Comprehensive profiling of EGFR mutation subtypes reveals genomic-clinical associations in non-small-cell lung cancer patients on first-generation EGFR inhibitors.

Common sensitizing mutations in epidermal growth factor receptor (cEGFR), including exon 19 deletions (19-Del) and exon 21 L858R substitution, are associated with high sensitivity to EGFR-TKIs in NSCLC patients. The treatment for NSCLC patients with uncommon EGFR (uEGFR) mutations remains a subject of debate due to heterogeneity in treatment responses. In this manuscript, the targeted next-generation sequencing (NGS) data of a large cohort of EGFR-mutated NSCLC patients was assessed to elucidate genomic profiles of tumors carrying cEGFR or uEGFR mutations. The results showed that NSCLC patients with uEGFR mutations were more likely to harbor co-occurring genetic alterations in the Hippo pathway and a higher TMB compared with cEGFR-positive patients. Smoking-related mutations were found to significantly enriched in uEGFR-positive patients. Subgroup analyses were performed to identify potential prognostic biomarkers in patients harboring various EGFR subtype mutations. L858R-positive patients with co-existing ARID2 mutations had shorter progression-free survival (PFS) than those who were L858R- or 19-Del-positive but ARID2-negative (median: 2.3 vs. 12.0 vs. 8.0 months, P = 0.038). Furthermore, mutational profiles, such as top frequently mutated genes and mutational signatures of patients with various EGFR subtype mutations were significantly different. Our study analyzed the mutational landscape of NSCLC patients harboring cEGFR and uEGFR mutations, revealing specific genomic characteristics associated with uEGFR mutations that might explain the poor prognosis of first-generation EGFR-TKIs.

C-C motif ligand 8 promotes atherosclerosis via NADPH oxidase 2/reactive oxygen species-induced endothelial permeability increase.

Chemokines have been reported to play important roles in atherosclerotic development. Recently, we found C-C motif ligand 8 (CCL8), a rarely studied chemokine in atherosclerosis, was highly expressed in the endothelium of advanced human carotid plaques. We hypothesized whether CCL8 promotes atherosclerosis through endothelial dysfunction. Apolipoprotein E-deficient mice under the Western diet were used to construct atherosclerosis models. Adeno-associated viruses (AAV) with CCL8 and the CCL8-antibody were injected into mice respectively to conduct CCL8 overexpression and suppression. The results showed that atherosclerotic lesions were significantly increased in the AAV-CCL8 group, while, lesions in the aortic sinus were reduced in the CCL8-antibody group. With CCL8 treatment (200 ng/ml, 24 h) in vitro, the permeability of human aortic endothelial cells (HAECs) increased and the expression of junctional proteins Zonula occluden-1, and Vascular endothelial cadherin were decreased. This effect was dependent on reactive oxygen species (ROS) generation, which could be blocked by l-Ascorbic acid and Apocynin. Results showed that NADPH oxidase 2 (NOX2) expression also increased with CCL8 stimulation and the ROS, and permeability increase of HAECs could be inhibited when NOX2 interfered with the specific siRNA. Additionally, we further found ERK1/2, PI3K-AKT, and NF-κB pathways were involved in the activation of CCL8. Our results indicated that CCL8 might also play important roles in atherosclerosis and this effect, at least in part, was caused by NOX2/ROS-induced endothelial permeability increase. This study might contribute to a deeper understanding of the connection between chemokines and atherosclerosis.

Predictors of Ipsilateral New Ischemic Lesions on Diffusion-Weighted Imaging after Carotid Artery Stenting in Asymptomatic Patients: A Retrospective Observational Study with Conventional Multicontrast MRI.

