[Refractory Dyspnea in Advanced COPD: Palliative Treatment with Opioids]. / Refraktäre Dyspnoe bei fortgeschrittener COPD: Palliative Therapie mit Opioiden.

Dyspnea is a leading symptom in COPD. Bronchodilators (long acting anticholinergics and long acting beta agonists) are the mainstay of medical treatment. Non pharmacological therapies like pulmonary rehabilitation, long-term oxygen therapy or lung volume reduction can help to further improve dyspnea. Nevertheless, patients with advanced disease may develop refractory dyspnea. Randomized controlled trials demonstrated that the palliative treatment with low-dose systemic opioids is an effective treatment option in these patients. A low starting dose (e. g. 1.0 mg morphine, immediate release) is recommended. Subsequent doses are titrated to achieve the lowest effective dose based on whether dyspnea relief has been achieved and whether any side effects have developed. This low-dose opioid treatment has been demonstrated to be safe for symptom reduction in severe COPD and is not associated with increased hospital admissions or deaths. Physicians should offer a trial of low-dose oral opioids to patients with refractory dyspnea that affects their daily activities and quality of life.

[Rebiopsy for Patients with Lung Cancer - Joint Opinion from both the Endoscopic and Thoracic Oncology Sections of the German Society of Pneumology (DGP)]. / Empfehlung der Sektionen 2 und 11 der DGP zur Rebiopsie bei Lungenkarzinomen.

Performing rebiopsies for primary lung cancer and/or their metastases is becoming more and more prominent in daily practice, as the therapeutical spectrum increases and some newer strategies are dependent on immunohistochemical and/or molecular factors. In general, nearly all recurrent lesions or metastases can be reached. However, frequently invasive procedures are necessary with the need to carefully weigh risks and benefits of rebiopsies for the patient in each case. In this review indications for recurrent and progressive disease as well as risks are discussed and alternatives to rebiopsies are shown. This work is the joint opinion from both the endoscopic and thoracic oncology sections of the German Society of Pneumology (DGP).

[Haemoptysis : Intensive care management of pulmonary hemorrhage]. / Hämoptoe : Intensivmedizinisches Management von Lungenblutungen.

There is a wide spectrum of severities in patients with pulmonary bleeding with a range from mild haemoptysis to severe bleeding with an acute risk of asphyxiation. For the management of acute pulmonary haemorrhage, it is essential to identify the underlying cause in order to initiate a target-oriented or causal therapy. The most common causes of localized pulmonary bleeding are lung cancer as well as infections, anticoagulant therapy or bronchiectasis. Diffuse alveolar haemorrhage is mostly due to pulmonary vasculitis or connective tissue disease, but may also occur in pulmonary metastasis, congestive heart failure, coagulation disorders and from many other causes. In a case of severe pulmonary bleeding it is essential to secure the airways and ensure sufficient ventilation, i. e. by intubation with a double-lumen endotracheal tube and by appropriate positioning of the patient. Stabilizing haemodynamics is crucial. Simultaneously basic diagnostic measures, i. e. appropriate laboratory tests, chest X­ray, computed tomography scan of the chest and bronchoscopy, are performed. Localized pulmonary bleeding usually requires local treatment, like bronchoscopic therapy, bronchial artery embolization or surgery. Diffuse alveolar haemorrhage must be treated systemically, i. e. by immunosuppressive therapy in cases of vasculitis or by medical treatment of coagulation disorders. Even with optimal interdisciplinary management the in-hospital mortality of severe pulmonary bleeding remains high. There is a significant risk of recurrent bleeding depending on the cause of haemorrhage. In patients with "cryptogenic" haemoptysis there is an increased rate of lung cancer within the following years and follow-up of these patients is recommended.

[Liquid Biopsy: Detection of Molecular Markers for Treatment Decisions in Lung Cancer]. / "Liquid biopsy": Analyse molekularer Marker aus Blutproben zur Therapiesteuerung beim Lungenkarzinom.

