A newly developed surgeon-controlled suction device in robotic-assisted thoracoscopic surgery.

INTRODUCTION: Assistant surgeons usually clean the surgical field with a suction cannula in robotic-assisted surgery. This manipulation requires skill and experience to avoid interfering with the operation of the console surgeon. Recently, we created a new suction device that a console surgeon can manipulate with the robotic arms. MATERIALS AND SURGICAL TECHNIQUE: A small metal suction tip with as a lumen and small side pores for suction and can be connected to a silicone tube connected to wall suction. The tip of the silicone tube can be grasped with robotic forceps and used for organ retraction as well as suction. The suction device has been used in eight lung lobectomy cases and four lung segmentectomy cases to date. There were no major difficulties related to the new suction device except for metal tip disconnection and blood clots clogging. DISCUSSION: Our newly developed surgeon-controlled suction device is inexpensive, easy to handle, and useful for suction, blunt dissection, and organ retraction in robotic-assisted thoracoscopic surgery, especially when performing lymph node dissection.

Postoperative tegafur-uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis.

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

Association between oxygen consumption and stepping exercise standardized with a triaxial accelerometer.

OBJECTIVE: According to the current American College of Chest Physicians (ACCP) guideline, a cardiopulmonary exercise test (CPET) is indicated in patients with lung cancer being considered for lung surgery. The measurement of maximum oxygen consumption ([Formula: see text] max) is not sufficiently prevalent because it requires special technical equipment. Considering that stepping is a simple and common exercise, we aimed to establish a simple and reproducible test with standardization of exercise intensity using a triaxial accelerometer. METHODS: Twenty healthy volunteers (10 male, 10 female) were included in the study. The subjects were obliged to step on the same spot at the rate of 80 and 110 counts for 1 min each and then step as quickly as possible for the last minute. Oxygen consumption ([Formula: see text]) (mL/kg/min) for every breath was continuously measured during the exercise. A triaxial accelerometer was attached to the hip of test subjects whereby metabolic equivalents (METs) at each test level were measured. RESULTS: The mean age of the study subjects was 42.9 ± 11.4 (mean ± SD). The mean value of [Formula: see text] at each level increased linearly along with the stepping level in each individual but varied among subjects. Using METs instead of step counts minimized the difference in regression lines among subjects. A receiver operating characteristic analysis revealed the possibility of [Formula: see text] prediction for the critical values of 10 and 20 mL/kg/min using METs. CONCLUSION: A simple and reproducible stepping test was suggested as applicable to standardizing the intensity of exercise using a triaxial accelerometer.

Epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma: a multi-institutional retrospective study.

OBJECTIVES: The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma. METHODS: Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I-III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan-Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS. RESULTS: The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15-2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96-0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00-1.07), smoking history (HR: 2.31, 95% CI: 1.35-3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32-4.00) were significantly associated with shorter OS. CONCLUSIONS: First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS.

Ex vivo delivery of regulatory T-cells for control of alloimmune priming in the donor lung.

BACKGROUND: Survival after lung transplantation (LTx) is hampered by uncontrolled inflammation and alloimmunity. Regulatory T-cells (Tregs) are being studied as a cellular therapy in solid organ transplantation. Whether these systemically administered Tregs can function at the appropriate location and time is an important concern. We hypothesised that in vitro-expanded recipient-derived Tregs can be delivered to donor lungs prior to LTx via ex vivo lung perfusion (EVLP), maintaining their immunomodulatory ability. METHODS: In a rat model, Wistar Kyoto (WKy) CD4+CD25high Tregs were expanded in vitro prior to EVLP. Expanded Tregs were administered to Fisher 344 (F344) donor lungs during EVLP; left lungs were transplanted into WKy recipients. Treg localisation and function post-transplant were assessed. In a proof-of-concept experiment, cryopreserved expanded human CD4+CD25+CD127low Tregs were thawed and injected into discarded human lungs during EVLP. RESULTS: Rat Tregs entered the lung parenchyma and retained suppressive function. Expanded Tregs had no adverse effect on donor lung physiology during EVLP; lung water as measured by wet-to-dry weight ratio was reduced by Treg therapy. The administered cells remained in the graft at 3 days post-transplant where they reduced activation of intra-graft effector CD4+ T-cells; these effects were diminished by day 7. Human Tregs entered the lung parenchyma during EVLP where they expressed key immunoregulatory molecules (CTLA4+, 4-1BB+, CD39+ and CD15s+). CONCLUSIONS: Pre-transplant Treg administration can inhibit alloimmunity within the lung allograft at early time points post-transplant. Our organ-directed approach has potential for clinical translation.

