Expression Profiles of Circulating MicroRNAs in XELOX-Chemotherapy-Induced Peripheral Neuropathy in Patients with Advanced Gastric Cancer.

Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer deaths around the world. Chemotherapy is one of the most effective treatments for cancer patients, and has remarkably enhanced survival rates. However, it has many side effects. Recently, microRNAs (miRNAs) have been intensively studied as potential biomarkers for cancer diagnosis and treatment monitoring. However, definitive biomarkers in chemotherapy-induced peripheral neuropathy (CIPN) are still lacking. The aim of this study was to identify the factors significant for neurological adverse events in GC patients receiving XELOX (oxaliplatin and capecitabine) chemotherapy. The results show that XELOX chemotherapy induces changes in the expression of hsa-miR-200c-3p, hsa-miR-885-5p, and hsa-miR-378f. Validation by qRT-PCR demonstrated that hsa-miR-378f was significantly downregulated in CIPN. Hsa-miR-378f was identified as showing a statistically significant correlation in GC patients receiving XELOX chemotherapy according to the analysis of differentially expressed (DE) miRNAs. Furthermore, 34 potential target genes were predicted using a web-based database for miRNA target prognostication and functional annotations. The identified genes are related to the peptidyl-serine phosphorylation and regulation of alternative mRNA splicing with enrichment in the gastric cancer, neurotrophin, MAPK, and AMPK signaling pathways. Collectively, these results provide information useful for developing promising strategies for the treatment of XELOX-chemotherapy-induced peripheral neuropathy.

Neuroprotective properties of ethanolic extract of Citrus unshiu Markovich peel through NADPH oxidase 2 inhibition in chemotherapy-induced neuropathic pain animal model.

The present study aimed to determine the antioxidant effect of Citrus unshiu Markovich (CUM) extract in neuronal cell lines under oxidative stress and to investigate the effect of chemotherapy-induced peripheral neuropathy (CIPN) on the nociceptive response in a preclinical mice model. We tested the inhibition of H2 O2 in Neuro2A cells treated with CUM. Experimental animals were treated with oxaliplatin to induce CINP, and then administered oral CUM for 4 weeks in order to observe the effect of CUM. Animals were evaluated weekly for thermal hyperalgesia and digital motor nerve conduction velocity (NCV). Lumbar dorsal root ganglia (DRG) isolated from each animal were evaluated through immunochemical and western blot analysis for nerve damage, inflammatory response, and expression of redox signaling factors. The main mechanisms were determined to be decreased inducible nitric oxide synthase (iNOS) production due to the inhibition of NADPH oxidase 2 (NOX2). To determine the functional role of NOX2 in CINP, we administrated CUM into NOX2-deficient mice with neuropathic pain. Therefore, we suggest that CUM controls the expression levels of inflammatory factors in CINP via NOX2 inactivation. This study demonstrated that a complementary medicine such as CUM might be a potential novel therapeutic agent for the treatment of CINP.

Exploring microRNA patterns as biomarkers of FOLFOX chemotherapy-induced peripheral neuropathy in patients with colorectal cancer.

FOLFOX is a combination of chemotherapeutic agents (5-fluorouracil, leucovorin, and oxaliplatin) and is used to treat advanced colorectal cancer (CRC) but induces various side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most critical side effects that compromise the quality of life of patients with CRC undergoing FOLFOX chemotherapy. This study aimed to evaluate circulating miRNA, cortisol and catecholamine as potential biomarkers that can predict FOLFOX-CIPN symptoms. High-throughput microRNA (miRNA) sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤3 cycles and those who underwent ≥6 cycles of FOLFOX chemotherapy. The identified miRNAs were validated in 27 patients with CRC who underwent FOLFOX chemotherapy using quantitative reverse transcription polymerase chain reaction. Target genes were predicted using bioinformatics and functional analyses. Cortisol and catecholamine concentrations in peripheral plasma were measured using an enzyme-linked immunosorbent assay. miR-3184-5p was differentially expressed when miRNA expression was compared between the groups that underwent ≤3 and ≥6 cycles of FOLFOX chemotherapy. Cortisol levels were significantly higher in the group that underwent ≥6 cycles of FOLFOX chemotherapy than in the group that underwent ≤3 cycles. This study suggests that miR-3184-5p may be a potential marker for predicting CIPN.