Personalized, individualized, targeted therapy has successfully found entrance in the palliative treatment of lung cancer as they enable a personalized and individualized strategy going ahead with biomarker testing. Due to the crescending amount of predictive molecular and immunhistochemical analyses at different time points during therapy the need for more and actual tumor tissue increases; however these samples cannot always be obtained without major discomfort for the patients. Therefore, analyses from blood, the so called "liquid biopsy", is an alternative or additional method. Activating mutations in the EGFR gene and the inhibitory mutation T790 M can already be detected from blood during clinical routine. This review presents the status of liquid biopsy for diagnosis, prognosis and as predictive parameter during the course of therapy in lung cancer and gives an outlook on future developments.

[Estrogen Receptors and their Impact for Prognosis and Therapy of Lung Cancer - New Insights to an Underestimated Mechanism]. / Östrogenrezeptoren und ihre Bedeutung für die Prognose und Therapie des Lungenkarzinoms - neue Erkenntnisse zu einem bisher unterschätzten Mechanismus.

Though tobacco smoking is the leading cause of lung cancer, during the last decades the prevalence increased in never smoking patients, especially in women. Sex steroid hormones and particularly the estrogen receptors (ERs) seem to play an important but still underestimated role in non-small cell lung cancer (NSCLC). Beside long existing hints that hormone replacement therapy (HRT) increases the risk of lung tumors recent analyses on cell lines, xenografts and human tumors of both sexes gave clear evidence of ER expression and proliferation in NSCLC. Most recently, the expression of ERs apparently has prognostic and predictive value. Recently, an intracellular "cross-talk" between the ER and the epithelial growth factor receptor (EGFR) could be demonstrated. EGFR are important targets of approved tyrosinkinases (TKIs), like gefitinib, erlotinib or afatinib. Currently, clinical studies are enrolling lung tumor patients for combination treatment with EGFR TKI and antihormonal drugs, e. g. fulvestrant.

[Current status of erlotinib and gefitinib in palliative therapy for NSCLC--does the EGF-R mutation state have any significance?]. / Aktueller Stellenwert von Erlotinib und Gefitinib in der palliativen Therapie des NSCLC--welche Bedeutung hat der EGF-R-Mutationsstatus?

In spite of intensive research and a huge amount of chemotherapy trials, the prognosis of metastastic non-small cell lung cancer (NSCLC) is still poor. Erlotinib and Gefitinb are tyrosine kinase inhibitors (TKIs) which act against the EGF receptor (EGF-R). Activation of mutations in the tyrosine kinase domain leads to an increase in effectiveness. What is the clinical impact of EGF-R mutation screening? What value do TKIs in 1st, 2nd and 3rd line have in therapy for metastatic NSCLC? Which treatment options exist after failure of TKI in the 1st line? These and other clinically relevant questions in the context of TKIs are discussed in the present comprehensive review.

[Drug therapy for small-cell lung cancer (SCLC)--new molecular strategies for therapy]. / Medikamentöse Therapie des kleinzelligen Bronchialkarzinoms (SCLC)--neue molekulare Therapieansätze.

Small-cell lung cancer accounts for up to 20 % of lung cancer and is the most aggressive type. Although responding to chemotherapy, it often relapses early. In spite of more than thirty years of intensive research, its prognosis has not been improved. Through increasing knowledge about molecular mechanisms and the involved genes, translational research into antibodies, small molecules and even vaccines, might result in interesting new strategies for the near future. After a short introduction about the function of the relevant genes, the diagnostic and prognostic value will be described. In the second part of this review the focus will lie on current studies (mostly phases I and II) for the treatment of SCLC.

[An approach to individualised therapy of non-small cell lung carcinoma (NSCLC)--relevance of molecular predictive and prognostic factors]. / Auf dem Weg zu einer individualisierten Therapie des nicht-kleinzelligen Bronchialkarzinoms (NSCLC)---Stellenwert molekularer Prädiktions- und Prognosefaktoren.

The treatment of patients with non-small cell lung carcinoma (NSCLC) is guided by results from clinical studies. Data about molecular changes in the tumour are not used (up to now) to decide for an individualised, tumour-tailored therapy. High-throughput technologies and modern analytical methods (e. g., microarrays) lead to exponentially increasing knowledge about genetic changes in the cells and the interaction of proteins. This results in the discovery of molecular factors with high predictive (prediction of tumour response) and prognostic (prediction of survival) value in NSCLC. Among these are ERCC1, RRM1 and some receptor tyrosine kinases. Preliminary data of prospective studies have shown promising results for the selection of specific drugs, when these tumour markers were analysed. Therefore, this review focuses on the actual value of molecular markers for decision-making in the adjuvant and palliative setting and their probable future introduction into clinical practice.

