Surgery for pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma.

BACKGROUND: There has been little information on the actual diagnosis of pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma (TCC) and short- and long- outcomes of pulmonary resection for these patients. METHODS: In the present study, the data of 37 consecutive patients with a history of TCC who underwent pulmonary resection for solitary pulmonary lesions were reviewed, and the clinical factors and short- and long-term outcomes were analyzed. RESULTS: The study population included 35 male patients, and 2 female patients. The mean age was 72.5 years. Twenty patients (80%) were smokers and showed a high incidence of chronic obstructive pulmonary disease. Pulmonary lesions and primary TCC were detected simultaneously in 5 patients and metachronously in 32 patients. The median interval between treatment for primary TCC and the detection of pulmonary lesion was 43 months. The mean tumor diameter was 23 mm. The types of resection included lobectomy (n = 19), segmentectomy (n = 8), and partial resection (n = 10). Twelve of 37 patients (32%) developed postoperative complications. The pathological diagnoses included primary lung cancer (n = 28), pulmonary metastasis from TCC (n = 7), and others (n = 2). The 5-year overall survival rate for all patients was 72%. The 5-year overall survival rate of patients with primary lung cancer was 74%, while that of patients with pulmonary metastasis from TCC was 57%. CONCLUSIONS: Surgery can be proactively considered for treating pulmonary lesions in patients with a previous history of TCC, as it provides favorable long-term outcomes.

CKAP4 is a potential exosomal biomarker and therapeutic target for lung cancer.

Background: Globally, lung cancer causes the most cancer death. While molecular therapy progress, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has provided remarkable therapeutic effects, some patients remain resistant to these therapies and therefore new target development is required. Cytoskeleton-associated membrane protein 4 (CKAP4) is a receptor of the secretory protein Dickkopf-1 (DKK1) and the binding of DKK1 to CKAP4 promotes tumor growth via Ak strain transforming (AKT) activation. We investigated if CKAP4 functions as a diagnostic biomarker and molecular therapeutic target for lung cancer. Methods: CKAP4 secretion with exosomes from lung cancer cells and the effect of CKAP4 palmitoylation on its trafficking to the exosomes were examined. Serum CKAP4 levels were measured in mouse xenograft models, and 92 lung cancer patients and age- and sex-matched healthy controls (HCs). The lung cancer tissues were immunohistochemically stained for DKK1 and CKAP4, and their correlation with prognosis and serum CKAP4 levels were investigated. Roles of CKAP4 in the lung cancer cell proliferation were examined, and the effects of the combination of an anti-CKAP4 antibody and osimertinib, a third generation TKI, on anti-tumor activity were tested using in vitro and in vivo experiments. Results: CKAP4 was released from lung cancer cells with exosomes, and its trafficking to exosomes was regulated by palmitoylation. CKAP4 was detected in sera from mice inoculated with lung cancer cells overexpressing CKAP4. In 92 lung cancer patients, positive DKK1 and CKAP4 expression patients showed worse prognoses. Serum CKAP4 positivity was higher in lung cancer patients than in HCs. After surgical operation, serum CKAP4 levels were decreased. CKAP4 overexpression in lung cancer cells promoted in vitro cell proliferation and in vivo subcutaneous tumor growth, which were inhibited by an anti-CKAP4 antibody. Moreover, treatment with this antibody or osimertinib, a third generation TKI, inhibited AKT activity, sphere formation, and xenograft tumor growth in lung cancer cells harboring EGFR mutations and expressing both DKK1 and CKAP4, while their combination showed stronger inhibition. Conclusions: CKAP4 may represent a novel biomarker and molecular target for lung cancer, and combination therapy with an anti-CKAP4 antibody and osimertinib could provide a new lung cancer therapeutic strategy.

Utility of the surgical Apgar score for predicting the short- and long-term outcomes in non-small-cell lung cancer patients who undergo surgery.

