Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA): long-term outcomes of a multicentre, double-blind, randomised controlled trial.

Background: Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. Methods: In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan-Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Findings: Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4-64.8), 24.7% (95% CI: 12.7-38.8), 29.8% (95% CI: 17.9-42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248-0.614, p < 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309-0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Interpretation: Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. Funding: B. Braun.

Quantifying the Disadvantage of Small Recipient Size on the Liver Transplantation Waitlist, a Longitudinal Analysis Within the Eurotransplant Region.

BACKGROUND: Small adult patients with end-stage liver disease waitlisted for liver transplantation may face a shortage of size-matched liver grafts. This may result in longer waiting times, increased waitlist removal, and waitlist mortality. This study aims to assess access to transplantation in transplant candidates with below-average bodyweight throughout the Eurotransplant region. METHODS: Patients above 16 y of age listed for liver transplantation between 2010 and 2015 within the Eurotransplant region were eligible for inclusion. The effect of bodyweight on chances of receiving a liver graft was studied in a Cox model corrected for lab-Model for End-stage Liver Disease (MELD) score updates fitted as time-dependent variable, blood type, listing for malignant disease, and age. A natural spline with 3 degrees of freedom was used for bodyweight and lab-MELD score to correct for nonlinear effects. RESULTS: At the end of follow-up, the percentage of transplanted, delisted, and deceased waitlisted patients was 49.1%, 17.9%, and 24.3% for patients with a bodyweight <60 kg (n = 1267) versus 60.1%, 15.1%, and 18.6% for patients with a bodyweight ≥60 kg (n = 10 520). To reach comparable chances for transplantation, 60-kg and 50-kg transplant candidates are estimated to need, respectively, up to 2.8 and 4.0 more lab-MELD points than 80-kg transplant candidates. CONCLUSIONS: Decreasing bodyweight was significantly associated with decreased chances to receive a liver graft. This resulted in substantially longer waiting times, higher delisting rates, and higher waitlist mortality for patients with a bodyweight <60 kg.

European Society of Organ Transplantation (ESOT) Consensus Report on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma.

Liver transplantation offers the best chance of cure for most patients with non-metastatic hepatocellular carcinoma (HCC). Although not all patients with HCC are eligible for liver transplantation at diagnosis, some can be downstaged using locoregional treatments such as ablation and transarterial chemoembolization. These aforementioned treatments are being applied as bridging therapies to keep patients within transplant criteria and to avoid them from dropping out of the waiting list while awaiting a liver transplant. Moreover, immunotherapy might have great potential to support downstaging and bridging therapies. To address the contemporary status of downstaging, bridging, and immunotherapy in liver transplantation for HCC, European Society of Organ Transplantation (ESOT) convened a dedicated working group comprised of experts in the treatment of HCC to review literature and to develop guidelines pertaining to this cause that were subsequently discussed and voted during the Transplant Learning Journey (TLJ) 3.0 Consensus Conference that took place in person in Prague. The findings and recommendations of the working group on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma are presented in this article.

Safety of Intraoperative Blood Salvage During Liver Transplantation in Patients With Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

OBJECTIVE: The effects of intraoperative blood salvage (IBS) on time to tumor recurrence, disease-free survival and overall survival in hepatocellular carcinoma (HCC) patients undergoing liver transplantation were assessed to evaluate the safety of IBS. BACKGROUND: IBS is highly effective to reduce the use of allogeneic blood transfusion. However, the safety of IBS during liver transplantation for patients with HCC is questioned due to fear of disseminating malignant cells. METHODS: Comprehensive searches through June 2021 were performed in 8 databases. The methodological quality of included studies was assessed using the Robins-I tool. Meta-analysis with the generic inverse variance method was performed to calculate pooled hazard ratios (HRs) for disease-free survival, HCC recurrence and overall survival. RESULTS: Nine studies were included (n=1997, IBS n=1200, no-IBS n=797). Use of IBS during liver transplantation was not associated with impaired disease-free survival [HR=0.90, 95% confidence interval (CI)=0.66-1.24, P=0.53, IBS n=394, no-IBS n=329], not associated with increased HCC recurrence (HR=0.83, 95% CI=0.57-1.23, P=0.36, IBS n=537, no-IBS n=382) and not associated with impaired overall survival (HR=1.04, 95% CI=0.79-1.37, P=0.76, IBS n=495, no-IBS n=356). CONCLUSIONS: Based on available observational data, use of IBS during liver transplantation in patients with HCC does not result in impaired disease-free survival, increased HCC recurrence or impaired overall survival. Therefore, use of IBS during liver transplantation for HCC patients is a safe procedure.

