Endoscopic capsule robot-based diagnosis, navigation and localization in the gastrointestinal tract.

The proliferation of video capsule endoscopy (VCE) would not have been possible without continued technological improvements in imaging and locomotion. Advancements in imaging include both software and hardware improvements but perhaps the greatest software advancement in imaging comes in the form of artificial intelligence (AI). Current research into AI in VCE includes the diagnosis of tumors, gastrointestinal bleeding, Crohn's disease, and celiac disease. Other advancements have focused on the improvement of both camera technologies and alternative forms of imaging. Comparatively, advancements in locomotion have just started to approach clinical use and include onboard controlled locomotion, which involves miniaturizing a motor to incorporate into the video capsule, and externally controlled locomotion, which involves using an outside power source to maneuver the capsule itself. Advancements in locomotion hold promise to remove one of the major disadvantages of VCE, namely, its inability to obtain targeted diagnoses. Active capsule control could in turn unlock additional diagnostic and therapeutic potential, such as the ability to obtain targeted tissue biopsies or drug delivery. With both advancements in imaging and locomotion has come a corresponding need to be better able to process generated images and localize the capsule's position within the gastrointestinal tract. Technological advancements in computation performance have led to improvements in image compression and transfer, as well as advancements in sensor detection and alternative methods of capsule localization. Together, these advancements have led to the expansion of VCE across a number of indications, including the evaluation of esophageal and colon pathologies including esophagitis, esophageal varices, Crohn's disease, and polyps after incomplete colonoscopy. Current research has also suggested a role for VCE in acute gastrointestinal bleeding throughout the gastrointestinal tract, as well as in urgent settings such as the emergency department, and in resource-constrained settings, such as during the COVID-19 pandemic. VCE has solidified its role in the evaluation of small bowel bleeding and earned an important place in the practicing gastroenterologist's armamentarium. In the next few decades, further improvements in imaging and locomotion promise to open up even more clinical roles for the video capsule as a tool for non-invasive diagnosis of lumenal gastrointestinal pathologies.

Delivering siRNA Compounds During HOPE to Modulate Organ Function: A Proof-of-concept Study in a Rat Liver Transplant Model.

BACKGROUND: Apoptosis contributes to the severity of ischemia-reperfusion injury (IRI), limiting the use of extended criteria donors in liver transplantation (LT). Machine perfusion has been proposed as a platform to administer specific therapies to improve graft function. Alternatively, the inhibition of genes associated with apoptosis during machine perfusion could alleviate IRI post-LT. The aim of the study was to investigate whether inhibition of an apoptosis-associated gene (FAS) using a small interfering RNA (siRNA) approach could alleviate IRI in a rat LT model. METHODS: In 2 different experimental protocols, FASsiRNA (500 µg) was administered to rat donors 2 h before organ procurement, followed by 22 h of static cold storage, (SCS) or was added to the perfusate during 1 h of ex situ hypothermic oxygenated perfusion (HOPE) to livers previously preserved for 4 h in SCS. RESULTS: Transaminase levels were significantly lower in the SCS-FASsiRNA group at 24 h post-LT. Proinflammatory cytokines (interleukin-2, C-X-C motif chemokine 10, tumor necrosis factor alpha, and interferon gamma) were significantly decreased in the SCS-FASsiRNA group, whereas the interleukin-10 anti-inflammatory cytokine was significantly increased in the HOPE-FASsiRNA group. Liver absorption of FASsiRNA after HOPE session was demonstrated by confocal microscopy; however, no statistically significant differences on the apoptotic index, necrosis levels, and FAS protein transcription between treated and untreated groups were observed. CONCLUSIONS: FAS inhibition through siRNA therapy decreases the severity of IRI after LT in a SCS protocol; however the association of siRNA therapy with a HOPE perfusion model is very challenging. Future studies using better designed siRNA compounds and appropriate doses are required to prove the siRNA therapy effectiveness during liver HOPE liver perfusion.

