Minimally invasive versus open gastrectomy for gastric cancer. A pooled analysis of two European randomized controlled trials.

INTRODUCTION: Minimally invasive techniques have shown better short term and similar oncological outcomes compared to open techniques in the treatment of gastric cancer in Asian countries. It remains unknown whether these outcomes can be extrapolated to Western countries, where patients often present with advanced gastric cancer. MATERIALS AND METHODS: A pooled analysis of two Western randomized controlled trials (STOMACH and LOGICA trial) comparing minimally invasive gastrectomy (MIG) and open gastrectomy (OG) in advanced gastric cancer was performed. Postoperative recovery (complications, mortality, hospital stay), oncological outcomes (lymph node yield, radical resection rate, 1-year survival), and quality of life was assessed. RESULTS: Three hundred and twenty-one patients were included from both trials. Of these, 162 patients (50.5%) were allocated to MIG and 159 patients (49.5%) to OG. A significant difference was seen in blood loss in favor of MIG (150 vs. 260 mL, p < 0.001), whereas duration of surgery was in favor of OG (180 vs. 228.5 min, p = 0.005). Postoperative recovery, oncological outcomes and quality of life were similar between both groups. CONCLUSION: MIG showed no difference to OG regarding postoperative recovery, oncological outcomes or quality of life, and is therefore a safe alternative to OG in patients with advanced gastric cancer.

Three-year survival and distribution of lymph node metastases in gastric cancer following neoadjuvant chemotherapy: results from a European randomized clinical trial.

BACKGROUND: Adequate lymphadenectomy is an important step in gastrectomy for cancer, with a modified D2 lymphadenectomy being recommended for advanced gastric cancers. When assessing a novel technique for the treatment of gastric cancer, lymphadenectomy should be non-inferior. The aim of this study was to assess completeness of lymphadenectomy and distribution patterns between open total gastrectomy (OTG) and minimally invasive total gastrectomy (MITG) in the era of peri-operative chemotherapy. METHODS: This is a retrospective analysis of the STOMACH trial, a randomized clinical trial in thirteen hospitals in Europe. Patients were randomized between OTG and MITG for advanced gastric cancer after neoadjuvant chemotherapy. Three-year survival, number of resected lymph nodes, completeness of lymphadenectomy, and distribution patterns were examined. RESULTS: A total of 96 patients were included in this trial and randomized between OTG (49 patients) and MITG (47 patients). No difference in 3-year survival was observed, this was 57.1% in OTG group versus 46.8% in MITG group (P = 0.186). The mean number of examined lymph nodes per patient was 44.3 ± 16.7 in the OTG group and 40.7 ± 16.3 in the MITG group (P = 0.209). D2 lymphadenectomy of 71.4% in the OTG group and 74.5% in the MITG group was performed according to the surgeons; according to the pathologist compliance to D2 lymphadenectomy was 30% in the OTG group and 36% in the MITG group. Tier 2 lymph node metastases (stations 7-12) were observed in 19.6% in the OTG group versus 43.5% in the MITG group (P = 0.024). CONCLUSION: No difference in 3-year survival was observed between open and minimally invasive gastrectomy. No differences were observed for lymph node yield and type of lymphadenectomy. Adherence to D2 lymphadenectomy reported by the pathologist was markedly low.

Health related quality of life following open versus minimally invasive total gastrectomy for cancer: Results from a randomized clinical trial.

