Achalasia: The Current Clinical Dilemma and Possible Pathogenesis

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients’ quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

The normal values of water-perfused high resolution esophageal manometry: a multicenter study / 中华消化杂志

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Symptom Severity Related With Contraction Peaks in Patients With Jackhammer Esophagus

Background/Aims@#Jackhammer esophagus is an uncommon heterogeneous motility disorder associated with a distal contractile integral > 8000 mmHg · sec · cm. The spectrum of abnormality ranges from a relatively normal looking contraction to chaotic repetitive contractions akin to a jackhammer. Although previous studies have shown an uncertain correlation between peristaltic vigor and symptoms, we hypothesize that symptoms may be more severe with repetitive contractions as opposed to an elevated contractile measure. Thus, this study aims to investigate whether symptom severity is related to the contraction pattern in the patients with hypercontractile esophagus. @*Methods@#Patients with hypercontractile esophagus were retrospectively identified, their demographic and high-resolution manometry characteristics were collected. Contraction pattern on high-resolution manometry was categorized into single-peak and multiple-peak.Comparison was performed between patients with single-peak and multiple-peak. @*Results@#Altogether 35 patients (age range, 45-70 years; female:male, 24:11) were included. Seven patients presented with single-peak hypercontractile swallows, while 28 patients presented with multiple-peak hypercontractile swallows. The patients with multiple-peak showed higher Brief Esophageal Dysphagia Questionnaire scores compared with patients with single-peak. The jackhammer swallows with multiple-peak were associated with higher distal contractile integral values, longer distal latency intervals, and a lower integrated relaxation pressure. @*Conclusions@#Repetitive contractions akin to a jackhammer were common amongst patients with hypercontractile esophagus. Patients with the jackhammer pattern also presented with more severe symptoms. Further distinction of hypercontractile esophagus into a jackhammer dominant subtype may be warranted.

Upright Integrated Relaxation Pressure Predicts Symptom Outcome for Esophagogastric Junction Outflow Obstruction

Background/Aims@#Esophagogastric junction outflow obstruction (EGJOO) is characterized by elevated integrated relaxation pressure (IRP) and preserved esophageal peristalsis. The clinical significance of EGJOO is uncertain. This study aim to describe the clinical characteristics of these patients and to find out potential parameters to predict patients’ symptom outcome. @*Methods@#Consecutive patients who received high-resolution manometry examination in our hospital in 2013-2019 and met the diagnostic criteria of EGJOO were retrospectively included. Motility and reflux parameters as well as endoscopy and barium esophagogram results were studied and compared. Patients were also followed up to record their treatment methods and symptom outcomes. @*Results@#A total of 138 EGJOO (accounting for 5.2% of total patients taking high-resolution manometry examination in our hospital) patients were included. Only 2.9% of these patients had persistent dysphagia. A total of 81.8% of EGJOO patients had symptom resolution during follow-up. Patients with persistent dysphagia had significantly higher upright IRP (16.6 [10.3, 19.8] vs 7.8 [3.2, 11.5]; P = 0.026) than those without. Upright IRP can effectively distinguished patients with persistent dysphagia (area under curve: 0.826; P = 0.026) using optimal cut-off value of 9.05 mmHg. @*Conclusion@#EGJOO patients with persistent dysphagia and higher upright IRP (median > 9.05 mmHg) needs further evaluation and aggressive management.

Acid Exposure Time > 6% Might Not Improve the Therapeutic Outcome in Chinese Gastroesophageal Reflux Disease Patients

