Exploring the Modulatory Effect of High-Fat Nutrition on Lipopolysaccharide-Induced Acute Lung Injury in Vagotomized Rats and the Role of the Vagus Nerve

During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate inflammation and can be activated by a high-fat nutrition via the release of acetylcholine. This binds to α7 nicotinic acetylcholine receptors (α7nAChR) and inhibits α7nAChR-expressing inflammatory cells. This study investigates the role of the vagus nerve and the effect of high-fat nutrition on lipopolysaccharide (LPS)-induced lung injury in rats. Firstly, 48 rats were randomized in 4 groups as follows: sham (sparing vagus nerve), abdominal (selective) vagotomy, cervical vagotomy and cervical vagotomy with an α7nAChR-agonist. Secondly, 24 rats were randomized in 3 groups as follows: sham, sham with an α7nAChR-antagonist and cervical vagotomy with an α7nAChR-antagonist. Finally, 24 rats were randomized in 3 groups as follows: fasting, high-fat nutrition before sham and high-fat nutrition before selective vagotomy. Abdominal (selective) vagotomy did not impact histopathological lung injury (LIS) compared with the control (sham) group (p > 0.999). There was a trend in aggravation of LIS after cervical vagotomy (p = 0.051), even after an α7nAChR-agonist (p = 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury (p = 0.004). Furthermore, cervical vagotomy increased macrophages in bronchoalveolar lavage (BAL) fluid and negatively impacted pulmonary function. Other inflammatory cells, TNF-α and IL-6, in the BALF and serum were unaffected. High-fat nutrition reduced LIS after sham (p = 0.012) and selective vagotomy (p = 0.002) compared to fasting. vagotomy. This study underlines the role of the vagus nerve in lung injury and shows that vagus nerve stimulation using high-fat nutrition is effective in reducing lung injury, even after selective vagotomy

Surgical quality and prospective quality control of the D2-gastrectomy for gastric cancer in the multicenter randomized LOGICA-trial

Background: Quality of gastric cancer surgery is crucial for favorable prognosis. Generally, prospective trials lack quality control measures. This study assessed surgical quality and a novel D2-lymphadenectomy photo-scoring in the LOGICA-trial. Methods: The multicenter LOGICA-trial randomized laparoscopic versus open total/distal D2-gastrectomy for resectable gastric cancer (cT1-4aN0-3M0) in 10 Dutch hospitals. During the trial, two reviewers prospectively analyzed intraoperative photographs of dissected nodal stations for quality control, and provided centers weekly feedback on their D2-lymphadenectomy, as continuous quality-enhancing incentive. After the trial, these photographs were reanalyzed to develop a photo-scoring for future trials, rating the D2-lymphadenectomy dissection quality (optimal-good-suboptimal-unevaluable). Interobserver variability was calculated (weighted kappa). Regression analyses related the photo-scoring to nodal yield, recurrence and 5-years survival. Results: Between 2015 and 2018, 212 patients underwent total/distal D2-gastrectomy (n = 122/n = 90), and 158 (75%) received neoadjuvant chemotherapy. R0-resection rate was 95%. Rate of ≥15 retrieved lymph nodes was 95%. Moderate agreement was obtained in stations 8 + 9 (κ = 0.522), 11p/11d (κ = 0.446) and 12a (κ = 0.441). Consensus was reached for discordant cases (30%). Stations 8 + 9, 11p/11d and 12a were rated ‘optimal’ in 76%, 63% and 68%. Laparoscopic photographs could be rated better than open (2% versus 12% ‘unevaluable’; 73% versus 50% ‘optimal’; p = 0.042). The photo-scoring did not show associations with nodal yield (p = 0.214), recurrence (p = 0.406) and survival (p = 0.988). Conclusions: High radicality and nodal yield demonstrated good quality of D2-gastrectomy. The prospective quality control probably contributed to this. The photo-scoring did not show good performance, but can be refined. Laparoscopic D2-gastrectomy was better suited for standardized surgical photo-evaluation than open surgery.</p

Body Composition Is a Predictor for Postoperative Complications After Gastrectomy for Gastric Cancer:a Prospective Side Study of the LOGICA Trial

