Prevalence of Obstructive Sleep Apnea Using Home Sleep Test in Taiwan During the Coronavirus Disease Pandemic.

Background: Obstructive sleep apnea syndrome (OSAS) is a common disorder associated with serious sequelae. The current gold standard diagnostic method, polysomnography, is costly and time consuming and requires patients to stay overnight at a facility. Aim: This study aimed to reveal the prevalence of OSAS in general adult population using a home sleep test (HST) during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This prospective cohort study was conducted by the Department of Otolaryngology, Taipei City Hospital, Taipei, Taiwan, between January 2020 and December 2021. A total of 1372 patients aged 30-70 years completed an HST using a Type 3 portable sleep monitor (PM). The apnea-hypopnea index (AHI) was analyzed to assess the association of OSAS with age, body mass index (BMI), sex, Epworth Sleepiness Scale (ESS) and the Sleep Apnea Risk Assessment questionnaire (STOP-Bang questionnaire) rating. Results: The mean age of the patients (782 men, 57%; 590 women, 43%) was 49.24 ± 11.04 years. OSAS was detected in 954 (69.5%) patients with 399 (29.1%) mild OSAS; 246 (17.9%) moderate OSAS; and 309 (22.5%) severe OSAS. Among these, the prevalence of moderate-to-severe OSAS was 143 (10.4%) in women and 412 (30.0%) in men. The mean age was the highest (51.29 ± 11.29) in the mild OSAS group and lowest (47.08 ± 10.87) in the healthy group. OSAS severity was greater with increasing BMI, 23.39 ± 3.44 in the healthy group and 29.29 ± 5.01 in the severe OSAS group. A positive correlation was also noted between the ESS/STOP-Bang questionnaire rating and OSAS severity. Conclusion: The prevalence of OSAS in Taiwan was 69.5% in our study. It showed strong evidence that OSAS has important public health consequences and PMs are simple, fast, feasible, and cost-effective tools for OSAS screening in the home environment, especially during the COVID-19 pandemic.

Comparison the acute toxicity of two different induction chemotherapy schedules with cisplatin and fluorouracil in nasopharyngeal carcinoma patients.

PURPOSE: To compare the acute toxicity of two different induction chemotherapy (IndCT) regimen followed by the same IMRT in patients with advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From July 2015 to December 2016, 110 NPC patients with stage III-IV diseases were prospectively randomized to receive either a conventional triweekly cisplatin + 5-fluorouracil (PF) for 3 cycles or weekly P-F for 10 doses, followed by the same IMRT to both arms. The primary endpoints of this study were grade 3/4 and any grade acute toxicities during IndCT period. The secondary endpoints included tumor response and various survivals. RESULTS: Baseline patient characteristics were comparable in both groups. Patients who received weekly P-F experienced significant reduction of grade 3/4 acute toxicities, including neutropenia (12.7% vs. 40.0%, P = 0.0012), anorexia (0% vs. 14.6%, P = 0.0059), mucositis (0% vs. 14.6%, P = 0.0059), and hyponatremia (0% vs. 16.4%, P = 0.0027), compared with the triweekly PF group, resulting in fewer IndCT interruptions (1.8% vs. 16.4%, P = 0.0203), emergency room visits (0% vs. 12.7%, P = 0.0128), and additional hospitalizations (0% vs. 9.1%, P = 0.0568). The acute toxicities during IMRT period were similar. Weekly P-F arm had higher complete response rates (83.6% vs. 61.8%, P = 0.0152) and lower relapse rates (16.4% vs. 33.3%, P = 0.0402) after a median follow-up of 67 months. Kaplan-Meier survival analyses revealed a better trend of locoregional failure-free (P = 0.0892), distant metastasis failure-free (P = 0.0775), and progression-free (P = 0.0709) survivals, favoring the weekly P-F arm. CONCLUSION: IndCT of weekly schedule does reduce acute toxicities without compromised tumor response and survivals.

Critical Test Result Recall Supporting System (CTR RSS) Improves Follow-Up among Patients in the Community.

