Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking.

BACKGROUND: Tactile and mechanical pain are crucial to our interaction with the environment, yet the underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) is an evolutionarily conserved protein that is documented in the endocytosis pathway. However, the role of EndoA2 in the regulation of mechanical sensitivity and its underlying mechanisms are currently unclear. METHODS: Male and female C57BL/6 mice (8-12 weeks) and male cynomolgus monkeys (7-10 years old) were used in our experiments. Nerve injury-, inflammatory-, and chemotherapy-induced pathological pain models were established for this study. Behavioral tests of touch, mechanical pain, heat pain, and cold pain were performed in mice and nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation and patch-clamp recordings were performed to gain insight into the mechanisms. RESULTS: The results showed that EndoA2 was primarily distributed in neurofilament-200-positive (NF200+) medium-to-large diameter dorsal root ganglion (DRG) neurons of mice and humans. Loss of EndoA2 in mouse NF200+ DRG neurons selectively impaired the tactile and mechanical allodynia. Furthermore, EndoA2 interacted with the mechanically sensitive ion channel Piezo2 and promoted the membrane trafficking of Piezo2 in DRG neurons. Moreover, as an adaptor protein, EndoA2 also bound to kinesin family member 5B (KIF5B), which was involved in the EndoA2-mediated membrane trafficking process of Piezo2. Loss of EndoA2 in mouse DRG neurons damaged Piezo2-mediated rapidly adapting mechanically activated currents, and re-expression of EndoA2 rescued the MA currents. In addition, interference with EndoA2 also suppressed touch sensitivity and mechanical hypersensitivity in nonhuman primates. CONCLUSIONS: Our data reveal that the KIF5B/EndoA2/Piezo2 complex is essential for Piezo2 trafficking and for sustaining transmission of touch and mechanical hypersensitivity signals. EndoA2 regulates touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking in sensory neurons. Our findings identify a potential new target for the treatment of mechanical pain.

Combined Ultrasound-Guided Thoracic Paravertebral Nerve Block with Subcostal Transversus Abdominis Plane Block for Analgesia After Total Minimally Invasive Mckeown Esophagectomy: A Randomized, Controlled, and Prospective Study.

INTRODUCTION: Thoracic paravertebral block (TPVB) and subcostal transverse abdominis plane block (TAP) have been considered to provide an effective analgesic effect for laparoscopic and thoracoscopic surgery, respectively. The purpose of this randomized, controlled, and prospective study was to evaluate the analgesic effect of TPVB combined with TAP in patients undergoing total minimally invasive Mckeown esophagectomy. METHODS: Between February 2020 and December 2021, a total of 168 esophageal cancer patients undergoing McKeown esophagectomy at the Cancer Center of Sun Yat-Sen University, China, were randomly assigned to receive patient-controlled epidural analgesia alone (group PCEA, n = 56), patient-controlled intravenous analgesia alone (group PCIA, n = 56), and TPVB combined with TAP and patient-controlled intravenous analgesia (group PVB, n = 56). The primary outcome was a visual analogue scale (VAS) pain score on movement 48 h postoperatively. Secondary endpoints were pain scores at other points, intervention-related side effects, surgical complications, and length of intensive care unit and hospital stay. For the VAS pain score, the Kruskal-Wallis method was conducted for comparison of 3 treatment groups and further pairwise comparison with Bonferroni correction. RESULTS: On movement, the VAS in the PVB group was higher than that in the PCEA group at 48 h, 72 h, 96 h, and 120 h postoperatively (p < 0.05) except in the postoperative anesthesia care unit (PACU) and 24 h postoperatively. The VAS in the PCIA group was higher than the PCEA and PVB groups in the first 4 days after surgery. The pulmonary complication rate in the PCIA group was significantly higher than the rate in the PCEA [95% Confidence Interval 0.214 (0.354, 0.067), p = 0.024]. CONCLUSIONS: Combined TPVB and TAP was more effective than intravenous opioid analgesia alone, while PCEA was more effective than TPVB combined with TAP and intravenous opioid analgesia for patients after McKeown esophagectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry; ChiCTR2000029588.

