Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.

Systematic review and meta-regressions: management of eosinophilic esophagitis requires histologic assessment.

Treatment endpoints in eosinophilic esophagitis (EoE) are response of eosinophilic inflammation and of symptoms. Steroids and diet therapy are effective in inducing histologic response in EoE, but there may be poor correlation between histologic and symptomatic response. Despite this, we find that in clinical practice symptoms are commonly used to guide management without assessing histologic response. We hypothesized that symptom response alone is not reliable in assessing response to therapy and is confounded by endoscopic dilation. We conducted a systematic review and meta-regressions to estimate the association of histologic and symptomatic response, stratified by whether concurrent dilation was permitted. We performed a systematic search of PubMed, EMBASE, and Web of Science for studies describing both histologic and symptomatic responses to dilation, steroid, and diet therapies. We abstracted the proportion of histologic response and symptom response. Studies were stratified by whether dilation was permitted. We performed meta-regressions of the association between the proportions with histologic and symptomatic response, stratified by whether dilation was permitted. We identified 1359 articles, of which 62 articles were assessed for eligibility, and 23 were included providing data on 1202 patients with EoE. Unstratified meta-regression of histologic versus symptomatic response showed moderate association and large heterogeneity (inconsistency index [I2] = 89%). In adult studies in which dilation was allowed, there was weak association between symptomatic and histologic response (ß1 = 0.21), minimal symptomatic response of 67% and the heterogeneity persisted, I2 = 77%. In studies that prohibited dilation, maximal symptomatic response was 72% and was moderately associated with histologic response (ß1 = 0.39) with less heterogeneity, I2 = 59%. Studies of EoE that permit dilation obscure the relation between histologic and symptomatic response and have a high floor effect for symptomatic response. Studies that prohibit dilation demonstrate moderate association between histologic and symptomatic response, but have a ceiling effect for symptomatic response. Our results demonstrate that success of dietary or medical management for EoE cannot be judged by symptoms alone, and require histologic assessment, particularly if dilation has been performed.

Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study.

Despite optimal pharmacotherapy and cognitive-behavioral treatments, a proportion of patients with obsessive-compulsive disorder (OCD) remain refractory to treatment. Neurosurgical ablative or nondestructive stimulation procedures to treat these refractory patients have been investigated. However, despite the potential benefits of these surgical procedures, patients show significant surgery-related complications. This preliminary study investigated the use of bilateral thermal capsulotomy for patients with treatment-refractory OCD using magnetic resonance-guided focused ultrasound (MRgFUS) as a novel, minimally invasive, non-cranium-opening surgical technique. Between February and May 2013, four patients with medically refractory OCD were treated with MRgFUS to ablate the anterior limb of the internal capsule. Patients underwent comprehensive neuropsychological evaluations and imaging at baseline, 1 week, 1 month and 6 months following treatment. Outcomes were measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A), and treatment-related adverse events were evaluated. The results showed gradual improvements in Y-BOCS scores (a mean improvement of 33%) over the 6-month follow-up period, and all patients showed almost immediate and sustained improvements in depression (a mean reduction of 61.1%) and anxiety (a mean reduction of 69.4%). No patients demonstrated any side effects (physical or neuropsychological) in relation to the procedure. In addition, there were no significant differences found in the comprehensive neuropsychological test scores between the baseline and 6-month time points. This study demonstrates that bilateral thermal capsulotomy with MRgFUS can be used without inducing side effects to treat patients with medically refractory OCD. If larger trials validate the safety, effectiveness and long-term durability of this new approach, this procedure could considerably change the clinical management of treatment-refractory OCD.

Characterization and analysis of finite-beam Bragg diffraction in a periodically poled lithium niobate electro-optic grating.

We report the study, both theoretical and experimental, of the finite-beam Bragg diffraction behavior of an electro-optic (EO) volume grating made of a periodically poled lithium niobate (PPLN) crystal. When a Gaussian laser beam is used, the experimental observations show that the diffraction characteristics of the PPLN EO Bragg device, including the diffraction mode pattern and diffraction efficiency, are closely related to the interaction beam size and applied voltage, which cannot be modeled properly by a simplified theory using the plane-wave approximation. In this work, we have developed a theoretical model for describing the diffraction behavior of a PPLN EO Bragg device based on the coupled-wave theory with the aid of the plane-wave decomposition method. Specifically, we found that it is the angular distribution (or the dephasing bandwidth) of the plane wave elements decomposed from the incident Gaussian beam and grating strength that determine the Bragg coupling behavior of the device. We also identified some other electro-optically induced effects in the PPLN grating as an important mechanism in affecting the diffraction performance of the present device, especially at high working voltages.

