Paravertebral versus EPidural Analgesia in Minimally Invasive Esophageal ResectioN (PEPMEN): A Randomized Controlled Multicenter Trial.

OBJECTIVE: To compare quality of recovery in patients receiving epidural or paravertebral analgesia for minimally invasive esophagectomy (MIE). SUMMARY BACKGROUND DATA: Paravertebral analgesia may be a promising alternative to epidural analgesia, avoiding potential side effects and improving postoperative recovery. METHODS: This randomized controlled superiority trial was conducted across four Dutch centers with esophageal cancer patients scheduled for transthoracic MIE with intrathoracic anastomosis, randomizing patients to receive either epidural or paravertebral analgesia. The primary outcome was Quality of Recovery (QoR-40) on the third postoperative day (POD). Secondary outcomes included quality of life, postoperative pain, opioid consumption, inotropic/vasopressor medication use, hospital stay, complications, readmission, and mortality. RESULTS: From December 2019 to February 2023, 192 patients were included: 94 received epidural and 98 paravertebral analgesia. QoR-40 score on POD3 was not different between groups (mean difference 3.7, 95%CI -2.3 to 9.7; P=0.268). Epidural patients had significant higher QoR-40 scores on POD1 and 2 (mean difference 7.7, 95%CI 2.3-13.1; P=0.018 and mean difference 7.3, 95%CI 1.9-12.7; P=0.020) and lower pain scores (median 1 versus 2; P=<0.001 and median 1 versus 2; P=0.033). More epidural patients required vasopressor medication on POD1 (38.3% versus 13.3%; P<0.001). Urinary catheters were removed earlier in the paravertebral group (median POD3 versus 4; P=<0.001). No significant differences were found in postoperative complications or hospital/Intensive Care Unit stay. CONCLUSIONS: This randomized controlled trial did not demonstrate superiority of paravertebral over epidural analgesia regarding quality of recovery on POD3 after MIE. Both techniques are effective and can be offered in clinical practice.

The Current State of Robot-Assisted Minimally Invasive Esophagectomy (RAMIE): Outcomes from the Upper GI International Robotic Association (UGIRA) Esophageal Registry.

BACKGROUND: Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted in centers worldwide, with ongoing refinements to enhance results. This study aims to assess the current state of RAMIE worldwide and to identify potential areas for improvement. METHODS: This descriptive study analyzed prospective data from esophageal cancer patients who underwent transthoracic RAMIE in Upper GI International Robotic Association (UGIRA) centers. Main endpoints included textbook outcome rate, surgical techniques, and perioperative outcomes. Analyses were performed separately for intrathoracic (Ivor-Lewis) and cervical anastomosis (McKeown), divided into three time cohorts (2016-2018, 2019-2020, 2021-2023). A sensitivity analysis was conducted with cases after the learning curve (> 70 cases). RESULTS: Across 28 UGIRA centers, 2012 Ivor-Lewis and 1180 McKeown procedures were performed. Over the time cohorts, textbook outcome rates were 39%, 48%, and 49% for Ivor-Lewis, and 49%, 63%, and 61% for McKeown procedures, respectively. Fully robotic procedures accounted for 66%, 51%, and 60% of Ivor-Lewis procedures, and 53%, 81%, and 66% of McKeown procedures. Lymph node yield showed 27, 30, and 30 nodes in Ivor-Lewis procedures, and 26, 26, and 34 nodes in McKeown procedures. Furthermore, high mediastinal lymphadenectomy was performed in 65%, 43%, and 37%, and 70%, 48%, and 64% of Ivor-Lewis and McKeown procedures, respectively. Anastomotic leakage rates were 22%, 22%, and 16% in Ivor-Lewis cases, and 14%, 12%, and 11% in McKeown cases. Hospital stay was 13, 14, and 13 days for Ivor-Lewis procedures, and 12, 9, and 11 days for McKeown procedures. In Ivor-Lewis and McKeown, respectively, the sensitivity analysis revealed textbook outcome rates of 43%, 54%, and 51%, and 47%, 64%, and 64%; anastomotic leakage rates of 28%, 18%, and 15%, and 13%, 11%, and 10%; and hospital stay of 11, 12, and 12 days, and 10, 9, and 9 days. CONCLUSIONS: This study demonstrates favorable outcomes over time in achieving textbook outcome after RAMIE. Areas for improvement include a reduction of anastomotic leakage and shortening of hospital stay.

