Pieter C. van der Sluis

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

BackgroundFor esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%).Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer.Methods/designThis is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ≥18 and ≤80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien–Dindo classification of surgical complications.DiscussionThis is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient.Trial registrationDutch trial register: NTR3291 ClinicalTrial.gov: NCT01544790

A New Clinical Scoring System to Define Pneumonia following Esophagectomy for Cancer

Background: Pneumonia is a frequently observed complication following esophagectomy. The lack of a uniform definition of pneumonia leads to large variations of pneumonia rates in literature. This study was designed to develop a scoring system for diagnosing pneumonia following esophagectomy at the hospital ward. Methods: In a prospective cohort study of esophagectomy patients, known risk factors for pneumonia, temperature, leukocyte count, pulmonary radiography and sputum culture added were evaluated. Primary outcome was defined as the decision to treat suspected pneumonia. Multivariate Cox regression analysis with backward selection was used to identify predictors of pneumonia treatment. Results: The majority of postoperative pneumonia treatments (88.2%) occurred at the hospital ward, where treatment was observed in 67 (36.2%) of 185 patients. Independent diagnostic determinants for pneumonia treatment were temperature (hazard ratio (HR) = 1.283, p = 0.073), leukocyte count (HR = 1.040, p = 0.078) and pulmonary radiography (HR >11.0, p = 0.000). Sputum culture did not influence the decision to treat pneumonia. These findings were used to develop a scoring system which includes temperature, leukocyte count and pulmonary radiography. Conclusion: The decision to treat pneumonia is based on temperature, leukocyte count and pulmonary radiography findings. The proposed clinical scoring system for pneumonia following esophagectomy at the hospital ward has the potential to aid clinical practice and improve comparability of future research in esophageal cancer surgery.

Trends in worldwide volume and methodological quality of surgical randomized controlled trials

Objective: To assess worldwide trends in volume and methodological quality of published surgical randomized controlled trials (RCTs) over the past decade. Background: Randomized controlled trials are essential for clinical decision making. It has repeatedly been suggested that surgical RCTs are scarce and of mediocre quality. Methods: We systematically searched PubMed for surgical RCTs published in 1999 and 2009. Characteristics and risks of bias were extracted. Trials where compared between study years and geographical regions. Primary outcome was “low risk of bias,” defined by all of the following: adequate allocation generation and concealment, intention-to-treat analysis, and adequate dropout handling. Results: The volume of published surgical RCTs increased by 50%, from 300 in 1999 to 450 in 2009. Volume increased in Europe (27% increase), Asia/Oceania (160% increase), and Africa/South America (416% increase) but decreased in North America (23% decrease), although the United States remained the country with the highest number of published RCTs. In 2009, methodological quality of surgical trials improved in terms of sample size calculation, adequate generation of randomization sequence, concealment of randomization sequence, and use of intention-to-treat analysis as compared with 1999 (P < 0.001 for all). The proportion of low risk of bias trials increased from 6% to 14% (prevalence ratio 2.59; 95% confidence interval 1.55–4.32). In 2009, the highest proportion of low risk of bias trials was from Europe (23%), whereas the lowest was from Asia/Oceania (5%). Conclusions: Volume and quality of surgical RCTs improved although striking differences exist between continents and countries. Structured education in trial methodology, enforced adherence to existing guidelines, and improved research infrastructure may guide further improvements.

Internal and External Validation of a multivariable Model to Define Hospital-Acquired Pneumonia After Esophagectomy

BackgroundPneumonia is an important complication following esophagectomy; however, a wide range of pneumonia incidence is reported. The lack of one generally accepted definition prevents valid inter-study comparisons. We aimed to simplify and validate an existing scoring model to define pneumonia following esophagectomy.Patients and methodsThe Utrecht Pneumonia Score, comprising of pulmonary radiography findings, leucocyte count, and temperature, was simplified and internally validated using bootstrapping in the dataset (n = 185) in which it was developed. Subsequently, the intercept and (shrunk) coefficients of the developed multivariable logistic regression model were applied to an external dataset (n = 201)ResultsIn the revised Uniform Pneumonia Score, points are assigned based on the temperature, the leucocyte, and the findings of pulmonary radiography. The model discrimination was excellent in the internal validation set and in the external validation set (C-statistics 0.93 and 0.91, respectively); furthermore, the model calibrated well in both cohorts.ConclusionThe revised Uniform Pneumonia Score (rUPS) can serve as a means to define post-esophagectomy pneumonia. Utilization of a uniform definition for pneumonia will improve inter-study comparability and improve the evaluations of new therapeutic strategies to reduce the pneumonia incidence.

