Peri- and postoperative morbidity and mortality in older patients with non-small cell lung cancer: a matched-pair study.

BACKGROUND: Reports from case series suggest that operative outcomes are comparable amongst different age groups following surgery with curative intent for non-small cell lung cancer (NSCLC). The purpose of this study was to compare morbidity and mortality after NSCLC surgery in older patients (≥ 75 years) versus younger patients (< 75 years) and identify independent predictive risk factors. METHODS: We identified 2015 patients with postoperative stages IA to IIIA according to AJCC/UICC 7th edition who had undergone NSCLC surgery with curative intent at a single specialized lung cancer center from January 2010 to December 2015. A matched-pair analysis was performed on 227 older patients and corresponding 227 younger patients. Short-term surgical outcomes were postoperative morbidity, length of hospital stay, 30-day and 90-day mortality. Long-term operative outcomes were disease-free and overall survival. RESULTS: 454 patients were included in the matched-pair analysis. 36% of younger patients developed postoperative complications versus 42% in older patients (p = 0.163). Age was not significantly associated with the occurrence of postoperative complications. Median length of hospital stay was 14 days in older patients and 13 days in younger patients (p = 0.185). 90-day mortality was 2.2% in younger patients compared to 4% in older patients (p = 0.424). In patients aged 75 and older impaired performance status (ECOG ≥ 1) was associated with decreased overall survival (HR = 2.15, CI 1.34-3.46), as were preoperative serum C-reactive protein / albumin ratio ≥ 0.3 (HR = 1.95, CI 1.23-3.11) and elevated preoperative serum creatinine levels ≥ 1.1 mg/dl (HR = 1.84, CI 1.15-2.95). In the younger cohort male sex (HR = 2.26, CI 1.17-4.36), postoperative stage III disease (HR 4.61, CI 2.23-9.54) and preoperative anemia (hemoglobin < 12 g/dl) (HR 2.09, CI 1.10-3.96) were associated with decreased overall survival. CONCLUSIONS: Lung resection for NSCLC in older patients is associated with postoperative morbidity and mortality comparable to those of younger patients. In older patients, physical activity, comorbidities and nutritional status are related to survival and should influence the indication for surgery rather than age alone.

[Anatomical Lung Resection Following Neoadjuvant Chemoimmunotherapy: Technical Aspects and Case Reports]. / Anatomische Lungenresektion nach neoadjuvanter Chemo-Immuntherapie: technische Aspekte und klinische Fallbeispiele.

Since the approval of neoadjuvant chemo-immunotherapy in Europe, treatment options for resectable stage II-III NSCLC have also significantly improved in clinical routine. Surgical excision of the tumour by anatomic lung resection still remains the most essential component of multimodal therapy. However, with the increasing use of the new treatment concepts in clinical routine, questions also arise regarding safety, adverse events and technical resectability following neoadjuvant chemo-immunotherapy. This review summarises the current data on perioperative safety following neoadjuvant chemo-immunotherapy and discusses aspects of surgical technique, the extent of resection and intraoperative challenges illustrated by clinical case reports.

[Robot-assisted Thoracic Surgery: Learning Curve and Cost Analysis in a German High-Volume Centre]. / Roboterassistierte Thoraxchirurgie: Ökonomie und Lernkurve an einem High-Volume-Zentrum.

Robot-assisted thoracic surgery (RATS) is a rapidly evolving surgical technique in Europe. The aim of the study was to analyse the learning curve and safety during the establishment of a RATS-program at a high-volume thoracic surgery centre and to quantify the costs of the surgical procedure in Germany. Within a period of 33 months, 255 patients were prospectively enrolled in the study and all perioperative process times and complications were recorded. Mediastinal procedures were performed in 46%, anatomical lung resections in 38%, wedge resections in 7% and diaphragm plications in 6% of patients. The mean operating time was 130 min and the total length of stay was 7 days. The conversion rate was 3.2% and 30-day mortality 1.2%. Mean costs for surgical consumables per intervention amounted to 2,039 €; the average reimbursement was 9,568 €. In summary, RATS can be safely established, performed and trained with low complication rates and acceptable costs for consumables.

Thoracic surgery in the non-intubated spontaneously breathing patient.

