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Impact of spleen preservation in patients with gastric cancer.

BACKGROUND: Resection of the spleen en bloc with the stomach for gastric cancer is still widely performed for a curative resection (R0), but the presence of the spleen may have a favorable effect on recurrence control and survival. The hypothesis that the spleen suppresses tumor growth from minimal residual disease in the critical early postsurgical period and reduces the risk of recurrent disease was tested. PATIENTS AND METHODS: Patients were included who underwent gastrectomy, with or without splenectomy, for gastric adenocarcinoma. Standardized, strongly-defined criteria were used to accurately stratify patients, who had an extended (D2) lymph node dissection, into the curative and non-curative resection groups. Limited, D1 resection confounds appropriate R-stratification and thus D1 patients were excluded. Prospectively-defined primary endpoints were early (within two years) and overall recurrence and death from any cause and secondary endpoints were postsurgical risks (morbidity, mortality) and metastases to the splenic hilum nodes. RESULTS: Overall survival for the total population studied (n = 202) was better for preservation-versus-resection of the spleen among R0 patients (p = 0.0001), but not for those with non-curative resection (p = 0.42). For the R0 D2 group of patients, preservation (n = 59) over resection (n = 67) of the spleen, there was no significant difference in in-hospital postoperative morbidity or mortality (3.4% vs. 0%). At a median follow-up of 112 months, significantly the preservation of the spleen, lowered the risks of early recurrence (HR, 0.33; 95% CI, 0.16 to 0.69; p = 0.003) and death from any cause (p = 0.009) after adjustment analysis. Since at baseline there was a significant imbalance of tumor stage in favor of the spleen-preservation group, we conducted a stage-stratified subgroup analysis. This treatment effect remained consistent in the subgroup analyses according to nodal and serosal status, while in multivariate analysis preservation of the spleen was an independent predictor of outcome. An overestimation of the risk for residual disease in the splenic hilum nodes in the case of spleen preservation was obtained in 94% of splenectomized patients. CONCLUSION: Our findings indicate that preservation of the spleen may be associated with a reduced risk of early and overall recurrence translated into a better survival in patients receiving curative surgery for gastric cancer. A large randomized trial is needed to confirm this finding. Indications for splenectomy are few, being limited to those patients with advanced proximal cancers.

Adenocarcinoma↗

Selective localization of tumor-immune spleen cells at the tumor challenge site after adoptive transfer of line 10 tumor immunity in strain 2 guinea pigs.

In this study, the distribution of immune spleen cells was investigated after adoptive transfer of immunity in inbred strain 2 guinea pigs. Spleen cells obtained from line 10 immune donor animals became specifically restimulated in vitro with 3 M KCl-extracted line 10 soluble proteins, but not with 3 M KCl-extracted line 1 or liver proteins. After 4 days culture in vitro, these specifically restimulated immune spleen cells retained their antitumor activity in vivo after adoptive transfer. The specifically restimulated immune spleen cells were radiolabeled with [3H]thymidine, 1 X 10(8) viable cells were adoptively transferred in tumor-bearing guinea pigs, and their distribution was investigated. As controls for the specific localization of the immune cells at the line 10 tumor, the presence of labeled cells was studied in the contralateral transplanted line 1 hepatoma as well as in cellular inflammatory reactions elicited by injection with incomplete Freund's adjuvant (IFA) and complete Freund's adjuvant (CFA). A significantly higher localization of the labeled immune spleen cells in the line 10 tumor and the first and second draining lymph nodes of the line 10 challenge site were found when compared to the influx of these cells in the line 1 tumor and the nontumor antigen-related inflammatory reactions. Because our immune donor animals were immunized with a mixture of line 10 cells and BCG, these animals are immune to both. Line 10 immune spleen cells were restimulated in vitro with PPD and were radiolabeled. These PPD-restimulated immune spleen cells showed no preferential localization at the line 10 tumor challenge site but, as expected, a tendency for localization at the CFA (H37Ra) injection site. Furthermore, PPD-reactive spleen cells from BCG-immunized guinea pigs showed a significantly higher accumulation at the CFA injection site compared to the IFA injection site and the line 10 and line 1 tumor challenge site. From the results, it is concluded that line 10 tumor-immune and BCG-immune spleen cells are two distinct cell populations, and that the existence of cross-reacting antigens between BCG and the line 10 hepatocarcinoma are of no importance for the rejection of the line 10 tumor by immune spleen cells.