Impacts of neoadjuvant chemoradiotherapy on the immune landscape of esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the most common approach for locally advanced resectable esophageal squamous cell carcinoma (ESCC) patients. How neoCRT impacts ESCC tumor immune microenvironment (TIME) has not been fully understood. METHODS: Single-cell RNA sequencing (scRNA-seq) was conducted to examine the neoCRT-driven cellular and molecular dynamics in 8 pre- and 7 post-neoCRT ESCC samples from 8 male patients. FINDINGS: scRNA-seq data of about 112,000 cells were obtained. Expression programs of cell cycle, epithelium development, immune response, and extracellular structure in pre-treatment tumor cells were related to neoCRT response. Spearman correlation between CD8+ T cells' cytotoxicity and expression of checkpoint molecules was prominent in pre-neoCRT intermediate activated/exhausted CD8+ T cells. NeoCRT increased CD8+ T cells' infiltration but promoted their exhaustion in both major and minor responders. NeoCRT promoted differentiation of Th but demoted that of Treg cells in major responders. Maturation of cDC1s and expression of M2 macrophage markers increased while the number of cDC2s decreased after neoCRT. Higher activities of immune-related pathways in pre-neoCRT CD8+ T cells and macrophages, as well as a pronounced decrease of them after neoCRT, correlated with better neoCRT response. Interactions between intermediate activated/exhausted CD8+ T and macrophages, cDC1s, and LAMP3+ cDCs decreased after neoCRT. INTERPRETATION: Our comprehensive picture of the neoCRT-related immune changes provides deeper insights into immunological mechanisms associated with ESCC response to neoCRT, which may aid in future development of immune-strategies for improving ESCC treatment. FUNDING: This work was supported by the National Natural Science Foundation of China (82072607).

More Liver Metastases Detected Intraoperatively Indicates Worse Prognosis for Colorectal Liver Metastases Patients after Resection Combined with Microwave Ablation.

Background: Whether more tumor numbers detected in surgery compared to preoperative image affecting survival of colorectal liver metastases (CRLM) patients after hepatectomy combined with microwave ablation (MWA) remains unclear. Methods: From 2013 to 2018, 85 CRLM patients who underwent hepatectomy combined with MWA were retrospectively assessed. Compared to the tumor numbers in preoperative image, patients with equal intraoperative tumor numbers were defined as the equal number group (n = 45); patients detected more tumor numbers in surgery were defined as the more number group (n = 40). Clinicopathological factors and prognosis were compared between two groups. Results: Compared to the equal number group, the more number group was characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5 (all P < 0.05). Median survival time was 46.7 months and 26.8 months in the equal and more number group. Significantly worse overall survival (OS) was found in more number group to the equal number group (P = 0.027). In Cox analysis, more tumor number than image and high level of carbohydrate antigen 19-9 (CA19-9) were poor prognostic factors for OS. Conclusion: In patients receiving hepatectomy combined with MWA, detecting more liver metastases in surgery than preoperative image indicates poor long-term survival. These patients were characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5. Intensive follow-up to detect early recurrence and potent postoperative therapy to improve survival may be justified in patients detected more tumor numbers in surgery with a high CA19-9 level.

Ground Glass Opacity and Adjuvant Chemotherapy in Pathological Stage IB-IIA Lung Adenocarcinoma.

