Should We Care About Subclinical Primary Sclerosing Cholangitis with Inflammatory Bowel Disease?

Posted on October 26, 2016 by gutsandgrowth

A recent study (AK Lunder et al. Gastroenterol 2016; 151: 660-69, editorial 590-3) provides more information about the prevalence of subclinical primary sclerosing cholangitis (PSC) in the setting of long-term inflammatory bowel disease. From a cohort of 756 Norwegian patients in the “IBSEN” cohort of patients with inflammatory bowel disease, the authors analyzed 327 patients with magnetic resonance cholangiography (MRC).

Key findings:

24 (7.5%) of 327 patients who had been followed for 20 years were found to have PSC lesions. Only 7 (2.2%) were known to have PSC based on biochemical or clinical features. Subsequently, a missed case of small-duct PSC was recognized increasing the rate to 8.1%.
Subclinical PSC, interestingly, was detected more often in Crohn’s patients (9.0%) compared with ulcerative colitis (6.8%)
Extensive colitis, high prevalence of colectomy, and refractory IBD symptoms were more common in patients with suspected PSC compared with those without PSC features (P= .029, P= .002, and P= .012 respectively)

The natural history of these subclinical cases of PSC is unclear. Studies have shown that patients with PSC with normal alkaline phosphatase values have an excellent outlook. Yet, there should be some concern. PSC has been associated with 400-fold higher chance of cholangiocarcinoma and 5-fold increased risk of developing colorectal cancer. This could indicate the need for more intensive surveillance in these patients –though the exact risks in those with subclinical disease is unknown.

My take: Until we know more, I doubt looking for subclinical PSC makes sense outside research protocols.

Related blog posts:

Primary Sclerosing Cholangitis 2016

Posted on October 25, 2016 by gutsandgrowth

Though this blog has reviewed primary sclerosing cholangitis (PSC), it has been a while since I’ve posted much. As such, I thought I would place a post of a recent review (KN Lazaridis, NF LaRusso. NEJM 2016; 375; 1161-70).

Key points:

Epidemiology:

Strongly associated with inflammatory bowel disease with 70-80% of PSC patients having IBD
Median age at diagnosis 41 years with ~6-% male

Clinical manifestations:

Insidious disease in most. “About half the patients with this condition do not have symptoms but receive a diagnosis after liver-function tests are found to be abnormal.”
Diagnostic criteria include increased alkaline phosphatase for more than 6 months
In adults, a liver biopsy is not need for diagnosis
Tends to be slowly progressive
Bacterial cholangitis is reported as initial presentation in ~6% and can be recurrent and intractable
Colon cancer is more frequent in patients with PSC. “Colonoscopy is warranted in all patients who have received a new diagnosis”

Subtypes:

Classic subtype (90%) involves the entire biliary tree
~5% have only small intrahepatic bile duct involvement
~5% of adults have overlap syndrome with autoimmune hepatitis. In children, overlap syndrome is present in ~35%.
There are numerous “secondary” PSC causes including AIDS-related cholangiopathy, amyloidoiss, eosinophilic cholangiopathy, histiocytosis X, IgG4-associated cholangitis, and sarcoidosis (most extensive list -see Table 1)

Pathogenesis:

The exact reasons remain unclear. There are associations with environmental triggers but these have not been proven to be causally related. For example, patients with PSC are more likely to consume steak or hamburger compared with controls and less likely to consume similar amounts of fish.
Due to its association with IBD, there are “microbiota hypothesis” to account for the aberrant cholangiocytic response.

Treatment:

“As of this writing, no effective medical therapy exists.”
The authors detail eight potential treatments that are being studied: obeticholic acid, simtuzumab, 24-nor-ursodeoxycholic acid, an apical sodium-dependent bile acid transporter inhibitor (LUM001), a human monoclonal antibody that targets vascular adhesion protein 1 (BTT1023), oral vancomycin (NCT01802073 -pediatric trial), and fecal microbiota transplantation.
Management: includes managing varices in those with cirrhosis, following for benign and malignant biliary strictures, following for gallbladder disease (eg. polyps or masses), colon cancer surveillance (typically yearly screening), and managing metabolic bone disease.

Briefly noted: M Bramuzzo et al. JPGN 2016; 63: 259-64. Using an Italian Pediatric IBD registry, the authors noted 6.8% of 677 patients had autoimmune liver disease: 61% with PSC and 33% with overlap syndrome.

Related blog posts:

Nonsteroidal Analgesics and Risk of Empyema

Posted on October 21, 2016 by gutsandgrowth

A recent study (M Le Bourgeois et al. J Pediatr 2016; 175: 47-53) from 15 medical centers in France showed an association between nonsteroidal anti-inflammatory drugs (NSAIDs) and the development of empyema.

Methods: a case-control design with 83 cases of children with empyema and recent acute viral infection (w/in 15 days) and 83 controls who had recent acute viral infection but no emyema. Age range: 3 months-15 years. To ascertain the underlying initial viral etiology, the investigators utilized molecular techniques and identified respiratory viruses in about half of both groups of children.

Key finding: Exposure to NSAIDs was associated with a modest increase in the rate of empyema (aOR 2.79). The risk of empyema associated with NSAIDs was diminished if the child had been prescribed an antibiotic.

My take: This study, by minimizing confounding factors, suggests that the casual use of NSAIDs during acute viral illnesses increases the chance of developing empyema.

