SLC/CCL21, normally expressed in high endothelial venules and in T cell zones of spleen and lymph... more SLC/CCL21, normally expressed in high endothelial venules and in T cell zones of spleen and lymph nodes, strongly attracts T cells and dendritic cells (DC). We have previously shown that SLC/CCL21-mediated anti-tumor responses are accompanied by significant induction of IFNgamma and the CXC chemokines, monokine induced by IFNgamma (MIG/CXCL9) and IFNgamma-inducible protein-10 (IP-10/CXCL10). We assessed the importance of IFNgamma, IP-10/CXCL10 and MIG/CXCL9 in SLC/CCL21 therapy. In vivo depletion of IP-10/CXCL10, MIG/CXCL9 or IFNgamma significantly reduced the anti-tumor efficacy of SLC/CCL21. Assessment of cytokine production at the tumor site showed an interdependence of IFNgamma, MIG/CXCL9 and IP-10/CXCL10; neutralization of any one of these cytokines caused a concomitant decrease in all three cytokines. Similarly, neutralization of any one of these cytokines led to a decrease in the frequency of CXCR3+ve T cells and CD11c+ve DC at the tumor site. These findings indicate that the...
BACKGROUND Radiomics is a promising tool for the identification of new prognostic biomarkers. Rad... more BACKGROUND Radiomics is a promising tool for the identification of new prognostic biomarkers. Radiomic features can be affected by different scanning protocols, often present in retrospective and prospective clinical data. We compared a CT based radiomics model based on a large but highly heterogeneous multi-centric image dataset with robust feature pre-selection to a model based on a smaller but standardized image dataset without pre-selection. MATERIALS AND METHODS Primary tumor radiomics was extracted from pre-treatment CTs of IIIA/N2/IIIB NSCLC patients from a prospective Swiss multi-centric randomized trial (npatient = 124, ninstitution = 14, SAKK-16/00) and a validation dataset (npatient = 31, ninstitution = 1). Four robustness studies investigating inter-observer delineation variation, motion, convolution kernel and contrast were conducted to identify robust features using an intra-class correlation coefficient threshold > 0.9. Two 12-months overall survival (OS) logistic regression models were trained: (1) on the entire multi-centric heterogeneous dataset but with robust feature pre-selection (MCR) and (2) on a smaller standardized subset using all features (STD). Both models were validated on the validation dataset acquired with similar reconstruction parameters as the STD dataset. The model performances were compared using the DeLong test. RESULTS In total, 113 stable features were identified (nshape = 8, nintensity = 0, ntexture = 7, nwavelet = 98). The convolution kernel had the strongest influence on the feature robustness (less than 20% stable features). The final models of MCR and STD consisted of one and two features, respectively. The features of STD were identified both as non-robust. MCR did not show performance significantly different from STD on the validation cohort (AUC [95%CI] = 0.72 [0.48-0.95] and 0.79 [0.63-0.95], p=0.59). CONCLUSION Prognostic OS CT radiomics model for NSCLC based on a heterogeneous multi-centric imaging dataset with robust feature pre-selection performed equally well as a model on a standardized dataset.
(a) Proteomics relies on protein digestion into smaller fragments/peptides and converge to proteo... more (a) Proteomics relies on protein digestion into smaller fragments/peptides and converge to proteome sequence information, classification, and expression levels without a screen of the cellular protein activities. Activity-based proteome profiling (ABPP) is emerging as a tool for functional proteomics based on mass spectrometry. We established an ABPP-SWATH/DIA MS platform compatible with OCT-embedded biopsies for differential global serine hydrolase (SHs) activity profiling and determine the Relative Depletion-Detected Activity (RDDA) index that reflects the relative activity of SHs in type IIIA lung adenocarcinoma biopsies. (b) To prevent digestion on streptavidin beads and MS spectra contamination, we used SWATH/DIA-MS2 signal intensities for the assessment of the ratio between the biopsy-extract solution either treated with DMSO or which had earlier been depleted with chemical probe for active enzyme molecules. We processed 24 lung biopsies (having a solution of depleted and non-depleted proteome) of long and short survivors with type IIIA lung adenocarcinoma tumor and their normal tissue counterparts and included peptides of 65 known endogenous inhibitors of SH. In parallel experiments, we analyzed the catalytically depleted part of the molecule by conventional ABPP-MS approach integrated on bead sample digestion. (c) We quantified 117 proteins annotated to the serine hydrolase family, of which as much as 60% was depleted with a CI of 90% in the biopsy-extract solution incubated with chemical probe. Among 133 enzymes monitored over the entire clinical cohort, we found as many as 89 enzymes with significant depletion that we further used to generate the activity SH profiles of each biopsy. We found 36 enzymes exclusively depleted in tumor tissue, both in short and long survivals, and with depletion absent from normal counterparts. By quantification of the catalytically active part of the molecule on the streptavidin bead sample pull-down digest, we found only 9 proteins that contained quality data for spectral counting comparisons. Partial Least Squares Discriminant Analysis (PLS-DA) analysis revealed the activity profiles of 9 enzymes perfectly discriminating the tumor tissues of short survivals, and these enzyme signatures were enhanced by the elevated activity of 2 enzymes - ADH1C and IAH1- in short-term survivors. (d) We have demonstrated that this approach can substantially increase the differential detection of protease activity between oncogenic lung tissue and their normal tissue counterparts. Citation Format: Tatjana Sajic, Stephan Arni, Rudolf Aebersold, Sven Hillinger. Activity based protein profiling by SWATH/DIA-MS mode (ABPP-SWATH/DIA-MS) from OCT-embedded tissues biopsies reveals lung tumor-specific protease profiles [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6482.
