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BACKGROUND: Findings from two recently published randomised controlled trials have shown favourable oncological results of segmentectomy for early-stage NSCLC < 2 cm. This has generated a growing interest in this procedure, which is however considered technically more challenging than lobectomy. The aim of the working group of the German Society for Thoracic Surgery (DGT) was to address, via an expert consensus project, topics concerning implementation of segmentectomy in lung cancer surgery. METHODS: The assigned group of the DGT designed and conducted two electronic rounds of questions in all major thoracic and lung cancer centres in Germany. The steering group predefined a priori the threshold of consensus of 75% or greater. The results were discussed in an expert meeting, leading to a final Delphi poll for selected topics and questions. RESULTS: Thirty-eight questions on segmentectomy for NSCLC were proposed in two rounds and voted on. After the final Delphi process, a consensus was reached for the following topics: non-inferiority of segmentectomy vs. lobectomy for tumours < 2 cm, segmentectomy as an alternative if lobectomy is functionally not feasible, use of intraoperative techniques for identification of intersegmental borders. No consensus could be reached for topics such as frozen section for intraoperative ascertainment of radicality, as also for the indication of a re-do lobectomy in case of an occult N1 lymph node status. CONCLUSION: Our manuscript depicts the results of a Delphi process in 2020/2021 involving experts of the German Society for Thoracic Surgery on the implementation of segmentectomy in lung cancer patients. In general, a very high rate of consensus was documented for the majority of the topics concerning the indication and execution of lung segmentectomy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Cirurgia Torácica , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Pneumonectomia/métodos , Consenso , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
BACKGROUND: The aim of this working group of the German Society for Thoracic Surgery (DGT) was to develop an expert consensus based on the Delphi method to define "tissue handling" and depict intraoperative handling of specific anatomical structures during thoracic surgery. METHODS: Invited experts (thoracic surgery specialists; n = 93) completed two consecutive rounds of electronic Delphi questions on four main topics: transection of lung parenchyma, dissection/separation of pulmonary vessels, angioplasty/vascular anastomoses, and bronchus settling closure/plasty/anastomosis. Consensus was set at ≥ 75% agreement. At the subsequent expert conference, the results of the Delphi surveys were discussed and TED voting was used to try to reach consensus. RESULTS: In each case, 66 (71%) answers were given in the first round of questions and 33 (35%) in the second round. Disputed questions were evaluated again by a final vote at the expert conference (54 participants; average participation 55%). The term "tissue handling" includes all procedures for dissection, transection, sealing, and reconstruction of various autologous tissues in the context of thoracic surgery (100% consensus). Similarly, the term "angioplasty expansion" was defined with a 97% consensus. Consensus was reached mainly for the technique of transecting the lung parenchyma using stapling suture devices, the recommendation of covering anastomoses as well as bronchial stump after pretreatment (> 75%). CONCLUSIONS: This expert consensus describes for the first time the concept of tissue handling in thoracic surgery. Furthermore, this Delphi process led to a comprehensive current inventory of different intraoperative procedures in German thoracic surgery with derived consensual recommendations for tissue handling of lung parenchyma, vessels and bronchial structures.
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Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Consenso , Humanos , PulmãoRESUMO
BACKGROUND: The aim of the consensus approach was to improve the quality of care by agreement on definitions and standards, in order to harmonise lymphadenectomy during lung metastasectomy. METHODS: The Delphi process consisted of two rounds of anonymous voting before discussion at a consensus meeting to reach final consensus within a group of experts. Consensus was assumed when > 75% of the panel agreed. RESULTS: Of 76 invited experts (board certified thoracic surgeons leading high-volume thoracic departments), 49 and 47 participated in the first and second round questionnaire, respectively. 43 experts attended the consensus meeting and reached consensus on the following: surgical approach for solitary subpleurally located lung metastasis is videothoracoscopy compared to anterolateral thoracotomy for multiple lung metastases. Lymphadenectomy is performed irrespective of the surgical approach. Systematic lymphadenectomy or sampling are core elements of pulmonary metastasectomy for colorectal, renal and non-seminomatous testicular cancer. The size of pulmonary metastasis does not influence lymphadenectomy per se. Pulmonary metastasectomy is not abolished in case of intraoperatively detected lymph node metastases. CONCLUSIONS: An expert group agreed on recommendations for lymphadenectomy during pulmonary metastasectomy using the Delphi process.
