OBJECTIVE: To explore the genetic basis for a Chinese pedigree featuring congenital profound syndromic deafness and chronic constipation, and provide prenatal diagnosis for a high-risk fetus. METHODS: Whole-exome sequencing was carried out to analyze the sequences of genes associated with hereditary deafness, and multiplex ligation-dependent probe amplification (MLPA) was used to verify the candidate variant in the proband's parents and the fetus. RESULTS: The proband was found to have harbored a heterozygous deletion of SOX10, a pathogenic gene associated with Waardenburg syndrome type 4C (WS4C). The same deletion was found in her mother (with profound syndromic deafness and chronic constipation) and the fetus, but not in her father with normal hearing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the SOX10 gene deletion was predicted to be a pathogenic variant (PVS1+PM2_Supporting+PP1+PP4). CONCLUSION The pedigree was diagnosed with WS4C, which has conformed to an autosomal dominant inheritance. Deletion of the entire SOX10 gene, as a loss-of-function variant, probably underlay its pathogenesis. Above finding has facilitated genetic counseling and prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Pedigree ; Waardenburg Syndrome/genetics* ; East Asian People ; Genetic Testing ; Prenatal Diagnosis ; Hearing Loss, Sensorineural/genetics* ; Deafness/genetics* ; Mothers ; Constipation/genetics* ; Mutation ; SOXE Transcription Factors/genetics*

Objective: To analyze the clinicopathological characteristics and prognosis of patients with small bowel tumors. Methods: This was a retrospective, observational study. We collected clinicopathological data of patients with primary jejunal or ileal tumors who had undergone small bowel resection in the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between January 2012 and September 2017. The inclusion criteria included: (1) older than 18 years; (2) had undergone small bowel resection; (3) primary location at jejunum or ileum; (4) postoperative pathological examination confirmed malignancy or malignant potential; and (5) complete clinicopathological and follow-up data. Patients with a history of previous or other concomitant malignancies and those who had undergone exploratory laparotomy with biopsy but no resection were excluded. The clinicopathological characteristics and prognoses of included patients were analyzed. Results: The study cohort comprised 220 patients with small bowel tumors, 136 of which were classified as gastrointestinal stromal tumors (GISTs), 47 as adenocarcinomas, and 35 as lymphomas. The median follow-up for all patient was 81.0 months (75.9-86.1). GISTs frequently manifested as gastrointestinal bleeding (61.0%, 83/136) and abdominal pain (38.2%, 52/136). In the patients with GISTs, the rates of lymph node and distant metastasis were 0.7% (1/136) and 11.8% (16/136), respectively. The median follow-up time was 81.0 (75.9-86.1) months. The 3-year overall survival (OS) rate was 96.3%. Multivariate Cox regression-analysis results showed that distant metastasis was the only factor associated with OS of patients with GISTs (HR=23.639, 95% CI: 4.564-122.430, P<0.001). The main clinical manifestations of small bowel adenocarcinoma were abdominal pain (85.1%, 40/47), constipation/diarrhea (61.7%, 29/47), and weight loss (61.7%, 29/47). Rates of lymph node and distant metastasis in patients with small bowel adenocarcinoma were 53.2% (25/47) and 23.4% (11/47), respectively. The 3-year OS rate of patients with small bowel adenocarcinoma was 44.7%. Multivariate Cox regression-analysis results showed that distant metastasis (HR=4.018, 95%CI: 2.108-10.331, P<0.001) and adjuvant chemotherapy (HR=0.291, 95% CI: 0.140-0.609, P=0.001) were independently associated with OS of patients with small bowel adenocarcinoma. Small bowel lymphoma frequently manifested as abdominal pain (68.6%, 24/35) and constipation/diarrhea (31.4%, 11/35); 77.1% (27/35) of small bowel lymphomas were of B-cell origin. The 3-year OS rate of patients with small bowel lymphomas was 60.0%. T/NK cell lymphomas (HR= 6.598, 95% CI: 2.172-20.041, P<0.001) and adjuvant chemotherapy (HR=0.119, 95% CI: 0.015-0.925, P=0.042) were independently associated with OS of patients with small bowel lymphoma. Small bowel GISTs have a better prognosis than small intestinal adenocarcinomas (P<0.001) or lymphomas (P<0.001), and small bowel lymphomas have a better prognosis than small bowel adenocarcinomas (P=0.035). Conclusions: The clinical manifestations of small intestinal tumor are non-specific. Small bowel GISTs are relatively indolent and have a good prognosis, whereas adenocarcinomas and lymphomas (especially T/NK-cell lymphomas) are highly malignant and have a poor prognosis. Adjuvant chemotherapy would likely improve the prognosis of patients with small bowel adenocarcinomas or lymphomas.
Humans ; Prognosis ; Intestinal Neoplasms/diagnosis* ; Duodenal Neoplasms ; Gastrointestinal Stromal Tumors ; Lymphoma ; Adenocarcinoma/surgery* ; Constipation ; Abdominal Pain ; Retrospective Studies

