Diagnostic yield using electromagnetic navigation bronchoscopy for peripheral pulmonary nodules <2 cm.

BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

The power and the promise of synthetic lethality for clinical application in cancer treatment.

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.

Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus.

OBJECTIVES: Knowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity. MATERIALS AND METHODS: This multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods. RESULTS: The 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients' OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases. CONCLUSIONS: EBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden.

Asymmetric Low-Frequency Pulsed Strategy Enables Ultralong CO2 Reduction Stability and Controllable Product Selectivity.

Copper-based catalysts are widely explored in electrochemical CO2 reduction (CO2RR) because of their ability to convert CO2 into high-value-added multicarbon products. However, the poor stability and low selectivity limit the practical applications of these catalysts. Here, we proposed a simple and efficient asymmetric low-frequency pulsed strategy (ALPS) to significantly enhance the stability and the selectivity of the Cu-dimethylpyrazole complex Cu3(DMPz)3 catalyst in CO2RR. Under traditional potentiostatic conditions, Cu3(DMPz)3 exhibited poor CO2RR performance with the Faradaic efficiency (FE) of 34.5% for C2H4 and FE of 5.9% for CH4 as well as the low stability for less than 1 h. We optimized two distinguished ALPS methods toward CH4 and C2H4, correspondingly. The high selectivities of catalytic product CH4 (FECH4 = 80.3% and above 76.6% within 24 h) and C2H4 (FEC2H4 = 70.7% and above 66.8% within 24 h) can be obtained, respectively. The ultralong stability for 300 h (FECH4 > 60%) and 145 h (FEC2H4 > 50%) was also recorded with the ALPS method. Microscopy (HRTEM, SAED, and HAADF) measurements revealed that the ALPS method in situ generated and stabilized extremely dispersive and active Cu-based clusters (∼2.7 nm) from Cu3(DMPz)3. Meanwhile, ex situ spectroscopies (XPS, AES, and XANES) and in situ XANES indicated that this ALPS method modulated the Cu oxidation states, such as Cu(0 and I) with C2H4 selectivity and Cu(I and II) with CH4 selectivity. The mechanism under the ALPS methods was explored by in situ ATR-FTIR, in situ Raman, and DFT computation. The ALPS methods provide a new opportunity to boost the selectivity and stability of CO2RR.

Anticancer activity of oleanolic acid and its derivatives modified at A-ring and C-28 position.

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.

Preclinical characterization and phase I clinical trial of CT053PTSA targets MET, AXL, and VEGFR2 in patients with advanced solid tumors.

Background: CT053PTSA is a novel tyrosine kinase inhibitor that targets MET, AXL, VEGFR2, FLT3 and MERTK. Here, we present preclinical data about CT053PTSA, and we conducted the first-in-human (FIH) study to evaluate the use of CT053PTSA in adult patients with pretreated advanced solid tumors. Methods: The selectivity and antitumor activity of CT053PTSA were assessed in cell lines in vitro through kinase and cellular screening panels and in cell line-derived tumor xenograft (CDX) and patient-derived xenograft (PDX) models in vivo. The FIH, phase I, single-center, single-arm, dose escalation (3 + 3 design) study was conducted, patients received at least one dose of CT053PTSA (15 mg QD, 30 mg QD, 60 mg QD, 100 mg QD, and 150 mg QD). The primary objectives were to assess safety and tolerability, to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended dose of CT053PTSA for further study. Secondary objectives included pharmacokinetics, antitumor activity. Results: CT053 (free-base form of CT053PTSA) inhibited MET, AXL, VEGFR2, FLT3 and MERTK phosphorylation and suppressed tumor cell angiogenesis by blocking VEGF and HGF, respectively, in vitro. Moreover, cell lines with high MET expression exhibited strong sensitivity to CT053, and CT053 blocked the MET and AXL signaling pathways. In an in vivo study, CT053 significantly inhibited tumor growth in CDX and PDX models. Twenty eligible patients were enrolled in the FIH phase I trial. The most common treatment-related adverse events were transaminase elevation (65%), leukopenia (45%) and neutropenia (35%). DLTs occurred in 3 patients, 1/6 in the 100 mg group and 2/4 in the 150 mg group, so the MTD was set to 100 mg. CT053PTSA was rapidly absorbed after the oral administration of a single dose, and the Cmax and AUC increased proportionally as the dose increased. A total of 17 patients in this trial underwent tumor imaging evaluation, and 29.4% had stable disease. Conclusions: CT053PTSA has potent antitumor and antiangiogenic activity in preclinical models. In this FIH phase I trial, CT053PTSA was well tolerated and had a satisfactory safety profile. Further trials evaluating the clinical activity of CT053PTSA are ongoing.