BACKGROUND: The interest in non-intubated video-assisted thoracic surgery (NIVATS) has risen over the last decade and numerous terms have been used to describe this technique. They all have in common, that the surgical procedure is performed in a spontaneously breathing patient under locoregional anaesthesia in combination with intravenous sedation but have also been performed on awake patients without sedation. Evidence has been generated favouring NIVATS compared to one-lung-ventilation under general anaesthesia. MAIN BODY: We want to give an overview of how NIVATS is performed, and which different techniques are possible. We discuss advantages such as shorter length of hospital stay or (relative) contraindications like airway difficulties. Technical aspects, for instance intraoperative handling of the vagus nerve, are considered from a thoracic surgeon's point of view. Furthermore, special attention is paid to the cohort of patients with interstitial lung diseases, who seem to benefit from NIVATS due to the avoidance of positive pressure ventilation. Whenever a new technique is introduced, it must prove noninferiority to the state of the art. Under this aspect current literature on NIVATS for lung cancer surgery has been reviewed. CONCLUSION: NIVATS technique may safely be applied to minor, moderate, and major thoracic procedures and is appropriate for a selected group of patients, especially in interstitial lung disease. However, prospective studies are urgently needed.

Population-Based Analysis of Sex-Dependent Risk Factors for Mortality in Thoracic Surgery for Lung Cancer.

OBJECTIVE: Sex is an important predictor for lung cancer survival and a favorable prognostic indicator for women compared to men. Specific surgery-related sex differences of patients with lung cancer remain unclear. The aim of this study is to analyze sex-specific differences after lung cancer resections to identify factors for an unfavorable prognosis. METHODS: This is a retrospective analysis of a German nationwide discharge register of every adult inpatient undergoing pulmonary resection for lung cancer from 2014 until 2017. DRG data and OPS procedures were analyzed with the help of the Federal Statistical Office using remote controlled data. A multivariable regression model was established in a stepwise process to evaluate the effect of sex on inpatient mortality. RESULTS: A total of 38,806 patients underwent surgical resection for lung cancer between January 2014 and December 2017 in Germany. Women were significantly younger at admission than men (mean 64.7 years [SD 10.1] vs. 66.6 years [SD 9.5]; p < 0.0001). They had fewer unreferred admissions (risk ratio 0.83 [0.77, 0.90], p < 0.0001) and were significantly less likely to have recorded comorbidities. Raw in-hospital mortality was 1.8% for women and 4.1% for men. In the multivariable analysis of in-hospital mortality, the likelihood of death for women compared to men was 21% reduced (OR 0.79 [CI: 0.66, 0.93, p = 0.005]). The risk of postoperative complications such as ventilation >48 h, ARDS, tracheotomy, or pneumonia was significantly lower for women. CONCLUSIONS: Women undergoing lung cancer surgery were younger and had less comorbidities than men in Germany. Female sex was associated with lower mortality and less postoperative complications.

Incidental Pulmonary Nodules - What Do We Know in 2022.

Lung cancer (LC) is the leading cause of cancer-related mortality worldwide, and early LC diagnosis can significantly improve outcomes and survival rates in affected patients. Implementation of LC screening programs using low-dose computed tomography CT in high-risk subjects aims to detect LC as early as possible, but so far, adoption of screening programs into routine clinical care has been very slow. In recent years, the use of CT has significantly increased the rate of incidentally detected pulmonary nodules. Although most of those incidental pulmonary nodules (IPNs) are benign, some of them represent early-stage LC. Given the large number of IPNs detected in the range of several millions each year, this represents an additional, maybe even larger, opportunity to drive stage shift in LC diagnosis, next to LC screening programs. Comprehensive evaluation and targeted work-up of IPNs are mandatory to identify the malignant nodules from the crowd, and several guidelines provide radiologists and physicians' guidance on IPN assessment and management. However, IPNs still seem to be inadequately processed due to various reasons including insufficient reporting in the radiological report, missing communication between stakeholders, absence of patient tracking systems, and uncertainty regarding responsibilities for the IPN management. In recent years, several approaches such as lung nodule programs, patient tracking software, artificial intelligence, and communication software were introduced into clinical practice to address those shortcomings. This review evaluates the current situation of IPN management and highlights recent developments in process improvement to achieve first steps toward stage shift in LC diagnosis.

Surgical Lung Biopsy for Interstitial Lung Disease: A Two Center Propensity Score Matching Analysis.

