ADPGK-AS1 long noncoding RNA switches macrophage metabolic and phenotypic state to promote lung cancer growth.

Long noncoding RNAs (lncRNAs) influence the transcription of gene networks in many cell types, but their role in tumor-associated macrophages (TAMs) is still largely unknown. We found that the lncRNA ADPGK-AS1 was substantially upregulated in artificially induced M2-like human macrophages, macrophages exposed to lung cancer cells in vitro, and TAMs from human lung cancer tissue. ADPGK-AS1 is partly located within mitochondria and binds to the mitochondrial ribosomal protein MRPL35. Overexpression of ADPGK-AS1 in macrophages upregulates the tricarboxylic acid cycle and promotes mitochondrial fission, suggesting a phenotypic switch toward an M2-like, tumor-promoting cytokine release profile. Macrophage-specific knockdown of ADPGK-AS1 induces a metabolic and phenotypic switch (as judged by cytokine profile and production of reactive oxygen species) to a pro-inflammatory tumor-suppressive M1-like state, inhibiting lung tumor growth in vitro in tumor cell-macrophage cocultures, ex vivo in human tumor precision-cut lung slices, and in vivo in mice. Silencing ADPGK-AS1 in TAMs may thus offer a novel therapeutic strategy for lung cancer.

CEACAM6 as a Novel Therapeutic Target to Boost HO-1-mediated Antioxidant Defense in COPD.

Rationale: Tobacco smoking and air pollution are primary causes of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop COPD. The mechanisms underlying the defense against nitrosative/oxidative stress in nonsusceptible smokers to COPD remain largely unresolved. Objectives: To investigate the defense mechanisms against nitrosative/oxidative stress that possibly prevent COPD development or progression. Methods: Four cohorts were investigated: 1) sputum samples (healthy, n = 4; COPD, n = 37), 2) lung tissue samples (healthy, n = 13; smokers without COPD, n = 10; smoker+COPD, n = 17), 3) pulmonary lobectomy tissue samples (no/mild emphysema, n = 6), and 4) blood samples (healthy, n = 6; COPD, n = 18). We screened 3-nitrotyrosine (3-NT) levels, as indication of nitrosative/oxidative stress, in human samples. We established a novel in vitro model of a cigarette smoke extract (CSE)-resistant cell line and studied 3-NT formation, antioxidant capacity, and transcriptomic profiles. Results were validated in lung tissue, isolated primary cells, and an ex vivo model using adeno-associated virus-mediated gene transduction and human precision-cut lung slices. Measurements and Main Results: 3-NT levels correlate with COPD severity of patients. In CSE-resistant cells, nitrosative/oxidative stress upon CSE treatment was attenuated, paralleled by profound upregulation of heme oxygenase-1 (HO-1). We identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a negative regulator of HO-1-mediated nitrosative/oxidative stress defense in human alveolar type 2 epithelial cells (hAEC2s). Consistently, inhibition of HO-1 activity in hAEC2s increased the susceptibility toward CSE-induced damage. Epithelium-specific CEACAM6 overexpression increased nitrosative/oxidative stress and cell death in human precision-cut lung slices on CSE treatment. Conclusions: CEACAM6 expression determines the hAEC2 sensitivity to nitrosative/oxidative stress triggering emphysema development/progression in susceptible smokers.

[Adjuvant Lung Cancer Therapy in the Elderly: Comparative Analysis of Indication, Adherence to Therapy, and Long Term Survival]. / Adjuvante Therapie betagter Lungenkrebspatienten: Komparative Analyse von Indikationsstellung, Therapieadhärenz und Langzeitüberleben.

