Autologous splenic transplantation for splenic trauma.

OBJECTIVE: The authors reviewed the experimental evidence, surgical technique, complications, and results of clinical trials evaluating the role of autologous splenic transplantation for splenic trauma. SUMMARY BACKGROUND DATA: Splenorrhaphy and nonoperative management of splenic injuries have now become routine aspects in the management of splenic trauma. Unfortunately, not all splenic injuries are readily amenable to conventional spleen-conserving approaches. Heterotopic splenic autotransplantation has been advocated for patients with severe grade IV and V injuries that would otherwise mandate splenectomy. For this subset of patients, splenic salvage by autotransplantation would theoretically preserve the critical role the spleen plays in the host's defense against infection. METHODS: The relevant literature relating to experimental or clinical aspects of splenic autotransplantation was identified and reviewed. Data are presented on the experimental evaluation of autogenous splenic transplantation, methods and complications of autotransplantation, choice of anatomic site and autograft size, and results of clinical trials in humans. RESULTS: The most commonly used technique of autotransplantation in humans involves implanting tissue homogenates or sections of splenic parenchyma into pouches created in the gastrocolic omentum. Most authors have observed evidence of splenic function with normalization of postsplenectomy thrombocytosis, immunoglobulin M levels, and peripheral blood smears. Some degree of immune function of transplanted grafts has been demonstrated with in vivo assays, but the full extent of immunoprotection provided by human splenic autotransplants is currently unknown. CONCLUSIONS: Multiple human and animal studies have established that splenic autotransplantation is a relatively safe and easily performed procedure that results in the return of some hematologic and immunologic parameters to baseline levels. Some aspects of reticuloendothelial function are also preserved. Whether this translates into a real reduction in the morbidity or mortality rates from overwhelming bacterial infection is unknown and requires further investigation.     

自体移植脾组织VEGF、KDR表达与血管再生的实验研究

目的 研究自体移植脾组织血管再生及VEGF、KDR表达规律，阐明VEGF、KDR对移植脾组织血管再生的调控作用，为脾脏外科临床及实验研究提供理论依据。方法 健康Wistar大鼠70只，体重100—120g，随机分为7组，每组10只中又设脾切除自体脾移植组5只，假手术组5只，分别于术后7，14，30，60，90，120，180d进行：(1)自体移植脾组织病理学检测；(2)大鼠行主动脉插管灌注墨汁，光镜观测再生血管并采用图像分析测定其密度；(3)免疫组化抗VEGF、KDR抗体染色，图像分析定量，阐明其表达规律及与血管再生的关系。结果 (1)自体脾组织移植术后7d即有血管从大网膜向脾组织内伸展，移植脾组织内血管密度逐渐增大，至术后180d血管再生接近正常；(2)自体脾组织移植术后7d、14d，VEGF、KDR阳性染色细胞密度迅速升高，术后60d达高峰，以后逐渐降低，至术后180d VEGF、KDR阳性染色细胞密度趋向正常。结论 自体脾组织大网膜内移植术是简便有效的脾移植方法；移植脾组织新生血管由大网膜再生而来；术后移植脾组织内VEGF、KDR表达量升高，促进血管形成，血管再生完成后恢复正常水平。     

腹膜后自体脾移植治疗外伤性脾破裂的前瞻性研究

目的 探讨腹膜后自体脾移植在严重脾外伤保脾手术中应用的可行性及价值。方法 采用前瞻性病例对照研究,将66例严重脾外伤病人分为腹膜后自体脾移植组例、大网膜自体脾移植组,其中腹膜后自体脾移植组32例,大网膜自体脾移植组34例。观察术后一般情况,术后1天～ 12个月血常规,血IgA、IgM、IgG、C3、Tuftsin水平变化。结果 腹膜后自体脾移植组手术时间短于大网膜自体脾移植组（P<0.05）,术后其它一般情况变化、术后1天～ 12个月血IgA、IgM、IgG、C3、Tuftsin水平两组无统计学差异（P> 0.05）。结论 腹膜后自体带蒂脾移植术能够保留脾脏的部分免疫功能,且手术操作简便,在临床上推广应用是可行的。     

Failure of autotransplantation of the spleen in dogs: an anatomic, radionuclide imaging, and pathologic study

Although splenic autotransplantation is successful in mice and rats, with regeneration occurring in any location, no extensive study had been performed on dogs. We transplanted the spleen into subcutaneous and intraperitoneal locations on 40 dogs. Four to six months later, splenic scanning and reexploration was carried out. Spleens were removed, weighed, and microscopic sections were made. Months later, no uptake was present on scanning, weight was less than 6% of original weight, and little identifiable splenic tissue was present on microscopic sections. When 15 small sections were transplanted to the omentum in a "necklace" fashion, good uptake and preservation were seen after six months. The small amount of spleen transplanted by this method, however, makes this an unsatisfactory option. We conclude, therefore that our large-animal experiments do not provide a basis on which to recommend autotransplantation of the spleen in humans. Preservation of splenic tissue by splenorrhaphy is still the treatment of choice.     

