Analgesia in esophagectomy: a narrative review.

Background and Objective: Optimal pain management for esophagectomy facilitates prevention of postoperative complications such as pneumonia, but also chronic pain. Historically, multimodal intravenous analgesia was employed. In the last decades, regional anesthesia including epidural and paravertebral analgesia is frequently used. In this narrative review, we provide a comprehensive overview of the available evidence for the different analgesia regimens for esophagectomy. Methods: A search was conducted in the PubMed/MEDLINE database in November 2022. Only reports in English or Dutch were included. Editorials or articles lacking full text were excluded. A review of different analgesia regimens after esophagectomy is provided. Key Content and Findings: Epidural analgesia (EA) was suggested to reduce postoperative pneumonia and prevent chronic postsurgical pain (CPSP) as compared to opioid-based systemic analgesia and was considered the gold standard of pain management for esophagectomy. In the last decades, the side-effects of EA became more evident. Next to mild or moderate side-effects such as hypotension and urinary retention, several reports emphasized the incidence of serious neurologic complications to be much higher than estimated before. In addition, minimally invasive surgery fostered that other regional analgesia (RA) techniques are potential alternatives for EA. Paravertebral catheter placement can be performed under videoscope view during the thoracic phase of esophagectomy, making it a safe and easily placed block. Evidence on the effectiveness of erector spinae plane block (ESPB) is limited in this context. Conclusions: Several analgesia regimens after esophagectomy are described. EA is most common, however paravertebral analgesia is a good alternative. Other techniques are also gaining ground but randomized clinical trials are lacking. Future studies should focus on the efficacy of paravertebral and erector spinae blocks for postoperative pain management for esophagectomy.

Opioid-free anesthesia: A systematic review and meta-analysis.

STUDY OBJECTIVE: To evaluate all available evidence thus far on opioid based versus opioid-free anesthesia and its effect on acute and chronic postoperative pain. DESIGN: Systematic review and meta-analysis of randomized clinical trials. SETTING: Operating room, postoperative recovery room and ward. PATIENTS: Patients undergoing general anesthesia. INTERVENTIONS: After consulting MEDLINE, EMBASE and Cochrane database, studies which compared opioid free anesthesia (OFA) with opioid based anesthesia (OBA) were included (last search April 15th 2022). MEASUREMENTS: Primary outcomes were acute and chronic pain scores in NRS or VAS. Secondary outcomes were quality of recovery and postoperative opioid consumption. Risk of bias was assessed using the RoB2 tool and a random effects model for the meta-analysis was conducted. MAIN RESULTS: We identified 1245 citations, of which 38 studies met our inclusion criteria. There is moderate quality evidence showing no clinically relevant difference of Numeric Rating Scale (NRS) scores or opioid consumption in the postoperative period (pooled mean difference of 0.39 points with a CI of 0.19-0.59 and 4.02 MME with a CI of 1.73-6.30). We found only one small-sized study reporting no effect of opioid-free anesthesia on chronic pain. The quality of recovery was superior in patients with opioid-free anesthesia (mean difference of 8.26 points), however, this pooled analysis was comprised of only two studies. Postoperative nausea and vomiting (PONV) occurred less in opioid-free anesthesia, but bradycardia was more frequent. CONCLUSIONS: We concluded that we cannot recommend one strategy over the other. Future studies could focus on quality of recovery as outcome measure and adequately powered studies on the effects of opioid-free anesthesia on chronic pain are eagerly awaited.

C-Reactive Protein as a Negative Predictive Marker for Anastomotic Leakage After Minimally Invasive Esophageal Surgery.

BACKGROUND: Serum C-reactive protein (CRP) is commonly used by surgeons to raise suspicion of anastomotic leakage and other infectious complications, but most studies on optimal cut-off values are retrospective with a small sample of patients. The aim of this study was to determine the accuracy and optimal cut-off value of CRP for anastomotic leakage in patients following esophagectomy for cancer. MATERIALS AND METHODS: Consecutive minimally invasive esophagectomy for esophageal cancer patients was included in this prospective study. Anastomotic leakage was confirmed if a defect or leakage of oral contrast was seen on a CT scan, by endoscopy or if saliva was draining from the neck incision. Diagnostic accuracy of CRP was assessed by receiver operator curve (ROC) analysis. Youden's index was adopted to determine the cut-off value. RESULTS: A total of 200 patients were included between 2016 and 2018. Postoperative day 5 showed the highest area under the ROC (0.825) and optimal cut-off value of 120 mg/L. This resulted in a sensitivity of 75%, specificity of 82%, negative predicting value of 97%, and positive predicting value of 32%. CONCLUSIONS: CRP on postoperative day 5 can be used as a negative predictor for and can be used as a marker to raise suspicion of anastomotic leakage following esophagectomy for esophageal cancer. When CRP exceeds 120 mg/L on postoperative day 5, additional investigations should be considered.

