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Acute antibody-mediated rejection (AMR) remains a challenge after kidney transplantation (KT). As there is no clear-cut treatment recommendation, accurate information on current therapeutic strategies in real-life practice is needed. KT recipients from the multicenter Swiss Transplant Cohort Study treated for acute AMR during the first post-transplant year were included retrospectively. We aimed at describing the anti-rejection protocols used routinely, as well as patient and graft outcomes, with focus on infectious complications. Overall, 65/1669 (3.9%) KT recipients were treated for 75 episodes of acute AMR. In addition to corticosteroid boluses, most common therapies included plasmapheresis (56.0%), intravenous immunoglobulins (IVIg) (38.7%), rituximab (25.3%), and antithymocyte globulin (22.7%). At least one infectious complication occurred within 6 months from AMR treatment in 63.6% of patients. Plasmapheresis increased the risk of overall (hazard ratio [HR]: 2.89; P-value = 0.002) and opportunistic infection (HR: 5.32; P-value = 0.033). IVIg exerted a protective effect for bacterial infection (HR: 0.29; P-value = 0.053). The recovery of renal function was complete at 3 months after AMR treatment in 67% of episodes. One-year death-censored graft survival was 90.9%. Four patients (6.2%) died during the first year (two due to severe infection). In this nationwide cohort we found significant heterogeneity in therapeutic approaches for acute AMR. Infectious complications were common, particularly among KT recipients receiving plasmapheresis.

Positron Emission Tomography (PET) using (18)F-fluorodeoxyglucose (FDG) associated with computed tomography (CT) is increasingly used for the detection and the staging of pancreatic cancer, but data regarding its clinical added value in pre-surgical planning is still lacking. The aim of this study is to investigate the performance of FDG PET associated with contrast-enhanced CT in detection of pancreatic cancer.

Embryonic stem cells (ESC) can differentiate into all cell lineages, and ESC-like cells were shown to induce hematopoietic chimerism and tolerance in allogeneic models. The aim of our study was to test the capacity of mouse ESC (mESC) to engraft in rats in a xenotransplantation setting. Forty-six rats were transplanted intravenously with 1 million mESC, without immunosuppression (group 1, n = 23) or with cyclosporine (group 2, n = 23). Three months after mESC transplantation, skin grafts were performed from allogeneic, xenogeneic identical to mESC, or xenogeneic third party donors. At day 27 post-transplant, we detected circulating mouse cells in the blood of 4/23 and 5/23 animals of group 1 and group 2, respectively. Chimerism was confirmed by PCR. We also identified long-term surviving murine cells within livers of chimeric animals. Skin grafts showed no difference in survival between allogeneic and xenogeneic donors. Transplantation of xenogeneic mouse ESC induced short-term chimerism in the blood and persistent tissue chimerism in the liver of recipient rats, but did not induce tolerance to skin grafts. Improved immunosuppressive protocols should be tested to prolong chimerism and allow tolerance.

During the past 30 years, there has been remarkable progress in our understanding of the pathogenesis of squamous cell carcinoma of the anus. It is now accepted that anal cancer is a sexually transmitted disease, which can be cured using a combination of chemo- and radiotherapy. The biology of anal cancer remains to be elucidated, as do the molecular mechanisms involved in resistance to chemoradiation. The contribution of HIV infection to tumour progression currently represents an area of intensive investigation. Finally, the growing numbers of AIDS patients who experience prolonged survival represent a population at risk. In the future, cytological screening of male homosexuals with an anal Papanicolaou test may help in identifying high-grade dysplasia and preventing anal cancer.

The aim of the present study was to determine whether certain components of nonmyeloablative regimens for hematopoietic cell transplantation might compromise the growth of hematopoietic progenitors.Porcine peripheral blood progenitor cells (PBPC) were cytokine-mobilized, collected by leukapheresis, and cryopreserved using 5% dimethyl sulfoxide and 6% hydroxyethyl starch. The influence of cryopreservation on PBPC was tested in vitro by enumeration of colony-forming units (CFUs) in methylcellulose and cobblestone area-forming cell (CAFC) subsets in stromal-associated long-term cultures on fresh and frozen PBPC. The effects of mycophenolate mofetil (MMF) on porcine PBPC and baboon and human bone marrow (BM) were tested in vitro by adding varying doses of MMF to the CFU assays. One baboon was treated with increasing doses of MMF (100-500 mg/kg per day continuously intravenous), and sequential BM aspirations were tested for CFU content.Fresh cytokine-mobilized PBPC had similar frequencies of progenitor cells when compared with porcine BM. Freezing-thawing of PBPC had no effect on porcine CFUs but reduced the recovery of CAFCs by more than 90%. In vitro, MMF completely inhibited the development of porcine and human CFUs at a concentration of 1 microg/mL and of baboon CFUs at levels between 10 and 100 microg/mL. Plasma-free mycophenolic acid levels of 10 to 30 microg/mL were associated with decreased CFUs in the BM.Cryopreservation and MMF potentially prevent engraftment of porcine PBPC by reducing the content or development of progenitor cells. These results indicate that the use of fresh PBPC might improve the induction of mixed hematopoietic chimerism and raise the possibility that use of high doses of MMF in the poststem cell transplant may compromise engraftment.

