Disorders of coagulation unrelated to xenograft rejection following pig-to-cynomolgus kidney transplantation.
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Animals↗
Biomedical subjects
J Klempnauer
Publications and source records attributed to J Klempnauer.
Changes of antigenicity and loss of immunogenicity in long-standing class I MHC disparate pancreas allografts.
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Animals↗
A primate model for discordant pig to primate kidney xenotransplantation without hyperacute graft rejection.
Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to intragraft deposition of preformed recipient immunoglobulin M (IgM) antibodies with subsequent complement activation finally leading to complete and rapid destruction of the xenograft (hyperacute graft rejection, HAR). Current therapeutic strategies for abrogation of HAR include pretransplant antibody absorption by specific or nonspecific extracorporeal column perfusion, ex vivo donor organ perfusion, the administration of substances interfering with complement activation, or even the genetic alteration of the donor. Here, in the pig to cynomolgus monkey species combination, we are describing an experimental model for abrogation of HAR by using large, relative to the recipient weight, oversized donor kidneys as xenotransplants. Porcine kidney xenotransplantation (n = 15) was performed using large white pigs of different weights and ages as organ donors and cynomolgus monkeys as recipients. In grafts with an organ weight below 50 g (20 to 48 g, median 25 g), primary nonfunction (PNF) of the porcine kidney was observed in 11 out of 12 cases and complete HAR in 5 out of 12 experiments. In contrast, none of three grafts with a donor organ weight >70 g showed signs of HAR or PNF. In one animal, a second porcine kidney from the same donor (23 g) was successfully transplanted immediately after HAR and subsequent removal of a first porcine kidney (20 g). By using appropriate immunohistochemistry stainings of reperfusion biopsies, profound deposition of recipient natural antibodies in both small and large xenografts was shown, with only scarce deposition of C3 and C5b-9 in the latter, indicating only incomplete intragraft activation of the complement cascade in these organs. Intraoperative cardiac output (CO) measurements performed in 7 experiments demonstrated a 20 to 50% decrease in CO following reperfusion in 6 out of 7 grafts irrespective of the donor organ weight. The intraoperative decrease in CO was not associated with perioperative morbidity or mortality. The use of oversized doner kidneys can enable the study of a variety of immunologic and physiologic sequela beyond HAR associated with life-supporting discordant primate kidney transplantation.
Acute Disease↗
Influence of suture material and technique on end-to-end reconstruction in tracheal surgery: an experimental study in sheep.
Resection and end-to-end anastomosis of the trachea represent the preferred treatment for various benign and malignant diseases involving the trachea. Various studies have reported conflicting results with alternative techniques and suture materials for tracheal anastomosis. Our objective was to evaluate three frequently used techniques concerning stenosis rate and histological reaction in a large-animal species. Tracheal resection of 3 cm and end-to-end anastomosis were performed in 15 sheep with the use of three different techniques. In the first group, an interrupted suture with polyglactin, in the second group an interrupted suture with polydioxanone, and in the last group a continuous suture with polypropylene were used. The animals were killed 1, 2, 4, 8, and 24 weeks postoperatively. The luminal stenosis was determined by means of computerized planimetry. All three techniques appeared to be appropriate for tracheal anastomosis. The luminal stenosis developed within the first 8 weeks after surgery. A cross-sectional area of approximately 40-70% was finally achieved. Differences dependent on the suture material are less important than the technical details of the operation.
Anastomosis, Surgical↗
Breaking strength of native and sutured trachea. An experimental study on sheep trachea.
Tracheal anastomoses are, even more so than other sutures, often only possible to prepare under tension and thus in danger of breakage. No information is available regarding native tracheae and freshly sutured tracheae. For this reason, our objective was to examine the tensile strength of native tracheae and compare it with freshly sutured specimens. Fresh tracheae were collected from the local slaughterhouse within 30 min of slaughter. With the help of a suitable holding device, 24 fresh tracheae were mounted on a material testing machine and stretched to breaking point, during which the force and distance required were recorded. The same study was carried out on each 10 freshly anastomosed tracheae using three different suturing techniques. The mean value of the maximum force required for native tracheae was 198 N. With continuous suturing (polypropylene), a mean value of 171 N was attained, and with single interrupted suturing (polydioxanone and polyglactin 910), 123 N, respectively, 108 N. Differences between the groups proved to be highly significant. With respect to the mechanical strain from traction, the continuous suture proved to be statistically identical to native tracheae, whereas single interrupted sutures revealed a considerably lower stability under burden. Therefore, the continuous suture is of advantage in respect of the mechanical strain from traction and the suture protection of tracheal anastomoses. Further studies with differing survival times in vivo with this method provide insight into the stability of tracheal anastomoses during the healing process.
