Comparison of gastrointestinal ultrasound with capsule endoscopy in patients with small bowel Crohn's disease.

OBJECTIVE: We aimed to investigate the association between gastrointestinal ultrasound (GIUS) and capsule endoscopy (CE) in assessing disease activity in patients with small bowel Crohn's disease (CD). METHODS: Medical records of 74 patients with small bowel CD who were treated at our hospital between January 2020 and March 2022 were retrospectively reviewed, including 50 men and 24 women. All patients underwent both GIUS and CE within one week after their admissions. The Simple Ultrasound Scoring of Crohn's Disease (SUS-CD) and Lewis score were used to assess disease activity during GIUS and CE, respectively. P < 0.05 was considered as statistically significant. RESULTS: The area under the receiver operating characteristic curve (AUROC) of SUS-CD was 0.90 (95% confidence interval [CI] 0.81-0.99; P < 0.001). And the diagnostic accuracy of GIUS was 79.7%, with a sensitivity of 93.6%, a specificity of 81.8%, a positive predictive value of 96.7%, a negative predictive value of 69.2% in predicting active small bowel CD. Furthermore, the agreement between GIUS and CE was assessed using Spearman's correlation analysis and SUS-CD was correlated with Lewis score (r = 0.82, P < 0.001) CONCLUSION: Our findings demonstrate a strong correlation between GIUS and CE in assessing the disease activity in patients with CD affecting the small intestine.

Correlation Between Ultrasonographic Response and Anti-Tumor Necrosis Factor Drug Levels in Crohn's disease.

BACKGROUND: Ultrasound is valuable in tight control algorithms for Crohn's disease (CD). However, the correlation between ultrasonographic response and anti-tumor necrosis factor (TNF) drug levels remains unknown. Elucidating this correlation would be helpful in optimizing the use of anti-TNF drugs. Thus, the authors aimed to investigate this correlation. METHODS: Between June 2020 and June 2021, all patients with CD who completed anti-TNF induction therapy were retrospectively included. Ultrasound was performed at week 0 and week 14, and proactive therapeutic drug monitoring of anti-TNF drugs was performed at week 14. The receiver operating characteristic (ROC) curve was used in the correlation analysis. RESULTS: Ninety-two patients (60 treated with infliximab and 32 with adalimumab) were included. At week 14, an ultrasonographic response was detected in 43 patients. Patients with ultrasonographic response had significantly higher median drug levels (5.9 mcg/mL for infliximab; 18.2 mcg/mL for adalimumab) than those without (0.9 mcg/mL for infliximab, P < 0.001; 4.8 mcg/mL for adalimumab, P < 0.001). The ROC curve showed a significant correlation between ultrasonographic response and anti-TNF drug levels (area under the curve = 0.79 for infliximab, P < 0.001; area under the curve = 0.86 for adalimumab, P < 0.001). The optimal cut-off values for infliximab and adalimumab correlated with ultrasonographic response were 5.0 and 10.5 mcg/mL, respectively. An incremental increase was observed in ultrasonographic response with higher anti-TNF drug levels. CONCLUSIONS: Higher anti-TNF drug levels are associated with an increased likelihood of ultrasonographic response in patients with CD.

Predictors of infliximab-induced deep remission in treatment-naïve patients with isolated small bowel Crohn's disease.

OBJECTIVES: Deep remission should be induced early in the disease course of Crohn's disease (CD), because it significantly prevents disease progression. Identifying predictors of deep remission before treatment is important to guide therapeutic strategy. Little is known about the predictors of infliximab-induced deep remission in treatment-naïve patients with isolated small bowel CD. We aimed to investigate the predictors of infliximab-induced deep remission in these patients. MATERIALS AND METHODS: From January 2015 to December 2019, all consecutive treatment-naïve patients with isolated small bowel CD who started infliximab induction therapy (5 mg/kg at week 0, 2, and 6) and underwent capsule endoscopy (CE) at week 14 were retrospectively included. Deep remission was defined as clinical remission in combination with CE-identified mucosal healing. Logistic regression was used to investigate the predictors of 14-week deep remission. RESULTS: Ninety-one patients were included. At week 14 after infliximab induction therapy, deep remission was found in 42 patients. Multivariate logistic regression analysis showed that a moderate-to-severe endoscopic disease [odds ratio (OR), 0.28; p = .01] and the presence of fibrofatty proliferation (OR, 0.26; p = .04) at baseline were independently associated with a decreased possibility of deep remission. CONCLUSIONS: In treatment-naïve patients with isolated small bowel CD, a moderate-to-severe endoscopic disease and the presence of fibrofatty proliferation at baseline reduce the possibility of infliximab-induced deep remission. Patients with such risk factors may need more aggressive treatment at the beginning of induction therapy to promote deep remission at an early stage.

