Diaphragm Rupture in a Liver Transplant Patient Receiving Chronic Immunosuppressive Therapy with Sirolimus

摘要

We read with great interest the article by Wagner et al.~1 recently published in Liver Transplantation. The authors presented a patient with massive, asymptomatic diaphragmatic hepatic herniation after orthotopic liver transplantation. They discussed all the possible potential causes of the diaphragm rupture, such as a devitalized diaphragmatic muscle, extubation with an acute reduction of the intrathorax pressure, surgical techniques, blunt trauma, a preexisting Bochdalek hernia, an intraoperative diaphragmatic injury, and the presence of preoperative ascites in conjunction with increased intra-abdominal pressure. However, we have to add a few comments. In our opinion, the authors did not consider a possible role of the primary immunosuppressant. To support this hypothesis, we report a patient with a spontaneous, nontraumatic diaphragmatic rupture with gastric herniation into the thorax occurring 16 months after orthotopic liver transplantation with no clear etiology. Whole graft liver transplantation was uneventful; preexisting Bochdalek hernias, intraoperative diaphragm injuries, and massive ascites were not present in our patient. The only relevant connection was the chronic immunosuppressive regimen, which was maintained with mammalian target of rapamycin inhibitors in both cases. It has already been reported in the literature that the mammalian target of rapamycin class of immunosuppressive drugs (sirolimus and everolimus) is related to incisional hernias and impaired wound healing after transplantation because of the drugs’ well-known antiproliferative effects.~(2-6) By blocking angiogenetic activity, sirolimus has shown a potent indirect mechanism in addition to its direct effects on tumor cells; this effect is linked to a decrease in the production of vascular endothelial growth factor and to a markedly inhibited response of vascular endothelial cells to stimulation by vascular endothelial growth factor.~(7.8)