OBJECTIVES: The surgical Apgar score (SAS) is a simple score that predicts postoperative complications based on 3 intraoperative valuables. The present study evaluated the association between the SAS and postoperative outcomes in non-small-cell lung cancer patients who underwent surgery. METHODS: A total of 585 patients who underwent lung resection were enrolled in the present study. We calculated the SAS of each patient and investigated its influence on the short- and long-term outcomes. RESULTS: Postoperative complications of any grade were detected in 164 cases (28%). The morbidity rate increased with decreasing SAS. When all the patients were divided into 2 groups (SAS <7 vs ≥7), postoperative complications were observed more frequently in the SAS <7 group than in the SAS ≥7 group (41% vs 25%, P < 0.001). In the multivariate analysis, the SAS was an independent risk factor for postoperative complications (odds ratio: 1.64 [1.03-2.61], P = 0.036). In terms of long-term outcomes, the 5-year disease-free survival (54.1% vs 73.2%, P < 0.001) and overall survival (73.8% vs 83.0%, P = 0.031) were significantly worse in the SAS <7 group than in the SAS ≥7 group. In a multivariate analysis, however, the SAS was not found to be an independent prognostic factor for either disease-free survival (hazard ratio: 1.39 [0.97-2.00], P = 0.075) or overall survival (hazard ratio: 0.90 [0.57-1.42], P = 0.642). CONCLUSIONS: The SAS reflected preoperative and intraoperative characteristics and was able to stratify the morbidity rate, suggesting it to be a useful predictor of short-term outcomes in non-small-cell lung cancer patients who undergo surgery.

Risk factors for non-cancer death after surgery in patients with stage I non-small-cell lung cancer.

OBJECTIVES: With improvements in the outcome of treatment for non-small-cell lung cancer (NSCLC), other diseases may account for a high death rate after surgery in patients with stage I NSCLC. In the present study, we analysed the associations between the clinical factors and non-cancer death after surgery in these patients. METHODS: The records of 514 patients with stage I NSCLC who underwent surgery were retrospectively reviewed; a proportional hazards model for the subdistribution of a competing risk was conducted to define the risk factors for non-cancer death. RESULTS: The mean patient age was 67 years. A total of 367 patients (71%) underwent bilobectomy or lobectomy while 147 (29%) underwent sublobar resection. The pathological stage was IA in 386 (75%) and IB in 128 (25%) patients. Three patients (0.6%) died within 90 days after surgery, and 108 (21%) experienced postoperative complications. Until the time of writing this report, 83 patients had died during the follow-up. The cause of death was primary lung cancer in 38 (46%) patients and other diseases in 45 (54%) patients, including non-cancer causes in 29 patients, such as pneumonia, cardiac death and cerebral stroke. According to a multivariable competing risk analysis for non-cancer death age (≥70 years), sex (male), body mass index (BMI <18.5), postoperative complications and % forced expiratory volume in 1 s (<80) were identified as risk factors for postoperative non-cancer death. CONCLUSIONS: Advanced age (≥70 years), male sex, low BMI (<18.5), postoperative complications and low preoperative % forced expiratory volume in 1 s (<80) were found to be the risk factors for postoperative non-cancer death after surgery in patients with stage I NSCLC.

Mechanism of monolayer to bilayer silicene transformation in CaSi2 due to fluorine diffusion.

Calcium disilicide (CaSi2) possesses a layered structure composed of alternating monolayers of silicene (MLSi) and calcium. Here the mechanism by which fluorine (F) diffusion into CaSi2 leads to a phase transformation from MLSi to bilayer silicene (BLSi) was investigated. Disorder in intra-layer atomic arrangements and F aggregation were observed using HAADF-STEM in areas of low F concentration. Transformation of MLSi to BLSi in CaSi2Fx was predicted to occur at x = 0.63 based on cluster expansion (CE) and density functional theory (DFT) analyses, and these results agreed well with HAADF-STEM observations. The occurrence of F aggregation at low concentrations was also confirmed by Monte Carlo simulations using the interaction parameters obtained in CE analysis. Bader charge analysis, DFT calculations of charged states, and ab initio molecular dynamics simulations indicated that the aggregated F atoms withdrew electrons from MLSi, destabilizing the buckled honeycomb structure of MLSi in CaSi2. This charge imbalance caused the transformation of MLSi to the covalent-like BLSi.

Validation of Eurolung risk models in a Japanese population: a retrospective single-centre analysis of 612 cases.

