Sang Hyun Ahn

Current strategy for the treatment of symptomatic spontaneous isolated dissection of superior mesenteric artery

OBJECTIVEnSpontaneous isolated dissection of the superior mesenteric artery (SIDSMA) is extremely rare. Various treatment options are currently available, including conservative management, anticoagulation, endovascular stenting, and surgical repair. Herein, we present our experience in the treatment of symptomatic SIDSMA.nnnMETHODSnA retrospective study was conducted on 14 consecutive patients with symptomatic SIDSMA between January 2000 and January 2010. All patients had acute onset abdominal pain. The decision to intervene was based on patient symptoms and signs, as well as the morphologic characteristics of superior mesenteric artery (SMA) dissection on computed tomography (CT) angiography. Endovascular stenting (ES) was indicated in patients with severe compression of the true lumen or dissecting aneurysm likely to rupture. Self-expandable stents were placed via a right common femoral approach. None of the patients underwent anticoagulation, and patients who underwent ES were maintained on antiplatelet therapy for 3 months postoperatively.nnnRESULTSnThe median age of the study subjects was 59 years (range, 50-75 years). The median follow-up time was 27.5 months (range, 2-64 months). Treatment included conservative management without the use of anticoagulation in seven patients, ES in six, and necrotic bowel resection in one. Four patients with severe compression of the true lumen or large dissecting aneurysm underwent ES as a primary treatment. ES was additionally performed in two patients in whom initial conservative treatment failed (increasing dissecting aneurysm at 7-day follow-up CT scan in one and a reappearance of abdominal pain after resuming diet in the other). The median fasting time was significantly shorter in patients with primary ES (2.5 days) than in those managed conservatively (8.0 days). No complications associated with the SIDSMA or ES were developed. The patency of stents was demonstrated on follow-up CT scans up to 60 months (range, 1-60 months).nnnCONCLUSIONSnConservative management without anticoagulation can be applied successfully to the patients with symptomatic SIDSMA. Primary endovascular stenting is indicated if patients have suspected bowel ischemia, compression of the true lumen of the SMA >80%, or SMA aneurysm of >2.0 cm in diameter on initial CT scan. Endovascular stenting can also be provided to the patients in whom initial conservative treatment failed, as a rescue therapy.

CYP3A5 *1 allele: impacts on early acute rejection and graft function in tacrolimus-based renal transplant recipients.

Background. Tacrolimus is a major immunosuppressant, which has a narrow therapeutic range and wide interindividual variation. The effects of genetic polymorphisms of cytochrome P450 3A (CYP3A) 5 and Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) genes on the achievement of target tacrolimus trough levels and clinical outcomes in renal transplants were evaluated. Methods. A total of 62 patients participated in this prospective study. After an initial fixed oral dose (0.08 mg/kg two times per day), tacrolimus doses were adjusted to a target range based on daily measurement of blood trough concentration. Every patient underwent 10-day scheduled biopsy. Both the patients and investigators were blinded for the genetic polymorphisms. Results. Those subjects expressing CYP3A5 (n=29) evidenced significantly lower tacrolimus trough levels between days 1 and 5 after transplantation, when compared with nonexpressers (n=33). Significantly higher overall incidences of early T-cell-mediated rejection (TCR) of at least Banff grade 1 in severity (P=0.017), including clinical rejection within 10 days and subclinical rejection in biopsies at postoperative day 10 were detected in CYP3A5 expressers. The severity of TCR according to Banff 07 classification was associated with CYP3A5 genotypes (P=0.012). Moreover, multivariate analysis identified CYP3A5 expression as an independent risk factor for TCR (odds ratio: 2.79; P=0.043). Significantly lower estimated glomerular filtration rates until 1 month and numerically lower estimated glomerular filtration rates by 12 months were noted in the CYP3A5 expressers. The genetic polymorphisms of the ABCB1 genes exerted no significant effects. Conclusion. We confirmed the significant effects of CYP3A5 polymorphism on the achievement of target tacrolimus trough levels and the development of acute rejection in early period after transplantation and consequent renal allograft function.

Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in de novo kidney transplant patients

BACKGROUNDnThere is a growing concern about the therapeutic equivalence of the generic tacrolimus formulation (GEN Tacrolimus) to the reference tacrolimus (REF Tacrolimus) in solid organ transplantation.nnnMETHODSnA prospective, randomized study of 126 de novo renal transplant patients was conducted to compare the efficacy, safety and pharmacokinetic (PK) profiles between GEN tacrolimus (n = 63) and REF tacrolimus (n = 63). The PK of tacrolimus was evaluated on Day 10 and 6 months under steady-state condition. Crossover study was carried out in 66 patients at 6 months.nnnRESULTSnOn Day 10, 117 patients completed PK profiles (54 GEN tacrolimus and 63 REF tacrolimus) and GEN tacrolimus showed comparable C(0) (9.8 ± 2.5 versus 9.7 ± 3.0 ng/mL, P = 0.80) but significantly higher dose-normalized C(max) (309.1 ± 191.9 versus 192.5 ± 95.2 ng/mL/mg/kg, P < 0.001). The dose-normalized AUC(0-12) tended to be higher in the GEN tacrolimus than in the REF tacrolimus group (1513.4 ± 935.4 versus 1262.5 ± 593.5 ng.h/mL/mg/kg, P = 0.084). Because of this early and high C(max) with a rapid decline in GEN tacrolimus concentration, the trough concentration was maintained lower than that of REF tacrolimus. At 6 months, GEN tacrolimus showed equivalent dose-normalized AUC(0-12) (1882.2 ± 935.6 versus 1718.1 ± 946.3 ng.h/mL/mg/kg, P = 0.429) but still higher dose-normalized C(max) (346.3 ± 184.4 versus 273.2 ± 148.9 ng/mL/mg/kg, P = 0.056), despite a reduced trough concentration (5.7 ± 1.6 versus 6.9 ± 2.2 ng/mL, P = 0.004). PK profiles evaluated at 9 months showed that generic substitution also resulted in an early and high C(max). Efficacy and safety data were comparable over the 9-month study period.nnnCONCLUSIONSnTherapeutic equivalence and the PK of GEN tacrolimus should be evaluated in patients undergoing de novo renal transplantation.

Optimized Tacrolimus Therapy in the Early Stage after Renal Transplantation

Purpose: Immunosuppressive regimen based on reduced-dose Tacrolimus (TAC) is widely accepted in the field of renal transplantation. However, optimal targetsfor TAC whole blood trough concentrations during the early period after kidney transplantation remain uncertain. Methods: A total of 184 consecutive adult renal transplant recipients with triple immunosuppression (TAC/Mycophenolate/corticosteroid) were included in this study. According to the trough level of TAC at day 7 after transplantation, patients were classified as low TAC concentration (LT, <10 ng/ml, n=85), intermediate TAC concentration (IT, 10∼15 ng/ml, n=75), and high TAC concentration (HT, >15 ng/ml, n=24) groups. Rate of acute rejection, graft function and side effects of TAC within 1 yr after transplantation were evaluated. Results: There was no difference in trough concentrations of TAC at 2 weeks, 1 month, 3 months, 6 months and 12 months after transplantation among the three groups. Significantly higher incidence of acute rejection within 2 weeks after transplantation was observed in LT group compared with IT and HT groups (17.4%, 5.6% and 4.8%, respectively, P=0.037). HT patients showed significantly better estimated glomerular filtration rates until 6 months after transplantation than IT and LT patients (75.5±24.8 vs. 63.8±12.8 and 64.3±15.2 ml/min at 6 months, P=0.03). There was no significant difference in TAC toxicity in terms of post-transplant diabetes and renal toxicity. Conclusion: Short-term high TAC exposure immediately after kidney transplantation may provide lower incidence of acute rejection and better restoration of graft function compared with low or intermediate TAC exposure. (J Korean Surg Soc 2010;79:428-435)