In Vivo and Ex Vivo Mitochondrial Function in COVID-19 Patients on the Intensive Care Unit.

Mitochondrial dysfunction has been linked to disease progression in COVID-19 patients. This observational pilot study aimed to assess mitochondrial function in COVID-19 patients at intensive care unit (ICU) admission (T1), seven days thereafter (T2), and in healthy controls and a general anesthesia group. Measurements consisted of in vivo mitochondrial oxygenation and oxygen consumption, in vitro assessment of mitochondrial respiration in platelet-rich plasma (PRP) and peripheral blood mononuclear cells (PBMCs), and the ex vivo quantity of circulating cell-free mitochondrial DNA (mtDNA). The median mitoVO2 of COVID-19 patients on T1 and T2 was similar and tended to be lower than the mitoVO2 in the healthy controls, whilst the mitoVO2 in the general anesthesia group was significantly lower than that of all other groups. Basal platelet (PLT) respiration did not differ substantially between the measurements. PBMC basal respiration was increased by approximately 80% in the T1 group when contrasted to T2 and the healthy controls. Cell-free mtDNA was eight times higher in the COVID-T1 samples when compared to the healthy controls samples. In the COVID-T2 samples, mtDNA was twofold lower when compared to the COVID-T1 samples. mtDNA levels were increased in COVID-19 patients but were not associated with decreased mitochondrial O2 consumption in vivo in the skin, and ex vivo in PLT or PBMC. This suggests the presence of increased metabolism and mitochondrial damage.

Normothermic Machine Perfusion-Improving the Supply of Transplantable Livers for High-Risk Recipients.

The effectiveness of liver transplantation to cure numerous diseases, alleviate suffering, and improve patient survival has led to an ever increasing demand. Improvements in preoperative management, surgical technique, and postoperative care have allowed increasingly complicated and high-risk patients to be safely transplanted. As a result, many patients are safely transplanted in the modern era that would have been considered untransplantable in times gone by. Despite this, more gains are possible as the science behind transplantation is increasingly understood. Normothermic machine perfusion of liver grafts builds on these gains further by increasing the safe use of grafts with suboptimal features, through objective assessment of both hepatocyte and cholangiocyte function. This technology can minimize cold ischemia, but prolong total preservation time, with particular benefits for suboptimal grafts and surgically challenging recipients. In addition to more physiological and favorable preservation conditions for grafts with risk factors for poor outcome, the extended preservation time benefits operative logistics by allowing a careful explant and complicated vascular reconstruction when presented with challenging surgical scenarios. This technology represents a significant advancement in graft preservation techniques and the transplant community must continue to incorporate this technology to ensure the benefits of liver transplant are maximized.

Favorable Outcomes After Retro-Rectus (Rives-Stoppa) Mesh Repair as Treatment for Noncomplex Ventral Abdominal Wall Hernia, a Systematic Review and Meta-analysis.

