[Surgical Therapy for Lung Cancer: Why it Should be Performed in High Volume Centres]. / Chirurgische Therapie des Lungenkarzinoms: Argumente für die Behandlung in großen Zentren.

Data on surgical lung cancer cases were extracted from the German Federal Statistics on Diagnosis-related groups (DRG) and a possible association between hospital volume and surgical mortality was explored. All treatment cases documented between 2005 and 2015 with the main diagnosis of lung cancer (International Classification of Disease code C34) and the German Operations and Procedure Key (OPS) codes 5-323 to 5-328 for anatomical lung resections were analysed. The treatment cases were assigned to hospital groups, defined according to the number of procedures performed per year. The total number of anatomical lung resections for the diagnosis of lung cancer increased by 24 % from 9376 resections in 2005 to 11,614 resections in 2015. In 2015, 57 % of anatomical lung resections in patients with lung cancer were performed in 47 high volume centres (hospitals with ≥ 75 resections/year); the remaining 43 % of the resections were distributed among 271 hospitals performing fewer than 75 resections per year. In hospitals performing fewer than 25 procedures/year, hospital mortality was almost twice as high as in large centres with ≥ 75 resections per year (5.7 vs. 3.0 %, mean value 2005 to 2015). In summary, our data indicate that a small number of high-volume hospitals perform the major part of lung resections of lung cancer in Germany with better survival as compared to low-volume hospitals. Based on current nationwide data a clear association between hospital volume and surgical mortality could be demonstrated.

[Surgical Therapy of Acquired Unilateral Diaphragmatic Paralysis: Indication and Results]. / Chirurgische Therapie bei erworbener einseitiger Zwerchfelllähmung: Indikation und Ergebnisse.

Unilateral elevation of the diaphragm may be due to various causes and requires further elucidation when the aetiology is unknown. Elevation of the diaphragm is often caused by diaphragmatic paralysis, either due to damage to the phrenic nerve or to the phrenic muscle. Patients typically complain of increased respiratory distress when lying down, bending or swimming. Basic diagnostic testing consists of a chest X-ray, as well as spirometry and computer tomography of the neck and chest. In many cases, no cause can be identified for the diaphragmatic paralysis. In symptomatic patients, diaphragm plication leads to fixation and thus to a reduction in the paradoxal respiratory movement of the paralysed diaphragm. In a large majority of studies, this results in significant and lasting improvement in vital capacity and respiratory distress. Spontaneous recovery of diaphragm paralysis is possible, even after several months, so a waiting period of at least 6 months should elapse before diaphragmatic plication is performed, if the clinical situation allows. The procedure can be performed minimally invasively, with low morbidity and mortality. When cutting the phrenic nerve, a nerve suture is recommended, if possible, or otherwise diaphragm plication during the procedure, especially in the case of pneumonectomy. This review provides an overview of the causes, pathophysiology, symptoms, diagnosis, therapy and results of diaphragmatic plication in acquired, unilateral diaphragmatic paralysis in adults, and suggests an algorithm for diagnostic testing and therapy.

[Typical and Atypical Carcinoids of the Lung: a Surgical Treatment Strategy]. / Typische und atypische Karzinoide der Lunge: chirurgische Behandlungsstrategie.

Pulmonary typical (TC) and atypical carcinoids (AC) are lung tumors with neuroendocrine differentiation. Pulmonary carcinoids account for < 2 % of all lung cancers and the incidence is around 0,5/100 000. Depending on localization and extension they present incidentally or symptomatically with cough, hemoptysis and postobstructive pneumonia. Less than 1 % are associated with endocrine activity. TC and AC are differentiated by defined histopathologic criteria (mitotic rate, necrosis). Patients with TC have excellent long-term survival after non-anatomical lung resection. AC are associated with higher recurrence rates and anatomical lung resection should be preferred. Radical mediastinal lymph node dissection should be performed for both TC and AC. Complete surgical resection is the most significant prognostic factor for localized carcinoids. Surgical metastasectomy should also be considered in case of resectable metastatic disease.