Background: Chronic granulomatous disease (CGD) is caused by a malfunctioning nicotinamide adenin... more Background: Chronic granulomatous disease (CGD) is caused by a malfunctioning nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex in phagocytes, leading to impaired bacterial and fungal killing and hyperinflammation. Objective: To characterize macrophage subsets and cytokine/chemokine signaling loops involved in CGD tissue hyperinflammation. Methods: Cytokine/chemokine production and surface marker expression were analyzed in inflamed tissue of four CGD patients and compared to cytokine/chemokine released by CGD macrophages upon priming to different macrophage subpopulations. Furthermore, the re-priming capacity of CGD pro-inflammatory M1 to M2a antiinflammatory macrophages was evaluated. Results: In human CGD inflammatory tissue, IL-18 and IFN-γ were detected in significant quantity. Immunofluorescence analysis identified macrophages as one source of IL-18 in inflamed tissue. In vitro, CGD macrophages could be primed and re-primed into all inflammatory/anti-inflammatory macrophage subpopulations. IL-18 was also released by M1 CGD and control macrophages. Conclusion: CGD pro-inflammatory M1 macrophages remain M1 primed in vivo. As CGD M1 macrophages can be re-primed to anti-inflammatory M2a phenotype in vitro, macrophages are kept in M1 state in vivo by a persistent pro-inflammatory environment. Our results suggest a paracrine signaling loop between M1 macrophage derived IL-18 and non-macrophage derived IFN-γ maintaining macrophage pro-inflammatory activity in CGD tissue.
The use of optimal cutting temperature (OCT) medium has served to improve the long-term preservat... more The use of optimal cutting temperature (OCT) medium has served to improve the long-term preservation of surgical tissue specimens. Unfortunately, the presence of polymers in OCT has been found to generate signal interference in proteomic-based techniques. Indeed the presence of OCT medium in tissue lysates precludes the analysis of activity based proteomic profiles obtained from lung adenocarcinoma (LuAdCa) resection specimens. In order to probe this question further tissue lysates were prepared from 47 lung non-neoplastic and tumour, node, metastasis (TNM) stage 1 LuAdCa resection specimens embedded with or without OCT, and data of activity based multiplex profiles of protein tyrosine kinase peptide substrates were obtained. We found that changes in overall phosphorylation level coincided with the use of OCT and subsequently developed an OCT per peptide median correcting strategy by performing median centering on the values of each peptide. Application of this post-analytical strategy not only can identify changes in kinase activity but can also assist in identifying novel targets for therapeutic intervention against LuAdCa.
Hydatosis is a clinical entity known since the time of Hippocrates with Echinococcus granulosus a... more Hydatosis is a clinical entity known since the time of Hippocrates with Echinococcus granulosus as most common cause of hydatidosis. Humans as well as herbivores are infected as intermediate hosts and the zoonosis is most commonly observed in the liver and lungs. Intrathoracic extrapulmonary cysts are uncommon. We present the rare presentation of concomitant intrathoracic extrapulmonary and cervical hydatid cysts after a follow-up of 10 years. The patient presented with a soft palpable supraclavivular mass and increasing pain. Thoracoscopic exploration (VATS, video-assisted thoracic surgery) revealed a cystic lesion at the apex of the left hemithorax without contact to the lung. We performed a cystotomy and removed the laminated membrane. Later, the cervical hydatid cyst was removed. Five years later, a recurrence of the disease was again resected. Currently, 10 years after initial referral, the patient remains without any signs of active disease. To our knowledge, this is the first report of an intrathoracic extrapulmonary hydatidosis removed by VATS. Our report presents VATS as a surgical option in the treatment of intrathoracic extrapulmonary hydatid disease of the thoracic apex and confirms the feasibility of minimal invasive surgery for intrathoracic hydatid disease.
Background: Many studies have shown that long non-coding RNAs (lncRNAs) are implicated in cancer ... more Background: Many studies have shown that long non-coding RNAs (lncRNAs) are implicated in cancer progress including lung cancer. In our previous studies, we screened the differentially expressed lncRNAs between lung adenocarcinoma with lymph node metastasis and lung adenocarcinoma without lymph node metastasis by microarray analysis. XLOC_000090, an lncRNA without a known function, was identified. Here, we investigated the functions of XLOC_000090 in lung cancer. Method: The expression of XLOC_000090 was detected by qRT-PCR in 96 pairs of NSCLC tissues and the adjacent normal lung tissues. Then, we investigated the correlation between XLOC_000090 expression and clinicopathological variables and prognosis. Cell invasion and migration assay was used to detect cell invasion and migration ability in vitro. Murine model of lung cancer was used to detect the effect of XLOC_000090 on pulmonary metastasis in vivo. Dual luciferase reporter assay was used to determine the direct binding between XLOC_000090 and miR-4505. Result: Compared with normal lung tissues, XLOC_000090 expression was higher in NSCLC tissues (P<0.05). XLOC_000090 expression was associated with lymph node metastasis (P<0.05) and pathological stage (P<0.05). Patients with high XLOC_000090 expression exhibited significantly poorer diseasefree survival and overall survival (P<0.05). XLOC_000090 overexpression increased tumor cell migration and invasion ability, whereas downregulation of XLOC_000090 expression decreased tumor cell migration and invasion ability in both A549 and Calu3 lung cancer cells. Murine model of lung cancer also showed that XLOC_000090 promoted metastasis of lung cancer cells in vivo. Furthermore, a potential XLOC_000090-targeting miRNA, miR-4505, was identified by ceRNA regulatory network prediction analysis. miR-4505 expression was significantly downregulated in lung cells transfected with XLOC_000090, and significantly upregulated in lung cells transfected with sh-XLOC_000090. Dual-luciferase reporter assay showed the direct binding between miR-4505 and XLOC_000090. XLOC_000090promoted cell migration and invasion ability was diminished in miR-4505 overexpressed cells. Conclusion: Our results demonstrated that XLOC_000090 promoted the migration and invasion of lung cancer cells through regulating miR-4505. XLOC_000090 could be served as a new molecular marker for the progression and prognosis of patients with NSCLC.
We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, w... more We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, when both donor and recipient were pretreated intravenously. However, systemic treatment of multiorgan donors may not be clinically relevant. Thus, we hypothesized that ex vivo treatment of donors with nebulized NAC would be adequate to prevent from ischemia-reperfusion injury after lung transplantation. Lungs were retrieved from domestic pigs and stored at 4°C for 24 h followed by 2 h of ex vivo lung perfusion (EVLP) to administer 50 mg/kg of NAC via nebulization in the NAC group (n = 6). The control group received nebulized saline (n = 5). Left lungs were transplanted and isolated at 1 h of reperfusion by occluding the right main bronchus and pulmonary artery, followed by 5 h of observation. Physiological data during EVLP and after reperfusion were recorded. Inflammatory response, markers of oxidative stress, and microscopic lung injury were analyzed. There was a trend toward better oxy...
