Surgical Splenectomy Research Articles

Extramedullary Hematopoiesis and Splenic Vein Thrombosis, a Unique Presentation Of Pre-Clinical Essential Thrombocythemia

Essential thrombocythemia (ET) is of the BCR-ABL-Negative myeloproliferative neoplasms (MPN). The incidence of ET is approximately 2.5 in every 100,000 person per year. However, given the good prognosis, associated long life expectancy, and increasing detection in younger populations,ET is associated with a higher prevalence rate estimated to be 24 in every 100,000 person per year. ET is characterized by thrombocytosis, vasomotor symptoms, and a variable but increased risk of thrombosis and bleeding. Half of all ET patients will have a positive JAK2 and/or MPL mutation(s).Extramedullary hematopoiesis (EMH) is not a common finding in ET. Nonetheless, ET and other MPNs are associated with the mobilization of CD34+ cells into the peripheral blood. This process can ultimately lead to the seeding of extramedullary sites with primitive hematopoietic capacity, resulting in EMH within the spleen and liver, as well as a variety of other organs. Herein we describe a case that presented with life-threatening thrombosis and was found to have hepatic EMH several months prior to a clinical and pathologic diagnosis of ET. Case descriptionA 22 year-old woman presented 10 days post Cesarean section with abdominal pain and hematemesis. Abdominal imaging showed hepatomegaly, splenomegaly, along with splenic and portal vein thrombosis. The patient underwent an emergency surgical splenectomy due to severe portal hypertension and endoscopic evidence of gastric variceal bleeding. A random liver biopsy was also performed intra-operatively. The splenectomy resulted in resolution of the GI bleeding and the varices normalized on follow up. Her platelet count was normal at the time of operation, but post-splenectomy her platelet count peaked at 1,217 K/ µL. Extensive testing did not unravel any identifiable inherited and/or acquired hypercoaguable factors. Subsequently anticoagulation therapy was recommended for 6 months.On pathology review, the spleen histology showed congestion, but otherwise no diagnostic abnormalities were noted. The liver biopsy showed evidence of EMH but did not identify any liver parenchymal disease.On subsequent follow up, the patient had persistent and marked thrombocytosis for over a year. A bone marrow biopsy was performed which showed a hypercellular bone marrow and megakaryocytic hyperplasia with a few large forms. There was no dysplasia or significant reticulin fibrosis. JAK2 mutation and BCR-ABL translocation were negative. Hydroxyurea and aspirin were started due to high risk of thrombosis. DiscussionWe report this unique case in which there was evidence of extramedullary hematopoiesis, along with pathologic and life threatening visceral thrombosis several months before the patient met criteria for diagnosis of ET. This supports the notion that neoplastic cells can mobilize and seed other organs early in the course of MPNs, including ET. Thrombotic risk in MPNs can also occur in the preclinical phase of MPNs as has been suggested in other reports. We also conclude that the demonstration of EMH in individuals with no preexisting hematologic neoplasm should warrant close follow up and assessment. Disclosures:No relevant conflicts of interest to declare.

Myelodysplastic/Myeloproliferative Neoplasms, Unclassifiable (MDS/MPN, U): Natural History and Clinical Outcome By Therapeutic Approach