Follow-up care of patients in the community is an important topic for improving patient outcomes, especially when medical personnel receives a notification of the critical test result (CTR) when the CTR becomes available after patients have been out of hospital; how to recall the patient back to the hospital and follow-up treatment is essential for preventing the healthcare risk of neglecting or delayed intervention with respect to the patient's CTR. We are concerned that the follow-up of CTR and timely recall of our patients in the community improves and facilitates patient safety. We built the CTR Recall Supporting System (RSS) to follow up and recall our patients in the community. Measures were introduced to evaluate the effectiveness of CTR RSS; the rate of return of patients within 7 days increased from 58.5% to 88.8%, an increase of 30.3%, the patients in the community's return follow-up interval days decreased from 10.9 days to 6.2 days, reduced by 4.7 days (p < 0.001), and the mortality rate of the patients in the community within 48 h decreased from 8.0% to 1.9%, a decrease of 6.1%, p < 0.001. The implementation of the CTR RSS significantly increases the discharged patient in he community's CTR return follow-up within 7 days rate, decreases CTR return follow-up interval days, and reduces the CTR mortality rate within 48 h. This effectively improves the effects of CTR on return follow-up visits and provides a prototype system for hospitals that intend to improve this issue.

Maintenance metronomic chemotherapy for metastatic/recurrent nasopharyngeal carcinoma.

BACKGROUND: We investigated the survival impact and toxicity of maintenance metronomic chemotherapy in patients with metastatic/recurrent nasopharyngeal carcinoma (met/rec NPC). METHODS: Ninety-eight patients with met/rec NPC were first salvaged by IV cisplatin-based chemotherapy and showed nonprogression disease; then maintenance metronomic chemotherapy for at least 12 months was recommended. We analyzed the treatment outcome between patients who received (n = 51) and did not receive (n = 47) maintenance chemotherapy. RESULTS: Baseline patient characteristics showed no significant differences between both arms. Median overall survival for patients with and without maintenance chemotherapy was 36.0 and 12.3 months, respectively (p < 0.0001). Similarly, median progression-free survival was 24.7 and 7.3 months, respectively (p < 0.0001). Furthermore, toxicities during maintenance oral chemotherapy period were usually mild. Transient grade 3 leucopenia (9.8%), anemia (3.9%), thrombocytopenia (7.8%), and no grade 4 toxicity were observed. CONCLUSION: After IV salvage chemotherapy, maintenance oral metronomic chemotherapy significantly improved overall and progression-free survivals while demonstrating low toxicity in patients with met/rec NPC.

Comparison between botulinum toxin and steroid septal injection in the treatment of allergic rhinitis.

OBJECTIVE: To compare the effects of botulinum toxin and steroid septal injections in treating allergic rhinitis (AR) by evaluating improvements in the rhinitis control assessment test (RCAT), visual analog scale (VAS), nasal obstruction symptom evaluation (NOSE) scores, and active anterior rhinomanometry (RMM) measurements. METHODS: This prospective, single-blinded cohort study was conducted at the Department of Otolaryngology, Taipei City Hospital between January 2017 and December 2018. Ninety-five patients were randomized to receive botulinum toxin, dexamethasone, or normal saline (group A, group B, and placebo, respectively). The main outcome measures were pretreatment subjective nasal symptoms (RCAT, VAS, and NOSE) and active anterior RMM measurements. All measurements were repeated during posttreatment 1, 2, and 3 months. RESULTS: No significant difference was observed in pretreatment questionnaire scores and RMM values between the study and placebo groups. The mean posttreatment RCAT, VAS, and NOSE scores after 1 and 2 months significantly improved in the treatment groups compared to placebo. The VAS and NOSE at posttreatment 2 months and RCAT, VAS, and NOSE at posttreatment 3 months were significantly different comparing group A to group B. All RMM parameters showed better values in group A than in group B at 1, 2, and 3 months posttreatment, with significant differences in four parameters in posttreatment 3 months. CONCLUSIONS: Botulinum toxin septal injection is a safe treatment option for AR and improves subjective nasal symptoms for 3 months. Botulinum toxin A injection tended to be more effective than steroid septal injection in terms of duration and degree.Level of Evidence: 2b, individual cohort study.

Survival impacts of different nodal characteristics and T-classification in N3 nasopharyngeal carcinoma patients.