BACKGROUND: Lung cancer is frequently diagnosed among elderly patients. However, this patient group is under-represented in or excluded from clinical trials and, therefore, evidence-based treatment is challenging. It is uncertain whether there are differences in the feasibility of adjuvant therapies between older and younger patients with NSCLC. The objective of this study was the analysis of treatment recommendations, adherence to adjuvant therapy, and overall survival in patients of at least 70 years of age with resected stage II, III or oligometastatic IV NSCLC in comparison to younger patients. METHODS: 316 patients with NSCLC stage II to IV oligo resected with curative intent at the Giessen University Hospital between 2008 and 2019 were included, 115 of them 70 years or older. Patient and tumor characteristics, treatment type and survival data were extracted from the oncological database of the Mittelhessen lung cancer centre. Primary endpoints were indication and adherence to adjuvant treatment. Secondary endpoints were therapy-associated morbidity and overall survival. RESULTS: Elderly received significantly fewer recommendations for adjuvant therapy, both chemotherapy (OR=0.509) and radiochemotherapy (OR=0.455). Compared to younger patients, elderly patients commenced therapy significantly less often (OR=4.49) and were less likely to complete treatment (OR=0.423). The 5-year survival rates of treated elderly patients treated exceeded those of untreated elderly (Stage II, 51.9 vs 31.8%; stage III, 29.0 vs 25.8%), and were inferior to the survival rates of the younger patients (stage II, 69.8 vs. 69.8%; stage III 52.8 vs. 19.7%). CONCLUSION: In general, adjuvant therapy appears to be useful and feasible in selected patients over 70 years of age. However, its implementation and success are limited compared to younger patients. Adjuvant therapy is recommended and performed less frequently in older patients. The number of elderly patients treated remained unchanged over time, despite an increasing amount of therapy recommendations. Since the postoperative course, comorbidities, frailty and the toxicity of the therapy play a major role, the assessment of each individual case in an interdisciplinary oncological conference should serve as the basis for therapy decisions instead of age. Further studies are needed to collect representative data for the general elderly population. Newer, potentially better tolerated drugs such as tyrosine kinase inhibitors or immune checkpoint inhibitors appear to be promising.

Cyclophilin inhibitors restrict Middle East respiratory syndrome coronavirus via interferon-λ in vitro and in mice.

While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use.We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection.Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model.Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication in vivo, correlating with elevated lung IFNλ levels and improved outcome.We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replication in vitro and in vivo via upregulation of inflammatory antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate for treating MERS-CoV infection.

Management of Persistent Air Leaks with Intrabronchial Valves.

Persistent air leaks (PALs) are regarded as a frequent complication after thoracic surgery resulting in prolonged hospitalization and increased morbidity. Several more or less invasive therapeutic approaches are available for treatment of PAL with varying degrees of success. The endoscopic placement of one-way intrabronchial valves in the segment(s) in which the air leak has been located offers a highly effective and well-tolerated minimal invasive option for patients with PAL.

Stage-directed therapy of pleural empyema.

PURPOSE: Intensivists and surgeons are often confronted with critically ill patients suffering from pleural empyema. Due to it' s multifactorial pathogenesis and etiology, medicals should be sensitized to recognize the different stages of the disease. Besides a whole bundle of different established classification systems, the progress of pleural effusions can be subdivided into the early exudative, the intermediate fibropurulent and the late organized phase according to the classification of the American Thoracic Society. RESULTS: Rapid diagnosis of pleura empyema is essential for patients' survival. Due to the importance of stage-adapted therapeutic decisions, different classification systems were established. Depending on the stage of pleural empyema, both antimicrobial and interventional approaches are indicated. For organized empyema, minimally invasive and open thoracic surgery are gold standard. Surgery is based on the three therapeutic columns: removal of pleural fluid, debridement and decortication. In general, therapy must be intended stage-directed following multidisciplinary concepts including surgeons, intensivists, anesthesiologists, physiotherapists and antibiotic stewards. Despite an established therapeutic algorithm is presented in this review, there is still a lack of randomized, prospective studies to evaluate potential benefits of minimally invasive (versus open) surgery for end-stage empyema or of catheter-directed intrathoracic fibrinolysis (versus minimally invasive surgery) for intermediate-stage pleural empyema. Any delay in adequate therapy results in an increased morbidity and mortality. CONCLUSION: The aim of this article is to review current treatment standards for different phases of adult thoracic empyema from an interdisciplinary point of view.

Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia.