Current Controversies Concerning Capsule Endoscopy.

Video capsule endoscopy became a reality in 2001. This device enabled us to directly view the mucosa of the small intestine for the first time. The main indications for the video capsule remain the detection of small intestinal bleeding and iron deficiency anemia, diagnosis and management of Crohn's disease, and detection of tumors. The device is extraordinarily safe and can be used in the very young to the very old. However, there remain several areas of controversy and difficulty. These are covered in this article and include details of indications and contraindications, whether to prepare patients, whether or not to use simethicone and prokinetics. Detection of location of the capsule remains a major engineering challenge. Reading the videos reliably and quickly remains challenging. However, artificial intelligence and machine learning are already on the horizon to provide assistance. New uses for capsule endoscopy promise more accurate diagnosis and hence improved management of acute gastrointestinal bleeding. The colon capsule may eventually help those who refuse conventional colonoscopy, and robotically controlled capsules may be helpful in screening for serious disease in patients with upper abdominal complaints. The advent of the broadening use of video capsule endoscopy is, though it will be controversial, embraced by some and derided by others; such is the nature of technological development. In the long run, if the use of the video capsule, based on sound evidence-based studies, can be shown to improve the care of our patients and reduce the cost of health care, its use will continue to expand.

Role of Mucosal Protrusion Angle in Discriminating between True and False Masses of the Small Bowel on Video Capsule Endoscopy.

The diagnosis of small-bowel tumors is challenging due to their low incidence, nonspecific presentation, and limitations of traditional endoscopic techniques. In our study, we examined the utility of the mucosal protrusion angle in differentiating between true submucosal masses and bulges of the small bowel on video capsule endoscopy. We retrospectively reviewed video capsule endoscopies of 34 patients who had suspected small-bowel lesions between 2002 and 2017. Mucosal protrusion angles were defined as the angle between the small-bowel protruding lesion and surrounding mucosa and were measured using a protractor placed on a computer screen. We found that 25 patients were found to have true submucosal masses based on pathology and 9 patients had innocent bulges due to extrinsic compression. True submucosal masses had an average measured protrusion angle of 45.7 degrees ± 20.8 whereas innocent bulges had an average protrusion angle of 108.6 degrees ± 16.3 (p < 0.0001; unpaired t-test). Acute angle of protrusion accurately discriminated between true submucosal masses and extrinsic compression bulges on Fisher's exact test (p = 0.0001). Our findings suggest that mucosal protrusion angle is a simple and useful tool for differentiating between true masses and innocent bulges of the small bowel.

A randomized controlled trial comparing efficacy of early video capsule endoscopy with standard of care in the approach to nonhematemesis GI bleeding (with videos).

BACKGROUND AND AIMS: Patients presenting with nonhematemesis GI bleeding (NHGIB) represent a diagnostic challenge for physicians. We performed a randomized controlled trial to assess the benefits of deployment of a video capsule soon after admission in the management of patients presenting with melena, hematochezia, or severe anemia compared with standard of care management. METHODS: Patients admitted with NHGIB were randomized and placed into 1 of 2 study groups. In the experimental group, patients ingested a video capsule soon after admission to the hospital. These patients had further endoscopic workup based on the findings from the capsule. Patients in the control group underwent endoscopic evaluation (ie, upper endoscopy, capsule endoscopy, and/or colonoscopy) to identify the source of bleeding as directed by the attending gastroenterologist's interpretation of their clinical presentation. The primary endpoint for this study was the rate of localization of bleeding during hospitalization. RESULTS: Eighty-seven patients were included in this study: 45 randomized to the standard of care arm and 42 to the early capsule arm. A bleeding source was localized in 64.3% of the patients in the early capsule arm and in 31.1% of the patients in the standard of care arm (P < .01). The likelihood of endoscopic localization of bleeding over time was greater for patients receiving early capsule endoscopy compared with those in the standard of care arm (adjusted hazard ratio, 2.77; 95% confidence interval, 1.36-5.64). CONCLUSIONS: For patients admitted to the hospital for NHGIB, early capsule endoscopy is a safe and effective alternative for the detection of the source of bleeding. (Clinical trial registration number: NCT02442830.).