Animals↗

In vivo treatment with anti-I-A antibodies: differential effects on Ia antigens and antigen-presenting cell function of spleen cells and epidermal Langerhans cells.

The in vivo activation of T cells by a variety of antigens can be inhibited by the administration of anti-I-A antibodies (Ab) at the time of antigen priming. This inhibition can partially be explained by the temporary loss of Ia molecules from Ia-bearing antigen-presenting cells (APC) in the spleen. In this study, the effects of i.p. injected monoclonal Ab specific for I-A glycoproteins of different H-2 haplotypes on Ia antigen expression and APC function of spleen cells and epidermal Langerhans cells were compared. It was found that anti-I-A Ab quickly bound to both spleen cell and Langerhans cell Ia antigens. Although spleen cell Ia antigens were modulated and thus temporarily disappeared, Ia antigen expression by epidermal Langerhans cells was not modulated. In functional studies, the capacity of spleen cells and epidermal cells from anti-I-A Ab treated vs control animals to function as APC for antigen-specific, I-A- or I-E-restricted T cell clones was tested. A single injection of anti-I-A Ab completely abolished the APC function of spleen cells as shown in several inbred mouse strains, F1 animals, and with the use of several different Ab and T cell clones. In contrast, Langerhans cell-dependent APC function of epidermal cells remained completely unaltered. Even multiple injections of high doses of Ab never caused any inhibition of Langerhans cell function. Experiments with anti-I-Ak or anti-I-Ad Ab in an (H-2k X H-2d)F1 animal showed abrogation of APC function of spleen cells, but again not of Langerhans cells. Thus in vivo anti-I-A Ab administration appears to differentially affect Ia antigen expression and APC function from spleen and epidermis: Ia antigens are modulated from spleen cells but not from epidermis, and APC function disappears in the spleen but not in the epidermis. The abrogation of splenic but not of Langerhans cell APC function with anti-I-A Ab will facilitate the dissection of the relative contributions of Langerhans cells as compared with other APC in the generation of cutaneous immune responses.

Animals↗

Effect of high level of endogenous corticosterone on glucocorticoid receptors in the spleen of rats bearing AH130 tumors.

Increase in spleen weight and in the number of spleen cells was observed in rats bearing AH130 (solid-type) tumors, which have high plasma corticosterone concentrations. In contrast, decrease in the number of spleen cells was observed in adrenalectomized rats without tumors which were injected every 3 hr with a dose of corticosterone sufficient to produce a plasma level close to the physiological range in rats with advanced stage tumors. In the spleen of adrenalectomized, corticosterone-treated rats, the binding capacity and affinity of cytosol receptors for dexamethasone decreased and were low on day 3 after the last injection of corticosterone, when no corticosterone was detectable in the spleen and the receptors in the liver cytosol showed maximal binding capacity. Neither the level of cytosol receptors in the spleen nor their affinity for dexamethasone, however, were changed in tumor-bearing rats on day 3 after adrenalectomy when the level of cytosol receptors and affinity for steroid of the thymus were still very low. The activity of alanine aminotransferase increased appreciably in the spleen cytosol of glucocorticoid-treated rats, but not in tumor-bearing rats, which have high plasma corticosterone levels. These data show that administration of corticosterone at physiological concentrations affected the spleen cells, the glucocorticoid receptors and alanine aminotransferase, but that in AH130 tumor-bearing rats, which have a high level of endogenous corticosterone, the spleen enlarged without change in the above parameters. Thus spleen cells from rats with tumors were more resistant to glucocorticoid than those from animals without tumors. However, there seemed to be no correlation between the level of glucocorticoid receptors and glucocorticoid resistance.

Adrenal Cortex Neoplasms↗

Interleukin-2-induced activation of natural killer activity in spleen cells from old and young mice.