BackgroundMyelodysplastic/myeloproliferative neoplasm, Unclassifiable (MDS/MPN-U) is a distinct entity among the myeloid neoplasms, characterized by the simultaneous presence of both dysplastic and proliferative features. The natural history, clinical characteristics, response to treatment and patient outcome of patients with MDS/MPN-U has not been well described, apart from the MDS/MPN-U provisional entity of Refractory Anemia with Ringed Sideroblasts and Thrombocytosis (RARS-T). AimsClinicopathologic features of 85 patients with MDS/MPN-U and without RARS-T were evaluated, along with clinical outcomes based on treatment strategy. MethodsAll patients with MDS/MPNs treated from July 1986 to February 2013 at MDACC were reviewed. Patients seen prior to 2006 with a recorded diagnosis of MDS/MPD or chronic MPD-U were reviewed by two hematopathologists and diagnoses were revised as appropriate according to the current WHO criteria. All RARS-T patients per WHO 2008 definition were excluded, and patients were excluded if the de novo presence of both myelodysplastic and proliferative features at diagnostic presentation per WHO criteria was unable to be confirmed. ResultsMDS/MPN-U patients were predominantly over the age of sixty (92%), with a median age of 70 years (range 22 – 90), and 61 patients (72%) were male. 29 patients (35%) had splenomegaly at presentation. Median presenting white blood cell (WBC) count was 17 x 10⁹/L (1 – 141 x 10⁹/L), median hemoglobin was 10 g/dL (5 – 15 g/dL), and median platelet (PLT) count was 85 x 10⁹/L (6 – 1168 x 10⁹/L). Of 56 patients with known JAK2 status, 17 patients (30%) had the presence of the JAK2 V617 mutation. The majority of patients had either diploid cytogenetics (49%) or trisomy 8 as the sole abnormality (15%); 10 patients (12%) had a complex karyotype.Median OS was 12.4 months (range 0.3 – 138.7). A uniquely favorable outcome was seen in the 11 patients presenting with a PLT count ≥ 450 x 10⁹/L, with median OS 52.5 vs 11.9 months (p<0.001) {Figure 1}. Other variables associated with favorable outcome included age <60 (p < 0.001), lack of circulating blasts (p = 0.023) and <5% bone marrow blasts (p = 0.017). Neither JAK2 V617F mutant status nor karyotype associated with outcome, and in multivariate analysis, only platelet count retained prognostic significance (p=0.001). Whereas the IWG-MF score was not prognostic, the MDS IPSS score imparted a statistically significant classification for the MDS/MPN-U cohort, with a median OS by IPSS score of 15.4, 17.7, 8.3 and 6.9 m, respectively (p = 0.039) {Figure 2}.Overall, 36 patients (42%) received hypomethylating agent (HMA) therapy. 13 (15%) were treated with an immunomodulatory approach (e.g. lenalidomide, interferon-α), five (6%) underwent splenectomy and five (6%) received stem cell transplant (SCT). HMA-treated patients had an OS of 16.4 vs 11.5 months with other approaches (p=0.57); patients on immunotherapy had a non-significant trend towards worse OS of 11.4 vs 15.4 months (p=0.07). The five patients receiving splenectomy had OS 51.1 m vs 10.0 mo (p=0.12), and with SCT 12.4 vs 12.5 months (p=0.16). [Display omitted] [Display omitted] ConclusionOverall, our analysis validates the diagnosis of MDS/MPN-U as a unique pathologic entity, with features and prognostic variables distinctive from either PMF or MDS. While no statistically significant differences in OS were identified based on therapy; in terms of the various diagnostic, prognostic and treatment strategies, MDS/MPN-U patients without RARS-T appear to have characteristics and outcome most analogous to MDS. The favorable outcome of surgical splenectomy among those MDS/MPN-U patients with splenomegaly suggests this may also be part of a a reasonable therapeutic approach. Disclosures:No relevant conflicts of interest to declare.

Spleen Injuries in Spain: At What Point Are We?

IntroductionManagement of spleen trauma has changed over last few decades, although there are no data on its treatment in Spain. The aim of this study is to determine the characteristics of spleen injuries in adults with severe abdominal injuries and how we manage them. MethodsA prospective study using the databases of six Spanish hospitals: Gregorio Marañón Hospital, Virgen de la Vega Hospital, Torrevieja Hospital, Getafe Hospital, Doce de Octubre Hospital and Corporació Sanitària Parc Taulí. ResultsA total of 566 patients who had sustained spleen injuries were analyzed (448 males and 118 females), most of them were due to blunt trauma (94%), and the most frequent mechanism of injury was motor vehicle accident. The mean Injury Severity Score (ISS) was 25.2. The initial treatment was surgical in 56.6% of the patients (85.3% total splenectomy and 14.7% other conservative surgical procedures, of which 4.6% finally failed and required total splenectomy). The remaining 43.4% were initially managed conservatively, but 6.5% of them finally required surgical splenectomy, and in 8.8% angioembolization was performed. ConclusionIn Spain, management of spleen trauma is mainly surgical (particularly splenectomy). Angioembolization and conservative surgical procedures are now hardly used.

Health of adults living with a clinically significant haemoglobinopathy in New South Wales, Australia

