Wednesday, September 24, 2014

The 4T's: Thymoma, Terrible Lymphoma, Teratoma, Thyroid cancer

Today in morning report we discussed an approach to a patient presenting with an anterior mediastinal mass.

Differential Diagnosis:  

The differential diagnosis for a mass in the anterior mediastinum includes the classic 4T's.

The most common primary tumours associated with this location are the following:

Thymoma - (30% of the time)
(Terrible) Lymphoma  - (20%)
Teratoma - and other germ cell tumours (18%)
Thyroid cancer (other carcinomas) - (13%)

Secondary tumours are more common in this region and include: lung, esophagus, and testicular cancers.

Clinical Presentation:

The presentation of patients with an anterior mediastinal mass is usually in the 3rd to 5th decade of life.
The main symptoms of a mass in this area include compressive symptoms (stridor, dysphagia, hoarseness) related to the mass impinging on surround structures.

Also, chest pain, cough, dyspnea are all common presenting complaints.

There can also be paraneoplastic phenomena related to the underlying malignancy, and we discussed how hypercalcemia can be associated with with lymphomas, and myasthenia gravis can be associated with thymomas.

The other important consideration is to not miss an aortic dissection in a patient presenting with chest pain and mediastinal fullness on a chest x ray.


There were a couple of important management considerations that we discussed.

1.) Assessing airway patency - if there is any evidence of stridor, or respiratory distress than a call to anesthesia or ICU to help intubate the patient is warranted.

2.) Ruling out Dissection - CT-angiogram to assess the mass and make sure this is not an aortic dissection.

3.) Obtaining a tissue sample - This can be performed via interventional radiology (IR) or respirology/thoracic surgery via EBUS (Endobronchial Ultrasound) guided biopsy.

Thymic epithelial tumours:

Thymomas have a predilection for females and usually present in the 5th and 6th decades of life.  Approximately 35% of patients with thymomas have myasthenia gravis, and 15% of patients with myasthenia gravis will have a thymoma.

Other associations with thymoma include pure red cell aplasia, hypogammaglobuminaemia, and SLE.

The bottom line as Dr. Mark Cheung would say, "When tumour is the rumour, tissue is the issue"

Reference: Imaging of anterior mediastinal tumours. Ching Ching Ong, Lynette L.S. Teo. 2012. Cancer Imaging. 12, 506-515.

Wednesday, September 10, 2014

SPICE: Inducible beta-lactamase in gram negative organisms


Today in Dr. HPK's morning report we discussed a very interesting case of sepsis secondary to a line infection.  In this case the blood cultures were positive for both Serratia and E.coli.  This brought up an interesting management question which we posed to the senior residents in the room:

What antimicrobial would you select empirically for such a patient?

There are a couple of questions to consider when faced with this particular management question:

1.) What is SPICE?

SPICE refers to a group of organisms that have a chromosomal beta-lactamase gene called ampC.  This beta-lactamase is active against beta-lactam antibiotics including cephalosporins, penicillin, and piperacillin/tazobactam.  The interesting point about this class of organisms is that they will produce the beta-lactamase enzyme only when stimulated by the presence of the antibiotic, hence the term "inducible".

The induced enzyme will be released into the periplasmic space and "eat up" the antibiotic, rendering it ineffective, resulting in treatment failure.

SPICE stands for: Serratia, Providencia, Indole-positive Proteus species, Citrobacter, and Enterobacter.  There are other gram negatives that have inducible beta-lactamase genes, but these are the most widely known species.

Indole-positive Proteus species

The various mechanisms that gram-negative bacteria can develop antibiotic resistance (NEJM, 2010)

2.) What antibiotics can I use to treat SPICE organisms?

The most important point to consider, is the avoidance of beta-lactam antibiotics.  

Beta-Lactam ring

Ceftriaxone - can you see the beta-lactam ring?

 Classes of antibiotics that do not induce the ampC gene include the following antibiotics:

TMP / SMX (Septra)  - oral / IV
Carbapenems (i.e. Meropenem) - IV
Aminoglycosides (i.e. gentamycin) - IV
Fluoroquinolones (i.e. moxifloxacin) - oral / IV

Comparison (by me): of the commonly used antibiotics to treat SPICE organisms

If a patient is septic (or for severe infections), than empiric therapy with an intravenous carbapenem is the ideal choice.

Consultation with an Infectious Diseases specialist and discussion with Antimicrobial Stewardship is also advisable in these cases.

Please check out the Antimicrobial Stewardship Website from UHN/MSH for more details, It is an amazing resource related to infections and antibiotics and can be accessed via mobile devices!

For further reading:
Hospital-Acquired Infections Due to Gram-Negative BacteriaAnton Y. Peleg, M.B., B.S., M.P.H. and David C. Hooper, M.D. The New England Journal of Medicine. 2010 May 13; 362(19): 1804–1813.