S. S. Gisbertz

Minimally Invasive Versus Open Esophageal Resection: Three-year Follow-up of the Previously Reported Randomized Controlled Trial: the TIME Trial

Objective: The aim of this study was to investigate 3-year survival following a randomized controlled trial comparing minimally invasive with open esophagectomy in patients with esophageal cancer. Background: Research on minimally invasive esophagectomy (MIE) has shown faster postoperative recovery and a marked decrease in pulmonary complications. Debate is ongoing as to whether the procedure is equivalent to open resection regarding oncologic outcomes. The study is a follow-up study of the TIME-trial (traditional invasive vs minimally invasive esophagectomy, a multicenter, randomized trial). Methods: Between June 2009 and March 2011, patients with a resectable intrathoracic esophageal carcinoma, including the gastroesophageal junction tumors (Siewert I), were randomized between open and MI esophagectomy with curative intent. Primary outcome was 3-year disease-free survival. Secondary outcomes include overall survival, lymph node yield, short-term morbidity, mortality, complications, radicality, local recurrence, and metastasis. Analysis was by intention-to-treat. This trial is registered with the Netherlands Trial Register, NTR TC 2452. Both trial protocol and short-term results have been published previously. Results: One hundred fifteen patients were included from 5 European hospitals and randomly assigned to open (n = 56) or MI esophagectomy (n = 59). Combined overall 3-year survival was 40.4% (SD 7.7%) in the open group versus 50.5% (SD 8%) in the minimally invasive group (P = 0.207). The hazard ratio (HR) is 0.883 (0.540 to 1.441) for MIE compared with open surgery. Disease-free 3-year survival was 35.9% (SD 6.8%) in the open versus 40.2% (SD 6.9%) in the MI group [HR 0.691 (0.389 to 1.239). Conclusions: The study presented here depicted no differences in disease-free and overall 3-year survival for open and MI esophagectomy. These results, together with short-term results, further support the use of minimally invasive surgical techniques in the treatment of esophageal cancer.

Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer

BACKGROUND AND PURPOSE Neoadjuvant chemoradiation (nCRT) followed by surgery is considered curative intent treatment for patients with resectable esophageal cancer. The aim was to establish hemodynamic aspects of changes in heart volume and to explore whether changes in heart volume resulted in clinically relevant changes in the dose distribution of radiotherapy. METHODS A prospective study was conducted in patients who were treated with nCRT consisting of carboplatin and paclitaxel concomitant with radiotherapy (41.4 Gy/1.8 Gy per fraction). Physical parameters, cardiac volume on CT and Cone beam CT, cardiac blood markers and cardiac ultrasound were obtained. RESULTS In 23 patients a significant decrease of 55.3 ml in heart volume was detected (95% CI 36.7-73.8 ml, p<0.001). There was a decrease in both systolic (mean decrease 18 mmHg, 95% CI 11-26 mmHg, p<0.001) and diastolic blood pressure (mean decrease 8 mmHg, 95% CI 2-14 mmHg, p=0.008) and an increase in heart rate with 6 beats/min (95% CI 1-11 beats/min, p=0.021). Except for Troponin T, no change in other cardiac markers and echocardiography parameters were observed. The change in heart volume did not result in a clinically relevant change in radiation dose distribution. CONCLUSION Heart volume was significantly reduced, but was not accompanied by overt cardiac dysfunction. All observed changes in hemodynamic parameters are consistent with volume depletion. Adaptation of the treatment plan during the course of radiotherapy is not advocated.

Role of omentectomy as part of radical surgery for gastric cancer

A complete omentectomy is recommended as part of radical (sub)total gastrectomy for gastric cancer, but there is little evidence to suggest any survival benefit. The aim of this study was to evaluate the incidence of, and risk factors for, metastases in the greater omentum in patients undergoing gastrectomy for gastric cancer.

Intrathoracic versus cervical anastomosis and predictors of anastomotic leakage after oesophagectomy for cancer

Studies comparing the anastomotic leak rate in patients with an intrathoracic versus a cervical anastomosis after oesophagectomy are equivocal. The aim of this study was to compare clinical outcome after oesophagectomy in patients with an intrathoracic or cervical anastomosis, and to identify predictors of anastomotic leakage in a nationwide audit.

Pilot-study on the feasibility of sentinel node navigation surgery in combination with thoracolaparoscopic lymphadenectomy without esophagectomy in early esophageal adenocarcinoma patients

High-risk submucosal esophageal adenocarcinomas might be treated curatively by means of radical endoscopic resection, followed by thoracolaparoscopic lymphadenectomy without concomitant esophagectomy. A preclinical study has shown the feasibility and safety of this approach; however, no studies are performed in a clinical setting. In addition, sentinel node navigation surgery could be valuable in tailoring the extent of the lymphadenectomy. This study aimed to evaluate the feasibility and safety of thoracolaparoscopic lymphadenectomy without esophagectomy (phase I) and sentinel node navigation surgery (phase II) in patients with early esophageal adenocarcinoma. Patients with T1N0M0 early esophageal adenocarcinoma scheduled for esophagectomy without neoadjuvant therapy were included. Phase I: Two-field, esophagus preserving, thoracolaparoscopic lymphadenectomy was performed, followed by esophagectomy in the same session. Primary outcome parameters were the number of lymph nodes resected, and number of retained lymph nodes in the esophagectomy specimen. Phase II: A radioactive tracer was injected endoscopically the day before surgery. Static imaging was performed 15 and 120 minutes after injection. The day of surgery, sentinel node navigation surgery followed by esophagectomy was performed. Primary outcome parameters were the percentage of patients with a detectable sentinel node, and the concordance between static imaging and probe-based detection of sentinel node. Phase I: Five patients were included, and a median of 30 (IQR: 25-46) lymph nodes was resected. A median of 6 (IQR: 2-9) retained lymph nodes was found in the esophagectomy specimen. No acute adverse events occurred, but near the end of lymphadenectomy esophageal discoloration was observed, possibly indicating ischemia. Phase II: In all five included patients sentinel nodes could be visualized and resected, at a median of 3 (IQR: 2-5) locations. There was a high concordance between imaging and probe-based detection of sentinel nodes. In conclusion, sentinel node navigation surgery followed by lymphadenectomy without concomitant esophagectomy seems feasible in patients with high-risk submucosal early esophageal adenocarcinoma. More evidence is however needed before applying this technique in clinical practice.

