Takeshi Kurosaki

Prolonged administration of twice-daily bolus intravenous tacrolimus in the early phase after lung transplantation

BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

Therapeutic Effect of Sirolimus for Lymphangioleiomyomatosis Remaining in the Abdominopelvic Region After Lung Transplantation: A Case Report

PURPOSEnSirolimus (SRL) is used to treat pulmonary lymphangioleiomyomatosis (P-LAM). There is limited evidence that SRL has systemic efficacy for the patients with extrapulmonary lymphangioleiomyomatosis (E-LAM) remaining after lung transplantation (LT) for P-LAM. This report examines the efficacy of SRL treatment for the patient with E-LAM remaining after an LT for P-LAM.nnnCASE SUMMARYnThe course of the patients recovery from an LT for P-LAM was complicated by lymphedema in the left femoral region that was caused by two E-LAM lesions remaining in the left pelvic cavity and in the retroperitoneal area. After the LT was performed, the patient started SRL treatment to reduce the E-LAM lesions. The daily SRL dose, selected based on the standard SRL dose for P-LAM, was initiated at 1 mg/d and was maintained at 2 mg/d. The remaining E-LAM lesions and lymphedema in the left femoral region improved in approximately 9 months after the LT with the administration of both SRL and the standard immunosuppressive therapy used by Okayama University Hospital, including tacrolimus, mycophenolate mofetil, and prednisolone. The SRL and tacrolimus trough concentrations in whole blood were maintained within the therapeutic window for the next 1.5 years after initiation of SRL treatment. The patient experienced no severe adverse events that required discontinuation of the SRL treatment during this time.nnnCONCLUSIONnThe patients with remaining E-LAM lesions may receive SRL treatment to improve the quality of life after LT for P-LAM as effective therapy in cases where the patients recovery is complicated by E-LAM lesions.

Unilateral lung transplantation using intact bilateral upper lobes

From the Department of Thoracic Surgery/Organ Transplant Center, Okayama University Hospital, Okayama, Japan. This study was supported in part by a grant from the Ministry of Health, Labor, and Welfare, Japan and the Japan Society for the Grants-in-Aid for Scientific Research #16K1998008 (to S.O.) Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Nov 27, 2017; revisions received Feb 28, 2018; accepted for publication March 3, 2018; available ahead of print March 30, 2018. Address for reprints: Takahiro Oto, MD, Department of Thoracic Surgery/Organ Transplant Center, Okayama University Hospital, 2-5-1 Shikata, Kita-ku, Okayama 700-8558, Japan (E-mail: oto@md.okayama-u.ac.jp). J Thorac Cardiovasc Surg 2018;156:e35-8 0022-5223/

Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients

36.00 Copyright 2018 by The American Association for Thoracic Surgery https://doi.org/10.1016/j.jtcvs.2018.03.003 Schema of anastomoses of this unilateral LTx using upper-lobe grafts.

Feasibility of lung transplantation from donors mechanically ventilated for prolonged periods

PurposeAirway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes.MethodsWe reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT.ResultsThe incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (pu2009=u20090.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (pu2009=u20090.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (pu2009=u20090.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (pu2009=u20090.25).ConclusionACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

Low-risk donor lungs optimize the post-lung transplant outcome for high lung allocation score patients

PurposeWhen patients are mechanically ventilated for more than 5 days, they are usually declined as donors for lung transplantation (LTx); thus, the long-term outcomes of LTx from such donors remain unclear. We investigated the feasibility of LTx from donors that had been mechanically ventilated for prolonged periods.MethodsThe subjects of this retrospective comparative investigation were 31 recipients of LTx from donors who had been mechanically ventilated for <u20095 days (short-term group) and 50 recipients of LTx from donors who had been mechanically ventilated for ≥u20095 days (long-term group).ResultsThe median duration of donor mechanical ventilation was 3xa0days in the short-term group and 8.5xa0days in the long-term group. However, other than the difference in the duration of donor ventilation, there were no significant differences in the clinical characteristics of the donors or recipients between the groups. The overall survival rate after LTx was comparable between the long-term group and short-term group (5-year survival rate, 66.6% vs. 75.2%).ConclusionThe potential inclusion of donors who have been on mechanical ventilation for more than 5 days could be a feasible strategy to alleviate donor organ shortage.

