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BACKGROUND: According to statistics of the Ministry of Health and Welfare in 2017, the second leading cause of death in Taiwan was lung cancer. OBJECTIVE: Routine treatment planning does not consider photoneutron dose equivalent (PNDE) of patient induced secondary radiation resulting from primary exposure of lung cancer. However, such treatment is potentially important for improving estimates of health risks. METHODS: This study used 10, 30, 50, 70, and 90 kg of polymethylmethacrylate (PMMA) phantoms as patient to measure PNDE varying anatomical area during lung cancer of intensity modulated radiotherapy (IMRT) treatment. Paired thermoluminescent dosimeters (TLD-600 and 700) were calibrated using university reactor neutrons. TLDs were inserted into phantom which was closely corresponded of the represented tissues or organs. RESULTS: Neutron doses (ND) of organ or tissue (N⁢DT) were determined in these phantoms using paired TLDs approach. The risks of incurring fatal secondary malignancies, maximum statistical and total errors were estimated. Evaluated PNDE ranged from 0.80 ± 0.12 to 0.56 ± 0.08 mSv/Gy for these phantoms. CONCLUSION: The estimated N⁢DT decreased with increasing distance that is from the central axis. Evaluated PNDE and N⁢D𝑠𝑘𝑖𝑛 for these phantoms were discussed. This investigation also identified secondary risks associated with PNDE relating to radiation protection.

Fast Radio Bursts (FRBs) are bright millisecond-duration radio transients that appear about 1,000 times per day, all-sky, for a fluence threshold 5 Jy ms at 600 MHz. The FRB radio-emission physics and the compact objects involved in these events are subjects of intense active debate. To better constrain source models, the Bustling Universe Radio Survey Telescope in Taiwan (BURSTT) is optimized to discover and localize a large sample of rare, high-fluence, nearby FRBs. This is the population most amenable to multi-messenger, multi-wavelength follow-up, allowing deeper understanding of source mechanisms. BURSTT will provide horizon-to-horizon sky coverage with a half power field-of-view (FoV) of $\sim$10$^{4}$ deg$^{2}$, a 400 MHz effective bandwidth between 300-800 MHz, and sub-arcsecond localization, made possible using outrigger stations hundreds to thousands of km from the main array. Initially, BURSTT will employ 256 antennas. After tests of various antenna designs and optimization of system performance we plan to expand to 2048 antennas. We estimate that BURSTT-256 will detect and localize $\sim$100 bright ($\geq$100 Jy ms) FRBs per year. Another advantage of BURSTT's large FoV and continuous operation will be greatly enhanced monitoring of FRBs for repetition. The current lack of sensitive all-sky observations likely means that many repeating FRBs are currently cataloged as single-event FRBs., Published version

The aim is to investigate the effect of lotus (

BACKGROUND: The routine radiation therapy treatment planning does not include secondary radiation and peripheral doses resulting from radiotherapy exposure in patients with nasopharyngeal carcinoma (NPC) undergoing Volumetric Modulated Arc Therapy (VMAT) using an linear accelerator (linac) of Axesse (Elekta 2538). OBJECTIVE: VMAT has a better dose conformity of the tumor and is also operated by adjusting the shapes of mulileaf collimator. However, such treatment is potentially important to improve the accuracy of estimated health risks. METHODS: This study aimed to evaluate the equivalent dose of organ or tissue (DT) and effective dose (E) for normal organs using the Alderson Rando phantom as an equivalent of the human body. Thermoluminescent dosimeters (TLD-100H) were calibrated by 6 MV X-ray originated by the linac. A total of 252 TLDs were used. These TLDs were inserted into phantom organ or tissue which closely approximated to these places. RESULTS: The thyroid dose (D𝑡ℎ𝑦) had the highest dose, 1840 ± 202 mSv/treatment. The E of the Rando was 7.11 ± 0.61 mSv/treatment, as estimated using ICRP 103. The skin doses (D𝑠𝑘𝑖𝑛) varied significantly outside the treatment field and decreased as the distance from the treatment field increased. CONCLUSIONS: This study can be referred to practical guidance regarding radiation protections of the public.

In approximately 50% of patients with oral cavity squamous cell carcinoma (OCSCC), the disease progresses after curative surgery. However, the role of salvage surgery (SS) is controversial, and life expectancy after SS is unknown.In this study, 262 patients with OCSCC with locoregional recurrence and second primary OCSCC were retrospectively enrolled and divided into a resectable (55.0%, 144/262) and unresectable (45.0%, 118/262) groups. After excluding neck recurrence only, SS had been performed 195 times in the resectable group. The corresponding preoperative clinicopathologic factors and postsurgery survival (PSS) of each SS were pooled for analysis.Median survival after disease progression was 64.2 and 10.4 months for the resectable and unresectable groups, respectively. In the resectable group, one-fifth (19.5%, 37/190) of the patients died within 1 year of SS (PSS 1 year), and one-third (32.8%, 64/195) of the patients had undergone SS two or more times. The interval from the last surgery ≤ 12 months, depth of invasion of the last surgery 1 cm, and clinical evidence of nodal disease at the preoperative evaluation were independent predictors of poor PSS. A scoring prediction model was established with 1 point for each factor. The results revealed 1-year postsurgery death rates of 10.3% in the low-risk group (score: 0-1) and 48.6% in the high-risk group (score: 2 or 3) (P 0.001).In conclusion, an effective scoring model predicting life expectancy after SS for patients with OCSCC was established.