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Neoplasias Pulmonares , Metastasectomia , Neoplasias Testiculares , Consenso , Humanos , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , MasculinoRESUMO
BACKGROUND: Chest tubes are a valuable instrument and are used on a daily basis - not only by thoracic surgeons but also by a variety of medical specialists who treat pneumothorax or pleural effusions. The goal of the working group of the German Thoracic Society (DGT) was to achieve a consensus on the management of chest tube/drainage using the Delphi process. METHODS: The assigned group of the DGT designed and conducted two electronic rounds of questions in all major thoracic and lung cancer centres. Consensus was considered as rate of ≥ 75%. After statistical analysis of the results, an expert meeting took place and a final Delphi process poll was used in order to reach consensus for controversial topics. RESULTS: Thirteen questions on the management of chest tubes were proposed and voted on. A consensus was reached for the following topics: conditions for chest tube insertion, size of drainage/tube, technique of insertion, diagnostic measures after insertion and prior to removal, post-interventional management, documentation, number of chest tubes after anatomical lung resection, use of fibrinolytic agents, type of negative pressure. No consensus was reached for the following topics: autologous blood pleurodesis, reduction of suction in cases of persistent air leakage. CONCLUSION: Our manuscript depicts the results of a Delphi process in 2017â-â1018 involving experts of the German Thoracic Society from high volume departments certified for thoracic surgery. A very high rate of consensus was documented for topics such as chest tube insertion, peri-interventional management and removal algorithm. The most important topic for which there was no consensus was the case of persistent air leakage. The resulting expert recommendations of the Delphi process could be used as a starting point for internal clinical procedures.
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Pneumotórax , Procedimentos Cirúrgicos Torácicos , Tubos Torácicos , Consenso , Drenagem , Humanos , Cirurgia TorácicaRESUMO
BACKGROUND: Anatomical lung resection for curative treatment of a tumour disease is the most common selective procedure in oncological thoracic surgery. The goal of the working group of the German Thoracic Surgery Society (DGT) was to achieve a consensus on the perioperative management of selective oncological lung resection procedures. METHODS: The assigned group of the DGT designed and conducted two electronic rounds of questions in all major thoracic and lung centres. Consensus was considered as a rate of ≥ 75%. After statistical analysis of the results, an expert meeting took place and a final Delphi process poll was used in order to reach consensus for controversial topics. RESULTS: Fourteen questions on the perioperative management of anatomical oncological lung resections were proposed and voted on. A consensus was reached for the following topics: preoperative infectiological screening, extended respiratory diagnostics for impaired lung function, use of a cardiac risk assessment score, postoperative monitoring, prophylaxis for venous thromboembolism, control bronchoscopy after sleeve resections or pneumonectomy, blood gas test before discharge from the hospital. No consensus was reached for the following topics: preoperative endobronchial microbiological diagnostics, pleural rinsing, standardised clinical chemistry blood test postoperatively. CONCLUSION: Our manuscript depicts the results of a Delphi process in 2018/2019 involving experts of the German Thoracic Surgery Society from high volume departments certified for thoracic surgery and/or lung cancer surgery. In general, a very high rate of consensus was documented for the majority of the topics concerning the perioperative management of oncological anatomical selective lung resection procedures. The most important topic for which no consensus could be reached was preoperative endobronchial microbiological diagnostic testing.