Efficacy of infliximab in treatment-naïve patients with stricturing small bowel Crohn's disease.

OBJECTIVES: The efficacy of infliximab in treatment-naïve patients with stricturing small bowel Crohn's disease (CD) has not been well studied. We aimed to evaluate the efficacy of infliximab in these patients. MATERIALS AND METHODS: This was a retrospective study of all consecutive treatment-naïve patients with newly diagnosed CD with small bowel stricture who started regular infliximab therapy in Nanfang Hospital between January 2015 and December 2019. An effective infliximab therapy was defined as infliximab continuation without the use of steroids, new biologics, endoscopic interventions or intestinal surgery. RESULTS: Seventy-nine patients were included. After a median 38 months follow-up, an effective infliximab therapy was achieved in 37 patients. Long diagnostic delay (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.19-0.78; p= .008), pre-stenotic dilatation (HR 0.17, 95%CI 0.09-0.35; p < .001), long segmental stricture (HR 0.20, 95%CI 0.10-0.41; p < .001), and penetrating disease (HR 0.22, 95%CI 0.10-0.49; p < .001) were negatively correlated with an effective infliximab therapy. CONCLUSIONS: Infliximab is effective in nearly 50% of treatment-naïve patients with CD with small bowel stricture, and an effective therapy is more likely to be achieved in patients without long diagnostic delay, pre-stenotic dilatation, long segmental stricture or penetrating disease.

Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients: a multicenter randomized-controlled trial.

BACKGROUND: Data from single-center experience or small sample-sized studies have shown that chromoendoscopy (CE) might be superior to white-light endoscopy (WLE) for dysplasia surveillance in ulcerative colitis (UC) patients. We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies (WLT), WLE with random biopsies (WLR), and dye-based CE with targeted biopsies (CET) in UC patients. METHODS: Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms (WLT, WLR, and CET). Only high-definition endoscopy was used in all three groups. The patients were followed up by annual endoscopy with biopsies through December 2017. RESULTS: With a median follow-up time of 55 months, a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set: WLT (n = 43), WLR (n = 40), and CET (n = 39). A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients. WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT (8.1% and 9.7% vs 1.9%; P = 0.014 and 0.004, respectively). WLR obtained more biopsied samples than WLT and CET (16.4 ± 5.1 vs 4.3 ± 1.4 and 4.3 ± 1.4; both P < 0.001). During the second half of the follow-up (37 - 69 months), CET could identify more colonoscopies that diagnosed dysplasia than WLT (13.3% vs 1.6%, P = 0.015) and showed a trend for increasing the detection rate compared with WLR (13.3% vs 4.9%, P = 0.107). CONCLUSIONS: For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC, CET appeared to be more effective than WLT and less tedious than WLR. CET was found to be particularly useful when a long-term (>3 years) follow-up was conducted for dysplasia surveillance. The trial was registered on www.chictr.org.cn (ChiCTR1900023689).

Short-term high-dose gavage of hydroxychloroquine changes gut microbiota but not the intestinal integrity and immunological responses in mice.

AIMS: Hydroxychloroquine (HCQ), a widely used antimalarial drug, is proposed to treat coronavirus disease 2019 (COVID-19). However, no report is currently available regarding the direct effects of HCQ on gut microbiota, which is associated with the outcomes of elderly patients with COVID-19. Here, we first investigated the effects of HCQ on intestinal microecology in mice. MAIN METHODS: Fifteen female C57BL/6J mice were randomly divided into two groups: HCQ group (n = 10) and control group (n = 5). Mice in the HCQ group were administered with HCQ at dose of 100 mg/kg by gavage daily for 14 days. The feces of mice were collected before and on the 7th and 14th days after HCQ challenge, and then analyzed by 16S rRNA amplicon sequencing. At the end of the experiment, the hematology, serum biochemistry and cytokines were determined, respectively. The mRNA expression of tight junction proteins in colonic tissues were also studied by RT-PCR. KEY FINDINGS: HCQ challenge had no effects on the counts of white blood cells, the levels of serum cytokines, and the gene expression of tight junction proteins in colon. HCQ also did not increase the content of serum d-lactate in mice. Notably, HCQ significantly decreased the diversity of gut microbiota, increased the relative abundance of phylum Bacteroidetes whereas decreased that of Firmicutes. SIGNIFICANCE: Short-term high dose HCQ challenge changes gut microbiota but not the intestinal integrity and immunological responses in mice. Special attention should be paid to the effects of HCQ on intestinal microecology in future clinical use.

