Monday, April 25, 2011

From BMC: more about physician-patient communication

BMC Med Ethics. 2011 Apr 21;12(1):7. [Epub ahead of print]
Physicians' explanatory behaviours and legal liability in decided medical malpractice litigation cases in Japan.
Hamasaki T, Hagihara A.

A physician's duty to provide an adequate explanation to the patient is derived from the doctrine of informed consent and the physician's duty of disclosure. However, findings are extremely limited with respect to physicians' specific explanatory behaviours and what might be regarded as a breach of the physicians' duty to explain in an actual medical setting. This study sought to identify physicians' explanatory behaviours that may be related to the physicians' legal liability.

We analysed legal decisions of medical malpractice cases between 1990 and 2009 in which the pivotal issue was the physician's duty to explain (366 cases). To identify factors related to the breach of the physician's duty to explain, an analysis was undertaken based on acknowledged breaches with regard to the physician's duty to explain to the patient according to court decisions. Additionally, to identify predictors of physicians' behaviours in breach of the duty to explain, logistic regression analysis was performed.

When the physician's explanation was given before treatment or surgery (p = 0.006), when it was relevant or specific (p = 0.000), and when the patient's consent was obtained (p = 0.002), the explanation was less likely to be deemed inadequate or a breach of the physician's duty to explain. Patient factors related to physicians' legally problematic explanations were patient age and gender. One physician factor was related to legally problematic physician explanations, namely the number of physicians involved in the patient's treatment.

These findings may be useful in improving physician-patient communication in the medical setting.

Academic medicine and comparative effectiveness research

Acad Med. 2011 Apr 20. [Epub ahead of print]
The Implications of Comparative Effectiveness Research for Academic Medicine.
Rich EC, Bonham AC, Kirch DG.
Dr. Rich is director, Center on Health Care Effectiveness, Mathematica Policy Research, Washington, DC. Dr. Bonham is chief science officer, Association of American Medical Colleges, Washington, DC. Dr. Kirch is president and CEO, Association of American Medical Colleges, Washington, DC.
With growing constraints on government spending, policy makers are investing in comparative effectiveness research (CER) to attempt to bring the power of science to bear on the problems of suboptimal outcomes and high cost in the U.S. health care system. This commitment of resources to CER reflects confidence that better evidence can help clinicians and patients make better decisions, consistent with the long tradition of medical schools' and teaching hospitals' use of science to inform medical care. Thus, CER offers a great opportunity, albeit with some considerable challenges, for academic medicine to play a central role in comprehensive health care reform. Certainly, many scientists conducting CER will learn their methodological rigor in the training programs of academic health centers. Numerous new CER research teams will be needed, establishing effective partnerships far outside the walls of the traditional academic setting. And the clinicians interpreting the medical literature and applying the insights from CER to the unique problems of individual patients will need to learn this evidence-based, patient-centered care from the educators, mentors, and role models at U.S. medical and other health science schools and teaching hospitals. Achieving this will require investment in research infrastructure, adaptations of institutional culture, development of new disciplines and research methods, establishment of new collaborations, training of new faculty, and the expansion and refocusing of educational capacity. By successfully responding to this challenge, academic medicine can further strengthen its long-standing commitment to the scientific practice of medicine and the use of evidence in patient-centered, personalized care.

Lymphatic involvement in early lung cancer

Ann Surg Oncol. 2011 Apr 22. [Epub ahead of print]
Lymphatic Vessel Invasion is a Significant Prognostic Indicator in Stage IA Lung Adenocarcinoma.
Funai K, Sugimura H, Morita T, Shundo Y, Shimizu K, Shiiya N.
First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan,
A radical resection is considered to be the most effective treatment for resectable non-small cell lung cancer. However, even when resected in early stages (T1aN0, T1bN0) up to 20% of patients will experience recurrence. The aim of this retrospective study was to evaluate the prognostic influence of lymphatic vessel invasion (LVI) in stage IA adenocarcinoma patients.

From January 1983 to June 2003, a total of 229 consecutive patients with pT1a or T1b N0 M0 lung adenocarcinoma who had undergone radical resection and lymph node dissection were retrospectively reviewed. Sections stained by the hematoxylin-eosin and the Elastica van Gieson method were examined for the presence of LVI. The overall survival was estimated using the Kaplan-Meier method, log-rank test, and the Cox proportional hazards analysis.

The median follow-up was 81 months. A total of 143 patients (62%) were able to be diagnosed with regard to the presence of LVI, while information was not provided for 86 patients (38%), who were therefore excluded from the study. LVI was noted in 22 of the evaluable patients (15%) and was not seen in the other 121 patients (85%). The 5-year overall survival rate of the LVI-negative group and the LVI-positive group was 94.5 and 70.9%, respectively (P = .003). A multivariate analysis revealed LVI to be an independent predictive factor (hazard ratio: 0.202; P = .001).

LVI is an independent poor prognostic factor in patients with pathologic stage IA adenocarcinoma. The T1a and T1b patients with LVI both might benefit from adjuvant chemotherapy.

Friday, April 22, 2011

From UNC: Global obesity and women's health

Obstet Gynecol. 2011 May;117(5):1213-22.
Global Obesity and the Effect on Women's Health.
Chescheir NC.

From the University of North Carolina, Department of Obstetrics and Gynecology, Chapel Hill, North Carolina.

The rates of obesity are increasing in all areas of the world. The pattern of diseases in many areas of the world is shifting rapidly to diseases that are chronic and noncommunicable. These changes are occurring so rapidly that existing health care infrastructure in many parts of the world are likely to be stressed. Many aspects of women's health will be worsened as they become more obese. Coordinated efforts to reverse the obesity trend are being made and individuals and teams working within women's health globally should coordinate with existing efforts to provide data and consistent messages.

From Harvard: Physician emapthy

Otolaryngol Head Neck Surg. 2011 Jan;144(1):120-2.
Improving empathy and relational skills in otolaryngology residents: a pilot study.
Riess H, Kelley JM, Bailey R, Konowitz PM, Gray ST.

Psychiatry Department, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.

