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1.
Sci Rep ; 11(1): 21246, 2021 10 28.
Article in English | MEDLINE | ID: mdl-34711891

ABSTRACT

To study the impact of total splenectomy (TS) on peripheral lymphocytes and their subsets in patients with hypersplenism associated with cirrhotic portal hypertension (CPH). We studied 102 consecutive patients who received TS from January 2008 to January 2020 due to CPH-related hypersplenism. A similar number of healthy individuals are used as healthy controls (HC). The total lymphocyte counts and their percentages of B lymphocytes, total T lymphocytes (cluster of differentiation (CD)3+) and their subsets (CD4+, CD8+), and natural killer (NK) cells in preoperative peripheral blood samples in hypersplenism patients were significantly lower than that of the HCs (both P < 0.05). The total lymphocyte counts and percentages of B lymphocytes in peripheral blood were significantly increased 1 week and 1 month after TS when compared with the pre-TS values (P < 0.05). There was no significant difference in the percentages of NK cells before or after surgery (P > 0.05). However, the percentages of CD3+ cells was significantly higher 1 month after than before surgery (P < 0.001). The percentages of CD4+, and CD8+ T lymphocytes were significantly lower 1 week after surgery (P < 0.05), but they were significantly higher 1 month after surgery (P < 0.01). The CD4+:CD8+ ratio was not significantly different from those before surgery, and 1 week or 1 month after surgery (P > 0.05). Patients with hypersplenism associated with CPH were significantly immunosuppressed preoperatively. After TS, the total lymphocyte count and percentages of B lymphocytes, and total T lymphocytes and their subsets increased significantly, resulting in improved immune functions.


Subject(s)
Hypersplenism/etiology , Hypertension, Portal/etiology , Liver Cirrhosis/complications , Lymphocyte Count , Lymphocyte Subsets/immunology , Adult , Biomarkers , Disease Susceptibility , Female , Humans , Hypersplenism/metabolism , Hypersplenism/pathology , Hypertension, Portal/metabolism , Hypertension, Portal/pathology , Lymphocyte Subsets/metabolism , Male , Middle Aged
2.
Platelets ; 31(8): 1019-1027, 2020 Nov 16.
Article in English | MEDLINE | ID: mdl-31851564

ABSTRACT

Thrombocytopenia is a common hematological abnormality in patients with cirrhotic hypersplenism. Splenectomy with paraesophagogastric devascularization (SPD) is a conventional surgical therapy which can reverse pancytopenia in these patients. Platelets are traditionally recognized for their central role in hemostasis. However, the status of platelet aggregation in chronic hepatitis B patients with cirrhotic hypersplenism before and after SPD has not been reported yet. A total of 41 cirrhotic patients and 31 healthy controls were included in this study. Platelet aggregation was detected by AggRAM® Advanced Modular System (Helena Laboratories, USA). ELISA was used to detect the cytokines closely related to platelet aggregation. Expressions of platelet membrane glycoproteins (GPs) were evaluated by flow cytometric analysis. Platelet aggregation was found to be decreased distinctly in the cirrhotic patients, and to be restored to normal level after SPD. The cirrhotic patients showed higher plasma levels of the cytokines HMGB1, PEDF, vWF, cAMP and cGMP, which also improved partially after SPD. Moreover, the cirrhotic patients had much lower expression of GPIIb/IIIa, GPIbα and P-selectin than either the healthy controls or SPD patients at basal or activated level. Generally, SPD benefits cirrhotic patients with bleeding tendencies by improving platelet counts and aggregation. GPIIb/IIIa may be the key membrane protein responsible for the change in platelet aggregation before and after SPD.


Subject(s)
Fibrosis/etiology , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/surgery , Hypersplenism/etiology , Platelet Aggregation/physiology , Splenectomy/methods , Adult , Case-Control Studies , Female , Fibrosis/pathology , Hepatitis B, Chronic/blood , Humans , Hypersplenism/pathology , Male , Middle Aged
3.
Dig Dis Sci ; 63(7): 1860-1867, 2018 07.
Article in English | MEDLINE | ID: mdl-29721775

