Use of shear wave imaging with intestinal ultrasonography in patients with chronic diarrhea.

OBJECTIVE: A retrospective study was designed to determine the role of shear wave elastography (SWE) and intestinal ultrasonography to differentiate between inflammatory and fibrotic bowel strictures by determining Young's modulus (E) and shear wave dispersion (SWD) and to compare its role with contrast-enhanced computed tomography (CECT) in patients with chronic diarrhea and pain abdomen. METHODS: Seventy-six patients who had increased small bowel thickness (SBWT) >3 mm, and large bowel wall thickness (LBWT) >4 mm on intestinal ultrasonography (IUS) were evaluated in a two-step manner. The first step involved classifying patients with increased SBWT >3 mm and LBWT >4 mm by use of SWE and dispersion into three groups that is group I (fibrotic), group II (inflammatory) thickening, and group III (mixed-fibrosis and inflammatory) wall thickening. In the second step, etiological classification was done using six gray scale features of IUS that is length and degree of bowel thickening, presence of bowel stratification, Limberg grade of vascularity, status of mesenteric fat, juxta bowel status-nodes, fluid, and fistula formation to reach to a definitive diagnosis. These findings were compared with findings on CECT. Twenty-three patients had diagnosis confirmed by biopsy while 18 underwent surgery with histologic confirmation of operative findings. The sensitivity, specificity and AUROC for both modalities were compared. RESULTS: Group I that is fibrotic group had 33 patients with fibrotic strictures of which fibrotic Crohn's disease (CD)and tuberculosis of the bowel were the dominant types followed by neoplastic and infective causes. In Group II that is inflammatory there were 32 patients with predominantly infective ileo-colitis, and ulcerative colitis patients while 11 patients were present in group III that is (mixed fibrotic and inflammatory) type of bowel wall thickening and were patients of inflammatory CD, infective ileo-colitis. The presence of length of bowel involvement, Limberg grade, mesenteric fat proliferation, and SBWT>9 mm were the statistically significant parameters on IUS which helped to reach to final diagnosis. The sensitivity and specificity of combined SWE with SWD and IUS were 100% and 99% while that of CECT was 78% and 96% respectively with AUROC of 100% and 64%. CONCLUSION: SWI combined with IUS in a two-step manner is an accurate way to evaluate patients with chronic diarrhea who have increased SBWT and is not only able to differentiate inflammatory from fibrotic bowel wall thickening but also helps to form an etiological diagnosis.

75SeHCAT whole body retention for unexplained chronic diarrhoea based on early first whole body counting.

BACKGROUND: There are many protocol variations in the whole-body 75SeHCAT retention test [whole-body retention (WBR)] for investigation of bile acid diarrhoea. The time between capsule consumption and first count, however, is widely taken, without debate, to be 3 h. In the Covid-19 era, it is desirable to limit the time patients spend in the department. We, therefore, questioned the need for a 3 h interval between capsule administration and the initial count. METHODS: Using an uncollimated gamma camera, whole-body counting was performed at 5, 30 and 180 min after capsule ingestion in 24 patients with chronic diarrhoea. Geometric mean was taken of counts acquired from posterior and anterior projections. WBR was expressed as the ratio of 7 day-to-initial whole-body counts (%) to give WBR5, WBR30 and WBR180. A small meal was given at 60 min after capsule ingestion. RESULTS: There was a close correlation between WBR30 and WBR180 (y = 1.0x - 0.29%; r = 0.99). For WBR180 values of <15% (lower limit of normal), there was close agreement between WBR30 and WBR180 (bias 0.03%; precision 0.7%). WBR5 overestimated WBR180. However, cWBR5, obtained by multiplication of WBR5 by 0.75, also correlated closely with WBR180 (y = 1.2x - 4.5%; r = 0.97), and there was close agreement between cWBR5 and WBR180 for WBR180 values <15% (bias 0.08%, precision 1.3%). CONCLUSION: The first whole-body count in the 75SeHCAT test can be undertaken at 30 min postcapsule without loss of accuracy, or even 5 min if only subnormal values are considered relevant. No food is required after capsule consumption.

