Native Spleen Research Articles

Modified Multivisceral Transplantation With Spleen-Preserving Pancreaticoduodenectomy for Patients With Familial Adenomatous Polyposis “Gardner's Syndrome”

Liver-sparing "modified" multivisceral transplantation (MMVTx) has recently been more used for patients with diffuse gastrointestinal disorders and preserved hepatic functions. Evisceration techniques with preservation of native spleen were also introduced to reduce risk of posttransplant lymphoproliferative disorders. This study focuses on the indications of MMVTx for patients with familial adenomatous polyposis (FAP) and the technical feasibility of performing spleen-preserving pancreaticoduodenectomy (SPPD). Between 1993 and 2009, 10 FAP patients required MMVTx. Nine were adults and one was a child, with a female:male ratio of 1:1. Short gut with duodenal adenomatosis and extensive desmoid tumors with pancreaticoduodenal involvement dictated need for MMVTx. SPPD was technically feasible in four recipients, and conventional evisceration including splenectomy was performed in remaining six recipients. With an overall cumulative survival of 90% at 1 year and 77% at 10 years, all SPPD recipients were alive with no single example of posttransplant lymphoproliferative disorder, graft-versus-host disease, or chronic rejection. However, SPPD was associated with an increase (P>0.3) in total ischemia time, operative time, and packed red blood cells requirement but with shorter (P=0.6) length of hospital stay. With a mean follow-up of 50±45 months (range 18-128 months), none of the 10 recipients experienced intraabdominal desmoid tumor recurrence or developed de novo visceral allograft neoplasm. MMVTx is a valuable therapeutic option for FAP patients who are in need for visceral transplantation with pathologic involvement of the pancreaticoduodenal complex. SPPD is technically feasible, and efforts should always be made to preserve native spleen because of the reported herein therapeutic advantages.

Modified “Liver-Sparing” Multivisceral Transplant with Preserved Native Spleen, Pancreas, and Duodenum: Technique and Long-Term Outcome

BackgroundModification of the originally described multivisceral transplant operation was introduced at our institution 17 years ago. Donor liver was spared, and native spleen along with pancreaticoduodenal complex was preserved. MethodsThirty-six modified multivisceral grafts that include stomach, duodenum, pancreas, and intestine were given to 30 adults and six children. Leading causes of intestinal failure were pseudo-obstruction and Gardner’s syndrome. Native spleen was preserved in 24 (67%) recipients along with pancreaticoduodenal complex in 18 (50%). Immunosuppression was tacrolimus-based, and recipient preconditioning was utilized in 80% of patients. ResultsPatient survival was 94% at 1 year and 75% at 5 years with graft survival of 91% and 51%; respectively. With mean follow-up of 51 ± 35 months, full nutritional autonomy was achieved in 89% of current survivors with no single example of disease recurrence. Preservation of native spleen was associated with increased survival and reduced risk of PTLD, life-threatening infections, and GVHD with no significant impact on graft loss due to rejection. Concomitant preservation of pancreaticoduodenal complex eliminated risks of biliary complications and glucose intolerance. ConclusionModified multivisceral transplantation with and without preservation of native spleen, pancreas, and duodenum is a valid therapeutic option for patients with diffuse gastrointestinal disorders and preserved hepatic functions.

Small bowel transplantation: technical advances/updates

The field of intestinal transplantation continues to grow, both in terms of overall transplants performed each year and number of centers adopting this procedure. Numerous advances in technical and management procedures have resulted in improvements of patient and graft survival. This review focuses on the technical advances that have emerged over the last year. Multiple variations of the original technique of intestinal transplantation are now utilized according to the patients' original diagnoses and/or degree of liver dysfunction. Multivisceral grafts can include both donor spleen and large intestine; preservation of the native spleen and pancreas is possible in some cases. Living donor intestinal transplantation is being described as alternative technique to minimize death on the waitlist. Constant evolution in the surgical aspects of intestinal transplantation parallels the improvements that have taken place in the medical management and immunosuppression. The transplant surgeon with full knowledge of all variations of intestinal transplant techniques will be able to tailor the type of surgery to each individual patient.

1P-006 異常X線小角散乱法によるネイティブおよび再構成ウマ脾臓フェリチン内の鉄イオンコアの構造研究(蛋白質-構造,第47回日本生物物理学会年会)

1P-006 異常X線小角散乱法によるネイティブおよび再構成ウマ脾臓フェリチン内の鉄イオンコアの構造研究(蛋白質-構造,第47回日本生物物理学会年会)

Preservation of the Native Spleen, Duodenum, and Pancreas in Patients With Multivisceral Transplantation: Nomenclature, Dispute of Origin, and Proof of Premise

Preservation of the Native Spleen, Duodenum, and Pancreas in Patients With Multivisceral Transplantation: Nomenclature, Dispute of Origin, and Proof of Premise