Generation of natural killer (NK) activity in response to a partially purified preparation of rat interleukin-2 (IL-2) was compared in spleen cells derived from young (8-10 weeks old) and old (greater than 2 years old) female C57BL/6 mice. Significant NK activation was observed in both young and old mouse spleen cells incubated with 100 U IL-2/ml for 1-4 days, but the levels of cytotoxic activity generated in old mouse spleen cells was always lower than those of similarly treated young mouse spleen cells. Differences in IL-2-induced NK activation in old and young mouse spleen cells was obtained irrespective of the concentration of IL-2 used (25-400 U/ml). Quantitative comparisons indicated that old spleen cells activated by 3 day incubation with IL-2 acquired about two-fold higher NK activity than fresh young mouse spleen cells but still had only one-fourth of the levels of NK activity attained by IL-2-activated young mouse spleen cells. Cytotoxic activity of IL-2-activated young or old mouse spleen cells were totally abrogated by anti-asialo GM-1 antiserum + C but not by anti-Ly-2 + C treatment, indicating that the activated cytotoxic cells fell in the NK cell category. An analysis of NK precursor (NK-p) frequency by limiting dilution assay indicated that the NK-p frequency was about 4-fold higher in young as compared to old mouse spleen cells. The level of cytotoxic activity attained per NK-p cell was not significantly different for NK-p cells of old or young mice.

Aging↗

Power Doppler sonographic diagnosis of torsion in a wandering spleen.

A wandering spleen is a rare clinical entity resulting from congenital maldevelopment or acquired laxity of the spleen's suspensory ligaments; it may result in torsion of the spleen. We report the gray-scale sonographic, power Doppler sonographic, and CT findings in a case of wandering spleen torsion. The gray-scale sonograms showed a displaced spleen that appeared as a homogeneous, hypoechoic mass suggestive of an enlarged, ectopic spleen in the central abdomen. Power Doppler sonograms showed no blood flow in the parenchyma or hilum of the spleen and were consistent with torsion and infarction in the spleen. Contrast-enhanced CT scans showed a homogeneous, unenhanced mass that was diagnosed as a torsioned wandering spleen. The hilar vessels of the spleen were also unenhanced.

Adult↗

Radical resection of gastric carcinoma with pancreas and spleen preservation and functional cleaning of lymph nodes.

OBJECTIVE: To study the clinical value of radical resection of gastric carcinoma with pancreas and spleen preservation (PSP) and functional cleaning of lymph nodes (LNs) of the spleen hillus and along the splenic artery. METHODS: Pancreas and spleen involvement was retrospectively reviewed among 439 cases of resectable carcinoma of the gastric cardia, gastric corpus and total stomach. During gastric surgery, 2 ml of methylene blue was injected into the subserosal space of the gastric cardia or corpus to observe the spread of lymphatic flow in 54 cases of gastric carcinoma. The metastatic rate of LNs in splenic hillus and along the trunk of the splenic artery (No10, No11), postoperative complications and survival rates were investigated in 63 gastric carcinoma patients that had received gastrectomy with pancreas and spleen preservation (PSP). These were compared with the pancreas preservation (PP) group and pancreas and spleen combined resection (PSR) group. RESULTS: Among these 439 cases, only 25 cases were observed with direct invasion to the pancreas (5.7%), and 10 cases with direct invasion to the spleen (2.3%). After pathological examination of the pancreatic body and tail, we found 22 cases with pancreas and spleen combined resection, 4 cases (18.2%, 4/22) with direct invasion of the capsule and 2 with invasion to the superficial parenchyma (9.1%, 2/22), without metastasis to the lymph nodes within the pancreas and spleen. The metastatic rate of No10, No11 lymph nodes were 17.5% (11/63) and 19.1% (12/63) in the PSP group, 20.8% (45/216) and 25% (54/216) in the PP group, and 20% (6/30) and 23.3% (7/30) in the PSR group. There were no statistically significant differences (P > 0.05). Injection of methylene blue into the subserosal space of the stomach did not diffuse into the spleen or pancreatic parenchyma. Postoperative complications, diabetes and mortality in PSP (0%, 0%, 0%) were lower than in PP (4.2%, 0.9%, 0.9%) or PSR (40%, 10%, 3.3%). The 5-year survival rate (5-YSR) and 10-YSR in PSP (57.5%, 52.0%) were higher than in PSR (37.5%, 30.0%). Those patients with stage II and III(a) treated by PSP, improved markedly. CONCLUSIONS: The surgical procedure of pancreas and spleen preservation for gastric cancer is a safe and organ function protected method. Postoperative complications were lower and survival rates were higher, the radicality was not reduced. These results indicate that PSP is preferred in patients with gastric carcinoma of stage II or III(a).