Blended learning in situated contexts: 3-year evaluation of an online peer review project.

BACKGROUND: Situated and sociocultural perspectives on learning indicate that the design of complex tasks supported by educational technologies holds potential for dental education in moving novices towards closer approximation of the clinical outcomes of their expert mentors. A cross-faculty-, student-centred, web-based project in operative dentistry was established within the Universitas 21 (U21) network of higher education institutions to support university goals for internationalisation in clinical learning by enabling distributed interactions across sites and institutions. This paper aims to present evaluation of one dental faculty's project experience of curriculum redesign for deeper student learning. METHODS: A mixed-method case study approach was utilised. Three cohorts of second-year students from a 5-year bachelor of dental surgery (BDS) programme were invited to participate in annual surveys and focus group interviews on project completion. Survey data were analysed for differences between years using multivariate logistical regression analysis. Thematic analysis of questionnaire open responses and interview transcripts was conducted. RESULTS: Multivariate logistic regression analysis noted significant differences across items over time indicating learning improvements, attainment of university aims and the positive influence of redesign. Students perceived the enquiry-based project as stimulating and motivating, and building confidence in operative techniques. Institutional goals for greater understanding of others and lifelong learning showed improvement over time. Despite positive scores, students indicated global citizenship and intercultural understanding were conceptually challenging. CONCLUSIONS: Establishment of online student learning communities through a blended approach to learning stimulated motivation and intellectual engagement, thereby supporting a situated approach to cognition. Sociocultural perspectives indicate that novice-expert interactions supported student development of professional identities.

Double-prism domain PPLN for simultaneous laser Q-switching and optical parametric oscillation in a Nd:YVO4 laser.

We report a design and demonstration of an electro-optically Q-switched intracavity optical parametric oscillator (IOPO) based on a unique ramped duty-cycle periodically poled lithium niobate (PPLN) in a diode-pumped 1064-nm Nd:YVO(4) laser. The PPLN crystal, having a double-prism domain (DPD) structure with a domain period of 30 µm, can work simultaneously as an electro-optic (EO) beam deflector (and therefore an EO Q-switch in the laser cavity) and an optical parametric down converter. The characterized deflection sensitivity of the DPD PPLN device was 1.15°/kV-cm. At a 180-V Q-switching voltage and a 1-kHz switching rate, we measured a down-converted signal at 1550 nm with pulse energy of >8.1 µJ (or peak power of >2.3 kW) from the constructed IOPO at 7.5-W diode pump power. Continuous wavelength tuning of the IOPO signal was also demonstrated.

Tunable, pulsed multiline intracavity optical parametric oscillator using two-dimensional MgO: periodically poled lithium niobate-aperiodically poled lithium niobate.

We report a tunable, pulsed multiline intracavity optical parametric oscillator (IOPO) realized in an Nd:YVO4 laser using a two-dimensionally domain engineered MgO:LiNbO3 as simultaneously an electro-optic Bragg Q switch and a multichannel optical parametric downconverter. The MgO:LiNbO3 was periodically and aperiodically poled along the crystallographic y and x axes, respectively, to simultaneously satisfy the phase-matching conditions required by the two quasi-phase-matching devices. When Q switched by 1 kHz, 300 V pulses, three signal lines at 1518, 1526, and 1534 nm were simultaneously generated, each with a peak power of ∼1 kW from the IOPO at 8.3 W diode power at 50°C. Spectral tuning of the three-line IOPO with temperature was demonstrated.

Serum apolipoprotein C-II is prognostic for survival after pancreatic resection for adenocarcinoma.

