Splenic Autotransplantation Research Articles

Optimal site and amount of splenic tissue for autotransplantation.

Clinical and basic studies have documented a high susceptibility to pneumococcal infection in asplenic humans and animals. It has been suggested that autotransplantation of splenic tissue might be a method of providing host resistance when total splenectomy is necessary. However, the effect of splenic autograft has remained controversial. This study was performed to evaluate the most effective site and amount of splenic autograft using rats. Rats were divided into five groups for the purpose of determining the site of splenic autotransplantation: splenectomy, sham operation, implantation into the omental pouch, intraperitoneal implantation, and intramuscular implantation. For determining the amount for autotransplantation, the rats were divided into seven groups: splenectomy, sham operation, and implantations of 25, 50, 100, 200, or 300 mg of splenic tissue. All animals were challenged with Streptococcus pneumoniae type 6, 16 weeks after surgery. Howell-Jolly bodies appeared postsplenectomy, but disappeared in the implanted rats 16 weeks after the operation. Histologically, the implanted tissue was indistinguishable from that of a normal spleen. Pneumococcal clearance from the bloodstream and survival rate were significantly higher in rats implanted in the omental pouch as compared with splenectomized rats. Intraperitoneal and intramuscular implanted rats did not show a significant difference from the splenectomized rats. More than 50% of splenic tissue for autograft showed a significant increase in pneumococcal clearance and survival rate as compared with that of splenectomized rats. It was suggested that the most effective site of autotransplantation is the omental pouch and approximately 50% of the whole spleen would be necessary for prevention from sepsis.

Splenic autotransplantation and the immune system. Adequate testing required for evaluation of effect.

The risk of severe infections after splenectomy, even after many years, is now well established. In attempts to prevent these infections, spleen-saving techniques, including autotransplantation of spleen fragments, have been performed, when possible in combination with vaccination. The problem in autotransplantation is the evaluation of functional activity. The results of the tests used until now often do not seem to correlate very well with the risk of developing an overwhelming postsplenectomy infection (OPSI). This may be related to the fact that the tests used evaluate general functions, and not specific spleen-related functions, such as the capacity to mount a primary response to certain polysaccharide antigens present in the capsule of bacteria known to cause OPSI. In this review, the significance of the spleen in the human immune system is discussed and the effects of splenectomy are described, including the precautions that can be taken to diminish the risk of postsplenectomy infections and sepsis. It appears that postsplenectomy vaccination is more successful when recently developed protein-conjugated polysaccharide vaccines are used. Because the present testing of the function of spleen autotransplants is not adequate, we suggest that new tests should be developed, employing appropriate polysaccharide antigens.

Splenic autotransplantation: I. Experimental study : T. Ohya. J Jpn Soc Pediatr Surg 26:83–89, (February), 1990

Splenic autotransplantation: I. Experimental study : T. Ohya. J Jpn Soc Pediatr Surg 26:83–89, (February), 1990

Splenic autotransplantation: II. Clinical study in patients with idiopathic thrombocytopenic purpura : T. Ohya. J Jpn Soc Pediatr Surg 26:90–96, (February), 1990

Splenic autotransplantation: II. Clinical study in patients with idiopathic thrombocytopenic purpura : T. Ohya. J Jpn Soc Pediatr Surg 26:90–96, (February), 1990

Splenectomy Does Not Influence Outcome of Pneumococcal Septicemia in a Porcine Model

The existence of the overwhelming postsplenectomy infection syndrome in adults after traumatic splenectomy is controversial. Due to the similarity of the porcine immune system to man we chose the pig to study subsets of peripheral mononuclear cells after splenectomy and resistance to experimental Pneumococcal infection after splenic surgery and specific immunization. Female miniature pigs were assigned to four operative groups: sham operation, splenectomy, splenic resection, and heterotopic splenic autotransplantation. Hematologic and flow cytometric analysis of mononuclear cells and their subsets revealed a marked leukocytosis following splenectomy and autotransplantation but no significant shift in monocyte and B-cell numbers. Response of leukocytes to septicemia, bacterial elimination from peripheral blood, and mortality were not affected by splenectomy or spleen-preserving operations. Mortality of splenectomized animals was 18%, compared to 42% in sham-operated controls (difference not significant). Immunization protected animals from development of leukopenia, and led to an enhanced bacterial elimination, and a significantly decreased mortality of 5%, compared to 48% in nonimmune animals. Thus our data do not show significant effects of splenectomy on subsets of porcine mononuclear cells or on resistance to experimental Pneumococcal septicemia.

