In vivo lung perfusion for prompt recovery from primary graft dysfunction after lung transplantation.

BACKGROUND: No proven treatment after the development of primary graft dysfunction (PGD) is currently available. Here, we established a novel strategy of in vivo lung perfusion (IVLP) for the treatment of PGD. IVLP involves the application of an in vivo isolated perfusion circuit to an implanted lung. This study aimed to explore the effectiveness of IVLP vs conventional post-lung transplant (LTx) extracorporeal membrane oxygenation (ECMO) treatment using an experimental swine LTx PGD model. METHODS: After 1.5-hour warm ischemia of the donor lungs, a left LTx was performed. Following the confirmation of PGD development, pigs were divided into 3 groups (n = 5 each): control (no intervention), ECMO, and IVLP. After 2 hours of treatment, a 4-hour functional assessment was conducted, and samples were obtained. RESULTS: Significantly better oxygenation was achieved in the IVLP group (p ≤ 0.001). Recovery was confirmed immediately and maintained during the following 4-hour observation. The IVLP group also demonstrated better lung compliance than the control group (p = 0.045). A histologic evaluation showed that the lung injury score and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed significantly fewer injuries and a better result in the wet-to-dry weight ratio in the IVLP group. CONCLUSIONS: A 2-hour IVLP is technically feasible and allows for prompt recovery from PGD after LTx. The posttransplant short-duration IVLP strategy can complement or overcome the limitations of the current practice for donor assessment and PGD management.

Large esophageal gastrointestinal stromal tumors resected thoracoscopically after oral imatinib therapy: a report of two cases.

Esophageal gastrointestinal stromal tumors (GISTs) are very rare, accounting for 2-5% of all GISTs. As with other GISTs, the principle of surgical treatment is complete resection with negative margins. In addition to biological grades of GISTs itselves, local recurrence due to capsular damage is a known risk. We describe two cases of massive esophageal GISTs that were successfully resected thoracoscopically after 2 months administration of 400 mg imatinib, with some discussion of the literature. Case 1, the patient was a 51-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtMtAeG, 110 × 95 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 11 months postoperatively. Case 2, the patient was a 70-years-old man. After treated with 400 mg of imatinib as preoperative chemotherapy for 2 months, we performed surgery that included right thoracoscopic subtotal esophagectomy, gastric tube reconstruction, and jejunostomy. The resection specimen and histopathology were esophageal GIST-LtAeG, 90 × 52 mm. The postoperative course was uneventful, and was discharged on postoperative day 14. The patient has been recurrence free for 9 months postoperatively.

[Paclitaxel plus Bevacizumab Combination Therapy for Esophageal Metastasis of Breast Cancer-A Case Report].

An 80-year-old woman with a history of left breast cancer complained of dysphagia. At the age of 67 years, she had undergone a left modified radical mastectomy, chemotherapy, and endocrine therapy for left breast cancer. Six years after adjuvant therapy completion, she developed dysphagia. Chest CT showed only midesophageal stenosis. Endoscopic examination revealed whole circumferential stenosis without mucosal abnormality located 25 cm from the incisors, and a biopsy showed histologically normal mucosa. Endoscopic balloon dilatation was performed 5 times in 1 year and 3 months. Subsequently, a biopsy specimen revealed adenocarcinoma, which suggested metastasis from the previous breast cancer. One month after the initiation of tamoxifen administration, dyspnea due to pleural effusion was encountered. We treated this via pleural adhesion therapy and changed the treatment to paclitaxel plus bevacizumab combination therapy. She continued paclitaxel plus bevacizumab therapy for 1 year and 4 months without any signs of recurrence.

Primary esophageal cancer treated by esophagectomy with distal pancreatectomy: a report of three cases.