Laparoscopic splenic autotransplantation

Since 1990, we have performed splenic autotransplantation in more than 100 patients to treat splenic trauma, portal hypertension, myeloid metaplasia due to myelofibrosis, chronic lymphocytic leukemia, and Gaucher disease. The aim of this present study was to present splenic autotransplantation performed by laparoscopic means. A 33-year-old woman with severe splenic pain due to ischemia caused by multiple focal thromboses of splenic arterial branches was successfully treated by laparoscopic splenectomy and splenic tissue autotransplantation. The spleen was removed and cut in 20 fragments that were sutured to the greater omentum. This procedure was safely conducted with minor bleeding and no technical difficulties or complications. The postoperative follow-up of 12 months has been uneventful; the patient's pain disappeared on the first postoperative day. Hematologic, immunologic, tomographic, and scintigraphic examinations confirmed the functions of the splenic autotransplants. It is feasible and safe to perform splenic autotransplants by laparoscopic means.     

Splenic autotransplantation for treatment of portal hypertension.

BACKGROUND: When total splenectomy is unavoidable it is important to preserve splenic function in some form in order to prevent the complications of asplenism. Splenic autotransplantation is a good alternative in such cases. We describe the use of splenic autotransplantation for the treatment of portal hypertension. METHODS: We carried out total splenectomy on 31 patients (21 men, 10 women), ranging in age from 21 to 68 years, with schistosomal portal hypertension. From each removed spleen, we took 20 fragments and implanted them on the greater omentum. This procedure was combined with abdominal portal-variceal disconnection. Transgastric running suture of the lower esophageal and gastric varices completed the treatment of portal hypertension. All patients underwent clinical, hematologic, immunologic and scintigraphic assessment. The results with respect to morbidity and mortality, and hematologic and immunologic findings were compared with those in 36 patients submitted to other splenic procedures. RESULTS: There was no complication related to the splenic implants and none of the patients died. Hematologic and immunologic findings were normal. Scintigraphy registered images of splenic tissue in all cases. CONCLUSION: The implantation of splenic fragments on the greater omentum seems to be a safe and useful procedure for maintaining splenic function after total splenectomy.     

自体脾组织移植后病理学变化的实验研究

目的　研究自体脾组织移植后不同时相点病理形态学变化规律。　方法　健康Wistar大鼠 5 6只 ,雌雄不限 ,体重 10 0～ 12 0 g ,随机分为 7组 ,每组 8只中又设脾切除自体组织大网膜内脾移植组 5只 ,假手术组 3只 ,分别于术后 7、14、3 0、60、90、12 0、180d取脾组织 ,光镜、透射电镜观察。　结果　移植脾组织之重量在术后 7d最轻 ,为 0 .0 72 g ,其后逐渐增加 ,180d时为 0 .5 11g ,各时相点之间有明显差异 (P <0 .0 5 )。病理检查提示移植脾组织经历急性期、缓解期、修复期三个病理时期 ,逐步恢复并接近正常的组织结构。　结论　自体脾组织大网膜内移植术是简便有效的脾移植方法。自体移植脾组织再生过程可分为 :急性期、缓解期与修复期     

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.     

Complications of splenic tissue reimplantation.

Splenic tissue reimplantation employing the omental implantation technique was applied in 23 patients undergoing splenectomy for traumatic or iatrogenic splenic injury. Four complications were encountered after autotransplantation (17.4%). Two of these consisted of small bowel obstruction due to postoperative adhesions and were successfully managed by lysis of the adhesions. The other two complications were aseptic necrosis of the splenic transplants and were treated with ablation of the autolysed transplants. A case of abnormal splenic tissue reimplantation in a male patient with unsuspected myelofibrosis is also discussed. He underwent an emergency laparotomy for rupture of a subcapsular splenic haematoma. It is concluded that splenic tissue implantation in the greater omentum is associated with important early morbidity and this should be taken into account whenever application of the method is considered.     

Exogenous and endogenous angiogenic stimuli do not augment splenic autotransplantation.

