Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH

Background/Aims@#Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. @*Methods@#We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. @*Results@#A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. @*Conclusion@#Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Distal Mean Nocturnal Baseline Impedance Predicts Pathological Reflux of Isolated Laryngopharyngeal Reflux Symptoms

Background/Aims@#Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. @*Methods@#In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. @*Results@#Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH– (ILPRS in pH+ vs pH–: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH–: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH– subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH– subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). @*Conclusion@#Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Inhibitory effect of ginsenoside Rg3 on the tube-like structure formation in human nasopharyngeal carcinoma HNE-1 cell line in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the anti-angiogenic effect of ginsenoside Rg3 (Rg3 in abbreviation) in human nasopharyngeal carcinoma HNE-1 cells in vitro.</p><p><b>METHODS</b>The tube-like structure (TLS) formation of HNE-1 cells, cultured in medium with different concentrations of Rg3, was determined by in vitro anti-angiogenic test based on preliminary experiment observing the TLSs formed by HNE-1 cells on Matrigel and their structural characteristics. The VEGF expression level in HNE-1 cells was determined by immunohistochemistry (IHC) and Western-blot test after 48-hour cultured in medium with different concentrations of Rg3.</p><p><b>RESULTS</b>HNE-1 cells could form TLSs and mosaic vessels when mix-cultured with CRL-2480 on Matrigel. Rg3 could inhibit the TLS formation of HNE-1 cells. After 24-hour culture in medium with Rg3 at concentrations of 0, 50, 100 and 200 µg/ml, the number of TLSs were 75.50 ± 6.86, 55.00 ± 11.92, 39.75 ± 7.93 and 24.50 ± 6.25, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.928; P < 0.01). After 48 hours of culture, the expressions of VEGF significantly declined by IHC test with results as 0.19 ± 0.03, 0.13 ± 0.02, 0.11 ± 0.01, and 0.08 ± 0.01, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.911; P < 0.01). The expressions of VEGF also gradually decreased as revealed by Western blot test, with corresponding results as 119.49, 111.51, 86.45, and 38.29. All of the tests showed significantly declined results in the group at the concentration of 200 µg/ml Rg3.</p><p><b>CONCLUSION</b>Rg3 can inhibit the vasculogenic mimicry of HNE-1 cells, and the possible mechanism might be associated with the down-regulation of VEGF protein expression in HNE-1 cells.</p>

Relationship between radiotherapy enhancing effect of arsenic trioxide and the proliferation and apoptosis of related protein in nasopharyngeal carcinoma patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mechanism of arsenic trioxide (ATO) in enhancing radiotherapy in nasopharyngeal carcinoma (NPC) patients.</p><p><b>METHODS</b>Seventy-four patients with NPC of T(1-4) N(0-1)M0 were randomized into two groups: 35 patients in Group A were treated with conventional radiotherapy alone, and the 39 in Group B received radiotherapy and additional administering of ATO. The regressions of nasopharyngeal lesions and cervical lymph nodes were compared between the two groups at 40 Gy of radiation was given. And biopsy of the tissue from NPC was taken before treatment and 24 h after radiation of 20 Gy to determine the-expressions of proliferating cell nuclear antigen (PCNA), Bcl-2, Bax and p53 protein by immunohistochemistry.</p><p><b>RESULTS</b>When irradiation for 40 Gy, the completely regression rates of nasopharyngeal lesion were 20.0% (7/35) in Group A and 43.6% (17/39) in Group B, showing significant difference between them (chi2 = 4.684, P = 0.003), but no significant difference was shown between the two groups in regression rate of cervical lymph node. Expression of PCNA, Bax, Bcl-2 and p53 protein was reduced in both groups, but significant difference only showed between pre- and post-treatment in PCNA (Z = -2.449, P = 0.014) and Bax protein (Z = -3.031, P = 0.002) in Group B. Significantly reduction of PCNA (Z = -2.656, P = 0.008), Bax (Z = -2.359, P = 0.018) and p53 protein (Z = -1.999, P = 0.046) in patients with complete tumor regression at radiation for 20 Gy, while in those with no complete tumor regression only PCNA showed significant reduction (Z = -32.815, P = 0.015).</p><p><b>CONCLUSION</b>ATO shows effect in enhancing radiotherapy on NPC patients, its mechanism might be associated with the down-regulation of PCNA and apoptosis related protein and the inhibition on tumor proliferation and apoptosis inducing.</p>

Phase I/II clinical trial of weekly administration of docetaxel plus cisplatin for advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime.</p><p><b>METHODS</b>In phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial.</p><p><b>RESULTS</b>In the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia.</p><p><b>CONCLUSION</b>Weekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.</p>