OBJECTIVES: We investigated the survival impacts of various nodal characteristics and T-classification on nasopharyngeal carcinoma (NPC) patients with the 8th AJCC/UICC staging criteria N3. MATERIALS AND METHODS: Pretreatment MRIs from 110 staged N3 NPC patients were reviewed. There were 23 T1, 25 T2, 32 T3, and 30 T4, respectively. All except one patient belonged to WHO type II pathology. All patients received curative radiotherapy 68.0-76.8 Gy plus different chemotherapy, including induction, concurrent, adjuvant or any combination. Various endpoints, including OS (overall survival), DFS (disease-free survival), LRFFS (locoregional failure-free survival), DMFFS (distant metastasis failure-free survival) were compared between different nodal characteristics and T-classification. RESULTS: There were no statistically significant differences in all analyzed survival curves between various nodal characteristics, including unilateral N3 vs. bilateral N3, "large" nodes (>6 cm) alone vs. "low" nodes (below the caudal border of cricoid cartilage) alone vs. combined "large" and "low" nodes, risk score 1 vs. 2 vs. 3 vs. 4 (by counting the sum of "large" and "low" nodes in the same case), and radiologic extra-nodal extension. Patients with T4, compared with those of T1-3 have worse OS (5-year rates, 42.2% vs. 82.8%, P < 0.0001), DFS (5-year rates, 43.9% vs. 68.9%, P = 0.0037), LRFFS (5-year rates, 69.3% vs. 82.7%, P = 0.0432), and DMFFS (5-year rates, 57.2% vs. 77.7%, P = 0.0163). CONCLUSIONS: Our results support merging previous N3a and N3b as a N3 category in the 8th edition new staging system. Patients with T4N3 diseases have extremely poor outcome and deserve to strengthen the treatment intensity in future trials.

Effects of Epstein-Barr virus viral load and different treatment modality for stage III nasopharyngeal carcinoma.

BACKGROUND: We investigated treatment results, the effects of different treatment modality, and pretreatment Epstein-Barr virus (EBV) viral load for stage III nasopharyngeal carcinoma (NPC) patients. METHODS: The initial definitive treatment for 356 stage III NPC patients consisted of concurrent chemoradiotherapy (CCRT) or induction chemotherapy plus radiotherapy (IndCT-RT). The pretreatment EBV DNA level separated patients into a high (n = 106) or low (n = 250) viral load (≥ or < 1000 copies/mL) subgroup. Outcome measures include relapse rates and various survivals. RESULTS: The 5-year rates of overall survival (OS), progression-free survival (PFS), distant metastasis failure-free survival (DMFFS), and locoregional failure-free survival (LRFFS) were 88.6%, 83.0%, 90.5%, and 90.5%, respectively. Patient characteristics and pretreatment viral load between IndCT-RT and CCRT were no significant differences except for a higher percentage of N2 disease in the IndCT-RT subgroup. Both treatment modality resulted in similar relapse rates (P = .56), OS (P = .20), PFS (P = .53), DMFFS (P = .89), and LRFFS (P = .35). However, patients with a high viral load experienced a higher relapse rate (33.0% vs 12.4%, P < .001) and worse OS (5-year rate, 79.0% vs 92.8%, P < .001), PFS (73.7% vs 88.4%, P < .001), DMFFS (80.2% vs 95.0%, P < .001), and LRFFS (85.6% vs 92.6%, P = .005) than those with a low viral load. CONCLUSION: Long-term treatment results for stage III NPC patients are rather good. IndCT-RT can achieve the same treatment outcome as CCRT. Risk grouping by pretreatment viral load identified a subgroup (30%) of patients associated with a significantly higher relapse rates and worse survivals. These high-risk patients need to strengthen treatment intensity in future trials.

The effect of olfactory training on odor identification in patients with traumatic anosmia.