BACKGROUND: Surgical lung biopsy (SLB) is recommended for patients with nonclassified interstitial lung disease (nILD) if high resolution computed tomography and/or transbronchial lung biopsy did not achieve a definitive diagnosis. Current literature suggests better patient tolerability and less postoperative complications if surgery is performed under spontaneous ventilation. OBJECTIVES: We conducted a propensity score matching (PSM) analysis of our nILD patients undergoing SLB under spontaneous ventilation or general anesthesia to investigate postprocedural AE-ILD, 30-/90-day mortality and perioperative variables in two academic high-volume centers (Hannover, Heidelberg). METHODS: All patients undergoing SLB for nILD under general anesthesia (GAVATS) and spontaneous ventilation (NIVATS) at both centers from February 2013 until April 2021 were analyzed retrospectively. Data of 132 patients were used for PSM resulting in 40 pairs. RESULTS: There was one death in the NIVATS group 60 days after SLB and one AE-ILD in each cohort. Chest tube indwelling time, chest tube total effusion, length of hospital stay, and operative time were all in favor of NIVATS. CONCLUSIONS: In our PSM analysis, NIVATS is associated with faster postprocedural recovery. However, a reduction in postoperative AE-ILD or 30-/90-day mortality was not observed.

Major clinical benefit from adjuvant chemotherapy for stage II-III non-small cell lung cancer patients aged 75 years or older: a propensity score-matched analysis.

BACKGROUND: Data are currently insufficient to support the use of adjuvant chemotherapy (ACT) after surgical resection for stage II or III non-small cell lung cancer (NSCLC) in patients aged ≥ 75 years. In this study we evaluated efficacy and safety profile of ACT in this population. METHODS: We retrospectively evaluated 140 patients ≥ 75 years who underwent curative surgical resection for stage II-III NSCLC from 2010 to 2018 with an indication to ACT according to current guidelines. A propensity score-matched analysis was performed to avoid cofounding biases. RESULTS: Thirty of 140 patients (21%) received ACT. Most patients (n = 24, 80%) received carboplatin in combination with vinorelbine, while 5 patients (17%) received cisplatin plus vinorelbine and one patient (3%) carboplatin plus gemcitabine. The occurrence of adverse events led to treatment discontinuation in 8 (27%) cases, while 19 (63%) patients completed 4 chemotherapy cycles. Common reported adverse events with ACT were anemia (n = 20, 67%), neutropenia (n = 18, 60%), thrombocytopenia (n = 9, 30%), renal impairment (n = 4, 13%) and transaminase elevation (n = 4, 13%). No toxic deaths occurred. The median follow-up was 67 months (IQR: 53-87). ACT was associated with a significant benefit in both relapse-free survival (median 36 vs. 18.5 months, p = 0.049) and overall survival (median not reached [NR] vs. 33.5 months, p = 0.023) in a propensity score-matched analysis which controlled for cofounders. CONCLUSION: ACT confers a survival benefit after curative resection of stage II-III NSCLC in selected patients aged 75 years or older with a manageable toxicity profile.

[Surgical Therapy of Malignant Lung and Chest Wall Tumours in Children]. / Chirurgische Therapie maligner Lungen- und Brustwandtumoren bei Kindern.

Primary lung and chest wall tumours as well as lung metastases are rare diseases in children. As part of multimodal cancer treatment, thoracic surgery can significantly improve survival in children suffering from paediatric solid tumours. The aim of the review article is to summarise the indications and the current surgical treatment options for malignant chest wall and lung tumours as well as to shed light on the current role of pulmonary metastasectomy in children.

Role of Synaptophysin, Chromogranin and CD56 in adenocarcinoma and squamous cell carcinoma of the lung lacking morphological features of neuroendocrine differentiation: a retrospective large-scale study on 1170 tissue samples.