A Phase Ib Study of Lucitanib (AL3810) in a Cohort of Patients with Recurrent and Metastatic Nasopharyngeal Carcinoma.

BACKGROUND: Lucitanib is a novel multi-target inhibitor of FGFR1-3, VEGFR 1-3, and PDGFR α/ß. Here, we evaluated the safety, tolerability, and preliminary efficacy of lucitanib in recurrent and metastatic nasopharyngeal carcinoma (RM-NPC). METHODS: Patients with pretreated RM-NPC were randomly divided into two treatment arms: continuous or intermittent treatment. The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). RESULTS: One hundred percent of patients in the continuous arm and 90% of patients in the intermittent arm had at least one treatment-related AE (TRAE). Grade ≥3 related TRAEs occurred in 5 patients in the continuous arm (5/10, 50%). No TRAEs grade >3 occurred in the intermittent arm. The ORR and DCR of the continuous arm was 20% and 90%, and the intermittent arm was 10% and 60%, respectively. All responses were observed by the first evaluation. The duration of response was more than 1 year, with two patients still on treatment with sustained response at more than 3 years. CONCLUSION: Lucitanib has promising clinical activity and tolerable safety profile in heavily pretreated patients with NPC. Patients who responded to lucitanib treatment generally achieved a long DoR. Lucitanib is now being evaluated in phase II/III studies. CLINICALTRIALS.GOV IDENTIFIER: NCT03260179.

The clinicopathological significance and predictive value for immunotherapy of programmed death ligand-1 expression in Epstein-Barr virus-associated gastric cancer.

The effect of anti-programmed cell death 1 (PD-1) antibody in Epstein-Barr virus-associated gastric cancer (EBVaGC) was debatable, and no predictive biomarkers for efficacy have been reported. Public reports on anti-PD-1 antibody monotherapy-treated EBVaGC with available programmed death ligand-1 (PD-L1) expression status were summarized and analyzed. Relevance with clinicopathologic characteristics of PD-L1 expression by immunohistochemistry was analyzed in 159 patients diagnosed with EBVaGC. Relevance with genomic transcriptome and mutation profile of PD-L1 status in EBVaGC was assessed with three datasets, the cancer genome atlas (TCGA), Gene Expression Omnibus (GEO) GSE51575, and GSE62254. Based on the data from 8 reports, patients with positive PD-L1 expression (n = 30) had significantly superior objective response rate (ORR) than patients with negative PD-L1 expression (n = 9) (63.3% vs. 0%, P = .001) in EBVaGC receiving anti-PD-1 antibody monotherapy. PD-L1 positivity was associated with less aggressive clinicopathological characteristics and was an independent predictor for a longer disease-free survival (hazard ratio [HR] and 95% CI: 0.45 [0.22-0.92], P = .03) and overall survival (HR and 95% CI: 0.17 [0.06-0.43], P < .001). Analysis of public EBVaGC transcriptome and mutation datasets revealed enhanced immune-related signal pathways in PD-L1high EBVaGC and distinct mutation patterns in PD-L1low EBVaGC. PD-L1 positivity indicates a subtype of EBVaGC with 'hot' immune microenvironment, lower aggressiveness, better prognosis, and higher sensitivity to anti-PD-1 immunotherapy.

