Institutional experience with laparoscopic partial splenectomy for hereditary spherocytosis

Background/Purpose

Moderate to severe hereditary spherocytosis (HS) is treated with splenectomy. However, total splenectomy leads to decreased immunologic function with the risk of overwhelming postsplenectomy sepsis. Splenic preservation is postulated as a method to avoid this potentially fatal complication. Although mainly performed through laparotomy, we report our experience with a laparoscopic approach to partial splenectomy for HS.

Methods

A retrospective review was conducted on 9 laparoscopic partial splenectomies performed for HS at our institution. Follow-up was from 1 to 3.5 years. Data included preoperative and postoperative hemoglobin, absolute reticulocyte count, splenic size, operative time, complications, and length of stay.

Results

All patients successfully underwent laparoscopic partial splenectomy with a radiologically determined upper-pole remnant of 10% to 30% and preservation of the blood supply through the upper short gastric arteries. The mean preoperative spleen length was 13 cm. Mean hospital stay was 3.6 days (range, 1-6 days). There was 1 intraoperative complication (a small bowel tear during spleen extraction) and 2 minor postoperative complications (ileus and wound infection). One patient underwent completion total splenectomy 2 years after partial splenectomy.

Conclusion

Laparoscopic partial splenectomy is a feasible and effective procedure that addresses the hematologic consequences of HS while retaining a portion of functional spleen, in addition to conferring the advantages of laparoscopy.     

Laparoscopic partial vs total splenectomy in children with hereditary spherocytosis

Background

Open partial splenectomy provides reversal of anemia and relief of symptomatic splenomegaly while theoretically retaining splenic immune function for hereditary spherocytosis. We recently developed a laparoscopic approach for partial splenectomy. The purpose of the present study is to compare the outcomes in a group of patients undergoing laparoscopic partial splenectomy (LPS) with those in a group of children undergoing laparoscopic total splenectomy (LTS) over the same period.

Methods

Systematic chart review was conducted of all children with hereditary spherocytosis who had LTS or LPS from 2000 to 2006 at the Hospital for Sick Children, Toronto, Ontario, Canada. T tests were used for continuous data, and χ² for proportional data; P value of less than .05 was considered significant.

Results

There were 9 patients (14 males) in each group. Groups were similar in sex, age, concomitant cholecystectomy, and preoperative hospitalizations, transfusions, and spleen size. Estimated blood loss was greater in the LPS group (188 + 53 vs 67 + 17 mL; P = .02), but transfusion requirements were similar (1/9 vs 0/9). Complication rate was similar between groups. The LPS group had higher morphine use (4.1 + 0.6 vs 2.4 + 0.2 days; P = .03), greater time to oral intake (4.4 + 0.7 vs 2.0 + 0.2 days; P = .01), and longer hospital stay (6.3 + 1.0 vs 2.7 + 0.3 days; P = .005) than the LTS group. Nuclear scan 6 to 8 weeks postoperatively demonstrated residual perfused splenic tissue in all LPS patients. No completion splenectomy was necessary after a mean follow-up of 25 months.

Conclusion

These data suggest that LPS is as effective as LTS for control of symptoms. However, LPS is associated with more pain, longer time to oral intake, and longer hospital stay. These disadvantages may be balanced by retained splenic immune function, but further studies are required to assess long-term splenic function in these patients.     

Splenectomy and partial splenectomy improve hematopoietic stem cell engraftment in hypersplenic mice

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 × 10⁶ 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 χ² 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.     

The Efficacy and Safety of Ezetimibe for Treatment of Dyslipidemia After Heart Transplantation

Introduction

Statins, although the treatment of choice for dyslipidemia after heart transplantation (HT), are not always well tolerated or effective. In such cases, administration of ezetimibe may be useful.

Aim

The aim of this study was to assess the efficacy and safety of ezetimibe, with or without statins, after HT.

Method

Thirty-six HT patients, 97% of whom were males of overall mean age of 57 ± 13 years, were all unable to reach target lipid levels with statins alone and/or were intolerant of statins. They were prescribed ezetimibe, with or without a statin. Efficacy and safety were evaluated after 1, 3, 6, and 12 months.

