Adjuvante und palliative Therapie des Pankreaskarzinoms

The only curative treatment of pancreatic cancer is complete resection (R0), however, at the time of diagnosis resection is only possible in a maximum of 20% of patients. Surgery-associated mortality is low in selected surgical centers, but the majority of patients suffer a recurrence even after complete resection and die of the disease. The mean survival time after resection lies between 11 and 23 months and the 5-year survival time of surgical patients between 10 and 25%. According to current inormation adjuvant chemotherapy is becoming increasingly more accepted. The good results with gemcitabin in two studies have shown that the data position for adjuvant therapy is stable. In the United States radiochemotherapy with 5-fluorourcil is recommended as possible standard adjuvant therapy based on the results of a randomized study of the Gastrointestinal Tumor Study Group (GITSG) but radiochemotherapy is normally not employed in Europe. This discrepancy results from contradictions between published studies, which showed partly low case numbers or methodological shortcomings. Therapy with gemcitabim has been the established standard therapy in the palliative situation since its introduction 10 years ago. The additional administration of the tyrosine kinase inhibitor erlotinib results in a clear advantage for survival in selected patients with a skin reaction. Patients in a good general physical condition can primarily be treated with a combined intensified therapy depending on the individual preferences because a survival advantage was shown here for the subgroups in the corresponding studies     

Palliative Therapie des fortgeschrittenen Pankreaskarzinoms

In spite of advances in the management of other malignancies, the prognosis of patients with advanced pancreatic cancer remains poor. Palliative therapy is an essential element of the treatment strategy. In this review we discuss important areas of the palliative therapy of advanced pancreatic cancer. We focus on complications of pancreatic cancer, such as stenosis of the common bile duct, duodenal obstruction and thrombosis as well as on supportive therapy. The endoscopic implantation of self-expanding metal stents is a safe procedure with a high success rate to obtain adequate biliary drainage. In cases of malignant duodenal obstruction palliation is also mainly achieved by endoscopic stenting. A main area of supportive care is an appropriate pain treatment, following the WHO scheme for pain therapy. Weight loss in patients with pancreatic cancer is often due to pancreatic exocrine insufficiency, which is treated by supplementation of pancreatic enzymes.     

Palliative interventionelle und chirurgische Therapie des Pankreaskarzinoms

The majority of patients with pancreatic cancer are found to be unresectable due to infiltrative growth of the tumor into the celiac axis and the superior mesenteric vessels and/or due to distal metastases. Pancreatic cancer arises predominantly in the head of the pancreas. The patients come to medical attention when they develop jaundice secondary to obstruction of the distal common bile duct. Biliary decompression with stenting can be achieved by either endoscopic methods (ERC) or percutaneous transhepatic cholangiodrainage (PTCD) into the duodenum or outside. Plastic stents tend to occlude faster than metal stents and have to be exchanged after 3 months. Mechanical obstruction of the duodenum with nausea and vomiting requires gastrojejunostomy. In individual cases duodenal stents are used to bypass duodenal obstruction. The aim of these procedures is to guarantee quality of life for the patient. Endoscopic versus surgical palliation has to be balanced for each patient individually.     

Molekularbiologie des Pankreaskarzinoms

Pancreatic ductal adenocarcinoma contributes to over 90% of pancreatic malignancies and each year 6,050 people develop pancreatic cancer in Germany. At present surgery is the only therapy with curative intention. Conventional oncological therapies, such as radiation therapy, chemotherapy or combined therapy could not satisfactorily prolong survival in advanced pancreatic carcinoma. In addition to continuous advances in conventional therapy, we see a development in basic research which might contribute to future new therapeutic strategies. The present review will focus on these new insights into the molecular biology of pancreatic ductal adenocarcinoma.     

Molekulare Genetik des Pankreaskarzinoms

Das exokrine Karzinom des Pankreas ist einer der aggressivsten humanen Tumore. Aufgrund erst sp?t auftretender, nicht-spezifischer Symptome und schnellen, metastasierenden Wachstums haben Patienten mit dieser Erkrankung eine extrem schlechte Prognose. Das 5-Jahresüberleben liegt dabei unter 5%. Die einzige, potentiell kurative Therapie ist die chirurgische Resektion, die leider bei weniger als einem Drittel der Patienten in Betracht kommt. Der Schlüssel zu einer erfolgreicheren Therapie liegt daher eindeutig in einer frühen Diagnose von kleinen, organbegrenzten Tumoren.     

