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.

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.

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.

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.

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.

Attenuated Accumulation of Novel Fluorine (19F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice.

Our work has focused on defining the utility of fluorine (19F)-labeled bile acid analogues and magnetic resonance imaging (MRI) to identify altered bile acid transport in vivo. In the current study, we explored the ability of this approach to differentiate fibroblast growth factor-15 (FGF15)-deficient from wild-type (WT) mice, a potential diagnostic test for bile acid diarrhea, a commonly misdiagnosed disorder. FGF15 is the murine homologue of human FGF19, an intestinal hormone whose deficiency is an underappreciated cause of bile acid diarrhea. In a pilot and three subsequent pharmacokinetic studies, we treated mice with two 19F-labeled bile acid analogues, CA-lys-TFA and CA-sar-TFMA. After oral dosing, we quantified 19F-labeled bile acid analogue levels in the gallbladder, liver, small and large intestine, and plasma using liquid chromatography mass spectrometry (LC-MS/MS). Both 19F bile acid analogues concentrated in the gallbladders of FGF15-deficient and WT mice, attaining peak concentrations at approximately 8.5 h after oral dosing. However, analogue levels in gallbladders of FGF15-deficient mice were several-fold less compared to those in WT mice. Live-animal 19F MRI provided agreement with our LC-MS/MS-based measures; we detected robust CA-lys-TFA 19F signals in gallbladders of WT mice but no signals in FGF15-deficient mice. Our finding that 19F MRI differentiates FGF15-deficient from WT mice provides additional proof-of-concept for the development of 19F bile acid analogues and 19F MRI as a clinical test to diagnose bile acid diarrhea due to FGF19 deficiency and other disorders.

Prenatal Bowel Findings in Male Siblings With a Confirmed FOXP3 Mutation.

There are multiple etiologies for fetal dilated bowel loops on ultrasonography (US), and we present a unique case of male siblings with a forkhead box P3 (FOXP3) mutation. Both children presented with fetal bowel anomalies on prenatal US. Family histories of cystic fibrosis and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome were reported. Amniocentesis in both pregnancies identified a normal male karyotype and the familial mutation associated with IPEX syndrome. IPEX syndrome is one of a group of conditions known as congenital diarrhea disorders. Other congenital diarrhea disorder cases have presented with similar prenatal US findings. As a result of these associations, we suggest considering IPEX syndrome as a potential cause of fetal bowel anomalies, particularly with a known family history. However, continued research into the phenotypic and genotypic correlations for IPEX syndrome is likely needed to better understand this possible prenatal presentation.

Distinct Abnormalities of Small Bowel and Regional Colonic Volumes in Subtypes of Irritable Bowel Syndrome Revealed by MRI.

OBJECTIVES: Non-invasive biomarkers which identify different mechanisms of disease in subgroups of irritable bowel syndrome (IBS) could be valuable. Our aim was to seek useful magnetic resonance imaging (MRI) parameters that could distinguish each IBS subtypes. METHODS: 34 healthy volunteers (HV), 30 IBS with diarrhea (IBS-D), 16 IBS with constipation (IBS-C), and 11 IBS with mixed bowel habit (IBS-M) underwent whole-gut transit and small and large bowel volumes assessment with MRI scans from t=0 to t=360 min. Since the bowel frequency for IBS-M were similar to IBS-D, IBS-M and IBS-D were grouped together and labeled as IBS non-constipation group (IBS-nonC). RESULTS: Median (interquartile range): fasting small bowel water content in IBS-nonC was 21 (10-42), significantly less than HV at 44 ml (15-70), P<0.01 as was the postprandial area under the curve (AUC) P<0.01. The fasting transverse colon volumes in IBS-C were significantly larger at 253 (200-329) compared with HV, IBS-nonC whose values were 165 (117-255) and 198 (106-270) ml, respectively, P=0.02. Whole-gut transit time for IBS-C was prolonged at 69 (51-111), compared with HV at 34 (4-63) and IBS-D at 34 (17-78) h, P=0.03. Bloating score (VAS 0-10 cm) correlated with transverse colon volume at t=405 min, Spearman r=0.21, P=0.04. CONCLUSIONS: The constricted small bowel in IBS-nonC and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease.

Clinicopathological and Ileocolonoscopic Characteristics in Patients with Nodular Lymphoid Hyperplasia in the Terminal Ileum.

Nodular lymphoid hyperplasia (NLH) in the small intestine is a rare benign lesion, characterized by the presence of multiple small nodules on the surface of the intestine. To define the clinicopathological and colonoscopic characteristics in Chinese patients with ileal NLH, we collected 65 patients with NLH in the terminal ileum from the endoscopic database in our hospital and clinical data from medical records. Histology and immunohistochemical staining were performed in the biopsies. The results demonstrated that the main symptoms included diarrhea (70.8%), abdominal pain (60.0%), hematochezia (46.2%), anemia (40.0%), and hypoproteinemia (21.5%). Enteroscopy revealed multiple, sporadic, granular or round-shaped nodules with diameters between 2 and 5 mm in the terminal ileum. The histology revealed the nodules consisted of mass lymphoid follicles in the lamina propria and submucosa of the terminal ileum. The follicles contained mitotically active germinal centers surrounded by well-defined lymphocyte mantles and composed predominantly of CD20+ B cells. The diseases found in patients with NLH included chronic diarrhea, Crohn's disease, ischemic enterocolitis and allergic purpura. The level of hemoglobin in NLH patients who had diarrhea and hematochezia remarkably decreased as compared with those in patients with chronic diarrhea. In conclusion, ileocolonoscopic screening is an important step to find the NLH in terminal ileum patients with diarrhea, abdominal pain, hematochezia, and hypoproteinemia. Histological examination is necessary for the exclusion of malignancy and chronic inflammation.