OBJECTIVE: To assess prevalence of hernia recurrence, surgical site infection (SSI), seroma, serious complications, and mortality after retro-rectus repair. SUMMARY BACKGROUND DATA: Ventral abdominal wall hernia is a common problem, tied to increasing frailty and obesity of patients undergoing surgery. For noncomplex ventral hernia, retro-rectus (Rives-Stoppa) repair is considered the gold standard treatment. Level-1 evidence confirming this presumed superiority is lacking. METHODS: Five databases were searched for studies reporting on retro-rectus repair. Single-armed and comparative randomized and non-randomized studies were included. Outcomes were pooled with mixed-effects, inverse variance or random-effects models. RESULTS: Ninety-three studies representing 12,440 patients undergoing retro-rectus repair were included. Pooled hernia recurrence was estimated at 3.2% [95% confidence interval (CI): 2.2%-4.2%, n = 11,049] after minimally 12months and 4.1%, (95%CI: 2.9%-5.5%, n = 3830) after minimally 24 months. Incidences of SSI and seroma were estimated at respectively 5.2% (95%CI: 4.2%-6.4%, n = 4891) and 5.5% (95%CI: 4.4%-6.8%, n = 3650). Retro-rectus repair was associated with lower recurrence rates compared to onlay repair [odds ratios (OR): 0.27, 95%CI: 0.15-0.51, P < 0.001] and equal recurrence rates compared to intraperitoneal onlay mesh (IPOM) repair (OR: 0.92, 95%CI: 0.75-1.12, P = 0.400). Retro-rectus repair was associated with more SSI than IPOM repair (OR: 1.8, 95%CI: 1.03 -3.14, P = 0.038). Minimally invasive retro-rectus repair displayed low rates of recurrence (1.3%, 95%CI: 0.7%-2.3%, n = 849) and SSI (1.5%, 95%CI: 0.8%-2.8%, n = 982), albeit based on non-randomized studies. CONCLUSIONS: Retro-rectus (Rives-Stoppa) repair results in excellent outcomes, superior or similar to other techniques for all outcomes except SSI. The latter rarely occurred, yet less frequently after IPOM repair, which is usually performed by laparoscopy.

Full-left-full-right split liver transplantation for adult recipients: a systematic review and meta-analysis.

Full-left-full-right split liver transplantation (FSLT) for adult recipients, may increase the availability of liver grafts, reduce waitlist time, and benefit recipients with below-average body weight. However, FSLT may lead to impaired graft and patient survival. This study aims to assess outcomes after FSLT. Five databases were searched to identify studies concerning FSLT. Incidences of complications, graft- and patient survival were assessed. Discrete data were pooled with random-effect models. Graft and patient survival after FSLT were compared with whole liver transplantation (WLT) according to the inverse variance method. Vascular complications were reported in 25/273 patients after FSLT (Pooled proportion: 6.9%, 95%CI: 3.1-10.7%, I2 : 36%). Biliary complications were reported in 84/308 patients after FSLT (Pooled proportion: 25.6%, 95%CI: 19-32%, I2 : 44%). Pooled proportions of graft and patient survival after 3 years follow-up were 72.8% (95%CI: 67.2-78.5, n = 231) and 77.3% (95%CI: 66.7-85.8, n = 331), respectively. Compared with WLT, FSLT was associated with increased graft loss (pooled HR: 2.12, 95%CI: 1.24-3.61, P = 0.006, n = 189) and patient mortality (pooled HR: 1.81, 95%CI: 1.17-2.81, P = 0.008, n = 289). FSLT was associated with high incidences of vascular and biliary complications. Nevertheless, long-term patient and graft survival appear acceptable and justify transplant benefit in selected patients.

Safety of intra-operative blood salvage during liver transplantation in patients with hepatocellular carcinoma, a propensity score-matched survival analysis.

Intra-operative blood salvage (IBS) reduces the use of allogeneic blood transfusion. However, safety of IBS during liver transplantation (LT) for hepatocellular carcinoma (HCC) is questioned due to fear for dissemination of circulating malignant cells. This study aims to assess safety of IBS. HCC patients who underwent LT from January 2006 through December 2019 were included. Patients in whom IBS was used were propensity score matched (1:1) to control patients. Disease-free survival and time to HCC recurrence were assessed with Cox regression models and competing risk models. IBS was used in 192/378 HCC LT recipients, and 127 patients were propensity score matched. Cumulative disease-free survival at 12 and 60 months was 85% and 63% for the IBS group versus 90% and 68% for the no-IBS group. Use of IBS was not associated with impaired disease-free survival (HR 1.07, 95%CI: 0.65-1.76, P = 0.800) nor with increased HCC recurrence (Cause-specific cox model: HR 0.79, 95%CI: 0.36-1.73, P = 0.549, Fine and Gray model: HR: 0.79, 95%CI 0.40-1.57, P = 0.50). In conclusion, IBS during LT did not increase the risk for HCC recurrence. IBS is a safe procedure in HCC LT recipients to reduce the need for allogenic blood transfusion.

