Formation of pulmonary vein stump thrombus after anatomical lung resection and anticoagulant therapy.

OBJECTIVE: It has recently been suggested that the formation of pulmonary vein stump thrombus (PVST) after anatomical lung resection is an underlying cause of arterial thromboembolism including cerebrovascular infarction. This study aimed to investigate the incidence and risk factors of PVST and to evaluate the efficacy and safety of anticoagulant therapy for PVST. METHODS: Patients who underwent anatomical lung resection for malignant lung tumors were eligible for inclusion in this study. Chest contrast-enhanced (CE) computed tomography (CT) was performed after surgery to detect PVST. If PVST was observed, patients received anticoagulant therapy. The size of the PVST was followed-up by repeated chest CE-CT. RESULTS: In total, 176 patients were enrolled in this study. Chest CE-CT was performed on postoperative day 1-13 (median, postoperative day 6). PVST was detected in 22 (12.5%) patients. The median size of PVST was 9.5 (4.1-33.4) mm. Thrombus was most commonly observed in patients who underwent left upper lobectomy (9/36, 25.0%). Hypertension, dyslipidemia, arteriosclerosis, and arrhythmia were not associated with PVST formation. Anticoagulant therapy was administered to all 22 patients with PVST until the PVST disappeared. The median duration between the detection and disappearance of PVST was 77 days (range: 6-146 days). During the period between the detection and disappearance of PVST, cerebrovascular infarction or arterial thromboembolic events were not observed. CONCLUSIONS: Postoperative PVST is commonly observed, especially in patients who undergo left upper lobectomy. Anticoagulant therapy for PVST was safely introduced and was efficient to improve PVST without subsequent arterial thromboembolic events.

Long-Term Outcome of Chest Wall and Diaphragm Repair with Biological Materials.

INTRODUCTION: Chest wall and/or diaphragm reconstruction aims to preserve, restore, or improve respiratory function; conserve anatomical cavities; and upkeep postural and upper extremity support. This can be achieved by utilizing a wide range of different grafts made of synthetic, biological, autologous, or bioartificial materials. We aim to review our experience with decellularized bovine pericardium as graft in the past decade. PATIENTS AND METHODS: We conducted a retrospective analysis of patients who underwent surgical chest wall and/or diaphragm repair with decellularized bovine pericardium between January 1, 2012 and January 13, 2022 at our institution. All records were screened for patient characteristics, intra-/postoperative complications, chest tube and analgesic therapy duration, length of hospital stay, presence or absence of redo procedures, as well as morbidity and 30-day mortality. We then looked for correlations between implanted graft size and postoperative complications and gathered further follow-up information at least 2 months after surgery. RESULTS: A total of 71 patients either underwent isolated chest wall (n = 51), diaphragm (n = 12), or pericardial (n = 4) resection and reconstruction or a combination thereof. No mortality was recorded within the first 30 days. Major morbidity occurred in 12 patients, comprising secondary respiratory failure requiring bronchoscopy and invasive ventilation in 8 patients and secondary infections and delayed wound healing requiring patch removal in 4 patients. There was no correlation between the extensiveness of the procedure and extubation timing (chi-squared test, p = 0.44) or onset of respiratory failure (p = 0.27). CONCLUSION: A previously demonstrated general viability of biological materials for various reconstructive procedures appears to be supported by our long-term results.

α1-Antitrypsin attenuates acute rejection of orthotopic murine lung allografts.

BACKGROUND: α1-Antitrypsin (AAT) is an acute phase glycoprotein, a multifunctional protein with proteinase inhibitory, anti-inflammatory and cytoprotective properties. Both preclinical and clinical experiences show that the therapy with plasma purified AAT is beneficial for a broad spectrum of inflammatory conditions. The potential effects of AAT therapy have recently been highlighted in lung transplantation (LuTx) as well. METHODS: We used a murine fully mismatched orthotopic single LuTx model (BALB/CJ as donors and C57BL/6 as recipients). Human AAT preparations (5 mg, n = 10) or vehicle (n = 5) were injected to the recipients subcutaneously prior to and intraperitoneally immediately after the LuTx. No immune suppressive drugs were administered. Three days after the transplantation, the mice were sacrificed, and biological samples were assessed. RESULTS: Histological analysis revealed significantly more severe acute rejection in the transplanted lungs of controls than in AAT treated mice (p < 0.05). The proportion of neutrophil granulocytes, B cells and the total T helper cell populations did not differ between two groups. There was no significant difference in serum CXCL1 (KC) levels. However, when compared to controls, human AAT was detectable in the serum of mice treated with AAT and these mice had a higher serum anti-elastase activity, and significantly lower proportion of Th1 and Th17 among all Th cells. Cleaved caspase-3-positive cells were scarce but significantly less abundant in allografts from recipients treated with AAT as compared to those treated with vehicle. CONCLUSION: Therapy with AAT suppresses the acute rejection after LuTx in a mouse model. The beneficial effects seem to involve anti-protease and immunomodulatory activities of AAT.

Surgical treatment of non-cystic fibrosis bronchiectasis in Central Europe.