Surgical treatment of esophago-tracheobronchial fistulas after esophagectomy.

The aim of this study was to evaluate the surgical treatment of esophago-tracheobronchial fistulas (ETBFs) that occurred after esophagectomy with gastric conduit reconstruction in a tertiary referral center for esophageal surgery. All patients who underwent surgical repair for an ETBF after esophagectomy with gastric conduit reconstruction were included in a tertiary referral center. The primary outcome was successful recovery after surgical treatment for ETBF, defined as a patent airway at 90 days after the surgical fistula repair. Secondary outcomes were details on the clinical presentation, diagnostics, and postoperative course after fistula repair. Between 2007 and 2022, 14 patients who underwent surgical repair for an ETBF were included. Out of 14 patients, 9 had undergone esophagectomy with cervical anastomosis and 5 esophagectomy with intrathoracic anastomosis after which 13 patients had developed anastomotic leakage. Surgical treatment consisted of thoracotomy to cover the defect with a pericardial patch and intercostal flap in 11 patients, a patch without interposition of healthy tissue in 1 patient, and fistula repair via cervical incision with only a pectoral muscle flap in 2 patients. After surgical treatment, 12 patients recovered (86%). Mortality occurred in two patients (14%) due to multiple organ failure. This study evaluated the techniques and outcomes of surgical repair of ETBFs following esophagectomy with gastric conduit reconstruction in 14 patients. Treatment was successful in 12 patients (86%) and generally consisted of thoracotomy and coverage of the defect with a bovine pericardial patch followed by interposition with an intercostal muscle.

Trends in Distal Esophageal and Gastroesophageal Junction Cancer Care: The Dutch Nationwide Ivory Study.

OBJECTIVE: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer. SUMMARY OF BACKGROUND DATA: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer. METHODS: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods. RESULTS: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% ( P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P <0.001), median lymph node harvest increased from 15 to 19 ( P <0.001), and median survival increased from 35 to 41 months ( P = 0.027). CONCLUSION: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

Implementation of the robotic abdominal phase during robot-assisted minimally invasive esophagectomy (RAMIE): results from a high-volume center.

BACKGROUND: Evidence on the added value of robotic-assistance in the abdominal phase during esophagectomy is scarce. In 2003, our center implemented the robotic thoracic phase for esophagectomy. In November 2018 the robot was also implemented in the abdominal phase. The aim of this study was to evaluate the implementation of the abdominal phase during robot-assisted minimally invasive esophagectomy (RAMIE). METHODS: Consecutive patients who underwent full RAMIE with intrathoracic anastomosis for esophageal cancer were included. Patients were extracted from a prospectively maintained institutional database. A cumulative sum (CUSUM) analysis was performed for abdominal operation time and abdominal lymph node yield. Intraoperative, postoperative and oncological outcomes including collected lymph nodes per abdominal lymph node station were reported. RESULTS: Between 2018 and 2021, 70 consecutive patients were included. The majority of the patients had an adenocarcinoma (n = 55, 77%) and underwent neoadjuvant chemo(radio)therapy (n = 65, 95%). The median operative time for the abdominal phase was 180 min (range 110-233). The CUSUM analysis for abdominal operation time showed a plateau at case 22. There were no intraoperative complications or conversions during the abdominal phase. The most common postoperative complications were pneumonia (n = 18, 26%) and anastomotic leakage (n = 14, 20%). Radical resection margins were achieved in 69 (99%) patients. The median total lymph node yield was 42 (range 23-83) and the median abdominal lymph node yield was 16 (range 2-43). The CUSUM analysis for abdominal lymph node yield showed a plateau at case 21. Most abdominal lymph nodes were collected from the left gastric artery (median 4, range 0-20). CONCLUSIONS: This study shows that a robotic abdominal phase was safely implemented for RAMIE without compromising intraoperative, postoperative and oncological outcomes. The learning curve is estimated to be 22 cases in a high-volume center with experienced upper GI robotic surgeons.