Adult↗

[Histopathology of spleen deficiency syndrome of chronic atrophic gastritis and its ultrastructural changes].

Pathologic change of gastric mucosa in 247 CAG patients of Spleen Qi (Yang) Deficiency (QYD) and Spleen-Stomach Yin Deficiency(YD) Syndrome were observed. The surface of gastric antrum mucosa of 26 patients with scanning electron microscope as well as the gastric mucosa of 34 patients with transmission electron microscope was observed for their intracellular structure. It was found that the CSAG and CAG I of Spleen QYD amounted to 165 cases (66.8%), and CAG II and III of Spleen-Stomach YD amounted to 34 cases (64.2%). It denoted that the Spleen QYD belonged to mild case, while the Spleen-Stomach YD belonged to severe case. The mitochondria of all kinds of gastric antrum mucosa cells showed retrograded degeneration, the pathologic basis of Spleen Deficiency of CAG, those of Spleen-Stomach QD had sparse broken and swollen mitochondria (82.3%), while the 53.3% of Spleen-Stomach YD displayed vacuolation as its predominant change. The different severity of retrograde degeneration and damage of mitochondria yielded various stage in atrophy of gastric mucosa which was the basis of Syndromes evolution from Defi. to QYD and then YD. Inflammatory change of the gastric mucosa was predominant in Spleen-Stomach YD (45.3%), and far less in QYD (27.1%), P < 0.01.

Gastric Mucosa↗

Allotransplantation of whole spleen in patients with hepatic malignant tumors or hemophilia A. Operative technique and preliminary results.

BACKGROUND: It has been reported that the spleen performs a vital function in the fight against malignant tumors. The spleen is the primary producer of tuftsin, which can directly or indirectly kill tumor cells or inhibit their growth. The spleen is also believed to produce coagulating factor VIII. Therefore, allotransplantation of the spleen can be used in the treatment of patients with malignant tumors and hemophilia A. DESIGN: Heterotopic allotransplantation of whole spleen was performed in six patients with advanced hepatocellular carcinoma and hemophilia A. An adjuvant immunotherapy with interferon alfa was simultaneously administered in the patients with liver cancer. SETTING: Tongji Hospital, Tongji Medical University, Wuhan, China. RESULTS: Among six cases of allografting of whole spleen, five grafts were successful; one failed because of torsion of the splenic hilum. Three patients with hepatocellular carcinoma survived 9, 11, and 5 months after transplantation. Marked shrinkage of hepatic tumors and reduced serum alpha-fetoprotein levels were observed in these patients. On 5-year follow-up, three patients with hemophilia who had undergone splenic allografts were alive, and two had experienced substantial clinical improvement. In these two patients, when the grafts were functioning well and the recipients were free of acute rejection or graft-vs-host reaction, the mean plasma factor VIII activity remained between 30% and 36%, with peak factor VIII activities of 53.7% and 66.6%. We also evaluate operative technique and posttransplantation complications. CONCLUSION: Our results strongly imply that the spleen is one of the primary sites of synthesis of factor VIII and that the spleen has an inherent ability to fight malignant diseases. Allografting of whole spleen may be a promising technique for the treatment of patients with unresectable hepatocellular carcinoma and severe hemophilia A.

Adult↗

Mechanisms of splenic control of murine malaria: reticular cell activation and the development of a blood-spleen barrier.

By complex stromal responses, the spleen controls the course of nonlethal Plasmodium yoelii murine malaria. The course of disease may be divided into four phases. In the immediate postinfective phase, lasting several days, the filtration beds of the spleen are open. Parasitized and nonparasitized erythrocytes, many plasma cells, lymphocytes, and macrophages are sequestered from the blood; and most or all of the parasitized erythrocytes are phagocytized. In the following precrisis phase, approximately 1 week long, there is increasing parasitemia and anemia. The filtration beds of the spleen support large-scale erythropoiesis, lymphopoiesis, plasmacytopoiesis, and monocyte-to-macrophage differentiation. Reticular cells, the stromal cells which form the splenic filtration beds, become activated, showing signs of intense protein secretion and increased branching and mitosis. The locules of the filtration beds appear sealed off from the blood by branches of activated reticular cells. A blood-spleen barrier is thereby formed, protecting splenic hematopoiesis from the parasite. Factors are produced, moreover, which damage intraerythrocytic parasites, producing crisis forms. Crisis follows. It may occur over several days, presaged by the appearance of circulating crisis forms. The filtration beds are opened to the blood. Circulating crisis forms are trapped within the locules of the filtration beds and phagocytized while the stores of reticulocytes produced there in the precrisis period are released to the blood. The malaria, as a result, is no longer patent and the anemia is relieved. In the fourth or postcrisis phase, lasting many months, the normal structure of the spleen is approached. We postulate that reticular cells, normal and activated, have the following functions: to fabricate the locules of the filtration beds; to control the migration of free cells through these beds; to trap free cells, including parasitized erythrocytes, by cell-surface adherence; to open or close the filtration locules, creating a dynamic blood-spleen barrier; to control the circulation of the spleen--by contraction and alignment in normal spleens and by activation and closing of locules in enlarged spleens; to synthesize collagen III; to synthesize factors which influence marrow release of monocytes; and to secrete antiplasmodial substances.

