Poor consistency between reflux symptom index and laryngopharyngeal pH monitoring in laryngopharyngeal reflux diagnosis in Chinese population.

BACKGROUND: It is unknown whether the reflux symptom index (RSI) can replace pH monitoring as a diagnostic tool for laryngopharyngeal reflux (LPR) in Chinese people. The relationships between reflux parameters and LPR symptoms also require further research. METHODS: A total of 216 Chinese patients underwent laryngopharyngeal pH monitoring and filled out an RSI questionnaire. Laryngopharyngeal pH monitoring indicated a diagnosis of LPR for patients with 7 or more episodes of reflux or a reflex area index (RAI) of 6.3 or more. The RSI questionnaire indicated a diagnosis of LPR for patients with RSI scores of 14 or higher. RESULTS: Of the 216 patients, 85 were diagnosed with LPR as assessed by the RSI, and 72 were diagnosed with LPR through laryngopharyngeal pH monitoring. The Cohen's kappa coefficient comparing LPR diagnosis consistency between RSI score and laryngopharyngeal pH monitoring was 0.133 (P=0.007). This indicated the two diagnostic methods were consistent to a low degree; the total consistency rate was only 59.7% (129/216). The sensitivity of the RSI was 48.6% (35/72), and its specificity was 82.5% (94/114). For convenience, we named the nine symptom groups in the RSI sequentially as P1-P9. P1, P2, P3, P5, P6, and P7 were all correlated with at least one reflux parameter (P<0.05), but P4, P8, and P9 were not correlated with any reflux parameters (P>0.05). A total of 72 patients were diagnosed using pH monitoring, the gold standard for LPR diagnosis. The most common symptoms of LPR were found to be P9, P3, P8, P7, and P2 in these patients. The symptoms that most seriously affected patients were P9, P8, P3, P7, and P2. CONCLUSIONS: The consistency in diagnosis of LPR between the RSI and laryngopharyngeal pH monitoring was poor, meaning the RSI is not a suitable LPR initial screening tool and cannot replace pH monitoring. Additionally, reflux symptoms P4, P8, and P9 were not correlated with any reflux parameters. The most prevalent LPR symptom was P9, followed by P3, P8, P7, and P2. The most severe symptom was also P9, followed by P8, P3, P7, and P2.

The Relationship Between Gastroesophageal Reflux Disease and Laryngopharyngeal Reflux Based on pH Monitoring.

OBJECTIVES: Many studies on the relationship between gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) were based on symptoms, but there are few research on it using reflux monitoring. This study was designed to investigate the relationship between GERD and LPR based on pH monitoring. METHODS: All patients were scheduled for esophageal manometry and pH monitoring sequentially. They were stratified into 4 groups as no reflux disease, isolated GERD, isolated LPR (iLPR), and GERD combined with LPR (GERD&LPR) according to pH monitoring. RESULTS: The incidence of LPR in GERD was 46.3%, while the probability of combining GERD in LPR was 52.7%. The reflux profile in the laryngopharynx showed a significant difference in the total reflux time (17.82 ± 18.4 vs 9.62 ± 9.58, P = .023) and the percentage of total reflux time (1.31% ± 1.37% vs 0.71% ± .0.73%, P = .023) between the GERD&LPR and iLPR groups. CONCLUSION: Laryngopharyngeal reflux can be combined with GERD or it can exist as an independent diagnosis. In patients with GERD&LPR, the total reflux time and the percentage of reflux time in the laryngopharynx are higher than those in the iLPR group. Reflux episodes in the laryngopharynx of patients with GERD&LPR may be derived from GERD.

Occurrence of gastric cancer in patients with atrophic gastritis during long-term follow-up.

