10/10 HUP Report – Small Bowel Mass

Today we discussed an interesting case of a patient with longstanding Crohn’s disease, well-managed off immunosuppression, who presented with an enterovesicular fistula. This is actually a really RARE complication of Crohn’s disease (approximately 3%), and almost always requires surgical intervention. Aside from being secondary to active inflammation from his IBD, this new clinical finding could be secondary to a small bowel neoplasm (small bowel cancer is also really rare, but the rate is increased in Crohn’s disease patients).

Here is our basic differential for a small bowel mass:

Malignant

  • Neuroendocrine tumor
  • Adenocarcinoma
  • Sarcoma
  • Lymphoma
  • Metastatic disease (hematogenous spread or direct spread from peritoneal carcinomatosis)

Benign

  • Lipoma
  • Fibroma
  • Leiomyoma
  • Adenoma
  • Desmoid tumor

Infectious

  • Tuberculosis
  • Abscess
  • Histoplasma

This patient’s biopsy was consistent with neuroendocrine tumor, and he had numerous metastases — this is a common finding at the time of diagnosis due to indolent and asymptomatic growth in many patients. First line treatment for neuroendocrine tumors is usually somatostatin receptor analogues. Symptomatic surgical debulking or curative surgical resection can be considered in appropriate candidates, but is less common. Prominent symptomatic liver mets can be managed with ablation techniques. Systemic chemotherapy can be attempted for refractory disease — everolimus, bevacizumab, and sunitinib have been used.

 

 

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9/21 HUP Report: Evidence-Based Management of Severe Pancreatitis

Today we talked about management of severe pancreatitis and reviewed some of the evidence informing our practices.

First of all, how do we stratify severity of pancreatitis and why does it matter? It is really important to stratify severity because aggressive intervention for patients more likely to progress to severe pancreatitis can improve mortality.

Determining Severity

Revised Atlanta Criteria (for severity of acute pancreatitis):

  • Mild – no organ failure or systemic/local complications
  • Moderate – no or transient organ failure (<48 hrs) and/or local complications
  • Severe – organ failure >48 hrs, complications involving one or more organs

 

Lots of scoring systems have been devised, including Ranson’s Criteria, CT Severity Index, APACHE II, BISAP. They take into account variables like hemoconcentration (third-spacing in severe disease, studies with mixed findings based on cut-offs used), creatinine (possibly correlated with risk of necrosis), procalcitonin (most rapid acute phase reactant), CRP (most useful at 48 hours, >150 = severe), BUN (>20 at admission associated with increased risk of death). Some logistical considerations of the scoring systems:

  • BISAP is easy to clinically implement and comparable to APACHE II in predicting progression to severe disease
  • Ranson’s cannot be completed until 48 hours
  • APACHE II involves several clinical and lab data points that are not routinely obtained for all patients
  • CT Severity Index requires imaging, which is not always indicated

Overall, the American College of Gastroenterology recommends incorporating several clinical and laboratory parameters into an overall assessment of severity without relying on any particular scoring framework.

 

Fluid Resuscitation

Best results have been seen with aggressive fluid resuscitation in the first 12-24 hours. Lactated Ringers has been shown to be associated with lower incidence of SIRS at 24 hours than normal saline, with a theorized mechanism involving the development of metabolic acidosis with NS which potentiates activation of trypsinogen to trypsin (one of the active pancreatic enzymes causing autodigestion and inflammation).

 

Nutrition

Several studies support early enteral nutrition in severe pancreatitis, as compared with bowel rest and/or total parenteral nutrition. One theory suggests that bowel rest causes mucosal atrophy, which then may increase bowel translocation and risk of infection.

 

Prophylactic Antibiotics

Meta-analyses now suggest that there is no benefit to prophylactic antibiotics in this patient population. Antibiotics are only indicated if there is clinical concern for superinfection (which may be difficult to clinically differentiate from severe pancreatitis!). Antibiotics with good pancreatic penetration include carbapenems, high dose cephalosporins, metronidazole, and fluorquinolones.

 

 

Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013; 62:102.

Tenner S, Baillie J, DeWitt J, et al. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013; 108:1400.

