| ObjectiveLaryngeal cancer is common occurrence in head and neck cancer, almost accounting for 2.1～7.6% of generalized malignancy, accounting for 7.9%-35% of the ear, nose and throat cancer, the incidence is still rising in recent years. The vast majority of laryngeal Squamous Cell Carcinoma, which 90% of larynx cancer derived from epithelial precancerous lesions. Laryngeal precancerous is mean laryngeal Squamous in the middle stages between normal tissue and cancerous. Laryngeal precancerous lesions include:laryngeal Keratosis, laryngeal Papilloma in adult chronic hypertrophic laryngitis. During the process of development of laryngeal cancer and laryngeal precancerous lesions is an important stage. Although the increase in early diagnosis of laryngeal cancer in recent years, surgical advances, and the comprehensive application of radiotherapy and chemotherapy, postoperative laryngeal cancer quality of life has improved greatly in the past, but the overall 5-year survival rate of patients with laryngeal cancer has not been significantly improved. Therefore, specific pathogenic factors and pathogenesis of laryngeal cancer, reduce the incidence of laryngeal cancer is very important.Previous epidemiological investigation found possible etiologies of laryngeal cancer and laryngeal precancerous lesions such as smoking, alcohol consumption, air pollution, occupational factors. However, the decline of smoking rates in recent years in Europe and the United States, also the improvement of the environment, no significant decline in the incidence of laryngeal Carcinoma reciprocal. there could be other factors involved in the occurrence and development of laryngeal cancer and precancerous lesions. More than 10 years ago, scholars have found in the follow-up of patients with partial resection of the stomach increases the risk of laryngeal cancer and laryngeal precancerous lesions, continuing studies found gastric reflux after resection of part of the stomach to the throat increased, it is recommended that after partial resection of the stomach, throat should be enhanced to observe and is conducive to the early diagnosis of laryngeal cancer. Multiple clinical studies have found in recent years in patients with laryngeal carcinoma and laryngeal precancerous lesions, pathological reflux were significantly higher than normal, suggesting that laryngopharyngeal reflux associated with laryngeal precancerous lesions such as vocal cords Leukoplakia.Laryngopharyngeal reflux disease (LPRD) refers to reflux of gastric contents into the throat and upper airway and digestive tract and damage mucous membranes of the throat, causing a range of symptoms and signs in general. Research think stomach content real main through following two aspects caused throat of Pathology change, while reflux real in the gastric acid and the stomach protease, caused injury on throat and the around organization, as hypertrophy laryngitis; On the other hand, distal esophageal within of gastric acid can stimulus vagus nerve caused repeatedly clear throat, and cough, similar action makes vocal substantially movement, intensified vocal friction, also will led injury on throat and the around organization. Both cooperative work, speeding up the laryngeal Epithelial Hyperplasia, promotes the formation and atypical hyperplasia and Cornification.In recent years,24 hours more channel cavity Impedance -PH monitoring gradually get application in clinical, which has more advantage than traditional PH monitoring, it can objective, and precise of quantitative analysis judge reflux, can recognition acid, and acid, and weak base reflux, even can discriminant gas, and liquid gas liquid mixed reflux. The diagnosis sensitivity high effective, and it can distinguish no acid of liquid reflux.24 hour impedance-pH monitoring for reflux evaluation accuracy, can provides a good basis for clinical research and treatment.Laryngopharyngeal reflux-related treatment for vocal cord Leukoplakia is definitely concluded. Anti-reflux therapy in treatment of vocal cord Leukoplakia, were not fully researched. The question that whether all vocal Leukoplakia require anti-reflux treatment, whether anti-reflux treatment should succession of diagnose such as PH monitoring. The details of anti-reflux treatment such as how to choice of drug, dose and treatment time, still no answer. No treatment guidelines are due to lack of an existing understanding and study of laryngopharyngeal reflux.This research using a multiple impedance-pH monitoring techniques to assess patients with early glottic cancer and vocal cord Leukoplakia of pharyngeal reflux and gastro-esophageal reflux, preliminary study on pharyngeal reflux and correlation of early vocal cord cancer and vocal Leukoplakia, combined with the history of smoking, drinking, exploring whether pharyngeal reflux are independent risk factors of early vocal cord cancer and vocal cord Leukoplakia.MethodsSubjects:prospective study. Study included a group of early vocal cord cancer, a group of vocal Leukoplakia and a healthy volunteers group. Inclusion criteria:1. Laryngeal cancer group:Patients with early vocal cord cancer hospitalization in Nanfang hospital from December 2012 to January 2014. Patient consent 24H more combined impedance-pH monitoring.2. Group of vocal Leukoplakia:Patients with vocal Leukoplakia hospitalization in Nanfang hospital from December 2012 to January 