松田 安史

BACKGROUND: Despite the low number of lung transplantations (LTs) in Japan, 10 LT facilities are accredited and good outcomes have been reported. A database review was conducted to clarify the impact of case volume at LT facilities in Japan on short- and long-term outcomes. METHODS: All cadaveric LT cases treated between 2000 and 2021 in Japan were analyzed using the database of the Japanese Society of Lung and Heart-Lung Transplantation (JSLHT). The nine institutions represented were categorized into the low-volume (LV; <80 cumulative LT cases, <8 LTs/year, n=5) and high-volume (HV; ≥80 cumulative LT cases, ≥8 LTs/year, n=4) centers. Ninety-day and 1-year mortality, as well as 5- and 10-year survival data were evaluated. RESULTS: A total of 658 cadaveric LTs were performed at the nine institutions. The 90-day rates of mortality at the HV and LV centers were 3.5% and 3.9%, respectively (P=0.801), while the 1-year mortality rates were 9.2% and 11.5%, respectively (P=0.199). Additionally, log-rank analysis of Kaplan-Meier curves showing case volume did not reveal a significant difference in long-term survival between the HV and LV centers (P=0.272), though the LV centers had wide differences for long-term outcomes (P=0.030). CONCLUSIONS: Case volume did not have effects on short- or long-term outcomes following LT in Japan, while there were large variations in long-term outcomes among the LV centers compared to those of the HV centers.

OBJECTIVES: Standard bilateral lung transplantation (BLT) is not feasible for patients with pulmonary arterial hypertension (PAH) complicated with a giant pulmonary arterial aneurysm (PAA). This study aimed to describe the outcomes of BLT with pulmonary artery reconstruction (PAR) using donor aorta for such patients. METHODS: This is a retrospective single-centre study reviewing PAH patients with a PAA who received BLT with PAR using donor aorta from January 2010 through December 2020. We compared the characteristics and short- and long-term outcomes of recipients receiving PAR (PAR group) with those who had no PAA and received standard BLT (non-PAR group). RESULTS: Nineteen adult PAH patients underwent cadaveric lung transplantation during the study period. Among them, 5 patients with a giant PAA (median pulmonary artery trunk diameter, 69.9 mm) underwent BLT with PAR using donor aorta and the others received standard BLT. Although the operation time tended to be longer in the PAR group compared with the non-PAR group (1239 vs 958 mins, P = 0.087), 90-day mortality (PAR group: 0% vs non-PAR group: 14.3%, P > 0.99), and 5-year survival rate (PAR group: 100% vs non-PAR group: 85.7%, P = 0.74) was comparable between the groups. No dilatation, constriction or infection of the aortic grafts were recorded during the study period with a median follow-up time of 94 months in the PAR group. CONCLUSIONS: Lung transplantation with PAR using donor aorta is a valid surgical option for PAH patients complicated with a giant PAA.

PURPOSE: To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. METHODS: Patients' data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. RESULTS: Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient's age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. CONCLUSION: The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

PURPOSE: The phase angle (PhA), calculated by bioelectrical impedance analysis, is used as a nutritional risk indicator. A low preoperative PhA has been reported as a marker of postoperative complications in patients with cancer; however, the relationship between the PhA and postoperative complications in patients with lung cancer remains unknown. We conducted this study to assess the predictive ability of the preoperative PhA for postoperative complications in patients undergoing surgery for primary lung cancer. METHODS: We reviewed the data on 240 patients who underwent surgery for primary lung cancer at our institution between August, 2019 and August, 2021. RESULTS: The PhA value in this study was 4.7 ± 0.7°. According to the Clavien-Dindo classification, grade ≥ II postoperative complications occurred in 53 patients (22.0%). Based on the multivariate logistic analysis, only the PhA (odds ratio, 0.51, 95% confidence interval, 0.29-0.90, p = 0.018) was an independent predictor of Clavien-Dindo grade ≥ II postoperative complications. CONCLUSIONS: The PhA may be a valuable marker for predicting the risk of postoperative complications following lung cancer surgery.