OBJECTIVE: To find out if angiogenic stimulation improves the ability of the spleen to regenerate. DESIGN: Experimental study. SETTING: Teaching hospital, Republic of Ireland. ANIMALS: 27 male Sprague-Dawley rats. INTERVENTIONS: Each spleen was removed and half was reimplanted in the greater omentum. The rats were randomised into three groups of 9 each: the first (control) group was given no stimulation; the second had the implanted spleen sutured into the omentum with 6/0 polypropylene; and in the third group the implanted spleen was injected with human recombinant vascular endothelial growth factor (VEGF) 500 microg. MAIN OUTCOME MEASURES: Clearance of Howell-Jolly bodies, and the weight and histological appearance of the splenic remnant at 3 months. RESULTS: The splenic remnant was significantly larger at 3 months in the control group (p = 0.0006). Histological examination of the tissue from the control group showed that it was architecturally similar to that of normal functioning spleen, whereas the tissue from the two treated groups contained less lymphoid tissue and showed widespread acute and chronic inflammatory changes. There was a significantly greater clearance of Howell-Jolly bodies (an index of splenic function) from the peripheral blood of the control group (p = 0.0009). CONCLUSION: The excellent recovery of the splenic remnant in the control group suggests that the procedure of splenic autotransplantation might warrant further consideration and study.     

Autotransplantation of splenic tissue after splenectomy

The authors have performed heterotopic autotransplantation of the spleen tissue into the greater omentum pocket as a suspension or tissue sections in 14 patients with emergency splenectomies. The method of autotransplantation is described. No complications resulting from autotransplantation were noted.     

Autotransplantation of splenic tissue

Autotransplantation of splenic fragments has already been carried out in humans. The optimal size of the particles and amount of tissue required for this procedure has yet to be found. In normal young pigs and miniature piglets, autologous splenic tissue was transplanted into the greater omentum. The regenerated splenic mass, splenic blood flow, and histology were studied six months later. Implanting small splenic particles produced comparable results to implanting thin slices of splenic tissue. The mass of regenerated splenic tissue was only 3.1 g after implanting the whole spleen and 4.5 g after transplanting half of the spleen, which means 5.3% and 7.8% respectively of the weight of control spleens. The blood flow per gram in the regenerated splenic tissue was much lower than in the normal spleen. The blood flow in the whole of the splenic tissue is important for the clearance function of the spleen. Six months after transplanting the whole or half of the spleen, the blood flow to the regenerated splenic tissue was only 1% of that in the control minipigs. When half of the spleen was left in situ, as a model for a partial splenectomy, and the other half transplanted, the regenerated mass was only 3.4% of all splenic tissue and the blood flow 1.5% of the total splenic blood flow. In this model the regenerated splenic mass was independent of the size of the implants and the mass of implanted tissue. The extremely low blood flow indicates an inadequate clearance function and thus the protective function would probably be negligible.     

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.     

Assessment of post-splenectomy residual splenic function. Splenic autotransplants

Splenectomy increases the risk of fulminant sepsis. The present study assesses residual splenic function in patients splenectomized due to traumatic rupture of the spleen; and six cases with splenic autotransplants. Splenic tissue was observed in only 48% of the splenectomized patients and 100% of the autotransplant cases. The two most reliable analytical parameters to assess the presence of functional splenic tissue, were the absence of Howell-Jolly bodies and normal IgM blood levels. In cases where total splenectomy is indicated, it has proved useful to perform autotransplantation of splenic tissue at omentum major level.     

脾创伤保脾手术术式的选择（附158例分析体会）

目的　探讨脾创伤保脾术的术式选择。方法　对脾创伤采用术中保脾的 15 8例手术方式进行分析 ,其中氩气刀止血 5例 ,ZT生物胶止血 3例 ,单纯脾修补术 2 6例 ,脾部分切除术 77例 ,修补加脾部分切除术 12例 ,脾切除自体脾组织片网膜囊内移植术 35例。结果　全组病例治愈出院。脾切除自体脾组织片网膜囊内移植术组 35例中 ,2例出现粘连性肠梗阻 ,11例出现各类术后感染 ,而其它术中保脾组 12 3例中 ,10例出现术后感染 ,两组总感染数比较 ,P <0 .0 1。结论　脾创伤术中保脾术的术式选择 ,应根据病人个体情况及脾破裂的类型而定 ,必要时采用联合多种术式保脾。对伴有空腔脏器破裂者也可选择性保脾。但应慎重选择脾切除自体脾组织片网膜囊内移植术。     

Heterotopic autotransplantation of the spleen in animal experiments

A new technique of heterotopic autotransplantation of pieces of the spleen is suggested. It differs from the methods used previously in that the pieces of the autologous transplant are placed between the layers of the greater omentum and not on its surface. Not only was the viability of the pieces of the autologous transplant maintained but the hazard of intraabdominal adhesions and their unfavourable consequences was reduced to a great measure.     

