High Superior-Middle Pharyngeal Constrictor Muscle Mean Dose Correlates with Severe Late Lung Infection and Survival in Nasopharyngeal Cancer Patients.

Purpose: The study aimed to evaluate 1) the correlation of doses of swallowing-related organs at risk (OAR) with severe swallowing-related late adverse effects (AE) in nasopharyngeal carcinoma (NPC) patients and 2) the effect of high mean doses of OARs on overall survival (OS). Patients and Methods: This retrospective cohort study enrolled non-metastatic Stage I-IV NPC patients from January 2012 to June 2017. OAR mean doses and severe (≥G3) swallowing-related late AE (xerostomia, dysphagia, and lung infection) were evaluated by t-test and validated using receiver operating characteristic curves. The risk factors of OS were calculated by Cox regression methods. Results: This study enrolled 185 (43 female, 142 male) NPC patients, mean age 52.4 years, primarily with Stage III (93, 50.3%) or Stage IV (67, 36.2%) disease. The mean doses of pharyngeal constrictor muscle (PCM), superior-middle PCM (SMPCM), and superior PCM (SPCM) were significantly higher in those with severe (≥G3) lung infection than in those without (65.7 vs 62.2 Gy, p = 0.036; 68.1 vs 64.2 Gy, p = 0.015; and 70.0 vs 65.9 Gy, p = 0.012, respectively). Patients with severe (≥G3) dysphagia had significant higher mean doses of base of tongue (56.2 vs 50.2 Gy, p = 0.008), laryngeal box (50.6 vs 46.4 Gy, p = 0.036), PCM (65.4 vs 62.1 Gy, p = 0.008), SMPCM (67.1 vs 64.2 Gy, p = 0.014), and SPCM (69.3 vs 65.8 Gy, p = 0.004). Mean SMPCM dose >64.9 Gy (adjusted hazard ratio [aHR] = 3.2, 95% confidence interval [CI] 1.2-8.8, p = 0.021), age >62 years (aHR = 2.7, 95% CI 1.1-6.9, p = 0.032), N3 status (aHR = 4.0, 95% CI 1.8-9.0, p = 001), and severe late AE of lung infection (aHR = 4.6, 95% CI 1.5-14.0, p = 0.007) significantly affected OS. Conclusion: Severe lung infection and dysphagia were associated with significantly higher mean doses of PCM, SMPCM, and SPCM. Among these OARs, only a high SMPCM mean dose was a risk factor for OS in NPC patients.

Contralateral lymph node recurrence rate and its prognostic factors in stage IVA-B well-lateralized oral cavity cancer.

PURPOSE: To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. MATERIALS AND METHODS: Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. RESULTS: From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. CONCLUSIONS: Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.

[An experience applying the teaching strategies of cooperative learning and creative thinking in a mental-health nursing practicum for undergraduates at a technical college].

Lack of knowledge and experience is prevalent in undergraduate students who are taking their clinical practicum for mental-health nursing. This issue negatively affects the learning process. This article shares an experience of implementing a practicum-teaching program. This program was developed by the authors to facilitate the cooperative learning and clinical care competence of students. A series of multidimensional teaching activities was designed by integrating the strategies of peer cooperation and creative thinking to promote group and individual learning. Results indicate that the program successfully encouraged the students to participate more actively in the learning process. Additionally, the students demonstrated increased competence in empathetic caring toward patients, stronger friendship relationships with peers, and improved self-growth. The authors hope this teaching program provides a framework to increase the benefits for students of participating in clinical practicums and provides a teaching reference for clinical instructors.

Influence of prenatal nicotine exposure on development of the ventilatory response to hypoxia and hypercapnia in neonatal rats.