ABSTRACT

BACKGROUND: Hematopoietic abnormality is a common cause of cirrhotic hypersplenism (CH) complications and death; it causes serious adverse effects and is associated with bleeding, anemia, infection in CH patients. However, the underlying mechanism is unclear. AIMS: We aimed to investigate the effects of the spleen on hematopoiesis and hematopoietic stem/progenitor cells (HSPCs) in CH patients. METHODS: Eleven CH patients were enrolled to assess the effects of the spleen on HSPC functions. Hematopoietic changes were examined by flow cytometry analysis. HSPC functions were detected with colony-forming assays and in vitro cell cultures. Enzyme-linked immunosorbent assay (ELISA) was used to test the concentration of epithelial growth factor (EGF). RESULTS: The number of HSPCs was decreased in CH patients and was rescued after splenectomy. Serum from CH patients dysregulated HSPCs function, and serum from splenectomy patients restored the dysregulated HSPC function in vitro. The concentration of EGF was decreased in CH patients and was restored to normal level after splenectomy. EGF rescued the dysregulated HSPCs function in vitro. CONCLUSIONS: The spleen can regulate the functions of HSPCs in CH patients by regulating EGF signaling. EGF may be a therapeutic target for CH treatment.


Subject(s)
Epidermal Growth Factor/metabolism , Hematopoiesis, Extramedullary , Hematopoietic Stem Cells/metabolism , Hypersplenism/etiology , Liver Cirrhosis/complications , Spleen/metabolism , Cell Proliferation , Cells, Cultured , Epidermal Growth Factor/blood , Female , Hematopoietic Stem Cells/pathology , Humans , Hypersplenism/metabolism , Hypersplenism/pathology , Hypersplenism/surgery , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Male , Middle Aged , Signal Transduction , Spleen/pathology , Spleen/surgery , Splenectomy , Time Factors , Treatment Outcome
4.
Trop Doct ; 47(1): 26-30, 2017 Jan.
Article in English | MEDLINE | ID: mdl-26989144

ABSTRACT

BACKGROUND: Non-cirrhotic portal fibrosis (NCPF) is one of the important causes of upper gastrointestinal haemorrhage in patients in tropical countries. The aim of this study was to describe the clinical and laboratory profile of 68 patients with NCPF. MATERIAL AND METHODS: NCPF is defined as liver disease with: (1) evidence of portal hypertension; (2) a liver biopsy showing no cirrhosis or a Tc-labelled sulphur colloid scan showing a pattern suggestive of NCPF; and (3) a patent splenoportal axis. The clinical, laboratory and demographic features of 68 patients with such criteria were studied and analysed. RESULTS: NCPF was common in women (73.5%) in the fourth decade of life. The median duration of illness was 24 months (range, 1 month-28 years). Patients presented to hospital with the sensation of a mass in the abdomen (50%) or with haematemesis (26.5%). They had splenomegaly (95.6%) and thrombocytopenia (88.2%). The majority of patients had normal liver function tests. Abdominal ultrasonography showed increased periportal and peri gallbladder echoes (72%), spontaneous collaterals (41.2%) and ascites (19.1%). Liver biopsy revealed portal venous sclerosis (76.3%) and periportal fibrosis (55.3%). Tc-labelled sulphur colloid scan was suggestive of NCPF in the remaining 30 cases. CONCLUSION: NCPF is common in South India. Transient ascites occurs due to decompensation of liver function after variceal bleeding and in long standing cases of NCPF. Our study used Tc-sulphur scan for diagnosing NCPF in patients where liver biopsy was contraindicated in view of severe thrombocytopenia; however, the diagnostic utility of Tc-sulphur nuclear scan to diagnose NCPF in patients with severe hypersplenism needs to be further evaluated in future studies.


Subject(s)
Hypersplenism/epidemiology , Hypertension, Portal/epidemiology , Adult , Cohort Studies , Female , Fibrosis/complications , Fibrosis/diagnostic imaging , Fibrosis/epidemiology , Fibrosis/pathology , Gastrointestinal Hemorrhage/etiology , Humans , Hypersplenism/complications , Hypersplenism/diagnostic imaging , Hypersplenism/pathology , Hypertension, Portal/complications , Hypertension, Portal/diagnostic imaging , Hypertension, Portal/pathology , India/epidemiology , Male , Middle Aged , Portal System , Risk Factors , Tertiary Care Centers
5.
J Huazhong Univ Sci Technolog Med Sci ; 36(4): 519-522, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27465326

