Duodenal villous atrophy: a cause of chronic diarrhea after solid-organ transplantation.

Persistent diarrhea is commonly observed after solid organ transplantation (SOT). A few cases of mycophenolate mofetil (MMF)-induced duodenal villous atrophy (DVA) have been previously reported in kidney-transplant patients with chronic diarrhea. Herein, we report on the incidence and characteristics of DVA in SOT patients with chronic diarrhea. One hundred thirty-two SOT patients with chronic diarrhea underwent an oesophago-gastroduodenoscopy (OGD) and a duodenal biopsy after classical causes of diarrhea have been ruled out. DVA was diagnosed in 21 patients (15.9%). It was attributed to mycophenolic acid (MPA) therapy in 18 patients (85.7%) (MMF [n = 14] and enteric-coated mycophenolate sodium [n = 4]). MPA withdrawal or dose reduction resulted in diarrhea cessation. The incidence of DVA was significantly higher in patients with chronic diarrhea receiving MPA compared to those who did not (24.6% vs. 5.1%, p = 0.003). DVA was attributed to a Giardia lamblia parasitic infection in two patients (9.5%) and the remaining case was attributed to azathioprine. In these three patients, diarrhea ceased after metronidazole therapy or azathioprine dose reduction. In conclusion, DVA is a frequent cause of chronic diarrhea in SOT recipients. MPA therapy is the most frequent cause of DVA. An OGD should be proposed to all transplant recipients who present with persistent diarrhea.

Pharmacodynamics of immunosuppressive drugs.

The inability to measure the effects of immunosuppressive drugs on immune cells in vivo has always severely limited preclinical drug development, the design and interpretation of clinical trials and the optimal clinical use of this drug class in transplantation. Now, new technologies using microliter samples of whole blood and exploiting the specificity, sensitivity and versatility of flow cytometry have been developed. These novel techniques not only are illuminating the 'black box' that has obscured the pharmacodynamic effects of immunosuppressants but also are uncovering new mechanisms of action of these drugs. Pharmacodynamic assays measure biologically relevant events in vivo, since changes in lymphocyte functions in blood collected from immunosuppressed graft recipients faithfully reflect histopathologic events within allograft tissue.

Aspergillus fumigatus-related spondylodiscitis in a heart transplant patient successfully treated with voriconazole.

Organ transplant patients, such as heart transplant (HT) recipients, are prone to infections, among which are yeast infections. Of these, aspergillosis is usually associated with pneumopathy or facial sinusitis, and Aspergillus fumigatus is rarely responsible for osteomyelitis or spondylodiscitis. Herein we have reported a case of an 18-year-old male HT patient presenting with subacute lumbar spondylodiscitis at 6 months posttransplantation and 3 months after antirejection therapy with antithymocyte globulins. A percutaneous needle biopsy of the intervertebral disc yielded Aspergillus fumigatus. The patient had no evidence of lung aspergillosis, but did have maxillary sinusitis. He was successfully treated with voriconazole.

[Late complications of a pseudo aneurysm of the left ventricle: thrombus infection and purulent pericarditis]. / Complications tardives d'un faux anévrisme du ventricule gauche: infection du thrombus et péricardite purulente.

Pseudoaneurysm is a rare complication of left ventricle myocardial infarction. Rupture with tamponade and sudden death is the usual outcome. Surgical intervention remains the treatment of choice. Long term survival cases without surgery are rare. Infection of the thrombus is also a possible event. We report the case of a patient with postinfarction left ventricular pseudoaneurysm complicated by infection of the thrombus and purulent pericarditis involving a peptostreptococcus. Infection must be considered a potential complication of left ventricular pseudoaneurysms.

[Endografts (or stent-grafts) and diseases of the descending thoracic aorta]. / Endoprothèses (ou stent-grafts) et pathologies de l'aorte thoracique descendante.