The purpose of this study was to assess various volume-based PET quantification metrics, includin... more The purpose of this study was to assess various volume-based PET quantification metrics, including metabolic tumor volume and total lesion glycolysis (TLG) with different thresholds, as well as background activity-based PET metrics (background-subtracted lesion activity [BSL] and background-subtracted volume) as prognostic markers for progression-free and overall survival (PFS and OS, respectively) in early-stage I and II non-small cell lung cancer (NSCLC) after resection. Methods: Patients (n 5 133) underwent an adequate 18 F-FDG PET/CT scan before surgery between January 2003 and December 2010. All PET activity metrics showed a skewed distribution and were log-transformed before calculation of the Pearson correlation coefficients. Survival tree analysis was used to discriminate between high-and low-risk patients and to select the most important prognostic markers. The Akaike information criterion was used to compare 2 univariate models. Results: Within the study time, 36 patients died from NSCLC and 26 patients from other causes. At the end of follow-up, 70 patients were alive, with 67 patients being free of disease. All log-transformed PET metrics showed a strong linear association, with a Pearson correlation coefficient between 0.703 and 0.962. After multiple testing corrections, only 1 prognostic marker contributed a significant split point in the survival tree analysis. Of 10 potential predictors including 7 PET metrics, a BSL greater than 6,852 (P 5 0.017) was chosen as split point, assigning 13 patients into a high-risk group. If BSL was removed from the set of predictors, a 42% TLG (TLG 42%) of greater than 4,204 (P 5 0.023) was chosen as split point. When a dichotomized BSL or TLG 42% variable was used for a univariate Cox model, the Akaike information criterion difference of both models was smaller than 2; therefore, the data do not provide evidence that 1 of the 2 prognostic factors is superior. Conclusion: Volume-based PET metrics correlate with PFS and OS and could be used for risk assessment in stage I-II NSCLC. The different PET metrics assessed in this study showed a high correlation; therefore, it is not surprising that there was no significant difference to predict PFS or OS within this study. Overall, patients with large and metabolically active tumors should be considered high risk and might need further treatment after resection. Because all analysis steps were done with the same data, these results should be validated on new patient data.
Posters/Basic science~Celt and molecular biology $127 estimated. However, a number of other works... more Posters/Basic science~Celt and molecular biology $127 estimated. However, a number of other works have shown that the theoretic analysis and results of cellular automaton model are in agreement with data from the ideal differeotlal equation logistic tumor growth (R. Hu, & X. Ruan. 2003). Methods: In multlvanable logistic regression analysis, longer time since smoking exposure remained a significant predictor of adenocaJ'~nomas (p < 0 02), but history of asbestos ev, posure did not predict tumor histology ON. L. Burton. C. W. John, et. al.. '1998). Tango and Toshiro (1994) also described a Poisson regression model for time trends of mortality to detect the Iong4erm effects of common laveis of aJr pollution on lung cancer The conclusions of Burton (1998) and Tango (1994) had been used to calculate the regression we~ghtlngs for the geo~c and behavioral determinants. Other data for celibratlon and validation of the models are mainly from MSKCC (Memorial Sloan Kettenng Cancer Center. http://wwwski.mskcc.org/) and Guangdong province of China. Results: Here in this study focusing on the logistic lung tumor growth model, we proposed a statistical modei for the estimation of lung tumor growth doubling time. which combines the genetic and behavioral determinants. We defined the lavels of the environmental ev, posure nsk classification by using the regression welghtings Conclusions: The statistical models for the estimation of lung tumor growth doub4ing time are well in agreement with data from what we had Keywords: lung cancer, tumor growth, environmental exposure, statistical modeling [~7 ] Growt~ inhibition and apoptosis induction of protopenaxtnol on human lung cancer cells
Due to an increased life expectancy in a healthy aging population and a progressive incidence of ... more Due to an increased life expectancy in a healthy aging population and a progressive incidence of lung cancer, curative pulmonary resections can be performed even in octogenarians. The present study aims to investigate whether surgery is justified in patients reaching the age of 80 years and older who undergo resection for non-small cell lung cancer (NSCLC). In this retrospective multi-centre analysis, the morbidity, mortality and long-term survival of 88 patients (24 females) aged ≥80 who underwent complete resection for lung cancer between 2000 and 2013 were analysed. Only fit patients with few comorbidities, low cardiopulmonary risk, good quality of life and a life expectancy of at least 5 years were included. Curative resections from three thoracic surgery centres included 61 lobectomies, 9 bilobectomies, 6 pneumonectomies and 12 segmentectomies or wide wedge resections with additional systematic mediastinal lymphadenectomy in all cases. Final histology revealed squamous cell car...
In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lu... more In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted Pseudomonas strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted Pseudomonas populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential Pseudomonas isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and Pseudomonas populations. We show that Pseudomonas invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator mutL lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy, Pseudomonas dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities. Pseudomonas was replaced after 95 days by a microbiota dominated by Actinobacillus. In conclusion, mucoid Pseudomonas adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of Pseudomonas to the non-CF allograft. Lung transplantation (LT) is recognized as the ultimate therapeutic intervention for cystic fibrosis (CF) patients with end-stage lung disease. Unfortunately, allograft infections and development of chronic rejection lead to loss of graft function in about 50% of patients at five years 1. CF lung-recipients suffer from chronic pre-transplant infections with microorganisms including Staphylococcus aureus, Burkholderia cepacia, and Pseudomonas aeruginosa, the latter predominating in adults 2. P. aeruginosa outcompetes other bacteria and remarkably adapts to the particular CF-airway microenvironment by accumulating mutations over years 3. Whereas lung transplantation removes the major infectious site, Pseudomonas potentially residing in the recipient's sinuses may seed the allograft 4,5. The success of Pseudomonas in colonizing the allograft airways depends on antibiotic treatments, the host response hampered by immunosuppressive therapies and initial mucosal damage 6 , as well as inter-species competition. Despite this challenging situation, allograft airway colonization by Pseudomonas is frequent 7. Little is known to date about the microbiota of lung transplant recipients. It remains unclear whether particular pre-LT infections/colonization are associated with poor post-LT outcomes. Several studies demonstrated that CF-patients infected by P. aeruginosa had more post-LT respiratory infections than non-infected non-CF patients 8,9. However, no significant difference in survival was reported. In addition, CF-patients infected with
Extracorporeal life support (ECLS) as a bridge to lung retransplantation has been reported only a... more Extracorporeal life support (ECLS) as a bridge to lung retransplantation has been reported only anecdotally. Thus, we analyzed combined data from our center with pooled data from published studies to identify selection criteria for this advanced therapy. Four patients at our center were bridged on ECLS to lung retransplantation. Patient data were retrospectively retrieved from electronic records. The MEDLINE database was searched using the PubMed engine and yielded 13 relevant studies that included a minimum of 3 patients bridged to lung retransplantation, and four studies described detailed data on 17 patients. Patient data from our center (n = 4) were pooled with data from the MEDLINE database (n = 17) and analyzed. Of 21 patients, 3 (14%) died on ECLS awaiting retransplantation, and 18 (86%) underwent retransplantation after a median of 37 months (range, 0 to 168 months) after primary transplantation. Type of ECLS was extracorporeal carbon dioxide removal (ECCO2R) in 4, venovenou...