Background: The prognostic value of ground glass opacity (GGO) in stage IA non-small cell lung cancer (NSCLC) has been widely recognized. However, studies investigating its value in the related stage IB-IIA lung adenocarcinoma (LUAD) remains lacking. The impact of adjuvant chemotherapy (ACT) on pathological stage IB-IIA LUAD is also controversial. Materials and Methods: We retrospectively reviewed the clinical records of 501 patients with pathological stage IB-IIA LUAD at the Sun Yat-sen University Cancer Center from January 2008 to June 2018. We calculated and compared survival curves using the Kaplan-Meier test and log-rank test. Cox regression models were performed to determine independent prognostic factors of disease-free survival (DFS) and overall survival (OS). We established nomograms to predict the OS and DFS of LUAD patients. Calibration and receiver operator characteristic curves were conducted to assess the predictive performance of two nomograms. Based on the nomogram, we identified candidate patients that may most benefit from ACT after surgery. Results: The number of patients with pure solid, part GGO, and pure GGO nodules was 240, 242, and 19, respectively, and 125 patients who received ACT. Patients with consolidation-to-tumor ratio (CTR) <0.75 had longer OS (P = 0.026) and DFS (P = 0.003). Pathological tumor size and at least 10 lymph nodes (LNs) resection were independent prognostic factors of both OS and DFS. CTR <0.75 was positively associated with DFS. The C-index of nomograms predicting individual OS and DFS was 0.660 and 0.634, respectively. Based on the nomogram for OS, ACT was found to be a positive prognostic indicator of OS (P = 0.031, HR = 0.5141, 95% CI 0.281-0.942) in patients with nomogram total points ≥5. Conclusion: CTR <0.75 is associated with a better DFS in patients with stage IB-IIA LUAD. Nomograms developed by integrating pathological tumor size, at least 10 LNs resection, and CTR ≥0.75 for predicting individual OS and DFS displayed a good predictive capacity and clinical value, which were also proved to be a useful tool for selecting patients most benefiting from ACT.

Integrative Analysis of a Pyroptosis-Related Signature of Clinical and Biological Value in Multiple Myeloma.

Purpose: Pyroptosis is an inflammation-based programmed cell death that holds great potential as a novel cancer therapeutic target in patients with multiple myeloma (MM). However, thus far, the function of pyroptosis-related genes (PRGs) in MM and their prognostic relevance remains undetermined. Methods: The model was established by the LASSO analysis, based on the Gene Expression Omnibus (GEO) dabatase, and its efficacy was verified using two external datasets. The model's predictive ability was assessed by the Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) curves. Finally, a nomogram was established for clinical application. We also confirmed the validity of our model using specimens and in vitro experiments. Results: We established an 11-PRG signature profile, and verified its efficacy using two validation cohorts (VCs). In both cohorts, patients were separated into two subpopulations, according to their median risk scores (RS). Our analysis revealed that high-risk (HR) patients experienced considerably lower overall survival (OS), compared to the low-risk (LR) patients. Using functional enrichment and immune infiltration analyses, we demonstrated that the immunologic status was strongly related to RS. Furthermore, using a pyroptosis inhibitor Q-VD-OPh, we revealed that MM cell proliferation and progression was drastically suppressed and the doxorubicin (DOX)-induced apoptosis was reversed. Conclusion: Based on our analysis, pyroptosis not only serves as a measure of MM treatment efficiency and patient prognosis, but is also a possible target for anti-MM therapy.

Prognostic Nomograms Based on Ground Glass Opacity and Subtype of Lung Adenocarcinoma for Patients with Pathological Stage IA Lung Adenocarcinoma.

The value of lung adenocarcinoma (LUAD) subtypes and ground glass opacity (GGO) in pathological stage IA invasive adenocarcinoma (IAC) has been poorly understood, and reports of their association with each other have been limited. In the current study, we retrospectively reviewed 484 patients with pathological stage IA invasive adenocarcinoma (IAC) at Sun Yat-sen University Cancer Center from March 2011 to August 2018. Patients with at least 5% solid or micropapillary presence were categorized as high-risk subtypes. Independent indicators for disease-free survival (DFS) and overall survival (OS) were identified by multivariate Cox regression analysis. Based on these indicators, we developed prognostic nomograms of OS and DFS. The predictive performance of the two nomograms were assessed by calibration plots. A total of 412 patients were recognized as having the low-risk subtype, and 359 patients had a GGO. Patients with the low-risk subtype had a high rate of GGO nodules (p < 0.001). Multivariate Cox regression analysis showed that the high-risk subtype and GGO components were independent prognostic factors for OS (LUAD subtype: p = 0.002; HR 3.624; 95% CI 1.263-10.397; GGO component: p = 0.001; HR 3.186; 95% CI 1.155-8.792) and DFS (LUAD subtype: p = 0.001; HR 2.284; 95% CI 1.448-5.509; GGO component: p = 0.003; HR 1.877; 95% CI 1.013-3.476). The C-indices of the nomogram based on the LUAD subtype and GGO components to predict OS and DFS were 0.866 (95% CI 0.841-0.891) and 0.667 (95% CI 0.586-0.748), respectively. Therefore, the high-risk subtype and GGO components were potential prognostic biomarkers for patients with stage IA IAC, and prognostic models based on these indicators showed good predictive performance and satisfactory agreement between observational and predicted survival.