BACKGROUND: The purpose of this study was to identify the independent risk factors for ipsilateral new ischemic lesions (NILs) during carotid artery stenting (CAS). METHODS: In patients treated with CAS, the association between postoperative ipsilateral NILs on diffusion-weighted imaging (DWI) and patient demographics, intraoperative factors, the presence of plaque components, the semiquantitative grading of component size on multicontrast magnetic resonance imaging (MRI) were retrospectively analyzed. RESULTS: Ipsilateral NILs on DWI were detected in 85 (39.2%) patients. The debris was observed on the surface embolic protection devices in 70.97% of patients. Univariate analysis showed that different stages of intraplaque hemorrhage (IPH) (along with lipid-rich necrotic core [LRNC]) (P < 0.001), size of IPH (P < 0.001), calcification (CA) (P = 0.045), and LRNC (without IPH) (P < 0.001) as well as postdilation (P < 0.001)), stent type (P = 0.001), and aortic arch ulcer (P = 0.004) were associated with postoperative ipsilateral NILs. Multivariate logistic regression analysis showed that the acute and recent IPH (along with LRNC) (odds ratio [OR]: 5.77, P < 0.002 and OR: 28.66, P < 0.001, respectively), LRNC size in Grade 2 (OR: 6.10, P < 0.001) were independent risk factors for ipsilateral NILs. Aortic arch ulcer (OR: 3.44, P = 0.002), postdilation (OR: 4.72, P = 0.04) and open cell stent (OR: 2.88, P < 0.016) were also significantly related to ipsilateral NILs on DWI after CAS. There was a significant correlation between IPH at different stages and their grade of size (correlation coefficient: 0.89; P < 0.001). CONCLUSION: The IPH and larger LRNC along with the aortic arch ulcer, postdilation and open cell stent are associated with increased risk of ipsilateral NILs on DWI after CAS procedure. Preoperative staging of IPH and semiquantitative grading of size of plaque components based on multi-contrast MRI may be useful for predicting ipsilateral cerebral ischemic events after CAS.

C-C Motif Chemokine 8 promotes angiogenesis in vascular endothelial cells.

OBJECTIVES: Angiogenesis is an important progress associated with several pathological situations. Several chemokines have been reported to act as regulators of angiogenesis. The current study aimed to find whether C-C Motif Chemokine 8 is involved in angiogenesis regulation. METHODS: To verify whether C-C Motif Chemokine 8 is related to angiogenesis in plaques, carotid plaques were collected from patients with severe carotid stenosis and analysed using CD31 immunohistochemistry and real-time PCR. To further clarify the relation between C-C Motif Chemokine 8 and angiogenesis, human umbilical vein endothelium cells and human dermal microvascular endothelial cells were treated with C-C Motif Chemokine 8 in the presence or absence of C-C motif chemokine receptor 2-Ab and extracellular regulated MAP kinase 1/2 inhibition (FR180204). Proliferation and migration of human umbilical vein endothelium cells and human dermal microvascular endothelial cells were examined with Cell Counting Kit-8 and Transwell chamber assay, respectively. In vitro angiogenesis stimulated by C-C Motif Chemokine 8 was examined using tube formation assay. Ex vivo and in vivo angiogenesis were assessed by mice aortic ring assay and Matrigel plug assay, respectively. C-C motif chemokine receptors of human umbilical vein endothelium cells were examined with real-time PCR, and C-C motif chemokine receptor 1, C-C motif chemokine receptor 2, extracellular regulated MAP kinase 1/2 and phosphorylation-extracellular regulated MAP kinase 1/2 were examined with western blotting assay. RESULTS: C-C Motif Chemokine 8 was increased in carotid plaques with severe angiogenesis in both RNA and protein level. C-C Motif Chemokine 8 (5 ng/ml) weakly increased human umbilical vein endothelium cell proliferation, but not on human dermal microvascular endothelial cells. Migration and tube formation could be induced by C-C Motif Chemokine 8 in both human umbilical vein endothelium cells and human dermal microvascular endothelial cells. In mice aortic ring assay and Matrigel plug assay, C-C Motif Chemokine 8 could promote angiogenesis compared to vehicle groups. Phosphorylation of extracellular regulated MAP kinase 1/2 was increased with C-C Motif Chemokine 8 stimulation. The migration and tube formation promoted by C-C Motif Chemokine 8 could be largely blocked by C-C motif chemokine receptor 2-Ab or extracellular regulated MAP kinase 1/2 inhibition (FR180204). CONCLUSIONS: C-C Motif Chemokine 8 could promote both in vitro and in vivo angiogenesis. C-C motif chemokine receptor 2 played an important role in the activation of C-C Motif Chemokine 8 and extracellular regulated MAP kinase 1/2 signalling pathway was involved in this mechanism.

Protective effects of SS-31 against SDHB suppression-mitochondrial dysfunction-EndMT axis-modulated CBT sclerosis and progression.

