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Dionisios Spyratos, Eleni Papadaki, Sofia Lampaki, Theodoros Kontakiotis Pulmonary Department, Lung Cancer Oncology Unit, Aristotle University of Thessaloniki, G. Papanicolaou Hospital, Thessaloniki, Greece Abstract: Chronic obstructive pulmonary disease (COPD) and lung cancer share a common etiological factor (cigarette smoking) and usually coexist in everyday clinical practice. The prevalence of COPD among newly diagnosed patients with lung cancer sometimes exceeds 50%. COPD is an independent risk factor (2–4 times higher than non-COPD subjects) for lung cancer development.The presence of emphysema in addition to other factors (e.g., smoking history, age) could be incorporated into risk scores in order to define the most appropriate target group for lung cancer screening using low-dose computed tomography. Clinical management of patients with coexistence of COPD and lung cancer requires a multidisciplinary oncology board that includes a pulmonologist. Detailed evaluation (lung function tests, cardiopulmonary exercise test) and management (inhaled drugs, smoking cessation, pulmonary rehabilitation) of COPD should be taken into account for lung cancer treatment (surgical approach, radiotherapy). Keywords: lung cancer, COPD, coexistence, risk factor, therapy decisions

Konstantinos Zarogoulidis,1 Efimia Boutsikou,1 Paul Zarogoulidis,1,2 Kaid Darwiche,2 Lutz Freitag,2 Konstantinos Porpodis,1 Dimitrios Latsios,1 Theodoros Kontakiotis,1 Haidong Huang,3,4 Qiang Li,4 Wolfgang Hohenforst-Schmidt,5 Maria Kipourou,1 J Francis Turner,6 Dionysios Spyratos11Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 3Bronchoscopy and Interventional Pulmonology, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, School of Medicine, Detroit, MI, USA; 4Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People’s Republic of China; 5II Medical Clinic, “Coburg” Regional Hospital, University of Wuerzburg, Coburg, Germany; 6Pulmonary Medicine, University of Nevada School of Medicine, National Supercomputing Center for Energy and the Environment University of Nevada, Las Vegas, NV, USABackground: To evaluate the benefit of second-line chemotherapy with platinum-based treatment in patients with recurrent small cell lung cancer (SCLC).Patients and methods: A total of 535 patients continued with follow-up or best supportive care if needed, and 229 patients who progressed after the completion of first-line chemotherapy were treated with second-line chemotherapy at the time of progression. In total, 103/229 patients received paclitaxel 190 mg/m2 and carboplatin 5.5 area under the curve while 126/229 patients received etoposide 200 mg/m2 and carboplatin 5.5 area under the curve every 28 days.Results: Patients administered second-line chemotherapy lived significantly longer, with a median survival of 422 days compared to 228 days in patients with best supportive care alone (P

Konstantinos Zarogoulidis,1 Eftimios Ziogas,1 Efimia Boutsikou,1 Paul Zarogoulidis,1,2 Kaid Darwiche,2 Theodoros Kontakiotis,1 Kosmas Tsakiridis,3 Konstantinos Porpodis,1 Dimitrios Latsios,1 Olga Chatzizisi,4 Ilias Karapantzos,5 Qiang Li,6 Georgios Kyriazis21Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 3Thoracic Surgery Department, "Saint Luke" Private Hospital, Panorama, Thessaloniki, Greece; 4Immunology Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Ear, Nose and Throat Department, "Saint Luke" Private Hospital, Panorama, Thessaloniki, Greece; 6Respiratory Diseases Department, Shanghai hospital, Second Military Medical University, Shanghai, People's Republic of ChinaPurpose: To evaluate the effect of immunotherapy on response, survival, and certain immune markers in patients with small cell lung cancer (SCLC) who are receiving chemotherapy.Patients and methods: Patients with SCLC (n = 164) were assigned to receive either chemotherapy alone (group A) or a combination of chemotherapy and immunotherapy as follows: interferon α (IFN-α; 3 million IU) 3 times per week (group B); IFN-γ (3 million IU) 3 times per week (group C); and IFN-α and IFN-γ (1.5 million IU of each) 3 times per week (group D). Chemotherapy was the same for all groups and consisted of eight cycles with carboplatin 5.5 mg/m2 intravenously on day 1, ifosfamide 3.5 mg/m2 intravenously on day 1, and etoposide 200 mg/m2 total dose taken orally on days 1 through 3, every 28 days. Patients completing chemotherapy were restaged, and those who were found to have limited disease received primary site and prophylactic cranial irradiation. Immunotherapy was continued throughout these treatments and during the follow-up period. Blood was taken before each course of chemotherapy and during follow-up to measure CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, natural killer cells, and natural killer T cells.Results: Differences in response and survival were not significantly different when all patients were considered. However, among patients with limited disease, Kaplan–Meier analysis disclosed a survival benefit for group B (P < 0.05). The analysis of immunologic measurements revealed that the improvement of immune markers was always accompanied by clinical improvement, whereas deterioration of all markers was accompanied by disease progression (result not statistically significant except for group C; P < 0.05).Conclusion: Among cytokines used in the study, only IFN-α seems to confer a survival benefit to patients with SCLC with limited disease. However, immunotherapy remains a challenge in the treatment of lung neoplasms and should be further explored.Keywords: interferon, SCLC, lung cancer, immunomodifiers