BACKGROUND: Additional data on the incidence of gastric neoplasia in the Chinese atrophic gastritis (AG) population during long-term follow-up are needed and the influence of the endoscopic surveillance interval on gastric neoplasia occurrence remains unknown. AIMS: Retrospectively investigated the occurrence of gastric cancer (GC) and precancerous lesions in AG patients during long-term follow-up and assessed risk factors, such as the endoscopic surveillance interval for the development of gastric neoplasia. METHODS: This study enrolled 332 AG patients who underwent initial gastroscopy from 2002 to 2005. Following parameters were collected: age, gender, smoking history, H. pylori infection, location of atrophy and intestinal metaplasia (IM), surveillance interval, follow-up duration, and neoplasia occurrence. RESULTS: Gastric neoplasia was diagnosed in 16 patients. The annual incidence rates per person-year of total gastric neoplasia, gastric high-grade intraepithelial neoplasia (HGIN), early GC and advanced GC were 0.53%, 0.07%, 0.20% and 0.33%, respectively. A multivariate Cox analysis not accounting for the extent of AG and/or IM showed that the risk factors for GC development among AG patients included the presence of AG and/or IM involving both antral and corporal (p<.001, HR 2.898) and H. pylori infection (p=.018, HR 3.946). In the extensive AG and/or IM group, a 2- to 3-year surveillance interval might be instructive in early detection of GC (p=.008, HR 0.015). CONCLUSIONS: Our data reveal an annual incidence rate of 0.53% per person-year for GC and HGIN in AG patients. A 2- to 3-year surveillance interval may be suitable for patients with extensive AG and/or IM.

Rapamycin reverses the senescent phenotype and improves immunoregulation of mesenchymal stem cells from MRL/lpr mice and systemic lupus erythematosus patients through inhibition of the mTOR signaling pathway.

We have shown that bone marrow (BM)-derived mesenchymal stem cells (BM-MSCs) from SLE patients exhibit senescent behavior and are involved in the pathogenesis of SLE. The aim of this study was to investigate the effects of rapamycin (RAPA) on the senescences and immunoregulatory ability of MSCs of MRL/lpr mice and SLE patients and the underlying mechanisms. Cell morphology, senescence associated ß-galactosidase (SA-ß-gal) staining, F-actin staining were used to detect the senescence of cells. BM-MSCs and purified CD4+ T cells were co-cultured indirectly. Flow cytometry was used to inspect the proportion of regulatory T (Treg) /T helper type 17 (Th17). We used small interfering RNA (siRNA) to interfere the expression of mTOR, and detect the effects by RT-PCR, WB and immunofluorescence. Finally, 1x106 of SLE BM-MSCs treated with RAPA were transplanted to cure the 8 MRL/lpr mice aged 16 weeks for 12 weeks. We demonstrated that RAPA alleviated the clinical symptoms of lupus nephritis and prolonged survival in MRL/lpr mice. RAPA reversed the senescent phenotype and improved immunoregulation of MSCs from MRL/lpr mice and SLE patients through inhibition of the mTOR signaling pathway. Marked therapeutic effects were observed in MRL/lpr mice following transplantation of BM-MSCs from SLE patients pretreated with RAPA.

A bama minipig model of laryngopharyngeal reflux and the change of laryngopharyngeal mucosal ultrastructure.

BACKGROUND/AIMS: To establish an animal model of laryngopharyngeal reflux (LPR) and study the effect of LPR on the laryngopharyngeal mucosal ultrastructure. METHODS: Ten Bama minipigs were randomly divided into control group and stent group. Every pig underwent endoscope, and baseline pH was monitored for 4 hours at laryngopharynx and distal esophagus, then specimens from laryngopharyngeal mucosa were biopsied. For the control group, these procedures were repeated on the 14th day. In the stent group, a custom-designed esophageal stent suit was implanted into esophagus, laryngopharyngeal and distal esophageal pH monitoring lasted for 2 hours, then stent suit was removed 3 days later. At last, the same procedures were done as the control group on the 14th day. Specimens were observed under transmission electron microscope to measure the intercellular space and desmosome number. RESULTS: In the control group, there was no laryngopharyngeal reflux on the first day and 14th day. Before the stent was implanted, there was also no laryngopharyngeal reflux in the stent group. In both 2 hours and 14 days after stent implantation, the num-ber of reflux, reflux time, and percentage time of pH < 4.0 were significantly increased (P < 0.05) in the stent group. There was no difference in intercellular space and desmosomes in the control group between baseline and 14th day. In the stent group, intercellular space of laryngopharyngeal mucosa was significantly increased (0.37 µm vs 0.96 µm, P = 0.008), and the number of desmosomes was significantly decreased (20.25 vs 9.5, P = 0.003). CONCLUSIONS: A Bama minipig model of LPR was established by implanting a custom-designed stent suit. LPR might destroy the laryngophar yngeal mucosal barrier.

A Study to Draw a Normative Database of Laryngopharynx pH Profile in Chinese.