Grinnell Glacier, Glacier Nat’l Park

World Congress 2016 Postgraduate Course

Posted on October 19, 2016 by gutsandgrowth

I’ve attached (with permission) the syllabus from the World Congress 2016 Postgraduate Course: 2016-world-congress-postgraduate-course-syllabus

One lecture that I will highlight with a few slides is from Dr. Martin Martin (pg 53-62) which emphasizes a new model for evaluating neonatal intestinal failure/congenital diarrhea by using whole exome sequencing –see slides below.

Other pointers:

Pg 82. Breastmilk associated with shorter duration of TPN dependence in short bowel syndrome
Pg 137. Look for vasculopathy (MRI/MRA) and renal disease in Alagille syndrome
Pg 152. Lactated ringer’s likely better in acute pancreatitis than normal saline.
Pg 171. If constipation at less than 1 year is untreated, >60% have issues with constipation at age 3.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. 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.

Total Pancreatectomy with Islet Autotransplantation for Refractory Recurrent Pancreatitis

Posted on October 18, 2016 by gutsandgrowth

A recent study (MD Bellin et al. Clin Gastroenterol Hepatol 2016; 14: 1317-23) describes the use of Total Pancreatectomy with Islet Autotransplantation (TPIAT) in 49 patients (mean age 32.8 years). This study included 6 children.

All of these patients met strict criteria for recurrent acute pancreatitis and lacked imaging or functional evidence for chronic pancreatitis. All 49 required narcotics for pain management prior to TPIAT.

The surgical technique for TPIAT is well-described in the report. Patients underwent total pancreatectomy, splenectomy, cholecystectomy and partial duodenectomy with continuity restored via doudenoduodenostomy or Roux-en-Y duodenojejunostomy. The islets were isolated and then infused intraportally.

Key findings:

At 1 year following TPIAT, 22 (46%) reported no use of narcotic pain medications.
Health-related quality of life scores improved (see Figure 3)
Diabetes is a common post-op concern. Approximately half were insulin-independent at 1 and 2 years out from surgery, with one-third remaining so at 5 years.
Histopathology was consistent with chronic pancreatitis in 37 (76%) indicating that current imaging/functional features do not reliably identify chronic pancreatitis with adequate sensitivity.

In the discussion, the authors note the selected patients, due to having normal caliber pancreatitis ducts, were not candidates for surgical drainage procedures like the Puestow procedure. They also note that the Puestow procedure can compromise later islet cell isolation.

My take: TPIAT is an important option in those with severe recurrent or persistent pancreatitis disease.

Related blog posts:

Quiet spot on Univ Virginia Grounds

Smart Doctors Still Better Than Smartphones

Posted on October 17, 2016 by gutsandgrowth

The LA Times has reviewed a recent study: JAMA Intern Med. Published online October 10, 2016. doi:10.1001/jamainternmed.2016.6001

LA Times: Your phone may be smart, but your doctor still know more than an app

An excerpt:

In a head-to-head comparison, real human physicians outperformed a collection of 23 symptom-checker apps and websites by a margin of more than 2 to 1, according to a report published Monday in the journal JAMA Internal Medicine.

Even when the contestants got three chances to figure out what ailed a hypothetical patient, the diagnostic software lagged far behind actual doctors. Indeed, the apps and websites suggested the right diagnosis only slightly more than half of the time, the report says…

Though the humans trounced the computers across the board, there were situations in which doctors did a particularly good job of naming the correct diagnosis first. For instance, their margin in cases with common conditions was 70% to 38%. In cases with uncommon conditions, it grew to 76% to 28%.

My take: According to the study, doctors still beat computer symptom algorithms. But, there may be bias: “three of the study authors are doctors, and none are apps.” At the same time, there is a likelihood of increased collaboration between physicians and computers.

NPR: Computerized Assistant for Cancer

Thermal Injury and Subsequent Esophageal Damage

Posted on October 16, 2016 by gutsandgrowth

In this picture of a ‘candy cane appearance’ of the esophagus, the 19 year old patient subsequently admitted to drinking boiling hot tea. A complete recovery was noted.

Briefly Noted: Inflammatory Bowel Disease Updates

Posted on October 13, 2016 by gutsandgrowth

Gut Microbial Diversity is Reduced in Smokers with Crohn’s Disease. JL Opstelten et al. Inflamm Bowel Dis 2016; 22: 2070-77. This study compared stools from 21 nonsmoking patients with Crohn’s disease (CD) with 21 smokers with CD. Smoking was accompanied by a reduced relative abundance of multiple genera. My take: It is unclear whether smoking’s effect on the microbiome directly contributes to worsened outcomes or whether the changes in the microbiome are only an epiphenomenon. Regardless, smoking increases the likelihood of worse outcomes in CD.

A Systematic Review on Infliximab and Adalimumab Drug Monitoring Levels, Clinical Outcomes and Assay. F Silva-Ferreira et al. Inflamm Bowel Dis 2016; 22: 2289-2301. This review selected 20 studies from an initial query of 1654 articles. Key points:

Different studies are difficult to compare due to distinct assays with different limitations. Thus, specific cutoffs are based on the specific assay used.
The authors state that proactive monitoring may be helpful at week 6, 14, 30 and 54 for infliximab. They recommend checking infliximab level and antidrug antibodies in those with loss of response, mucosal ulceration or elevated biomarkers (eg. CRP, Fecal calprotectin).