The endovascular treatment of aorta diseases with S-Graft is considered as an alternative to surgery, especially interesting in patients with severe comorbidities. Indeed, the mid-term morbidity and mortality are comparable to surgery in relatively large series, and S-Graft implantation appeared as a safe, less invasive and efficient treatment for different affections of the thoracic aorta. This article reviews technical aspects, indications and results of endovascular repairs of thoracic aorta lesions. We will also assess the advantages and limitations of S-Graft therapy.

Acute traumatic aortic rupture: a comparison of surgical and stent-graft repair.

OBJECTIVE: The study's objective was to comparatively evaluate surgery and stent-graft repair of acute or subacute traumatic aortic rupture. METHODS: A total of 76 patients (14-76 years old; mean, 37 years; male/female ratio, 63/11) with a traumatic aortic injury were admitted to our hospital between 1981 and 2003. Six patients died within 1 to 9 days of another associated severe traumatic lesion. The 70 remaining patients were divided according to the type of rupture repair. In group 1, 35 patients were treated surgically: 28 with immediate repair and 7 with delayed repair (average time interval 66 days, 5-257 days). In group 2, 29 patients were treated with stent grafting of the aortic isthmus. In group 3, 6 patients with minor aortic lesions were treated medically with a close follow-up. RESULTS: In the 28 patients treated surgically in the emergency department, the mortality and paraplegia rates were 21% and 7%, respectively. No death or paraplegia was observed in the group with delayed surgical repair. With stent grafting, complete exclusion of the pseudoaneurysmal sac was observed in all patients. Except for 1 iliac rupture treated during the same procedure, there was no major morbidity or mortality during the mean follow-up of 46 months (13-90 months). No major complication was observed in group 3. CONCLUSIONS: In stable rupture of the aorta, initial conservative treatment is safe and allows management of the major associated lesions. Stent grafting of the aortic isthmus is a valuable therapeutic alternative to surgical repair, especially in patients considered high risk for conventional thoracotomy.

Use of human mesenteric arteries to study chronic vascular rejection in SCID/beige mice reconstituted with human spleen cells.

We wanted to establish a preclinical model of chronic vascular rejection (CVR) by transplanting small arteries from the mesentery of cadaveric organ donors by the rapid "sleeve" technique into SCID/beige mice reconstituted with human allogeneic spleen cells. After institutional authorization and with informed consent from relatives, we obtained tissues and cells from cadaveric organ donors. A piece of mesentery was recovered from the donor and kept in buffered solution at 4 degrees C until use. After dissection of the mesentery, small arteries of suitable size were transplanted in place of the infrarenal aorta of the mice. Cells for the immunological reconstitution of the mice were spleen cells from the same or other organ donors. Twenty-three suitable arterial segments were obtained from the mesentery of three cadaveric donors. Ten of the mice received 3 x 10(7) human spleen cells intraperitoneally 1 week after the arterial graft and they all showed circulating human CD3+ and CD19+ cells 2 weeks after injection. The mice were sacrificed 5 weeks after the arterial graft. SCID/beige mice reconstituted with allogeneic spleen cells showed a typical CVR, whereas mice that received no cells had a normal vascular anatomy. We believe our model is well suited for the study of treatment of CVR under human allograft conditions.

Chronic vascular rejection: histologic comparison between two murine experimental models.

BACKGROUND: We previously developed an experimental model to study chronic vascular rejection (CVR) in mice, the orthotopic aortic allograft. More recently we performed human arterial grafts into SCID/Beige mice reconstituted with human spleen cells. We report herein the differences in CVR lesions. MATERIAL AND METHODS: In the first model, recipient mice were C57BL/6 (H-2b), and donor mice were DBA/2 (H-2d). In the second model, terminal branches of the human superior mesenteric artery were transplanted into SCID/Beige mice in the infrarenal aorta. Human immune reconstitution was achieved by a single intraperitoneal injection of 30 x 10(6) human spleen cells. The presence of human lymphocytes and IgG was verified weekly. In both models, the vascular grafts were inserted in the infrarenal aortic position using the sleeve technique. The transplanted mice were sacrificed at 35 days after the operation. The grafts were analyzed by histology and morphometry. The mean intimal thickening was calculated based on transverse sections at 0.1-mm intervals. RESULTS: Typical CVR lesions developed with neointimal thickening, T-cell infiltration, and smooth muscle cell (SMC) proliferation in both models. In the mouse aortic model, disappearance of SMC in the media was noted in contrast to human arterial transplants, where the media remained intact. CONCLUSION: Other groups have noted that arteries conserve their media in clinical organ transplants. From this point of view, the lesions in the second experimental model (human arteries) better reflect the pathology of CVR in clinical transplantation than the murine aortic transplant model.

