Lung cancer is one of the most common human malignancies and remains the leading cause of cancer related deaths worldwide. Many recent technological advances led to improved diagnostics and staging of lung cancer. With development of new treatment options such as targeted therapies there might be improvement in progression free survival of patients with advanced stage non-small cell lung cancer (NSCLC). Improvement in overall survival is still reserved for selected patients and selected treatments. One of the mostly investigated therapeutic options is adjuvant treatment. There are many open issues in selection of patients and administration of appropriate adjuvant treatment.
Adjuvant therapy; chemotherapy; non-small cell lung cancer (NSCLC); radiotherapy
Lung cancer is the leading cause of cancer death for male and the second most usual cancer for women after breast cancer. Currently there are available several non-specific cytotoxic agents and several targeted agents for lung cancer therapy. However; early stage diagnosis is still unavailable and several efforts are being made towards this direction. Novel biomarkers are being investigated along with new biopsy techniques. The occupational and environmental exposure to carcinogenic agents is an everyday phenomenon. Therefore until efficient early diagnosis is available, avoidance of exposure to carcinogenic agents is necessary. In the current mini-review occupational and environmental carcinogenic agents will be presented.
Lung cancer; occupational disease; environmental exposure
Pleuroscopy; medical; thoracoscopy; surgical; video-assisted thoracic surgery (VATS); Jakobaeus; awake; sedation
Involvement of the pleura in lung cancer is a common manifestation accompanying with reduced life expectancy. Symptoms relief and improvement of the quality of life are the primary goals of the management of malignant pleural effusion (MPE). Histological confirmation is essential for optimal patient management. Lung cancer patients, with life expectancy more than 3 months, resistant to chemotherapy should be treated with thoracentesis, intercoastal tube drainage and installation of a sclerosant agent or pleurodesis through thoracospopic procedures or placement of an indwelling pleura catheter. Talc pleurodesis (sterile asbestos-free graded, particle size >15 μm), as “poudrage” or “slurry” still remains the treatment of choice in patients with MPE resistant to chemotherapy.
Malignant pleural effusion (MPE); pleurodesis; suicide gene therapy; thoracoscopy
Small cell lung cancer (SCLC) represents 12.95% of all lung cancer diagnoses and continues to be a major clinical problem, with an aggressive clinical course and short disease-free duration after 1st line therapy. Treatment of SCLC remains challenging because of its rapid growth and development of drug resistance during the course of the disease. Chemotherapy remains the current optimal treatment and radical thoracic radiotherapy representing the best treatment option for fit patients with LD. Platinum-based chemotherapy is the treatment of choice in patients with good performance status, and the effect of cisplatin is important for concurrent chemoradiotherapy in LD cause of his radiosensitivity. Patients with progress disease after first-line chemotherapy have poor prognosis. Second-line therapy may produce a modest clinical benefit. A number of targeted agents have been investigated in LD and ED, mostly in unselected populations, with disappointing results. Prophylactic cranial irradiation (PCI) is recommended only for patients who had full response to first line chemotherapy, as target of improving overall survival and decreasing possibilities of brain metastases. New factors for target therapy are the hope for the management of this systematic disease. If we identify these targets for treatment of SCLC and overcome drug-resistance mechanisms, we will create new chemo-radiotherapy schedules for future.
Small cell lung cancer (SCLC); treatment; chemotherapy; targeted
According to the International Agency for Research on Cancer (IARC) GLOBOCAN World Cancer Report, lung cancer affects more than 1 million people a year worldwide. In Greece according to the 2008 GLOBOCAN report, there were 6,667 cases recorded, 18% of the total incidence of all cancers in the population. Furthermore, there were 6,402 deaths due to lung cancer, 23.5% of all deaths due to cancer. Therefore, in our country, lung cancer is the most common and deadly form of cancer for the male population. The most important prognostic indicator in lung cancer is the extent of disease. The Union Internationale Contre le Cancer (UICC) and the American Joint Committee for Cancer Staging (AJCC) developed the tumour, node, and metastases (TNM) staging system which attempts to define those patients who might be suitable for radical surgery or radical radiotherapy, from the majority, who will only be suitable for palliative measures. Surgery has an important part for the therapy of patients with lung cancer. “Lobectomy is the gold standard treatment”. This statement may be challenged in cases of stage Ia cancer or in patients with limited pulmonary function. In these cases an anatomical segmentectomy with lymph node dissection is an acceptable alternative. Chest wall invasion is not a contraindication to resection. En-bloc rib resection and reconstruction is the treatment of choice. N2 disease represents both a spectrum of disease and the interface between surgical and non-surgical treatment of lung cancer Evidence from trials suggests that multizone or unresectable N2 disease should be treated primarily by chemoradiotherapy. There may be a role for surgery if N2 is downstaged to N0 and lobectomy is possible, but pneumonectomy is avoidable. Small cell lung cancer (SCLC) is considered a systemic disease at diagnosis, because the potential for hematogenous and lymphogenic metastases is very high. The efficacy of surgical intervention for SCLC is not clear. Lung cancer resection can be performed using several surgical techniques. Video-assisted thoracoscopic surgery (VATS) lobectomy is a safe, efficient, well accepted and widespread technique among thoracic surgeons. The 5-year survival rate following complete resection of lung cancer is stage dependent. Incomplete resection rarely is useful and cures the patient.