Wu BU, Johannes RS, Sun X, et al. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut 2008; 57:1698.

Wu BU, Hwang JQ, Gardner TH, et al. Lactated Ringer’s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol 2011; 9:710.

Li J-Y, Yu T, Chen G-C, et al. Enteral Nutrition within 48 Hours of Admission Improves Clinical Outcomes of Acute Pancreatitis by Reducing Complications: A Meta-Analysis. Rakonczay Z, ed. PLoS ONE. 2013;8(6):e64926. doi:10.1371/journal.pone.0064926.

9/20 PPMC report: extra-intestinal manifestations of celiac disease

We discussed a young woman who presented with psychotic episodes and multiple micronutrient deficiencies, and was ultimately diagnosed with celiac disease.

Celiac disease is a systemic immune-mediated disease triggered by exposure to gluten (found in wheat, rye, barley) in genetically susceptible patients, who can then have a broad range of systemic manifestations and variable damage to the small intestinal mucosa.

PEARLS

  • It affects many races and ethnic groups (not just Caucasians)
  • There can be a variety of very subtle clinical manifestations
    • Chronic diarrhea, weight loss, abdominal distention (40-50%), recurrent abdominal pain
    • Iron deficiency (w/ or w/o anemia)
    • High transaminase levels, recurrent oral ulcers
    • Chronic fatigue
  • Untreated celiac disease can lead to neurologic disorders, infertility or recurrent abortion, and rarely cancer (T-cell lymphoma and adenocarcinoma of the jejunum)

Remember that celiac disease has a number of extra-intestinal manifestations

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NEJM 2016

Diagnosis: the IgA anti-tissue transglutaminase (TTG) antibody, which has excellent test characteristics (94% Se, 97% Sp). This is the single best initial test.

  • IgA anti-endomysial antibodies are nearly 100% specific, but should only be used to confirm a borderline +TTG (if there’s concern that it’s a false positive)
  • A small bowel biopsy is required to confirm the diagnosis if TTG+
  • If the diagnosis is uncertain, consider sending HLA DQ2/DQ8 testing; being negative for those haplotypes essentially rules out celiac (ie it has a very high NPV)

Remember: sensitivity of testing is markedly decreased when patients are on a gluten free diet, so don’t be too eager to restrict their diet! Biopsy findings on endoscopy can also be falsely negative if the patient is on immune suppression (steroids, etc).

A note on screening: no clear consensus exists on this, but consider screening 1st degree relatives of patients with celiac, and other high risk groups (unexplained IDA, Down syndrome, other autoimmune diseases w/ suggestive sx, etc)

In this case, the patient presented with psychosis at the age of 45, which is unusual: psychosis usually presents in the early 20s, and there’s also a small peak around menopause. While psychosis as a manifestation of celiac is rare, it’s important to remember the more (and more common) subtle neuropsychiatric signs of celiac.

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NEJM 2016

It’s very hard to avoid gluten- it’s present in tons of food (especially processed food) in subtle ways, and even in certain medications as a binder/filler; this makes adherence with a gluten free diet very difficult.

References

  1. Jackson J et al. Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity. Psychiatr Q. 2012.
  2. Kabbani et al. Celiac Disease or Non-Celiac Gluten Sensitivity? An Approach to Clinical Differential Diagnosis. Am J Gastroenterology 2014.
  3. Celiac disease. NEJM.

9/18 HUP Report: IBS and Porphyria

Today we reviewed a case of a patient with chronic bouts of acute abdominal pain.  In doing so, we discussed the differential for chronic abdominal pain, reviewed the diagnostic criteria for the key diseases of chronic abdominal pain, and discussed porphyria.  Some of the key features of the case are noted below, and you can read more about this topic in the most recent NEJM.  Remember, this diagnosis is no rarer than pheochromocytoma, and we work that up all the time!

 

IBS Diagnostic Criteria – Symptoms 1 day per week for 3 months and 2-of-3 of the below symptoms:

  1. change in stool frequency
  2. change in stool form
  3. pain relieved by defecation

IBS can then be classified as predominanty diarrhea or constipation.  If a patient is in the diarrhea category, you must also think about IBD and Celiac disease.  The screen for IBD is ESR/CRP or Fecal Calprotectin, and the screen for Celiac is a CBC to look for anemia.