Results

Thirty-four patients were evaluated at 1 month and 12 months. Ezetimibe was prescribed to 27 patients (75%) because of statin inefficacy, and to 9 patients (25%) because of statin intolerance, manifested by myalgia in 4 cases (11%), hepatotoxicity in 2 cases (6%), and rhabdomyolysis in 3 cases (8%). Lipid levels (mg/dL; baseline vs 1 year) were as follows: cholesterol, 235 ± 49 versus 167 ± 32 (P = .013); LDL cholesterol, 137 ± 47 versus 89 ± 29 (P = .001); HDL cholesterol, 54 ± 13 versus 51 ± 10 (P = .235); and triglycerides, 243 ± 187 versus 143 ± 72 (P = .022). There were no cases of liver toxicity, renal dysfunction, or significant alteration of immunosuppressive pharmacokinetics. Ezetimibe was withdrawn from 2 patients because of hand edema or asymptomatic recurrence of rhabdomyolysis first caused by statins.

Conclusions

With or without a statin, ezetimibe was generally well tolerated, reducing total cholesterol, LDL cholesterol, and triglyceride levels with no long-term alteration of HDL cholesterol levels. CPK surveillance is recommended because of a slight continued risk of adverse effects. Further studies should evaluate the benefit for survival.     

Partial splenectomy prevents splenic sequestration crises in sickle cell disease

Purpose

Acute splenic sequestrations (SSs) are potentially fatal complications in sickle cell disease (SCD). Total splenectomies in young patients may predispose them to a higher risk of overwhelming infections, whereas partial splenectomy may maintain immunocompetence. We present our series of partial splenectomies in patients with multiple SS episodes.

Methods

We retrospectively reviewed the records of 6 patients who underwent open partial splenectomies for SS. Data on their clinical courses were collected and analyzed.

Results

None of the 6 patients had SS postprocedure, down from 2.1 ± 1.0 (P = .003) sequestrations per year and 3.5 ± 1.4 (P = .002) total sequestrations per patient. The transfusion requirements were significantly reduced postoperatively (10.2 ± 5.6 vs 2.0 ± 3.1 per year; P = .002). There was no increase in the infection-related hospital admissions during the period of follow-up (1.5 ± 1.8 vs 0.8 ± 0.8 per year after partial splenectomy; P = .363). The upper pole was preserved in all cases with blood supply off the main splenic artery.

Conclusions

Partial splenectomy decreases the risk of SS in SCD and reduces the need for blood transfusions. Infection rates did not increase after the procedure during the follow-up period. Partial splenectomy should be considered for patients who experience multiple acute SS crises or have long-term transfusion requirements.     

Does Everolimus Associated With a Low Dose of Cyclosporine in Long-Term Cardiac Transplant Recipients Improve Renal Function? Initial Experience

Background

Cyclosporine (CsA) renal toxicity is a well-known side effect. Various immunosuppressive strategies have been developed to minimize renal insufficiency. The use of everolimus associated with low levels of CsA can be an alternative strategy.

Methods

From October 2007 to April 2008, everolimus was started with a lower dose of cyclosporine (trough levels from 109.3 ± 27.5 to 93.7 ± 30.1 ng/mL after 45 days) in 21 cardiac transplant recipients (18 male and 3 female patients, mean age 56.4 ± 10.7 years). Pre-everolimus therapy creatinine levels, creatinine clearances, and glomerular filtration rates were 1.9 ± 0.9 mg/dL, 54.2 ± 18.1 mL/mins and 44.3 ± 16.5 mL/min/m², respectively.

Results

We observed a significant reduction in creatinine levels (from 1.9 ± 0.9 to 1.4 ± 0.3 mg/dL, P = .022) as well as a significant improvement in creatinine clearances (from 54.2 ± 18.1 to 69.0 ± 19.0 mL/min, P = .020) and glomerular filtration rates (from 44.3 ± 16.5 to 57.1 ± 16.3 mL/min/m², P = .010) after 7 days of everolimus therapy. Upon univariate analysis patient age, pretransplantation creatinine clearance, creatinine clearance after everolimus introduction, glomerular filtration rate at 45 days, and time from transplantation were associated with renal improvement. Upon multivariate analysis, only creatinine clearance at 7 days was related to the renal improvement.