Hybrid laparoscopic versus fully robot-assisted minimally invasive esophagectomy: an international propensity-score matched analysis of perioperative outcome.

BACKGROUND: Currently, little is known regarding the optimal technique for the abdominal phase of RAMIE. The aim of this study was to investigate the outcome of robot-assisted minimally invasive esophagectomy (RAMIE) in both the abdominal and thoracic phase (full RAMIE) compared to laparoscopy during the abdominal phase (hybrid laparoscopic RAMIE). METHODS: This retrospective propensity-score matched analysis of the International Upper Gastrointestinal International Robotic Association (UGIRA) database included 807 RAMIE procedures with intrathoracic anastomosis between 2017 and 2021 from 23 centers. RESULTS: After propensity-score matching, 296 hybrid laparoscopic RAMIE patients were compared to 296 full RAMIE patients. Both groups were equal regarding intraoperative blood loss (median 200 ml versus 197 ml, p = 0.6967), operational time (mean 430.3 min versus 417.7 min, p = 0.1032), conversion rate during abdominal phase (2.4% versus 1.7%, p = 0.560), radical resection (R0) rate (95.6% versus 96.3%, p = 0.8526) and total lymph node yield (mean 30.4 versus 29.5, p = 0.3834). The hybrid laparoscopic RAMIE group showed higher rates of anastomotic leakage (28.0% versus 16.6%, p = 0.001) and Clavien Dindo grade 3a or higher (45.3% versus 26.0%, p < 0.001). The length of stay on intensive care unit (median 3 days versus 2 days, p = 0.0005) and in-hospital (median 15 days versus 12 days, p < 0.0001) were longer for the hybrid laparoscopic RAMIE group. CONCLUSIONS: Hybrid laparoscopic RAMIE and full RAMIE were oncologically equivalent with a potential decrease of postoperative complications and shorter (intensive care) stay after full RAMIE.

The Impact of Paratracheal Lymphadenectomy on Lymph Node Yield and Short-Term Outcomes in Esophagectomy for Cancer: A Nation-Wide Propensity Score-Matched Analysis.

INTRODUCTION: The balance between potential oncological merits and surgical risks is unclear for the additional step of performing paratracheal lymphadenectomy during esophagectomy for cancer. This study aimed to investigate the impact of paratracheal lymphadenectomy on lymph node yield and short-term outcomes in patients who underwent this procedure in the Netherlands. METHODS: Patients who underwent neoadjuvant chemoradiotherapy followed by transthoracic esophagectomy were included from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). After propensity score matching Ivor Lewis and McKeown approaches separately, lymph node yield and short-term outcomes were compared between patients who underwent paratracheal lymphadenectomy versus patients who did not. RESULTS: Between 2011 and 2017, 2,128 patients were included. Some 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 lymph node yield in Ivor Lewis (23 vs. 19 nodes, p < 0.001) and McKeown (21 vs. 19 nodes, p = 0.015) esophagectomy. There were no significant differences in complications or mortality. After Ivor Lewis esophagectomy, paratracheal lymphadenectomy was associated with longer length of stay (12 vs. 11 days, p < 0.048). After McKeown esophagectomy, paratracheal lymphadenectomy was associated with more re-interventions (30% vs. 18%, p = 0.002). CONCLUSIONS: Paratracheal lymphadenectomy resulted in a higher lymph node yield but also in longer length of stay after Ivor Lewis and more re-interventions following McKeown esophagectomy.

Trends in surgical techniques for the treatment of esophageal and gastroesophageal junction cancer: the 2022 update.

