Treatment Of Early Lung Cancer Research Articles

Update on Interventional Bronchoscopy for the Thoracic Radiologist

Interventional bronchoscopy, together with other domains of interventional pulmonology, has experienced tremendous technological advances. Diagnostic applications include endobronchial ultrasound, which enables endoscopists to see through airway walls. White light videobronchoscopy, autofluorescence imaging, and narrow band imaging have enhanced the ability to detect early lung cancer at a preinvasive stage. Electromagnetic navigational bronchoscopy, ultrathin bronchoscopy, and virtual bronchoscopy increase the diagnostic yield of biopsy of small peripheral lung lesions. The options that are currently available for the relief of central airway obstruction are also numerous, with both flexible and rigid bronchoscopic applications. Stents, although dichotomized to silicone and metal, come in various sizes and shapes to suit the requirements of the pathology being treated. Ablative techniques are categorized into those with an immediate effect and those with a delayed effect. Laser, electrocautery, and argon plasma coagulation can immediately relieve obstruction and control hemoptysis, whereas cryosurgery, brachytherapy, and photodynamic therapy have established roles in subacute airway obstruction and in the treatment of early lung cancer. Microdebriders have recently been added to the armamentarium of modalities for mechanical debulking of tumor. Distal airway obstruction has also been targeted with bronchial thermoplasty treatment of refractory asthma and with bronchoscopic lung volume reduction for the management of severe emphysema. This array of new technology has fostered collaborative work with a wide range of other medical specialties to deliver safer, more effective, minimally invasive treatment.

A new efficient 2D combined with 3D CAD system for solitary pulmonary nodule detection in CT images

Lung cancer has become one of the leading causes of death in the world. Clear evidence shows that early discovery, early diagnosis and early treatment of lung cancer can significantly increase the chance of survival for patients. Lung Computer-Aided Diagnosis (CAD) is a potential method to accomplish a range of quantitative tasks such as early cancer and disease detection. Many computer- aided diagnosis (CAD) methods, including 2D and 3D approaches, have been proposed for solitary pulmonary nodules (SPNs). However, the detection and diagnosis of SPNs remain challenging in many clinical circumstances. One goal of this work is to develop a two-stage approach that combines the simplicity of 2D and the accuracy of 3D methods. The experimental results show statistically significant differences between the diagnostic accuracy of 2D and 3Dmethods. The results also show that with a very minor drop in diagnostic performance the two-stage approach can significantly reduce the number of nodules needed to be processed by the 3D method, streamlining the computational demand. Finally, all malignant nodules were detected and a very low false-positive detection rate was achieved. The automated extraction of the lung in CT images is the most crucial step in a computer-aided diagnosis (CAD) system. In this paper we describe a method, consisting of appropriate techniques, for the automated identification of the pulmonary volume. The performance is evaluated as a fully automated computerized method for the detection of lung nodules in computed tomography (CT) scans in the identification of lung cancers that may be missed during visual interpretation. Index Terms—Lung Cancer, Computer-aided Diagnosis, Solitary pulmonary nodules, 3D, Automated

Pulmonary Parenchyma Segmentation by Watershed Transform

Lung cancer has become one of the leading causes of death in the world. Clear evidence shows that early discovery, early diagnosis and early treatment of lung cancer can significantly increase the chance of survival for patients. Lung Computer-Aided Diagnosis (CAD) is a potential method to accomplish a range of quantitative tasks such as early cancer and disease detection, In computer-aided diagnosis of lung disease, accurate and fast pulmonary parenchyma segmentation is the core step. Watershed algorithm is used in this paper to segment and extract lung parenchyma. To reduce over-segmentation, an improved watershed segmentation method which marks foreground and background is proposed. This method is based on watershed algorithm using “Sobel” operator on edge detection and then using mathematical morphology opening and closing operations and morphological reconstruction to mark the foreground. Extracting the local maximum associated with object will constitute the binary marker image. By testing different types of images, it proposes that the algorithm in this paper can be consistent with human visual characteristics and get more accurate, continuous object boundary. Compared with other watershed improvement methods, this proposed one requires less computational complexity, more simple parameters, and can effectively reduce oversegmentation.

The Clinical Outcomes of Photodynamic Therapy in Early Lung Cancer Patients

Background: Photodynamic therapy (PDT) is effective in managing small superficial early lung cancer patients who were deemed nonsurgical candidates. However, we do not have any previous report on the usefulness of PDT in early lung cancer in South Korea. Thus we report here our experience of PDT in early lung cancer patients. Methods: 10 patients who underwent PDT for managing early lung cancer between June 2006 and July 2010 were analyzed. PDT was carried out 48 hours after photosensitizer injection. Re-bronchoscopy was carried out 48 hours after PDT in order to remove a necrotic tissue from the PDT site. For evaluation of PDT response, bronchoscopy and chest computed tomography (CT) were performed after 3 months. Results: The median age of patients was 69 (49~77) and all patients were male. The smoking history of patients was 48 (20~75) pack-year and the median follow up of patients was 25 (11~52) months. Complete remission was observed in 10 patients and the recurrence of lung cancer was observed in 3 patients. Out of 10 patients, 3 patients died (one case of lung cancer progression and two cases of pneumonia). Conclusion: The PDT is a safe and effective treatment in early lung cancer patients who are not suitable for surgical resection. The PDT in clinical practice is an attractive option in the treatment of early lung cancer.