Conclusions

These preliminary data suggested that everolimus with a low dose of CsA may be safe and effective to reduce CsA-related renal insufficiency among selected, heart transplant patients.     

Erythropoietin increases reticulocyte counts and maintains hematocrit in neonates requiring surgery

Background

Limited erythropoietin (Epo) production diminishes neonates' ability to regenerate blood removed by phlebotomy. Neonates requiring surgery are at risk to receive multiple transfusions. We sought to determine if recombinant Epo administration to neonates requiring surgery would stimulate erythropoiesis.

Methods

Infants were randomized in double-masked fashion to receive Epo (200 units kg⁻¹ d⁻¹) or placebo for 14 days. Complete blood count, absolute reticulocyte count (ARC), phlebotomy losses, and transfusions were measured during the study period. Infants were transfused using a strict transfusion protocol.

Results

In the Epo group (n = 10, 2034 ± 308 g, 8 ± 2 days old; mean ± SEM), ARC increased significantly, whereas in the placebo group (n = 10, 2400 ± 184 g, 7 ± 2 days old), ARC remained low. Hematocrits in the Epo group trended upward from 34.4 1.7% to 37.3 1.9% (although not statistically significant) despite phlebotomy losses of 53 ± 12 mL/kg. Hematocrits in the placebo group were 35.9 1.8% and 33.2 1.6% on days 1 and 15, respectively, with phlebotomy losses of 27 ± 5 mL/kg. There were no differences in absolute neutrophil counts or platelet counts between groups at the end of the study. No adverse effects were noted.

Conclusions

Infants randomized to Epo increased reticulocyte counts and hematocrits without adverse effects. Erythropoietin administration may provide an adjunct to present care in decreasing or eliminating erythrocyte transfusions in surgical neonates.     

The second STEP: the feasibility of repeat serial transverse enteroplasty

Background

Serial transverse enteroplasty (STEP) lengthens and tapers dilated bowel. Redilation of the STEP segment occurs in some patients with intestinal failure. The feasibility of a repeat STEP procedure in a pig model is evaluated.

Methods

Six pigs underwent reversal of an intestinal segment distal to the ligament of Treitz. At 6-week intervals after reversal, each animal had 2 STEP procedures on the bowel proximal to the reversed segment. Necropsy was performed up to 6 weeks after repeat STEP.

Results

Bowel length increased by 11.3 ± 3.9 cm and bowel diameter decreased from a mean of 5.3 ± 0.8 to 1.8 ± 0.4 cm (P < .0001) after the first STEP. After repeat STEP, bowel length increased by 16.7 ± 13.3 cm (P < .01), and the bowel was tapered from a mean of 5.4 ± 0.9 to 2.2 ± 0.4 cm (P < .01). Five pigs did well after repeat STEP, and 1 pig had early necropsy for bowel obstruction. None had histologic evidence of bowel ischemia in the repeat STEP segment.

Conclusions

A second STEP operation is feasible in a pig model and may be considered to optimize bowel length and function in select patients with intestinal failure.     

Patterns of cerebral injury in a series of infants with congenital diaphragmatic hernia utilizing magnetic resonance imaging

Background

Congenital diaphragmatic hernia (CDH) is a condition with significant mortality and respiratory morbidity. Long-term neurodevelopmental outcome is not yet well documented.

Methods

The authors examined all cases of CDH at their institution over a 12-month period and performed magnetic resonance imaging (MRI) of the brain postoperatively.

Results

Eight of 10 patients survived to have an MR brain scan. All 8 patients had cerebral injury detected on MRI, with a predominance of white matter and deep nuclear gray matter injury.