Correlation of diet, microbiota and metabolite networks in inflammatory bowel disease.

OBJECTIVES: Microbiota dysbiosis in inflammatory bowel disease (IBD) has been widely reported. The gut microbiota connect diet to the metabolism by producing small molecules via diverse metabolic pathways. In this study we aimed to investigate the dietary preferences of IBD patients, and to explore the interactions among gut microbiota composition, dietary components, and metabolites in relation to IBD. METHODS: Dietary preferences of IBD patients (including those with ulcerative colitis [UC] and Crohn's disease [CD]) and health controls were investigated, and their gut microbiota were analyzed using 16S rRNA gene sequencing and metagenomic analyses of fecal and biopsy samples. The metabolite profiles of the samples were then analyzed using gas and liquid chromatography-mass spectrometry analyses. RESULTS: The daily intake of folic acid, niacin, vitamins C and D, calcium, and selenium differed significantly between patients with IBD and healthy controls. A decrease in long-chain (such as arachidic, and oleic acid) and medium-chain fatty acids (sebacic acid and isocaproic acid) as well as bile acid was observed in patients with IBD. Compared with healthy controls, 22 microbial species (including Sulfolobus acidocaldarius, and Clostridium clostridioforme CAG132) in the UC group and 37 microbial species (such as Bacteroides fragilis and Fusobacterium nucleatum) in the CD group were found to be correlated to diet and metabolites. Bacteroides fragilis was enriched in patients with IBD and associated with multi-nutrients, and 21 metabolites including 25-hydroxyvitamin D3 and taurolithocholic acid. CONCLUSIONS: This study provides an interaction network to identify key micronutrients, microbiota components and metabolites that contribute to IBD.

Impact of capsule endoscopy on prevention of postoperative recurrence of Crohn's disease.

BACKGROUND AND AIMS: Capsule endoscopy (CE) can detect lesions outside the scope of ileocolonoscopy in postoperative patients with Crohn's disease (CD). However, the impact of such findings on patient outcomes remains unknown. This study is intended to evaluate the impact of CE findings on clinical management and outcomes in asymptomatic patients with CD without pharmacologic prophylaxis after ileocolonic resection. METHODS: In this retrospective cohort study, 37 patients (group 1) received ileocolonoscopy together with CE within 1 year after surgery, whereas 46 patients (group 2) only received ileocolonoscopy. Patients with endoscopic recurrence detected by either ileocolonoscopy or CE received pharmacologic therapy with azathioprine or infliximab. One year later, disease activity was re-evaluated. RESULTS: In group 1, all patients with ileocolonoscopy-identified recurrence also had CE-identified recurrence. In addition, CE detected endoscopic recurrence in 11 patients missed by ileocolonoscopy. Endoscopic remission identified by ileocolonoscopy was confirmed by CE in 13 patients. One year later, endoscopic remission identified by ileocolonoscopy was maintained in all 24 patients, and none had clinical recurrence. Conversely, in group 2, of those with ileocolonoscopy-identified remission, both ileocolonoscopy-identified recurrence and clinical recurrence occurred in 9 of 31 patients 1 year later. The total clinical recurrence rate was 2.7% (1/37) in group 1 versus 21.7% (10/46) in group 2 (P = .019). CONCLUSIONS: If endoscopic remission identified by ileocolonoscopy was confirmed by CE, patients could remain free of pharmacologic prophylaxis. If recurrence outside the scope of ileocolonoscopy was detected by CE, initiation of active pharmacologic therapy would be needed.

H. pylori attenuates TNBS-induced colitis via increasing mucosal Th2 cells in mice.

There is an epidemiological inverse relationship between Helicobacter pylori (H. pylori) infection and Crohn's disease (CD). However, whether H. pylori plays a protective role against CD remains unclear. Since 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis is thought to resemble CD, we investigated whether H. pylori can attenuate TNBS-induced colitis in mice. Here we show that H. pylori can attenuate the severity of TNBS-induced colitis. In addition, H. pylori not only down-regulates Th17 and Th1 cytokine expression, but can up-regulate Th2 cytokine expression and increase the Th2:Th17 ratio of CD4+ T in the colonic mucosa of TNBS-induced colitis. Our results indicate that H. pylori attenuates TNBS-induced colitis mainly through increasing Th2 cells in murine colonic mucosa. Our finding offers a novel view on the role of H. pylori in regulating gastrointestinal immunity, and may open a new avenue for development of therapeutic strategies in CD by making use of asymptomatic H. pylori colonization.

Role of esophagogastroduodenoscopy in detecting distal duodenal lesions: A single-center pilot study in Southern China.