Background/Aims@#There is less acid burden in Chinese gastroesophageal reflux disease (GERD) patients. However, the Lyon consensus proposed a higher threshold of acid exposure time (AET > 6%) for GERD. The aims are to apply the updated criteria in Chinese GERD patients and clarify its influence on clinical outcome. @*Methods@#Patients who were referred for both esophageal high-resolution manometry and 24-hour esophageal pH monitoring due to reflux symptoms were retrospectively screened. Those patients with AET > 4% was included and grouped into either AET 4-6% or AET > 6%. Their manometric profile, reflux profile, and response to proton pump inhibitors (PPIs) were evaluated. Adjunctive evidence proposed in the Lyon consensus was added in patients with AET 4-6% for therapeutic gain. Another group of patients (n = 144) with AET 6% (74.9%). GERD patients with AET > 4% were with more male, older patients, and higher body mass index compared with non-GERD patients. Meanwhile, GERD patients were less competent in esophagogastric junction pressure. However, the manometric and reflux profile were similar between patients with AET > 6% and 4-6%. The response rate of PPI therapy was 64.6% and 63.2%, respectively, in groups of AET > 6% and 4-6% (P > 0.05). When adjunctive evidence was added in patients with AET 4-6%, no therapeutic gain was obtained. @*Conclusions@#The efficacy of PPI therapy was similar in patients with AET > 6% and 4-6%. The increase of the AET threshold did not influence the clinical outcome of Chinese GERD patients.

Knowledge, Attitude, and Practice Survey of Gastroparesis in Asia by Asian Neurogastroenterology and Motility Association

Background/Aims@#Gastroparesis is identified as a subject that is understudied in Asia. The scientific committee of the Asian Neurogastroenterology and Motility Association performed a Knowledge, Attitude, and Practices survey on gastroparesis among doctors in Asia. @*Methods@#The questionnaire was created and developed through a literature review of current gastroparesis works of literature by the scientific committee of Asian Neurogastroenterology and Motility Association. @*Results@#A total of 490 doctors from across Asia (including Bangladesh, China, Hong Kong, Indonesia, Japan, Malaysia, Myanmar, the Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam) participated in the survey. Gastroparesis is a significant gastrointestinal condition. However, a substantial proportion of respondents was unable to give the correct definition and accurate diagnostic test. The main reason for lack of interest in diagnosing gastroparesis was “the lack of reliable diagnostic tests” (46.8%) or “a lack of effective treatment” (41.5%). Only 41.7% of respondents had access to gastric emptying scintigraphy. Most doctors had never diagnosed gastroparesis at all (25.2%) or diagnosed fewer than 5 patients a year (52.1%). @*Conclusions@#Gastroparesis can be challenging to diagnose due to the lack of instrument, standardized method, and paucity of research data on normative value, risk factors, and treatment studies in Asian patients. Future strategies should concentrate on how to disseminate the latest knowledge of gastroparesis in Asia. In particular, there is an urgent need to estimate the magnitude of the problems in high risk and idiopathic patients as well as a standardized diagnostic procedure in Asia.

Symptom Severity Related With Contraction Peaks in Patients With Jackhammer Esophagus

Background/Aims@#Jackhammer esophagus is an uncommon heterogeneous motility disorder associated with a distal contractile integral > 8000 mmHg · sec · cm. The spectrum of abnormality ranges from a relatively normal looking contraction to chaotic repetitive contractions akin to a jackhammer. Although previous studies have shown an uncertain correlation between peristaltic vigor and symptoms, we hypothesize that symptoms may be more severe with repetitive contractions as opposed to an elevated contractile measure. Thus, this study aims to investigate whether symptom severity is related to the contraction pattern in the patients with hypercontractile esophagus. @*Methods@#Patients with hypercontractile esophagus were retrospectively identified, their demographic and high-resolution manometry characteristics were collected. Contraction pattern on high-resolution manometry was categorized into single-peak and multiple-peak.Comparison was performed between patients with single-peak and multiple-peak. @*Results@#Altogether 35 patients (age range, 45-70 years; female:male, 24:11) were included. Seven patients presented with single-peak hypercontractile swallows, while 28 patients presented with multiple-peak hypercontractile swallows. The patients with multiple-peak showed higher Brief Esophageal Dysphagia Questionnaire scores compared with patients with single-peak. The jackhammer swallows with multiple-peak were associated with higher distal contractile integral values, longer distal latency intervals, and a lower integrated relaxation pressure. @*Conclusions@#Repetitive contractions akin to a jackhammer were common amongst patients with hypercontractile esophagus. Patients with the jackhammer pattern also presented with more severe symptoms. Further distinction of hypercontractile esophagus into a jackhammer dominant subtype may be warranted.