Splenectomy Does Not Influence Outcome of Pneumococcal Septicemia in a Porcine Model

The existence of the overwhelming postsplenectomy infection syndrome in adults after traumatic splenectomy is controversial. Due to the similarity of the porcine immune system to man we chose the pig to study subsets of peripheral mononuclear cells after splenectomy and resistance to experimental Pneumococcal infection after splenic surgery and specific immunization. Female miniature pigs were assigned to four operative groups: sham operation, splenectomy, splenic resection, and heterotopic splenic autotransplantation. Hematologic and flow cytometric analysis of mononuclear cells and their subsets revealed a marked leukocytosis following splenectomy and autotransplantation but no significant shift in monocyte and B-cell numbers. Response of leukocytes to septicemia, bacterial elimination from peripheral blood, and mortality were not affected by splenectomy or spleen-preserving operations. Mortality of splenectomized animals was 18%, compared to 42% in sham-operated controls (difference not significant). Immunization protected animals from development of leukopenia, and led to an enhanced bacterial elimination, and a significantly decreased mortality of 5%, compared to 48% in nonimmune animals. Thus our data do not show significant effects of splenectomy on subsets of porcine mononuclear cells or on resistance to experimental Pneumococcal septicemia.

Does Survival Depend on the Amount of Autotransplanted Splenic Tissue?

Susceptibility to Streptococcus pneumoniae infection was studied in 11 groups of rats allocated to sham operation, splenectomy, or splenic autotransplantation of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the removed spleen. Three months later, all rats were exposed intravenously to type 1 Streptococcus pneumoniae (median lethal dose, LD50, for control group). Survivors were killed 13 days after the bacterial challenge. Autopsy showed that more splenic tissue was recovered in rats that received less than 50% splenic tissue compared with those that received 50% or more. More survivors were found among sham-operated rats (47.5%; 95% confidence intervals, 32 to 68) and rats that had 40% splenic tissue implanted (35%; confidence interval, 20 to 54) or those that were found to have regenerated 40% splenic tissue. We conclude that 40% of the spleen should be autotransplanted to protect the rat optimally against infection after splenectomy.

The Value of Splenic Autotransplantation

<i>To the Editor</i>.—Mizrahi et al¹conclude that "... autotransplantation of the spleen is a safe alternative method for preserving splenic function..." Their results confirm previously reported findings that splenic autotransplants regenerate, and that there is a negative correlation between the number of pitted red blood cells in the peripheral blood and the estimates of residual splenic tissue.² There is, however, no evidence that a reduction in the number of circulating pitted red blood cells is related in any way to the role of the spleen in phagocytosis or in the regulation of the immune response. The removal of pits results from mechanical amputation as the red blood cell passes through the interendothelial pores in the lining of the splenic sinuses. The use of this as an index of the return of splenic phagocytic or immunologic function is inappropriate.³ The reported return of IgM immunoglobulin concentrations to normal

Phagocyte Function After Splenic Autotransplantation

This study was designed to examine the role of splenectomy and autotransplantation with regard to the leukocyte/differential cell counts and the function of peripheral blood phagocytes. Eleven groups of 40 Wistar male rats in each group either underwent total splenectomies or sham operations. The splenectomized groups underwent autotransplantations with 10% through 90% of the weight of the intact spleen. The leukocyte count and the oxidative burst response of the blood leukocytes were measured in each group. It was shown that a total splenectomy did not alter the leukocyte/differential cell counts. Furthermore, the blood picture remained basically unchanged after an autotransplantation with 10% through 90% of the weight of the intact spleen. The phagocyte oxidative burst response was measured by chemiluminescence. The chemiluminescence response of these cells was reduced after a total splenectomy. The phagocyte oxidative burst response returned to normal levels following an autotransplantation. There was no correlation between the amount of autotransplanted spleen and the degree of the oxidative burst response. These findings indicated that a splenectomy results in a diminished phagocyte oxidative burst response and that a spleen autotransplantation returns this function to normal levels.