ABSTRACT

This study aimed to examine the efficacy of the laparoscopic vs. traditional open splenectomy for hepatocellular carcinoma (HCC) with hypersplenism. Between 2002 and 2013, 51 Chinese HCC patients with hypersplenism underwent either simultaneous laparoscopic splenectomy plus anticancer therapies (Lap-S&A) (n=25) or traditional open splenectomy plus anti-cancer therapies (TOS&A) (n=26). The outcomes were reviewed during and after the operation. Anti-cancer therapies for HCC included laparoscopic hepatectomy (LH) and laparoscopic microwave ablation (LMA). The results showed that there was no significant difference in the operating time between the two groups, but the blood loss and blood transfusion were less, pain intensity after surgery was weaker, the time to first bowel movement, time to the first flatus and postoperative hospital stay were shorter, and the postoperative complication rate and the readmission rate were lower in the Lap-S&A group than in the TO-S&A group. Two patients in the Lap-S&A group and one patient in the TO-S&A group died 30 days after surgery. However, no significant difference in the mortality rate was noted between the two groups. It was concluded that simultaneous Lap-S&A holds the advantages of more extensive indications, lower complication incidence and less operative expenditure than conventional open approach and it is a feasible and safe approach for HCC with hypersplenism.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hypersplenism/surgery , Liver Neoplasms/surgery , Adult , Aged , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/pathology , Female , Hepatectomy , Humans , Hypersplenism/complications , Hypersplenism/pathology , Laparoscopy , Liver/pathology , Liver/surgery , Liver Neoplasms/complications , Liver Neoplasms/pathology , Male , Middle Aged , Spleen/pathology , Spleen/surgery , Splenectomy , Treatment Outcome
6.
Intern Med ; 54(17): 2179-83, 2015.
Article in English | MEDLINE | ID: mdl-26328643

ABSTRACT

A 52-year-old man underwent partial splenic embolization (PSE) for hypersplenism. The intrasplenic artery targeted for the embolization was large, and the distance between its trifurcated branches was short; therefore, Guglielmi detachable coils (GDC) 360° Complex Shape were used, as well as conventional metal coils, to prevent coil migration. GDC are equipped with a shape-memory function and are more physically stable than conventional metallic coils because they form three-dimensional loops. In this case, an ideal extent of the splenic infarction was successfully achieved using a small number of coils. This is the first report of the use of GDC in PSE for hypersplenism.


Subject(s)
Embolization, Therapeutic/instrumentation , Hypersplenism/therapy , Liver Cirrhosis/therapy , Splenic Artery/pathology , Embolization, Therapeutic/methods , Equipment Design , Humans , Hypersplenism/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Male , Middle Aged , Treatment Outcome
7.
PLoS One ; 10(4): e0124569, 2015.
Article in English | MEDLINE | ID: mdl-25910248

ABSTRACT

Splenomegaly and pancytopenia are common in Wilson's disease (WD) and splenectomy is one of the conventional treatments for splenomegaly and the associated pancytopenia. However, splenectomy remained controversial for hypersplenism in WD as it was reported that splenectomy leaded to serious emotional and neurological deterioration in WD patients with hypersplenism. In the current study, we present our experiences in 70 WD patients with hypersplenism who had undergone splenectomy, outlining the safety and efficacy of splenectomy in WD. The clinical database of 70 WD patients with hypersplenism who had undergone splenectomy in our hospital between 2009 and 2013 were reviewed and followed-up regularly. Before splenectomy, all the patients accepted a short period of anti-copper treatment with intravenous sodium 2, 3-dimercapto-1-propane sulfonate (DMPS). All the patients demonstrated a marked improvement in platelet and leucocyte counts after splenectomy. No severe postoperative complication was observed. In particular, none of the 37 patients with mixed neurologic and hepatic presentations experienced neurological deterioration after splenectomy, and none of the patients with only hepatic presentations newly developed neurological symptoms. During the one year follow-up period, no patient presented hepatic failure or hepatic encephalopathy, no hepatic patient newly developed neurological presentations, and only 3 patients with mixed neurologic and hepatic presentations suffered neurological deterioration and these 3 patients had poor compliance of anti-copper treatment. Quantative analysis of the neurological symptoms in the 37 patients using the Unified Wilson's Disease Rating Scale (UWDRS) showed that the neurological symptoms were not changed in a short-term of one week after splenectomy but significantly improved in a long-term of one year after splenectomy. Additionally, compared to that before splenectomy, the esophageal gastric varices in most patients significantly improved one year after splenectomy. Thus, we may conclude that splenectomy is a safe and effective therapeutic measure for hypersplenism in WD patients who had been preoperatively treated with DMPS for powerful anti-copper therapy.