Lung cancer; non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC); surgery; staging; video-assisted thoracoscopic surgery (VATS); lobectomy
Radical surgery is the standard of care for fit stage I non-small cell lung cancer (NSCLC) patients. Adjuvant treatment should be offered only as part of an investigation trial. Stage II and IIIA adjuvant cisplatin-based chemotherapy remains the gold standard for completely resected NSCLC tumors. Additionally radiotherapy should be offered in patients with N2 lymph nodes. In advanced stage IIIB/IV or inoperable NSCLC pts, a multidisciplinary treatment should be offered consisted of 4 cycles of cisplatin-based chemotherapy plus a 3rd generation cytotoxic agent or a cytostatic (anti-EGFR, anti-VEGFR) drug.
Non-small cell lung cancer (NSCLC); lung cancer; treatment; targeted treatment
The role of advanced brochoscopic diagnostic techniques in detection and staging of lung cancer has steeply increased in recent years. Bronchoscopic imaging techniques became widely available and easy to use. Technical improvement led to merging in technologies making autofluorescence or narrow band imaging incorporated into one bronchoscope. New tools, such as autofluorescence imagining (AFI), narrow band imaging (NBI) or fuji intelligent chromo endoscopy (FICE), found their place in respiratory endoscopy suites. Development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions. Linear EBUS proven to be complementary to mediastinoscopy. This technique is now available in almost all high volume centers performing bronchoscopy. Radial EBUS with mini-probes and guiding sheaths provides accurate diagnosis of peripheral pulmonary lesions. Combining EBUS guided procedures with rapid on site cytology (ROSE) increases diagnostic yield even more. Electromagnetic navigation technology (EMN) is also widely used for diagnosis of peripheral lesions. Future development will certainly lead to new improvements in technology and creation of new sophisticated tools for research in respiratory endoscopy. Broncho-microscopy, alveoloscopy, optical coherence tomography are some of the new research techniques emerging for rapid technological development.
Autofluorescence bronchoscopy (AFB); endobronchial ultrasound (EBUS); interventional bronchoscopy; narrow band imagning (NBI)
Pulmonary metastases from colorectal cancer present as systemic manifestation of the disease. As a general principle, the presence of metastases predispose to a poor prognosis. However, the application of some criteria of “operability” permitted the surgical resection resulting in prolonged survival (reported 5-year survival up to 50%), in better quality of life and in the cure of some patients. When the primary tumor site is controlled, and the metastatic disease is limited in lungs without extrapulmonary location (except for resectable or resected hepatic lesion) surgical removal is indicated. As significant prognostic factors in metastasectomies have been reported the synchronous or metachronous caracter of the metastases, the disease free survival, the complete removal of the metastases, the thoracic lymph node invasion, the CEA level before metastasectomy and 1 month after, the solitary vs. multiple pulmonary metastatic locations, the induction chemotherapy, the histological type and differentiation grade, as well as the vascular emboli in histopathological examination. Thorough preoperative evaluation of the patient includes oncological assessment and respiratory functional tests. Alternatively, when the patient is not a good surgical candidate, radiofrequency ablation is an option. Many surgical accesses have been validated, as posterolateral or lateral or even posterior thoracotomy, sternotomy, clamshell incision, and thoracoscopic techniques that offer the advantages of less pain, fast recovery, and less morbidity. Though thoracoscopic metastasectomies have been questioned concerning to the completeness of metastatic removal, no statistical difference in survival has been revealed in many series comparing thoracotomy to thoracoscopic techniques. As a conclusion, there are many advances in the management of pulmonary metastases from colorectal cancer during last decade, the results have been essentially optimized, the role of surgery has been established, and the multimodality approach has been recognized as the cornerstone of a successful outcome.