Lymphocyte Subsets in the Blood

Removal of the largest single lymphoid organ, the spleen, leads to an increase in severe infections. To prevent this, transplantation of splenic fragments can be performed, which may, however, cause an increase in CD8+ lymphocytes in the blood of these patients. This is controversial since in the clinical situation it is often difficult to account for the different age of the patients, the time point after the operation and many other factors known to influence the number of lymphocyte subsets. Using a well-defined animal model, B, T, CD4+, and CD8+ lymphocytes were determined preoperatively in adult rats. Then, either sham splenectomy, splenectomy, or splenic autotransplantation was performed and the animals were followed up for 15 months after the operation. The surgical procedure itself, the site of blood sampling and ageing all influenced the number of lymphocyte subsets profoundly. Furthermore, giving the data as relative or absolute numbers leads to different results. Splenectomy caused lymphocytosis, due to a significant increase in B and CD8+ lymphocytes, as did splenic autotransplantation, which indicates that the number of lymphocyte subsets in the blood should not be used to argue in favour of or against splenic autotransplantation. This study demonstrates that the number of lymphocyte subsets in the blood is influenced by many factors and therefore should be determined in a highly standardized fashion.

Quantitative and functional restorations and alterations of peripheral lymphocytes in patients with autologous spleen implantation

To reduce the risk of severe infections in splenectomized patients, new methods for splenic preservation or heterotopic autologous spleen implantation have been established. In the latter case, the immunological and functional benefits are still under discussion. In this study we compared immunological parameters in 16 splenectomized patients with and without heterotopic autologous spleen implantation with a nonsplenectomized control group. The total lymphocyte counts--T-cells, CD4+ -, as well as CD8+ - lymphocytes, CD16+ - and B-cells--were highly elevated in both groups, whereby the B-cells were relatively and absolutely higher in the implanted group than in the nonimplanted group. Splenectomized patients had a significantly reduced serum IgM level. The serum IgM of patients with splenic autotransplantation was not significantly lower than that of the controls. In contrast to the impaired in vitro immunoglobulin synthesis in the splenectomized group, the autotransplanted patients showed a normal PWM-induced IgG and IgM synthesis and an increased IgA production compared with the controls. The latter results support the findings of elevated serum IgA levels in this group. The mitogenic-induced proliferation with PHA, ConA, PWM, and OKT3 was not clearly different within the tested groups. The results may indicate a benefit of autologous spleen implantation in regard to the humoral immune response.

Early and late results of splenic autotransplantation in pediatric splenic trauma: C. Büyükünal, Y. Söylet, N. Danismend, et al. Z Kinderchir 43:394–397, (December), 1988

Early and late results of splenic autotransplantation in pediatric splenic trauma: C. Büyükünal, Y. Söylet, N. Danismend, et al. Z Kinderchir 43:394–397, (December), 1988

Posttraumatic Autotransplantation of Spleen Tissue

Clinical and laboratory studies have documented high susceptibility to pneumococcal infection in asplenic humans and animals. Splenic autotransplantation has been suggested as a method of preserving function. Autotransplantation of irreparably damaged spleens in humans preserved splenic functions. Ten patients operated on for blunt abdominal trauma required unavoidable splenectomy. In each, autotransplantation of the removed spleen (roughly 50 g) was performed. Postoperative studies of splenic functions revealed disappearance of Howell-Jolly bodies from peripheral blood. Levels of IgM, which were initially significantly depressed, returned to normal and there were normal technetium Tc 99m sulfur colloid scans ten weeks after surgery. All patients are alive and healthy. Our data suggest that autotransplantation of spleen is a safe alternative method for preserving splenic function when total splenectomy is mandatory for hemostasis.

