Effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection: A prospective randomized, double-blind, placebo-controlled study.

AIMS: Esketamine may reduce acute postoperative pain in several settings. However, the effects of low-dose esketamine on postoperative pain after vestibular schwannoma (VS) resection with propofol/remifentanil total intravenous anaesthesia (TIVA) are unclear. The aim of this study is to observe the effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection. METHODS: This single-centre, randomized, placebo-controlled, double-blind trial included 90 adults undergoing VS resection via the retrosigmoid approach with TIVA. The patients were randomly allocated to two groups: esketamine or control (n = 45 in each group). Patients received low-dose esketamine (0.2 mg/kg) or a similar volume of normal saline after dural closure. The primary outcome was the pain score during movement (gentle head movement) at 24 h postoperatively. Secondary outcomes included recovery time, bispectral index (BIS) values and haemodynamic profiles during the first 30 min after esketamine administration, and adverse effects. RESULTS: Low-dose esketamine did not reduce pain scores at rest (P > .05) or with movement (P > .05) within the first 24 h after surgery. Esketamine moderately increased BIS values for at least 30 min after administration (P < .0001) but did not affect heart rate (P = .992) or mean arterial blood pressure (P = .994). Esketamine prolonged extubation time (P = .042, 95% confidence interval: 0.08 to 4.42) and decreased the effect-site concentration of remifentanil at extubation (P = .001, 95% confidence interval: -0.53 to -0.15) but did not affect the time to resumption of spatial orientation. Postoperative nausea and vomiting rates did not differ between groups, and no hallucinations or excessive sedation was observed. CONCLUSION: Intraoperative low-dose esketamine did not significantly reduce acute pain after VS resection with propofol/remifentanil TIVA. However, BIS values increased for at least 30 min after esketamine administration.

Effect of early peri-operative arterial lactate concentration level ratios on post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. METHODS: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. RESULTS: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). CONCLUSIONS: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.

Recent advances in the treatment of renal stones using flexible ureteroscopys.

Upper urinary tract stones are a common urological disease that can be treated by flexible ureteroscopy (FURS) through the natural urinary tract, in addition to extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCNL). The advantages of FURS are less trauma, faster recovery, and fewer complications, while its disadvantages include poor results of lithotripsy and stone extraction when dealing with larger stones, and prolonged operation time. Over the last two decades, the emergence of new technologies such as FURS combined with negative pressure suction, robot-assisted FURS, and artificially intelligent FURS, coupled with improvements in laser technology (the use of thulium fiber lasers (TFL) and the invention of single-use flexible ureteroscopes (su-fURS) suitable for primary level application, have significantly increased the global adoption of FURS. This surge in usage holds a promising future in clinical application, benefiting a growing number of patients with renal calculi. Accompanied by changes in technical concepts and therapeutic modalities, the scope of indications for FURS is broadening, positioning it as a potential primary choice for urolithiasis treatment in the future. This review outlines the progress in employing flexible ureteroscopy for the treatment of renal calculi in order to generate insights for further research.

Naples Prognostic Score is an Independent Prognostic Factor in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

Background: Nutritional and inflammatory status has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC), but many studies did not include all biomarkers simultaneously. The present study aimed to determine the impact of Naples prognostic score (NPS) on the long-term survival in patients undergoing hepatectomy for HCC. Methods: Patients with HCC after curative resection were eligible. Then, all patients were stratified into three groups according to the NPS. Clinical features and survival outcomes were compared among the three groups. Independent prognostic factors were determined by COX analysis. The time dependent receiver operating characteristic (ROC) curves were used to compare prognostic performance with other immunonutrition scoring systems. Results: A total of 476 patients were enrolled eventually. Baseline characteristics showed that patients with higher NPS had a higher proportion of poor liver function and advanced tumor features. Accordingly, Kaplan-Meier survival curves showed that patients with higher NPS had a lower rate of overall survival (OS) and recurrence-free survival (RFS). Multivariable COX analysis demonstrated that NPS was an independent risk factor of OS (NPS group 2 vs 1: HR=1.958, 95% CI: 1.038-3.369, p = 0.038; NPS group 3 vs 1: HR=2.608, 95% CI: 1.358-5.008, p=0.004, respectively) and RFS (NPS group 2 vs 1: HR=2.014, 95% CI: 1.299-2-3.124, p=0.002; NPS group 3 vs 1: HR=2.002, 95% CI: 1.262-3.175, p=0.003, respectively). The time-dependent ROC curve showed that NPS was superior to other models in prognostic performance and discriminatory power for long-term survival (median AUC 0.675, 95% CI: 0.586-0.712, P < 0.05). Conclusion: The NPS is a simple tool strongly associated with long-term survival in patients undergoing curative hepatectomy for HCC.

