Victor Chedid

Herbal Therapy Is Equivalent to Rifaximin for the Treatment of Small Intestinal Bacterial Overgrowth

Objective: Patients with small intestine bacterial overgrowth (SIBO) have chronic intestinal and extraintestinal symptomatology which adversely affects their quality of life. Present treatment of SIBO is limited to oral antibiotics with variable success. A growing number of patients are interested in using complementary and alternative therapies for their gastrointestinal health. The objective was to determine the remission rate of SIBO using either the antibiotic rifaximin or herbals in a tertiary care referral gastroenterology practice. Design: One hundred and four patients who tested positive for newly diagnosed SIBO by lactulose breath testing (LBT) were offered either rifaximin 1200 mg daily vs herbal therapy for 4 weeks with repeat LBT post-treatment. Results: Three hundred ninety-six patients underwent LBT for suspected SIBO, of which 251 (63.4%) were positive 165 underwent treatment and 104 had a follow-up LBT. Of the 37 patients who received herbal therapy, 17 (46%) had a negative follow-up LBT compared to 23/67 (34%) of rifaximin users (P=.24). The odds ratio of having a negative LBT after taking herbal therapy as compared to rifaximin was 1.85 (CI=0.77-4.41, P=.17) once adjusted for age, gender, SIBO risk factors and IBS status. Fourteen of the 44 (31.8%) rifaximin non-responders were offered herbal rescue therapy, with 8 of the 14 (57.1%) having a negative LBT after completing the rescue herbal therapy, while 10 non-responders were offered triple antibiotics with 6 responding (60%, P=.89). Adverse effects were reported among the rifaximin treated arm including 1 case of anaphylaxis, 2 cases of hives, 2 cases of diarrhea and 1 case of Clostridium difficile. Only one case of diarrhea was reported in the herbal therapy arm, which did not reach statistical significance (P=.22). Conclusion: SIBO is widely prevalent in a tertiary referral gastroenterology practice. Herbal therapies are at least as effective as rifaximin for resolution of SIBO by LBT. Herbals also appear to be as effective as triple antibiotic therapy for SIBO rescue therapy for rifaximin non-responders. Further, prospective studies are needed to validate these findings and explore additional alternative therapies in patients with refractory SIBO.

Relamorelin for the treatment of gastrointestinal motility disorders

ABSTRACT Introduction: Current treatments for gastroparesis are limited. Chronic idiopathic constipation (CIC) has more treatment options, but none are efficacious for severe cases. Areas covered: Molecular targets to accelerate GI motility are being identified, and relamorelin, a synthetic ghrelin analog, has been promising. In humans, relamorelin increases growth hormone levels and accelerates gastric emptying. Relamorelin was superior to placebo for symptom relief in phase IIA studies for diabetic gastroparesis (DG) and CIC. In phase IIB studies in DG, relamorelin did not significantly reduce vomiting frequency when compared to placebo, but it reduced four symptoms of DG (nausea, fullness, bloating and abdominal pain) and accelerated gastric emptying. To date, relamorelin has been well tolerated and safe in humans without cardiac or neurologic adverse effects. It is still in clinical trial stages and not yet approved by the Food and Drug Administration. Phase III studies are underway. Expert opinion: Relamorelin shows promise in treating DG, with a reduction in core symptoms. Relative to available treatments, it appears to be efficacious and well tolerated. The absence of neurological or cardiovascular adverse effects places it at an advantage over other available therapies. Once approved, it will likely become the drug of first choice for DG.

Association between delayed gastric emptying and upper gastrointestinal symptoms: a systematic review and meta-analysis