INTRODUCTION: Minimally invasive techniques show improved short-term and comparable long-term outcomes compared to open techniques in the treatment of gastric cancer and improved survival has been seen with the implementation of multimodality treatment. Therefore, focus of research has shifted towards optimizing treatment regimens and improving quality of life. MATERIALS AND METHODS: A randomized trial was performed in thirteen hospitals in Europe. Patients were randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG) after neoadjuvant chemotherapy. This study investigated patient reported outcome measures (PROMs) on health-related quality of life (HRQoL) following OTG or MITG, using the Euro-Qol-5D (EQ-5D) and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires, modules C30 and STO22. Due to multiple testing a p-value < 0.001 was deemed statistically significant. RESULTS: Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. A response compliance of 80% was achieved for all PROMs. The EQ5D overall health score one year after surgery was 85 (60-90) in the open group and 68 (50-83.8) in the minimally invasive group (P = 0.049). The median EORTC-QLQ-C30 overall health score one year postoperatively was 83,3 (66,7-83,3) in the open group and 58,3 (35,4-66,7) in the minimally invasive group (P = 0.002). This was not statistically significant. CONCLUSION: No differences were observed between open total gastrectomy and minimally invasive total gastrectomy regarding HRQoL data, collected using the EQ-5D, EORTC QLQ-C30 and EORTC-QLQ-STO22 questionnaires.

Open versus minimally invasive total gastrectomy after neoadjuvant chemotherapy: results of a European randomized trial.

BACKGROUND: Surgical resection with adequate lymphadenectomy is regarded the only curative option for gastric cancer. Regarding minimally invasive techniques, mainly Asian studies showed comparable oncological and short-term postoperative outcomes. The incidence of gastric cancer is lower in the Western population and patients often present with more advanced stages of disease. Therefore, the reproducibility of these Asian results in the Western population remains to be investigated. METHODS: A randomized trial was performed in thirteen hospitals in Europe. Patients with an indication for total gastrectomy who received neoadjuvant chemotherapy were eligible for inclusion and randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG). Primary outcome was oncological safety, measured as the number of resected lymph nodes and radicality. Secondary outcomes were postoperative complications, recovery and 1-year survival. RESULTS: Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. The mean number of resected lymph nodes was 43.4 ± 17.3 in OTG and 41.7 ± 16.1 in MITG (p = 0.612). Forty-eight patients in the OTG group had a R0 resection and 44 patients in the MITG group (p = 0.617). One-year survival was 90.4% in OTG and 85.5% in MITG (p = 0.701). No significant differences were found regarding postoperative complications and recovery. CONCLUSION: These findings provide evidence that MITG after neoadjuvant therapy is not inferior regarding oncological quality of resection in comparison to OTG in Western patients with resectable gastric cancer. In addition, no differences in postoperative complications and recovery were seen.

Autologous Activated Fibrin Sealant for the Esophageal Anastomosis: A Feasibility Study.

BACKGROUND: Esophageal cancer is surgically treated by means of an esophagectomy. However, esophagectomies are associated with high morbidity rates with dehiscence of the anastomosis occurring in 19% of these procedures in the Netherlands. Application of a fibrin sealant may improve mechanical strength of the anastomosis. The aim of this study was to determine the technical feasibility of the application of an autologous fibrin sealant by aerosolized spraying on esophageal anastomoses. METHODS: This study was designed as a single-center feasibility study. Patients undergoing elective minimal invasive esophageal surgery with the creation of a thoracic or a cervical anastomosis were eligible. Fibrin sealant (Vivostat) was applied to the anastomosis intraoperatively. Feasibility was measured using a nine-item checklist, designed for intraoperative application. RESULTS: In total, fifteen patients, between the ages of 43-79 y, were included in this study. One procedure scored eight out of nine points on the feasibility checklist, so application was considered as unsuccessful. The other fourteen procedures obtained a 100% score and were documented as successful procedures. Together, this led to a success rate of 93%. Grade III anastomotic leakage occurred in one of the fifteen patients (6.7%). CONCLUSIONS: This study showed that application of fibrin sealant on esophageal anastomoses is technically feasible and safe. Future studies may investigate the possible protective effects of fibrin sealant application on the development of anastomotic leakage. NCT03251040.

Short-term outcomes in minimally invasive versus open gastrectomy: the differences between East and West. A systematic review of the literature.