Objective: To investigate the effects of high risk factors questionnaire (HRFQ), Asia-Pacific colorectal screening (APCS) score and their combinations with fecal immunochemical test (FIT) in screening advanced colorectal neoplasia, in order to provide an evidence for further optimization of cancer screening program. Methods: A retrospective cohort study method was used to summarize and analyze the results of colorectal tumor screening in Jiashan County, Zhejiang Province from March 2017 to July 2018. Those with severe diseases that were not suitable for colonoscopy and those with mental and behavioral abnormalities who can not cooperate with the screening were excluded. Those who met any one or more of the followings in the HRFQ questionnaire were classified as high-risk people of HRFQ: (1) first-degree relatives with a history of colorectal cancer; (2) subjects with a history of cancer or any other malignant tumor; (3) subjects with a history of intestinal polyps; (4) those with two or more of the followings: chronic constipation (constipation lasted for more than 2 months per year in the past two years), chronic diarrhea (diarrhea lasted for more than 3 months in the past two years, and the duration of each episode was more than one week), mucus and bloody stools, history of adverse life events (occurring within the past 20 years and causing greater trauma or distress to the subject after the event), history of chronic appendicitis or appendectomy, history of chronic biliary disease or cholecystectomy. In this study, those who were assessed as high risk by HRFQ were recorded as "HRFQ (+)", and those who were not at high risk were recorded as "HRFQ (-)". The APCS questionnaire provided risk scores based on 4 risk factors including age, gender, family history and smoking: (1) age: 2 points for 50-69 years old, 3 points for 70 years old and above; (2) gender: 1 point for male, 0 point for women; (3) family history: 2 points for first-degree relatives suffering from colorectal cancer; (4) smoking: 1 point for current or past smoking, 0 point for non-smokers. The population was divided into low-risk (0-1 point), intermediate-risk (2-3 points), and high-risk (4-7 points). Those who were assessed as high risk by APCS were recorded as "APCS (+)", and those with intermediate and low risk were recorded as "APCS (-)". The hemoglobin threshold for a positive FIT was set to 100 μg/L. Those who were assessed as high risk by APCS with positive FIT were recorded as "APCS+FIT (+)". Those who were assessed as high risk by APCS with negative FIT, those who were assessed by APCS as low-middle risk with positive FIT, and those who were assessed by APCS as low-middle with negative FIT were all recorded as "APCS+FIT(-)". Observation indicators in this study were as follows: (1) the screening compliance rate of the cohort and the detection of advanced colorectal tumors; (2) positive predictive value, negative predictive value, sensitivity and specificity