A novel HIV-1 transgenic rat model of childhood HIV-1-associated nephropathy

BACKGROUND: A characteristic finding of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the presence of heavy proteinuria, focal or global glomerulosclerosis, and microcystic tubular dilatation leading to renal enlargement, and rapid progression to end-stage renal disease (ESRD). METHODS: We have recently developed the first HIV-1 transgenic rat model that carry a noninfectious HIV-1 DNA construct lacking 3.1 kb of sequence overlapping the gag and pol sequences, and develop many of the clinical lesions seen in HIV-infected patients, including HIVAN. To gain further insight into the pathogenesis of childhood HIVAN, we followed the clinical and renal pathologic outcome of 165 HIV-1 transgenic (HIV-Tg) rats and their respective control littermates for a period of 18 months. RESULTS: HIV-1 Tg rats progressively developed proteinuria and renal histologic lesions similar to those seen in children with HIVAN, leading to chronic renal failure. By in situ hybridization, HIV-1 genes were detected in glomerular and tubular epithelial cells and infiltrating mononuclear cells, which also expressed the HIV-1 envelop protein gp120. The development of HIVAN was associated with the accumulation of basic fibroblast growth factor (bFGF) in the kidney. CONCLUSION: These data support the notion that HIV-1 plays a direct role in the pathogenesis of HIVAN, by affecting the function and growth of renal epithelial cells, inducing the recruitment of mononuclear cells, and accumulating bFGF in the kidney, even in the absence of viral replication. These rats may provide an excellent model system to study the pathogenesis of childhood HIVAN.     

Coronary artery bypass in idiopathic thrombocytopenia without splenectomy

A patient with coronary artery disease and idiopathic thrombocytopenia purpura underwent coronary artery bypass grafting without splenectomy. Our experience indicates that use of cardiopulmonary bypass in patients with idiopathic thrombocytopenic purpura does not invariably mandate splenectomy.     

The role of splenectomy in multimodality treatment of thrombotic thrombocytopenic purpura.

Current treatment modalities for thrombotic thrombocytopenic purpura (TTP) include plasmapheresis (PP), splenectomy, steroids, dextran, other antiplatelet agents, and vinca alkaloids. Prior to the development of PP and use of multimodality treatment for TTP, mortality rates exceeded 50%. This report reviews 11 patients treated for TTP, demonstrates the successful use of splenectomy as salvage therapy, and defines our indications for splenectomy in the treatment of this disorder. Ten of 11 patients were initially treated with PP; three responded completely and one died of fulminant disease. Six patients had a transient partial response to plasmapheresis and were subsequently treated with splenectomy, steroids, and dextran-70. Initial plasmapheresis resulted in improvement in laboratory values and clinical status in those patients requiring splenectomy. Durable remission (6-48 months) was achieved in 91% of patients with minimal morbidity.     

Hand-assisted laparoscopic splenectomy for thrombocytopenia in patients with cirrhosis

Purpose

Although splenectomy plays an important role in the management of patients with liver cirrhosis, the optimal technique, open surgery, total laparoscopic surgery or hand-assisted laparoscopic surgery (HALS), has not yet been defined. The present study evaluated the outcomes of HALS splenectomy for cirrhotic patients.

Methods

A total of 28 consecutive patients with cirrhosis that underwent HALS splenectomy were enrolled into this study. The preoperative laboratory and morphometric data, intraoperative variables and postoperative outcomes were reviewed from the hospital charts.

Results

The postoperative platelet count was remarkably elevated in all cases. A re-operation was required in 1 patient complicated with postoperative hemorrhage. Enhanced CT on POD 7 revealed a high incidence of portal or splenic vein thrombosis (PSVT; 22 patients, 78.6 %). PSVT was significantly associated with higher serum bilirubin, higher indocyanine green retention value at 15 min (ICG R-15), and larger splenic vein diameter.

Conclusion

HALS splenectomy was a very feasible and appropriate procedure for cirrhotic patients with hypersplenism. PSVT was a frequent complication and large splenic vein diameter, high serum bilirubin, and high ICG R-15 were found to be significant risk factors for PSVT after HALS splenectomy in cirrhotic patients.     

Outcome of splenectomy for thrombocytopenia associated with systemic lupus erythematosus

OBJECTIVE: To determine the efficacy of splenectomy for treating thrombocytopenia associated with systemic lupus erythematosus (SLE). SUMMARY BACKGROUND DATA: The role of splenectomy has been controversial in this patient population. METHODS: Between 1975 and 2001, 25 consecutive adults with SLE underwent splenectomy specifically for thrombocytopenia. Surgical indications, operative mortality and morbidity, and hematological outcomes were followed in both the short-term (first 30 days) and the long-term (last recorded platelet count, last contact, or death). Response to splenectomy was rated as: complete (CR: platelets >/=150 x 10/L for at least 4 weeks), partial (PR: platelets 50-149 x 10/L for at least 4 weeks), or none (NR: platelets < 50 x 10/L at all times). Relapse occurred if platelets fell below 50 x 10/L after CR or PR. RESULTS: Indications for splenectomy included: thrombocytopenia refractory to (64%), dependent on (20%), or patient intolerance of (16%) medical treatments. Perioperative mortality was 0% and morbidity was 24%. After a median of 9.5 years, 9 patients (36%) had died, with only 1 death being secondary to bleeding. Early partial or complete response rate to splenectomy was 88%. After a median follow-up of 6.6 years, 16 (64%) patients had sustained complete or partial response without relapse. Eight (32%) of these patients required adjunctive medical therapy, whereas the other 8 (32%) did not. The remaining 9 (36%) patients relapsed, but 5 (20%) of the 9 patients were subsequently salvaged to at least partial response with further treatments. The overall PR or CR to splenectomy combined with medical therapy was 84%. CONCLUSION: Splenectomy should be considered safe and efficacious for thrombocytopenia associated with SLE.     

