Geschlechtsspezifische Charakteristika und Prognose des Nierenzellkarzinoms

BACKGROUND: Renal cell carcinoma (RCC) occurs twice as often in men as in women; however, the influence of gender on stage, grade, subtype and prognosis has not been studied in detail. METHODS: This study included 780 patients treated by (partial) nephrectomy at our institution in Marburg between 1990 and 2005. The mean follow-up was 5.44 years. RESULTS: Of the 780 patients, 486 (62%) were men and 294 (38%) were women. Women were significantly older (mean, 65.3 vs. 62.2 years; p<0.001, t-test), presented at lower T stages (p=0.046, chi(2)) and suffered metastasis less frequently at diagnosis (p=0.026, chi(2)). In addition, women more frequently had clear cell tumours (85.2% vs. 78.3%) and less frequently papillary tumours (11.0% vs. 18.8%) than men (p=0.026, chi(2)). In contrast, men had an increased risk of death from RCC (HR 1.23, CI 0.92-1.63); Kaplan-Meier curves revealed a significant difference in tumour-specific survival between men and women (p=0.033, log rank; 5-year survival 74% vs. 83%). However, unlike tumour stage and tumour grade, gender could not be retained as a significant independent prognostic marker in multivariate analysis. CONCLUSION: In general, RCC in men is characterized by higher tumour stages and more frequent metastasis at diagnosis along with inferior tumour-specific survival. However, as gender failed to qualify as an independent prognostic marker for tumour-specific survival, delayed diagnosis due to insufficient routine medical check-up and/or a more aggressive tumour biology might be be a concurrent cause. Thorough regular medical check-ups for men, also with regard to RCC, are thus mandatory.     

66. Die Prognose des Magenstumpfcarcinoms

Zusammenfassung Das Erfahrungsgut der Chirurgischen Universitätsklinik Innsbruck stützt sich auf 102 Fälle, die von 1959 bis 1969 wegen eines Magenstumpfcarcinoms stationär behandelt wurden. Einleitend werden die Fragen der Carcinom gefährdung des Resektionsstumpfes, die hierfür verantwortlichen Ursachen und die sich ergebenden Konsequenzen für die Indikationsstellung zur Resektionsbehandlung besprochen. Von 102 Magenstumpfcarcinomen waren 42 (41%) radikal operabel, die postoperative Mortalität betrug 26% (11 Patienten). Die Dauerergebnisse nach chirurgischer Behandlung des Stumpfcarcinoms sind nach wie vor bedrückend schlecht. Trotzdem ist eine Resignation nicht gerechtfertigt, da durch die Radikaloperation die Überlebenszeit eindeutig verbessert werden kann. In Einzelfällen sind auch Fünfjahresheilungen möglich.

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Summary The experiences of the Surgical Department, University Hospitals, Innsbruck, are based on 102 cases, which from 1959–69 were treated as in-patients on account of carcinoma of the gastric stump. In the introduction the risk of carcinoma of the resection stump, the causes responsible, and the consequences arising out of this so far as indications for resection treatment were discussed. Out of 102 carcinomas of the gastric stump 42 (41%) were radically operable; the post-operative mortality amounted to 26% (11 patients). The long-term results after surgical treatment of the carcinoma of the stump are depressingly poor, as before. Nevertheless, an attitude of resignation is not justified, as survival time is clearly improved by radical operation. In individual cases five-year survival is possible.

     

Bildgebung des Nierenzellkarzinoms

Renal cell cancer is the most frequently encountered malignant tumor of the kidney. The modern imaging techniques computed tomography (CT) and magnetic resonance imaging (MRI) play a vital role in the diagnostic work-up of renal masses. Contrast-enhanced ultrasound (CEUS) is able to visualize subtle enhancement in hypovascular tumors with high sensitivity. Recent advances in multidetector CT (MDCT) enable high resolution imaging of local findings. CT is able to provide large volume coverage of the chest and abdomen within seconds for the assessment of lymph node and distant metastasis staging. Local renal cell cancer staging can be achieved with similar diagnostic accuracy using CT or MRI. Both modalities allow visualization of a tumor’s relationship to the renal collecting system and pelvis, the renal artery and veins including the IVC. It is the radiologist’s task to accurately detect and stage renal malignances in order that each individual patient receives the therapy best suited to them.     

