How do Senna laxatives work?

My frustration with my inability to find a good reference that explains how Senna based laxatives work (before I prescribed it to one of my patients with HD and encopresis) was relieved by one of our fine Pedi GI folks.  She promptly sent me this paper from the deep archives of an appropriately name journal.

Here's the answer.

Senna, an anthraquinone laxative, is a glycoside that is metabolized in the GI tract into oxy-methyl anthraquinone.  OMA's (just made that up; not the official name) soften the stool by decreasing water absorption from the colon and promote colonic contraction by stimulating the Auerbach plexus of nerves.

There you go.

In the realm of surgical oncology, biology is King!

A gem from grand rounds today:

Law of the land in surgical oncology

Biology is King
Selection is Queen
Technical maneuvers are the Prince and Princess

Occasionally the prince and princess try to
overthrow the powerful forces of the King and
Queen, sometimes with temporary apparent
victories, but usually to no long term avail.


Blake Cady, MD

GIST tumors in kids

Looking down at the path report that read "Wild type gastrio-intestinal stormal tumor", I had to reach deep into my memories of adult general surgery training, and all I could come up with was Gleevec. Clearly not enough to formulate a management plan for my 12 year old patient.

Off to Pubmed...

Talk about children not being just small adults!  Pediatric GISTs, it turns out, are a whole different animal.

Adult GISTs are tumors of mesenchymal origin that carry a tyrosine kinase receptor activating mutation. 85% of tumors in adults will have a mutation in either oncogenic KIT, PDGRRA, or (less commonly) BRAF. The presence of a tyrosine kinase mutation is the basis for tumor response to tyrosine kinase inhibitors such as Imatinib (Gleevec).

The pediatric counterpart, a rare entity, differs in a critical way; namely the absence of a tyrosine kinase mutation in the majority (>90%) of cases. Gastrointestinal stromal tumors with no tyrosine kinase mutation are referred to as wild type GISTs.  The absence of these mutations translates to the lack of efficacy of tyrosine kinase inhibitors such as Imatinib. Essentially, no effective neo-adjuvant or adjuvant therapy is available for WT GISTs.

Because of the rare nature of GISTs in children, we do not have a clear idea about behavior. The general impression is that these are insidious lesions, that grow slowly and have a high recurrence rate, even in the setting of complete surgical resection.

What does this mean for us, the pediatric surgeons faced with the responsibility of primum non nocere?  this is a chronic disease that needs management and not cure; more like hypertension that appendicitis.  So avoid big morbid resections if possible, and plan for this disease coming back.

Reference:
Pediatric Gastrintestinal stromal tumor

Bilateral Wilm's Tumor

Now that the dust has settled on the move to the west coast... back to some reading.

A recent discussion about an infant with bilateral renal masses prompted a review of the COG recommendations and protocols for the management of patients with bilateral Wilm's tumor.

Obviously, the basic impetus behind the special consideration for this group of patients is the the need for preservation of functional renal tissue.  Kids with bilateral WT have several factors that contribute to potential renal failure.  These include  intrinsic disease in predisposed kidneys, loss of functional renal tissue after surgery, and injury from chemo and radiation therapy.

Historically, all pediatric patients with bilateral renal tumors have been found to have Wilm's tumor. This, along with the fact that biopsy upstages patients, increases the risk of local recurrence, and can not effectively rule out anaplasia, contributed to the current COG recommendation to proceed with chemotherapy without tissue biopsy.

Once chemotherapy is started, the pattern of tumor response after 6 and 12 weeks determines whether and how therapy is adjusted.

The COG protocol for bilateral renal masses calls for upfront three drug chemotherapy (no biopsy), with re-imaging in 6 weeks.  If, after 6 weeks, there is good response (>30% decrease in size), and the tumor is now resectable with partial renal preservation, then the surgeon proceeds with nephron sparing surgery.

For patients with partial response, but not enough for nephron sparing surgery after 6 weeks, three drug chemotherapy is continued.  At 12 weeks, all patients undergo operative resection; partial nephrectomy if made possible by further reduction in tumor size, or radical nephrectomy.

If there is no good response, then resection is needed to rule out an anaplastic component (chemotherapy needs to be adjusted) or to make sure this is not a benign lesion (further chemotherapy is unnecessary and surgical resection is curative)

Reference:
COG AREN 0534 Protocol: Treatment for Patients with Bilateral, Multicentric, or 
Bilaterally-Predisposed Unilateral Wilms Tumor