Conclusions

Cerebral injury detected with MRI is common in infants with congenital diaphragmatic hernia. The long-term significance of these MRI abnormalities is unknown, although the need for good long-term neurodevelopmental follow-up of infants with CDH is highlighted.     

Intramedullary Cavity as Implantation Site for Bioartifical Pancreas: Preliminary In Vivo Study

Background

The intramedullary cavity is a widely distributed well-vascularized microenvironment capable of sustaining grafts, and is a potential site for islet transplantation. The bone marrow offers sufficient space that may also be suitable for bioartificial pancreas (BAP) implantation.

Objective

To evaluate the feasibility of bone marrow as an implantation site for BAPs.

Materials and Methods

A calcium phosphate cement chamber satisfies the criteria for immunoisolation. Mouse insulinoma cells were suspended with agarose gel and enclosed in a calcium phosphate cement chamber to create a BAP, which was implanted in the intramuscular space in diabetic swine or the intramedullary cavity in diabetic dogs. Blood glucose and C-peptide concentrations were determined perioperatively.

Results

In the swine, the mean ± SD blood glucose concentration decreased from 413 ± 24 mg/dL to 285 ± 47 mg/dL, and was maintained in the range of 285 to 336 mg/dL for 15 days. It increased to 368 to 450 mg/dL after the BAPs were implanted in the intramuscular space. In the dogs, the blood glucose concentration decreased from 422 ± 32 mg/dL to 247 ± 52 mg/dL, and was maintained in the range of 247 to 347 mg/dL after the BAPs were implanted in the intramedullary cavity. The C-peptide concentration increased from 6.1 ± 2.8 pmol/L to 104.7 ± 16.4 pmol/L when the BAPs were implanted in the intramedullary cavity.

Conclusion

This study indicates superior effectiveness of BAPs implanted in the intramedullary cavity compared with the intramuscular space. This observation may be attributed to the greater oxygen tension in the bone marrow. The BAPs in direct contact with the circulatory system receive sufficient blood flow for function and survival. This preliminary study demonstrates that the intramedullary cavity may be an implantation site for BAP transplantation.     

Las hepatectomías mayores en pacientes con colangiocarcinoma e ictericia son seguras

Background

Surgical resection is the only possibility of long term survival in patients with Klatskin tumours. However, surgical resection is a challenging problem and hepatic resection is often necessary.

Objective

The aim of our study was to assess the need for biliary drainage, resection rate and outcome of hilar cholangiocarcinoma in a single tertiary referral centre.

Patients and methods

From 2005 to 2008, 26 patients with Klatskin tumours were identified and assessed prospectively with multidetector CT and MR cholangiography in special cases. Seven patients (27%) were deemed to be unresectable in pre-operative staging. A total of 19 surgical procedures were performed, 8 left hepatectomies, 5 right hepatectomies and 6 resections exclusively of the biliary tree.

Results

Resection rate was 73%, transfusion rate 53% and preoperative biliary drainage was performed only in 7 cases (37%). Major complications occurred in 11 (58%), including two post-operative deaths (10%).There were no differences in the epidemiological data, when we separately analysed the outcomes of the 9 patients with bilirubin <15 mg/dL and the 10 patients with bilirubin >15 mg/dL. Biliary drainage was required in 6 (67%) patients in the group with low bilirubin levels vs. 1(10%) in the other group (P=0.02). The mean bilirubin level in the jaundiced group was 22.1±3.9 vs. 4.7±4.3 (P<0.001) in the other group. There were no differences in the postoperative outcome between both groups.

Conclusion

Resection and survival rates have increased recently but still carries the risk of significant morbidity and mortality. Major hepatectomies in selected patients without percutaneous biliary drainage are safe.     

Impact of venous tumour thrombus consistency (solid vs friable) on cancer-specific survival in patients with renal cell carcinoma

Background

To our knowledge, the impact of venous tumour thrombus (VTT) consistency in patients affected by renal cell carcinoma (RCC) has never been addressed.

Objective

To analyse the effect of VTT consistency on cancer-specific survival (CSS).