Esophagectomy and pancreatectomy are recognized as highly invasive procedures with relatively high complication rates; therefore, careful indication decisions are required. The depth of tumors invading adjacent organs, such as the aorta, vertebral body, and trachea, is defined as T4, and are estimated to have a low survival rate even after treatment. Conversely, pancreatic invasion of esophageal cancer is uncommon and not clearly defined as T4. Thus, it is often difficult to decide on a treatment strategy for locally advanced esophageal cancer. In this study, we describe three cases of esophagectomy with combined resection of the pancreas and spleen for esophageal cancer or esophagogastric junction cancer with invasion of the pancreatic body or tail. To the best of our knowledge, this is the first report of esophagectomy and combined resection of the pancreas and spleen in multiple patients from a single institution.

Efficacy of thoracotomy and thoracoscopic-assisted esophageal surgery in conversion and salvage surgeries: a retrospective study.

BACKGROUND: The esophagus has no serosa; therefore, esophageal cancer may quickly invade its adjacent organs. In recent years, reports of conversion surgery (CS) and salvage surgery (SS) have described resection of esophageal cancer previously considered unresectable, with the addition of intensive preoperative chemotherapy or chemoradiotherapy. Currently, there is no established method for determining whether tumor excision is possible. Additionally, differences in surgical approaches between facilities may influence outcome after resection. However, the option for resection is considered a significant factor in determining a patient's prognosis. METHODS: Patients who were diagnosed with advanced-stage (T3 or higher) squamous cell carcinoma of the esophagus and subsequently underwent resection with CS or SS were included in the study. Resection was performed through a small thoracotomy using a thoracoscope. Clinicopathologic factors, such as complete resection rate (R0) and prognosis, were investigated. RESULTS: A total of 49 surgeries were conducted: 39 CS and 10 SS cases. The male-to-female ratio was 37:12. R0:R1:R2 equals 42:3:4, and the R0 resection rate was 85.7%. The 5-year survival rates for CS and SS cases were 69.2% and 32.1%, respectively. The 5-year survival rates for R0, R1, and R2 resections were 63.4%, 0.0%, and 25.0%, and those for R0 and R1 + 2 resections were 63.4% and 14.3%, respectively, indicating that the prognosis for R0 resection cases was significantly better (P = 0.001 and P = 0.001, respectively). Regarding chemotherapy for CS, 29 patients received 5-FU and cisplatin therapy, whereas 10 patients received 5-FU, cisplatin, and docetaxel (DCF) therapy. After 2015, the ratio of DCF was significantly high, and the R0 resection rate was 100% in patients who received DCF therapy. CONCLUSIONS: In this study, a satisfactory R0 rate was achieved using the magnifying effect of the thoracoscope while ensuring safety during thoracotomy. TRIAL REGISTRATION: This was a single-center cohort study wherein clinical data were retrospectively registered. This study was approved by the Chiba Cancer Center review board (H29-262). All procedures adhered to the ethical standards of the responsible committee on human experimentation and the Helsinki Declaration of 1964 and its later amendments.

A right pulmonary vein abnormality treated with 3D CT assistance in thoracoscopic surgery for esophageal cancer: a case report.