Adding Preoperative Radiotherapy Plus Cetuximab to Perioperative Chemotherapy for Resectable Esophageal Adenocarcinoma: A Single-Center Prospective Phase II Trial

BACKGROUND Local and systemic recurrence are important sources of treatment failure following surgical resection of esophageal adenocarcinoma. We hypothesized that adding preoperative cetuximab and radiotherapy (cetux-RT) to perioperative chemotherapy would increase treatment efficacy with acceptable toxicity. METHODS In this prospective phase II trial, patients were treated with three cycles of epirubicin, cisplatin, and capecitabine (ECX), followed by cetux-RT. After surgery with curative intent, patients received three more cycles of ECX. Primary endpoints were efficacy, determined by histopathological complete response (pCR) rate, and safety, which was assessed with resectability rate. RESULTS Of the 12 patients enrolled in this trial, six received at least one dose of cetux-RT. In five patients, cetux-RT was not started because of adverse events (AEs) related to preoperative chemotherapy; one patient had progressive disease. Addition of cetux-RT was well tolerated and did not interfere with the resectability rate (100%). However, the pCR rate was 0, and 50% of patients experienced serious adverse events (SAEs) postoperatively. CONCLUSION With 12 patients enrolled, the lack of initial signs of efficacy and a high incidence of postoperative SAEs prompted us to end this study prematurely. Perioperative ECX was associated with considerable toxicity, and further treatment intensification is problematic.

Perioperative chemotherapy versus neoadjuvant chemoradiotherapy for esophageal or GEJ adenocarcinoma: A propensity score‐matched analysis comparing toxicity, pathologic outcome, and survival

To evaluate toxicity, pathologic outcome, and survival after perioperative chemotherapy (pCT) compared to neoadjuvant chemoradiotherapy (nCRT) followed by surgery for patients with resectable esophageal or gastroesophageal junction (GEJ) adenocarcinoma.

Gastric Conduit Resection and Jejunal Interposition for Recurrent Esophageal Cancer

We describe the case of a 58-year-old man with recurrent adenocarcinoma at the site of an esophagogastrostomy that we treated by radical surgical resection and jejunal interposition. Oral intake was started on the 6th postoperative day and the patient was discharged on the 11th postoperative day. Seven months after the surgical procedure no signs of tumor recurrence were detected. Resection of localized (recurrent) esophageal cancer may well be a valuable treatment option and is therefore an interesting therapeutic option in patients with recurrent disease. However this needs to be investigated in a randomized controlled trial.

Incarcerated hiatal hernia after robot-assisted esophagectomy: transhiatal versus thoracoscopic approach

With interest we read the article by Sutherland et al. [1] in which they reported their initial experience with transhiatal robot-assisted total esophagectomy in 36 patients with esophageal cancer. Seven (19.4%) patients had postoperative incarcerated hiatal hernias and of those seven patients one died due to complications of the hernia repair. According to the authors, because the mediastinal dissection is done via laparoscopy, the hiatus is extensively dilated by the angles of the robotic arms, thereby increasing the risk of postoperative hiatal hernia. They therefore recommend performing a primary closure and reinforcement with mesh sutured to the gastric wall. In 2009 we published the largest series of robot-assisted thoracolaparoscopic esophagectomies (RTE) [2]. We have performed this procedure in more than 140 patients. Minimally invasive esophagectomy substantially reduces blood loss and postoperative hospital and intensive care stay compared to open esophagectomy [3]. We adhere to the combined thoracic and abdominal approach to provide optimal oncological clearance. To date, the largest study that compares transhiatal with transthoracic surgery showed an important trend toward improved survival after transthoracic esophagectomy [4]. The survival benefit is attributed to a more extensive lymphadenectomy in the mediastinum. Furthermore, studies have shown that distal esophageal carcinomas frequently metastasize to lymph nodes in the upper mediastinum [2, 5] We have not experienced any postoperative hiatal hernias in our patients so far. In our opinion, this is the result of performing the mediastinal dissection of the esophagus and surrounding lymph nodes through thoracoscopy instead of through the diaphragm. During the laparoscopic phase of RTE, the stomach is mobilized, regional abdominal lymph nodes are dissected, and the esophagus is pulled out of the mediastinum. By performing the mediastinal dissection thoracoscopically, the integrity of the hiatus is preserved and no incarcerated hiatal hernias will be encountered postoperatively. In this way, the above-mentioned recommendation of the authors can be abandoned. We would encourage Sutherland et al. to continue performing robot-assisted esophagectomies and to experience the many advantages of the robot-assisted thoracoscopic approach.

Robot Assisted Minimally Invasive Esophagectomy (RAMIE)

Esophageal cancer is the sixth most common cause of cancer death worldwide, with occurrence rates varying greatly by geographic location [1]. The standard treatment for locally advanced esophageal cancer with curative intent is multimodality treatment containing either preoperative chemoradiation or perioperative chemotherapy followed by open esophagectomy [2, 3]. However, the open transthoracic esophagectomy is associated with high morbidity and mortality [4, 5].

Robotic Utilization in Esophageal Cancer Surgery

Minimally invasive esophagectomy (MIE) was designed to reduce surgical trauma, resulting in lower rates of morbidity and mortality. MIE has been shown to decrease blood loss, reduce postoperative complications, and shorten hospital stay, with comparable oncological results.