The impact of the 30-day postoperative complications on the quality of life following gastrectomy for gastric carcinoma: A prospective study.

BACKGROUND: The effect of postoperative complications on long-term quality of life (QoL) is controversial in abdominal surgery. This study aimed to investigate the impact of 30-day postoperative complications on long-term QoL after gastrectomy. METHOD: This is a longitudinal cohort study that enrolled 908 patients undergoing gastrectomy for gastric cancer between 2016 and 2017. QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) generic cancer (QLQ C-30) and gastric module (STO-22) preoperatively and at 1, 6, 12, and 24 months postoperatively. Patients were divided into the morbidity (30-day postoperative complications) and no-morbidity groups, and the postoperative QoL change was compared using a linear mixed model. RESULTS: The mean age was 62.5 ± 12.0 years. Subtotal and total gastrectomy was performed in 763 (84.0%) and 145 (16.0%) patients, respectively. There were 189 (20.8%) patients developing postoperative complications. The morbidity group showed worse scores in several functions and symptoms of QoL at the baseline. However, the two groups showed no significant difference in postoperative changes in most functions and symptoms of the QLQ C-30 and STO-22 (Pgroup × time > 0.05). The recovery of global health (Pgroup × time < 0.001) and anxiety (Pgroup × time = 0.008) was slightly better in the morbidity group. The subgroup analysis of patients developing major abdominal complications showed similar results. CONCLUSION: The morbidity group showed worse QoL in several functions and symptoms at the baseline. However, postoperative complications had little influence on QoL change following gastrectomy for gastric cancer.

Identification of miR-143-3p as a diagnostic biomarker in gastric cancer.

BACKGROUND: Gastric cancer (GC) is among the most common types of gastrointestinal cancers and has a high incidence and mortality around the world. To suppress the progression of GC, it is essential to develop diagnostic markers. MicroRNAs regulate GC development, but a clearer insight into their role is needed before they can be applied as a molecular markers and targets. METHODS: In this study, we assessed the diagnostic value of differentially expressed microRNAs as potential diagnostic biomarkers for GC using data for 389 tissue samples from the Cancer Genome Atlas (TCGA) and 21 plasma samples from GC patients. RESULTS: The expression of hsa-miR-143-3p (also known as hsa-miR-143) was significantly downregulated in GC according to the TCGA data and plasma samples. The 228 potential target genes of hsa-miR-143-3p were analyzed using a bioinformatics tool for miRNA target prediction. The target genes correlated with extracellular matrix organization, the cytoplasm, and identical protein binding. Furthermore, the pathway enrichment analysis of target genes showed that they were involved in pathways in cancer, the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, and proteoglycans in cancer. The hub genes in the protein-protein interaction (PPI) network, were matrix metallopeptidase 2 (MMP2), CD44 molecule (CD44), and SMAD family member 3 (SMAD3). CONCLUSIONS: This study suggests that hsa-miR-143-3p may be used as a diagnostic marker for GC, contributing via the pathways involved in the development of GC.

Intolerability to postoperative early oral nutrition in older patients (≥70 years) undergoing gastrectomy for gastric cancer: A case-control study.

BACKGROUND: Postoperative early oral nutrition has increasingly been adopted for patients undergoing gastrectomy. However, intolerability to early oral nutrition remains a major concern, especially in older patients. This study aimed to investigate early oral nutrition intolerability in older patients who had undergone gastrectomy. METHODS: We retrospectively reviewed 825 patients who had undergone gastrectomy for gastric carcinoma between 2017 and 2019. All patients received an oral diet on postoperative day 1. Patients were divided into older (≥70 years) and younger (<70 years) adult groups, and short-term outcomes and intolerability to oral nutrition were compared. Intolerability to early oral nutrition was defined as oral diet cessation due to adverse gastrointestinal symptoms. RESULTS: Among the 825 patients (≥70 years, n = 286; <70 years, n = 539), 151 (18.3%) developed intolerability to early oral nutrition, of whom 100 patients were < 70 years old and 51 were ≥70 years old. The most common symptom causing intolerability was abdominal distension. The mean duration of fasting after developing intolerability was 2.8 ± 2.4 days. The incidence of intolerability in the older and younger adult groups was 17.8% and 18.6%, respectively (p = 0.799). In terms of sex, operative approach, gastric resection, lymph node dissection, reconstruction, and tumor stage subgroups, the older adult group did not exhibit a significant increase in intolerability. Postoperatively, the older adult group showed a higher incidence of systemic complications; however, anastomotic complications did not significantly differ between the two groups. CONCLUSIONS: Postoperative early oral nutrition can safely be adopted for older patients undergoing gastrectomy, with acceptable intolerability and surgical outcomes.