Swiss Medical Weekly Official Journal of the Swiss Society of Infectious Diseases the Swiss Society of Internal Medicine the Swiss Society of Pneumology, Apr 1, 2007
remarkably low rate of BOS (Ͻ10% after 4.5 years) was seen in patients treated according to this ... more remarkably low rate of BOS (Ͻ10% after 4.5 years) was seen in patients treated according to this new protocol (pϽ0.0003 versus the occurrence of BOS during the previous protocol). Survival, from four months after transplantation, also significantly improved (pϽ0.05). Conclusions: We conclude that EBV-DNA guided pre-emptive reduction of immunosuppression is a safe procedure after lung transplantation and may not only reduce the incidence of PTLD but also improve the BOS free survival.
Reduced activity of histone deacetylase 2 (HDAC2) has been described in patients with chronic obs... more Reduced activity of histone deacetylase 2 (HDAC2) has been described in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms resulting in decreased expression of this important epigenetic modifier remain unknown. Here, we employed several in vitro experiments to address the role of microRNAs (miRNAs) on the regulation of HDAC2 in endothelial cells. Manipulation of miRNA levels in human pulmonary artery endothelial cells (HPAEC) was achieved by using electroporation with anti-miRNAs and miRNA mimics. Target prediction software identified miR-223 as a potential repressor of HDAC2. In subsequent stimulation experiments using inflammatory cytokines known to be increased in patients with COPD, miR-223 was found to be significantly induced. Functional analysis demonstrated that overexpression of miR-223 decreased HDAC2 expression and activity in HPAEC. Conversely, HDAC2 expression and activity was preserved in anti-miR-223-treated cells. Direct miRNAtarget interaction was confirmed by reporter gene assay. In a next step, reduced expression of HDAC2 was found to increase the levels of the chemokine fractalkine (CX3CL1). In vivo studies confirmed elevated expression levels of miR-223 in mice exposed to cigarette smoke and in emphysematous lung tissue from LPS-treated mice. Moreover, a significant inverse correlation of miR-223 and HDAC2 expression was found in two independent cohorts of COPD patients. These data emphasize that miR-223, the most prevalent miRNA in COPD, controls expression and activity of HDAC2 in pulmonary cells, which, in turn, might alter the expression profile of chemokines. This pathway provides a novel pathogenic link between dysregulated miRNA expression and epigenetic activity in COPD. KEY MESSAGES: Histone deacetylase 2 is directly targeted by miR-223. Levels of miR-223 are induced by interleukin-1 and tumor necrosis factor-. miR-223 controls the expression of fractalkine by targeting histone deacetylase 2. miR-223 levels are increased in COPD mouse models. miR-223 levels inversely correlate with HDAC2 expression in COPD patients.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 28, 2016
Assessment of tumor response after chemotherapy using FDG PET metrics is gaining acceptance. Seve... more Assessment of tumor response after chemotherapy using FDG PET metrics is gaining acceptance. Several studies have suggested that the parameters metabolically active tumor volume (MTV) or total lesion glycolysis (TLG) are superior for measuring the tumor burden compared to the maximum standardized uptake value (SUVmax). However, the measurement of MTV and TLG is still controversial; the most commonly method uses an absolute threshold of 42% of SUVmax. Recently we implemented a background adaptive method to determine the background subtracted lesion activity (BSL) and the background subtracted volume (BSV). In this study we investigated the correlation between such PET metrics and histopathological response in non-small cell lung carcinoma (NSCLC). Forty-four NSCLC patients were retrospectively identified. Their PET/CT data before and after neo-adjuvant chemotherapy was analyzed regarding SUVmax, MTV, TLG, BSL, and BSV on both scans and the relative changes (delta = d) were calculated...
Therapeutische Umschau Revue Therapeutique, Jun 1, 2008
The idea of follow-up visits in lung cancer patients treated in a curative intent is on one side ... more The idea of follow-up visits in lung cancer patients treated in a curative intent is on one side early detection and management of treatment related complications and on the other side a long term surveillance program for early detection of new primary lung cancers or recurrences of the primary lung cancer allowing curative (re)-treatment. The first is best performed by the specialists (thoracic surgeons, oncologists, radiotherapists) and the intervals of the follow-up visits are 3-6 months. In this phase adjuvant therapies as well as a specific surveillance program should be determined. Smoking cessation is strongly recommended and an adequate support should be offered. Patients treated in a curative intent and who are in an adequate performance status should be seen in six months intervals in the first three years and thereafter annually by assessing the medical history, physical exam and for applying imaging modalities such as chest X-ray or CT-Scan of the chest and upper abdomen. The patient should be instructed to detect symptoms and react accordingly. Positron Emission Tomography, sputum cytology, tumor markers and blood tests as well as fluorescence bronchoscopy are not recommended for routine follow-up except in controlled randomized trial protocol. These statements are based on guidelines from several societies as well as from a literature research.
