Nonacid reflux episodes reaching the pharynx are important factors associated with cough

BACKGROUND: Gastroesophageal reflux is implicated in the pathogenesis of asthma and chronic cough. To date most studies have focused on acid reflux measured by pH below the upper esophageal sphincter (UES). The aim of this study was to assess the relationship between cough and reflux through the UES into the pharynx. METHODS: Thirty-seven patients with asthma (19) and chronic cough (18) were recruited from the respiratory clinic. Reflux was monitored using a combined multichannel intraluminal impedance and pH probe by detecting (1) bolus reflux episodes within the esophagus and in the pharynx and (2) acidic reflux episodes within the esophagus and in the pharynx. All acid suppressive therapy was stopped for at least 7 days before the study. Demonstration of cough being linked to reflux was achieved using the symptom association probability (SAP). This was calculated using a 2-minute association window between symptoms and bolus entry into the esophagus. SAP was considered positive if >95%. RESULTS: A positive SAP for cough was noted in 7/26 patients reporting symptoms on the day of monitoring. Compared with SAP-negative patients, SAP-positive patients had both a greater number [median (interquartile range), 5(2 to 8) vs. 2(0 to 4), P<0.05] and a higher proportion of reflux episodes crossing the UES into the pharynx [25%(14% to 28%) vs. 7% (2% to 14%), P<0.02]. There was no difference in the number of reflux episodes or acid exposure time in the distal esophagus between SAP-positive and SAP-negative patients. Only 1% to 2% of episodes were detected by the pharyngeal pH sensor. CONCLUSIONS: Impedance detected pharyngeal reflux episodes are important factors in symptom production in cough patients.

Autophagy in malignant transformation and cancer progression.

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

BACKGROUND Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION ISRCTN71502099 on 19 May 2014.