Heart Rate Variability as a Non-invasive Objective Parameter for Predicting the Occurrence of Chemotherapy-induced Peripheral Neuropathy in Patients With Gastrointestinal Cancer.

BACKGROUND/AIM: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common chemotoxicities. However, no effective clinical CIPN screening methods have been reported. This study aimed to investigate whether changes in heart rate variability (HRV) could predict the development of CIPN for early symptom control in chemotherapy-prescribed patients with gastrointestinal (GI) cancer. PATIENTS AND METHODS: Fifty-five GI cancer outpatients undergoing palliative chemotherapy including taxanes and/or platinum compounds were enrolled. CIPN was diagnosed using National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI-CTCAE). HRV measures were derived from electrocardiogram signals. RESULTS: Twelve weeks after starting chemotherapy, 39 (70.9%) patients who complained of NCI-CTCAE grade 1-3 sensory changes were diagnosed with CIPN. Standard deviation of normal-to-normal R-R intervals (SDNN), high frequency (HF), low frequency (LF), and LF/HF ratio changed significantly during 3 assessment periods. Percentage changes in SDNN and HF were related to the occurrence of CIPN symptoms. A decision tree model indicated that patients with a rapid percentage change decrease in SDNN and HF were CIPN-positive. CONCLUSION: Using SDNN and HF, our decision tree predicted CIPN occurrence. The changes in HRV may occur earlier than sensory CIPN symptoms.

The benefits of enhanced recovery after surgery for gastric cancer: A large before-and-after propensity score matching study.

BACKGROUND & AIMS: The benefits of enhanced recovery after surgery (ERAS) in patients undergoing gastrectomy have been reported in several studies; however, there is limited evidence supporting the efficacy of ERAS in clinical settings. We aimed to identify the benefits of ERAS in the clinical setting by investigating short-term surgical outcomes before and after the implementation of ERAS in patients who underwent gastrectomy. METHODS: We searched our gastric cancer database from 2008 to 2018 to identify patients who underwent gastrectomy before ERAS was implemented (2008-2009) and after the final version of ERAS was implemented (2016-2018). We enrolled 424 patients who were treated before ERAS was implemented and 565 patients who received our completed version of ERAS. After propensity score matching, each group included 219 patients, and short-term surgical outcomes were compared between the two groups. RESULTS: The length of hospital stay was significantly shorter in the ERAS group (8.8 vs. 11.5 days, p = 0.001), but the readmission rates were similar in the two groups, at 2.3%. There were no significant differences in morbidity, mortality, and complications of ≥ grade III between the groups. Of the complications, intra-abdominal bleeding (0% vs. 4.1%, p = 0.002) and intra-abdominal abscess (0% vs. 2.7%, p = 0.038) were significantly lower, whereas postoperative ileus was significantly higher in the ERAS group (8.6% vs. 0.5%, p < 0.001). In subgroup analyses by age, operative approach, and the extent of gastric resection, the ERAS group experienced a shorter hospital stay without increased readmission in all subgroups. CONCLUSIONS: These results demonstrated that ERAS was associated with a 3-day reduction in hospital stay without increased readmission after gastrectomy. This study validated the benefits of ERAS in the clinical setting of gastrectomy.

Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer.