BACKGROUND/AIMS: To draw a normative database of laryngopharynx pH profile in Chinese subjects. METHODS: Normal volunteers were recruited from "www.Ganji.com" and People's hospital between May 2008 and December 2009. The Restech pH Probes were calibrated in pH 7 and pH 4 buffer solutions according to the manufacturer's instructions. Each volunteer was asked to wear the device for a 24-hour period and was encouraged to participate in normal daily activities. RESULTS: The healthy volunteers consisted of 20 males and 9 females with a median age of 23 years (interquartile range, 21 to 32 years). The 95th percentiles for % total times at pH < 4, pH < 4.5, pH < 5.0 and pH < 5.5 for the oropharynx pH catheter were 0.06%, 1.01%, 7.23% and 27.34%, respectively. The 95th percentile for number of reflux events within the 24-hour period at pH < 4, pH < 4.5, pH < 5.0 and pH < 5.5 were 2.0, 18.0, 107.5 and 284.5, respectively. CONCLUSIONS: This is the first study to systematically assess the degree of reflux detected by the new pH probe in healthy asymptomatic Chinese volunteers and to report normative values in Chinese people. Using an oropharyngeal pH catheter to monitor laryngopharyngeal reflux indicated that in healthy Chinese, reflux should be considered normal if the percent time at pH less than 4.5 is no more than 1%.

Relationship among symptoms, mucosal injury, and acid exposure in gastroesophageal reflux disease.

BACKGROUND: Symptoms, endoscopy, and pH monitoring form the basis of diagnosis of gastroesophageal reflux disease (GERD). Their relationship was meaningful for primary care physicians, but still unclear. Our research aimed to compare questionnaire, endoscopy, and pH monitoring and to analyze their correlations. METHODS: Three hundred patients who underwent the Reflux Disease Questionnaire (RDQ), endoscopy, and esophageal 24-hour pH monitoring from March 2007 to December 2010 in Peking University People's Hospital were enrolled. We analyzed the characteristics of different investigations and their relationships. RESULTS: Male (OR for mild reflux esophagitis (RE) = 2.433, severe RE = 8.386), body mass index (BMI) (OR for mild RE = 1.222, severe RE = 1.297), and hernia (OR for mild RE = 6.059, severe RE = 17.547), were found to be the risk factors for RE; age (OR = 1.074) was correlated with severe RE. The consistency of questionnaire, endoscopy, and pH monitoring was poor: RDQ did not agree well with pH monitoring (κ = 0.061), nor with endoscopy (κ = 0.044); pH monitoring did not agree well with endoscopy (κ = 0.316). However, the severity of mucosa injury in RE was associated with pathological acid exposure (PAE): reflux episodes of >5 minutes (P = 0.035), the percentage time pH <4 (P = 0.017), and the DeMeester score (P = 0.016) increased significantly in patients with severe RE. Chest pain had poor relationship with RE or PAE. CONCLUSIONS: Male, age, BMI, and hernia were probably risk factors for esophagitis. RDQ, endoscopy, and pH monitoring have their own focus and reinforce each other in diagnosis. Of the GERD symptoms, chest pain had negative correlation with RE or PAE.

[Clinical analysis of 20 cases of synchronous multi-primary esophageal carcinomas].

OBJECTIVE: To explore the clinicopathologic findings, endoscopic features and preoperative diagnostic rates of synchronous multi-primary esophageal carcinomas. METHODS: A total of 602 inpatients were diagnosed as esophageal carcinomas from January 1990 to April 2012. According to Warren's criteria, 20 cases of synchronous multi-primary esophageal carcinomas were enrolled. There were 13 males and 7 females with a mean age of (62 ± 11) years at the onset of diagnosis. Clinicopathologic features and diagnostic methods were studied retrospectively. RESULTS: There were a total of 45 synchronous multi-primary esophageal carcinomas. Most lesions occurred in middle and lower thoracic esophagus (40 lesions, 88.9%) and were of fungating type (27 lesions, 60.0%) under endoscopy. Histologically the most common type was squamous cell carcinoma (36 lesions, 80.0%). Eleven cases of upper gastro-enterography (n = 15) and 6 cases of endoscopy (n = 11) were miss-diagnosed respectively. CONCLUSIONS: Because of a high rate of missed diagnosis, a clinician should be aware of multi-esophageal carcinomas. It is important to perform upper gastro-enterography, abdominal computed tomography and endoscopy conscientiously to improve the diagnosis.