Design, setting, and participants

We retrospectively analysed 174 consecutive patients with RCC and renal vein or inferior vena cava (IVC) VTT who underwent surgical treatment between 1989 and 2007 at our institute.

Intervention

All patients underwent radical nephrectomy and thrombectomy.

Measurements

Pathologic specimens were reviewed by a single uropathologist. In addition to traditional pathologic features, the morphologic aspect of the tumour thrombus was evaluated to distinguish solid from friable patterns. The prognostic role of thrombus consistency (solid vs friable) on CSS was assessed by means of Cox regression models.

Results and limitations

The VTT was solid in 107 patients (61.5%) and friable in 67 patients (38.5%). The presence of a friable VTT increased the risk of having synchronous nodal or distant metastases, higher tumour grade, higher pathologic stage, and simultaneous perinephric fat invasion (all p < 0.05). The median follow-up was 24 mo. The median CSS was 33 mo; the median CSS was 8 mo in patients with a friable VTT and 55 mo in patients with a solid VTT (p < 0.001). On multivariable analyses, the presence of a friable VTT was an independent predictor of CSS (p = 0.02). The power of our conclusion may be somewhat limited by the relatively small study population and the retrospective nature of the study.

Conclusions

In patients with RCC and VTT, the presence of a friable thrombus is an independent predictor of CSS. If our finding is confirmed by further studies, the consistency of the tumour thrombus should be introduced into routine pathologic reports to provide better patient risk stratification.     

Risk factors for acute chest syndrome in children with sickle cell disease undergoing abdominal surgery

Background/purpose

The reported incidence of acute chest syndrome (ACS) in children with sickle cell disease (SCD) is 15% to 20%. Our current objective was to assess risk factors and morbidity associated with ACS.

Methods

The authors reviewed the outcome of children with SCD undergoing abdominal surgery over a 10-year period.

Results

From 1991 to 2003, 60 children underwent laparoscopic cholecystectomy (LC; n = 29), laparoscopic splenectomy (LS; n = 28), or both (LB; n = 3). Mean age was 8.6 (0.7 to 20) years, and 35 (58%) were boys. Fifty-four (90%) had a preoperative hemoglobin greater than 10 g/dL, but only 22 (37%) received routine oxygen after surgery. No surgery was converted to an open procedure. Four children (6.6%), all of whom underwent either LS or LB, had ACS associated with an increased length of stay (7.4 ± 2.4 days) but no mortality. Factors associated with the development of ACS were age (3.0 ± 1.7 v 9.4 ± 5.7 years; P = .03), weight (12.1 ± 3.0 v 32.6 ± 18.2 kg; P = .04), operative blood loss (3.2 ± 0.5 v 1.4 ± 1.2 mL/kg; P = .03), and final temperature in the operating room (OR; 36.2 ± 0.4 v 37.6 ± 0.4 °C; P = .01). ACS was not significantly related to duration of surgery, OR fluids, or oxygen usage.

Conclusions

Younger children with greater blood and heat loss during surgery appear more prone to ACS. Splenectomy also seems to increase the risk of ACS. The authors’ current incidence (6.6%) of ACS in children with SCD undergoing abdominal surgery is much lower than previously reported. This may be explained by the aggressive use of preoperative blood transfusion or more routine use of laparoscopy.     

Assessment of mitochondrial DNA as an indicator of islet quality: an example in Goto Kakizaki rats

Background

Diabetic Goto Kakizaki (GK) rats represent an established model of type 2 diabetes that exhibit an onset of pancreatic islet (PI) pathology characterized by islet hypertrophy with a decreased number of insulin-secreting β-cells. Among the remaining β-cells, oxidative phosphorylation (OXPHOS) and consequently glucose-stimulated insulin secretion (GSIS) are impaired, perhaps owing to a deficit in mitochondrial DNA (mtDNA). We sought to identify this abnormality.

Methods

β-Cells were obtained from Accutase-dissolved PI isolated from GK or Wistar rats and sorted based on the positive Zn²⁺ signal of Newport Green. The mtDNA copy number per cell was quantified as the amplicon ratio by polymerase chain reaction using specific primers against the rat ND5 mt gene and UCP2 nuclear gene.