To comprehensively review the health needs of patients living with clinically significant haemoglobinopathies (thalassaemia and sickle-cell disease (SCD)) in New South Wales, Australia. A survey-based health needs assessment was undertaken in outpatients cared for at five tertiary institutions in metropolitan and regional centres. Sixty-three of 121 adults (approximately 80-90% of adult patients with transfusion-requiring haemoglobinopathies in New South Wales) completed an in-house and commercial health-related quality assessment survey (SF-36v2). Subjects came from more than eight world regions, with those with SCD being more likely to be born outside of Australia than subjects with thalassaemia (P < 0.001, likelihood ratio 20.64) as well as more likely to have been refugees (26% vs 2%). The population contained socially disadvantaged subjects with 13 subjects (20.6%) having incomes below the Australian poverty line. Complications of thalassaemia were comparable to previous international reports although our subjects had a high rate of secondary amenorrhea (>12 months = 27%) and surgical splenectomy (55.6%). Use of hydroxyurea in SCD was less than expected with only 46.6% of subjects having prior use. Lack of universal access to magnetic resonance imaging-guided chelation (international best practice) was evident, although 65.5% had been able to access magnetic resonance imaging through clinical trial, or self-funding. Patients with SCD and thalassaemia experience considerable morbidity and mortality and require complex, multidisciplinary care. This study revealed both variance from international best practice and between specialist units. The results of this research may provide the impetus for the development of clinical and research networks to enable the uniform delivery of health services benchmarked against international standards.

First experience with single incision laparoscopic surgery in Slovakia: Concomitant cholecystectomy and splenectomy in an 11-year-old girl with hereditary spherocytosis

Hereditary spherocytosis is an autosomal dominant inheritance disorder of the red blood cell membrane characterized by the presence of spherical-shaped erythrocytes (spherocytes) in the peripheral blood. The main clinical features include haemolytic anemia, variable jaundice, splenomegaly and cholelithiasis caused by hyperbilirubinemia from erythrocyte hemolysis. Splenectomy does not solve the congenital genetic defect but it stops pathological hemolysis in the enlarged spleen. If gallstones are present, it is appropriate to perform cholecystectomy at the time of splenectomy, although the patient has symptoms of gall bladder disease. We present the case of single incision laparoscopic surgical (SILS) concomitant splenectomy and cholecystectomy performed with conventional laparoscopic instruments in an 11-year-old girl with the diagnosis of hereditary spherocytosis. A 2-3 cm umbilical incision was used for the placement of two 5 mm trocars and one 10 mm flexible videoscope. Conventional laparoscopic dissector, grasper, Ligasure, Harmonic Ace and hemoclips were the main tools during surgical procedure. We prefer Single Incision Laparoscopic Surgery Foam Port (Covidien) as the single umbilical device for introduction into the abdominal cavity. First, we performed cholecystectomy, then the gallbladder was put aside over the liver and after that we peformed splenectomy. To remove the detached spleen and gallbladder, a nylon extraction bag is introduced through one of the port sites. The spleen is than morcellated in the bag with forceps and removed in fragments. After that we removed them and the umbilical fascial incision was closed. Splenectomy is the only effective therapy for this disorder and often it is performed in combination with cholecystectomy. Conventional surgery requires a wide upper abdominal incision for correct exposure of the gallbladder and spleen. Our experience shows that SILS splenectomy and cholecystectomy is feasible even in young children and despite the small number of cases in the world, we consider the combined laparoscopic approach safe and effective for the treatment of hereditary spherocytosis. According to actually published guidelines, the laparoscopic approach to concomitant splenectomy and cholecystectomy is recommended, but it depends on the availability of appropriately trained surgeons and suitable equipment.

Surgical Splenectomy Indications in Benign and Malignant Splenic Diseases and the Role of Minimally Invasive Surgery

Surgical Splenectomy Indications in Benign and Malignant Splenic Diseases and the Role of Minimally Invasive Surgery

Nonsurgical management of complicated splenic rupture in infectious mononucleosis

We report on a 35-year-old man who presented to the emergency department with acute abdominal pain, postural hypotension, and tachycardia after having been diagnosed with Epstein-Barr virus infection 1 week before. Abdominal ultrasound and computed tomography revealed splenic rupture, and the patient underwent successful proximal angiographic embolization of the splenic artery. The course was complicated by painful splenic necrosis and respiratory insufficiency due to bilateral pleural effusions. Six weeks later, he additionally developed severe sepsis with Propionibacterium granulosum due to an intrasplenic infected hematoma, which required drainage. All complications were treated without surgical splenectomy, and the patient finally made a full recovery.

Traumatismo esplénico en España: ¿en qué punto estamos?