Expansion of the ophthalmic phenotype of SPINT2-related syndromic congenital sodium diarrhea.

A 5-year-old girl presented with treatment-refractory dry eye and recurrent episodes of eye pain. She had been previously diagnosed with syndromic congenital sodium diarrhea (SCSD) caused by a pathogenic variant in SPINT2. Her local pediatric ophthalmologist had made the diagnosis of severe dry eye with corneal erosions, based on which, we arranged an eye exam under anesthesia (EUA) and punctal plug placement. Anterior segment optical coherence tomography (OCT) and corneal photographs were taken during the procedure. There are reports describing similar ophthalmic findings in this syndrome. However, to the best of our knowledge, this is the first case report to document OCT imaging and corneal photographs in a patient with SCSD, which we feel expands the ophthalmic phenotype of this rare genetic disorder.

Colonoscopic evaluation of diarrhea/colitis occurring as an immune-related adverse event.

OBJECTIVE: Diarrhea is often observed as an immune-related adverse event. In this study, we conducted a retrospective review of the severity of diarrhea, its treatment and the endoscopic findings in patients developing diarrhea as an immune-related adverse event. METHODS: From August 2015 to June 2019, a total of 369 patients received treatment with immune checkpoint inhibitors at our hospital. For this study, development of grade 2 or more diarrhea in these patients was defined as an immune-related adverse event. We analyzed the histopathological severity of the bowel lesions according to the Nancy histological index for ulcerative colitis. RESULTS: Of the 369 patients, 27 (7.3%) developed diarrhea as an immune-related adverse event. Of these 27 patients, 18 received steroid treatment. Colonoscopy was performed in 17 patients and culture of the feces in 18. The tests revealed evidence of bacterial colitis (Aeromonas hydrophila) in two patients. The Nancy histological index was 4, 3, 2, 1 and 0 in two, three, two, two and seven patients, respectively. No findings on colonoscopy were observed in 7 of the 17 patients (41%) who underwent colonoscopy, and most of these patients recovered without steroid treatment. Patients with lower values of the Nancy histological index tended to show better responses to steroid treatment. CONCLUSIONS: To avoid unnecessary steroid administration, colonoscopic evaluation is essential in patients receiving treatment with immune checkpoint inhibitors who present with diarrhea as an immune-related adverse event. In addition, the endoscopic findings could be useful to predict the response to steroid treatment.

A rare case of diarrhea and ascites.

BACKGROUND: Eosinophilic enterocolitis is a rare condition included in the spectrum of the eosinophilic gastrointestinal disorders. Diagnosis is based on clinical presentation combined with an increase infiltration of eosinophils in the gastrointestinal tract, in the absence of other secondary causes of eosinophilic infiltration. CASE PRESENTATION: We report a case of a 22-year-old male with eosinophilic enterocolitis presenting with malabsorption syndrome (diarrhea, vomiting, weight loss), bowel wall thickening, and ascites. Secondary causes of intestinal eosinophilia were excluded, and diagnosis was established in a timely manner. Treatment plan included a 6-food elimination diet and corticosteroid therapy, with clinical remission after 2 weeks of therapy. The patient remains asymptomatic after 12 months of follow-up, with no relapse.

Larger regional volume of the thalamus in diarrhea-predominant irritable bowel syndrome: a cross-sectional study.