 

In this case, the key to the diagnosis was that the patient had a history of depression, her abdominal symptoms were associated with neurologic symptoms (brain fog), and her labs revealed a mild hyponatremia.  This is a classic presentation for Acute Intermittent Porphyria (AIP), although neurologic manifestations can be as severe as seizures.  We then reviewed a clinical approach to porphyria.

 

Visceral Porphyria – AIP is the most common form, although there are many other rarer types that you will probably never see.  If you suspect any visceral porphyria, check a urine porphobilinogen during a flare.  A positive test is diagnostic of AIP; if that test is negative, but you really think it’s porphyria, refer to online algorithms for next steps to evaluate the rarer forms of visceral porphyria.  Treatment is centered around giving Hematin therapy and avoiding offending medications.

 

Cutaneous Porphyria – These diseases do not cause abdominal pain, and were not implicated in this case, but we reviewed them for completeness.  The most common type is Porphyria Cutanea Tarda, and is often associated with other underlying causes (HIV, HCV, Hemochromatosis, Alcoholic Cirrhosis).   You should suspect this diagnosis when a patient burns too easily and has more severe sun reactions like blistering.  The diagnostic test is serum porphyrins.

9/5 (HUP): solid/cystic liver lesions and possible VHL syndrome

(Late post) Thanks to Shaz for presenting a fascinating case of an older man who presented with abdominal pain and jaundice and was found to have a large hemorrhagic solid+cystic lesion in the right lobe of his liver.

Approach to liver lesions

Screen Shot 2017-09-07 at 9.23.17 AM.png

PEARLS

  • Conditions that can lead to HCC without cirrhosis: NASH, chronic HBV infection, and malignant transformation of a hepatic adenoma (and aflatoxin exposure, but that’s really rare)
  • Recall that the liver gets 80% of its blood flow from the portal vein and 20% from the hepatic artery
    • This principle is not true for certain liver masses (classic example: HCC) which may get more of their blood flow from the hepatic artery, thus altering the pattern of contrast enhancement on cross sectional imaging. See this article for more information on principles of liver imaging.
  • HCC is one of the only malignancies where tissue is not required for diagnosis, as it has a characteristic appearance: early arterial enhancement with venous washout (see below) on triple phase (1- arterial/2- venous/3- equilibrium phase) CT; this finding is enough to diagnose HCC without biopsy; it may also have a pseudo-capsule
  • Screen Shot 2017-09-07 at 10.24.22 AM.png

    Radiology Assistant

  • Hypervascular metastases (thyroid, melanoma, RCC) also tend to enhance rapidly in the arterial phase
  • Hepatic adenomas are usually seen in young women of reproductive age, especially those on OCPs; there is a 5-10% risk of malignant transformation. On CT: well-demarcated with peripheral enhancement.

Things to consider in your diagnostic approach to liver masses

  1. Careful history and physical (may give clues to etiology)
  2. Triple phase CT or MRI with contrast
  3. AFP (although may be normal in 20-40% of HCC, particularly fibrolamellar variant of HCC) or CA 19-9
  4. Consider search for primary site of tumor elsewhere
  5. Tissue diagnosis by biopsy

This patient was ultimately found to have malignant-appearing bilateral renal masses, a pancreatic mass and a separate liver mass concerning for HCC, all of which is suspicious for Von-Hippel Lindau syndrome (see review below).

References

  1. Baron, R. Radiographic characterization of liver masses. 
  2. Bahirwani R and Reddy R. The evaluation of solitary liver masses. Alimentary Pharmacology and Therapeutics 2008.
  3. Maher et al. Von Hippel Lindau syndrome. 2011.

 

8/15 (HUP): alcoholic hepatitis

Late post thanks to boards! A big thanks to Dr. Vandana Khungar for helping us through the case of a young man who presented with jaundice and abdominal pain with a bilirubin of 51 and was ultimately diagnosed with acute alcoholic hepatitis (for which he got a liver transplant).

