is the preferred procedure in terms of postoperative morbidity, survival and short- and long-term health-related quality of life (HR-QoL). All patients after THE or TTE for distal esophageal or gastroesophageal junction carcinoma performed between 2003 and 2016 received EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. All questionnaires with a follow-up of more than two years after surgery were analysed. Three HR-QoL domains were chosen as primary endpoints: problems with eating, reflux and nausea and vomiting. The secondary endpoints were the remaining HR-QoL domains, postoperative complications and pathology results. The results were corrected for possible confounders such as age and gender. Results The questionnaire response rate was 47.6%, with 56 patients in the THE group and 134 in the TTE group. The mean age was 63.5 years and a median follow-up of 3.7 years (range 24-137 months) was reached. No significant difference was found in any of the HR-QoL domains or postoperative complications between the two groups. Significantly more lymph nodes were resected in the TTE group (p Conclusion After a long follow-up of more than two years no differences in HR-QoL or postoperative complications were found between patients with distal esophageal or gastroesophageal junction carcinoma undergoing THE or TTE esophagectomy. Based on this study we conclude that long-term quality of life should not influence the decision making for surgical approach between THE and TTE esophagectomy.

Aim This study aimed to investigate the impact of paratracheal lymphadenectomy on lymph node yield and short-term outcomes in patients undergoing esophagectomy for cancer. Background & Methods Although the addition of paratracheal lymphadenectomy to a standard two-field lymphadenectomy possibly may provide survival benefits for patients undergoing esophagectomy for esophageal cancer, the required dissection along the recurrent laryngeal nerves might be associated with increased morbidity. To investigate the impact of paratracheal lymphadenectomy on short-term oncological outcomes and postoperative complications, this nation-wide population-based cohort study included esophageal cancer patients who underwent neoadjuvant chemoradiotherapy followed by elective transthoracic esophagectomy with at least subcarinal and para-esophageal lymphadenectomy from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). After propensity score matching Ivor Lewis and McKeown approaches separately, the lymph node yield and clinical outcomes were compared between patients who underwent paratracheal lymphadenectomy versus patients who did not. Results Between 2011-2017, a total of 2128 patients were included. A total of 770 patients (n=385 vs. n=385) and 516 patients (n=258 vs. n=258) were matched for the Ivor Lewis and McKeown approaches, respectively. Paratracheal lymphadenectomy was associated with a higher total lymph node yield in both Ivor Lewis (23 vs. 19 nodes, P Conclusion In patients undergoing transthoracic esophagectomy for cancer, the addition of paratracheal lymphadenectomy results in a higher lymph node yield with comparable complication and mortality rates.

Aim The purpose of this study was to investigate the difference in long-term health-related quality of life (HR-QoL) between McKeown and Ivor Lewis esophagectomy in a tertiary referral center. Background & Methods The therapy of esophageal cancers consist of (neo)adjuvant chemo(radio)therapy and surgery. Often different surgical approaches are possible such as transthoracic esophagectomy with a cervical anastomosis (McKeown) or an intrathoracic anastomosis (Ivor Lewis). Evidence is scarce on whether either of these approaches is better in terms of survival, perioperative morbidity, pathology results and quality of life. Patients with mid-, distal esophageal, gastroesophageal (GEJ) or cardia carcinoma who have undergone a McKeown or an Ivor lewis esophagectomy in the period of 2003 – 2018 were included in this study. EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires were handed out during the outpatient clinic visits and a follow-up of at least one year was ensured. Problems with eating, reflux and nausea and vomiting were chosen as primary HR-QoL domain endpoints while the remaining HR-QoL domains, postoperative complications and pathology results were observed as secondary endpoints. Correction for confounders age and gender was performed. Results 147 patients were included in the McKeown group and 120 in the Ivor Lewis group. Mean age was 63.5 years and median follow-up was three years (range 12-137 months). No significant difference was found in problems with eating, reflux and nausea and vomiting. Significantly more problems with eating with others were found in McKeown group (β=10.435, 95% CI 4.474 – 16.395) and anastomotic leakage was significantly more common after McKeown esophagectomy (p=0.004). No significant difference was found in Clavien Dindo classification. During Ivor Lewis esophagectomy significantly more lymph nodes were resected (p Conclusion No major differences in long-term HR-QoL were found in patients with mid-, distal esophageal, GEJ or cardia carcinoma following McKeown or Ivor Lewis esophagectomy. Problems with eating with others and anastomotic leakages were more common after McKeown esophagectomy, however, Clavien Dindo classification and radicality of surgery were similar between the two groups. Results of this study could assist the patient during the decision-making process prior to the surgery.

Contains fulltext : 215779.pdf (Publisher’s version ) (Open Access) BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.

Background and Purpose: Decreased muscle mass and muscle strength are independent predictors of poor postoperative recovery in patients with esophageal cancer. If there is an association between muscle mass and muscle strength, physiotherapists are able to measure muscle strength as an early predictor for poor postoperative recovery due to decreased muscle mass. Therefore, in this cross-sectional study, we aimed to investigate the association between muscle mass and muscle strength in predominantly older patients with esophageal cancer awaiting esophagectomy prior to neoadjuvant chemoradiation. Methods: In patients with resectable esophageal cancer eligible for surgery between March 2012 and October 2015, we used computed tomographic scans to assess muscle mass and compared them with muscle strength measures (handgrip strength, inspiratory and expiratory muscle strength, 30 seconds chair stands test). We calculated Pearson correlation coefficients and determined associations by multivariate linear regression analysis. Results and Discussion: A tertiary referral center referred 125 individuals to physiotherapy who were eligible for the study; we finally included 93 individuals for statistical analysis. Multiple backward regression analysis showed that gender (95% confidence interval [CI], 2.05-33.82), weight (95% CI, 0.39-1.02), age (95% CI, -0.91 to -0.04), left handgrip strength (95% CI, 0.14-1.44), and inspiratory muscle strength (95% CI, 0.08-0.38) were all independently associated with muscle surface area at L3. All these variables together explained 66% of the variability (R2) in muscle surface area at L3 (P