Results

The 12-month-old GK rats exhibited drastically reduced copy numbers per remaining β-cell, from 7,400 ± 600 in 12-month old Wistar rats (100%) to 24 ± 4%; mtDNA content in heart and liver was 70 ± 25% and 60 ± 20%, respectively. Versus age-paired Wistar rats, 6- and 4-month-old GK rats showed reductions to 60 ± 15% and 50 ± 20%, respectively.

Conclusions

OXPHOS of remnant β-cells in diabetic GK was drastically impaired due to the lack of sufficient mtDNA levels. We suggest the use of mtDNA quantification to quickly assess PI quality before transplantation.     

Prospective validation of a simple laboratory score to predict outcome after orthotopic liver transplantation

Objective

To establish a score to predict 30-day mortality and graft loss retrospectively and to validate the score prospectively.

Patients and Methods

Retrospectively in 296 liver transplant recipients, a score was developed that included the peak aspartate aminotransferase concentration within the first week and γ-glutamyltransferase and bilirubin concentrations at day 7 to predict graft loss or patient death within 30 days. The score was then prospectively validated in 86 patients undergoing liver transplantation.

Results

From the retrospective training cohort, cut-off values for prediction of adverse outcomes were determined using receiver operating characteristic curve analysis for peak aspartate aminotransferase (>1870 IU/mL), γ-glutamyltransferase (<214 IU/mL), and bilirubin (>5.75 mg/dL). Sensitivity and specificity of the score to predict an end point from the retrospective cohort were excellently reproduced in the prospective cohort. Overall, fulfilment of at least 2 criteria predicted graft loss or death within 30 days with sensitivity of 0.70 and specificity of 0.78. No patients with values that remained below all 3 thresholds experienced graft loss or death within 30 days.

Conclusions

This simple score calculated from standard laboratory values within the first week after liver transplantation enables prediction of graft loss and patient death within 30 days after transplantation. Early identification of patients at risk may help to improve outcomes by observing these patients more closely and allocating resources for them.     

Subcutaneous transplantation may not be an appropriate approach for the islets embedded in the collagen gel scaffolds

Background

Synthetic extracellular matrix (ECM) has been shown to be efficient to preserve the function of transplanted islets. In this study using a mouse model, we sought to determine whether subcutaneous transplantation was a convenient procedure for achieving normoglycemia.

Methods

We performed in vitro tests as well as morphologic observations and Western blotting to establish that embedded islets survived better than non-embedded islets. Streptozotocin-induced diabetic mice (BALB/c) were transplanted with ECM-embedded syngeneic islets via the subcutaneous (SC; n = 5) or subrenal capsule (SRC; n = 6) routes. We measured mean blood glucose levels at various points from pretransplantation to postoperative day 14, and examined immunohistochemistry staining for insulin in the transplant grafts on day 14.

Results

Islets transplanted with ECM gel retained better structure and developed a functional vasculature. Western blotting showed more caspase-3 expressed in the non-embedded islets, which indicated more islet cells undergoing apoptosis. On the first day after transplantation, glucose levels were significantly decreased in the SRC group compared with the SC group: 383.33 ± 44.50 mg/dL to 80.67 ± 16.85 mg/dL versus 414.00 ± 92.33 mg/dL to 278.28 ± 121.80 mg/dL (P < .05). Glucose levels were better maintained in the SRC group than the SC group over 14 days. Immunohistochemistry staining for insulin showed fewer islets in the SC group.

Conclusion

Embedded islets with ECM gel functioned better than non-embedded ones in vitro. However, the subcutaneous route may not be an ideal site for islet transplantation.     

Portal vein thrombosis after splenectomy in pediatric hematologic disease: risk factors, clinical features, and outcome

Background/Purpose

A retrospective study was performed to evaluate risk factors, clinical features, and treatment modalities of portal vein thrombosis (PVT) after splenectomy in pediatric hematologic disease.