Subject(s)
Hepatolenticular Degeneration/pathology , Hepatolenticular Degeneration/surgery , Hypersplenism/pathology , Splenectomy , Adolescent , Adult , Blood Cell Count , Child , China , Combined Modality Therapy , Copper/blood , Female , Hepatolenticular Degeneration/blood , Hepatolenticular Degeneration/therapy , Humans , Liver Function Tests , Male , Splenectomy/adverse effects , Splenomegaly/pathology , Time Factors , Treatment Outcome , Young Adult
9.
Hepatogastroenterology ; 60(127): 1689-92, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23933787

ABSTRACT

BACKGROUND/AIMS: The management of hepatocellular carcinoma with hypersplenic thrombocytopenia remains controversial, because of the high surgical morbidity and mortality. Splenectomy has been reported to be useful for patients with hypersplenic thrombocytopenia, but the timing and route of splenectomy and hepatic resection remains unclear. This report evaluated the efficacy of laparoscopic surgery for simultaneous splenectomy and hepatic resection in the treatment of hepatocellular carcinoma with hypersplenic thrombocytopenia. METHODOLOGY: Among 65 patients with hypersplenic thrombocytopenia who underwent hepatic resection for hepatocellular carcinoma, 20 patients underwent simultaneous splenectomy and hepatic resection. Initially, ten patients underwent the procedure by conventional laparotomy (open group) and ten patients underwent by laparoscopy (laparoscopic group). The clinicopathological results from the two groups were compared retrospectively. RESULTS: The blood loss in the laparoscopic group was significantly less and the postoperative morbidity rate in the laparoscopic group was lower than that in the open group. The duration of the postoperative hospital stay in the laparoscopic group was significantly shorter and rate of patients administered interferon in the laparoscopic group was significantly higher than that in open group. CONCLUSIONS: Simultaneous splenectomy and hepatic resection under laparoscopy is a safe and useful in the treatment of hepatocellular carcinoma with hypersplenic thrombocytopenia.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Hypersplenism/surgery , Laparoscopy , Liver Neoplasms/surgery , Splenectomy/methods , Thrombocytopenia/surgery , Aged , Blood Loss, Surgical/prevention & control , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/pathology , Female , Hepatectomy/adverse effects , Humans , Hypersplenism/etiology , Hypersplenism/pathology , Kaplan-Meier Estimate , Laparoscopy/adverse effects , Length of Stay , Liver Cirrhosis/complications , Liver Neoplasms/etiology , Liver Neoplasms/pathology , Male , Middle Aged , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/prevention & control , Retrospective Studies , Splenectomy/adverse effects , Thrombocytopenia/etiology , Thrombocytopenia/pathology , Time Factors , Treatment Outcome
10.
Asian Pac J Trop Med ; 6(8): 663-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23790341

ABSTRACT

OBJECTIVE: To explore peripheral blood cell variations in hepatic cirrhosis portal hypertension patients with hypersplenism. METHODS: Clinical data of 322 hypersplenism patients with decreased peripheral blood cells, admitted with cirrhotic portal hypertension, was retrospectively studied over the last 17 years. RESULTS: In 64% (206/322) of patients, more than 2 kinds of blood cell were decreased, including 89 cases of pancytopenia (43.2%), 52 cases of WBC + PLT decrease (25.2%), 29 cases of RBC + PLT decrease (14.1%), and 36 cases of WBC + RBC decrease (17.5%); in 36% (116/322) of patients, single type blood cell decrease occurred, including 31 cases of PLT decrease (26.7%), 29 cases of WBC decrease (25%) and 56 cases of RBC decrease (48.3%). Of 227 routine bone marrow examinations, bone marrow hyperplasia was observed in 118 cases (52.0%), the remainder showed no hyperplasia. For the distinct scope and extent of peripheralblood cell decreases, preoperative blood component transfusions were carried out, then treated by surgery, after whole group splenectomy, the peripheral blood cell count was significantly higher (P<0.05). CONCLUSIONS: Of portal hypertensive patients with splenomegaly and hypersplenism, 64% have simultaneous decrease in various blood cells, 36% have decrease in single type blood cells, 52% of patients have bone marrow hyperplasia. A splenectomy can significantly increase the reduction of peripheral blood cells.


