Octreotide Treatment and Intestinal Lymphangiectasia

Octreotide in intestinal lymphangiectasia: lack of a clinical response and failure to alter lymphatic function in a guinea pig model.

Makhija S, von der Weid PY, Meddings J, Urbanski SJ, Beck PL. Department of Medicine, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada.

Intestinal lymphangiectasia, which can be classified as primary or secondary, is an unusual cause of protein-losing enteropathy. The main clinical features include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical management generally includes a low-fat diet and supplementation with medium chain triglycerides. A small number of recent reports advocate the use of octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used in these studies; although octreotide can alter splanchnic blood flow and intestinal motility, its actions on lymphatic function has never been investigated. A case of a patient with intestinal lymphangiectasia who required a shunt procedure after failing medium chain triglycerides and octreotide therapy is presented. During the management of this case, all existing literature on intestinal lymphangiectasia and all the known actions of octreotide were reviewed. Because some of the case reports suggested that octreotide may improve the clinical course of intestinal lymphangiectasia by altering lymphatic function, a series of experiments were undertaken to assess this. In an established guinea pig model, the role of octreotide in lymphatic function was examined. In this model system, the mesenteric lymphatic vessels responded to 5-hydroxytryptamine with a decrease in constriction frequency, while histamine administration markedly increased lymphatic constriction frequency. Octreotide failed to produce any change in lymphatic function when a wide range of concentrations were applied to the mesenteric lymphatic vessel preparation. In conclusion, in this case, octreotide failed to induce a clinical response and laboratory studies showed that octreotide did not alter lymphatic function. Thus, the mechanisms by which octreotide induced clinical responses in the cases reported elsewhere in the literature remain unclear, but the present study suggests that it does not appear to act via increasing lymphatic pumping.

PMID: 15565209 [hands@hanyang.ac.kr

A 47-yr-old man with hepatitis B virus associated liver cirrhosis was admitted to our hospital with diarrhea and generalized edema and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia by intestinal biopsy and 99mTc albumin scan. During hospitalization, he received subcutaneous octreotide therapy. After 2 weeks of octreotide therapy, follow-up albumin scan showed no albumin leakage, and the serum albumin level was sustained. We speculate that liver cirrhosis can be a cause of intestinal lymphangiectasia and administration of octreotide should be considered for patients with intestinal lymphangiectasia whose clinical and biochemical abnormalities do not respond to a low-fat diet. 2004 Jun; 19 (3): 466- 469 Journal of Korean Medical Science

PubMed - indexed for MEDLINE]

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IS THERE A ROLE FOR OCTREOTIDE IN INTESTINAL LYMPHANGIECTASIA?

S Makhija, P-Y von der Weid, J Meddings, PL Beck GI and Mucosal Inflammation Research Groups, University of Calgary, Calgary, Alberta

We present two patients with intestinal lymphangiectasia. Intestinal lymphangiectasia is rare cause of protein losing enteropathy. Management is often ineffective and generally includes a low fat diet and medium chain triglyceride (MCT) oil. Several medications have also been tried without success. Recently octreotide has been used in a small number of patients with mixed results. It is unclear why octreotide was used in these cases for there have been no studies to date assessing the actions of this agent on lymphatic function.

AIM:

Assess the role of octreotide on lymphatic function.

METHODS:

To investigate whether octreotide directly affects lymphatic pumping function, we assessed its effect on lymphatic vessels of the ileal portion of the guinea-pigs mesentery. This intra-vital preparation is a well-established model that has been used to characterize physiological and pharmacological properties of lymphatic pumping. The contractile activity of lymphatic vessels was monitored via video microscopy and vessel diameter was analyzed in real time using a video-dimension analyzer. A 5 min control period of contractile activity was recorded before octreotide (Sandostatin, Novartis, Basle, CH) was applied for 4 min, at various concentrations.

RESULTS:

Octreotide had no effect on lymphatic vessel pumping activity over a wide range of concentrations (20 nM to 10 µM). Despite the absence of response to octreotide, the same vessels responded to treatments with 5-HT with a decrease in constriction frequency (47.3±10.5% of control) and to application of histamine with an increase in pumping (125.3±20.9% of control). Thus, although pumping of guinea-pig mesenteric lymphatic vessels could be altered by known modulatory agents, it was not affected by octreotide. Of our two clinical cases, one patient was managed with MCT oil with a good response while the second patient failed MCT oil therapy and was then tried empirically on octreotide without clinical response.

CONCLUSION:

In a bedside-to-bench approach we could not find any evidence that octreotide enhanced lymphatic function in our animal model nor did the one patient that empirically received octreotide respond to this intervention.

Article

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