BACKGROUND: Synaptophysin, chromogranin and CD56 are recommended markers to identify pulmonary tumors with neuroendocrine differentiation. Whether the expression of these markers in pulmonary adenocarcinoma and pulmonary squamous cell carcinoma is a prognostic factor has been a matter of debate. Therefore, we investigated retrospectively a large cohort to expand the data on the role of synaptophysin, chromogranin and CD56 in non-small cell lung cancer lacking morphological features of neuroendocrine differentiation. METHODS: A cohort of 627 pulmonary adenocarcinomas (ADC) and 543 squamous cell carcinomas (SqCC) lacking morphological features of neuroendocrine differentiation was assembled and a tissue microarray was constructed. All cases were stained with synaptophysin, chromogranin and CD56. Positivity was defined as > 1% positive tumor cells. Data was correlated with clinico-pathological features including overall and disease free survival. RESULTS: 110 (18%) ADC and 80 (15%) SqCC were positive for either synaptophysin, chromogranin, CD56 or a combination. The most commonly positive single marker was synaptophysin. The least common positive marker was chromogranin. A combination of ≤2 neuroendocrine markers was positive in 2-3% of ADC and 0-1% of SqCC. There was no significant difference in overall survival in tumors with positivity for neuroendocrine markers neither in ADC (univariate: P = 0.4; hazard ratio [HR] = 0.867; multivariate: P = 0.5; HR = 0.876) nor in SqCC (univariate: P = 0.1; HR = 0.694; multivariate: P = 0.1, HR = 0.697). Likewise, there was no significant difference in disease free survival. CONCLUSIONS: We report on a cohort of 1170 cases that synaptophysin, chromogranin and CD56 are commonly expressed in ADC and SqCC and that their expression has no impact on survival, supporting the current best practice guidelines.

Cytoreductive Thoracic Surgery Combined with Hyperthermic Chemoperfusion for Pleural Malignancies: A Single-Center Experience.

BACKGROUND: Lung-sparing cytoreductive surgery by extended pleurectomy and decortication (EPD) in combination with hyperthermic intrathoracic chemoperfusion (HITOC) forms a promising treatment strategy for malignant pleural mesothelioma and recurrent pleural thymic malignancies. OBJECTIVES: The objective of this study was to scrutinize the surgical procedure and perioperative patient management with emphasis on perioperative morbidity and local tumor control. METHODS: In 2014, a standardized EPD and HITOC procedure was implemented at the Thoraxklinik Heidelberg. This retrospective analysis included clinical data of consecutive patients with pleural mesothelioma and pleural metastasized malignancies treated by EPD and HITOC. The surgical procedure, perioperative management, lung function data, and progression-free survival (PFS) were analyzed. RESULTS: In the time range between April 2, 2014 and July 2018, 76 patients with pleural malignancies have been treated with EPD and HITOC, and were analyzed retrospectively. It included 61 patients with pleural mesothelioma and 15 patients with pleural metastases of thymic malignancies (12), non-small cell lung cancer (1), colorectal carcinoma (1), and sarcoma (1). Perioperative morbidity following EPD and HITOC treatments represented 23.7% of overall malignancies, while 30- and 90-day mortality were 0 and 1.3%, respectively. Median PFS lasted 18.4 months for mesothelioma and 72.2 months for thymic malignancies. CONCLUSION: Combining EPD with HITOC can be performed in patients with either pleural mesothelioma or pleural metastases resulting in low perioperative morbidity and mortality as well as remarkable local tumor control.

[Robot-assisted Mediastinal Mass Resection]. / Roboterassistierte Thoraxchirurgie bei Mediastinaltumoren.

In recent years, robot-assisted thoracic surgery is gaining more and widespread interest in Europe. Due to the narrow space and the complexity of anatomical structures, conventional minimally invasive mediastinal surgery may be challenging for the thoracic surgeon. Robot-assisted mediastinal surgery opens up new possibilities for minimally invasive surgery, as it permits greater dexterity, a three-dimensional view, and tremor adjustment, which allows the surgeon to perform complex procedures in small thoracic spaces. As robotic platforms continue to evolve, more complex mediastinal thoracic surgical interventions will be facilitated, translating to improved outcomes for patients. This article provides an overview of the current status of robot-assisted mediastinal surgery and summarises general aspects of the indication, set-up and steps of robot-assisted thoracoscopic surgery in mediastinal mass resections.

[Expert Recommendation for the Implementation of Hyperthermic Intrathoracic Chemotherapy (HITOC) in Germany]. / Expertenempfehlung zur Anwendung der hyperthermen intrathorakalen Chemotherapie (HITOC) in Deutschland.