Sclerosis variant in carotid body tumor (CBT) is characterized by extensive stromal sclerosis, which results in an uncommon pattern of growth that closely resembles that of an invasive malignant neoplasm. However, the clinical significance and the mechanism remains unclear. In this study, we provide evidence that SS-31 exerts protective effects against SDHB suppression-mitochondrial dysfunction-EndMT axis-modulated CBT sclerosis and progression. In human CBT specimens, sclerosis extent was consistently related to decreased recurrence-, death-, systematic metastasis-, and major adverse event-free survival, decreased SDHB expression, and aggravated EndMT. In human umbilical vein endothelial cells (HUVECs), SDHB KD aggravated hypoxia-induced EndMT, mitochondrial dysfunction and metabolic switch, while SS-31 treatment could significantly attenuate these changes caused by SDHB KD and hypoxia. In patient-derived xenograft (PDX) mice models of CBT, we also observed increased tumor growth speed and extent of EndMT, mitochondrial dysfunction, and metabolic switch in sclerosing carotid body tumor (SCBT) group than in conventional carotid body tumor (CCBT) group. And treating with SS-31 could significantly retard SCBT progression by rescuing the mitochondrial dysfunction-induced EndMT. Altogether, these results show that SDHB suppression-mitochondrial dysfunction-EndMT axis is a critical part of the CBT sclerosis and progression, while mitochondria-targeted drug SS-31 exerts an inhibitive effect on the above-mentioned axis, which opens new strategies to prevent and treat malignancies of CBT.

Contemporary Outcomes of Open and Endovascular Intervention for Extracranial Carotid Artery Aneurysms: A Single Centre Experience.

OBJECTIVE: The objective of this study was to evaluate the outcomes of open surgery (OS) and endovascular surgery (ES) for extracranial carotid aneurysm (ECCA) in the authors' centre. METHODS: Fifty-seven consecutive patients who were diagnosed with ECCA and underwent intervention from January 2005 to July 2019 at Zhongshan Hospital, Fudan University, were reviewed retrospectively. Patient characteristics and surgical outcomes for OS and ES were analysed. ECCAs were divided into three morphological subgroups: subgroup Ⅰ, no severe tortuosity of the internal carotid artery (ICA) or common carotid artery (CCA) proximal to the aneurysm, tortuosity of the aneurysm and 1 cm of peri-aneurysmal carotid artery ≤ 90°; subgroup Ⅱ, severe ICA or CCA tortuosity proximal to the aneurysm, tortuosity of the aneurysm and 1 cm of peri-aneurysmal carotid artery ≤ 90°; subgroup Ⅲ, aneurysm tortuosity and 1 cm peri-aneurysmal carotid artery > 90°. RESULTS: 35 patients underwent OS, 20 patients underwent ES and 2 patients underwent OS after the failure of ES. Thirty-six cases were classified in subgroup Ⅰ, 11 cases in subgroup Ⅱ, and 10 cases in subgroup Ⅲ. ES was achieved successfully in all 18 cases of subgroup I, but failed in three of four cases in subgroups Ⅱ and Ⅲ. With a mean duration of 62.9 ± 44.5 months of follow up, five deaths were recorded in the OS group, two of which were caused by ipsilateral stroke and three were not neurologically related. There was no stroke or death in the ES group during follow up. One case of stroke and two cases of death occurred in symptomatic patients, while one case of stroke and three cases of death occurred in asymptomatic patients. CONCLUSION: This series demonstrates that ES may be a safe and durable option for ECCA in subgroup Ⅰ, while in subgroups Ⅱ and Ⅲ, ES alone may be difficult to apply. A 30 day stroke rate around 5% existed in ECCAs with interventions, which should be considered before the intervention.

Tizanidine (Hydrochloride) Inhibits A549 Lung Cancer Cell Proliferation and Motility Through Regulating Nischarin.