Ultrasound-guided quadratus lumborum block for perioperative analgesia in robot-assisted partial nephrectomy: a randomized controlled trial.

BACKGROUND: Recently, several case reports and limited randomized studies have shown that quadratus lumborum blocks (QLB) are effective in providing pain relief after intra-abdominal and retroperitoneal operations. Additionally, robot-assisted partial nephrectomy (RAPN) has been proposed as a promising operative treatment for renal carcinoma because it enables early recovery and ambulation. Therefore, we aimed to evaluate the analgesic and opioid-sparing effects of a single-injection QLB in patients undergoing RAPN to determine its role in an early recovery program. METHODS: Fifty-six patients undergoing elective RAPN under general anesthesia were randomized to two equally sized groups. Patients were randomly allocated to receive either a unilateral QLB (n = 28) with 0.375% bupivacaine 0.5 mL/kg (QLB group) or a conventional scheme (n = 28) (control group). The QLB technique, termed QLB2, was performed as first described by Blanco. The primary outcome was visual analog scale (VAS) scores with movement at 6 h postoperatively. The secondary endpoints were morphine consumption at different time periods after surgery, morphine-related side effects, and assessment of postoperative rehabilitation. RESULTS: Both the VAS pain scores and cumulative opioid consumption were significantly lower in the QLB group at 6 h after surgery as compared with results in the control group (all P < 0.05). There were significant differences in pain scores at all time points except at 4 h with movement and 48 h at rest. However, at 12-24 h no significant differences between the two groups were observed in cumulative opioid consumption or in the duration of PACU and hospital stays. The patient recovery scores were significantly higher in the QLB group. CONCLUSIONS: Single-injection pre-emptive QLB applied to RAPN was effective and provided satisfactory analgesia and opioid-sparing effects in combination with typical patient-controlled analgesia. In addition, it may provide an effective technique for early recovery in the perioperative period for RAPN.

MicroRNA-599 suppresses glioma progression by targeting RAB27B.

[This retracts the article DOI: 10.3892/ol.2018.8727.].

Learning curve of robotic portal lobectomy for pulmonary neoplasms: A prospective observational study.

BACKGROUND: We aim to assess the learning curve of robotic portal lobectomy with four arms (RPL-4) in patients with pulmonary neoplasms using prospectively collected data. METHODS: Data from 100 consecutive cases with lung neoplasms undergoing RPL-4 were prospectively accumulated into a database between June 2018 and August 2019. The Da Vinci Si system was used to perform RPL-4. Regression curves of cumulative sum analysis (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) were fit to identify different phases of the learning curve. Clinical indicators and patient characteristics were compared between different phases. RESULTS: The mean operative time, console time, and docking time for the entire cohort were 130.6 ± 53.8, 95.5 ± 52.3, and 6.4 ± 3.0 min, respectively. Based on CUSUM analysis of console time, the surgical experience can be divided into three different phases: 1-10 cases (learning phase), 11-51 cases (plateau phase), and >51 cases (mastery phase). RA-CUSUM analysis revealed that experience based on 56 cases was required to truly master this technique. Total operative time (p < 0.001), console time (p < 0.001), and docking time (p = 0.026) were reduced as experience increased. However, other indicators were not significantly different among these three phases. CONCLUSIONS: The RPL-4 learning curve can be divided into three phases. Ten cases were required to pass the learning curve, but the mastery of RPL-4 for satisfactory surgical outcomes requires experience with at least 56 cases.

ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking.

Effective treatments for patients suffering from heat hypersensitivity are lacking, mostly due to our limited understanding of the pathogenic mechanisms underlying this disorder. In the nervous system, activating transcription factor 4 (ATF4) is involved in the regulation of synaptic plasticity and memory formation. Here, we show that ATF4 plays an important role in heat nociception. Indeed, loss of ATF4 in mouse dorsal root ganglion (DRG) neurons selectively impairs heat sensitivity. Mechanistically, we show that ATF4 interacts with transient receptor potential cation channel subfamily M member-3 (TRPM3) and mediates the membrane trafficking of TRPM3 in DRG neurons in response to heat. Loss of ATF4 also significantly decreases the current and KIF17-mediated trafficking of TRPM3, suggesting that the KIF17/ATF4/TRPM3 complex is required for the neuronal response to heat stimuli. Our findings unveil the non-transcriptional role of ATF4 in the response to heat stimuli in DRG neurons.

Continuous Paravertebral Analgesia versus Continuous Epidural Analgesia after Video-Assisted Thoracoscopic Lobectomy for Lung Cancer: A Randomized Controlled Trial.

BACKGROUND: Whether continuous thoracic epidural analgesia (TEA) and continuous paravertebral block (PVB) have similar analgesic effects in patients undergoing video-assisted thoracic surgery (VATS) lobectomy was compared in this study. METHODS: In all, 86 patients undergoing VATS lobectomy were enrolled in the prospective, randomized clinical trial. Group E received TEA. Group P received PVB. The primary endpoint was postoperative 24-hour visual rating scale (VAS) on coughing. Side effects and postoperative complications were also analyzed. RESULTS: Pain scores at rest or on coughing at 24 and 48 h postoperatively were significantly lower in group E than in group P (P <0.05). At 24 h postoperatively, more patients in group E suffered from vomiting (32.6% vs 11.6%, P = 0.019), dizziness (55.8% vs 12.9%, P = 0.009), pruritus (27.9% vs 2.3%, P = 0.002), and hypotension (32.6% vs 4.7%, P = 0.002) than those in group P. Patients in group E were more satisfied (P = 0.047). Four patients in group P and two patients in group E suffered from pulmonary complications (P >0.05). The length of hospital and intensive care unit (ICU) stays were not significantly different. CONCLUSIONS: Though TEA has more adverse events than PVB, it may be superior to PVB in patients undergoing VATS lobectomy.

Foxo1 selectively regulates static mechanical pain by interacting with Nav1.7.

ABSTRACT: Mechanical allodynia is a debilitating condition for millions of patients with chronic pain. Mechanical allodynia can manifest in distinct forms, including brush-evoked dynamic and filament-evoked static allodynia. In the nervous system, the forkhead protein Foxo1 plays a critical role in neuronal structures and functions. However, the role of Foxo1 in the somatosensory signal remains unclear. Here, we found that Foxo1 selectively regulated static mechanical pain. Foxo1 knockdown decreased sensitivity to static mechanical stimuli in normal rats and attenuated static mechanical allodynia in rat models for neuropathic, inflammatory, and chemotherapy pain. Conversely, Foxo1 overexpression selectively enhanced sensitivity to static mechanical stimuli and provoked static mechanical allodynia. Furthermore, Foxo1 interacted with voltage-gated sodium Nav1.7 channels and increased the Nav1.7 current density by accelerating activation rather than by changing the expression of Nav1.7 in dorsal root ganglia neurons. In addition, the serum level of Foxo1 was found to be increased in chronic pain patients and to be positively correlated with the severity of chronic pain. Altogether, our findings suggest that serum Foxo1 level could be used as a biological marker for prediction and diagnosis of chronic pain. Moreover, selective blockade of Foxo1/Nav1.7 interaction may offer a new therapeutic approach in patients with mechanical pain.