Postoperative complications and respiratory function following segmentectomy of the lung - comparison of the methods of making an inter-segmental plane

Segmentectomy could be one of the standard modes of surgery for the treatment of early lung cancer. However, segmentectomy could be more difficult than lobectomy as to the management of inter-segmental plane. The relationship between methods of dividing an inter-segmental plane and postoperative complication/pulmonary function was investigated in this study. A retrospective study was conducted on 49 patients who underwent segmentectomy of the lung between February 2008 and April 2009 at our institute. Eighteen (36.7%) were male and 31 (63.3%) were female. The inter-segmental plane was divided with only a mechanical stapler in 18 patients, and electrocautery was used in the other 31 patients. There were no significant relationships between clinicopathological features and both procedures, except gender, operative time, and pleurodesis (P<0.05). Preserved forced expiratory volume in one second (FEV(1)) was not affected by the procedures. Patients who underwent left upper division segmentectomy had significantly more complications. On multivariate analysis, resected segment and intraoperative blood loss were found to be significant predictors for postoperative complications. There were no significant relationships between the methods of making inter-segmental planes and postoperative complications and/or lung functions. Resected segment and intraoperative blood loss were predictors for postoperative complication in segmental resection of the lung.

Intratracheally Administered 5-Azacytidine Is Effective Against Orthotopic Human Lung Cancer Xenograft Models and Devoid of Important Systemic Toxicity

Introduction: Hypermethylation of key tumor suppressor genes plays an important role in lung carcinogenesis. The purpose of this study is to explore the therapeutic potential of regional administration (via the airways) of the demethylating agent 5-azacytidine (5-Aza) for the treatment of early lung cancer. Patients and MethodsWe administered 5-Aza solution directly into the trachea in imprinting control region (ICR) mice (to study its toxicity) and in nude mice bearing orthotopic human lung cancer xenografts (to assess its antitumor activity). ResultsIn vitro, 5-Aza inhibited the growth of human lung cancer cell lines H226, H358, and H460 in a dose-dependent manner. The concentrations to inhibit cell growth by 50% (IC50) were about 0.6-4.9 μg/mL. 5-Azacytidine reversed hypermethylation in the promoter of tumor suppressor gene RASSF1a in the H226 cells at a 6000-fold lower concentration than its IC50. In animal studies, intratracheal (I.T.) administration of 90 mg/kg 5-Aza (the maximum tolerated dose of 5-Aza intravenous injection [I.V.]) resulted in moderate pulmonary toxicity and 5-fold reduced myelosuppression compared with the same dose of I.V. 5-Aza. Using an optimized multiple dose schedule, I.T. 5-Aza was about 3-fold more effective than I.V. 5-Aza in prolonging the survival of mice bearing orthotopic H460 and H358 xenografts, and did not cause any detectable toxicity. Conclusion5-Azacytidine can reverse the hypermethylation in the human lung cancer cell lines at a nontoxic dose. Regional administration to the airways enhances the therapeutic index of 5-Aza by 75-fold. The potential of regional administration of 5-Aza (including by aerosolization) for the treatment of advanced bronchial premalignancy deserves further investigation.

Physician's perspectives and racial disparity in the surgical treatment of early lung cancer.

6041 Background: Racial differences in the treatment of early lung cancer continue to exist. African-Americans (AA) receive less staging (Lathan et al J Clin Onc 2006; 24:413), less surgery, and have poorer lung cancer outcomes than Caucasians. (Bach et al N Engl J Med 1999; 341:1198). Methods: 437 patients with early stage lung cancer were evaluated in five health systems in North and South Carolina before treatment recommendation with a survey including questions about trust, physician-patient communication, attitudes toward cancer, and functional status. Results: 386 patients were eligible for lung cancer surgery. Median age 66 years and 29% were AA. 66% of Caucasians (C) underwent surgery compared to 55% of AAs (p = 0.05). Surgical rates for AA patients were particularly low when 2 or more co-morbidities were present (odds ratio [OR] .04; 95% CI 0.01-0.25) compared to C (OR .45; 95% CI 0.10-2.0) and when there was no regular source of care (OR 0.20; 95% CI 0.10-0.43) compared to C (OR 1.3; 95% CI 0.32-5.3). Increased trust in physician (10 of 100 difference on Safron's Trust Scale) lowered surgical rates in AA (OR .54; 95% CI 0.35-0.85) but not C (OR 1.0; 95% CI 0.76-1.4). Conclusions: Physician perceptions of 2 or more comorbidities and a lack of regular source of care greatly lessened the use of lung cancer surgery in AAs far more than Caucasians. Higher physician trust by this AA population paradoxically lowered the rate of lung cancer surgery supporting the impact that physician perceptions of patients have in a lung cancer surgery recommendation. The racial disparity in the treatment of early lung cancer may rest in a physician's differing perceptions of similar factors in AA and Caucasian patients. No significant financial relationships to disclose.