BACKGROUND: Anomalous bifurcation of the right superior pulmonary vein is an important anomaly that should be recognized not only in respiratory and cardiac surgeries, but also in esophageal surgery for the safe performance of surgery. We report a case in which thoracoscopic esophagectomy was safely performed using preoperative three-dimensional computed tomography (3D CT) imaging. CASE PRESENTATION: An 81-year-old male patient received an upper gastrointestinal endoscopy, which revealed a 20-cm incisor at the entrance, 43-cm EGJ, and 30-mm large type 1 + IIc lesion between the 23-cm and 26-cm incisors; biopsy showed squamous cell carcinoma (SCC). Contrast-enhanced CT showed wall thickening in the anterior wall of the upper thoracic esophagus, without evidence of multi-organ invasion or lymph node metastasis. In addition, a break in the right pulmonary vein passing dorsal to the right main bronchus and flowing directly into the left atrium was observed, and 3D CT was performed preoperatively to confirm the 3D positioning. Positron emission tomography (PET)-CT showed a high degree of accumulation (SUVmax 19.95) in the upper thoracic esophagus. The patient was diagnosed with upper thoracic esophageal cancer, cT2N0M0 cStage II, and underwent thoracoscopic subtotal esophagectomy (three-region dissection) and gastric tube reconstruction. The dorsal inflow of the pulmonary vein in the right main bronchus, which was recognized on preoperative CT, was confirmed and preserved. The pathological diagnosis was basaloid squamous cell carcinoma, pT1b(SM1)N0(0/58)M0 pStage I. The postoperative course was uneventful, and the patient was discharged on postoperative day 20. CONCLUSIONS: The anomalous bifurcation of the pulmonary vein in the right upper lobe area required attention because of its potential to cause massive bleeding and difficulty in securing the operative field if misidentified and damaged during surgery. Although it is not frequently encountered, it is the bifurcation anomaly that esophageal surgeons must bear in mind due to its severe consequences. Preoperative image-reading and intraoperative manipulation of this vessel are imperative for surgical safety.

Circulating anti-human leukocyte antigen IgM antibodies as a potential early predictor of allograft rejection and a negative clinical outcome after lung transplantation.

PURPOSE: Anti-human leukocyte antigen (HLA) immunoglobulin (Ig) M production stimulated by an alloantigen is sensitive, making IgM a novel potential marker of allorejection after organ transplantation. This study examined the relationship between the serum levels of anti-HLA IgM early after clinical lung transplantation (LTx) and the post-transplant outcomes. METHODS: Thirty-one consecutive patients who underwent deceased LTx were included. Immunoreactivity against HLA was retrospectively analyzed by measuring the anti-HLA IgM levels in the serum sampled for the first 14 days after LTx. The flow panel reactive antibody technique was used. The ratio of the anti-class I IgM level at each day to baseline was obtained, and the peak IgM level was determined for each case. The correlation between the peak IgM level and subsequent development of acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival outcomes were examined. RESULTS: The peak IgM level was a significant risk factor for AR within 90 days in univariate and multivariate analyses. In the long term, the patients with positive IgM (peak level > 1.8) tended to have a poorer CLAD-free and overall survival than those with negative IgM. CONCLUSION: Elevation of anti-HLA IgM levels early after LTx may be correlated with a higher incidence of rejection and negative clinical outcomes.

Tumor PD-L1 and VEGF Expression, and CD8 T Cell Infiltration Predict Clinical Response to Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer.

BACKGROUND/AIM: We evaluated the efficacy of "the tumor immune microenvironment (TIME) classification" for predicting clinical response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). In addition, we aimed to evaluate the "modified TIME classification", which adds the vascular endothelial growth factor (VEGF) status to TIME. MATERIALS AND METHODS: Programmed cell death receptor ligand-1 (PD-L1), CD8 T cell tumor-infiltrating lymphocytes (CD8+TILs) count and VEGF expression analyses were performed using immuno - histochemistry in 44 patients who had undergone ICI monotherapy. RESULTS: Regarding TIME classification, type-I (PD-L1 high and CD8+TILs high) had a significantly higher response than the other types. Using the modified TIME classification, type-IA (PD-L1 high, CD8+TILs high, and VEGF low) had a significantly higher response than the other types. CONCLUSION: The modified TIME classification, which adds tumor VEGF expression to "the TIME classification", could be useful in predicting clinical response to ICI monotherapy.

CA19-9-producing esophageal adenocarcinoma originating from the esophageal cardia of the mid-thoracic esophagus: a case report.

