Long-term survival analysis of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA levels.

BACKGROUND: The objective of this study was to confirm the relation between plasma Epstein-Barr virus (EBV) DNA (pEBV DNA) load and treatment outcomes after long-term follow-up in patients with nasopharyngeal carcinoma (NPC). METHODS: In total, 210 patients with NPC were enrolled, including 99 previously reported patients and 111 new patients. They prospectively received treatment with induction chemotherapy plus radiotherapy and were followed for at least 6 years. In these patients, pEBV DNA levels were measured before treatment and 1 week after treatment. The plasma viral load was correlated with treatment outcomes in the group of new patients and in the entire group. RESULTS: By using previously defined pEBV DNA cutoff values (1500 copies/mL pretreatment and 0 copies/mL post-treatment), there was a significant correlation between the pEBV DNA value and relapse-free survival, overall survival, and subsequent relapse rates in the new, independent patient cohort. Outcome analyses for the entire group revealed a higher relapse rate (45.6% vs 21.5% [P = .0037] or 76.7% vs 26.1% [P < .0001]), a worse relapse-free survival rate (56.5% vs 79.3% [P < .0001] or 23.3% vs 75.6% [P < .0001]), and poorer overall survival (59.2% vs 86% [P = .0003] or 33.3% vs 79.4% [P < .0001]) in patients who had high pretreatment or persistently detectable post-treatment pEBV DNA levels, respectively, versus their respective counterparts. Multivariate Cox analysis also confirmed these results. CONCLUSIONS: In this expanded study, the prognostic significance of pEBV DNA was confirmed using predefined cutoff values in an independent patient group, and pEBV DNA was identified as an independent prognostic marker for NPC.

Plasma Epstein-Barr virus DNA screening followed by ¹8F-fluoro-2-deoxy-D-glucose positron emission tomography in detecting posttreatment failures of nasopharyngeal carcinoma.

BACKGROUND: The authors investigated the clinical implication of plasma Epstein-Barr virus (EBV) DNA assay and (18) F-fluoro-2-deoxy-D-glucose ((18) F-FDG) positron emission tomography (PET) in the detection of recurrent nasopharyngeal carcinoma (NPC). METHODS: Two hundred forty-five patients with NPC who had previously received treatment and were in a state of remission were monitored prospectively using a plasma EBV DNA assay every 3 to 6 months. (18) F-FDG PET studies were obtained when abnormal EBV DNA or clinically suggestive signs of recurrence were noted. RESULTS: Thirty-six of 245 patients (14.7%) patients had abnormal EBV DNA tests and underwent PET scans. In the remaining 209 patients, 3658 blood tests were negative. PET scans also were obtained in 5 patients who had undetectable EBV DNA levels but signs that were clinically suggestive of disease recurrence. Subsequent analyses focused on 41 patients who had PET studies. In lesion-based analyses, the sensitivity, specificity, and accuracy of PET by visual interpretation were 81.8%, 77.1%, and 79.2%, respectively, for all 125 lesions. In patient-based analyses, the accuracy of PET by visual interpretation was 51.2%. All 36 patients who had detectable plasma levels of EBV DNA had demonstrable NPC recurrences, whereas no recurrences were noted in 5 patients who had undetectable EBV DNA levels but signs that clinically mimicked a recurrence. Compared with annual PET, the annual cost of blood tests every 3 to 6 months per patient saved approximately 77% ∼ 88% in expenses. CONCLUSIONS: The plasma EBV DNA assay correctly predicted all NPC recurrences, and PET had high capacity to localize potential lesion sites. The authors concluded that applying the strategy of EBV DNA screening followed by PET scanning may guide appropriate further treatment planning in a cost-effective manner.

Investigation of physicochemical, nutritional, and sensory qualities of muffins incorporated with dried brewer's spent grain flours as a source of dietary fiber and protein.