A single-nucleotide polymorphism in a gene modulating glucocorticoid sensitivity is associated with the decline in total lung capacity after lung transplantation

PurposeThe lung allocation score (LAS) has been generally recognized as a contributor to the overall survival in lung transplant candidates. However, donor-related risks have never been taken into consideration in previous research that validated the LAS. This study aimed to determine whether or not the role of the LAS as a predictor of the posttransplant outcome is influenced by the quality of the donor lungs.MethodsWe retrospectively reviewed 108 patients who underwent lung transplantation at Okayama University Hospital since 1998. The cohort was divided into two groups based on the lung donor score (DS; ≤xa04/>xa04). Correlations between the LAS and posttransplant outcomes were investigated in both groups.ResultsIn the high-DS group, an elevated LAS was strongly associated with posttransplant PaO2/FiO2 (pu2009=u20090.018). However, in the low-DS group, no correlation was found between them. There was no significant difference in the long-term survival according to the LAS in the low-DS group. The LAS effectively predicted the posttransplant outcome only when lungs with DSu2009>u20094 were transplanted; the LAS was not reliable if high-quality lungs were transplanted.ConclusionLung transplantation can be feasible and provides a survival benefit even for high-LAS patients if lungs from a low-risk donor are transplanted.

Donor-derived cell-free DNA is associated with acute rejection and decreased oxygenation in primary graft dysfunction after living donor-lobar lung transplantation

PurposeGlucocorticoids are used to prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). Our study was aimed at assessing the association between the glucocorticoid-induced transcript 1 gene (GLCCI1) variant, which modulates glucocorticoid sensitivity, and the postoperative lung function and development of CLAD after LT.MethodsA total of 71 recipients of LT were genotyped for the GLCCI1 variant (rs37972) and divided into three groups: the homozygous mutant allele (TT) group, the heterozygous mutant allele (CT) group, and the wild-type allele (CC) group. The results of pulmonary function tests were compared with the postoperative baseline values.ResultsThe total lung capacity (TLC) in the TT group was significantly lower than that in the CC group at 3xa0years after LT (Pu2009=u20090.029). In the recipients of cadaveric LT, the TLC and forced expiratory volume in 1xa0s in the TT group were significantly lower than those in the CC groups, resulting in a significant worse CLAD-free survival at 3xa0years after LT (Pu2009=u20090.016).ConclusionThe GLCCI1 variant was associated with a significant decrease of the TLC at 3xa0years after LT and the development of CLAD at 3 years, especially in patients undergoing cadaveric LT.

Pneumatosis intestinalis after lung transplantation for pulmonary graft-versus-host disease

Donor-derived cell-free DNA (dd-cf-DNA) has been shown to be an informative biomarker of rejection after lung transplantation (LT) from deceased donors. However, in living-donor lobar LT, because small grafts from blood relatives are implanted with short ischemic times, the detection of dd-cf-DNA might be challenging. Our study was aimed at examining the role of dd-cf-DNA measurement in the diagnosis of primary graft dysfunction and acute rejection early after living-donor lobar LT. Immediately after LT, marked increase of the plasma dd-cf-DNA levels was noted, with the levels subsequently reaching a plateau with the resolution of primary graft dysfunction. Increased plasma levels of dd-cf-DNA were significantly correlated with decreased oxygenation immediately (pu2009=u20090.022) and at 72u2009hours (pu2009=u20090.046) after LT. Significantly higher plasma dd-cf-DNA levels were observed in patients with acute rejection (median, 12.0%) than in those with infection (median, 4.2%) (pu2009=u20090.028) or in a stable condition (median, 1.1%) (pu2009=u20090.001). Thus, measurement of the plasma levels of dd-cf-DNA might be useful to monitor the severity of primary graft dysfunction, and plasma dd-cf-DNA could be a potential biomarker for the diagnosis of acute rejection after LT.

Favorable survival in lung transplant recipients on preoperative low-dose, as compared to high-dose corticosteroids, after hematopoietic stem cell transplantation

Pneumatosis intestinalis, which could complicate a spectrum of clinical conditions ranging from benign to life-threatening, is a rarely encountered complication after lung transplantation (LT). We describe two cases in which PI developed as a complication following LT for pulmonary graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In addition to the long-term immunosuppression administered for pulmonary GVHD, the intense immunosuppression needed after LT might increase the risk of PI in lung transplant recipients after HSCT. Conservative therapy should be considered for the treatment of PI developing after LT.