PURPOSE: There is a lack of prospective studies evaluating the effects of body composition on postoperative complications after gastrectomy in a Western population with predominantly advanced gastric cancer. METHODS: This is a prospective side study of the LOGICA trial, a multicenter randomized trial on laparoscopic versus open gastrectomy for gastric cancer. Trial patients who received preoperative chemotherapy followed by gastrectomy with an available preoperative restaging abdominal computed tomography (CT) scan were included. The CT scan was used to calculate the mass (M) and radiation attenuation (RA) of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). These variables were expressed as Z-scores, depicting how many standard deviations each patient’s CT value differs from the sex-specific study sample mean. Primary outcome was the association of each Z-score with the occurrence of a major postoperative complication (Clavien-Dindo grade ≥ 3b). RESULTS: From 2015 to 2018, a total of 112 patients were included. A major postoperative complication occurred in 9 patients (8%). A high SM-M Z-score was associated with a lower risk of major postoperative complications (RR 0.47, 95% CI 0.28–0.78, p = 0.004). Furthermore, high VAT-RA Z-scores and SAT-RA Z-scores were associated with a higher risk of major postoperative complications (RR 2.82, 95% CI 1.52–5.23, p = 0.001 and RR 1.95, 95% CI 1.14–3.34, p = 0.015, respectively). VAT-M, SAT-M, and SM-RA Z-scores showed no significant associations. CONCLUSION: Preoperative low skeletal muscle mass and high visceral and subcutaneous adipose tissue radiation attenuation (indicating fat depleted of triglycerides) were associated with a higher risk of developing a major postoperative complication in patients treated with preoperative chemotherapy followed by gastrectomy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11605-022-05321-0

Pain and Opioid Consumption After Laparoscopic Versus Open Gastrectomy for Gastric Cancer:A Secondary Analysis of a Multicenter Randomized Clinical Trial (LOGICA-Trial)

Background:Laparoscopic gastrectomy could reduce pain and opioid consumption, compared to open gastrectomy. However, it is difficult to judge the clinical relevance of this reduction, since these outcomes are reported in few randomized trials and in limited detail. Methods: This secondary analysis of a multicenter randomized trial compared laparoscopic versus open gastrectomy for resectable gastric adenocarcinoma (cT1-4aN0-3bM0). Postoperative pain was analyzed by opioid consumption in oral morphine equivalents (OME, mg/day) at postoperative day (POD) 1–5, WHO analgesic steps, and Numeric Rating Scales (NRS, 0–10) at POD 1–10 and discharge. Regression and mixed model analyses were performed, with and without correction for epidural analgesia. Results: Between 2015 and 2018, 115 patients in the laparoscopic group and 110 in the open group underwent surgery. Some 16 patients (14%) in the laparoscopic group and 73 patients (66%) in the open group received epidural analgesia. At POD 1–3, mean opioid consumption was 131, 118, and 53 mg OME lower in the laparoscopic group, compared to the open group, respectively (all p &lt; 0.001). After correcting for epidural analgesia, these differences remained significant at POD 1–2 (47 mg OME, p = 0.002 and 69 mg OME, p &lt; 0.001, respectively). At discharge, 27% of patients in the laparoscopic group and 43% patients in the open group used oral opioids (p = 0.006). Mean highest daily pain scores were between 2 and 4 at all PODs, &lt; 2 at discharge, and did not relevantly differ between treatment arms. Conclusion: In this multicenter randomized trial, postoperative pain was comparable between laparoscopic and open gastrectomy. After laparoscopic gastrectomy, this was generally achieved without epidural analgesia and with fewer opioids. Trial Registration: NCT02248519.</p

Recurrent laryngeal nerve injury after esophagectomy for esophageal cancer : Incidence, management, and impact on shortand long-term outcomes

Background: Recurrent laryngeal nerve (RLN) injury caused by esophagectomy may lead to postoperative morbidity, however data on long-term recovery are scarce. The aim of this study was to evaluate the consequences of RLN palsy (RLNP) in terms of pulmonary morbidity and long-term functional recovery. Methods: Patients who underwent a 3-stage transthoracic (McKeown) or a transhiatal esophagectomy for esophageal carcinoma in the University Medical Center Utrecht (UMCU) between January 2004 and March 2016 were included from a prospective database. Multivariable analyses were conducted to assess the association between RLNP and pulmonary complications and hospital stay. Data regarding long-term recovery were summarized using descriptive statistics. Results: Out of the 451 included patients, 47 (10%) were diagnosed with RLNP. Of the patients with RLNP, 34 (7%) had a unilateral lesion, 8 (2%) had a bilateral lesion, and in 5 (1%) the location of the lesion was unknown. The incidence of RLNP was 3/127 (2%) in the transhiatal group, and 44/324 (14%) in the McKeown group. RLNP after McKeown esophagectomy was associated with a higher incidence of pulmonary complications (OR 2.391; 95% CI 1.222-4.679; P=0.011), as well as a longer hospital stay (+4 days) (P=0.001). Of the RLNP patients with more than 6 months follow up almost half recovered fully (median follow-up of 17.5 [7-135] months). Of the remainder, six required a surgical intervention and the others had residual symptoms. Conclusions: RLNP after McKeown esophagectomy is associated with an increased pulmonary complication rate, longer hospital stay, and a moderate long-term recovery. Further studies are necessary that examine technologies, which may reduce RLNP incidence and contribute to the early detection and treatment of RLNP