The aim of this study was to evaluate the current practice in surgical techniques for esophageal and gastroesophageal junction cancer surgery worldwide and to compare the results to the previous surveys in 2007 and 2014. An online survey was sent out among surgical members of the International Society for Diseases of the Esophagus, the World Organization for Specialized Studies on Disease of the Esophagus, the International Gastric Cancer Association, the Association of Upper Gastrointestinal Surgery of Great Britain and Ireland and Dutch gastroesophageal surgeons via the network of the investigators. In total, 260 surgeons completed the survey representing 52 countries and 6 continents; Europe 56%, Oceania 14%, Asia 14%, South-America 9%, North-America 7%. Of the responding surgeons, 39% worked in a hospital that performed >51 esophagectomies per year. Total minimally invasive esophagectomy was the preferred technique (53%) followed by hybrid esophagectomy (26%) of which 7% consisted of a minimally invasive thoracic phase and 19% of a minimally invasive abdominal phase. Total open esophagectomy was preferred by 21% of the respondents. Total minimally invasive esophagectomy was significantly more often performed in high-volume centers compared with non-high-volume centers (P = 0.002). Robotic assistance was used in 13% during the thoracic phase and 6% during the abdominal phase. Minimally invasive transthoracic esophagectomy has become the preferred approach for esophagectomy. Although 21% of the surgeons prefer an open approach, 26% of the surgeons perform a hybrid procedure which may reflect further transition towards the use of total minimally invasive esophagectomy.

Management of anastomotic leakage after robot-assisted minimally invasive esophagectomy with an intrathoracic anastomosis.

Anastomotic leakage is a feared complication after esophagectomy and associated with increased post-operative morbidity and mrotality. The aim of this study was to evaluate the management of leakage after robot-assisted minimally invasive esophagectomy (RAMIE) with intrathoracic anastomosis. From a single center prospectively maintained database, all patients with anastomotic leakages defined by the Esophageal Complications Consensus Group between 2016 and 2021 were included. Contained leakage was defined as presence of air or fluid at level of the anastomosis without the involvement of the mediastinum or thorax. Non-contained leakage was defined as mediastinitis and/or mediastinal/pleural fluid collections. The primary outcome was 90-day mortality and the secondary outcome was successful recovery. In this study, 40 patients with anastomotic leakage were included. The 90-day mortality rate was 3% (n = 1). Leakage was considered contained in 29 patients (73%) and non-contained in 11 patients (27%). In the contained group, the majority of the patients were treated non-surgically (n = 27, 93%) and management was successful in 22 patients (76%). In the non-contained group, all patients required a reoperation with thoracic drainage and management was successful in seven patients (64%). Management failed in 11 patients (28%) of whom 7 developed an esophagobronchial fistula, 3 had a disconnection of the anastomosis and 1 died of a septic bleeding. In conclusion, this study demonstrates that the management anastomotic leakage in patients who underwent RAMIE with an intrathoracic anastomosis was successful in 73% of the patients with a 90-day mortality rate of 3%. A differentiated approach for the management of intrathoracic anastomotic leakage is proposed.

Worldwide Techniques and Outcomes in Robot-assisted Minimally Invasive Esophagectomy (RAMIE): Results From the Multicenter International Registry.

OBJECTIVE: This international multicenter study by the Upper GI International Robotic Association aimed to gain insight in current techniques and outcomes of RAMIE worldwide. BACKGROUND: Current evidence for RAMIE originates from single-center studies, which may not be generalizable to the international multicenter experience. METHODS: Twenty centers from Europe, Asia, North-America, and South-America participated from 2016 to 2019. Main endpoints included the surgical techniques, clinical outcomes, and early oncological results of ramie. RESULTS: A total of 856 patients undergoing transthoracic RAMIE were included. Robotic surgery was applied for both the thoracic and abdominal phase (45%), only the thoracic phase (49%), or only the abdominal phase (6%). In most cases, the mediastinal lymphadenectomy included the low paraesophageal nodes (n=815, 95%), subcarinal nodes (n = 774, 90%), and paratracheal nodes (n = 537, 63%). When paratracheal lymphadenectomy was performed during an Ivor Lewis or a McKeown RAMIE procedure, recurrent laryngeal nerve injury occurred in 3% and 11% of patients, respectively. Circular stapled (52%), hand-sewn (30%), and linear stapled (18%) anastomotic techniques were used. In Ivor Lewis RAMIE, robot-assisted hand-sewing showed the highest anastomotic leakage rate (33%), while lower rates were observed with circular stapling (17%) and linear stapling (15%). In McKeown RAMIE, a hand-sewn anastomotic technique showed the highest leakage rate (27%), followed by linear stapling (18%) and circular stapling (6%). CONCLUSION: This study is the first to provide an overview of the current techniques and outcomes of transthoracic RAMIE worldwide. Although these results indicate high quality of the procedure, the optimal approach should be further defined.