Brewers' spent grain (BSG) is the major byproduct of brewing beer, rich in protein and dietary fiber. This study investigated the effect of two drying methods (impingement and hot-air drying) on chemical composition, physicochemical properties, and bioactive compounds of BSGs from three different brewers (BSG1, BSG2, and BSG3), and then evaluated the quality and consumer acceptance of BSG flour fortified muffins. Results showed that impingement drying led to significantly lower moisture content (MC, 1.33-1.87 g/100g) and water activity (aw , 0.04-0.07) of BSGs than hot-air drying (5.44 to 5.57 g/100 g and 0.19 to 0.20, respectively). Among different dried BSGs, impingement dried BSG3 achieved the highest protein (18.03 g/100 g dry matter [DM]), total phenolic content (TPC, 2.21 mg GAE/g DM), radical scavenging activity (RSA, 1.58 mg AAE/g DM), and total flavonoid content (TFC, 0.68 mg QE/g DM), and retained lighter color (L*, 54.68) and higher total dietary fiber (TDF, 42.40 g/100 g DM), which was selected for making BSG-fortified muffins. BSG3 was substituted 1:1 as white: whole wheat flour at three concentrations (10, 15, and 20 g/100 g flour mix) for muffins (BSG10, BSG15, and BSG20, respectively). BSG15 provided higher protein (13.11 g/100 g DM), TDF (16.88 g/100 g DM), and higher bioactive compounds compared to control and retained brighter color of muffin compared to BSG20, showing no difference in firmness and overall liking compared to the control muffin. This study demonstrated that impingement dried BSG could be utilized as a functional ingredient in muffins to add value to the food chain providing nutritional and environmental benefits. PRACTICAL APPLICATION: This study reported the benefit of impingement drying method for the retention of physicochemical quality and bioactive compounds of brewer's spent grains (BSG) produced from three different brewers in comparison with hot-air drying. The study also reported that muffins fortified with BSG flours (15% replacement of wheat flour) yielded a 23% increase in total dietary fiber and 13% increase in protein without affecting consumer acceptance of the products. This information is essential for developing value-added applications of BSG, a byproduct from brewing industry, as a functional ingredient to make nutritive baking goods, such as muffins, for promoting human health.

Predictors and outcome of seizures after spontaneous intracerebral hemorrhage. Clinical article.

OBJECT: Seizures are an important neurological complication of spontaneous intracerebral hemorrhage (ICH). A better understanding of the risk factors of seizures following ICH is needed to predict which patients will require treatment. METHODS: Two hundred and forty-three adult patients were enrolled in this 1-year retrospective study. Multiple logistic regression was used to evaluate the relationship between baseline clinical factors and the presence or absence of seizure during the study period. RESULTS: Seizures occurred in 20 patients with ICH, including acute symptomatic seizures in 9 and unprovoked seizures in 11. None progressed to status epilepticus during hospitalization. After a minimum 3-year follow-up period, the mean Glasgow Outcome Scale score was 3.8+/-1.1 for patients who had had seizures and 3.5+/-1.3 for those who had not. The multiple logistic regression model demonstrated that the mean ICH volume was independently associated with seizures, and any increase of 1 mm3 in ICH volume increased the seizure rate by 2.7%. CONCLUSIONS: Higher mean ICH volumes at presentation were predictive of seizure, and the presence of late seizures was predictive of developing epilepsy. Most seizures occurred within 2 years of spontaneous ICH over a minimum of 3 years of follow-up.

Enhancing clinical effectiveness of pre-radiotherapy workflow by using multidisciplinary-cooperating e-control and e-alerts: A SQUIRE-compliant quality-improving study.

Radiotherapy (RT) is useful in managing cancer diseases. In clinical practice, early initiation of RT is crucial for enhancing tumor control. But, delivering precise RT requires a series of pre-RT working processes in a tight staff-cooperation manner. In this regard, using information system to conduct e-control and e-alerts has been suggested to improve practice effectiveness; however, this effect is not well defined in a real-world RT setting.We designed an information system to perform e-control and e-alerts for the whole process of pre-RT workflow to shorten processing time, to improve overall staff satisfaction, and to enhance working confidence.A quality-improving study conducted in a large RT center.Externally validated data were retrospectively analyzed for comparison before (from Sep. 2012 to Dec. 2012, n = 223) and after (from Sep. 2013 to Dec. 2013, n = 240) implementation of pre-RT e-control and e-alerts.Applying the e-control with delay-working e-alerts in pre-RT workflow was the main intervention.Nine workstations were identified in pre-RT workflow. The primary outcome measure was the processing time in each pre-RT workstations before and after implementing the e-control and e-alerts. Secondary measures were staff-working confidence and near-missing cases during the process of pre-RT workflow.After implementing e-control, overall processing time of pre-RT workflow was shortened from 12.2 days to 8.9 days (P < .001). Follow-up data (till Jul. 2016) showed a durable effect of 9.2 days, being still below the predefined threshold of <10 days.Using a multidisciplinary-cooperating information system is useful to conduct e-control and e-alerts in the whole process of pre-RT workflow. Clinical effectiveness, staff satisfaction, and working confidence are able to be enhanced obviously.

Significant symptoms alleviation and tumor volume reduction after combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy in a patient with unresectable bulky hepatocellular carcinoma: A care-compliant case report.