Modified Multivisceral Transplantation With Splenopancreatic Preservation

A common requirement of multivisceral transplantation has been removal of the native duodenum, pancreas and spleen in the process of abdominal exenteration. Oftentimes, though, the indication for their removal has not been underlying disease states in those organs. In order to avoid adverse sequelae of pancreas and splenic removal for purely anatomic reasons, we have designed a new approach and have performed a multivisceral transplantation with splenopancreatic preservation. In this modified multivisceral technique, the native spleen and pancreas are preserved with venous outflow through a native portocaval shunt, and native pancreatic exocrine drainage is established to the donor jejunum. Risk of transplant pancreatic insufficiency, posttransplant lymphoproliferative disorder, and postsplenectomy sepsis may be avoided utilizing this technique. This new modification of multivisceral transplantation allows pancreaticosplenic preservation while facilitating stomach replacement for those patients requiring intestinal replacement therapy. It represents another step towards minimizing morbidities associated with these lifesaving transplants.

Early biological and immune response to semi-identical liver or kidney allograft in miniature swine

In inbred miniature swine, semi-identical liver allograft recipients survive up to 3 months without immunosuppression, whereas similarly mismatched kidney allografts are uniformly rejected within 2 weeks. The early biological and immunological events were assessed in this unique model. SLA(d/d) pigs (MGH, Harvard Medical School, Boston, MA, USA) received liver or kidney allograft from heterozygous SLA(c/d) miniature swine. Survival, graft function, histology, intragraft cytokines, peripheral lymphocyte and platelet count, plasma cortisol level and cellular/humoral anti-donor immune response were assessed. Kidney allografts were uniformly rejected within 2 weeks, whereas liver allografts survived for up to 87 days. After both liver and kidney transplantation, the peripheral lymphocyte count decreased during the first week concomitantly to a significant elevation of plasma cortisol level. Early decrease of peripheral platelet count was observed after liver but not renal transplantation. Up-regulation of transforming growth factor beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) was observed during the first postoperative week in semi-identical liver allografts and IFN-gamma as well as IL-10 in kidney allografts. In liver recipients, labelled autologous lymphocytes accumulated in the liver graft and native spleen, whereas after renal allograft, lymphocytes accumulated in the native spleen and liver but never in the kidney allograft. Specific cellular anti-donor unresponsiveness was observed from the first post-transplant day in both liver and kidney recipients, while the humoral anti-donor response remained intact. In semi-identical liver allograft, recipient rejection is milder and slower than in similarly matched kidney allograft. The intragraft up-regulation of TGF-beta1 in semi-identical liver allograft might be one mediator to explain the modulation of rejection after liver transplant. The rapid, nonspecific accumulation of recipient lymphocytes in the liver allograft but not in kidney allograft might also play a role in the different survival time in this model.

Symptomatic wandering accessory spleen in the pelvis: Sonographic findings

We describe the case of a mobile left lower quadrant mass associated with recurrent abdominal pain; at surgical exploration, the mass was found to be an accessory pelvic spleen. Although accessory spleens are present in 10–30% of individuals, a wandering accessory spleen located in the pelvis is not frequently seen. On sonography, the mass in our patient appeared well-defined and homogeneous. Spectral analysis and color Doppler imaging demonstrated a normal vascular branching pattern and high diastolic flow due to low resistance in the vascular bed. The parenchymal resistance index of the mass was similar to that of the native spleen. © 1999 John Wiley & Sons, Inc. J Clin Ultrasound 27:534–536, 1999.

Analysis of the Kveim-Siltzbach test reagent for bacterial DNA.

The sarcoid spleen-derived reagent for the Kveim-Siltzbach test (KST) elicits a sarcoid-specific, granulomatous, cutaneous response used to establish the diagnosis of sarcoidosis. In the context of the ongoing discussion of a bacterial cause of sarcoidosis we asked the question whether bacterial DNA could be found in the KST reagent. For this purpose two different KST reagents, an identical preparation from a normal spleen, and a native sarcoid spleen were analyzed by polymerase chain reaction (PCR) employing universal primers detecting conserved DNA sequences coding for bacterial ribosomal 16S RNA. Neither KST reagents, the control preparation, nor the spleen yielded a positive signal, indicating that the preparations are free of bacterial contamination. Because the KST reagent elicits granuloma, these results do not support the hypothesis of a bacterial cause of sarcoid granuloma.