Subject(s)
Blood Cell Count , Hypersplenism/pathology , Hypertension, Portal/complications , Hypertension, Portal/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Hypersplenism/surgery , Male , Middle Aged , Retrospective Studies , Splenectomy , Young Adult
11.
Eur Radiol ; 23(5): 1429-42, 2013 May.
Article in English | MEDLINE | ID: mdl-23160664

ABSTRACT

OBJECTIVES: To evaluate the use of diffusion-weighted imaging (DWI) for estimating infarcted splenic volume during partial splenic embolisation (PSE) using n-butyl cyanoacrylate (NBCA). METHODS: Twenty consecutive patients (57.2 ± 11.7 years) with hypersplenism underwent PSE. Intrasplenic branches were embolised using NBCA via a 2.1-French microcatheter aiming at infarction of 50 to 80 % of total splenic volume. Immediately after PSE, signal intensities (SI) of embolised and non-embolised splenic parenchyma were measured on DWI. Semi-automated volumetry (SAV) on DWI was compared with conventional manual volumetry (MV) on contrast-enhanced CT 1 week after PSE. Platelet counts were recorded before and after PSE. RESULTS: The SI on DWI in the embolised parenchyma decreased significantly (P < 0.01) to 24.7 ± 8.1 % as compared to non-embolised parenchyma. SAV and MV showed a strong correlation (r = 0.913 before PSE, r = 0.935 after PSE, P < 0.01) and significant (P < 0.01) reduction of normal splenic volume was demonstrated on both SAV (71.9 ± 12.4 %) and MV (73.6 ± 9.3 %) after PSE. Based on the initial SAV, three patients (15 %) underwent additional branch embolisation to reach sufficient infarction volume. Platelet counts elevated significantly (522.8 ± 209.1 %, P < 0.01) by 2 weeks after PSE. No serious complication was observed. CONCLUSION: Immediate SI changes on DWI after PSE allowed semi-automated splenic volumetry on site. KEY POINTS: • Partial splenic embolisation (PSE) is an important interventional technique for hypersplenism • Diffusion-weighted MR reveals an immediate decrease in signal in the embolised parenchyma • Such signal reduction permits semi-automated splenic volumetry on site. • This allows precise quantification of the amount of parenchyma infarcted, avoiding additional PSE.


Subject(s)
Embolization, Therapeutic/methods , Enbucrilate/therapeutic use , Hemostatics/administration & dosage , Hypersplenism/pathology , Hypersplenism/therapy , Magnetic Resonance Imaging, Interventional/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Tissue Adhesives/therapeutic use , Treatment Outcome
12.
J Laparoendosc Adv Surg Tech A ; 22(10): 962-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23067068

ABSTRACT

BACKGROUND: The current laparoscopic splenectomy (LS) procedure used for cirrhotic patients still has limitations. The aim of our study was to determine a standard according to the splenic size for hand-assisted LS (HALS) in patients with splenomegaly and hypersplenism due to cirrhosis. PATIENTS AND METHODS: We conducted a retrospectively review of cirrhotic patients who underwent splenectomy between 2008 and 2011. All patients were divided into two groups: Group A (19 patients), in which patients' operations were conducted by HALS, and Group B (20 patients), in which patients were treated with LS. Then the patients in Group A were classified on the basis of the spleen size: massive splenomegaly (Group A1) and supramassive splenomegaly (Group A2). Likewise, so were patients in Group B: massive splenomegaly (Group B1) and supramassive splenomegaly (Group B2). Perioperative outcomes of these patients were compared. RESULTS: The comparison of HALS and LS based on spleen size demonstrated that in the massive splenomegaly groups, Group A1 and Group B1 had similar estimated blood loss and morbidity, and no transfusion was required in these patients. In the supramassive splenomegaly groups, compared with Group A2, Group B2 had longer operative time, more estimated blood loss, more patients requiring transfusion, and more complications that needed surgical intervention. However, no significant differences were observed in the requirement of analgesia, time of returning to oral intake, and length of hospitalization in these paired groups. CONCLUSIONS: In cirrhotic patients with supramassive splenomegaly, HALS should be considered because of its safety, feasibility, and effectiveness.


Subject(s)
Hypersplenism/etiology , Hypersplenism/surgery , Laparoscopy , Liver Cirrhosis/complications , Splenectomy/methods , Splenomegaly/etiology , Splenomegaly/surgery , Female , Humans , Hypersplenism/pathology , Male , Middle Aged , Retrospective Studies , Splenomegaly/pathology
13.
Hematology ; 17(2): 100-5, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22664048

ABSTRACT

Pancytopenia is not a disease but an important clinico-haematological entity encountered in our day-to-day clinical practice with findings that may result from a number of disease processes. A total of 100 patients of pancytopenia admitted in medicine wards of Civil Hospital, Ahmedabad, Gujuarat, India, were studied. The most common cause of pancytopenia was megaloblastic anaemia (45%) followed by infections (20%) and hypersplenism (15%). As compared with other causes, megaloblastic anaemia was statistically significant cause (P < 0.01) of pancytopenia, in our study. The most common clinical presentation of patients with megaloblastic anaemia was lethargy (100%) and pallor (100%). In patients with megaloblastic anaemia, mean haemoglobin (Hb) was 5.6 ± 1.7 g/dl, mean white blood corpuscle (WBC) count was 2735 ± 4152 and mean platelet count was 52,250 ± 24,213. Mean corpuscular volume (MCV) was 101.2 ± 11 in patients of megaloblastic anaemia. Morphology of RBC was marocytic in 95% of patients with megaloblastic anaemia, whereas hypersegmented neutrophils and macrovalocytes were seen in 60-65% patients of megaloblastic anaemia.