Palliative second-line treatment with weekly high-dose 5-fluorouracil as 24-hour infusion and folinic acid (AIO) plus oxaliplatin after pre-treatment with the AIO-regimen in colorectal cancer (CRC).

BACKGROUND AND AIMS: The aim of this work was to evaluate the efficacy and safety of second-line treatment with weekly high-dose 5-Fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) and folinic acid (FA) (AIO-regimen) plus Oxaliplatin (L-OHP) after pre-treatment with the AIO regimen, focusing in particular on the efficacy of palliative first- and second-line treatment in colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients with non-resectable distant CRC metastases were enrolled in a prospective phase II study for palliative second-line treatment after previous palliative first-line treatment in accordance with the AIO regimen. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m2 L-OHP in the form of a 2-hour intravenous (i.v.) infusion and 500 mg/m2 FA as a 1 to 2-hour i.v. infusion, followed by 2,600 mg/m2 5-FU administered as a 24-h inf. i.v. once weekly. A single treatment cycle comprised 6 weekly infusions followed by 2 weeks of rest. RESULTS: During second-line treatment, a total of 26 patients received 340 chemotherapy applications. As the main symptom of toxicity, diarrhoea (NCI-CTC toxicity grade 3+4) presented in 5 patients (19%; 95% CI: 4-34), followed by nausea (CTC grade 3) in one patient (4%; 95% CI: 0-11). Twenty-three patients were evaluable for treatment response. The remission data can be summarised as follows: Complete remission (CR): n=1 (4%; 95% CI: 0-13); partial remission (PR): n=3 (13%; 95% CI: 0-27); stable disease (SD): n=11 (48%; 95% CI: 27-68) and progressive disease (PD): n=8 (35%; 95% CI: 15-54). The median progression-free survival (PFS) rate (n=26) was 3.3 months (range 0-11.5), the median survival time counted from the start of second-line treatment (n=26) 11.6 months (range 2.1-33.0) and the median survival time counted from the start of first-line treatment (n=26) 19.9 months (range 7.7-49.8). CONCLUSION: Palliative second-line treatment according to the AIO regimen plus L-OHP is feasible in an outpatient setting and well tolerated by the patients. Tumour control (CR + PR + SD) was achieved in 65% of the patients, the median survival time being 11.6 months. The AIO regimen followed by the 'AIO regimen plus L-OHP' therapy sequence led to a promising median survival time of 19.9 months (range 7.7-49.8).

[Retroperitoneal desmoid tumor with kidney failure in familial adenomatous polyposis]. / Retroperitonealer Desmoidtumor mit Niereninsuffizienz bei familiärer adenomatöser Polyposis.

HISTORY AND FINDINGS: A 39-year-old man was hospitalized because of continually rising urinary creatinine and blood urea nitrogen concentration. He was known to have familial adenomatous polyposis (FAP), first diagnosed 18 years previously and re-Physical examination was unremarkable except for pain on percussion over both kidney regions. There was a well-healed laparotomy scar. INVESTIGATIONS: Ultrasound revealed chronic bilateral obstructive renal disease, grade II-III, and computed tomography showed a conglomerate retroperitoneal tumour with obstruction of both ureters at the level of the lower pelvis. This tumour had first been noted first 3 years after the colectomy when the patient complained of abdominal pain. It had been identified histologically as a nonresectable retroperitoneal desmoid tumour. TREATMENT AND COURSE: An external fistula was made, relieving the renal retention. To suppress growth of the desmoid tumour Sulindac, a nonsteroid anti-inflammatory drug, was administered. Genetic molecular analysis revealed a germ line defect in codon 1690 of the APC gene. It is intended to examine other members of the family for the presence of this defect. CONCLUSION: Desmoid tumours are more common in persons with FAP and are among the most frequent extracolic causes of their death. Treatment options are critically analysed.