Spleen transplantation from mother to child induces prolonged immunotolerance to intestinal transplantation in rats

In phase 1 eight standard pregnant Wistar rats were used. After delivery of a litter, each mother underwent splenectomy and autotransplantation of a piece of her spleen, which has been divided into eight pieces of equal size in the omentum. The weaning rats were divided into four groups (A–D). Rats in group A (N 5 18) underwent splenectomy, and each received a transplanted piece of the mother’s spleen. Group B (N 5 18) rats each received a transplanted piece of the mother’s spleen. Group C rats (N 5 21) underwent splenectomy only, and group D rats (N 5 20) underwent sham operations. All animals were anesthetized with pentobarbital (40 mg/kg IP) for surgical intervention. Neither immunosuppressive agents nor antibiotics were administered. The animals were weighed daily and underwent extirpation of the native spleen and transplanted spleen to measure the organ weight and evaluate the organ histologically and immunologically at 4 weeks or 6 months after surgery. In phase 2 another group of rats was used to evaluate the effects of combining splenectomy and splenotransplantation on tolerance to other transplants. Weaning rats were divided into four groups and prepared as in phase 1; in addition, they underwent skin transplantation from the mother to the offspring’s back, and the condition of the transplanted skin was evaluated daily and immunohistologic studies were conducted. Histological evaluation was done using hematoxylin and eosin stain.

Isolation of Human Immunodeficiency Virus (HIV) at Autopsy One to Six Days Postmortem

Blood and tissue were studied for potential infectivity at autopsy of ten patients with human immunodeficiency virus (HIV) infection. Special attention was paid to the possibility of detecting HIV in bone at craniotomy. Postmortem intervals were one to six days. Specimens for HIV isolation included skull bone, brain, blood, bone marrow, spleen, and lymph node, and cerebrospinal fluid in one case. HIV grew in culture from at least one specimen from eight autopsies, one of which was performed six days postmortem. HIV was recovered from the blood of five patients and the tissue of five patients, including three with negative blood cultures. Skull bone contained HIV in two cases. HIV also grew from native spleen specimens stored for up to 14 days postmortem at 20 degrees C. Recommended precautions, including those for bone, are indicated at autopsy of HIV-infected patients even after long postmortem intervals.

Simultaneous cell cycle analysis and two-color surface immunofluorescence using 7-amino-actinomycin D and single laser excitation: applications to study of cell activation and the cell cycle of murine Ly-1 B cells.

The DNA-binding, fluorescent dye 7-amino-actinomycin D (7AAD) is efficiently excited by the 488 nm laser line commonly used in flow cytometry, but yields fluorescence emission further into the red spectrum than alternative DNA-specific fluorochromes. In this report, we show that the spectral properties of 7AAD allow single-laser analysis of DNA content and cell cycle simultaneously with two cell surface markers labeled with fluorescein (green)-and phycoerythrin (orange)-conjugated antibodies. The use of 7AAD makes three-color analysis practical and feasible, using the most widely available flow cytometric instruments. The power of this technique was demonstrated in two systems. Staining of human peripheral blood lymphocytes (PBL) with 7AAD was demonstrated to be dependent on cell activation and chromatin conformation; PHA-stimulated cells which have become activated and express IL 2 receptors had greater 7AAD fluorescence than nonactivated, IL 2 receptor-negative cells. Cell cycle analysis of mouse splenocytes stained with fluorescent antibodies to IgM and to Ly-1 demonstrated that the proportion of S and G2 phase cells in native spleen varies strongly among the subsets of cells identified with these markers. Of particular interest was the striking finding that the Ly-1+/IgM+ subset (Ly-1 B cells) is greatly enriched for cells in the S phase fraction. This is important because Ly-1 B cells have been associated with the production of autoantibodies, and is consistent with reports that these cells have a lymphoblastoid or a plasmablast morphology. We hypothesize that Ly-1 B cells may belong to a subset of in vivo activated cells which are either rapidly proliferating or are arrested in S phase.

Cloned cell lines with natural killer activity. Specificity, function, and cell surface markers.

Cell lines with natural killer (NK) activity grown from native spleen cells cultured in medium conditioned by spleen cells proliferating in the presence of concanavalin A (Con A) were characterized. One NK cell line was cloned and assayed on several human and mouse NK-sensitive targets to analyze whether target specificities segregate upon cloning. Results showed that NK clones display target specificities identical to NK cells in normal spleen. This suggests that NK cells have no clonally distributed specific receptors to a given target. They may, however, have receptors which recognize identical antigens on all NK-sensitive targets or may possess multiple receptors for different target specificities. NK lines could not be demonstrated to possess activity in antibody-dependent cell-mediated cytotoxicity, nor did they effect mutual lysis. In the presence of Con A, NK cells exhibited dramatically enhanced lysis of NK-sensitive targets but only a slight increase in lysis of NK-insensitive targets. This indicates that the degree of lysis of an NK target is a function of two variables: effector binding to the target and target sensitivity to lysis. Furthermore, it suggests that the affinity of the putative antigen receptors on NK effectors must be rather weak. Cell surface marker analysis reveals that NK cell lines are Thy 1.2+, Lt-1-2-, T200+, asialo GM1+, and asialo GM2+. These markers distinguish NK cells from cytolytic thymus-derived lymphocytes, without resolving the question of classification within a give hematopoietic cell lineage.