OBJECTIVE: Minimally invasive surgical techniques for gastric cancer are gaining more interest worldwide. Several Asian studies have proven the benefits of minimally invasive techniques over the open techniques. Nevertheless, implementation of this technique in Western countries is gradual. The aim of this systematic review is to give insight in the differences in outcomes and patient characteristics in Asian countries in comparison to Western countries. METHODOLOGY: An extensive systematic search was conducted using the Medline, Embase, and Cochrane databases. Analysis of the outcomes was performed regarding operative results, postoperative recovery, complications, mortality, lymph node yield, radicality of the resected specimen, and survival. A total of 12 Asian and 8 Western studies were included. RESULTS: Minimally invasive gastrectomy shows faster postoperative recovery, fewer complications, and similar outcomes regarding mortality in both the Eastern and Western studies. However, patient characteristics such as age and BMI differ between these populations. Comparison of overall outcomes in minimally invasive and open procedures between East and West showed differences in complications, mortality, and number of resected lymph nodes in favor of the Asian population. CONCLUSION: Improved outcomes are observed following minimally invasive gastrectomy in comparison to open procedures in both Western and Asian studies. There are differences in patient characteristics between the Western and Asian populations. Overall outcomes seem to be in favor of the Asian population. These differences may fade with centralization of care for gastric cancer patients in the West and increasing surgical experience.

Surgical anatomy of the omental bursa and the stomach based on a minimally invasive approach: different approaches and technical steps to resection and lymphadenectomy.

BACKGROUND: It is imperative for surgeons to have a proper knowledge of the omental bursa in order to perform an adequate dissection during minimally invasive surgery (MIS) of the upper gastrointestinal (GI) tract. This study aimed to describe (1) the various approaches which can be used to enter the bursa and to perform a complete lymphadenectomy, (2) the boundaries and anatomical landmarks of the omental bursa as seen during MIS, and (3) whether a bursectomy should be performed for oncological reasons in upper GI cancer. METHODS: In this observational study, videos of 20 patients undergoing different MIS procedures were reviewed, and the findings were verified prospectively in 5 patients undergoing a total gastrectomy and in a transversely sectioned cadaver. A systematic literature review (PubMed) was performed on the additive value of bursectomy during gastrectomy for cancer. RESULTS: The omental bursa can be surgically entered through the hepatogastric ligament, gastrocolic ligament, gastrosplenic ligament or through the transverse mesocolon. Anatomical boundaries of the omental bursa could be clearly identified, and new anatomical landmarks were described (gastro-omental folds). The cranial part of the omental bursa consists of two compartments (splenic recess and superior recess), separated by the gastropancreatic fold, communicating at the level of the pancreas, and extending distally as the inferior recess. There is no clear evidence regarding beneficial effect of a bursectomy in upper GI oncology. CONCLUSIONS: The description of the omental bursa in this study may help surgeons perform a more adequate oncological dissection during MIS. Bursectomy should not be routinely performed during oncological resections.

Perioperative management of obstructive sleep apnea in bariatric surgery: a consensus guideline.

BACKGROUND: The frequency of metabolic and bariatric surgery (MBS) is increasing worldwide, with over 500,000 cases performed every year. Obstructive sleep apnea (OSA) is present in 35%-94% of MBS patients. Nevertheless, consensus regarding the perioperative management of OSA in MBS patients is not established. OBJECTIVES: To provide consensus based guidelines utilizing current literature and, when in the absence of supporting clinical data, expert opinion by organizing a consensus meeting of experts from relevant specialties. SETTING: The meeting was held in Amsterdam, the Netherlands. METHODS: A panel of 15 international experts identified 75 questions covering preoperative screening, treatment, postoperative monitoring, anesthetic care and follow-up. Six researchers reviewed the literature systematically. During this meeting, the "Amsterdam Delphi Method" was utilized including controlled acquisition of feedback, aggregation of responses and iteration. RESULTS: Recommendations or statements were provided for 58 questions. In the judgment of the experts, 17 questions provided no additional useful information and it was agreed to exclude them. With the exception of 3 recommendations (64%, 66%, and 66% respectively), consensus (>70%) was reached for 55 statements and recommendations. Several highlights: polysomnography is the gold standard for diagnosing OSA; continuous positive airway pressure is recommended for all patients with moderate and severe OSA; OSA patients should be continuously monitored with pulse oximetry in the early postoperative period; perioperative usage of sedatives and opioids should be minimized. CONCLUSION: This first international expert meeting provided 58 statements and recommendations for a clinical consensus guideline regarding the perioperative management of OSA patients undergoing MBS.