Multicentre, prospective, observational study investigating the most appropriate surgical option that can prevent the recurrence of primary spontaneous pneumothorax after surgery: the PATCH study, protocol.

INTRODUCTION: Thoracoscopic surgery is performed for refractory or recurrent primary spontaneous pneumothorax (PSP). To reduce postoperative recurrence, additional treatment is occasionally adopted during surgery after bulla resection. However, the most effective method has not been fully elucidated. Furthermore, the preference for additional treatment varies among countries, and its efficacy in preventing recurrence must be evaluated based on settings tailored for the conditions of a specific country. The number of registries collecting detailed data about PSP surgery is limited. Therefore, to address this issue, a prospective multicentre observational study was performed. METHODS AND ANALYSIS: This multicentre, prospective, observational study will enrol 450 participants aged between 16 and 40 years who initially underwent PSP surgery. Data about demographic characteristics, disease and family history, surgical details, and CT scan findings will be collected. Follow-up must be conducted until 3 years after surgery or in the event of recurrence, whichever came first. Patients without recurrence will undergo annual follow-up until 3 years after surgery. The primary outcome is the rate of recurrence within 2 years after surgery. A multivariate analysis will be performed to compare the efficacy of different surgical options. Then, adverse outcomes correlated with various treatments and the feasibility of treatment methods will be compared. ETHICS AND DISSEMINATION: This study was approved by the local ethics committee of all participating centres. The findings will be available in 2025, and they can be used as a basis for clinical decision-making regarding appropriate options for the initial PSP surgery. TRIAL REGISTRATION NUMBER: NCT04758143.

Thoracic composite hemangioendothelioma with neuroendocrine marker expression.

BACKGROUND: Composite hemangioendothelioma is an extraordinarily rare form of vascular neoplasm which develops predominantly in the skins and soft tissues of the adults. Neuroendocrine marker expression in composite hemangioendothelioma is considered as specifically relevant to the more aggressive behavior. CASE PRESENTATION: The patient was a 71-year-old man complaining continuous back pain. Computed tomography (CT) showed that 10 cm of contrast-enhanced soft tissue mass was occurring on the right posterior chest wall and developing adjacent to the spinal canal. Via the laminectomy, the tumor end was identified and separated from the dura mater. Then, via the posterolateral thoracotomy, the en bloc resection was achieved by separating the tumor from the diaphragm and vertebras. Histologic examination showed a complex combination of epithelioid and retiform hemangioendothelioma areas which were positive for anti-synaptophysin staining. At 12-month follow-up, there were no signs of tumor recurrence on CT, and the patient had no symptom. CONCLUSIONS: We achieved the complete resection of a huge thoracic neuroendocrine composite hemangioendothelioma developing adjacent to the spinal canal. The combination of the posterior lumbar laminectomy and the following posterior thoracotomy is a viable approach to radically resect a thoracic neuroendocrine composite hemangioendothelioma involving chest wall.

Lymph node dissection in thymic carcinomas and neuroendocrine carcinomas.