Circulating tumor cells (CTCs) are known to be heterogeneous and clustered with tumor-associated cells, such as macrophages, neutrophils, fibroblasts, and platelets. However, their molecular profile and clinical significance remain largely unknown. Thus, we aimed to perform a comprehensive gene expression analysis of single CTCs and CTC clusters in patients with pancreatic cancer and to identify their potential clinical relevance to provide personalized medicine. Epitope-independent, rapid (>3 mL of whole blood/min) isolation of single CTCs and CTC clusters was achieved from a prospective cohort of 16 patients with unresectable pancreatic cancer using a centrifugal microfluidic device. Forty-eight mRNA expressions of individual CTCs and CTC clusters were analyzed to identify pancreatic CTC phenotype. CTC clusters had a larger proportion of mesenchymal expression than single CTCs (p = 0.0004). The presence of CTC clusters positively correlated with poor prognosis (progression-free survival, p = 0.0159; overall survival, p = 0.0186). Furthermore, we found that most CTCs in these patients (90.7%) were cloaked with platelets and found the presence of a positive correlation between the increase in CTC clusters and rapid disease progression during follow-ups. Efficient CTC cluster isolation and analysis techniques will enhance the understanding of complex tumor metastasis processes and can facilitate personalized disease management.

Vimentin-Positive Circulating Tumor Cells as Diagnostic and Prognostic Biomarkers in Patients with Biliary Tract Cancer.

Biliary tract cancer (BTC) has poor prognosis; thus, early diagnosis is important to decrease mortality. Although vimentin-positive circulating tumor cells (V-CTCs) are a good candidate for diagnostic and prognostic biomarkers, studies on the topic are limited. We aimed to evaluate the diagnostic efficacy of V-CTCs between BTC and benign biliary disease (BBD) and determine the prognostic value of V-CTCs in BTC patients. We recruited 69 participants who had BTCs and BBDs from a single tertiary referral center. We analyzed CTCs and V-CTCs in peripheral blood using the CD-PRIMETM system. Seven patients were excluded due to a technical failure of CTC detection. CTCs were detected in all 62 patients. CTC count > 40/mL blood (55.8% vs. 20%, p = 0.039), V-CTC count > 15/mL blood (57.7% vs. 10%, p = 0.005), and V-CTC/CTC ratio > 40% (48.1% vs. 10%, p = 0.025) were significantly different between BTCs and BBDs. Two or more of these three parameters (61.5% vs. 10%, p = 0.002) increased the accuracy. A combination of CTC markers with CA19-9 and biopsy increased the accuracy (90.4% vs. 10%, p = 0.000). V-CTC > 50/mL blood was a significant factor affecting survival (140 (66.6-213.3) vs. 253 (163.9-342.1) days, p = 0.008). V-CTC could be a potential biomarker for early diagnosis and predicting prognosis in patients with BTC.

Postprandial Hypotension as a Risk Factor for the Development of New Cardiovascular Disease: A Prospective Cohort Study with 36 Month Follow-Up in Community-Dwelling Elderly People.

Postprandial hypotension (PPH) is common among the elderly. However, it is unknown whether the presence of PPH can predict the development of new cardiovascular disease (CVD) in the elderly during the long-term period. This study aimed to prospectively evaluate the presence of PPH and the development of new CVD within a 36 month period in 94 community-dwelling elderly people without a history of CVD. PPH was diagnosed in 47 (50.0%) participants at baseline and in 7 (7.4%) during the follow-up period. Thirty participants (31.9%) developed new CVD within 36 months. We performed a time-dependent Cox regression analysis with PPH, hypertension, diabetes, and body mass index (BMI) as time-varying covariates. In the univariate analyses, the presence of PPH, higher BMI, hypertension, diabetes mellitus, and higher systolic and diastolic blood pressure were associated with the development of new CVD. The multivariate analysis indicated that the relationship between PPH and the development of new CVD remained (adjusted hazard ratio 11.18, 95% confidence interval 2.43-51.38, p = 0.002) even after controlling for other variables as covariates. In conclusion, the presence of PPH can predict the development of new CVD. Elderly people with PPH may require close surveillance to prevent CVD.

Tolerability of early oral nutrition and factors predicting early oral nutrition failure after gastrectomy.