Upright Integrated Relaxation Pressure Predicts Symptom Outcome for Esophagogastric Junction Outflow Obstruction

Background/Aims@#Esophagogastric junction outflow obstruction (EGJOO) is characterized by elevated integrated relaxation pressure (IRP) and preserved esophageal peristalsis. The clinical significance of EGJOO is uncertain. This study aim to describe the clinical characteristics of these patients and to find out potential parameters to predict patients’ symptom outcome. @*Methods@#Consecutive patients who received high-resolution manometry examination in our hospital in 2013-2019 and met the diagnostic criteria of EGJOO were retrospectively included. Motility and reflux parameters as well as endoscopy and barium esophagogram results were studied and compared. Patients were also followed up to record their treatment methods and symptom outcomes. @*Results@#A total of 138 EGJOO (accounting for 5.2% of total patients taking high-resolution manometry examination in our hospital) patients were included. Only 2.9% of these patients had persistent dysphagia. A total of 81.8% of EGJOO patients had symptom resolution during follow-up. Patients with persistent dysphagia had significantly higher upright IRP (16.6 [10.3, 19.8] vs 7.8 [3.2, 11.5]; P = 0.026) than those without. Upright IRP can effectively distinguished patients with persistent dysphagia (area under curve: 0.826; P = 0.026) using optimal cut-off value of 9.05 mmHg. @*Conclusion@#EGJOO patients with persistent dysphagia and higher upright IRP (median > 9.05 mmHg) needs further evaluation and aggressive management.

The Practice of Gastrointestinal Motility Laboratory During COVID-19 Pandemic: Position Statements of the Asian Neurogastroenterology and Motility Association (ANMA-GML-COVID-19 Position Statements)

During the Coronavirus Disease 2019 (COVID-19) pandemic, practices of gastrointestinal procedures within the digestive tract require special precautions due to the risk of contraction of severe acute respiratoy syndrome coronavirus-2 (SARS-CoV-2) infection. Many procedures in the gastrointestinal motility laboratory may be considered moderate to high-risk for viral transmission. Healthcare staff working in gastrointestinal motility laboratories are frequently exposed to splashes, air droplets, mucus, or saliva during the procedures. Moreover, some are aerosol-generating and thus have a high risk of viral transmission. There are multiple guidelines on the practices of gastrointestinal endoscopy during this pandemic. However, such guidelines are still lacking and urgently needed for the practice of gastrointestinal motility laboratories. Hence, the Asian Neurogastroenterology and Motility Association had organized a group of gastrointestinal motility experts and infectious disease specialists to produce a position statement paper based-on current available evidence and consensus opinion with aims to provide a clear guidance on the practices of gastrointestinal motility laboratories during the COVID-19 pandemic. This guideline covers a wide range of topics on gastrointestinal motility activities from scheduling a motility test, the precautions at different steps of the procedure to disinfection for the safety and well-being of the patients and the healthcare workers. These practices may vary in different countries depending on the stages of the pandemic, local or institutional policy, and the availability of healthcare resources. This guideline is useful when the transmission rate of SARS-CoV-2 is high. It may change rapidly depending on the situation of the epidemic and when new evidence becomes available.

Clinical efficacy of modified peroral endoscopic myotomy in the treatment of 51 cases of achalasia / 中华消化杂志