Targeting the NCOA3-SP1-TERT axis for tumor growth in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate and lacks an effective therapeutic target. Elevated expression of human telomerase reverse transcriptase (TERT) is an important hallmark in cancers, but the mechanism by which TERT is activated differentially in cancers is poorly understood. Here, we have identified nuclear receptor coactivator-3 (NCOA3) as a new modulator of TERT expression and tumor growth in HCC. NACO3 specifically binds to the TERT promoter at the -234 to -144 region and transcriptionally activates TERT expression. NCOA3 promotes HCC cell growth and tumor progression in vitro and in vivo through upregulating the TERT signaling. Knockdown of NACO3 suppresses HCC cell viability and colony formation, whereas TERT overexpression rescues this suppression. NCOA3 interacts with and recruits SP1 binding on the TERT promoter. Knockdown of NCOA3 also inhibits the expression of the Wnt signaling-related genes but has no effect on the Notch signaling-targeting genes. Moreover, NCOA3 is positively correlated with TERT expression in HCC tumor tissues, and high expression of both NCOA3 and TERT predicts a poor prognosis in HCC patients. Our findings indicate that targeting the NCOA3-SP1-TERT signaling axis may benefit HCC patients.

The Postoperative Analgesic Effect of Ultrasound-Guided Bilateral Transversus Abdominis Plane Combined with Rectus Sheath Blocks in Laparoscopic Hepatectomy: A Randomized Controlled Study.

BACKGROUND: Our aim was to investigate the postoperative analgesic effect of ultrasound (US)-guided bilateral transversus abdominis plane (TAP) blocks combined with rectus sheath blocks (RSBs) in laparoscopic hepatectomy. PATIENTS AND METHODS: A total of 126 patients were allocated into two groups for analysis. Group 1 (n = 63) did not receive any local anesthetics. Group 2 (n = 63) received US-guided bilateral TAP blocks and RSBs using 20 mL 0.25% ropivacaine in each block. Postoperative pain scores, the dose of intraoperative remifentanil, 24 h consumption of oxycodone, adverse events such as postoperative dizziness, nausea and vomiting, and the length of postoperative hospital stay were recorded. RESULTS: In the postanesthesia care unit, patients in group 2 had significantly lower pain visual analog scale (VAS) scores at rest than those in group 1 (P < 0.001). The VAS scores both at rest and during movement were significantly lower in group 2 than in group 1 at 2, 4 and 6 h postoperatively (all P < 0.001). There was no difference in VAS scores between the two groups at rest 24 h postoperatively (P = 0.477). However, the VAS score during movement at 24 h in group 2 was significantly lower than that in group 1 (P < 0.001). No significant differences in the incidence of adverse events or the dose of intraoperative remifentanil were observed between the two groups (all P > 0.05). Patients in group 2 had a significantly lower 24 h consumption of oxycodone than patients in group 1 (P < 0.001). The mean length of postoperative hospital stay of group 2 was shorter than that of group 1 (P = 0.032). CONCLUSION: US-guided bilateral TAP blocks combined with RSBs provide effective postoperative analgesia for laparoscopic hepatectomy, and they could shorten the postoperative hospital stay without increasing the incidence of adverse events from opioids.

Effects of Anesthetic Technique on Postoperative Pulmonary Metastasis in Patients Undergoing Laryngectomy.