Influenza A virus (IAV) infection mobilizes bone marrow-derived macrophages (BMDM) that gradually undergo transition to tissue-resident alveolar macrophages (TR-AM) in the inflamed lung. Combining high-dimensional single-cell transcriptomics with complex lung organoid modeling, in vivo adoptive cell transfer, and BMDM-specific gene targeting, we found that transitioning ("regenerative") BMDM and TR-AM highly express Placenta-expressed transcript 1 (Plet1). We reveal that Plet1 is released from alveolar macrophages, and acts as important mediator of macrophage-epithelial cross-talk during lung repair by inducing proliferation of alveolar epithelial cells and re-sealing of the epithelial barrier. Intratracheal administration of recombinant Plet1 early in the disease course attenuated viral lung injury and rescued mice from otherwise fatal disease, highlighting its therapeutic potential.

New developments in videomediastinoscopy: video-assisted mediastinoscopic lymphadenectomy and mediastinoscopic ultrasound.

BACKGROUND: Mediastinal lymphadenectomy is usually performed at thoracotomy together with lung resection. It is a prerequisite for accurate nodal staging and has an impact on survival. METHODS: VAMLA (video-assisted mediastinoscopic lymphadenectomy) dissection is guided by anatomical landmarks. It includes en bloc resection of the right and central compartments, and dissection and lymphadenectomy of the left-sided compartment. RESULTS: VAMLA harvested significantly more mediastinal lymph nodes than open lymphadenectomy (p < 0.001). Mean duration was 54 min, the complication rate 4.6%, sensitivity 93.8%, specificity 100%, and the false-negative rate 0.9%. 16 of 24 cT4 tumors were correctly predicted to be resectable by MUS (mediastinoscopic ultrasound). For minimally invasive oncological lung resections, combined VATS + VAMLA harvested significantly more lymph nodes than VATS alone without impact on operation time and complication rate (p < 0.05). CONCLUSION: VAMLA is a well-tolerated minimally invasive method for accurate mediastinal staging and radical mediastinal dissection. VAMLA can be carried out independently from tumor resection. We suggest its application together with neoadjuvant strategies, trials, VATS lobectomy, and radiation therapy for curatively intended involved field radiation. Additional MUS is helpful to detect resectable cT4 cases, and offer them curative treatment.

Who Is Afraid of CRP? Elevated Preoperative CRP Levels Might Attenuate the Increase in Inflammatory Parameters in Response to Lung Cancer Surgery.

During surgery, ATP from damaged cells induces the release of interleukin-1ß, a potent pro-inflammatory cytokine that contributes to the development of postoperative systemic inflammation, sepsis and multi-organ damage. We recently demonstrated that C-reactive protein (CRP) inhibits the ATP-induced release of monocytic interleukin-1ß, although high CRP levels are deemed to be a poor prognostic marker. Here, we retrospectively investigated if preoperative CRP levels correlate with postoperative CRP, leukocyte counts and fever in the context of anatomical lung resection and systematic lymph node dissection as first line lung cancer therapy. No correlation was found in the overall results. In men, however, preoperative CRP and leukocyte counts positively correlated on postoperative days one to two, and a negative correlation of CRP and fever was seen in women. These correlations were more pronounced in men taking statins and in statin-naïve women. Accordingly, the inhibitory effect of CRP on the ATP-induced interleukin-1ß release was blunted in monocytes from coronary heart disease patients treated with atorvastatin compared to monocytes obtained before medication. Hence, the common notion that elevated CRP levels predict more severe postoperative inflammation should be questioned. We rather hypothesize that in women and statin-naïve patients, high CRP levels attenuate trauma-induced increases in inflammatory markers.

Does endoesophageal ultrasound-guided fine-needle aspiration replace mediastinoscopy in mediastinal staging of thoracic malignancies?

