Search

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., Competing Interests: Disclosure: Mark van Berge Henegouwen: Consulting or advisory role: Viatris, Johnson & Johnson, BBraun, Stryker, Medtronic. Philippe Rouanet, Anne Mourregot, Gijs van Boxel, Marc van Det, Ewout A. Kouwenhoven: Consulting or advisory role: Intuitive Surgical. Peter Grimminger: Consulting or advisory role: Intuitive Surgical, Medicaroid. Guillaume Piessen: Consulting or advisory role: BMS, Nestlé, Astellas Pharma, Daiichi; travel or accommodation: Medtronic, MSD. Inderpal Sarkaria: Teaching, consulting, research grants, co-founder and/or advisory: CMR, Intuitive, Medtronic, Stryker, OTL, Activ Surgical, AMSI, VAIM, Oncolys. Takahiro Kinoshita: Honorarium for lectures for Intuitive Surgical. Jelle Ruurda: Consulting or advisory role: Intuitive Surgical, Medtronic. Richard van Hillegersberg: Consulting or advisory role: Intuitive Surgical, Medtronic, Olympus. Cas de Jongh: Research grant in 2018 for a period of 1 year to make a start with establishing the UGIRA Esophageal Registry, provided by Intuitive (this is mentioned in the manuscript). Philip Chiu: Cornerstone Robotics Co. Ltd; serves as a Board member with stock options. Nicholas Carter: Proctor for Intuitive Surgical teaching robotic surgery to other hospitals. Christiane Bruns: Advisory board, Medtronic; oral presentations, AstraZeneca; grant support, Sirtex; Editorial Board, MedUpdate; research grant, Stryker. James Luketich: Owns stock in Intuitive Surgical but this represents <5% of his investments and does not influence his research. Suzanne Gisbertz: J&J (money paid to institution, not to her personally); Medicaroid (money paid to institution, not to her personally); Olympus (money paid to institution, not to her personally). Cezanne D. Kooij, B. Feike Kingma, Yin-Kai Chao, Arul Immanuel, Tom Mala, Hecheng Li, Hans F. Fuchs, Simone Giacopuzzi, Jörg C. Kalff, Jens-Peter Hölzen, Mazen A. Juratli, Frank Benedix, Eric Lorenz, Jan-Hendrik Egberts, Jan W. Haveman, Boudewijn van Etten, Beat P. Müller, Felix Berlth, Jan W. van den Berg, Marco Milone, Rubens A.A. Sallum, Matthias Brüwer, Tomas Harustiak, Takeo Fujita, Hiroyuki Daiko, and Zhigang Li have declared no conflicts of interest that may be relevant to the contents of this study., (© 2024. The Author(s).)

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy., Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.4 Gy and carboplatin and paclitaxel) plus surgery. Eligibility criteria included a primary tumor with a clinical stage of cT1 cN+, cT2-4a cN+, or cT2-4a cN0 disease, in which T indicates the size and extent of the tumor (higher numbers indicate a more advanced tumor), and N indicates the presence (N+) or absence (N0) of cancer spread to the lymph nodes, without evidence of metastatic spread. The primary end point was overall survival., Results: From February 2016 through April 2020, we assigned 221 patients to the FLOT group and 217 patients to the preoperative-chemoradiotherapy group. With a median follow-up of 55 months, overall survival at 3 years was 57.4% (95% confidence interval [CI], 50.1 to 64.0) in the FLOT group and 50.7% (95% CI, 43.5 to 57.5) in the preoperative-chemoradiotherapy group (hazard ratio for death, 0.70; 95% CI, 0.53 to 0.92; P = 0.01). Progression-free survival at 3 years was 51.6% (95% CI, 44.3 to 58.4) in the FLOT group and 35.0% (95% CI, 28.4 to 41.7) in the preoperative-chemoradiotherapy group (hazard ratio for disease progression or death, 0.66; 95% CI, 0.51 to 0.85). Among the patients who started the assigned treatment, grade 3 or higher adverse events were observed in 120 of 207 patients (58.0%) in the FLOT group and in 98 of 196 patients (50.0%) in the preoperative-chemoradiotherapy group. Serious adverse events were observed in 98 of 207 patients (47.3%) in the FLOT group and in 82 of 196 patients (41.8%) in the preoperative-chemoradiotherapy group. Mortality at 90 days after surgery was 3.1% in the FLOT group and 5.6% in the preoperative-chemoradiotherapy group., Conclusions: Perioperative chemotherapy with FLOT led to improved survival among patients with resectable esophageal adenocarcinoma as compared with preoperative chemoradiotherapy. (Funded by the German Research Foundation; ESOPEC ClinicalTrials.gov number, NCT02509286.)., (Copyright © 2025 Massachusetts Medical Society.)