Human immune reconstitution with spleen cells in SCID/Beige mice.

BACKGROUND: We developed an original experimental model to study chronic vascular rejection (CVR) consisting of a graft of human mesenteric artery followed by human immune reconstitution into CB.17 SCID/Beige mice. Human immune reconstitution achieved after human PBMC injection has often been variable and incomplete. The aim of this work was to develop an alternative method to achieve a complete, functional human immune reconstitution. METHOD: After institutional authorizations, spleen cells were recovered from cadaveric organ donors. Single intraperitoneal injections of various doses of spleen cells were made into 70 CB.17 SCID/Beige mice. Reconstitution of the human immune system was monitored by flow cytometry (circulating human cells) and ELISA (human IgG). Colonization of murine lymphoid organs by human cells was studied by immunohistochemistry and flow cytometry. Evaluation of the immune function consisted of examination of CVR lesions in human arterial grafts. The animals were humanely killed at day 28. RESULTS: After injection of 30 to 40 x 10(6) spleen cells, the mice showed significant human CD3(+), CD19(+), and CD56(+) populations in peripheral blood. The mean human cells levels were, respectively, 8.2% +/- 5.4%, 2.9% +/- 1.2%, and 5.3% +/- 5.1%. Murine spleen and mesenteric lymph nodes were colonized by human T and B cells, while the murine thymus was only colonized by human T cells. Human IgG was detected in murine serum (65.9 +/- 63.3 mg/L) and typical CVR lesions were observed within the allogeneic grafts. CONCLUSION: Intraperitoneal injection of 30 to 40 x 10(6) human spleen cells into CB.17 SCID/Beige mice induces complete and functional human immune reconstitution allowing the study of CVR under human allogeneic conditions.

Stent-graft repair of thoracic aortic aneurysms.

Endovascular treatment of aortic disease has emerged as an alternative mode of treatment that is particularly attractive for patients with severe comorbidities who would not be ideal candidates for open surgery. Actually, short-term morbidity and mortality rates, of large series, compare favorably with those from surgery, and stent-graft placement is proving to be a safe, minimally invasive, and effective treatment for thoracic aortic diseases. However, although endoluminal interventions are minimally invasive, they are associated with complications, as are surgical methods. In this article, indications, technical aspects, and results of endovascular TAA repairs will be reviewed. We will also examine the advantages and limitations of stent-graft treatment. Finally, we will discuss the management of complications following aortic stent-graft implantation. We intentionally do not cover the topic of thoracic dissection, as it is being covered in another article in this volume.

Orthotopic aortic transplantation in mice: a new model of allograft arteriosclerosis.

BACKGROUND: Graft arteriosclerosis is a major cause of death after allotransplantation of organs such as the heart or the kidney. Aortic allotransplantation in mice is a useful experimental model to study the mechanisms of this pathology. However, the conventional heterotopic aortic model is limited by a high morbidity and is technically difficult to perform. We developed a new simple method for aortic transplantation in mice. METHODS: The infrarenal aorta from the donor mouse was anastomosed to the recipient's aorta at the same position using a sleeve technique. Orthotopic aortic transplantation was performed in 45 mice, 5 isografts and 40 allografts. No immunosuppression was given, and the mice were killed at day 15 or 30. The graft was examined macroscopically, and several histologic sections were made. RESULTS: The overall survival rate was 78%. The incidence of thrombosis was low (4 cases) compared with previously published series. Histology of aortas revealed typical aspects of rejection in the allografts with a chronic picture at day 30. No significant lesion was observed in isografts. CONCLUSIONS: We have developed a model of orthotopic aortic transplantation in mice. This new model is easy to carry out and has a low incidence of thrombosis, probably because there is no size discrepancy between donor and recipient aortic segment.