Xenogeneic islets could provide an unlimited source of tissue for the treatment of diabetes, and could in theory be transplanted repeatedly in a recipient. However, little is known on the consequences of islet re-transplantation in a recipient who has rejected a first graft. In this study, we investigated the functional consequence of xeno islet re-transplantation in mice sensitized with islets from different species. Sprague-Dawley (SD)-rat islets transplanted in sensitized C57/Bl6 mice that rejected either SD- or Lewis-rat islets underwent accelerated rejection. However, accelerated rejection was not found in mice sensitized with pig or human islets, suggesting that accelerated rejection was species specific. Immunohistochemistry showed increased binding of antibodies and accelerated leucocyte infiltration on re-grafted islets in sensitized mice. In situ apoptosis detection indicated that islet cell apoptosis was correlated with the time of leucocyte infiltration, but not with the time of antibody binding. In vitro experiments with cultured islet cells showed that although antibody binding was increased after incubation with sensitized mouse serum, islet cell cytotoxicity was not increased, suggesting that humoral immunity did not play a direct role in islet destruction. These results indicate that there is a cell-mediated, species-specific accelerated rejection after re-transplantation of xenogeneic islets.

The pig is being investigated as an organ donor for humans. Induction of immunologic tolerance to pig tissues in primates would overcome the major immunologic barriers to xenotransplantation. A proven method of inducing tolerance to allografts is by the induction of mixed hematopoietic chimerism by bone marrow transplantation. We are therefore investigating induction of mixed hematopoietic chimerism in the pig-to-baboon model.To obtain large numbers of pig hematopoietic cells, leukapheresis was used to collect blood cell products in miniature swine (n = 5) after progenitor cell mobilization by use of a course of hematopoietic growth factors (cytokines), consisting of porcine interleukin 3, porcine stem cell factor, and human granulocyte colony-stimulating factor.Cytokine therapy and leukapheresis were well tolerated. Cytokine therapy increased the total white blood cell count and allowed large numbers of leukocytes (60 x 10(10)) to be obtained by apheresis, of which approximately 0.1% were granulocyte-erythrocyte-monocyte-megakaryocyte colony-forming units (CFU-GEMMs), which are considered to be representative of hematopoietic progenitors with multi-lineage potential.The combination of cytokine therapy and leukapheresis enables hematopoietic progenitor cells to be obtained safely from miniature swine.

Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose alpha1-3 galactose (alphaGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-alphaGal IgG. Levels of PRA, anti-alphaGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%). Anti-alphaGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-alphaGal IgG, catabolism of anti-alphaGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-alphaGal IgG level it would be necessary to use IVIG depleted of this antibody.

Although aneurysms and pseudoaneurysms of the splenic artery may result in life-threatening hemorrhage, their etiology, mode of presentation, and surgical strategy seem to differ. In an attempt to clarify their management, we reviewed our experience with aneurysms and pseudoaneurysms of the splenic artery.Between 1977 and 1997, 10 patients were operated on for true aneurysm and 6 for pseudoaneurysm of the splenic artery.True aneurysms required resection because of rupture (n=7), size (n=2), and anticipated pregnancy (n=1). They remained asymptomatic unless rupture had occurred. Treatment consisted in aneurysmectomy with preservation of the pancreas and spleen when asymptomatic and required splenectomy or splenopancreatectomy when ruptured. Pseudoaneurysms were always associated with chronic pancreatitis and symptoms had lasted from several hours to 4 weeks prior to hospitalization. Caudal splenopancreatectomy was required in all but one case.To contrast true aneurysms, pseudoaneurysms most often present with massive or intermittent bleeding. While the spleen and pancreas should be preserved when treating asymptomatic true aneurysms, management of ruptured aneurysms and pseudoaneurysms of the splenic artery usually consists of splenectomy or splenopancreatectomy.

Pig islets are considered the best alternative to human islets in the treatment of insulin-dependent diabetes. Pigs could represent a potential islet donor for xenotransplantation in humans because of the close similarity between human and porcine insulin and the theoretically unlimited availability of porcine pancreas. From November 1991 to January 1997 we performed 221 pig islet isolations from 3 pig sources: group 1: minipigs (age 9-18 months) and white pigs (3-8 months), group 2: large white pigs (5-8 months), group 3: large white pigs (12-24 months). Islets were isolated according to a semi-automated method using enzymatic digestion and purification through discontinuous Euro-Ficoll gradients. The pancreases were surgically removed in our laboratory for group 1, while pancreases from groups 2 and 3 were removed at the slaughterhouse with an average warm ischemia time of 15 minutes. In vitro islet function was assessed by static incubations and perifusions, and in vivo islet function by transplantation under the kidney capsule of nude diabetic mice. The results were as follows: [table: see text] Insulin secretion increased twofold after in vitro glucose stimulation. We obtained restoration of euglycemia in diabetic mice which survived > 3 months after the graft and returned to diabetes after nephrectomy. This study shows that our isolated pig islets are viable and functional in vitro and in vivo after transplantation.