Recurrent Disease After Esophageal Cancer Surgery: A Substudy of The Dutch Nationwide Ivory Study.

OBJECTIVE: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery. BACKGROUND: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission. METHODS: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival. RESULTS: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6-4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4-23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65-0.84). CONCLUSIONS: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

The Value of Paratracheal Lymphadenectomy in Esophagectomy for Adenocarcinoma of the Esophagus or Gastroesophageal Junction: A Systematic Review of the Literature.

BACKGROUND: The role of upper mediastinal lymphadenectomy for distal esophageal or gastroesophageal junction (GEJ) adenocarcinomas remains a matter of debate. This systematic review aims to provide a comprehensive overview of evidence on the incidence of nodal metastases in the upper mediastinum following transthoracic esophagectomy for distal esophageal or GEJ adenocarcinoma. METHODS: A literature search was performed using Medline, Embase and Cochrane databases up to November 2020 to include studies on patients who underwent transthoracic esophagectomy with upper mediastinal lymphadenectomy for distal esophageal and/or GEJ adenocarcinoma. The primary endpoint was the incidence of metastatic nodes in the upper mediastinum based on pathological examination. Secondary endpoints were the definition of upper mediastinal lymphadenectomy, recurrent laryngeal nerve (RLN) palsy rate and survival. RESULTS: A total of 17 studies were included and the sample sizes ranged from 10-634 patients. Overall, the median incidence of upper mediastinal lymph node metastases was 10.0% (IQR 4.7-16.7). The incidences of upper mediastinal lymph node metastases were 8.3% in the 7 studies that included patients undergoing primary resection (IQR 2.0-16.6), 4,4% in the 1 study that provided neoadjuvant therapy to the full cohort, and 10.6% in the 9 studies that included patients undergoing esophagectomy either with or without neoadjuvant therapy (IQR 8.9-15.8%). Data on survival and RLN palsy rates were scarce and inconclusive. CONCLUSIONS: The incidence of upper mediastinal lymph node metastases in distal esophageal adenocarcinoma is up to 10%. Morbidity should be weighed against potential impact on survival.

Safety and feasibility of minimally invasive surgical interventions for esophageal and gastric cancer in the acute setting: a nationwide cohort study.

BACKGROUND: Minimally invasive esophagectomy and gastrectomy are increasingly performed and might be superior to their open equivalents in an elective setting. The aim of this study was to evaluate whether minimally invasive approaches can be safely applied in the acute setting as well. METHODS: All patients who underwent an acute surgical intervention for primary esophageal or gastric cancer between 2011 and 2017 were identified from the nationwide database of the Dutch Upper GI Cancer Audit (DUCA). Conversion rates, postoperative complications, re-interventions, postoperative mortality, hospital stay and oncological outcomes (radical resection rates and median lymph node yield) were evaluated. RESULTS: Between 2011 and 2017, surgery for esophagogastric cancer was performed in an acute setting in 2% (190/8861) in The Netherlands. A total of 14 acute resections for esophageal cancer were performed, which included 7 minimally invasive esophagectomies and 7 open esophagectomies. As these numbers were very low, no comparison between minimally invasive and open esophagectomies was made. A total of 122 acute resections for gastric cancer were performed, which included 39 minimally invasive gastrectomies and 83 open gastrectomies. Conversion occurred in 9 patients (23%). Minimally invasive gastrectomy was at least comparable to open gastrectomy regarding postoperative complications (36% versus 51%), median hospital stay (9 days [IQR: 7-16 days] versus 11 days [IQR: 7-17 days]), readmissions (8% versus 11%) and oncological outcomes (radical resection rate: 87% versus 66%, median lymph node yield: 21 [IQR: 15-32 days] versus 16 [IQR: 11-24 days]). CONCLUSIONS: Minimally invasive surgery for gastric cancer is safe and feasible in the acute setting, with at least comparable postoperative clinical and short-term oncological outcomes compared to open surgery but a relatively high conversion rate.