BACKGROUND: Bronchiectasis is a mostly irreversible bronchial dilatation induced by the destruction of elastic and muscular fibers of the bronchial wall. Surgical treatment is usually reserved for focal disease, and whenever complications, like hemoptysis or secondary aspergilloma, arise. In this study, we report our experience and outcomes in surgical bronchiectasis management between 2016 and 2020. METHODS: We retrospectively searched our database for patients admitted for surgical treatment of bronchiectasis between 2016 and 2020. All records were screened for pre-surgical management. Age, gender, distribution of bronchiectatic lesions, type of surgery, perioperative complications, chest tube duration, length of hospital stay as well as 30-day-mortality were recorded, and a brief follow-up was made. RESULTS: A total of n=34 patients underwent pulmonary resection with bronchiectasis. Mean age on admission was 56.2±15.1 years and n=21 patients (62%) were female. In n=23 cases the right lung was affected, in n=9 cases the left side and in two cases both lungs. Indications for surgery included persistent major alterations after conservative therapy (n=9), massive hemoptysis (n=4), and full-blown "destroyed lobe" (n=7). All patients received anatomical lung resection (n=21 lobectomies, n=2 bilobectomies and n=11 segmentectomies), either by uniportal video assisted thoracoscopic surgery (n=28) or by lateral thoracotomy (n=6). Average length of hospital stay was 7.9±6.3 days; one patient died on POD 7 due to myocardial infarction. CONCLUSIONS: In spite of a decreasing number of patients with bronchiectasis referred to surgery due to improvements in preventing and managing the disease, pulmonary resection still plays a significant role in treating this pathology in Central Europe. Surgery remains a viable approach for localized forms of bronchiectasis, and the only option in treating acute deterioration and complications like massive hemoptysis.

Intraoperative Diagnosis and Surgical Procedure with Imprint Cytology for Small Pulmonary Adenocarcinoma.

Objectives: For patients with multiple small-sized pulmonary cancers, a lobectomy can disrupt future therapeutic options for other lesions. It was recently reported that limited pulmonary resections were not inferior to lobectomy for the management of selected peripheral small-sized pulmonary adenocarcinomas. Patients with adenocarcinoma in situ or minimally invasive adenocarcinoma, as proposed by the International Association for the Study of Cancer classification, have been reported to have 100% survival after 5 years. However, that classification can be applied postoperatively. Since 2005, we have been intentionally performing limited pulmonary resection procedures for small-sized adenocarcinoma cases based on intraoperative imprint cytological diagnosis and our classification (Nakayama-Higashiyama's classification). Materials and Methods: A total of 120 consecutive cases were included in this study. Lung tumors were removed intraoperatively by wedge resection, and stump smear cytology was performed, from which the cases were classified into 5 groups based on our classification. When the tumor was classified as Group I or II, the operation was finished. When diagnosed as a more advanced classification, a lobectomy and lymph node dissection were additionally performed. Results: The 5-year survival rate for Group I and II was 100%, while those for Group III and IV-V were 95.8% and 94.4%, respectively. The 5-year disease-free survival rates for Group I and Group II were 100% and 97.1%, respectively, and for Group III and IV-V they were 100% and 94.1%, respectively. Conclusion: Use of cytological findings along with Nakayama-Higashiyama's classification for determining operation procedure is effective for treatment of patients with small-sized pulmonary adenocarcinoma.

Novel Imprint Cytological Classification for Small Pulmonary Adenocarcinoma Using Surgical Specimens: Comparison with the 8th Lung Cancer Staging System and Histopathological Classification.

Objectives: Small-size lung lesions suspected of being cancer are now often being identified on computed tomography. Correspondingly, a new lung cancer staging system has been proposed by the International Association for the Study of Lung Cancer (IASLC), in which the T1 factor and adenocarcinoma are re-subclassified. Previously, we proposed an intraoperative cytological diagnosis and its classification of small-size lung adenocarcinoma, which correlated significantly with clinical malignancy, to be used for selecting the surgical strategy. In the current study, the correlation of our intraoperative cytological classification with the new 8th IASLC classification was investigated. Materials and Methods: A total of 139 consecutive small-size lung adenocarcinoma cases were surgically resected from 2000 to 2006 and included in this study. Intraoperative stump imprint cytology using these specimens was performed, and the cases were classified into 5 groups based on our classification. The cytological classification was compared with the IASLC classification and the WHO histopathological grading. Results: According to our classification, 32 patients were in Group I, 38 in Group II, 24 in Group III, 27 in Group IV, and 18 in Group V. Compared with the IASLC classification, most of Group I was pTis or pT1mi, and most of Group II was pT1mi or pT1a (p<0.001). There was also a significant relationship between lymph node metastasis and our cytological classification (p<0.001). The histological patterns according to the WHO classification also had a significant relationship with our classification (p<0.001). Conclusion: Our cytological classification correlated not only with the T classification, but also with the adenocarcinoma subclassification of the 8th IASLC classification.

Increased frequency of CD4+ CD25high CD127low T cells early after lung transplant is associated with improved graft survival - a retrospective study.