[Analysis of anorectal manometry in 40 women with posterior vaginal prolapse].

OBJECTIVE: To study abnormal defecation in patients with posterior vaginal prolapse combined with anorectal manometry. METHODS: From Jan. 2008 to Nov. 2009, clinical documents and examination of anorectal manometry of 40 patients with posterior vaginal prolapse were studied retrospectively. Anal physiologic testing was performed for 40 patients. These patients were classified into group A (stage 0 and I posterior vaginal prolapse, represented normal) and group B (stage II-IV). Results of anorectal manometry, constipation and symptoms of defecation were compared. RESULTS: The average anal canal resting pressure and squeeze pressure of 40 patients were (40 ± 21) and (96 ± 33) mm Hg (1 mm Hg = 0. 133 kPa). In group A, the anal canal resting pressure and squeeze pressure were (37 ± 21) and (78 ± 43) mm Hg, rectal sensation threshold and rectal maximum volume were (106 ± 61) and (183 ± 51) ml. In group B, the anal canal resting pressure and squeeze pressure were (42 ± 21) and (102 ± 30) mm Hg, rectal sensation threshold and rectal maximum volume were (90 ± 44) and (171 ± 61) ml. Apart from maximum squeeze pressure (P = 0.039), the other clinical index did not show statistical difference (P > 0.05). Rectal sensation threshold, intended volume and maximum capacity of (116 ± 69), (170 ± 90), (191 ± 75) ml in patients with constipation were higher than (84 ± 31), (121 ± 37), (169 ± 45) ml in patients without constipation. In addition to maximum capacity (P = 0.281), the other clinical index reached statistical difference between patients with and without constipation (P < 0.05). Patients with defecation symptoms have higher rectal sensation threshold, intended volume and maximum capacity than those of patients without defecation symptoms. CONCLUSIONS: As gradually increased in the degree of prolapse, resting pressure and squeeze pressure tend to be increased, while the rectal sensation threshold and rectal maximum volume tend to be decreased. Patients with defecation symptoms and constipation have increased the initial feeling of volume and maximum tolerated volume.

[Symptom-based relationship between gastroesophageal reflux disease and laryngopharyngeal reflux disease].

OBJECTIVE: To explore the relationship between gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux disease (LPRD) based on symptoms. METHODS: A total of 1090 patients undergoing upper digestive tract motility test were invited to complete the surveys of reflux disease questionnaire and reflux symptom index from August 2007 to October 2010. And 895 responders provided valid answers. There were 474 females and 421 males. RESULTS: Among 895 responders, 351 patients had neither, 218 suffered both conditions, 237 were diagnosed as GERD alone and 89 LPRD alone. No difference was found in age (P = 0.383)or gender ratio (P = 0.227). In 455 GERD patients, there were 218 LPRD cases (47.9%). In 307 LPRD patients, 218 (71.0%) had concurrent GERD. In GERD patients, the frequency and degree of feeling of stomach content reflux into mouth were correlated with RSI (r = 0.115, 0.141, P = 0.007, 0.001). CONCLUSION: GERD and LPRD may coexist or occur alone. Because of a high concurrent ratio of LPRD in GERD, the treatment strategy of GERD should be modified accordingly. In GERD patients, the feeling of stomach content reflux into mouth may suggest a possibility of LPRD.

[A pilot study on diagnosing laryngopharyngeal reflux disease by pH monitoring in laryngopharynx].