Recurrent laryngeal nerve injury after esophagectomy for esophageal cancer : Incidence, management, and impact on shortand long-term outcomes

Background: Recurrent laryngeal nerve (RLN) injury caused by esophagectomy may lead to postoperative morbidity, however data on long-term recovery are scarce. The aim of this study was to evaluate the consequences of RLN palsy (RLNP) in terms of pulmonary morbidity and long-term functional recovery. Methods: Patients who underwent a 3-stage transthoracic (McKeown) or a transhiatal esophagectomy for esophageal carcinoma in the University Medical Center Utrecht (UMCU) between January 2004 and March 2016 were included from a prospective database. Multivariable analyses were conducted to assess the association between RLNP and pulmonary complications and hospital stay. Data regarding long-term recovery were summarized using descriptive statistics. Results: Out of the 451 included patients, 47 (10%) were diagnosed with RLNP. Of the patients with RLNP, 34 (7%) had a unilateral lesion, 8 (2%) had a bilateral lesion, and in 5 (1%) the location of the lesion was unknown. The incidence of RLNP was 3/127 (2%) in the transhiatal group, and 44/324 (14%) in the McKeown group. RLNP after McKeown esophagectomy was associated with a higher incidence of pulmonary complications (OR 2.391; 95% CI 1.222-4.679; P=0.011), as well as a longer hospital stay (+4 days) (P=0.001). Of the RLNP patients with more than 6 months follow up almost half recovered fully (median follow-up of 17.5 [7-135] months). Of the remainder, six required a surgical intervention and the others had residual symptoms. Conclusions: RLNP after McKeown esophagectomy is associated with an increased pulmonary complication rate, longer hospital stay, and a moderate long-term recovery. Further studies are necessary that examine technologies, which may reduce RLNP incidence and contribute to the early detection and treatment of RLNP

Minimally invasive esophagectomy : a propensity score-matched analysis of semiprone versus prone position

Background: The preferred surgical approach for esophageal cancer is a minimally invasive transthoracic esophagectomy with a two-field lymph node dissection. The thoracoscopic phase may be performed either in prone- or in left lateral decubitus (LLD) position. Prone positioning has been associated with better pulmonary outcomes compared to LLD positioning; however, conversion to a classic thoracotomy is more difficult. The semiprone position has been proposed as an alternative approach. Methods: A retrospective review of a prospectively maintained database (2008–2014) was performed to compare postoperative complications, surgical radicality, and lymph node yield between patients who underwent three-stage minimally invasive transthoracic esophagectomy in either the prone or semiprone position. Comparative analyses were conducted before and after propensity score matching. Results: One hundred and twenty-one patients were included. In total, 82 patients underwent minimally invasive esophagectomy (MIE) in semiprone position and 39 patients in prone position. After propensity score matching, both groups consisted of 39 patients. The operative time in the semiprone group was longer (368 vs. 225 min, P < 0.001) and in this group the lymph node yield was significantly higher (16 (range 6–80) vs. 13 (range 3–33), P = 0.019). There were no statistically significant differences regarding radical resections, postoperative complications, and hospital stay. Conclusion: The use of semiprone positioning in MIE is safe, feasible, and at least comparable to MIE in prone position in terms of oncological clearance and postoperative complications

Liver Resection for Hepatic Metastases from Soft Tissue Sarcoma : A Nationwide Study