BACKGROUND: Clinically, elderly patients with unresectable bulky hepatocellular carcinoma (HCC) are difficult to manage, especially in those with co-infections of hepatitis B and C virus. Herein, we reported such a case treated with radiotherapy (RT) by using combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy (SIEB-VMAT). After RT, significant symptoms alleviation and durable tumor control were observed. CASE SUMMARY: At presentation, an 85-year-old male patient complained abdominal distention/pain, poor appetite, and swelling over bilateral lower limbs for 1 month. On physical examination, a jaundice pattern was noted. Laboratory studies showed impaired liver and renal function. Abdominal computed tomography (CT) revealed a 12.5-cm bulky tumor over the caudate lobe of the liver. Biopsy was done, and hepatocellular carcinoma (HCC) was reported histopathologically. As a result, AJCC stage IIIA (cT3aN0M0) and BCLC stage C were classified. Surgery, radiofrequency ablation (RFA), trans-catheter arterial chemoembolization (TACE), and sorafenib were not recommended because of his old age, central bulky tumor, and a bleeding tendency. Thus, RT with SIEB-VMAT technique was given alternatively. RT was delivered in 26 fractions, with dose gradience as follows: 39 Gy on the outer Plan Target Volume (PTV), 52 Gy in the middle PTV, and 57.2 Gy in the inner PTV. Unexpectedly, cyproheptadine (a newly recognized potential anti-HCC agent) was retrospectively found to be prescribed for alleviating skin itching and allergic rhinitis since the last 2 weeks of the RT course (2 mg by mouth Q12h for 24 months).After RT, significant symptoms alleviation and tumor volume reduction were observed for 32 months till multiple bone metastases. Before and after RT, a large tumor volume reduction rate of 88.7% was observed (from 608.4 c.c. to 68.7 c.c.). No severe treatment toxicity was noted during and after RT. The patient died due to aspiration pneumonia with septic shock at 4 months after bone metastases identified. CONCLUSIONS: SIEB-VMAT physically demonstrated double benefits of intratumor dose escalation and extra-tumor dose attenuation. Significant tumor regression and symptoms alleviation were observed in this elderly patient with unresectable bulky HCC. Further prospective randomized trials are encouraged to demarcate effective size of SIEB-VMAT with or without cyproheptadine.

Implementing web-based ping-pong-type e-communication to enhance staff satisfaction, multidisciplinary cooperation, and clinical effectiveness: A SQUIRE-compliant quality-improving study.

BACKGROUND: Frequent multidisciplinary communication is essential in conducting daily radiotherapy (RT) practice. However, traditional oral or paper-based communication has limitations. E-communication has been suggested, but its effects are still not well demarcated in the field of radiation oncology. OBJECTS: In our web-based integrated information platform, we constructed a ping-pong-type e-communication function to transfer specific notations among multidisciplinary RT staffs. The purpose was to test whether applying this e-communication can increase effectiveness of multidisciplinary cooperation when compared with oral or paper-based practice. Staff satisfaction and clinical benefits were also demonstrated. DESIGN AND SETTING: A real-world quality-improving study was conducted in a large center of radiation oncology. PARTICIPANTS AND DATASET USED: Before and after applying multidisciplinary e-communication (from 2014 to 2015), clinical RT staffs were surveyed for their user experience and satisfaction (n = 23). For measuring clinical effectiveness, a secondary database of irradiated head and neck cancer patients was re-analyzed for comparing RT toxicities (n = 402). INTERVENTIONS: Applying ping-pong-type multidisciplinary reflective e-communication was the main intervention. OUTCOME MEASURES: For measuring staff satisfaction, eight domains were surveyed, such as timeliness, convenience, and completeness. For measuring clinical effectiveness of multidisciplinary cooperation, event rates of severe (i.e., grade 3-4) RT mucositis and dermatitis were recorded. RESULTS: Overall, when compared with oral communication only, e-communication demonstrated multiple benefits, particularly on notation-review convenience (2.00 ±â€Š1.76 vs 9.19 ±â€Š0.81; P < 0.0001).When compared with paper-based practice, e-communication showed statistically significant benefits on all eight domains, especially on notation-review convenience (5.05 ±â€Š2.11 vs 9.19 ±â€Š0.81; P < 0.0001) and convenience of feedback notation (4.81 ±â€Š1.72 vs 8.76 ±â€Š1.09; P < 0.0001).Moreover, staff satisfaction was gradually increased from oral (3.57 ±â€Š1.94), paper-based (5.57 ±â€Š2.06), to e-communication (8.76 ±â€Š0.70; P < 0.0001). Secondary measurement confirmed these observations.Before and after facilitating multidisciplinary cooperation by using e-communication, severe (i.e., grade 3-4) mucositis and dermatitis were decreased from 21.7% to 10% then to 5.1%. CONCLUSIONS: Replacing oral or paper-based practice with e-communication is useful in facilitating RT multidisciplinary teamwork. Staff satisfaction and clinical effectiveness can be increased.

