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Biomedical subjects

V Donckier

Publications and source records attributed to V Donckier.

At least 19 recordsLinked to original sources

Domino hepatic transplantation using the liver from a patient with primary hyperoxaluria.

BACKGROUND: We report a case of domino liver transplantation using the liver harvested from a patient who underwent a combined liver and kidney transplantation for primary hyperoxaluria (PH). METHOD: A cadaveric liver transplantation was performed in a 19-year-old man with PH. In a second step, the PH liver harvested from the first patient was transplanted in a 69-year-old man with hepatitis C-related cirrhosis, not a candidate for a classic liver graft owing to multifocal hepatocellular carcinoma. RESULTS: At 8 months after transplantation, the domino recipient has normal hepatic function and no signs of tumoral recurrence, but he progressively developed hyperoxalemia, hyperoxaluria, and renal insufficiency. CONCLUSION: Regarding the favorable postoperative clinical evolution, domino liver transplantations using livers from PH patients may represent a new opportunity for marginal candidates for liver transplantation. However, the progressive renal insufficiency expected in such domino recipients should limit this procedure to selected cases.

Adult↗

Nondetection of sentinel lymph node with lymphoscintigraphy as a result of massive malignant invasion shown by positron emission tomography.

PURPOSE: The authors report the complementary roles of lymphoscintigraphy in sentinel node mapping and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in a massively invaded sentinel node. MATERIALS AND METHODS: A 49-year-old woman was referred to the authors' institution after the resection of a malignant melanoma (Clark IV, Breslow 5.25) of the right buttock. No evidence of regional or distant organ metastases was observed on bone scintigraphy or thoracoabdominal or cerebral computed tomographs. Preoperative lymphoscintigraphy showed drainage around a circular structure, without any node detected. F-18 FDG PET imaging detected an area of focal, markedly hypermetabolic activity at the same location. RESULTS: The focal, markedly hypermetabolic activity detected by F-18 FDG PET corresponded to a massively invaded sentinel node not shown by lymphoscintigraphy but found and removed at the time of surgery. Radical regional lymphadenectomy showed only one small additional lymph node micrometastasis detected after immunohistochemical staining for S-100 protein and HMB45 antigen. CONCLUSIONS: This case emphasizes the complementary roles of lymphoscintigraphy sentinel node mapping and F-18 FDG PET. Indeed, a massively invaded sentinel node may be detected by PET but missed by lymphoscintigraphy.

Female↗

Transplantation tolerance and mixed chimerism: at the frontier of clinical application.

Although the persistence of donor-type hematopoietic cells in low numbers (microchimerism) is well established in some transplant recipients, its relevance for graft acceptance is still a matter of debate. On the other hand, clonal deletion of donor-specific alloreactive cells associated with mixed chimerism (macrochimerism) has reliably produced long-term graft tolerance in pre-clinical models. So far, the cytoablative conditioning regimens required to achieve mixed chimerism have hampered the clinical development of such protocols. Here, we discuss recent observations suggesting that the deliberate induction of hematopoietic cell chimerism might become a feasible strategy to achieve transplantation tolerance in clinics.

Animals↗

Helical CT signs in the diagnosis of intestinal ischemia in small-bowel obstruction.

OBJECTIVE: The purpose of our study was to determine prospectively the value of helical CT and of various signs of ischemia in the context of acute bowel obstruction. SUBJECTS AND METHODS: All patients seen over a 3-year period with a CT diagnosis of small-bowel obstruction were included. There were 144 examinations in 142 patients. Images were interpreted prospectively with consensus by a fellow and an experienced gastrointestinal radiologist. Attention was focused on the presence of the following signs of strangulation and ischemia: reduced enhancement of the small-bowel wall, mural thickening, mesenteric fluid, congestion of small mesenteric veins, and ascites. A diagnosis of ischemia was made if enhancement of the bowel wall was reduced or if at least two of the other signs were found. Results were correlated with surgical findings in 73 cases and clinical follow-up in 71 cases. RESULTS: A diagnosis of ischemia was made at surgery in 24 patients. CT diagnosis was correct in 23 patients (96% sensitivity). There were nine false-positive diagnoses (93% specificity). The negative predictive value of CT was 99%. Reduced enhancement of the bowel wall had a sensitivity of 48% and specificity of 100%, mural thickening had a sensitivity of 38% and specificity of 78%, mesenteric fluid had a sensitivity of 88% and specificity of 90%, congestion of mesenteric veins had a sensitivity of 58% and specificity of 79%, and ascites had a sensitivity of 75% and specificity of 76%. CONCLUSION: Helical CT is a highly sensitive method to diagnose or rule out intestinal ischemia in the context of acute small-bowel obstruction.