Methods

Sixty-eight patients who underwent splenectomy for various hematologic diseases were evaluated with regard to age, sex, blood count, and splenic mass. Patients who developed PVT were also reviewed for clinical features, treatment modalities, and outcome.

Results

Patients with PVT (n = 4, 5.88%) and without PVT (n = 64, 94.2%) had a mean age and female/male ratio of 13.2 years (range, 10-16 years) and 4:0, and 10.2 years (range, 1-16 years) and 29:35, respectively. Postoperative thrombocyte levels and splenic mass with and without PVT was 804 × 10³/mm³ and 752.5 g, and 465.2 × 10³/mm³ and 441g, respectively. Three patients with PVT presented with abdominal pain, fever, and vomiting. The diagnosis of PVT was made by Doppler ultrasonography in all patients including the asymptomatic case. Protein C, protein S, and antithrombin III levels were mostly decreased and/or normal and di-dimer levels were increased and/or normal after the development of PVT. Antiplatelet (acetylsalicylic acid) and antithrombotic therapy (low molecular weight heparin) were treatment agents. None of the patients needed surgery. During a mean follow-up period of 55.5 months, by Doppler ultrasonography, 1 patient was found to be free of thrombosis, whereas 1 had partial thrombosis. Two patients developed cavernomatous transformation leading to portal hypertension.

Conclusions

Portal vein thrombosis is a rare but significant complication of splenectomy done for hematologic diseases. According to our results, female gender and decreased levels of coagulation inhibitors seem to be risk factors in addition to previously mentioned thrombocytosis and greater splenic mass. Doppler ultrasonography may be performed in all patients after splenectomy to screen PVT. In the presence of well-known risk factors, prophylactic antiplatelet and antithrombotic therapy should be considered after splenectomy.     

Long-term evolution of the mineral metabolism after renal transplantation: a prospective, single-center cohort study

Background

Abnormalities in bone and mineral metabolism are common after renal transplantation (RT) but information on their long-term time course is scarce.

Objectives

(1) Evaluate the time course of biochemical parameters of bone and mineral metabolism over 60 months after RT; (2) identify predictors for persistent hyperparathyroidism (HPT).

Design

Prospective, longitudinal, single-center cohort study.

Methods

We determined serum levels (mean values ± standard deviations) of intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase (APh), calcitriol, and creatinine (Cr) preoperatively as well as 6, 12, 24, 36, 48, and 60 months after cadaveric RT in 49 patients. We in addition recorded demographic, clinical, and therapeutic data.

Results

Pretransplantation iPTH stabilized from 194.2 ± 273.5 to 71.5 ± 50.7 ng/L at 6 months. Serum Ca (9.5 ± 1.1 mg/dL) and APh (81.9 ± 42.1 U/L) did not change. Baseline serum P (5.7 ± 1.8 mg/dL) and serum Mg (2.4 ± 0.4 mg/dL) decreased to normal ranges from month 6 onward. Low baseline calcitriol (22.4 ± 21.8 pmol/L) normalized slowly by 12 months (95.4 ± 46.7 pmol/L). Stable graft function (53.2 ± 15.8 mL/min) was achieved from 6 months onward. By 60 months, 26.5% of patients had a serum Ca above 9.8 mg/dL and serum P below 2.7 mg/dL; 22.4%, an Mg below 1.7 mg/dL and 8.2%, a serum iPTH more than 2.5-fold the upper limit of normal. Upon multiple regression analyses the iPTH at 60 months was influenced by a dialysis duration ≥ 2 years (β = 0.259, P = .003), body mass index > 25 kg/m² (β = 0.257, P = .006), baseline iPTH (β = 0.182, P = .036), serum Cr (β = 0.268, P = .002) and Mg (β = − 0.242, P = .006).

Conclusions

Hypercalcemia, hypophosphatemia, hypomagnesemia, and elevated iPTH persist in a subset of post-RT patients. Pretransplantation iPTH and obesity, dialysis duration, and posttransplant serum creatininemia and hypomagnesemia independently contribute to persistent HPT.     

