Studies & Trials

B. Feike Kingma, Peter P. Grimminger, Pieter C. van der Sluis, Marc J. van Det, Ewout A. Kouwenhoven, Yin-Kai Chao, Chun-Yi Tsai, Hans F. Fuchs, Christiane J. Bruns, Inderpal S. Sarkaria, James D. Luketich, Jan W. Haveman, Boudewijn van Etten, Philip W. Chiu, Shannon M. Chan, Philippe Rouanet, Anne Mourregot, Jens-Peter Hölzen, Rubens A. Sallum, Ivan Cecconello, Jan-Hendrik Egberts, Frank Benedix, Mark I. van Berge Henegouwen, Suzanne S. Gisbertz, Daniel Perez, Kristina Jansen, Michal Hubka, Donald E. Low, Matthias Biebl, Johann Pratschke, Paul Turner, Kish Pursnani, Asif Chaudry, Myles Smith, Elena Mazza, Paolo Strignano, Jelle P. Ruurda, Richard van Hillegersberg, UGIRA Study Group

Objective: This international multicenter study by the Upper GI International Robotic Association (UGIRA) 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: 20 centers from Europe, Asia, North-America, and South-America participated from 2016- 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 para-esophageal 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 (26%), 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.

Full text available in the Annals of Surgery.

B. Feike Kingma, Edin Hadzijusufovic, Pieter C. Van der Sluis, Erida Bano, Hauke Lang, Jelle P. Ruurda, Richard van Hillegersberg, Peter P. Grimminger

Abstract: 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

Full text available in the Diseases of the Esophagus.

Pieter C. van der Sluis, Sylvia van der Horst, Anne M. May, Carlo Schippers, Lodewijk A.A. Brosens, Hans C.A. Joore, Christiaan C. Kroese, Nadia Haj Mohammad, Stella Mook, Frank P. Vleggaar, Inne H.M. Borel Rinkes, Jelle P. Ruurda, Richard van Hillegersberg

Background: The standard curative treatment for patients with esophageal cancer is perioperative chemotherapy or preoperative chemoradiotherapy followed by open transthoracic esophagectomy (OTE). Robot-assisted minimally invasive thoracolaparoscopic esophagectomy (RAMIE) may reduce complications.
Methods/design: A single-center randomized controlled trial was conducted, assigning 112 patients with resectable intrathoracic esophageal cancer to either RAMIE or OTE. The primary endpoint was the occurrence of overall surgery-related postoperative complications (modified Clavien-Dindo classification grade 2-5).
Results: Overall surgery-related postoperative complications occurred less frequently after RAMIE (59%) compared to OTE (80%) [risk ratio with RAMIE (RR) 0.74; 95% confidence interval (CI), 0.57-0.96; P = 0.02]. RAMIE resulted in less median blood loss (400 vs 568 mL, P <0.001), a lower percentage of pulmonary complications (RR 0.54; 95% CI, 0.34-0.85; P = 0.005) and cardiac complications (RR 0.47; 95% CI, 0.27-0.83; P = 0.006) and lower mean postoperative pain (visual analog scale, 1.86 vs 2.62; P < 0.001) compared to OTE. Functional recovery at postoperative day 14 was better in the RAMIE group [RR 1.48 (95% CI, 1.03-2.13; P = 0.038)] with better quality of life score at discharge [mean difference quality of life score 13.4 (2.0-24.7, p = 0.02)] and 6 weeks postdischarge [mean difference 11.1 quality of life score (1.0-21.1; P = 0.03)]. Short- and long-term oncological outcomes were comparable at a medium follow-up of 40 months.
Discussion: RAMIE resulted in a lower percentage of overall surgery-related and cardiopulmonary complications with lower postoperative pain, better short-term quality of life, and a better short-term postoperative functional recovery compared to OTE. Oncological outcomes were comparable and in concordance with the highest standards nowadays., NCT01544790
Full text available in the Annals of Surgery.

Yin-Kai Chao, Zhi-Gang Li, Yu-Wen Wen, Dae-Joon Kim, Seong-Yong Park, Yu-Ling Chang, Pieter C. van der Sluis, Jelle P. Ruurda and Richard van Hillegersberg

Background: Radical lymph node dissection (LND) along the left recurrent laryngeal nerve (RLN) is surgically demanding and can be associated with substantial postoperative morbidity. The question  of  whether  robot- assisted esophagectomy (RE) might be superior to video-assisted thoracoscopic esophagectomy (VATE) for performing  LND along  the  RLN in patients with esophageal squamous  cell carcinoma  (ESCC)  remains  open.
Methods/design: We will conduct a multicenter, open-label, randomized controlled trial (Robotic-assisted Esophagectomy vs Video-Assisted Thoracoscopic Esophagectomy (REVATE)) enrolling patients with ESCC scheduled to undergo LND along the RLN. Patients will be randomly assigned to either RE or VATE. The  primary outcome measure will be the rate of unsuccessful LND  along the left RLN, which will be defined as: failure to remove lymph nodes along the left RLN (i.e., no identifiable nodes on pathology reports); or occurrence of permanent (duration > 6 months) left RLN palsy following LND. Secondary outcomes will include the number of successfully removed RLN nodes, postoperative recovery, length of hospital stay, 30-day and 90-day mortality, quality of life, and oncological outcomes.
Discussion: The REVATE study provides an  opportunity to explore whether RE could facilitate LND along the   left RLN—a complex surgical procedure that, as of now and with the use of VATE, remains difficult to perform and associated with a significant burden of morbidity., NCT03713749. Registered on 22 October 2018.
Full study protocol accessible via Trials.