BACKGROUND: Lung cancer frequently occurs in lungs with background idiopathic interstitial pneumonias (IIPs). Limited resection is often selected to treat lung cancer in patients with IIPs in whom respiratory function is already compromised. However, accurate surgical margins are essential for curative resection; underestimating these margins is a risk for residual lung cancer after surgery. We aimed to investigate the findings of lung fields adjacent to cancer segments affect the estimation of tumor size on computed tomography compared with the pathological specimen. METHODS: This analytical observational study retrospectively investigated 896 patients with lung cancer operated on at Fujita Health University from January 2015 to June 2020. The definition of underestimation was a ≥10 mm difference between the radiological and pathological maximum sizes of the tumor. RESULTS: The lung tumors were in 15 honeycomb, 30 reticulated, 207 emphysematous, and 628 normal lungs. The ratio of underestimation in honeycomb lungs was 33.3% compared to 7.4% without honeycombing (P=0.004). Multivariate analysis showed that honeycombing was a significant risk factor for tumor size underestimation. A Bland-Altman plot represented wide 95% limits of agreement, -40.8 to 70.2 mm, between the pathological and radiological maximum tumor sizes in honeycomb lungs.

Recessive gene mutations in ABCA3 cause lethal neonatal respiratory distress, and pediatric and adult interstitial lung disease. The effectiveness of medical treatments is limited and a subset of such patients will eventually require lung transplantation. A 20 months old boy developed interstitial lung disease and was treated with hydroxychloroquine, which had a significant effect. Sequence analysis of ABCA3 gene revealed newly discovered compound heterozygous mutations. His respiratory dysfunction gradually progressed over years and he underwent living-donor lobar lung transplantation (LDLLT) at 8 years of age with his parents serving as bilateral lobar donors. The parents had been genetically examined beforehand and found to be carriers who had one allele with an ABCA3 gene mutation and the other with no mutation. The recipient has been well without chronic lung allograft dysfunction and his parents have been enjoying healthy social lives for 7 years since the operations. LDLLT appears to be a valid option for selected children with ABCA3 gene mutations who are too ill to wait for cadaveric lung transplantation. When relatives of the recipient with ABCA3 gene mutation are deemed potential donors for LDLLT, sequence analyses of the donors are indispensable to exclude the possibility that they are late-onset patients of this recessive hereditary disease.

Traumatic diaphragmatic injury( TDI) is rare in traumas, however TDI is associated with high mortality. We follow the notation method by The Japanese Association for The Surgery of Trauma. There are blunt trauma and penetrating trauma of TDI;blunt trauma causes mainly traffic accidents, and penetrating trauma is induced stub or gunshot. Penetrating trauma is more frequent than blunt trauma in Western countries, however there are mainly blunt traumas in Japan. The timing of diagnosis are three points;acute phase, subacute phase and delayed phase. In acute phase we often experienced unstable vital sign, so the patients of TDI need treatment immediately, however in delayed phase the patients of TDI are stable in vital signs. In order to diagnose for TDI, we use chest X-ray and computed tomography (CT), which is useful to diagnose by multi-planar reconstruction of multi-detector row CT. The ways to approach to TDI are from thoracotomy, laparotomy or both. When we repair the diaphragmatic injury, usually interrupted or horizontal mattress suture was applied with non-absorbable string. The mortality is about 8.8 to 19.8% by TDI, so we need to carefully diagnose TDI as soon as possible whether complication and abdominal viscera injury exist or not.

OBJECTIVES: The objective of the present study was to examine the effect of venovenous extracorporeal membrane oxygenation (VV ECMO) use on the hemodynamics during single lung transplantation (SLT) and post-operative course. METHODS: Forty-seven patients who underwent SLT for end-stage lung diseases in our lung transplant center between January 2010 and December 2019 were included in this study. The recipients were divided into 3 groups according to the type of intra-operative ECMO. No type of ECMO was intra-operatively used in the patients of the NO ECMO group. The patients in the venoarterial (VA) and VV ECMO groups were put on VA and VV ECMO during the surgery, respectively. The data were compared among the three groups. RESULTS: There were 13 SLT cases in the NO ECMO group, 23 SLT cases in the VA ECMO group and 11 SLT cases in the VV ECMO group. Re-exploration for bleeding was performed in 3 (13.0%) recipients in the VA ECMO group. No recipients required re-exploration in the other groups. In the NO ECMO group, systolic pulmonary arterial pressure (sPAP) was significantly elevated during the main pulmonary artery clamp on the SLT side and it was decreased in the VA ECMO group because of the bypass flow. Interestingly, sPAP was significantly decreased in the VV ECMO group as well. CONCLUSIONS: VV ECMO decreases the PAP during SLT which could be a choice for extracorporeal life support during lung transplant surgery for patients, even those with pulmonary hypertension.