Multimodality bronchoscopic imaging of recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP) of the central airways requires removal to potentially reduce recurrence and risk for malignant transformation. Analogous to the principles of treatment for early lung cancer, a precise determination of the extent of cartilage invasion could help guide therapeutic decisions and monitor response to treatment. The purpose of this study was to determine whether a bronchoscopy platform comprised of white light bronchoscopy (WLB), endobronchial ultrasound (EBUS), and optical coherence tomography (OCT) could identify layered microstructure of RRP and underlying cartilage. Case study. A bronchoscopy platform consisting of commercially available WLB, EBUS using a 7.5 MHz convex probe (BF-UC 160F; Olympus Optical Co. Ltd, Tokyo, Japan), and a time-domain OCT with front imaging and inside actuation (Niris Imaging System; Imalux Corp., Cleveland, OH) was used in a patient with tracheal stenosis from RRP. Findings are compared with results of histology and the characteristics of imaging modalities are discussed. WLB revealed tracheal pedunculated lesions. EBUS showed a 1-cm hypoechogenic density corresponding to the papilloma, visualized above a hyperechogenic density corresponding to tracheal cartilage. There was no sonographic evidence of cartilage disruption or adjacent lymphadenopathy. OCT revealed a layer of heterogeneous light backscattering suggesting the mucosal papilloma, and a layer of high-degree scattering, corresponding to the central fibrovascular core noted on histology. Layered microstructures of RRP and underlying airway cartilage can be identified using a combination of acoustic and optical bronchoscopic imaging modalities with different resolution and depth of penetration characteristics.

P53 Aerosol Formulation with Low Toxicity and High Efficiency for Early Lung Cancer Treatment

To develop an optimal nonviral aerosol formulation for locoregional treatment of early lung cancer. The formulation was made of polylysine/protamine combination (AND) as the carrier and p53 gene (p53sm) as therapeutic agent. To estimate the aerosol deposition, the aerodynamic size of the AND-p53sm was measured with extrusion-precipitation method. To accurately determine the dose, the aerosol efficiency in mice was measured with a fluorescent dye. The transfection efficiency and DNA protection function of the aerosolized formulation in cultured cells and mouse lungs were detected with reporter gene assays and/or reverse transcription-PCR. The preclinical safety and efficacy of AND-p53sm were studied in healthy mice and mice bearing orthotopic human non-small-cell lung cancer (NSCLC) xenograft. After aerosolization, AND is 3- to 17-fold more effective than commonly used PEI or cationic lipid formulations in transfecting the NSCLC cells (relative light units, 1,494 versus 534 and 86; P < 0.003). Aerodynamic size of AND-p53sm ranged 0.2 to 3 mum is the optimal aerosol droplets for deposition in the entire human respiratory tract. Significant gene expression was detected in the lungs of mice given aerosolized AND-p53sm and AND-luciferase. Aerosolized AND-p53sm significantly prolonged the life of mice bearing orthotopic human NSCLC xenografts, and it was more effective than an optimal i.v. cisplatin chemotherapy (increased life span, 93% versus 25%; P = 0.014). Inhalation of AND produced low and reversible pulmonary toxicity and no systemic toxicity. This optimal formulation is suitable for delivering biological materials to human lung with aerosol administration. This therapeutic strategy is an option for patients with early lung cancer and bronchoalveolar carcinoma.

Predictive value of image cytometry for diagnosis of lung cancer in heavy smokers

