International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in completely resected stage II-IIIA non-small-cell lung cancer.

BACKGROUND: Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. PATIENTS AND METHODS: Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). RESULTS: Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. CONCLUSION: In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.

[Laryngo-Tracheal Resection as an Alternative to Permanent Tracheostomy]. / Die laryngotracheale Resektion als Alternative zum permanenten Tracheostoma.

INTRODUCTION: Cervical stenosis of the trachea caused by tracheotomy, tumor or without defined reason (idiopathic) can be treated by resection and anastomosis with good early and long-term results. Involvement of the ring cartilage makes the procedure technically demanding and increases the risk of morbidity. We describe our technique of laryngotracheal resection and reconstruction and compare the perioperative results with standard tracheal resection. PATIENTS AND METHODS: Between January 2005 and December 2015, we performed about 800 procedures on the trachea including 76 standard cervical tracheal resections and 35 laryngotracheal resection. Resections were carried out with direct anastomosis without intraoperative tracheotomy or intralaryngeal stenting. Patient records were retrospectively analysed for perioperative data. RESULTS: The main cause of stenosis or defect of the trachea and operation was preceding tracheotomy. Idiopathic stenosis, tumors and subglottic stenosis in Wegener disease were less common. There were no disturbances of healing of the anastomosis in any patient. Tracheotomy in the course of treatment for intralaryngeal swelling or recurrent nerve palsy was necessary in 3 (standard) and 2 (laryngotracheal) patients. Postoperative tracheostomy was closed in all patients within 3 months. Pulmonary complications and recurrent nerve palsy occurred in 5/4 and 2/2 of the patients without significant differences between the 2 groups. One patient died in each group from pulmonary complications. CONCLUSION: The laryngotracheal resection is a relevant part of cervical tracheal surgery. It can be performed without significantly higher morbidity and can restore lung function and quality of voice.

[Diagnosis and Treatment of Diaphragmatic Dysfunction]. / Diagnostik und Therapie der gestörten Zwerchfellfunktion.

There are many reasons for an impairment of the diaphragmatic function potentially affecting all components of the respiratory pump. Particularly, diagnosis and treatment of unilateral and bilateral phrenic nerve paralysis are challenging. Neuromuscular disorders, trauma, iatrogenic conditions, tumor compression, but also infectious and inflammatory conditions in addition to neuralgic amyotrophy and idiopathic phrenic nerve paralysis are reasons for phrenic nerve paralysis. Primarily, diagnostic procedures include the anamnesis, physical examination, blood gas analysis, lung function testing and the diagnosis of the underlying disease. In addition, specific respiratory muscle testing and respiratory imaging are available today. Current established treatment options include respiratory muscle training, long-term non-invasive ventilation and surgical diaphragm plication in selected patients.

[Review of the Literature for Interpretation of Endobronchial Wound Healing after Tracheobronchial Sleeve Resection]. / Literaturbasierte Empfehlung zur bronchoskopischen Interpretation einer Anastomose nach Manschettenresektion.

Sleeve resection comprises 3.1 % to 27.7 % of all anatomic lung resections performed in Germany. Anastomotic insufficiency is a feared complication that should be avoided. When anastomotic insufficiency does lead to secondary pneumonectomy, postoperative morbidity and mortality is high (30 % to 80 %). It is therefore very important to standardize the technique of sleeve resection as well as postoperative care. The time-point of postoperative follow-up and the interpretation of endobronchial healing have not yet been defined. In this paper anastomotic healing is described and interpreted with the help of a 5-step classification that allows bronchoscopic evaluation and classification of the anastomosis. The aim is to provide a standardized algorithm for postoperative care after sleeve resection. The basis of this classification and postoperative care measures derived from it are described and illustrated with the help of clinical examples.

[Reduction of Tracheotomy Associated Tracheal Stenosis by Surgical Closure of the Tracheostomy]. / Reduktion Tracheostoma-assoziierter Trachealstenosen durch chirurgischen Stomaverschluss.