The role of tissue adhesives in esophageal surgery, a systematic review of literature.

BACKGROUND: Anastomotic leakage following esophageal surgery is a major contributor to mortality. According to the national database leakage occurs in 20% of esophagectomies carried out in the Netherlands. Therefore anastomotic leakage has been the topic of many studies. However, studies discussing application of tissue adhesives for either prevention or management of anastomotic leakage are limited. This article systematically reviewed all available literature on the potential use of tissue adhesives in esophageal surgery. METHODS: Medline, Embase and Cochrane were searched to identify studies that used tissue adhesives as anastomotic sealants to prevent esophageal anastomotic leakage or used tissue adhesives to treat esophageal anastomotic leakage. Two authors independently selected nineteen out of 3107 articles. RESULTS: Eight articles, of which five were experimental and three clinical, discussed prevention of anastomotic leakage. Eleven articles, of which one was experimental and ten clinical, discussed treatment of anastomotic leakage. Most articles reported positive results, however overall quality was low due to a high degree of bias and lack of homogeneity. CONCLUSION: This study shows mainly positive results for the use of tissue adhesives for the esophageal anastomosis both in prevention of leakage as treating anastomotic leakage. However, the quality of current literature is poor.

Systematic Review of Exocrine Pancreatic Insufficiency after Gastrectomy for Cancer.

BACKGROUND: Survival rates after a total gastrectomy with adequate lymphadenectomy are improving, leading to a shift in outcomes of interest from survival to postoperative outcomes and symptoms. In this systematic review, we investigate gastrointestinal symptoms that occur after a gastrectomy in relation to exocrine pancreatic insufficiency and the effect of pancreatic exocrine enzyme supplementation on these symptoms. METHODS: Online databases PubMed, Embase, and Cochrane Library were systematically searched in accordance with the PRISMA guidelines. Studies that researched gastrointestinal symptoms, exocrine pancreatic function, and enzyme supplementation were identified and assessed. RESULTS: The search resulted in a total of 1,023 articles after exclusion of duplicates. After performing a thorough assessment, 4 studies were included for systematic review. Exocrine pancreatic insufficiency was investigated by 2 studies; the results showed a significant decrease of total exocrine pancreatic function of up to 76%. The other 2 studies investigated the effect of pancreatic enzyme supplementation and found minor improvement in fecal consistency and a decrease in high-degree steatorrhea. No differences in individual symptom scores were reported. CONCLUSION: Gastrointestinal symptoms such as steatorrhea, bloating, and dumping syndrome may be related to exocrine pancreatic function, initiated by total gastrectomy. Treatment with pancreatic enzymes had a minor positive effect on patients. It should be noted that these studies were of a small sample size and low quality. New and larger RCTs are necessary to either prove or disprove the benefit of pancreatic enzyme replacement therapy in the treatment of the gastrointestinal symptoms after total gastrectomy.

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.

Mastering minimally invasive esophagectomy requires a mentor; experience of a personal mentorship.