A new rejection criteria in the heterotopically placed rat heart by non-invasive measurement of Dp/Dtmax.

BACKGROUND: The heterotopic heart of rats has been a useful model in the evaluation of immunomodulatory protocols. Graft palpation usually determines the day of rejection. We present in this paper an original method of graft monitoring in allograft rejection. METHODS: Heterotopic cardiac abdominal transplantation was performed in Lewis isografts (n = 15) and in ACI to Lewis allograft (n = 15). A balloon connected to a measurement device was inserted in the left ventricle, and calculation of Dp/Dtmax was possible by recording the intra-left ventricular pressure. A ten-day follow-up was achieved with a daily comparison of palaption, ECG, and Dp/Dtmax. RESULTS: In transplanted hearts, Dp/Dtmax did not change in isografts but significantly decreased in allograft on posttransplantation Day 5 (PTD 5) vs PTD 0.1 and 3 (p < .01). Dp/Dtmax values on PTD 5 and 6 were also statistically significant in allograft vs isograft group (p < .01). Histological analysis at this time showed the occurrence of acute rejection in the allograft group. Graft palpation, and ECG remained normal until PTD 10 and no difference was observed between iso and allo groups. CONCLUSION: This study shows that daily measurement of Dp/Dtmax in heterotopic heart is made possible by our implantable system without interrupting the graft, and gives a more accurate definition of graft rejection than a combination of palpation and ECG. In addition, this method would seem desirable when differences in survival may be expected to be of lesser magnitude.

Simultaneous orthotopic transplantation of carotid and aorta in the rat by the sleeve technique.

Graft vascular disease (GVD) remains the major limitation to long-term survival after solid organ transplantation. Aortic or carotid allografts in rats have been shown to be useful models because similar changes to those observed in man develop within weeks. Both immunological and non-immunological factors influence the process of GVD and a method that could permit rapid multiple arterial allotransplantation in the rat would be of great value. We performed simultaneous orthotopic aortic and carotid allotransplantations in 25 rats. The vessels were anastomosed using a sleeve technique. No immunosuppression was given. The animals were killed at 15, 30, or 60 days and histological analyses of the grafts were performed. The overall survival rate was 80% and the incidence of technical failure was very low. The histopathological aspect revealed typical progressive GVD. In conclusion, we have developed a new model of simultaneous aortic and carotid transplantation in rats. This model, which incorporates a modification of the sleeve anastomosis, is rapid and yields an easy tool to investigate immunological and non-immunological processes driving GVD.

[Transhepatic percutaneous embolisation of a post-traumatic pseudoaneurysm of hepatic artery]. / Embolisation transhépatique percutanée d'un pseudoanévrisme post-traumatique de l'artère hépatique.

Pseudoaneurysm of the hepatic artery is a rare complication of blunt abdominal trauma. We report a case of post-traumatic pseudoaneurysm diagnosed several months after the initial traumatism in a 18-year-old man who presented recurrent abdominal pain. This pseudoaneurysm was successfully treated by association of both classical endovascular treatment and transhepatic percutaneous embolization.

[Towards a new management of acute traumatic aortic ruptures]. / Vers une nouvelle prise en charge des ruptures traumatiques aiguës de l'isthme aortique.