BACKGROUND: Pancreaticoduodenectomy remains a major undertaking. A preoperative blood test, which could confidently predict the benefits of surgery would improve the selection of pancreatic cancer patients for surgery. This study aimed to identify protein biomarkers prognostic for long-term survival and to validate them with clinico-pathological information. METHODS: Serum from 40 preoperative patients was used to train for predictive biomarkers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI), and the results were verified on 21 independent samples. Two predictive proteins were identified by tryptic peptide mass fingerprinting and sequencing, and validated on serum from another 57 patients by enzyme-linked immunosorbent assay (ELISA). The influence of these proteins on growth and invasion of two cancer cell lines was tested in-vitro. RESULTS: The SELDI panel of m/z 3700, 8222 and 11 522 peaks predicted <12 months' survival (ROC AUC: 0.79, 0.64-0.90; P<0.039). When CA19-9 was added, the ROC AUC increased to 0.95 (0.84-0.99; P<0.0001). The six subjects in the verification group who died within 12 months were correctly classified. The m/z 8222 and 11 522 proteins were identified as Serum ApoC-II and SAA-1, respectively. In the validation samples, ELISA results confirmed that ApoC-II was predictive of survival (Kaplan-Meier P<0.009), but not SAA-I. ApoC-II, CA19-9 and major-vessel involvement independently predicted survival. ApoC-II and SAA-1 increased cell growth and invasion of both cancer cell lines. CONCLUSION: Serum ApoC-II, CA19-9 and major-vessel invasion independently predict survival and improves selection of patients for pancreaticoduodenectomy.

Electro-optically tunable, multi-wavelength optical parametric generators in aperiodically poled lithium niobates.

We report on the design and demonstration of electro-optically tunable, multi-wavelength optical parametric generators (OPGs) based on aperiodically poled lithium niobate (APPLN) crystals. Two methods have been proposed to significantly enhance the electro-optic (EO) tunability of an APPLN OPG constructed by the aperiodic optical superlattice (AOS) technique. This is done by engineering the APPLN domain structure either in the crystal fabrication or in the crystal design process to increase the length or block-number difference of the two opposite-polarity domains used in the structure. Several orders of magnitude enhancement on the EO tuning rate of the APPLN OPGs constructed by the proposed techniques for simultaneous multiple signal wavelength generation over a conventional one has been demonstrated in a near infrared band (1500-1600 nm).

Internal Q-switching and self-optical parametric oscillation in a two-dimensional periodically poled Nd:MgO:LiNbO3 laser.

We report on an internally Q-switched self-optical parametric oscillator (SOPO) based on a monolithic two-dimensional (2D) periodically poled Nd:MgO:LiNbO(3) (Nd:MgO:PPLN) integrating three device functionalities of a laser gain medium, an electro-optic Bragg Q-switch, and an optical parametric gain medium (OPGM). The quasi-phase-matching conditions required by the Bragg Q-switch and OPGM are both satisfied in the 2D nonlinear photonic crystal (NPC) structure formed in the Nd:MgO:PPLN. A 1525 nm signal with a pulse energy of ∼3.3 µJ (>350 W peak power) was obtained from the SOPO at 8.5 W diode pump power. An off-angle signal at 1612 nm, amplified by a unique gain-enhancement effect in this 2D NPC, was also observed. Tuning of the SOPO in the eye-safe region was demonstrated.

Higher rate of colorectal cancer among patients with pyogenic liver abscess with Klebsiella pneumoniae than those without: an 11-year follow-up study.

AIM: Pyogenic liver abscess (PLA) has been reported as an early manifestation of colorectal cancer (CRC) in adults, but few studies have investigated this relationship. It is unclear if patients with Klebsiella pneumoniae PLA are at increased risk of subsequent CRC. Our aims were to estimate the incidence of CRC among patients with PLA and to compare the incidence of CRC between K. pneumoniae PLA and non-K. pneumoniae PLA groups. METHOD: We conducted a retrospective study of patients with PLA diagnosed between 2000 and 2009 at a medical centre in northern Taiwan. CRC status and survival status were determined until December 2010. Incidence data from the general population were retrieved from the Taiwan Cancer Registry. Outcome measures were defined as standardized incidence ratio and the incidence rate per 100,000 person-years. RESULTS: This study included 2294 patients, of whom 1194 (52%) had K. pneumoniae infection. During the follow-up period, 54 (2.3%) patients were diagnosed with CRC, corresponding to an overall incidence rate of 669.1 (95% CI, 490.7-847.6) per 100,000 person-years. The adjusted hazard ratio of CRC was 2.68 times greater for patients with K. pneumoniae PLA than for those with non-K. pneumoniae PLA (95% CI, 1.40-5.11). CONCLUSION: Patients with K. pneumoniae PLA had a significantly higher rate of subsequent CRC than did patients with non-K. pneumoniae PLA. Colonoscopy is recommended to detect occult colonic malignancy in patients with PLA, particularly for patients over 60 years of age and with K. pneumoniae.

Evaluation of fiber post-supported restorations under simulated occlusal loading.