The pre- and postoperative nomograms to predict the textbook outcomes of patients who underwent hepatectomy for hepatocellular carcinoma.

Background and aims: An increasing number of studies have confirmed that non-textbook outcomes (non-TO) are a risk factor for the long-term outcome of malignant tumors. It is particularly important to identify the predictive factors of non-TO to improve the quality of surgical treatment. We attempted to construct two nomograms for preoperative and postoperative prediction of non-TO after laparoscopic hepatectomy for hepatocellular carcinoma (HCC). Methods: Patients who underwent curative-intent hepatectomy for HCC between 2014 and 2021 at two Chinese hospitals were analyzed. Using univariate and multivariate analyses, the independent predictors of non-TO were identified. The prediction accuracy is accurately measured by the receiver operating characteristic (ROC) curve and calibration curve. ROC curves for the preoperative and postoperative models, Child-Pugh grade, BCLC staging, and 8th TNM staging were compared relative to predictive accuracy for non-TO. Results: Among 515 patients, 286 patients (55.5%) did not achieve TO in the entire cohort. Seven and eight independent risk factors were included in the preoperative and postoperative predictive models by multivariate logistic regression analysis, respectively. The areas under the ROC curves for the postoperative and preoperative models, Child-Pugh grade, BCLC staging, and 8th TNM staging in predicting non-TO were 0.762, 0.698, 0.579, 0.569, and 0.567, respectively. Conclusion: Our proposed preoperative and postoperative nomogram models were able to identify patients at high risk of non-TO following laparoscopic resection of HCC, which may guide clinicians to make individualized surgical decisions, improve postoperative survival, and plan adjuvant therapy against recurrence.

Immunotherapies for advanced hepatocellular carcinoma.

Primary liver cancer is the second leading cause of tumor-related deaths in China, with hepatocellular carcinoma (HCC) accounting for 80%-90% of these. Since there is a lack of symptoms in the early stages of HCC, a large proportion of patients were identified with unresectable HCC when diagnosed. Due to the severe resistance to chemotherapy, patients with advanced HCC were traditionally treated with systematic therapy in the past decades, and the tyrosine kinase inhibitor (TKI) sorafenib has remained the only treatment option for advanced HCC since 2008. Immunotherapies, particularly immune checkpoint inhibitors (ICIs), have shown a strong anti-tumor effect and have been supported by several guidelines recently. ICIs, for example programmed cell death-1 (PD-1) inhibitors such as nivolumab and pembrolizumab, programmed cell death ligand 1 (PD-L1) inhibitors such as atezolizumab, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors such as ipilimumab, the ICI-based combination with TKIs, and VEGF-neutralizing antibody or systematic or local anti-tumor therapies, are being further studied in clinical trials. However, immune-related adverse events (irAEs) including cutaneous toxicity, gastrointestinal toxicity, and hepatotoxicity may lead to the termination of ICI treatment or even threaten patients' lives. This review aims to summarize currently available immunotherapies and introduce the irAEs and their managements in order to provide references for clinical application and further research.

Survival benefit of adjuvant transcatheter arterial chemoembolization for patients with hepatocellular carcinoma after anatomical hepatectomy.

BACKGROUND & AIMS: Although anatomical hepatectomy (AH) is widely used in the treatment of hepatocellular carcinoma (HCC), the prognosis is still unsatisfactory. The present study aimed to evaluate the survival benefit of adjuvant transcatheter arterial chemoembolization (TACE) for patients with HCC after AH. METHODS: A total of 832 patients were stratified into with adjuvant TACE (443, 53.2%) and without adjuvant TACE group (389, 46.8%) AH. Propensity score matching (PSM) was performed to control for confounding factors, and multivariable Cox regression was performed to determine the independent risk factors. RESULTS: After PSM, the results showed that the adjuvant TACE group had better overall survival (OS) and recurrence-free survival (RFS). Among the patients with tumor recurrence, adjuvant TACE was associated with a high rate of early-stage tumor at recurrence, a lower recurrence rate around the frontal margin and extrahepatic metastases, and a higher rate of receiving curative treatment. Multivariable Cox regression analysis showed that adjuvant TACE was an independent prognostic factor for OS (HR 0.673, P = 0.001) and RFS (HR 0.650, P = 0.001). CONCLUSIONS: Patients with HCC after AH can benefit from postoperative adjuvant TACE. Therefore, adjuvant TACE should be considered for patients with a high risk of recurrence.

Could C3, 4, and 5 Nerve Root Block be a Better Alternative to Interscalene Block Plus Intermediate Cervical Plexus Block for Patients Undergoing Surgery for Midshaft and Medial Clavicle Fractures? A Randomized Controlled Trial.