PURPOSE: The aim of this study was to evaluate the feasibility and safety of endovascular repair in acute traumatic aortic rupture on the basis of our experience with 16 patients. MATERIALS AND METHODS: From January 1996 to December 2001,16 patients, with a mean age 36 years, underwent repair of traumatic rupture of the aorta with the use of stent-grafts. All patients presented with coexisting injuries and 9 of 16 patients were hemodynamically unstable because of other injury. After a delay ranging from 9 to 245 days (mean 78 days), aortic stent-grafting was performed by a multidisciplinary team. All patients had regular follow-up with spiral CT and transesophageal echocardiogram. RESULTS: Stent-graft placement was successful in all patients with exclusion of false aneurysm. The duration of the procedure was about 120 min and mechanical respiratory assistance could be removed immediately in 80% of patients. Mean stay in the intensive care unit was 24 hours. One complication was noted: compression of the left main stem bronchus successfully treated with endoprosthesis. Maximum follow-up was 7 years. CONCLUSION: Endovascular stent-graft repair is a valuable technique and is emerging as an alternative technique for treating thoracic aortic injury in patients in whom coexisting injury increases the surgical risk.

[Indication of endovascular stent grafts for traumatic rupture of the thoracic aorta]. / Place des endoprothèses dans le traitement des ruptures traumatiques de l'aorte thoracique.

OBJECTIVE: The usual treatment of traumatic aortic rupture (TAR) is surgical. This invasive technique necessitating thoracotomy and ECC is associated with a mortality rate of more than 20% and a paraplegia risk of about 10%. New minimally-invasive techniques (aortic stent-grafting) are emerging as less risky alternatives to surgery. We report our experience in the percutaneous treatment of TAR with stent-graft via a surgical femoral cut-down. PATIENTS AND METHODS: Between 1996 and 2002, 23 patients (16-65-year-old, mean 36 years) were treated by thoracic stent-grafting. An informed consent was obtained for every patients. Thirteen patients had an acute or sub-acute TAR (1-8 months, mean 5 months) and five patients had chronic TAR (13-24 years, mean 17 years). The technique was done under general anaesthesia and each patient received a preoperative blood-pressure reduction treatment. During the procedure, anticoagulation (heparin) was given and hypotension was induced when the stent-graft was deployed. Direct positioning control was obtained by means of TEE. RESULTS: Eighty percent of patients were extubed immediately after the procedure. Bleeding was <150 ml. The primary success rate was 100% with one minor type 2 endoleak that was spontaneously resolved after 2 months. There was no case of mortality or paraplegia. There were three minor complications (17%), two haematomas at the arteriotomy site and one inflammatory syndrome characterised by slight fever, raised biological markers but with negative blood culture. CONCLUSION: Percutaneous aortic stent-grafting for TAR is a minimally-invasive technique, which constitute an interesting alternative to surgery. It only necessitates a femoral surgical cut-down compared to the thoracotomy and ECC associated with surgery. The complication rate is low and no mortality or major complication was encountered in our patients. Eventually, the long-term follow-up will allow a widening of indications.

[Leiomyosarcoma of the inferior vena cava]. / Léiomyosarcome de la veine cave inférieure.

Leiomyosarcoma of the inferior vena cava is a rare tumor of mesenchymal origin most commonly found in women. Clinical signs are non-specific. Imagery with ultrasound, CT, or MRI may strongly suggest the diagnosis, but it can only be confirmed by histologic examination of tissue obtained pre or intra-operatively. The tumor is slow growing but nonetheless carries a bad prognosis; it may grow to a large size before directly invading adjacent structures. Systemic spread is a late occurrence. Radical surgical resection is the only treatment which offers any hope for prolonged survival. Standard vascular surgical techniques are usually sufficient. Progress in the techniques of hepatectomy and liver transplantation have allowed the experienced surgeon to undertake the removal of retrohepatic lesions once considered unresectable. High-lying lesions adjacent to the hepatic veins or with thrombus extending into the proximal vena cava may require extracorporeal circulation with or without profound hypothermic circulatory arrest. The efficacy of chemotherapy, whether pre-operative for inaccessible tumors or post-operative for incompletely resected or recurrent tumor, is poorly defined and very limited.