of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors; (3) comparison of the detection rate between HRFQ and APCS questionnaire for different colorectal lesions. Using SPSS 21.0 software, the receiver operating characteristic (ROC) curve was drawn to evaluate the clinical value of HRFQ and APCS combined with FIT in screening advanced colorectal tumors. Results: From 2017 to 2018 in Jiashan County, a total of 53 268 target subjects were screened, and 42 093 people actually completed the questionnaire, with a compliance rate of 79.02%. A total of 8145 cases underwent colonoscopy. A total of 3607 cases among HRFQ positive population (5320 cases) underwent colonoscopy, and the colonoscopy compliance rate was 67. 80%; 8 cases were diagnosed with colorectal cancer and 88 cases were advanced colorectal adenoma. A total of 2977 cases among APCS positive population (11 942 cases) underwent colonoscopy, and the colonoscopy compliance rate was 24.93%; 17 cases were diagnosed with colorectal cancer and 148 cases were advanced colorectal adenoma. The positive rate of HRFQ screening was lower than that of APCS [12.6% (5320/42 093) vs. 28.4% (11 942/42 093), χ²=3195. 547, P<0.001]. In the FIT positive population (6223 cases), a total of 4894 cases underwent colonoscopy, and the colonoscopy compliance rate was 78.64%; 34 cases were diagnosed with colorectal cancer and 224 cases were advanced adenoma. The positive predictive values of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors were 2.67%, 5.54%, 5.44%, and 8.56%; negative predictive values were 94.89%, 96.85%, 96.11% and 96.99%; sensitivity was 29.27%, 50.30%, 12.20 % and 39.02%; specificity was 55.09%, 64.03%, 91.11% and 82.51%, respectively. The ROC curves constructed by HRFQ, APCS, FIT, HRFQ+FIT and APCS+FIT indicated that APCS+FIT presented the highest efficacy in screening advanced colorectal tumors (AUC: 0.608, 95%CI: 0.574-0.642). The comparison of the detection rates of different colorectal lesions between HRFQ and APCS questionnaires showed that there were no significant differences in detection rate of inflammatory polyps and hyperplastic polyps between the two questionnaires (both P>0.05). However, as compared to HRFQ questionnaire, APCS questionnaire had higher detection rates in non-advanced adenomas [26.10% (777/2977) vs. 19.43% (701/3607), χ²=51.228, P<0.001], advanced adenoma [4.97% (148/2977) vs. 2.44% (88/3607), χ²=30.249, P<0.001] and colorectal cancer [0.57% (17 /2977) vs. 0.22% (8/3607), χ²=5.259, P=0.022]. Conclusions: APCS has a higher detection rate of advanced colorectal tumors than HRFQ. APCS combined with FIT can further improve the effectiveness of advanced colorectal tumor screening.
Adenoma/diagnosis* ; Aged ; Asia ; Colonoscopy ; Colorectal Neoplasms/pathology* ; Constipation ; Diarrhea ; Early Detection of Cancer/methods* ; Feces ; Female ; Humans ; Male ; Mass Screening/methods* ; Middle Aged ; Retrospective Studies ; Risk Factors ; Surveys and Questionnaires