BACKGROUND: The most common long-term complication of tracheotomy is the benign stenosis of the trachea, which is described for up to 20% of the cases. Typically, the stenosis occurs after decannulation in the context of secondary wound healing. This study examined whether the closure of the tracheostomy by surgical procedure reduces stenosis. METHOD: With the help of our clinical database a retrospective analysis of 401 surgical tracheotomies was performed. Variables that were recorded were the indication for tracheotomy, the clinical course and complications occurred. RESULTS: 155 patients were successfully decannulated. In 92 of these patients the tracheostomy was closed by a surgical procedure, in 63 cases the closure occurred spontaneously by wound healing. After decannulation 3% (n=3) of the surgically closed and 22% (n=14) of the spontaneously closed tracheostomies developed a symptomatic tracheal stenosis (p<0.001). CONCLUSION: Secondary wound healing of the tracheostomy often leads to symptomatic tracheal stenosis. The incidence of symptomatic tracheal stenosis was significantly reduced applying closure of the tracheostomy by surgical procedure.

[Unilateral agenesis of pulmonal artery in adults: a rare disease frequently undiagnosed]. / Unilaterale Agenesie der Pulmonalarterie bei Erwachsenen. Eine häufig nicht diagnostizierte seltene Erkrankung.

INTRODUCTION: Unilateral absence of a pulmonary artery (UAPA) in adults without any other cardiovascular anomalies is a very rare clinical entity. Usually UAPA in adults remains undetected because of the symptom-free clinical course. The most common symptoms are hemoptysis and recurrent pulmonary infections. PATIENTS AND THERAPY: During 2006 - 2014 four adult patients with UAPA were diagnosed and treated in our institution. Recurrent pulmonary infections in combination with existing bronchiectasis and hemoptysis led to hospital treatment for three of the patients. In two cases, because of persevering hemoptysis and pathologically enlarged systemic arteries (intercostal, bronchial, diaphragm), pneumonectomy was indicated. Preoperative embolization of the enlarged arteries reduced the systemic arterial perfusion of the lung and led to minimal intraoperative blood loss. DISCUSSION: UAPA in the adulthood can frequently lead to hypertrophic systemic arterial perfusion of the lung. This abnormal systemic perfusion in combination with the co-existing bronchiectasis and persevering hemoptysis can cause a life-threatening clinical scenario. A combined interdisciplinary treatment through pneumology, thoracic surgery and radiology is therefore indicated.

[Perioperative anticoagulant and antiplatelet treatment in general thoracic surgery]. / Perioperativer Umgang mit Antikoagulanzien und Thrombozytenaggregationshemmern in der Thoraxchirurgie.

The perioperative use of anticoagulants in general thoracic surgery can be considered to be a "two-edged sword": the goal to minimise the risk of a thromboembolic episode is contrary to the ongoing effort of the surgeon to minimise the risk of intra- and postoperative blood loss. Dispositional factors such as excessive tobacco use are common for thoracic surgery patients and often lead to cardiovascular comorbidity which necessitates the use of anticoagulants or antiplatelet drugs. For deep venous thrombosis prophylaxis and for the indication and use of vitamin K antagonists or antiplatelet drugs it is proven in the literature that the risk profile of the patient and his/her classification in the appropriate risk group are of major importance. Through the individual risk profile of the patient it is possible to plan the appropriate perioperative anticoagulant therapy which will safely assist the surgeon and his/her patient during the peri- and postoperative phase on the knife-edge between blood loss and eminent thromboembolism. Unfortunately there are not enough existing data and published literature for evidence-based guidelines referring to the correct perioperative management for the new oral anticoagulants. Management algorithms are being recommended according to the multiple aspects of anticoagulant-treatment.

[Potentially curative surgical therapy in oligometastatic non-small cell lung cancer]. / Potenziell kurative chirurgische Therapie beim oligometastasierten nicht-kleinzelligen Lungenkarzinom.

Lung cancer is a leading cause of cancer related death worldwide. Non-small cell lung cancer (NSCLC) represents 85 % of all lung cancer cases and approximately 40 % of all patients impress with a metastatic disease at the time of diagnosis. Stage IV NSCLC has a poor prognosis and is incurable. The recommended standard therapy in this case is a palliative supportive systemic chemotherapy. However, a distinctive subgroup of patients with stage IV NSCLC appear clinically with an oligometastatic disease and may qualify for surgical therapy. There is evidence that patients with synchronous or metachronus solitary satellite nodules, either located intrapulmonary or extrapulmonary, benefit from surgical resection.