SLC/CCL21, normally expressed in high endothelial venules and in T cell zones of spleen and lymph... more SLC/CCL21, normally expressed in high endothelial venules and in T cell zones of spleen and lymph nodes, strongly attracts T cells and dendritic cells (DC). We have previously shown that SLC/CCL21-mediated anti-tumor responses are accompanied by significant induction of IFNgamma and the CXC chemokines, monokine induced by IFNgamma (MIG/CXCL9) and IFNgamma-inducible protein-10 (IP-10/CXCL10). We assessed the importance of IFNgamma, IP-10/CXCL10 and MIG/CXCL9 in SLC/CCL21 therapy. In vivo depletion of IP-10/CXCL10, MIG/CXCL9 or IFNgamma significantly reduced the anti-tumor efficacy of SLC/CCL21. Assessment of cytokine production at the tumor site showed an interdependence of IFNgamma, MIG/CXCL9 and IP-10/CXCL10; neutralization of any one of these cytokines caused a concomitant decrease in all three cytokines. Similarly, neutralization of any one of these cytokines led to a decrease in the frequency of CXCR3+ve T cells and CD11c+ve DC at the tumor site. These findings indicate that the...
BACKGROUND Radiomics is a promising tool for the identification of new prognostic biomarkers. Rad... more BACKGROUND Radiomics is a promising tool for the identification of new prognostic biomarkers. Radiomic features can be affected by different scanning protocols, often present in retrospective and prospective clinical data. We compared a CT based radiomics model based on a large but highly heterogeneous multi-centric image dataset with robust feature pre-selection to a model based on a smaller but standardized image dataset without pre-selection. MATERIALS AND METHODS Primary tumor radiomics was extracted from pre-treatment CTs of IIIA/N2/IIIB NSCLC patients from a prospective Swiss multi-centric randomized trial (npatient = 124, ninstitution = 14, SAKK-16/00) and a validation dataset (npatient = 31, ninstitution = 1). Four robustness studies investigating inter-observer delineation variation, motion, convolution kernel and contrast were conducted to identify robust features using an intra-class correlation coefficient threshold > 0.9. Two 12-months overall survival (OS) logistic regression models were trained: (1) on the entire multi-centric heterogeneous dataset but with robust feature pre-selection (MCR) and (2) on a smaller standardized subset using all features (STD). Both models were validated on the validation dataset acquired with similar reconstruction parameters as the STD dataset. The model performances were compared using the DeLong test. RESULTS In total, 113 stable features were identified (nshape = 8, nintensity = 0, ntexture = 7, nwavelet = 98). The convolution kernel had the strongest influence on the feature robustness (less than 20% stable features). The final models of MCR and STD consisted of one and two features, respectively. The features of STD were identified both as non-robust. MCR did not show performance significantly different from STD on the validation cohort (AUC [95%CI] = 0.72 [0.48-0.95] and 0.79 [0.63-0.95], p=0.59). CONCLUSION Prognostic OS CT radiomics model for NSCLC based on a heterogeneous multi-centric imaging dataset with robust feature pre-selection performed equally well as a model on a standardized dataset.
(a) Proteomics relies on protein digestion into smaller fragments/peptides and converge to proteo... more (a) Proteomics relies on protein digestion into smaller fragments/peptides and converge to proteome sequence information, classification, and expression levels without a screen of the cellular protein activities. Activity-based proteome profiling (ABPP) is emerging as a tool for functional proteomics based on mass spectrometry. We established an ABPP-SWATH/DIA MS platform compatible with OCT-embedded biopsies for differential global serine hydrolase (SHs) activity profiling and determine the Relative Depletion-Detected Activity (RDDA) index that reflects the relative activity of SHs in type IIIA lung adenocarcinoma biopsies. (b) To prevent digestion on streptavidin beads and MS spectra contamination, we used SWATH/DIA-MS2 signal intensities for the assessment of the ratio between the biopsy-extract solution either treated with DMSO or which had earlier been depleted with chemical probe for active enzyme molecules. We processed 24 lung biopsies (having a solution of depleted and non-depleted proteome) of long and short survivors with type IIIA lung adenocarcinoma tumor and their normal tissue counterparts and included peptides of 65 known endogenous inhibitors of SH. In parallel experiments, we analyzed the catalytically depleted part of the molecule by conventional ABPP-MS approach integrated on bead sample digestion. (c) We quantified 117 proteins annotated to the serine hydrolase family, of which as much as 60% was depleted with a CI of 90% in the biopsy-extract solution incubated with chemical probe. Among 133 enzymes monitored over the entire clinical cohort, we found as many as 89 enzymes with significant depletion that we further used to generate the activity SH profiles of each biopsy. We found 36 enzymes exclusively depleted in tumor tissue, both in short and long survivals, and with depletion absent from normal counterparts. By quantification of the catalytically active part of the molecule on the streptavidin bead sample pull-down digest, we found only 9 proteins that contained quality data for spectral counting comparisons. Partial Least Squares Discriminant Analysis (PLS-DA) analysis revealed the activity profiles of 9 enzymes perfectly discriminating the tumor tissues of short survivals, and these enzyme signatures were enhanced by the elevated activity of 2 enzymes - ADH1C and IAH1- in short-term survivors. (d) We have demonstrated that this approach can substantially increase the differential detection of protease activity between oncogenic lung tissue and their normal tissue counterparts. Citation Format: Tatjana Sajic, Stephan Arni, Rudolf Aebersold, Sven Hillinger. Activity based protein profiling by SWATH/DIA-MS mode (ABPP-SWATH/DIA-MS) from OCT-embedded tissues biopsies reveals lung tumor-specific protease profiles [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6482.