In this retrospective study, we analyzed the presence of any association of three CD4+ CD25high regulatory T-cell subpopulations at 3 weeks after lung transplantation with the later incidence of chronic lung allograft dysfunction and graft survival. Among lung-transplanted patients between January 2009 and April 2018, only patients with sufficient T-cell measurements at 3 weeks after transplantation were included into the study. Putative regulatory T cells were defined as CD4+ CD25high T cells, detected in peripheral blood and further analyzed for CD127low , FoxP3+ , and CD152+ using fluorescence-activated cell sorting (FACS) analysis. Associations of regulatory T cells with chronic lung allograft dysfunction (CLAD) and graft survival were evaluated using Cox analysis. During the study period, 724 (71%) patients were included into the study. Freedom from chronic lung allograft dysfunction (CLAD) and graft survival amounted to 66% and 68% at 5 years. At the multivariable analysis, increasing frequencies of CD127low were associated with better freedom from CLAD (hazard ratio for each 1% increase of %CD127low , HR = 0.989, 95% CI = 0.981-0.996, P = 0.003) and better graft survival (HR = 0.991, 95% CI = 0.984-0.999, P = 0.026). A higher frequency of CD127low regulatory T cells in peripheral blood early after lung transplantation estimated a protective effect against chronic lung allograft dysfunction, mortality, and re-transplantation.

Surgical Treatment following Chemo-Targeted Therapy with Bevacizumab for Lung Metastasis from Colorectal Carcinoma: Analysis of Safety and Histological Therapeutic Effects in Patients Treated at a Single Institution.

BACKGROUND: Recently, therapeutic strategies for a metastasectomy from colorectal carcinoma after chemo-targeted therapy with bevacizumab have been presented, with which some uncommon but serious adverse events have been reported. However, only few reports have investigated the safety of lung resection after such therapy or the histological effects. We retrospectively analyzed the both of them at our institute. METHODS: Of 69 colorectal carcinoma patients who underwent pulmonary metastasectomy procedures from 2009 to 2014, we investigated 11 who also received chemo-targeted therapy prior to surgery. RESULTS: In addition to bevacizumab, 5 fluorouracil (FU)/leucovorin + oxaliplatin or capecitabine was given in 6 cases and 5 FU/leucovorin + irinotecan in 5 cases. The mean period from the end of chemo-targeted therapy to surgery was 2.7 ± 0.9 months. The response to therapy shown in imaging findings was progressive disease in 6, stable disease in 3, and partial response in 2 (response rate, 18.2%). The operation modes were wedge resection (n = 8, 72.3%), segmentectomy (n = 2, 1 in bilateral lobes, 1 in the right lobe, 18.2%), and lobectomy (n = 1, left lower lobectomy, 9.1%). All patients safely underwent a complete resection. As for postsurgical complications, chylothorax occurred in 1 case and prolonged pulmonary air leakage in 1 case. The histological effects of chemo-targeted therapy were slight. There was no relationship between histological findings with imaging findings obtained prior to the operation (p = 0.63). The 5-year disease-free survival rate after metastasectomy was 10.9%. CONCLUSIONS: Pulmonary metastasectomy after chemo-targeted therapy for colorectal carcinoma patients obtained acceptable results. In addition, there was no correlation between imaging and histopathologic results following chemo-targeted therapy.

Pleuropneumonectomy for a large thymoma with multiple pleural dissemination using median sternotomy followed by posterolateral thoracotomy.

We present 2 cases of a large thymoma with invasion to the hilum of the lung and pleural dissemination. Case 1: a 47-year-old woman was diagnosed with a type B3 thymoma with abundant left pleural effusion and multiple pleural masses, Masaoka stage IVa. A radical resection was planned after chemical pleurodesis and systemic chemotherapy. The left main pulmonary artery and left upper and inferior veins were dissected and resected in the pericardium, while the left main bronchus was cut behind the pericardium through a median sternotomy. Next, the median incision was closed and a left posterolateral thoracotomy was made, thus allowing the pleuropneumonectomy to be safely performed. Case 2: a 47-year-old woman was diagnosed with a type B3 thymoma with lymph node swelling and multiple pleural masses, indicating Masaoka stage IVb. Following induction chemotherapy, a thymothymectomy combined with a right pleuropneumonectomy was performed under a median sternotomy followed by a right posterolateral thoracotomy. The left brachiocephalic vein (BCV) was reconstructed with a ringed polytetrafluoroethylene (PTFE) graft, followed by resection of the right BCV. Next, the right main pulmonary artery and right upper and inferior veins were resected in the pericardium, and the right main bronchus was cut behind the pericardium, followed by reconstruction of the right BCV. Finally, the median incision was closed and a right posterolateral thoracotomy was made, thus allowing performance of a safe pleuropneumonectomy. The median sternotomy allowed safe dissection of pulmonary vessels surrounding the hilum of the lung and, in combination with a posterolateral thoracotomy, was required for performing a pleuropneumonectomy in patients with a huge thymoma with pleural dissemination.