PURPOSE: Tizanidine hydrochloride (TZN) is a centrally acting α2-adrenergic agonist. In this study, we aimed to explore the role of TZN on human lung cancer and to elucidate its underlying mechanisms. METHODS: The effect of TZN treatment in A549 cell proliferation, migration, invasion and apoptosis was evaluated by CCK8, transwell and flow cytometer assays. The expression of apoptosis-related proteins and the activation of AKT and Wnt3a/ß-catenin pathways were detected by Western blot. From the data of DrugBank, TZN could act as an agonist to target Nischarin in humans. We next investigated the function of Nischarin receptor in lung cancer and its role in the anti-tumor activity of TZN. RESULTS: The treatment of TZN inhibited the proliferation, migration and invasion of A549 cells, and induced apoptosis. These results were further confirmed by that TZN treatment increased the Bax/Bcl-2 ratio in A549 cells. We also observed that TZN treatment changed the expression and phosphorylation of proteins of AKTand Wnt3a/ß-catenin signaling pathway members. By bioinformatics analysis, we found that Nischarin was down-regulated in human lung cancer tissues and patients with high Nischarin expression had a better survival. Moreover, Nischarin functioned as a tumor suppressor in the survival and metastasis of A549 cells through the regulation of AKT and Wnt3a/ß-catenin pathways. Knockdown of Nischarin promoted the proliferation, invasion, migration of A549 cells and inhibited the apoptosis, which were reversed by the TZN treatment. CONCLUSION: Summary, our data revealed that treatment of TZN inhibited the growth of lung cancer cell line A549 and may be used as a novel strategy for lung cancer therapy.

Recent Intraplaque Hemorrhage Is Associated with a Higher Risk of Ipsilateral Cerebral Embolism During Carotid Artery Stenting.

OBJECTIVE: The purpose of this study was to identify which stage of intraplaque hemorrhage (IPH) is an independent risk factor for ipsilateral new ischemic lesions (NILs) after carotid artery stenting (CAS). METHODS: In 268 patients treated with CAS, the association between postoperative ipsilateral NILs on diffusion-weighted imaging (DWI) and patient demographics, intraoperative factors, and plaque characteristics on multicontrast atherosclerosis characterization sequence was retrospectively analyzed. RESULTS: A total of 268 patients were enrolled in the study. Ipsilateral NILs on DWI were detected in 32.8% of patients. Univariate analysis showed that the stage of IPH (along with lipid-rich necrotic core [LRNC]) (P < 0.001) in the carotid plaque, predilation (P = 0.012), stent type (P = 0.002), and aortic arch ulcer (P = 0.009) were associated with postoperative ipsilateral NILs, whereas other patient-related factors (P >0.05), type of embolic protection device (P = 0.072), postdilation (P = 0.388), calcification (P = 0.140), and LRNC (without IPH) (P = 0.086) were not. Multivariate logistic regression analysis showed that the acute and recent IPH (along with LRNC) (odds ratio [OR], 3.78, P = 0.011 and OR, 16.73, P < 0.001, respectively), aortic arch ulcer (OR, 2.46; P = 0.006), predilation (OR, 4.78; P = 0.015), and open cell stent (OR, 4.19; P < 0.001) were significantly associated with postoperative ipsilateral NILs on DWI. CONCLUSIONS: Screening for recent IPH in carotid plaques using multicontrast atherosclerosis characterization sequence may identify plaques at a higher risk for cerebral embolism during CAS.

CLOCK disruption aggravates carotid artery stenosis through endoplasmic reticulum stress-induced endothelial-mesenchymal transition.

Carotid artery stenosis is a leading cause of ischemic stroke, but the underlying mechanism remains unclear. We aimed to determine the molecular mechanisms of carotid plaque progression. We analyzed the molecular and morphometric characteristics of carotid plaque samples obtained from 30 patients who underwent carotid endarterectomy. Additionally, we established a mouse model of carotid atherosclerosis by partially ligating the left common carotid arteries of male ClockΔ19/Δ19 (Clk) and wild-type (WT) C57BL/6J mice fed a high-fat diet. Clk and WT primary mouse aortic endothelial cells (pMAECs) were exposed to disturbed flow (DF) or undisturbed flow (UF) with or without treatment with the IRE-1α inhibitor STF-083010 or the PERK inhibitor GSK2606414. In human carotid artery plaques, CLOCK expression was lower in the lipid-rich necrotic core than in transitional regions, especially in the endothelium. Decreased CLOCK mRNA levels were associated with more extensive stenosis, intraplaque hemorrhage, and complex plaque in human carotid plaques. In mice, the ClockΔ19/Δ19 mutation significantly increased neointima formation and neovascularization but decreased collagen content and lumen area in partially ligated carotid arteries. In addition, ClockΔ19/Δ19 mutants exhibited significantly decreased Cdh5 expression and increased expression of endothelial-mesenchymal transition (EndMT) and endoplasmic reticulum (ER) stress markers in mice with partially ligated carotid arteries and pMAECs exposed to DF. Notably, inhibition of the IRE1α-XBP1 axis abrogated the increased EndMT caused by ClockΔ19/Δ19 mutation and DF in pMAECs. In conclusion, the disruption of CLOCK function aggravates EndMT via the IRE1α-XBP1 axis, contributing to carotid artery stenosis.