Physician empathy and relational skills are critical factors predicting quality of care, patient safety, patient satisfaction, and decreasing malpractice claims. Studies indicate that physician empathy declines throughout medical training, yet little is published about methods to enhance empathy, especially in surgical residency training. The Accreditation Council for Graduate Medical Education requires competencies in 6 areas, including interpersonal skills and communication. To address this important problem, the first author developed an innovative empathy-relational skills training protocol focusing on the underlying neurobiological mechanisms of empathy and the interpersonal processes that positively affect the patient-doctor relationship. The authors tested the effectiveness of this protocol in a pilot study with 11 otolaryngology residents. Results showed that a brief series of 3 empathy training sessions can significantly improve physicians' knowledge of the neurobiology and physiology of empathy, as well as their self-reported capacity to empathize with patients. A trend toward increased patient satisfaction was observed.

From NEJM: Hard choices indeed

N Engl J Med. 2011 Apr 20. [Epub ahead of print]
Hard Choices - Alternatives for Reining in Medicare and Medicaid Spending.
Rosenthal MB.
From the Department of Health Policy and Management, Harvard School of Public Health, Boston.
The U.S. national debt looms like a black cloud on the horizon, and Medicare and Medicaid, which account for about 20% of the federal budget, are responsible for a disproportionate share of projected growth in federal spending. During the past several months, the debate over how to control this growth has intensified, and alternative blueprints for reform have emerged.(1),(2) The two most prominent proposals have been put forward by Congressman Paul Ryan (R-WI), chair of the House Budget Committee, and the White House (see table). Medicare and Medicaid must be key to any deficit-reduction plan, since their growth outpaces . . .

From MD Anderson: PET/CT's utility in lung cancer patients

J Thorac Imaging. 2011 May;26(2):132-46.
Positron emission tomography/computed tomography in lung cancer staging, prognosis, and assessment of therapeutic response.

Truong MT, Viswanathan C, Erasmus JJ.

Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston, TX.

Positron emission tomography (PET)/computed tomographic scanning, using 18F-2-deoxy-D-glucose, complements conventional imaging evaluation of patients with lung cancer. The strength of PET scanning lies in the detection of nodal and extrathoracic metastases. PET scanning is also currently being studied in the assessment of prognosis and therapeutic response and has the potential to alter management of oncologic patients. This review will discuss the role of PET/computed tomographic scanning in the diagnosis, staging, and evaluation of prognosis and treatment response in patients with lung cancer.

From Mass General: Ablative therapies for lung cancer

J Thorac Imaging. 2011 May;26(2):162-74.
How I do it: radiofrequency ablation and cryoablation of lung tumors.
Sharma A, Moore WH, Lanuti M, Shepard JA.

Departments of *Radiology †Stony Brook University Medical Center, Stony Brook, NY ‡Thoracic Surgery, Massachusetts General Hospital, Boston, MA.

Lung cancer is the most common cause of death in adults. The treatment of choice is surgical resection with lobectomy, but a significant number of patients are non-surgical candidates due to comorbidities or limited pulmonary reserve. Patients may also have recurrent disease after resection or radiotherapy. Image ablation has recently been introduced as a safe, alternative treatment for localized disease in carefully selected patients. This article discusses the principles, technique, and follow-up of the 2 main ablative therapies currently used in the lung, radiofrequency ablation and cryoablation.

CDC on state smoke-free laws

MMWR Morb Mortal Wkly Rep. 2011 Apr 22;60(15):472-5.
State smoke-free laws for worksites, restaurants, and bars --- United States, 2000--2010.
Centers for Disease Control and Prevention (CDC).

Secondhand smoke (SHS) exposure causes lung cancer and cardiovascular and respiratory diseases in nonsmoking adults and children, resulting in an estimated 46,000 heart disease deaths and 3,400 lung cancer deaths among U.S. nonsmoking adults each year. Smoke-free laws that prohibit smoking in all indoor areas of a venue fully protect nonsmokers from involuntary exposure to SHS indoors. A Healthy People 2010 objective (27-13) called for enacting laws eliminating smoking in public places and worksites in all 50 states and the District of Columbia (DC); because this objective was not met by 2010, it was retained for Healthy People 2020 (renumbered as TU-13). To assess progress toward meeting this objective, CDC reviewed state laws restricting smoking in effect as of December 31, 2010. This report summarizes the changes in state smoking restrictions for private-sector worksites, restaurants, and bars that occurred from December 31, 2000 to December 31, 2010. The number of states (including DC) with laws that prohibit smoking in indoor areas of worksites, restaurants, and bars increased from zero in 2000 to 26 in 2010. However, regional disparities remain in policy adoption, with no southern state having adopted a smoke-free law that prohibits smoking in all three venues. The Healthy People 2020 target on this topic is achievable if current activity in smoke-free policy adoption is sustained nationally and intensified in certain regions, particularly the South.

From Yale: Evaluation of patients with interstitial lung disease

Prim Care Respir J. 2011 Apr 20. pii: pcrj-2010-07-0078. doi: 10.4104/pcrj.2010.00079. [Epub ahead of print]
Diagnostic assessment of patients with interstitial lung disease.
Gulati M.

Department of Pulmonary & Critical Care, Yale University School of Medicine, New Haven, Connecticut, USA.

The diagnosis of interstitial lung disease (ILD) is frequently delayed because clinical clues are neglected and respiratory symptoms are ascribed to more common pulmonary diagnoses such as chronic obstructive pulmonary disease (COPD) in the primary care setting. While ILD cases ultimately require referral to a pulmonologist, general practitioners can play a crucial role in recognising the need for, and initiating, a diagnostic evaluation. An initial assessment hinges upon a structured history and physical examination with careful attention paid to occupational, environmental and drug exposures as well as a history of symptoms suggesting connective tissue disease. Ultimately a surgical lung biopsy may be indicated, but high resolution computed tomography (HRCT) chest scans are essential to the diagnostic workup since each ILD form is characterised by a specific pattern of abnormalities.

Cancer-related chronic pain: As cancer patients do better, this becomes increasingly important

Cancer. 2011 May 1;117(9):1994-2003. doi: 10.1002/cncr.25761. Epub 2010 Nov 18.
Cancer-related chronic pain: Examining quality of life in diverse cancer survivors.
Green CR, Hart-Johnson T, Loeffler DR.

Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan; Department of Health Management and Policy, University of Michigan, Ann Arbor, Michigan.

Disparities in cancer survival and pain rates negatively impact quality of life (QOL). This study examines cancer-related chronic pain (CP) and its impact on QOL in diverse cancer survivors.

This survey study focused on current and past pain, health, and QOL in black and white cancer survivors. Participants with breast, colorectal, lung, and prostate cancer and multiple myeloma were recruited through the Michigan State Cancer Registry. Analysis of variance was used to examine outcome differences by pain status, race, and sex. Hierarchical regressions explored predictors for experiencing pain.

The subjects (N = 199) were 31% black, 49% female, and 57 to 79 years old; 19.5% experienced current pain, and 42.6% reported pain since diagnosis. Women experience more pain (P < .001) and greater pain severity (P = .04) than men. Blacks experienced more pain interference and disability (P < .05). Experiencing pain is related to greater depressive symptoms, poorer functioning, and more symptoms. In hierarchical regressions, female sex predicted pain since diagnosis; pain severity for pain since diagnosis was predicted by black race and female sex.

The authors extend the literature by showing that 20% of diverse cancer survivors had cancer-related CP, and 43% had experienced pain since diagnosis, revealing racial and sex disparities in cancer-related CP's incidence and impact on QOL. Having pain was related to poorer QOL in several domains and was more frequently experienced by women. Although black race was not related to pain prevalence, it was related to greater severity. This study reveals an unaddressed cancer survivorship research, clinical, and policy issue. Cancer 2011. © 2010 American Cancer Society.

Thursday, April 21, 2011

From Bryan Liang: More about direct to consumer medical advertising

JAMA. 2011 Feb 23;305(8):824-5.
Direct-to-consumer advertising with interactive internet media: global regulation and public health issues.
Liang BA, Mackey T.
Institute of Health Law Studies, California Western School of Law, 350 Cedar St, San Diego, CA 92101, USA.
PMID: 21343583 [PubMed - indexed for MEDLINE]

Friday, April 15, 2011

Pulmonary Langerhans cell histiocytosis

Eur Radiol. 2011 Feb 11. [Epub ahead of print]
Pulmonary langerhans cell histiocytosis in adults: high-resolution CT-pathology comparisons and evolutional changes at CT.
Kim HJ, Lee KS, Johkoh T, Tomiyama N, Lee HY, Han J, Kim TS.

Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea.
OBJECTIVE: To compare high-resolution (HR) CT and histopathological findings and to evaluate serial CT findings in pulmonary Langerhans cell histiocytosis (PLCH).

METHODS: We reviewed CT of lung lesions in 27 adults (M:F = 20:7, mean age, 41 ± 12.3 years) with PLCH. After evaluating lung abnormalities including nodules, micronodules, thick-walled, thin-walled, and bizarre-shaped cysts and reticulation, observers compared CT findings obtained at lung biopsy sites with histopathological findings. The final CT was compared with the initial CT to determine disease extent changes.

RESULTS: The most frequently observed patterns of lung abnormalities were micronodules (n = 24, 89%), thick-walled (n = 22, 82%), and thin-walled (n = 22, 82%) cysts. Even thin-walled and bizarre cysts harboured active inflammatory Langerhans cell sheets and eosinophils in their walls. In thin-walled cysts, we noted pericystic inflammatory cell infiltrations along the alveolar walls, as well as pericystic emphysema. Thin-walled or bizarre cysts demonstrated a tendency to coalesce with surrounding cysts via their cystic wall destruction. Fourteen (52%) patients showed improvement and nine (33%) showed progressing disease.

CONCLUSION: More than half of patients with pulmonary PLCH show improvement at follow-up CT. Even thin-walled cysts harbour active inflammatory cells on histopathology and exhibit improvement at follow-up CT.

Health care reform: Lessons from Massachusetts

Mark Health Serv. 2011 Winter;31(1):7-9.
Health care reform 1.0. Lessons learned from Massachusetts' health care reform.
Gordon D.

Network Health, Medford, MA, USA.
PMID: 21473499 [PubMed - in process]

The future of health care: patient-centered, integrated

Issue Brief (Commonw Fund). 2011 Apr;6:1-23.
A call for change: the 2011 Commonwealth Fund Survey of Public Views of the U.S. Health System.
Stremikis K, Schoen C, Fryer AK.

The Commonwealth Fund, USA.
More than seven of 10 adults believe the U.S. health system needs fundamental change or complete rebuilding. Most adults surveyed reported difficulties accessing care, poor care coordination, and struggles with the costs and administrative hassles of health insurance. In addition, the survey finds substantial evidence of inefficient and wasteful delivery of health services. When looking toward the future, nearly three of four adults worry about getting high-quality care or paying medical bills. Respondents favor policies that encourage more patient-centered and integrated care, and nearly nine of 10 think it is important for private and public payers to work together to negotiate prices and improve quality. These experiences attest to the value of reforms aimed at stimulating and supporting the spread of more patient-centered, accountable care organizations. To the extent reforms succeed, patients and their families stand to gain from more accessible, safer, responsive, and less wasteful care.

Medical tourism: Continuing to mature as an option

J Med Ethics. 2011 Apr 8. [Epub ahead of print]
The 'patient's physician one-step removed': the evolving roles of medical tourism facilitators.
Snyder J, Crooks VA, Adams K, Kingsbury P, Johnston R.

Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
Background Medical tourism involves patients travelling internationally to receive medical services. This practice raises a range of ethical issues, including potential harms to the patient's home and destination country and risks to the patient's own health. Medical tourists often engage the services of a facilitator who may book travel and accommodation and link the patient with a hospital abroad. Facilitators have the potential to exacerbate or mitigate the ethical concerns associated with medical tourism, but their roles are poorly understood. Methods 12 facilitators were interviewed from 10 Canadian medical tourism companies. Results Three themes were identified: facilitators' roles towards the patient, health system and medical tourism industry. Facilitators' roles towards the patient were typically described in terms of advocacy and the provision of information, but limited by facilitators' legal liability. Facilitators felt they played a positive role in the lives of their patients and the Canadian health system and served as catalysts for reform, although they noted an adversarial relationship with some Canadian physicians. Many facilitators described personally visiting medical tourism sites and forming personal relationships with surgeons abroad, but noted the need for greater regulation of their industry. Conclusion Facilitators play a substantial and evolving role in the practice of medical tourism and may be entering a period of professionalisation. Because of the key role of facilitators in determining the effects of medical tourism on patients and public health, this paper recommends a planned conversation between medical tourism stakeholders to define and shape facilitators' roles.

