Markus W. Büchler

Pancreatic Cancer: Current Options for Diagnosis, Staging and Therapeutic Management

Background: Pancreatic cancer is characterized by frequently delayed diagnosis and aggressive tumor growth which hampers most of the current treatment modalities. This review aims to summarize the available evidence about the diagnostic and therapeutic aspects of resectable and non-resectable pancreatic cancer therapy. Summary: Embedded in the concept of multimodal therapy, surgery plays the central role in the treatment of pancreatic cancer. With advantageous tumor characteristics and complete tumor resection as the most relevant positive prognostic factors, the detection of premalignant or early invasive lesions combined with safe and oncologic adequate surgery is the major therapeutic aim. Most pancreatic adenocarcinomas are locally advanced or metastatic when diagnosed and need to be treated by the combination of surgery and (radio)chemotherapy or by palliative chemotherapy. Key Message An interdisciplinary, multimodal approach to therapy is critical for improving the outcomes of patients with pancreatic cancer. Practical Implications Cross-sectional imaging techniques (such as contrast-enhanced multidetector computed tomography) are useful for assessing tumor resectability. For localized, non-metastatic, resectable tumors, the necessity of preoperative biopsies remains controversial. Important prognostic parameters are tumor size, invasion of surrounding tissue, lymph node metastasis and distant metastasis. Various classification systems based on the TNM system have been used for tumor staging and prognosis. The presence of distant metastases is regarded as non-resectable disease, requiring chemotherapy as first treatment. The definition of borderline resectable tumors is still under debate, although a recent definition has been provided by an expert consensus statement. Standard lymphadenectomy is the recommended procedure in pancreatoduodenectomy, based upon the guidelines of the International Study Group of Pancreatic Surgery (ISGPS). Adjuvant chemotherapy is applied in generally all cases of pancreatic ductal adenocarcinoma following macroscopic complete tumor resection. The benefits of adjuvant chemoradiotherapy or immunochemoradiotherapy, or neoadjuvant therapy, however, remain a matter of controversy. For palliative treatment gemcitabine monotherapy is widely used; the FOLFIRINOX protocol provides an alternative for a minority of patients.

Pancreatic Metastases from Tumors in the Urogenital Tract

Background: Isolated pancreatic metastases or pancreatic metastases with limited extrapancreatic disease are uncommon and account for only 2-4% of resected malignant pancreatic lesions in surgical series. However, clear-cell renal cell carcinoma is the predominant primary tumor and accounts for more than 60% of cases with isolated pancreatic metastases. Pancreatectomy is the treatment of choice for most patients with isolated pancreatic metastases from renal cell cancer. Summary: This review provides an overview of clinical presentation and diagnosis as well as surgical management, including patient selection for surgery and surgical technique for pancreatic metastases of renal cell carcinoma. Key Message: Although there is no high-level evidence that surgical resection of pancreatic metastases improves survival, the survival results of several observational series and of systematic reviews are promising and support pancreatic resection as part of a multimodal treatment. The reported median survival and 5-year survival rates after pancreatic resection range from 6 to 10 years and from 55 to 75%, respectively. Pancreatic resection is effective for local control. However, extrapancreatic progression frequently occurs. With the introduction of novel systemic therapy options such as tyrosine kinase inhibitors, the prognosis of metastatic renal cell carcinoma has improved, and this will affect the role of pancreatic resection for metastases. Practical Implications: Pancreatic resection for isolated renal cell carcinoma is safe and effective, may confer a survival benefit and should, therefore, be considered in patients for whom no contraindication for surgery exists.

Sterile Necrosis in Acute Necrotizing Pancreatitis: Current Concepts and Management Strategies

Acute necrotizing pancreatitis is possibly the most severe form of acute pancreatitis. While results have improved significantly in the past decade, acute necrotizing pancreatitis still carries a high morbidity and mortality. However, it is the infected necrosis of acute necrotizing pancreatitis that accounts for a major share of this high morbidity and mortality.1 On the other hand, management of sterile necrosis has evolved considerably in recent years with improved results. This article discusses the current understanding of sterile necrosis and the approach to its management.

Progress by Collaboration: ESPAC Studies

Pancreatic cancer is amongst the top ten fatal cancers of the Western world, accounting for 57 000 deaths per year in Europe and 29 000 deaths per year in the United States.1 It is particularly difficult to treat because of its inaccessible location, late presentation, and frequently aggressive tumour biology. Five-year survival in the 10–15% of affected patients who undergo potentially curative surgery is limited to 17–24%,2,3 whilst overall 5-year survival in all patients is less than 0.5%.4 Although significant improvements in surgical outcome have been obtained with increasing specialisation and case-load,3,5 and further benefits may be anticipated with earlier investigation and referral of high risk groups, 6 the role of adjuvant and neo-adjuvant treatment accompanying surgery remains uncertain.7-10 Interestingly, chemotherapy is the principal modality in the treatment of advanced pancreatic cancer.11