STATEMENT OF PROBLEM: There is a lack of information comparing the effect of a rigid versus flexible post on the marginal seal of post-and-core supported crowns subjected to long-term repeated loading. PURPOSE: The purpose of this study was to examine the leakage pattern of complete coverage restorations retained with either a metal or fiber-reinforced resin post under simulated occlusal loads. MATERIAL AND METHODS: Thirty-six maxillary central incisors were endodontically treated and provided with a post-and-core supported crown. One group was restored with a fiber-post (EasyPost Lux) and another was restored with a metal post (Parapost) (n=12). Both groups were loaded for 120,000 cycles to 70 N while immersed in a dye solution. A control group (n=12), similarly restored with a fiber post but not loaded, was also included. All teeth were transversely sectioned serially from the tooth-core interface towards the apex. Digital photographs were made to determine the extent of leakage on the buccal, mesial, palatal, and distal aspects along the depth of the post. A nonparametric Kruskal-Wallis test was used to determine any difference between groups (α=.05). RESULTS: Dye penetration occurred in all stress-cycled specimens and was more extensive on the palatal than other aspects. The fiber-post group cyclically stressed to 70 N showed a significantly greater amount of leakage than the control or the Parapost group (P<.05). CONCLUSIONS: In in vitro testing, the rigidity of the post influenced the seal of post-and-core-supported crowns at the palatal margin.

Performance of the new biological small- and wide-angle X-ray scattering beamline 13A at the Taiwan Photon Source.

Recent developments in the instrumentation and data analysis of synchrotron small-angle X-ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small- and wide-angle X-ray scattering (SAXS-WAXS or SWAXS). The endstation features an in-vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size-exclusion chromatography system incorporating several optical probes including a UV-Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS-WAXS data collection and data reduction for high-throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal-model fittings to the data in the q range ∼0.005-2.0 Å-1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration-dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.

Two-dimensional PPLN for simultaneous laser Q-switching and optical parametric oscillation in a Nd:YVO4 laser.

We report on a tunable intracavity optical parametric oscillator (IOPO) achieved using a two-dimensional (2D) periodically poled lithium niobate (PPLN) as simultaneously an electro-optic (EO) Bragg Q-switch and an optical frequency mixer (OFM) in a diode-pumped Nd:YVO(4) laser. The 2D periodic domain inversion structure is designed to provide two orthogonal reciprocal vectors to respectively satisfy the phase-matching conditions required by the two quasi-phase-matching devices (i.e., the PPLN EO Bragg deflector and the PPLN OFM). At a ~140-V Q-switching voltage and a 1-kHz switching rate, we obtained a signal wave at 1550 nm with a pulse energy of 9.7 µJ (corresponding to a peak power of ~2.4 kW) from the IOPO at 9.1-W diode pump power. Simultaneously we also observed multi-wavelength generation from the system originating in the single-pass parametric conversions in the 2D nonlinear photonic crystal structure. Temperature tuning of the IOPO signal wavelength in the eye-safe region was also demonstrated.

Recurrent disease following endoscopic ablation of Barrett's high-grade dysplasia with spray cryotherapy.

BACKGROUND AND AIMS: Recurrent disease after endoscopic ablation of Barrett's esophagus should be detected early to prevent malignant progression. We assessed the incidence and patterns of disease recurrence in patients after liquid nitrogen spray cryotherapy ablation of Barrett's esophagus with high grade dysplasia (HGD), including the area below the neosquamocolumnar junction (NSCJ). PATIENTS AND METHODS: This is a single-center, retrospective study of prospectively collected data on consecutive cases of endoscopic ablation with liquid nitrogen spray cryotherapy for Barrett's HGD. Post-treatment surveillance biopsies were obtained of suspicious lesions and in 4 quadrants every 1 cm in the treated esophagus and just below the NSCJ. Primary outcome measures were location and histology of recurrent disease. RESULTS: 36 patients (median age 62 years, 92% men) were enrolled, and 11 (30%) developed recurrent disease in a median of 6.5 months; three developed a second recurrence. Ten recurrences (71%) were identified below the NSCJ in 9 patients, including HGD (4), low grade dysplasia (LGD) (2), and intestinal metaplasia (4). Six recurrences were identified in the treated esophagus in five patients, including intramucosal cancer (1), HGD (1), and intestinal metaplasia (4). Two patients had recurrent disease involving both locations. Ultimately 33 patients (92%) achieved a complete response. Diagnosis in the remaining three was LGD (1) and intestinal metaplasia (2). CONCLUSION: Most patients with recurrent intestinal metaplasia with or without dysplasia after ablation achieve a complete response. Recurrent disease commonly involves the area just below the NSCJ. Surveillance endoscopies should include this area to accurately identify patients with disease recurrence.