Medialization after combined anterior and posterior component separation in giant incisional hernia surgery, an anatomical study.

BACKGROUND: To obtain tension-free closure for giant incisional hernia repair, anterior or posterior component separation is often performed. In patients with an extreme diameter hernia, anterior component separation and posterior component separation may be combined. The aim of this study was to assess the additional medialization after simultaneous anterior component separation and posterior component separation. METHODS: Fresh-frozen post mortem human specimens were used. Both sides of the abdominal wall were subjected to retro-rectus dissection (Rives-Stoppa), anterior component separation and posterior component separation, the order in which the component separation techniques were performed was reversed for the contralateral side. Medialization was measured at 3 reference points. RESULTS: Anterior component separation provided most medialization for the anterior rectus sheath, posterior component separation provided most medialization for the posterior rectus sheath. After combined component separation techniques total median medialization ranged between 5.8 and 9.2 cm for the anterior rectus sheath, and between 10.1 and 14.2 cm for the posterior rectus sheath (depending on the level on the abdomen). For the anterior rectus sheath, additional posterior component separation after anterior component separation provided 15% to 16%, and additional anterior component separation after posterior component separation provided 32% to 38% of the total medialization after combined component separation techniques. For the posterior rectus sheath, additional posterior component separation after anterior component separation provided 50% to 59%, and additional anterior component separation after posterior component separation provided 11% to 17% of the total medialization after combined component separation techniques. Retro-rectus dissection alone contributed up to 41% of maximum obtainable medialization. CONCLUSION: Anterior component separation provided most medialization of the anterior rectus sheath and posterior component separation provided most medialization of the posterior rectus sheath. Combined component separation techniques provide marginal additional medialization, clinical use of this technique should be carefully balanced against additional risks.

Outcomes of Incisional Hernia Repair Surgery After Multiple Re-recurrences: A Propensity Score Matched Analysis.

BACKGROUND: Patients with a re-recurrent hernia may account for up to 20% of all incisional hernia (IH) patients. IH repair in this population may be complex due to an altered anatomical and biological situation as a result of previous procedures and outcomes of IH repair in this population have not been thoroughly assessed. This study aims to assess outcomes of IH repair by dedicated hernia surgeons in patients who have already had two or more re-recurrences. METHODS: A propensity score matched analysis was performed using a registry-based, prospective cohort. Patients who underwent IH repair after ≥ 2 re-recurrences operated between 2011 and 2018 and who fulfilled 1 year follow-up visit were included. Patients with similar follow-up who underwent primary IH repair were propensity score matched (1:3) and served as control group. Patient baseline characteristics, surgical and functional outcomes were analyzed and compared between both groups. RESULTS: Seventy-three patients operated on after ≥ 2 IH re-recurrences were matched to 219 patients undergoing primary IH repair. After propensity score matching, no significant differences in patient baseline characteristics were present between groups. The incidence of re-recurrence was similar between groups (≥ 2 re-recurrences: 25% versus control 24%, p = 0.811). The incidence of complications, as well as long-term pain, was similar between both groups. CONCLUSION: IH repair in patients who have experienced multiple re-recurrences results in outcomes comparable to patients operated for a primary IH with a similar risk profile. Further surgery in patients who have already experienced multiple hernia re-recurrences is justifiable when performed by a dedicated hernia surgeon.

Infectious Complication in Relation to the Prophylactic Mesh Position: The PRIMA Trial Revisited.