Early progression, defined as a disease-free interval (DFI) of less than 6 months after completion of adjuvant platinum-based chemoradiotherapy (CRT), leads to poor outcomes in locally advanced oral cavity squamous cell carcinoma (OCSCC). However, appropriate biomarkers for predicting early progression remain unknown.In this study, 346 patients with OCSCC, who underwent curative surgical resection and platinum-based adjuvant CRT at the Taipei Veterans General Hospital (202 patients, training cohort) and Chung Shan Medical University Hospital (144 patients, validation cohort) were enrolled. The clinical-pathological variables were compared using the χOne-fifth (20.5%, 71/346) of all patients experienced progression within 6 months. Each of the independent factors for the DFI in the training cohort, including pT3-4, extracapsular spread, and perineural invasion, were assigned a score of one point to establish a scoring system. The 6-month DFIs of the low-risk (score 0-1), intermediate-risk (score 2), and high-risk (score 3) groups were 97.8%, 78.7%, and 35.7% and 88.2%, 77.6%, and 42.1% in the training and validation cohorts, respectively. If the cutoff level was ≥2 or2, the sensitivity/specificity/area under the curve for the training and validation cohorts were 94.4%/56.1%/0.837, and 73.3%/56.6%/0.703, respectively.The established scoring system effectively predicted early progression after adjuvant CRT for locally advanced OCSCC.

Background Acetaminophen (APAP) is one of the most widely used analgesic agents while overdose APAP will lead to severe hepatotoxicity. Lotus seedpod, a traditional herbal, is rich in polyphenol and has been shown to possess antioxidant, radioprotective and anti-cancer activities. This study examined the hepatoprotective role of lotus seedpod extracts (LSE) in vitro and in vivo. Methods Firstly, LSE or its main compound epigallocatechin (EGC) dose-dependently improved the survival of human hepatocyte HepG2 cells from APAP-induced loss of viability. In vivo study, the BALB/c mice were supplemented with or without LSE (1% and 2%) during the 9-week treatment period in the presence or absence of APAP (i.p.; 400 mg/kg) twice per week. Results In vitro study revealed that LSE or EGC showed potential in reducing APAP-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the distribution of hypodiploid phase, apoptotic bodies formation, and caspases activation. Molecular data showed that antiapoptotic effects of LSE or EGC mediated via intrinsic, extrinsic and ASK 1/JNK apoptotic signaling pathways. Further data showed that LSE inhibited the APAP-induced the protein expression of iNOS to decrease inflammation. In vivo study showed that LSE treatments significantly decreased the serum levels of the hepatic enzyme markers GOT and GPT induced by APAP. LSE also inhibited the serum levels of inflammatory cytokines (IL-6 and IL-1β) during APAP treatment. LSE at 1% significantly restored the decrease in glutathione (GSH) content and elevated the levels of antioxidant enzymes, including catalase and glutathione reductase (GRd), in the liver. Western blotting data demonstrated that LSE inhibited the expression of caspase − 3, -8, -9 in APAP-induced liver injury. Conclusions LSE protected APAP-induced hepatotoxicity which could be a novo strategy for treatment.

The World Health Organization regards betel quid (BQ) as a human carcinogen. The current study analyzes whether the BQ cues can elicit activity in the chewers' craving-related brain areas. We adopted a cue-reactivity paradigm to examine the changes in the brain activities. The urge intensity was also included to examine whether it can moderate the brain areas stimulated by BQ cues. Sixteen male BQ chewers and 16 healthy male controls were recruited and analyzed. Four types of cues were adopted: BQ cues, matched food cues, visual control cues, and resting crosshair cued. The most direct and important comparison was between the brain activities elicited by the BQ cues versus those by the food cues. Furthermore, to test the current urge intensity effect, we compared BQ chewers with a strong urge versus those with a weak urge. All of the three-dimension anatomical and multi-slice task-based functional images were acquired using 3 T MRI. We found that (1) the BQ chewers and the healthy controls had similar brain activation patterns when comparing any two cue types, (2) the high-urge (not the low-urge) chewers showed craving-related activations (e.g., anterior cingulate cortex, medial orbitofrontal gyrus, and superior frontal gyrus) in the critical BQ cues vs. the food cue comparisons. (3) The high-urge chewers had larger contrast activations (BQ - Food) in many craving-related brain areas than low-urge chewers did (e.g., frontal gyrus). The urge states endorsed by the chewers can moderate the neural responses to BQ cues. Multisensory cues should be considered to elicit more intense and consistent cravings.

Purpose: The effective dose (HE) and organ or tissue equivalent dose (HT) of a Rando phantom undergoing two brain computed tomography (CT) examination protocols were evaluated using thermoluminescent dosimeters (TLD-100H) and dose length product (DLP) methods. Materials and methods: TLDs were inserted into the correlated positions of an organ or tissue of Rando phantom, such as thyroid, brain, and salivary gland, using (A) axial scan: scanning the maxillae ranging from external auditory meatus to the parietal bone, and (B) helical scan: scanning from the mandible to the parietal bone. CT examinations were performed on a Philips computer tomography (Brilliance CT) at Lukang Christian Hospital. TLDs were measured using a Harshaw 3500 TLD reader. The HT of organ and tissue during the two protocols was discussed. Results and conclusion: HE were calculated using ICRP 60 and 103 at 2.67 ± 0.18 and 1.89 ± 0.23 mSv based on an axial scan, and 4.70 ± 0.38 and 4.39 ± 0.37 mSv based on a helical scan, respec...