[Management of Hemoptysis: Results of an Algorithm-Based Interdisciplinary Treatment Scheme]. / Management von Hämoptysen: Ergebnisse einer algorithmusbasierten interdisziplinären Versorgung.

INTRODUCTION: Hemoptysis is a worrying symptom for the majority of patients, is frequently a sign for a severe disease and can develop into a life-threatening situation. Various therapeutic methods and medical specialties can be involved in the management of these patients. Guidelines or evidence-based recommendations on this issue are not available. Based on our long-term experience and considering all established diagnostic and therapeutic means, we propose an algorithm to manage this condition. PATIENTS AND METHODS: This is a retrospective analysis of a cohort from a single thoracic surgical institution. Data regarding the used diagnostic and therapeutic methods with focus on outcome parameters are presented. Based on our experience and the published data we discuss the proposed algorithm. RESULTS: Between 01.2009 and 12.2013, 204 patients were hospitalised and treated for hemoptysis. Malignancies were the most frequent (50 %) cause of hemoptysis, followed by infectious/inflammatory diseases (25 %), cardiovascular disorders (6 %), rare (12 %) and unclear (7 %) circumstances. In 71 cases the bleeding stopped spontaneously, in 124 (61 %) one invasive measure (interventional bronchoscopy 43, bronchial artery embolisation 34 or operation 12) or a combination of methods (35 combinations of two or all three methods) were necessary to stop the hemoptysis. Six patients died without intervention. The bronchial artery embolisation showed a 79 % success rate and a morbidity of 11 %. Lung resections were performed in 30 cases (morbidity 43 %, mortality 0 %). The mortality directly due to massive hemoptysis was 4.5 %. CONCLUSIONS: Even small hemoptysis can be the warning signal for serious conditions and immediate diagnostic evaluation and therapy, preferentially in an inpatient setting, is often mandatory. A prompt diagnostic bronchoscopy is advocated. The therapeutic method of first choice is non-surgical for the most cases (interventional bronchoscopy, bronchial artery embolisation). Lung resections retain an important role in the management of hemoptysis and are the only available therapy for some diseases. It is advisable to delay surgery until the bleeding is controlled and the patient is stabilised. Best results for managing hemoptysis can be achieved with a multidisciplinary approach (interventional bronchoscopy, angiology and thoracic surgery) in a high expertise centre.

Downregulation of MTSS1 expression is an independent prognosticator in squamous cell carcinoma of the lung.

BACKGROUND: The metastasis suppressor 1 (MTSS1) is a newly discovered protein putatively involved in tumour progression and metastasis. MATERIAL AND METHODS: Immunohistochemical expression of MTSS1 was analysed in 264 non-small-cell lung carcinomas (NSCLCs). RESULTS: The metastasis suppressor 1 was significantly overexpressed in NSCLC compared with normal lung (P=0.01). Within NSCLC, MTSS1 expression was inversely correlated with pT-stage (P=0.019) and histological grading (P<0.001). NSCLC with MTSS1 downregulation (<20%) showed a significantly worse outcome (P=0.007). This proved to be an independent prognostic factor in squamous cell carcinomas (SCCs; P=0.041), especially in early cancer stages (P=0.006). CONCLUSION: The metastasis suppressor 1 downregulation could thus serve as a stratifying marker for adjuvant therapy in early-stage SCC of the lung.

Cancer cell invasion and EMT marker expression: a three-dimensional study of the human cancer-host interface.

Cancer cell invasion takes place at the cancer-host interface and is a prerequisite for distant metastasis. The relationships between current biological and clinical concepts such as cell migration modes, tumour budding and epithelial-mesenchymal transition (EMT) remains unclear in several aspects, especially for the 'real' situation in human cancer. We developed a novel method that provides exact three-dimensional (3D) information on both microscopic morphology and gene expression, over a virtually unlimited spatial range, by reconstruction from serial immunostained tissue slices. Quantitative 3D assessment of tumour budding at the cancer-host interface in human pancreatic, colorectal, lung and breast adenocarcinoma suggests collective cell migration as the mechanism of cancer cell invasion, while single cancer cell migration seems to be virtually absent. Budding tumour cells display a shift towards spindle-like as well as a rounded morphology. This is associated with decreased E-cadherin staining intensity and a shift from membranous to cytoplasmic staining, as well as increased nuclear ZEB1 expression.