Subject(s)
Anemia, Megaloblastic/pathology , Communicable Diseases/pathology , Hypersplenism/pathology , Pancytopenia/pathology , Adult , Aged , Anemia, Megaloblastic/complications , Blood Cell Count , Communicable Diseases/complications , Community Health Centers , Erythrocyte Indices , Humans , Hypersplenism/complications , India , Lethargy/physiopathology , Middle Aged , Pallor/physiopathology , Pancytopenia/etiology
14.
Cell Biochem Biophys ; 62(1): 245-55, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21904911

ABSTRACT

Current large animal models that could closely resemble the typical features of cirrhotic portal hypertension in human have not been well established. Thus, we aimed to develop and describe a reliable and reproducible canine cirrhosis model of portal hypertension. A total of 30 mongrel dogs were randomly divided into four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3 (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months modeling period, liver and spleen CT perfusion, abdominal CT scans, portal hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow, liver, and spleen histology were studied. The animals in group 2 (PVS) developed extrahepatic portosystemic collateral circulation, particularly esophageal varices, without hepatic cirrhosis and portal hypertension. Animals from group 3 (TAA) presented mild cirrhosis and portal hypertension without significant symptoms of esophageal varices and hypersplenism. In contrast, animals from group 4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis, associated with significant portal hypertension and hypersplenism. The combination of PVS and TAA represents a novel, reliable, and reproducible canine cirrhosis model of portal hypertension, which is associated with the typical characteristics of portal hypertension, including hypersplenism.


Subject(s)
Constriction, Pathologic/pathology , Disease Models, Animal , Fibrosis , Hypersplenism/complications , Hypersplenism/pathology , Hypertension, Portal/chemically induced , Hypertension, Portal/complications , Animals , Constriction, Pathologic/complications , Dogs , Fibrosis/complications , Fibrosis/pathology , Gastroscopy , Hemodynamics , Male , Portal Vein , Random Allocation , Thioacetamide , Tomography, X-Ray Computed
15.
Dig Surg ; 28(1): 9-14, 2011.
Article in English | MEDLINE | ID: mdl-21293126

ABSTRACT

BACKGROUND: Splenectomy is gaining increasing importance for cirrhotic patients with hypersplenism. However, its safety and efficacy for patients with chronic liver disease remain unclear. METHODS: We retrospectively examined the medical records of 38 consecutive cirrhotic patients who underwent splenectomy or simultaneous hepatectomy and splenectomy for hepatocellular carcinoma. RESULTS: White blood cell and platelet counts significantly increased 3 months after splenectomy. Serum levels of total bilirubin and prothrombin time significantly improved 1 year after splenectomy. Interferon therapy was administered to 25 patients after splenectomy. A sustained viral response was achieved in 8 patients (42%). The total incidence of portal or splenic vein thrombosis (PSVT) detected by postoperative dynamic computed tomography was 13/38 (34.2%). Multivariate analysis revealed preoperative spleen volume (SV) to be the sole independent predictor of postoperative PSVT. Receiver-operator characteristic curve analysis showed that a cut-off SV of 450 ml corresponded to a sensitivity of 85% and a specificity of 56%. CONCLUSIONS: Splenectomy improved the liver function and facilitated effective interferon therapy in cirrhotic patients with hypersplenism, although preoperative SV was frequently associated with postoperative PSVT.


Subject(s)
Hypersplenism/surgery , Liver Cirrhosis/physiopathology , Liver Cirrhosis/surgery , Liver/physiopathology , Portal Vein/physiopathology , Splenectomy , Splenic Vein/physiopathology , Venous Thrombosis/etiology , Adult , Aged , Antiviral Agents/therapeutic use , Bilirubin/blood , Female , Hepatectomy/adverse effects , Humans , Hypersplenism/pathology , Interferons/therapeutic use , Leukocyte Count , Male , Middle Aged , Multivariate Analysis , Organ Size , Platelet Count , Prothrombin Time , ROC Curve , Retrospective Studies , Spleen/pathology , Splenectomy/adverse effects , Venous Thrombosis/physiopathology
16.
Res Vet Sci ; 91(2): 240-2, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21185577

