INTRODUCTION
Small bowel diseases are difficult to diagnose at times. Evaluation of many small bowel diseases are now becoming easier because of advent of some novel diagnostics. With the introduction of video capsule endoscopy the visualization of whole small bowel is now becoming possible. It has revolutionized the diagnostic of bowel pathology. Other developments in serological test and breath test biomarkers are also creating newer insights in evaluation of many small bowel diseases.
ADVANCES IN IMAGING IN ENDOSCOPY
Endoscopy is an important tool in evaluation of many small bowel disorders. In last few years there has been tremendous development in the imaging system of the endoscopes. Visual diagnoses are becoming more sensitive and accurate. From the conventional endoscopy, endoscopists have shifted to many improvised endoscopic techniques like high definition endoscopy, dye based and digital chromoendoscopy, endosonography and capsule endoscopy. Moreover advanced technologies like full-spectrum endoscopy, endocytoscopy, autofluorescence, laser endoscopy, and endomicroscopy, including molecular imaging have changed the scenario in endoscopy.1
Capsule Endoscopy (CE)
Capsule endoscopy, also known as wireless video endoscopy or video capsule endoscopy (VCE) is a very powerful tool for diagnosis of small bowel diseases2 (Figs. 1 and 2). It was first introduced in 2001.2 Capsule endoscopy offers a perfect view of small bowel.3 Like conventional endoscopy CE does not need typical maneuvers like probing and sampling of tissues. But, it needs knowledge of normal anatomy, its variations and the anatomical changes that are occurring because of the disease.3 Recognition of anatomical landmarks is essential. The reader should be aware of artifact, unfamiliar normal anatomy in interpreting any pathology of the bowel. Image seen in small bowel CE is more magnified than conventional endoscopy. One must be very careful not to interpret a normal finding seen as huge in CE. Training and experience is essential for competency.3
In CE mucosa of small bowel can be inspected and diagnosis relies on visible findings.2 Initial CE system had primarily white light imaging (WLI) 2incorporated to it.2 Till now it is used. WLI may not detect subtle mucosal microlesion. Submucosal and/or transmural pathology may not be clearly detected. There are now some new developments in CE system where modalities like microultrasonography and infrared light are incorporated.2 They enhanced detection of pathologies and limitations of WLE are minimized. There is improved differentiation between and benign lesion.2 There are some studies on clinical efficacy of these new capsules. But study population is small. Further studies are required to know about their clinical efficacy.2
Improved computer aided diagnosis will be a possibility from the newer diagnostic capsules.2 People will also get benefit from virtual biopsy and capsule localization from the newer capsules.2 Research is going on to 3incorporate sensors to capsules to measure physiological parameters or find out new biomarkers. It will increase sensitivity, specificity and clinical utility of the capsule.2
Device assisted endoscopy (DAE) is another development in history of small bowel endoscopy. It is used for both diagnostic and therapeutic purpose. DAE can help at times to overcome the limitations in CE.3
Advances in Radiological Imaging
Conventional barium studies have limited role in diagnosis of bowel diseases. Often additional CT studies are required to characterize small bowel lesions.4 Ultrasound is useful for assessing small gut specially in combination with oral or intravenous contrast agent.5 Contrast-enhanced ultrasound (CEUS) can detect bowel wall inflammation.6 Ultrasound Shear Wave Elastography (SWE) are found to be safe and effective.6 Point-of-care ultrasound (POCUS) is new modality used by the clinicians in an emergency set up for evaluation of acute abdomen. POCUS is an extension of the clinical examination when used by acute care clinicians in evaluating an acute abdomen.7 A trained physician can use POCUS findings for detection of specific intestinal pathologies.7 Conventional CT with intravenous (IV) and oral contrast is used as investigation for small bowel disease. Inflammatory and neoplastic diseases are usually detected.4
CT enteroclysis and CT enterography are used for many small bowel diseases like tumor, inflammatory diseae, celiac disease, malabsorption, low-grade small bowel obstruction and gastrointestinal (GI) bleed.4,5
Though CT is a good modality MR has some advantages over CT. Soft tissue contrast resolution, multiplane imaging and free from ionizing radiations are its advantages.4 MR is the preferred imaging modality in inflammatory bowel diseases (IBD) because of its capacity for multiparametric approach and evaluation of bowel motility. There is no radiation exposure for MRI.5 MRI is now considered important for evaluation of small bowel disease.8
Other than MR enterography novel MRI techniques such as DWI, motility studies, PET-MRI and molecular imaging are increasingly used for diagnosis of bowel disease.8 PET-CT is emerging as a new investigative tool for IBD patients.4 PET-CT with FDG increases the capacity of spatial localization in comparison with PET-FDG without CT.4,8 PET/CT can show functional and morphological picture of GIT with extraintestinal involvements.8 There is reduced uptake in fibrous areas of intestine in PET-CT.8 As PET-CT has better detection of colonic inflammation in comparison to CT or MRE it is more advantageous in evaluation of IBD.8
Serological Tests
For evaluation of Crohn's disease and ulcerative colitis newer serological markers named as antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) are added to previously available markers like antibodies against the outer membrane porin C (OmpC) of E. coli, antibodies against subtypes of flagellins (CBir1) and various anti-glycan antibodies.9 They act as predictors before the diagnosis.4
Breath Test Biomarkers
Breath tests are used for diagnosis of small intestinal bacterial overgrowth (SIBO) in IBD.10,11 Breath H2S is a new addition to breath test biomarker for assessment of SIBO.11
NOVEL DIAGNOSTICS IN SOME SPECIFIC SMALL BOWEL DISORDERS