In order to overcome challenges of serious short supply of donor organs, a unique partnership between transplant consultant doctors and local physicians, named medical consultant( MC) system, started in 2002 to maximize the organ utilization rate. As the first step of this system, skillfull heart transplant surgeons were sent to procurement hospitals as MCs to assess donor organ function and provide intensive care to donors. Since 2006, the MC doctors have requested the donors' attending physicians to perform aggressive bronchial suctioning using bronchoscopy, leading to an improved lung utilization rate and better graft survival. Since 2011, more than 25 lung MCs have been registered to assess donor lungs and provide advices on intensive respiratory care to donors. The effects of this system on lung transplantation opportunities and outcomes were retrospectively reviewed in 187 brain-dead lung donor candidates, which were chronologically divided into 3 phases:Ⅰ( May 1998 to November 2006, n=44) and Ⅱ( December 2006 to January 2011, n=64), before and after MCs requested local attending physicians to perform aggressive bronchial suctioning using bronchoscopy, respectively;and phase Ⅲ (February 2011 to January 2013, n=79), after the emergence of lung MCs( Hoshikawa Y, et al. Transplant Proc 47( 3):746-750, 2015). The lung utilization rates in phases Ⅰ, Ⅱ, and Ⅲ, were 61, 72, and 75%( per donor);51, 65, and 68% (per lung, p=0.03). Graft death due to primary graft dysfunction was significantly more frequent in phase Ⅰ (13.3%) than in phases Ⅱ (3.6%) and Ⅲ (3.7%, per lung, p=0.04). The lung utilization rate of 63 brain-dead lung donor candidates for a period of one year from June 2020 to May 2021, which was analyzed anew for this article, was 83%( per donor) and 72%( per lung). We discussed current status and tasks of the lung MC system which has been operated for 10 years.

BACKGROUND: Tracheobronchial injury in children is rare but can be highly fatal in severe cases. Therefore, prompt diagnosis and treatment are required. The appropriate treatment method depends on the extent and severity of the injury. CASE PRESENTATION: An 8-year-old girl fell from the fifth floor and was transported to a local hospital. She had a tracheobronchial injury, went into cardiopulmonary arrest during transportation to our hospital. She was revived with cardiopulmonary resuscitation, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was commenced. Subsequently, we performed tracheobronchial reconstruction by inverted Barclay's method for tracheobronchial injury. She was switched from VA-ECMO to venovenous (VV)-ECMO 4 days postoperatively, and VV-ECMO was eventually discontinued 27 days after the surgery. The patient was awake and weaned off the ventilator on postoperative day 58. She was discharged 97 days after the surgery. CONCLUSIONS: Tracheobronchial reconstruction by inverted Barclay's method is the preferred surgical technique when other reconstruction techniques are expected to cause excessive tension on the anastomosis of the right main bronchus.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that occurs in premature infants and the prognosis is variable depending on the comorbidities including fibrosis, emphysema, or pulmonary hypertension (PH). We present a case of a 9-year-old girl who developed PH associated with severe BPD (BPD-PH) and underwent bilateral lung transplantation (BLTx). Case description A 9-year-old girl was admitted to our department to undergo BLTx. She was born at 23 weeks and 4 days gestation with a weight of 507 g. She received ventilation for the first 2 months and required further respiratory care due to repetitive, severe respiratory infections. She was diagnosed with BPD-PH at 6 months of age and oral administration of pulmonary vasodilators were initiated. She was registered as a lung transplant candidate at 4 years of age after the life-threatening exacerbation. Chest computed tomography (CT) revealed severe lung conditions with ground-glass opacities and emphysematous low-density areas in the upper and lower lobes. BLTx from a brain-dead male donor was performed. The pathological findings of her resected lung revealed saccular, hypoplastic lung with alveolar repair/regeneration, and medial hypertrophy and muscularization of peripheral arteries. The postoperative course was mostly uneventful. She was free from oxygen administration and showed no signs of PH after 6 months of the surgery. CONCLUSION: This is the first case report of BLTx in a pediatric, irreversible BPD-PH patient with detailed pathohistological findings and clinical examination. Lung transplantation is one of the treatment options for severe BPD-PH.

