Application Research And Function Expansion Of String Capsule Endoscopy For Esophageal Diseases

Capsule endoscopy(CE),since its advent,has opened a new era in the diagnosis of small bowel diseases.With the development and innovation of capsule endoscopy technologies,its examination scope has been further expanded from the small bowel to the upper digestive tract and colon.String capsule endoscopy(SCE),which allows controllable movement of the capsule in the esophagus and enables complete visualization of the esophagus,has gradually demonstrated its advantage in the diagnosis of esophageal diseases.In Part I,we evaluated the diagnostic accuracy of detachable string magnetically maneuvered capsule endoscopy(ds-MCE)in patients with esophageal diseases who were indicated for endoscopic follow-up.In addition,as the application of SCE for esophageal diseases is limited to the esophageal surface,we further explored whether SCE could be combined with ultrasound technology,to effectively acquire esophageal submucosal information and distinguish esophageal subepithelial lesions(SEL).A novel ultrasound capsule endoscopy system(USCE)incorporates ultrasound technology with string capsule endoscopy,enabling simultaneous mucosal observation and submucosal imaging of the esophagus.In Part II,we tested and verified the performance of this USCE system for gastrointestinal imaging in a porcine model.On this basis,in Part III,we further evaluated the feasibility and safety of this USCE system for esophageal submucosal diagnosis in human.Part I: Detachable string magnetically maneuvered capsule endoscopy for follow-up of patients with esophageal diseasesBackground and objectives: Esophagogastroduodenoscopy(EGD)is recognized as the gold standard for detection and follow-up of many esophageal diseases.For some common esophageal diseases,including severe reflux esophagitis(RE),post endoscopic submucosal dissection(ESD)of esophageal tumors,and esophageal varices(EVs),the clinical guidelines recommend a regular endoscopic follow-up.However,EGD is an invasive and uncomfortable procedure,and some patients require anesthesia or sedation support,which increases the risk of complications and leads to a low compliance to endoscopic follow-up.The newly developed detachable string magnetically maneuvered capsule endoscopy(ds-MCE)provides a safe and comfortable method for esophageal visualization.Besides,after the esophageal examination,the capsule enables further evaluation of the stomach and small bowel.We conducted this study to explore the diagnostic performance of ds-MCE for follow-up of patients with esophageal diseases,with EGD as the gold standard.Methods: This study was a multicenter,diagnostic accuracy study.Patients with previous esophageal diseases indicated for endoscopic follow-up were enrolled.For each patient,ds-MCE was performed first,and then followed by EGD.The primary outcome was the sensitivity and specificity of ds-MCE in diagnosing esophageal diseases,using EGD as the reference standrad.Secondary outcomes included: the diagnostic accuracy of ds-MCE in identification of reflux esophagitis and Barrett’s esophagus(BE)in gastroesophageal reflux disease(GERD)populations,in identification of ESD-related lesions(esophageal stenosis and suspicious lesions after ESD surgery)in post-ESD populations,and in identification of esophageal varices in EV populations;the accuracy of ds-MCE for grading reflux esophagitis and esophageal varices;the detection of lesions in the stomach and small bowel;capsule transit time of ds-MCE procedures;patients’ overall evaluation of ds-MCE and safety analysis.Results:(1)270 patients with esophageal diseases indicated for EGD examinations were prospectively recruited from May 2020 to Janurary 2022.12 patients were dropped out,and 258 patients who completed both ds-MCE and EGD examinations were included in the diagnositic accuracy analysis.The indication of the 258 patients included: 110 patients clinically diagnosed with GERD or diagnosed with RE under endoscopy;9post-POEM patients with GERD symptoms,56 post-ESD patients,and 83 patients with diagnosed EVs.(2)Compared to EGD,the sensitivity and specificity of ds-MCE for diagnosing esophageal diseases were 97.6%(95% confidence interval [CI],92.62 to 99.38)and 93.23%(95% CI,87.17 to 96.66).The positive predictive value(PPV)and negative predictive value(NPV)were 93.13%(95% CI,86.99 to 96.61)and 97.64%(95% CI,92.73 to 99.34),respectively,and the overall accuracy was 95.35%(95%CI 91.97%,97.40%).(3)Compared to EGD,the sensitivity and specificity of ds-MCE for diagnosing RE were 100%(95% confidence interval [CI],90.20 to 100)and 94.59%(95% CI,86.02 to 98.25)in GERD populations.The accuracy of ds-MCE for grading RE was 97.8%(44/45).(4)Compared to EGD,the sensitivity and specificity of ds-MCE for diagnosing ESD-related lesions were 100%(95% confidence interval [CI],90.20 to 100)and 90.70%(95%CI76.94%,96.98%)in post-ESD populations.(5)Compared to EGD,the sensitivity and specificity of ds-MCE for diagnosing EVs were 98.33%(95% confidence interval [CI],89.86 to 99.91)and 95.65%(95% CI,76.03 to 99.77)in EV populations.And ds-MCE had a sensitivity of 97.82%(95% confidence interval [CI],87.03 to 99.89)and a specificity of94.59%(95% CI,80.47 to 99.06)for the identification of high-risk EVs.(6)Among the182 patients who underwent stomach examinations,75 gastric lesions were detected by ds-MCE.Among the 111 patients who underwent small bowel examinations,60 small bowel lesions were detected by ds-MCE.(7)For overall evaluation of ds-MCE,the score of ds-MCE is significantly better than that of EGD in comfort(1 vs 2,p<0.01),preference(1 vs 1,p<0.01)and convenience(1 vs 1,p<0.01)of the procedures.