Animals↗

Immunosuppressor cells from newborn mouse spleen are macrophages differentiating in vitro from monoblastic precursors.

Newborn mouse spleen, whose cells strongly suppress the in vitro humoral response of adult spleen cells, is essentially a hematopoietic organ. It contains a large percentage of proliferating cells, among which about 50% are erythroblasts (identified by their spectrin content) and about 15% are cells of the myelocytic and monocytic lineage. Lymphoid cells are a minority, with about 20% B and only 1-2% T lymphocytes. After a 4 days, a culture of newborn spleen cells contains 5-10 times more macrophages than that of an adult spleen. Most of these macrophage precursors from the newborn spleen are proliferating cells, partially glass- or plastic-adherent, which differentiate in culture into activated macrophages producing large amounts of plasminogen activator. It is this macrophage excess which is responsible for the immunosuppressive effect of newborn spleen cells in culture, as indicated by (a) the effect of silica particles added to the cultures, which both relieve the suppression and prevent the accumulation of macrophages and (b) the suppression of the humoral response of adult spleen cells when they are cultured on the adherent cells from a newborn but not from an adult spleen. The suppressive effect of macrophages seems to result, at least in part, from the production of prostaglandin, since it can be relieved by indomethacin or aspirin. Suppression is not related to arginine depletion of the medium or to production of an excess of plasminogen activator. T lymphocytes from newborn spleen or lymph nodes have no suppressive capability.

Aging↗

EL-4 metastases in spleen and bone marrow suppress the NK activity generated in these organs.

The relationship between metastatic cells in the spleen and bone marrow of tumor-bearing mice and the NK activity generated in vitro by cells obtained from these organs was investigated. EL-4 lymphoma and B16 melanoma cells injected intraperitoneally into syngeneic mice (10(6) cells/animal) killed the recipients in 16 days. These tumors had a different metastatic profile: EL-4 metastasized to the spleen and bone marrow while B16 did not. The number of metastatic cells was evaluated by plating spleen or bone-marrow cells of tumor-bearing mice in agarose cultures; in parallel, the ability of spleen and bone-marrow cells to generate NK activity in vitro was assessed. The presence of 10(5) EL-4 cells/10(6) spleen or bone-marrow cells correlated with a total lack of NK activity in these organs; in contrast, no decrease in NK activity was evident in the spleen or bone marrow of B16-bearing mice. The removal of metastatic EL-4 cells (by antibody and complement) from the spleen or bone marrow did not rescue the NK activity. The lack of NK activity in spleen and bone marrow colonized by metastatic cells was not due to induction of a suppressor cell in the host. Metastatic EL-4 cells appeared to have a direct and irreversible suppressive effect on the generation of NK activity by spleen or bone marrow. A possible cause-effect relationship between metastatic colonization of lymphoid organs and suppression of local NK activity is considered.

Animals↗

The small spleen: sonographic patterns of functional hyposplenia or asplenia.