Pulmonary metastases; lung; colorectal cancer; resection metastasectomy
Mesothelioma still remains an occupational related cancer with severe outcome. It is usually diagnosed at advanced stage since it does not demonstrate early symptoms. Several efforts have been made towards removing all materials inducing mesothelioma in the work setting and new work protection measures have been applied. Although we have new targeted treatments and radical surgery as arrows in the quiver, the type of mesothelioma and early diagnosis still remain the best treatment approach. Novel treatment modalities have been explored and several others are already on the way. In the current review we will present current data for mesothelioma and future perspectives.
Mesothelioma; pathogenesis; diagnosis; treatment; targeted treatment
Endobronchial tumors are a rare entity that presents with different pathological findings. The interventional pulmonologist, but also the thoracic surgeon have at their disposal the same techniques for diagnosis, however; the two modalities differentiate in the treatment approach. Diagnosis evaluation should include lymph node evaluation. Minimal invasive techniques under local or general anesthesia are usually preferred by the interventional pulmonologists, whereas in the surgical approach of the thoracic surgeons the general anesthesia is necessary. A more extensive surgical approach either lobotomy or pneumonectomy should be performed in cases with positive intrapulmonary lymph nodes. Carinal reconstruction should be performed skillfully to get a negative proximal margin whenever needed. In the current manuscript we will present the methods of patient evaluation and surgical techniques for the management of these lesions.
Endobronchial tumor; lung cancer; local treatment
Lung cancer treatment has evolved during the last decade from the non-specific cytotoxic drugs to targeted therapy. New diagnostic equipment such as the endobronchial ultrasound bronchoscopy and positron emission tomography has enhanced early lung cancer diagnosis. However; we still need additional novel biomarkers to assist the already used diagnostic techniques. Surgery is the still the best treatment for early lung cancer treatment. Several surgical techniques are being used based on the tumour location and cardiothoracic centre’s experienced. There are however marginal situations where neo-adjuvant chemotherapy provides a “pre-step” for the patient. In the current work we will provide current data for the patients needing neo-adjuvant chemotherapy before proceeding to curative surgery.
Lung cancer; neo-adjuvant; early stage
Pancoast tumors account for less than 5% of all bronchogenic carcinomas. These tumors are located in the apex of the lung and involve through tissue contiguity the apical chest wall and/or the structures of the thoracic inlet. The tumors become clinically evident with the characteristic symptoms of the “Pancoast-Tobias syndrome” which includes Claude-Bernard-Horner syndrome, severe pain in the shoulder radiating toward the axilla and/or scapula and along the ulnar distribution of the upper arm, atrophy of hand and arm muscles and obstruction of the subclavian vein resulting in edema of the upper arm.
The diagnosis will be made by the combination of the characteristic clinical symptoms with the radiographic findings of a mass or opacity in the apex of the lung infiltrating the 1st and/or 2nd ribs. A tissue diagnosis of the tumor via CT-guided FNA/B should always be available before the initiation of treatment. Bronchoscopy, thoracoscopy and biopsy of palpable supraclavicular nodes are alternative ways to obtain a tissue diagnosis. Adenocarcinomas account for 2/3 of all Pancoast tumors, while the rest of the tumors are squamous cell and large cell carcinomas. Magnetic resonance imaging of the thoracic inlet is always recommended to define the exact extent of tumor invasion within the thoracic inlet before surgical intervention.
Pancoast tumors are by definition T3 or T4 tumors. Induction chemo-radiotherapy is the standard of care for any potentially resectable Pancoast tumor followed by an attempt to achieve a complete tumor resection. Resection can be made through a variety of anterior and posterior approaches to the thoracic inlet. The choice of the approach depends on the location of the tumor (posterior - middle - anterior compartment of the thoracic inlet) and the depth/extent of invasion.