INTRODUCTION: During the last few years, hyperthermic intrathoracic chemotherapy (HITOC) has been performed in several departments for thoracic surgery in Germany. The objective of this expert recommendation is to provide elementary recommendations for a standardised HITOC treatment, which are based on clinical experiences and research data. METHODS: Between October and December 2018, a group of experts for thoracic surgery in five departments of thoracic surgery developed recommendations for the HITOC procedure in Germany. These experts were selected by the latest national survey for HITOC and had the most clinical experience with HITOC. All recommendations are based on clinical experience, the experts' research data and recent literature. RESULTS: All recommendations were evaluated by all participating departments in one consensus survey. Finally, a total of six main conclusions including a total of 17 recommendations were developed. For each recommendation, the strength of the consensus is presented in percentages. 100% agreement was established for nomenclature, technique, the chemotherapeutic agent, the perioperative management, the safety measures and the indications for HITOC. All experts recommended cisplatin as the first choice chemotherapeutic agent for HITOC. The dosage of cisplatin is specified in mg/m2 body surface area (BSA) and should be between 150 and 175 mg/m2 BSA. The volume of the perfusion fluid (approximately 4 - 5 l) seems to play a role for the concentration gradient of cisplatin and should therefore also be taken into account. CONCLUSIONS: These expert recommendations provide a standardised and consistent implementation of the HITOC procedure. On this basis, postoperative complications associated to HITOC should be reduced and comparison of the results should be improved.

Neoadjuvant anti-programmed Death-1 immunotherapy by Pembrolizumab in resectable nodal positive stage II/IIIa non-small-cell lung cancer (NSCLC): the NEOMUN trial.

BACKGROUND: Immunotherapies targeting the PD1/PD-L1 pathway have had a large impact on the treatment of advanced NSCLC. Concerning multimodality tumor therapy, only few trials until today have been performed investigating neoadjuvant treatment with anti PD-1 immunotherapy prior to curative intent surgery. Aim of the NEOMUN investigator initiated trial (EudraCT-Number: 2017-000105-20; ClinicalTrials.gov Identifier: NCT03197467) is to assess feasibility and safety of pre-surgical anti PD-1 treatment in order to improve long term survival. METHODS: The study is designed as an open-label, single arm, prospective, monocenter, phase II study including 30 patients with NSCLC stage II/IIIA suitable for curative intent surgery. Investigational drug is Pembrolizumab. After 2 cycles of immunotherapy (à 200 mg q3w i.v.), tumor resection with lobectomy or bilobectomy will be performed. Primary objectives are to assess the feasibility and safety of a neoadjuvant immunotherapy and to assess antitumor activity of Pembrolizumab with regard to clinical and pathological tumor response. Secondary objective is disease free and overall survival. Exploratory objective is to analyze potential predictive biomarkers and to evaluate the therapeutic efficacy of Pembrolizumab by extended immune cell and cytokine analysis of tumor tissue. The study protocol was approved by the local ethics committee and the federal authority. Start of patient enrollment is scheduled for June 2018. DISCUSSION: The NEOMUN trial will be one of the first clinical trials investigating a multimodal treatment strategy including neoadjuvant immunotherapy using Pembrolizumab as an investigational drug. Assessing the safety and therapeutic potential of neoadjuvant immunotherapy in connection with lung surgery will be of great interest for thoracic surgeons. TRIAL REGISTRATION: Prospectively, the NEOMUN study has been registered on www.clinicaltrials.gov ; NCT03197467 (first post: June 23rd, 2017).

The reproducibility of psychiatric evaluations of work disability: two reliability and agreement studies.

BACKGROUND: Expert psychiatrists conducting work disability evaluations often disagree on work capacity (WC) when assessing the same patient. More structured and standardised evaluations focusing on function could improve agreement. The RELY studies aimed to establish the inter-rater reproducibility (reliability and agreement) of 'functional evaluations' in patients with mental disorders applying for disability benefits and to compare the effect of limited versus intensive expert training on reproducibility. METHODS: We performed two multi-centre reproducibility studies on standardised functional WC evaluation (RELY 1 and 2). Trained psychiatrists interviewed 30 and 40 patients respectively and determined WC using the Instrument for Functional Assessment in Psychiatry (IFAP). Three psychiatrists per patient estimated WC from videotaped evaluations. We analysed reliability (intraclass correlation coefficients [ICC]) and agreement ('standard error of measurement' [SEM] and proportions of comparisons within prespecified limits) between expert evaluations of WC. Our primary outcome was WC in alternative work (WCalternative.work), 100-0%. Secondary outcomes were WC in last job (WClast.job), 100-0%; patients' perceived fairness of the evaluation, 10-0, higher is better; usefulness to psychiatrists. RESULTS: Inter-rater reliability for WCalternative.work was fair in RELY 1 (ICC 0.43; 95%CI 0.22-0.60) and RELY 2 (ICC 0.44; 0.25-0.59). Agreement was low in both studies, the 'standard error of measurement' for WCalternative.work was 24.6 percentage points (20.9-28.4) and 19.4 (16.9-22.0) respectively. Using a 'maximum acceptable difference' of 25 percentage points WCalternative.work between two experts, 61.6% of comparisons in RELY 1, and 73.6% of comparisons in RELY 2 fell within these limits. Post-hoc secondary analysis for RELY 2 versus RELY 1 showed a significant change in SEMalternative.work (- 5.2 percentage points WCalternative.work [95%CI - 9.7 to - 0.6]), and in the proportions on the differences ≤ 25 percentage points WCalternative.work between two experts (p = 0.008). Patients perceived the functional evaluation as fair (RELY 1: mean 8.0; RELY 2: 9.4), psychiatrists as useful. CONCLUSIONS: Evidence from non-randomised studies suggests that intensive training in functional evaluation may increase agreement on WC between experts, but fell short to reach stakeholders' expectations. It did not alter reliability. Isolated efforts in training psychiatrists may not suffice to reach the expected level of agreement. A societal discussion about achievable goals and readiness to consider procedural changes in WC evaluations may deserve considerations.