Key features of alcoholic hepatitis

  1. Even though we often think of alcoholic hepatitis as ‘acute’, its actually more often a manifestation of chronic heavy alcohol intake (>80g/day for a decade or more).

Ever wonder how much alcohol is in a ‘standard’ drink? Take a look!

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Remember that alcoholic hepatitis (AH) can be superimposed on underlying cirrhosis/chronic liver disease.

  • Patients can present with fever, tender hepatomegaly and leukocytosis; it can sometimes be difficult to distinguish from other causes of acute hepatitis, as well as sepsis/infection
  • Some series have shown that >50% of patients have abdominal bruits; other stigmata of liver disease (ascites, encephalopathy) may be present either with or without underlying liver disease
  • The AST:ALT ratio will usually be >2:1: thought to be due to hepatic deficiency of pyridoxal 5′-phosphate in alcoholics (a cofactor for the enzymatic activity of ALT); so the ratio is really a failure of ALT to increase appropriately

Risk stratification for alcoholic hepatitis

There are several risk scores used for EtOH hepatitis:

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Lucey. NEJM 2009.

 

Maddrey’s discriminant function: estimates EtOH severity; a score >32 is considered severe.
Glasgow score: used to estimate likelihood of benefit from steroids. Rarely used in clinical practice
Lille score: helps decide whether to stop or continue steroids after 1 week (ie which patients won’t benefit from steroids no matter what given the severity of their hepatitis)

How is alcoholic hepatitis managed?

  • Supportive care (fluids, antibiotics if needed, abstinence, nutritional support)
  • The big debate is over the role of prednisolone and pentoxifylline (a TNF-a inhibitor) in the treatment of alcoholic hepatitis. You can read the details of the STOPAH trial below (which compared the two), but the short answer is that it’s not totally clear that one is better than the other.
  • One major flaw of STOPAH may have been that in the groups randomized to steroids, the investigators continued prednisolone for 28 days instead of using the Lille score to stop steroids for those people that wouldn’t have benefited; in doing so, they may have driven up mortality due to infection in the steroid group and diminished any apparent benefit of prednisolone!
  • In clinical practice (at least at Penn), prednisolone is often started after 48 hours of negative infectious workup, as long as they don’t have renal failure (a population that was excluded in STOPAH, due at least in part to concerns about bleeding risk)

See reference #2 below for more information about the role of liver transplant in treating alcoholic hepatitis!

References

  1. Thursz M et al. Prednisolone or Pentoxifylline for Alcoholic Hepatitis (STOPAH). NEJM 2015.
  2. Saberi, B. et al. 2016. Current Management of Alcoholic Hepatitis and Future TherapiesJournal of Clinical and Translational Hepatology. 4, 2 (2016), 113–122.
  3. Lucey et al. 2009. Alcoholic Hepatitis. NEJM.

7/31 PPMC Report: Acute Diarrhea!

Acute Diarrhea

Today’s resident intake report from the effervescent Nancy Aitcheson was a 31 yo M p/w 4 days of nausea, vomiting and diarrhea.

As discussed — the differential is in the HISTORY! Most acute diarrhea can be lumped into inflammatory or non-inflammatory based on history alone and occasionally a quick peek at the stool.

We reviewed that extensive testing, including stool cultures, CDiff, fecal leukocytes and O+P are for the most part unnecessary, but discussed the few times when those tests SHOULD be run.

We also highlighted the treatment options:

  1. Rehydrate the patient! — oral is better than IV. If they can’t keep fluids down (like the case presented) then they are likely to need an admission.
  2. Early re-feeding — don’t keep your patient on a clear liquid diet. It turns out letting them eat what they can ASAP helps reduce bowel permeability and decreases illness duration
  3. Loperamide — we’ve all been nervous about giving this to patients, but if the diarrhea ISN’T bloody and they aren’t at risk for CDiff then go ahead!
  4. Pepto Bismol — it’s a tried and true medicine cabinet staple for a reason. Almost ALL patients can take this medication (even if they have fevers and inflammatory diarrhea)!
  5. Probiotics and Zinc — the data backing this up primarily comes from the pediatric population, but if your patient is at home and needs to feel empowered, go ahead and recommend these two treatments. There’s very little downside and potentially some benefit (studies pending).