Anti-Angiogenics in Pancreatic Cancer Therapy

Pancreatic cancer is a highly lethal disease. Up to date, the only curative approach is surgical resection, which is only possible in a limited number of patients by the time of diagnosis. Thus, the development of new therapeutic options besides chemotherapy is extremely important for patients who do not qualify for surgery due to local irresectability or systemic tumor spread. During development and progression of pancreatic tumors, angiogenesis is an important mechanism to supply blood, oxygen, and nutrients for the growing tumor mass. Several angiogenic factors play a critical role during this process, including vascular endothelial growth factor (VEGF), as well as multiple factors involved in tyrosine kinase pathways, all of which are potential targets for systemic treatment approaches. Pancreatic ductal adenocarcinoma represents the biggest proportion among all pancreatic tumor entities. It is histopathologically characterized by a hypovascular appearance and pronounced peritumoral desmoplastic tissue as well as extracellular matrix. In numerous experimental and clinical studies, antiangiogenic therapy has been evaluated for pancreatic ductal adenocarcinoma with early promising results. However, in clinical phase III studies, only limited effects were achieved with targeted antiangiogenic approaches. In contrast, pancreatic neuroendocrine tumors, which are typically hypervascularized, are much more sensitive to antiangiogenic substances. After a successful phase III study, sunitinib – a multi-targeted kinase inhibitor – has been approved for the treatment of this entity and is incorporated in current international guidelines as a second-line therapy recommendation. The pathogenesis, diagnostic measures, as well as current experimental and clinical studies regarding angiogenesis and antiangiogenic therapy of both pancreatic ductal adenocarcinoma and neuroendocrine tumors are summarized described in this chapter.

Das Heidelberger Modell: Ganzheitliches Management im Wettbewerberumfeld

Jedes funfte Krankenhaus in Deutschland schreibt rote Zahlen. Es entsteht ein zunehmender uberregionaler Konkurrenzdruck zwischen medizinischen Leistungserbringern. Krankenhauser fusionieren haufiger oder werden privatisiert. Eine strukturelle Neuorientierung von Krankenhausern mit zunehmendem Bettenabbau erfordert strategische Neuausrichtungen (vgl. kna/aerzteblatt.de 2010).

Unterscheiden sich neoadjuvant therapierte Adenokarzinome des oberen Gastrointestinaltraktes genderspezifisch

Einleitung: Die Inzidenz, Risikofaktoren, Lokalisation und histopathologische Aspekte wie Laurenklassifikation sind bei Adenokarzinomen des oberen Gastrointestinaltraktes (GI) geschlechtsabhangig. Fur den oberen GI existiert in der Literatur nur eine einzige geschlechtsabhangige Analyse[for full text, please go to the a.m. URL]

Evidenzbasierte offene und minimal-invasive Nekrosektomie bei akuter Pankreatitis

Patienten mit nekrotisierender schwerer Pankreatitis benotigen heute nur noch selten eine interventionelle oder chirurgische Therapie. Bei Verdacht auf infizierte Nekrosen und septischem Krankheitsbild sollte im Rahmen des „Step up Approach“ primar eine interventionelle oder ggf. eine endoskopische Drainage des infizierten Pankreasareals erfolgen. Bei fehlender klinischer Stabilisierung muss die Nekrosektomie erfolgen. Der ideale Zeitpunkt ist die 3.–4. Krankheitswoche, da sich zu dieser Zeit die Nekrosen demarkiert haben. Die konventionelle offene Nekrosektomie ist durch eine niedrige Mortalitat, geringe Morbiditat und einen guten Langzeitverlauf charakterisiert. In den letzten Jahren sind mit den perkutanen, in der Regel retroperitoneoskopischen minimal-invasiven Techniken Alternativen entwickelt worden, die heute in ca. 70 % der Falle erfolgreich eingesetzt werden konnen.

Individualisierte Chirurgie bei Rektumkarzinomen

Die anteriore oder tiefe anteriore Rektumresektion in Kombination mit einer partiellen (PME) oder totalen mesorektalen Exzision (TME) sind die derzeitigen Standardverfahren in der Chirurgie der Rektumkarzinome. Diese Operationen werden laparoskopisch oder in konventioneller Technik durchgefuhrt. Die wesentlichen Phasen der Operation sind: 1. Mobilisierung von Sigma und Colon descendens; 2. Durchtrennung der A. und V. mesenterica inferior; 3. Durchtrennung des Colon descendens; 4. Mobilisierung des Rektums in PME- oder TME-Technik; 5. Absetzen des Rektums; 6. Anastomosierung; 7. Anlage eines protektiven Stomas (optional). Technische Probleme und schwierige Entscheidungssituationen entstehen meistens bei der ventralen Praparation im kleinen Becken, beim Absetzen des Rektums und bei der Anastomosierung.

Die Entwicklung des „Europäischen Pankreaszentrums Heidelberg“ (EPZ)

Das Pankreaskarzinom mit seinem aggressiven Tumorwachstum, fruhen Metastasierung und Therapieresistenz und daraus resultierend schlechten Prognose bestimmtwesentlich die Bauchspeicheldrusen-Chirurgie. In rund einem Drittel der Falle sind jedoch gutartige Erkrankungen (chronische Entzundung, gutartige Tumore) die Indikation fur eine Pankreasoperation, und stellen damit andere, nicht weniger komplexe Herausforderungen an die behandelnden Arzte.