Konstantinos Zarogoulidis,1 Dimitrios Latsios,1 Konstantinos Porpodis,1 Paul Zarogoulidis,1,2 Kaid Darwiche,2 Nick Antoniou,1 Wolfgang Hohenforst-Schmidt,3 Ellada Eleftheriadou,1 Efimia Boutsikou,1 Theodoros Kontakiotis11Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2University Pulmonary Department- Interventional Unit, Ruhrlandklinik, University, University of Duisburg-Essen, Essen, Germany; 3II Medical Clinic, Hospital of Coburg, University of Wuerzburg, Coburg, GermanyBackground: Many patients with limited disease (LD) behave similarly to those with extensive disease (ED) from a prognostic point of view. On the other hand, a proportion of patients with ED small-cell lung cancer (SCLC) behave similarly to those with LD.Patients and methods: In this retrospective study analysis, 764 patients with proven SCLC were included and managed with the same therapeutic protocols. Of these patients, 278 (36.4%) had LD, while 486 (63.6%) had ED.Results: No statistically significant difference was observed for survival for IA and IB disease stages (P = 0.254) and between IIA and IIB stages (P = 0.256) according to the new tumor, node, metastasis (TNM) staging classification classification. In addition, no statistical significant difference was observed for survival between patients with (IIA + IIB) and IIIA (P = 0.951), (IIA + IIIA, P = 0.658), and (IIB + IIIA, P = 0.573) stages. Statistical significant difference was observed for survival among the LD SCLC patients with (IA + IB), (IIA + IIB + IIIA), and IIIB stages (P < 0.001). Similarly, statistical significance was observed for ED SCLC patients with (IIA + IIB + IIIA), IIIB, and IV stages (P < 0.001).Conclusions: Although stratification of SCLC patients in LD and ED is generally satisfactory, the TNM staging system is recommended for more detailed prognostic information and treatment evaluation in these patients.Keywords: small-cell lung cancer, staging, lung cancer

Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC). We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5) and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group), 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically significant difference in survival and time to progression between the four treatment groups. After two cycles of chemotherapy, responders and nonresponders were divided according to their response in order to examine the role of initial response as an independent factor in survival and response when a biological agent is combined with chemotherapy. Nonresponders, who received additional therapy with bevacizumab or combination therapy, had a survival benefit [657 days (95% confidence interval 349–970) and 681 days (95% confidence interval 315–912), respectively], which was statistically significant compared with continuation of cytotoxic chemotherapy (P < 0.001). The combination therapy had a safety profile comparable with that of bevacizumab and erlotinib taken individually.Conclusion: Administration of bevacizumab and erlotinib in combination with first-line chemotherapy, followed by bevacizumab and erlotinib monotherapy as maintenance, showed promising results in patients with NSCLC, with reduced toxicity as compared with chemotherapy alone, but did not translate into longer overall survival.Keywords: vascular endothelial growth factor, epidermal growth factor receptor, erlotinib, bevacizumab, non-small cell lung cancer