Prognosis depends mainly on T stage of tumor, response to preoperative chemo-radiotherapy and completeness of resection. Resection of the invaded strictures of the thoracic inlet should me made en bloc with pulmonary parenchyma resection, preferably an upper lobectomy. Invasion of the vertebral column is not a contraindication for surgery which, however, should be performed in oncologic centers with experience in spinal surgery. Surgery for Pancoast tumors is associated with 5% mortality rate and the complication rate varies from 7-38%. The overall 2-year survival rate after induction chemo-radiotherapy and resection varies from 55% to 70%, while the 5-year survival for R0 resections is quite good (54-77%). The main pattern of recurrence is that of distant metastases, especially in the brain.
Pancoast; lung cancer; treatment
Lung cancer still remains the leading cause of cancer death among males. Several new methodologies are being used in the everyday practise for diagnosis and staging. Novel targeted therapies are being used and others are being investigated. However; early diagnosis still remains the cornerstone for efficient treatment and disease management. Lung cancer patients requires in many situations intensive care unit (ICU) admission, either due to the necessity for supportive care until efficient disease symptom control (respiratory distress due to malignant pleural effusion) or disease adverse effect management (massive pulmonary embolism). In any case guidelines indicating the patient that has to be intubated have not yet been issued. In the current review we will present current data and finally present an algorithm based on the current published information for lung cancer patients that will probably benefit from admission to the ICU.
Intensive care unit (ICU); lung cancer; respiratory distress
Many healthcare workers were infected while looking after the SARS patients on the medical wards in 2003. The high infectivity of the SARS coronavirus with peak viral load on day 10 of illness when patients were ill, overcrowding of the old medical wards with low air changes/hr (ACH), and aerosol-generating procedures while resuscitating the patients were the major factors. Procedures reported to present an increased risk of SARS transmission include tracheal intubation, non-invasive ventilation, tracheotomy and manual ventilation before intubation whereas oxygen therapy and bed distance <1 m were also implicated. Studies based on laser visualization technique with smoke particles as smokers in the human patient simulator has shown that oxygen therapy via Hudson mask and nasal cannula could disperse exhaled air of patients to 0.4 and 1 m respectively whereas jet nebulizer could disperse exhaled air >0.8 m from the patient. Bigger isolation rooms with 16 ACH are more effective than smaller isolation rooms with 12 ACH in removing exhaled air and preventing room contamination but at the expense of more noise and electricity consumption. Non-invasive ventilation via face masks and single circuit can disperse exhaled air from 0.4 to 1 m. Both higher inspiratory pressures and use of whisper swivel device (to facilitate carbon dioxide removal) could increase the exhaled air leakage and isolation room contamination during on-invasive ventilation. Addition of a viral-bacterial filter during manual ventilation by bagging may reduce the exhaled air leakage forward and yet increase the sideway leakage. N95 mask was more effective than surgical mask in preventing expelled air leakage during patient’s coughing but there was still significant sideway leakage to 15 cm. Clinicians should be aware of air leakage from the various face masks and adopt strict infection control measures during resuscitation of patients with severe respiratory infections. Carefully designed clinical trials are required to determine the optimal timing and dosage of any antiviral agents, convalescent plasma, and immuno-modulating agents in the treatment of the possibly immune-mediated lung injury in SARS and newly emerged infection such as the Middle East Respiratory Syndrome.
Severe acute respiratory syndrome (SARS); management; lessons; Middle East Respiratory Syndrome (MERS)
Four coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) are endemic in humans and mainly associated with mild respiratory illnesses; whereas the other two coronaviruses [Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV)] present as emerging infections causing severe respiratory syndrome. Coronaviruses evolve by accumulation of point mutations and recombination of genomes among different strains or species. Mammalian coronaviruses including those infect humans are evolved from bat coronaviruses. While SARS-CoV and MERS-CoV are genetically closely related to bat coronaviruses, intermediate host(s) is (are) likely to be involved in the emergence and cross-species transmission of these novel human viruses. High prevalence of SARS-like coronaviruses have been found from masked palm civet cats and raccoon dogs collected from markets around the time of outbreaks in humans, but these animals are likely to be a transient accidental host rather than a persisting reservoir. More research is needed to elucidate the ecology of coronaviruses. Vigilance and surveillance should be maintained to promptly identify newly emerged coronaviruses.