As a relay center between the cerebral cortex and various subcortical brain areas, the thalamus is repeatedly associated with the dysfunction of brain-gut interaction in patients with irritable bowel syndrome (IBS). However, the regional morphological alterations of the thalamus in IBS are not well defined. We acquired structural magnetic resonance data from 34 patients with IBS and 34 demographically similar healthy subjects. Data processing was performed using FMRIB's Integrated Registration and Segmentation Tool (FIRST). Volumetric analysis and surface-based vertex analysis were both carried out to characterize the morphology of the thalamus and other subcortical structures. Our results suggested that the majority (31 cases) of the patients with IBS had diarrhea-predominant symptoms. Volumetric analysis revealed a larger normalized volume of the right thalamus and left caudate nucleus in patients with IBS than in healthy controls. Surface analysis indicated that the difference arose mainly from the laterodorsal nucleus of the right thalamus, and the body of the left caudate nucleus. In addition, patients with IBS had different hemispheric asymmetries of the thalamus (rightward) and caudate nucleus (leftward) from controls (leftward for the thalamus and rightward for the caudate nucleus). In general, our results indicated that patients with diarrhea-predominant IBS had enlarged thalamus and caudate nucleus volumes, as well as altered hemispheric asymmetries of these two structures, compared with healthy controls. The neuroimaging evidence of these structural alterations helps clarify the underlying pathophysiology of diarrhea-predominant IBS.

Gammagrafía con 75Se-ácido tauroselcólico (75SeHCAT(R)), ¿prueba de referencia en la malabsorción de ácidos biliares? / 75Se-Homocholic acid taurine scintigraphy (75SeHCAT(R)), a standard benchmark test in bile acid malabsorption?

La diarrea crónica por malabsorción de ácidos biliares (MAB) es una patología infradiagnosticada. Se dispone de diferentes herramientas diagnósticas, aunque en la actualidad no existe consenso sobre cuál de estas sería la prueba de referencia o gold standard. En esta revisión se valora la posibilidad de utilizar la gammagrafía con 75Se-ácido tauroselcólico (75SeHCAT(R)) como prueba diagnóstica de referencia y su perspectiva de futuro. Se realizó una búsqueda bibliográfica en Pubmed y OVID, obteniéndose un total de 57 trabajos y usándose finalmente 26 de ellos tras ser seleccionados bajo los conceptos de gold standard, exactitud diagnóstica y otros biomarcadores. Valoramos las ventajas e inconvenientes de las diferentes herramientas diagnósticas: 14C-glicocolato, medición de ácidos biliares en heces, C4 en suero, FGF19 en suero, colestiramina y gammagrafía con ácido tauroselcólico. Consideramos que la gammagrafía con 75SeHCAT(R) es la prueba diagnóstica más recomendada en Europa para el diagnóstico de MAB al presentar los índices más elevados de sensibilidad y especificidad. Presenta una gran relación coste-beneficio, por lo que es la prueba con mayor grado de recomendación. Sin embargo, aún no es posible su uso de forma reconocida como gold standard debido a la falta de estudios que proporcionen datos concluyentes que permitan su consenso. Mientras tanto, se podría aconsejar el uso combinado de la prueba con colestiramina en todos los pacientes que queramos evaluar, independientemente del resultado gammagráfico, como uso de patrón de referencia

Chronic diarrhoea due to bile acid malabsorption (BAM) is an underdiagnosed pathology. Different diagnostic tools are available. However, there is currently no consensus on which of these would be the benchmark test or gold standard. This review evaluates the possibility of using 75Se-taurocholic acid (75SeHCAT(R)) scintigraphy as a benchmark diagnostic test and its perspective for the future. A literature review was conducted in Pubmed and OVID obtaining a total of 57 papers, 26 of which were finally used after being selected under the concepts of gold standard, diagnostic accuracy and other biomarkers. We evaluated the advantages and disadvantages of the different diagnostic tools: 14C-glycocholate, measurement of bile acids in faeces, C4 in serum, FGF19 in serum, cholestyramine, and 75Se-tauroselcolic acid scintigraphy. We consider that the 75SeHCAT(R) scan is the most recommended diagnostic test in Europe for diagnosing BAM as it presents the highest values of sensitivity and specificity. It has a significant cost-benefit ratio, making it the test with the highest degree of recommendation. However, it is still not possible to use it in a recognised way as a gold standard due to the lack of studies that provide conclusive data that allow consensus. In the meantime, the combined use of cholestyramine testing in all patients we want to evaluate, regardless of the scintigraphy result, could be encouraged as a benchmark standard

Use of X-ray to Assess Fecal Loading in Patients with Gastrointestinal Symptoms.