Reticuloendothelial clearance and splenic mononuclear cell populations after resection and autotransplantation

Although the preservation of splenic tissue may prevent overwhelming infection after splenectomy, the degree of protection conferred by small remnants has not been optimal. We investigated whether either splenic reticuloendothelial clearance of a blood flow-dependent colloid or macrophage and T-cell populations might be altered by resection or autotransplantation of the spleen. Our results have shown that bloodstream reticuloendothelial clearance of technetium 99m sulfur colloid is not impaired by splenectomy, partial resection of the spleen, or splenic autotransplantation. Such clearance is dependent on spleen weight and is not related to differences in either macrophage or helper or suppressor T-cell populations. This suggests that autotransplantation of the spleen is inferior to preservation of even a small hilar remnant and implies that repair or partial resection of the spleen will provide greater protection than autotransplantation.     

Early clinical experience with postoperative monitoring of a patient after laparoscopic splenectomy combined with spleen autotransplantation. A case report

We performed splenectomy combined with spleen autotransplantation after blunt abdominal trauma by minimally invasive technique at the County Teaching Hospital in Kecskemét. In case of advanced post traumatic spleen injury, spleen autotransplantation (Furka's spleen chips) is a well-known method to try to avoid postsplenectomy syndrome. During the operation, when in situ preservation of the spleen is not possible, chips of spleen tissue are transplanted into the omentum. Function of the transplanted spleen tissue was monitored by scintigraphy. We describe two different types of spleen scintigraphy to check the viability of spleen chips.     

Influence of donor and host age on the regeneration and blood flow of splenic transplants

After splenectomy there is an increased risk of fatal overwhelming postsplenectomy sepsis, especially in children. If all alternatives to splenectomy fail, autotransplantation of splenic fragments is indicated. These fragments regenerate after a necrotic phase to small splenic nodules. Regulatory factors governing the regeneration process are largely unknown. Inbred rats were used as a model to define the influence of recipient and donor age on the regenerated mass and the blood flow of transplanted splenic fragments. These are both important factors for the protective function of the spleen. Fetal, newborn, weanling, or adult spleens were implanted into the greater omentum of newborn, weanling, or adult rats. The younger the recipient and donor, the better the regeneration and perfusion of transplants. However, these did not reach more than 40% of the normal splenic mass. In addition, no experimental group achieved more than one third of the normal splenic blood flow. There is an obvious age dependency in splenic regeneration and blood flow, but the transplants are far from attaining a normal splenic mass and perfusion.     

Autotransplantation of Spleen Mitigates Drug-Induced Liver Damage in Splenectomized Mice

Purpose: The spleen presents numerous functions, including the production of immunoglobulins and blood filtration, removing microorganisms and cellular debris. The spleen also has anatomical and functional relationship with the liver, but there are few studies on this topic. The aim of this study was to assess the effect of splenectomy and autologous spleen transplantation on both filtering functions of spleen and acetaminophen-induced hepatotoxicity. Materials and Methods: Fifty-two BALB/c mice were randomized into four groups: splenectomized; splenectomy and splenic autotransplantation in the greater omentum; sham operated control; and non-operated control. At day 7th, 14th, and 28th after surgery, splenic filtration was assessed by counting Howell-Jolly bodies (HJB) and pitted red cells (PIT). The animals received 400 mg/kg acetaminophen by gavage at day 28^th and after 12 or 24 hours were euthanized for evaluation of splenic and hepatic morphology. Results: The splenectomized group demonstrated reduced filtration of HJB and PIT in all analyzes, while the autotransplanted group developed progressive recovery of function after the 14th day. At day 28 after surgery the implants showed similar histology in comparison to normal spleen. Liver histology showed more intense centrilobular necrosis in splenectomized group in comparison to the others, suggesting a protective role of spleen in acetaminophen-induced liver injury. Conclusions: Splenic implants showed structural and functional recovery, demonstrating the ability of autologous implant to rescue filtering function of intact spleen. Furthermore, the integrity of splenic function appears to influence liver morphology, since the presence of the splenic implants mitigated the effects of chemically-induced liver damage.