BACKGROUND: Whether laryngeal cancer is directly implanted into the lungs during orotracheal intubation is still unclear. Therefore, this study aimed to find whether orotracheal intubation is an independent risk factor for postoperative pulmonary metastasis in patients undergoing laryngectomy. PATIENTS AND METHODS: Medical records from January 1, 2006, to December 31, 2016, were reviewed. According to similar propensity scores, patients who received orotracheal intubation (tracheal intubation group, n = 515) were matched 1:1 with those who received tracheotomy (tracheotomy group, n = 326) in the induction of general anesthesia. The primary outcome was postoperative pulmonary metastasis. Secondary outcomes included local recurrence, lymphatic metastasis, tracheostomal recurrence and overall survival. RESULTS: Between the two groups, there was no significant difference in postoperative pulmonary metastasis (P = 0.688), local recurrence (P = 0.215), lymphatic metastasis (P = 0.480), tracheostomal recurrence (P = 0.246) or all-cause death (P = 0.299). The primary site of cancer was an independent risk factor for pulmonary metastasis [HR 0.29, 95% CI 0.13-0.68; P = 0.013] and local recurrence (HR 2.69, 95% CI 1.39-5.21; P = 0.003). Type of surgery (HR 3.13, 95% CI 2.03-4.84; P < 0.001) and N classification of TNM (HR 0.27, 95% CI 0.10-0.75; P = 0.012) were risk factors for local recurrence. Postoperative chemotherapy was an independent risk factor for lung metastasis (HR 7.58, 95% CI 3.11-18.47; P < 0.001) and lymphatic metastasis (HR 5.18, 95% CI 2.57-11.91; P < 0.001), and 5-year overall survival was associated with age (P = 0.028), clinical stage (P < 0.001) and postoperative chemotherapy (P = 0.003) but not with anesthetic technique (P = 0.473). CONCLUSION: This retrospective study suggests that orotracheal intubation in laryngectomy is not a risk factor for postoperative pulmonary metastasis, local recurrence, lymphatic metastasis or overall survival.

Intention to control low central venous pressure reduced blood loss during laparoscopic hepatectomy: A double-blind randomized clinical trial.

BACKGROUND: Excessive intraoperative hemorrhage is a critical factor of poor prognoses after hepatectomy. Low central venous pressure during parenchymal transection is recognized to effectively reduce intraoperative hemorrhage in open procedures. However, the role of controlled low central venous pressure in laparoscopic hepatectomy is still controversial. METHODS: In the present randomized clinical trial, we set up a standard boundary of low central venous pressure according to our Pilot Study, then enrolled patients scheduled for elective laparoscopic hepatectomy and allocated them randomly to a group undergoing central venous pressure reduction by anesthesiologic interventions or a control group. The primary efficacy endpoint was total intraoperative blood loss and perioperative adverse events. Analyses were performed following the intention-to-treat principle, and patients and surgeons were blinded (ClinicalTrials.gov, Number: NCT03422913). RESULTS: Between January 2017 and October 2018, 146 out of 469 patients were randomized and eligible for inclusion in the final analyses. Based on the retrospective training cohort, we set a central venous pressure of 5 cm H2O as a cutoff value (standard low central venous pressure). Compared with patients in the control group, those in the controlled low central venous pressure group had a significantly lower central venous pressure during resection (4.83 ± 3.41 cm H2O vs 9.26 ± 3.38 cm H2O; P < .001) and significantly reduced total intraoperative blood loss (188.00 ± 162.00 mL vs 346.00 ± 336.00 mL; P < .001). The perioperative adverse events were comparable in both study groups (P = .313). CONCLUSION: The safety and efficacy of controlled low central venous pressure were demonstrated in complex laparoscopic hepatectomy for the first time by our study, and this technique is recommended to be applied routinely in laparoscopic hepatectomy.

Duration of one-lung ventilation as a risk factor for postoperative pulmonary complications after McKeown esophagectomy.

OBJECTIVE: To assess whether the duration of one-lung ventilation (OLV) affects postoperative pulmonary complications after McKeown esophagectomy for esophageal cancer. METHODS: A retrospective analysis of data stored in a database for esophageal cancer was carried out to identify predictors of postoperative pulmonary complications in patients undergoing McKeown esophagectomy at Sun Yat-sen University Cancer Center between 2010 and 2012. RESULTS: Patients in the OLV ⩾150 minutes group had a higher incidence of postoperative pulmonary complications than those in the OLV <150 minutes group (18.0% vs 7.3%, p < 0.001). Among them, the number of patients who developed pneumonia and atelectasis was also significantly higher (9.0% vs 4.1% [p = 0.031] and 8.7% vs 3.7% [p = 0.018] for the OLV ⩾150 minutes group vs OLV <150 minutes group, respectively). OLV ⩾150 minutes was associated with a prolonged hospital stay (24.2 ± 9.7 vs 21.5 ± 9.2 days, p = 0.001). Multivariate analysis revealed that history of diabetes (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.65-7.68; p = 0.001), chronic obstructive pulmonary disease (OR, 10.65; 95% CI, 5.65-20.08; p < 0.001), and OLV ⩾150 minutes (OR, 3.80; 95% CI, 1.97-7.31; p < 0.001) were independent predictors of postoperative pulmonary complications. CONCLUSION: Long duration of OLV appears to be an important risk factor for postoperative pulmonary complications after McKeown esophagectomy. OLV <150 minutes appears to be the better approach for thoracic surgery. Lung protective measures should be taken when prolonged OLV is anticipated.