Prognostic impact of extracapsular lymph node involvement after neoadjuvant therapy and oesophagectomy.

The significance of extracapsular lymph node involvement (LNI) is unclear in patients with oesophageal cancer who have undergone neoadjuvant treatment followed by oesophagectomy. The aim of this study was to assess the incidence and prognostic significance of extracapsular LNI in a large multicentre series of consecutive patients with oesophageal cancer treated by neoadjuvant chemotherapy or chemoradiotherapy and surgery.

Overall survival before and after centralization of gastric cancer surgery in the Netherlands: Centralization of gastric cancer surgery

Centralization of surgery has been shown to improve outcomes for oesophageal and pancreatic cancer, and has been implemented for gastric cancer since 2012 in the Netherlands. This study evaluated the impact of centralizing gastric cancer surgery on outcomes for all patients with gastric cancer.

Can we predict necrosis intra-operatively? Real-time optical quantitative perfusion imaging in surgery: study protocol for a prospective, observational, in vivo pilot study

BackgroundCompromised perfusion as a result of surgical intervention causes a reduction of oxygen and nutrients in tissue and therefore decreased tissue vitality. Quantitative imaging of tissue perfusion during reconstructive surgery, therefore, may reduce the incidence of complications. Non-invasive optical techniques allow real-time tissue imaging, with high resolution and high contrast. The objectives of this study are, first, to assess the feasibility and accuracy of optical coherence tomography (OCT), sidestream darkfield microscopy (SDF), laser speckle contrast imaging (LSCI), and fluorescence imaging (FI) for quantitative perfusion imaging and, second, to identify/search for criteria that enable risk prediction of necrosis during gastric tube and free flap reconstruction.MethodsThis prospective, multicenter, observational in vivo pilot study will assess tissue perfusion using four optical technologies: OCT, SDF, LSCI, and FI in 40 patients: 20 patients who will undergo gastric tube reconstruction after esophagectomy and 20 patients who will undergo free flap surgery. Intra-operative images of gastric perfusion will be obtained directly after reconstruction at four perfusion areas. Feasibility of perfusion imaging will be analyzed per technique. Quantitative parameters directly related to perfusion will be scored per perfusion area, and differences between biologically good versus reduced perfusion will be tested statistically. Patient outcome will be correlated to images and perfusion parameters. Differences in perfusion parameters before and after a bolus of ephedrine will be tested for significance.DiscussionThis study will identify quantitative perfusion-related parameters for an objective assessment of tissue perfusion during surgery. This will likely allow early risk stratification of necrosis development, which will aid in achieving a reduction of complications in gastric tube reconstruction and free flap transplantation.Trial registrationClinicaltrials.gov registration number NCT02902549. Dutch Central Committee on Research Involving Human Subjects registration number NL52377.018.15.

Thoracolaparoscopic dissection of esophageal lymph nodes without esophagectomy is feasible in human cadavers and safe in a porcine survival study

High-risk early esophageal adenocarcinoma (i.e. submucosal invasion >500 nm, poor differentiation, and/or presence of lymphovascular invasion) is currently treated with esophagectomy with lymph node (LN) dissection given the high rates of LN metastases. However, esophagectomy is associated with substantial morbidity and mortality. Endoscopic radical resection followed by thoracolaparoscopic LN dissection without concomitant esophagectomy could be an alternative. The study aim was to evaluate the feasibility and safety of thoracolaparoscopic dissection of esophageal LNs in a preclinical setting. (i) In human cadavers, thoracolaparoscopic dissection of LNs involved in drainage of the esophagus was performed. Subsequently, esophagectomy was performed to be able to detect retained LNs. Outcome parameters included the number of dissected LNs, the number of retained LNs in the esophagectomy specimen (ES), and technical success. (ii) In swine, thoracolaparoscopic LN dissection was also performed. After the procedure, the swine survived for 28 days. Thereafter, the swine were sacrificed and esophagectomy was performed. Outcome parameters included the presence of ischemia and/or stenosis in the ES and other complications. (i) In five human cadavers, a median of 26 LNs (interquartile range 22-46) were dissected. In two ES, one retained LN was found: one high paraesophageal, one low paraesophageal. Technical success rate was 100%. (ii) None of the seven porcine ES showed signs of ischemia or stenosis. One swine died because of ventricular fibrillation during surgery; during follow up no complications were observed. Thoracolaparoscopic dissection of LNs involved in the drainage of the esophagus is feasible in human cadavers and swine. The porcine survival study suggests that the esophageal vascularity is not severely compromised by the procedure. As anatomy differs between swine and humans, safety of the procedure will have to be investigated thoroughly before applying this new technique as the treatment of choice.

The evolution of surgical approach for esophageal cancer

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.