OBJECTIVE: To determine the impact of endoesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) on management of thoracic malignancies. METHODS: One hundred and twenty patients referred for invasive diagnostic and resection of thoracic malignancies were studied prospectively. Negative and inconclusive EUS-FNA findings were assessed by video-assisted mediastinoscopic lymphadenectomy (VAMLA) or open lymphadenectomy. RESULTS: One hundred and twenty patients, aged 64.1 years (range 38-85) underwent 120 EUS-FNA, 53 video-assisted mediastinoscopic and 48 open lymphadenectomies for diagnosis and treatment of 99 lung carcinoma, six lung metastases, five mesothelioma, three lymphoma, and eight other conditions. EUS-FNA showed T4 in 15/120 and adrenal or hepatic metastases in 9/120 cases. Prevalence of mediastinal lymph node metastases was 51.7%. EUS-FNA false-negative rate was 25.3%. EUS-FNA sensitivity was 91.7%, 78.1% and 43.8% for bulky disease, enlarged mediastinal nodes or normal nodes on CT scan, 50% and 96.6% for right- and left-sided tumours, and 80.6%, 78.9%, 23.8% and 25.0% for the lymph node stations 7, 5/6, 4R, and 4L. A 38.3% respectively 100% cut-down of mediastinoscopies leads in 7.5% respectively 20.8% to incorrect treatment decisions. CONCLUSIONS: EUS-FNA sensitivity depends on the localisation of the primary tumour, and extent and location of mediastinal disease. For left-sided tumours, EUS-FNA improves mediastinal staging by assessing stations 5 and 6 inaccessible to conventional mediastinoscopy. For extended mediastinal disease, mediastinoscopy can be avoided or spared for restaging after neoadjuvant therapy. Exclusion of mediastinal involvement requires mediastinoscopy or open lymphadenectomy. Beyond mediastinal nodal staging, EUS-FNA may detect T4 and M1 situations. Thus, EUS-FNA is a useful supplement to and not the replacement of mediastinoscopy.

Combined human papillomavirus typing and TP53 mutation analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second primary lung squamous cell carcinoma (SCC). However, this differentiation is crucial because the recommended treatments for metastatic HNSCC and second primary lung SCC differ profoundly. METHODS: We analyzed the origin of lung tumors in 32 patients with HNSCC using human papillomavirus (HPV) typing and targeted next generation sequencing of all coding exons of tumor protein 53 (TP53). RESULTS: Lung tumors were clearly identified as HNSCC metastases or second primary tumors in 29 patients, thus revealing that 16 patients had received incorrect diagnoses based on clinical and morphological data alone. CONCLUSION: The HPV typing and mutation analysis of all TP53 coding exons is a valuable diagnostic tool in patients with HNSCC and concurrent lung SCC, which can help to ensure that patients receive the most suitable treatment.

Comparative intention-to-treat analysis of the video-assisted thoracoscopic surgery approach to pulmonary segmentectomy for lung carcinoma‡.

OBJECTIVES: To compare the video-assisted thoracoscopic surgery (VATS) with the open thoracotomy access to pulmonary segmentectomy by the clinical outcomes and long-term survival in lung carcinoma. METHODS: Non-randomized comparative intention-to-treat study of prospective institutional registry data and survival data of 100 consecutive patients undergoing segmentectomy. RESULTS: Within one decade (2002-12), 100 patients with proven or highly suspected lung carcinoma underwent 100 anatomical sub-lobar pulmonary resections (52 typical and 20 atypical segmentectomies, 28 split-lobe procedures). Fifty-six patients were operated by VATS and 44 by thoracotomy access. Comparison of demographic, medical, oncological and surgical baseline data did not provide evidence for differences between the VATS and thoracotomy groups. The surgery time for the VATS group was 225 ± 62 min and 195 ± 57 min for the thoracotomy group (P = 0.014). Postoperative hospitalization was 9 days for the VATS group and 12 days for the thoracotomy group (P = 0.034). Postoperative morbidity was 35.7% for the VATS group and 50% for the thoracotomy group (P = 0.161). Both groups had no 30-day mortality. Conversion to thoracotomy occurred in 30.4% of the VATS group. Conversion was more frequent in patients with male gender, critical and prohibitive lung function, tumours with diameters exceeding 3 cm and atypical segmentectomies. The fractions of the pathological Union international contre le cancer (UICC) stages I, II and III were 74.4, 11.6 and 14% in the VATS group, and 70, 20 and 10% in the thoracotomy group (P = 0.445), respectively. Five-year overall survival was 86% in the VATS group and 69.9% in the thoracotomy group (P = 0.047), and 5-year recurrence-free survival was 58.5 and 48.6% (P = 0.480), respectively. CONCLUSIONS: Compared with thoracotomy access, the VATS approach to segmentectomy was associated with less postoperative morbidity and a 25% decrease in median hospital stay, despite a conversion rate of 30% due to the inclusion of atypical segmentectomies, higher tumour stages and patients with critical function for single lung ventilation. Five-year survival estimates suggested a small but significant overall survival benefit and a 10% difference of recurrence-free survival in favour of VATS. Although not fully conclusive, long-term results indicate that the thoracoscopic access to segmentectomy is probably not inferior to the thoracotomy approach. Confirmation by a larger number of risk-adjusted outcome data is required.

