Teus J. Weijs

Routes for early enteral nutrition after esophagectomy. A systematic review

BACKGROUND Early enteral feeding following surgery can be given orally, via a jejunostomy or via a nasojejunal tube. However, the best feeding route following esophagectomy is unclear. OBJECTIVES To determine the best route for enteral nutrition following esophagectomy regarding anastomotic leakage, pneumonia, percentage meeting the nutritional requirements, weight loss, complications of tube feeding, mortality, patient satisfaction and length of hospital stay. DESIGN A systematic literature review following PRISMA and MOOSE guidelines. RESULTS There were 17 eligible studies on early oral intake, jejunostomy or nasojejunal tube feeding. Only one nonrandomized study (N = 133) investigated early oral feeding specifically following esophagectomy. Early oral feeding was associated with a reduced length of stay with delayed oral feeding, without increased complication rates. Postoperative nasojejunal tube feeding was not significantly different from jejunostomy tube feeding regarding complications or catheter efficacy in the only randomised trial on this subject (N = 150). Jejunostomy tube feeding outcome was reported in 12 non-comparative studies (N = 3293). It was effective in meeting short-term nutritional requirements, but major tube-related complications necessitated relaparotomy in 0-2.9% of patients. In three non-comparative studies (N = 135) on nasojejunal tube feeding only minor complications were reported, data on nutritional outcome was lacking. Data on patient satisfaction and long-term nutritional outcome were not found for any of the feeding routes investigated. CONCLUSION It is unclear what the best route for early enteral nutrition is after esophagectomy. Especially data regarding early oral intake are scarce, and phase 2 trials are needed for further investigation. REGISTRATION International prospective register of systematic reviews, CRD42013004032.

Reduced local immune response with continuous positive airway pressure during one-lung ventilation for oesophagectomy

BACKGROUND Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This randomized controlled trial studied the influence of CPAP applied to the collapsed right lung during thoracoscopic oesophagectomy on local and systemic inflammatory response. METHODS Broncho-alveolar lavage fluid (BALF) from the right collapsed and left ventilated lung and serum samples were obtained during surgery from 30 patients undergoing thoracolaparoscopic oesophagectomy for cancer who were randomized for one-lung ventilation with or without CPAP applied to the collapsed right lung. Concentrations of cytokines and chemokines, in BALF and serum, were determined with Luminex. RESULTS Patients from the control (no CPAP) group had significantly increased concentrations of interleukin (IL)-1α, IL-1β, IL-10, tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-1α, pulmonary and activation-regulated chemokine (PARC), and IL-8 in the collapsed (right) lung when compared with patients from the CPAP group (P<0.05). The ventilated (left) lung of the control group showed increased concentrations of monocyte chemoattractant protein (MCP)-1 and MIP-1α (P<0.05). Serum concentrations of cytokines and chemokines increased during surgery, but did not differ between the control and CPAP groups. CONCLUSIONS A significantly lower local immune response was observed during one-lung ventilation when CPAP was applied to the collapsed lung. The findings suggest a beneficial effect of CPAP on the collapsed lung during oesophagectomy with one-lung ventilation.

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.

A new concept of the anatomy of the thoracic oesophagus: the meso-oesophagus. Observational study during thoracoscopic esophagectomy

BackgroundDuring thoracoscopic oesophageal surgery, we observed not previously described fascia-like structures. Description of similar structures in rectal cancer surgery was of paramount importance in improving the quality of resection. Therefore, we aimed to describe a new comprehensive concept of the surgical anatomy of the thoracic oesophagus with definition of the meso-oesophagus.MethodsWe retrospectively evaluated 35 consecutive unedited videos of thoracoscopic oesophageal resections for cancer, to determine the surgical anatomy of the oesophageal fascia’s vessels and lymphatic drainage. The resulting concept was validated in a prospective study, including 20 patients at three different centres. Additional confirmation was sought by a histologic study of a cadaver’s thorax.ResultsA thin layer of connective tissue around the infracarinal oesophagus, involving the lymph nodes at the level of the carina, was observed during thoracoscopic esophagectomy in 32 of the 35 patients included in the retrospective study and in 19 of the 20 patients included in the prospective study. A thick fascia-like structure from the upper thoracic aperture to the lower thoracic aperture was visualized in all patients. This fascia is encountered between the descending aorta and left aspect of the infracarinal oesophagus. Above the carina it expands on both sides of the oesophagus to lateral mediastinal structures. This fascia contains oesophageal vessels, lymph vessels and nodes and nerves. The histologic study confirmed these findings.ConclusionsHere we described the concept of the “meso-oesophagus”. Applying the description of the meso-oesophagus will create a better understanding of the oesophageal anatomy, leading to more adequate and reproducible surgery.