BACKGROUND/AIMS: There is currently no gold standard for evaluating stool burden in the colon for patients with gastrointestinal symptoms. We aim to examine the relationship between fecal loading on single view abdominal X-ray imaging and gastrointestinal symptoms such as constipation, diarrhea, bloating, and accidental bowel leakage in adult outpatients. METHODS: This retrospective, cross-sectional study examined patients seen at University of Michigan from 2005 to 2017. Chart review of demographic information, reported gastrointestinal symptoms, past medical history, and abdominal radiographic imaging was performed. Bivariate analysis was performed to assess associations between these characteristics and fecal loading. Factors independently associated with fecal loading were identified using logistic regression. Significance was established at p < 0.05. RESULTS: In total, 319 patients who had an X-ray were included in the final analysis, with 84.0% demonstrating fecal loading on the initial X-ray and most reporting constipation as a symptom (n = 214, 84.3%, p = 0.0334). In logistic regression, a chief complaint of constipation had higher odds of being associated with fecal loading on X-ray compared to diarrhea (adjusted OR 6.41; CI 1.51-27.24, p = 0.0118). Bloating as a reported symptom was statistically significant with an adjusted OR of 2.56 (CI 1.10-5.96, p = 0.0286). CONCLUSIONS: Constipation (as a chief complaint) and bloating (as a symptom) were associated with fecal loading on X-ray imaging, while accidental bowel leakage and diarrhea were not.

Prevalence of, and predictors of, bile acid diarrhea in outpatients with chronic diarrhea: A follow-up study.

BACKGROUND: 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning to rule out bile acid diarrhea (BAD) in patients with chronic diarrhea has a high yield. Our previous study showed that patients with terminal ileal (TI) Crohn's disease, TI resection, or cholecystectomy were highly likely to have an abnormal scan. As a result, we encouraged clinicians to use a therapeutic trial of a bile acid sequestrant in these patients, instead of scanning. This may have reduced diagnostic yield of the test, so we examined this issue, as well as factors predicting an abnormal scan, in a large cohort of patients referred subsequently. METHODS: We retrospectively identified 1,071 consecutive patients with chronic diarrhea undergoing SeHCAT scanning at Leeds Teaching Hospitals Trust from 2012 to 2016. We reviewed electronic patient records to obtain information on presenting gastrointestinal symptoms and any proposed risk factors for BAD. BAD was categorized according to subtype and severity. KEY RESULTS: As expected, indications for scanning changed between 2012 and 2016, with a significant reduction in referrals with TI Crohn's disease or resection year-on-year (P < 0.001). Despite this, 457 (42.7%) patients had BAD and there was no downward trend in yield of SeHCAT during the 5 year period (P = 0.39). Overall, 51.6% had type II BAD, 36.1% type III, and 12.3% type I. BAD was mild in 31.7%, moderate in 34.4%, and severe in 33.9%. In total, 653 (61.0%) patients had no known risk factors, other than chronic diarrhea, but 233 (35.7%) of these individuals had BAD, and in 143 (61.4%), this was moderate or severe. CONCLUSIONS AND INFERENCES: Despite reduced referrals for SeHCAT scanning in those with clear risk factors for BAD, the yield remained > 40%. One-third of those without known risk factors had BAD.

75Se-Homocholic acid taurine scintigraphy (75SeHCAT®), a standard benchmark test in bile acid malabsorption? / Gammagrafía con 75Se-ácido tauroselcólico (75SeHCAT®), ¿prueba de referencia en la malabsorción de ácidos biliares?