BACKGROUND: Prophylactic mesh reinforcement has proven to reduce the incidence of incisional hernia (IH). Fear of infectious complications may withhold the widespread implementation of prophylactic mesh reinforcement, particularly in the onlay position. STUDY DESIGN: Patients scheduled for elective midline surgery were randomly assigned to a suture closure group, onlay mesh group, or sublay mesh group. The incidence, treatment, and outcomes of patients with infectious complications were assessed through examining the adverse event forms. Data were collected prospectively for 2 years after the index procedure. RESULTS: Overall, infectious complications occurred in 14/107 (13.3%) patients in the suture group and in 52/373 (13.9%) patients with prophylactic mesh reinforcement (p = 0.821). Infectious complications occurred in 17.6% of the onlay group and 10.3% of the sublay group (p = 0.042). Excluding anastomotic leakage as a cause, these incidences were 16% (onlay) and 9.7% (sublay), p = 0.073. The mesh could remain in-situ in 40/52 (77%) patients with an infectious complication. The 2-year IH incidence after onlay mesh reinforcement was 10 in 33 (30.3%) with infectious complications and 15 in 140 (9.7%) without infectious complications (p = 0.003). This difference was not statistically significant for the sublay group. CONCLUSIONS: Prophylactic mesh placement was not associated with increased incidence, severity, or need for invasive treatment of infectious complications compared with suture closure. Patients with onlay mesh reinforcement and an infectious complication had a significantly higher risk of developing an incisional hernia, compared with those in the sublay group.

Disadvantage of Small (<60 kg) Adult Candidates on the Liver Transplantation Waitlist.

BACKGROUND: Small adult patients with lower bodyweight wait-listed for liver transplantation may face a shortage of size-matched whole-liver grafts. The objective of this study is to compare time to transplantation in adult patients with a bodyweight of <60 kg to patients with bodyweight ≥60 kg. METHODS: A matched case-control study was conducted. Patients aged 18 years and older listed for liver transplantation at our transplant center, from 2007 to 2016 with a bodyweight <60 kg were manually matched 1:2 to control patients ≥ 60 kg. Matching was performed based on ABO blood type, model for end-stage liver disease score, (non)-standard exception status, and eligibility for donation after cardiac death. Time to transplantation was assessed with univariable Cox-regression. RESULTS: In total, 23 cases with a bodyweight < 60 kg were matched to 46 average-sized control patients. Small adults were significantly disadvantaged for receiving a liver transplantation as compared to their average-sized counterpart (hazard ratio 0.47; 95% confidence interval 0.29-0.75, P = .002). At the end of follow-up, 14/23 (60.9%) of cases versus 35/46 of controls (76.1%) had received a liver transplantation. CONCLUSION: Small adults with a bodyweight below 60 kg are disadvantaged on the waitlist for a size-matched whole liver graft.

Functional outcomes in symptomatic versus asymptomatic patients undergoing incisional hernia repair: Replacing one problem with another? A prospective cohort study in 1312 patients.

BACKGROUND: Incisional hernias can be associated with pain or discomfort. Surgical repair especially mesh reinforcement, may likewise induce pain. The primary objective was to assess the incidence of pain after hernia repair in patients with and without pre-operative pain or discomfort. The secondary objectives were to determine the preferred mesh type, mesh location and surgical technique in minimizing postoperative pain or discomfort. MATERIALS AND METHODS: A registry-based prospective cohort study was performed, including patients undergoing incisional hernia repair between September 2011 and May 2019. Patients with a minimum follow-up of 3-6 months were included. The incidence of hernia related pain and discomfort was recorded perioperatively. RESULTS: A total of 1312 patients were included. Pre-operatively, 1091 (83%) patients reported pain or discomfort. After hernia repair, 961 (73%) patients did not report pain or discomfort (mean follow-up = 11.1 months). Of the pre-operative asymptomatic patients (n = 221), 44 (20%, moderate or severe pain: n = 14, 32%) reported pain or discomfort after mean follow-up of 10.5 months. Of those patients initially reporting pain or discomfort (n = 1091), 307 (28%, moderate or severe pain: n = 80, 26%) still reported pain or discomfort after a mean follow-up of 11.3 months postoperatively. CONCLUSION: In symptomatic incisional hernia patients, hernia related complaints may be resolved in the majority of cases undergoing surgical repair. In asymptomatic incisional hernia patients, pain or discomfort may be induced in a considerable number of patients due to surgical repair and one should be aware if this postoperative complication.

Anterior and posterior rectus abdominis sheath stiffness in relation to diastasis recti: Abdominal wall training or not?