OBJECTIVE: Esophagogastroduodenoscopy (EGD) is a standard instrument for detecting upper gastrointestinal lesions. However, the distal duodenum is often missed. This study aimed to clarify the diagnostic role of EGD in the distal duodenum. METHODS: This retrospective study enrolled patients with distal duodenal lesions who underwent EGD between January 2004 and July 2016 at our center. The rate of missed diagnosis using EGD examination was calculated. Logistic regression analysis was performed to identify the factors associated with the missed diagnoses. RESULTS: Sixty-three patients were included in the study. The overall diagnostic rate of distal duodenal lesions on EGD was 58.7%. After excluding the patients in whom the EGD did not reach the distal duodenum, this rate rose to 82.2%. In univariate analysis, intravenous sedation (26.8% vs 68.2%, odds ratio [OR] 0.171, P = 0.002), signs of lesions adjacent to the stomach (19.4% vs 62.5%, OR 0.099, P = 0.001), prior enteroscopy experience (15.0% vs 87.0%, OR 0.026, P < 0.001), and endoscopists with experiences of over 10 years (13.8% vs 64.7%, OR 0.087, P = 0.000) were associated with a decreased risk of missed diagnosis. In multivariate analysis, signs of lesions adjacent to the stomach (OR 0.167, P = 0.039) and prior enteroscopy experience (OR 0.035, P < 0.001) were significant independent protective factors. CONCLUSION: EGD may be important in diagnosing distal duodenal lesions. Patients with gastric retention, blood in the stomach or erosion in the proximal duodenum may benefit from the deep insertion of EGD.

Endoscopic resection of gastric submucosal tumors: A comparison of endoscopic nontunneling with tunneling resection and a systematic review.

BACKGROUND/AIM: Endoscopic tunneling resection is a relatively novel endoscopic technology for removing gastric submucosal tumors. Our study aimed to compare the differences between tunneling and nontunneling resection for gastric submucosal tumors. MATERIALS AND METHODS: Resections of gastric submucosal tumors (n = 97) performed from 2010 to 2015 at our endoscopy center were reviewed, and PubMed was searched for clinical studies on gastric submucosal tumor resection by endoscopic nontunneling and tunneling techniques. RESULTS: At our endoscopy center, nontunneling (Group 1) and tunneling resection (Group 2) were performed for 78 and 19 submucosal tumors, respectively; median tumor diameters were 15 and 20 mm (P = 0.086), median procedural times were 50 and 75 min (P = 0.017), successful resection rates were 94.9% (74/78) and 89.5% (17/19) (P = 0.334), and en bloc resection rates were 95.9% (71/74) and 94.1% (16/17) (P = 0.569) in the Groups 1 and 2, respectively. Postoperative fever, delayed hemorrhage and perforation, hospitalization time, and hospitalization expense were statistically similar between the 2 groups. A literature review on gastric submucosal tumor resection suggested that the en bloc resection rates of the two methods for tumors with a median diameter of 15-30 mm were also high, and there were no relapses during the follow-up period. CONCLUSIONS: Both endoscopic nontunneling and tunneling resection seem to be effective and safe methods for removing relatively small gastric submucosal tumors. Compared with endoscopic nontunneling, tunneling resection does not seem to have distinct advantages for gastric submucosal tumors, and has a longer mean operative time.

Diagnostic classification of endosonography for differentiating colorectal ulcerative diseases: A new statistical method.

AIM: To establish a classification method for differential diagnosis of colorectal ulcerative diseases, especially Crohn's disease (CD), primary intestinal lymphoma (PIL) and intestinal tuberculosis (ITB). METHODS: We searched the in-patient medical record database for confirmed cases of CD, PIL and ITB from 2008 to 2015 at our center, collected data on endoscopic ultrasound (EUS) from randomly-chosen patients who formed the training set, conducted univariate logistic regression analysis to summarize EUS features of CD, PIL and ITB, and created a diagnostic classification method. All cases found to have colorectal ulcers using EUS were obtained from the endoscopy database and formed the test set. We then removed the cases which were easily diagnosed, and the remaining cases formed the perplexing test set. We re-diagnosed the cases in the three sets using the classification method, determined EUS diagnostic accuracies, and adjusted the classification accordingly. Finally, the re-diagnosing and accuracy-calculating steps were repeated. RESULTS: In total, 272 CD, 60 PIL and 39 ITB cases were diagnosed from 2008 to 2015 based on the in-patient database, and 200 CD, 30 PIL and 20 ITB cases were randomly chosen to form the training set. The EUS features were summarized as follows: CD: Thickened submucosa with a slightly high echo level and visible layer; PIL: Absent layer and diffuse hypoechoic mass; and ITB: Thickened mucosa with a high or slightly high echo level and visible layer. The test set consisted of 77 CD, 30 PIL, 23 ITB and 140 cases of other diseases obtained from the endoscopy database. Seventy-four cases were excluded to form the perplexing test set. After adjustment of the classification, EUS diagnostic accuracies for CD, PIL and ITB were 83.6% (209/250), 97.2% (243/250) and 85.6% (214/250) in the training set, were 89.3% (241/270), 97.8% (264/270) and 84.1% (227/270) in the test set, and were 86.7% (170/196), 98.0% (192/196) and 85.2% (167/196) in the perplexing set, respectively. CONCLUSION: The EUS features of CD, PIL and ITB are different. The diagnostic classification method is reliable in the differential diagnosis of colorectal ulcerative diseases.