BACKGROUND: Variable innervation of the clavicle is a major challenge in surgery of clavicle fractures with patients under regional anesthesia. An interscalene block (ISB) combined with an intermediate cervical plexus block (ICPB) provides analgesia in clavicle fracture surgery, but this combination does not completely block sensation in the midshaft or medial clavicle. Cervical nerve root block is an alternative to deep cervical plexus block and has recently been used as an analgesic method in the neck and shoulder. Whether it should be used as an alternative for midshaft and medial clavicle fractures is unknown. QUESTIONS/PURPOSES: In this randomized controlled trial, we compared a C3, 4, and 5 nerve root block to ISB combined with ICPB in surgery of midshaft and medial clavicle fractures in terms of the (1) proportion of patients achieving a sensory block that is sufficient for surgery, (2) onset time and duration of the block, and (3) effectiveness of postoperative analgesia, as measured by pain scores and consumption of analgesics. METHODS: Between November 2021 and December 2021, we treated 154 patients for clavicle fractures. A total of 122 were potentially eligible, 91 of whom agreed to participate in this study. Twenty-nine patients were excluded because the patients chose general anesthesia or declined to undergo surgery. Ultimately, 62 patients were randomly allocated into the C3, 4, and 5 group or ISB + ICPB group, with 31 patients in each group; there were no dropouts. All patients were analyzed in the group they were randomized to under intention-to-treat principles. The assessor and patients were blinded to randomization throughout the trial. The two groups did not differ in any important ways, including age, gender, BMI, American Society of Anesthesiologists classification, and type of clavicle fracture. The two groups received either an ultrasound-guided C3, 4, and 5 nerve root block with 2, 3, and 5 mL of 0.5% ropivacaine or ultrasound-guided ISB with ICPB with 20 mL of 0.5% ropivacaine. The primary outcome was the proportion of patients in each group with a successful nerveba block who did not receive general anesthesia; this was defined as nerve block success. Secondary outcomes included the onset time and duration of the sensory block, defined as the onset to the moment when the patients felt pain and sought rescue analgesia; pain assessment in terms of the numeric rating scale (NRS) score (range 0 to 10) for pain after nerve block before and during surgery; and the median amount of sufentanil consumed intraoperatively and postoperatively in the recovery room. The dosing of sufentanil was determined by the assessor when the NRS score was 1 to 3 points. If the NRS score was more than 3 points, general anesthesia was administered as a rescue method. Complications after the two inventions such as toxic reaction, dyspnea, hoarseness, pneumothorax, and Horner syndrome were also recorded in this study. RESULTS: A higher proportion of patients in the C3, 4, and 5 group had a successful nerve block than in the ISB + ICPB group (97% [30 of 31] versus 68% [21 of 31], risk ratio 6 [95% CI 1.5 to 37]; p < 0.01). The median onset time was 2.5 minutes (range 2.0 to 3.0 minutes) in the C3, 4, and 5 group and 12 minutes (range 9 to 16 minutes) in the ISB + ICPB group (difference of medians 10 minutes; p < 0.001). The sensory block duration was 10 ± 2 hours in the C3, 4, and 5 group and 8 ± 2 hours in the ISB + ICPB group (mean difference 2 hours [95% CI 1 to 3 hours]; p < 0.001). The median sufentanil consumption was lower in the C3, 4, 5 group than in the ISB + ICPB (median 5 µg [range 0.0 to 5.0 µg] versus median 0 µg [range 0.0 to 0.0 µg]; difference of medians 5.0 µg; p < 0.001). There were no differences between the two groups regarding NRS scores after nerve blocks and NRS score for incision and periosteum separation, with the minimum clinically important difference set at a 2-point difference (of 10). There were no severe complications in this study. CONCLUSION: Based on our analysis of the data, a C3, 4, and 5 nerve root block was better than ISB combined with ICPB for surgery to treat medial shaft and medial clavicle fractures. When choosing the anesthesia method, however, the patient's basic physiologic condition and possible complications should be considered. LEVEL OF EVIDENCE: Level I, therapeutic study.

Short- and long-term outcomes of laparoscopic versus open liver resection for large hepatocellular carcinoma: a propensity score study.

PURPOSE: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. METHODS: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). RESULT: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80-1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88-1.70, P = 0.238). CONCLUSION: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection.

Impact of metabolic syndrome on the long-term prognosis of patients with hepatitis B virus-related hepatocellular carcinoma after hepatectomy.