OBJECTIVE: To analyze the significance of pH monitoring and reflux symptom index (RSI) in the diagnosis of laryngopharyngeal reflux disease (LPRD) and the characteristics of LPRD in symptoms and pH monitoring. METHODS: RSI questionnaire survey and laryngopharyngeal pH monitoring were conducted on. 31 patients with laryngopharyngeal reflux-related symptoms, 15 males aged (50 +/- 13) years and 16 females aged (48 +/- 11) years, Gastroscopy was conducted on 13 patients to detect reflux esophagitis. The patients with the RSI scores > or = 13 were suspected as with LPRD and those with the reflux times > or = 7 or reflux area index (RAI) > or = 6.3 were diagnosed as with LPRD. McNemar test and Kappa test were performed on the RSI scores and reflux area indexes. RESULTS: Seventeen patients met the pH criteria. There were 8 patients suffering from voice disorders, 17 from clearing throat, 13 from excess throat mucus, 11 from dysphagia, 9 from cough after eating or with supine posture, 9 from dyspnea, 13 from cough, 12 from foreign body sensation, and 14 from digestive symptoms with the foregoing symptoms' mean scores of 1.4, 3.1, 2.1, 2.0, 1.1, 1.6, 1.8, 2.9, and 2.9 respectively. The P value with McNemar test on pH monitoring and RSI scoring was 0.289, and the P value with kappa test was 0.007. RSI was correlated with RAI(r(s) = 0.302, P = 0.049), reflux time (r(s) = 0.454, P = 0.005), and reflux time percentage (r(s) = 0.439, P = 0.007), but not correlated with the reflux frequency (r(s) = 0.252, P = 0.086). Supine reflux was seen in only 7 of the 224 reflux events in 17 patients, lasting only 96 seconds during the 84.6 minutes' supine acid exposure time. CONCLUSION: The common symptoms of LPRD are clearing throat, digestive symptoms, excess throat mucus, and foreign body sensation. Laryngopharyngeal pH monitoring and RSI scoring have the same value in diagnosing LPRD. Acid exposure in laryngopharynx is correlation to patients' self-report symptom. Almost all reflux events occur when the patients are in upright position.

Frequent mutation related with overexpression of DNA polymerase beta in primary tumors and precancerous lesions of human stomach.

To explore whether DNA polymerase beta (pol beta) contributes to the malignant transformation of gastric mucosa, we examined pol beta in gastric tumor cell lines, primary tumors and precancerous lesions. Point mutations of pol beta were detected in 6 of 13 cell lines and 23 of 104 tissues including 35.0% (14/40) of gastric cancer (GC), 30.0% (3/10) of dysplasia (Dys), 28.6% (4/14) of intestinal metaplasia (IM) and 10.5% (2/19) of chronic atrophic gastritis (CAG), respectively. A frequent mutation was a T to C transition at nucleotide 889, which was observed in 4 GC cell lines, 7 GC, 2 Dys, and 2 IM. The level of pol beta expression in tumors was higher than that of their matched normal tissues and gradual changes from GC, Dys, CAG to IM. These results indicate that the mutation and overexpression of pol beta may influence the progression during gastric carcinogenesis.

[A study on the relationship of Helicobacter pylori, gastrin and gastroesophageal reflux disease].

OBJECTIVE: To study the relationship of Helicobacter pylori, lower esophageal sphincter pressure and gastrin in gastroesophageal reflux disease, to evaluate the effect of Helicobacter pylori on gastroesophageal reflux disease. METHODS: 20 patients were underwent 24-hour ambulatory esophageal pH monitoring to confirm the diagnosis of gastroesophageal reflux disease, and their lower esophageal sphincter pressure was measured by esophageal manometry. The patients were diagnosed endoscope negative GERD and endoscope positive GERD by endoscopy, and 3 biopsy specimens obtained from the gastric antrum at the same time were used for Helicobacter pylori culture, rapid urease test and Warthin-Starry stain. Hp infection was affirmed when at least two of the three tests were positive, then the patients were divided into Hp-negative group and Hp-positive group. Fasting serum gastrin concentration was determined by radioimmunoassay in 13 patients. RESULTS: Hp-positive patients were 8 (male 4, endoscope negative GERD 2, mean age 55 +/- 9), Hp-negative patients were 12 (male 10, endoscope negative GERD 3, mean age 55 +/- 10). 13 of these patients were performed fasting serum gastrin measurement. The mean lower esophageal sphincter pressure, gastrin concentration and 24-hour pH monitoring DeMeester score in Hp-positive patients group were 11.25 mm Hg, 87.437 pg/ml and 72.30 respectively, and those in Hp-negative patients group were 13.75 mm Hg, 88.725 pg/ml and 55.64. Between the two groups, there was no significant difference in LESP, gastrin and DeMeester score (P = 0.193, P = 0.932 and P = 0.479); There was no correlation between LESP and gastrin, while serum gastrin level is associated strongly with DeMeester score (r = 0.902, P < 0.01). CONCLUSION: The study showed that Helicobacter pylori had no effect on LESP by gastrin, however serum fasting gastrin concentration and DeMeester score were associated with each other.