BACKGROUND: Although there are many studies on primary esophageal adenocarcinoma arising from Barrett's esophagus or ectopic gastric mucosa, reports on adenocarcinoma arising from esophageal cardiac glands are extremely rare. Herein, we report a case of mid-thoracic cancer antigen 19-9 (CA 19-9)-producing primary esophageal adenocarcinoma, which presumably originated from the cardiac glands. CASE PRESENTATION: A 74-year-old man was referred to our department with advanced esophageal cancer, which initially presented with dyspepsia. Serum levels of cancer antigen 19-9 (CA 19-9) were elevated (724.89 U/ml). Upper gastrointestinal endoscopy revealed a type 2 tumor on the posterior wall of the mid-thoracic esophagus approximately 29-32 cm from the incisor. Mucosal biopsy was consistent with a diagnosis of adenocarcinoma. Contrast-enhanced computed tomography showed a circumferential wall thickening in the mid-thoracic esophagus without enlarged lymph nodes or distant metastasis. Positron emission tomography-computed tomography showed accumulation in the primary tumor, but no evidence of lymph node or distant metastasis. According to these findings, the adenocarcinoma was staged as cT3N0M0, thereby, requiring subtotal esophagectomy with lymph node dissection. Postoperative course was uneventful. Histopathologic analysis revealed a 50 × 40 mm moderately differentiated adenocarcinoma with invasion to the thoracic duct and lymph node metastasis at #108(1/4), #109R(1/3), and #109L(1/3). After surgery, the stage was revised to moderately differentiated pT4apN2pM0 (pStage III). Immunostaining revealed expression of CA19-9 and suggested esophageal cardiac gland origin of the tumor. Three months after the surgery, the patient showed no recurrence and is undergoing outpatient observation. CONCLUSIONS: We experienced a case of mid-thoracic CA19-9-producing primary esophageal adenocarcinoma, which was presumed to have originated in the esophageal cardiac glands. Due to the scarcity of studies regarding this condition, specific management needs to be further clarified.

Effectiveness of scheduled intravenous acetaminophen in the postoperative pain management of video-assisted thoracic surgery.

PURPOSE: The scheduled administration of intravenous acetaminophen (scheduled-IV-AcA) is one of the more effective multimodal analgesic approaches for postoperative pain in abdominal/orthopedic surgeries. However, there is little evidence concerning scheduled-IV-AcA after general thoracic surgery, especially when limited to video-assisted thoracoscopic surgery (VATS). We investigated the efficacy of scheduled-IV-AcA administration in patients after undergoing VATS. METHODS: Ninety-nine patients who underwent VATS lobectomy or segmentectomy via an 8-cm access window and 1 camera port were retrospectively reviewed by categorizing them into groups either with scheduled-IV-AcA (Group AcA: n = 29) or without it (Group non-AcA: n = 70). Group AcA received 1 g of IV-AcA every 6 h from the end of the operation until the end of POD2. Postoperative pain was measured using a numeric rating scale (NRS) three times per day until discharge. RESULTS: NRS scores were significantly lower in Group AcA with motion (on POD1 to the first point of POD2) than in Group non-AcA. Group non-AcA was also more likely to use additional analgesics than Group AcA (39% vs. 17%, p = 0.058). CONCLUSIONS: Scheduled-IV-AcA administration is a safe and effective multimodal analgesic approach in patients undergoing VATS pulmonary resection via an 8-cm access window.

The neutrophil-to-lymphocyte ratio as a novel independent prognostic factor for multiple metastatic lung tumors from various sarcomas.

PURPOSE: Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas. METHODS: The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan-Meier method and prognostic factors were evaluated by multivariate analysis. RESULTS: Multivariate analysis revealed significantly better survival of the group with an NLR < 2.26 immediately before the most recent pulmonary metastasectomy, in addition to such factors as the largest resected lesion being < 22 mm, a disease-free interval of > 2 years, and 3 or more pulmonary metastasectomies. CONCLUSION: The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy.

Favorable survival even with high disease-specific complication rates in lymphangioleiomyomatosis after lung transplantation-long-term follow-up of a Japanese center.