IntroductionManagement of spleen trauma has changed over last decades, although there is no data on its treatment in Spain. The aim of this study is to determine the characteristics of spleen injuries in adults with severe abdominal injuries and how we manage them. MethodsA prospective study using the databases of six Spanish hospitals: Gregorio Marañón Hospital, Virgen de la Vega Hospital, Torrevieja Hospital, Getafe Hospital, Doce de Octubre Hospital and Corporació Sanitària Parc Taulí. ResultsA total of 566 patients who had sustained spleen injuries were analyzed (448 males and 118 females), most of them were due to blunt trauma (94%), and the most frequent mechanism of injury was motor vehicle accident. The mean Injury Severity Score (ISS) was 25.2. The initial treatment was surgical in 56.6% of the patients (85.3% total splenectomy and 14.7% other conservative surgical procedures, of which 4.6% finally failed and required total splenectomy). The remaining 43.4% were initially managed conservatively, but 6.5% of them finally required surgical splenectomy, and in 8.8% angio-embolization was performed. ConclusionIn Spain, management of spleen trauma is mainly surgical (particularly splenectomy). Angio-embolization and conservative surgical procedures are now hardly used.

Kyste splénique et grossesse : une pathologie rare de prise en charge difficile

Maternal splenic cyst during pregnancy seems to be a rare disease whose treatment is not codified. The most feared complication of these cysts is the rupture. In case of rupture, 60% of cases occur during the third trimester of pregnancy and result in a significant maternal and fetal morbidity and mortality. We examine the two main modes of treatment used nowadays: surgical splenectomy or radiological drainage.

Higher Baseline Hemoglobin and Splenectomy Are Risk Factors for Venous Thromboembolism in Adults with Sickle Cell Variant Genotypes

AbstractAbstract ▪3243▪This icon denotes a clinically relevant abstract Background:Sickle cell disease (SCD) is a hypercoagulable state, leading to increased rates of thrombotic complications such as stroke and venous thromboembolism (VTE). We have previously demonstrated an increased risk of non-catheter-related VTE among patients with sickle cell variant syndromes compared to those with sickle cell anemia (SS/Sβ0) genotypes. Variations in baseline laboratory values, including hemoglobin and hemolytic rate, have been shown to modify the risk of developing complications such as acute chest syndrome and retinopathy in SCD patients. In addition, splenectomy has been identified as a risk factor for VTE in patients with other hemoglobinopathies such as β-thalassemia intermedia. Therefore, we sought to determine the hematologic and clinical risk factors associated with VTE among our cohort of patients with SC and Sβ+thalassemia genotypes. Methods:We conducted a retrospective cohort study of all patients with hemoglobin SC or Sβ+thalassemia genotypes cared for at the Sickle Cell Center for Adults at Johns Hopkins between August 2008 and July 2012. Baseline hematologic parameters were recorded for all patients and were defined as steady-state outpatient laboratory values that were taken at least 1 month after a hospitalization and at least 3 months after a transfusion. Clinical data such as SCD-specific comorbidities and history of surgical splenectomy were also collected for all patients. A history of VTE was confirmed by radiography in the majority of cases. In cases where radiology was not available, only patients with a verified history of anticoagulation were included. Patients with a history of catheter-related VTE only were excluded (n=2). Results:Ninety-five patients with sickle variant genotypes had complete data and were included for analysis. The median age at follow-up was 42 years (range 21–72 years), and 55.8% of patients were female. Twenty-six (27.4%) patients had a history of VTE, 28.6% (8/28) with Sβ+thalassemia genotype and 26.9% (18/67) with SC genotype. Patients with a history of VTE had higher baseline hemoglobin levels compared to those without history of clot (11.6 g/dL vs. 10.8 g/dL, p<0.001). Additional laboratory parameters, including baseline WBC, platelet levels, and reticulocyte counts, did not significantly correlate to a history of VTE. A history of splenectomy was noted in 26.9% (7/26) of patients with VTE, 4 of whom developed a pulmonary embolism (PE) only, 2 of whom had a history of both deep venous thrombosis (DVT) and PE, and 1 of whom experienced an abdominal vein thrombosis. Splenectomy was significantly correlated to VTE on bivariate analysis (p=0.001), whereas other prevalent comorbidities such as avascular necrosis and retinopathy did not appear to be associated with VTE. On multivariate analysis controlling for demographics and genotype, older age (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01–1.10, p=0.015), hemoglobin level (OR 3.82, CI 1.83–7.98, p<0.001) and history of splenectomy (OR 4.93, CI 1.10–22.14, p=0.038) were found to be independent risk factors for VTE in our cohort. On subgroup analysis by VTE type, increased hemoglobin level persisted as a risk factor for both DVT (OR 5.69, CI 2.04–15.83, p=0.001) and PE (OR 3.55, CI 1.65–7.68, p=0.001), but splenectomy was statistically correlated to PE only (OR 4.79, CI 1.05–21.78, p=0.043). Conclusions:In patients with SC and Sβ+ thalassemia genotypes, VTE is common complication and is associated with higher baseline hemoglobin levels. In addition, splenectomy appears to be a risk factor for VTE, and specifically PE, in this population. These findings suggest that increased whole blood viscosity and surgical splenectomy may play a role in the development of venous thrombosis in SCD. Further studies will be needed to determine if functional asplenia is also associated with VTE in patients with sickle cell variant genotypes, and whether laboratory parameters can be used to predict VTE risk in SCD. Disclosures:Naik:NHLBI (K12): Research Funding. Streiff:sanofi-aventis: Consultancy, Honoraria; BristolMyersSquibb: Research Funding; Eisai: Consultancy; Janssen Healthcare: Consultancy; Daiichi-Sankyo: Consultancy. Lanzkron:Hemaquest: Membership on an entity's Board of Directors or advisory committees; NHLBI: Research Funding.