Background The relationship between delayed gastric emptying and upper GI symptoms (UGI Sx) is controversial. Objective To assess association between gastric emptying and UGI Sx, independent of treatment. Design We performed a systematic review and meta-analysis of the literature from 2007 to 2017, review of references and additional papers identified by content expert. We included studies evaluating the association between gastric emptying and nausea, vomiting, early satiety/postprandial fullness, abdominal pain and bloating. Covariate analyses included optimal gastric emptying test method, gastric emptying type (breath test or scintigraphy) and patient category. Meta-regression compared the differences based on type of gastric emptying tests. Results Systematic review included 92 gastric emptying studies (26 breath test, 62 scintigraphy, 1 ultrasound and 3 wireless motility capsule); 25 of these studies provided quantitative data for meta-analysis (15 scintigraphy studies enrolling 4056 participants and 10 breath test studies enrolling 2231 participants). Meta-regression demonstrated a significant difference between optimal and suboptimal gastric emptying test methods when comparing delayed gastric emptying with nausea and vomiting. On evaluating studies using optimal gastric emptying test methodology, there were significant associations between gastric emptying and nausea (OR 1.6, 95% CI 1.4 to 1.8), vomiting (OR 2.0, 95% CI 1.6 to 2.7), abdominal pain (OR 1.5, 95% CI 1.0 to 2.2) and early satiety/fullness (OR 1.8, 95% CI 1.2 to 2.6) for patients with UGI Sx; gastric emptying and early satiety/fullness in patients with diabetes; gastric emptying and nausea in patients with gastroparesis. Conclusions The systematic review and meta-analysis supports an association between optimally measured delayed gastric emptying and UGI Sx.

Obstructing Colonic Mass: A Case of Recurrent Endometrial Cancer

A 71-year-old female with a history of endometrial cancer presented to our hospital with bilateral lower quadrant abdominal pain, which had been worsening over the past two months. The pain was associated with constipation, pencil-thin stools, and a 60 lb weight loss. On physical examination, the patient had suprapubic and left lower quadrant abdominal tenderness. Contrast-enhanced CT scan revealed a 6 cm pelvic mass in the left lower quadrant. It was unclear if this mass was arising from the sigmoid colon or abutting it. A colonoscopy to further investigate the mass was pursued and this revealed a moderate 5 cm long stenosis in the sigmoid colon starting at 15 cm from the anal verge. The stenosis was not ulcerated but had a bluish/purplish hue to it circumferentially. Multiple biopsies were obtained from that area and these revealed architectural changes with mild fibrosis but no malignancy. The mass was further explored with CT-guided fine needle aspiration. The results obtained were positive for cytokeratin-7, CA-125, estrogen receptor protein, and PAX-8 confirming that the mass was endometrial in origin.

Mo2092 Wireless Motility Capsule Alters Diagnosis and Affects Clinical Management in Patients With Suspected Gastrointestinal Dysmotility

BACKGROUND: The wireless motility capsule (WMC) is a novel device which is FDAapproved for the evaluation of suspected gastroparesis and slow-transit constipation. WMC provides information regarding pH, temperature and pressure throughout the GI tract and can be used to assess regional and whole-gut transit and pressure patterns. Several studies have validated WMC findings versus standard motility testing; however, there is limited data examining how WMC findings affect clinical care. AIMS: Aims were to investigate (1) the diagnostic yield of WMC in patients with suspected dysmotility and (2) change in clinicalmanagement afterWMC testing, includingmedication changes, referrals for additional diagnostic tests, and outside referrals. METHODS: We retrospectively reviewed 51 consecutive patients referred for WMC at a single, academic tertiary care center from April 2009 to October 2012. Information on demographics, past medical and surgical history, indications for WMC, WMC transit times, and relevant diagnostic studies were collected. Changes in clinical management at the first clinic visit after WMC testing were identified. Patients were excluded if WMC testing was incomplete or if no follow-up information was available. RESULTS: Patient characteristics including demographics and indications are summarized in Table 1. Results of positive WMC testing are summarized in Table 2A. Pan-GI dysmotility was present in 53% of patients with positive WMC testing. Effects of WMC results on diagnosis and management are summarized in Table 2B. Medication changes were more commonly seen in patients with an abnormal WMC test and included the addition or removal of prokinetics, antibiotics, herbal supplements, and neuromodulators. There were no statistically significant differences in additional imaging studies and referrals between the two groups. Referrals to non-GI providers included psychiatry, surgery, nutrition, acupuncture, and biofeedback. The presence of existing psychiatric comorbidities was also similar between groups. Of note, 80% of patients had other diagnostic studies obtained concurrently with WMC testing; however, attempts were made to isolate clinical changes made from WMC results specifically. CONCLUSIONS:WMC affects clinical management in the majority of patients referred for suspected dysmotility. Alteration in diagnosis was frequent, and change in medication was made for the majority of patients with abnormal WMC testing. Pan-GI dysmotility was common in patients referred for suspected regional dysmotility. Normal WMC testing changed clinical management in over 50% of cases. Our results suggest that WMC testing impacts patient care by altering diagnosis and clinical management. Prospective studies are needed to determine how WMC may affect long-term outcomes. Table 1. Patient Characteristics (N=51)