[Mediastinitis: Clinical Presentation and Therapy]. / Mediastinitis: Klinik und Behandlungsoptionen.

Acute infection of the mediastinum remains a condition with high morbidity and lethality rates. The manifestation and course of the illness vary widely depending on the cause of infection. Lack of knowledge or awareness of the illness and mostly unspecific clinical symptoms often delay diagnosis and thereby the start of adequate therapy. Computed tomography (CT) of the neck and thorax is the method of choice for diagnostics and control of therapeutic success. An early diagnosis with immediate surgical debridement and drainage of all infected tissue compartments, as well as strict sepsis therapy, are decisive for the prognosis.

[Lung cancer: is surgery an option for persisting N2 after induction therapy?]. / Lungenkarzinom: Gibt es eine Indikation zur Resektion bei persistierendem N2 nach neoadjuvanter Chemotherapie?

BACKGROUND: Induction chemotherapy followed by surgical resection has been a treatment option for stage IIIA3 N2 non-small cell lung cancer since publication of some small randomised trials during the 1990s. Later on other studies suggested a poor prognosis in cases of persistent N2 disease, so surgical treatment for these patients was not recommended. This study analyses the outcome of patients with persisting N2 disease and tries to identify prognostic parameters within that group of patients. METHODS: We conducted a retrospective cohort study with 50 patients after induction therapy for stage IIIA N2 NSCLC. We analysed the influence of the postoperative lymph node involvement as well as the number of involved lymph nodes on the overall survival. RESULTS: 50 patients with potentially resectable stage IIIA N2 were included in the analysis. In 25 cases (50 %) a persisting N2 remained after induction therapy with cisplatin/gemcitabine, 11 patients had a mediastinal downstaging. 14 patients did not qualify for surgery because of disease progression or comorbidities. The resection consisted in 29 cases of a lobectomy or bilobectomy; two times pneumonectomy was necessary and 4 segmentectomies and one atypical resection were performed. The median survival of patients with persisting N2 (ypN2) was 14.6 months, if mediastinal downstaging was achieved (ypN0/1) it was 22.3 months (p = 0.172). The number of involved mediastinal lymph nodes was a significant prognostic factor. If less than 6 lymph nodes were involved the mean survival was 17.5 months, while it was 8.6 months in patients with more than 6 involved lymph nodes (p < 0.01). CONCLUSIONS: The median survival for patients with persisting N2 disease is less favourable compared to patients with mediastinal downstaging. However, the long-term survival for patients with less than 6 involved lymph nodes is 17.5 months. Therefore surgical resection for these patients seems to be justified. After induction therapy a rigorous restaging should be performed to rule out persisting multilevel N2 disease.

[Postoperative pain in the acute phase after surgery: VATS lobectomy vs. open lung resection - results of a prospective randomised trial]. / Schmerzen in der frühen postoperativen Phase: VATS-Lobektomie vs. offene Lungenresektion - Ergebnisse einer prospektiv-randomisierten Studie.