A Systematic Review and Updated Metaanalysis for Carotid Near-Occlusion.

BACKGROUND: Carotid near-occlusion (CNO) is distal luminal collapse of the internal carotid artery beyond a tight stenosis. CNO is a relatively rare condition accounting for 3% in symptomatic carotid stenosis and about 20% in severe (≥70%) symptomatic stenosis. The optimal treatment for CNO remains controversial. METHODS: This systematic review and metaanalysis were performed in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines (MOOSE). We searched MEDLINE, the Cochrane Library, and EMBASE for articles published from inception date to November 2018. Methodological Index for Non-randomized Studies (MINORS) was used to evaluate the methodological quality of studies. We defined primary outcome as any stroke, death and myocardial infarction (MI) within 30 days after intervention and the operative risks of carotid endarterectomy (CEA) and carotid artery stenting (CAS) were evaluated by the incidence rate (IR) of the primary outcome. Secondary outcome was defined as ipsilateral stroke, neurogenic or cardiac death and MI during the follow-up. Long-term risk was evaluated by the IR of secondary outcome. The analyses used the IRs of secondary outcome and restenosis per person-year (p-y) were performed to evaluate long-term risk and restenosis. Pooled analyses of different therapy groups were calculated. RESULTS: Twenty-eight articles of 26 studies met the inclusion criteria and were eligible for pooled analysis. Pooled IR of secondary outcome was 4.26 per 100 p-ys (95% CI, 2.92-6.20 per 100 p-ys) in intervention group (heterogeneity, I2 = 56.1%, P < 0.01; Egger test, P = 0.73) and 13.3 per 100 p-ys (95% CI, 5.54-31.95 per 100 p-ys) in best medical treatment (BMT) group (heterogeneity, I2 = 88.3%, P < 0.01; Egger test, P = 0.76). No significant difference was demonstrated in operative risk (CEA: 4.82%, 95% confidence interval [CI]: 3.07-7.55%; CAS: 5.39%, 95% CI: 3.69-7.88%) and long-term risk (CEA: 4.47 per 100 p-ys, 95% CI: 3.35-5.97 per 100 p-ys; CAS: 4.71 per 100 p-ys, 95% CI: 2.37-9.37 per 100 p-ys) between CEA and CAS group. CONCLUSIONS: BMT alone may be not enough to support a better prognosis than CEA or CAS for patients with CNO. No significant difference was found between patients with CNO who underwent CAS and CEA in both perioperative period and long-term follow-up.

Effect of intraoperative fluid administration on perioperative outcomes in patients undergoing McKeown esophagogastrectomy.

OBJECTIVE: Fluid therapy is one of the key components of perioperative management. However, evidence of intraoperative fluid (IOF) administration affecting clinical outcomes following McKeown esophagogastrectomy remains limited. This study investigated the impact of IOF on clinical outcomes after McKeown esophagogastrectomy. METHODS: Patients who underwent McKeown esophagogastrectomy between July 2013 and July 2016 were identified. Preoperative, intraoperative and postoperative variables for each eligible patient were retrospectively collected from our electronic medical records and anesthetic records. IOF rates were determined and their relationships to postoperative clinical outcomes were compared. RESULTS: A total of 546 patients were enrolled in the analysis. The median IOF rate was 8.87 mL/kg/h. We divided the patients into two groups: a low fluid volume group (LFVG <8.87 mL/kg/h, n=273) and a high fluid volume group (HFVG ≥8.87 mL/kg/h, n=273). No statistically significant differences in postoperative clinical outcomes were found between LFVG and HFVG either before or after propensity score matching. CONCLUSIONS: No effect of IOF administration on clinical outcomes in patients undergoing McKeown esophagogastrectomy was identified. Further high-quality studies examining the influence of IOF administration on clinical outcomes following McKeown esophagogastrectomy are still needed.