Selective Splenic Artery Embolization for the Treatment of Thrombocytopenia and Hypersplenism in Paroxysmal Nocturnal Hemoglobinuria (PNH)

Abstract 4408PNH is a hemolytic disorder resulting from dysregulation of complement on the rbc, and is associated with immune mediated marrow failure and marked hypercoagulability. Thrombosis can be prevented with anticoagulation or the complement inhibitor eculizumab, and it often involves the hepatic, portal, and splenic veins. This can result in an increase in portal pressure and complications that we term the “Thrombosis-Splenomegaly-Thrombocytopenia” syndrome (TST). TST is frequently associated with abdominal pain, and thrombocytopenia may be simultaneously exacerbated by marrow failure. Particularly, thrombocytopenia can complicate efforts at anticoagulation, leaving the patient exposed to the risk of further events. In some patients thromboses can reversed with tPA, but others will not be candidates because they have presented late after their thromboses. Ablating splenic function would be desirable: however, with a high risk of perioperative thrombosis, surgical splenectomy may be hazardous, particularly in patients who have already had thrombosis, and will confer a risk of sepsis. Here we report on 4 patients with PNH and late-presenting TST. We referred these 4 patients for selective splenic artery embolization (SSAE), which involves cannulating branches of the splenic artery– beyond the hilum– and introducing gelfoam and microcoils. We planned a multi-session stepwise approach: we started with the inferior branches of the splenic artery, to decrease the risk of pleural effusions. We planned to infarct no more than 1/3 of the spleen at any one time and to allow weeks to months for recovery. We routinely administered vaccinations and discontinued anticoagulation temporarily, and patients were given prophylactic antibiotics, fluids, analgesics, and antipyretics, and they were observed in the hospital with a back-up surgical team. Prior to the procedure, the median platelet count was 17 and the median spleen size was 22 cm. Patients 1–4 were treated with 3,2,1, and 3 procedures respectively, which resulted in a significant reduction in spleen volume in all 4 patients. The post procedure platelet counts were respectively 123, 12, 44, and 90, which represented a significant increase for all patients except patient 2, who remained thrombocytopenic; since there was evidence of bone marrow failure, she underwent a successful unrelated SCT. Patients 1,2, and 4 all had had abdominal pain before the procedure, which very significantly improved after recovery from the procedure, which we attribute to decreased venous return from the spleen into the portal circulation. Patients 1–3 were treated before eculizumab was available and patient 1, 3, and 4 are now on it. Patient 4 is a special case in that she had been on eculizumab for several months prior to the SSAE, but had had only a partial reduction in the red cell transfusion requirement; C3d deposition on rbcs was documented by flow cytometry, and it was thought that extravascular hemolysis was limiting her response to eculizumab, as has been described. Of note, her hemoglobin began to rise after the embolization procedure, concurrent with the increase in the platelet count, and a significant further reduction in the red cell transfusion requirement, suggesting that partially reducing splenic function markedly reduced C3-mediated extravascular hemolysis. Of the 9 procedures performed on these 4 patients, only one was complicated by a clinically significant left sided pleural effusion, which was drained by thorascope. All patients are doing well between 3.5 and 11 years after their procedures. We conclude that SSAE, when performed by an experienced interventional radiologist, is relatively safe in patients with PNH and TST, it produces sustained correction of hypersplenism without the risk associated with surgery or the asplenic state, and can be of benefit to patients on eculizumab who have hypersplenism.PtAge at diagnosisLowest plt count pre-SSAESpleen size (cm) pre-SSAEAbdominal pain pre-SSAEBone marrowPlt count post SSAESpleen size post SSAEAbdominal pain after recovery from SSAEComplications of SSAEFollow up (yrs)1304221+Hypercellular Megakaryocyte aggregates12312NoAbd pain and fever102181919+Hypocellular Megas reduced1212NoPain, pleural effusionSCT3271436–Erythroid hyperplasia Megas adequate44NANoAbd pain11426<1022+Normocellular Megas adequate9012NoNone3.5 Disclosures:No relevant conflicts of interest to declare.