Approach to the Diagnostic Workup and Management of Small Bowel Lesions at a Tertiary Care Center.

BACKGROUND: Small bowel lesions (SBL) are rare, representing diagnostic and management challenges. The purpose of this cross-sectional study was to evaluate diagnostic modalities used and management practices of patients with SBL at an advanced endoscopic referral center. METHODS: We analyzed patients undergoing surgical management for SBL from 2005 to 2015 at a single tertiary care center. Patients were stratified into gastrointestinal bleed/anemia (GIBA) or obstruction/pain (OP). RESULTS: One hundred and twelve patients underwent surgery after presenting with either GIBA (n = 67) or OP (n = 45). The mean age of our study population was 61.8 years and 45% were women. Patients with GIBA were more likely to have chronic or acute-on-chronic symptoms (100% vs 67%) and more often referred from outside hospitals (82 vs. 44%) (p < 0.01). The most common preoperative imaging modalities were video capsule endoscopy (VCE) (96%) for GIBA and computer tomography CT (78%) for OP. Findings on VCE and CT were most frequently concordant with operative findings in GIBA (67%) and OP (54%) patients, respectively. Intraoperatively, visual inspection or palpation of the bowel successfully identified lesions in 71% of patients. When performed in GIBA (n = 26), intraoperative enteroscopy (IE) confirmed or identified lesions in 69% of patients. Almost all (90%) GIBA patients underwent small bowel resections; most were laparoscopic-assisted (93%). Among patients with OP, 58% had a small bowel resection and the majority (81%) were laparoscopic-assisted. Surgical exploration failed to identify lesions in 10% of GIBA patients and 24% of OP patients. Among patients who underwent resections, 20% of GIBA patients had recurrent symptoms compared with 13% of OP patients. CONCLUSION: Management and identification of SBL is governed by presenting symptomatology. Optimal management includes VCE and IE for GIBA and CT scans for OP patients. Comprehensive evaluation may require referral to specialized centers.

Re-evaluating osteoporosis and fracture risk in Crohn's disease patients in the era of TNF-alpha inhibitors.

INTRODUCTION: Patients with Crohn's disease (CD) are at increased risk for osteoporosis and fractures as compared to the general population. Recently, various cytokines including tumor necrosis factor (TNF)-alpha are found to play a major role in bone health. In this study, we aimed to gain a better understanding of the risk factors for osteoporosis and vitamin D deficiency in the era of TNF-alpha inhibitors. METHODS: We conducted a retrospective review of 464 consecutive patients with CD in our GI clinic between 2008 and 2015. Statistical analysis was performed using the student t-test and chi-square test. RESULTS: CD patients treated with TNF-alpha inhibitors (TNF) and those who are anti-TNF naïve (NB) had similar rates of vitamin D deficiency, insufficiency and normal vitamin D-25-OH levels. Similarly, rates of osteoporosis (16% vs 18%), osteopenia (53% vs 57%) and normal bone density (31% vs 25%) were comparable between the TNF and NB groups respectively. However, Z-scores at the spine (-0.47 vs -0.05) were significantly lower in the TNF group (p = .03). Interestingly, rates of osteoporosis in the NB group were drastically different before and after age 60 (3.6% vs 30%) with no major difference in the TNF group (15% vs 18%). Bone density was positively correlated with BMI (Pearson's R = 0.39) and negatively correlated with age and smoking status (R= -0.25). CONCLUSIONS: TNF group patients were diagnosed with osteoporosis from an earlier age compared to NB group but with a smaller increase in osteoporosis after menopause. Further prospective studies are necessary to further determine the role of anti-TNF medications in osteoporosis.

ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding.