Background: Chronic granulomatous disease (CGD) is caused by a malfunctioning nicotinamide adenin... more Background: Chronic granulomatous disease (CGD) is caused by a malfunctioning nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex in phagocytes, leading to impaired bacterial and fungal killing and hyperinflammation. Objective: To characterize macrophage subsets and cytokine/chemokine signaling loops involved in CGD tissue hyperinflammation. Methods: Cytokine/chemokine production and surface marker expression were analyzed in inflamed tissue of four CGD patients and compared to cytokine/chemokine released by CGD macrophages upon priming to different macrophage subpopulations. Furthermore, the re-priming capacity of CGD pro-inflammatory M1 to M2a antiinflammatory macrophages was evaluated. Results: In human CGD inflammatory tissue, IL-18 and IFN-γ were detected in significant quantity. Immunofluorescence analysis identified macrophages as one source of IL-18 in inflamed tissue. In vitro, CGD macrophages could be primed and re-primed into all inflammatory/anti-inflammatory macrophage subpopulations. IL-18 was also released by M1 CGD and control macrophages. Conclusion: CGD pro-inflammatory M1 macrophages remain M1 primed in vivo. As CGD M1 macrophages can be re-primed to anti-inflammatory M2a phenotype in vitro, macrophages are kept in M1 state in vivo by a persistent pro-inflammatory environment. Our results suggest a paracrine signaling loop between M1 macrophage derived IL-18 and non-macrophage derived IFN-γ maintaining macrophage pro-inflammatory activity in CGD tissue.
The use of optimal cutting temperature (OCT) medium has served to improve the long-term preservat... more The use of optimal cutting temperature (OCT) medium has served to improve the long-term preservation of surgical tissue specimens. Unfortunately, the presence of polymers in OCT has been found to generate signal interference in proteomic-based techniques. Indeed the presence of OCT medium in tissue lysates precludes the analysis of activity based proteomic profiles obtained from lung adenocarcinoma (LuAdCa) resection specimens. In order to probe this question further tissue lysates were prepared from 47 lung non-neoplastic and tumour, node, metastasis (TNM) stage 1 LuAdCa resection specimens embedded with or without OCT, and data of activity based multiplex profiles of protein tyrosine kinase peptide substrates were obtained. We found that changes in overall phosphorylation level coincided with the use of OCT and subsequently developed an OCT per peptide median correcting strategy by performing median centering on the values of each peptide. Application of this post-analytical strategy not only can identify changes in kinase activity but can also assist in identifying novel targets for therapeutic intervention against LuAdCa.
Hydatosis is a clinical entity known since the time of Hippocrates with Echinococcus granulosus a... more Hydatosis is a clinical entity known since the time of Hippocrates with Echinococcus granulosus as most common cause of hydatidosis. Humans as well as herbivores are infected as intermediate hosts and the zoonosis is most commonly observed in the liver and lungs. Intrathoracic extrapulmonary cysts are uncommon. We present the rare presentation of concomitant intrathoracic extrapulmonary and cervical hydatid cysts after a follow-up of 10 years. The patient presented with a soft palpable supraclavivular mass and increasing pain. Thoracoscopic exploration (VATS, video-assisted thoracic surgery) revealed a cystic lesion at the apex of the left hemithorax without contact to the lung. We performed a cystotomy and removed the laminated membrane. Later, the cervical hydatid cyst was removed. Five years later, a recurrence of the disease was again resected. Currently, 10 years after initial referral, the patient remains without any signs of active disease. To our knowledge, this is the first report of an intrathoracic extrapulmonary hydatidosis removed by VATS. Our report presents VATS as a surgical option in the treatment of intrathoracic extrapulmonary hydatid disease of the thoracic apex and confirms the feasibility of minimal invasive surgery for intrathoracic hydatid disease.
Background: Many studies have shown that long non-coding RNAs (lncRNAs) are implicated in cancer ... more Background: Many studies have shown that long non-coding RNAs (lncRNAs) are implicated in cancer progress including lung cancer. In our previous studies, we screened the differentially expressed lncRNAs between lung adenocarcinoma with lymph node metastasis and lung adenocarcinoma without lymph node metastasis by microarray analysis. XLOC_000090, an lncRNA without a known function, was identified. Here, we investigated the functions of XLOC_000090 in lung cancer. Method: The expression of XLOC_000090 was detected by qRT-PCR in 96 pairs of NSCLC tissues and the adjacent normal lung tissues. Then, we investigated the correlation between XLOC_000090 expression and clinicopathological variables and prognosis. Cell invasion and migration assay was used to detect cell invasion and migration ability in vitro. Murine model of lung cancer was used to detect the effect of XLOC_000090 on pulmonary metastasis in vivo. Dual luciferase reporter assay was used to determine the direct binding between XLOC_000090 and miR-4505. Result: Compared with normal lung tissues, XLOC_000090 expression was higher in NSCLC tissues (P<0.05). XLOC_000090 expression was associated with lymph node metastasis (P<0.05) and pathological stage (P<0.05). Patients with high XLOC_000090 expression exhibited significantly poorer diseasefree survival and overall survival (P<0.05). XLOC_000090 overexpression increased tumor cell migration and invasion ability, whereas downregulation of XLOC_000090 expression decreased tumor cell migration and invasion ability in both A549 and Calu3 lung cancer cells. Murine model of lung cancer also showed that XLOC_000090 promoted metastasis of lung cancer cells in vivo. Furthermore, a potential XLOC_000090-targeting miRNA, miR-4505, was identified by ceRNA regulatory network prediction analysis. miR-4505 expression was significantly downregulated in lung cells transfected with XLOC_000090, and significantly upregulated in lung cells transfected with sh-XLOC_000090. Dual-luciferase reporter assay showed the direct binding between miR-4505 and XLOC_000090. XLOC_000090promoted cell migration and invasion ability was diminished in miR-4505 overexpressed cells. Conclusion: Our results demonstrated that XLOC_000090 promoted the migration and invasion of lung cancer cells through regulating miR-4505. XLOC_000090 could be served as a new molecular marker for the progression and prognosis of patients with NSCLC.
We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, w... more We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, when both donor and recipient were pretreated intravenously. However, systemic treatment of multiorgan donors may not be clinically relevant. Thus, we hypothesized that ex vivo treatment of donors with nebulized NAC would be adequate to prevent from ischemia-reperfusion injury after lung transplantation. Lungs were retrieved from domestic pigs and stored at 4°C for 24 h followed by 2 h of ex vivo lung perfusion (EVLP) to administer 50 mg/kg of NAC via nebulization in the NAC group (n = 6). The control group received nebulized saline (n = 5). Left lungs were transplanted and isolated at 1 h of reperfusion by occluding the right main bronchus and pulmonary artery, followed by 5 h of observation. Physiological data during EVLP and after reperfusion were recorded. Inflammatory response, markers of oxidative stress, and microscopic lung injury were analyzed. There was a trend toward better oxy...