Decrease of physical fitness during neoadjuvant chemoradiotherapy predicts the risk of pneumonia after esophagectomy.

Although neoadjuvant chemoradiotherapy (nCRT) is frequently used in esophageal cancer patients undergoing treatment with curative intent, it can negatively impact patients' physical fitness. A decline in physical fitness during chemoradiotherapy may be an indication of vulnerability. The aim of this study was to evaluate whether changes in physical fitness, weight, and fat-free mass index (FFMI) during nCRT can predict the risk of postoperative pneumonia. A retrospective longitudinal observational cohort study was performed in patients who received curative treatment for esophageal cancer between September 2016 and September 2018 in a high-volume center for esophageal cancer surgery. Physical fitness (handgrip strength, leg extension strength, and exercise capacity), weight, and FFMI were measured before and after chemoradiotherapy. To be included in the data analyses, pre- and post-nCRT data had to be available of at least one of the outcome measures. Logistic regression analyses were performed to evaluate the predictive value of changes in physical fitness, weight, and FFMI during nCRT on postoperative pneumonia, as defined by the Uniform Pneumonia Scale. In total, 91 patients were included in the data analyses. Significant associations were found between the changes in handgrip strength (odds ratio [OR] 0.880, 95% confidence interval [CI]: 0.813-0.952) and exercise capacity (OR 0.939, 95%CI: 0.887-0.993) and the occurrence of postoperative pneumonia. All pneumonias occurred in patients with declines in handgrip strength and exercise capacity after nCRT. A decrease of handgrip strength and exercise capacity during nCRT predicts the risk of pneumonia after esophagectomy for cancer. Measuring physical fitness before and after chemoradiotherapy seems an adequate method to identify patients at risk of postoperative pneumonia.

Machine learning to predict early recurrence after oesophageal cancer surgery.

BACKGROUND: 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.

ANTECEDENTES: la recidiva precoz del cáncer tras esofaguectomía es un problema frecuente con una incidencia del 20-30% a pesar del uso generalizado del tratamiento neoadyuvante. La cuantificación de este riesgo es difícil y los modelos actuales funcionan mal. Este estudio se propuso desarrollar un modelo predictivo para la recidiva precoz después de la cirugía para el adenocarcinoma de esófago utilizando una gran cohorte multinacional y enfoques con aprendizaje automático. MÉTODOS: Se analizaron pacientes consecutivos sometidos a esofaguectomía por adenocarcinoma y que recibieron tratamiento neoadyuvante en 6 unidades de cirugía esofagogástrica del Reino Unido y 1 de los Países Bajos. Con la utilización de características clínicas y la histopatología postoperatoria se generaron modelos mediante regresión de red elástica (elastic net regression, ELR) y métodos de aprendizaje automático Random Forest (RF) y XG boost (XGB). Finalmente, se generó un modelo combinado (Ensemble) de dichos métodos. La importancia relativa de los factores respecto al resultado se calculó como porcentaje de contribución al modelo. RESULTADOS: En total se incluyeron 812 pacientes. La tasa de recidiva a menos de 1 año fue del 29,1%. Todos los modelos demostraron una buena discriminación. Las áreas bajo la curva ROC (AUC) validadas internamente fueron similares, con el modelo Ensemble funcionando mejor (ELR = 0,791, RF = 0,801, XGB = 0,804, Ensemble = 0,805). El rendimiento fue similar cuando se utilizaba validación interna-externa (validación entre centros, Ensemble AUC = 0,804). En el modelo final, las variables más importantes fueron el número de ganglios linfáticos positivos (25,7%) y la invasión linfovascular (16,9%). CONCLUSIÓN: El modelo derivado con la utilización de aproximaciones con aprendizaje automático y un conjunto de datos internacional proporcionó un rendimiento excelente para cuantificar el riesgo de recidiva precoz tras la cirugía y será útil para clínicos y pacientes a la hora de establecer un pronóstico.