BACKGROUND & AIMS: Many studies have suggested the feasibility and safety of early oral nutrition after gastrectomy; however, the tolerability of early oral nutrition has rarely been investigated. This study aimed to investigate the tolerability of early oral nutrition and factors affecting early oral nutrition failure after gastrectomy. METHODS: We retrospectively reviewed 565 patients with gastric cancer who had undergone gastrectomy and who had received oral nutrition on postoperative day 1. Failure of early oral nutrition was defined as cessation of at least one meal for any reason. Preoperative clinical information and operative factors were analyzed concerning an association with early oral nutrition failure. RESULTS: The tolerability of early oral nutrition after gastrectomy was 74.7%. Of 565 patients, 72 (12.7%) failed early oral nutrition due to adverse gastrointestinal symptoms, 52 (9.2%) failed due to gastric stasis or ileus, and 19 (3.4%) patients failed due to other postoperative complications. In the univariate analysis, age (≥70 years), male sex, preoperative tumor obstruction, remnant stomach cancer, open surgery, operating time (≥4 h), and an advanced preoperative stage were associated with failed early oral nutrition. Multivariable analysis of these factors revealed that male sex, preoperative tumor obstruction, operating time, and advanced preoperative stage were independent predictive factors for early oral nutrition failure after gastrectomy. CONCLUSIONS: The tolerability of early oral nutrition after gastrectomy was comparable to that of other gastrointestinal surgeries. A tailored approach for postoperative oral nutrition is required based on identified risk factors for early oral nutrition failure.

Early Postoperative Oral Feeding After Total Gastrectomy in Gastric Carcinoma Patients: A Retrospective Before-After Study Using Propensity Score Matching.

BACKGROUND: Despite its clinical benefits, early oral nutrition after total gastrectomy is not widely implemented because of concerns about tolerability and safety. We investigated the feasibility and safety of early oral nutrition after total gastrectomy in gastric carcinoma patients. METHODS: This is a retrospective before-after study. From 2008-2016, 301 patients received conventional oral feeding (COF) before May 2012, and 454 patients, early oral feeding (EOF) after May 2012. The EOF group received oral diet on postoperative day 1, and the COF group was maintained nil-by-mouth until patients demonstrated gas passage. After balancing potential confounders using propensity score matching, 203 patients were selected in each group. RESULTS: Both matched groups demonstrated well-balanced baseline characteristics. The EOF group demonstrated significantly earlier first flatus time (2.9 vs 3.1 days, P = .013) and hospital discharge (8.9 vs 12.6 days, P < .001) than the COF group. No significant differences were observed for overall morbidity and mortality, but the EOF group demonstrated lower incidence of abdominal infection (3.0% vs 7.4%, P = .044) and anastomosis leakage (1.5% vs 4.9%, P = .048). Subgroup analyses by age, sex, operative approach, lymph node dissection, and tumor stage demonstrated no increased risk of morbidity, anastomosis leakage, and short hospital stay in the EOF group. CONCLUSION: Early oral nutrition may be feasible and safe after total gastrectomy, with no increase in postoperative complications. Large, randomized, controlled trials are warranted to further investigate the clinical benefits of early oral nutrition after total gastrectomy.

Physical Activity and Gastric Cancer Risk in Patients with and without Helicobacter pylori Infection in A Korean Population: A Hospital-Based Case-Control Study.

Although physical activity (PA) is beneficial for prolonging lifespan, evidence for the protective role of PA against the development of gastric cancer (GC) is not yet well established. This study assessed the association between PA and GC risk in patients with and without Helicobacter pylori (H. pylori) infection in a Korean population. In total, 415 GC patients and 830 controls were enrolled at the National Cancer Center, Korea. The International Physical Activity Questionnaire-Short Form was used to collect PA data. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. In the H. pylori-positive group, subjects who engaged in regular exercise showed a significantly reduced risk of GC in the entire population (OR = 0.52, 95% CI = 0.38⁻0.70) and in females (OR = 0.60, 95% CI = 0.21⁻0.64). Subjects who engaged in a high level of total PA showed a significantly reduced risk of GC relative to subjects in the lowest tertile in the fully adjusted model (OR = 0.46, 95% CI = 0.32⁻0.65, p-trend < 0.001). There was an inverse association between PA and GC risk in the entire population, and in the H. pylori-positive subgroup. Our data indicate the need for the promotion of all domains of PA, especially for Korean populations.