Since the first laparoscopic procedure, there has been an steady increase in advanced minimally invasive surgery. These procedures include oncological colorectal, hepatobiliary and upper gastrointestinal surgery. Implementation of these procedures requires different and new skills for the surgeons who wish to perform these procedures. To accomplish this surgical teaching program, a mentorship seems the most ideal method to teach the apprentice surgeon these specific skills. At the VU medical center a teaching program for a minimally-invasive esophagectomy for esophageal cancer started in 2009. At first it started in different centers in the Netherlands and later on we also started mentoring other institutes throughout Europe, Latin America and India. In this article we describe our experience and the outcomes of this mentorship in advanced minimally invasive surgery.

Techniques and short-term outcomes for total minimally invasive Ivor Lewis esophageal resection in distal esophageal and gastroesophageal junction cancers: pooled data from six European centers.

INTRODUCTION: Esophagectomy for cancer can be performed in a two-stage procedure with an intrathoracic anastomosis: the Ivor Lewis esophagectomy. A growing incidence of distal and gastroesophageal junction adenocarcinomas and increasing use of minimally invasive techniques have prompted interest in this procedure. The aim of this study was to assess short-term results of minimally invasive Ivor Lewis esophagectomy (MIE-IL). METHODS: A retrospective cohort study was performed from June 2007 until September 2014, including patients that underwent MIE-IL for distal esophageal and gastroesophageal junction cancer in six different hospitals in the Netherlands and Spain. Data were collected with regard to operative techniques, pathology and postoperative complications. RESULTS: In total, 282 patients underwent MIE-IL, of which 90.2 % received neoadjuvant therapy. Anastomotic leakage was observed in 43 patients (15.2 %), of whom 13 patients (4.6 %) had empyema, necessitating thoracotomy for decortication. With an aggressive treatment of complications, the 30-day and in-hospital mortality rate was 2.1 %. An R0-resection was obtained in 92.5 % of the patients. After neoadjuvant therapy, 20.1 % of patients had a complete response. CONCLUSIONS: Minimally invasive Ivor Lewis esophagectomy for distal esophageal and gastroesophageal junction adenocarcinomas is an upcoming approach for reducing morbidity caused by laparotomy and thoracotomy. Anastomotic leakage rate is still high possibly due to technical diversity of anastomotic techniques, and a high percentage of patients treated by neoadjuvant chemoradiotherapy. An aggressive approach to complications leads to a low mortality of 2.1 %. Further improvement and standardization in the anastomotic technique are needed in order to perform a safe intrathoracic anastomosis.

Surgical anatomy of the supracarinal esophagus based on a minimally invasive approach: vascular and nervous anatomy and technical steps to resection and lymphadenectomy.

BACKGROUND: During esophageal dissection and lymphadenectomy of the upper mediastinum by thoracoscopy in prone position, we observed a complex anatomy in which we had to resect the esophagus, dissect vessels and nerves, and take down some of these in order to perform a complete lymphadenectomy. In order to improve the quality of the dissection and standardization of the procedure, we describe the surgical anatomy and steps involved in this procedure. METHODS: We retrospectively evaluated twenty consecutive and unedited videos of thoracoscopic esophageal resections. We recorded the vascular anatomy of the supracarinal esophagus, lymph node stations and the steps taken in this procedure. The resulting concept was validated in a prospective study including five patients. RESULTS: Seventy percent of patients in the retrospective study had one right bronchial artery (RBA) and two left bronchial arteries (LBA). The RBA was divided at both sides of the esophagus in 18 patients, with preservation of one LBA or at least one esophageal branch in all cases. Both recurrent laryngeal nerves were identified in 18 patients. All patients in the prospective study had one RBA and two LBA, and in four patients the RBA was divided at both sides of the esophagus and preserved one of the LBA. Lymphadenectomy was performed of stations 4R, 4L, 2R and 2L, with a median of 11 resected lymph nodes. Both recurrent laryngeal nerves were identified in four patients. In three patients, only the left recurrent nerve could be identified. Two patients showed palsy of the left recurrent laryngeal nerve, and one showed neuropraxia of the left vocal cord. CONCLUSIONS: Knowledge of the surgical anatomy of the upper mediastinum and its anatomical variations is important for standardization of an adequate esophageal resection and paratracheal lymphadenectomy with preservation of any vascularization of the trachea, bronchi and the recurrent laryngeal nerves.