Histopathologie des Nierenzellkarzinoms

By integrating genetic data into the traditional histology and immunohistochemistry-based classification system, the revised WHO classification of malignant tumors (2004) defined additional renal cell carcinoma subtypes, thereby enabling the application of additional diagnostic procedures.     

Immuntherapie des Nierenzellkarzinoms

Interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha) induce remissions and prolong life in patients with metastatic renal cell carcinoma when carefully selected for a possibly toxic treatment. However, better-tolerated and more effective therapies are needed, especially in the elderly and patients with comorbidities. Recent achievements in the treatment of advanced renal cell carcinoma highlight potentially significant improvements. Immune cells within the tumor correlate with response and survival indicating the importance of local immune modulation. Such modulation has allowed introducing well-tolerated treatments such as inhalation of IL-2 to control lung metastases, which results in a significant survival benefit for high-risk patients as suggested by a recent cohort study in 200 patients. Antibody-based tumor targeting against cG250, specifically expressed on RCC, seems to stabilize progressive metastatic disease and does not induce toxicity. Vaccination strategies are also well tolerated, but have not shown convincing results in advanced disease so far. Other approaches have not fulfilled expectations. Stem cell transplantation still has significant toxicity and cannot be recommended for the elderly.     

Die Prognose des Wilms-Tumors im Verlauf der SIOP-Studien

Wilms' tumor is the most common malignant renal tumor in children. Dramatic improvements in survival have occurred as the result of advances in anesthetic and surgical management, irradiation, and chemotherapy. Today treatments are based on several multicenter trials and studies conducted by the SIOP in Europe and NWTS in the USA. The main objectives of these trials and studies are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity, and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy whereas patients treated according to NWTS are primarily operated.     

Die Erfassung der Progression des Nierenzellkarzinoms in Kleintieren mittels Flachdetektor-Volumen-CT

PURPOSE: We investigated the feasibility of using flat panel volumetric computer tomography (fpVCT) for the detection of orthotopically implanted renal carcinomas in nude mice. MATERIALS AND METHODS: One million renal cell carcinoma cells [A-498 line (Braunschweig, Germany), in 0.2 ml phosphate-buffered solution (PBS), pH 7.4] were injected into the left kidney of each of the eight nude mice. Each mouse was imaged twice (12 and 16 weeks after implantation) with fpVCT (GE prototype with circular gantry with two 1024 x 1024, 200 microm pixel size, aSi/CsI flat panel detector) after injection of 200 microl contrast medium to check for tumour spread. After 16 weeks the mice were killed and dissected, and the imaging findings in liver, kidneys and lung were compared with the macroscopic findings. RESULTS: No local evidence of tumour or of metastatic spread was seen on fpVCT after 12 weeks in any of the mice. After 16 weeks fpVCT revealed tumour growth in 6 of the 16 kidneys. Two mice had each developed a multifocal renal cell carcinoma and one mouse, a bilateral renal tumour manifestation. In one mouse liver metastases were seen. The fpVCT findings correlated well with the observations recorded in the pathological examination. CONCLUSION: fpVCT is an innovative and noninvasive imaging procedure that can be used for longitudinal investigation of tumour progression following orthotopic implantation of renal cell carcinoma to small animals. The use of a system of this kind will make a decisive contribution to reducing the number of animals used in experimental test projects.     

Immuntherapie des fortgeschrittenen Nierenzellkarzinoms

Zusammenfassung Beim Nierenzellkarzinom hat sich die Überlebenszeit der Patienten in frühen Stadien durch verbesserte chirurgische Therapie deutlich erhöht. Für Patienten mit fortgeschrittenen Stadien hat sich die Prognose aber nur unwesentlich verändert. Behandlung mit IFN- führte zur moderaten Verlängerung des Überlebens, zusätzlich kann eine Nephrektomie dazu beitragen. Die Kombination IFN-, 5-FU und Interleukin-2 führte ebenfalls in einer Studie zu verlängerter Überlebenszeit. Die häufig erhebliche Toxizität dieser Strategien machen jedoch eine sorgfältige Risiko-Nutzen-Abwägung im Einzelfall erforderlich. Auch wenn die Erwartungen an die Immuntherapie bisher nur teilweise erfüllt sind, zeigen erste Ergebnisse mit spezifischen Immuntherapien, dass eine immunologische Kontrolle des metastasierten Nierenzellkarzinoms möglich ist. Die Hoffnung auf effektive Behandlungsverfahren in naher Zukunft erscheint realistisch.     