Anastomosis, Surgical↗
Prevention of peritoneal carcinomatosis from human gastric cancer cells by adjuvant-type intraperitoneal immunotherapy in a SCID mouse model.
PURPOSE: We analyzed the effect of intraperitoneal immunotherapy in an animal model mimicking locoregional dissemination of tumor cells during resection of advanced tumors. METHODS: We first established a tumor model with human gastric cancer cells (MKN-45) in the peritoneal cavity of CB-17-SCID mice. Three hours following the injection of tumor cells into the peritoneal cavity, mAb 17-1A alone and in combination with human LAK cells were given intraperitoneally at different dosages. The results were quantified by determining the weight of the peritoneal tumor masses. RESULTS: After intraperitoneal administration of 17-1A mAb, a tumor reduction could be shown (median tumor mass after 10 microg mAb: 171 microg; after 100 microg: 130 microg) when compared with the control group (632 microg). Following a combined therapy with mAb and LAK cells, a statistically significant tumor reduction could be observed (after 10 microg mAb + 20-50 x 10(6) LAK cells: 80 microg; after 100 microg mAb + 20-50 x 10(6) LAK cells: 12 microg, p = 0.0005). With specific dosages of antibody and LAK cells it was even possible to achieve complete tumor clearance. CONCLUSIONS: Intraperitoneal immunotherapy reduces the peritoneal tumor masses and can even prevent the peritoneal carcinomatosis formation.
Animals↗
Surgery for exocrine pancreatic cancer--who are the 5- and 10-year survivors?
38 of 306 patients survived beyond 5 years after resection of an exocrine pancreatic carcinoma during a period from 1971 to 1993. Amongst the long-term survivors there were 12 patients with ductal, 22 with ampullary, 3 with distal bile duct and 1 with duodenal cancer. An active operative strategy was employed in order to resect the tumor whenever this was surgically possible. In a a retrospective analysis we have identified prognostic factors influencing long-term survival. The long-term prognosis was largely dependent on the tumor entity. Ampullary carcinomas had a significant advantage in terms of long-term survival over all other tumor entities. Other prognostic factors associated with long term survival were curative tumor resection, absence of lymphatic and distant metastases and a low tumor malignancy.
Adult↗
Extended resections of ductal pancreatic cancer--impact on operative risk and prognosis.
114 patients received a standard and 75 patients an extended resection of ductal pancreatic carcinoma at the Hanover Medical School, Germany, from 1971 until 1993. Standard pancreatic resections were combined with vascular resection and reconstruction in 46 and additional organ resections in 45 cases. Vascular resections affected the mesentericoportal vein in 37, the common hepatic in 10 and the superior mesenteric artery in 7 cases. Pancreas resections were combined with total gastrectomy in 23, partial colectomy in 17, hemihepatectomy in 14, adrenalectomy in 8 and nephrectomy in 5 patients. Curative resections could be accomplished in 86% of patients without and 81% with extended resections. Additional vascular resections neither increased the operative risk nor deteriorated the long-term prognosis after resection. Additional organ resections, however, significantly increased the risk of lethality and impaired the long-term prognosis. Especially resections of synchronous hepatic metastases and colectomies were associated with a poor survival probability.
Carcinoma↗
Benign schwannoma of the liver with cystic changes misinterpreted as hydatid disease.
The rare event of a benign mesenchymal tumor of the liver is described since its cystic transformation resembled hydatid disease through the presence of Echinococcus. Ultrasound and computerized tomography showed a cystic mass within the liver of a 57 year-old woman with upper abdominal pain. This was interpreted as hydatid disease and an evacuation procedure was performed. The histopathology of a minute specimen was interpreted as consistent with chronic inflammation in a cyst wall. Five years later, a recurrence of the parasite was suspected, and complete excision of the mass and resection of a bile fistula was performed. The histopathological examination revealed a large benign schwannoma with regressive cystic changes, proven by positive immunoreaction for the neurogenic marker S-100 protein. Revision of old paraffin blocks of tissue taken during the first operation was able to retrospectively confirm the identical tumor by the same markers. Occurrence of schwannomas in parenchymatous organs or the retroperitoneum is extremely rare and may lead to asymptomatic growth with cystic changes, causing considerable difficulties in imaging procedures. Overall, the primary complete excision of cystic masses within the liver seems to be the best approach in discovering their real nature and to ultimately cure them.
Diagnostic Errors↗