INTRODUCTION: Minimally invasive procedures, e.g. video-assisted thoracoscopic lobectomy, are less traumatic and thus one may expect a lower level of postoperative pain compared to open procedures. This assumption is supported by several studies/metaanalyses. However, confirmation by larger prospective randomised studies is lacking. In the present study we analysed 2 groups of patients with lobectomy for early-stage lung cancer performed by VATS or by antero-lateral thoracotomy. MATERIAL AND METHODS: 66 patients with early-stage NSC lung cancer were randomised to VATS lobectomy (A) or open resection (B). Two patients from A were excluded. The 2 groups were equally large (n = 32). All patients received the same analgetic therapy regime during and after surgery. We defined the early postoperative period as the first 10 days after operation and evaluated the intensity of pain (assessed by NAS) and the medication. Data acquisition was performed until discharge or the 10th postoperative day. RESULTS: 21 values for mean NAS were calculated for both groups and each situation (at rest or under movement). For 8 a significant difference resulted in favour of VATS. In open thoracotomy the postoperative pain level was acceptable (NAS < 4) due to our well established pain control management. Also, 3 categories of patients with a very low pain profile were defined: patients with NAS not over 4 at any point, patients without any pain (NAS = 0) after a certain point or patients discharged without any pain. The VATS procedure showed a higher proportion of patients in all 3 categories: 17 in A vs. 7 in B had a max. NAS of 4 during the course; 20 vs. 11 were free of pain at certain times and 22 vs. 12 were discharged without pain. For both groups a painless postoperative course was achieved on day 6 (range, 4-10 days for A/3-10 for B). The medication was adjusted according to intensity. A difference was seen in favour of VATS for Sufentanil + Ropivacain via PDK and for Piritramid i. v. CONCLUSIONS: Regardless of procedure (VATS vs. open) pain control can be achieved with an adequate analgetic regime. For VATS during the first days a lower amount of medication is required. The VATS group showed a higher proportion of patients with very low postoperative pain profile: patients with pain score always under 4 and patients without pain at certain points before the 10th postoperative day or at discharge.

Combined paravertebral and intrathecal vs thoracic epidural analgesia for post-thoracotomy pain relief.

BACKGROUND: Although thoracic epidural analgesia (TEA) is considered the gold standard for post-thoracotomy pain relief, thoracic paravertebral block (PVB) and intrathecal opioid (ITO) administration have also been shown to be efficacious. We hypothesized that the combination of PVB and ITO provides analgesia comparable with that of TEA. METHODS: After local ethics committee approval, 84 consecutive patients undergoing open thoracic procedures were randomized to the TEA (ropivacaine 0.2%+sufentanil) or the PVB (ropivacaine 0.5%)+ITO (sufentanil+morphine) group. The primary endpoints were pain intensities at rest and during coughing/movement at 1, 2, 4, 8, 12, 24, 48, and 72 h after operation assessed by visual analogue scale (VAS) score. Data were analysed by multivariate analysis (anova; P<0.05). RESULTS: Patient and surgical characteristics were comparable between the groups. The mean and maximal VAS scores were lower in the TEA (n=43) than in the PVB+ITO group (n=37) at several time points at rest (P<0.026) and during coughing/movement (P<0.021). However, in the PVB+ITO group, the mean VAS scores never exceeded 1.9 and 3.5 at rest and during coughing/movement, respectively; and the maximal differences between the groups (TEA vs PVB+ITO) in the maximal VAS scores were only 1.2 (3.4 vs 4.6) at rest, and 1.3 (4.4 vs 5.7) during coughing/movement. CONCLUSIONS: Although VAS scores were statistically lower in the TEA compared with the PVB+ITO group at some observation points, the differences were small and of questionable clinical relevance. Thus, combined PVB and ITO can be considered a satisfactory alternative to TEA for post-thoracotomy pain relief. ClinicalTrials.gov number. NCT00493909.

[Pulmonary metastasectomy: an analysis of technical and oncological outcomes in 301 patients with a focus on laser resection]. / Pulmonale Metastasektomie: Analyse technischer und onkologischer Ergebnisse bei 301 Patienten mit Fokus auf die Laserresektion.