Split-lobe resections versus lobectomy for lung carcinoma of the left upper lobe: a pair-matched case-control study of clinical and oncological outcomes.

OBJECTIVES: To compare left upper split-lobe procedures, being upper trisegmentectomy and resection of the lingula, with left upper lobectomy for surgical treatment of lung carcinoma originating from the left upper lobe. METHODS: A pair-matched control study comparing the clinical and oncological outcomes of 22 consecutive patients after left upper split-lobe resections with those of 44 pair-matched controls that received left upper lobectomy for non-small-cell lung carcinomas. The control group was matched 1:2 for tumour diameter, histology, nodal status and patient age. In both groups, diagnosis and surgical treatment adhered to the principles of tissue-based preoperative mediastinal staging, intraoperative systematic nodal dissection, and gross surgical margins equal to the tumour diameter or at least 2 cm, a sufficient preoperative pulmonary function given. RESULTS: As intended by the study design, the split-lobe and lobectomy groups had similar median tumour diameters of 22.5 (range, 11-63) and 25 (range, 7-68) mm, respectively (P = 0.98), identical histologies (45.5% adenocarcinoma, 4.5% adenocarcinoma in situ, 45.5% squamous cell carcinoma and 4.5% neuroendocrine carcinoma) and identical pN stages (pN0 77.3%, pN1 9.1%, pN2 9.1% and ypN0 4.5%). In the split-lobe group, a lower preOP forced expiratory volume in one second (median 2.0 vs 2.3 l), a higher comorbidity (median Charlton score of 3 vs 2) and a preponderance of video-assisted thoracoscopy procedures (63.6 vs 27.3%) were prevalent (all P < 0.05). There were no significant outcome differences detected, neither with regard to the postoperative clinical course assessed by intra- and postoperative complications, operation time, tissue margins, duration of drainage and hospital stay and 30-day mortality, nor with regard to 5-year overall (0.89 vs 0.81, P = 0.90). CONCLUSIONS: Left upper lobectomy might be an overtreatment for selected cases of lung carcinoma whose resection by a split-lobe procedure produces adequate margins and a complete lymphadenectomy. Tumour diameters exceeding 2 cm, nodal involvement and previous neoadjuvant treatment do not necessarily exclude this option for selected patients under the condition of a meticulous nodal dissection. In this context, we would like to suggest a translational research of the split-lobe concept to other large pulmonary lobes.

Extended cervical mediastinoscopy revisited.

OBJECTIVES: To describe the diagnostic value of selective extended cervical mediastinoscopy (ECM) in combination with video-assisted mediastinoscopic lymphadenectomy (VAMLA) in mediastinal staging of potentially resectable left-sided lung carcinoma. METHODS: Institutional report on 110 ECM procedures indicated for enlarged lymph nodes within the aorto-pulmonary (AP) zone on computed tomography. Staging sensitivity, negative predictive value (NPV) and specificity of ECM, combined VAMLA and ECM, VAMLA alone and systematic dissection for lung resection via left-sided video-assisted thoracoscopic surgery (VATS) or thoracotomy were calculated from a subset of 92 patients with left-sided lung carcinoma. RESULTS: Selective ECM was performed in 12.6% of all video-mediastinoscopic procedures, and added, except for one vascular complication, there was no morbidity. ECM had an impact on mediastinal staging in 78.0% of the lung cancer cases. Sensitivity, NPV and specificity were 0.94, 0.96 and 1 for ECM to detect nodal involvement within the AP zone. Sensitivity, NPV and specificity to detect any mediastinal diseases were 0.94, 0.96 and 1 for the combination of ECM and VAMLA; 0.64, 0.80 and 1 for VAMLA alone and 0.76, 0.84 and 1 for systematic mediastinal dissection via left-sided VATS or thoracotomy approach. CONCLUSIONS: ECM complements VAMLA in comprehensive mediastinal dissection. Selective ECM is a valuable addendum to mediastinoscopic staging procedures for left-sided tumours, as it enhances sensitivity and NPV. Precaution and experience are required to circumvent the rare risk of potentially fatal vascular accidents.