OBJECTIVES: The objective of this study was to evaluate the validity of Eurolung risk models in a Japanese population and assess their utility as predictive indicators for the prognosis. METHODS: Between 2007 and 2014, 612 anatomic lung resections were performed among 694 lung cancer patients in our institution. We analysed the cardiopulmonary morbidity and mortality and compared them with the predicted results. We also investigated the association between the Eurolung aggregate risk scores and the long-term outcomes using the Kaplan-Meier method and a multivariable analysis. RESULTS: The percentage of cardiopulmonary complications was lower than that predicted by Eurolung 1 (22.4% vs 24.6%). The mortality rate was significantly lower than predicted by Eurolung 2 (0.7% vs 3.0%). The morbidity rate was stratified by Aggregate Eurolung 1. The stratification of the mortality rate by the Eurolung 2 aggregate score was also in line with the increase in score, although the observed number of deaths was quite small (4 cases). The 5-year overall survival was clearly separated according to the stratified Aggregate Eurolung 1 and 2 (P < 0.01 and P < 0.01, respectively). Besides pathological stage, both the Aggregate Eurolung 1 (score 0-7 vs 8-20) and 2 (score 0-8 vs 9-19) scores were shown to be independently associated with overall survival on multivariable. CONCLUSIONS: Eurolung risk models cannot be directly applied to the patients in our institution. However, Eurolung aggregate risk scores were helpful not only for stratifying morbidity and mortality after anatomic lung resection but also for predicting the long-term outcomes.

Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience.

BACKGROUND: In recent years, the anti-programmed cell death 1 (PD-1) drug pembrolizumab (Keytruda) was approved for treatment of unresectable advanced non-small cell lung cancer (NSCLC) as first- or second-line therapy depending on the clone 22C3-programmed death-ligand 1 (PD-L1) immunohistochemical expression score by the companion diagnostic assay. We herein evaluated 22C3-PD-L1 expression of NSCLC in a single institution experience and compared it with clinicopathologic features. MATERIALS AND METHODS: We assessed 22C3-PD-L1 expressions of 411 patients with NSCLC from our institution, including in past specimens. Programmed death-ligand 1 immunohistochemistry (IHC) testing was performed using the PD-L1 clone 22C3 pharmDx kit (Agilent Technologies/Dako, Carpinteria, CA, USA). Patients were separated into 3 groups with <1% (no expression), 1% to 49% (low expression), or ⩾50% (high expression) positive tumor cells. RESULTS: In all, 137 patients (33%) did not express PD-L1, 155 (38%) showed low expression, and 119 (29%) demonstrated high expression. Archival samples showed lower PD-L1 expression than that of recent samples, and the ratios of no expression case significantly increased by using paraffin blocks embedded particularly in more than 4 years ago. Programmed death-ligand 1 positivity was significantly associated with male sex, smoking, higher tumor grade, squamous cell carcinoma in histologic type, wild-type EGFR, and ALK rearrangement positive. CONCLUSIONS: The rate of 22C3-PD-L1 expression of NSCLC detected in this study was similar to the frequencies of the previous reports, although the ratio of expression case decreased when using old paraffin blocks.

Successful treatment of a bowel fistula in the open abdomen by perforator flaps and an aponeurosis plug.

In this report, we present a case of successful treatment of a bowel fistula in the open abdomen by perforator flaps and an aponeurosis plug. A 70-year-old man underwent total gastrectomy and developed anastomotic leakage and dehiscence of the abdominal wound a week later. He was dependent upon extracorporeal membrane oxygenation, continuous hemodiafiltration, and a respirator. Bowel fluids contaminated the open abdomen. Two months after the gastric operation, a plastic surgery team, in consultation with general surgeons, performed perforator flaps on both sides and constructed, as it were, a bridge of skin sealing the orifice of the fistula. The aponeurosis of the external oblique muscle was elevated with the flap to be used as a plug. The perforators of the flaps were identified on preoperative and intraoperative ultrasonography. This modality allowed us to locate the perforators precisely and to evaluate the perforators by assessing their diameters and performing a waveform analysis. The contamination decreased dramatically afterwards. The bare areas were gradually covered by skin grafts. The fistula was closed completely 18 days after the perforator flap. An ultrasoundguided perforator flap with an aponeurosis plug can be an option for patients suffering from an open abdomen with a bowel fistula.

Assessment of ALK gene rearrangement in lung cancer using a new rapid automated SureFISH (Dako Omnis) assay.