Contrast-Enhanced Radiologic Evaluation of Gastric Conduit Emptying After Esophagectomy.

BACKGROUND: Nasogastric tube (NGT) insertion is the standard of care in many hospitals after esophagectomy for gastric conduit decompression. An upper gastrointestinal contrast passage evaluation (UGI-CE) is a diagnostic test to evaluate passage through the gastric conduit. The authors hypothesized that introducing routine UGI-CE after esophagectomy results in earlier removal of the NGT and resumption of oral intake. METHODS: This retrospective study evaluated two consecutive series of patients undergoing esophagectomy, one before (control group) and one after the introduction of a routine UGI-CE on postoperative day (POD) 3 or 4 (UGI-CE group). If contrast passage was found on the UGI-CE, the NGT was capped and removed. In the control group, the NGT was routinely capped and removed on day 5 after surgery. The primary outcome was the POD on which oral diet was initiated. The secondary outcomes were the day of NGT removal, NGT reinsertions, postoperative complications, and length of hospital stay. RESULTS: Each cohort included 74 patients. In the UGI-CE group, the contrast test was performed on median POD 3.5 (IQR, 3-4). The median day of NGT removal, initiation of clear liquids, and full liquid and solid intake was 1 to 2 days earlier in the UGI-CE group than in the control group (i.e. POD 4, 4, 5, and 6 vs. POD 5, 5, 6.5, and 8; all p < 0.001). The study found no significant differences in NGT reinsertions, pneumonias, anastomotic leakages, or hospital stay. CONCLUSION: The routine use of a UGI-CE after esophagectomy led to earlier removal of the NGT and earlier resumption of oral intake.

End-to-side circular stapled versus side-to-side linear stapled intrathoracic esophagogastric anastomosis following minimally invasive Ivor-Lewis esophagectomy: comparison of short-term outcomes.

PURPOSE: The search for the optimal procedure for creation of a safe gastroesophageal intrathoracic anastomosis with a lower risk of leakage in totally minimally invasive Ivor-Lewis esophagectomy (TMIIL) is ongoing. In the present study, we compared the outcomes of end-to-side (with circular stapler [CS]) and side-to-side (with linear stapler [LS]) techniques for intrathoracic anastomosis during TMIIL performed in 2 European high-volume centers for upper gastrointestinal surgery. A propensity score method was used to compare the CS and LS groups. METHODS: We retrospectively evaluated patients with lower esophageal cancer or Siewert type 1 or 2 esophagogastric junction carcinoma who underwent a planned TMIIL esophagectomy, performed from January 2017 to September 2020. The anastomosis was created by a semi-mechanical technique using a LS in one center and by a mechanical technique using a CS in the other center. General features, operative techniques, pathology data, and short-term outcomes were analyzed. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. The primary endpoint of the study was the rate of anastomotic leakage in the two groups. Secondary endpoints included rates of anastomotic stricture and overall postoperative complications. RESULTS: Considering the whole population, 256 patients were included; of those, 220 received the anastomosis with a circular stapler (CS group), and 36 received the anastomosis with a linear stapler (LS group). No significant differences by group in terms of sex, age, American Society of Anesthesiologists physical status classification, and type of neoplasm were showed. The rate of anastomotic leakage did not differ in the two groups (9.6% CS vs. 5.6% LS, p = 0.438), as well as the rate of anastomotic stricture in the 3-month follow-up (0.9% CS vs. 2.8% LS, p = 0.367). The rate of chyle leakage and of pulmonary, cardiac, and infective complications was not significantly different in the groups. After propensity score matching, 72 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups. CONCLUSIONS: The results of our study suggest that both techniques for esophagogastric anastomosis during TMIIL are feasible, safe, and effective, with comparable rates of postoperative anastomotic leakage and stricture.