Bleeding from the small intestine remains a relatively uncommon event, accounting for ~5-10% of all patients presenting with gastrointestinal (GI) bleeding. Given advances in small bowel imaging with video capsule endoscopy (VCE), deep enteroscopy, and radiographic imaging, the cause of bleeding in the small bowel can now be identified in most patients. The term small bowel bleeding is therefore proposed as a replacement for the previous classification of obscure GI bleeding (OGIB). We recommend that the term OGIB should be reserved for patients in whom a source of bleeding cannot be identified anywhere in the GI tract. A source of small bowel bleeding should be considered in patients with GI bleeding after performance of a normal upper and lower endoscopic examination. Second-look examinations using upper endoscopy, push enteroscopy, and/or colonoscopy can be performed if indicated before small bowel evaluation. VCE should be considered a first-line procedure for small bowel investigation. Any method of deep enteroscopy can be used when endoscopic evaluation and therapy are required. VCE should be performed before deep enteroscopy if there is no contraindication. Computed tomographic enterography should be performed in patients with suspected obstruction before VCE or after negative VCE examinations. When there is acute overt hemorrhage in the unstable patient, angiography should be performed emergently. In patients with occult hemorrhage or stable patients with active overt bleeding, multiphasic computed tomography should be performed after VCE or CTE to identify the source of bleeding and to guide further management. If a source of bleeding is identified in the small bowel that is associated with significant ongoing anemia and/or active bleeding, the patient should be managed with endoscopic therapy. Conservative management is recommended for patients without a source found after small bowel investigation, whereas repeat diagnostic investigations are recommended for patients with initial negative small bowel evaluations and ongoing overt or occult bleeding.

Preliminary colonoscopy facilitates retrograde double-balloon enteroscopy.

BACKGROUND AND STUDY AIMS: Retrograde double-balloon enteroscopy (RDBE) has a high failure rate due to difficulty intubating the ileo-cecal (IC) valve. We examined the utility of a pre-RDBE colonoscopy using a pediatric colonoscope to clean the cecum and perform an initial intubation of the IC valve. PATIENTS AND METHODS: This study is a retrospective review of RDBE procedures for 45 patients at a single tertiary-care center to examine the success of IC intubation, maximal depth of enteroscope insertion, and duration of the procedure. RESULTS: The IC intubation success rate among patients who underwent RDBE using this novel method was 100 % as compared to 72.7 % using the traditional method (P < 0.003). CONCLUSIONS: RDBE preceded by colonoscopy had a significantly higher IC intubation success rate, compared to RDBEs performed using the traditional method. RESULTS support the use of this novel method when IC valve intubation using standard methods is difficult, and it may limit the need for repeat procedures or the use of other modalities for examining the small bowel.

Capsule endoscopy is superior to small-bowel follow-through and equivalent to ileocolonoscopy in suspected Crohn's disease.

BACKGROUND & AIMS: Evaluation of the small intestine for inflammation has traditionally relied on small-bowel follow-through (SBFT), but multiple studies have demonstrated its low diagnostic accuracy. Capsule endoscopy (CE) transmits high-quality images of the small intestinal mucosa; it can be used to visualize the entire length of the small bowel and much of the mucosa. We compared the diagnostic yields of CE vs SBFT in a prospective study of patients with suspected small-bowel Crohn's disease. METHODS: Eighty patients with signs and/or symptoms of small-bowel Crohn's disease (age, 10-65 years) underwent CE, followed by SBFT and ileocolonoscopy. Readers were blinded to other test results. The primary outcome was the diagnostic yield for inflammatory lesions found with CE before ileocolonoscopy compared with SBFT and ileocolonoscopy. A secondary outcome was the incremental diagnostic yield of CE compared with ileocolonoscopy and CE compared with SBFT. RESULTS: The combination of CE and ileocolonoscopy detected 107 of 110 inflammatory lesions (97.3%), whereas the combination of SBFT and ileocolonoscopy detected only 63 lesions (57.3%) (P < .001). The diagnostic yield of CE compared with ileocolonoscopy was not different (P = .09). The diagnostic yield was higher for CE than for SBFT (P < .001). Of the 80 patients with suspected Crohn's disease, 25 (31.3%) had the diagnosis confirmed. Eleven were diagnosed by CE findings alone and 5 by ileocolonoscopy findings alone. In the remaining 9 patients, diagnostic findings were identified by at least 2 of the 3 modalities. No diagnoses were made on the basis of SBFT findings alone. CONCLUSIONS: CE was better than SBFT and equivalent to ileocolonoscopy in detecting small-bowel inflammation. Although ileocolonoscopy remains the initial diagnostic test of choice, CE is safe and can establish the diagnosis of Crohn's disease in patients when ileocolonoscopy results are negative or the terminal ileum cannot be evaluated. ClinicalTrials.gov Number: NCT00487396.