Betel quid (BQ) is a common addictive substance in many Asian countries. However, few studies have focused on the influences of BQ on the brain. It remains unclear how BQ can affect structural brain abnormalities in BQ chewers. We aimed to use generalized q-sampling imaging (GQI) to evaluate the impact of the neurological structure of white matter caused by BQ. The study population comprised 16 BQ chewers, 15 tobacco and alcohol controls, and 17 healthy controls. We used GQI with voxel-based statistical analysis (VBA) to evaluate structural brain and connectivity abnormalities in the BQ chewers compared to the tobacco and alcohol controls and the healthy controls. Graph theoretical analysis (GTA) and network-based statistical (NBS) analysis were also performed to identify the structural network differences among the three groups. Using GQI, we found increases in diffusion anisotropy in the right anterior cingulate cortex (ACC), the midbrain, the bilateral angular gyrus, the right superior temporal gyrus (rSTG), the bilateral superior occipital gyrus, the left middle occipital gyrus, the bilateral superior and inferior parietal lobule, and the bilateral postcentral and precentral gyrus in the BQ chewers when compared to the tobacco and alcohol controls and the healthy controls. In GTA and NBS analyses, we found more connections in connectivity among the BQ chewers, particularly in the bilateral anterior cingulum. Our results provided further evidence indicating that BQ chewing may lead to brain structure and connectivity changes in BQ chewers.

The use of multi-detector row computed tomography in cardiac examinations is increasing globally. Several hospitals are yet to establish a practical method for evaluating the extra scattering dose in the lungs (Dlung) of male examinees with different body-weights undergoing cardiac computed tomography. To measure the dose in each slice of a lung (Dlung,i), thermoluminescent dosimeters are inserted into Rando and tissue-equivalent phantoms made of polymethylmethacrylate and derived from ICRU 48 with masses from 10 to 90 kg. Dlung was evaluated by weighing the scanned volume of each slice. A practical method for determining Dlung involves 64-slice computed tomography scans using a Philips Brilliance computed tomography at 120 kV and 200 mAs, with a thickness of 1.0 mm. Dlung,i increased with distance from the scanning region. This experiment yielded Dlung values from 12.1 ? 2.1 mSv (90 kg) to 23.0 ? 3.8 mSv (10 kg). Finally, a simple equation can be used to derive the relationship between Dlung and the body-weights of a male examinee. Experimental results are compared with others in the literature.

Delineating organs for a long time may cause exhaustion to radiologist’s eyes and mental health, it could lead to results that show different sizes of organs with therapeutic target volume. In this work, we expand on the idea of automatically delineating the organs in Computed Tomography (CT) images of head and neck through the generative adversarial network, which is a deep learning algorithm. In image preprocessing, we generate a bitmap (BMP) image by the combination of CT image and RT structure (RS) file and input it to generator network, which will improve the color and texture quality, last generate a fake Radiation Therapy (RT) image. Finally, the discriminator network takes the fake RT image as an example to compare with the original RT image. To build the predictive model, we continuously train this model to let it learn the rules of delineating organs in CT image, generating more and more images that are similar to the original samples. The approach that proposed in this paper is actually well applied in medicine, and the results of testing are similar to the selected organs or therapeutic targets’ volume that was delineated by the radiologist. We can see that it not only effectively reduces the false positive rate but also promises in applying to other related images.

The effective dose (HE) and organ or tissue equivalent dose (HT) for use in brain computed tomography (CT) examinations with various body weights were evaluated. Thermoluminescent dosimeters (TLD-100H) were inserted into Rando and five anthropomorphic phantoms. These phantoms were made of polymethylmethacrylate (PMMA), according to the specifications of ICRU 48, with masses from 10 to 90 kg. Brain CT examinations were conducted, scanning the maxillae from the external auditory meatus to the parietal bone using a 128-slice multi-detector CT (MDCT) scanner. To reduce errors, three independent trials were conducted. Calculated HE,TLD, based on the weighting factor recommended by ICRP 103, was 1.72 ± 0.28 mSv, which slightly exceeds the HE,DLP of 1.70 mSv, that was calculated from the dose–length product (DLP) of the Rando phantom. This experiment yielded HE,TLD values of ICRP 103 from the highest 1.85 ± 0.28 (90 kg) to the lowest 1.47 ± 0.22 (10 kg) mSv. HE,TLD (mSv) = 5.45×10−3 W(kg) + 1.361, with an R2 of 0.87667. Using the DLP protocol, HE,DLP was estimated from CTDIvol that was recorded directly from the console display of the CT unit and multiplied by the conversion coefficient (k) recommended by the ICRP 103. Finally, the experimental results obtained herein are compared with those in the literature. Physicians should choose and adjust protocols to prevent the exposure of patients to unnecessary radiation, satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists and the public.