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Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Consenso , Pulmão , PneumonectomiaRESUMO
Genome-wide enrichment of methylated DNA followed by sequencing (MeDIP-seq) offers a reasonable compromise between experimental costs and genomic coverage. However, the computational analysis of these experiments is complex, and quantification of the enrichment signals in terms of absolute levels of methylation requires specific transformation. In this work, we present QSEA, Quantitative Sequence Enrichment Analysis, a comprehensive workflow for the modelling and subsequent quantification of MeDIP-seq data. As the central part of the workflow we have developed a Bayesian statistical model that transforms the enrichment read counts to absolute levels of methylation and, thus, enhances interpretability and facilitates comparison with other methylation assays. We suggest several calibration strategies for the critical parameters of the model, either using additional data or fairly general assumptions. By comparing the results with bisulfite sequencing (BS) validation data, we show the improvement of QSEA over existing methods. Additionally, we generated a clinically relevant benchmark data set consisting of methylation enrichment experiments (MeDIP-seq), BS-based validation experiments (Methyl-seq) as well as gene expression experiments (RNA-seq) derived from non-small cell lung cancer patients, and show that the workflow retrieves well-known lung tumour methylation markers that are causative for gene expression changes, demonstrating the applicability of QSEA for clinical studies. QSEA is implemented in R and available from the Bioconductor repository 3.4 (www.bioconductor.org/packages/qsea).
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Metilação de DNA , Genômica/métodos , Análise de Sequência de DNA/métodos , Animais , Teorema de Bayes , Regulação da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Camundongos , Regiões Promotoras Genéticas , Sulfitos , Fluxo de TrabalhoRESUMO
OBJECTIVES: The oncological equivalence of anatomical segmentectomy for early stage non-small cell lung cancer (NSCLC) is still controversial. Primary aim of this study was survival outcomes in combination with improved quality of life after segmentectomy compared with lobectomy in patients with pathological stage Ia NSCLC (up to 2 cm, 7th edition) MATERIALS AND METHODS: We conducted a prospective, randomized, multicenter phase III trial to confirm the non-inferiority of segmentectomy to lobectomy in regard to prognosis (trial No. DRKS00004897). Patients were randomized to undergo either segmentectomy or lobectomy and followed up for 5-years survival and tumor recurrence. The 5-year hazard ratio comparing lobectomy with segmentectomy was required to remain above 0.5. RESULTS: Between October 2013 and June 2016, 108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled; 54 were assigned to lobectomy and 54 (1 drop-out) to segmentectomy. In-hospital and 90 days mortality was 0% in both groups. Overall survival at 5 years was 86.52% in the lobectomy compared to 78.21% in the segmentectomy group (HR = 0.61, (95% CI 0.23-1.66), p-value of non-inferiority test, p-ni = 0.687). Disease free survival was 77.29% for the lobectomy and 77.96% for the segmentectomy patients (HR = 1.50, (95% CI 0.60-3.76), p-ni = 0.019). At a median follow-up of 5 years, no differences were noted in either the locoregional or distant recurrent disease in both groups (9.4% vs 7.4%, p-ni = 0.506). CONCLUSION: Overall survival, locoregional and distant recurrences was not significantly difference for patients undergoing either segmentectomy or lobectomy for stage Ia NSCLC. The targeted non-inferiority of segmentectomy to lobectomy could not be proven for primary endpoint overall survival, but was significant for the secondary endpoint of disease free survival.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Pneumonectomia , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: The European Society of Thoracic Surgeons and the European Association for Cardio-Thoracic Surgery designed a questionnaire to assess the impact of gender bias on a cardiothoracic surgery career. METHODS: A 46-item survey investigating gender bias was designed using online survey software from December 2020 to January 2021. All European Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery members and non-members included in the mailing lists were invited to complete an electronic survey. Descriptive statistics and a comparison between gender groups were performed. RESULTS: Our overall response rate was 11.5% (1118/9764), of which 36.14% were women and 63.69% were men. Women were more likely to be younger than men (P < 0.0001). A total of 66% of the women reported having no children compared to only 19% of the men (P < 0.0001). Only 6% of women vs 22% of men were professors. More women (72%) also reported never having been a formal mentor themselves compared to men (38%, P < 0.0001). A total of 35% of female respondents considered leaving surgery because of episodes of discrimination compared to 13% of men; 67% of women said that they experienced being unfairly treated due to gender discrimination. Of the male surgeons, 31% reported that they were very satisfied with their career compared to only 17% of women (P < 0.0001). CONCLUSIONS: Women in cardiothoracic surgery reported significantly high rates of experiences with bias that may prevent qualified women from advancing to positions of leadership. Efforts to mitigate bias and support the professional development of women are at the centre of newly formed European committees.