BACKGROUND: This study investigates the effect of olfactory training on odor identification in patients with traumatic anosmia. METHODS: Patients with a clear history of loss of smell after head injury, and whose phenyl ethyl alcohol (PEA) odor detection thresholds remained at -1 after steroid and zinc treatment, were included in this study between July 2016 and July 2018. They were randomly divided into 2 groups, with patients in the 4-odorant group given 4 bottles of PEA, lemon, eucalyptus, and clove oils and those in the PEA group given a bottle of PEA for 6-month olfactory training. After 3-month and 6-month training, the olfactory function was evaluated by both the PEA threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). Magnetic resonance imaging was performed to measure the volume of olfactory bulbs after training. RESULTS: There were 45 patients completing 4-odorant training and another 45 completing PEA training. The birhinal PEA threshold decreased significantly in both groups after 6-month training, but the decrease was not significantly different between the 2 groups. The UPSIT-TC score increased significantly in the PEA group but not in the 4-odorant group. The volume of olfactory bulbs was not significantly different between these 2 groups. CONCLUSION: Our results show that olfactory training can slightly improve odor threshold levels in patients with traumatic anosmia, but did not improve the odor identification ability. Nevertheless, clinical improvement or benefit in quality of life from olfactory training needs further investigation.

Fibronectin promotes nasopharyngeal cancer cell motility and proliferation.

Nasopharyngeal cancer (NPC) is an Epstein-Barr virus (EBV)-associated carcinoma. Fibronectin is regarded as a prognosticator in NPC and its involvement in cell motility has been reported in EBV infection and viral latent membrane protein 1 (LMP1) overexpression NPC cell lines. However, its malignant potential in NPC cell lines without harbouring the EBV genome has not been investigated. We investigatd and compared among four NPC cell lines, and the results revealed a positive association between fibronectin levels and NPC cell motility as well as proliferation. Studies of antibody neutralization, exogenous addition, overexpression, and RNA interference confirmed a migration role of fibronectin in NPC cells involving integrin α5, Src, Rac1, and Cdc42, implying a mesenchymal-like cell movement. Furthermore, hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-ß1 (TGF-ß1) were identified as alternative activators of fibronectin expression and NPC cell migration. Besides cell migration, studies of RNA interference also showed a stimulatory effect of fibronectin in NPC cell proliferation. Mechanistic studies further revealed a subsequent reduction of HIF-1α, TGF-ß1, cyclin D1, ß-catenin, vimentin, and Slug together with decreased Src and Akt phosphorylation after fibronectin knockdown. Parallel studies in a xenograft tumor mice model further showed that tumor growth correlated well with elevation of circulating fibronectin and activation of the identified intracellular signaling molecules. The results of our study highlight a role of fibronectin in NPC cell motility and proliferation in concerted action with HIF-1α and TGF-ß1 possibly through linking molecules Src and Akt. Fibronectin overexpression and autoantibody are known to have potential prognostic value in patients with NPC. Our findings shed light on the biochemical and molecular mechanisms underlying the pathogenic role of fibronectin in this disease.

Comparison the clinical outcomes with altered versus conventional fractionated radiotherapy plus concurrent chemotherapy for advanced nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to compare the long-term survivals between altered fractionated and conventional fractionated radiotherapy with the same concurrent chemoradiotherapy (concurrent CRT) for patients with advanced nasopharyngeal carcinoma (NPC). METHODS: We retrospectively reviewed 203 patients with NPC who received radiotherapy (RT) by either a conventional fractionated (70-74 Gy/35-37 fractions/7-8 weeks) or altered fractionated (72-75 Gy/45 fractions/6 weeks) schedule plus the same concurrent CRT. RESULTS: The patient characteristics between conventional fractionated and altered fractionated groups showed similar distribution. The 5-year rates of nasopharyngeal failure-free, neck failure-free, and distant metastasis failure-free survival between conventional fractionated and altered fractionated groups were 88% versus 86% (P = .7781), 95% versus 93% (P = .4176), and 76% versus 73% (P = .4029), respectively. The overall survival (OS; 5-year rates were 64% versus 62%; P = .4812) and progression-free survival (PFS; 5-year rates were 67% versus 63%; P = .3829) rates also showed no significant differences. The acute and late toxicities were similar between both groups. CONCLUSION: Altered fractionated and conventional fractionated RT achieved similar survival outcome when concurrent CRT strategy was used for advanced NPC.

Comparison Long-term Outcome of Definitive Radiotherapy plus Different Chemotherapy Schedules in Patients with Advanced Nasopharyngeal Carcinoma.