Background & aims: The long-term prognosis of patients with metabolic syndrome (MS) and hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after radical hepatectomy remains unclear. The purpose of this study was to elucidate the effect of MS on long-term survival for patients with HBV-related HCC after hepatectomy. Methods: Patients with HBV-HCC after hepatectomy were included. Patients were stratified into MS-HBV-HCC and HBV-HCC groups. Clinical features and surgical outcomes were compared between the two groups, and COX regression analysis was used to determine independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Result: 389 patients (MS-HBV-HCC group: n=50, HBV-HCC group: n=339) were enrolled for further analysis. Baseline characteristics showed that patients with MS-HBV-HCC were associated with a high rate of elderly patients, ASA score, and co-morbid illness, but a lower rate of anatomy hepatectomy. There were no significant differences in perioperative complications. After excluding patients who relapsed or died within 90 days after surgery, multivariate Cox regression analysis showed MS was an independent risk factor of OS (HR 1.68, 95% CI 1.05-2.70, P = 0.032) and RFS (HR 1.78, 95% CI 1.24-2.57, P = 0.002). Conclusion: MS is an independent risk factor for poor OS and RFS in HBV-infected HCC patients after radical hepatectomy. This suggests that we need to strengthen postoperative follow-up of the relevant population and encourage patients to develop a healthy lifestyle.

Association of preoperative albumin-bilirubin with surgical textbook outcomes following laparoscopic hepatectomy for hepatocellular carcinoma.

Background and aims: Recently, the effectiveness of "textbook outcomes (TO)" in the evaluation of surgical quality has been recognized by more and more scholars. This study tended to examine the association between preoperative albumin-bilirubin (ALBI) grades and the incidence of achieving or not achieving TO (non-TO) in patients with hepatocellular carcinoma (HCC) undergoing laparoscopic hepatectomy. Methods: The patients were stratified into two groups: ALBI grade 1 (ALBI ≤ -2.60) and ALBI grade 2/3 (ALBI > -2.60). The characteristics of patients and the incidence of non-TO were compared. Multivariate analyses were performed to determine whether ALBI grade was independently associated with TO. Results: In total, 378 patients were enrolled, including 194 patients (51.3%) in the ALBI grade 1 group and 184 patients (48.7%) in the ALBI grade 2/3 group. In the whole cohort, 198 patients (52.4%) did not achieve TO, and the incidence of non-TO in the ALBI grade 2/3 group was obviously higher than that in the ALBI grade 1 group (n = 112, 60.9% vs. n = 86, 44.3%, P = 0.001). The multivariate analyses showed that ALBI grade 2/3 was an independent risk factor for non-TO (OR: 1.95, 95%CI: 1.30-2.94, P = 0.023). Conclusions: More than half (52.4%) of the patients with hepatocellular carcinoma did not achieve TO after laparoscopic hepatectomy, and preoperative ALBI grade 2/3 was significantly associated with non-TO. Improving the liver function reserve of patients before operation, thereby reducing the ALBI grade, may increase the probability for patients to reach TO and enable patients to benefit more from surgery.

Prognostic impact of tumor size on isolated hepatocellular carcinoma without vascular invasion may have age variance.

Background: Previous studies suggested that tumor size was an independent risk factor of prognosis for hepatocellular carcinoma (HCC). However, the general prognostic analysis did not consider the interaction between variables. The purpose of this study was to investigate whether the effect of tumor size on the prognosis of isolated HCC without vascular invasion varies according to covariates. Methods: Patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database to investigate whether there was an interaction between age and tumor size on the prognosis. Then the trend test and the value of per 1 SD of tumor size were calculated. In addition, the data of Zhejiang Provincial People's Hospital meeting the requirements were selected to verify the obtained conclusions. Results: Multivariable Cox regression analysis of the database cohort showed that age, gender, tumor size, pathological grade and marital status were independent risk factors for prognosis. Interaction test showed that there was an interaction between age and tumor size (P for interaction < 0.05). Stratified analysis by age showed that tumor size was an independent risk factor for prognosis when age ≤65 years old (HR:1.010,95%CI1.007-1.013 P < 0.001), while tumor size was not an independent risk factor for prognosis when age >65 years old. This result was confirmed by trend analysis (P for trend < 0.001), and the prognostic risk increased by 42.1% for each standard deviation increase of tumor size among patients age ≤65 years. Consistent conclusion was obtained by multivariable cox regression analysis and interaction test on the verification cohort. In the validation cohort, for each standard deviation increase of tumor size in patients ≤65 years old, the risk of prognosis increased by 52.4%. Conclusion: Tumor size is not an independent risk factor for the prognosis of isolated HCC without vascular invasion when patient's age >65 years. Therefore, when analyzing the relationship between tumor size and prognosis, stratified analysis should be performed according to age.