Salmonella colitis as an unusual cause of elevated serum lipase.

Authors and clinicians advocate lipase as the preferred serological test for the diagnosis for acute pancreatitis. While acute pancreatitis is among the differential diagnosis for elevated lipase levels, several other causes of elevated lipase levels have been identified including several reports Salmonella species as a causative agent. There also have been retrospective studies that have reported clinical pancreatitis associated with Salmonella infection. These studies concluded that clinical pancreatitis should be considered as a complication of Salmonella infections. However, Salmonella infections may induce elevated pancreatic enzyme levels without clinical pancreatitis or morphological pancreatic abnormalities through a variety of proposed mechanisms. The following is a case that describes a patient who developed Salmonella colitis and demonstrated elevated serum lipase levels without clinical pancreatitis.

Clinical and endoscopic features in patients with hospital-acquired diarrhea associated with Clostridium difficile infection. / Características clínicas y endoscópicas en diarrea hospitalaria asociada a infección por Clostridium difficile.

INTRODUCTION AND AIMS: Clostridium difficile infection is the main cause of hospital-acquired diarrhea, and the clinical and endoscopic findings in those patients have been studied very little in Mexico. The aim of the present study was to describe those findings. MATERIALS AND METHODS: A prospective cohort study was conducted that included patients with hospital-acquired diarrhea associated with Clostridium difficile diagnosed through polymerase chain reaction. The hypervirulent NAP027 strain was also determined. The clinical and endoscopic findings in the study patients, as well as the variables associated with severity, were analyzed. RESULTS: Of the 127 patients with hospital-acquired diarrhea, 97 were excluded from the study due to lack of colonoscopy. The remaining 39 study patients had a mean age of 48 years, and their most common signs/symptoms were abdominal pain (49%), mucus in stools (41%), and blood in stools (10%). The most common alterations in the laboratory results were leukocytosis in 49%, fecal leukocytes (61%), and hypoalbuminemia (67%). The main risk factor was antibiotic use in 62%, and ceftriaxone was the most widely used. The hypervirulent strain was present in 54% of the cases. Endoscopic abnormalities were found in 87% of the patients. Thirty-eight percent presented with pseudomembranous colitis, with lesions in the left colon in 53%, and in the right colon in 13%. No association was found between proton-pump inhibitor use and Clostridium difficile-associated diarrhea. There was a significant association between hypoalbuminemia (< 3.3g/dL) and a greater risk for severe colitis, with a RR of 8.2 (p=0.008). CONCLUSIONS: Pseudomembranous colitis lesions associated with the hypervirulent Clostridium difficile strain were predominant in the left colon. Hypoalbuminemia was a significant severity predictor.

Incidence of bowel wall oedema on computed tomography exams and association with diarrhoea in renal cell carcinoma patients treated with sunitinib.

OBJECTIVES: The purpose of this study was to retrospectively assess the incidence of bowel wall oedema on computed tomography (CT) in patients with renal cell carcinoma (RCC) treated with sunitinib, and to investigate its association with diarrhoea. METHODS: We conducted a retrospective analysis of all RCC patients treated with sunitinib at our hospital between December 2005 and December 2011. The presence or absence of bowel wall oedema on these CT examinations was scored. The presence of diarrhoea preceding, during, or after sunitinib treatment was identified from the patient files and retrospectively graded. RESULTS: For 54 of 87 patients, bowel wall oedema was present on at least one CT examination. Of these 54 patients, the right-sided colonic segment was affected in 87%. Diarrhoea was the most common reported adverse event during treatment, with 58 patients (67%) having grade 1/2 diarrhoea and 9 patients (10%) having grade 3. There was a statistically significant correlation between the incidence of CT-scored bowel oedema and diarrhoea during sunitinib treatment (P = 0.004). CONCLUSIONS: This study shows a very high incidence of bowel wall oedema and a strong correlation between the incidence of bowel wall oedema and diarrhoea in patients treated with sunitinib. KEY POINTS: • Sunitinib is routinely used in patients with advanced renal cell carcinoma. • Diarrhoea is the most common reported adverse event during sunitinib treatment. • Incidence of bowel oedema and diarrhoea during sunitinib treatment is correlated. • Radiologists should avoid misinterpretation of bowel oedema as infectious colitis.

Are bile acid malabsorption and bile acid diarrhoea important causes of loose stool complicating cancer therapy?

AIM: Gastrointestinal (GI) symptoms during and after cancer therapy can significantly affect quality of life and interfere with treatment. This study assessed whether bile acid malabsorption (BAM) or bile acid diarrhoea (BAD) are important causes of diarrhoea associated with cancer treatment. METHOD: A retrospective analysis was carried out of consecutive patients assessed for BAM using ((75) Se) Selenium homocholic acid taurocholate (SeHCAT) scanning, after reporting any episodes of loose stool, attending a gastroenterology clinic in a cancer centre. RESULTS: Between 2009 and 2013, 506 consecutive patients (54.5% male; age range: 20-91 years), were scanned. BAM/BAD was diagnosed in 215 (42.5%). It was mild in 25.6%, moderate in 29.3% and severe in 45.1%. Pelvic chemoradiation had induced BAM in > 50% of patients. BAM was also frequent after treatment for conditions not previously associated with BAM, such as anal and colorectal cancer, and was present in > 75% of patients referred after pancreatic surgery. It was also unexpectedly frequent in patients who were treated for malignancy outside the GI tract, such as breast cancer and haematological malignancy. CONCLUSION: BAM/BAD are very common and under-appreciated causes of GI symptoms after cancer treatment. Health professionals should have a low threshold in suspecting this condition, as diagnosis and treatment can significantly improve quality of life.