The ALK fluorescence in situ hybridisation (FISH) method is the examination essential for pathological diagnosis and choice of molecular-targeted therapy in ALK-rearranged lung cancer. Here, for detection of ALK gene rearrangement in patients with lung cancer, we evaluated the rapid FISH technology (ALK SureFISH), a newly developed assay for the automated staining platform Dako Omnis, using 21 formalin-fixed paraffin-embedded (FFPE) samples. All cases could be evaluated with the SureFISH method. SureFISH provided excellent quality signals without any background staining. The SureFISH assay was able to offer a rapid turnaround time (approximately 3.5 hours) and was 100% concordant with prior Vysis FISH results in our laboratory.

Graphene/nitrogen-functionalized graphene quantum dot hybrid broadband photodetectors with a buffer layer of boron nitride nanosheets.

A high performance hybrid broadband photodetector with graphene/nitrogen-functionalized graphene quantum dots (NGQDs@GFET) is developed using boron nitride nanosheets (BN-NSs) as a buffer layer to facilitate the separation and transport of photoexcited carriers from the NGQD absorber. The NGQDs@GFET photodetector with the buffer layer of BN-NSs exhibits enhanced photoresponsivity and detectivity in the deep ultraviolet region of ca. 2.3 × 106 A W-1 and ca. 5.5 × 1013 Jones without the application of a backgate voltage. The high level of photoresponsivity persists into the near-infrared region (ca. 3.4 × 102 A W-1 and 8.0 × 109 Jones). In addition, application in flexible photodetectors is demonstrated by the construction of a structure on a polyethylene terephthalate (PET) substrate. We further show the feasibility of using our flexible photodetectors towards the practical application of infrared photoreflectors. Together with the potential application of flexible photodetectors and infrared photoreflectors, the proposed hybrid photodetectors have potential for use in future graphene-based optoelectronic devices.

Graphene Quantum Dots: Molecularly Designed, Nitrogen-Functionalized Graphene Quantum Dots for Optoelectronic Devices (Adv. Mater. 23/2016).

H. Tetsuka and co-workers develop a versatile technique to tune the energy levels and energy gaps of nitrogen-functionalized graphene quantum dots (NGQDs) continuously through molecular structure design, as described on page 4632. The incorporation of layers of NGQDs into the structures markedly improves the performance of optoelectronic devices.

Molecularly Designed, Nitrogen-Functionalized Graphene Quantum Dots for Optoelectronic Devices.

Nitrogen-functionalized graphene quantum dots (NGQDs) with tailorable optical properties are prepared by a versatile technique, which allows the highest occupied molecular orbital/lowest unoccupied molecular orbital energy levels and energy gaps to be continuously varied. The integration of NGQD layers into the structures significantly improves the performance of optoelectronic devices.

Ectopic cervical thymoma accompanied by Good's syndrome.

Ectopic cervical thymoma (ECT) is a rare tumor that is frequently misdiagnosed as a thyroid tumor or other malignancy. A 34-year-old male with a right palpable neck mass had been mistakenly diagnosed with T-cell lymphoblastic lymphoma even after an open biopsy. The atypical clinical course, including hypogammaglobulinemia, led us to the correct diagnosis; ECT accompanied by Good's syndrome (GS). After the intravenous infusion of gammaglobulin, tumor resection and a subsequent video-assisted thoracoscopic extended thymectomy were performed. The final diagnosis was type AB thymoma, Masaoka stage I. This report is, to the best of our knowledge, the first description of this extremely rare combination.

Optically tunable amino-functionalized graphene quantum dots.

Amino-functionalized graphene quantum dots (af-GQDs) with discrete molecular weights and specific edges were self-limitedly extracted from oxidized graphene sheet. Their optical properties can be precisely controlled only by the selective and quantitative functionalization at the edge sites. The af-GQDS exhibit bright colorful fluorescence under a single-wavelength excitation.

Adsorption states of methylthiolate on the Au(111) surface.

We have studied the adsorption structures of methylthiolate (MeS) on the Au(111) surface using density functional theory. The most stable adsorption structure of MeS is the MeS-Au-MeS configuration, which has been proposed by Maksymovych and co-workers (2006 Phys. Rev. Lett. 97 146103), followed by the bridge configuration. The calculated work function change and vibrational mode analysis for the two configurations agree quite well with the experimental results. These results strongly support the conclusion that the MeS-Au-MeS and the bridge configurations coexist on the MeS adsorbed Au(111) surface.