Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus minimally invasive esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT-2 trial).

Our hypothesis is that RAMIE has superior lymph node dissection compared to

MIE. Therefore, the primary outcome of this study is the number of dissected

lymph nodes. The resected specimen will be marked by the surgical team for the

position of lymph node dissection. Evaluation will be performed by an

experienced pathologist using standard protocols. Stage grouping will take

place according to the Union Internationale Contre le Cancer (UICC) protocol

using the TNM-8 classification. The exact localization of the lymph nodes is an

essential part of the pathologic examination.

Secondary outcomes include:

- Overall postoperative complications according to the modified Clavien Dindo

classification (MCDC grade I-V) and definitions stated by the Esophagectomy

Complications Consensus Group (ECCG). Postoperative complications include:

anastomotic leakage, mediastinitis, gastric conduit necrosis, chylothorax and

recurrent laryngeal nerve injury, delayed gastric emptying, pulmonary

complications (pneumonia, pneumothorax, pulmonary embolus, acute respiratory

distress syndrome (ARDS)), cardiac complications (atrial fibrillation, cardiac

asthma, myocardial infarction) and postoperative bleeding. The incidence of

incisional hernias and diaphragmatic hernias will be recorded.

- Length of ICU-MCU stay (days), length of hospital stay (days)

- In hospital mortality (IHM) and mortality within 30, 60 and 90 days

postoperatively will be reported. For all patients, the cause of death will be

noted.

- Pathology results: The pathology report contains the following parameters:

site of tumor, type and gradation, extension in the esophageal wall, margins of

the resection, extent of resection (R0, R1 or R2), lymph node status with the

number of lymph nodes (primary endpoint) (TNM 8)21. Quality control of the

pathologic analysis of the resection specimen will be provided by a specialized

gastrointestinal pathologist.

- Overall and disease-free survival (2, 3 and 5 years). Overall survival (OS)

was calculated from the date of surgery to the date of death or last follow-up.

Disease free survival was calculated from the date of surgery to recurrence or

death related to disease and/or treatment or last date of follow-up.

- Operation time is defined as time from incision until closure (minutes) for

both the thoracic and the abdominal phase of the procedure. Unexpected events

and complications occurring during the operation will be recorded (e.g.

hemorrhage requiring transfusion, perforation of other organs) as well as blood

loss during operation (ml, per phase). In case of conversion to thoracotomy or

laparotomy the reason for conversion has to be explained (absolute

numbers/percentage).

- Visual Analogue Scale (VAS) for pain will be noted at following times:

pre-operatively and the first 14 days after surgery and a fixed periods during

follow up (6 weeks, 6 months and yearly post-operatively up to 5 years).

- Quality of life questionnaires will be required at following times: SF-36,

EORTC QLQ-C30 (Dutch), EORTC OES18 (Dutch) and EQ-5D (Appendix 1 & 2)

pre-operative < 5 days and 6 weeks, 6 months and yearly up to 5 years

post-operatively.

- Postoperative functional recovery was defined as: removal of thoracic tubes,

no requirement of intravenous fluid resuscitation, tolerance for solid oral

intake, the ability to mobilize independently and adequate pain control with

oral analgesics. All items will be assessed daily.

- Cost analysis: The approach for the cost-analysis is comparing actual direct

medical costs incurred with both strategies up until 5 years after the

operation. Costs estimates will be based on the recorded volumes and unit costs

associated with both procedures. This includes the costs of operation rooms,

hospital and ICU stay, costs associated with complications and re-operations.

- Surgeons fatigue assessed by Psychomotor Vigilance tests (PVT) before and

after esophagectomy.