2014. Patient consent 24H more combined impedance-pH monitoring.3. Control group:select group of healthy volunteers as controls, volunteers have no phonation disorders, no long-term history of smoking and drinking, without a throat disease. Guiding the participants through physician self-administered RSI scales, electronic laryngoscope throat structure properly, had no previous history of throat surgery.Exclusion criteria:Requires no history of related diseases of the digestive system and the neuromuscular system, history of asthma or cardiovascular and other significant, patients with a history of chronic disease. Selected check 2 weeks ago no upper respiratory tract infection, without taking drugs such as proton pump inhibitors, and promote gastrointestinal. All of them accepted impedance-pH monitoring. Ruled out participation but failed to complete the test (including the 2 impedance-pH monitoring in patients with intolerance,2 cases of gastro-esophageal reflux monitoring only),3 cases in healthy volunteers (2 cases without impedance-pH monitoring,1 patients with hiatal hernia). All are voluntary and informed consent of patients and healthy volunteers participated in the study and signed a consent form. History collectionCollect the patient details include smoking, drinking and drug use history, and throat symptoms and timing, and data of electronic laryngoscope. Positive of smoking refers of still smoking before treatment, and smoking more than 2 a day and last for more than 1 year; alcohol-positive prior to admission were still drinking, and drinking more than 2 times per week, lasting more than 1 year.24 hour impedance-pH (24hMII-pH) monitoring:Zephr portable multichannel impedance-pH monitoring system (Sandhill Scientific Inc, USA) and type ZAI-BL-48E electrodes. Monitoring in patients with at least 8 hours no drinking, take the recumbent monitoring catheters from nasal, according to dynamic monitoring and orientation of the esophagus LES positions, fixed external reference electrode on the chest. Adjust Zephr multi-channel portable systems began recording the impedance-pH monitoring data of reflux and gastro-esophageal reflux, mealtimes and 5min after meals are not included in the reflux time. Inform the patient notes, avoid acid-alkaline food, avoid strenuous exercise, and returned to gastrointestinal examination room at the same time the 2nd day (make sure monitoring time more than 24 h), dismantle the instrument, then put the record. Monitoring data processing using by Bioview reflux analysis software (Sandhill Scientific) the output wave about the data reporting. Bioview reflux monitoring data analysis software handle the output waveform data given reflux figure.Analysis laryngopharyngeal reflux include stand position, recumbent position, number of throat acid reflux, acid reflux, pharyngeal acid exposure time, the percent (%) and mean acid clearance time. Analysis on esophageal acid reflux include total of pH<4%,5min times, the longest reflux time, pH<4 reflux time, frequency.Diagnostic criteria:DeMeester analysis software based on the score is made up of Bioview reflux esophageal acid exposure (pH) 6 parameters (parameters are based on 24-hour standard) is given to assess acid reflux condition. According to Johnson and DeMeester standard definition of gastro-esophageal reflux DeMeester>14.7Laryngopharyngeal reflux event judge standard:① throat pH<4.0, continued more than 5 seconds; ②throat pH declined not before than distal electrode pH value, its minimum value not below distal pH value; ③ pH declined is fast, not gradually, otherwise that pseudo; ④pH declined not occurred in eating or swallowing,laryngopharyngeal reflux positive criteria:reflux times more than or equal to 2 times. Analysis of laryngopharyngeal reflux (impedance) proximal reflux number, total number of liquid reflux and longest average cleaning time of bolus, reflux events. Reflux events according to the pH can be divided into:acid reflux, acid reflux, weak base reflux. Acid reflux:Esophageal pH values fell below 4, or esophageal PH value below 4. Acid reflux:Esophageal pH value felled, but still between 4-7. Weak base reflux:reflux events cannot be to lower esophageal pH values below 7. Among them, the weak acid and weak base reflux are property of no acid reflux. In addition, according to heights of different reflux, this research uses will reach above the LES 15cm MII-pH electrode types defined as proximal reflux, and vice versa for distal reflux.Statistical analysis:This research data is processed using statistical software SPSS 17.0. Continuous data are mean ± standard deviation (Mean ± SD) that the discrete information number of cases (%) (n (%)). Normally distributed continuous data using t test, non-normal distributed continuous data using the Wilcoxon rank-sum test. Analysis of the correlation between two variables, normally distributed data select the Pearson correlation coefficient expresses the correlation between two variables, select Spearman rank correlation coefficient not normally distributed data. Select test level P<0.05 the difference was statistically significant.Results1. Total take into laryngeal cancer patients 19 cases, which male 18 cases, female 1 cases, average age 60.2 ±8.2 age, distribution range 46～78 years old; vocal blaze patients are for male, total 17 people, average age 52.1 ± 8.6 age, distribution range 41-66 years