PURPOSE: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). METHODS: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. RESULTS: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P < 0.01). However, Kaplan-Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m2 vs. 1 year post-transplant, 15.6 ± 2.5 kg/m2; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01). CONCLUSIONS: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

OBJECTIVES: One of the serious problems after lung transplantation is chronic lung allograft dysfunction (CLAD). Most CLAD patients pathologically characterized by obliterative bronchiolitis (OB). Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)-Ig is a combination protein of the Fc fragment of human IgG1 linked to the extracellular domain of CTLA4. The aim of the study was to examine the effect of CTLA4-Ig therapy on OB using a mouse intrapulmonary tracheal transplantation (IPTT) model. METHODS: IPTT was performed between BALB/c (donor) and C57BL/6 (recipient) mice. Abatacept, which is a commercially available form of CTLA4-Ig, was intraperitoneally injected in recipient mice immediately after surgery, on days 7, 14, and 21. The mice in the control group received human IgG. RESULTS: We performed semi-quantitative analysis of graft luminal obliteration at post-transplant day 28. We calculated the obliteration ratio of the lumen of the transplanted trachea in each case. The obliteration ratio was significantly lower in the CTLA4-Ig group than that in the control group (91.2 ± 2.1% vs. 47.8 ± 7.9%, p = 0.0008). Immunofluorescent staining revealed significantly decreased lymphoid neogenesis in the lung. CONCLUSIONS: CTLA4-Ig therapy attenuated tracheal obliteration with fibrous tissue in the mouse IPTT model. The attenuation of fibrous obliteration was correlated with the inhibition of lymphoid neogenesis.

BACKGROUND: The median sternotomy approach in sleeve pneumonectomy enables diseased lung ventilation in selected cases, which may reduce the difficulty in achieving anastomosis under intubation of the left main bronchus. However, with median sternotomy, the ascending aorta requires repeated mobilization to expose the operative field for anastomosis, which can cause an aortogenic embolic stroke. CASE PRESENTATION: A 70-year-old Asian man presenting 6 months after developing hemoptysis was diagnosed with right upper lobe lung cancer (stage T4N0M0), invading the lower trachea and basal bronchus. Preoperative computed tomography revealed ascending aorta calcification. Right sleeve pneumonectomy was performed using median sternotomy with diseased lung ventilation. The ascending aorta was repeatedly mobilized to adequately expose the tracheobronchial bifurcation. Surgery was uneventful, but he did not recover complete consciousness even after termination of anesthesia. Mild paralysis of both upper extremities was observed. Head magnetic resonance imaging on postoperative day 1 revealed multiple small acute infarctions in the brain, possibly caused by mobilization of the aorta. He received anticoagulation therapy and rehabilitation and was discharged on postoperative day 30. CONCLUSION: The median sternotomy approach in sleeve pneumonectomy enables diseased lung ventilation. However, the possibility of aortogenic embolic stroke should be considered when calcification of the ascending aorta is observed on preoperative computed tomography.