Scoring System to Predict the Risk of Surgical Site Infection in Patients with Esophageal Cancer after Esophagectomy with Cervical Anastomosis.

BACKGROUND: Surgical site infection (SSI) surveillance has become increasingly important during the peri-operative period of esophagectomy with cervical anastomosis (McKeown esophagectomy). This study sought to clarify the risk factors for SSI and to develop a stratification scoring system to predict SSI after esophagectomy with cervical anastomosis. PATIENTS AND METHODS: All patients who underwent elective esophagectomy with cervical anastomosis were studied between January 2010 and December 2016 in the Chinese Academy of Medical Sciences Cancer Hospital (CAMS). Univariable analysis and multivariable logistic regression were used to screen the independent risk factors. A risk stratification scoring system was developed based on multivariable logistic regression parameters. The model derivation set involved 711 consecutive cases, and the validation set involved 168 consecutive cases. RESULTS: In the model derivation set, there were 711 patients, of whom 146 were found to have SSI and the incidence rate was 20.53%. Multivariable analysis found that SSI was associated independently with the following adverse risk factors: peripheral vascular disease, prior chest surgery, no pre-operative surgical antibiotic prophylaxis (SAP) administration within 120 minutes prior to incision, low serum albumin, and low pre-albumin at post-operative day zero to three, respectively. Each of these factors contributed one point to the risk score and a risk stratification scoring system was established. The SSI rates were increased gradually in the low, intermediate, high, and extremely high-risk groups (p < 0.001). The area under the receiver operating characteristic (AUROC) curve was 0.706 for the logistic regression model and 0.704 for the scoring system. In the validation set, the model performed equivalently (AUC = 0.824). CONCLUSIONS: The validated stratification scoring system could predict accurately the risk of SSI after esophagectomy with cervical anastomosis. This could be helpful in the selection of high-risk patients requiring frequent monitoring and more aggressive interventions to decrease the incidence of SSI.

Loss of CLOCK under high glucose upregulates ROCK1-mediated endothelial to mesenchymal transition and aggravates plaque vulnerability.

BACKGROUND AND AIMS: Carotid atherosclerotic plaque is one of the main sources of ischemic stroke, and endothelial-to-mesenchymal transition (EndMT) is a major feature of atherosclerosis. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) activation, stimulated by high glucose, plays an important role in EndMT, and circadian locomotor output cycles protein kaput (Clock) deficiency leads to hyperglycemia and enhanced atherosclerosis in ClockΔ19/Δ19apolipoprotein E (ApoE)-/- mice. These findings point to a mechanism whereby CLOCK exerts a protective effect against EndMT and atherosclerotic plaque accumulation. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with 66 mM glucose for 120 h to induce EndMT. The expression of CLOCK and ROCK1 was assayed, as were their effects on EndMT. We also conducted molecular and morphometric examination of carotid artery plaques from patients with carotid artery stenosis to assess the clinical relevance of these findings. RESULTS: Upon EndMT, HUVECs exhibited decreased CLOCK expression and increased ROCK1 expression. Notably, CLOCK silencing increased high glucose-induced EndMT, migration ability, and ROCK1 activation, while overexpressing CLOCK attenuated these characteristics. Moreover, inhibition of ROCK1 largely blocked EndMT induced by high-glucose or transforming growth factor (TGF)-ß1 but failed to rescue the reduced CLOCK expression. The vulnerability of human carotid artery plaque was strongly correlated with loss of CLOCK expression, activation of TGF-ß/ROCK1 signaling, and the extent of EndMT. CONCLUSIONS: The data indicate that loss of protective endothelial CLOCK expression aggravates TGF-ß/ROCK1-modulated EndMT progression, which contributes to the vulnerability of human carotid plaque.

[Overexpression of OLC1 in Lung Squamous Cell Carcinoma Tissues is Associated with Poor Prognosis of Patients].