Multimodale palliative Behandlung des Pankreaskarzinoms

Exhibiting a rising incidence, pancreatic carcinoma is the fourth most common cause of death in the Western world. In Germany more than 4900 men and 5500 women suffer from pancreatic carcinoma every year, about 3% of all newly diagnosed cases of cancer. Because of the non specific symptoms, pancreatic carcinoma is detected in 80–90% of cases in an advanced or metastatic stage. In only 20% of all patients is an operation possible and after complete resection the 5-year survival rate is 20%. Palliative chemotherapy is supposed to be the standard treatment in advanced and metastatic pancreatic carcinoma. The value of radiochemotherapy is currently being evaluated in several phase III studies. In the palliative situation sufficient analgesic treatment is necessary as well as early initiation of nutritional support.     

Stellenwert der Strahlentherapie im Therapiekonzept des Pankreaskarzinoms

Pancreatic cancer affects approximately 200,000 people every year worldwide and most of them die of the disease. There are no early symptoms therefore approximately 70% of patients have locally advanced disease or even distant metastases (60%) at the time of diagnosis. At this time more than 80% of the patients cannot be treated by a microscopically complete resection (R0). Even if a microscopically complete resection is achieved local recurrence of pancreatic carcinoma can be expected in 35–90% of patients. Hepatic and peritoneal metastases are expected in 50–90%. There have been great advances in surgical techniques but 5-year survival rates still remain at less than 25% and also median survival times are not longer than 15 months after microscopically complete resection. Randomized clinical trials have shown an additional improvement in median survival times of 20–23 months for adjuvant chemotherapy with 5-fluorouracil or gemcitabine compared to surgery alone. Palliative chemotherapy also extends the medial survival time of patients with distant metastases or locally advanced disease for 1–2 months. The standard of cytostatic therapy with 5-fluorouracil was replaced by gemcitabine 10 years ago. A concept of multimodal therapy is needed in order to increase the rate of complete resections as well as the possibility of surgery to get a better local and systemic control, therefore integration of radiotherapy in the treatment of pancreatic carcinoma seems to be necessary. How radiotherapy can contribute to a better prognosis of pancreatic carcinoma in a neoadjuvant, adjuvant and palliative situation in the context of these concepts is the main topic of this article.     

Aktueller Stand der bildgebenden Diagnostik des Pankreaskarzinoms

Pancreatic cancer is the 4th–5th leading cause of cancer-related death in the western world. Overall the prognosis of patients with pancreatic cancer is dismal with a 5-year survival rate of less than 5%. At the time of diagnosis about 80% of pancreatic tumors are non-resectable. In most cases biphasic contrast-enhanced multi-slice CT (MSCT) is the imaging modality of choice in the diagnosticsof patients with pancreatic cancer as most questions relevant for the clinician, such as local tumor extent and invasion of peripancreatic vessels, can be answered with a high degree of accuracy. However, in cases with equivocal CT findings (e.g. isodense tumor) MR imaging can be applied for the detection of small tumors or for the characterization of cystic lesions. This article provides an overview on typical imaging findings of pancreatic tumors, discusses the radiologic staging of adenocarcinomas of the pancreas and alludes to recent developments in MR imaging such as diffusion-weighted imaging.     

Therapie des Aderhautmelanoms

The treatment of choroidal melanoma needs multidisciplinary efforts. Nowadays most of the tumors are treated by radiation, and enucleation of the eye is rare. Technical developments in lasers and eye surgery procedures have influenced the novel therapeutic modalities in recent years. However, the rate of metastatic spread remains unchanged, and to date no established adjuvant therapy exists. The treatment of patients with stage IV disease has achieved some success in the recent past, which raises the hope of developing an adjuvant therapy.     