The characteristics and prognostic significance of esophageal squamous cell carcinoma with synchronous multiple lesions: over 10-year experience.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is occasionally observed with synchronous multiple tumor lesions. Our study is aiming to define the clinical and prognostic features of this pathological subtype. METHODS: This study included a large cohort of 1126 ESCC patients received esophagectomy with systemic lymph-node dissection between 2003 and 2013 in Sun Yat-sen University Cancer Center. The characteristics and prognostic significance of ESCC with multiple lesions were analyzed. The propensity score matching was performed to balance the baseline clinical characteristics. RESULTS: A total of 103 patients (9.1%) with 216 synchronous multiple lesions were identified from postoperative gross samples. Among them, 94 patients had two lesions, and 8 patients had three lesions, while only one patient had four lesions. The consistency of pT stages and histological grade among tumor lesions from the same gross sample were 19.4% (20/103) and 37.9% (39/103), respectively. Additionally, the tumor sites, sizes, and even the pathological subtypes can be variant in one patient. The preoperative upper gastrointestinal endoscopy could only identified 80.1% of the multiple tumor lesions. The male gender (P = 0.012), positive personal cancer history (P < 0.001), and higher pN stages (P < 0.001) were independent risk factors for synchronous multiple lesions. Patients with multiple lesions showed significantly lower survival rate (P = 0.002), and the multiple-lesion was an independently adverse prognostic factor in operable ESCC (P = 0.002). CONCLUSION: ESCC with multiple lesions had unique clinical features and should not be simply treated as the one-lesion ESCC. Due to its worse prognostic impact, advanced multidisciplinary therapies should be considered for patients with multiple esophageal tumor lesions.

Home enteral nutrition after esophagectomy for esophageal cancer: A systematic review and meta-analysis.

BACKGROUND: Not only has the placement rate of enteral feeding tubes during operations for esophageal cancer increased, but also has number of patients who choose to continue enteral feeding at home instead of removing the feeding tube at discharge. The impacts of home enteral nutrition (HEN) after esophagectomy in esophageal cancer patients are analyzed. METHODS: A systematic review was conducted in accordance with PRISMA and Cochrane guidelines. English and Chinese databases, including PubMed, Embase, Web of Science, The Cochrane Library, Scopus, CBM, CNKI, and Wan Fang were searched from inception to December 7, 2019. Randomized controlled trials evaluating the short-term outcomes of HEN following esophagectomy in cancer patients were included. The risk of bias of the included studies was appraised according to the Cochrane risk of bias tool. The summary of relative risk/weighted mean difference (WMD) estimates and corresponding 95% confidence interval (95% CI) were calculated using fixed- and random-effects models. RESULTS: Nine randomized controlled trials involving 757 patients were included in the meta-analysis. Compared with oral diet, HEN was associated with significantly increased body weight (WMD 3 kg, 95% CI 2.36-3.63, P < .001), body mass index (WMD 0.97 kg/m, 95% CI 0.74-1.21, P < .001), albumin (WMD 3.43 g/L, 95% CI 2.35-4.52, P < .001), hemoglobin (WMD 7.23 g/L, 95% CI 5.87-8.59, P < .001), and total protein (WMD 5.13 g/L, 95% CI 3.7-6.56, P < .001). No significant differences were observed in prealbumin and gastrointestinal adverse reactions. Physical (WMD 8.82, 95% CI 6.69-10.95, P < .001) and role function (WMD 12.23, 95% CI 2.72-21.74, P = .01) were also significantly better in the HEN group. The nausea/vomiting (WMD -5.43, 95% CI -8.29 to -2.57, P = .002) and fatigue symptoms (WMD -11.76, 95% CI -16.21 to -7.32, P < .001) were significantly reduced. Appetite loss (WMD -8.48, 95% CI -14.27 to -4.88, P = .001), diarrhea (WMD -3.9, 95% CI -7.37 to -0.43, P = .03), and sleep disturbance (WMD -7.64, 95% CI -12.79 to -2.5, P = .004) in the HEN group were also significantly less than the control group. CONCLUSIONS: HEN improved nutrition status, physical and role function, and reduced nausea/vomiting, fatigue, appetite loss, diarrhea, and sleep disturbance compared with an oral diet in esophageal cancer patients postsurgery. HEN did not increase adverse reactions.