Background Anastomotic leakage is one of the most severe complications following esophageal surgery, leading to significant morbidity, prolonged hospital stay, considerable costs, decreased quality of life, and increased mortality. Management of anastomotic leakage is complicated and has currently not been standardized. The objective of this research is to gain insight into the different opinions on anastomotic leakage management among upper gastrointestinal surgeons and verify the need for diagnostic and treatment guidelines. Methods Surgeons with interest in esophageal surgery were invited to participate in an international online questionnaire. The survey consisted of questions pertaining to the surgeons' experience, operation techniques, management routine, and opinion on future international guidelines on the treatment of anastomotic leakage. Results Of the 331 invited surgeons, 40% participated in the survey. Among the 129 responders, 90.7% use laboratory diagnostics and 62.8% use imaging or endoscopy postoperatively on a routine basis to detect anastomotic leakage. In case of suspected anastomotic leakage, the most chosen diagnostic imaging modalities were computed tomography scan (35.7%) or dynamic swallow investigation (33.3%). Independent from the clinical manifestations, participants of this survey treat patients very differently. More than 70% of the responders agreed that there is a need for diagnostic and therapeutic international guidelines on anastomotic leakage management. Conclusions This survey shows that there is no standardized guideline for diagnostic workup or management of anastomotic leakage and that there is a need for an international guideline regarding the optimal management of anastomotic leakage.

Background For patients with locally advanced esophageal cancer, radical esophageal resection with gastric tube reconstruction preceded by chemo(radio)therapy offers the best chance for cure. Anastomotic leakage (AL) is one of the most severe complications following esophageal surgery, leading to significant morbidity, prolonged hospital stay, considerable costs, decreased quality of life and increased mortality. Management is complicated and not standardized. The objective is to gain insight into the different opinions on AL management among upper gastrointestinal surgeons and to verify the need for a diagnostic and treatment guideline. Methods Surgeons with particular interest in esophageal surgery, were invited to participate in an online questionnaire. The survey consisted of questions pertaining to the surgeons’ experience, operation characteristics, management routine and their opinion on international guidelines on the diagnosis and therapy of AL. Results Of the 331 invited physicians, 40% participated in the survey. 90.7% Use laboratory diagnostics and 62.8% imaging and/or endoscopy postoperatively on routine basis. In case of suspected AL, the first choice of diagnostic imaging modalities was mostly a CT scan (35.7%) or a dynamic swallow investigation (33.3%). In case of AL, indepently of the clincal manifestations (local symptoms only, medianstinal manifestations or In case of gastric conduit necrosis) the treatment strategies differed widely between surgeons (table 1). Over 70% of the responders agree that there is a need for a solid international guideline on AL management. Conclusion There is no general consensus in the management of AL. There is a need for an international guideline regarding the optimal management of AL. Disclosure All authors have declared no conflicts of interest.

Background Muscle function loss and loss of skeletal muscle have been associated with worse outcomes following surgery for malignancies of gastrointestinal origin. The influence on post-operative outcomes and survival after esophageal surgery remains unclear. Primary objectives of this study were to evaluate the incidence of sarcopenia and malnutrition and to evaluate the influence of skeletal muscle surface area and muscle strength on postoperative outcomes and overall survival in esophageal cancer patients. Methods A retrospective cohort study from a prospective database was conducted in patients with resectable esophageal cancer who underwent curative-intent treatment between January 2011 and January 2016. Skeletal muscle surface area was calculated with CT scans at L3 level and corrected for height and weight before start of treatment and in the interval between neoadjuvant treatment and surgery. Muscle strength was evaluated with various tests on muscle functions and lung function tests. Nutritional status was evaluated using BMI. Results 273 Patients were included. There were 4 patients with sarcopenia before neoadjuvant therapy and only one patient with sarcopenia after completion of neoadjuvant therapy. Median skeletal muscle surface area was 78cm2/m2 for men and 61cm2/m2 for woman. Table 1 shows skeletal muscle surface area, muscle strength and BMI in relation to no, minor or major complications. Muscle strength and nutritional status did not have a significant influence on postoperative complications and overall survival. Conclusion Sarcopenia did not occur frequently in this cohort with potentially curable esophageal cancer patients. Muscle function, skeletal muscle index and BMI did not statistically influence post-operative complications or survival. Disclosure All authors have declared no conflicts of interest.

Background Lymph node status is an important prognostic parameter in esophageal carcinoma and an independent predictor of survival. Distribution of metastatic lymph nodes may vary with tumor location within the proximal or distal esophagus, tumor histology, tumor invasion depth and neoadjuvant therapy. Surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy differs worldwide. Especially for adenocarcinoma the distribution of lymph node metastases has not yet been described in large series. Aim of the present study is to evaluate the distribution of lymph node metastases in esophageal carcinoma specimens following transthoracic esophagectomy with a 2-or 3-field lymphadenectomy. Methods The TIGER-study is an international observational cohort study with 58 participating centers. All 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. Results We aim to start inclusion on 1/03/2018 and will present the first results during the congress. Conclusion 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 on the basis of these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. Disclosure All authors have declared no conflicts of interest.