Comparison of endoscopic submucosal tunneling dissection and thoracoscopic enucleation for the treatment of esophageal submucosal tumors.

BACKGROUND AND AIMS: Endoscopic submucosal tunneling dissection (ESTD) has been proved to be safe and effective for removal of esophageal submucosal tumors (SMTs) and can maintain the mucosal integrity compared with other endoscopic methods. The aim of the study was to estimate the safety and efficacy of ESTD as well as compare its efficacy with thoracoscopic enucleation for esophageal SMTs, which is used increasingly as a minimally invasive approach. METHODS: We retrospectively collected the clinical data of patients with esophageal SMTs <40 mm who underwent ESTD or thoracoscopic enucleation at Nanfang Hospital between January 2008 and August 2016. Epidemiologic data (sex, age), tumor location, tumor size, en bloc resection rate, adverse events, pathologic results, length of postoperative hospital stay, and cost were compared between ESTD and thoracoscopic enucleation. RESULTS: A total of 126 patients were included. A total of 74 patients underwent ESTD, and the other 52 underwent thoracoscopic enucleation. There was no significant difference between the 2 groups in sex, age, tumor size, hospitalization expense, infection, adverse events, and en bloc resection rate (P < .05). However, patients in the ESTD group had a shorter operating time, less estimated blood loss, shorter length of postoperative hospital stay, and lower chest pain level (P < .05). Kaplan-Meier curves for disease-free survival also showed no statistically significant difference between ESTD and thoracoscopic enucleation groups during the median follow-up of 19.5 and 42 months, respectively. CONCLUSIONS: The treatment efficacy was comparable between the ESTD and thoracoscopic enucleation for esophageal SMTs <40 mm. However, there was a significant advantage in the ESTD group for a shorter operating time, reduced postoperative chest pain, and shorter hospitalization.

Slow-pull and different conventional suction techniques in endoscopic ultrasound-guided fine-needle aspiration of pancreatic solid lesions using 22-gauge needles.

AIM: To evaluate the cytological diagnostic capacity and sample quality of the slow-pull technique and compare them with different suction techniques. METHODS: From July 2010 to December 2015, 102 patients with pancreatic solid lesions who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with 22-gauge needles were retrospectively evaluated. EUS-FNA diagnosis was based on a cytological examination, and final diagnosis was based on a comprehensive standard of cytological diagnosis, surgical pathology and clinical or imaging follow-up. Cytological specimens were characterized for cellularity and blood contamination. The cytological diagnostic capacity and sample quality of the slow-pull technique and suction techniques with 5-mL/10-mL/20-mL syringes were analyzed. RESULTS: Of all of the EUS-FNA procedures, the slow-pull technique and suction techniques with 5-mL/10-mL/20-mL syringes were used in 31, 19, 34 and 18 procedures, respectively. There were significant differences between these four suction techniques in terms of cytological diagnostic accuracy (90.3% vs 63.2% vs 58.8% vs 55.6%, P = 0.019), sensitivity (88.2% vs 41.7% vs 40.0% vs 36.4%, P = 0.009) and blood contamination (score ≥ 2 for 29.0% vs 52.6% vs 70.6% vs 72.2%, P = 0.003). The accuracy and sensitivity of the slow-pull technique were significantly higher than those of the suction techniques using 5-mL (P = 0.03, P = 0.014), 10-mL (P = 0.005; P = 0.006) and 20-mL syringes (P = 0.01, P = 0.01). Blood contamination was significantly lower in the slow-pull technique than in the suction techniques with 10-mL (P = 0.001) and 20-mL syringes (P = 0.007). CONCLUSION: The slow-pull technique may increase the cytological diagnostic accuracy and sensitivity with slight blood contamination during EUS-FNA when using 22-gauge needles for solid pancreatic masses.