(8)The median esophageal transit time was 5.48 minutes(interquartile range [IQR],3.03–8.89).The median gastric transit time was 39.19 minutes(IQR,20.10-91.63).The median small bowel transit time was 5.24 hours(IQR,4.14-7.11).The total recording time of ds-MCE was 0.65 hours(IQR,0.28-10.36).(9)Two adverse events were reported during the entire study process.One case was vomiting caused by excessive water intake during gastric preparation before ds-MCE examination.The other case was bucking during the EGD examination under general anesthesia.Conclusions: The ds-MCE is safe,accurate,and highly accepted for review and follow-up of patients with esophageal diseases.Further studies with large sample size are warranted to validate the performance of ds-MCE for follow-up of single esophageal disease.Part II: Novel tethered ultrasound capsule endoscopy for gastrointestinal scanning: an in-vivo animal studyBackground and objectives: The results of Part I demonstrated that ds-MCE is accurate and highly accepted for follow-up of patients with esophageal diseases.However,although SCE has shown its high application value in the diagnosis of esophageal diseases,its observation of the esophagus is limited to the surface of the esophagus,and subepithelial lesions cannot be observed.Endoscopic ultrasound(EUS)is an important modality for diagnosis and assessment of gastrointestinal(GI)subepithelial lesions(SEL).Following the pattern of EUS,a novel tethered ultrasound capsule endoscopy(USCE) system was developed for superficial and submucosal imaging of the esophagus,which incorperates both white-light and ultrasound imaging modalities.This animal study aimed to evaluate the feasibility and efficacy of the USCE system for upper GI tract and small bowel scanning.Methods: Three Bama miniature pigs were selected to scan their esophagus,stomach,small bowel and simulated submucosal lesions.USCE was performed first,followed by EUS,to acquire both optical and ultrasound images of specified locaitons.The primary goal of this animal study was the feasibility and efficacy of USCE.The feasibility of USCE was measured by obtaining ultrasound images of normal GI walls and submucosal lesions under the guidance of optical viewing.The efficacy of USCE was evaluated by comparing tissue structures and lesion features showed on ultrasound images obtained with both instruments.Results:(1)USCE and EUS procedures were completed on all the three Bama pigs.(2)Under the optical mode of USCE,the GI tract was well visualized and all simulated lesions were located.Clear ultrasound images of normal GI tract and submucosal lesions were acquired.(3)Ultrasound images of the esophagus,stomach and small bowel were characterized by differentiated 9-layer,5-layer,and 4-layer structures on USCE,which was consistent with the structures displayed on EUS.And the visualization of submucosal lesions,using both USCE and EUS,was characterized by a hypoechoic and well-demarcated mass in the layer of submucosa.Conclusions: This animal study indicated the feasibility and potential clinical efficacy of this USCE for simultaneous optical mucosal visualization and transmural ultrasound imaging of upper GI tract and small bowel,providing possibility of using this technology in clinical application.Part III: Novel tethered ultrasound capsule endoscopy for superficial and submucosal imaging of esophagus: the first-in-human studyBackground and aims: Part II demonstrated the feasibility and efficacy of the novel USCE system for simultaneous optical mucosal visualization and transmural ultrasound imaging of upper GI tract and small bowel in a porcine mode.Baed on the primary results of the animal study,we conducted this pilot study to assess the feasibility and safety of this USCE system for human esophageal examinations.Methods: This study was a prospective,single-center,pilot study.Healthy volunteers or patients who were diagnosed with esophageal diseases under esophagogastroduodenoscopy(EGD)and scheduled to undergo an indicated EUS were enrolled.Participants first underwent USCE,and subsequently EUS within 48 hours.The primary outcome was the technical success rate of USCE.The secondary outcomes included safety,visualization of the esophagus and comfort assessment.Results:(1)From August 2021 to October 2022,a total of 20 participants were prospectively enrolled in this study: 10 healthy volunteers and 10 patients with esophageal lesions who were scheduled for EUS examinations.(2)The technical success rate of USCE was 95% as one patient failed to swallow the capsule.(3)None adverse event was observed throughout the study.(4)Under USCE optical mode,the esophagus was well visualized and all known lesions were detected.For healthy volunteers,the ultrasound images of normal esophageal walls were all characterized by differentiated 7-layer architecture under both USCE and EUS.For the 9 patients,the features of esophageal lesions(echogenicity,the layer of origin,and the margin of the lesion)were recognized clearly under USCE ultrasound mode,which were consistent with those on EUS.Thus the presumptive diagnoses derived from USCE were all consistent with those from EUS,including esophageal cyst(n=3),esophageal leiomyoma(n=5),and one esophageal cancer infiltrating the muscularis propria.(5)The mean comfort score of 19 participants was 2.63±0.90.Most participants preferred USCE compared to EUS.Conclusions: The novel USCE is feasible and safe to observe the esophageal mucosa and acquire submucosal information.Further multicenter studies to validate the performance of this capsule are warranted.