Optimal Perioperative Pain Management in Esophageal Surgery: An Evaluation of Paravertebral Analgesia.

BACKGROUND: For esophagectomy, thoracic epidural analgesia (TEA) is the standard of care for perioperative pain management. Although effective, TEA is associated with moderate to serious adverse events such as hypotension and neurologic complications. Paravertebral analgesia (PVA) may be a safe alternative. The authors hypothesized that TEA and PVA are similar in efficacy for pain treatment in thoracolaparoscopic Ivor Lewis esophagectomy. METHODS: This retrospective cohort study compared TEA with PVA in two consecutive series of 25 thoracolaparoscopic Ivor Lewis esophagectomies. In this study, TEA consisted of continuous epidural bupivacaine and sufentanil infusion with a patient-controlled bolus function. In PVA, the catheter was inserted by the surgeon under thoracoscopic vision during surgery. Administration of PVA consisted of continuous paravertebral bupivacaine infusion after a bolus combined with patient-controlled analgesia using intravenous morphine. The primary outcome was the median highest recorded Numeric Pain Rating Scale (NRS) during the 3 days after surgery. The secondary outcomes were vasopressor consumption, fluid administration, and length of hospital stay. RESULTS: In both groups, the median highest recorded NRS was 4 or lower during the first three postoperative days. The patients with PVA had a higher overall NRS (mean difference, 0.75; 95% confidence interval 0.49-1.44). No differences were observed in any of the other secondary outcomes. CONCLUSION: For the patients undergoing thoracolaparoscopic Ivor Lewis esophagectomy, TEA was superior to PVA, as measured by NRS during the first three postoperative days. However, both modes provided adequate analgesia, with a median highest recorded NRS of 4 or lower. These results could form the basis for a randomized controlled trial.

Influence of body composition and muscle strength on outcomes after multimodal oesophageal cancer treatment.

BACKGROUND: Influence of sarcopenia in combination with other body composition parameters and muscle strength on outcomes after oesophageal surgery for oesophageal cancer remains unclear. The objectives were (i) to describe the incidence of sarcopenia in relation to adipose tissue quantity and distribution and muscle strength; (ii) to evaluate if neoadjuvant chemoradiation (nCRTx) influences body composition and muscle strength; and (iii) to evaluate the influence of body composition and muscle strength on post-operative morbidity and long-term survival. METHODS: This retrospective study included patients with oesophageal cancer who received nCRTx followed by surgery between January 2011 and 2016. Skeletal muscle, visceral, and subcutaneous adipose tissue cross-sectional areas were calculated based on computed tomography scans, and muscle strength was measured using hand grip tests, 30 seconds chair stand tests, and maximal inspiratory and expiratory pressure tests prior to nCRTx and after nCRTx. RESULTS: A total of 322 patients were included in this study. Sarcopenia was present in 55.6% of the patients prior to nCRTx and in 58.2% after nCRTx (P = 0.082). Patients with sarcopenia had a significantly lower muscle strength and higher fat percentage. The muscle strength and incidence of sarcopenia increased while the mean body mass index and fat percentage decreased during nCRTx. A body mass index above 25 kg/m2 was associated with anastomotic leakage (P = 0.032). Other body composition parameters were not associated with post-operative morbidity. A lower handgrip strength prior to nCRTx was associated with pulmonary and cardiac complications (P = 0.023 and P = 0.009, respectively). In multivariable analysis, a lower number of stands during the 30 seconds chair stand test prior to nCRTx (hazard ratio 0.93, 95% confidence interval 0.87-0.99, P = 0.017) and visceral adipose tissue of >128 cm2 after nCRTx (hazard ratio 1.81, 95% confidence interval 1.30-2.53, P = 0.001) were associated with worse overall survival. CONCLUSIONS: Sarcopenia occurs frequently in patients with oesophageal cancer and is associated with less muscle strength and a higher fat percentage. Body composition changes during nCRTx did not influence survival. Impaired muscle strength and a high amount of visceral adipose tissue are associated with worse survival. Therefore, patients with poor fitness might benefit from preoperative nutritional and muscle strengthening guidance, aiming to increase muscle strength and decrease visceral adipose tissue. However, this should be confirmed in a large prospective study.