ABSTRACT

Trypanosoma evansi infections in domestic animals are characterized by anemia and thrombocytopenia. The cause of the platelets decrease is unknown, but researchers suggest that thrombocytopenia may result from damage of the bone marrow, reduced survival of platelets, auto-immune thrombocytopenia, disseminated intravascular coagulation and splenic sequestration. Some of these causes have already been tested by our research group and found to be unrelated. Therefore, this study has the objective of testing the hypothesis that splenic sequestration might be responsible for thrombocytopenia in T. evansi-infected rats. A total of 28 rats assigned to four groups were used in the experiment. Group A rats were splenectomized and infected with T. evansi, group B rats were infected with T. evansi, group C rats were splenectomized, but not infected and group D rats were normal controls. Five days post-infection all rats were anesthetized and blood was collected in order to measure the number of circulating platelets, fibrinogen levels, prothrombin time (PT) and activated partial thromboplastin time (aPTT). The spleens of groups B and D were weighed at necropsy. The infected animals (groups A and B) showed a significant reduction in platelets and increased PT and aPTT when compared to negative control groups (groups C and D). Animals from group A showed increased levels of fibrinogen. The mean weight of spleen differed between group B (2.62g) and group D (0.55g). It was concluded that there is no relationship between thrombocytopenia and splenic sequestration in infection by T. evansi.


Subject(s)
Hypersplenism/etiology , Rodent Diseases/etiology , Spleen/pathology , Thrombocytopenia/etiology , Trypanosomiasis/complications , Animals , Female , Fibrinogen/analysis , Hypersplenism/blood , Hypersplenism/pathology , Platelet Count/veterinary , Prothrombin/analysis , Rats , Rodent Diseases/blood , Rodent Diseases/pathology , Splenectomy/veterinary , Thrombocytopenia/blood , Thrombocytopenia/pathology , Thromboplastin/analysis , Trypanosoma/physiology , Trypanosomiasis/blood , Trypanosomiasis/pathology
17.
Pathol Res Pract ; 206(11): 760-7, 2010 Nov 15.
Article in English | MEDLINE | ID: mdl-20846792

ABSTRACT

Phosphatidylinositol 3-kinase (PI3K) plays a central role in the metabolic actions of insulin. One 85 kDa regulatory subunit of PIK3 is encoded by phosphoinositide-3-kinase, the regulatory subunit 1 (PIK3R1). Our previous study has demonstrated that PIK3R1 was up-regulated significantly in the splenic macrophage (MΦ) of portal hypertensive spleen. In the present study, RNA interference specific to PIK3R1 was employed to investigate its inhibitive effects on the activity of MΦ associated with hypersplenism due to portal hypertension (HS-PHT). The expression of PIK3R1 in the spleen was detected by immunohistochemical staining. Plasmid vector pGenesil-1 expressing specific small hairpin RNA (shRNA) against PIK3R1 and the scrambled shRNA control was constructed. MΦ were isolated and purified by anchored cultivation from patients with HS-PHT (HS-PHT-MΦ) and traumatic rupture of the spleen (Con-MΦ). After transfection into MΦ, PIK3R1 expression at both the mRNA and the protein level was examined by real-time polymerase chain reaction and Western blot. The activities of MΦ were determined, and the expression and activity of NF-κB were also detected. Immunohistochemistry revealed expression and cellular distribution of PIK3R1 in the spleen. The PIK3R1-shRNA was successfully synthesized and cloned into the plasmid vector pGenesil-1, and specifically suppressed PIK3R1 expression at both the mRNA and the protein level. After transfection into HS-PHT-MΦ and Con-MΦ, PIK3R1 knockdown inhibited the viability of MΦ, reduced the phagocytic rate, the rate of antigen-presenting positive cells, the metabolic rate, and the secretion of IL-1ß and TNF-α (all p<0.05), and decreased the expression and activity of NF-κB. Our data showed that the knocking down of PIK3R1 with shRNA produced by pGenesil-1 led to inhibition of viability and to decreased activity of MΦ associated with HS-PHT in vitro. Therefore, it is tempting to speculate that PIK3R1 might play a considerable role in the pathogenesis of HS-PHT, and inhibition of PIK3R1 expression might be a novel therapeutic strategy for HS-PHT.