Follow-up study on symptom distress in esophageal cancer patients undergoing repeated dilation.

BACKGROUND: Repeated endoscopic probe dilatation is the most preferred treatment for esophageal stenosis which may cause high levels of symptom distress in the patient's home rehabilitation stage. AIM: To explore the changes in the symptom distress level and its correlation with the dilation effect in patients with esophageal carcinoma undergoing repeated dilations for lumen stenosis. METHODS: The difference (R2-R1) between the diameter of the esophageal stenosis opening (R1) of the patients before dilation (R1) and after dilation (R2) was calculated to describe the extent and expansion of the esophageal stenosis before and after dilation. The M.D. Anderson Symptom Inventory was used to describe the symptom distress level of patients with dilation intermittence during their stay at home and to explore the correlation between the dilation effect and symptom distress level. RESULTS: The diameter of the esophagus (R1) increased before each dilation in patients undergoing esophageal dilation (P < 0.05). The diameter (R2) increased after dilation (P < 0.05); the dilation effect (R2-R1) decreased with the number of dilations (P < 0.05). The total symptom distress score significantly increased with the number of dilations (P < 0.05). The symptom distress scores of the patients were negatively correlated (P < 0.05) with the previous dilation effect (R2-R1) and the esophageal diameter (R2) after the previous dilation. After the 1st to 4th dilations, the patient's symptom distress score was negatively correlated with the esophageal diameter (R12) before the next dilation, while there was no significant correlation (P > 0.05) with the other dilations. CONCLUSION: In patients who have undergone repeated dilations, better effect stands for lower symptom distress level and the increase in symptom distress has a prompt effect on the severity of the next occurrence of restenosis.

Prophylactic thoracic duct ligation is associated with poor prognosis and regional lymph node relapse in esophageal squamous cell carcinoma.

OBJECTIVES: The ligation of thoracic duct interrupts the normal lymphatic circulation. Whether the ligation of thoracic duct would affect tumor recurrence and patient survival is unclear. METHODS: The correlations between prophylactic thoracic duct ligation (PLG) and prognosis were examined in patients with esophageal squamous cell carcinoma. Patients who received Ivor Lewis or McKeown esophagectomy with systemic lymph node dissection and R0 resection between 2003 and 2013 in Sun Yat-sen University Cancer Center were included in the study. RESULTS: A total number of 473 and 462 were included in the PLG group and non-prophylactic thoracic duct ligation (NPLG) group, respectively. The PLG group had a lower 5-year survival rate (48.2% vs 61.6%, P < .001). After a 1:1 propensity score matching, 874 cases (437 pairs) were included and the survival analysis showed that PLG was associated with worse 5-year cumulative survival of 48.6% vs 61.6% in those patients without ligation (P < .001). The multivariate analysis revealed that PLG was an independent factor for poor prognosis after esophagectomy (hazard ratio, HR = 1.56; 95% confidence interval, 95% CI, 1.26-1.93, P < .001). Additionally, PLG was associated with regional lymph node relapse (P = .015). CONCLUSIONS: PLG should not be performed routinely if no sign of thoracic duct rupture or tumor invasion were identified.

Molecular Mechanistic Insights into Drosophila DHX36-Mediated G-Quadruplex Unfolding: A Structure-Based Model.

Helicase DHX36 plays essential roles in cell development and differentiation at least partially by resolving G-quadruplex (G4) structures. Here we report crystal structures of the Drosophila homolog of DHX36 (DmDHX36) in complex with RNA and a series of DNAs. By combining structural, small-angle X-ray scattering, molecular dynamics simulation, and single-molecule fluorescence studies, we revealed that positively charged amino acids in RecA2 and OB-like domains constitute an elaborate structural pocket at the nucleic acid entrance, in which negatively charged G4 DNA is tightly bound and partially destabilized. The G4 DNA is then completely unfolded through the 3'-5' translocation activity of the helicase. Furthermore, crystal structures and DNA binding assays show that G-rich DNA is preferentially recognized and in the presence of ATP, specifically bound by DmDHX36, which may cooperatively enhance the G-rich DNA translocation and G4 unfolding. On the basis of these results, a conceptual G4 DNA-resolving mechanism is proposed.