OBJECTIVES: Although lymph node (LN) metastases are not uncommon in thymic carcinomas, preoperative LN evaluation, intraoperative lymph node dissection (LND) and postoperative outcomes remain unknown. The aim of this study was to elucidate the characteristics of and outcomes in patients with thymic carcinomas and thymic neuroendocrine carcinomas undergoing LND. METHODS: A retrospective chart review was performed using our multi-institutional database to identify patients who underwent resection and LND for thymic carcinoma or thymic neuroendocrine carcinoma between 1991 and 2018. An enlarged mediastinal LN was defined as having a short-axis diameter >1 cm. We assessed survival outcomes using the Kaplan-Meier analysis. RESULTS: N1-level LND was performed in 41 patients (54.6%), N2-level LND in 14 patients (18.7%) and both-level LND in 16 patients (21.3%). Pathological LN metastasis was detected in 20 patients (26.7%) among the 75 patients undergoing LND. There was a significant difference in the number of LN stations (P = 0.015) and metastasis factor (P = 0.0042) between pathologically LN-positive and pathologically LN-negative patients. The sensitivity of enlarged LNs on preoperative computed tomography was 18.2%. There was a tendency towards worse overall survival of pathologically N2-positive patients, although the difference was not statistically significant (P = 0.15). CONCLUSIONS: Preoperative CT appears to play a limited role in detecting pathological LN metastases. Our findings suggest that the significance of N1- and N2-level LND should be evaluated in prospective studies to optimize the postoperative management of patients with thymic carcinomas and neuroendocrine carcinomas.

LPS-induced Airway-centered Inflammation Leading to BOS-like Airway Remodeling Distinct From RAS-like Fibrosis in Rat Lung Transplantation.

BACKGROUND: Localization of inflammatory stimuli may direct lung allografts to different phenotypes of chronic dysfunction, such as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). We hypothesized that airway stimulation with lipopolysaccharide (LPS) in rats leads to airway-centered inflammation similar to human BOS. METHODS: Rat left lung transplantation was conducted (donor: Brown Norway, recipient: Lewis). Allotransplant recipients received cyclosporine A (CsA) until postoperative day 56 with airway instillation of LPS (Allo-LPS, n = 8), phosphate buffered saline (Allo-PBS, n = 5) from days 35 to 46 (3 times a wk), or no further treatment (n = 4). Some allotransplant recipients received CsA until day 14 and were immunosuppression free after day 15 until day 56. Bronchial and pleural fibrosis were semiquantified; alveolar fibrosis was evaluated with a histological scale. RESULTS: The Allo-LPS group had significantly increased International Society for Heart and Lung Transplantation rejection grades (grade A, P = 0.005; grade B, P = 0.004), bronchial obstructive proportion (0.34 ± 0.04% [Allo-LPS] versus 0.11 ± 0.04% [Allo-PBS], P = 0.006), and airway resistance (3.05 ± 1.78 cm H2O·s/mL [Allo-LPS] versus 0.83 ± 0.58 cm H2O·s/mL [Allo-PBS], P = 0.007) compared with other groups. Allotransplant recipients that underwent a short course of CsA developed RAS-like fibrosis involving the airways, alveoli, and pleura. CONCLUSIONS: Airway instillation of LPS in allografts under immunosuppression resulted in BOS-like airway-centered inflammation and fibrosis distinct from RAS-like diffuse fibrosis, which was induced by a shortened course of immunosuppression. We propose novel animal models for BOS and RAS after lung transplantation.

Trametinib Attenuates Delayed Rejection and Preserves Thymic Function in Rat Lung Transplantation.