Incidence of late-onset pneumonia in patients after treatment with radiotherapy for nasopharyngeal carcinoma: A nationwide population-based study.

BACKGROUND: The purpose of this study was to assess the incidence of late-onset pneumonia in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: Data were retrieved from the National Health Institute Research Database of Taiwan. We identified patients diagnosed with NPC (International Classification of Disease 9th revision-Clinical Modification [ICD-9-CM] code 147) from January 2005 to December 2008 who received curative radiotherapy as the study cohort. Incidences of pneumonia and related sequelae after 90 days of radiotherapy were calculated. RESULTS: A total of 3814 patients were enrolled in this study and 210 (5.5%) had late-onset pneumonia. The correlation coefficient between pneumonia and tube feeding was 0.332 (p < .001). The hazard ratio of pneumonia was 0.81 (95% confidence interval [CI] = 0.57-1.15) between patients with and without chemotherapy, and was 2.37 (95% CI = 1.73-3.24) between patients with and without re-radiation. CONCLUSION: Late-onset pneumonia is not uncommon in patients with NPC after radiotherapy. The risks of associated sequelae and mortality cannot be ignored.

Field Emission Characteristics of the Structure of Vertically Aligned Carbon Nanotube Bundles.

In this study, we performed thermal chemical vapor deposition for growing vertically aligned carbon nanotube (VACNT) bundles for a field emitter and applied photolithography for defining the arrangement pattern to simultaneously compare square and hexagonal arrangements by using two ratios of the interbundle distance to the bundle height (R) of field emitters. The hexagon arrangement with R = 2 had the lowest turn-on electric field (E to) and highest enhancement factor, whereas the square arrangement with R = 3 had the most stable field emission (FE) characteristic. The number density can reveal the correlation to the lowest E to and highest enhancement factor more effectively than can the R or L. The fluorescent images of the synthesized VACNT bundles manifested the uniformity of FE currents. The results of our study indicate the feasibility of applying the VACNT field emitter arrangement to achieve optimal FE performance.

Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.

PURPOSE: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. METHODS AND MATERIALS: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. RESULTS: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). CONCLUSIONS: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

Inhibitory effect and mechanisms of an anthocyanins- and anthocyanidins-rich extract from purple-shoot tea on colorectal carcinoma cell proliferation.

One newly bred variety of tea cultivar, purple-shoot tea, was selected to evaluate its antiproliferative effects on colorectal carcinoma cells, as well as normal colon cells. The phytochemicals and identified catechins of purple-shoot tea extract (PTE) were significantly higher than that of ordinary tea, especially the anthocyanins (surpassed by 135-fold) and anthocyanidins (surpassed by 3.5-fold). PTE inhibited the proliferation of COLO 320DM (IC(50) = 64.9 µg/mL) and HT-29 (IC(50) = 55.2 µg/mL) by blocking cell cycle progression during the G(0)/G(1) phase and inducing apoptotic death. Western blotting indicated that PTE induced cell cycle arrest by reducing the expression of cyclin E and cyclin D1 in COLO 320DM and the upregulation of p21 and p27 cyclin-dependent kinase inhibitors in HT-29. Two cells treated with PTE also indicated the cleavage of PARP, activation of caspase 3, and an increased Bax/Bcl-2 ratio. Our results showed that PTE is a potential novel dietary agent for colorectal cancer chemoprevention.

The volume of retropharyngeal nodes predicts distant metastasis in patients with advanced nasopharyngeal carcinoma.

We investigated the effect of retropharyngeal nodal volumes (RNV) on distant metastasis in patients with advanced nasopharyngeal carcinoma (NPC). From February 2000 to June 2006, a total of 181 patients with biopsy-proven NPC, no distant metastasis, and available pre-treatment magnetic resonance imaging (MRI) were retrospectively reviewed. Most of the patients (95.6%) had stage III/IV diseases. The contour of retropharyngeal nodes ≥5mm was delineated on the axial slides of pre-treatment T2-weighted MRI without contrast enhancement. The RNV was calculated by the Eclipse™ treatment planning software. The primary end-points were subsequent distant failure rates and distant metastasis failure-free survival (DMFFS). The pre-treatment RNV in patients who developed distant failure was higher than in those without distant failure (P=0.0536). The distant failure rates between the patients with RNV > and ≤4.68cm(3) were 33.3% and 16.0%, respectively (P=0.0112). The rates of 7-year DMFFS in patients with RNV > and ≤4.68cm(3) were 66.4% and 83.5%, respectively (P=0.0043). Multivariate Cox analysis showed N-stage (P<0.001), gender (P=0.026), and RNV (P=0.088) were important predictors for DMFFS. We conclude that the RNV measured by MRI is a potential predictor of distant metastasis in patients with advanced NPC.