Purpose: In 2012, the CROSS trial implemented a new neoadjuvant radiochemotherapy protocol for patients with locally advanced, resectable cancer of the esophagus prior to scheduled surgery. There are only limited studies comparing the CROSS protocol with a PF-based (cisplatin/5-fluorouracil) nRCT protocol., Methods: In this retrospective, monocentric analysis, 134 patients suffering from esophageal cancer were included. Those patients received either PF-based nRCT (PF group) or nRCT according to the CROSS protocol (CROSS group) prior to elective en bloc esophagectomy. Perioperative mortality and morbidity, nRCT-related toxicity, and complete pathological regression were compared between both groups. Logistic regression analysis was performed in order to identify independent factors for pathological complete response (pCR)., Results: Thirty-day/hospital mortality showed no significant differences between both groups. Postoperative complications ≥ grade 3 according to Clavien-Dindo classification were experienced in 58.8% (PF group) and 47.6% (CROSS group) (p = 0.2) respectively. nRCT-associated toxicity ≥ grade 3 was 30.8% (PF group) and 37.2% (CROSS group) (p = 0.6). There was no significant difference regarding the pCR rate between both groups (23.5% vs. 30.5%; p = 0.6). In multivariate analysis, SCC (OR 7.7; p < 0.01) and an initial grading of G1/G2 (OR 2.8; p = 0.03) were shown to be independent risk factors for higher rates of pCR., Conclusion: We conclude that both nRCT protocols are effective and safe. There were no significant differences regarding toxicity, pathological tumor response, and postoperative morbidity and mortality between both groups. Squamous cell carcinoma (SCC) and favorable preoperative tumor grading (G1 and G2) are independent predictors for higher pCR rate in multivariate analysis., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

Introduction: Anastomotic insufficiency after oesophagectomy contributes significantly to morbidity and mortality of affected patients. A safe surgical technique can reduce the incidence of such anastomotic insufficiencies., Indication: In the treatment of oesophageal cancer, the German guideline recommends minimally invasive or hybrid surgical procedures. In most cases, Ivor-Lewis oesophagectomy and continuity reconstruction using a gastric sleeve are performed. Circular stapler anastomosis seems to be superior., Method: The preparation of the anastomosis starts intra-abdominally with mobilisation of the stomach and sparing of the gastroepiploic vessels. After the subsequent intrathoracic mobilisation of the oesophagus, the actual anastomosis construction can take place. Here, the oesophagus is either transected with a stapler closure or openly with scissors. This is followed by a purse-string suture on the open oesophageal stump. Alternatively, partial oesophageal opening with prior purse-string suture may later facilitate insertion of the stapler anvil. The anvil is placed in the oesophageal stump via minithoracotomy or alternatively transorally using a special gastric tube system. Subsequently, the anvil is fixated using the previously performed purse-string suture. Now the gastric sleeve can be pulled into the thorax. The oesophagus and small gastric curvature are placed extrathoracically through the minithoracotomy and a circular stapler is inserted into the gastric tube via an opening of the small curvature. The anastomosis then must be placed remotely from the gastroepiploic arcade. After construction of the anastomosis, the gastric sleeve is separated using a linear stapler. Eventually, the oesophagus and small gastric curvature can be completely recovered. Optionally, an additional suturing over the anastomosis and dissection margin of the gastric sleeve can be performed., Conclusion: In robot-assisted oesophagectomy, the reconstruction of continuity with a circular stapler anastomosis is quite possible and seems comparatively easier to learn. Nevertheless, variations are still possible within this procedure. However, there is no scientific evidence on the advantage for any method in a direct comparison., Competing Interests: Felix von Bechtolsheim, Frank Benedix, Andre Mihaljevic, Jürgen Weitz und Marius Distler geben an, keine Interessenskonflikte zu haben. Richard Hummel gibt an, einen „Educational Grant Funding from Intuitive 2021“ erhalten zu haben., (Thieme. All rights reserved.)