Delayed immunological rejection after human lung transplantation causes chronic lung allograft dysfunction, which is associated with high mortality. Delayed rejection may be attributable to indirect alloantigen presentation by host antigen-presenting cells; however, its pathophysiology is not fully understood. The mitogen-activated protein kinase pathway is activated in T cells upon stimulation, and we previously showed that the MEK inhibitor, trametinib, suppresses graft-versus-host disease after murine bone marrow transplantation. We investigated whether trametinib suppresses graft rejection after two types of rat lung transplantation and analyzed its immunological mode of action. Major histocompatibility complex-mismatched transplantation from brown Norway rats into Lewis rats and minor histocompatibility antigen-mismatched transplantation from Fischer 344 rats into Lewis rats were performed. Cyclosporine (CsA) and/or trametinib were administered alone or consecutively. Acute and delayed rejection, lymphocyte infiltration, and pulmonary function were evaluated. Administration of trametinib after CsA suppressed delayed rejection, reduced inflammatory cell infiltration and fibrosis within the graft, and preserved pulmonary functions at Day 28. Trametinib suppressed functional differentiation of T and B cells in the periphery but preserved thymic T cell differentiation. Donor B cells within the graft disappeared by Day 14, indicating that delayed graft rejection at Day 28 was mainly due to indirect presentation by host antigen-presenting cells. Finally, trametinib administration without CsA preconditioning suppressed rejection after minor histocompatibility antigen-mismatched transplantation. Trametinib attenuates delayed rejection upon major histocompatibility complex-mismatched transplantation by suppressing indirect presentation and is a promising candidate to treat chronic lung allograft dysfunction in humans.

Transition of the programmed death 1 pathway from the primary colorectal cancer to its corresponding pulmonary metastasis.

BACKGROUND AND OBJECTIVES: The inhibition of the programmed death 1 (PD-1)/its ligand 1 (PD-L1) pathway may be associated with clinical responses in colorectal cancer (CRC). We aimed to characterize the transition of PD-1/PD-L1 expression through pulmonary metastasis (PM) and its clinical relevance. METHODS: This study retrospectively reviewed 50 patients who had curative resection of primary CRC and its PM. We evaluated the presence of PD-1+ tumor-infiltrating lymphocytes (TILs) and PD-L1+ tumor cells in both the primary tumor and its PM by immunohistochemistry. RESULTS: PD-L1 was expressed 34.0% of primary lesions and in 38.0% of their PM. A discrepancy in PD-L1 expression between the primary site and its PM was found in 34.0% of our patients. The presence of PD-1+ TILs in the PM was significantly associated with that in its corresponding primary lesion (P = 0.003). The longer interval between the primary site and its PM was statistically significant in predicting higher expression of PD-L1 in the PM (P = 0.010). CONCLUSIONS: The discordance of PD-L1 expression between the primary tumor and its PM was found in one-third of our patients with CRC. Temporally distant PM from CRC could be associated with the positive expression of PD-L1 in the PM.

GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, hepatocyte nuclear factor 4α expression, and KRAS mutations.

AIMS: GATA6 is known to play a role in lung development. However, its role in the carcinogenesis of lung cancer is not well studied. The aim of this study was to analyse GATA6 expression in lung adenocarcinomas (LAs) by immunohistochemistry (IHC) in order to define its association with clinicopathological characteristics. METHODS AND RESULTS: IHC analysis of GATA6 was performed with tissue microarray slides containing 348 LAs. The association between GATA6 expression and clinicopathological parameters was evaluated. GATA6 expression in epithelial tumours other than lung cancer was also evaluated. GATA6 expression was found in 47 LAs (13.5%). This occurred more frequently in younger patients (P = 0.005), and was associated with the absence of lymph node metastasis (P =0.024), well-differentiated to moderately differentiated tumours (P < 0.001), the absence of lymphatic invasion (P = 0.020), and the absence of vascular invasion (P = 0.011). GATA6 expression was associated with mucin production (P < 0.001), the invasive mucinous adenocarcinoma subtype (P < 0.001), KRAS mutations (P = 0.026), expression of MUC2 (P < 0.001), CDX2 (P = 0.049), and MUC5AC (P < 0.001), and absence of expression of TTF-1 (P = 0.002). GATA6 expression was also associated with hepatocyte nuclear factor 4α (HNF4α) expression (P < 0.001). GATA6 expression tended to indicate better prognoses, whereas patients with HNF4α expression had significantly worse prognoses (P = 0.033). Of 270 tumours other than lung cancer, 110 expressed GATA6. CONCLUSIONS: These findings suggest that GATA6 might interact with HNF4α and contribute to the development of mucinous-type LAs.