The prognostic impact of tumor volume on stage I non-small cell lung cancer.

OBJECTIVES: The purpose of this study was to investigate the prognostic impact of tumor volume (TV) on patients with stage I non-small cell lung cancer (NSCLC) after complete resection. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological characteristics of 274 patients with stage I NSCLC who had received preoperative chest computed tomography (CT) scans and complete resection. TV was semi-automatically measured from chest CT scans by using an imaging software program. The optimal cutoff values of TV were determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were compared using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify risk factors for DFS and OS. RESULTS: By using 3.046cm3 and 8.078cm3 as two optimal cutoff values of TV, the patients were separated into three groups. The 5-year DFS and OS for patients with TV≤3.046cm3, 3.046-8.078cm3, and>8.078cm3 were 88.0%, 73.6%, and 62.1%, respectively (P<0.001), and 91.4%, 84.5%, and 73.3%, respectively (p<0.001). Multivariate analysis showed that age and TV were independent factors associated with DFS. Sex, age, histology, visceral pleural invasion, and TV were independent factors associated with OS. Stage Ia patients might be separated into three groups on the basis of TV with significantly different DFS and OS. Patients with tumor diameter≤2cm and 2-3cm were also stratified into two groups with significantly different DFS and OS on the basis of TV, respectively. CONCLUSION: TV is an independent risk factor for DFS and OS for stage I NSCLC after complete resection. TV might provide additional prognostic information over tumor diameter in patients with stage I NSCLC.

The epithelial-mesenchymal transition phenotype of metastatic lymph nodes impacts the prognosis of esophageal squamous cell carcinoma patients.

Epithelial-mesenchymal transition (EMT) plays a key role in tumor metastasis, but the significance of EMT phenotype to the prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. We used immunohistochemistry to examine the expression of the EMT-related proteins E-cadherin, N-cadherin and vimentin in samples of T3N1-3M0 ESCC from 155 primary tumors (PTs) with paired metastatic lymph nodes (MLNs) and 58 PTs without paired MLNs. Based on the expression pattern of the EMT markers, PTs and MLNs were classified as EMT wild, hybrid, null or complete type. The hybrid (42.7%) and complete (39.4%) types predominated among PTs, whereas the wild (34.2%) and hybrid (52.9%) types predominated among MLNs, and EMT phenotypes differed between the paired PTs and MLNs (P < 0.001). Univariate analysis revealed that, for PTs, the EMT phenotype was associated with N-stage (P = 0.039) but not patient survival, and that patients with complete or hybrid type MLNs had better overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.005) than patients with null and wild type MLNs, especially those with N1-stage disease (P = 0.017 for OS, and P = 0.017 for DFS, respectively). Multivariate analysis revealed that wild and null type MLNs as well as older age and N2-3 stage were independent predictors of OS and DFS (P < 0.05). Thus MLNs exhibit EMT phenotypes that are distinct from those of their PT and may serve as a novel independent prognostic indicator in ESCC.

MIIP expression predicts outcomes of surgically resected esophageal squamous cell carcinomas.

The migration and invasion inhibitory protein (MIIP) was shown to function as a tumor suppressor gene in gliomas by inhibiting tumor cell growth, migration, and invasion. However, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) have not been elucidated. We investigated the correlation of MIIP expression and clinical outcome in a group of surgically resected ESCCs. Tissue microarrays constructed of 253 surgically resected ESCC primary tumors and paired paracancerous normal esophageal epithelia were used for MIIP evaluation by immunohistochemistry. The clinical and prognostic significance of MIIP expression was analyzed statistically. The expression of MIIP expression in cancer tissues was increased significantly in comparison with the paired paracancerous normal epithelia (P < 0.001). And, MIIP expression was associated with ESCC cells' differentiation (P < 0.001). By Kaplan-Meier analysis, patients with low MIIP expression exhibited significantly improved overall survival (OS, P = 0.039) and a tendency of improved disease-free survival (DFS, P = 0.086) than those with high MIIP expression. In addition, MIIP expression could distinguish OS or DFS of patients with tumors in stage T3-4 (P = 0.020, 0.028), N0 (P = 0.008, 0.032), and stage II (P = 0.004, 0.019), as well as at lower thoracic esophagus (P = 0.024, 0.090). Multivariate analysis showed that MIIP expression was an independent prognostic factor in ESCC OS and DFS. In conclusion, MIIP expressed higher in ESCCs than in paracancerous normal esophageal epithelia and was a positive, independent prognostic factor in resected ESCCs.