Infections caused by the Scedosporium genus have become recognized as a fatal complication after lung transplantation in Europe and Australia, but the reports have been rare from Asian countries including Japan. We present a case of pneumonia caused by a mixed infection of Scedosporium apiospermum (SA) and Lomentospora prolificans (LP) that developed after augmentation of immunosuppression for chronic lung allograft dysfunction (CLAD) after lung transplantation. A 13-year-old man underwent bilateral lung transplantation for pulmonary hypertension. One year after surgery, he was treated with a series of augmented immunosuppressive therapy for severe acute rejection and subsequent CLAD. Three months following the first steroid pulse therapy, his serum β-D-glucan elevated without any sign of fungal infection by other tests. The serum β-D-glucan once returned to a normal level by empirical administration of micafungin; however, the patient's condition worsened again by discontinuation of it. He did not recover by restarting micafungin, and computed tomography (CT) scans eventually demonstrated new infiltrates in his lung field 6 weeks after the elevation of serum β-D-glucan. Microscopic findings of transbronchial lung biopsy specimens showed filamentous fungi, and the culture of bronchoalveolar lavage fluid revealed the growth of SA and LP. Despite subsequent voriconazole administration, he died 14 days after the start of voriconazole. Early and aggressive inspection including bronchoscopy should be performed for the diagnosis of Scedosporium infection in immunocompromised patients, even if CT scans and sputum culture show no evidence of infection.

Solitary fibrous tumors are typically benign and usually develop in the pleura. We herein report the first case of a solitary fibrous tumor that was pathologically malignant and developed in the left atrial endocardium. A 24-year-old woman underwent resection of a malignant solitary fibrous tumor in her right forearm at another hospital. Computed tomography demonstrated a mass in her right pleura 2 months after the surgery. She was referred to our hospital, and a tumor in her left atrium was subsequently found. She underwent resection of these tumors, and pathological examination showed that they were both malignant solitary fibrous tumors.

Several drugs are administered to lung-transplanted patients, which are monitored using therapeutic drug monitoring (TDM). Therefore, we developed and validated a liquid chromatography-tandem mass spectrometry method to simultaneously analyze immunosuppressive drugs such as mycophenolic acid, antifungal drugs such as voriconazole and itraconazole, and its metabolite hydroxyitraconazole. Chromatographic separation was achieved using a C18 column and gradient flow of mobile phase comprising 20 mM aqueous ammonium formate and 20 mM ammonium formate-methanol solution. A simple protein precipitation treatment was performed using acetonitrile/methanol and mycophenolic acid-2 H3 , voriconazole-2 H3 , itraconazole-2 H4 , and hydroxyitraconazole-2 H4 as internal standards. The linearity ranges of mycophenolic acid, voriconazole, itraconazole, and hydroxyitraconazole were 100-20,000, 50-10,000, 5-1000, and 5-1000 ng/mL, respectively. The retention time of each target was less than 2 min. The relative errors in intra- and inter-day were within ±7.6%, the coefficient of variation was 8.9% or less for quality control low, medium, and high, and it was 15.8% or less for lower limit of quantitation. Moreover, the patient samples were successfully quantified, and they were within the linear range of measurements. Therefore, our new method may be useful for TDM in lung-transplanted patients.

BACKGROUND: The therapeutic drug monitoring of mycophenolic acid (MPA) has been investigated for renal and heart transplantations; however, its usefulness in lung transplantation is unclear. METHODS: The MPA area under the plasma concentration-time curve (AUC) was calculated in 59 adult lung transplant recipients. The MPA AUC0-12 s were compared among the three groups determined by the presence of adverse events (no events, infection, and chronic lung allograft dysfunction [CLAD]). Next, MPA AUC0-12 thresholds for the adverse events were identified by receiver operating characteristic analysis. Cumulative occurrence rate of the adverse events was compared between two groups (adequate and inadequate groups) according to the thresholds. RESULTS: The MPA AUC0-12 s in the no event, infection, and CLAD groups were 30.3 ± 6.5, 36.8 ± 10.7, and 20.6 ± 9.6 µg·h/mL, respectively (P = .0027), while the tacrolimus trough levels were similarly controlled in the groups. The thresholds of MPA AUC0-12 for the occurrence of infection and CLAD were 40.5 and 22.8 µg·h/mL, respectively. The cumulative occurrence rate of adverse events of adequate group (15.3%) was significantly lower than that of inadequate group (56.0%) (P = .0050). CONCLUSIONS: The MPA AUC0-12 may affect the occurrence of adverse events in lung transplant recipients.