Acute Splenic Irradiation Reduces Brain Injury in the Rat Focal Ischemic Stroke Model

Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain.

Transcatheter Embolization of Extensive Left Gastric Artery Collaterals Presenting With Massive Upper Gastrointestinal Bleed

We report a case of extensive left gastric artery collaterals that were formed in the region of gastric fundus due to splenic artery occlusion and resulted in massive hematemesis. These collaterals were thought to be portosystemic collaterals related to portal hypertension during upper endoscopy study and single-phase venous computed tomography studies. The collaterals were treated by transcatheter endovascular coil embolization. Our case highlights the importance of recognizing and differentiating left gastric artery collaterals from gastric venous varices as a cause of hematemesis since the treatment approach for each condition is totally different. It also introduces the feasibility of percutaneous left gastric artery embolization as a treatment for this condition, without the need for surgical splenectomy and partial gastrectomy which have a higher mortality and morbidity.

Endovascular treatment of visceral artery aneurysms and pseudoaneurysms: our experience

The aim of this study was to analyse our 8 years of experience with endovascular treatment of visceral aneurysms and pseudoaneurysms. From January 2002 to September 2009, we used an endovascular approach to treat 30 patients (22 men, eight women) affected by aneurysm (n=18) or pseudoaneurysm (n=13) of the splenic (n=11), hepatic (n=6), renal (n=5), pancreaticoduodenal (n=3), left gastric (n=2), gastroduodenal (n=1), rectal (n=1) or middle colic (n=1) arteries and the coeliac axis (n=1). Of these, 26/31 were treated with metal coils, 3/31 with Cardiatis multilayer stent, 1/31 with a coated stent and 1/31 with coils and Amplatzer plug. Procedures were performed electively in 10/30 cases and during haemorrhage in 20/30 cases. Follow-up was performed clinically (cessation of bleeding) and at 1, 6 and 12 months by colour-Doppler ultrasound (CDUS) and computed tomography (CT) angiography. In 31/31 aneurysms and pseudoaneurysms we obtained immediate exclusion. In four patients with aneurysm and in four with pseudoaneurysm, parenchymal ischaemia occurred; one was treated with surgical splenectomy. One patient with pseudoaneurysm of the coeliac axis died 10 days later because of new bleeding. During follow-up, all aneurysms and pseudoaneurysms remained excluded. Percutaneous treatment is effective and safe, with a small number of complications, especially when compared with traditional surgery.

Apo-Transferrin Injections Reduce Transferrin Receptor 1 Concentration on Erythroid Precursors and Reverse Ineffective Erythropoiesis In Splenectomized Beta-Thalassemic Mice