Therapie des Nierenzellkarzinoms

Over the past 5 years, the treatment of renal cell carcinoma (RCC) has undergone a dramatic change. Surgery in the early disease stages is still the only known curative treatment modality, while palliative nephrectomy, nephron sparing surgery and partial resection have now enriched the surgical repertoire. During the early 1980s, immunotherapies remained the mainstay of systemic treatment of metastatic RCC. Sorafenib and sunitinib were the first new drugs to be approved for the treatment of advanced or metastatic RCC in the past 10 years. Both drugs show tremendous potency and provide novel future perspectives for drug treatment in RCC. Currently, the optimal combination of drugs is being explored in clinical studies and results are thought to elucidate the role of combined targeted therapies in RCC.     

Therapie des Analkarzinoms

Anal cancer is a rare tumor, which should be considered in patients with risk factors, e.g., HIV (human immunodeficiency virus) infection, immunosuppression, and history of cervical carcinoma. Based on recent published data, the principles of diagnosis, treatment, and follow-up are presented. Concurrent chemoradiotherapy with 5-FU (5-flurouracil) and mitomyin C is the treatment of choice for anal cancer, which can provide sphincter preservation in most cases. In patients with persistent tumor after chemoradiotherapy or local recurrence, cure can still be provided with abdominoperineal resection as salvage treatment. Thus, there is need of regular follow-up examinations to diagnose this indication at an early stage. The use of new substances and the addition of induction or maintenance chemotherapy could not improve the results in randomized trials and could not replace the established protocol. Achieving good treatment results requires close cooperation of all involved medical specialties.     

Therapie des Low-grade-Harnblasenkarzinoms

best practice onkologie -     

Therapie des Mantelzelllymphoms

Mantle cell lymphoma is characterized by a specific overexpression of cyclin D1 and a rapid relapse pattern. The histological results and clinical course may differ significantly so that histological, clinical and biological factors should be considered for the individual risk profile. However, treatment should be immediately initiated in the vast majority of cases. In younger patients, the advantage of dose intensification with autologous stem cell transplantation has been proven in numerous trials and a recent randomized phase III study confirmed the additional benefit of a cytarabine-containing regimen. In elderly patients combined immunochemotherapy achieves an initial high response rate but additional consolidation is crucial to achieve long lasting remission. In a recent study of the European MCL network a rituximab maintenance achieved a median duration of remission of almost 6 years. Current study concepts investigate the addition of molecular targeted approaches (proteasome inhibitors, IMIDS and mTOR inhibitors).     

Chirurgische Therapie des Analkarzinoms

The primary therapy of anal cancer is curative radiochemotherapy. Following a confirmed diagnosis the role of the surgeon is the treatment of local complications of anal cancer by securing bowel passage and protection of the perineum by laparoscopic placement of a preternatural anus or stoma. For patients with a persistent or recurrent tumor following radiochemotherapy a clear improvement in the oncological process can be achieved by surgical salvage therapy using an abdominoperineal rectum extirpation. However, this is accompanied by a high morbidity of up to 80%. Of particular importance here are disturbances in wound healing in the perineum; therefore, a primary myocutaneous flap surgery can be used to cover the perineal resection wound and the rate of disturbances in wound healing can be substantially reduced.     

Radioonkologische Therapie des Ovarialkarzinoms

Grundlage der Diagnostik und Therapie von malignen Ovarialtumoren bildet die gyn?kologische Chirurgie. Ziel ist dabei die optimale Reduktion des Tumorvolumens. Die Reduktion auf einen maximalen Tumorduchmesser <2 cm ist hierbei die wesentliche Voraussetzung für eine Verbesserung der Heilungsraten. Die überwiegende Mehrzahl der Patientinnen mit malignen Ovarialtumoren befindet sich jedoch bei Diagnosestellung bereits in fortgeschrittenen Stadien. Die Ergebnisse alleiniger operativer Ma?nahmen sind in diesen F?llen unbefriedigend. Priv.-Doz.Dr. F.Würschmidt Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie der TU München, Klinikum rechts der Isar, Ismaninger Stra?e 22, 81675 München, E-Mail: wuerschmidt@gmx.de