BACKGROUND: OLC1 (overexpressed in lung cancer 1), screened out and cloned in our previous research, is a new gene associated with lung cancer. It is highly expressed in lung cancer and many other malignant tumors, and is associated with poor prognosis of esophageal squamous cell carcinoma, ovarian cancer, breast cancer and colorectal cancer. The aim of this research was to detect the expression level of OLC1 in the tumor tissues of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) and explore its relationship with the prognosis of lung cancer patients. METHODS: Lung cancer tissues of 108 SCC and 90 ADC was dealed with immunohistochemical staining to detect the expression level of OLC1. The relationship between the expression level of OLC1 and clinical parameters and prognosis was analyzed. RESULTS: The rate of high expression of OLC1 staining in ADC was significantly higher than that in SCC (87.5% vs 55.3%, P<0.001). The overexpression of OLC1 in tumor tissues did not have a significant relationship with the prognosis of patients with ADC, but it was related with a poor prognosis of SCC patients as the univariate analysis showed. However the multivariate regression analysis showed that correlation between the overexpression of OLC1 and poor prognosis of SCC patients did not have a statistical significance (P=0.05). CONCLUSIONS: The expression of OLC1 in ADC might be higher than that in SCC. A higher score of OLC1 staining in tumor tissue was associated with a poorer prognosis of patients with SCC, but could not be an independent predictor for a shorter overall survival in patients with SCC.

Risk factors for anastomotic leakage following esophagectomy: Impact of thoracic epidural analgesia.

BACKGROUND AND OBJECTIVES: Anastomotic leakage (AL) is one of common complications after esophageal cancer surgery. Thoracic epidural analgesia (TEA) is often recommended in patients undergoing esophagectomy. However, the impact of TEA on AL is still controversial. Thus, we conducted this study to evaluate the effect of TEA on the occurrence of AL and identify risk factors for the development of AL following esophagectomy. METHODS: Our retrospective study identified patients who underwent elective esophagectomy between July 2013 and July 2016. Univariate and multivariate logistics analyses and propensity score matching analysis were conducted to identify the risk factors for AL occurring within 30 days after operation. RESULTS: Overall 30-day AL was 7.9%. Multivariate analysis revealed that surgical procedure (Sweet: referent; Ivor-Lewis: OR 2.854; 95%CI 1.726-4.718; Three-incision: OR 4.837; 95%CI 3.457-6.768) and surgeon (high-volume: referent; low-volume: OR 1.740; 95%CI 1.269-2.384) were independent risk factors for AL after esophagectomy. No statistically significant difference was observed in the incidences of AL between the epidural analgesia group and the intravenous analgesia group either before or after propensity score matching (9.1% vs 7.7%, P = 0.359; 8.3% vs 9.2%, P = 0.683). CONCLUSIONS: TEA does not affect the AL risk after esophagectomy.

Calcification of arteries supplying the gastric tube increases the risk of anastomotic leakage after esophagectomy with cervical anastomosis.

BACKGROUND: Anastomotic leak is an important cause of morbidity and mortality after esophagectomy for esophageal cancer patients. Calcification of the arteries supplying the gastric tube has been found to be associated with leakage after esophagectomy with cervical anastomosis in Europeans. The purpose of this study is to evaluate the association between calcifications of the supplying arteries of the gastric tube and the occurrence of anastomotic leakage after esophagectomy with cervical anastomosis in Chinese patients with esophageal cancer. METHODS: The demographic, clinical, and pathological features as well as the vascular calcification of arteries of 709 esophageal cancer patients who had undergone esophagectomies with cervical anastomosis were analyzed. Univariable and multivariable logistic regression were used to identify the association between the postoperative anastomotic leakage and calcifications of the arteries supplying the gastric tube. RESULTS: Among the 709 patients, 122 (17.2%) had developed anastomotic leakage. Thirty-day mortality and length of hospital stay were higher for patients with anastomotic leakage. Upper digestive tract ulcer, peripheral vascular disease, renal insufficiency, American society of Anesthesiologists (ASA) risk class, and calcifications of aorta and celiac axis were found to be independent risk factors for the anastomotic leakage. CONCLUSIONS: Calcification of the aorta and celiac axis that supply the gastric tube is an independent risk factor for cervical anastomotic leakage after esophagectomy in Chinese esophageal cancer patients.