Objective:To evaluate the effects of modified peroral endoscopic myotomy (POEM) on esophageal dynamics and clinical efficacy in achalasia (AC) patients.Methods:From January 2013 to December 2014, 51 patients diagnosed with AC and received modified POEM at The First Affiliated Hospital of Sun Yat-sen University were retrospectively enrolled. AC patients were classified as type Ⅰ, type Ⅱ and type Ⅲ according to Chicago classification. The changes of esophageal dynamics before and after the modified POEM were compared by high resolution manometry (HRM). The reflux after the operation was evaluated by 24-hour esophageal impedance-pH monitoring. The clinical symptoms and the quality of life of AC patients were assessed by impaction dysphagia questionnaire (IDQ), Eckardt scale and short-form 36 item health survey (SF-36). Paired t test, independent sample t test, Wilcoxon rank sum test and Pearson correlation analysis were used for statistical analysis. Results:At three months and one year after operation, lower esophageal sphincter pressure (LESP) and integrated relaxation pressure (IRP) were all lower than those before operation ((23.89±12.68) and (23.44±12.56) mmHg (1 mmHg=0.133 kPa) vs. (39.29±16.14) mmHg; (16.13±9.43) and (15.37±8.36) mmHg vs. (30.57±11.31) mmHg), and the differences were statistically significant ( t=7.520, 7.866, 7.641 and 8.909, all P<0.05). There were no statistically significant differences in LESP and IRP during the same period between patients with type Ⅰ AC and type Ⅱ AC (all P>0.05). The LESP of patients with partial esophageal peristalsis function recovered one year after operation was lower than that of patients with unrecovered esophageal peristalsis function ((15.38±4.54) mmHg vs. (25.65±13.19) mmHg), and the difference was statistically significant ( t=0.039, P<0.05). The proportions of pathologic acid reflux of AC patients at three months and one year after operation were 7.8%(4/51) and 2.0%(1/51), respectively. The IDQ and Eckardt scores of patients with AC at three months and one year after operation were both lower than those before operation (4 points, 0 points to 10 points and 4 points, 0 points to 11 points vs. 23 points, 18 points to 30 points; 2 points, 1 points to 3 points and 1 points, 0 points to 1 points vs. 5 points, 4 points to 5 points), and the differences were statistically significant ( Z=-6.036, -6.104, -5.971 and -6.209, all P<0.01). According to Eckardt score, the proportions of clinical remission at three months and one year after operation were higher than that before operation (98.0%, 50/51 and 100.0%, 51/51 vs. 19.6%, 10/51), and the differences were statistically significant ( χ2=64.76 and 68.56, both P<0.05). The SF-36 general health and social function scores at three months and one year after operation were both higher than those before operation (0.55 points, 0.45 points to 0.70 points and 0.55 points, 0.45 points to 0.70 points vs. 0.45 points, 0.30 points to 0.55 points; 0.88 points, 0.75 points to 1.00 points and 0.88 points, 0.75 points to 1.12 points vs. 0.75 points, 0.75 points to 1.00 points); and the differences were statistically significant ( Z=-4.439, -4.225, -2.123 and -2.320, all P<0.05); and the health change scores were lower than those before operation (3.00 points, 2.00 points to 3.00 points and 2.00 points, 1.00 points to 3.00 points vs. 4.00 points, 3.00 points to 4.00 points), and the differences were statistically significant ( Z=-4.827 and -4.841, both P<0.05). Before and after modified POEM, the changes of LESP were positively correlated with the changes of IRP ( r=0.624 and 0.592, both P<0.01). Conclusion:Modified POEM can significantly improve the symptoms and LES relaxation function of AC patients, with a low incidence of post-operative reflux.

Esophagogastric Junction Contractility Integral Reflect the Anti-reflux Barrier Dysfunction in Patients with Gastroesophageal Reflux Disease

BACKGROUND/AIMS: Anti-reflux barrier dysfunction is one of the primary mechanisms in gastroesophageal reflux disease (GERD) pathogenesis. The esophagogastric junction contractile integral (EGJ-CI) is a new metric adopted to evaluate the EGJ contractility, which implies the anti-reflux barrier function. The aim of the current study was to validate this new metric in patients with GERD and its correlation with the esophageal acid exposure, as well as the efficacy of proton pump inhibitor treatment. METHODS: Ninety-eight patients with GERD and 21 healthy controls were included in the study. Upper endoscopy, high-resolution manometry (HRM) and 24-hour multichannel intraluminal impedance-pH monitoring were performed in all patients. Three respiration cycles were chosen at the initial HRM resting frame and the value computed with distal contractile integral tool was then divided by the duration of the cycles to yield EGJ-CI. All the patients were treated with esomeprazole 20 mg twice-daily for 8 weeks. RESULTS: EGJ-CI was lower in the patients with GERD than that of the controls (P < 0.05). For patients with GERD, EGJ-CI was lower in those with hiatal hernia (P < 0.05). The new metric correlated with esophageal acid exposure in the supine position (P < 0.05), and it also negatively correlated to the total reflux episodes (P < 0.05). There was no significant difference on EGJ-CI between patients with and without response to the esomeprazole treatment (P = 0.627). CONCLUSIONS: EGJ-CI reflected the dysfunction of the anti-reflux barrier in patients with GERD, but it had little impact on the esomeprazole response.