Immersing lungs in hydrogen-rich saline attenuates lung ischaemia-reperfusion injury.

Objectives: Anti-oxidant effects of hydrogen have been reported in studies examining ischaemia-reperfusion injury (IRI). In this study, we evaluated the therapeutic efficacy of immersing lungs in hydrogen-rich saline on lung IRI. Methods: Lewis rats were divided into three groups: (i) sham, (ii) normal saline and (iii) hydrogen-rich saline. In the first experiment, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline for 1 h. Then, we measured the hydrogen concentration in the left lung using a sensor gas chromatograph ( N = 3 per group). In the second experiment, lung IRI was induced by occlusion of the left pulmonary hilum for 1 h, followed by reperfusion for 3 h. During the ischaemic period, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline. After reperfusion, we assessed lung function, histological changes and cytokine production ( N = 5-7 per group). Results: Immersing lungs in hydrogen-rich saline resulted in an elevated hydrogen concentration in the lung (6.9 ± 2.9 µmol/1 g lung). After IRI, pulmonary function (pulmonary compliance and oxygenation levels) was significantly higher in the hydrogen-rich saline group than in the normal saline group ( P < 0.05). Similarly, pro-inflammatory cytokine levels (interleukin-1ß and interleukin-6) in the left lung were significantly lower in the hydrogen-rich saline group than in the normal saline group ( P < 0.05). Conclusions: Immersing lungs in hydrogen-rich saline delivered hydrogen into the lung and consequently attenuated lung IRI. Hydrogen-rich solution appears to be a promising approach to managing lung IRI.

Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I With the Progression of Chronic Rejection of Lung Allografts.

BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically. RESULTS: By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63. CONCLUSIONS: DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.

Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1+ Tumor-Associated Neutrophils through CCL15-CCR1 Axis.

PURPOSE: We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer to recruit CCR1+ myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of colorectal cancer. EXPERIMENTAL DESIGN: In a mouse model, we examined whether SMAD4 could affect the metastatic activity of colorectal cancer cells to the lung through the CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15, and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We also characterized the CCR1+ myeloid cells using several cell-type-specific markers. RESULTS: In a mouse model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1+ cells, promoting their metastatic activities to the lung. Immunohistochemical analysis of lung metastases from colorectal cancer patients revealed that CCL15 expression was significantly correlated with loss of SMAD4, and that CCL15-positive metastases recruited approximately 1.9 times more numbers of CCR1+ cells than CCL15-negative metastases. Importantly, patients with CCL15-positive metastases showed a significantly shorter relapse-free survival (RFS) than those with CCL15-negative metastases, and multivariate analysis indicated that CCL15 expression was an independent predictor of shorter RFS. Immunofluorescent staining showed that most CCR1+ cells around lung metastases were tumor-associated neutrophil, although a minor fraction was granulocytic myeloid-derived suppressor cell. CONCLUSIONS: CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung metastasis. CCL15 can be a biomarker indicating poor prognosis of colorectal cancer patients with lung metastases. Clin Cancer Res; 23(3); 833-44. ©2016 AACR.

Protective Effect of Inhaled Rho-Kinase Inhibitor on Lung Ischemia-Reperfusion Injury.