Concurrent chemoradiotherapy (CCRT) is the current standard of care for advanced nasopharyngeal carcinoma (NPC). We hypothesize that shifting CCRT to neoadjuvant chemotherapy followed by radiotherapy (NeoCT-RT) is an alternative option. From December 2004 to January 2009, 256 NPC patients with stage II-IVB were treated by either CCRT or NeoCT-RT. All patients received the same dosage and fractionation schedule of RT. After long-term follow-up, 26.8% (34/127) and 23.3% (30/129) of patients who received CCRT and NeoCT-RT respectively, developed a tumor relapse (P = 0.6134). Overall survival (HR = 1.52, 95%CI = 0.91-2.55, P = 0.1532) and progression-free survival (HR = 1.22, 95%CI = 0.75-1.99, P = 0.4215) were similar in both groups. However, acute toxicities during RT period revealed a significant reduction of grade 3/4 vomiting (23% vs. 0%, P < 0.0001), mucositis (55% vs. 16%, P < 0.0001), and neck dermatitis (31% vs. 16%, P = 0.0041) in the NeoCT-RT group, resulting in fewer emergency room visits (10.2% vs. 1.6%, P = 0.0071). Severe treatment-related late toxicity (15% vs. 14%, P = 0.9590) and the occurrence of second malignancy (3.9% vs. 5.4%, P = 0.7887) also showed no differences. We concluded that NeoCT-RT could be an attractive alternative option of CCRT for advanced NPC.

Efficacy of nasal irrigation with 200 µg/mL amphotericin B after functional endoscopic sinus surgery: a randomized, placebo-controlled, double-blind study.

BACKGROUND: Previous studies have shown controversial results of topical amphotericin B (AMB) nasal irrigation for chronic rhinosinusitis (CRS). The purpose of this study was to evaluate the efficacy of 200 µg/mL AMB nasal irrigation as an adjuvant therapy after functional endoscopic sinus surgery (FESS). METHODS: Patients with CRS who had received FESS for treatment were recruited and assigned to 1 of 2 groups at random at 1 month postsurgery. In the AMB group patients received nasal irrigation with 200 µg/mL of AMB for 2 months on a daily basis. In the control group normal saline irrigation was given instead. Before FESS and before and after nasal irrigation, patients' sinonasal symptoms were assessed through a questionnaire that was a Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22). In addition, patients received endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and bacterial cultures obtained from their middle meati. RESULTS: A total of 73 patients completed the study between December 2014 and January 2017. Among them, 37 received nasal irrigation with AMB solution, and 36 with saline. In the AMB group, scores of TWSNOT-22 dropped significantly after irrigation compared with before (p = 0.005). In the control group, TWSNOT-22 scores did not changed after irrigation (p = 0.451). However, there were no significant differences in TWSNOT-22, endoscopic score, smell test, saccharine transit test, and bacterial culture rate after irrigation between 2 groups. CONCLUSION: Our study showed that in post-FESS care, nasal irrigation with 200 µg/mL of AMB did not provide additional benefit compared with saline irrigation.

The effect of olfactory training on the odor threshold in patients with traumatic anosmia.

BACKGROUND: Olfactory training is a novel intervention that has been used to treat olfactory dysfunction. This study attempted to investigate the effect of olfactory training in patients with traumatic anosmia. METHODS: Patients with a clear history of anosmia after experiencing a head injury and whose phenyl ethyl alcohol (PEA) odor detection thresholds were -1 after steroid and zinc treatment were included. The patients were randomly divided into two groups, with patients in one group given a bottle of PEA and those in another group given a bottle of mineral oil for 3-month olfactory training. All the patients were followed up with a PEA threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). Magnetic resonance imaging was performed to measure the volume of the olfactory bulbs. Any patient whose PEA threshold result was below -1.01 or whose UPSIT-TC score increased four or more points was considered to have shown improvement in their olfactory function. RESULTS: Forty-two patients received PEA olfactory training, whereas 39 received olfactory training with mineral oil. The improvement of PEA thresholds function was observed in 10 patients within the PEA group and in 2 patients in the mineral oil group. The frequency of improvement of threshold within the PEA group was significantly higher than that of the mineral oil group. Neither olfactory bulb volume nor UPSIT-TC score was significantly different between the two groups. CONCLUSION: Our results showed that olfactory training with PEA can improve PEA odor threshold levels in patients with traumatic anosmia.