Prospective Evaluation of Pharmacogenomics and Metabolite Measurements upon Azathioprine Therapy in Inflammatory Bowel Disease: An Observational Study.

Up to approximately 40% to 50% of patients discontinue thiopurine therapy during the course of inflammatory bowel disease (IBD). We investigated the role of the metabolite thiopurine in IBD treatment. This was a prospective study. IBD patients receiving azathioprine (AZA) were prospectively included. Thiopurine methyltransferase (TPMT) genotypes were examined before therapy, and thiopurine metabolite levels were examined at weeks 2, 4, 8, 12, 24, and 48. In total, 132 patients were included. The frequency of leucopenia increased at 6-thioguanine nucleotide (6-TGN) levels ≥420  pmol/8 × 10(8) RBC (odds ratio [OR] = 7.9; 95% confidence interval (95%CI): 3.5-18.0; P < 0.001) and increased more during the initial 12 weeks of thiopurine therapy (OR = 16.0; 95%CI: 5.7-44.9; P < 0.001). The patients with 6-TGN levels ≥420 pmol/8 × 10 RBC at weeks 4, 8, and 12 had an increased likelihood of leucopenia. Clinical response increased at 6-TGN levels ≥225 pmol/8 × 10(8) RBC (OR = 13.5; 95% CI: 3.7-48.9; P < 0.001) in Crohn disease (CD) patients. The CD patients with 6-TGN levels ≥225 pmol/8 × 10(8) RBC at weeks 8, 12, and 24 had an increased likelihood of successful clinical response. TPMT*3C had a specificity of 100%, but a sensitivity of 8% for predicting leucopenia.A 6-TGN level between 225 and 420 pmol/8 × 10(8) RBC could be a therapeutic window in patients receiving AZA therapy, and it could likely predict leucopenia in the initial 12 weeks of AZA therapy and a reasonable chance of successful clinical response in CD patients. The value of TPMT genotyping before thiopurine therapy is limited in Chinese patients with IBD, considering the low sensitivity of predicting leucopenia.

Characteristics of achalasia:a high-resolution manometry study / 中华消化内镜杂志

Objective To evaluate the clinical and manometric characteristics of achalasia.Meth-ods Patients diagnosed as having achalasia from July 2010 to July 2014 at our hospital were enrolled.High resolution manometry(HRM)results were analyzed.Data of Eckardt scale,MDADI and SF-36 were ana-lyzed.Results All subjects had dysphagia,35.6% (37 /104)accompanied with regurgitation,26.9%(28 /104)with heartburn and 17.3%(18 /104)with weight loss.According to HRM results and Chicago classification criteria,16.35%(17 /104)of the subjects were classified as type Ⅰ,76.92%(80 /104)as type Ⅱ and 6.73%(7 /104)as type Ⅲ.27.9%(29 /104),19.2%(20 /104)and 24.0%(25 /104)of the subjects finished Eckardt scale,MDADI and SF-36,respectively.Eckardt score was positively correlated with integrated relaxation pressure(IRP)(r =0.421,P <0.05)and MDADI physical score was negatively with IRP(r =-0.530,P <0.05).Conclusion Dysphagia often occurs as the chief complaint among acha-lasia patients.And type Ⅱ is the most common.IRP is an indicator of the severity of clinical symptoms and impairment of quality of life.