The role of prophylactic cholecystectomy during splenectomy in children with hereditary spherocytosis.

BACKGROUND/PURPOSE: Hereditary spherocytosis is an autosomal dominant disorder associated with an intrinsic defect in the red blood cell membrane often necessitating splenectomy to prevent sequestration of spherocytes. When cholelithiasis is present, these patients undergo cholecystectomy at the same surgical setting as splenectomy. After splenectomy alone, it is uncertain whether the amount of hemolysis is adequately decreased to prevent subsequent gallstone formation. This study set out to evaluate the frequency in which symptomatic cholelithiasis subsequently develops in children treated by splenectomy alone. METHODS: All patients less than 18 years old with hereditary spherocytosis who underwent splenectomy without cholecystectomy at our institution during the past 27 years were included in this study. A retrospective chart review and telephonic patient follow-up was performed. Gallstones were excluded in these patients either by preoperative ultrasound scan, or by intraoperative palpation of the gallbladder. The main study outcomes of this group included documented cases of cholelithiasis, subsequent need for cholecystectomy secondary to cholelithiasis, and questionnaire to determine the incidence of "subclinical" cholelithiasis (not reported to a physician). RESULTS: Twenty-three subjects were identified who met the inclusion criteria. Complete follow-up data were obtained for 17 of these patients (74%). The mean age at splenectomy was 6.6 +/- 0.69 years, and the mean follow-up was 15.65 +/- 2.03 years (median, 18 years). None of the patients in this series subsequently have undergone cholecystectomy, nor have any had either clinical or subclinical evidence of cholelithiasis since splenectomy. CONCLUSION: Prophylactic cholecystectomy at the time of splenectomy is not indicated in patients with hereditary spherocytosis who do not have gallstones.     

Cesarean section combined with splenectomy in severely resistant immune thrombocytopenia

Immune thrombocytopenic purpura (ITP) associated with pregnancy often involves considerable risk both for mother and child, and usually worsens in the third trimester of gestation. Pregnancy and delivery are especially difficult in patients with severe ITP (platelet count below 20 x 10(9)/L), who are resistant to prednisone and high dose intravenous immunoglobulin (IVIgG). In those cases we applied cesarean section (CS), to prevent intracranial haemorrhage due to fetal/neonatal ITP, and splenectomy at the same time as an effective therapeutic strategy for ITP. We present 5 patients (4 with chronic ITP and 1 with ITP associated with HIV infection), aged 21-35 years, with severe ITP (platelet count 2-10 x 109/L), resistant to prednisone (1-2 mg/kg), and 2/3 were resistant to IVIgG (0.4 g/kg x 5 d). Four patients with severe resistant ITP were supported with 1-2 doses of platelets from cell separator before CS and 1-3 dose during splenectomy. One patient increased platelet count to 55 x 109/L after treatment with IVIgG and splenectomy following CS were done without platelet transfusion. Splenectomy was performed immediately after CS in all patients, and two of them were hysterectomised (one with HIV infection). After splenectomy, platelet count was normalised in all patients, and they had no haemorrhage, wound haematoma formation or any adverse events. But ITP relapsed in 2/5 patients after 1-2 months. Two newborns had severe thrombocytopenia, which solved spontaneously after 3 days in one or after treatment with IVIgG in other. We propose that splenectomy following cesarean section should be considered as approach for delivery and treatment option for mothers with severe resistant ITP.     

Defining the learning curve for laparoscopic splenectomy for immune thrombocytopenia purpura

Background

The current study was undertaken to define the learning curve for laparoscopic splenectomy (LS) in patients with immune thrombocytopenic purpura (ITP).

Methods

The data of 50 patients who underwent LS for ITP between March 1996 and February 2003 were reviewed. Patients were divided into sequential groups of 10. Operative time, estimated blood loss, conversion to open procedure, length of stay (LOS), time to oral intake, complications, and mortality rates were analyzed.

Results

The mean OR time in the 3rd, 4th, and 5th groups of 10 were significantly shorter than the 1st and 2nd groups of 10. There were no significant differences in estimated blood loss, LOS, or time to oral intake between the groups. Three conversions to open splenectomy occurred; one each in the 2nd, 3rd, and 4th groups of 10. Complications were evenly distributed between groups. There were no deaths.

Conclusion

The learning curve for LS in patients with ITP is a minimum of 20 cases.     

The role of splenectomy in the treatment of thrombocytopenic purpura due to systemic lupus erythematosus.

Splenectomy in the treatment of thrombocytopenic purpura associated with lupus erythematosus has afforded satisfactory overall results in a group of ten patients. Postoperative deaths occurred in two patients, each of whom had significant underlying problems. Clinical manifestations of SLE-induced thrombocytopenic purpura included ecchymoses, petechiae, menorrhagia, epistaxis, and hematuria. Splenectomy in this disorder should be reserved for cases in whom corticosteroids do not produce satisfactory results, or in whom unacceptably high doses are required. Follow-up indicates long term control of thrombocytopenic purpura following splenectomy.