Diabetic Neuropathy: Potential for molecular-based therapy

Proteomics Clin Appl. 2011 Mar 11. doi: 10.1002/prca.201000136. [Epub ahead of print]
Mapping of molecular pathways, biomarkers and drug targets for diabetic nephropathy.
Fechete R, Heinzel A, Perco P, Mönks K, Söllner J, Stelzer G, Eder S, Lancet D, Oberbauer R, Mayer G, Mayer B.

emergentec biodevelopment GmbH, Vienna, Austria.
Purpose: For diseases with complex phenotype such as diabetic nephropathy (DN), integration of multiple Omics sources promises an improved description of the disease pathophysiology, being the basis for novel diagnostics and therapy, but equally important personalization aspects. Experimental design: Molecular features on DN were retrieved from public domain Omics studies and by mining scientific literature, patent text and clinical trial specifications. Molecular feature sets were consolidated on a human protein interaction network and interpreted on the level of molecular pathways in the light of the pathophysiology of the disease and its clinical context defined as associated biomarkers and drug targets. Results: About 1000 gene symbols each could be assigned to the pathophysiological description of DN and to the clinical context. Direct feature comparison showed minor overlap, whereas on the level of molecular pathways, the complement and coagulation cascade, PPAR signaling, and the renin-angiotensin system linked the disease descriptor space with biomarkers and targets. Conclusion and clinical relevance: Only the combined molecular feature landscapes closely reflect the clinical implications of DN in the context of hypertension and diabetes. Omics data integration on the level of interaction networks furthermore provides a platform for identification of pathway-specific biomarkers and therapy options.

Cystic Fibrosis: Ceramides and possible new treatements

J Lipids. 2011;2011:674968. Epub 2010 Dec 28.
Ceramide in Cystic Fibrosis: A Potential New Target for Therapeutic Intervention.
Wojewodka G, De Sanctis JB, Radzioch D.

Human Genetics, McGill University Health Center Research Institute, 1650 Cedar Avenue L11-218, Montreal, QC, Canada H3G 1A4.
Patients with cystic fibrosis (CF) are afflicted with many symptoms but the greatest challenge is the fight against chronic bacterial infections, leading to decreased lung function and ultimately death. Our group has recently found reduced levels of ceramides in CF patients and mice. Ceramides are sphingolipids involved in the structure of cell membranes but also participate in the inflammatory response, in cell signalling through membrane microdomains (lipid rafts), and in apoptosis. These characteristics of ceramides make them strong candidates for therapeutic intervention in CF. As more studies have come to evaluate the role of ceramide in CF, conflicting results have been described. This paper discusses various views regarding the potential role of ceramide in CF, summarizes methods of ceramide detection and their role in the regulation of cellular and molecular processes.

Med mal risk after Texas tort reform

J Am Coll Surg. 2011 Apr;212(4):463-467.e42.
Malpractice risk and cost are significantly reduced after tort reform.
Stewart RM, Geoghegan K, Myers JG, Sirinek KR, Corneille MG, Mueller D, Dent DL, Wolf SE, Pruitt BA Jr.

Department of Surgery, University of Texas Health Science Center at San Antonio, and University Hospital, San Antonio, TX.
BACKGROUND: Rising medical malpractice premiums have reached a crisis point in many areas of the United States. In 2003 the Texas legislature passed a comprehensive package of tort reform laws that included a cap at $250,000 on noneconomic damages in most medical malpractice cases. We hypothesized that tort reform laws significantly reduce the risk of malpractice lawsuit in an academic medical center. We compared malpractice prevalence, incidence, and liability costs before and after comprehensive state tort reform measures were implemented.

STUDY DESIGN: Two prospectively maintained institutional databases were used to calculate and characterize malpractice risk: a surgical operation database and a risk management and malpractice database. Risk groups were divided into pretort reform (1992 to 2004) and post-tort reform groups (2004 to the present). Operative procedures were included for elective, urgent, and emergency general surgery procedures.

RESULTS: During the study period, 98,513 general surgical procedures were performed. A total of 28 lawsuits (25 pre-reform, 3 postreform) were filed, naming general surgery faculty or residents. The prevalence of lawsuits filed/100,000 procedures performed is as follows: before reform, 40 lawsuits/100,000 procedures, and after reform, 8 lawsuits/100,000 procedures (p < 0.01, relative risk 0.21 [95% CI 0.063 to 0.62]). Virtually all of the liability and defense cost was in the pretort reform period: $595,000/year versus $515/year in the postreform group (p < 0.01).

CONCLUSIONS: Implementation of comprehensive tort reform in Texas was associated with a significant decrease in the prevalence and cost of surgical malpractice lawsuits at one academic medical center.

From MD Anderson: Nanocarriers!

J Drug Deliv. 2011;2011:465845. Epub 2011 Jan 24.
Tumor Suppressor Gene-Based Nanotherapy: From Test Tube to the Clinic.
Shanker M, Jin J, Branch CD, Miyamoto S, Grimm EA, Roth JA, Ramesh R.

Department of Thoracic and Cardiovascular Surgery, The University of Texas of MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.

From Tours, France: Molecular therapy for lung cancer via the airways

Pharm Res. 2011 Apr 14. [Epub ahead of print]
The Airways, a Novel Route for Delivering Monoclonal Antibodies to Treat Lung Tumors.
Maillet A, Guilleminault L, Lemarié E, Lerondel S, Azzopardi N, Montharu J, Congy-Jolivet N, Reverdiau P, Legrain B, Parent C, Douvin DH, Hureaux J, Courty Y, De Monte M, Diot P, Paintaud G, Le Pape A, Watier H, Heuzé-Vourc'h N.

