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At the start of this thesis there were several unanswered questions with regard to optimal patient selection for different treatments of bronchial carcinoid. Also, there were unanswered questions with regard to classification of bronchial carcinoid on small histological samples and with regard to prognostic value of several new tissue biomarkers. The aim of this thesis was to further optimize patient selection for parenchyma sparing techniques, and to explore the potential value of biomarkers in the treatment of bronchial carcinoid. Part one (chapter 2-5) of this thesis describes the classification of bronchial carcinoid on small histological samples and the use of diagnostic and prognostic biomarkers. In Chapter 2 we analyze patient selection for endobronchial treatment and underscore the importance of radiological assessment of bronchial carcinoids. Differentiation between typical and atypical carcinoid according to the current WHO classification is accomplished by obtaining the mitotic count and the presence of necrosis. As outlined above, TC is defined as a neuroendocrine tumour with less than 2 mitoses per 2 mm2 and absence of necrosis, while AC is defined by 2-10 mitoses per 2 mm2 and/or the presence of (dot-like) necrosis. However, it is known that small biopsies have limited diagnostic value for the distinction between TC and AC. In Chapter 3 and Chapter 4 we analyzed biopsy-resection paired specimens of patients referred for treatment for bronchial carcinoid to measure accuracy of pretreatment biopsies and analyze the value of tumor biopsy size. Furthermore, we describe the reliability of different immunohistochemical markers on different biopsies and resection specimens, and assessed the impact of specimen size on the accuracy of the diagnosis. Because the current classification of TC and AC only partially reflects their metastatic potential, there is a need for more accurate prognostic biomarkers for bronchial carcinoids. In Chapter 5 we investigated a co

Objective: It is widely accepted that exercise tolerance tests are applicable in perioperative risk assessment for patients who undergo pulmonary resection; however, the relevance of desaturation during the test is unclear. The purpose of this study was to investigate whether the occurrence of desaturation during a stair-climbing test can be a predictor of postoperative complications among patients who will undergo pulmonary resection and are considered "normal risk" according to published guidelines. Methods: Desaturation was defined as a depression of more than 4% points on a pulse oximeter during stair climbing. Among 186 consecutive patients who underwent pulmonary resection, 162 patients who could climb to the 6th floor were selected for the study (excluding 21 patients who could not stair-climb and 3 patients who could not climb from the first floor to the sixth floor). The relationship of desaturation with postoperative complication was investigated using parameters of cardio-pulmonary status associated with additional foci of oxygen supply duration, intensive care unit stay duration, and hospital stay duration. Results: The occurrence ratio of postoperative complications > grade 3 (Clavien-Dindo classification) was 0.75% (1/133) among patients without desaturation and 17.2% (5/29) in patients with desaturation (difference: p = 0.0002). In addition, DS was an indicator of prolonged oxygen supply duration, intensive care unit stay duration, and hospital stay duration. Conclusion: The occurrence of desaturation during a stair-climbing test for patients who will undergo pulmonary resection can be a predictor of postoperative complications among patients who are classified as having normal risk., 博士（医学）・乙第1457号・令和2年6月30日, © The Japanese Association for Thoracic Surgery 2019, © 2019 Springer Nature Switzerland AG. Part of Springer Nature., This is a post-peer-review, pre-copyedit version of an article published in General thoracic and cardiovascular surgery. The final authenticated version is available online at: http://doi.org/10.1007/s11748-019-01153-z., 発行元が定める登録猶予期間終了の後、本文を登録予定（2021.01）