[The small lung nodule: dealing with a frequent radiological finding]. / Der kleine Lungenrundherd: Umgang mit einem häufigen radiologischen Befund.

Small pulmonary nodules less than 10 mm in size are frequently found by multidetector CT in high-risk patients. The risk of malignancy is rather low. The individual cancer risk, the radiological appearance and the presence or absence of growth are guides towards the indication for invasive procedures. A risk adjusted algorithm should avoid unnecessary invasive procedures without missing a lung cancer.

[Bronchus insufficiency: prevention and therapy]. / Bronchusinsuffizienz: Prävention und Therapie.

In order to achieve respectable postoperative outcomes after lung resection it is essential to understand the mechanism of bronchus healing. The bronchus seal should be air-tight and consist of monofilament suture or staples. The bronchus suture should be covered with vital tissue (lung, mediastinum, muscle flap). A complication in the process of bronchus healing should be diagnosed as early as possible in order to stop the destructive effect of the infection as rapidly as possible.

[Influence of nosocomial infections on resection of tracheal stenosis after tracheotomy]. / Bedeutung nosokomialer Infektionen bei derResektion trachealer Stenosen nach Tracheotomie.

BACKGROUND: Complications located at the tracheostoma often occur in combination with nosocomial infections. We posed the question: how is the surgical result in tracheal resections influenced by bacterial contamination with multiresistant germs? PATIENTS AND METHODS: Between 2005 and 2009 we performed a primary end-to-end-resection of the trachea after tracheotomy in 30 patients. The demographic basic data, the diagnostic data on tracheal stenosis after decanullation and type of tracheotomy were documented. Preoperatively all patients underwent a flexible bronchoscopy with bronchial lavage. All patients received an antibiotic inhalation therapy postoperatively. RESULTS: 16 patients presented a status post-permanent tracheotomy (PT), in 14 cases after percutaneous dilatative tracheotomy (PDT). In 64 % of all cases the preoperative bronchial lavage was positive for bacterial contamination. The major pathogen was with 23 % a multiresistant Pseudomonas aeruginosa (MR). In three cases long-term-complications occurred, all of which were bacterially contaminated. CONCLUSION: After long-term intubation a bacterial contamination is very common and presents a negative predictor for the outcome of primary tracheal end-to-end resections. A prophylactic postoperative antibiotic therapy can improve the short- and long-term results.

[Interventional lung assist membrane ventilator. Successful use despite heparin-induced thrombocytopenia type II]. / "Interventional-lung-assist"-Membranventilator. Erfolgreiche Anwendung trotz heparininduzierter Thrombozytopenie II.

Pumpless extracorporeal carbon dioxide elimination using the interventional lung assist (iLA) membrane ventilator is a modern concept for the treatment of hypercapnia due to respiratory failure which cannot be sufficiently treated by conventional strategies. Heparin-induced thrombocytopenia type II (HIT II) is considered to be an absolute contraindication for placement of an iLA because of the system's heparin-coated diffusion membrane. The example demonstrates that iLA therapy can be continued despite occurrence of a HIT II in terms of an "off label use". In the case described, postoperative therapy using the iLA membrane ventilator was installed in a 69-year-old patient with severe ARDS after elective lung resection. Despite a confirmed HIT II detected in the course of iLA, this therapy was continued after changing systemic anticoagulation to argatroban. The platelet count increased again and the patient could be successfully weaned from the iLA membrane and finally transferred to a rehabilitation centre.

[Multimodality therapy for lung cancer]. / Multimodale Therapie des Lungenkarzinoms.