Die Prognose des apallischen Syndroms Ein Literaturüberblick

This study evaluates the available literature about the prognosis of patients with apallic syndrome and similar illnesses. Different therapeutic strategies are not relevant in this review. The variation of the reported material did not permit a statistical metaanalysis. However, many interesting points of view could be elaborated leading to positive assistance in everyday situations. The chance of survival and the long-term outcome of comatose patients decrease with an increase in the age of the patient, the length and the degree of the coma. Cerebral predamage worses the long-term prognosis. Traumatic head injuries have a better prognosis than nontraumatic. Children (under 18 years of age) have a better prognosis than adults.The course of the oculomotoric symptoms can be used as a prognostic criterion. The somatosensory evoked potentials in the early phase correlate with the survival-chance and the long-term prognosis. The initial speed of recovery correlates with the long term outcome. Children and adults with traumatic apallic syndrome may recover over a period of 12 months. For apallic patients with other etiologies this time limit is 3 months. Few cases of recovery have been described outside these time limits. The average survival limit of permanent apallic patients is between 3 and 5 years. Particular patients have survived decades.     

Paraneoplastische Syndrome des Nierenzellkarzinoms

Renal cell carcinoma associated paraneoplastic symptoms include constitutional symptoms as well as specific metabolic and biochemical abnormalities. These are present in up to 40% of patients with renal cell carcinoma during the course of the disease. This report provides information on the most common manifestations and their therapy; some rare variants are also mentioned. The importance of paraneoplasia lies partly in the fact that paraneoplastic symptoms may be the precursor of either primary or recurrent disease. The presence of paraneoplastic manifestations does not necessarily imply a poor prognosis or metastatic disease.     

Systemtherapie des metastasierten Nierenzellkarzinoms

In the last 5 years the paradigms for the treatment of metastatic renal cell cancer have fundamentally changed. Until 2005 systemic therapy was limited to the immunomodulating cytokines interferon-alfa and interleukin-2, in recent years, however, tyrosine kinase inhibitors, mTor inhibitors and monoclonal antibodies have been established for this therapeutic situation. Without validated predictive biomarkers it is currently not possible to select patients who are likely to benefit from a certain therapy. Therefore, most current guidelines stratify the patients into risk groups according to the MSKCC risk score. The resulting treatment algorithm for first-line therapy is limited to these new drugs within all risk groups. Since approval for more tyrosine kinase inhibitors and mTOR inhibitors is currently awaited, the number of treatment options will expand further in the near future. The present paper reviews the present study data and aims to provide practical advice for the treatment of patients suffering from metastatic renal cell cancer.     

Operative Therapie des Nierenzellkarzinoms

Renal cell carcinoma represents the fifth most frequent malignant tumor in humans. At the time of diagnosis, 20% of the patients already manifest metastases. A further 20–30% of the patients develop systemic metastases in the postoperative course. Despite continued advances in pharmacological treatment options, cancer surgery tailored to the individual tumor findings constitutes the only curative treatment option.     

Die Prognose des Rumpftraumas unter Berücksichtigung seiner Begleitverletzungen

Zusammenfassung Von 1970 bis 1984 wurden 480 polytraumatisierte Patienten behandelt, von denen 301 (62,7%) ein Rumpftrauma erlitten hatten. Dieses Patientenkontingent war zu 85% belastet durch Begleitverletzungen am Schädel (69,1%) und am Bewegungsapparat (66,1 %). Die Rate der Thoraxverletzungen lag bei 81,4%, die der Abdominalverletzungen bei 52,5%. Notfallmäßige operative Eingriffe erfolgten am Thorax bei 34,7%, am Abdomen bei 50% bezüglich der Verletzungsrate. Bei Operationsindikation lag die Letalität der Thoraxverletzung bei 70,6%, die der Abdominalverletzung bei 40,5%. Die Todesursachen waren zu 2/3 durch Verletzungskombinationen, zu 1/3 durch isolierte Läsionen bedingt. Von 245 Thoraxverletzungen verstarben 33,1%, von 158 Abdominalverletzten 42,4%. Das multiple Organversagen stellt bei schweren Verletzungskombinationen das entscheidende Kriterium für die voraussichtliche Prognose dar. In der rechtzeitigen Indikationsstellung nach Behandlungsprioritäten liegt der Schlüssel zum Erfolg oder Mißerfolg.