PURPOSE: Functional hyposplenia or asplenia (FAS) can be associated with potential fatal infections. The diagnosis of FAS is traditionally made on liver-spleen scintigraphy and finding Howell-Jolly bodies within erythrocytes. In this retrospective study, our goal was to identify any characteristic sonographic findings of the spleen in patients with FAS in an attempt to determine whether the diagnosis of FAS can be made sonographically. METHODS: In a review of all medical and sonographic records from the period of January 1, 1985, through December 31, 2001, we identified 24 patients (11 men, 13 women) in whom FAS had been diagnosed by liver-spleen scintigraphy (n = 13) or the finding of Howell-Jolly bodies (n = 11). The following sonographic parameters were determined: size of spleen (small, normal, or large), echotexture of the spleen (homogeneous versus inhomogeneous), echogenicity (isoechoic versus hyperechoic), presence of focal splenic lesions, and patterns of splenic vascularization as determined by color Doppler sonography (absent flow, hilar flow, or parenchymal flow). RESULTS: The spleen was small in 20 patients (83%) and normal in the other 4 (17%). Echotexture was homogeneous in 13 patients (54%) and inhomogeneous in 11 (46%). The spleen was isoechoic in 18 cases (75%) and hyperechoic in 6 (25%). Six patients (25%) had focal lesions. Color Doppler sonography showed absent flow in 4 patients (17%), hilar flow in 17 (71%), and hilar and parenchymal vascularization in 3 (12%). CONCLUSIONS: Sonographic findings in the spleen of patients with FAS are characterized predominantly by a small spleen with absence of parenchymal vascularization on color Doppler sonography in most cases. Future prospective studies will be necessary to confirm these findings and to determine whether FAS can be diagnosed reliably with sonography.

Adolescent↗

Transplantation of spleen cells in patients with hemophilia A. A report of 20 cases.

It has been reported that coagulation factor VIII (F. VIII) is produced in the spleen and other organs. Transplantation of splenic whole organ and spleen cells may, therefore, be used to treat patients with hemophilia A. The donor spleen from brain-dead donors was used to prepare spleen cell suspension for transplantation. Twenty-two spleen cell transplantations were performed on 20 patients suffering from severe hemophilia A at our institutes. Two of them underwent a second infusion of spleen cells since there was no increase in plasma F. VIII activity after the first transplantation. All but two patients showed a marked clinical improvement. Increased plasma F. VIII activity was observed in 18 of 20 cases. The peak plasma F. VIII activity in these recipients rose to 10%-15% posttransplantation in 14 cases and to over 15% in 4 cases from pretransplant levels of 0%-3%. Generally, the elevation of plasma F. VIII activity could be detected 4-7 days following transplantation of spleen cells and this lasted from 22 to 58 weeks. Four patients whose peak plasma F. VIII activity was greater than 15% experienced an uneventful course after transplantation. The patients with plasma F. VIII activity over 10% showed less frequent bleeding and prolonged intervals between bleed as well as improvement in hemophilic arthrosis. Two patients who had interval hematuria before transplantation did not have any relapse for up to 2 years after infusion of the spleen cells. These results indicate that spleen cell transplantation may be a promising method for the management of patients with hemophilia A.

Adolescent↗

Handheld gamma probe used to detect accessory spleens during initial laparoscopic splenectomies.

BACKGROUND: Preoperative determination of the accessory spleen still is a major factor in the failure of both laparoscopic and conventional techniques. This study aimed to evaluate the practicability and efficacy of a handheld gamma probe in identifying accessory spleens at the initial intervention. METHODS: This study evaluated 17 patients undergoing laparoscopic splenectomy attributable to benign hematologic disorders. All the patients had preoperative ultrasonography, computed tomography (CT) scan, and nuclear scintigraphic examination of the abdominal cavity to assess the size of the spleen, and to determine the existence of the accessory spleen or spleens. For all the patients, a handheld gamma probe count was used intraoperatively as an adjuvant method to define the presence and location of the accessory splenic tissue. Control nuclear scintigraphic examinations of all the patients were performed 1 month after the surgical procedure. RESULTS: In two cases, intraoperatively accessory splenic tissue was detected by gamma probe, confirming the preoperative CT findings for the patients. One of these patients had three accessory spleens, although preoperative CT scan showed only two of them. However, by the help of the gamma probe, a third spleen located retroperitoneally was defined. For two patients, laparoscopic exploration and handheld gamma probe count did not identify any accessory splenic tissue, although preoperative CT scan indicated accessory spleens. For detecting accessory splenic tissue, the sensitivities of the studied techniques were 0% for ultrasonography, 75% for CT scan, 0% for preoperative nuclear scintigraphy, 75% for laparoscopic exploration, and 100% for perioperative gamma probe examination. CONCLUSION: Preoperative imaging methods for accessory spleen determination still have limited benefits because of their limited sensitivity. Thus, the handheld gamma probe technique may be an adjuvant method for laparoscopic exploration ensuring that no accessory splenic tissue is missed during the initial surgical treatment of benign hematologic disorders.

