Michael Böhmig

Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors-the international lanreotide and interferon alfa study group

PURPOSE Somatostatin analogs and interferon alfa control hormone-active/functional neuroendocrine gastroenteropancreatic tumors. In addition to hormonal control, variable degrees of antiproliferative effects for both agents have been reported. Until now, however, no prospective, randomized studies in therapy-naive patients have compared somatostatin analogs or interferon alfa alone with a combination of the two. METHODS Eighty therapy-naive patients with histologically verified neuroendocrine tumor disease (primary localization: foregut, n = 36; midgut, n = 30; hindgut, n = 3; unknown, n = 11; functional, n = 29; nonfunctional, n = 51) were randomly treated either with lanreotide (1 mg three times a day administered subcutaneously [SC]) or interferon alfa (5 x 106 U three times a week SC) or both. All patients had disease progression in the 3 months before study entry, verified with imaging procedures. RESULTS Twenty-five patients were treated with lanreotide, 27 patients were treated with interferon alfa, and 28 patients were treated with the combination. Partial tumor remission was seen in four patients (one patient who received lanreotide, one patient who received interferon alfa, and two patients who received the combination). During the 12 months of therapy, stable disease was observed in 19 patients (seven patients who received lanreotide, seven patients who received interferon alfa, and five patients who received the combination), whereas tumor progression occurred in 14 of 25 patients (lanreotide), 15 of 27 patients (interferon alfa), and 14 of 28 patients (combination). Side effects leading to an interruption of therapy were more frequent in the combination group than in the monotherapy arms. CONCLUSION This prospective, randomized, multicenter study shows for the first time that somatostatin analogs, interferon alfa, or the combination of the two had comparable antiproliferative effects in the treatment of metastatic neuroendocrine gastroenteropancreatic tumors. Response rates were lower compared with those published in previous, nonrandomized studies. The antiproliferative effect of the tested substances was similar for functional and nonfunctional neuroendocrine tumors.

Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours.

Neuroendocrine tumours (NET) of the gastroenteropancreatic system comprise a malignant entity with a low incidence. Only limited information is available on long-term clinical outcome and clinically applicable prognostic factors. We performed a retrospective analysis of a large, well-characterized centre-based patient cohort of 399 patients with histologically proven NET. Data were analysed according to epidemiological, clinical and histopathological characteristics. Detailed survival analyses using the Kaplan-Meier method were performed. Prognostic factors were tested by log-rank testing and independent risk factors were analysed using a Cox regression model. In the studied cohort, primary tumours originated in the fore-, mid- and hindgut in 46.1, 37.1 and 4.5% respectively. Extra-intestinal or unknown primary tumours were present in 8.4 and 10.5% respectively. Distant metastasis was present at initial diagnosis in 69.4%. Most frequent metastatic sites were liver (85%), peritoneal cavity (18%), bones (8%), other intra-abdominal sites (6%) and lungs (4%). Overall, 5- and 10-year survival rates were 78 and 63% respectively. Time to progression after initial diagnosis was significantly shorter in pancreatic as compared with ileal NET. Survival analysis revealed significantly better clinical outcome for primary tumours smaller than 25 mm, absence of metastasis, absence of any clinical symptoms, positive immunohistochemical staining for chromogranin A and a lower Ki67 index. These results were confirmed as independent by multivariate analysis. Therefore, this large retrospective analysis of a well-documented cohort of patients with NET demonstrates several prognostic factors of clinical relevance and wide availability, which should be considered for risk stratification in the management of NET.

Diagnostik und Therapie gastroenteropankreatischer neuroendokriner Tumore aus internistischer Sicht

Neuroendokrine Tumoren (NET) sind seltene Neoplasien mit einer geschätzten Inzidenz von 0,1–1/100.000 [31], wobei etwa 75% der NET im gastroenteropankreatischen System lokalisiert sind [25]. Diese Tumoren zeigen einen deutlich protrahierten Erkrankungsverlauf im Vergleich zu anderen gastrointestinalen Neoplasien; so liegt die Fünfjahresüberlebenszeit in Abhängigkeit von Primärlokalisation und Metastasierung bei ca. 50% [25].