Serum Antibody Responses to Pneumococcal Vaccine after Splenic Autotransplantation

Immunization with pneumococcal capsular polysaccharide vaccines is advocated after splenectomy; however, experimental and clinical data suggest an impaired antibody response in splenectomized individuals. This study examined the value of splenic autotransplantation at various sites in augmenting the antibody response to Type III pneumococcal capsular polysaccharide in mice immunized 3 months after operation. Splenectomy resulted in impaired antibody responses compared to sham-operated mice (p less than 0.001) using an enzyme-linked immunosorbent assay. Mice with intraperitoneal splenic autotransplants, but not mice with subcutaneous or intramuscular transplants, had greater antibody responses compared to splenectomized mice (p less than 0.05). Antibody responses were elevated only in mice autotransplanted with 50% or more of the original splenic mass. Since autotransplantation of splenic tissue augments the antibody response to pneumococcal capsular polysaccharides, the combination of splenic autotransplantation and pneumococcal vaccination may confer more protection than either modality alone in individuals who must undergo splenectomy.

Migration pattern of lymphocyte subsets in the normal rat and the influence of splenic tissue.

Lymphocyte subsets leave the blood and appear in the thoracic duct of normal rats at different rates. The aim of the present study was to investigate their migration pattern through blood, spleen, bone marrow, mesenteric lymph nodes, and Peyer's patches in normal Lewis rats and to study the role of the spleen using splenectomized and spleen-transplanted animals. Fluorescein isothiocyanate (FITC)-labelled thoracic duct lymphocytes (TDL) were injected intravenously into rats and after 15 min, 1, 6, and 24 h the percentages of B, T, T helper (TH) and T-cytotoxic/suppressor (TC/S) lymphocytes in the FITC+ cells were determined in cell suspensions by means of monoclonal antibodies. B and T lymphocytes are preferentially localized in different organs, e.g. B cells in Peyer's patches and T cells in mesenteric lymph nodes. The migration of TH lymphocytes differed from that of TC/S lymphocytes in all the organs investigated. In the late phase after injection the migration of B and TH lymphocytes was influenced by the spleen, since after splenectomy the number of injected B lymphocytes increased and that of TH lymphocytes decreased in all organs investigated except the bone marrow. Splenic autotransplantation could not normalize the disturbed migration.

Improved survival with splenic autotransplantation and fibronectin therapy following endotoxin administration in rats.

The risk of overwhelming infections is greatly increased after splenectomy. In this experimental study in rats, we investigated whether the administration of fibronectinrich cryoprecipitate can improve the survival rate of splenectomized autotransplanted rats subjected to an intravenous challenge with endotoxin. Inbred Lewis rats were divided into four groups: A, splenectomy; B, splenectomy + splenic autotransplantation; C, splenectomy, splenic autotransplantation + fibronectin treatment, and D, sham. Five months after surgery, rats were challenged intravenously with Escherichia coli endotoxin. Immunoglobulin (IgG, IgM, IgA), complement and fibronectin levels were measured before surgery and endotoxin challenge, and 48 h after endotoxin challenge. The survival rate of splenectomized rats was not significantly improved by autotransplantation of splenic tissue, but was significantly (p less than 0.05) improved by autotransplantation and fibronectin treatment. The levels of fibronectin, immunoglobulins and/or complements were significantly decreased after endotoxin challenge in control and in autotransplanted fibronectin-treated rats. The survival improvement of autotransplanted rats treated by fibronectin is probably due to increased endotoxin phagocytosis and clearance.

Clinical Study on Splenic Autotransplantation after Splenectomy in Idiopathic Thrombocytopenic Purpura

Clinical Study on Splenic Autotransplantation after Splenectomy in Idiopathic Thrombocytopenic Purpura

Ultrastructural study on endothelial cells in splenic autotransplantation

AbstractThe splenic tissue of the rat was autotransplanted into the greater omentum to investigate the angiogenic process during splenic regeneration. Chronological observations showed the following two stages. Initially surviving subcapsular sinus endothelial cells migrated to form a preliminary vascular network, which anastomosed with ingrowing omental capillaries to form a circulatory system. In this way, splenic autotransplants would not undergo necrosis and would rapidly form endothelial and reticular cells. At a later stage, the preliminary vascular network differentiated into arteries (arterioles, capillaries), splenic sinuses, and veins. Marked morphologic changes occurred in the endothelial cells, such as vacuole formation, fenestration, and the condensation of intraendothelial microfilaments, resulting in interendothelial slits. These results showed that the formation of a preliminary vascular network caused distinct splenic regeneration and that splenic autotransplantation is a suitable model to study angiogenesis in vivo.