Sevoflurane promotes migration, invasion, and colony-forming ability of human glioblastoma cells possibly via increasing the expression of cell surface protein 44.

Surgical resection of primary solid tumor under anesthesia remains a common practice. It has been concerned whether general anesthetics, especially volatile anesthetics, may promote the growth, migration, and invasion of cancer cells. In this study, we examined the effects of sevoflurane on human glioblastoma cells and determined the role of cluster of differentiation (CD) 44, a cell surface protein involved in cell growth, migration, and invasion, in sevoflurane's effects. We showed that exposure to 1%-4% sevoflurane did not change the cell proliferation, but concentration-dependently increased the invasion of human glioblastoma U251 cells. Furthermore, 4% sevoflurane significantly increased the migration and colony-forming ability of U251 cells. Similar results were observed in human glioblastoma A172 cells. Exposure to sevoflurane concentration-dependently increased the activity of calpains, a group of cysteine proteinases, and CD44 protein in U251 and A172 cells. Knockdown of CD44 with siRNA abolished sevoflurane-induced increases in calpain activity, migration, invasion, and colony-forming ability of U251 cells. Inhalation of 4% sevoflurane significantly increased the tumor volume and invasion/migration distance of U87 cells from the tumor mass in the nude mice bearing human glioblastoma U87 xenograft in the brain. The aggravation by sevoflurane was attenuated by CD44 silencing. In conclusion, sevoflurane increases the migration, invasion, and colony-forming ability of human glioblastoma cells in vitro, and their tumor volume and invasion/migration in vivo. Sevoflurane enhances these cancer cell biology features via increasing the expression of CD44.

The incidence and distribution of mediastinal lymph node metastasis and its impact on survival in patients with non-small-cell lung cancers 3 cm or less: data from 2292 cases.

OBJECTIVES: Our goal was to investigate the incidence and distribution of mediastinal lymph node metastases (MLNM) in non-small-cell lung cancers (NSCLC) 3 cm or less, with the purpose of guiding mediastinal lymph node dissection. METHODS: A total of 2292 cases seen between January 2001 and December 2014 were included. These patients were grouped according to the lobes with the primary tumours. The incidence and distribution of pathological MLNM were compared among the groups. The impact of MLNM on overall survival was also compared. RESULTS: The most common mediastinal metastatic sites for different primary tumour lobes were as follows: right upper lobe, 17.7% (87/492) for level 4R; right middle lobe, 14.9% (28/188) for level 7; right lower lobe, 19.8% (82/414) for level 7; left upper lobe, 18.2% (96/528) for level 5; and left lower lobe, 16.6% (42/253) for level 7. For patients with tumours in the upper lobe, the median survival time was 32 months for those with MLNM in the subcarinal zone or lower zone compared with 83 months for those with MLNM only in the upper zone (P < 0.01). When the tumours were 1 cm or less, the incidence of MLNM to the lower zone for upper lobe tumours and of MLNM to the upper zone for lower lobe tumours was zero. CONCLUSIONS: Different primary NSCLC lobe locations have a different propensity to be sites of MLNM for those tumours that are 3 cm or less. For tumours no larger than 1 cm, a lower zone mediastinal lymph node dissection might be unnecessary for upper lobe tumours and an upper zone mediastinal lymph node dissection might be unnecessary for lower lobe tumours.