Bleeding: Use of capsule endoscopy has improved detection rate of source in GI bleed and obscure gastrointestinal bleeding (OGIB).10,12 American Gastroenterological Association has defined OGIB as persistent or recurring bleeding condition of unknown origin after negative upper and lower endoscopies.4 The source of bleed in OGIB has is in small bowel in 5–10% of these patients. It is found to be up to 27% of patients I some studies.4 A large systematic review showed the diagnostic yield of video capsule endoscopy as 59.4% in OGIB. Out of these > 50% had angiodysplasias.13 Another study shows its sensitivity in OGIB 42–80%.4,48 Common causes of OGIB are angioectasia (AE), Dieulafoy's lesion (DL), arteriovenous malformation (AVM).12 Subsequent to VCE deep enteroscopy is done for diagnosis of small bowel Ads and also to control active bleed or to improve anemia.12 The indications for DE and VCE are same. But, VCE can visualize almost 90% of the bowel.12 Real time viewing or increased battery capacity can increase more visualization.12 Diagnostic yield of VCE is highest when it is done at the time of bleeding.12 Many GI societies recommend VCE as first line investigation for evaluation of small bowel bleed.12
Celiac disease: Diagnosis of celiac disease is usually done by demonstrating histological small-bowel mucosal damage induced by gluten. New noninvasive serological tools are available now.14 Breath tests and other biomarkers are also used for diagnosis of the disease.10 Endoscopic biopsy is essential for a definitive diagnosis. MR studies may be done for diagnosis in patients with atypical symptoms.4 MR enterography is helpful for complications in known patients with celiac disease.4 VCE was also evaluated as an alternative to invasive endoscopic biopsies.10
Inflammatory bowel disase: In last few years many diagnostic modalities are developed for diagnosis of IBD and for its follow up in the course of the disease. MRI has been increasingly used. Advanced development of MRI like diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MR perfusion and MR motility is enhancing diagnostic accuracy in assessment of the disease.15 Use of spectroscopy, PET-MRI and molecular imaging are currently under investigation to improve the diagnosis, follow-up and management of the disease.8 MR enterography has become a part of standard diagnostic modality in Crohn's disease (CD).8 DWI for detecting and assessing ileal inflammation in CD.8 Fibrosis in bowel wall can be seen directly magnetization transfer imaging technique.15
Horsthuis K et al found that CTE and MRE have similar capacity to diagnose CD. CT5 PET and PET-CT are now increasingly used for assessment of CD.15 Hybrid imaging (PET/MRI) has also shown its potentiality.155
Ultrasound findings are non-specific in IBD. But it can be used as initial guide for further investigations.8
Recent use of EUS in assessing perianal fistulas in CD and chromoendoscopy for dysplasia surveillance has widened the role of USG.16 In a recent study by Cathy Lu et al CEUS (Contrast-enhanced ultrasound) and SWE (Ultrasound Shear Wave Elastography) are found to be safe and effective. CEUS can detect bowel wall inflammation. Measurement of bowel wall thickness can be measured by SWE. They can act as noninvasive objective biomarkers in management of strictures in Crohn's disease.6
Early detection of SIBO in Irritable Bowels Syndrome (IBS) is a strategy in management of IBS. Current method based on hydrogen breath test (HBT) has limitations and drawbacks. Most of the times it fails to detect SIBO caused by ‘non-hydrogen-producing’ bacteria of colon. Breath H2S is a novel biomarker for assessment of SIBO. It can detect SIBO in cases where often HBT fails to detect it. It is non-invasive and rapid.11 Study showed it useful for accurately identifying SIBO either at onset or after eradication of disorder.11
Endoscopy is an important tool in diagnosis of inflammatory bowel disease. Endoscopists are getting advantages from newer advances in endoscopic techniques like dye-based and digital chromoendoscopy, high-definition endoscopy, capsule endoscopy, and endosonography. Advanced experimental technologies like full-spectrum endoscopy, endocytoscopy, auto fluorescence, laser endoscopy, and endomicroscopy, including molecular imaging are used for evaluation of inflammatory bowel disease.1
CE has high sensitivity and high specificity for Crohn's disease.2 It is useful for monitoring activity of the disease and its response to therapy.2,10
Crohn's Disease Endoscopic Index of Severity (CDEIS) is used for measuring mucosal disease in Crohn's disease.17 For Capsule Endoscopy a newer index is developed. It is known as Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score). A comprehensive view of small intestine is possible with capsule endoscopy in CD patients.2,17
With the advent of the second generation of the CE of the colon (PillCam 2 or “IBD” capsule), a new score (CECDAIic) is developed as this generation of CE has ability to visualize both small bowel and colonic inflammation.17
Genetic and serological tests are tried for diagnosis of inflammatory bowel disease. But, ECCO-ESGAR Guideline (2018) does not recommend Genetic or serological testing for routine diagnosis of CD or UC.18
INTESTINAL TUBERCULOSIS
The diagnosis of intestinal tuberculosis is a challenge to the physician. Use of ultrasound, CT and MRI has been tried with varied success. Ultrasound guided aspiration followed by diagnostic laparoscopy is an option.19 Diagnostic laparotomy is the last resort.19 CE and Enteroscopy are not in diagnostic algorithm because of limited data from the use of these investigations.19 There is also a possibility of capsule causing complete obstruction in tuberculous small bowel stricture.19
MR images may be helpful by showing circumferential wall thickening of cecum and terminal ileum, mesenteric lymphadenopathy, wall ulcerations and peritoneal involvement.46
Role of gene Xpert is studied for diagnostic efficacy. In one study diagnostic sensitivity is found to be very poor (8.1%), but specificity was found very high (100%).20
Small Intestinal Cancer
Three to six percent of all gastrointestinal neoplasms are found in small bowel.5 The types of neoplasm are adenocarcinoma (30–45%), neuroendocrine tumor (20–40%), lymphoma (10–20%), and sarcoma (10–15%).5 Molecular tools are new development in diagnostics for some neoplasm of small bowel.