Background: This study aims to evaluate the feasibility and safety of resection of sarcoma liver metastases, and to identify possible prognostic factors for long-term survival. Methods: All patients who underwent resection of liver metastases of sarcoma in the Netherlands from 1998 to 2014 were included. Study data was retrospectively collected from patient files. Survival rates were calculated using Kaplan-Meier survival analysis. Results: Some 38 patients treated in 16 hospitals were included (15 male, 23 female). The median age was 57 years (37-80 years). The most common histological subtype was leiomyosarcoma (63%). The predominant site of primary tumour was the abdomen (59%). R0 resection was achieved in 16 patients. Mortality was 3 and 16% of included patients had 1 or more complications. The median follow-up period was 18 months (range 1-161). After liver resection, 1-, 3-, and 5-year survival were 88, 54, and 42% respectively. Median overall survival was 46 months (1-161 months). One- and three-year progression-free survival (PFS) after liver resection were 54 and 19% respectively. Median PFS was 16 months (1-61 months). Conclusions: Liver surgery for sarcoma metastases is safe and leads to a relatively good survival. The choice for surgical treatment should always be discussed in a multidisciplinary sarcoma and liver team

A Propensity Score Matched Analysis of Open Versus Minimally Invasive Transthoracic Esophagectomy in the Netherlands

Objective: The aim of this study was to compare open esophagectomy (OE) with minimally invasive esophagectomy (MIE) in a population-based setting.  Background: Randomized controlled trials and cohort studies have shown that MIE is associated with reduced pulmonary complications and shorter hospital stay as compared to OE.  Methods: Patients who underwent transthoracic esophagectomy for cancer between 2011 and 2015 were selected from the national Dutch Upper Gastrointestinal Cancer Audit. Hybrid, transhiatal, and emergency procedures were excluded. Patients who underwent OE were compared with those treated by MIE. Propensity score matching was used to correct for differences in baseline characteristics. The primary endpoint was postoperative pulmonary complications; secondary endpoints were morbidity, mortality, convalescence, and pathology.  Results: Some 1727 patients were included. After propensity score matching the percentage of patients with 1 or more complications was 62.6% after OE (N = 433) and 60.2% after MIE (N = 433) (P = 0.468). Pulmonary complication rate did not differ between groups: 34.2% (OE) versus 35.6% (MIE) (P = 0.669). Anastomotic leak (15.5% vs 21.2%, P = 0.028) and reintervention rates (21.1% vs 28.2%, P = 0.017) were higher after MIE. Mortality was 3.0% in the OE group and 4.7% in the MIE group (P = 0.209). Median hospital stay was shorter after MIE (14 vs 13 days, P = 0.001). Percentages of R0 resections (93%) did not differ between groups. The median (range) lymph node count was 18 (2-53) (OE) versus 20 (2-52) (MIE) (P < 0.001).  Conclusions: This population-based study showed that mortality and pulmonary complications were similar for OE and MIE. Anastomotic leaks and reinterventions were more frequently observed after MIE. MIE was associated with a shorter hospital stay

A Propensity Score Matched Analysis of Open Versus Minimally Invasive Transthoracic Esophagectomy in the Netherlands

Objective: The aim of this study was to compare open esophagectomy (OE) with minimally invasive esophagectomy (MIE) in a population-based setting.  Background: Randomized controlled trials and cohort studies have shown that MIE is associated with reduced pulmonary complications and shorter hospital stay as compared to OE.  Methods: Patients who underwent transthoracic esophagectomy for cancer between 2011 and 2015 were selected from the national Dutch Upper Gastrointestinal Cancer Audit. Hybrid, transhiatal, and emergency procedures were excluded. Patients who underwent OE were compared with those treated by MIE. Propensity score matching was used to correct for differences in baseline characteristics. The primary endpoint was postoperative pulmonary complications; secondary endpoints were morbidity, mortality, convalescence, and pathology.  Results: Some 1727 patients were included. After propensity score matching the percentage of patients with 1 or more complications was 62.6% after OE (N = 433) and 60.2% after MIE (N = 433) (P = 0.468). Pulmonary complication rate did not differ between groups: 34.2% (OE) versus 35.6% (MIE) (P = 0.669). Anastomotic leak (15.5% vs 21.2%, P = 0.028) and reintervention rates (21.1% vs 28.2%, P = 0.017) were higher after MIE. Mortality was 3.0% in the OE group and 4.7% in the MIE group (P = 0.209). Median hospital stay was shorter after MIE (14 vs 13 days, P = 0.001). Percentages of R0 resections (93%) did not differ between groups. The median (range) lymph node count was 18 (2-53) (OE) versus 20 (2-52) (MIE) (P < 0.001).  Conclusions: This population-based study showed that mortality and pulmonary complications were similar for OE and MIE. Anastomotic leaks and reinterventions were more frequently observed after MIE. MIE was associated with a shorter hospital stay