Adult↗

Arachidonic acid metabolism in murine leishmaniasis (Donovani): ex-vivo evidence for increased cyclooxygenase and 5-lipoxygenase activity in spleen cells.

This study examined the metabolism of arachidonic acid (20:4) by splenic mononuclear cells from BALB/c mice infected with Leishmania donovani. Spleen cells removed from mice after either 4 or 8 weeks of infection and cultured in the presence of phytohemagglutinin (PHA) incorporated 60-70% less [3H]thymidine and synthesized 2- to 5-fold more prostaglandin E2 than did spleen cells from normal mice. Inhibition of cyclooxygenation by sodium meclofenamate was associated with restoration of PHA-induced spleen cell blastogenesis. Thin-layer chromatography of spleen cell extracts showed that PHA-stimulated spleen cells from infected animals synthesized 54 and 27% more 5-hydroxyeicosatetraenoic acid (5-HETE) and 12/15-HETE respectively, when compared to spleen cells from noninfected mice. Culture medium of spleen cells from infected mice also contained 25% more immunoreactive leukotriene C4. Nordihydroguaiaretic acid (3 microM) reduced spleen cell synthesis of 12/15-HETE while minimally affecting 5-HETE production. These data indicated that increased cyclooxygenase and lipoxygenase activities in spleen cells from mice infected with L. donovani resulted in the generation of 20:4 metabolites with the capability of altering T-lymphocyte function.

Animals↗

Remarkable activation of polyamine biosynthesis in hematopoiesis and hyperplasia of spleen in mice with hemolytic anemia caused by infection with Plasmodium berghei.

Ornithine decarboxylase (ODC) activity was markedly induced in the spleen of mice infected with Plasmodium berghei, showing maximal activity at 8 days after the infection. The increase of spleen weight, on the other hand, reached its peak after 14 days of infection. In the blood of P. berghei-infected mice, no increase of ODC activity was observed. This indicated that ODC was induced in the spleen cells, but not in the parasites themselves which existed in the blood. Polyamines (putrescine, spermadine and spermine) were also elevated in the spleen following induction of the ODC activity. On the other hand, increases of ODC activity and spleen weight were observed in the spleen of mice with hemolytic anemia induced by acetylphenylhydrazine, but the extent of these increases were smaller than those in the spleen of mice infected with P. berghei. The present results suggest that increases in ODC activity and polyamine levels in the spleen of P. berghei-infected mice are related to hyperplasia of the spleen (splenomegaly) where the formation of leukocytes and erythrocytes (hematopoiesis) was dramatically stimulated by the infection.

Anemia, Hemolytic↗

Augmentation of the phagocytic activity of murine spleen cell populations induced by Adriamycin.

C57B1/6 mice were injected i.v. with Adriamycin (5 mg/kg) and various days later, spleen cells were tested for Fc dependent phagocytic activity by measuring protection of 51Cr-labelled, antibody coated SRBC from hyptonic shock. No difference in phagocytic activity was observed with spleen cells from untreated mice or mice treated with Adriamycin 1-7 days prior to killing. Increases in phagocytic activity were, however, seen with spleen cells from mice treated 9 to 13 days prior to killing. Phagocytic activity of spleen cells from mice treated 5 days prior to killing was increased after these cells were cultured for 5 days when compared to cultured cells from untreated mice. Despite depletion of mature phagocytic cells from spleen cells suspensions by silica treatment, followed 24 hours later by silica removal by density gradient centrifugation, phagocytic activity was observed with spleen cells from ADM treated mice (day-5) after 5 days in culture. No phagocytic activity was seen with spleen cells from untreated mice using the same silica treatment and culture conditions. When cultured spleen cells from untreated or ADM treated mice (day-5) were fractionated by plastic adherence, twice as many adherent cells were removed compared to controls. Their phagocytic activity (per cell) was, however, the same. Thus, ADM may increase the number of immature nonphagocytic macrophages in the spleen resulting in increased mature macrophages after culture.

Adjuvants, Immunologic↗