A multicenter, prospective, randomized comparison of a novel signal transmission capsule endoscope to an existing capsule endoscope.

BACKGROUND: MiroCam, a capsule endoscope, uses a novel transmission technology, electric-field propagation, which uses the human body as a conduction medium for data transmission. OBJECTIVE: To compare the ability of the MiroCam (MC) and PillCam (PC) to identify sources of obscure GI bleeding (OGIB). DESIGN: Prospective, multicenter, comparative study. SETTING: Six academic hospitals. PATIENTS: A total of 105 patients with OGIB. INTERVENTION: Patients ingested both the MC and PC capsules sequentially in a randomized fashion. MAIN OUTCOME MEASUREMENTS: Concordance of rates in identifying a source of OGIB, operational times, and rates of complete small-bowel examination. RESULTS: Data analysis resulted in 43 (48%) "abnormal" cases identifying a source of OGIB by either capsule. Twenty-four cases (55.8%) were positive by both capsules. There was negative agreement in 46 of 58 cases (79.3%). The κ index was 0.547 (χ(2) = 1.32; P = .36). In 12 cases, MC positively identified a source that was not seen on PC, whereas in 7 cases, PC positively identified a source that was not seen on MC. MC had a 5.6% higher rate of detecting small-bowel lesions (P = .54). MC captured images at 3 frames per second for 11.1 hours, and PC captured images at 2 frames per second for 7.8 hours (P < .0001). Complete small-bowel examination was achieved in 93.3% for MC and 84.3% for PC (P = .10). LIMITATIONS: Readers were not blinded to the particular capsule they were reading. CONCLUSION: A positive diagnostic finding for OGIB was identified by either capsule in 48% of cases. The concordance rate between the 2 capsules was comparable to that of prior studies in identifying sources of small-bowel bleeding. The longer operational time of the MC may result in higher rates of complete small-bowel examination, which may, in turn, translate into a higher rate of detecting small-bowel lesions. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00878982.).

Evaluation of small bowel bleeding.

PURPOSE OF REVIEW: The review focuses on the latest techniques that are evolving in the management of small bowel bleeding. RECENT FINDINGS: Video capsule endoscopy has the highest yield of diagnosis when it is performed within 48 h of the bleeding event (78 versus 48%). The pooled detection rate of double balloon endoscopy was noted to be 68.1% for obscure gastrointestinal bleeding according to a systematic review of 66 studies in the last 10 years. Also a recent review, which focused on analysis of 68 studies found that the procedural characteristics were comparable for double balloon, single balloon and spiral enteroscopy though the procedure time was fastest for the spiral enteroscopy group. Medical therapy for vascular lesions is in its infancy but shows promise. SUMMARY: Advanced diagnostic and therapeutic endoscopic techniques are changing the paradigm of care for patients with small bowel bleeding.

Technology Insight: current status of video capsule endoscopy.