The primary treatment of lung cancer depends on tumor stage. In case of lung cancer in clinical stage I to IIb and T3N1 surgical treatment is recommended. The use of adjuvant chemotherapy is indicated in stage II and IIIa. In case of limited N2-disease trimodality therapy with chemo- or radiochemotherapy followed by surgery and eventual adjuvant radiotherapy leads to five year survival rate of about 20-40. Non resectable or extended mediastinal lymph node metastases are an indication for definite combined radiochemotherapy. Secondary resection may be evaluated in experienced centers. If the tumor has infiltrated the mediastinum or the upper sulcus (T3/4) or in case of solitary metastasis an individual trimodal treatment plan has to be elaborated. Also for small cell lung cancer surgery combined with chemotherapy can be applied in stage I and II, else and especially in stage III radiochemotherapy should be applied. Additional prophylactic cranial irradiation is used. The majority of lung cancer patients suffers from metastatic disease. The value of systemic chemotherapy is limited with significant, but small improvement in overall survival. Also treatment with the new molecularly targeted drugs does not result in a breakthrough in unselected patient cohorts. Recently, substantial progress could be achieved by personalized treatment approaches for patients harbouring special genetic alterations.

[Pulmonary nodules in underlying malignant diseases--not necessarily metastases of the primary tumour]. / Der pulmonale Rundherd bei maligner Grunderkrankung--nicht zwingend eine Metastase des Primärtumors.

BACKGROUND: In this study the histological examination of pulmonary nodules and a comparison of the number of pre-, intra- and post-operative lung metastases in patients with a previous history of malignant disease were assessed. PATIENTS AND METHODS: Between 1998 and 2003 we operated on 276 patients with suspected lung metastases. The histology of the primary tumour, the number of preoperatively diagnosed nodules, the number of lesions removed during surgery and the number of histologically confirmed metastases of 276 patients are presented. RESULTS: In 276 patients a resection was performed. 161 of the patients were men (58.1%). The median age was 62 years (range: 21-86 years). In 110 cases a left-sided thoracotomy was performed (39.8%), in another 110 cases a right-sided thoracotomy was performed and in 56 cases we performed a bilateral thoracotomy (20.4%). In 15.2% the histology of the resected nodules was benign. In 8.6% of the cases the histological examination showed a primary lung cancer in stage I, in 74.4% of the cases the histology confirmed a metastasis of the primary cancer. CONCLUSIONS: Solitary pulmonary nodules in patients with a previous history of malignant disease should always be resected for histological examination. Multiple pulmonary nodules should be histologically reappraised if there is any doubt about the entity.

[Surgical therapy for malignant pleural effusions]. / Chirurgische Therapie des malignen Pleuraergusses.

Symptomatic malignant pleural effusions are common in patients with neoplastic disease (50 %). Frequently, they are a sign of advanced disease. These patients have an average life expectancy of 3 to 12 months. The therapeutic aim should be an efficient treatment with a short hospital stay. Chest tube drainage gives rapid relief of symptoms and information on the expansion of the lungs. When complete expansion of the lung is possible, VATS insufflation of talc is recommended. Talc is the most effective sclerosant (80 %) followed by doxycycline (70 %). VATS pleurodesis has a higher complication rate but is more effective than a talc slurry instilled through the chest tube. When the lung is trapped, long-term indwelling pleural drainage and pleuroperitoneal shunts are alternatives.

[Multimodal treatment of non small cell lung cancer]. / Multimodale Therapie des nichtkleinzelligen Bronchialkarzinoms.

The primary treatment of lung cancer depends on tumor stage. Chest CT scan and bronchoscopy are used to define the TNM stage and resectability. In case of lung cancer without mediastinal lymph node enlargement or direct mediastinal involvement (clinical stage I-IIb + T3N1) surgical treatment is recommended. The use of adjuvant chemotherapy has to be defined, but will be indicated in stage II and IIIa. Expected 5-year survival achieves 40 to 80 % depending on tumor stage. Exceeds the shorter diameter of mediastinal lymph nodes in chest CT scan more than 1 cm (or in case of positive PET scan) mediastinoscopy is indicated. In case of N2-disease and after tumor response to preoperative chemotherapy (about 60 %) secondary resection of the tumor leads to higher 5-year survival rates (20-40 %) compared to patients without induction therapy (5-20 %). In these patients and after unexpected detection of solitary lymph node metastasis by primary resection adjuvant mediastinal radiotherapy should be added. If the tumor has infiltrated the mediastinum or the upper sulcus (T3/4) and/or mediastinal lymph nodes are obviously tumor burden (e. g. > 3 cm, N2 bulky, N3) radical primary resection may not be possible. In these patients combined radio- and chemotherapy induces a high percentage of tumor regression and can be used before secondary resection (5-year survival 5-20 %). Locally advanced tumors infiltrating the main bronchus close to the carina or the carina itself and tumors with metastases in the same lobe, both without mediastinal lymph node metastases (T3/4N0-1), can be resected by sleeve pneumonectomy and lobectomy with satisfactory results respectively. In patients with resectable lung cancer and no clinical sign of tumor disease (f. e. anemia, weight loss, pain) limited staging procedure with chest CT scan including upper abdomen and bronchoscopy is reasonable. In the remaining patients complete staging is necessary. We recommend an interdisciplinary approach to patients with lung cancer.