Constipation is a common functional problem of the digestive system and may occur secondary to diet, drugs, endocrine diseases, metabolic diseases, neurological diseases, psychiatric disorders, or gastrointestinal obstruction. When there is no secondary cause, constipation is diagnosed as functional constipation. The first steps that should be taken to relieve symptoms are diet and lifestyle modifications, and if unsuccessful, laxative therapy should be initiated. If a patient does not respond to laxative therapy, diagnostic anorectal physiological tests are performed, though they are not routinely recommended. However, these tests may be considered earlier in patients strongly suspected to have a defecatory disorder. The revised guideline on the diagnosis and treatment of chronic constipation will undoubtedly aid the individualized management of chronic constipation in clinical practice.
Biofeedback, Psychology ; Constipation ; Diagnosis ; Diet ; Digestive System ; Digital Rectal Examination ; Endocrine System Diseases ; Humans ; Laxatives ; Life Style ; Metabolic Diseases

BACKGROUND/AIMS: Although symptoms related to the pelvic floor, such as pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS), are common in patients with chronic constipation (CC), its impact is not clear. Our aims were to investigate the following (1) compare pelvic floor symptom related dysfunction in irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC), and (2) symptom correlation with findings on anorectal manometry (ARM) and balloon expulsion test. METHODS: This was a retrospective analysis of patients with CC undergoing ARM. IBS-C and FC were diagnosed by Rome III criteria. Pelvic Floor Distress Inventory (PFDI-20) was used to measure pelvic floor symptom distress. Constipation Severity Scale was used to assess constipation severity. RESULTS: A total of 107 patients underwent ARM (64 FC, 43 IBS-C). The overall PFDI-20 score in IBS-C was higher compared with FC patients (118.0 vs 79.2, P = 0.001). In those with IBS-C, POP, LUTS, and colorectal symptoms subscales were all higher compared with FC patients (P < 0.05 for each). On multivariable regression, IBS-C (P = 0.001) and higher constipation severity (P = 0.001) were both independently associated with higher PFDI scores. ARM parameters and abnormal balloon expulsion test did not correlate with PFDI scores. CONCLUSIONS: Compared with FC patients, those with IBS-C have significantly higher distress from pelvic floor specific symptoms including POP and LUTS. Higher abdominal pain among IBS-C patients did not entirely explain these findings. A diagnosis of IBS-C and higher constipation severity correlated with PFDI-20 scores, but dyssynergia did not.
Abdominal Pain ; Arm ; Ataxia ; Constipation ; Defecation ; Diagnosis ; Humans ; Irritable Bowel Syndrome ; Lower Urinary Tract Symptoms ; Manometry ; Pelvic Floor ; Pelvic Organ Prolapse ; Retrospective Studies

BACKGROUND/AIMS: Functional constipation (FC) is aa frequent functional gastrointestinal disorder, diagnosed according to the Rome criteria. In this study, we compared Rome III and Rome IV criteria for the diagnosis of FC, and determined the prevalence of FC according to these criteria. METHODS: Consecutive children between infancy and 17 years old were recruited for the study, excluding those with a known organic gastrointestinal disease. A prospective longitudinal design has beenused. For the diagnosis of FC, questionnaires on Pediatric Gastrointestinal Symptoms (QPGS) based on the Rome III and Rome IV criteria (QPGS-RIII and QPGS-RIV) were used. The agreement between these 2 questionnaires was measured by Cohen's kappa coefficient. RESULTS: Two hundred fourteen children (mean age, 77.4 ± 59.5 months; 103 males) were screened. There was no statistically significant difference in the prevalence of FC evaluated using the QPGS-Rome IV vs the QPGS-Rome III in the overall sample (39/214 [18.2%] vs 37/214 [17.3.0%]; P = 0.831) as well as in any of the groups. The Cohen's kappa test showed a good agreement between the 2 criteria (κ = 0.65; 95% CI, 0.51 to 0.78). CONCLUSION: Our study demonstrates that the new Rome IV criteria have a good agreement with the Rome III criteria for the diagnosis of FC, without an increase in the number of potential diagnoses, despite the reduction in the duration of the symptoms. This conclusion is important in the management of childhood FC, since a late diagnosis negatively affects the prognosis.
Child ; Constipation ; Delayed Diagnosis ; Diagnosis ; Gastrointestinal Diseases ; Humans ; Prevalence ; Prognosis ; Prospective Studies

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].
Constipation ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Outcome Assessment (Health Care) ; Prospective Studies ; Randomized Controlled Trials as Topic

Excessive weight gain in children diagnosed with celiac disease (CD) is becoming more common. We describe 2 siblings (9-year and 6 months-old female and 6-year and 9 months-old male) with obesity showing attenuated gastrointestinal and atypical symptoms in which CD was diagnosed in the absence of a known family history of CD. After children's diagnosis, CD in their parents was also investigated. It was detected in their father affected by overweight. The presentation of patients with CD has changed. While patients with overweight and obesity commonly have symptoms such as abdominal pain, reflux, headache, and constipation due to lifestyle factors, CD should also be considered in patients with or without a family history of CD. Careful nutritional status assessment and follow-up monitoring after the diagnosis of CD are mandatory, especially in subjects who are already overweight at the presentation of this disease.
Abdominal Pain ; Celiac Disease ; Child ; Constipation ; Diagnosis ; Fathers ; Female ; Follow-Up Studies ; Headache ; Humans ; Life Style ; Nutritional Status ; Obesity ; Overweight ; Parents ; Recognition (Psychology) ; Siblings ; Weight Gain