Circulating and Tumor Myeloid-derived Suppressor Cells in Resectable Non-Small Cell Lung Cancer.

RATIONALE: Myeloid-derived suppressor cell (MDSC) expansion has been found to play a role in disease progression in patients with cancer. However, the characteristics of MDSCs in lung cancer are poorly understood. OBJECTIVES: We prospectively investigated MDSCs and inflammatory factors in tumor and peripheral blood samples from patients with resectable non-small cell lung cancer and studied their correlations with the disease prognosis. METHODS: A complex analysis of MDSC subsets and inflammatory mediators was performed using flow cytometry and a Bio-Plex assay. MEASUREMENTS AND MAIN RESULTS: A significant increase in the frequency of circulating monocytic (M)-MDSCs was observed in the patients with non-small cell lung cancer compared with the healthy donors (HDs). Moreover, the frequencies of M- and polymorphonuclear (PMN)-MDSCs were higher in tumors than in the peripheral blood of the same patients. This accumulation was associated with elevated concentrations of inflammatory mediators involved in MDSC migration to and activation in the tumor microenvironment. An analysis of the MDSC immunosuppressive pattern showed increased programmed death-ligand 1 expression on circulating cells from patients compared with HDs. Tumor PMN-MDSCs displayed higher programmed death-ligand 1 expression levels than the same cells in the peripheral blood. The frequency of CCR5 (C-C chemokine receptor 5) expression on circulating M-MDSCs was significantly higher in the patients than in the HDs. Clinical data analysis revealed negative correlations between recurrence-free survival and the frequencies of PMN-MDSCs and CCR5+ M-MDSCs in the circulation but not in tumors. CONCLUSIONS: Our findings suggest that the level of MDSCs in the peripheral blood but not in tumor tissues predicts recurrence after surgery.

[Surgical Therapy of Pulmonal Echinococcosis]. / Die chirurgische Therapie der pulmonalen Echinokokkose.

Human echinococcosis is a rare zoonotic infection caused by larvae of the tapeworm species Echinococcus. The most relevant two species to humans are Echinococcus multilocularis and the dog tapeworm Echinococcus granulosus. The latter causes cystic echinococcosis, which plays a dominant role in thoracic surgery due to its pulmonal involvement. The parasite develops characteristic hydatic cysts mostly in liver and lung. In 2016 a rise in cases of cystic echinococcosis in Germany was recorded, a probable cause could have been the refugee wave. The infection and advanced stages of the disease does not always cause symptoms and stays asymptomatic. Dry cough, thoracic pain and hemoptysis are uncharacteristic symptoms. Cysts may rupture and void into the bronchial system or thoracic cavity, which can result in empyema. Surgery remains the main therapeutic approach for pulmonary cystic echinococcosis. Surgical therapy includes peri- or endocystectomy, wedge and anatomic resections. Depending on size and localization of hydatid cysts the appropriate surgical technique should be chosen aiming on minimal loss of lung parenchyma. The treatment strategies need to be discussed in an interdisciplinary setting including infectiologists and thoracic or general surgeons. The respective treatment should be carried out in specialized centers due to the low incidence of the disease.

EML4-ALK fusion variant V3 is a high-risk feature conferring accelerated metastatic spread, early treatment failure and worse overall survival in ALK+ non-small cell lung cancer.