症例は36歳,男性.健康診断で胸部異常陰影を指摘され受診した.胸部CT上,両側下葉優位に小葉中心性の粒状影を認めた.診断目的に気管支鏡検査を施行したが確定診断に至らず,胸腔鏡下肺生検を施行した.病理組織学的には,肺胞壁隔壁に沿って分岐するような形態を示す径0.5mm大の石灰沈着と脂肪髄を伴う骨組織を認めたため,樹枝状肺骨化症と診断した.本疾患は,肺組織に異所性の骨化巣を生じる非常に稀な疾患であり,自覚症状に乏しく剖検で発見されることが多い.また,長期に経過観察された報告はほとんどなく予後も明らかではない.本症例は,術後4年を経過して画像上の変化なく生存中である.(著者抄録)

Sirolimus is used on patients after solid organ transplantation and on lymphangioleiomyomatosis (LAM) patients, and therapeutic drug monitoring is required in clinical practice. We have previously reported an accurate method for quantitative determination of sirolimus, but its sample preparation step was complicated. In this study, we developed a modified liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for sirolimus quantification. A supported liquid extraction cartridge was used to purify sirolimus from whole blood and ion suppression was mostly prevented. The validation results met the acceptance criteria. This method was compared with the antigen conjugated magnetic immunoassay (ACMIA) and our previously reported method, using whole blood samples from LAM patients. Comparison of the Bland-Altman plots of the currently developed method and the previous method revealed no significant difference between the two methods (mean bias, -2.02%; 95% CI, -7.81-3.78). The values obtained using ACMIA were significantly higher than those obtained using the current method by 13.87% (95% CI, 6.49-21.25) owing to cross-reactivity. The degrees of cross reactivities in LAM patients and in organ transplant patients were similar, and our LC/ESI-MS/MS method precisely measured the blood concentrations of sirolimus.

Background.Acute kidney injury (AKI) is a common complication after lung transplant (LTx), and continuous renal replacement therapy (CRRT) is increasingly of use to critically ill patients who have developed AKI. However, the optimal timing or threshold of kidney impairment for which to commence CRRT after LTx has been uncertain. There has also been limited information on the impact of CRRT among LTx recipients (LTRs) introduced in the early posttransplant period on survival, graft function, and renal function. We aimed to review LTRs who developed AKI requiring CRRT postoperatively and followed their long-term outcomes at Tohoku University Hospital (TUH).Methods.Medical records of consecutive patients who underwent LTx at TUH between 2000 and 2018 were reviewed, with follow-up to 2019 inclusive.Results.Although mortality in those who required CRRT (n = 21) was increased versus those who did not require CRRT (n = 85)(P = 0.024), conditional survival beyond 3-month posttransplant was not affected (P = 0.131). Additionally, the cumulative incidence of chronic lung allograft rejection (P = 0.160) and the development of chronic kidney disease (P = 0.757) were not significant between groups.Conclusions.The initiation of CRRT posttransplant may be a useful strategy to preserve cardiac and optimize volume management among critically ill patients.

PURPOSE: We developed an ex vivo lung CT (EVL-CT) technique that allows us to obtain detailed CT images and morphologically assess the retrieved lung from a donor for transplantation. After we recovered the lung graft from a brain-dead donor, we transported it to our hospital and CT images were obtained ex vivo before lung transplant surgery. The objective of this study was to investigate the correlation between the EVL-CT findings and post-transplant outcome in patients who underwent bilateral lung transplantation (BLT) or single lung transplantation (SLT). METHODS: We retrospectively reviewed the records of 70 patients with available EVL-CT data who underwent BLT (34 cases) or SLT (36 cases) in our hospital between October 2007 and September 2017. The recipients were divided into 2 groups (control group, infiltration group) according to the findings of EVL-CT of the lung graft in BLT and SLT, respectively. Recipients in the control group were transplanted lung grafts without any infiltrates (BLT control group, SLT control group). Recipients in the infiltration group received lung grafts with infiltrates (BLT infiltration group, SLT infiltration group). RESULTS: The recipients in the BLT infiltration group showed significantly slower recovery from primary graft dysfunction and a longer mechanical ventilation period and ICU stay period than those in the BLT control group. The mechanical ventilation period was significantly longer in the recipients in the SLT infiltration group than those in the SLT control group. CONCLUSION: EVL-CT may predict the outcome of the early phase after lung transplantation.