BACKGROUND: This study aimed to investigate the awareness and application of ROME IV criteria for functional constipation (FC) in real-world practices and assessed differences between pediatric gastroenterologists (PGs) and general pediatricians. METHODS: A total of 239 (47.8%) out of 500 nationwide pediatricians answered a questionnaire for diagnosis and management of pediatric FC; 60 were PGs (75% of total PGs in Korea). RESULTS: A total of 16.6% of pediatricians were aware of the exact ROME IV criteria. Perianal examination and digital rectal examination were practiced less, with a higher tendency among PGs (P < 0.001). Treatment duration was longer among PGs for > 6 months (63.8%) than < 3 months among general pediatricians (59.2%, P < 0.001). Fecal disimpaction and rectal enema were practiced among 78.8% and 58.5% of pediatricians, respectively. High dose medication for initial treatment phase was prescribed by 70.7% of pediatricians, primarily within the first 2 weeks (48.3%). The most commonly prescribed medications in children aged > 1-year were lactulose (59.1%), followed by polyethylene glycol (PEG) 4000 (17.7%), and probiotics (11.8%). Prescription priority significantly differed between PGs and general pediatricians; lactulose or PEG 4000 were most commonly prescribed by PGs (89.7%), and lactulose or probiotics (75.7%) were prescribed by general pediatricians (P < 0.001). For patients aged < 1-year, lactulose (41.6%) and changing formula (31.7%) were commonly prescribed. Most participants recommended diet modification, and PGs more frequently used defecation diary (P = 0.002). CONCLUSION: Discrepancies between actual practice and Rome IV criteria and between PGs and general pediatricians were observed. This survey may help construct practice guidelines and educational programs for pediatric FC.
Child ; Colonic Diseases, Functional ; Constipation ; Defecation ; Diagnosis ; Digital Rectal Examination ; Enema ; Food Habits ; Humans ; Lactulose ; Polyethylene Glycols ; Prescriptions ; Probiotics

BACKGROUND/AIMS: High-resolution anorectal manometry (HRAM) has been considered a first-line diagnostic tool for functional defecation disorder. However, clinical studies on HRAM used in constipation patients are very limited and few studies have reported the characteristics of anorectal pressure in Chinese patients. The aim of this study is to investigate the characteristics of motility data in a cohort of Chinese patients with functional constipation. METHODS: A total of 82 consecutive patients with functional constipation who underwent a standardized HRAM were retrospectively enrolled in this study. The functional defecation disorder was classified into Rao's types. RESULTS: The mean age of 82 patients was 51 years (range, 16–83 years). Indications for anorectal manometry were functional constipation for all patients. The mean resting pressure was 69.2 ± 21.2 mmHg (range, 24.5–126.9 mmHg). The mean maximum squeezing pressure was 198.4 ± 75.6 mmHg (range, 54.2–476.9 mmHg). The mean length of the anal high pressure zone was 3.4 ± 1.0 cm (range, 0.6–4.9 cm). Sixty (73.2%) patients were diagnosed as functional defecation disorder. In attempted defecation, type I was most common (n = 24), followed by type II (n = 12), type III (n = 11), and type IV (n = 13) that were present on HRAM according to Rao's classification. In all 60 patients with functional defecation disorder, 37 were women and 23 were men. Men were significantly more likely than women to have functional defecation disorder (92.0% vs 64.9%, P = 0.014). CONCLUSION: HRAM could be used as a test for the diagnosis of functional defecation disorder and functional defecation disorder is common in Chinese patients with functional constipation.
Asian Continental Ancestry Group ; Classification ; Cohort Studies ; Constipation ; Defecation ; Diagnosis ; Female ; Humans ; Male ; Manometry ; Retrospective Studies