BACKGROUND: Rho-kinase, an intracellular serine/threonine kinase, is a key regulator of cytoskeletal dynamics. Recent studies have demonstrated that Rho-kinase is involved in the ischemia-reperfusion injury (IRI) pathogenesis of many organs; however, its involvement with lung IRI remains unclear. This study assessed the association of Rho-kinase with lung IRI and evaluated the protective effect of inhaled Rho-kinase inhibitors in lung IRI. METHODS: The study included isolated rat lung perfusion models, divided into three groups: sham, Rho-kinase inhibitor, and warm ischemia (n = 6 each). The lungs were exposed to 60 minutes of warm ischemia by perfusion cessation. At the onset of ischemia, nebulized fasudil, a novel Rho-kinase inhibitor, and saline were inhaled in the Rho-kinase inhibitor and warm ischemia groups, respectively. Perfusion was restarted after the ischemic period, and physiologic data were collected for 90 minutes. Lungs in the sham group were continuously perfused without ischemia or drug administrations. Protein expression in tissue specimens related to the Rho-kinase pathway was evaluated by Western blotting. RESULTS: Warm ischemia and subsequent reperfusion enhanced Rho-kinase activity, and this was suppressed by fasudil inhalation. Fasudil inhalation significantly attenuated IRI pathophysiology, including pulmonary vascular contraction, dynamic compliance, lung edema, and oxygenation. Molecular analysis showed that Rho-kinase suppressed myosin phosphatase and endothelial nitric oxide synthase activities, suggesting these are downstream targets of Rho-kinase during lung IRI pathogenesis. CONCLUSIONS: The present study suggests that Rho-kinase activation is involved in lung IRI pathogenesis and that inhaled Rho-kinase inhibitors may attenuate this pathogenesis.

Bronchodilator Inhalation During Ex Vivo Lung Perfusion Improves Posttransplant Graft Function After Warm Ischemia.

BACKGROUND: We hypothesized that an injured lung graft from donation after cardiac death donors could be reconditioned before transplantation using an ex vivo lung perfusion (EVLP) system and ventilation with high-dose short-acting ß2-adrenergic receptor agonists. METHODS: Cardiac arrest was induced in a canine model by intravenous potassium chloride injection. Lungs were randomly assigned to two groups after 150 minutes of warm ischemia: inhalation of 1,400 µg of procaterol (BETA group, n = 5) or control group receiving solvent (CON group, n = 5) during EVLP. Left lungs were transplanted after 120 minutes of EVLP. Functional variables, tissue adenosine 5'-triphosphate levels, and tissue cyclic adenosine monophosphate levels were measured 240 minutes after transplantation. RESULTS: Physiologic pulmonary function was similar at the end of EVLP in both groups. However, significantly better graft oxygenation, dynamic pulmonary compliance, and reduced pulmonary vascular resistance were observed in the BETA group than in the CON group 240 minutes after transplantation. No severe adverse effects were observed after lung transplantation in the BETA group. Lung tissue adenosine 5'-triphosphate levels and cyclic adenosine monophosphate levels were significantly higher in the BETA group than in the CON group at the end of EVLP and at 240 minutes after transplantation. CONCLUSIONS: High-dose nebulized procaterol during EVLP ameliorated lung graft dysfunction at the early posttransplantation period without severe adverse effects. These data suggest that lung reconditioning with procaterol ventilation during EVLP improves lung graft function after transplantation.

Efficacy and safety of thoracoscopic pericardial window in patients with pericardial effusions: a single-center case series.

BACKGROUND: Pericardial effusion (PE) is a common finding in patients who had chronic cardiac failure, who had undergone cardiac surgery, or who had certain other benign and malignant diseases. PE ranges in severity from mild, asymptomatic effusions to cardiac tamponade. Although a thoracoscopic pericardial window (TPW) is a minimally invasive surgical option for patients with PE, there are few published data regarding the outcomes of TPW for PE. We investigated the contribution of the TPW to the treatment of PEs that are recurrent or difficult to drain percutaneously. METHODS: We conducted a retrospective chart review of the indications for TPW that included data on preoperative, intraoperative, and postoperative variables; morbidity; recurrence; and survival. Fourteen consecutive patients with PE that was recurrent or difficult to drain percutaneously and who underwent treatment with a TPW were enrolled in this study. Trocars for passage of the thoracoscope and surgical instruments were introduced through two or three incisions. Mini-thoracotomy was also performed in patients with hemopericardium and loculated fibrinous effusions. All patients were evaluated by face-to-face interviews, transthoracic echocardiography (TTE), and chest radiography 3-6 months after the TPW was obtained. RESULTS: The mean age of the patients was 70 years (range 28-83 years). The operative time was 72.1 ± 29.5 min. Six patients had undergone open heart surgery during the month prior to their presentation with PE. No intraoperative or postoperative complications occurred, although PE had recurred in one patient. Two patients died of malignant disease several months after the TPW. The cardiothoracic ratio (determined on chest radiographs) and the ejection fraction ratio (determined using TTE) had improved at the 3- and 6-month follow-up evaluations (p < 0.0001 and p = 0.012, respectively). Some patients could discontinue diuretics after the procedure, as assessed by the cardiologist based on symptom alleviation, chest radiography, and TTE findings. CONCLUSIONS: For patients with PEs that are recurrent or difficult to drain percutaneously, TPW is an effective, safe surgical approach in terms of cardiac function and radiological findings.