Paravertebral catheter versus EPidural analgesia in Minimally invasive Esophageal resectioN: a randomized controlled multicenter trial (PEPMEN trial).

BACKGROUND: Thoracic epidural analgesia is the standard postoperative pain management strategy in esophageal cancer surgery. However, paravertebral block analgesia may achieve comparable pain control while inducing less side effects, which may be beneficial for postoperative recovery. This study primarily aims to compare the postoperative quality of recovery between paravertebral catheter versus thoracic epidural analgesia in patients undergoing minimally invasive esophagectomy. METHODS: This study represents a randomized controlled superiority trial. A total of 192 patients will be randomized in 4 Dutch high-volume centers for esophageal cancer surgery. Patients are eligible for inclusion if they are at least 18 years old, able to provide written informed consent and complete questionnaires in Dutch, scheduled to undergo minimally invasive esophagectomy with two-field lymphadenectomy and an intrathoracic anastomosis, and have no contra-indications to either epidural or paravertebral analgesia. The primary outcome is the quality of postoperative recovery, as measured by the Quality of Recovery-40 (QoR-40) questionnaire on the morning of postoperative day 3. Secondary outcomes include the QoR-40 questionnaire score Area Under the Curve on postoperative days 1-3, the integrated pain and systemic opioid score and patient satisfaction and pain experience according to the International Pain Outcomes (IPO) questionnaire, and cost-effectiveness. Furthermore, the groups will be compared regarding the need for additional rescue medication on postoperative days 0-3, technical failure of the pain treatment, duration of anesthesia, duration of surgery, total postoperative fluid administration day 0-3, postoperative vasopressor and inotrope use, length of urinary catheter use, length of hospital stay, postoperative complications, chronic pain at six months after surgery, and other adverse effects. DISCUSSION: In this study, it is hypothesized that paravertebral analgesia achieves comparable pain control while causing less side-effects such as hypotension when compared to epidural analgesia, leading to shorter postoperative length of stay on a monitored ward and superior quality of recovery. If this hypothesis is confirmed, the results of this study can be used to update the relevant guidelines on postoperative pain management for patients undergoing minimally invasive esophagectomy. TRIAL REGISTRATION: Netherlands Trial Registry, NL8037. Registered 19 September 2019.

Two isothermal challenges yield comparable physiological and subjective responses.

PURPOSE: Ventilated vests are developed to reduce thermal stress by enhancing convective and evaporative cooling from skin tissue underneath the vest. The purpose of this study is to investigate whether thermal stress is equal when a ventilated vest is worn compared to a no-vest situation with similar dry thermal resistance. METHODS: Nine healthy males walked on a treadmill (7 km h-1) for 45 min in a desert climate (34 °C, 20% relative humidity) with and without ventilated vest. Gastrointestinal temperature (Tgi), heart rate (HR), and skin temperature (Tsk) were continuously monitored. Local sweat rate (LSR) was assessed two times on six skin locations. Subjective ratings were assessed every 10 min. RESULTS: Final Tgi (37.6 ± 0.1 °C for vest and 37.6 ± 0.1 °C for no-vest), HR (133 ± 7 bpm and 133 ± 9 bpm) and mean Tsk (34.8 ± 0.7 °C and 34.9 ± 0.6 °C) were not different between conditions (p ≥ 0.163). Scapula skin temperature (Tscapula) under the vest tended to be lower (baseline to final: ΔTscapula = 0.35 ± 0.37 °C) than without vest (ΔTscapula = 0.74 ± 0.62 °C, p = 0.096). LSR at locations outside the vest did not differ with and without vest (p ≥ 0.271). Likewise, subjective responses did not differ between conditions (χ2 ≥ 0.143). CONCLUSIONS: We conclude that two systems with similar dry thermal resistance and, therefore, similar required evaporation, resulted in similar thermal stress during paced walking in a hot-dry environment. Local ventilation did not alter the sweating response on locations outside the vest.