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Cirurgiões , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Feminino , Humanos , Masculino , Sexismo , Inquéritos e QuestionáriosRESUMO
BACKGROUND: DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples. METHODS: SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH. RESULTS: A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference. CONCLUSIONS: Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.
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Carcinoma/genética , Metilação de DNA , Amplificação de Genes/fisiologia , Proteínas de Homeodomínio/genética , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Carcinoma/diagnóstico , Carcinoma/metabolismo , Carcinoma/patologia , Hibridização Genômica Comparativa , Metilação de DNA/fisiologia , Análise Mutacional de DNA/métodos , Dosagem de Genes/fisiologia , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/fisiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Análise por Pareamento , Polimorfismo Genético , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Despite an increasing number of female surgeons it is still very difficult for them to get into high rank positions. What are the obstacles for women to achieve a professional level where they can lead teams, departments or organisations or be invited as speakers in meetings or for editorial comments? Besides the general attitude still existing in many societies that women are responsible for child care there is a clear difference in self-presentation of women compared to their male counterparts. Women tend to underestimate their competence and skills whereas (often male) decision makers expect candidates to present themselves in a rather self-confident way. This unrecognized bias and the "glass ceiling" are encountered by many women in their career. Prestigious activities like publishing papers, presenting at conferences or working in committees are predominantly searched for by male colleagues whereas it is not uncommon for women to be confined to tasks in clinical workflow. Another bias is calling women by their first names instead of their full names, professional titles and achievements. Women should always introduce themselves by full name. Mentoring is a helpful career tool for female surgeons. A mentor can assist a mentee with strategic planning and help to redefine her way especially after a setback. When she clearly communicates her needs and expectations to seniors it shows her ambition and willingness to advance her career. Finding sponsorship is even more beneficial as a sponsor can use his influence to promote a woman to a high rank position. Surgical women´s associations exist worldwide. They enable young professionals to get in contact to female leaders/role models and exchange views with female colleagues. Institutional programs for (gender) equity are installed in some places to facilitate scientific and professional career advancement. Women are as capable as men although it is a greater challenge.
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BACKGROUND: Endoscopic lung volume reduction (ELVR) with valves has been suggested to be the key strategy for patients with severe emphysema and concomitant low diffusing capacity of the lung for carbon monoxide (D LCO). However, robust evidence is still missing. We therefore aim to compare clinical outcomes in relation to D LCO for patients treated with ELVR. METHODS: We assessed D LCO at baseline and 3â months follow-up and compared pre- and postprocedural pulmonary function test, quality of life, exercise capacity and adverse events. This is a retrospective subanalysis of prospectively collected data from the German Lung Emphysema Registry. RESULTS: In total, 121 patients treated with ELVR were analysed. Thirty-four patients with a D LCO ≤20% and 87 patients with a D LCO >20% showed similar baseline characteristics. After ELVR, there was a decrease of residual volume (both p<0.001 to baseline) in both groups, and both demonstrated better quality of life (p<0.01 to baseline). Forced expiratory volume in 1â s (FEV1) improved significantly only in patients with a D LCO >20% (p<0.001 to baseline). Exercise capacity remained almost unchanged in both groups (p=0.3). The most frequent complication for both groups was a pneumothorax (D LCO ≤20%: 17.6% versus D LCO >20%: 16.1%; p=0.728). However, there were no significant differences in other adverse events between both groups. CONCLUSIONS: ELVR improves lung function as well as quality of life in patients with D LCO >20% and D LCO ≤20%. Adverse events did not differ between groups. Therefore, ELVR should be considered as a treatment option, even in patients with a very low D LCO.