Acute Disease↗

Sporadic carcinoid of the stomach: a highly proliferative disease with a probable role for p53 protein dysregulation.

We describe here one case of sporadic carcinoid of the stomach, occurring in a 65-year-old man. It is a rare, recently recognized entity, with only few cases reported in the literature. We were able to detect strong MIB-1 and p53 expression in this tumour, with 86 and 80% of tumoral cells positive, respectively. These data suggest that gastric sporadic carcinoids are a highly proliferative entity probably induced by dysregulation of p53 function.

Aged↗

Sentinel lymph node mapping in the management of high risk malignant melanoma.

In patients with malignant melanoma, the selective biopsy of the first draining lymph node, so-called the sentinel lymph node, allows to identify, with a low morbidity, the patients with nodal metastasis that require radical lymphadenectomy and adjuvant systemic chemotherapy. Herein, we report our initial experience in sentinel lymph node biopsy in 16 patients with malignant melanoma. The sentinel lymph node was localised using preoperative lymphoscintigraphy and injection of dye blue. Intraoperatively, the dissection was guided with a gamma probe and by the recognition of the blue nodes. In the 16 cases the sentinel lymph node was localised. In 50% of the cases, multiple sentinel nodes were demonstrated at lymphoscintigraphy and found during surgery. A limited postoperative morbidity was observed in three cases. Three patients presented nodal metastasis and underwent further radical lymphadenectomy. We conclude that sentinel lymph node mapping is a feasible and reproductive procedure. The preoperative lymphoscintigraphy is essential to identify multiple sentinel nodes and guide surgical dissection. The impact of this approach on the overall survival of patients with high-risk melanoma has still to be demonstrated in studies with a long follow-up.

Adult↗

CD40 ligation prevents neonatal induction of transplantation tolerance.

To investigate the consequences of CD40 engagement on the neonatal induction of transplantation tolerance, BALB/c mice were injected at birth with (A/J x BALB/c) F1 spleen cells together with activating anti-CD40 mAb and grafted 4 wk later with A/J skin. Whereas A/J allografts were accepted in mice neonatally injected with F1 cells and control Ab, they were acutely rejected in mice injected with F1 cells and anti-CD40 mAb. Neonatal administration of anti-CD40 mAb resulted in enhanced anti-A/J CTL activity, increased IFN-gamma, and decreased IL-4 production by donor-specific T cells in vitro. Experiments using anti-cytokine mAb and IFN-gamma-deficient mice demonstrated that CD40 ligation prevents neonatal allotolerance through an IFN-gamma- and IL-12-dependent pathway. Finally, we found that newborn T cells express less CD40L than adult T cells upon TCR engagement. Taken together these data indicate that insufficiency of CD40/CD40L interactions contribute to neonatal transplantation tolerance.

Animals↗

IL-12 prevents neonatal induction of transplantation tolerance in mice.