Monoanalyte biomarkers(CgA or other monolyte peptides/hormones) are found to be ineffective as diagnostic marker in gastroenteropancreatic neuroendocrine tumors.21 Elevated NETest, a multianalyte molecular signature is found to be effective in diagnosing PNETs (pancreatic neuroendocrine tumors) and SINETs (Small Intestine Neuroendocrine tumors). NETest was 92% concordant with anatomical imaging, 94% with Ga-SSA-PET/CT and 96% dual modality (CT/MRI and Ga-SSA-PET/CT).21 To observe accurate progression of the disease NETest can be used.21
CE was found to be superior to MRE for FAP and Peutz–Jeghers syndrome in a prospective study of 20 patients in identifying smaller polyps (<5 mm diameter).2 British Society of Gastroenterology recommended that CE should be done at interval of 1-3 years for surveillance of hereditary polyposis syndrome.2 Surveillance can also be done for small bowel cancer10 and other mucosal disorders. Differentiation between small bowel tumors and benign bulges has been improved after using a novel endoscopic algorithm.10 It is difficult to identify pathology and tumor type based on endoscopic appearance of lesions gained from CE. Missed rate of detection by CE for neoplastic disease can reach upto18,9%.4 Pennazio et al. described 51 patients showing polypoid lesions in CE without confirmation by further examinations (false positive capsule endoscopy).4 A positive CE requires further invasive examinations like endoscopic or surgical interventions.4
Capsule retention is seen in approximately 10–25% of cases of bowel neoplasms. So some favors MR enteroclysis for small bowel neoplasm.4
Newer cross-sectional radiologic techniques, such as CTE and MRE are favored for the detection of small bowel mass lesions (SBMLs) having predominant extraluminal component.4
Small Bowel Diverticula
MR and CT enteroclysis can detect small bowel diverticula. Because distension of the small bowel prevents collapse of diverticular segments of the intestine. It can also detect extraluminal abnormalities with inflammation.4
Intestinal Obstruction
Meckel diverticulum may present with gastrointestinal bleeding and obstruction. CT and ultrasound have a poor sensitivity for diagnosis of Meckel's diverticulum; MR can detect blind-ending cystic sac and blood products inside it.47
NSAIDs Enteropathy
Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause mucosal injury of small intestine. As a result ulcers and subsequently circumferential strictures can develop. The gold standard for detecting NSAID enteropathy is capsule endoscopy and balloon enteroscopy.5 Differential diagnoses at imaging are radiation strictures, CD strictures, potassium chloride tablets and eosinophilic gastroenteritis.5 These strictures are difficult to detect at CTE, MRE and barium examinations. These are weblike short segment strictures unlike longitudinal strictures of Crohn's disease.5
CONCLUSION
Diagnosing lesions of small bowel has traditionally been based on various traditional radiological investigations and at times on clinical judgment. In the recent past various novel diagnostic modalities have been proposed ranging from MRI to various methods of enteroscopy, capsule endoscopy, image enhancement and also various types of biomarkers. It is assumed that many of such novel diagnostic methods are likely to be the routine methods of investigation in suspected cases of inflammatory bowel disease, occult lesions causing melaena and various small bowel neoplasias in near future.
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- Abu-Zidan FM, Sheek-Hussein M. Diagnosis of abdominal tuberculosis: lessons learned over 30 years: pectoral assay. World Journal of Emergency Surgery. 2019; volume 14 Article number: 33.
- Kedia S, Das P, Madhusudan KS, Dattagupta S, Sharma R, Sahni P, et al. Differentiating Crohn's disease from intestinal tuberculosis. World J Gastroenterol. 2019; 25(4):418–32.
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