BACKGROUND: Lung transplantation (LT) is a reliable therapeutic option for end-stage pulmonary lymphangioleiomyomatosis (LAM). Long-term outcome of LAM recipients after LT remains unknown. The aim of this study was to describe the outcomes of LT for LAM with a long-term follow-up, comparing those for other diseases in the same period. METHODS: We retrospectively reviewed consecutive 145 LT recipients between 1998 and 2015 at Okayama University Hospital with minimum 3-year follow-up. RESULTS: Twelve LAM recipients including nine sporadic-LAM and three tuberous sclerosis complex -LAM were identified. Nine of 12 underwent bilateral LT including four living-donor lobar LT. There was no significant difference in overall survival between the two groups. (P = 0.15). Chronic lung allograft dysfunction free survival rate in LAM compared with other diseases tended to be better (P = 0.058). However, the rate of requiring hemodialysis was significantly higher in LAM recipients than in the recipients of other diseases (P = 0.047). Notably, 8 of 12 (67%) LAM patients encountered LAM-related complication including chylothorax and pneumothorax, seven (58%) had proliferative diseases consisting of renal angiomyolipoma and recurrent LAM. Nine patients required mTOR inhibitors for LAM-related problems, contributing to improved control of LAM-related problems. While all nine recipients of bilateral LT have still survived, two patients died of diseases in their native lungs and one required re-LT among three recipients of single LT. CONCLUSION: Although the rates of LAM-related complications were unexpectedly high in the long term, LT is a feasible therapeutic option for patients with advanced pulmonary LAM.

Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine model.

OBJECTIVE: In lung transplantation, unexpected pulmonary emboli, including thrombi and fat, have been observed with high probability and are associated with potential primary graft dysfunction. We evaluated a new perfusion method using warm retrograde flushing that removes more fat than conventional cold retrograde flushing. METHODS: We developed a novel porcine donor model for pulmonary fat embolism by administering autologous fat in the left pulmonary artery. The left pulmonary artery and the left superior and inferior pulmonary veins were cannulated for flushing and collecting these solutions. After flushing, the left lung was reperfused under observation for 3 h. Two groups underwent warm and cold additional retrograde flush (WS; warm solution group, CS; cold solution group). RESULTS: The fat removal rate in the antegrade flush was equal in both groups (3.0 ± 0.6% vs 3.0 ± 0.4%, p = 0.46); however, the rate was significantly greater in the WS group in retrograde flush (25.2 ± 3.2% vs 8.0 ± 1.4%, p = 0.01). Histology with Oil Red O staining and its software analysis showed more residual fat in the CS group (0.12 ± 0.01% vs 0.38 ± 0.07%, p = 0.01). There was no significant difference in the pulmonary function and hemodynamics during the 3-h period after reperfusion. CONCLUSION: Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine donor model.

Airway bacteria of the recipient but not the donor are relevant to post-lung transplant pneumonia.

BACKGROUND: Optimal management of early airway infection is essential for the survival of lung transplant (LTx) recipients during the first 12 months after transplantation. This study aimed to explore the main cause of post-lung transplant pneumonia (PLTP) within 30 days after LTx. METHODS: Forty LTx patients were retrospectively analyzed. Sputum sampling from donors' and recipients' airways was performed pretransplant and posttransplant daily for the first 30 days after LTx. Organisms in the recipient's and donor's original airways were compared to pathogens responsible for PLTP. Patients with and without PLTP were also compared to identify relevant risk factors. RESULTS: Seventeen (42.5%) patients developed pneumonia (PLTP group) and 23 had no episode of pneumonia (Non-PLTP group) during the first 30 days. In the PLTP group, median time from LTx to PLTP onset was 6 days. A significantly higher incidence of PLTP was caused by recipient's rather than donor's original airway bacteria (62% vs 13%, p < 0.01). Smoking history of the donor and pretransplant airway bacterial colonization of the recipient were independent risk factors of PLTP which was associated with prolonged posttransplant mechanical ventilation with longer intensive care unit stay and worse survival outcomes. CONCLUSIONS: The recipient's original airway microflora rather than the donor's, was highly associated with PLTP. A combination of donor smoking history and recipient airway infection should be avoided, while evidence of donor lung infection is not a contraindication for LTx.