Paul Zarogoulidis,1 Theodoros Kontakiotis,1 Kosmas Tsakiridis,2 Michael Karanikas,3 Christos Simoglou,4 Konstantinos Porpodis,1 Alexandros Mitrakas,3 Agisilaos Esebidis, 3 Maria Konoglou,5 Nikolaos Katsikogiannis,6 Vasilis Zervas,1 Christina Aggelopoulou,7 Dimitrios Mikroulis,4 Konstantinos Zarogoulidis11Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Cardiothoracic Department, Saint Luke Private Hospital, Thessaloniki, Greece; 31st University Surgery Department, 4Cardiothoracic Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece; 51st Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 6Surgery Department (NHS), 7Neurology Department (NHS), University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, GreeceAbstract: Management of a "difficult airway" remains one of the most relevant and challenging tasks for anesthesiologists and pulmonary physicians. Several conditions, such as inflammation, trauma, tumor, and immunologic and metabolic diseases, are considered responsible for the difficult intubation of a critically ill patient. In this case report we present the case of a 46-year-old male with postintubation tracheal stenosis. We will focus on the method of intubation used, since the patient had a "difficult airway" and had to be intubated immediately because he was in a life-threatening situation. Although technology is of utter importance, clinical examination and history-taking remain invaluable for the appropriate evaluation of the critically ill patient in everyday medical life. Every physician who will be required to perform intubation has to be familiar with the evaluation of the difficult airway and, in the event of the unanticipated difficult airway, to be able to use a wide variety of tools and techniques to avoid complications and fatality.Keywords: difficult airway, bronchoscopic intubation, predictive factors, predictive scales

Paul Zarogoulidis1, Dimitrios Glaros2,3, Theodoros Kontakiotis1, Marios Froudarakis4, loannis Kioumis1, loannis Kouroumichakis3, Anastasios Tsiotsios1, Anastasios Kallianos5, Paschalis Steiropoulos4, Konstantinos Porpodis1, Evagelia Nena6, Despoina Papakosta1, Aggeliki Rapti5, Theodoros C Constantinidis6, Theodora Kerenidi7, Maria Panopoulou8, Georgia Trakada9, Nikolaos Courcoutsakis10, Evangelia Fouka11, Konstantinos Zarogoulidis1, Efstratios Maltezos2,31Aristotle University of Thessaloniki, Pulmonary Department, "G Papanikolaou" Hospital, Exochi, Thessaloniki, 2Unit of Infectious Diseases, General University Hospital of Alexandroupolis, 3Second Department of Internal Medicine, 4Pulmonary Department, General University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 52nd Pulmonology Clinic, Hospital of Chest Diseases "SOTIRIA," Athens, 6Laboratory of Hygiene and Environmental Protection, Occupational Medicine Section, Teaching Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Greece, Alexandroupolis, 7Pulmonary Department, University of Larissa, Larissa, 8Microbiology Department, General University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 9Pulmonary Department, University of Athens, Athens, 10Radiology Department, General University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 111st Pulmonary Department, "G Papanikolaou" Hospital, Exochi, Thessaloniki, GreeceBackground: The first positive patient with influenza A (H1N1) was recorded in March 2009 and the pandemic continued with new outbreaks throughout 2010. This study's objective was to quantify the total cost of inpatient care and identify factors associated with the increased cost of the 2009–2010 influenza A pandemic in comparison with nonviral respiratory infection.Methods: In total, 133 positive and 103 negative H1N1 patients were included from three tertiary care hospitals during the two waves of H1N1 in 2009 and 2010. The health costs for protective equipment and pharmaceuticals and hospitalization (medications, laboratory, and diagnostic tests) were compared between H1N1 positive and negative patients.Results: The objective of the study was to quantify the means of daily and total costs of inpatient care. Overall, cost was higher for H1N1 positive (€61,0117.72) than for H1N1-negative patients (€464,923.59). This was mainly due to the protection measures used and the prolonged hospitalization in intensive care units. In H1N1-negative patients, main contributors to cost included additional diagnostic tests due to concern regarding respiratory capacity and laboratory values, as well as additional radiologic and microbial culture tests. The mean duration of hospitalization was 841 days for H1N1 positive and 829 days for negative patients.Conclusion: Cost was higher in H1N1 patients, mainly due to the protection measures used and the increased duration of hospitalization in intensive care units. An automated system to monitor patients would be desirable to reduce cost in H1N1 influenza.Keywords: cost effect, H1N1, health care resource utilization, respiratory infection