Endotoxin lipopolysaccharide (LPS) plays an important role in the acceleration of hepatic inflammation. Natural medicinal plants that can prevent inflammation by targeting LPS have potential therapeutic clinical application. The aim of the study is to examine the anti-inflammatory effects of lotus seedpod extract (LSE), used as a traditional Chinese herbal medicine with hemostasis function and for eliminating bruise, on the LPS-induced hepatic inflammation and its underlying molecular mechanisms in vitro and in vivo. In vitro, LSE and its purified compound (-)-epigallocatechin (EGC) dose-dependently inhibited the expressions of pro-inflammatory cytokines and mediators, including tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-6, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), without affecting cell viability in LPS-stimulated human hepatoma cell line HepG2. Molecular studies showed the anti-LPS effect of HLP or EGC might be mediated via downregulation of Toll-like receptor 4. (TLR4)-mediated both NF-[Formula: see text]B and p38 signaling, as demonstrated by the usage of pyrrolidine dithiocarbamate (PDTC), a specific NF-[Formula: see text]B inhibitor. In vivo, LPS-induced hepatic inflammation was significantly ameliorated in LSE-fed mice as gauged by dose-dependent inhibition of serum levels of biochemical markers of liver damage, the changes of hepatic lobular architecture and the secretion of pro-inflammatory mediators, as well as induction of anti-oxidant enzymes. As a result, our data presented the first evidence of EGC-enriched LSE as an anti-inflammatory agent in LPS-stimulated HepG2 cells and mice, and these findings may open interesting perspectives to the strategy in treatment for hepatic inflammation.

e18040 Background: Salvage surgery (SS) is one of the curative options for oral cavity squamous cell carcinoma (OCSCC) patients with locoregional recurrence (LRR) or secondary primary, but the role of SS should be reevaluated between life expectancy, morbidity, and quality of life. Selecting suitable OCSCC patients receiving SS is important. Methods: From 2010 to 2018, newly diagnosed OCSCC patients who progressed to LRR or secondary primary were recorded. Clinical outcomes, prognostic factors, and predictors were analyzed for the patients receiving SS. Cox regression analyses were performed for PSS, defined from the date of SS to the date of death or last follow-up. Survival was estimated using the Kaplan–Meier method and log-rank tests. Results: A total of 263 newly diagnosed OCSCC patients progressing to LRR or secondary primary were recorded. Half (55.1%, 145/263) of them received SS, and one-third (29.7%, 43/145) of the SS group received twice and more times SS. Median survivals after disease progression were 65.6 and 10.6 months for patients with or without SS, respectively (P < 0.001). A total of 214 SS events were enrolled for analysis. Nearly twenty percentage (20.1%, 39/194) of SS events would progress to death within 1 year after surgery (PSS < 1 year). PSSs of the first, secondary, third, and fourth or more times SS were 64.2, 47.6, 40.9, and 18.9 months, respectively (P = 0.217). Surgical features of the last surgery (perineural invasion and depth of invasion), the interval between the last and current surgery, and clinical N staging of the current surgery were the four independent factors for PSS. To predict the patients with PSS < 1 year, a scoring system was established that each of the independent factors was scored one point. The area under the curve of the scoring system was 0.755, and sensitivity, specificity, positive predictive value, and negative predictive value were 66.7%, 76.0%, 39.0%, and 90.8%, respectively (Table). Conclusions: A scoring system with a high negative predictive value was established to predict PSS < 1 year.[Table: see text]

Generally, radiation oncology applies evaluation and prediction in medical imaging and diagnosis, specifically for contouring organs, which results in the production of the clinical target volume (CTV) that corresponds to disease risk and organ exclusion. Medical physicists contour organs and combine computed tomography (CT) scans to digital imaging and communications in medicine (DICOM) radiation therapy (RT) to assist physicians for diagnosing tumors and calculating the dosages in treatments including radiation and chemotherapy. Thus, to generate RT images with high accuracy, this paper proposes a new Generator Adversarial Network (GAN) for RT images called radiation therapy GAN (RTGAN). We combine multiple loss functions with synthetic similarity DICOM-RT images and compare the results with Pinnacle, a radiation oncology treatment planning system. Further, we evaluate the method to get a score of 0.984 in structured similarity (SSIM) and 31.26 in peak signal-to-noise ratio (PSNR) and find that it costs 0.058 s to finish contouring one CT image. The proposed method is applied and tested in the department of radiation oncology at the Chung Shan Medical University Hospital, and the results are similar to the ground truth images. Thus, it not only effectively reduces the false-positive rate but also makes a breakthrough in medicine.

Environment radiations in vault rooms resulting from Axesse linac use was assessed at Medical University Hospital using Thermoluminescent dosimeters (TLDs) during the use of the new radiation treatment known as volumetric modulated arc therapy (VMAT) in the treatment of nasopharyngeal cancer (NPC). The TLD-100H was calibrated using linac 6 MV photons. A total of 75 measurement points of the TLD-100H were utilized for environmental monitoring. The measured environment radiations were then visualized as three-dimensional graphical representations. Environment radiations were visualized using colored three-dimentional graphical representations. The radiations in NPC treatment of Rando phantom was found to reach levels up to 370 mSv/treatment. Many researchers consider TLD, which is the most cost-effective method to environment radiations. The minimum detectable dose (MDD) was also identified to demonstrate the reliability of the TLD approach. Quantitative results that provide practical guidance with ...