Changes of esophageal intraluminal baseline impedance in 47 reflux esophagitis / 中华消化杂志

Objective To investigate the changes of esophageal intraluminal baseline impedance in patients with refluxesophagitis.Methods From December 2013 to August 2014,47 patients with reflux esophagitis and 17 healthy controls were enrolled.The patients with reflux esophagitis were graded according to Los Angeles classification (LA) grading standards.All subjects accepted 24 h multichannel intraluminal impedance (MII) pH examination,and the baseline value of impedance were measured.Independent sample t test was used to compare the difference in impedance between the two groups.Spearman rank correlation coefficient was performed to analyze the correlation between acid exposure time (AET) and the baseline impedance of patients with reflux esophagitis.Kruskal-Wallis test was used to compare the differences in baseline impedance of patients with different grades of reflux esophagitis.Results The impedance baseline value of reflux esophagitis group was (1 676.72±644.41) Ω,which was lower than that of healthy control group ((2 151.27± 322.05) Ω),and the difference was statistically significant (t =-3.883,P＜0.01).The AET of esophagus was negatively correlated with the baseline impedance of the patients with reflux esophagitis (r=-0.530,P＜0.01).The baseline impedance of patients with grade LA-A and grade LA-B reflux esophagitis were 1 823.62 Ω (1 515.38 52 Ω,2 208.38 Ω) and 1 771.81 Ω(1 304.75 52 Ω,2 080.50 Ω),respectively,and the difference was not statistically significant (Z=-0.630,P=0.529).The baseline impedance of patients with grade LA C/D reflux esophagitis was 300 Ω (300 Ω,500 Ω),which was obviously lower than those of patients with grade LA-A or grade LA-B (Z=-2.647 and-2.818,both P＜0.017).Conclusion The baseline impedance of patients with reflux esophagitis is low and correlated with AET.

Preliminary efficacy of thalidomide in refractory Crohn's disease treatment / 中华消化杂志

Objective To observe the efficacy and safety of thalidomide in refractory Crohn's disease (CD).Methods A total of 21 moderate or severe active CD patients were enrolled,who had no response to glucocorticoid and azathioprine treatment or steroid-dependent.The patients were administrated with thalidomide 100 mg/d before sleep and followed up for one year.The clinical efficacy,endoscopic findings and safety were evaluated.Results Among 21 refractory CD patients,six patients stopped medication due to adverse effect and two because of ineffectiveness,three patients continued medication not completed one year follow-up,10 patients completed one year follow-up.The clinical remission,effective and ineffective rates were 23.8％(5/21),19.0％(4/21) and 57.1％(12/21) respectively.Under endoscope,the mucosal healing,improvement and no improvement rates were 9.5％(2/21),14.3％(3/21) and 76.2％ (16/21) respectively.The adverse effect rate was 71.4％ (15/21) including rash,conspitation,sommolence,numbness of hands and feet,leucopenia and muscular soreness.The mean time of the adverse effects onset was 3.4 weeks.Conclusions Thalidomide is effective in refractory CD treatment and could be used in patients unwilling to use biological medication or receive surgery.But the adverse effects should be noted.

Clinical and endoscopic follow-up of infliximab with azathioprine combination therapy in Crohn's disease / 中华消化杂志