INSERM U618, Université François Rabelais de Tours, Tours, France.
PURPOSE: Lung cancer is the leading cause of cancer-related death worldwide. The efficacy of current systemic treatments is limited, with major side effects and only modest survival improvements. Aerosols routinely used to deliver drugs into the lung for treating infectious and inflammatory lung diseases have never been used to deliver monoclonal antibodies to treat lung cancer. We have shown that cetuximab, a chimeric anticancer anti-EGFR mAb, is suitable for airway delivery as it resists the physical constraints of aerosolization, and have evaluated the aerosol delivery of cetuximab in vivo.

METHODS: We developed an animal model of lung tumor sensitive to cetuximab by injecting Balb/c Nude mice intratracheally with A431 cells plus 10 mM EDTA and analyzed the distribution, pharmacokinetics and antitumor efficacy of cetuximab aerosolized into the respiratory tract.

RESULTS: Aerosolized IgG accumulated durably in the lungs and the tumor, but passed poorly and slowly into the systemic circulation. Aerosolized cetuximab also limited the growth of the mouse tumor. Thus, administering anticancer mAbs via the airways is effective and may limit systemic side effects.

CONCLUSION: Delivery of aerosolized-mAbs via the airways deserves further evaluation for treating lung cancers.

From Zurich: Screening for lung cancer

Swiss Med Wkly. 2011 Apr 13;141:w13185. doi: 10.4414/smw.2011.13185.
Lung cancer screening has the potential to safe lives, but shall we do it?
Russi EW.

Klinik für Pneumologie, Universitätsspital Zürich, Rämistrasse 100, 8091 Zürich, CH.
Almost three decades ago several controlled studies failed to show that lung cancer screening by chest x-ray (CXR) and sputum cytology improves survival in a screened population. A number of subsequent studies using chest computed tomography (CT) in smokers revealed lesions suspect for cancer in around 20% and had a lung cancer detection rate of approx. 1%. Since these trials lacked a control arm, the question whether screening has an impact on lung cancer mortality remained unproven. Recently, the preliminary results of the randomised controlled National Lung Screening Trial (NLST), a study organised by the US National Cancer Institute, confirmed for the first time that lung cancer screening by CT is associated with a reduction in lung cancer mortality (20.3%) and in all-cause mortality (7%) compared with a control group undergoing CXR at the same time intervals. However, before lung cancer CT screening can be recommended, many open questions need to be answered with respect to costs and reimbursement, duration of an appropriate screening programme and its psychological impact.

Tuesday, April 12, 2011

From London's Royal Brompton Hospital: Cystic fibrosis and inhaled dry powder mannitol

Eur Respir J. 2011 Apr 8. [Epub ahead of print]
Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study.
Bilton D, Robinson P, Cooper P, Gallagher CG, Kolbe J, Fox H, Jaques A, Charlton B.

* Royal Brompton Hospital London United Kingdom.
This international phase III study of inhaled dry powder mannitol was a randomised double blind 26 week study, followed by a further 26 week open-label extension. 324 subjects were randomised 3:2 to mannitol (400 mg bid) or control. The primary efficacy endpoint was to determine the change in FEV1 over the double-blind phase. Secondary endpoints included changes in FVC and pulmonary exacerbations. A significant improvement in FEV1 was seen over 26 weeks (p<0.001) and was apparent by 6 weeks irrespective of concomitant rhDNase use. At 26 weeks, there was a significant improvement of 92.9 mL in FEV1 for subjects receiving mannitol compared with control (change from baseline 118.9 mL [6.5%] vs. 26.0 mL [2.4%]; p<0.001). Improvements in FEV1 were maintained up to 52 weeks in the open-label part of the study. There was a 35.4% reduction in the incidence of having an exacerbation on mannitol (p=0.045). The incidence of adverse events (AE) was similar in both groups, though treatment related AEs were higher in the mannitol compared to the control group. The most common mannitol related AEs were cough, haemoptysis and pharyngolaryngeal pain. Mannitol shows sustained, clinically meaningful benefit in airway function in CF, irrespective of concomitant rhDNase use. Mannitol appears to have an acceptable safety profile for patients with CF.

From Mass General: ALK and targeted lung cancer threrapy

Clin Adv Hematol Oncol. 2011 Mar;9(3):207-14.
New Targets in Advanced NSCLC: EML4-ALK.
Crystal AS, Shaw AT.

Massachusetts General Hospital Cancer Center Center, Boston, MA 02114, USA.
Targeted therapies aimed at inhibiting oncogenic tyrosine kinases are becoming commonplace in the treatment of cancer. The EML4-ALK fusion gene was first identified as a potentially targetable oncogenic driver in non-small cell lung cancer in 2007. A small molecule ALK inhibitor, crizotinib, may now be on the verge of approval by the US Food and Drug Administration for the treatment of ALK-rearranged lung cancer. Here we review the discovery of EML4-ALK, the development of clinical diagnostics for ALK rearrangements, the clinical epidemiology of lung cancers driven by EML4-ALK, and ongoing ALK inhibitor-based clinical trials.

Sarcopenia and cancer-related fatigue

J Cachex Sarcopenia Muscle. 2010 Dec;1(2):177-185. Epub 2010 Dec 17.
Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer.
Kilgour RD, Vigano A, Trutschnigg B, Hornby L, Lucar E, Bacon SL, Morais JA.

BACKGROUND: Although exertional fatigue is directly and negatively related to skeletal muscle mass and strength, it is currently unknown if these variables are associated with cancer-related fatigue (CRF). Therefore, the purpose of this study was to determine if CRF is associated with measures of appendicular lean muscle mass and strength in advanced cancer patients (ACP).

METHODS AND RESULTS: Eighty-four patients (48 men, 36 women aged 61.6 ± 13.2 year) newly diagnosed (≤6 months) with inoperable (Stages III-IV) gastrointestinal or non-small cell lung cancer participated in this study. All patients completed the Brief Fatigue Inventory (BFI). Handgrip (HGS) and quadriceps (QS) strength were assessed using isometric and isokinetic dynamometry, respectively. Skeletal muscle mass index (SMMI) was calculated from the appendicular lean mass measured via dual-energy X-ray absorptiometry divided by body height squared. Univariate analysis showed BFI to be significantly associated with body mass index, weight loss, anemia, hypoalbuminemia, activity level, pain, depression, and sarcopenia along with SMMI, HGS, and QS. HGS (r = -0.34; p = 0.018), QS (r = -0.39; p = 0.024), and SMMI (r = -0.60; p < 0.001) were negatively correlated with BFI total scores in men but not in women. When adjusted for sex, age, diagnosis, survival, along with the above characteristics, multivariate analyses showed that BFI scores were negatively associated with HGS (B = -0.90; 95% CI -1.5:-0.3), QS (-0.2; -0.3:-0.01), and SMMI (-7.5; -13.0:-2.0). There was a significant sex × SMMI interaction (10.8; 1.2:20.5), where BFI decreased with increasing SMMI in men, but did not change with SMMI in women.

CONCLUSION: These results suggest that in ACP, CRF is related to muscle mass and strength, which may provide targets for future interventions.

From Memorial Sloan Kettering: Pleural anatomy

Thorac Surg Clin. 2011 May;21(2):157-163.
Anatomy of the Pleura.
Finley DJ, Rusch VW.

Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
The pleura is a monolayer of mesothelial cells covering the lung and inner surface of the chest cavity, creating the pleural space. The mesothelial cells rest on a matrix of collagen, elastic fibers, blood vessels, and lymphatics, which allow the lung and chest to expand and contract, protected from friction by the pleural fluid and properties of the mesothelial cells. With a rich blood supply and lymphatic system just deep to the mesothelial layer, the pleura is a dynamic layer protecting the lung and pleural cavity from infection while transmitting the forces of respiration without damage to the underlying lung parenchyma.

From Duke: Pulmonary toxicity related to lung cancer treatment

Int J Radiat Oncol Biol Phys. 2011 Apr 6. [Epub ahead of print]
Pulmonary Toxicity in Stage III non-small cell lung cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105.
Salama JK, Stinchcombe TE, Gu L, Wang X, Morano K, Bogart JA, Crawford JC, Socinski MA, Blackstock AW, Vokes EE; Cancer and Leukemia Group B.

Duke University Medical Center, Durham, NC.
PURPOSE: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity.

METHODS AND MATERIALS: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity.

RESULTS: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases.

CONCLUSIONS: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

Eating meat and fish, and lung cancer risk

Consumption of meat and fish and risk of lung cancer: results from the European Prospective Investigation into Cancer and Nutrition.
Linseisen J, Rohrmann S, Bueno-de-Mesquita B, Büchner FL, Boshuizen HC, Agudo A, Gram IT, Dahm CC, Overvad K, Egeberg R, Tjønneland A, Boeing H, Steffen A, Kaaks R, Lukanova A, Berrino F, Palli D, Panico S, Tumino R, Ardanaz E, Dorronsoro M, Huerta JM, Rodríguez L, Sánchez MJ, Rasmuson T, Hallmans G, Manjer J, Wirfält E, Engeset D, Skeie G, Katsoulis M, Oikonomou E, Trichopoulou A, Peeters PH, Khaw KT, Wareham N, Allen N, Key T, Brennan P, Romieu I, Slimani N, Vergnaud AC, Xun WW, Vineis P, Riboli E.

Institute of Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany,
Evidence from case-control studies, but less so from cohort studies, suggests a positive association between meat intake and risk of lung cancer. Therefore, this association was evaluated in the frame of the European Prospective Investigation into Cancer and Nutrition, EPIC. Data from 478,021 participants, recruited from 10 European countries, who completed a dietary questionnaire in 1992-2000 were evaluated; 1,822 incident primary lung cancer cases were included in the present evaluation. Relative risk estimates were calculated for categories of meat intake using multi-variably adjusted Cox proportional hazard models. In addition, the continuous intake variables were calibrated by means of 24-h diet recall data to account for part of the measurement error. There were no consistent associations between meat consumption and the risk of lung cancer. Neither red meat (RR = 1.06, 95% CI 0.89-1.27 per 50 g intake/day; calibrated model) nor processed meat (RR = 1.13, 95% CI 0.95-1.34 per 50 g/day; calibrated model) was significantly related to an increased risk of lung cancer. Also, consumption of white meat and fish was not associated with the risk of lung cancer. These findings do not support the hypothesis that a high intake of red and processed meat is a risk factor for lung cancer.

From MD Anderson: Surgical therapy for pleural diffuse malignant mesothelioma

Recent Results Cancer Res. 2011;189:97-125.
Surgical Therapy of Mesothelioma.
Rice D.

Department of Thoracic and Cardiovascular Surgery, Unit #445, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA,
The treatment of malignant pleural mesothelioma is controversial, particularly regarding the role of surgery. Though well accepted as a diagnostic modality, surgery is also frequently used to establish stage, provide palliation, and perhaps most controversially, to offer cytoreduction with the putative goal of delaying tumor progression and prolonging survival. Pleurectomy/decortication (PD) can achieve macroscopic complete resection; however, the ability to deliver effective postoperative radiation treatment is limited because of the risk of lung toxicity. Accordingly, it has been associated with higher rates of local recurrence compared to extrapleural pneumonectomy (EPP). Extrapleural pneumonectomy generally offers a more complete cytoreduction compared to PD but at the cost of increased morbidity and mortality. Adjuvant hemithoracic radiation is feasible following EPP and in most series local recurrence rates are lower after EPP than PD. There are no convincing data, however, to show that one procedure is superior to the other in terms of survival. Furthermore, no randomized data currently exist that demonstrate a survival benefit to any form of surgical cytoreduction over systemic treatment and supportive care. If cytoreductive surgery does have a beneficial effect on long-term survival, it will most likely be realized in patients with epithelioid tumors without nodal metastases.

From Japan: Comparison of lung cancer surgical procedures and outcomes

Thorac Cardiovasc Surg. 2011 Apr;59(3):137-141. Epub 2011 Apr 8.
Comparison of the Surgical Outcomes of Thoracoscopic Lobectomy, Segmentectomy, and Wedge Resection for Clinical Stage I Non-Small Cell Lung Cancer.
Nakamura H, Taniguchi Y, Miwa K, Adachi Y, Fujioka S, Haruki T, Takagi Y, Yurugi Y.