Video capsule endoscopy (VCE) is the most recent major practical and conceptual development in the field of endoscopy. The video capsule endoscope-a small, pill-sized, passive imaging device-has been demonstrated to be the pre-eminent imaging device for disorders of the small intestine. The initial use for VCE was to detect the origin of obscure gastrointestinal bleeding. Several other indications have now been justified, or are in the process of evaluation. More than 200,000 of these disposable devices have been used worldwide, with an extraordinarily good safety record: indeed, the device has been approved for use in children as young as 10 years of age. In addition, a double-ended capsule has now been approved for the evaluation of mucosal disease in the esophagus. The now-widespread deployment of the device into gastrointestinal practice in the US and many other countries suggests that VCE has achieved mainstream utility. The development of similar competitor devices, and devices whose movement can be controlled, is in progress.

A prospective study of the diagnostic accuracy of PillCam ESO esophageal capsule endoscopy versus conventional upper endoscopy in patients with chronic gastroesophageal reflux diseases.

INTRODUCTION: Endoscopy is commonly performed to evaluate for suspected or established esophageal diseases including gastroesophageal reflux disease (GERD) and its complications. The newly developed PillCam ESO Esophageal Capsule offers an alternative approach to visualize the esophagus and to evaluate patients with suspected esophageal disease. AIM: Compare the accuracy (specificity, sensitivity, positive predictive value [PPV], and negative predictive value [NPV]) of esophageal capsule endoscopy (ECE) compared with esophagogastroduodenoscopy (EGD) in evaluating patients with GERD. METHODS: A multicenter pivotal trial was conducted at seven sites. The PillCam ESO esophageal capsule is similar to the standard capsule endoscope used for the small bowel but acquires video images from both ends of the device at 2 frames/second/end. A total of 106 patients (93 GERD; 13 Barrett) underwent ECE followed by EGD. ECE videos were evaluated by an investigator blinded to EGD findings. A blinded adjudication committee reviewed all discrepant findings between ECE and EGD. RESULTS: Sixty-six of 106 patients had positive esophageal findings, ECE identified esophageal abnormalities in 61 (sensitivity, 92%; specificity, 95%). The per-protocol sensitivity, specificity, PPV, and NPV of ECE for Barrett esophagus were 97%, 99%, 97%, and 99%, respectively, and for esophagitis 89%, 99%, 97%, and 94%, respectively. ECE was preferred over EGD by all patients. There were no adverse events related to ECE. CONCLUSIONS: ECE is a convenient and sensitive method for visualization of esophageal mucosal pathology and may provide an effective method to evaluate patients for esophageal disease.

Hormonal and antihormonal therapy for epistaxis in hereditary hemorrhagic telangiectasia.

OBJECTIVES/HYPOTHESIS: Objectives were to assess available information on hormonal therapy for bleeding in hereditary hemorrhagic telangiectasia (HHT), to determine whether there is a role for hormonal therapy as an initial therapeutic option, and to report the second known case of response in HHT to antihormonal therapy. STUDY DESIGN: Literature review and case report. METHODS: The literature on hormonal and antihormonal therapy for HHT was reviewed. Medical records for the case reported in the present study were evaluated to confirm the diagnosis and assess responses to surgical and nonsurgical treatments. RESULTS: All reports of success using hormonal therapy for HHT-related bleeding were either retrospective or uncontrolled with the exception of two. Anecdotal evidence with high-dose estrogen appeared to show success, but serious side effects have discouraged use. One controlled trial found no benefit for intermediate dose, single-agent estrogen. The other controlled trial appeared to show benefit with low-dose estrogen-progesterone in HHT with gastrointestinal tract bleeding and was supported by an uncontrolled study showing efficacy in epistaxis. The case reported in the present study demonstrated long-term cessation of epistaxis with tamoxifen in a postmenopausal woman. CONCLUSIONS: Systemic estrogen-progesterone at doses used for oral contraception may eliminate bleeding in symptomatic HHT and is a reasonable initial option in fertile women. There is no information on possible effects of lower-dose estrogen-progesterone used in postmenopausal women for hormone replacement therapy. Tamoxifen has dramatically eliminated HHT-related bleeding in two cases. It is well tolerated in postmenopausal women and should be considered for randomized clinical trials.