Purpose: Minimally invasive en-bloc esophagectomy is associated with a reduction of postoperative morbidity. This was demonstrated for both total minimally invasive and hybrid esophagectomy. However, little is known about any benefits of robotic assistance compared to the conventional minimally invasive technique, especially in hybrid procedures., Methods: For this retrospective study, all consecutive patients who had undergone elective esophagectomy with circular stapled intrathoracic anastomosis using the open and the minimally invasive hybrid technique at the University Hospital Magdeburg, from January 2010 to March 2021 were considered for analysis., Results: In total, 137 patients (60.4%) had undergone open esophagectomy. In 45 patients (19.8%), the laparoscopic hybrid technique and in 45 patients (19.8%), the robot-assisted hybrid technique were applied. In propensity score matching analysis comparing the open with the robotic hybrid technique, significant differences were found in favor of the robotic technique (postoperative morbidity, p < 0.01; hospital length of stay, p < 0.01; number of lymph nodes retrieved, p = 0.048). In propensity score matching analysis comparing the laparoscopic with the robotic hybrid technique, a significant reduction of the rate of postoperative delayed gastric emptying (p = 0.02) was found for patients who had undergone robotic esophagectomy. However, the operation time was significantly longer (p < 0.01)., Conclusions: En-bloc esophagectomy using the robotic hybrid technique is associated with a significant reduction of postoperative morbidity and of the hospital length of stay when compared to the open approach. However, when compared to the laparoscopic hybrid technique, only few advantages could be demonstrated., (© 2022. The Author(s).)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies., Methods: Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established. The expression levels of miRNAs previously shown to be involved in the general regulation of stem cell pathways were analyzed by qRT-PCR. The effects of selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated both in vitro and in vivo. We identified a particular miRNA and analyzed its putative target genes in 14 pairs of human EC tumor specimens with surrounding normal tissue by qRT-PCR as well as Wnt pathway associated genes by immunohistochemistry in another 45 EAC tumor samples., Results: MiR-221 was overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue. DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU resistant cells resulted in reduced cell proliferation, increased apoptosis, restored chemosensitivity, and led to inactivation of the Wnt/β-catenin pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as well as significantly slower xenograft tumor growth in nude mice. RT profiler analysis identified a substantial dysregulation of 4 Wnt/β-catenin signaling and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44, MYC, and ABCG2., Conclusion: MiR-221 controls 5-FU resistance of EC partly via modulation of Wnt/β-catenin-EMT pathways by direct targeting of DKK2 expression. MiR-221 may serve as a prognostic marker and therapeutic target for patients with 5-FU resistant EAC.

Surgery remains the mainstay of potentially curative treatment of esophageal cancer; however, esophageal resection is still associated with a relevant morbidity and mortality. Furthermore, patients frequently suffer from concomitant comorbidities and present in a reduced nutritional status. The rationale of minimally invasive surgery is the reduction of surgical trauma with subsequent minimization of (pulmonary) complications and mortality without compromising oncological quality. Minimally invasive esophageal resection was established nearly two decades ago and since then some centers worldwide have adopted this approach as the preferred option for surgical treatment of esophageal cancer. Minimally invasive esophageal resection can be safely performed and provides excellent results in experienced hands. Currently, there is only one randomized trial available comparing open and minimally invasive resection. It was demonstrated that the latter significantly reduced pulmonary complications with comparable mortality and oncological outcome. However, in the majority of studies these convincing results could not be confirmed. Reduced blood loss and a shortened hospital stay were shown to be the main advantages of the minimally invasive approach. Due to technical modifications, patient selection and a remarkable heterogeneity of current studies, a final conclusion on the value of minimally invasive esophagectomy is difficult to be drawn. Based on the current evidence, a noncritical use of minimally invasive resection for esophageal cancer cannot be recommended; however, in selected patients and with appropriate expertise this approach is at least comparable to open esophagectomy.

Complications following esophagectomy significantly affect the outcome, including perioperative mortality, costs and survival. Pulmonary complications and anastomotic leaks still remain the most serious complications and early recognition and appropriate initial treatment are essential. Mortality associated with esophageal leaks is decreasing due in part to the increased use of computed tomography (CT) scanning and endoscopy for diagnosis and subsequent appropriate multidisciplinary therapy. In this respect, it is critically important to differentiate between leaks and conduit necrosis, and endoscopic examination is the best method for making this assessment. Endoscopic and interventional radiology techniques are being applied increasingly for detection of intrathoracic leaks but appropriate patient selection is important. Adequate external drainage of the leak and prevention of further contamination are the primary therapeutic goals. The spectrum of therapeutic options ranges from simple conservative treatment for smaller, well drained leaks, interventional placement of drains, to endoscopic intervention with closure of the fistula or placement of stents and reoperation or discontinuity resection for conduit necrosis.