Objective To inspect the efficacy and mucosa healing condition of infliximab with azathioprine combination therapy in Crohn's disease (CD) and its correlation with prognosis.Methods A total of 20 active CD patients who received infliximab and azathioprine combination therapy at The First Affiliated Hospital of Sun Yat-sen University were objects of this study.The clinical efficacy was evaluated at 10 weeks,30 weeks,54 weeks and 2 years respectively according to CD activity index.The efficacy was evaluated under endoscopy at 10 weeks,30 weeks,54 weeks and 2 years respectively according to mucosal response situation under endoscopy.The data were analyzed by analysis of variance or Fisher's exact test between two groups.The factor affecred mucosal healing was analyzed by Logistic regression analysis.Results The clinical remission rate of patients without steroid at week 10,30,54 and 2 year were 12/20,16/20,15/20 and 15/20 respectively.Mucosal healing rate at week 10,30 and 54 weeks were 8/20,12/20 and 10/20 respectively.Logistic regression analysis indicated that age was the only factor affected mucosal healing at 30 weeks (OR =0.774,95％ CI:0.630 to 0.950).There was significant differences in clinical remission between mucosa response patients and invalid under endoscopy at 30 weeks and 2 years without steroid (at 30 weeks:14/14 vs 2/6; at 2 years:14/14 vs 1/6; all P＜0.01).Infliximab were withdrawn in 4 of 16 patients who was in non-steroid clinical remission at 30 weeks,and the other 12 patients were continued with infliximab therapy.There was no significant difference in non-steroid clinical remission rate (4/4 vs 11/12) and mucosa healing rate (2/4 vs 7/12) between withdrawal and continue of infliximab therapy (all P＞0.05).Conclusions Infliximab with azathioprine combination therapy can effectively promote and maintain mucosa healing in CD.The mucosa response patients can maintain long time non-steroid clinical remission.

The clinical and endoscopic efficacy of step-up and top-down infliximab therapy in Crohn's disease / 中华内科杂志

ObjectiveTo compare the efficacy of step-up and top-down infliximab therapy on patients with Crohn's disease (CD).MethodsA prospective and open-label study was performed by the First Affiliated Hospital of SUN Yat-sen University during September 2007 to December 2010.Active CD patients who were refractory to steroid/immunomodulator or who were steroid-dependent were enrolled into step-up group.Active CD patients who had no steroid or immunomodulator therapy before were enrolled into top-down group. All patients were intravenously infused with infliximab of 5 mg/kg body weight in an induction regimen of 3 doses at week 0,2 and 6,followed by maintenance dosing every 8 weeks beginning at week 14.The clinical and endoscopic follow up lasted 30 weeks.Clinical symptoms and mucosal healing status under endoscopy were evaluated by follow-up at week 10 and 30.Results Forty-one CD patients were enrolled,with 24 in step-up group and 17 in top-down group. There were significant differences in disease duration (P =0.006),combination therapy (P ＜ 0.001 ) and severity of disease ( P =0.011 ) in baseline between step-up and top-down groups.At week 10 and 30 during treatment,the clinical remission rates in step-up group were 45.8％ (11/24) and 58.3％ (14/24) respectively; the mucosal healing rates in step-up group were 33.3％ (8/24) and 54.2％ (13/24) respectively; the clinical remission rates in topdown group were 70.6％ ( 12/17)and 82.4％ (14/17) respectively; and the mucosal healing rates in topdown group were 35.3％ (6/17) and 52.9％ (9/17) respectively.No significant differences in clinical remission and mucosal healing rates at both week 10 and 30 were observed between the two groups.The prevalences of adverse events in step-up and top-down group were 41.7％ (10/24) and 29.4％ (5/17)respectively ( P =0.422).ConclusionBoth step-up and top-down infliximab therapy can induce remission in more than half of CD patients,while top-down therapy might be more benefitiary to symptom and endoscopic remission.

Multi-centered stratified study of chronic constipation with anorectal pain in China / 中华消化杂志

Objective To investigate the prevalence of anorectal pain in chronic constipation (CO patients. Methods With multi-centered stratified questionnaires investigation,the face to face questionnaires investigation was carried out on the symptoms of constipation and intensity,frequency and duration of anorectal pain in CC patients. CC and anorectal pain was diagnosed according to Rome Ⅲ criteria. Results Total 921 CC patients were investigated,and 909 questionnaires were valid. Of those,there were 258 male cases and 651 female cases,the mean age was(48. 9±18. 7)years. About 15. 1%(137/909)CC patients reported anorectal pain in last six months;of those 26 cases(2. 9%)with chronic proctalgia(CP),111 cases(12. 2%)with proctalgia fugax(PF). The percentage of pain occurred frequently or regularly in CP and PF patients was 88. 5%(23/26)and 73. 9%(82/111)respectively. The pain of PF patients was milder than that of CP patients. The detection rate of CP was higher in tertiary hospitals than in primary cares(3. 6% vs 0. 6%,P= 0. 04). There was no significant difference of PF detection rate between different hospitals(P= 0. 09). The occurrence of pain was associated with anorectal symptoms,sleeping and psychosocial condition. Conclusions CC patients are frequently with anorectal pain and more common in female,which should cause extensive concern by physicians.If necessary,the prevalence of anorectal pain in general population as well as the mechanism of the symptom need further investigation.