Chronic diarrhoea due to bile acid malabsorption (BAM) is an underdiagnosed pathology. Different diagnostic tools are available. However, there is currently no consensus on which of these would be the benchmark test or gold standard. This review evaluates the possibility of using 75Se-taurocholic acid (75SeHCAT®) scintigraphy as a benchmark diagnostic test and its perspective for the future. A literature review was conducted in Pubmed and OVID obtaining a total of 57 papers, 26 of which were finally used after being selected under the concepts of gold standard, diagnostic accuracy and other biomarkers. We evaluated the advantages and disadvantages of the different diagnostic tools: 14C-glycocholate, measurement of bile acids in faeces, C4 in serum, FGF19 in serum, cholestyramine, and 75Se-tauroselcolic acid scintigraphy. We consider that the 75SeHCAT® scan is the most recommended diagnostic test in Europe for diagnosing BAM as it presents the highest values of sensitivity and specificity. It has a significant cost-benefit ratio, making it the test with the highest degree of recommendation. However, it is still not possible to use it in a recognised way as a gold standard due to the lack of studies that provide conclusive data that allow consensus. In the meantime, the combined use of cholestyramine testing in all patients we want to evaluate, regardless of the scintigraphy result, could be encouraged as a benchmark standard.

Bile acid malabsorption in patients with chronic diarrhea and Crohn's disease.

INTRODUCTION AND AIM: Crohn's disease (CD) is a form of inflammatory bowel disease and is mainly characterized by diarrhea and abdominal pain. The aim of our study was to analyze the usefulness of performing a 75SeHCAT scan in CD patients with chronic diarrhea and suspected bile acid malabsorption (BAM). In addition, we aimed to determine whether there was a relationship with the clinical features of the disease and a previous bowel resection. PATIENTS AND METHODS: this was an observational cross-sectional study of 39 patients with a diagnosis of CD and chronic diarrhea. All cases underwent a 75SeHCAT scan for BAM diagnosis, after discarding disease activity. RESULTS: the study cohort included 19 females and 20 males. The median age was 44 years and the majority of patients were A2 L1 B1 according to the Montreal classification; 84.6% of patients had undergone a previous bowel resection. BAM was present in 97.4% of patients (100% and 83.3% of patients with and without previous surgery, respectively), which was severe in 92.1% of cases. Treatment with bile acid sequestrants was initiated and a favorable response was obtained in 72.2% of patients. The relationship between BAM degree (moderate or severe), bowel surgery and the response to bile acid sequestrant treatment was also analyzed but not statistically significant. CONCLUSION: BAM is a frequent cause of diarrhea in CD patients in endoscopic or radiological remission. This condition was present in all patients with a history of a bowel resection. A response to bile acid sequestrants treatment was observed in 73% of patients.

A 19F magnetic resonance imaging-based diagnostic test for bile acid diarrhea.

In up to 50% of people diagnosed with a common ailment, diarrhea-predominant irritable bowel syndrome, diarrhea results from excess spillage of bile acids into the colon-data emerging over the past decade identified deficient release of a gut hormone, fibroblast growth factor 19 (FGF19), and a consequent lack of feedback suppression of bile acid synthesis as the most common cause. 75Selenium homotaurocholic acid (SeHCAT) testing, considered the most sensitive and specific means of identifying individuals with bile acid diarrhea, is unavailable in many countries, including the United States. Other than SeHCAT, tests to diagnose bile acid diarrhea are cumbersome, non-specific, or insufficiently validated; clinicians commonly rely on a therapeutic trial of bile acid binders. Here, we review bile acid synthesis and transport, the pathogenesis of bile acid diarrhea, the reasons clinicians frequently overlook this disorder, including the limitations of currently available tests, and our efforts to develop a novel 19F magnetic resonance imaging (MRI)-based diagnostic approach. We created 19F-labeled bile acid analogues whose in vitro and in vivo transport mimics that of naturally occurring bile acids. Using dual 1H/19F MRI of the gallbladders of live mice fed 19F-labeled bile acid analogues, we were able to differentiate wild-type mice from strains deficient in intestinal expression of a key bile acid transporter, the apical sodium-dependent bile acid transporter (ASBT), or FGF15, the mouse homologue of FGF19. In addition to reviewing our development of 19F-labeled bile acid analogue-MRI to diagnose bile acid diarrhea, we discuss challenges to its clinical implementation. A major limitation is the paucity of clinical MRI facilities equipped with the appropriate coil and software needed to detect 19F signals.