e18536 Background: At least 10% of patients with oral cavity squamous cell carcinoma (OCSCC) would progress to distant metastases (DM). Median overall survival (OS) after distant metastases is only one year and rare biomarkers are available to predict distant metastatic events. Methods: A total of 595 OCSCC patients who underwent curative surgical resection at Chung Shan Medical University Hospital were enrolled from Jan 2010 to Dec 2016. The clinical–pathological variables were compared using the χ2 test. Cox proportional-hazards analyses were performed for distant metastatic free survival (DMFS), defined from the date of initial diagnosis to the date of distant metastasis. Two scoring systems for predicting distant metastases were established for patients with pathologic regional lymph node –positive (pN+) or –negative (pN–), separately. Results: Nearly 10% (8.9%, 53/595) of patients with OCSCC would progress to DM during follow-up [20.6% (28/136) and 5.4% (25/459) for patients with pN+ and pN–, respectively]. Most of the distant metastatic lesions developed within 3 years after initial diagnosis (overall, 84.9%, 45/53; patients with pN+, 92.9%, 26/28; patients with pN–, 76.0%, 19/25). For patients with pN+, rapidly locoregional recurrence (≦6 months), lymphovascular invasion, and lymphocyte-monocyte ratio( 65), and close surgical margin(≦5mm) were independent for those with pN–. If each of the independent factors was scored one point to predict DM occurring within 3 years after the initial diagnosis, two scoring systems were established for the corresponding patients with pN+ or pN–, separately. The area under the curves of these two scoring systems for the corresponding patients with pN+ and pN– were 0.737 and 0.825, respectively (Table). Conclusions: The established scoring systems effectively predict distant metastases for OCSCC patients. [Table: see text]

Objective To investigate the association between antidepressant prescription and breast cancer. Methods The National Health Research Institute in Taiwan provided a database of 1 000 000 random subjects for this study. We identified 14 737 new antidepressant female users who were more than 15 years old during 1999–2005 with at least 10 prescriptions and one year exposure to an antidepressant. These were matched 1:1 by age and residence to non-antidepressant users from the same database to compare the risk of breast cancer. Results In a model adjusted by age, residence, insurance amount, and depressive disorder, antidepressant prescription was not associated with breast cancer risk. This held true for both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants. Conclusions There was no evidence for an association between antidepressant prescription and the risk of breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.

This study derived a simple equation of effective dose (E) versus normal organ of patients with varying body weights undergoing lung cancer treatment of helical tomotherapy (TOMO). Five tissue-equivalent and Rando phantoms were used to simulate lung cancer patients. This study then measured E and equivalent dose of organ or tissues (DT) using thermoluminescent dosimetry (TLD-100H). The TLD-100H was calibrated using TOMO 6 MV photons, then inserted into phantom positions that closely corresponded with the position of the represented organs and tissues. Both E and DT were evaluated by ICRP 103. Peripheral doses varied markedly at positions close to the tumor center. The maximum statistical and total errors were 16.7–22.3%. This analytical result indicates that E of Rando and tissue-equivalent phantoms was in the ranged of 9.44±1.70 (10 kg) to 4.58±0.83 (90 kg) mSv/Gy. Notably, E decreased exponentially as phantom weight increased. Peripheral doses were also evaluated by TLD as a function of distance from the tumor center. Finally, experimental results are compared with those in literature. These findings will prove useful to patients, physicians, radiologists, and the public.

Background Sinus mucosa abnormalities on image studies, which is the major diagnostic measure for sinusitis, were investigated in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Methods A retrospective review of the MRIs for patients with NPC was conducted. Sinus mucosa abnormalities were staged by the Lund–Mackay system. Results A total of 94 patients were enrolled in this study. The rate and severity of sinus abnormalities were highest on the third postradiotherapy month (p < .005, t test). There was no significant increase in the incidence of abnormalities on the fifth postradiotherapy year (t test). The anterior ethmoid and maxillary sinuses were the most affected sinuses before and after radiotherapy (p < .005, chi-square test). Conclusion Our data showed that the anterior ethmoid and maxillary sinuses were the most vulnerable sinuses for therapeutic toxicity after IMRT in patients with NPC. In the long run, however, the application of IMRT does not significantly increase the incidence of sinus toxicities. © 2015 Wiley Periodicals, Inc. Head Neck 38: 29–35, 2016

This study aimed to investigate the occurrences of post-irradiation chronic suppurative otitis media (CSOM), otitis media with effusion (OME), chronic rhinosinusitis (CRS), and their interrelationship in nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiotherapy (IMRT). A retrospective review of medical records and magnetic resonance imaging for NPC patients across a 5-year follow-up was conducted. Rhinosinusitis was diagnosed and staged by Lund-Mackay system. A total of 102 patients were enrolled in the study. On the 5th year following IMRT, 8 patients (7.8 %), 30 patients (29.4 %), and 17 patients (16.7 %) suffered from IMRT-induced CSOM, post-irradiation OME, and CRS, respectively. Analysis by logistic regression showed a lack of association between the occurrence of post-irradiation OME and CRS (P = 0.06). These observations indicated that the modern radiotherapy technique exhibits capability in decreasing the incidences of CSOM and CRS comparing to the data of traditional radiotherapy. But post-irradiation OME was still encountered in more than one-quarter of long-term survivors of NPC. Of note, rhinosinusitis in NPC survivors does not predispose to the development of post-irradiation OME, suggesting nasal irrigation might be unnecessary for the management of OME following radiotherapy.

Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. Through immunoprecipitation analysis, we found that BMI1 did not interact with Hsp90α and that the downregulation of BMI1 by 17-DMAG was mediated by the inhibition of c-Myc and enhancement of zeste homolog 2 (EZH2) expression. The transcriptional and BMI1 promoter-binding activities of c-Myc in BCSCs were inhibited by 17-DMAG treatment. The overexpression of EZH2 attenuated the inhibitory effect of 17-DMAG on BMI1 and c-Myc expression. Furthermore, Hsp90α could be co-immunoprecipitated with c-Myc and EZH2 and bind to the BMI1 promoter. Treatment with 17-DMAG decreased the nuclear expression of EZH2 and c-Myc but not that of Hsp90α. In conclusion, our data suggested that Hsp90α could positively regulate the self-renewal of BCSCs by facilitating the nuclear translocation of c-Myc and EZH2 to maintain BMI1 expression.

Extracts of Piper betle leaf (PBLs) are rich in bioactive compounds with potential chemopreventive ability. In this study, Hep3B cells which are p53 null were used to investigate the anti-tumor effect of PBLs in the cell and in the xenograft model. The results revealed that PBLs (0.1 to 1 mg mL(-1)) induced a dose- and time-dependent increase of cell toxicity. The underlying mechanisms as evidenced by flow cytometry and western blot analysis showed that PBLs triggered ATM, cAbl, and p73 expressions and activated JNK and p38 pathways that subsequently led to cell cycle arrest and mitochondria-dependent apoptosis. PBLs also inhibited tumor growth in Hep3B-bearing mice via inducing the MAPK-p73 pathway. Our results demonstrated the in vitro and in vivo anti-tumor potential of PBLs, supporting their application as a novel chemopreventive agent for the treatment of human hepatocellular carcinoma (HCC) in the future via targeting the p73 pathway.

e17536 Background: Early progression, usually defined disease-free interval (DFI) less than six months after completing adjuvant platinum-based chemoradiotherapy (CRT), has very poor outcome for oral cavity squamous cell carcinoma (OCSCC). But there are no biomarkers to predict such early progression. Methods: Locally advanced OCSCC patients, after complete surgical resection and followed-up platinum-based adjuvant CRT, were retrospectively enrolled from Chung Shan Medical University Hospital (CSMUH, training cohort) and Taipei Veterans General Hospital (TPE-VGH, validating cohort) in Taiwan. Clinicopathologic variables of patients with DFI < or ≥ 6 months were compared by using the χ2 test. The Cox proportional hazards model was applied to identify independent factors for DFI. Survival was estimated using the Kaplan-Meier method and log-rank test. Results: A total of 350 high-risk OCSCC patients were enrolled, including 146 patients in training cohort and 204 in validating cohort. In multivariate Cox regression, pN > 0, extracapular spread, and depth of invasion ( ≥ 1cm) were independent factors for DFI in training cohort. If each factor scored one point, the scoring system could effectively predict early progression that sensitivity/specificity/area under curve (AUC) of training and validating cohort were 57.7%/91.2%/0.771 and 58.1%/83.9%/0.730, respectively (the cutoff level ≤ 2 or > 2). DFI between lower- (score 0–2) and high- (score 3) risk groups were also significantly different in both training (median DFI, 59.6 vs. 4.5 months, P < 0.001) and validating cohorts (NA vs. 9.3 months, P < 0.001). Conclusions: The established score system was effective to predict early progression after adjuvant CRT for locally advanced OCSCC.

Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a rare, benign tumor. It is locally aggressive and prone to recurrence. Extensive synovectomy followed by low dose irradiation is the common therapy. Recently, “tumor landscaping” has been demonstrated to be involved in the etiology of this disease. In addition, new drugs have been developed to block the associated pathway. Here, we present a refractory case of D-TGCT over left ankle who received marginal excision followed by adjuvant radiotherapy. Disease relapse occurred 9 years later and he received repeat operation and adjuvant radiotherapy. After 30 months of follow-up, no disease progression or distant metastasis was observed.

Solitary plasmacytoma of bone (SPB), also called osseous plasmacytoma, is more common in males than in females with an estimated ratio of 2:1. The median age of SPB patients is approximately 55 years. Localized radiation therapy is the first-line treatment to avoid progression to multiple myeloma. A 46-year-old man visited our hospital due to lower back pain radiating to his lower limbs for 3 months. L-spine MRI showed S2 to S4 bone erosion with a large (8.8×6.2 centimeter) tumor over sacrum. Following partial tumor removal, pathology showed plasmacytoma. Adjuvant radiotherapy with 50 Gy in 25 fractions was administered to the gross tumor based on volumetric modulated arc therapy (VMAT). No adjuvant chemotherapy was given. Pelvic CT was arranged every 3 months during 24-month follow-up. There was no distant metastasis or newly diagnosed multiple myeloma during the follow-up period.

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44+ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G1 phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

Piper betel leaf (PBL) has the biological capabilities of detoxification and can work as an anti-inflammatory agent and an anti-oxidant. In this study, we evaluated the anti-oxidative activity of the extract of Piper betel leaves (PBLs) on the basis of Cu(2+)-mediated oxidation, and its ability to prevent foam cell formation in a model for oxidised low density lipoprotein (oxLDL)-induced lipid accumulation in macrophages. Our data demonstrated that PBLs were able to inhibit LDL oxidation in vitro and are able to reduce the lipid accumulation in macrophages. We showed the underlying mechanisms to be the following: PBLs up-regulated the protein levels of the class A and class B scavenger receptors, the membrane lipid transporter ABCA1, and its upstream regulator Liver X receptor (LXR) in the macrophages exposed to oxLDL. The results suggested that PBLs activated the reverse cholesterol transport mechanism to enhance the metabolism of the oxLDL that could prevent both lipid accumulation and foam cell formation and further minimise the possible damage of vessels caused by the oxLDL.

