Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials

Owing to the lack of randomised controlled trials no standard of chemotherapy exists in the treatment of advanced biliary tract carcinoma. 5-fluorouracil or gemcitabine is recommended based on small and predominately phase II trials. The aim of this analysis was to analyse existing trials, even small and nonrandomised, and identify superior regimens. Chemotherapy trials published in English from 1985 to July 2006 were analysed as well as ASCO abstracts from 1999 to 2006. Response rate (RR=CR+PR), tumour control rate (TCR=CR+PR+SD), time to tumour progression (TTP), overall survival (OS), and toxicity were analysed. One hundred and four trials comprising 112 trial arms and 2810 patients, thereof 634 responders and 1368 patients with tumour control were analysed. Pooled RR and TCR were 22.6 and 57.3%, respectively. Significant correlations of RR and TCR with survival times were found. Subgroup analysis showed superior RRs for gallbladder carcinoma (GBC) compared with cholangiocarcinoma, but shorter OS for GBC. Furthermore, superior RRs and TCRs of gemcitabine and platinum containing regimens were found with highest RRs and TCRs in the combination subgroup. Based on published results of predominately phase II trials, gemcitabine combined with platinum compounds represents the provisional standard of chemotherapy in advanced biliary tract cancer, unless a new evidence-based standard has been defined

The Right Stuff: biodegradable alternatives to plastic mulch

This project was a continuation of work started by Mark Ingman after he was bothered by the amount of plastic sheeting used in agriculture in China. He was determined to develop an alternative to this environmentally destructive use of plastic by farmers. The plastic “mulch” is used to prevent weeds and maintain soil moisture, but after a season of use the plastic is either thrown into a landfill or burned. Needless to say this creates a lot of unnecessary waste. Mark came back to the United States and put together a team to develop an alternative to the plastic mulch using wool and flax shive waste. The shive waste is an agricultural byproduct. It is composed of biomass available after processing the plant for fibers, oil and seeds. The project was sponsored by the EPA and given a P3 Phase 2 Grant after all initial work. Dr. Skip Rochefort was asked to consult to help develop the product further. He suggested using sodium alginate, a common food additive, to bind the flax shive into a sheet form. Sodium alginate is biodegradable and fit within the sustainability needs of the project. I was tasked with taking Dr. Rochefort's idea and turning it into the final mulch sheet product. The goal of the project was to make this sheet retain moisture and prevent weeds like other mulches but biodegrade over time. At the end of the season, this product would be tilled into the soil as a soil amendment

Gallbladder Cancer Predisposition: A Multigenic Approach to DNA-Repair, Apoptotic and Inflammatory Pathway Genes

Gallbladder cancer (GBC) is a multifactorial disease with complex interplay between multiple genetic variants. We performed Classification and Regression Tree Analysis (CART) and Grade of Membership (GoM) analysis to identify combinations of alleles among the DNA repair, inflammatory and apoptotic pathway genetic variants in modifying the risk for GBC. We analyzed 16 polymorphisms in 8 genes involved in DNA repair, apoptotic and inflammatory pathways to find out combinations of genetic variants contributing to GBC risk. The genes included in the study were XRCC1, OGG1, ERCC2, MSH2, CASP8, TLR2, TLR4 and PTGS2. Single locus analysis by logistic regression showed association of MSH2 IVS1+9G>C (rs2303426), ERCC2 Asp312Asn (rs1799793), OGG1 Ser326Cys (rs1052133), OGG1 IVS4-15C>G (rs2072668), CASP8 -652 6N ins/del (rs3834129), PTGS2 -1195G>A (rs689466), PTGS2 -765G>C (rs20417), TLR4 Ex4+936C>T (rs4986791) and TLR2 –196 to –174del polymorphisms with GBC risk. The CART analysis revealed OGG1 Ser326Cys, and OGG1 IVS4-15C>G polymorphisms as the best polymorphic signature for discriminating between cases and controls. In the GoM analysis, the data was categorized into six sets representing risk for GBC with respect to the investigated polymorphisms. Sets I, II and III described low intrinsic risk (controls) characterized by multiple protective alleles while sets IV, V and VI represented high intrinsic risk groups (GBC cases) characterized by the presence of multiple risk alleles. The CART and GoM analyses also showed the importance of PTGS2 -1195G>A polymorphism in susceptibility to GBC risk. In conclusion, the present multigenic approach can be used to define individual risk profiles for gallbladder cancer in North Indian population

Helicobacter species in cancers of the gallbladder and extrahepatic biliary tract

Helicobacter species have been found in human bile and biliary tract (BT) tissue and are suspected to cause BT diseases, including gallbladder and extrahepatic cancers, collectively referred to in this work as BT cancers. We conducted a literature review of the epidemiological evidence linking the presence of Helicobacter species in bile or BT biopsies to BT cancers and benign diseases. Reports showed great variability with respect to study methods. Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis. As our current knowledge relies on a few small studies that showed substantial differences, larger studies and more standardised protocols for detecting DNA and antibodies against Helicobacter species are needed to investigate a potential association with BT cancer

Epidemiology of Gallbladder Disease: Cholelithiasis and Cancer

Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps