The Value of Paratracheal Lymphadenectomy in Esophagectomy for Adenocarcinoma of the Esophagus or Gastroesophageal Junction: A Systematic Review of the Literature

Esophageal adenocarcinoma; Nodal metastases; Upper mediastinal lymphadenectomyAdenocarcinoma esofágico; Metástasis ganglionares; Linfadenectomía del mediastino superiorAdenocarcinoma esofàgic; Metàstasis ganglionars; Limfadenectomia del mediastí superiorBackground The role of upper mediastinal lymphadenectomy for distal esophageal or gastroesophageal junction (GEJ) adenocarcinomas remains a matter of debate. This systematic review aims to provide a comprehensive overview of evidence on the incidence of nodal metastases in the upper mediastinum following transthoracic esophagectomy for distal esophageal or GEJ adenocarcinoma. Methods A literature search was performed using Medline, Embase and Cochrane databases up to November 2020 to include studies on patients who underwent transthoracic esophagectomy with upper mediastinal lymphadenectomy for distal esophageal and/or GEJ adenocarcinoma. The primary endpoint was the incidence of metastatic nodes in the upper mediastinum based on pathological examination. Secondary endpoints were the definition of upper mediastinal lymphadenectomy, recurrent laryngeal nerve (RLN) palsy rate and survival. Results A total of 17 studies were included and the sample sizes ranged from 10-634 patients. Overall, the median incidence of upper mediastinal lymph node metastases was 10.0% (IQR 4.7-16.7). The incidences of upper mediastinal lymph node metastases were 8.3% in the 7 studies that included patients undergoing primary resection (IQR 2.0-16.6), 4,4% in the 1 study that provided neoadjuvant therapy to the full cohort, and 10.6% in the 9 studies that included patients undergoing esophagectomy either with or without neoadjuvant therapy (IQR 8.9-15.8%). Data on survival and RLN palsy rates were scarce and inconclusive. Conclusions The incidence of upper mediastinal lymph node metastases in distal esophageal adenocarcinoma is up to 10%. Morbidity should be weighed against potential impact on survival

Correlates of physical activity among colorectal cancer survivors:Results from the longitudinal population-based profiles registry

Contains fulltext : 172219.pdf (Publisher’s version ) (Open Access)PURPOSE: Physical activity can improve health of cancer survivors. To increase physical activity levels among colorectal cancer (CRC) survivors, we need to understand which factors affect physical activity. Therefore, this study examined the longitudinal relationship between symptom-related, functioning-related, and psychological barriers and socio-demographic and clinical factors with physical activity among CRC survivors. METHODS: CRC survivors identified from the population-based Eindhoven Cancer Registry (ECR) diagnosed between 2000 and 2009 were included. Survivors completed validated questionnaires measuring moderate-to-vigorous physical activity (MVPA) and barriers in 2010(T1), 2011(T2), and 2012(T3). Linear-mixed models and linear regression techniques were used. RESULTS: Response rates were 74 % (N = 2451, T1); 47 % (N = 1547, T2); and 41 % (N = 1375, T3). Several factors were negatively associated with MVPA: symptom-related barriers (e.g., fatigue, dyspnea, chemotherapy side effects, pain, appetite loss, and weight loss); psychological barriers (i.e., depressive symptoms and anxiety); functioning-related barriers (e.g., low physical or role functioning, unfavorable future perspective); socio-demographic (i.e., older age, female, no partner); and clinical factors (i.e., obesity). However, no within-subject effects were significantly associated with MVPA. Groups of functioning-related barriers, socio-demographic factors, symptom-related barriers, psychological barriers, and clinical factors explained 11, 3.9, 3.8, 2.4, and 2.2 % of the variance in MVPA at T1, respectively. CONCLUSIONS: Several functioning-related and symptom-related barriers and few socio-demographic factors were associated with physical activity among CRC survivors. Future interventions to promote physical activity among CRC survivors could benefit by taking into account functioning aspects and symptoms of cancer and its treatment, and assess the causal direction of these associations

Risk Factors for Failure of Direct Oral Feeding Following a Totally Minimally Invasive Esophagectomy

Càncer d'esòfag; Jejunostomia; NutricióCáncer de esófago; Yeyunostomía; NutriciónEsophageal cancer; Jejunostomy; NutritionRecently, it has been shown that directly starting oral feeding (DOF) from postoperative day one (POD1) after a totally minimally invasive Ivor-Lewis esophagectomy (MIE-IL) can further improve postoperative outcomes. However, in some patients, tube feeding by a preemptively placed jejunostomy is necessary. This single-center cohort study investigated risk factors associated with failure of DOF in patients that underwent a MIE-IL between October 2015 and April 2021. A total of 165 patients underwent a MIE-IL, in which DOF was implemented in the enhanced recovery after surgery program. Of these, 70.3% (n = 116) successfully followed the nutritional protocol. In patients in which tube feeding was needed (29.7%; n = 49), female sex (compared to male) (OR 3.5 (95% CI 1.5–8.1)) and higher ASA scores (III + IV versus II) (OR 2.2 (95% CI 1.0–4.8)) were independently associated with failure of DOF for any cause. In case of failure, this was either due to a postoperative complication (n = 31, 18.8%) or insufficient caloric intake on POD5 (n = 18, 10.9%). In the subgroup of patients with complications, higher ASA scores (OR 2.8 (95% CI 1.2–6.8)) and histological subtypes (squamous-cell carcinoma versus adenocarcinoma and undifferentiated) (OR 5.2 (95% CI 1.8–15.1)) were identified as independent risk factors. In the subgroup of patients with insufficient caloric intake, female sex was identified as a risk factor (OR 5.8 (95% CI 2.0–16.8)). Jejunostomy-related complications occurred in 17 patients (10.3%). In patients with preoperative risk factors, preemptively placing a jejunostomy may be considered to ensure that nutritional goals are met.The previous NUTRIENT II trial was funded by KWF Kankerbestrijding (Dutch Cancer Society, grant number 10495) and Medtronic (20130529)

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

Long-Term Survival Associated with Direct Oral Feeding Following Minimally Invasive Esophagectomy: Results from a Randomized Controlled Trial (NUTRIENT II)

Advancements in perioperative care have improved postoperative morbidity and recovery after esophagectomy. The direct start of oral intake can also enhance short-term outcomes following minimally invasive Ivor Lewis esophagectomy (MIE-IL). Subsequently, short-term outcomes may affect long-term survival. This planned sub-study of the NUTRIENT II trial, a multicenter randomized controlled trial, investigated the long-term survival of direct versus delayed oral feeding following MIE-IL. The outcomes included 3- and 5-year overall survival (OS) and disease-free survival (DFS), and the influence of complications and caloric intake on OS. After excluding cases of 90-day mortality, 145 participants were analyzed. Of these, 63 patients (43.4%) received direct oral feeding. At 3 years, OS was significantly better in the direct oral feeding group ( p = 0.027), but not at 5 years ( p = 0.115). Moreover, 5-year DFS was significantly better in the direct oral feeding group ( p = 0.047) and a trend towards improved DFS was shown at 3 years ( p = 0.079). Postoperative complications and caloric intake on day 5 did not impact OS. The results of this study show a tendency of improved 3-year OS and 5-year DFS, suggesting a potential long-term survival benefit in patients receiving direct oral feeding after esophagectomy. However, the findings should be further explored in larger future trials

Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2):study protocol for an international multicenter patient-blinded randomized controlled trial

Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023.</p

Implementation and outcome of minimally invasive pancreatoduodenectomy in Europe:a registry-based retrospective study A critical appraisal of the first 3 years of the E-MIPS registry