Department of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan.
BACKGROUND: Video-assisted thoracoscopic surgery (VATS) for clinical stage I non-small cell lung cancer (NSCLC) has been widely used as a less invasive surgical procedure, but the resection method is still controversial. We retrospectively compared the surgical outcomes of lobectomy, segmentectomy and wedge resection.

PATIENTS AND METHODS: A total of 411 patients with clinical stage I NSCLC who underwent VATS (218 males and 193 females, aged 69.3 years; 345 adenocarcinomas, 57 squamous cell carcinomas, and 9 others) were investigated. The surgical procedure was lobectomy in 289, segmentectomy in 38, and wedge resection in 84. Surgical outcomes were compared among these 3 groups.

RESULTS: Demographic characteristics showed that the rate of elderly and male patients was higher in the wedge resection group. The 5-year survival rates for the lobectomy, segmentectomy, and wedge resection groups were 82.1, 87.2, and 55.4 %, respectively. In the wedge resection group, the 5-year survival rate was 83.3 % in patients undergoing intentional low-risk operations for small tumors with ground glass opacity, and 41.1 % in those undergoing conservative high-risk operations because of comorbidities. Using Cox's proportional multivariate analysis and sex differences, histology, and tumor size as co-influential factors, the surgical procedure was found to be a significantly poor prognostic factor, and the hazard ratio of wedge resection relative to lobectomy was 4.30.

CONCLUSION: The outcomes of VATS lobectomy and segmentectomy procedures for clinical stage I NSCLC were equivalent, while the outcome for VATS wedge resection was inferior. VATS wedge resection for clinical stage I NSCLC should be carefully indicated and requires adequate patient selection.

Monday, April 11, 2011

GM-CSF in the lung protects against lethal influenza infection

Am J Respir Crit Care Med. 2011 Apr 7. [Epub ahead of print]

GM-CSF in the Lung Protects Against Lethal Influenza Infection.

Huang FF, Barnes PF, Feng Y, Donis R, Chroneos ZC, Idell S, Allen T, Perez DR, Whitsett JA, Dunussi-Joannopoulos K, Shams H.

Center for Pulmonary and Infectious Disease Control, University of Texas Health Science Center at Tyler, Tyler, Texas, United States.

RATIONALE: Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza

OBJECTIVE: To determine if increased expression of granulocyte-macrophage colony stimulating factor in the lung increases resistance to influenza

METHODS: Wild-type mice and transgenic mice that expressed granulocyte macrophage-colony stimulating factor in the lung were infected with influenza virus, and lung pathology, weight loss and mortality were measured. We also administered granulocyte-macrophage colony stimulating factor to the lungs of wild-type mice that were infected with influenza virus.

MEASUREMENTS AND MAIN RESULTS: Wild-type mice all died after infection with different strains of influenza virus, but all transgenic mice expressing granulocyte-macrophage colony stimulating factor in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showed histologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T-cells, B-cells or neutrophils. Transgenic mice had far more alveolar macrophages than wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal granulocyte macrophage-colony stimulating factor to wild-type mice also conferred resistance to influenza.

CONCLUSIONS: Granulocyte-macrophage colony stimulating factor confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.

Monday, April 4, 2011

Using MRI to assess cystic fibrosis patients

Eur J Radiol. 2011 Mar 21. [Epub ahead of print]
Morphologic and functional scoring of cystic fibrosis lung disease using MRI.
Eichinger M, Optazaite DE, Kopp-Schneider A, Hintze C, Biederer J, Niemann A, Mall MA, Wielpütz MO, Kauczor HU, Puderbach M.

Department of Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Magnetic resonance imaging (MRI) gains increasing importance in the assessment of cystic fibrosis (CF) lung disease. The aim of this study was to develop a morpho-functional MR-scoring-system and to evaluate its intra- and inter-observer reproducibility and clinical practicability to monitor CF lung disease over a broad severity range from infancy to adulthood. 35 CF patients with broad age range (mean 15.3years; range 0.5-42) were examined by morphological and functional MRI. Lobe based analysis was performed for parameters bronchiectasis/bronchial-wall-thickening, mucus plugging, abscesses/sacculations, consolidations, special findings and perfusion defects. The maximum global score was 72. Two experienced radiologists scored the images at two time points (interval 10weeks). Upper and lower limits of agreement, concordance correlation coefficients (CCC), total deviation index and coverage probability were calculated for global, morphology, function, component and lobar scores. Global scores ranged from 6 to 47. Intra- and inter-reader agreement for global scores were good (CCC: 0.98 (R1), 0.94 (R2), 0.97 (R1/R2)) and were comparable between high and low scores. Our results indicate that the proposed morpho-functional MR-scoring-system is reproducible and applicable for semi-quantitative evaluation of a large spectrum of CF lung disease severity. This scoring-system can be applied for the routine assessment of CF lung disease and maybe as endpoint for clinical trials.

Molecular pathobiology of COPD and lung cancer

Respiration. 2011;81(4):265-84. Epub 2011 Mar 24.
Chronic obstructive pulmonary disease and lung cancer: new molecular insights.
Adcock IM, Caramori G, Barnes PJ.

Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
Both chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death worldwide. In most cases this reflects cigarette smoke exposure which is able to induce an inflammatory response in the airways of smokers. Indeed, COPD is characterized by lower airway inflammation, and importantly, the presence of COPD is by far the greatest risk factor for lung cancer amongst smokers. Cigarette smoke induces the release of many inflammatory mediators and growth factors including TGF-β, EGFR, IL-1, IL-8 and G-CSF through oxidative stress pathways and this inflammation may persist for decades after smoking cessation. Mucus production is also increased by these inflammatory mediators, further linking airway inflammation to an important mechanism of lung cancer. A greater understanding of the molecular and cellular pathobiology that distinguishes smokers with lung cancer from smokers with and without COPD is needed to unravel the complex molecular interactions between COPD and lung cancer. By understanding the common signalling pathways involved in COPD and lung cancer the hope is that treatments will be developed that not only treat the underlying disease process in COPD, but also reduce the currently high risk of developing lung cancer in these patients.

Menthol cigarettes: lung cancer risk

J Natl Cancer Inst. 2011 Mar 23. [Epub ahead of print]
Lung Cancer Risk Among Smokers of Menthol Cigarettes.
Blot WJ, Cohen SS, Aldrich M, McLaughlin JK, Hargreaves MK, Signorello LB.

Affiliations of authors: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center (WJB, JKM, LBS), Department of Thoracic Oncology (MA), Vanderbilt University Medical Center, Nashville, TN; International Epidemiology Institute, Rockville, MD (WJB, SSC, JKM, LBS); Department of Internal Medicine, Meharry Medical College, Nashville, TN (MKH).
Background Menthol cigarettes, preferred by African American smokers, have been conjectured to be harder to quit and to contribute to the excess lung cancer burden among black men in the Unites States. However, data showing an association between smoking menthol cigarettes and increased lung cancer risk compared with smoking nonmenthol cigarettes are limited. The Food and Drug Administration is currently considering whether to ban the sale of menthol cigarettes in the United States. Methods We conducted a prospective study among 85 806 racially diverse adults enrolled in the Southern Community Cohort Study during March 2002 to September 2009 according to cigarette smoking status, with smokers classified by preference for menthol vs nonmenthol cigarettes. Among 12 373 smokers who responded to a follow-up questionnaire, we compared rates of quitting between menthol and nonmenthol smokers. In a nested case-control analysis of 440 incident lung cancer case patients and 2213 matched control subjects, using logistic regression modeling we computed odds ratios (ORs) and accompanying 95% confidence intervals (CIs) of lung cancer incidence, and applied Cox proportional hazards modeling to estimate hazard ratios (HRs) of lung cancer mortality, according to menthol preference. Results Among both blacks and whites, menthol smokers reported smoking fewer cigarettes per day; an average of 1.6 (95% CI = 1.3 to 2.0) fewer for blacks and 1.8 (95% CI = 1.3 to 2.3) fewer for whites, compared with nonmenthol smokers. During an average of 4.3 years of follow-up, 21% of participants smoking at baseline had quit, with menthol and nonmenthol smokers having equal odds of quitting (OR = 1.02, 95% CI = 0.89 to 1.16). A lower lung cancer incidence was noted in menthol vs nonmenthol smokers (for smokers of <10, 10-19, and ≥20 cigarettes per day, compared with never smokers, OR = 5.0 vs 10.3, 8.7 vs 12.9, and 12.2 vs 21.1, respectively). These trends were mirrored for lung cancer mortality. In multivariable analyses adjusted for pack-years of smoking, menthol cigarettes were associated with a lower lung cancer incidence (OR = 0.65, 95% CI = 0.47 to 0.90) and mortality (hazard ratio of mortality = 0.69, 95% CI = 0.49 to 0.95) than nonmenthol cigarettes. Conclusions The findings suggest that menthol cigarettes are no more, and perhaps less, harmful than nonmenthol cigarettes.

From Wurzburg Germany: Is PET-CT staging of lung cancer patients cost efficient?

Eur J Nucl Med Mol Imaging. 2011 Mar 26. [Epub ahead of print]
PET/CT for staging lung cancer: costly or cost-saving?
Buck AK, Herrmann K, Schreyögg J.

Dept. of Nuclear Medicine, Nuklearmedizinische Klinik und Poliklinik, Universitätsklinikum Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg,Germany.

Acquired resistance to EGFR-TK inhibitors in lung cancer patients

Curr Drug Targets. 2011 Mar 28. [Epub ahead of print]
Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and New Therapeutic Perspectives in Non Small Cell Lung Cancer.
Bonanno L, Jirillo A, Favaretto A.

Medical Oncology 2, Istituto Oncologico Veneto - IRCCS, Padova, Italy.

EGFR somatic mutations define a subset of NSCLCs that are most likely to benefit from EGFR tyrosine kinase inhibitors (TKIs). These tumors are dependent on EGFR-signaling for survival. Recently, tyrosine kinase domain somatic mutations have been approved as criterion to decide first-line therapy in this group of advanced NSCLCs. Anyway, all patients ultimately develop resistance to these drugs. Acquired resistance is linked to a secondary EGFR mutation in about a half of patients. Uncontrolled activation of MET, another tyrosine kinase receptor, has been implicated in neoplastic invasive growth. MET is overexpressed, activated and sometimes mutated in NSCLC cell lines and tumor tissues. MET increased gene copy number has also been documented in NSCLC and has been studied as negative prognostic factor. It has also been found in about 20% of patients developing acquired resistance to TKIs inhibitors. In this group, it seems to display a new mechanism, which is able to mark tumor independence from EGFR signaling. The study of delayed resistance mechanisms could lead to the development of new therapeutic strategies. Different molecular alterations could be specifically targeted in order to extend disease control in this group of NSCLCs with distinct clinical and molecular features. EGFR irreversible inhibitors, MET inhibitors and dual EGFR/VEGFR inhibitors represent one of the most challenging issues in current clinical research. Ongoing clinical trials and future perspectives are discussed.

VATS for lung cancer

Gen Thorac Cardiovasc Surg. 2011 Mar;59(3):164-8. Epub 2011 Mar 30.
Video-assisted thoracic surgery lobectomy for lung cancer: the point at issue.
Yamashita Y, Harada H, Misumi K.

Department of General Thoracic Surgery, National Hospital Organization, Kure Medical Center/Chugoku Cancer Center, 3-1 Aoyamacho, Kure, 737-0023, Japan,
Among the four subjects addressed in this article, the definition of video-assisted thoracic surgery (VATS) lobectomy is fundamentally the point at issue, which leads to various obstacles for upcoming clinical trials. It is strongly expected that VATS lobectomy will be identified as a standard operation for primary lung cancer with confirmed clinical evidence. Standard surgical procedure with a certain oncological validity for lung cancer should be minimally invasive, safe, and technically simple for general thoracic surgeons. In conclusion, most patients with resectable lung cancer will be able to benefit from a validated painless VATS lobectomy in the near future.