BACKGROUND: Resection of lung metastasis is an important component in the therapy of patients with metastatic solid tumours. The aim of this analysis was to compare the technical and oncological outcomes of laser-assisted pulmonary metastasectomy with those of standard resection techniques such as electrocautery and stapling. PATIENTS/MATERIAL AND METHODS: We retrospectively analysed all patients who had undergone curative intended pulmonary metastasectomy in our department between January 2005 and June 2010. Follow-up was accomplished by visits in the outpatient department of our medical centre or by questionnaires of the primary physicians. RESULTS: 301 patients were identified. In 62 patients (20.6 %) the Nd-YAG laser was used for resection. Despite a significantly higher number of resected lesions in the laser-assisted resection group in comparison to the group with wedge and anatomic resections (median: 7.0 vs. 2.0; p < 0.01), there was no significant difference in surgical and overall morbidity except for a higher rate of pneumonia (11.3 vs. 2.9 %; p < 0.01). Follow-up was completed for 85.4 % of the patients. After a median follow-up of 27.2 months (range: 2.3 to 60.6 months) 42.5 % of the patients suffered from recurrence and 29.2 % had died. Mean disease-free interval was 12.9 months (range: 0 to 60.6 months). Although a higher number of metastases was resected in the laser group, we did not see a significant correlation between surgical technique and long-term survival (p < 0.8). Regression analysis confirmed the number of metastases to be a significant factor influencing survival (p < 0.02), but subgroup analysis of laser-assisted resections no longer showed significance in respect to the number of metastases. CONCLUSION: The number of metastases has an influence on prognosis but seems to be of secondary importance, particularly if complete technical resectability with the aid of the laser is given.

Video-assisted thoracic surgery (VATS) evaluation of intrathoracic disease in patients with FIGO III and IV stage ovarian cancer.

OBJECTIVES: The aim of this study was to assess the influence of video-assisted thoracic surgery (VATS) on our treatment decisions in FIGO III and IV ovarian cancer patients. METHODS: Patients with ovarian cancer and suspected supra-diaphragmatic involvement (pleural effusions, pleural carcinomatosis, lung metastasis, or enlarged supra-diaphragmatic lymph nodes) at chest computer tomography (CT) scan underwent VATS with or without laparoscopy (LSC) to decide for primary cytoreduction or neoadjuvant chemotherapy. Operation time, VATS complications (intrapleural hematoma, secondary hemorrhage with intervention, pneumonia and empyema) and shift in the therapeutic strategy due to VATS were evaluated. RESULTS: 17 patients were included into this study (1 patient with FIGO stage IIIb, 1 with IIIc and 15 with stage IV). The median operation time for VATS only was 46.5 min (range: 20-50 min, n=3). Perioperatively, no complications occurred. After surgical staging, the tumor was confined to the abdomen in four patients in whom primary cytoreduction was attempted. All other 13 patients underwent neoadjuvant chemotherapy. VATS altered the therapeutic management in 6/17 ovarian cancer patients (3 times upstaging, 3 times downstaging). Negative predictive values (NPV) for local and diffuse pleural carcinomatosis ranged between 0.5 and 0.71. CONCLUSION: In this case series, VATS in addition to LSC showed negligible morbidity related to surgery and a short operation time. We were able to improve the accuracy of the FIGO staging and assessed operability more reliably in these patients than through imaging techniques alone.

[Pulmonary metastasectomy: indication and technique]. / Lungenmetastasenchirurgie: Indikationen und Technik.

Distant metastases of solid tumours are most frequently located in the lung. Most patients with lung metastases suffer from multiple pulmonary lesions or metastases in other organs, which makes these patients unsuitable for surgical treatment. However, several studies suggest a survival benefit if complete resection of all pulmonary metastases is possible. In some patients pulmonary metastasectomy may even be the only curative treatment option. If pulmonary metastases are suspected contrast-enhanced computed tomography is the diagnostic procedure of first choice. Generally accepted rules for intended curative pulmonary metastasectomy are control of the primary tumour, technically completely resectable metastases, the exclusion of extrapulmonary metastases except for potentially completely resectable hepatic metastases and a functional operability. The most important prognostic factors are complete resection, the exact entity of the tumour, disease-free interval and, to a limited extent, also the number of metastases. In bilateral disease sternotomy and sequentially staged or one-stage thoracotomy are the standard surgical approaches to be considered, whereby thoracotomy is more advantageous in cases of centrally located lesions and left lower lobe metastases. In unilateral disease, video-assisted resection may be considered under certain circumstances. Primary aim must be R0 resection. Tissue-sparing pulmonary dissection techniques are proposed besides anatomic resections. In particular in cases of centrally located or multiple lesions an extensive expertise in thoracic surgery is necessary to preserve as much functional lung parenchyma as possible. Secondary mediastinal lymph node involvement is associated with an adverse prognosis and should therefore be ruled out preoperatively.

