Comparison of Nasal Potential Difference and Intestinal Current Measurements as Surrogate Markers for CFTR Function.

OBJECTIVES: Nasal potential difference (NPD) measurement is part of the diagnostic criteria for cystic fibrosis (CF) and now used routinely as an endpoint in clinical trials of correcting the basic defect in CF. Intestinal current measurement (ICM), measured ex vivo on a rectal biopsy, has been used to study cystic fibrosis transmembrane conductance regulator (CFTR) function but has not been compared to NPD in the same subject in adults and children. The aim of the study is to evaluate the potential usefulness of ICM as a marker of CFTR function for treatment studies compared NPD in patients with CF and in healthy control subjects. METHODS: ICM and NPD were performed on healthy controls and patients with CF. The healthy adults were individuals undergoing routine screening colonoscopy at the Beth Israel Deaconess Medical Center. The healthy children were undergoing colonoscopy for suspicion of inflammation in Hadassah Hebrew University Medical Center. The CF adults were recruited from Boston Children's Hospital CF Center and CF Center Worcester Mass, the children with CF from Hadassah CF Center. RESULTS: ICM measurements in healthy control subjects (n = 16) demonstrated a mean (±SE) carbachol response of 16.0 (2.2) µA/cm, histamine response of 13.2 (2.1) µA/cm and a forskolin response of 6.3 (2.0) µA/cm. Basal NPD of -15.9 (1.9) and response to Cl free + isoproterenol of -13.8 (2.0). These responses were inverted in CF subjects (n = 12) for ICM parameters with carbachol response of -3.0 (0.5) µA/cm, histamine -1.0 (0.8) µA/cm and a forskolin response of 0.5 (0.3) and also for NPD parameters; basal NPD of -42.2 (4.3) and response to Cl free + isoproterenol of 4.3 (0.7). Pearson correlation test showed the comparability of ICM and NPD in assessing CFTR function. CONCLUSIONS: ICM is equivalent to NPD in the ability to distinguish patients with CF from controls and could be used as surrogate markers of CFTR activity in treatment protocols.

Primary surgery versus (chemo)radiotherapy in oropharyngeal cancer: the radiation oncologist's and medical oncologist's perspectives.

PURPOSE OF REVIEW: Radiotherapy is the traditional treatment for oropharyngeal cancer (OPC) because of its ability to preserve anatomic form and function compared with other conventional curative options. Recently, transoral robotic surgery (TORS) and transoral laser microsurgery (TLM) have emerged prominently for T1-T2 OPC. This review summarizes the recent literature pertaining to OPC outcomes following primary TORS/TLM versus primary radiotherapy with or without chemotherapy and addresses controversies surrounding indications for adjuvant treatment following TORS/TLM. RECENT FINDINGS: Articles regarding OPC outcomes after primary TORS/TLM or radiotherapy/chemoradiotherapy published over the past 12 months were identified. TORS/TLM studies reported encouraging oncologic and functional outcomes. Primary radiotherapy alone showed exemplary results for a similar group of patients. However, comparisons of outcomes between these two primary modalities rely on historical data vulnerable to selection bias, even in a matched cohort study. The majority of cases treated with TORS/TLM also received adjuvant treatment. Soft tissue necrosis complicating this approach has also been reported. Controversies exist regarding the definition of resection margin status, prognostic value of extracapsular spread in human papillomavirus-related OPC and indications for adjuvant treatment following TORS/TLM. SUMMARY: TORS/TLM is an attractive approach for selected T1-T2 OPC, but its role should be refined based on a high level of evidence.