Plasma exchange therapy for thrombotic thrombocytopenic purpura in pediatric patients with liver transplantation

Purpose

Sporadic cases of thrombotic thrombocytopenic purpura (TTP) have been reported in bone marrow and solid organ transplant patients receiving cyclosporine (CsA). We reported our experience with TTP using plasma exchange (PE) therapy in patients with liver transplantation (OLT).

Methods

Between March, 1993, and May, 2007, 400 patients underwent OLT, including 146 pediatric living-donor liver transplantation (LDLT). Four pediatric patients developed TTP after OLT: three were males and one female of mean age at the time of transplantation of 7.8 ± 3.6 years. The four recipients had the following indications for OLT: two glycogen storage disease, one biliary atresia, and one fulminant hepatic failure. Four patients initially received triple drug immunosuppression consisting of CsA, azathioprine, and steroids.

Results

Four (1%) patients developed TTP after OLT. All four patients were pediatric in the age group. The mean age at the time of TTP diagnosis was 8.0 ± 3.2 years, with a mean postoperative interval to TTP of 78.8 ± 114.2 days. The mean baseline platelet count was 7.0 ± 7.1 × 10,000. The eventual platelet count was 21.1 ± 20.8 × 10,000 after PE. These patients received PE 6.0 ± 4.2. The mean baseline serum creatinine was 0.8 ± 0.8 mg/dL. The mean peak serum creatinine was 2.3 ± 2.3 mg/dL. The mean serum CsA level was 717.5 ± 106.0 ng/mL before TTP diagnosis. Four patients were diagnosed by blood peripheral smears. The causes of TTP were CsA-associated in three patients and venoocclusive disease (VOD) in one patient. Three patients improved their platelet counts after PE therapy. Two patient changed from CsA to FK 506, one underwent reduced CsA dosage, and one stopped CsA. Three patients died of recurrent VOD, infection, and intrapulmonary hemorrhage. Only one patient survived.

Conclusions

The incidence of TTP in our series was lower. It only developed in pediatric patients. The causes of TTP were associated with CsA and/or VOD. The mortality was high after the TTP diagnosis. We concluded that TTP was a potentially fatal condition, but an early diagnosis with prompt institution of therapy with invasive PE therapy may reduce its mortal consequences.     

Mycophenolate Mofetil Dose Reduction in Renal Transplant Recipients: A 5-Year Follow-up Study

Objective

Mycophenolate mofetil (MMF), an immunosuppressant that is widely used in renal transplantation, is associated with several dose-dependent hematologic and gastrointestinal side effects that may require dose reduction or even discontinuation. The aim of this study was to compare renal allograft function and acute rejection episodes among kidney allograft recipients who were on 2 regimens of MMF for at least 5 years.

Materials and Methods

This prospective cohort of 55 kidney allograft recipients was followed for deterioration of allograft function, evidence of acute rejection, and allograft survival. Twenty-two patients (40%) underwent MMF dose reduction to 1.35 to 0.23 g/d due to perceived side effects or economic reasons (group 1). The mean time for this change was 4.2 ± 2.1 months after kidney transplantation. The remaining patients (group 2, n = 33) were continued on MMF (2 g/d). All patients were followed for at least 5 years after transplantation. Renal function tests (blood urea and serum creatinine) were measured monthly for 2 years and then every 2 months. Statistical analysis was performed using SPSS 11.0 (Student t test). P ≤ .05 was considered significant.

Results

The 2 groups were comparable regarding age, gender, and immunosuppressive medications. The renal function tests were comparable at the end of the study. Mean blood urea values were 44.8 ± 5.8 and 46.8 ± 6.8 mg/dL in groups 1 and 2 (P > .05); mean serum creatinine values were 1.32 ± 0.14 and 1.38 ± 0.21 mg/dL, respectively (P > .05). There were 2 graft losses and 1 patient loss in group 2. There were also 2 graft losses among group 1 patients.

Conclusion

Our study showed that MMF dose reduction was not associated with an increased risk of acute renal allograft rejection or impaired allograft function at 5 years.