Characterization of Upper Gastrointestinal Symptoms, Gastric Motor Functions, and Associations in Patients with Diabetes at a Referral Center

OBJECTIVES: Our aim was to characterize upper gastrointestinal (UGI) symptoms and associations in individuals with diabetes mellitus (DM) who had undergone evaluation of gastric emptying (GE) and accommodation (GA) at a referral center. METHODS: From the Mayo Clinic Rochester electronic medical records of adults with diabetes types 1 and 2 (DM1 and DM2) evaluated between January 1997 and December 2015, we extracted demographics, UGI symptoms, current medications, treatments for diabetes, GE solids by scintigraphy, GA by single photon emission computed tomography (SPECT), and diabetes complications. We compared subgroups with delayed (GE at 2 h <25% or GE at 4 h <75%), rapid (GE at 1 h > 35%), and normal GE, as well as reduced (<428 mL) and normal GA. RESULTS: We reviewed 108 patients (60.2% females, median age 49.0 years). Overall, 71.3% had DM2; one-third of these were insulin dependent and had fairly well-controlled diabetes (median HbA1c 6.7% (IQR 6.2; 7.9)). Manifestations of diabetic triopathy (peripheral neuropathy, nephropathy, and retinopathy) were uncommon at presentation with UGI symptoms. Nausea was the most common symptom (80.6%). There were single or combined GE (total 56%: rapid in 37%, slow in 19%) and GA (total 39%) abnormalities; there was normal GA and GE in 28%; 40.3% of the DM2 patients had accelerated GE at 1 h. GE at 1 h is associated with nausea/vomiting, and fasting gastric volume is associated with bloating. CONCLUSIONS: Among referred diabetic patients with UGI symptoms, GE and GA testing identifies potential targets for individualizing treatment and avoidance of empirical trials for the 28% with no disturbance of GE and GA.

47-Year-Old Man With Abdominal Pain and Diarrhea

Resident in Internal Medicine (D.C.C.) and Resident in Gastroenterology (V.C.), Mayo Clinic School of Graduate Medical Education, Rochester, MN; Advisor to residents and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (A.B.). A 47-year-old man presented with diffuse abdominal pain and multiple watery, nonbloody, nonmelenic bowel movements of 2 days’ duration. The patient stated that he had roughly 10 bowel movements daily but reported no fevers or chills. Over the preceding 3 months, the patient had experienced 2 episodes of Clostridium difficile infection (CDI), the most recent having occurred 7 weeks earlier. Each occurrence was treated with a 2-week course of oral vancomycin, with improvement seen after 3 days of treatment. He recovered fully between episodes and had no symptoms for 7 weeks preceding the current episode. He reported no recent antibiotic exposure, but he had been hospitalized briefly during his earlier episode of CDI. The patient’s medical history included remote cardiac and renal transplant. His medications included tacrolimus, prednisone, clonidine, escitalopram, bupropion, oxycodone, trazodone, and simvastatin. The patient had normal mentation but appeared fatigued. Vital sign testing revealed a blood pressure of 105/71 mm Hg, a heart rate of 82 beats/min, a temperature of 36.6 C, and a respiratory rate of 20 breaths/ min. Physical examination revealed dry mucus membranes, and skin examination revealed increased skin turgor in the supraclavicular region. His abdominal examination was notable for hyperactive bowel sounds with diffuse tenderness to palpation without rebound or guarding. Digital rectal examination revealed a scant amount of nonbloody stool. Laboratory studies yielded the following results (reference ranges provided parenthetically): white blood cell count (WBC), 7.1 10/L (3.5-10.5 10/L); hemoglobin, 13.517.5 10 g/dL (12.0-15.5 g/dL); platelet count, 138 10/L (150-450 10/L); creatinine, 2.6 mg/dL (0.8-1.3 mg/dL) (at his baseline); albumin, 3.1 g/dL (3.5-5.0 g/dL); and