AbstractAbstract 4283Beta-thalassemia results from a mutation in the beta-globin gene which leads to ineffective erythropoiesis (IE), shortened red blood cell (RBC) survival, and anemia requiring varying degrees of transfusion-dependence. Our previous data demonstrate that thalassemic (Hbbth1/th1) mice treated with apo-transferrin have more circulating RBCs, each with lower mean corpuscular hemoglobin (MCH), increased hemoglobin, and reversal of splenomegaly. These results suggest that anemia in beta-thalassemia is a consequence of excess intracellular heme in developing erythroblasts. Because iron in erythroid precursors is predominantly used for heme synthesis and iron uptake is limited to transferrin-bound iron through transferrin receptor 1 (TfR1), we hypothesized that exogenous apo-transferrin injections reduce MCH by decreasing surface TfR1 expression. To clarify the direct effect of splenic erythropoiesis in this experimental system, we analyzed splenectomized thalassemic mice for the effect of apo-transferrin injections on erythroid precursor differentiation and expression of TfR1 in the bone marrow as well as all RBC parameters, serum erythropoietin levels, and degree of extramedullary erythropoiesis (EMH) in the liver. We used intraperitoneal human apo-transferrin injection, 10 mg daily for 20 days. Apo-transferrin treated splenectomized thalassemic mice were compared with age and gender matched untreated splenectomized mice. A novel flow cytometry analysis using CD44 and TER119 in the bone marrow allowed us to measure the expression levels (using mean fluorescence intensity) of TfR1 at different stages of erythroid differentiation. Splenectomy in thalassemic mice resulted in decreased reticulocyte count (P<0.0001) and hemoglobin concentration (P<0.0001), an increase in serum erythropoietin (P<0.0001), and a higher concentration of TfR1 on erythroid precursors of all stages (P=0.003, 0.01, 0.02, and 0.003 for proerythroblasts, basophilic, polychromatophilic, and orthochromatophilic erythroblasts, respectively) relative to age and gender matched non-splenectomized thalassemic mice. Despite this deterioration, apo-transferrin injections increased RBC counts (P<0.0001) and hemoglobin concentration (P<0.0001) and decreased reticulocyte counts (P<0.0001), MCV (P<0.0001), and MCH (P=0.0002) to levels similar to non-splenectomized apo-transferrin treated thalassemic mice. Additionally, serum erythropoietin concentration decreased (P=0.009), RBC survival significantly improved (t½ = 33.5 vs. 10.6 days, P<0.0001), and EMH in the liver completely reversed relative to untreated splenectomized thalassemic mice. We also demonstrate that apo-transferrin treatment in splenectomized thalassemic mice reduces the amount of TfR1 expressed on erythroblasts at all stages of erythroid development (P=0.0007, 0.007, 0.01, and 0.004 for proerythroblasts, basophilic, polychromatophilic, and orthochromatophilic erythroblasts, respectively) compared with untreated splenectomized thalassemic mice. During a three month follow up after splenectomy, apo-transferrin injections decreased mortality in thalassemic mice (likely by reversal of severe anemia; hemoglobin of 11.3 vs. 7.5 g/dL in treated and untreated splenectomized thalassemic mice, respectively). In summary, exogenous apo-transferrin increases the efficiency of erythropoiesis in splenectomized thalassemic mice as previously documented in non-splenectomized thalassemic mice, relieving their dependence on EMH in the liver and spleen. Decreased iron uptake in erythroid precursors of apo-transferrin treated splenectomized thalassemic mice is associated with a reduction in the amount of TfR1 on all stages of erythroid precursor development and likely explains the reduction of MCH in apo-transferrin treated mice. Our findings demonstrate a novel feedback inhibition of TfR1 expression by exogenous apo-transferrin injection. Taken together, these results support the use of apo-transferrin to 1) delay or prevent the need for surgical splenectomy and 2) ameliorate anemia, IE, and EMH in splenectomized patients with beta-thalassemia. Disclosures:Cabantchik:Aferrix Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Partial Splenic Embolization as an Alternative to Splenectomy in Hypersplenism – Single Center Experience in 16 Years

In young patients with hypersplenism splenectomy implies a lifelong increased risk for post-splenectomy infection. Especially in children, whose immune system is not yet completely matured, the risk for some bacterial infection may increase after splenectomy because the spleen helps to defend against encapsulated bacteria like pneumococci, meningococci and haemophilus influenzae. We present partial splenic embolization as an alternative to surgical splenectomy. Partial splenic embolization was performed in 17 patients from 1-31 years with hypersplenism of various etiologies and was achieved by selective catheterization of splenic arteries and injection of 150-355 μm polyvinyl alcohol particles (Ivalon (®)). After the intervention the patients received an intensified analgesic regimen and antibiotics to avoid concurrent infectious complications. Partial splenic embolization represented between 30-60% of the splenic volume and was followed in general by an immediate increase of all blood cells and symptoms of hypersplenism were reduced. In 2 patients the procedure was repeated because the result of the first embolization was insufficient in one patient and became necessary in another in the long run. Post-procedural side effects included fever, abdominal pain, ascites and pleural effusions. There were no acute infections in any patient. Our monoinstitutional experiences over 16 years offer, partial splenic embolization in patients with hypersplenism from miscellaneous reasons as a low-risk alternative to surgical splenectomy. The procedure can be repeated as necessary, but it is always a temporary palliation depending on the underlying disease which often leads to liver transplantation. Using intensive analgesia and antibiotics side effects were tolerable, and patients could be discharged after a few days.

Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate

Patients with primary immune thrombocytopenia (ITP) may require treatment to reduce the risk of serious bleeding if platelets remain consistently below 30 × 10(9)/L. While approximately 70-80% of patients respond to an initial course of corticosteroids, relapse is common. For steroid-refractory patients, there is a choice between surgical splenectomy and further medical treatments, based on many factors including the patient's bleeding history, fitness for surgery, comorbidities, tolerance of adverse events, lifestyle and preferences. Treatments that have traditionally been used (corticosteroids, azathioprine, danazol) suppress the immune system, potentially predisposing patients to infection. Recent insights into the underlying pathophysiology of the disease have allowed the development of targeted therapies, including the thrombopoietin (TPO) receptor agonists, which enhance platelet production. Phase III trials have found romiplostim and eltrombopag to be well tolerated and effective in elevating platelet counts and reducing bleeding in both splenectomised and nonsplenectomised patients with chronic ITP. The B-cell targeted monoclonal antibody rituximab has also shown some potential in this setting, although data are currently limited and there are toxicity concerns. The decision whether to proceed to splenectomy or try other medical therapies in corticosteroid-refractory patients remains patient-specific. Splenectomy has its risks (including perioperative and long-term risks), and relapse/nonresponse are relatively common, but it offers the possibility of cure in the majority of patients. However, newer treatments may potentially allow splenectomy to be deferred for prolonged periods, as well as providing alternative treatment options for patients who fail splenectomy.

Contrast Enhanced Ultrasonography for the Evaluation of Coil Embolization of Splenic Artery Aneurysm

A 65-year-old woman with compensated liver cirrhosis secondary to hepatitis C virus infection was under surveillance for early detection of hepatocellular carcinoma with ultrasonography and, due to suboptimal ultrasound feasability, at longer intervals with computed tomography (CT). During follow-up, a splenic artery aneurysm appeared and progressively increased from 18 mm to ≈30 mm in diameter over a 9-month interval. The patient had severe splenomegaly secondary to portal hypertension and hypersplenism with a low platelet count (≈30.000/mL). Percutaneous arterial embolization was proposed to the patient1 because severe portal hypertension was considered a contraindication to surgical splenectomy. Embolization was carried out, preceded by platelet infusion, using “fibered” coils and interlocking detachable coils without complications. Eight weeks later, the patient underwent abdominal CT as part of the surveillance program for hepatocellular carcinoma; no nodule with pattern of hepatocellular carcinoma was identified; at the splenic level, frank metallic artifacts were evident and prevented assessment of treatment efficacy (Figure 1) as described in previous reports from the literature with this technique.2 Figure 1. CT scan of the upper abdomen at a level passing through the treated splenic aneurysm. Arrows, metallic artifacts (similar to rays departing from the coils) don’t allow adequate assessment of treatment efficacy. To investigate the splenic aneurysm status, an attempt was made with conventional ultrasound (Figure 2) and color duplex-doppler ultrasonography, which failed to provide definitive and unquestionable information about the success of the embolization. Doppler ultrasound …

Appendiceal hydatid cyst: a case report and review of literature.

Hydatid cyst has a predilection to involve liver and lungs. Most of the reported cases of appendiceal hydatid cyst are primary, and secondary involvement has been rarely reported in the English-language literature. Herein, we report a 47-year-old man who presented with abdominal pain, fatigue, and anorexia since 6months ago. He had history of surgery for hepatic hydatid cyst 7years ago. Diagnosis of secondary hydatidosis was made upon positive indirect hemagglutination assay and abdominopelvic computed tomography scan, which showed involvement of liver, appendix, and spleen. Albendazole was started, and surgical cystectomy, appendectomy, and splenectomy were performed. Albendazole was continued postoperatively for 6months. During this period, liver function test and abdominal sonography were normal. Despite its rarity, our case emphasizes that primary care physicians should have high index of clinical suspicion of secondary hydatidosis of appendix when they detect cystic mass, especially in patients with previous hepatic hydatid disease.

Clinical events after surgical splenectomy in children with sickle cell anemia

Despite advances in immune prophylaxis, sepsis remains the most feared complication following splenectomy for acute splenic sequestration crisis (ASSC) in children with sickle cell anemia (SCA). We seek to investigate the true prevalence of sepsis and other complications of splenectomy in this patient population. We reviewed the records of children with SCA (HbSS) who underwent splenectomy for ASSC between 1993 and 2008 at a single institution. Fifty-eight patients (33 males) at a median age of 2 years at splenectomy were included with an average post-splenectomy follow-up of 6.4 years (range 6 months-14 years). Thirty-seven patients (64%) underwent laparoscopic splenectomy, and acute chest syndrome (ACS) was the most common post-operative complication (6.9%). There was no difference in the incidence of sepsis pre- and post-splenectomy. The occurrence of vaso-occlusive pain crises (VOC) and ACS was significantly higher after splenectomy. In addition, 14 patients (24%) developed stroke (n = 5) or an abnormal transcranial Doppler (TCD) (n = 9) after splenectomy. Our data suggest that splenectomy can be safely performed in children with SCA given a low risk of sepsis. However, the increased incidence of VOC, ACS, and stroke or abnormal TCDs after splenectomy remains a concern.