Laparoscopic gastrectomy in Western European patients with advanced gastric cancer.

BACKGROUND The advantage of laparoscopic gastrectomy compared to open gastrectomy has been established in Asian patient series with early gastric cancer. However, its feasibility in Western European patients with locally advanced gastric cancer is unknown. METHODS Between 2006 and 2014 70 consecutive patients with advanced gastric cancer underwent laparoscopic gastrectomy with D2 lymph node dissection. A Billroth II reconstruction was performed after distal gastrectomy. In case of total gastrectomy a jejunal J-pouch reconstruction was performed. RESULTS Total gastrectomy was performed in 56 patients and distal gastrectomy in 14 patients. Perioperative chemotherapy was administered in 45/70 (64%) patients. A radical resection was achieved in 63/70 (90%). The median number of dissected lymph nodes was 17 (2-62). The median intraoperative blood loss was 305 (30-2700) milliliters. The median postoperative hospital stay was 11 (5-91) days. The 30-day mortality was 4.3%. CONCLUSIONS Laparoscopic gastrectomy can be performed in Western European patients with advanced gastric cancer and meets the oncologic standard with low intraoperative blood loss and short hospital stay.

Strategies to reduce pulmonary complications after esophagectomy.

Esophagectomy, the surgical removal of all or part of the esophagus, is a surgical procedure that is associated with high morbidity and mortality. Pulmonary complications are an especially important postoperative problem. Therefore, many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice. Here, we review these strategies, including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years. Furthermore, interventions such as methylprednisolone, neutrophil elastase inhibitor and epidural analgesia, which have been shown to reduce pulmonary complications, are discussed. Benefits of the commonly applied routine nasogastric decompression, delay of oral intake and prophylactic mechanical ventilation are unclear, and many of these strategies are also evaluated here. Finally, we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy.

Diagnostic value of drain amylase for detecting intrathoracic leakage after esophagectomy

AIM To investigate the value of elevated drain amylase concentrations for detecting anastomotic leakage (AL) after minimally invasive Ivor-Lewis esophagectomy (MI-ILE). METHODS This was a retrospective analysis of prospectively collected data in two hospitals in the Netherlands. Consecutive patients undergoing MI-ILE were included. A Jackson-Pratt drain next to the dorsal side of the anastomosis and bilateral chest drains were placed at the end of the thoracoscopic procedure. Amylase levels in drain fluid were determined in all patients during at least the first four postoperative days. Contrast computed tomography scans and/or endoscopic imaging were performed in cases of a clinically suspected AL. Anastomotic leakage was defined as any sign of leakage of the esophago-gastric anastomosis on endoscopy, re-operation, radiographic investigations, post mortal examination or when gastro-intestinal contents were found in drain fluid. Receiver operator characteristic curves were used to determine the cut-off values. Sensitivity, specificity, positive predictive value, negative predictive value, risk ratio and overall test accuracy were calculated for elevated drain amylase concentrations. RESULTS A total of 89 patients were included between March 2013 and August 2014. No differences in group characteristics were observed between patients with and without AL, except for age. Patients with AL were older than were patients without AL (P = 0.01). One patient (1.1%) without AL died within 30 d after surgery due to pneumonia and acute respiratory distress syndrome. Anastomotic leakage that required any intervention occurred in 15 patients (16.9%). Patients with proven anastomotic leakage had higher drain amylase levels than patients without anastomotic leakage [median 384 IU/L (IQR 34-6263) vs median 37 IU/L (IQR 26-66), P = 0.003]. Optimal cut-off values on postoperative days 1, 2, and 3 were 350 IU/L, 200 IU/L and 160 IU/L, respectively. An elevated amylase level was found in 9 of the 15 patients with AL. Five of these 9 patients had early elevations of their amylase levels, with a median of 2 d (IQR 2-5) before signs and symptoms occurred. CONCLUSION Measurement of drain amylase levels is an inexpensive and easy tool that may be used to screen for anastomotic leakage soon after MI-ILE. However, clinical validation of this marker is necessary.