old; control group:health volunteers 16 cases, hospital workers 4 cases and medical students 12 cases, which men and women each 8 cases, average age 26.6 ± 8.5 age, distribution 20-49 years old.2.24hMII-pH monitoring laryngopharyngeal reflux results:Laryngeal cancer group:Throat acid reflux≥ 1 times in 6 cases, acid reflux≥ 2 times in 5 cases (5/19,26.3%),0.0～42.0 Laryngeal acid reflux, acid reflux time from 0.0-174.8 minutes, acid clearance time of 0.0～1049.0 seconds. Vocal cord Leukoplakia group:Throat acid reflux≥ 1 times in 7 cases, throat acid reflux≥ 2 times in 6 cases (6/17,35.3%),0.0～156.0 throat acid reflux, acid reflux time 0.0-374.1 minutes, acid clearance time of 0.0～144.0 seconds. Control group lcase throat acid reflux in 2 times, throat acid reflux≥ 2 times in 2 cases (2/16,12.5%), acid reflux time 0.0-0.4 minutes, acid clearance time of 0.0-9.0 seconds.Vocal Cancer Group throat acid reflux times, and acid reflux time and acid cleared time are more than control group obviously (Z value respectively for-2.239,-2.631 and -2.480, P value< 0.05), differences are has statistics meaning; Vocal cord Leukoplakia group also are more than control group obviously (Z value respectively for-3.186, and-3.298 and -3.411, P value are <0.05), differences also are has statistics meaning. But laryngopharyngeal reflux positive rate showed no statistically difference (p-value of 0.415 and 0.225) between control group and Vocal CancerGroup or Vocal cord Leukoplakia group.3. DeMeester score of vocal Cancer Group more than control group, and the same as reflux> 5 minutes times and most long acid reflux time, differences are has statistics meaning (Z value respectively for-2.252, and-3.921 and 2.215, P value are <0.05); gastroesophageal reflux positive rate, and PH<4 reflux times more than control group but the differences are no statistics meaning (p value respectively for 0.187 and 0.132). DeMeester score of Vocal cord Leukoplakia group more than the control group, times of esophagus pH<4/ the longest time of reflux/gastroesophageal reflux and the positive rate compared with the control group showed no statistically significant difference (p>0.05), time of reflux> 5 minutes more than the control group, there was a statistically significant difference (Z-3.051, P<0.05).4. Laryngopharyngeal reflux and feature analysis of reflux:vocal cord Cancer Group, Vocal cord Leukoplakia group and the control group has one same that reflux events were dominated by standing, supine reflux is rare. Vocal cord Cancer Group median total number of reflux 31.0[26.0; 41.0] times, vocal cord Leukoplakia reflux overall median number of 34.0[21.0; 71.3], control group for 32.5[20.0; 36.3], total number of reflux in both groups and the control group showed no statistically significant difference (p>0.05). Chemical properties most in acid reflux and weak acid reflux, alkaline reflux ratio is rarely. Group of vocal Leukoplakia weak base reflux, supine standing acid reflux and lying weak base number significantly increased compared with the control group, there were significant differences (p <0.05). weak base reflux, supine standing acid reflux and lying weak base number of vocal cord cancer group has no statistically significant differences with the control group (p>0.05).5. The correlation between laryngopharyngeal reflux/gastro-esophageal reflux and smoking/drinking:36 cases with carcinoma or vocal Leukoplakia. According to ≥ 2 times the number of throat acid reflux judge positive laryngopharyngeal reflux 12 cases; 11 cases had a history of smoking; 8 cases had a history of drinking; laryngopharyngeal reflux in patients with negative 24 cases, smokers,21 cases had a history of drinking in 15 cases. According to DeMeester positive score ≥ 14.7 as gastro-esophageal reflux,9 patients with gastro-esophageal reflux,9 cases had a history of smoker,8 cases had a history of drinking; gastro-esophageal reflux negative 27 cases, smokers in 23 cases, had a history of drinking in 15 cases. Fisher exact probability analysis laryngopharyngeal reflux, gastro-esophageal reflux correlation with smoking history, drinking history, no founding that laryngopharyngeal reflux, gastro-esophageal reflux associated with smoking history/drinking history (p>0.05).Conclusions1. While no significant differences of laryngopharyngeal reflux positive rates in early laryngeal cancer/vocal cord Leukoplakia from control group, throat reflux event times, acid reflux and throat clearing time compared with the control group showed statistically differences, suggesting that laryngopharyngeal reflux associated with laryngeal and vocal cord Leukoplakia;2. In this study, found no correlation between laryngopharyngeal reflux and smoking/drinking. Laryngopharyngeal reflux possibly independent risk factors for laryngeal cancer and vocal cord Leukoplakia;3. All participating in the experimental group laryngopharyngeal reflux in orthostatic position, which mean the anti-reflux treatment should be strengthened in daytime;4. Through the observation of typical cases, we found that postoperative recovery in patients with sore positive laryngopharyngeal reflux and negative differences, laryngopharyngeal reflux can lead to adverse outcomes.5. Through typical case observation and literature review, the treatment of vocal cord leukoplakia should pay attention on reflux. |
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