Impact of chronic lung allograft dysfunction, especially restrictive allograft syndrome, on the survival after living-donor lobar lung transplantation compared with cadaveric lung transplantation in adults: a single-center experience.

PURPOSE: The differences in chronic lung allograft dysfunction (CLAD) between living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) remain unclear. We conducted this study to compare the impact of CLAD on the outcomes after LDLLT vs. CLT. METHODS: We conducted a retrospective review of the data of 97 recipients of bilateral lung transplantation, including 51 recipients of LDLLT and 46 recipients of CLT. RESULTS: The CLAD-free survival and overall survival after LDLLT were similar to those after CLT. CLAD and restrictive allograft syndrome (RAS), but not bronchiolitis obliterans syndrome (BOS), developed significantly later after LDLLT than after CLT (p = 0.015 and p = 0.035). Consequently, patients with CLAD and RAS, but not those with BOS, after LDLLT had a significantly better overall survival than those after CLT (p = 0.037 and p = 0.0006). Furthermore, after the diagnosis of CLAD, the survival of patients with RAS after LDLLT tended to be better than that after CLT (p = 0.083). CONCLUSION: CLAD, especially RAS, appears to develop later after LDLLT than after CLT and seems to have a lower impact on the overall survival after LDLLT than that after CLT.

Lung transplant candidates with idiopathic pulmonary fibrosis and long-term pirfenidone therapy: Treatment feasibility influences waitlist survival.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronically progressive lung disease with exceptionally poor prognosis. While lung transplantation (LTx) is considered the last-resort therapeutic option, dismal waitlist mortality still hampers the salvage of patients with IPF. Pirfenidone, originally designed for IPF treatment, has increasingly been utilized. This study aimed to evaluate whether Pirfenidone could influence outcomes of patients with IPF on the Japanese LTx waitlist. METHODS: This retrospective single-center cohort study included 25 consecutive patients with IPF who were registered as LTx candidates at our institution between July 1999 and August 2016. Patients with a history of pretransplant Pirfenidone therapy (Pirfenidone group) were compared with those with no history (non-Pirfenidone group). RESULTS: In total, 6 (24%) patients received Pirfenidone as pretransplant therapy for 45.2 (range, 18.6-66.8) months. During the treatment period, the Pirfenidone group achieved a significant reduction in the decline rate of the forced vital capacity (-6.2% vs. -0.3%, p = 0.04) and a lower lung allocation score (31 vs. 41, p = 0.013) compared with the non-Pirfenidone group. The Pirfenidone group exhibited 100% waitlist survival three years after registration that was comparable to other indications, and 66% of the patients were still alive at the time of organ availability. No patient in the Pirfenidone group developed Pirfenidone-related surgical complications postoperatively. CONCLUSIONS: Patients with IPF successfully managed with long-term Pirfenidone therapy achieved favorable outcomes after LTx registration, comparable to other patients with LTx indications. The tolerability to antifibrotic therapy can be a predictor of waitlist survival.

Lung transplantation via cardiopulmonary bypass: excellent survival outcomes from extended criteria donors.