Früh- und Spätresultate heterotoper Milzautotransplantation beim kindlichen Milztrauma

In this study, early and late results of heterotopic splenic autotransplantation in 18 children with type IV splenic injuries (Upadhyaya-Simpson classification) are presented. Splenic scintigrams, quantitative analysis of Howell-Jolly inclusion bodies, immunoglobulin (IgG, IgM, IgA) and complement C3 levels and T and B lymphocyte counts were analysed in the postoperative evaluation of the autotransplantation group. The total follow-up period was 7 years. According to our results, splenic implants increased complement C3 levels and improved filtration function of the splenectomized children. This autotransplantation group has two important characteristics: a) it is one of the largest series of the literature (pediatric age group), with b) longest follow-up period.

Splenic Tissue Autotransplantation

Letters to the EditorSplenic Tissue Autotransplantation Bernd Domres, MD, Facharzt Ram N. Goel, FRCS, MD M. Heitham Schammut, and MD, Facharzt Robert R. ToussaintMD, Facharzt Bernd Domres Department of Surgery, King Khaled Hospital, P.O. Box 1852, Hail, Saudi Arabia Search for more papers by this author , Ram N. Goel Department of Surgery, King Khaled Hospital, P.O. Box 1852, Hail, Saudi Arabia Search for more papers by this author , M. Heitham Schammut Department of Surgery, King Khaled Hospital, P.O. Box 1852, Hail, Saudi Arabia Search for more papers by this author , and Robert R. Toussaint Department of Surgery, King Khaled Hospital, P.O. Box 1852, Hail, Saudi Arabia Search for more papers by this author Published Online:1 Jul 1988https://doi.org/10.5144/0256-4947.1988.297aSectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutIntroductionAsplenic patients are at an increased risk of overwhelming bacterial infection. It appears as pneumococcal sepsis in about 2% of splenectomized patients and may occur as late as 20 years after the splenectomy. Mortality in infected patients exceeds 50%, and this high mortality rate is related to the absent splenic functions. Therefore, we autograft removed ruptured spleen into an omentum pouch. This procedure does not extend the operation time more than 10 minutes.After removal of the ruptured spleen, its capsule is removed. The organ is shredded with sharp sterile device (of the type used in the kitchen to shred vegetables). The site of splenic implantation is important. It should be placed in an area that will drain into the portal venous system when neovascularization occurs. Implants function better in an omentum pouch than in a subcutaneous or peritoneal pouch. To avoid the main complications of the procedure (splenosis of the abdominal cavity or adhesions) the omental pouch should be sutured tightly so that it will not leak.We try to reimplant as much tissue of the ruptured spleen as possible. Research into splenic autotransplantation could prove that the minimum total weight of the grafted spleen should exceed 100 g, about a third of the total organ, to preserve satisfactory splenic function.Autotransplantation of ruptured spleen was performed in 49 cases. Eleven of the 49 patients died as a result of accompanying multiple injuries and not due to the splenectomy or autotransplantation.The progress of spleen regeneration in the omental pouch can be monitored by splenic scans, and postoperatively 30 patients were followed with regular thrombocyte counts, blood smears for RBC morphology such as Howell-Jolly bodies and pitted RBCs, and quantitative immunoelectrophoresis of IgM levels. After an initial increase in the numbers of thrombocytes, Howell-Jolly bodies, and pitted RBCs in the first 4 weeks, the levels returned to near normal after 8 weeks. The decreased IgM fraction returned to normal after 6 months.These results encourage us to continue autotransplantation of splenic tissue after splenectomy. Previous article Next article FiguresReferencesRelatedDetails Volume 8, Issue 4July 1988 Metrics History Published online1 July 1988 InformationCopyright © 1988, Annals of Saudi MedicinePDF download