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PURPOSE: To assess the sensitivity of radiologists and a CAD system for the detection of lung metastases on thin-section computed tomographic (CT) scans prior to pulmonary metastasectomy. MATERIALS AND METHODS: All patients scheduled for resection of lung metastases were eligible for this prospective single-center trial. 95 patients with 115 surgical procedures (pulmonary metastasectomy using thoracotomy) were included. An experienced radiologist examined the CT scans for pulmonary metastases and documented his findings. A commercial CAD system was used as a second reader; additional CAD findings were recorded. A comparison of the sensitivity of the radiologist alone and with CAD was performed. Intraoperatively surgeons tried to identify the documented lesions and resected them as well as additionally palpable lesions. The standard of reference consisted of surgery and histopathology. Follow-up information for radiologically detected lesions missed during surgery was sought. RESULTS: 693 lesions (262 metastases) were detected radiologically or surgically, 646 of them were resected. The sensitivity of radiologists without CAD was 67.5â% for all lesions (87.4â% for metastases). CAD highly significantly (pâ<â0.001) increased the sensitivity to 77.9â% (92.7â%). During surgery, 143 additional lesions (19 metastases) were detected. 49 radiologically detected lesions were not palpable during surgery: 4 metastases, 5 benign lesions, and 40 lesions of an unknown nature. CONCLUSION: CAD provides significant additional sensitivity for detecting lung metastases using MDCT compared to the performance of a radiologist alone. CT reveals a relevant number of non-palpable pulmonary lesions. KEY POINTS: · CAD significantly increased the sensitivity for the detection of lung metastases on CT.. · Surgical palpation of the lungs missed 8.5â% of all radiologically detected lesions.. · CT with CAD may increase the chance for complete metastasectomy.. CITATION FORMAT: · Meybaum C, Graff M, Fallenberg EM etâal. Contribution of CAD to the Sensitivity for Detecting Lung Metastases on Thin-Section CT - A Prospective Study with Surgical and Histopathological Correlation. Fortschr Röntgenstr 2020; 192: 65â-â73.
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Diagnóstico por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Correlação de Dados , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVES: For early stage non-small cell lung cancer (NSCLC) retrospective data of functionally compromised patients undergoing segmentectomy showed equal outcomes for perioperative complications and quality of life (QoL) compared with lobectomy patients. However no prospectively randomized data comparing patients eligible for both procedures are available. MATERIALS AND METHODS: We conducted a prospective, randomized, multicenter phase III trial and investigated perioperative complications and QoL in patients with NSCLC stage IA (7th edition) undergoing segmentectomy versus lobectomy. The EORTC Questionnaire Core-30 (QLQ C-30) supplemented by thirteen-item lung cancer-specific module (LC13) was assessed before surgery, at discharge, 6 weeks, 3, 6 and 12 months post-surgery. RESULTS: 108 patients with verified or suspected NSCLC up to 2â¯cm diameter were enrolled, whereby 54 were assigned to lobectomy and 54 to segmentectomy. Due to nodal disease, tumor size and surgical reasons estimated during the operation, eight patients of the segmentectomy group received a lobectomy. In hospital and 90 days mortality was 0% in both groups. Perioperative complications were observed in 6 (11.3%) patients after segmentectomy and in 8 patients (14.8%) after lobectomy (pâ¯=â¯0.563), while the 90-day morbidity were 17% and 25.9% (9 and 14 patients), respectively (pâ¯=â¯0.452). Twelve months after surgery, there was a significant deterioration to the baselines of physical (pâ¯<â¯0.001) and cognitive functioning (pâ¯=â¯0.025), dyspnea (pâ¯<â¯0.001) and fatigue (pâ¯=â¯0.003) in the lobectomy group. Dyspnea showed a faster recovery in the segmentectomy compared to lobectomy group with statistical significance (pâ¯=â¯0.016 after 12 months). CONCLUSION: In patients with early-stage NSCLC, segmentectomy is associated with a statistically not significant lower perioperative morbidity and appears to provide a superior recovery in QoL compared with lobectomy patients.