TRPV6 plays a new role in predicting survival of patients with esophageal squamous cell carcinoma.

BACKGROUND: TRPV6 is over-expressed and promotes the proliferation and invasion in many cancers. The association between the expression of TRPV6 and clinical outcome in esophageal squamous cell carcinoma (ESCC) has not been studied yet. We aim to elucidate the role of TRPV6 in predicting prognosis of patients with ESCC. METHODS: In the retrospective study, mRNA level of TRPV6 was examined in patients (N = 174) from Sun Yat-sen University Cancer Center (mRNA cohort) and protein level of TRPV6 was examined in patients (N = 218) from Linzhou Cancer Hospital (protein cohort). Statistical analysis was performed to test the clinical and prognostic significance of TRPV6. RESULTS: TRPV6 was down-regulated in ESCC tissues and cell lines. Patients with downregulation of TRPV6 trended to have a higher rate of advanced pT stage in both mRNA cohort (P = 0.089) and protein cohort (P = 0.073), though not statistically significant. No significant association was observed between TRPV6 expression and disease-specific survival (DSS) in both two cohorts. However, stratified survival analysis based on the gender showed that in mRNA cohort, downregulation of TRPV6 was associated with an unfavorable 3-year DSS in patients with male (47.3 % vs 63.6 %, P = 0.027) and with favorable 3-year DSS in patients with female (66.7 % vs 43.0 %, P = 0.031). The result was confirmed in protein cohort. Male patients with downregulation of TRPV6 had a poor 3-year DSS (20.0 % vs 57.1 %,P < 0.001) while female counterparts showed an enhanced 3-year DSS (56.1 % vs 28.6 %, P = 0.005). CONCLUSION: TRPV6 is down-regulated in ESCC. As a predictive biomarker, TRPV6 plays a Janus-like role in predicting survival of male and female ESCC patients.

Resectable left lower lobe non-small cell lung cancer with lymph node metastasis is related to unfavorable outcomes.

BACKGROUND: Despite numerous previous studies, the consideration of tumor location as a prognostic factor in resectable non-small cell lung cancer (NSCLC) remains controversial. The present study analyzed the association between tumor location and clinical outcome in patients with resectable NSCLC who had undergone lobectomy with systematic lymphadenectomy and who had presented with varying nodal statuses. METHODS: The data from a cohort of 627 eligible patients treated in Sun Yat-sen University Cancer Center between January 2000 and December 2008 were retrospectively collected, and the nodal statuses of patients with different tumor locations were compared. Cox proportional hazards regression model was used to determine the independent factors related to cancer-specific survival (CSS). RESULTS: Multivariate analysis demonstrated that left lower lobe (LLL) tumors [hazard ratio (HR): 1.465, 95% confidence interval (CI) 1.090-1.969, P = 0.011], lymph node metastasis (HR: 2.742, 95% CI 2.145-3.507, P < 0.001), and a tumor size of >4 cm (HR: 1.474, 95% CI 1.151-1.888, P = 0.002) were three independent prognosticators in patients with resectable NSCLC. However, LLL tumors were associated only with CSS in node-positive patients (HR: 1.528, 95% CI 1.015-2.301, P = 0.042), and a tumor size of >4 cm was the only independent risk predictor in the node-negative subgroup (HR: 1.889, 95% CI 1.324-2.696, P < 0.001). CONCLUSIONS: Tumor location is related to the long-term CSS of NSCLC patients with lymph node metastasis. LLL tumors may be upstaged in node-positive patients to facilitate an optimal treatment strategy.