Prognostic impact of adjuvant chemotherapy in high-risk nasopharyngeal carcinoma patients.

OBJECTIVES: To investigate the prognostic impact of adjuvant chemotherapy (AdjCT) in patients with high-risk nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: A total 403 NPC patients with at least one of the following criteria (1) neck node>6cm; (2) supraclavicular node metastasis; (3) skull base destruction/intracranial invasion plus multiple nodes metastasis; or (4) multiple neck nodes metastasis with one of nodal size>4cm were retrospectively reviewed. All patients finished curative radiotherapy±neoadjuvant/concurrent chemotherapy. Post-radiation AdjCT consisted of tegafur-uracil (two capsules twice daily) for 12months. We analyzed the treatment outcome between patients with (n=154) and without (n=249) AdjCT. RESULTS: Baseline patient characteristics at diagnosis (age, gender, pathological type, performance status, T-classification, N-classification, and overall stage) were comparable in both arms. After a median follow-up of 72months for surviving patients, 31.8% (49/154) and 42.2% (105/249) in patients with and without AdjCT developed tumor relapse respectively (P=0.0377). AdjCT improved both overall survival (HR 1.89, 95% CI 1.37-2.61, P=0.0001) and progression-free survival (HR 1.42, 95% CI 1.03-1.96, P=0.0322). There were significant reduction in distant failures (P=0.0016) but not in local (P=0.8587) or regional (P=0.8997) recurrences for patients who received AdjCT. CONCLUSION: AdjCT can reduce distant failure and improve overall survival in high-risk NPC patients after curative radiotherapy±neoadjuvant/concurrent chemotherapy.

Long-term clinical outcome in nasopharyngeal carcinoma patients with post-radiation persistently detectable plasma EBV DNA.

PURPOSE: To investigate the long-term clinical outcome of nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma EBV (pEBV) DNA after curative radiotherapy (RT). RESULTS: The post-RT pEBV DNA levels were very lower copy number (median 21, interquartile range 8-206 copies/ml). After long-term follow-up, the relapse rate was 64.8%, the median time to progression 20 months, and 5-year overall survival (OS) 49.6%. Thirty-two of 39 (82.1%) patients with high viral load (≥ 100 copies/ ml) developed tumor relapse, whereas 57.0% (49/86) patients with low viral load (< 100 copies/ml) had tumor relapse (P = 0.0065). The 5-year OS rates were 20.5% and 62.9% for patients with viral load ≥ and < 100 copies/ml (median survival, 20 vs. 100 months; P < 0.0001). Patients who received adjuvant chemotherapy (AdjCT) experienced significant reduction in distant failures (66.2% vs. 31.6%; P = 0.0001) but similar locoregional recurrences (P = 0.2337). The 5-year OS rates were 69.4% for patients who received AdjCT compared with 33.2% for those of without AdjCT (median survival, 111 vs. 32 months; P < 0.0001). METHODS: We screened 931 newly diagnosed NPC patients who finished curative RT and found 125 patients (13.4%) with detectable pEBV DNA one week after RT. The clinical characteristics, treatment modality, subsequent failure patterns and survivals were analyzed. CONCLUSIONS: NPC patients with persistently detectable pEBV DNA after curative RT have a higher rate of treatment failure and poor survivals. Levels of the post-RT pEBV DNA and administration of AdjCT affect the final outcome significantly.