An increasing number of cyclotrons at medical centers in Taiwan have been installed to generate radiopharmaceutical products. An operating cyclotron generates immense amounts of secondary neutrons from reactions such the 18 O( p , n ) 18 F, used in the production of FDG. This intense radiation can be hazardous to public health, particularly to medical personnel. To increase the yield of 18 F-FDG from 4200 GBq in 2005 to 48,600 GBq in 2011, Chung Shan Medical University Hospital (CSMUH) has prolonged irradiation time without changing the target or target current to meet requirements regarding the production 18 F. The CSMUH has redesigned the CTI Radioisotope Delivery System shield. The lack of data for a possible secondary neutron doses has increased due to newly designed cyclotron rooms. This work aims to evaluate secondary neutron doses at a CTI cyclotron center using a thermoluminescent dosimeter (TLD-600). Two-dimensional neutron doses were mapped and indicated that neutron doses were high as neutrons leaked through self-shielded blocks and through the L-shaped concrete shield in vault rooms. These neutron doses varied markedly among locations close to the H 2 18 O target. The Monte Carlo simulation and minimum detectable dose are also discussed and demonstrated the reliability of using the TLD-600 approach. Findings can be adopted by medical centers to identify radioactive hot spots and develop radiation protection.

Objectives/Hypothesis Postirradiation otitis media with effusion (OME) is a common adverse otologic effect in nasopharyngeal carcinoma (NPC) patients treated by radiotherapy. The purpose of this study was to determine the long-term incidence of postirradiation OME in NPC patients following intensity-modulated radiotherapy (IMRT) and to evaluate the potential factors associated with the development of this otologic complication. Study Design Retrospective observational study. Methods A retrospective review of NPC patients treated by IMRT between January 2002 and June 2008 was conducted. Otologic complications were regularly evaluated during follow-up. Presence of OME was detected by findings of otoscopic exam, pure-tone audiometry, impedance audiometry, and tympanocentesis. Incidence of postirradiation OME and relevant factors were analyzed. Results A total of 105 patients (210 ears) were enrolled in the study. There were 34 patients (32.4%) with unilateral or bilateral postirradiation OME 3 years or more following radiotherapy. There was no correlation between the complication and the stage of primary tumor. The presence of pretreatment OME, however, was significantly associated with the development of postirradiation OME. Although there was no significant relationship between the radiation dose and post-treatment OME, the link with radiation toxicity was demonstrated by the finding that 28% of postirradiation OME developed in the ears contralateral to the side of primary nasopharyngeal tumor. Conclusions Postirradiation OME remains a common late toxicity in NPC patients treated by modern radiotherapy. Pretreatment injuries by the tumor and radiation-induced damages to the eustachian tube both play a major role in the development of the otologic complication. Level of Evidence Level of Evidence: 3b (nonconsecutive cohort study). Laryngoscope, 123:2148–2153, 2013

Cyclotrons are increasingly constructed at medical universities in Taiwan to produce nuclear medicine. However, their operation generates amounts of highly energetic photons from 18O(p, γn)18F reactions. This reaction posed a health hazard to the public. Chung Shan University Hospital had to increase its 2-deoxy-2-[18F]-fluoro-D-glucose products in 2011 to 11.5 times that in 2004 and redesign the self-shielded (CTI) Radioisotope Delivery System (RDS)-111 to meet guild requirements regarding the production of positron emission tomography (PET). This study is the first to evaluate air kerma in a CTI RDS-111 cyclotron center with a thermoluminescent dosimeter (TLD). Air kerma of up to 17.0±2.8 mGy/mo indicated that heavy leakage of photons penetrated the PET/CT facility. The new L-shaped concrete shield and added d2 door can adequately protect the public. The minimum detectable limit of air kerma is discussed to demonstrate the reliability of the TLD approach.

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. Mulberry fruit is rich in phenolic compounds and flavonoids and exhibits chemopreventive activities. In this study, mulberry water extract (MWE) was used as a supplement to synergize with the effects of paclitaxel in the treatment of the TSGH 8301 human bladder cancer cell line. Treatment with paclitaxel combined with MWE (paclitaxel/MWE) enhanced the cytotoxicity of paclitaxel and induced severe G2/M arrest, mitotic catastrophe and subsequent apoptosis, as shown by MTT assay, HE staining and flow cytometry analyses. Differences in the expression and activation of Aurora A and Plk1between cells treated with paclitaxel/MWE and paclitaxel alone suggested that the combined treatment caused a defect in the early steps of cytokinesis. Paclitaxel/MWE decreased EEA1immunofluorescence staining and increased the expression of PTEN, indicating that the regimen inhibited the formation of the recycling endosome, which is required for cytokinesis. Paclitaxel/MWE also retarded tumor growth in a TSGH 8301 xenograft model via activation of PTEN and Caspase 3. These data demonstrated a synergistic effect on the anticancer efficacy of paclitaxel through MWE supplementation by promoting mitotic catastrophe through the activation of PTEN, providing a novel and effective therapeutic option for bladder cancer treatment strategies.