An open prospective trial of azathioprine in treatment of patients with active Crohn's disease / 中华消化杂志

Objective To evaluate the efficacy and safety of azathioprine (AZA) in long term treatment of patients with active Crohn's disease (CD) in China. Methods Sixty patients with active CD,who needed to be treated with systemic steroids, were recruited. All patients initially received AZA combined with steroids therapy and AZA was maintained for treatment after withdrawal of steroids. Clinical efficacy, endoscopic healing of mucosa and adverse events were assessed at the end of the 12th, 24th, 48th, 72th and 96th weeks. Results The complete remission (CR) of the patients at the 12th, 24th, 48th, 72th and 96th weeks was 55.0%, 66. 7%, 61. 7%, 53. 3% and 53. 3%,respectively. Endoscopic examination was performed in 25 patients before treatment and at the end of the 48th week. Eight of them achieved mucosal healing that was kept to the end of 96th week (8/8).Whereas only 9 out of 17 patients without mucosal healing achieved CR at the end of 96th week (9/17,P=0. 026). The clinical features were compared between CR group and non-CR group at the end of 48th week. Logistic regression analysis showed that regaining of hs-CRP was the only independent factor for maintaining remission by AZA treatment ( P= 0. 009,OR 10.1,95 % CI 1.8 ～ 57.9). Sixteen patients (26.7 % ) had adverse events. Ten (16.7 % ) of them had to halt treatment because of serious adverse events. Leucopenia was the most common adverse event and could be occurred at any time during the treatment. Conclusion AZA combined with steroid therapy can effectively induce remission of active CD. Long term steroid-free remission is also effectively maintained by AZA treatment. The most common adverse event is leucopenia and some patients can get mucosal healing. Those who get mucosal healing may have longer duration of remission.

The impact of 5-aminosalicylic acid on bone marrow suppression caused by thiopurines / 中华消化杂志

Objective To evaluate the effect and mechanism of 5-aminosalicylic acid (5-ASA) on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases (IBD) patients.MethodsThe clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) concentration were tested.In prospective study, patients firstly treated with azathioprine (AZA) of 50 mg/d for 4 weeks, then combined with 5-ASA of 3 g/d for another 4 weeks.The concentration of 6-TGN in red blood cells (RBC) was analyzed at the end of 4th and 8th week.Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine (MP) combined with 5-ASA group, 94 patients were in AZA/6-MP.alone group.The incidence of bone marrow suppression in these two groups were 46.7％ and 16.0％, respectively.Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence (OR=3.45,95％ CI 1.31 ～ 9.04).There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6-MP alone group(t=-0.351 ,P=0.734).The 6-TGN concentration was significantly higher in AZA/6-MP combined with 5-ASA group than that of AZA/6-MP alone group (the median concentration was 384.9 pmol/8× 108 RBC and 286.4 pmol/8× 108 RBC,F=29.15,P=0.00).Prospective study was completed in 8 patients.After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 × 108 RBC.After added with 5-ASA of 3 g/d for another 4weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8 × 108 RBC, three patients of those was even higher than 420 pmol/8 × 108 RBC, and bone marrow suppression occurred in 2 patients.ConclusionsThe incidence of bone marrow suppression increased in Chinese IBD patients treated with recommended routine dossage of AZA/6-MP when conbined with 5-ASA.The mechanism may be related with the increased concentration of 6-TGN in RBC.To reduce the AZA dosage may possibly keep the efficacy while decrease the incidence of bone marrow suppression.