Peripheral compressing artifacts in brain tissue from stereotactic biopsy with sidecutting biopsy needle: a pitfall for adequate glioma grading.

AIMS: The stereotactic brain biopsy is an essential diagnostic procedure in modern neurologic patient management. A side-cutting biopsy needle is one of the most widely used needle types. Recently we found a characteristic tissue artifact named "peripheral compressing artifact" in the brain tissues biopsied using a side-cutting needle of Leksell's system. We investigate prevalence, possible cause and its clinical implication of this type of artifact. MATERIALS AND METHODS: We examined the biopsies from 80 patients (44 cases of gliomas, 13 lymphomas, 7 germ cell tumors, 2 other tumors, 1 metastatic carcinoma, 4 non-tumorous conditions such as demyelinating disease and 8 non-diagnostic) in the stereotactic biopsy group with a suspected brain tumor, who underwent a stereotactic brain biopsy using side-cutting needle of Leksell's system. We also evaluated 16 cases of open brain biopsies without Leksell's system as a control group. RESULTS: The artifact is a semi-circular or band-like tissue compression in the periphery of the biopsied tissue. This artifact was found in 30 (37.5%) out of 80 cases and 57 (11.9%) out of 477 biopsied pieces. It might be produced during rotating of the inner cannula of the biopsy needle. Histologically, it might be misinterpreted as "hypercellular", "spindle", "well circumscribed", or rarely as "pseudopalisading" especially in glioma. CONCLUSIONS: Awareness of this artifact would help making the appropriate pathological diagnosis for glioma.

EZH2 silencing by RNA interference inhibits proliferation in bladder cancer cell lines.

The Enhancer of Zeste homologue2 gene (EZH2) is frequently expressed at high levels in malignant tumours, including bladder cancer. It functions as a transcriptional regulator to the maintenance of cell identity, cell cycle regulation and oncogenesis. In the study, we detected EZH2 expression in bladder cancer tissues. These results showed EZH2 high expression in bladder cancer tissue at level of transcript and protein compared with normal bladder tissue and EZH2 expression correlated positively with tumour stage and grade. Then, we used RNA interference to inhibit EZH2 expression in bladder cancer EJ cell line. Efficient downregulation of EZH2 resulted in significantly decreased cell proliferation in EJ cells and retarded transition of G(1) phase to S phase. Our data suggest that EZH2 is involved in the tumourigenesis of bladder cancer and EZH2 downregulation contributes to inhibiting malignant growth by retarding cell entrance to S phase.

Electro-optic guided-to-radiation mode conversion in annealed proton-exchanged PPLN waveguides.

We report the design and experimental demonstration of electro-optically active TM-guided to TE-radiation mode converters in annealed proton-exchanged (APE) periodically poled lithium niobate (PPLN) channel waveguides in telecom S-C-L bands (1495-1640 nm). A maximum mode conversion efficiency of >95%/cm was obtained at 1520 nm from a 24-µm-period APE PPLN waveguide under an electro-optic (EO) field of ~6.3 V/µm at 35°C. This efficiency has been enhanced by a factor of >4.6 over a waveguide built in the single-domain (unpoled) LiNbO3; it is also to the best of our knowledge the most efficient guided-to-radiation (GTR) mode converter ever reported based on LiNbO3 on-axis waveguides. A conversion bandwidth of ~250 nm was also observed from this EO GTR mode converter.

Pulsed orange generation optimized in a diode-pumped Nd:YVO4 laser using monolithic dual PPLN electro-optic Q switches.

We report a pulsed intracavity sum-frequency generator in a diode-pumped, dual-wavelength Nd:YVO(4) laser whose operation was optimized with two electro-optic Q switches built in a monolithic periodically poled lithium niobate (PPLN) crystal. The dual PPLN Q switches, though integrated, are able to work separately at their respective working wavelengths of 1064 and 1342 nm. At 4.8 W diode pump power and 5 kHz Q-switching rate, a maximum orange (593 nm) output peak power of >480 W was achieved in this laser system using the Q-switch opening-time offset technique. This power is approximately 1.7 times higher than that obtained with the system operated in a conventional single-Q-switch mode.