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Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Assistência Perioperatória , Estudos Prospectivos , Qualidade de Vida , Carga TumoralAssuntos
Adenocarcinoma Bronquioloalveolar/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/patologia , Adenocarcinoma Bronquioloalveolar/patologia , Adenocarcinoma Bronquioloalveolar/cirurgia , Adulto , Vesícula/patologia , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , RadiografiaRESUMO
OBJECTIVE: Despite new technologies, mediastinoscopy remains the gold standard for mediastinal staging of lung cancer even though the procedure is not standardised. Introduction of video-mediastinoscopy (VM) may help to overcome this problem as it better visualises the anatomy and allows a more uniform dissection than conventional mediastinoscopy (CM). Does the use of VM result in more lymph node tissue, higher accuracy and lower complication rates as compared to CM? METHODS: All mediastinoscopies from June 2003 to December 2005 were analysed. In a protocol surgeons documented location of lymph node stations, number of lymph nodes resected or biopsied and technique (VM or CM). Two groups were created for analysis: group 1 (n=366) consisting of all mediastinoscopies was reviewed for complication rates; group 2 included all patients with lung cancer who had a pN0 status by mediastinoscopy and underwent subsequent thoracotomy (n=171). This group was studied for the number of lymph nodes resected or biopsied according to the technique (VM or CM), on accuracy and negative predictive value. RESULTS: Of 366 mediastinoscopies, 132 were CM (36.1%) and 234 VM (63.9%). Complications occurred in 17 patients (4.6%): 9 recurrent laryngeal nerve palsies (VM 2.1%, CM 3.0%), 5 mediastinal enlargement on routine chest radiography interpreted as postoperative bleeding (VM 0.9%, CM 2.3%), pneumonia (1), intraoperative laceration of the pleura (1) and main bronchus (1), both corrected during the procedure (all VM 1.3%). No intraoperative haemorrhage or death occurred. VM resected more lymph nodes (mean 8.1, range 3-25) then CM (mean 6.0, range 3-11), for all mediastinoscopies the mean lymph node yield was 7.6 (range 3-25). Comparison of lymphadenectomy via thoracotomy in patients classified pN0 by mediastinoscopy (n=171) showed an accuracy of 87.9% for VM versus 83.8% for CM (85.8% for all mediastinoscopies) with a negative predictive value of 0.83 for VM and 0.81 for CM (0.82 for all mediastinoscopies). CONCLUSION: This study demonstrates that in comparison with CM, VM routinely yields more lymph nodes with fewer complications with a tendency towards better accuracy and negative predictive value. For these reasons, we believe that VM should replace CM as the method of choice. Furthermore VM would allow standardisation, thereby having an advantage in comparison to the less invasive newer staging techniques. This way mediastinoscopy could remain the gold standard despite its invasiveness.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Excisão de Linfonodo , Mediastinoscopia/métodos , Cirurgia Vídeoassistida , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Mediastinoscopia/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Paralisia das Pregas Vocais/epidemiologia , Paralisia das Pregas Vocais/etiologiaAssuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Pneumonectomia/métodos , Adulto , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Feminino , Humanos , Metástase Linfática , Masculino , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide and is primarily treated with radiation, surgery, and platinum-based drugs like cisplatin and carboplatin. The major challenge in the treatment of NSCLC patients is intrinsic or acquired resistance to chemotherapy. Molecular markers predicting the outcome of the patients are urgently needed. METHODS: Here, we employed patient-derived xenografts (PDXs) to detect predictive methylation biomarkers for platin-based therapies. We used MeDIP-Seq to generate genome-wide DNA methylation profiles of 22 PDXs, their parental primary NSCLC, and their corresponding normal tissues and complemented the data with gene expression analyses of the same tissues. Candidate biomarkers were validated with quantitative methylation-specific PCRs (qMSP) in an independent cohort. RESULTS: Comprehensive analyses revealed that differential methylation patterns are highly similar, enriched in PDXs and lung tumor-specific when comparing differences in methylation between PDXs versus primary NSCLC. We identified a set of 40 candidate regions with methylation correlated to carboplatin response and corresponding inverse gene expression pattern even before therapy. This analysis led to the identification of a promoter CpG island methylation of LDL receptor-related protein 12 (LRP12) associated with increased resistance to carboplatin. Validation in an independent patient cohort (n = 35) confirmed that LRP12 methylation status is predictive for therapeutic response of NSCLC patients to platin therapy with a sensitivity of 80% and a specificity of 84% (p < 0.01). Similarly, we find a shorter survival time for patients with LRP12 hypermethylation in the TCGA data set for NSCLC (lung adenocarcinoma). CONCLUSIONS: Using an epigenome-wide sequencing approach, we find differential methylation patterns from primary lung cancer and PDX-derived cancers to be very similar, albeit with a lower degree of differential methylation in primary tumors. We identify LRP12 DNA methylation as a powerful predictive marker for carboplatin resistance. These findings outline a platform for the identification of epigenetic therapy resistance biomarkers based on PDX NSCLC models.