BACKGROUND: Sirolimus and tacrolimus require accurate drug dosing based on their target blood levels to produce better clinical outcomes, specifically, the avoidance of drug-induced adverse effects and the maintenance of efficacy. However, because the ideal dose of sirolimus and the schedule for measuring its blood levels are unclear in lung transplant patients, an index is required for estimating sirolimus blood concentrations. The aim of this work is to study the correlation between the trough concentration/dose normalized by body weight (C0/D) ratios of sirolimus and tacrolimus in lung transplant patients. METHODS: Thirteen lymphangiomyomatosis patients who underwent lung transplantation and were treated with sirolimus and tacrolimus from February 2015 to July 2018 were divided into 2 groups, one receiving twice-daily (TD, n = 6) and the other once-daily (OD, n = 7) tacrolimus formulations. The correlation between the C0/D ratio of sirolimus and patient background was evaluated using Spearman's rank correlation coefficient. Correlations between sirolimus and tacrolimus C0/D ratios or doses were analyzed by single regression analysis. RESULTS: Significant correlations were found between the C0/D ratios of sirolimus and tacrolimus. The regression equations from the initial data of TD and OD groups at steady state were y = 1.880x + 32.636 (adjusted R = 0.743, P = 0.017) and y = 1.684x + 38.816 (adjusted R = 0.919, P < 0.001), respectively. In addition, the regression equations from all data of TD and OD groups were y = 1.883x + 4.170 (adjusted R = 0.546, P < 0.001) and y = 1.950x + 43.188 (adjusted R = 0.898, P < 0.001), respectively. A significant correlation between the dosage of sirolimus and tacrolimus was observed only in the OD group, with relatively low accuracy. CONCLUSIONS: Blood sirolimus concentrations can be estimated using the C0/D ratio of tacrolimus, suggesting that the C0/D ratio of tacrolimus is an index of required sirolimus dosage and the frequency of blood sirolimus concentration measurements.

A 60-year-old man consulted a clinic complains of sore throat. Squamous cell carcinoma of the hypopharynx and adenocarcinoma of the stomach were pointed out and he was refered to our hospital. As a result of detailed systemic examination, squamous cell carcinoma of the esophagus and squamous cell carcinoma of the right lung were also pointed out, which led to a diagnosis of synchronous quadruple cancer. On the basis of discussions among multiple clinical departments, systemic chemotherapy with cisplatin(CDDP), fluorouracil (5-FU) and docetaxel(DTX) was preceded locolegional therapies. After that, complete thoracoscopic right lower lobectomy and then a laparoscopic distal gastrectomy was performed. Radiation therapy was applied for hypopharyngeal cancer. Finally, endoscopic submucosal dissection for esophageal cancer was performed. Twenty months have passed since the last treatment, the patient is alive with a relapse-free condition.

OBJECTIVES: Appropriate selection for surgery is particularly important in T4 non-small cell lung cancer patients. In clinical settings, patients those who are positive for T4 criteria occasionally are also positive for T3 factors which are independently defined from original T4 or even have multiple T4 factors. Significance of these factors on prognosis is still unknown. METHODS: We retrospectively reviewed clinicopathorogical data of 113 patients with T4 non-small cell lung cancer those who underwent surgery between 1990 and 2015 in Tohoku University Hospital. Significance on prognosis of single or multiple T4 factors and with or without independent T3 factors were statistically analyzed. RESULTS: No significant difference was seen in the 5-year survival rate between patients with single (35.6%) and multiple (31.4%) T4 factors (P = 0.94), but the rate was significantly lower when patients also had independent T3 factors (19.6%) compared with when they did not (42.5%) (P = 0.011). The 5-year survival rate was particularly lower among patients with invasion of the chest wall or parietal pleura (8.1%) than in those without (40.6%) (P = 0.0052). CONCLUSIONS: Invasion of the chest wall or parietal pleura is poor prognostic factors in T4 non-small cell lung cancer patients.