Therapie des Pankreasadenokarzinoms

BACKGROUND Despite significant advances in the areas of epidemiology, risk factors, molecular genetics and diagnosis pancreatic carcinoma is characterized by a dismal prognosis and ranks 5th among malignancy-associated deaths. This article attempts to critically review the current literature and analyze therapeutic recommendations based on published evidence. Therapeutic options are based on the stage of the disease. SURGICAL TREATMENT Surgical resection with curative intention is feasible only in a minority of patients presenting with locally confined tumor disease. RADIO- AND CHEMOTHERAPY: Adjuvant combined radiochemotherapy might potentially improve survival and can also be considered in unresectable, locally advanced disease. The role of chemotherapy in advanced disease is exclusively palliative. Up to now, no chemotherapeutic regimen has demonstrated convincing impact on survival. Newer substances, such as gemcitabine, appear to be of some value in respect to quality of life. Best supportive care oriented at clinical symptoms remains a cornerstone in the therapeutic concept of patients with pancreatic carcinoma. CONCLUSION Development of innovative therapeutic strategies is therefore mandatory.Zusammenfassung□ HintergrundTrotz erheblicher Fortschritte im Bereich der Epidemiologie, Molekulargenetik und Diagnostik ist das Adenokarzinom des Pankreas unverändert durch eine extrem schlechte Prognose gekennzeichnet. In der Häufigkeit tumorbedingter Todesfälle liegt es an fünfter Stelle Die vorliegende Arbeit gibt einen kritischen Überblick über die umfangreiche Datenlage und analysiert Therapieempfehlungen, die auf gesicherten Erkenntnissen beruhen.□ Chirurgische TherapieBei einer Minderheit von Patienten wird ein lokal begrenztes Krankheitsstadium diagnostiziert. Hier ist eine chirurgische Resektion unter kurativer Zielsetzung möglich und aufgrund der verbesserten Operationstechnik in erfahrenen Zentren gerechtfertigt.□ Radio-und ChemotherapieMöglicherweise führt eine adjuvante Radiochemotherapie zu einer Überlebensverbesserung. Eine kombinierte Radiochemotherapie kann ferner bei irresektabler, lokal fortgeschrittener Erkrankung indiziert sein. Der systemischen Chemotherapie kommt in fortgeschrittenem Krankheitsstadium eine rein palliative Rolle zu. Kein Behandlungsprotokoll hat bislang reproduzierbar eine eindeutige Lebensverlängerung demonstrieren können. Möglicherweise profitiert jedoch ein Teil der Patienten klinisch von einer Chemotherapie. Grundpfeiler in jedem Stadium stellt eine an Symptomen orientierte supportive Behandlung dar.□ SclußfolgerungAngesichts der aktuellen Datenlage ist die Entwicklung innovativer therapeutischer Strategien von herausragender Bedeutung.Abstract□ BackgroundDespite significant advances in the areas of epidemiology, risk factors, molecular genetics and diagnosis pancreatic carcinoma is characterized by a dismal prognosis and ranks 5th among malignancy-associated deaths. This article attempts to critically review the current literature and analyze therapeutic recommendations based on published evidence. Therapeutic options are based on the stage of the disease.□ Surgical TreatmentSurgical resection with curative intention is feasible only in a minority of patients presenting with locally confined tumor disease.□ Radio- and ChemotherapyAdjuvant combined radiochemotherapy might potentially improve survival and can also be considered in unresectable, locally advanced disease. The role of chemotherapy in advanced disease is exclusively palliative. Up to now, no chemotherapeutic regimen has demonstrated convincing impact on survival. Newer substances, such as gemcitabine, appear to be of some value in respect to quality of life. Best supportive care oriented at clinical symptoms remains a cornerstone in the therapeutic concept of patients with pancreatic carcinoma.□ ConclusionDevelopment of innovative therapeutic strategies is therefore mandatory.

Erkrankungen von Leber, Gallenwegen und Pankreas

Die wichtigsten therapierelevanten metabolischen und genetisch determinierten Lebererkrankungen sind die Hamochromatose und der Morbus Wilson. Beide Erkrankungen werden autosomal-rezessiv vererbt. Wahrend die Hamochromatose mit einer Haufigkeit von 1:200 bis 1:400 auftritt (Heterozygote 1:15), ist der Morbus Wilson deutlich seltener mit einer Frequenz von 1:30.000 (Heterozygote 1:90).