Vascular Endothelial-Cadherin Expression After Reperfusion Correlates With Lung Injury in Rat Lung Transplantation.

BACKGROUND: Vascular endothelial-cadherin (VEC), composing the adherens junction of endothelial cells, has been shown to regulate vascular permeability. The aim of this study was to investigate VEC expression during cold ischemia (CI) and reperfusion and whether a dibutyryl cyclic adenosine 3',5'-monophosphate (db-cAMP) and nitroglycerin (NTG) additive to preservation solution can maintain VEC. METHODS: Rat left lung transplantation after CI was performed, and reperfusion was done for 2 hours. The experimental groups were Control (n = 5), CI3 (n = 5), CI6 (n = 6), and CI6+AMP/NTG (n = 6) with minimum ischemic period, 3 hours and 6 hours of CI, respectively, and 6 hours of CI with db-cAMP and NTG additive to preservation solution, respectively. Lung mechanics, lung wet-to-dry weight ratio (W/D), and the histologic findings of the graft were evaluated. The expression of VEC was evaluated by Western blot analysis of the lung tissue lysates. RESULTS: The CI3 group showed a decrease in dynamic compliance with perivascular edema. Dynamic compliance, graft oxygenation, and W/D were substantially deteriorated, and intraalveolar edema with neutrophil infiltration was recognized in the CI6 group. They were improved in the CI6+AMP/NTG group. VEC expression was maintained during CI. After reperfusion, it reduced substantially in the CI6 group and was maintained in the CI6+AMP/NTG group. CONCLUSIONS: VEC expression was maintained during CI; however, it reduced early after reperfusion after 6 hours of CI, correlating with severe intraalveolar edema. db-cAMP/NTG additive to the preservation solution contributed to the maintenance of VEC expression after reperfusion.

Completely resected follicular dendritic cell sarcoma of the posterior mediastinum: report of a case.

Follicular dendritic cell sarcoma is a rare malignant neoplasm originating from follicular dendritic cells, and most of them develop in lymph nodes of the head and neck. One third of follicular dendritic cell sarcomas occur in the extranodal sites such as the tonsils, mesentery, and retroperitoneal organs, but those of mediastinal origin are rare. Here, we present the case of a 16-year-old female with a large follicular dendritic cell sarcoma of posterior mediastinal origin. The tumor was found by a chest X-ray mass examination at her high school, and she had no subjective symptoms or significant past medical history. The tumor was diagnosed as a follicular dendritic cell sarcoma by computed tomography-guided needle biopsy. Although the tumor compressed the mediastinal organs and showed moderate uptake in 18-fluorodeoxyglucose positron emission tomography imaging, it was completely resected through posterolateral incision. Histological examination revealed that spindle-shaped tumor cells formed fascicular or storiform pattern with cellular pleomorphism. By immunohistochemical examination, the tumor cells were found to be positive for CD21 and follicular dendritic cell antigen. Two years after surgery, the patient remains alive with no signs of tumor recurrence.