Topography and extent of pulmonary vagus nerve supply with respect to transthoracic oesophagectomy

Pulmonary complications are frequently observed after transthoracic oesophagectomy. These complications may be reduced by sparing the vagus nerve branches to the lung. However, current descriptions of the regional anatomy are insufficient. Therefore, we aimed to provide a highly detailed description of the course of the pulmonary vagus nerve branches. In six fixed adult human cadavers, bilateral microscopic dissection of the vagus nerve branches to the lungs was performed. The level of branching and the number, calibre and distribution of nerve branches were described. Nerve fibres were identified using neurofilament immunohistochemistry, and the nerve calibre was measured using computerized image analysis. Both lungs were supplied by a predominant posterior and a smaller anterior nerve plexus. The right lung was supplied by 13 (10–18) posterior and 3 (2–3) anterior branches containing 77% (62–100%) and 23% (0–38%) of the lung nerve supply, respectively. The left lung was supplied by a median of 12 (8–13) posterior and 3 (2–4) anterior branches containing 74% (60–84%) and 26% (16–40%) of the left lung nerve supply, respectively. During transthoracic oesophagectomy with en bloc lymphadenectomy and transection of the vagus nerves at the level of the azygos vein, 68–100% of the right lung nerve supply and 86–100% of the inferior left lung lobe nerve supply were severed. When vagotomy was performed distally to the last large pulmonary branch, 0–8% and 0–13% of the nerve branches to the right middle/inferior lobes and left inferior lobe, respectively, were lost. In conclusion, this study provides a detailed description of the extensive pulmonary nerve supply provided by the vagus nerves. During oesophagectomy, extensive mediastinal lymphadenectomy denervates the lung to a great extent; however, this can be prevented by performing the vagotomy distal to the caudalmost large pulmonary branch. Further research is required to determine the feasibility of sparing the pulmonary vagus nerve branches without compromising the completeness of lymphadenectomy.

Study protocol for the nutritional route in oesophageal resection trial: a single-arm feasibility trial (NUTRIENT trial)

Introduction The best route of feeding for patients undergoing an oesophagectomy is unclear. Concerns exist that early oral intake would increase the incidence and severity of pneumonia and anastomotic leakage. However, in studies including patients after many other types of gastrointestinal surgery and in animal experiments, early oral intake has been shown to be beneficial and enhance recovery. Therefore, we aim to determine the feasibility of early oral intake after oesophagectomy. Methods and analysis This study is a feasibility trial in which 50 consecutive patients will start oral intake directly following oesophagectomy. Primary outcomes will be the frequency and severity of anastomotic leakage and (aspiration) pneumonia. Clinical parameters will be registered prospectively and nutritional requirements and intake will be assessed by a dietician. Surgical complications will be registered. Ethics and dissemination Approval for this study has been obtained from the Medical Ethical Committee of the Catharina Hospital Eindhoven and the study has been registered at the Dutch Trial Register, NTR4136. Results will be published and presented at international congresses. Discussion We hypothesise that the oral route of feeding is safe and feasible following oesophagectomy, as has been shown previously for other types of gastrointestinal surgery. It is expected that early oral nutrition will result in enhanced recovery. Furthermore, complications related to artificial feeding, such as jejunostomy tube feeding, are believed to be reduced. However, (aspiration) pneumonia and anastomotic leakage are potential risks that are carefully monitored. Trial registration number NTR4136.

The peri‐esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri‐esophageal fascias have not been described and it is unclear whether this layer can be visualized by non‐invasive imaging. This study aimed to provide a comprehensive description of the peri‐esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2‐weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri‐esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion‐triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named ‘aorto‐esophageal ligament’ and the layer connecting aorta to the right pleural reflection ‘aorto‐pleural ligament’. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named ‘peri‐esophageal compartment’ and the posterior compartment ‘para‐aortic compartment’. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long‐standing paradigm that no such structure exists. A comprehensive, detailed description of the peri‐esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI.