Colorectal cancer and thoracic surgeons: close encounters of the third kind.

Resection of lung metastases from colorectal cancer (CRC) is increasingly performed with a curative intent. This strategy was made possible in the 1990s by the development of new chemotherapeutic approaches, improved surgical techniques and better imaging modalities. However, evidence-based data showing clinical benefits of lung metastasectomy in this setting are nonexistent, and there are no prospective randomized trials to support the routine performance of these procedures for stage IV CRC. Current evidence suggests that resection of pulmonary metastases in combination with new cytotoxic agents, such as oxaliplatin, irinotecan and bevacizumab, may result in prolonged survival for many, and cure for a small minority of CRC patients who experienced tumor spread beyond the limits of the abdomen. This review focuses on the results of surgical management of CRC patients with lung metastases: we report the outcome of published series according to the presence or the absence of liver metastasis (and hepatic resection) prior to lung resection.

Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging.

There has been confusion about the subunit stoichiometry of the degenerin family of ion channels. Recently, a crystal structure of acid-sensing ion channel (ASIC) 1a revealed that it assembles as a trimer. Here, we used atomic force microscopy (AFM) to image unprocessed ASIC1a bound to mica. We detected a mixture of subunit monomers, dimers and trimers. In some cases, triple-subunit clusters were clearly visible, confirming the trimeric structure of the channel, and indicating that the trimer sometimes disaggregated after adhesion to the mica surface. This AFM-based technique will now enable us to determine the subunit arrangement within heteromeric ASICs.

18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging in patients with liver metastases from uveal melanoma: results from a pilot study.

PURPOSE: F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and MRI are used for detecting liver metastases from uveal melanoma. The introduction of new treatment options in clinical trials might benefit from early response assessment. Here, we determine the value of FDG-PET/CT with respect to MRI at diagnosis and its potential for monitoring therapy. MATERIAL AND METHODS: Ten patients with biopsy-proven liver metastases of uveal melanoma enrolled in a randomized phase III trial (NCT00110123) underwent both FDG-PET coupled with unenhanced CT and gadolinium-diethylene triamine pentaacetic acid-enhanced liver MRI within 4 weeks. FDG-PET and MRI were evaluated blindly and then compared using the ratio of lesion to normal liver parenchyma PET-derived standardized uptake value (SUV). The influence of lesion size and response to chemotherapy were studied. RESULTS: Overall, 108 liver lesions were seen: 34 (31%) on both modalities (1-18 lesions/patient), four (4%) by PET/CT only, and 70 (65%) by MRI only. SUV correlated with MRI lesion size (r=0.81, P<0.0001). PET/CT detected 26 of 33 (79%) MRI lesions of more than or equal to 1.2 cm, whereas it detected only eight of 71 (11%) lesions of less than 1.2 cm (P<0.0001). MRI lesions without PET correspondence were small (0.6±0.2 vs. 2.1±1.1 cm, P<0.0001). During follow-up (six patients, 30 lesions), the ratio lesion-to-normal-liver SUV diminished in size-stable lesions (1.90±0.64-1.46±0.50, P<0.0001), whereas it increased in enlarging lesions (1.56±0.40-1.99±0.56, P=0.032). CONCLUSION: MRI outweighs PET/CT for detecting small liver metastases. However, PET/CT detected at least one liver metastasis per patient and changes in FDG uptake not related to size change, suggesting a role in assessing early therapy response.

Hypoxia and vasculature in models of lung cancer: implications for targeted therapeutics

Estudi realitzat a partir d’una estada a la Stanford University School of Medicine. Division of Radiation Oncology, Estats Units, entre 2010 i 2012. Durant els dos anys de beca postdoctoral he estat treballant en dos projectes diferents. En primer lloc, i com a continuació d'estudis previs del grup, volíem estudiar la causa de les diferències en nivells d'hipòxia que havíem observat en models de càncer de pulmó. La nostra hipòtesi es basava en el fet que aquestes diferències es devien a la funcionalitat de la vasculatura. Vam utilitzar dos models preclínics: un en què els tumors es formaven espontàniament als pulmons i l'altre on nosaltres injectàvem les cèl•lules de manera subcutània. Vam utilitzar tècniques com la ressonància magnètica dinàmica amb agent de contrast (DCE-MRI) i l'assaig de perfusió amb el Hoeschst 33342 i ambdues van demostrar que la funcionalitat de la vasculatura dels tumors espontanis era molt més elevada comparada amb la dels tumors subcutanis. D'aquest estudi, en podem concloure que les diferències en els nivells d'hipòxia en els diferents models tumorals de càncer de pulmó podrien ser deguts a la variació en la formació i funcionalitat de la vasculatura. Per tant, la selecció de models preclínics és essencial, tant pels estudi d'hipòxia i angiogènesi, com per a teràpies adreçades a aquests fenòmens. L'altre projecte que he estat desenvolupant es basa en l'estudi de la radioteràpia i els seus possibles efectes a l’hora de potenciar l'autoregeneració del tumor a partir de les cèl•lules tumorals circulants (CTC). Aquest efecte s'ha descrit en alguns models tumorals preclínics. Per tal de dur a terme els nostres estudis, vam utilitzar una línia tumoral de càncer de mama de ratolí, marcada permanentment amb el gen de Photinus pyralis o sense marcar i vam fer estudis in vitro i in vivo. Ambdós estudis han demostrat que la radiació tumoral promou la invasió cel•lular i l'autoregeneració del tumor per CTC. Aquest descobriment s'ha de considerar dins d'un context de radioteràpia clínica per tal d'aconseguir el millor tractament en pacients amb nivells de CTC elevats.

Mophological analysis of the human vasculature from medical imaging. Application to cerebral and coranary arteries

In this project, we have investigated new ways of modelling and analysis of human vasculature from Medical images. The research was divided in two main areas: cerebral vasculature analysis and coronary arteries modeling. Regarding cerebral vasculature analysis, we have studed cerebral aneurysms, internal carotid and the Circle of Willis (CoW). Aneurysms are abnormal vessel enlargements that can rupture causing important cerebral damages or death. The understanding of this pathology, together with its virtual treatment, and image diagnosis and prognosis, includes identification and detailed measurement of the aneurysms. In this context, we have proposed two automatic aneurysm isolation method, to separate the abnormal part of the vessel from the healthy part, to homogenize and speed-up the processing pipeline usually employed to study this pathology, [Cardenes2011TMI, arrabide2011MedPhys]. The results obtained from both methods have been also compared and validatied in [Cardenes2012MBEC]. A second important task here the analysis of the internal carotid [Bogunovic2011Media] and the automatic labelling of the CoW, Bogunovic2011MICCAI, Bogunovic2012TMI]. The second area of research covers the study of coronary arteries, specially coronary bifurcations because there is where the formation of atherosclerotic plaque is more common, and where the intervention is more challenging. Therefore, we proposed a novel modelling method from Computed Tomography Angiography (CTA) images, combined with Conventional Coronary Angiography (CCA), to obtain realistic vascular models of coronary bifurcations, presented in [Cardenes2011MICCAI], and fully validated including phantom experiments in [Cardene2013MedPhys]. The realistic models obtained from this method are being used to simulate stenting procedures, and to investigate the hemodynamic variables in coronary bifurcations in the works submitted in [Morlachi2012, Chiastra2012]. Additionally, another preliminary work has been done to reconstruct the coronary tree from rotational angiography, and published in [Cardenes2012ISBI].

Apports et limites de la scintigraphie pulmonaire dans le diagnostic de l'embolie pulmonaire [Value and limitation of pulmonary scintigraphy in the diagnosis of pulmonary embolism].

Perfusion lung scan, whether associated with a ventilation lung scan or not, is frequently used in the diagnosis of pulmonary emboli. The characteristics of perfusion lung scan are reviewed. The added diagnostic value of standard chest X-ray and of ventilation scan is discussed, as well as its use in the intensive care unit.

Lung cancer mortality in European women: trends and predictions.

Female lung cancer mortality increased by 50% between the mid 1960s and the early 2000s in the European Union (EU). To monitor the current lung cancer epidemic in European women, we analyzed mortality trends in 33 European countries between 1970 and 2009 and estimated rates for the year 2015 using data from the World Health Organization. Female lung cancer mortality has been increasing up to recent calendar years in most European countries, with the exceptions of Belarus, Russia, and Ukraine, with relatively low rates, and the UK, Iceland and Ireland, where high rates were reached in mid/late 1990s to leveled off thereafter. In the EU, female lung cancer mortality rates rose over the last decade from 11.3 to 12.7/100,000 (+2.3% per year) at all ages and from 18.6 to 21.5/100,000 (+3.0% per year) in middle-age. A further increase is predicted, to reach 14/100,000 women in 2015. Lung cancer mortality trends have been more favorable over the last decade in young women (20-44 years), particularly in the UK and other former high-risk countries from northern and central/eastern Europe, but also in France, Italy, and Spain where mortality in young women has been increasing up to the early 2000s. In the EU as a whole, mortality at age 20-44 years decreased from 1.6 to 1.4/100,000 (-2.2% per year). Although the female lung cancer epidemic in Europe is still expanding, the epidemic may be controlled through the implementation of effective anti-tobacco measures, and it will probably never reach the top US rates.

Trends in smoking and lung cancer mortality in Switzerland.

Patterns of cigarette smoking in Switzerland were analyzed on the basis of sales data (available since 1924) and national health surveys conducted in the last decade. There was a steady and substantial increase in cigarettes sales up to the early 1970s. Thereafter, the curve tended to level off around an average value of 3,000 cigarettes per adult per year. According to the 1981-1983 National Health Survey, 37% of Swiss men were current smokers, 25% were ex-smokers, and 39% were never smokers. Corresponding porportions in women were 22, 11, and 67%. Among men, smoking prevalence was higher in lower social classes, and some moderate decline was apparent from survey data over the period 1975-1981 mostly in later middle-age. Trends in lung cancer death certification rates over the period 1950-1984 were analyzed using standard cross-sectional methods and a log-linear Poisson model to isolate the effects of age, birth cohort, and year of death. Mortality from lung cancer increased substantially among Swiss men between the early 1950s and the late 1970s, and levelled off (around a value of 70/100,000 men) thereafter. Among women, there has been a steady upward trend which started in the mid-1960s, and continues to climb steadily, although lung cancer mortality is still considerably lower in absolute terms (around 8/100,000 women) than in several North European countries or in North America. Cohort analyses indicate that the peak rates in men were reached by the generation born around 1910 and mortality stabilized for subsequent generations up to the 1930 birth cohort. Among females, marked increases were observed in each subsequent birth cohort. This pattern of trends is consistent with available information on smoking prevalence in successive generations, showing a peak among men for the 1910 cohort, but steady upward trends among females. Over the period 1980-1984, about 90% of lung cancer deaths among Swiss men and about 40% of those among women could be attributed to smoking (overall proportion, 85%).

Reporting Guidance for Oncologic 18F-FDG PET/CT Imaging.

The written report (or its electronic counterpart) is the primary mode of communication between the physician interpreting an imaging study and the referring physician. The content of this report not only influences patient management and clinical outcomes but also serves as legal documentation of services provided and can be used to justify medical necessity, billing accuracy, and regulatory compliance. Generating a high-quality PET/CT report is perhaps more challenging than generating a report for other imaging studies because of the complexity of this hybrid imaging modality. This article discusses the essential elements of a concise and complete oncologic (18)F-FDG PET/CT report and illustrates these elements through examples taken from routine clinical practice.

A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial.

BACKGROUND: The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC). METHODS: Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). High-ICE cycles were supported by transfusion with PBPCs that were collected after two cycles of treatment with epidoxorubicin at 150 mg/m(2), paclitaxel at 175 mg/m(2), and filgrastim. The primary outcome was 3-year survival. Comparisons between response rates and toxic effects within subgroups (limited or extensive disease, liver metastases or no liver metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, normal or abnormal lactate dehydrogenase levels) were also performed. RESULTS: Median relative dose intensity in the High-ICE arm was 293% (range = 174%-392%) of that in the Std-ICE arm. The 3-year survival rates were 18% (95% confidence interval [CI] = 10% to 29%) and 19% (95% CI = 11% to 30%) in the High-ICE and Std-ICE arms, respectively. No differences were observed between the High-ICE and Std-ICE arms in overall response (n = 54 [78%, 95% CI = 67% to 87%] and n = 48 [68%, 95% CI = 55% to 78%], respectively) or complete response (n = 27 [39%, 95% CI = 28% to 52%] and n = 24 [34%, 95% CI = 23% to 46%], respectively). Subgroup analyses showed no benefit for any outcome from High-ICE treatment. Hematologic toxicity was substantial in the Std-ICE arm (grade > or = 3 neutropenia, n = 49 [70%]; anemia, n = 17 [25%]; thrombopenia, n = 17 [25%]), and three patients (4%) died from toxicity. High-ICE treatment was predictably associated with severe myelosuppression, and five patients (8%) died from toxicity. CONCLUSIONS: The long-term outcome of SCLC was not improved by raising the dose intensity of ICE chemotherapy by threefold.