Subject(s)
Hypersplenism/pathology , Hypertension, Portal/pathology , Macrophages/pathology , Phosphatidylinositol 3-Kinase/genetics , RNA Interference , RNA, Small Interfering/genetics , Adult , Aged , Cell Survival , Cells, Cultured , Down-Regulation , Female , Gene Knockdown Techniques , Humans , Hypersplenism/etiology , Hypersplenism/genetics , Hypertension, Portal/complications , Hypertension, Portal/genetics , Macrophages/metabolism , Male , Middle Aged , Phosphatidylinositol 3-Kinase/metabolism , Spleen/metabolism , Spleen/pathology
19.
J Gastroenterol Hepatol ; 25(9): 1578-86, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20796158

ABSTRACT

BACKGROUND AND AIM: Thrombocytopenia due to hypersplenism is usually a serious condition in cirrhotic patients who have undergone invasive procedures. We designed a new treatment method using a high-frequency alternating electromagnetic force to treat the disease condition in a rat model. METHODS: Sprague-Dawley rats were given thioacetamide in drinking water and injected with methylcellulose intraperitoneally to create a cirrhotic hypersplenism model. Spleen volume was determined using the Carlson method. The Control Group consisted of 14 rats, 15 weeks old, that were used to determine the normal platelet count and normal spleen size. Experimental Group I, consisting of 15 rats, received electromagnetic thermoablation of their spleens, after which the spleen was returned to the abdomen. Group II consisted of 13 rats, receiving the same electromagnetic thermoablation as Group I, but the ablated portion was removed. Group III consisted of 14 rats receiving total splenectomies. RESULTS: Cirrhotic hypersplenism was confirmed during laparotomy and pathological examination. Spleen volume enlarged from 1513 +/- 375 mm(3) (Control Group) to 7943 +/- 2822 mm(3) (experimental groups). Platelet counts increased from 0.35 +/- 0.21 x 10(6)/mm(3) to 0.87 +/- 0.24 x 10(6)/mm(3) for Group I, from 0.52 +/- 0.23 x 10(6)/mm(3) to 1.10 +/- 0.20 x 10(6)/mm(3) for Group II, and from 0.47 +/- 0.23 x 10(6)/mm(3) to 1.18 +/- 0.26 x 10(6)/mm(3) for Group III. No rats died due to the treatment in any of the experimental groups. CONCLUSIONS: Our animal model performed successfully and our proposed electromagnetic thermotherapy effectively treated thrombocytopenia due to cirrhotic hypersplenism.


Subject(s)
Catheter Ablation/methods , Electromagnetic Phenomena , Hypersplenism/surgery , Liver Cirrhosis, Experimental/complications , Splenectomy , Thrombocytopenia/surgery , Animals , Hypersplenism/chemically induced , Hypersplenism/complications , Hypersplenism/pathology , Liver Cirrhosis, Experimental/chemically induced , Male , Methylcellulose , Platelet Count , Rats , Rats, Sprague-Dawley , Thioacetamide , Thrombocytopenia/blood , Thrombocytopenia/etiology , Time Factors
20.
J Pediatr Surg ; 45(6): 1365-9, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20620346

ABSTRACT

BACKGROUND: Hematopoietic stem cell (HSC) engraftment is delayed after transplantation in children with hypersplenism, increasing the morbidity and costs of care. Preliminary clinical data suggest that splenectomy before HSC transplantation may improve HSC engraftment, although this observation has not been tested in an animal model. METHODS: We performed total splenectomy (n = 22), partial splenectomy (n = 16), or sham laparotomy (n = 21) on erythrocyte protein 4.2 knockout mice, a murine model of hereditary spherocytosis with hypersplenism. After 10 days, we lethally irradiated the mice, transplanted 3 x 10(6) allogeneic bone marrow cells, and then assessed engraftment using serial complete blood counts. Successful engraftment was defined as recovery of hemoglobin, neutrophil, or platelet counts. We compared engraftment rate using chi(2) test and time to engraftment using Student's t test analysis, with significance defined as P < .05. RESULTS: Total splenectomy increased the rate of successful HSC engraftment and decreased the interval to HSC engraftment compared with controls. Similarly, partial splenectomy decreased the interval to HSC engraftment, with a nonsignificant trend toward improved overall rate of successful HSC engraftment. CONCLUSION: Partial or total splenectomy before HSC transplantation improves HSC engraftment in hypersplenic mice. This model supports consideration of splenic resection in hypersplenic children requiring HSC transplantation.


Subject(s)
Hematopoietic Stem Cell Mobilization/methods , Hypersplenism/surgery , Splenectomy/methods , Animals , Disease Models, Animal , Graft Survival , Hypersplenism/pathology , Mice , Mice, Knockout , Postoperative Care , Treatment Outcome
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