Phase 2 trial of neoadjuvant bevacizumab plus pemetrexed and carboplatin in patients with unresectable stage III lung adenocarcinoma (GASTO 1001).

BACKGROUND: The objective of this phase 2 trial was to assess the efficacy and safety of induction bevacizumab plus chemotherapy followed by surgery in patients with unresectable stage III lung adenocarcinoma. METHODS: The authors investigated induction bevacizumab (7.5 mg/kg) plus pemetrexed (500 mg/m(2) and carboplatin (area under the receiver operating characteristic curve = 5) followed by surgery for patients with unresectable stage III lung adenocarcinoma ages 18 to 65 years. The patients received neoadjuvant therapy every 3 weeks for 4 cycles. Surgery was scheduled 3 to 4 weeks after the last neoadjuvant therapy; then, the medical team assessed each patient's resectability status. The primary endpoint was the resectability rate. RESULTS: From April 2012 to April 2014, 42 patients were enrolled and received bevacizumab plus pemetrexed and carboplatin. Grade 3 or 4 induction-related AEs included fatigue in 5 patients, neutropenia in 4 patients, hypertension in 1 patient, anemia in 1 patient, and thrombocytopenia in 1 patient. One patient achieved a complete response, 22 achieved a partial response, 17 had stable disease, and 2 had progressive disease. After neoadjuvant therapy, 31 patients (73.8%) underwent surgery, including 11 who underwent pneumonectomy. Complete (R0) resection was achieved in 22 patients (52.4%). Reoperation was required in 1 patient because of a bleeding intercostal artery. No perioperative thromboembolic events or wound-healing problems were observed. The median event-free survival was 15.4 months, and the 1-year event-free survival rate was 56.1%. CONCLUSIONS: Treatment with neoadjuvant bevacizumab in combination with pemetrexed and carboplatin followed by surgery appears to be feasible and safe in patients with unresectable stage III lung adenocarcinoma. Cancer 2016;122:740-747. © 2015 American Cancer Society.

Effectiveness of Mindfulness-based Therapy for Reducing Anxiety and Depression in Patients With Cancer: A Meta-analysis.

Anxiety and depression are common among patients with cancer, and are often treated with psychological interventions including mindfulness-based therapy.The aim of the study was to perform a meta-analysis of the effectiveness of mindfulness-based interventions for improving anxiety and depression in patients with cancer.Medline, the Cochrane Library, EMBASE, and Google Scholar were searched. The randomized controlled trials designed for patients diagnosed with cancer were included. Mindfulness-based interventions were provided.The outcomes assessed were the changes in anxiety and depression scores from before to after the intervention. The treatment response was determined by calculating the standardized mean difference (SMD) for individual studies and for pooled study results. Subgroup analyses by cancer type, type of therapy, and length of follow-up were performed.Seven studies, involving 469 participants who received mindfulness-based interventions and 419 participants in a control group, were included in the meta-analysis. Mindfulness-based stress reduction and art therapy were the most common interventions (5/7 studies). All studies reported anxiety and depression scores. The pooled SMD of the change in anxiety significantly favored mindfulness-based therapy over control treatment (-0.75, 95% confidence interval -1.28, -0.22, P = 0.005). Likewise, the pooled SMD of the change in depression also significantly favored mindfulness-based therapy over control (-0.90, 95% confidence interval -1.53, -0.26, P = 0.006). During the length of follow-ups less than 12 weeks, mindfulness-based therapy significantly improved anxiety for follow-up ≤12 weeks after the start of therapy, but not >12 weeks after the start of therapy.There was a lack of consistency between the studies in the type of mindfulness-based/control intervention implemented. Patients had different forms of cancer. Subgroup analyses included a relatively small number of studies and did not account for factors such as the severity of anxiety and/or depression, the time since diagnosis, and cancer stage.Mindfulness-based interventions effectively relieved anxiety and depression among patients with cancer. However, additional research is still warranted to determine how long the beneficial effects of mindfulness-based therapy persist.