Elobixibat for the treatment of constipation

ABSTRACT Introduction: Chronic idiopathic constipation (CC) is highly prevalent worldwide. A subset of patients with CC have reduced fecal (and by inference, intra-colonic) bile acids (BA). Elobixibat, a locally-acting ileal bile acid transporter (IBAT) inhibitor, leads to increased BA delivery to the colon and represents a new class of treatment for CC. BAs accelerate colonic transit and increase colonic secretion. Therefore, IBAT inhibitors have potential to treat patients with CC. Areas covered: Rationale for IBAT inhibitor in therapeutics, and preclinical and clinical pharmacology of elobixibat: In vitro, elobixibat is a highly potent, selective IBAT inhibitor. In humans, elobixibat accelerated colonic transit. In phase 2A, 2B and 3 studies in CC, elobixibat was efficacious, well tolerated and safe. An open-label, phase 3 trial (52 weeks) confirmed the safety of elobixibat. Elobixibat reduces LDL cholesterol, increases serum GLP-1, and has potential in metabolic syndrome. Expert commentary: Uniquely among current treatments of CC, elobixibat stimulates both motor and secretory functions in the colon. These dual effects suggest that, when approved, elobixibat may be a first-line choice for constipation associated with colonic BA deficiency and a second-line treatment for all patients with CC and constipation-predominant irritable bowel syndrome. Further studies are required to confirm efficacy for relief of CC. Once approved, elobixibat will likely become a second-line choice for treatment of CC.

A rational approach to the patient with hematochezia

Purpose of review Hematochezia is a common clinical presentation, with significant morbidity and economic burden. These patients often require costly interventions including hospitalization, blood transfusions, and radiologic or endoscopic procedures. The purpose of this review is to give a rational, concise approach to the patient with hematochezia, with special consideration of recent advances in the literature. Recent findings Recent studies pertaining to hematochezia have evaluated risk stratification, endoscopic intervention, evaluation of small bowel bleeding, and management of anticoagulation. Summary A step-wise approach to hematochezia helps determine the cause and provide the appropriate management of these patients. We propose five steps beginning with hemodynamic assessment and risk stratification, then focused history and physical examination, endoscopic intervention when warranted, and consideration of small bowel bleeding in selected instances.

Analysis of Fecal Primary Bile Acids Detects Increased Stool Weight and Colonic Transit in Patients With Chronic Functional Diarrhea

BACKGROUND & AIMS: Patients with bile acid diarrhea (BAD) are identified based on increased levels of BAs in fecal samples collected over a 48‐hr period while on a 100‐gram fat diet (48‐hr BA), retention of 75Se‐labeled homocholic acid taurine, or serum levels of C4 or FGF19. BAD increases fecal weight and colonic transit. We investigated whether results of tests for BAD associate with increased fecal weight and more rapid colonic transit over a 24‐ or 48‐hr period in patients with irritable bowel syndrome with diarrhea (IBS‐D). We also estimated the prevalence of increased 48‐hr fecal BAs in patients with chronic diarrhea. METHODS: We performed a retrospective study of 64 patients with IBS‐D, 30 patients with IBS‐constipation, 30 healthy volunteers (controls). We collected data on fecal weights (measured over a 48‐hr period), colonic transit over a 24‐hr period (measured by scintigraphy), and percentages of different BAs in stool samples. Colonic transit was measured as the geometric center (weighted average) of colonic counts on a scale of 1 (100% in ascending colon) to 5 (100% in stool). We performed area under the curve (AUC) analyses to assess the association between result of serum and stool tests and high fecal weight (>400g/48 hrs) or rapid colonic transit (>3.34, corresponding to isotope geometric center in sigmoid colon). We estimated the prevalence of increased 48‐hr fecal BAs among 938 patients with chronic diarrhea. RESULTS: Total fecal 48‐hr BA alone, or in combination with percentage of primary fecal BAs, identified patients with increased fecal weight with an AUROC of 0.86. Percentage of primary fecal BA alone identified patients with increased fecal weight with an AUROC of 0.73. Total fecal 48‐hr BA alone identified patients with increased colonic transit with an AUROC of 0.65 and percentage of primary fecal BA alone identified patients with increased colonic transit with an AUROC of 0.69; combined data on these features identified patients with increased colonic transit with an AUROC of 0.70. Serum level of C4 identified patients with increased colonic transit with an AUROC of 0.60. Primary BAs >10% identified patients with increased fecal weight (sensitivity 49% and specificity 91%) and rapid colonic transit (sensitivity 48% and specificity 87%). Among the patients with chronic diarrhea, 45.6% had fecal primary BAs >10% and 27% had increased total fecal BAs (>2337 &mgr;mol/48 hrs). CONCLUSIONS: In a retrospective analysis of patients with IBS‐D, we found percentage of primary BAs in fecal samples to provide an alternative to total fecal BAs in identification of patients with BAD or chronic diarrhea.