Daniel Inderbitzin

Octreotide in the treatment of lymphorrhea after axillary node dissection: a prospective randomized controlled trial

BACKGROUND Axillary lymph node dissection for staging and local control of nodal disease is an integral part of breast cancer therapy. Lymphorrea is a serious and disabling complication of axillary lymphadenectomy, but no effective therapy is currently available. Octreotide is a hormone with general antisecretory effects that has been used to control lymphorrhea in thoracic duct injury and after radical neck dissection. The aim of the study we describe in this article was to determine whether octreotide has a role in the treatment of post axillary lymphadenectomy lymphorrhea. STUDY DESIGN This is a prospective randomized controlled trial. Two hundred sixty-one consecutive patients with various stages of breast cancer who underwent axillary lymph node dissection were randomized and followed for 7 years. The treatment group received 0.1 mg octreotide subcutaneously three times a day for 5 days, starting on the first postoperative day, while the control group received no treatment. Of the 261 patients undergoing axillary node dissection, 136 were assigned to the control group and 125 composed the treatment group. The control group and the treatment group were evaluated for amount and duration of lymphorrhea as well as inflammatory and infectious complications. RESULTS In the control group, the mean quantity (+/- standard deviation) of lymphorrhea was 94.6 +/- 19 cc per day and the average duration was 16.7 +/- 3.0 days. In comparison, the mean quantity of lymphorrhea in the treatment group was 65.4 +/- 21.1 cc (p < 0.0001) per day and the average duration was 7.1 +/- 2.9 days (p < 0.0001). We did not find an important difference in the number of infectious complication or hematomas formation between the study groups. CONCLUSIONS Octreotide can be used successfully for the treatment of post-axillary dissection lymphorrea, and potentially, in the prevention of post-axillary lymph node dissection lymphosarcoma, since the amount and duration of lymphorrhea in this setting are known to be important risk factors for its development. Potentially, octreotide might be used in similar situations where lymphorrhea is detrimental, such as peripheral vascular surgery and regional lymph node dissection for melanoma.

Intrasplenic transplantation of encapsulated cells: a novel approach to cell therapy.

Cell therapy is likely to succeed clinically if cells survive at the transplantation site and are protected against immune rejection. We hypothesized that this could be achieved with intrasplenic transplantation of encapsulated cells because the cells would have instant access to oxygen and nutrients while being separated from the host immune system. In order to provide proof of the concept, primary rat hepatocytes and human hepatoblastoma-derived HepG2 cells were used as model cells. Rat hepatocytes were encapsulated in 100-kDa hollow fibers and cultured for up to 28 days. Rat spleens were implanted with hollow fibers that were either empty or contained 1 × 107 rat hepatocytes. Human HepG2 cells were encapsulated using alginate/poly-l-lysine (ALP) and also transplanted into the spleen; control rats were transplanted with free HepG2 cells. Blood human albumin levels were measured using Western blotting and spleen sections were immunostained for albumin. Hepatocytes in monolayer cultures remained viable for only 6–10 days, whereas the cells cultured in hollow fibers remained viable and produced albumin throughout the study period. Allogeneic hepatocytes transplanted in hollow fibers remained viable for 4 weeks (end of study). Free HepG2 transplants lost viability and function after 7 days, whereas encapsulated HepG2 cells remained viable and secreted human albumin at all time points studied. ALP capsules, with or without xenogeneic HepG2 cells, produced no local fibrotic response. These data indicate that intrasplenic transplantation of encapsulated cells results in excellent survival and function of the transplanted cells and that the proposed technique has the potential to allow transplantation of allo- and xenogeneic cells (e.g., pancreatic islets) without immunosuppression.

Increased Susceptibility of the Left Compared to the Right Ventricle to Remote Ischemia/Reperfusion Injury in Human C1-Inhibitor-Overexpressing Transgene Mice

Acute myocardial injury has been demonstrated as a remote sequela of severe lower torso ischemia-reperfusion (I/R) due to proinflammatory events. In a model of I/R injury, administration of C1 esterase inhibitor (C1-Inh) reduces myocardial necrosis. We investigated the susceptibility of the left (LV) versus right ventricle (RV) and the protective effect of transgenic C1-Inh-overexpressing mice. Two groups of mice ( n = 6) underwent a 2-h lower torso ischemia followed by 3 h of reperfusion: transgenic and wild type with sham-operated controls. Animals were then injected with 125 I bovine albumin. Heart was removed and samples from right and left ventricular free wall were harvested, weighted, and radioactivity was determined. Permeability index for wild-type animals in the RV was 0.22 - 0.04, compared to 0.17 - 0.07 in controls (NS), and in the LV 0.36 - 0.08, compared to 0.21 - 0.05 in controls ( p < .01). The LV showed a significantly higher value compared to the right (0.22 - 0.04 vs. 0.36 - 0.08, p < .01). No difference was seen in the RV between transgenic and wild-type mice; however, in the LV the values decreased significantly in transgenic animals ( p < .015). Thus, remote myocardial injury after lower torso I/R is present in both ventricles; however, the LV seems to be more susceptible as assessed by albumin permeability. Inhibition of the classic complement cascade may be a promising therapeutic approach for myocardial protection in reperfusion injury.

51 – Animal Models for the Study of Hepatocyte Transplantation

In the past three decades, a large number of in vitro and in vivo small and large animal studies of all aspects of hepatocyte transplantation have been carried out to improve the understanding of the process and thus make possible future clinical application of this important tool. Various isolation techniques, including mechanical dissolution by homogenization, pipetting, shaking, and chemical dispersion by citrate, EDTA, EGTA, and sodium tetraphenyl boron have been used in the early stages of hepatocyte harvest development. None of these techniques produced a high yield of viable hepatocytes. For a hepatocyte transplantation method to be useful, the technique must be simple, it should allow early engraftment, it should allow transplantation of an adequate number of hepatocytes, and transplanted hepatocytes should be able to express differentiated functions in vivo for prolonged periods of time. Although significant progress has been achieved in isolated hepatocyte transplantation, the optimal site of implantation has not been determined. In searching for the best transplantation technique and location, hepatocytes have been introduced virtually into every body site, including liver, spleen, thymus, testes, brain, pancreas, lungs, kidneys, peritoneal cavity, subcutaneous tissues, fat pads, and other locations.