In order to identify anaplastic lymphoma kinase-driven non-small cell lung cancer (ALK+ NSCLC) patients with a worse outcome, who might require alternative therapeutic approaches, we retrospectively analyzed all stage IV cases treated at our institutions with one of the main echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variants V1, V2 and V3 as detected by next-generation sequencing or reverse transcription-polymerase chain reaction (n = 67). Progression under tyrosine kinase inhibitor (TKI) treatment was evaluated both according to Response Evaluation Criteria in Solid Tumors (RECIST) and by the need to change systemic therapy. EML4-ALK fusion variants V1, V2 and V3 were found in 39%, 10% and 51% of cases, respectively. Patients with V3-driven tumors had more metastatic sites at diagnosis than cases with the V1 and V2 variants (mean 3.3 vs. 1.9 and 1.6, p = 0.005), which suggests increased disease aggressiveness. Furthermore, V3-positive status was associated with earlier failure after treatment with first and second-generation ALK TKI (median progression-free survival [PFS] by RECIST in the first line 7.3 vs. 39.3 months, p = 0.01), platinum-based combination chemotherapy (median PFS 5.4 vs. 15.2 months for the first line, p = 0.008) and cerebral radiotherapy (median brain PFS 6.1 months vs. not reached for cerebral radiotherapy during first-line treatment, p = 0.028), and with inferior overall survival (39.8 vs. 59.6 months in median, p = 0.017). Thus, EML4-ALK fusion variant V3 is a high-risk feature for ALK+ NSCLC. Determination of V3 status should be considered as part of the initial workup for this entity in order to select patients for more aggressive surveillance and treatment strategies.

[Implementation of Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Germany]. / Anwendung der hyperthermen intrathorakalen Chemotherapie (HITHOC) in Deutschland.

INTRODUCTION: For several years, hyperthermic intrathoracic chemotherapy (HITHOC) has been performed in a few departments for thoracic surgery in a multimodality treatment regime in addition to surgical cytoreduction. Specific data about HITHOC in Germany are still lacking. METHODS: Survey in written form to all departments of thoracic surgery in Germany. The objective is the evaluation of HITHOC with respect to number, indications, technique, perioperative protection measure and complications. RESULTS: A total of 116 departments of thoracic surgery were contacted, with a return rate of 43% (n = 50). HITHOC was not performed in 33 departments, due to lack of resources or experience (n = 17), missing efficacy of the procedure (n = 8) and fear of excessive complication rates (n = 3). Since 2008, a total of 343 HITHOC procedures have been performed in 17 departments. Eight departments have their own perfusion machine, whereas the remaining departments borrow the perfusion machine. Indications were malignant pleural mesothelioma in all departments (n = 17), thymoma with pleural spread (n = 11) and secondary pleural carcinosis (n = 7). The HITHOC was performed in nearly all departments after closing the chest (n = 16), with a temperature of 42 °C (n = 12) and for 60 minutes (n = 15). Cisplatin was always used, either alone (n = 9) or in combination (n = 8). In all the participating departments, the aims of the HITHOC were improvement in local tumor control and prolonged recurrence-free and overall survival. Relevant HITHOC-associated complications were low. CONCLUSIONS: HITHOC is performed in at least 17 departments of thoracic surgery in Germany, and is widely standardised with protective measures and a low rate of complications. The aims of the HITHOC are improvement in local tumor control in pleural malignancies combined with prolonged overall survival and better quality of life.

[Screening for Lung Cancer: Current Status]. / Lungenkrebsfrüherkennung: eine Bestandsaufnahme.

The evidence for the benefit and risks of lung cancer screening is based on a single large randomised controlled trial that showed a significant reduction in lung cancer mortality among lung cancer patients in the CT screening group compared to the control group. However, there are significant risks to the proven benefit. The large and unresolved problem in CT screening for lung cancer is the high rate of false positive findings. Further diagnostic work-up of these findings often requires invasive procedures. The complications that may occur are the main risk associated with CT screening for lung cancer. The German and European specialist associations are currently still holding back a recommendation for comprehensive CT screening for lung cancer. The risk benefit ratio is assessed as unfavourable. The results are awaited of the ongoing European studies ("NELSON" in the Netherlands and "LUSI" in Germany), which probably will be available by the end of 2018. Data are expected on more effective work-up algorithms with lower rates of false positive findings and thus lower complication rates. With these data, there will be a new risk benefit assessment.