Objective: It is widely accepted that exercise tolerance tests are applicable in perioperative risk assessment for patients who undergo pulmonary resection; however, the relevance of desaturation during the test is unclear. The purpose of this study was to investigate whether the occurrence of desaturation during a stair-climbing test can be a predictor of postoperative complications among patients who will undergo pulmonary resection and are considered "normal risk" according to published guidelines. Methods: Desaturation was defined as a depression of more than 4% points on a pulse oximeter during stair climbing. Among 186 consecutive patients who underwent pulmonary resection, 162 patients who could climb to the 6th floor were selected for the study (excluding 21 patients who could not stair-climb and 3 patients who could not climb from the first floor to the sixth floor). The relationship of desaturation with postoperative complication was investigated using parameters of cardio-pulmonary status associated with additional foci of oxygen supply duration, intensive care unit stay duration, and hospital stay duration. Results: The occurrence ratio of postoperative complications > grade 3 (Clavien-Dindo classification) was 0.75% (1/133) among patients without desaturation and 17.2% (5/29) in patients with desaturation (difference: p = 0.0002). In addition, DS was an indicator of prolonged oxygen supply duration, intensive care unit stay duration, and hospital stay duration. Conclusion: The occurrence of desaturation during a stair-climbing test for patients who will undergo pulmonary resection can be a predictor of postoperative complications among patients who are classified as having normal risk., 博士（医学）・乙第1457号・令和2年6月30日, © The Japanese Association for Thoracic Surgery 2019, © 2019 Springer Nature Switzerland AG. Part of Springer Nature., This is a post-peer-review, pre-copyedit version of an article published in General thoracic and cardiovascular surgery. The final authenticated version is available online at: http://doi.org/10.1007/s11748-019-01153-z., 発行元が定める登録猶予期間終了の後、本文を登録予定（2021.01）

Background and aim: Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers. Methods: All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR. Results: Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9–306) since LT and PMR was performed after 2.4 months (0–43.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50–365); median post-operative overall stay 5 days (2–11). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7–213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12–74), respectively, with a median OS of 51 month

Background : This study evaluated the clinical significance of perioperative levels of plasma blood coagulation factor XIII in patients undergoing pulmonary resection. / Methods : The study involved 27 patients with ≧2-day prolonged air leakage after pulmonary resection. The 27 pulmonary resection procedures comprised 25 lobectomies, 1 segmentectomy, and 1 partial resection. The preoperative and 5-day postoperative blood coagulation factor XIII levels were measured....

Background : This study evaluated the clinical significance of perioperative levels of plasma blood coagulation factor XIII in patients undergoing pulmonary resection. / Methods : The study involved 27 patients with ≧2-day prolonged air leakage after pulmonary resection. The 27 pulmonary resection procedures comprised 25 lobectomies, 1 segmentectomy, and 1 partial resection. The preoperative and 5-day postoperative blood coagulation factor XIII levels were measured....

A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalized in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams., SCOPUS: ar.j, info:eu-repo/semantics/published

The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective? split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy? the patient at prohibitive surgical risk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated? © 2009 European Association for Cardio-Thoracic Surgery., SCOPUS: ed.j, info:eu-repo/semantics/published

The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective? split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy? the patient at prohibitive surgical risk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated? © 2009 European Association for Cardio-Thoracic Surgery., SCOPUS: ed.j, info:eu-repo/semantics/published

A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalized in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction An air leak following pulmonary resection is generally defined as persistent, or prolonged, if it fails to resolve within the first post-operative week. The precise definition has varied from study to study. State of art Persistent air leak represents the most frequent complication in patients undergoing general thoracic procedures. The groups most at risk are elderly patients, patients with chronic obstructive pulmonary disease (COPD), and those who have general risk factors such as diabetes mellitus or who are taking oral steroids. The surgical procedures most commonly affected are upper lobectomies and lung volume reduction surgery for end-stage emphysema. Perspectives Technically, performing a pleural tent at the time of an upper lobectomy may decrease the incidence of prolonged air leak. Reinforcement or buttressing of the staple line has been shown to decrease both the incidence and the duration of air leaks, but this increases costs and should thus be reserved for patients with lung parenchyma at the highest risk. The use of biological glues can be helpful in reducing the duration of chest tube drainage when applied intraoperatively for moderate and/or severe parenchymal air leaks, however, their systematic use in not recommended. The management of chest tube drainage after pulmonary resection varies widely from one institution to another. Most recent reports have favoured early discontinuation of negative pressure drainage and a move to underwater seal drainage (from the second post-operative day), however, no large scale randomised study is yet available to compare this with a more conservative approach. Conclusions The management of persistent air leak following surgery requires identification of risk factors, good surgical technique and appropriate chest tube management.