Pretreatment with 2- [(18)F] fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) was evaluated as a predictor of local failure-free survival (LFFS), disease-free survival (DFS), and overall survival (OS) in patients with nonkeratinizing nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) alone or concurrently with chemotherapy (CCRT).Seventy-five M0 NPC patients who received FDG-PET before treatment were analyzed. The primary tumor FDG uptake was measured as the maximum standardized uptake value (SUVmax). The LFFS, DFS, and OS were calculated by the Kaplan-Meier method, and the differences were evaluated on log-rank test. The prognostic significance was assessed by univariate and multivariate analyses.Eighteen patients received IMRT alone and 57 received CCRT. The mean SUVmax was significantly higher in 12 patients with locoregional or distant failure than in those without failure (p0.001). On multivariate analysis, the SUVmax was the only significant variable for 5-year LFFS (p = 0.017) and DFS (p = 0.000) but not for OS (p = 0.065).SUVmax is a potential independent prognostic predictor of clinical outcomes in patients with nasopharyngeal carcinoma treated with IMRT alone or with CCRT. A high (18)F-FDG uptake (SUVmax5) indicates poor outcome in patients with NPC.

The indium foil activation technique has been employed to measure thermal neutron fluences ( Φ th ) among various locations in the treatment room with a 20×20 cm 2 field size and a 15 and 10 MV X-ray beam. Spatial Φ th are visualized using colored three-dimensional graphical representations; intensities are up to (1.97±0.13)×10 5 and (1.46±0.13)×10 4 n cm −2 /Gy-X at isocenter, respectively. The Φ th is found to increase with the X-ray energy of the LINAC and decreases as it moves away from the beam center. However, thermal neutron exposure is not assessed in routine dosimetry planning and radiation assessment of patients since neutron dose contributes Φ th were measured in water phantom irradiated with 15 MV X-ray beams. The shielding effect of the maze was also evaluated. The experimentally estimated Φ th along the maze distance was fitted explicate and the tenth-value layer (TVL) was calculated and discussed. Use of a 10 cm-thick polyethylene door placed at the maze was suitable for radiation shielding.

Mulberry fruit water extract (MWE) has been reported to synergistically enhance the cytotoxic effect of paclitaxel by promoting mitotic catastrophe to induce apoptosis in bladder cancer cells in our previous work. The aim of this study was to evaluate and to mechanistically explore the effects of MWE on bladder cancer responses to ionizing radiation (IR) by treating TSGH 8301 bladder carcinoma cells with MWE after exposing to IR. The results of MTT assay showed a synergistic cytotoxicity of IR with the co-treatment of MWE (IR/MWE) by inducing G2/M phase arrest as demonstrated by flow cytometry analysis in TSGH 8301, HT1367 and HT1197 bladder carcinoma cells lines. The IR/MWE-treated cells expressed increased levels of the G2/M phase arrest-related proteins cdc2/cyclin B1 and displayed giant multinucleated morphology, a typical characteristic of mitotic catastrophe. Immunofluorescent confocal microscopy revealed that the combined strategy inhibited Aurora B phosphorylation through Ras/Raf/MEK/ERK signaling cascade as demonstrated by Western blotting analysis. IR/MWE also caused an inhibitory effect on Plk1 and the subsequent downstream regulator RhoA repression and Cep55 induction, which would influence cell cycle progression in the early steps of cytokinesis. A profound tumor growth suppression and inactivation of Aurora B activity in the tumor tissues by IR/MWE treatment were confirmed in the TSGH 8301 xenograft model in vivo. These data demonstrated that MWE could be an effective auxiliary to synergize with radiation on the anticancer efficacy by promoting mitotic catastrophe through inhibition of Aurora B, providing a novel and effective therapeutic option for bladder cancer management.

Eur J Clin Invest 2010; 41 (1): 84–92 Abstract Background Cancer is often caused by disturbance in the regulation and/or execution of programmed cell death (PCD, including apoptosis and autophagy). Our aim was to investigate these two pathways simultaneously in the same samples to understand further the pathological roles of PCDs in colorectal cancer. Materials and methods Real time quantitative PCR (RT-qPCR) array was used to analyse the mRNA levels of 22 apoptosis and autophagy-related genes involved in pro- and anti-action of the pathways in 15 paired (tumour and non-cancerous part) colorectal samples using Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the reference gene. Results GAPDH mRNA content was significantly higher (approximately 4·01 fold) in tumour tissue than that of paired non-cancerous part. The absolute mRNA levels for most of the 22 genes were higher in the tumour tissue also. However, after normalization with GAPDH Ct, the expressions of all the analysed genes were decreased in the tumour tissues, except for damage-regulated autophagy modulator (DRAM). The expression of most of the genes involved in the same pathway was closely correlated to each other in both tumour and non-cancerous tissues, and the correlation of tumour necrosis factor receptor (TNFR) and Akt to other genes in the same pathway was increased in tumour tissues. Conclusions The high level expression of GAPDH might reflect the metabolic state of cancer cells, and PCDs were down-regulated in the tumour tissues when metabolic state was taken into consideration. This relative suppression of PCDs in tumour tissue is supposed to be in favour of cancer cell survival.