Severe acute respiratory syndrome (SARS); coronaviruses (CoV); evolution; animal reservoir
In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused one of the most devastating epidemics known to the developed world. There were two important lessons from this epidemic. Firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. Secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. Since then, researchers around the world, especially those in Asia where SARS-CoV was first identified, have turned their focus to find novel coronaviruses infecting humans, bats, and other animals. Two human coronaviruses, HCoV-HKU1 and HCoV-NL63, were identified shortly after the SARS-CoV epidemic as common causes of human respiratory tract infections. In 2012, a novel human coronavirus, now called Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in the Middle East to cause fatal human infections in three continents. MERS-CoV human infection is similar to SARS-CoV in having a high fatality rate and the ability to spread from person to person which resulted in secondary cases among close contacts including healthcare workers without travel history to the Middle East. Both viruses also have close relationships with bat coronaviruses. New cases of MERS-CoV infection in humans continue to occur with the origins of the virus still unknown in many cases. A multifaceted approach is necessary to control this evolving MERS-CoV outbreak. Source identification requires detailed epidemiological studies of the infected patients and enhanced surveillance of MERS-CoV or similar coronaviruses in humans and animals. Early diagnosis of infected patients and appropriate infection control measures will limit the spread in hospitals, while social distancing strategies may be necessary to control the outbreak in communities if it remained uncontrolled as in the SARS epidemic.
Severe acute respiratory syndrome coronavirus (SARS-CoV); novel coronaviruses; Middle East respiratory syndrome coronavirus (MERS-CoV)
Influenza surveillance is carried out in Guangdong province, southern China. A better understanding of influenza seasonality and predominant Subtypes of influenza virus in Guangdong can help to improve evidence-based prevention and control strategies for influenza in the future.
Materials and methods
There are three categories of influenza surveillance in Guangdong: Influenza-like Illness (ILI) Outpatient Surveillance, ILI Outbreak Surveillance and Influenza Virus Surveillance. This paper summarizes collected influenza surveillance data from January 2004 to December 2012 in Guangdong province. Time series analysis and “peak analysis” were performed to estimate seasonality and temporal trends of influenza activity.
During the 9-year study period, a total of 37,571,582 outpatients had been recorded, in which 1,889,684 ILI cases had been reported. The provincial ILI visiting percentage peaked at 6-10%. A total of 107,115 respiratory specimens of ILI outpatients were collected, 17,454 (16.29%) of them tested for influenza virus were positive. Influenza virus peaks appeared in summer mostly with a median epidemic duration of 6 months. A total of 925 outbreaks recorded and 45,322 cases in which were affected. The majority of reported outbreaks (832 outbreaks, 90%) occurred in institutional settings.
Influenza circulates periodically every year in Guangdong. Influenza activity had strong and clear seasonality with epidemic periods in summer for last decade. The presence of local unique seasonal pattern and its changes emphasizes the need to optimize timing of influenza vaccine delivery and other public health interventions.
Influenza; surveillance; seasonality
Influenza virus has caused seasonal epidemics and worldwide pandemics, which caused tremendous loss of human lives and socioeconomics. Nowadays, only two classes of anti-influenza drugs, M2 ion channel inhibitors and neuraminidase inhibitors respectively, are used for prophylaxis and treatment of influenza virus infection. Unfortunately, influenza virus strains resistant to one or all of those drugs emerge frequently. Hemagglutinin (HA), the glycoprotein in influenza virus envelope, plays a critical role in viral binding, fusion and entry processes. Therefore, HA is a promising target for developing anti-influenza drugs, which block the initial entry step of viral life cycle. Here we reviewed recent understanding of conformational changes of HA in protein folding and fusion processes, and the discovery of HA-based influenza entry inhibitors, which may provide more choices for preventing and controlling potential pandemics caused by multi-resistant influenza viruses.
Hemagglutinin (HA); influenza virus; viral entry; antiviral drugs
Advancements in next generation sequencing technology have provided means for the comprehensive profiling of the microbial community in the respiratory tract in both physiological and pathological conditions. Recent studies have analyzed the bacterial composition in the respiratory tract of chronic obstructive pulmonary disease (COPD), influenza and tuberculosis patients, and have identified novel targets that may potentially lead to secondary infections. Certain bacteria have also been found to regulate the lung immune system and have unexpected connections with respiratory diseases. Further studies in these areas are necessary to dissect the exact relationship between the dynamics of the microbiota and the health of the respiratory system.
Human microbiota; chronic obstructive pulmonary disease (COPD); influenza; tuberculosis; thoracic diseases; next generation sequencing