Revising You the Staging for Pancreatic Cancer in 2012

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State-of-the-art of historical earthquake investigation in Bulgaria

This paper deals with non-instrumental seismology development in Bulgaria (the central-eastern part of the Balkan peninsula). The first steps and products of this scientific branch are discussed because they have traced the road of present-day historical seismology in this country. The sources of information on long-term seismicity are critically reviewed. Some recent studies, which contribute to an improvement of the supporting data sets, are also discussed. A special emphasis is laid on the rules adopted to solve different cases as well as on the aspects, by which our understanding of the seismogenesis throughout the present-day Bulgarian lands has been enhanced

Current use and potential role of bevacizumab in the treatment of gastrointestinal cancers

Angiogenesis is essential for cancer growth and metastasis. Vascular endothelial growth factor (VEGF) is a key modulator of angiogenesis. In addition, overexpression of VEGF is correlated with advanced disease and poor prognosis. Bevacizumab, a recombinant humanized anti-VEGF monoclonal antibody, is the first anti-angiogenic agent approved by Food and Drug Administration for use in treatment of human solid cancers. Although bevacizumab has received most attention for first-line treatment of advanced colorectal and nonsmall-cell lung cancer, there is a rapidly growing body of evidence for its efficacy in treatment of a number of other solid tumors. We present the current status and potential use of bevacizumab therapy in gastrointestinal cancers

BRCA and Pancreatic Cancer: Selection of Chemotherapy

Germline mutations in BRCA genes are associated with increased risk of pancreatic cancer. There are pre clinical data which suggests that DNA cross linking agents should be used in pancreatic cancer patients with BRCA mutations. This review is an update from the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding recent developments in the treatment of pancreatic cancer with BRCA mutation. Only one study (Abstracts #217) was presented and it is described here

Resectable Pancreatic Cancer: Is Surgery the Best First Step?

 Controversy exist regarding the potential benefit of the neoadjuvant approach to pancreatic cancer as limited retrospective data exists comparing pre- with post-operative chemoradiation. The optimal treatment approach remains unclear as we await prospective randomized clinical trials evaluating the hypothesized benefit of the neoadjuvant therapy for resectable pancreatic cancer and as there has been no proven survival benefit to date. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium providing additional insight into the potential of neoadjuvant therapy in the treatment of pancreatic cancer. (Abstracts #156, #162, #168 and #177).

CoFactor: Folate Requirement for Optimization of 5-Fluouracil Activity in Anticancer Chemotherapy

Intracellular reduced folate exists as a “pool” of more than 6 interconvertable forms. One of these forms, 5,10 methylenetetrahydrofolic acid (CH2THF), is the key one-carbon donor and reduced folate substrate for thymidylate synthase (TS). This pathway has been an important target for chemotherapy as it provides one of the necessary nucleotide substrates for DNA synthesis. The fluoropyrimidine 5-fluorouracil (5-FU) exerts its main cytotoxic activity through TS inhibition. Leucovorin (5-formyltetrahydrofolate; LV) has been used to increase the intracellular reduced folate pools and enhance TS inhibition. However, it must be metabolized within the cell through multiple intracellular enzymatic steps to form CH2THF. CoFactor (USAN fotrexorin calcium, (dl)-5,10,-methylenepteroyl-monoglutamate calcium salt) is a reduced folate that potentiates 5-FU cytotoxicity. According to early clinical trials, when 5-FU is modulated by CoFactor instead of LV, there is greater anti-tumor activity and less toxicity. This review presents the emerging role of CoFactor in colorectal and nongastrointestinal malignancies

First-Line Treatment of Metastatic Pancreatic Cancer

Metastatic pancreatic cancer is an aggressive malignancy that is difficult to treat. Gemcitabine monotherapy has been used first line and many contemporary treatment approaches have focused on gemcitabine plus experimental agents. The 2012 ASCO Gastrointestinal Cancers Symposium Abstract #213 is a study of gemcitabine with IPI-926, a novel hedgehog pathway inhibitor. Abstract #227 is a study of gemcitabine with 90Y-hPAM4 radioimmunotherapy with yttrium labeled anti-mucin humanized antibody. Abstract #296 is a study of gemcitabine with temsirolimus, an mTOR inhibitor. Gemcitabine and erlotinib has shown slight advantages to gemcitabine alone. Abstract #253 takes this one step further and evaluates gemcitabine and erlotinib with apricoxib, a COX-2 inhibitor. FOLFIRINOX has shown superiority to gemcitabine; however, doing so at the cost of significantly greater toxicity. Abstract #199, is a study which examines the cost effectiveness of first line FOLFIRINOX approaches. Another cost effective study is portrayed in Abstract #372, a study evaluating the survival of unresectable pancreatic cancer patients treated with gemcitabine and the disease course is followed clinically without radiographic follow-up