Konstantinos Porpodis1, Michael Karanikas2, Paul Zarogoulidis1, Theodoros Kontakiotis1, Alexandros Mitrakas2, Agisilaos Esebidis2, Maria Konoglou3, Kalliopi Domvri1, Alkis Iordanidis4, Nikolaos Katsikogiannis5, Nikolaos Courcoutsakis4, Konstantinos Zarogoulidis11Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Greece; 21st University Surgery Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Greece; 31st Pulmonary Department, "G Papanikolaou" General Hospital, Thessaloniki, Greece; 4Radiology Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Greece; 5Surgery Department (NHS), University General Hospital of Alexandroupolis, GreeceAbstract: Carcinoid bronchopulmonary tumors represent approximately 25% of all carcinoid tumors and 1%–2% of all lung neoplasms. The most common symptoms are: persistent cough, asthma-like wheezing, chest pain, dyspnea, hemoptysis and obstructive pneumonitis. We present a case of a young adult diagnosed with a typical carcinoid tumor. The diagnosis was established on the basis of imaging examination and bronchoscopic biopsy. The patient was treated with bronchoscopic electrocautery therapy to relieve the obstructed airway, followed by surgical lobectomy in order to entirely remove the exophytic damage. This approach was not only a palliative management to bronchial obstruction but also avoided pneumonectomy. Recent studies support the use of such interventional resection methods, as they may result in a more conservative surgical resection.Keywords: carcinoid tumor, typical lung carcinoid, therapeutic bronchoscopy, surgical resection

Maria Konoglou1, Konstantinos Porpodis2, Paul Zarogoulidis2, Nikolaos Loridas1, Nikolaos Katsikogiannis3, Alexandros Mitrakas2, Vasilis Zervas2, Theodoros Kontakiotis2, Despoina Papakosta2, Panagiotis Boglou4, Stamatia Bakali5, Nikolaos Courcoutsakis6, Konstantinos Zarogoulidis21First Pulmonary Clinic, "G. Papanikolaou" General Hospital, Thessaloniki, Greece; 2Pulmonary Department, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Greece; 3Surgery Department (NHS), University General Hospital of Alexandroupolis, Greece; 4Pulmonary Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Greece; 5Microbiology Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Greece; 6Radiology Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, GreeceIntroduction: Williams–Campbell syndrome, also known as bronchomalacia, is a rare disorder characterized by a deficiency of cartilage in subsegmental bronchi, leading to distal airway collapse and bronchiectasis. There have been few reports about patients affected by saccular bronchiectasis, paracicatricial emphysema, and diminished cartilage. These are all characteristic of Williams–Campbell syndrome.Case presentation: This report presents a 57-year-old woman with progressive dyspnea, cough, sputum production, and fever. The clinical and laboratory examination revealed that the patient had a respiratory infection due to bronchiectasis caused by Williams–Campbell syndrome, which was undiagnosed in the patient until then.Conclusion: Although a rare syndrome, when patients' signs and symptoms include recurrent respiratory infections, bronchiectasis, productive cough, and dyspnea, Williams–Campbell syndrome should be included in the differential diagnosis.Keywords: bronchietasis, Williams–Campbell syndrome, bronchomalacia

Konstantinos Porpodis1, Maria Konoglou2, Paul Zarogoulidis1, Evangelos Kaimakamis2, Theodoros Kontakiotis1, Despoina Papakosta1, Vasilis Zervas1, Nikolaos Katsikogiannis3, Nikolaos Courcoutsakis4, Alexandros Mitrakas5, Panagiotis Touzopoulos5, Michael Karanikas5, Konstantinos Zarogoulidis1, Aikaterini Markopoulou2 1Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Greece; 2First Pulmonary Clinic, "G Papanikolaou" General Hospital, Thessaloniki, Greece; 3Surgery Department (NHS), University Hospital of Alexandroupolis, Greece; 4Radiology Department, University Hospital of Alexandroupolis, Democritus University of Thrace, Greece; 5First University Surgery Department, University Hospital of Alexandroupolis, Democritus University of Thrace, Greece Abstract: In recent years, there has been a major advance in the treatment of pulmonary hypertension. New medications are continually added to the therapeutic arsenal. The prostanoids are among the first agents used to treat pulmonary hypertension and are currently considered the most effective. This case study describes a 63-year-old man who was diagnosed with chronic thromboembolic pulmonary hypertension and successfully treated with subcutaneously administered treprostenil for 6 months before a successful pulmonary thromboendarterectomy. Treatment of chronic thromboembolic pulmonary hypertension often requires a multidisciplinary approach before surgery. Further evaluation of prostanoids is needed to define their role and time of initiation of medical therapy in these patients. Keywords: chronic thromboembolic pulmonary hypertension, prostanoids, treprostenil sodium, pulmonary thromboendarterectomy