BACKGROUND: International multicenter audit-based studies focusing on the outcome of minimally invasive pancreatoduodenectomy (MIPD) are lacking. The European Registry for Minimally Invasive Pancreatic Surgery (E-MIPS) is the E-AHPBA endorsed registry aimed to monitor and safeguard the introduction of MIPD in Europe. MATERIALS AND METHODS: A planned analysis of outcomes among consecutive patients after MIPD from 45 centers in 14 European countries in the E-MIPS registry (2019-2021). The main outcomes of interest were major morbidity (Clavien-Dindo grade ≥3) and 30-day/in-hospital mortality. RESULTS: Overall, 1336 patients after MIPD were included [835 robot-assisted (R-MIPD) and 501 laparoscopic MIPD (L-MIPD)]. Overall, 20 centers performed R-MIPD, 15 centers L-MIPD, and 10 centers both. Between 2019 and 2021, the rate of centers performing L-MIPD decreased from 46.9 to 25%, whereas for R-MIPD this increased from 46.9 to 65.6%. Overall, the rate of major morbidity was 41.2%, 30-day/in-hospital mortality 4.5%, conversion rate 9.7%, postoperative pancreatic fistula grade B/C 22.7%, and postpancreatectomy hemorrhage grade B/C 10.8%. Median length of hospital stay was 12 days (IQR 8-21). A lower rate of major morbidity, postoperative pancreatic fistula grade B/C, postpancreatectomy hemorrhage grade B/C, delayed gastric emptying grade B/C, percutaneous drainage, and readmission was found after L-MIPD. The number of centers meeting the Miami Guidelines volume cut-off of ≥20 MIPDs annually increased from 9 (28.1%) in 2019 to 12 (37.5%) in 2021 ( P =0.424). Rates of conversion (7.4 vs. 14.8% P &lt;0.001) and reoperation (8.9 vs. 15.1% P &lt;0.001) were lower in centers, which fulfilled the Miami volume cut-off. CONCLUSION: During the first 3 years of the pan-European E-MIPS registry, morbidity and mortality rates after MIPD were acceptable. A shift is ongoing from L-MIPD to R-MIPD. Variations in outcomes between the two minimally invasive approaches and the impact of the volume cut-off should be further evaluated over a longer time period.</p

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy:nationwide propensity-score-matched analysis

Background: Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. Methods: This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. Results: Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P &lt; 0.001), less intraoperative blood loss (200 ml versus 500 ml; P &lt; 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P &lt; 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). Conclusion: This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.</p

Implementation and outcome of minimally invasive pancreatoduodenectomy in Europe:a registry-based retrospective study A critical appraisal of the first 3 years of the E-MIPS registry

BACKGROUND: International multicenter audit-based studies focusing on the outcome of minimally invasive pancreatoduodenectomy (MIPD) are lacking. The European Registry for Minimally Invasive Pancreatic Surgery (E-MIPS) is the E-AHPBA endorsed registry aimed to monitor and safeguard the introduction of MIPD in Europe. MATERIALS AND METHODS: A planned analysis of outcomes among consecutive patients after MIPD from 45 centers in 14 European countries in the E-MIPS registry (2019-2021). The main outcomes of interest were major morbidity (Clavien-Dindo grade ≥3) and 30-day/in-hospital mortality. RESULTS: Overall, 1336 patients after MIPD were included [835 robot-assisted (R-MIPD) and 501 laparoscopic MIPD (L-MIPD)]. Overall, 20 centers performed R-MIPD, 15 centers L-MIPD, and 10 centers both. Between 2019 and 2021, the rate of centers performing L-MIPD decreased from 46.9 to 25%, whereas for R-MIPD this increased from 46.9 to 65.6%. Overall, the rate of major morbidity was 41.2%, 30-day/in-hospital mortality 4.5%, conversion rate 9.7%, postoperative pancreatic fistula grade B/C 22.7%, and postpancreatectomy hemorrhage grade B/C 10.8%. Median length of hospital stay was 12 days (IQR 8-21). A lower rate of major morbidity, postoperative pancreatic fistula grade B/C, postpancreatectomy hemorrhage grade B/C, delayed gastric emptying grade B/C, percutaneous drainage, and readmission was found after L-MIPD. The number of centers meeting the Miami Guidelines volume cut-off of ≥20 MIPDs annually increased from 9 (28.1%) in 2019 to 12 (37.5%) in 2021 ( P =0.424). Rates of conversion (7.4 vs. 14.8% P &lt;0.001) and reoperation (8.9 vs. 15.1% P &lt;0.001) were lower in centers, which fulfilled the Miami volume cut-off. CONCLUSION: During the first 3 years of the pan-European E-MIPS registry, morbidity and mortality rates after MIPD were acceptable. A shift is ongoing from L-MIPD to R-MIPD. Variations in outcomes between the two minimally invasive approaches and the impact of the volume cut-off should be further evaluated over a longer time period.</p

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy:nationwide propensity-score-matched analysis

Background: Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. Methods: This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. Results: Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P &lt; 0.001), less intraoperative blood loss (200 ml versus 500 ml; P &lt; 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P &lt; 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). Conclusion: This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.</p