We report on a patient with alcoholic chronic pancreatitis and intermittent upper gastrointestinal haemorrhage. Old blood was seen in the duodenum but no bleeding source could be identified by endoscopy. Computed tomography scanner and angiography disclosed an arterial pseudoaneurysm of the pancreatic tail, and left splenopancreatectomy was performed. In cases of upper gastrointestinal haemorrhage, the pancreas should be considered as a bleeding source if endoscopies remain negative and the patient presents with chronic pancreatitis.

Is surgery for primary hyperparathyroidism easier when methylene blue (MB) is given preoperatively? This retrospective study compares the durations of interventions for primary hyperparathyroidism carried out after i.v. MB administration to those when no MB was given. Over a period of 20 years (June 1976 to December 1996), 175 consecutive patients (56 men and 119 women, with ages ranging from 16 to 92, mean 59.6) were operated upon for primary hyperparathyrodism; 55 were operated before February 1986--the period when BM was introduced routinely, and 120 after. Thirty-two other patients were excluded from the study: 14 had had a previous cervicotomy and 18 another procedure in addition to the parathyroidectomy (usually on the thyroid gland), two conditions which prolonged the time devoted to parathyroid identification and excision. Preoperative calcemia averaged 2.97 mmol/L (2.34 to 4.59) and mean preoperative PTH was equal to 2.6 times the upper normal limit (0.5 to 24.1). Both groups were similar for as age, sex, preoperative calcium and PTH, and histologies. Methylene blue was administered intravenously (5 mg/kg diluted in 500 cc of 5% glucose) over a period of time of one hour starting two hours prior to surgery. All 175 procedures were performed by two surgeons and duration of surgery was recorded from the anesthesiologist's notes. There were 149 adenomas (85%), 24 hyperplasias (14%), a combination of both in two, and unspecified in two others. Except for a case of acute lower back pain synchronous to the injection of the dye (which was immediately stopped), MB was well tolerated. Mean duration for the 55 interventions performed without MB was 68 minutes (35 to 140, median 60), compared to 49 minutes for the 120 procedures carried out after MB had been given (20 to 155, median 45). Differences in operative, times were highly significant (p < 10(-6) and represented a gain of time of 27%. Surgery for primary hyperparathyroidism was significantly shorter when it was preceded by the administration of MB, a dye which facilitates the identification of pathologic parathyroid gland(s).

To review patients who presented lesions of the pancreas following blunt abdominal trauma, in order to determine which elements contributed to or on the contrary delayed the diagnosis. Construction of a diagnostic procedure which could be followed in order to maximize the rapidity and efficency of treatment.

Pseudocysts of the pancreas may require drainage or resection during their evolution. External drainage can be considered as a treatment of first resort with low related morbidity. It also offers a means of treating patients with major contraindications for surgery. In our experience, however, only 55% of external drainages prove successful. Therefore, surgical treatment, even at the cost of low-rate morbidity, remains the only final treatment for complications linked to pseudocysts of the pancreas. In the long term, however, these results depend on the etiology of the pseudocysts.

evaluation of the clinical and radiological criteria for laparotomy in intestinal lacerations after a blunt abdominal trauma. Determination of the different radiological signs from the CT scan and the sensitivity of this examination in the diagnosis of intestinal lacerations.

10% of chronic pancreatitis (CP) cases are complicated by splenic vein thrombosis (SVT) which is responsible for upper digestive haemorrhages. To improve our approach to treatment we reviewed 30 cases of SVT associated with CP treated in our centre from 1985 to 1995. 14 patients were treated conservatively. Six of them were refused for surgery due to extension of splenic vein thrombosis into the portal vein. Two patients without extrinsic compression of the vein were treated with anticoagulants. 16 patients were treated by surgery with low morbidity and without mortality. The standard treatment in fourteen cases was splenopancreatectomy. The average follow-up of seven years shows that these patients have preserved their body mass index (BMI). The results suggest that early surgical intervention is beneficial in preventing progression of SVT to the portomesenteric vein.

Preservation of physiological endocrine pancreatic function represents a major problem in pancreatectomised patients. In 40 to 100%, pancreatic resection can result in diabetes, which is often difficult to manage. Islet autotransplantation has been proposed to prevent this severe metabolic consequence.