Related blog posts:
In a patient who presented with trouble swallowing, his endoscopy showed candida esophagitis. “Oral antifungal therapy was initiated in the patient, and within 2 weeks after starting therapy, his pain on swallowing was reduced. A repeat endoscopy performed 12 weeks after the initiation of antifungal therapy showed a marked reduction in the number and severity of esophageal lesion.”
Here’s the link: FDA approves Trulance for Chronic Idiopathic Constipation (Jan 19.2017). Plecanatide is a guanylate cyclase-C agonist.
An excerpt:
Trulance, taken orally once daily, works locally in the upper GI tract to stimulate secretion of intestinal fluid and support regular bowel function.
The safety and efficacy of Trulance were established in two 12-week, placebo-controlled trials including 1,775 adult participants. Participants were randomly assigned to receive a placebo or Trulance, once daily. Participants in the trials were required to have been diagnosed with constipation at least six months prior to the study onset and to have less than three defecations per week in the previous three months, as well as other symptoms associated with constipation. Participants receiving Trulance were more likely to experience improvement in the frequency of complete spontaneous bowel movements than those receiving placebo, and also had improvements in stool frequency and consistency and straining.
Trulance should not be used in children less than six years of age due to the risk of serious dehydration… The safety and effectiveness of Trulance have not been established in patients less than 18 years of age.
The most common and serious side effects of Trulance was diarrhea.
Related posts:
In this new era of high resolution manometry, there is an increasing incidence of achalasia.
Briefly noted:
JA Duffield et al. Clin Gastroenterol Hepatol 2017; 15: 360-5. In this study from South Australia, using a large database (2004-2013), the annual incidence of achalasia was between 2.3 and 2.8 per 100,000 persons. Mean age at diagnosis was 62 years.
S Samo et al. Clin Gastroenterol Hepatol 2017; 15: 366-73. In a similar study from Chicago, the authors estimated that the yearly city-wide incidence averaged 1.07 per 100,000; however the average in the neighborhood closest to the hospital (and possibly with better case capture) was 2.92 per 100,000.
My take: These studies identified incidence rates that are about double the rates that were reported prior to the availability of high resolution manometry.
Related blog posts:
A recent study (SJ Ott et al. Gastroenterol 2017; 152: 799-811) followed 5 patients who were treated with a sterile fecal filtrate (via nasojejunal tube) for recurrent Clostridium difficile infection (CDI) for a minimum of 6 months. This open-label study noted that this fecal filtrate transfer eliminated the symptoms of CDI in all 5 patients.
A summary of this important study is available in the AGA blog:
Here’s an excerpt: What is the Active Ingredient in FMT for CDI?
Stool was collected from 5 donors selected by the patients and fully characterized according to FMT standards. The stool was then sterile filtered to remove small particles and bacteria, and the filtrate was transferred to patients in a single administration via nasojejunal tube.
Fecal samples were collected from patients before and at 1 week and 6 weeks after FFT. Microbiome, virome, and proteome profiles of donors and patients were compared….
They identified about 300 different proteins in each of the filtrates they analyzed—most proteins were of human origin, but the filtrates also contained 20–60 bacterial and fungal proteins. The major human proteins in the filtrate proteome were human enzymes such as intestinal-type alkaline phosphatase, chymotrypsin-like elastases, and α amylases. Bacterial proteins included metabolic enzymes and redox proteins without obvious microbiome-modifying properties, such as glyceraldehyde-3-phosphate dehydrogenase, phosphoenolpyruvate carboxykinase, glutaredoxin-1, or thioredoxin-1…
Ott et al propose that the active component of FMT therapy might not be living bacteria, but bacterial components, antimicrobial compounds of bacterial origin (bacteriocins), or bacteriophages that contribute to a healthy intestinal microenvironment. These could be common to all successful FMT therapies and even rather unspecific regarding the bacterial strain(s) used for therapies. They propose that bacteriophages affect community dynamics of gut microbiota to resolve dysbiosis.
My take: This is a provocative study that challenges us to rethink how FMT works. Ultimately, treating CDI needs to be more precise.
Related blog posts:
A recent study (JA Murray et al. Gastroenterol 2017; 152: 787-98) examined the effectiveness of latiglutenase for celiac disease. Latiglutenase (aka ALV003) is an oral medicine which is a mixture of two recombinant gluten-targeting proteases.
The concept of latigluenase is that a medicine that degrades the gluten protein could obviate the need for a gluten free diet. Unfortunately, in this study with 494 patients with celiac disease for at least 1 year, the medicine at various doses for 12 to 24 weeks was ineffective. There was no difference between the medicine and placebo with regard to villous height:crypt depth ratio, number of intraepithelial lymphocytes or serologic markers of celiac disease. Symptom scores increased in both the active treatment group and the placebo group. While this was a negative study, the authors did note some effect on symptom domains on higher dosing regimens. “This observation suggests that treatment with latiglutenase may affect symptoms before showing clinically meaningful effects on serologic and histologic end points.
A second study (RS Choung et al. Gastroenterol 2017; 152: 830-9) examined prevalence and morbidity of undiagnosed celiac disease in Olmstead County. After excluding patients with celiac disease, sera from 30,425 adults and 830 children were tested for tissue transglutaminase IgA antibody (tTG) and endomysial antibody (EMA). Case definition: patients were considered to have celiac serologically if tTG titer was 2.0 U/mL or greater with a positive EMA. The prevalence of celiac disease was 1.1% in adults and 1.0% in children. The majority of patients with celiac disease (>80%) have not received the diagnosis. By comparing those with positive celiac serology to matched controls (2 controls for each positive), the authors determined that undiagnosed celiac disease was associated with increased rates of hypothyroidism (OR 2.2) but no other significant morbidities. Median followup period was 6.3 years.
My take: A promising new therapy for celiac disease, latiglutenase, looks like it will not be effective and there are a lot of individuals with celiac disease who are unaware of their diagnosis.
Related blog posts:
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Shakespeare and Company Bookstore, Paris
From USA Today: Colon and rectal cancers surge in millennials and GenX
An excerpt:
Someone born in 1990 has double the risk of early colon cancer and quadruple the risk of early rectal cancer as someone born in 1950…
Most of the nation’s 135,000 annual cases and 50,000 deaths related to colon and rectal cancer still occur among people over age 55. But the share of cases involving younger adults has risen to 29% for rectal cancer and 17% for colon cancer, the study showed. About 11,000 people in their 40s and 4,000 under 40 were diagnosed in 2013…
Known risk factors for colon and rectal cancer include obesity, inactivity and diets high in red and processed meat and low fruits, vegetables and whole grains.
Recent guidelines for adults with chronic diarrhea (>4 weeks):
Full text link: LR Schiller, DS Pardi, JH Sellin. Clin Gastroenterol Hepatol 2017; 15: 182-193.
A few key points:
One of my colleagues questioned whether this product could be part of an effective cleanout
Abstract: The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence.
Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection.
Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection.
Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole.
Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis.
Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations.
Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection.
Related blog posts:
Link: ACG Clinical Guideline: Treatment of Helicobacter pylori Infection
The American Journal of Gastroenterology , (10 January 2017) | doi:10.1038/ajg.2016.563
, , and
Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.
My take: Recent draft guidelines from our pediatric group, NASPGHAN, suggested that triple therapy, in addition to quadruple therapy, would still be considered a first-line approach. When the NASPGHAN report is completed/published, it will be of interest to see whether this discrepancy persists.
Related blog posts:
gutsandgrowth 