A standardized approach for the thoracic dissection in robotic-assisted minimally invasive esophagectomy (RAMIE).

Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly being adopted as the preferred surgical treatment for esophageal cancer, as it is superior to open esophagectomy and a good alternative to conventional minimally invasive esophagectomy. This paper addresses the technical details of the thoracoscopic phase of RAMIE, including the operating room set-up, patient positioning, port placement, and surgical steps.

A structured training pathway to implement robot-assisted minimally invasive esophagectomy: the learning curve results from a high-volume center.

To ensure safe implementation of robot-assisted minimally invasive esophagectomy (RAMIE), the learning process should be optimized. This study aimed to report the results of a surgeon who implemented RAMIE in a German high-volume center by following a tailored and structured training pathway that involved proctoring. Consecutive patients who underwent RAMIE during the course of the program were included from a prospective database. A single surgeon, who had prior experience in conventional MIE, performed all RAMIE procedures. Cumulative sum (CUSUM) learning curves were plotted for the thoracic operating time and intraoperative blood loss. Perioperative outcomes were compared between patients who underwent surgery before and after a learning curve plateau occurred. Between 2017 and 2018, the adopting center adhered to the structured training pathway, and a total of 70 patients were included in the analysis. The CUSUM learning curves showed plateaus after 22 cases. In consecutive cases 23 to 70, the operating time was shorter for both the thoracic phase (median 215 vs. 249 minutes, P = 0.001) and overall procedure (median 394 vs. 440 minutes, P = 0.005), intraoperative blood loss was less (median 210 vs. 400 milliliters, P = 0.029), and lymph node yield was higher (median 32 vs. 23 nodes, P = 0.001) when compared to cases 1 to 22. No significant differences were found in terms of conversion rates, postoperative complications, length of stay, completeness of resection, or mortality. In conclusion, the structured training pathway resulted in a short and safe learning curve for RAMIE in this single center's experience. As the pathway seems effective in implementing RAMIE without compromising the early oncological outcomes and complication rates, it is advised for surgeons who are wanting to adopt this technique.

Robot-assisted minimally invasive thoracolaparoscopic esophagectomy versus open esophagectomy: long-term follow-up of a randomized clinical trial.

Initial results of the ROBOT, which randomized between robot-assisted minimally invasive esophagectomy (RAMIE) and open transthoracic esophagectomy (OTE), showed significantly better short-term postoperative outcomes in favor of RAMIE. However, it is not yet clarified if RAMIE is equivalent to OTE regarding long-term outcomes. The aim of this study was to report the long-term oncological results of the ROBOT trial in terms of survival and disease-free survival. This study is a follow-up study of the ROBOT trial, which was a randomized controlled trial comparing RAMIE to OTE in 112 patients with intrathoracic esophageal cancer. Both the trial protocol and short-term results were previously published. The primary outcome of the current study was 5-year overall survival. Secondary outcomes were disease-free survival and recurrence patterns. Analysis was by intention to treat. During the recruitment period, 109 patients were included in the survival analysis (RAMIE n = 54, OTE n = 55). Majority of patients had clinical stage III or IV (RAMIE 63%, OTE 55%) and received neoadjuvant chemoradiotherapy (80%). Median follow-up was 60 months (range 31-60). The combined 5-year overall survival rates for RAMIE and OTE were 41% (95% CI 27-55) and 40% (95% CI 26-53), respectively (log rank test P = 0.827). The 5-year disease-free survival rate was 42% (95% CI 28-55) in the RAMIE group and 43% (95% CI 29-57) in the OTE group (log rank test P = 0.749). Out of 104 patients, 57 (55%) developed recurrent disease detected at a median of 10 months (range 0-56) after surgery. No statistically difference in recurrence rate nor recurrence pattern was observed between both groups. Overall survival and disease-free survival of RAMIE are comparable to OTE. These results continue to support the use of robotic surgery for esophageal cancer.