Cotton-derived oxidized cellulose in minimally invasive thoracic surgery: a clinicopathological study.

OBJECTIVE: The aim of this study was to identify resorption, clinical performance, and safety of cotton-derived oxidized cellulose gauze applied as a hemostat in minimally invasive oncologic thoracic surgery. METHODS: This is a pilot prospective noncomparative observational human in vivo study. A piece of cotton-derived oxidized cellulose gauze measuring 5 × 20 cm was inserted into the subcarinal space of patients with potentially resectable lung carcinoma at the time of video-assisted mediastinoscopic lymphadenectomy and reexamined several days later for macroscopic and histologic evaluation at the time of subsequent lung resection. The primary endpoint was the local situation at the implantation site described by cellulose remnants, fluid collections, and adhesions. The secondary endpoint was safety, described by the number of adverse events and surgical reinterventions. RESULTS: Twenty-five consecutive eligible patients with potentially resectable lung carcinoma were included. The desired hemostatic effect was achieved in all cases. No adverse events were observed. At re-exploration 10.5 (5-28) days later, the cellulose gauze was found to lose its solid structure from the fifth day on. Remnants were last detected 14 days after insertion. The implantation site exhibited no inflammatory changes and a remarkable small amount of fluid collections and adhesions. CONCLUSIONS: Mediastinal application of cotton-derived oxidized cellulose is safe and effective. A piece of gauze measuring 5 × 20 cm seems to be absorbed completely within 15 days, thus precluding any interference with oncologic restaging and follow-up. The absence of relevant adhesions facilitates further surgical procedures. Larger comparative confirmatory studies are required. For large-scale resorption studies, our clinical model should be translated into a porcine model.

Complete video-assisted thoracoscopic surgery anatomic segmentectomy for clinical stage I lung carcinoma - technique and feasibility.

This paper describes a prospective, observational, single-centre study of 20 consecutive patients with clinical stage I lung carcinoma undergoing anatomical sublobar resections using complete video-assisted thoracoscopic surgery (cVATS). Thirteen male and seven female patients with a median age of 68 (range 57-84) years and a median of four (range 0-9) relevant comorbid conditions presented with five right-sided and 15 left-sided tumours, with a median diameter of 2.3 (range 1.0-5.2) cm. Thirteen segmentectomies, three bisegmentectomies and four trisegmentectomies with lymphadenectomy of the N1 stations and the mediastinum were performed, with a median duration of 212 (range 91-397) min, a conversion rate to open surgery of 20% and conversion to lobectomy of 10%. In five patients, we noted 10 postoperative adverse events but no transfusions, no readmissions and zero mortality. Median drainage time was six days, with a median hospital stay of 8.5 days. According to the pTNM classification, 10, three, one, and six patients were staged as Ia, Ib, IIb and IIIa, respectively. The distance between the tumour and the parenchymal stapling line exceeded the tumour diameter in 56%, 0% and 0% of T1a, T1b and T2 tumours, respectively. To conclude, cVATS anatomical sublobar resections are technically feasible. We observed a favourable postoperative course in 20 multimorbid or aged patients. In patients fit for lobectomy, the tumour diameter should not exceed 2 cm.

Combined videothoracoscopic and videomediastinoscopic approach improves radicality of minimally invasive mediastinal lymphadenectomy for early stage lung carcinoma.