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Biomarcadores Tumorais/genética , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA/genética , Epigenômica , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Biomarcadores Tumorais/metabolismo , Carboplatina/farmacologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Genes Supressores de Tumor , Genoma Humano , Humanos , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Neoplasias Pulmonares/genética , Camundongos Nus , Regiões Promotoras Genéticas , Resultado do TratamentoRESUMO
BACKGROUND: Video-assisted mediastinoscopy (VAM) represents the standard procedure for mediastinal lymph node biopsies. This operation results in a scar at prominent position at the anterior neck. Since there is a trend to less invasive procedures, natural orifice transluminal endoscopic surgery (NOTES) was introduced to different fields of surgery. Based on NOTES we developed a new approach for mediastinoscopy: transoral endoscopic mediastinal surgery (TOEMS). In previous studies using human cadavers and living pigs the feasibility of TOEMS was shown. It was unclear whether TOEMS could be safely applied in patients requiring mediastinal lymph node biopsies. METHODS: We conducted a clinical phase I study recruiting ten patients with unclear mediastinal lymphadenopathy not resolved by prior bronchoscopy. All patients underwent TOEMS for mediastinal lymph node biopsy. The duration of the procedure and complications were monitored. In addition, all patients were examined for pain, swallowing dysfunction and sensation disturbance. RESULTS: TOEMS was accomplished in eight patients. In two patients operation was converted to VAM due to technical problems. Mediastinal lymph nodes were dissected in all patients who finished with TOEMS. On average, two separate lymph stations were reached by TOEMS. Duration of the procedure was 159±22 min. Permanent palsy of the right recurrent laryngeal nerve was noticed in one patient postoperatively. CONCLUSIONS: This is the first report for a human application of NOTES in thoracic surgery. In fact, transoral endoscopic surgery seems to be a feasible approach for mediastinal lymph node biopsies. Further studies are needed to show whether this procedure has an advantage over VAM in terms of pain, complications and accessibility of mediastinal lymph node stations.
Assuntos
Anormalidades Múltiplas , Defeito do Septo Aortopulmonar , Circulação Colateral/fisiologia , Circulação Coronária , Anomalias dos Vasos Coronários/diagnóstico , Neoplasias Cardíacas/irrigação sanguínea , Idoso , Procedimentos Cirúrgicos Cardíacos/métodos , Angiografia Coronária , Anomalias dos Vasos Coronários/fisiopatologia , Anomalias dos Vasos Coronários/cirurgia , Feminino , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/fisiopatologia , HumanosRESUMO
This paper outlines the design and performance of an observational study on the profiles of volatile organic compounds (VOCs) in the breath of 37 lung cancer patients and 23 healthy controls of similar age. The need to quantify each VOC considered as a potential disease marker on the basis of individual calibration is elaborated, and the quality control measures required to maintain reproducibility in breath sampling and subsequent instrumental trace VOC analysis using solid phase microextraction-gas chromatography-mass spectrometry over a study period of 14 months are described. Twenty-four VOCs were quantified on the basis of their previously suggested potential as cancer markers. The concentration of aromatic compounds in the breath was increased, as expected, in smokers, while lung cancer patients displayed significantly increased levels of oxygenated VOCs such as aldehydes, 2-butanone and 1-butanol. Although sets of selected oxygenated VOCs displayed sensitivities and specificities between 80% and 90% using linear discriminant analysis (LDA) with leave-one-out cross validation, the effective selectivity of the breath VOC approach with regard to cancer detection is clearly limited. Results are discussed against the background of the literature on volatile cancer marker investigations and the prospects of linking increased VOC levels in patients' breath with approaches that employ sniffer dogs. Experience from this study and the literature suggests that the currently available methodology is not able to use breath VOCs to reliably discriminate between cancer patients and healthy controls. Observational studies often tend to note significant differences in levels of certain oxygenated VOCs, but without the resolution required for practical application. Any step towards the exploitation of differences in VOC profiles for illness detection would have to solve current restrictions set by the low and variable VOC concentrations. Further challenges are the technical complexity of studies involving breath sampling and possibly the limited capability of current analytical procedures to detect unstable marker candidates.