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Prognosis of thoracoabdominal injuries and concomitant lesions

Summary A total of 301 patients with thoracoabdominal lesions had concomitant craniocerebral lesions (69.1%) and injuries of the locomotor system (66.1%). In 65.4% operative intervention was necessary, while 34.6% could be primarily treated conservatively. Operative emergency therapy was required in the thorax in 34.7%, and in the abdomen in 50%. Under these conditions, the mortality for the thorax was 70.6% and for the abdomen 40.5%. As a result of mostly combined causes (66%), 101 patients died (33.6%). Multiple organ failure was in the high range (80%), while the most frequent single cause of death was craniocerebral trauma, ranking before thoracic and abdominal traumata.

     

Systemische Therapie des metastasierten Nierenzellkarzinoms

Cytokine-based immunotherapy was the only viable option in metastatic, nonresectable renal cell carcinoma (RCC) for many years. Systemic immunotherapy has become increasingly established as a standard therapy during the last 15 years. In this context, interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) turned out to be the most effective single agents in RCC. Subsequently, the approved subcutaneous application of these compounds was the preferred administration route in Germany. Response rates with cytokine combination therapy were almost similar to those of more aggressive concepts using additional chemotherapeutic agents.Currently, new compounds targeting specific signaling pathways are readily available and have passed clinical testing. Such small molecules like tyrosine kinase inhibitors, monoclonal antibodies, or the mTOR inhibitor CCI-779 may dramatically change the established concepts of systemic RCC treatment. This paper gives an overview of established, current, and evolving concepts of systemic therapy in RCC.     

Systemische Therapie des metastasierten Nierenzellkarzinoms

Once surgical options have been exhausted, systemic therapy is indicated for metastasizing renal cell carcinoma. Until recently this was carried out using mainly immunotherapeutic concepts with unsatisfactory results. Since the majority of clear cell renal cell carcinomas are well vascularised, angiogenetic inhibition offered an alternative therapy goal. To date, four substances have been approved to control angiogenesis in the therapy of renal cell carcinoma: sunitinib, sorafenib, temsirolimus, as well as a combination of bevacizumab and interferon alpha. Other substances, such as everolimus, pazopanib and axitinib, are currently the subject of clinical trials. Initial data on tolerance and efficacy was presented at this years annual conference of the American Society of Clinical Oncology (ASCO). This article examines current therapy options and ASCO data and discusses future trends.     

Die postoperative Funktion des Verdauungstraktes

Ohne ZusammenfassungMit 20 Textabbildungen     

Systemische Behandlung des metastasierten Nierenzellkarzinoms

Introduction

The goal of this work was to describe the change of treatment paradigms for metastatic renal cell carcinoma (mRCC) since 2006.

Patients and methods

We retrospectively investigated all mRCC patients who were treated with targeted therapy between June 2006 and June 2012 at the University of Münster.

Results

In all, 50 of 158 (31.6?%) patients were initially treated with immunotherapy. The most often used second line treatment after immunotherapy was sorafenib (29 patients, 58.0?%). The first line treatment chosen for therapy-naïve patients was sunitinib (68 patients, 63.0?%). There was no statistically significant difference between the two groups (572 vs. 554 days, p?=?0.745). A total of 77 patients had synchronous metastasis (48.8?%), 55 of whom underwent cytoreductive nephrectomy. There was a significant survival benefit in favor of surgically treated patients (510 vs. 186 days, p?=?0.002).

Conclusion

After introduction of the new agents treatment paradigms have changed substantially. Immunotherapy is used only rarely. Cytoreductive nephrectomy may continue to be regarded as standard treatment until prospective data are available.