OBJECTIVES: To assess the feasibility and radicality of a combined thoracoscopic and mediastinoscopic approach to mediastinal lymphadenectomy compared to thoracoscopy only for minimally invasive management of early stage lung carcinoma. METHODS: Prospective observational study of patients undergoing anatomical thoracoscopic lung resection for lung carcinoma in our department in 2007. Mediastinal lymphadenectomy was performed either thoracoscopically (VATS group) or by a combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy (VAMLA+VATS group). Inclusion criteria for the study were: stage Ia on CT scan, no central tumor at bronchoscopy, and no contraindications against lobectomy or segmentectomy. RESULTS: Eighteen VAMLA+VATS and fourteen VATS patients were studied. For histology, pTNM stage, type of resection, semiquantitative assessment of the fissure and vascular dissection plane, conversions, blood loss, operation time, adverse events and drainage time, no differences between the two groups were observed. In the VATS group, there was a slight preponderance of women, and right-sided tumors. In the VAMLA+VATS group, both the number of dissected mediastinal lymph node stations (mean, 6.4 stations vs 3.6 stations) and the weight of the mediastinal specimen (median, 11.2 groups vs 5.5 groups), were significantly higher than in the VATS group (p<0.05). CONCLUSIONS: A combined approach by VATS and VAMLA improves radicality of minimally invasive mediastinal lymphadenectomy without increase in operation time, morbidity, and drainage time.

Video-assisted mediastinoscopic lymphadenectomy.

Systematic mediastinal lymphadenectomy is usually done at thoracotomy together with lung resection. It is a prerequisite for accurate nodal staging and has an impact on survival. With the introduction of neoadjuvant therapy for stage III lung carcinoma, mediastinal staging before therapy became more important. Video-assisted mediastinoscopic lymphadenectomy (VAMLA) is a minimally invasive technique of systematic mediastinal dissection that equals radicality of open lymphadenectomy, and can be carried out before neoadjuvant treatment and independently from tumour resection. The VAMLA dissection technique follows the anatomical mediastinal structures, and includes the stations 7, 4R+L, 2R+L, and 3. Compared to open dissection, VAMLA harvested significantly more nodes. Dissection rates of 96%, 92%, 100% and 100% for the stations 2R, 4R, 7 and 4L were reported. In routine clinical use, the mean duration was 54 min, the complication rate was 4.6%. Accuracy data in 130 patients with radiologically normal mediastinum were: sensitivity 93.8%, specificity 100%, false negative rate 0.9%. VAMLA is an extremely accurate staging tool as well as definitive mediastinal surgery. Thus, VAMLA is valuable if neoadjuvant therapy is considered for minor mediastinal involvement, to avoid re-mediastinoscopies after induction treatment, to define the exact involved radiation field in functionally unresectable patients, for highly accurate pre-therapy staging in trials, and to improve mediastinal dissection with VATS lobectomy and left-sided tumours.

Video-assisted mediastinoscopic lymphadenectomy (VAMLA).

BACKGROUND: The development of a two-bladed spreadable videomediastinoscope in 1992 allowed increased exposure and bimanual dissection of mediastinal structures. Concurrent with technical progress in mediastinoscopy, neoadjuvant treatment of stage III lung cancer was introduced, and accuracy of pretreatment mediastinal staging became a topic at issue. In this setting, development of a videomediastinoscopic technique for complete mediastinal lymphadenectomy was the obvious thing to do. METHODS: Video-assisted mediastinoscopic lymphadenectomy (VAMLA) dissection is guided by anatomical landmarks, very similar to open lymphadenectomy. It includes en bloc resection of the right and central compartments and dissection and lymphadenectomy of the left-sided compartments. In a preliminary case-control study of 40 patients, VAMLA technique was standardized and evaluated against open lymphadenectomy. A second study investigated 130 patients with resectable lung cancer and radiographically normal mediastinum who underwent VAMLA and consecutive lung resection with mediastinal reexploration. RESULTS: VAMLA harvested significantly more nodes than open lymphadenectomy. With a mean duration of 54 minutes and a complication rate of 4.6%, VAMLA appeared applicable to clinical routine. We noted a sensitivity of 93.8%, a specificity of 100%, and a false-negative rate of 0.9%. CONCLUSIONS: In our experience, VAMLA is a feasible method of mediastinal staging. Its accuracy and radicality can equal open lymphadenectomy. However, VAMLA is minimally invasive and therefore pretherapeutically available. Its advantages might be of interest with neoadjuvant strategies, trials, involved field radiation, video-assisted thoroscopic lobectomy, and left-sided tumors.