Major abdominal surgery in octogenarians: should high age affect surgical decision-making?

BACKGROUND: Over the last decades longevity has increased significantly, with more octogenarians undergoing surgery. Here, we assess surgical outcomes after major abdominal surgery in octogenarians. METHODS: Observational cohort of 874 patients undergoing major abdominal elective surgery between January 2009 and March 2014. Seventy-six octogenarians were propensity matched to 76 younger patients, corrected for sex, body mass index, American Society of Anesthesiologists classification, comorbidity, indication, and type of surgery. RESULTS: Minor complications were more prevalent in octogenarians (P = .01) and consisted mainly of respiratory complications; progressing to respiratory insufficiency requiring intubation in 28.6%. Preoperative weight loss (odds ratio 3 [1.1 to 8.3]) and upper gastrointestinal surgery (odds ratio 11 [2 to 60]) were associated with minor complications. CONCLUSIONS: Octogenarians are at increased risk of minor complications after major abdominal surgery. Major complication rates were similar, indicating the importance of preoperative assessment and standardized surgical techniques. Taking into account preoperative morbidities and type of surgery and techniques. Implementation of quality control algorithms may further improve outcomes in octogenarians.

Video-assisted thoracoscopic esophagectomy: keynote lecture.

Minimally invasive esophagectomy (MIE) by thoracoscopy after neoadjuvant therapy results in significant short-term advantages such as a lower incidence of pulmonary infections and a better quality of life (QoL) with the same completeness of resection. After 1 year, a better QoL is still observed for MIE in comparison with the open approach, while having the same survival. Seven issues about implementation of MIE for cancer require discussion: (1) choice of the extension of esophageal resection and use of neoadjuvant therapy; (2) reasons to approach the esophageal cancer by MIE; (3) determining the best minimally invasive approach for gastro-esophageal junction cancers; (4) implementation of evidence-based MIE; (5) standardization of the surgical anatomy of the esophagus based on MIE; (6) future lines of research of MIE; and (7) learning process. In the time of imaging-integrated surgery it is clear that the MIE approach should be increasingly implemented in all centers worldwide having an adequate volume of patients and expertise.

Assessment of patient-reported outcome measures in the surgical treatment of patients with gastric cancer.

BACKGROUND: Gastric cancer is responsible for 10 % of all cancer-related deaths worldwide. With improved operative techniques and neo-adjuvant therapy, survival rates are increasing. Outcomes of interest are shifting to quality of life (QOL), with many different tools available. The aim of this study was to assess which patient-reported outcome measures (PROMs) are used to measure QOL after a gastrectomy for cancer. METHODS: A comprehensive search was conducted for original articles investigating QOL after gastrectomy. Two authors independently selected relevant articles, conducted clinical appraisal and extracted data (P.J. and J.S.). RESULTS: Out of 3414 articles, 26 studies were included, including a total of 4690 patients. These studies included ten different PROMs, which could be divided into generic, symptom-specific and disease-specific questionnaires. The EORTC and the FACT questionnaires use an oncological overall QOL module and an organ-specific module. Only one validation study regarding the use of the EORTC after surgery for gastric cancer was available, demonstrating good psychometric properties and clinical validity. CONCLUSIONS: A great variety of PROMs are being used in the measurement of QOL after surgery for gastric cancer. A questionnaire with a general module along with a disease-specific module for the assessment of QOL seems most desirable, such as the EORTC and the FACT with their specific modules. Both are developed in different treatment modalities, such as in surgical patients. EORTC is the most widely used questionnaire and therefore allows for comparison of new studies to existing data. Future studies are needed to assess content validity in surgical gastric cancer patients.