The Research Institute for Diagnosis and Treatment of Early Lung Cancer (RIDTELC) Lung Study was initiated to determine whether lung cancer screening by automated sputum cytometry combined with conventional sputum cytology and auto-fluorescence in addition to white light bronchoscopy could enhance the detection rate of early lung cancer. The present study analyses the initial findings to evaluate the efficiency of automated sputum cytology in predicting the diagnosis of lung cancer. In this study, malignancy grade was used as a predictive parameter for lung cancer. In total, 2,480 heavy smokers (>30 pack-yrs), aged 50-74 yrs, with no previous cancer in the last 5 yrs, received chest radiology, conventional sputum cytology and sputum cytometry screening. In total, twenty-seven lung cancers were diagnosed, representing a prevalence of 1.1%, 25 of which provided sputum samples. Positive automated sputum cytology results were seen in 176 smokers (7.2%), 10 (0.4%) of whom had severe dysplasia or higher lesions (positive results) by conventional sputum cytology examination. Out of 25 tumour cases, 20 had suspicious results using automated sputum cytology, representing 80% sensitivity. One patient out of 24 with tumours had positive results on conventional sputum cytology, representing a sensitivity of 4.2%. For all stages of squamous cell lung cancer and later stage adenocarcinoma the sensitivity of automated sputum cytology was 100%. For adenocarcinoma stage I sensitivity was 25%. In conclusion, DNA analysis of sputum slides by automated sputum cytology may be a suitable tool for the detection of early lung cancer and the characterisation of a high-risk group with pre-invasive lesions for follow-up.

Photodynamic Therapy (PDT) can induce airway scarring and stenosis

PURPOSE: PDT is the most extensively studied endobronchial treatment for early lung cancer in patients who are not candidates for surgical resection. Potential advantages of this localized therapeutical modality relative to other techniques include tumor selectivity and complete healing of the bronchial mucosa after illumination. However, some observations suggest that complete healing is not always present, and we reviewed our own experience with this treatment.

Diagnosis and Treatment of Early Lung Cancer: As It Stands Today

Treatment of "early" stage lung cancer should offer the patient the best chance for cure. Disease-free survival after surgical resection of lung carcinoma in situ has been reported as over 90%. For "microinvasive" lung cancer it may be similar. After resection of stage IA non-small cell lung cancer, survival at 5 years is approximately 60 to 70%. If endoscopic or bronchoscopic treatments of early stage lung cancer can offer similar disease-free survival with less perioperative mortality, morbidity, and cost, then they may be alternative front-line therapies. Regardless of therapeutic choice, the initial hurdle is developing a practical detection method for early stage disease. This article reviews early stage lung cancer detection by fluorescence bronchoscopy and potential treatment by the endoscopic techniques of photodynamic therapy, brachytherapy, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, electrocautery, and cryotherapy.

Role of biomarkers for early detection of lung cancer and chemoprevention.

Lung cancer is the leading cause of cancer deaths in developed countries. The poor prognosis associated with this disease is closely related to the fact that most lung cancer patients are not identified until their malignancy has reached an advanced stage. Recent advances have added to the understanding of the morphological and molecular characteristics of preinvasive bronchial lesions and early lung cancers. Such information is being used to provide new tests for the detection of lung cancer at early or preinvasive stages, and for identifying targets for therapeutic intervention that can prevent progression to advanced disease. Laser induced fluorescence endoscope bronchoscopy has improved the sensitivity with which preinvasive dysplastic bronchial lesions and early invasive malignancies can be detected. Morphological features of such lesions have been described and can be monitored by follow-up bronchoscopies in order to validate potential chemoprevention treatments. Distinct morphological characteristics such as angiogenic squamous dysplasia also suggest that processes like angiogenesis are present early in the development of lung cancer. Furthermore, tissue obtained from these early lesions has been used to describe alterations in the expression of a number of factors that distinguish these early lesions from normal bronchial epithelium. This could provide molecular markers and targets for the detection and treatment of early lung cancer. Studies to detect these alterations by polymerase chain reaction and/or immunhistochemical analyses of easily obtained specimens such as sputa are helping identifing molecular markers that could be utilized in effective screening programmes. The current article reviews new findings regarding the molecular biology of preinvasive bronchial lesions and early lung cancers, and describes new developments regarding their application in the early detection and chemoprevention of lung cancer.

How Golden is the Gold Standard?

RIDTELC™ (Research Institute for Diagnosis and Treatment of Early Lung Cancer), Augusta Teaching Hospital, Bochum, Germany. Address reprint requests to Dr. Barbara Khanavkar, Research Institute for Diagnosis and Treatment of Early Lung Cancer, Augusta Teaching Hospital, Bergstr. 26, D44791, Bochum, Germany.

S1-4 Photodynamic Therapy as Alternative to the Early Treatment of Lung Cancer

S1-4 Photodynamic Therapy as Alternative to the Early Treatment of Lung Cancer

Nonexperimental Evaluation of the Effectiveness of a Screening Program for Lung Cancer

The effectiveness of screening to control lung cancer was examined in the German Democratic Republic by analyzing data from a cancer registry and incidence and mortality rates for lung cancer relative to different screening policies, and by two case-control studies. Mortality from lung cancer did not appear to be affected by the screening programs studied. The high cost of mass screening, combined with uncertainty about the benefits of early treatment of lung cancer, outweigh the vague advantages of such screening.

肺門部早期肺癌の発見と治療

肺門部早期肺癌の発見と治療

The detection and treatment of early lung cancer.

The detection and treatment of early lung cancer.