Transplant recipients become immunocompromised through the use of immunosuppressive therapy to prevent allograft rejection. These recipients readily experience human cytomegalovirus (CMV) infection or reactivation. Therefore, CMV represents a life-threatening pathogen in transplant recipients. To demonstrate the serostatus and course of IgG maturation against CMV in transplant patients, we measured the transition of anti-CMV IgG and its affinity (avidity index; AI) as criteria for antibody maturation. Among 31 lung transplant recipients, 26 were infected with CMV before transplantation and maintained anti-CMV IgG and high AI values throughout the study period. Four of the 31 experienced primary infection with CMV through the allograft, with two of the 4 recipients presented high AI values even after 6 month post-transplantation. A significant portion of donor-derived plasma cells were detectable in one recipient. These results suggested that the plasma cells from donors are carried in through the transplanted lung and lymph nodes and produce matured high-avidity IgG from the early stage of transplantation.

PURPOSE: The purpose of this study was to assess the usefulness of positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of anterior mediastinal tumors. METHODS: A total of 94 patients with anterior mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17-84 years) were retrospectively evaluated. All patients were evaluated by PET/CT and the masses or nodules were histologically diagnosed in our institution. RESULTS: Anterior mediastinal masses and nodules were classified into two disease categories: Low (thymic hyperplasia, thymoma, mature teratoma, and MALT lymphoma) and High (thymic carcinoid, thymic cancer, diffuse large B-cell lymphoma, T-cell lymphoblastic lymphoma, Hodgkin's lymphoma, and malignant germ cell tumors) groups. The sensitivity and specificity of maximum standardized uptake value (SUVmax) 7.5 for the detection of High group were 77% and 100%, respectively. The SUVmax distributions of the WHO histological thymoma types and Masaoka stage thymomas extensively overlapped. Masaoka stage III thymomas had significantly higher SUVmax than Masaoka stage I thymomas. Regarding the TNM classification, the SUVmax of T3 and T1b thymomas was higher than T1a thymoma. CONCLUSION: Although the SUVmax of each disease overlapped, PET/CT findings provided useful information for the differential diagnosis of anterior mediastinal masses.

PURPOSE: The dose of mycophenolate mofetil (MMF) used to prevent rejection after lung transplantation is often adjusted based on the 12-hour area under the concentration-time curve (AUC0-12) of mycophenolic acid (MPA). A limited sampling strategy (LSS) is useful to define the pharmacokinetic (PK) profiles of MPA and mycophenolic acid acyl glucuronide (AcMPAG). Therefore, this study aimed to design a LSS based on multiple linear regression for estimating the AUC0-12 of MPA and AcMPAG at the minimum blood sampling points in Japanese lung transplant patients with concomitant tacrolimus. METHODS: Forty-five lung transplantation recipients were enrolled in a PK study of MPA, mycophenolic acid glucuronide (MPAG), and AcMPAG. The plasma MPA, MPAG, and AcMPAG concentrations were determined just before and at 0.5, 1, 2, 4, 8, and 12 hours after dosing. The AUC0-12 of MPA and AcMPAG was calculated using a linear trapezoidal rule from the plasma concentration of each blood sampling time. LSS was used to develop models for estimated AUC in the model group (n = 23) and was evaluated in the validation group (n = 22). RESULTS: The best three time-point equation was 4.04 + 1.64·C1 + 3.08·C4 + 5.17·C8 for MPA, and -0.13 + 3.01·C1 + 3.51·C4 + 5.74·C8 for AcMPAG. The prediction errors (PE) and the absolute prediction errors (APE) were within the clinically acceptable ± 5% and 15% range, respectively (MPA: PE = 2.00%, APE = 11.66%, AcMPAG: PE = 0.98%, APE = 14.69%). The percentage of estimated AUC0-12 within ± 15% of the observed AUC0-12 was 77.27% for MPA and 81.82% for AcMPAG. CONCLUSION: LSS using three time-point (C1, C4, and C8) provides the most reliable and accurate simultaneous estimation of the AUC0-12 of MPA and AcMPAG in Japanese lung transplant patients.