The purpose of this study was to assess various volume-based PET quantification metrics, includin... more The purpose of this study was to assess various volume-based PET quantification metrics, including metabolic tumor volume and total lesion glycolysis (TLG) with different thresholds, as well as background activity-based PET metrics (background-subtracted lesion activity [BSL] and background-subtracted volume) as prognostic markers for progression-free and overall survival (PFS and OS, respectively) in early-stage I and II non-small cell lung cancer (NSCLC) after resection. Methods: Patients (n 5 133) underwent an adequate 18 F-FDG PET/CT scan before surgery between January 2003 and December 2010. All PET activity metrics showed a skewed distribution and were log-transformed before calculation of the Pearson correlation coefficients. Survival tree analysis was used to discriminate between high-and low-risk patients and to select the most important prognostic markers. The Akaike information criterion was used to compare 2 univariate models. Results: Within the study time, 36 patients died from NSCLC and 26 patients from other causes. At the end of follow-up, 70 patients were alive, with 67 patients being free of disease. All log-transformed PET metrics showed a strong linear association, with a Pearson correlation coefficient between 0.703 and 0.962. After multiple testing corrections, only 1 prognostic marker contributed a significant split point in the survival tree analysis. Of 10 potential predictors including 7 PET metrics, a BSL greater than 6,852 (P 5 0.017) was chosen as split point, assigning 13 patients into a high-risk group. If BSL was removed from the set of predictors, a 42% TLG (TLG 42%) of greater than 4,204 (P 5 0.023) was chosen as split point. When a dichotomized BSL or TLG 42% variable was used for a univariate Cox model, the Akaike information criterion difference of both models was smaller than 2; therefore, the data do not provide evidence that 1 of the 2 prognostic factors is superior. Conclusion: Volume-based PET metrics correlate with PFS and OS and could be used for risk assessment in stage I-II NSCLC. The different PET metrics assessed in this study showed a high correlation; therefore, it is not surprising that there was no significant difference to predict PFS or OS within this study. Overall, patients with large and metabolically active tumors should be considered high risk and might need further treatment after resection. Because all analysis steps were done with the same data, these results should be validated on new patient data.
Posters/Basic science~Celt and molecular biology $127 estimated. However, a number of other works... more Posters/Basic science~Celt and molecular biology $127 estimated. However, a number of other works have shown that the theoretic analysis and results of cellular automaton model are in agreement with data from the ideal differeotlal equation logistic tumor growth (R. Hu, & X. Ruan. 2003). Methods: In multlvanable logistic regression analysis, longer time since smoking exposure remained a significant predictor of adenocaJ'~nomas (p < 0 02), but history of asbestos ev, posure did not predict tumor histology ON. L. Burton. C. W. John, et. al.. '1998). Tango and Toshiro (1994) also described a Poisson regression model for time trends of mortality to detect the Iong4erm effects of common laveis of aJr pollution on lung cancer The conclusions of Burton (1998) and Tango (1994) had been used to calculate the regression we~ghtlngs for the geo~c and behavioral determinants. Other data for celibratlon and validation of the models are mainly from MSKCC (Memorial Sloan Kettenng Cancer Center. http://wwwski.mskcc.org/) and Guangdong province of China. Results: Here in this study focusing on the logistic lung tumor growth model, we proposed a statistical modei for the estimation of lung tumor growth doubling time. which combines the genetic and behavioral determinants. We defined the lavels of the environmental ev, posure nsk classification by using the regression welghtings Conclusions: The statistical models for the estimation of lung tumor growth doub4ing time are well in agreement with data from what we had Keywords: lung cancer, tumor growth, environmental exposure, statistical modeling [~7 ] Growt~ inhibition and apoptosis induction of protopenaxtnol on human lung cancer cells
Due to an increased life expectancy in a healthy aging population and a progressive incidence of ... more Due to an increased life expectancy in a healthy aging population and a progressive incidence of lung cancer, curative pulmonary resections can be performed even in octogenarians. The present study aims to investigate whether surgery is justified in patients reaching the age of 80 years and older who undergo resection for non-small cell lung cancer (NSCLC). In this retrospective multi-centre analysis, the morbidity, mortality and long-term survival of 88 patients (24 females) aged ≥80 who underwent complete resection for lung cancer between 2000 and 2013 were analysed. Only fit patients with few comorbidities, low cardiopulmonary risk, good quality of life and a life expectancy of at least 5 years were included. Curative resections from three thoracic surgery centres included 61 lobectomies, 9 bilobectomies, 6 pneumonectomies and 12 segmentectomies or wide wedge resections with additional systematic mediastinal lymphadenectomy in all cases. Final histology revealed squamous cell car...
In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lu... more In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted Pseudomonas strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted Pseudomonas populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential Pseudomonas isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and Pseudomonas populations. We show that Pseudomonas invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator mutL lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy, Pseudomonas dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities. Pseudomonas was replaced after 95 days by a microbiota dominated by Actinobacillus. In conclusion, mucoid Pseudomonas adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of Pseudomonas to the non-CF allograft. Lung transplantation (LT) is recognized as the ultimate therapeutic intervention for cystic fibrosis (CF) patients with end-stage lung disease. Unfortunately, allograft infections and development of chronic rejection lead to loss of graft function in about 50% of patients at five years 1. CF lung-recipients suffer from chronic pre-transplant infections with microorganisms including Staphylococcus aureus, Burkholderia cepacia, and Pseudomonas aeruginosa, the latter predominating in adults 2. P. aeruginosa outcompetes other bacteria and remarkably adapts to the particular CF-airway microenvironment by accumulating mutations over years 3. Whereas lung transplantation removes the major infectious site, Pseudomonas potentially residing in the recipient's sinuses may seed the allograft 4,5. The success of Pseudomonas in colonizing the allograft airways depends on antibiotic treatments, the host response hampered by immunosuppressive therapies and initial mucosal damage 6 , as well as inter-species competition. Despite this challenging situation, allograft airway colonization by Pseudomonas is frequent 7. Little is known to date about the microbiota of lung transplant recipients. It remains unclear whether particular pre-LT infections/colonization are associated with poor post-LT outcomes. Several studies demonstrated that CF-patients infected by P. aeruginosa had more post-LT respiratory infections than non-infected non-CF patients 8,9. However, no significant difference in survival was reported. In addition, CF-patients infected with
Extracorporeal life support (ECLS) as a bridge to lung retransplantation has been reported only a... more Extracorporeal life support (ECLS) as a bridge to lung retransplantation has been reported only anecdotally. Thus, we analyzed combined data from our center with pooled data from published studies to identify selection criteria for this advanced therapy. Four patients at our center were bridged on ECLS to lung retransplantation. Patient data were retrospectively retrieved from electronic records. The MEDLINE database was searched using the PubMed engine and yielded 13 relevant studies that included a minimum of 3 patients bridged to lung retransplantation, and four studies described detailed data on 17 patients. Patient data from our center (n = 4) were pooled with data from the MEDLINE database (n = 17) and analyzed. Of 21 patients, 3 (14%) died on ECLS awaiting retransplantation, and 18 (86%) underwent retransplantation after a median of 37 months (range, 0 to 168 months) after primary transplantation. Type of ECLS was extracorporeal carbon dioxide removal (ECCO2R) in 4, venovenou...