Olfactory change after intensity-modulated radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Radiotherapy is the mainstay of treatment for nasopharyngeal cancer (NPC), but many side effects were reported in NPC patients receiving radiotherapy. This study was conducted to evaluate the long-term effects of intensity-modulated radiotherapy (IMRT) on olfactory function. METHODS: The olfactory function of 41 NPC patients was assessed by a traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). The patients also filled out a Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22) questionnaire and received imaging examinations of the sinuses before IMRT and 1 year after IMRT. The sinus imaging was scored according to the Lund-Mackay system. RESULTS: The mean UPSIT-TC scores were 30.6 before IMRT and 28.0 after IMRT and the decrease in UPSIT-TC scores was significant (p = 0.001). The mean TWSNOT-22 scores were 32.1 before IMRT and 28.8 after IMRT. The change in TWSNOT-22 scores was not significant, but the scores for item 5 "loss of smell or taste" significantly increased after IMRT (p = 0.035). The mean total computed tomography (CT) scores were 1.7 before IMRT and 3.2 after IMRT, and the mean ethmoid CT scores were 0.5 before IMRT and 1.2 after IMRT. The increase in total CT and ethmoid CT scores was both significant (p = 0.004 and 0.002). The decrease in UPSIT-TC scores was moderately negatively correlated with the increase in total CT and ethmoid CT scores (r = -0.348 and -0.423). CONCLUSION: Our results showed that the olfactory function of NPC patients was mildly impaired after IMRT, which can cause rhinosinusitis.

Medical treatment of traumatic anosmia.

OBJECTIVES: To study the effects of zinc and steroid in the treatment of traumatic anosmia. STUDY DESIGN: A prospective, randomized study. SETTING: Academic medical center. SUBJECTS AND METHODS: Patients with a clear history of loss of smell after head injury and whose thresholds were -1 measured by the phenyl ethyl alcohol threshold test were included in this study from January 2010 to May 2013. They were randomly divided into 4 groups. Patients in group 1 were treated with zinc gluconate for a month and high-dose prednisolone with tapering for 2 weeks. Those in group 2 took only zinc gluconate, and those in group 3 took only prednisolone. Patients in group 4 did not take any medicine. All patients were followed up by phenyl ethyl alcohol threshold testing, and magnetic resonance imaging was performed to measure the volume of olfactory bulbs. RESULTS: Thirty-nine patients in group 1, 35 in group 2, 34 in group 3, and 37 in group 4 completed the study. The recovery of olfactory function was observed in 11 patients (28.2%) in group 1, in 9 (25.7%) in group 2, in 4 (11.8%) in group 3, and in 1 (2.7%) in group 4. The recovery rates of olfactory function of groups 1 and 2 were significantly higher than the recovery rate of group 4. The volume of olfactory bulbs was not significantly different between those with and without improved olfactory function. CONCLUSION: Our results show that zinc gluconate has a promising effect in treating traumatic anosmia.

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.

Effect of oxygen tension on tissue-engineered human nasal septal chondrocytes.

Tissue-engineered nasal septal cartilage may provide a source of autologous tissue for repair of craniofacial defects. Although advances have been made in manipulating the chondrocyte culture environment for production of neocartilage, consensus on the best oxygen tension for in vitro growth of tissue-engineered cartilage has not been reached. The objective of this study was to determine whether in vitro oxygen tension influences chondrocyte expansion and redifferentiation. Proliferation of chondrocytes from 12 patients expanded in monolayer under hypoxic (5% or 10%) or normoxic (21%) oxygen tension was compared over 14 days of culture. The highest performing oxygen level was used for further expansion of the monolayer cultures. At confluency, chondrocytes were redifferentiated by encapsulation in alginate beads and cultured for 14 days under hypoxic (5 or 10%) or normoxic (21%) oxygen tension. Biochemical and histological properties were evaluated. Chondrocyte proliferation in monolayer and redifferentiation in alginate beads were supported by all oxygen tensions tested. Chondrocytes in monolayer culture had increased proliferation at normoxic oxygen tension (p = 0.06), as well as greater accumulation of glycosaminoglycan (GAG) during chondrocyte redifferentiation (p < 0.05). Chondrocytes released from beads cultured under all three oxygen levels showed robust accumulation of GAG and type II collagen with a lower degree of type I collagen immunoreactivity. Finally, formation of chondrocyte clusters was associated with decreasing oxygen tension (p < 0.05). Expansion of human septal chondrocytes in monolayer culture was greatest at normoxic oxygen tension. Both normoxic and hypoxic culture of human septal chondrocytes embedded in alginate beads supported robust extracellular matrix deposition. However, GAG accumulation was significantly enhanced under normoxic culture conditions. Chondrocyte cluster formation was associated with hypoxic oxygen tension.

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.