INTRODUCTION: This study explores the anatomical relation of the rectus abdominis muscles with the anterior and posterior rectus sheaths. The elastic behavior of these fascial sheets is also assessed. Both of these analyses form an anatomic-biomechanical basis for diagnosis and treatment, especially in relation to diastasis recti abdominis (DRA). METHOD: Fundamental observational, biomechanical study. Seven post-mortem, embalmed human specimens were dissected. The abdominal muscles and the fascial sheets of the abdominal wall were dissected. 4 × 4 cm samples of the anterior and posterior rectus sheaths were loaded in longitudinal and transverse direction, while recording elongation by means of a displacement sensor. The main outcome measures were anatomical descriptions and elongation of fascia samples in mm (mean and standard ±â€¯deviation). RESULTS: In longitudinal direction the posterior rectus sheath samples stretched over 1.67 ±â€¯0.48 mm, while in transverse direction the mean stretch was 0.29 ±â€¯0.18 mm (p = 0.001). In contrast, no significant difference between longitudinal (0.78 ±â€¯0.43 mm) and transversal displacement (0.50 ±â€¯0.23 mm) was observed in the anterior rectus sheath (p = 0.56). DISCUSSION AND CONCLUSION: The posterior rectus sheath is functionally more related to the transverse abdominis muscle than to the rectus abdominis muscle. From this connection, in combination with the specific stiffness of the posterior fascia in the lateral direction, it is assumed that the transverse abdominis muscles play an important role in the etiology but also in reduction of DRA. The transverse abdominis and rectus abdominis muscles collaborate in support of the abdominal wall.

Incisional Hernia Cannot Be Diagnosed by a Patient-Reported Diagnostic Questionnaire.

BACKGROUND: Incisional hernia (IH) is one of the most frequent complications after abdominal surgery. Follow-up with regard to IH remains challenging. Physical examination and imaging to diagnose IH are time-consuming and costly, require devotion of both the physician and patient, and are often not prioritized. Therefore, a patient-reported diagnostic questionnaire for the diagnosis of IH was developed. Objective of this study was to validate this questionnaire in a consecutive sample of patients. METHODS: All patients above 18 y of age who underwent abdominal surgery with a midline incision at least 12 mo ago were eligible for inclusion. Included patients visited the outpatient clinic where they filled out the diagnostic questionnaire and underwent physical examination. The questionnaire answers were compared with the physical examination results. The diagnostic accuracy of the entire questionnaire was assessed by multivariable logistic regression. RESULTS: In total, 241 patients visited the outpatient clinic prospectively. 54 (22%) patients were diagnosed with IH during physical examination. The area under the receiver operating characteristic curve of the diagnostic questionnaire was 0.82. Sensitivity and specificity were respectively 81.5% and 77.5%. The positive and negative predictive values were 51.2% and 94%, respectively. Ten (19%) patients with IH were missed by the questionnaire. CONCLUSIONS: The patient-reported diagnostic questionnaire as currently proposed cannot be used to diagnose IH. However, given the high negative predictive value, the questionnaire might be used to rule out an IH. Long-term follow-up for the diagnosis of IH should be performed by clinical examination.

The Effect of Perioperative Music on the Stress Response to Surgery: A Meta-analysis.

BACKGROUND: Current perioperative patient care aims to maintain homeostasis by attenuation of the stress response to surgery, as a more vigorous stress response can have detrimental effects on postoperative recovery. This systematic review and meta-analysis aims to assess the effect of perioperative music on the physiological stress response to surgery. METHODS: The Embase, Medline Ovid, Cochrane Central, Web of Science, and Google Scholar databases were searched from inception date until February 5, 2019, using a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines for randomized controlled trials investigating the effect of music before, during, and/or after surgery in adult surgical patients on the stress response to surgery. Meta-analysis was performed using a random effects model and pooled standardized mean differences were calculated with 95% confidence intervals. This study was registered in the PROSPERO database (CRD42018097060). RESULTS: The literature search identified 1076 articles. Eighteen studies (1301 patients) were included in the systematic review, of which eight were included in the meta-analysis. Perioperative music attenuated the neuroendocrine cortisol stress response to surgery (pooled standardized mean difference -0.30, [95% confidence interval -0.53 to -0.07], P = 0.01, I2 = 0). CONCLUSIONS: Perioperative music can attenuate the neuroendocrine stress response to surgery.