[Lung cancer from the perspective of internal medicine and surgery]. / Lungenkrebs aus Sicht der Inneren Medizin und Chirurgie.

In previous years numerous advances in diagnostics, staging and therapy of lung cancer have been achieved. Nevertheless, it remains the most frequent cause of death from cancerous diseases. Early diagnosis and exact staging enable multimodal therapy regimens adjusted to age and comorbidities, which result in complete remission in a few and in prolonged survival and good quality of life in most patients. Curative surgery is possible in stage I non-small cell lung cancer (NSCLC) and results in a 5-year survival rates of up to approximately 75%. Using multimodal therapy approaches long-term survival can even be achieved in 40-50% of patients with advanced T4 tumors. However, in NSCLC with distant metastases median survival time is only 8-12 months. In elderly patients with no surgical options low cytotoxic monotherapy can be employed with a palliative intent. In the limited disease stage of small cell lung cancer (SCLC) long lasting remission after polychemotherapy has been observed in a minority of patients. However, in the extensive disease stage polychemotherapy prolongs the survival time of SCLC patients from 1-2 months to approximately 12 months.

[Surgery of mediastinal tumors]. / Chirurgie der Mediastinaltumoren.

Thymomas, lymphomas, and germ cell tumors are the most frequent lesions of the anterior mediastinum, whereas endodermal (bronchogenic) cysts and lymphomas are the most frequent lesions of the middle mediastinum. In the posterior mediastinum, neurogenic tumors and soft-tissue sarcomas are the most frequent. Depending on tumor location, mediastinoscopy, mediastinotomy, and thoracoscopy are the preferred diagnostic methods. Surgical treatment of thymoma is the gold standard, and median sternotomy is the most frequently applied approach. The decisive prognostic and therapeutic criteria are Masaoka staging, WHO classification, and R0 status. Thoracoscopy should be performed only in patients with myasthenia gravis and with very small tumors. Surgical treatment is highly recommended in patients with locally recurrent tumors. The importance of surgical treatment of germ cell tumors is determined by a negative concentration of beta-HCG and alpha-fetoprotein and in cases of residual tumor after chemotherapy. Bronchogenic cysts always require resection because of their high complication rate (66%) after conservative treatment. In these cases complete resection is necessary due to the probability of recurrence. Ninety-eight percent of neurogenic tumors in adults are benign and usually resected via thoracoscopy or thoracotomy, depending on location and size.

[The use of Deep Inferior Epigastric Vessels to Revascularise Free Flaps for Reconstruction of Complex Oncosurgical Defects of the Thigh and the Abdomen]. / Epifaszial verlagerte tiefe inferiore epigastrische Gefäße als Anschlussgefäße für die mikrochirurgische Rekonstruktion komplexer onkochirurgischer Defekte des Abdomens und des Oberschenkels.

BACKGROUND: The resection of large soft-tissue sarcoma requires reconstruction with free flaps. The choice of recipient vessels is crucial for the success of surgery. PATIENTS: We report four cases with large soft-tissue sarcomas with complex anatomical relationships: two tumors of the thigh surrounding the femoral neurovascular structures and two tumors of the abdomen with infiltration of the thorax and the abdomen. All cases received multimodal interdisciplinary treatment. The anterolateral thigh (ALT) flap and the latissimus dorsi (LD) flap were employed twice for defect coverage in this series. In all cases the deep inferior epigastric (DIE) vessels were transposed to the subcutaneous compartment and used as recipient vessels. RESULTS: The mean duration of surgery was 694 ±â€…149 minutes. The mean weight of the tumor specimen was 3069 ±â€…1267 g. Three flaps healed primarily and one exhibited a minor necrosis, which was treated by excision and secondary suture. There were no cases of abdominal herniation due to the transposition of vessels. CONCLUSION: Transposition of DIE-vessels to the subcutaneus compartment is a good alternative for free flap revascularisation in this patient group. In this position, the vessels are easily accessed and used for microsurgery. This technical modification increases the reconstructive possibilities in large and previously irradiated surgical defects.