In a recent study (Huang YH et al. Respir Physiol Neurobiol 143: 1-8, 2004), we showed that prenatal nicotine exposure (PNE) increased the frequency of spontaneous apneic events on the first 2 days of life in unanesthetized neonatal rats. Here we test the hypothesis that PNE blunts chemoreceptor reflexes. Ventilatory responses to three levels each of hypoxia (inspired O(2) fraction: 16, 12, and 10%) and hypercapnia (3, 6, and 9% inspired CO(2) fraction, all in 50% O(2), balance N(2)), and one level each of combined hypoxia-hypercapnia (H/H; 12% inspired O(2) fraction/5% inspired CO(2) fraction) and hyperoxia (50% O(2), 50% N(2)) were recorded with head-out plethysmography in neonatal rats exposed to either nicotine (N = 12) or physiological saline (N = 12) in the prenatal period. Recordings were made on postnatal day 1 (P1), P3, P6, P9, P12, and P18, in each animal. The change in ventilation in response to hypoxia was blunted in PNE animals on P1 and P3, but there were no other treatment effects. Hyperoxia significantly depressed ventilation in both groups from P3-P18, but there were no significant treatment effects. The ventilatory response to 3, 6, and 9% inspired CO(2) was significantly blunted in PNE animals at all ages studied, due exclusively to a blunted tidal volume response. PNE also blunted the ventilatory response to H/H at all ages, due primarily to blunting of the tidal volume response. PNE had no significant effect on body mass or metabolic rate, except that PNE animals had a slightly higher mass on P18 and a lower metabolic rate on P1. As shown by others, PNE has small and inconsistent effects on hypoxic ventilatory responses, but here we show that responses to hypercapnia and H/H are consistently blunted by PNE due to a diminished tidal volume response. The combination of reduced hypoxic and hypercapnic sensitivity over the first 3 days of life may define an especially vulnerable developmental period.

Anatomic consequences of intrinsic tongue muscle activation.

We recently showed respiratory-related coactivation of both extrinsic and intrinsic tongue muscles in the rat. Here, we test the hypothesis that intrinsic tongue muscles contribute importantly to changes in velopharyngeal airway volume. Spontaneously breathing anesthetized rats were placed in a MRI scanner. A catheter was placed in the hypopharynx and connected to a pressure source. Axial and sagittal images of the velopharyngeal airway were obtained, and the volume of each image was computed at airway pressures ranging from +5.0 to -5.0 cm H2O. We obtained images in the hypoglossal intact animal (i.e., coactivation of intrinsic and extrinsic tongue muscles) and after selective denervation of the intrinsic tongue muscles, with and without electrical stimulation. Denervation of the intrinsic tongue muscles reduced velopharyngeal airway volume at atmospheric and positive airway pressures. Electrical stimulation of the intact hypoglossal nerve increased velopharyngeal airway volume; however, when stimulation was repeated after selective denervation of the intrinsic tongue muscles, the increase in velopharyngeal airway volume was significantly attenuated. These findings support our working hypothesis that intrinsic tongue muscles play a critical role in modulating upper airway patency.

Influence of prenatal nicotine exposure on postnatal development of breathing pattern.

To determine if prenatal nicotine exposure alters the postnatal development of the ventilatory pattern and the frequency and duration of apneas, we recorded respiratory airflow with head-out body plethysmography in awake neonates on postnatal days 1, 2, 6, 10, 14, and 18. Data from 12 nicotine-exposed animals were compared with data from 12 saline-exposed animals. Nicotine (6 mg/kg of nicotine tartrate per day) or saline exposure was induced by osmotic minipumps that were implanted subdermally on the fifth day of gestation in Sprague-Dawley Dams. Although both saline- and nicotine-exposed pups gained weight at the same rate throughout the studies, there were subtle differences in ventilatory indices between the two groups. Nicotine-exposed animals had a significantly higher breathing frequency on day 10, and a lower tidal volume on days 14 and 18. Although ventilation tended to be lower in the nicotine-exposed animals, the difference was not significant. There was a significantly higher frequency of apneas in the nicotine-exposed compared with the saline-exposed animals on postnatal days 1 and 2, but the apnea duration did not differ between the groups. No apneas were observed in any of the animals after the sixth postnatal day. Prenatal nicotine exposure is associated with a greater incidence of apneas on the first two postnatal days, and then an altered breathing pattern that manifests at a later stage of development.