[Resection of combined or sequential lung and liver metastases of colorectal cancer: indication for everyone?]. / Resektion kombinierter oder sequenziell auftretender Leber- und Lungenmetastasen kolorektaler Karzinome: Welche Patienten profitieren?

UNLABELLED: Successful sequential resection of isolated hepatic and pulmonary metastases of colorectal cancer (crc) has been reported, however long-term results of large series are lacking. Therefore, we retrospectively analysed data of patients in whom sequential hepatic and pulmonary resection for metastases was performed. PATIENTS AND METHOD: From the records of our hospital we identified 25 patients (19.5 % of all patients operated for hepatic or 33 % for lung metastases due to crc) with colorectal cancer who had pulmonary and hepatic resection for metastatic disease between 1991 and 2002. 11 of these had primary colonic cancer and 14 rectal cancer. None of the patients died perioperatively. Long-term results were correlated with the staging of the primary tumour, the number of metastases, disease free interval between primary tumour operation and occurrence of metastatic disease. RESULTS: Five-year survival rate was 33.5 % following the resection of the first metastasis. Three year survival after resection of the second metastasis was 39 %. The disease free interval was 20 months (mean). Long-term results were clearly influenced by the disease free interval: < 1 year (n = 6) median 50 months after resection of the crc; > 1 year median 90 months (n = 19). Further on R0 resection was important for long-term survival: Median survival was 32.5 (+/- 4.1) months following resection of the second metastasis but only 9.9 months after R > 0 resection. CONCLUSION: These results confirm that sequential resection of hepatic and pulmonary metastases can be performed with curative intention provided a systemic spread of the disease is excluded. The surgeon's opinion of resectability should be obtained in patients with such metastases before the patient is scheduled for palliative conservative treatment.

[Radiofrequency ablation of malignant lung tumours. Judicious approach?]. / Radiofrequenzablation maligner Lungentumore. Eine sinnvolle Methode?

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive technique and well established in the treatment of malignant hepatic tumours. This method could also find application in patients with malignant lung tumours who, for functional reasons, have to be excluded from standard surgery. Until now, however, very little data have been available on the application of RFA in malignant pulmonary tumours. PATIENTS AND METHODS: From November 2001 to January 2004, eleven malignant lesions of the lung were treated with RFA. The indication for RFA resulted from an inadequate pulmonary reserve and additional severe risk factors. RESULTS: Eleven lesions were treated in ten patients with RFA. The malignancies were primary non-small cell bronchial carcinomas (n=9) as well as metastases of non-small cell carcinomas (n=2). Early complications of RFA were pneumothorax, hemorrhagic intrapleural effusion, bronchopleural fistula and pericarditis. Two weeks after RFA, pneumonia appeared as a late complication. No patient's death was related to the RFA procedure. After a mean follow-up of 8.5 months five patients died. Five patients are still alive, two of whom exhibit no tumour recurrence. CONCLUSION: RFA in patients with lung tumours is possible from a technical viewpoint. It is possibly a therapeutic alternative for patients with localized tumours that are inoperable. However, in this series, the morbidity of the procedure -- taking the degree of invasiveness into account -- is high, and the oncological results are unsatisfactory, possibly due to a small cohort of patients.