Swiss Medical Weekly Official Journal of the Swiss Society of Infectious Diseases the Swiss Society of Internal Medicine the Swiss Society of Pneumology, Apr 1, 2007
remarkably low rate of BOS (Ͻ10% after 4.5 years) was seen in patients treated according to this ... more remarkably low rate of BOS (Ͻ10% after 4.5 years) was seen in patients treated according to this new protocol (pϽ0.0003 versus the occurrence of BOS during the previous protocol). Survival, from four months after transplantation, also significantly improved (pϽ0.05). Conclusions: We conclude that EBV-DNA guided pre-emptive reduction of immunosuppression is a safe procedure after lung transplantation and may not only reduce the incidence of PTLD but also improve the BOS free survival.
Reduced activity of histone deacetylase 2 (HDAC2) has been described in patients with chronic obs... more Reduced activity of histone deacetylase 2 (HDAC2) has been described in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms resulting in decreased expression of this important epigenetic modifier remain unknown. Here, we employed several in vitro experiments to address the role of microRNAs (miRNAs) on the regulation of HDAC2 in endothelial cells. Manipulation of miRNA levels in human pulmonary artery endothelial cells (HPAEC) was achieved by using electroporation with anti-miRNAs and miRNA mimics. Target prediction software identified miR-223 as a potential repressor of HDAC2. In subsequent stimulation experiments using inflammatory cytokines known to be increased in patients with COPD, miR-223 was found to be significantly induced. Functional analysis demonstrated that overexpression of miR-223 decreased HDAC2 expression and activity in HPAEC. Conversely, HDAC2 expression and activity was preserved in anti-miR-223-treated cells. Direct miRNAtarget interaction was confirmed by reporter gene assay. In a next step, reduced expression of HDAC2 was found to increase the levels of the chemokine fractalkine (CX3CL1). In vivo studies confirmed elevated expression levels of miR-223 in mice exposed to cigarette smoke and in emphysematous lung tissue from LPS-treated mice. Moreover, a significant inverse correlation of miR-223 and HDAC2 expression was found in two independent cohorts of COPD patients. These data emphasize that miR-223, the most prevalent miRNA in COPD, controls expression and activity of HDAC2 in pulmonary cells, which, in turn, might alter the expression profile of chemokines. This pathway provides a novel pathogenic link between dysregulated miRNA expression and epigenetic activity in COPD. KEY MESSAGES: Histone deacetylase 2 is directly targeted by miR-223. Levels of miR-223 are induced by interleukin-1 and tumor necrosis factor-. miR-223 controls the expression of fractalkine by targeting histone deacetylase 2. miR-223 levels are increased in COPD mouse models. miR-223 levels inversely correlate with HDAC2 expression in COPD patients.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 28, 2016
Assessment of tumor response after chemotherapy using FDG PET metrics is gaining acceptance. Seve... more Assessment of tumor response after chemotherapy using FDG PET metrics is gaining acceptance. Several studies have suggested that the parameters metabolically active tumor volume (MTV) or total lesion glycolysis (TLG) are superior for measuring the tumor burden compared to the maximum standardized uptake value (SUVmax). However, the measurement of MTV and TLG is still controversial; the most commonly method uses an absolute threshold of 42% of SUVmax. Recently we implemented a background adaptive method to determine the background subtracted lesion activity (BSL) and the background subtracted volume (BSV). In this study we investigated the correlation between such PET metrics and histopathological response in non-small cell lung carcinoma (NSCLC). Forty-four NSCLC patients were retrospectively identified. Their PET/CT data before and after neo-adjuvant chemotherapy was analyzed regarding SUVmax, MTV, TLG, BSL, and BSV on both scans and the relative changes (delta = d) were calculated...
Therapeutische Umschau Revue Therapeutique, Jun 1, 2008
The idea of follow-up visits in lung cancer patients treated in a curative intent is on one side ... more The idea of follow-up visits in lung cancer patients treated in a curative intent is on one side early detection and management of treatment related complications and on the other side a long term surveillance program for early detection of new primary lung cancers or recurrences of the primary lung cancer allowing curative (re)-treatment. The first is best performed by the specialists (thoracic surgeons, oncologists, radiotherapists) and the intervals of the follow-up visits are 3-6 months. In this phase adjuvant therapies as well as a specific surveillance program should be determined. Smoking cessation is strongly recommended and an adequate support should be offered. Patients treated in a curative intent and who are in an adequate performance status should be seen in six months intervals in the first three years and thereafter annually by assessing the medical history, physical exam and for applying imaging modalities such as chest X-ray or CT-Scan of the chest and upper abdomen. The patient should be instructed to detect symptoms and react accordingly. Positron Emission Tomography, sputum cytology, tumor markers and blood tests as well as fluorescence bronchoscopy are not recommended for routine follow-up except in controlled randomized trial protocol. These statements are based on guidelines from several societies as well as from a literature research.
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Papers by Sven Hillinger