We investigated the effect of IL-12 on the induction of transplantation tolerance by neonatal injection of allogenic cells. We first observed that injection of newborn BALB/c mice with IL-12 and (A/J x BALB/c)F1 spleen cells prevented the Th2 alloimmune response induced by neonatal inoculation of F1 cells alone and allowed the differentiation of T cells secreting high amounts of IL-2 and IFN-gamma in mixed lymphocyte cultures with donor-type stimulators. Furthermore, IL-12 administration resulted in the emergence of anti-donor cytotoxic T lymphocyte responses although at lower levels than in control uninjected mice. In parallel, we found that mice injected at birth with IL-12 and F1 cells did not develop chimerism and were able to reject a donor-type skin graft as efficiently as control mice. We conclude that IL-12 inhibits the Th2 polarization of the newborn response to alloantigens and prevents thereby the establishment of transplantation tolerance.

Animals↗

Contribution of computed tomography to decision making in the management of adhesive small bowel obstruction.

BACKGROUND: In adhesive small bowel obstruction, the early recognition of complications such as strangulation or volvulus is essential to choose between surgical or conservative initial treatment. The objective of this study was to determine prospectively the contribution of computed tomography (CT) to decision making in the management of these patients. METHODS: Patients with suspected adhesive small bowel obstruction had CT at admission. Patients with CT signs of volvulus or strangulation and/or clinical signs of peritoneal irritation underwent urgent surgery; other patients had conservative initial treatment. RESULTS: Fifty-four patients were evaluated. CT demonstrated signs of strangulation or volvulus in 19 patients, including three with signs of peritoneal irritation. Within this group, urgent laparotomy was performed in 17 patients and confirmed the CT diagnosis in 16. Thirty-seven patients without clinical or CT signs of complications had initial conservative treatment; among them, seven of 12 with a distal obstruction determined by CT required a delayed operation for persisting obstruction, compared with two of 25 patients with a proximal obstruction (P < 0.01). CONCLUSION: CT is useful for the evaluation of adhesive small bowel obstruction, to detect accurately patients with complications who require urgent operation and to determine the location of the adhesion, which represents a significant prognostic factor for success of conservative treatment.

Adult↗

Isolation and infusion of donor CD34+ bone marrow cells in cadaver kidney transplantation.

BACKGROUND: Infusion of donor bone marrow cells induces tolerance in allograft models. CD34+ stem cells present in human bone marrow could be endowed with tolerogenic properties. METHODS: CD34+ stem cells were isolated from bone marrow extracted from vertebral bodies of cadaveric donors. Donor CD34+ cells (0.6-3.7 x 10(6)/kg) were infused during surgery in 10 kidney transplant recipients receiving OKT3 as induction therapy. Chimerism was investigated using nested PCR for donor-specific HLA alleles. RESULTS: The infusion of CD34+ stem cells was perfectly tolerated. Five patients remained free of acute rejection at follow-up, 47-325 days post-operatively. The five other patients underwent a single episode of corticosensitive acute rejection. Long-term chimerism was not induced in the seven patients investigated for the persistence of donor DNA. CONCLUSIONS: Infusion of donor CD34+ stem cells in kidney transplantation is safe. The clinical usefulness of the procedure remains to be established.

Adult↗

Late liver metastases of small bowel leiomyoma. The difficulty in assessing malignancy in gastro-intestinal smooth muscle tumours.

Two cases of small bowel tumour, resected and considered as benign leiomyomas, are reported. Both developed late hepatic metastases, 6 and 8 years after surgery respectively, diagnosed as leiomyosarcoma. Emphasizing the difficulties in assessing malignancy of these tumours and considering local and far dissemination, a long-term follow-up is recommended after surgical resection.

Diagnosis, Differential↗

Long-term results after surgical treatment of renal hyperparathyroidism when fewer than four glands are identified at operation.