Complementary and Alternative Medicine Use and Its Association with Emotional Status and Quality of Life in Patients with a Solid Tumor: A Cross-Sectional Study.

OBJECTIVES: Complementary and alternative medicine (CAM) has been used widely in various populations for various purposes, including emotional support and improvement of quality of life (QOL). However, CAM use and purposes for using CAM are less clear among Korean patients with a solid tumor. The purpose of this study was to determine the prevalence and type of CAM use, and the association between CAM use and anxiety, depression, and QOL in patients with a solid tumor. DESIGN: A cross-sectional survey. SETTING: A cancer center in Korea. SUBJECTS: Two hundred and sixteen patients diagnosed with a solid tumor. OUTCOME MEASURES: Standard questionnaires on CAM use, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer QLQ-C30. RESULTS: One hundred thirty one patients (60.6%) reported using CAM. CAM users, compared with non-CAM users, were significantly younger (57.8 vs. 60.9 years, p = 0.05), had higher level of education (p = 0.008), had higher income (p = 0.008), were less likely to seek physician consultation on CAM use (p = 0.002), and had a more advanced stage of tumor (p = 0.003) with more distant metastasis (p = 0.001). The most commonly used CAM was herbal medicine (n = 89, 67.9%). CAM users had significantly lower anxiety (t = 5.21, p < 0.001) and depression (t = 4.90, p < 0.001) than non-CAM users. When the effects of CAM use were tested on anxiety, depression, and QOL, controlling for covariates, CAM use was significantly associated with 8.7% and 8.8% of variance in decreasing anxiety and depression, but there was no unique association of CAM use with variance in QOL. CONCLUSIONS: CAM use is prevalent and younger age, higher education levels, higher income, less physician consultation, and higher cancer stage are significant correlates to CAM use. Controlling for covariates (e.g., gender, BMI), CAM use is significantly associated with lower anxiety and depression compared with those of non-CAM users.

Effects of Cognitive Behavior Therapy on Heart Rate Variability in Young Females with Constipation-predominant Irritable Bowel Syndrome: A Parallel-group Trial.

BACKGROUND/AIMS: The relation between heart rate variability (HRV) as non-invasive biomarkers of autonomic function and cognitive behavior therapy (CBT) as non-pharmacological treatments has rarely been examined in patients with constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study is to evaluate the efficacy of an 8-week CBT intervention on HRV and IBS symptoms, and the correlation of changes in HRV with changes in IBS symptoms among young female nursing students with IBS-C. METHODS: This study consisted of an exploratory subgroup analysis of 43 participants with IBS-C who had been randomly assigned to receive either 8 weeks of CBT (n = 23) or general medical information (control, n = 20). At baseline and 8, 16, and 24 weeks, participants completed a questionnaire assessing their gastrointestinal (GI) symptoms, anxiety, depression, and stress, and their HRV was measured via electrocardiography. RESULTS: At the 8-week follow-up, the high-frequency (HF) power was significantly higher, and the low-frequency (LF)/HF ratio was lower in the CBT group than in the control group (P < 0.001 for both), and the severity of GI symptoms (P = 0.003), anxiety (P < 0.001), depression (P < 0.001), and stress (P < 0.001) was significantly lower in the CBT group than in the control group. Changes in the HF power were significantly and inversely associated with changes in GI symptoms, anxiety, depression, and stress at 16 and 24 weeks (P < 0.05 for all; range of r from -0.37 to -0.68). Changes in the LF/HF ratio were also significantly and positively associated with changes in GI symptoms, anxiety, depression, and stress at 16 and 24 weeks (P < 0.05 for all; range of r from 0.38 to 0.60). CONCLUSIONS: CBT was effective in managing symptoms in young IBS-C patients and the improvement of symptoms was sustained at 24 weeks following the completion of CBT. Furthermore, indirect measurement of autonomic function using HRV may be a useful objective parameter for assessing response to CBT in young IBS-C patients.