OBJECTIVES: The role of intraoperative cardiopulmonary bypass (CPB) in lung transplant (LTx) surgery is controversial. CPB enables slow pulmonary reperfusion and initial ventilation with low oxygen concentrations, both theoretically protective of transplanted lungs. In this study, we explored clinical outcomes following extended criteria donor LTx surgery implementing a thoroughly protective allograft reperfusion strategy using CPB. METHODS: Thirty-nine consecutive adult patients who underwent bilateral LTx with elective CPB and protective allograft reperfusion were reviewed. Bilaterally implanted lungs were reperfused simultaneously, via slow CPB flow reduction and initial ventilation with 21% oxygen and nitric oxide, followed by a brief modified ultrafiltration. During weaning from CPB, mean pulmonary arterial pressure was strictly maintained at 10-15 mmHg by controlling CPB and pulmonary flow. The clinical outcomes in 23 patients who received lungs from extended criteria donors (ECD group) were elucidated and compared to 16 patients undergoing LTx from standard criteria donors (SCD group). RESULTS: No life-threatening deterioration was observed to graft functionality during the first 72 h after LTx in the ECD group; however, only one patient required post-transplant extracorporeal membrane oxygenation. In three of 23 ECD LTx patients (12%), surgical revision for bleeding was required. Survival outcomes for the ECD group were favorable, with 100% survival at 6-months, 87.0% at 1-year, and 80.7% at 5-years. Outcomes in the ECD group were comparable to those in the SCD group. CONCLUSIONS: Despite a certain extent of risk associated with full-dose heparinization, use of CPB does not undermine survival outcomes after ECD LTx surgery if protective allograft reperfusion is securely performed.

SOCS3 overexpression in T cells ameliorates chronic airway obstruction in a murine heterotopic tracheal transplantation model.

PURPOSE: Suppressor of cytokine signaling-3 (SOCS3) is a negative feedback inhibitor of cytokine signaling with T-cell-mediated immunosuppressive effects on obliterative bronchiolitis (OB). In this study, we aimed to investigate the impact of T-cell-specific overexpression of SOCS3 using a murine heterotopic tracheal transplantation (HTT) model. METHODS: Tracheal allografts from BALB/c mice were subcutaneously transplanted into wild-type C57BL/6J (B6; WT) mice and SOCS3 transgenic B6 (SOCS3TG) mice. Tracheal allografts were analyzed by immunohistochemistry and quantitative polymerase chain reaction assays at days 7 and 21. RESULTS: At day 21, allografts in SOCS3TG mice showed significant amelioration of airway obstruction and epithelial loss compared with allografts in WT mice. The intragraft expression of IFN-γ and CXCL10 was suppressed, while that of IL-4 was enhanced in SOCS3TG mice at day 7. The T-bet levels were lower in SOCS3TG allografts than in WT allografts at day 7. CONCLUSION: We revealed that the overexpression of SOCS3 in T cells effectively ameliorates OB development in a murine HTT model by inhibiting the Th1 phenotype in the early phase. Our results suggest that the regulation of the T-cell response, through the modulation of SOCS expression, has potential as a new therapeutic strategy for chronic lung allograft dysfunction.

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

PURPOSE: Glucocorticoids 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. METHODS: A 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. RESULTS: The total lung capacity (TLC) in the TT group was significantly lower than that in the CC group at 3 years after LT (P = 0.029). In the recipients of cadaveric LT, the TLC and forced expiratory volume in 1 s in the TT group were significantly lower than those in the CC groups, resulting in a significant worse CLAD-free survival at 3 years after LT (P = 0.016). CONCLUSION: The GLCCI1 variant was associated with a significant decrease of the TLC at 3 years after LT and the development of CLAD at 3 years, especially in patients undergoing cadaveric LT.

Feasibility of lung transplantation from donors mechanically ventilated for prolonged periods.

PURPOSE: When 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. METHODS: The subjects of this retrospective comparative investigation were 31 recipients of LTx from donors who had been mechanically ventilated for < 5 days (short-term group) and 50 recipients of LTx from donors who had been mechanically ventilated for ≥ 5 days (long-term group). RESULTS: The median duration of donor mechanical ventilation was 3 days in the short-term group and 8.5 days 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%). CONCLUSION: The 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.