BACKGROUND: When fewer than four parathyroid glands are discovered during cervical exploration in cases of renal hyperparathyroidism, some have suggested that the glands could be resected and that no parathyroid tissue should be grafted. The aim of the present study was to evaluate this approach. Indeed, no detailed follow-up of such patients has been reported so far. STUDY DESIGN: Between September 1979 and July 1995, 157 patients underwent a cervical exploration for renal hyperparathyroidism in our department. In 23 cases, fewer than four parathyroid glands were found. The present study reports the results of 16 of these patients who did not undergo autotransplantation with parathyroid tissue after resection of all identified glands. RESULTS: At their last visit, four patients had normal blood levels of intact parathyroid hormone 14 to 71 months (median 60 months) after parathyroidectomy. The parathyroid hormone was not detectable in 2 patients at 16 and 76 months after operation. It was elevated in the 10 remaining patients, but the disease required no treatment or could be controlled medically in 7 patients with a follow-up ranging from 12 to 100 months (median 33 months). Two patients needed reoperation, one at 14 and one at 45 months after the first operation. An ectopic gland was found in both cases. The last patient refused further surgical treatment and died after 13 months. CONCLUSIONS: In most cases, autotransplantation of parathyroid tissue is not necessary when fewer than four glands are identified during parathyroidectomy. When grafting was omitted, 14 of 16 patients had normal or elevated blood levels of intact parathyroid hormone 10 to 100 months after parathyroidectomy (median 45 months). However, in two patients, intact parathyroid hormone was persistently undetectable for 16 to 76 months. This suggests that parathyroid tissue should be cryopreserved for delayed autotransplantation when the surgeon chooses not to graft parathyroid tissue.

Calcium↗

Tolerance in liver transplantation: facts and perspectives.

Today, liver transplantation is the treatment of choice for most of the patients with endstage liver failure. Nevertheless, immunosuppressive regimens are not yet optimal; rejection still represents the first cause of graft loss, and infections and malignancies related to the non specific immunosuppression are a major source of morbidity and mortality. Therefore, the development of protocols aiming to induce transplantation tolerance--the survival of the graft without immunosuppression--represents a crucial challenge for the future. In the present report, we discuss two different approaches in this perspective. First, as compared with other organ, liver graft may present a particular propension to induce chimerism. As this phenomenon could promote allograft survival, the enhancement of chimerism by administration of donor cells, simultaneously with the transplantation, may constitute a new therapeutic strategy to induce tolerance. Second, experimental observations indicate that the initiation of the immune reaction in the liver may preferentially induce a TH2-type response. As TH2 lymphocytes are poor effector of acute rejection, this phenomenon could contribute to the spontaneous survival of liver graft and their tolerogenic effect observed under some experimental conditions. However, the capacity of TH2 cells to induce lymphoproliferative disease and their possible role in chronic rejection will probably represent a major limitation for clinical use of this strategy.

Animals↗

Critical role of interleukin 4 in the induction of neonatal transplantation tolerance.

Neonatal injection of semiallogeneic cells is known to promote differentiation of donor-specific CD4+ T cells into TH2-like cells in the peripheral lymphoid organs. We reasoned that the propensity of neonatal T cells to synthesize high levels of IL-4 might be involved in this polarization of the alloreactive response and thereby in the development of neonatal transplantation tolerance. First, analysis of cytokine gene expression in lymph nodes after neonatal injection of 10(7) (A/J x BALB/c)F1 cells in BALB/c mice indicated that IL-4 but not IL-2 is rapidly produced by CD4+ cells after allogeneic challenge in vivo. To determine whether the early production of IL-4 was involved in the establishment of allotolerance, BALB/c mice neonatally injected with (A/J x BALB/c)F1 spleen cells received on days 1 and 3 after birth 1 mg of anti-IL-4 mAb (11B11) or the same amount of control mAb. When grafted with A/J skin at 4 weeks, 88% of mice treated with control mAb retained their graft for more than 50 days, whereas rejection occurred within 30 days in 93% of mice treated with anti-IL-4 mAb. Analysis of T cell functions after in vitro restimulation with A/J spleen cells indicated that early IL-4 neutralization did not prevent donor-specific CTL unresponsiveness but allowed the emergence of alloreactive T cells secreting increased levels of IL-2 and IFN-gamma. We conclude that early production of IL-4 is critical for the establishment of neonatal transplantation tolerance in this strain combination, which has disparities across the entire H-2 region.

Animals↗