Background & Aims Aflatoxin, which causes hepatocellular carcinoma, may also cause gallbladder cancer. We investigated whether patients with gallbladder cancer have higher exposure to aflatoxin than patients with gallstones. Methods We measured aflatoxin B1 (AFB1)–lysine adducts in plasma samples from the Shanghai Biliary Tract Cancer case–control study, conducted from 1997 through 2001. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs and the population-attributable fraction for 209 patients with gallbladder cancer and gallstones vs 250 patients with gallstones without cancer (controls). In 54 patients with gallbladder cancer, tumor tissue was examined for the R249S mutation in TP53, associated with aflatoxin exposure, through targeted sequencing. Results The AFB1–lysine adduct was detected in 67 of 209 patients with gallbladder cancer (32%) and 37 of the 250 controls (15%) (χ2 P <.0001), almost 3-fold more patients with gallbladder cancer than controls (OR, 2.71; 95% CI, 1.70–4.33). Among participants with detectable levels of AFB1–lysine, the median level of AFB1–lysine was 5.4 pg/mg in those with gallbladder cancer, compared to 1.2 pg/mg in controls. For patients in the 4th of quartile of AFB1–lysine level vs the 1st quartile, the OR for gallbladder cancer was 7.61 (95% CI, 2.01–28.84). None of the 54 gallbladder tumors sequenced were found to have the R249S mutation in TP53. The population-attributable fraction for cancer related to aflatoxin was 20% (95% CI, 15%–25%). Conclusions In a case–control study of patients with gallbladder cancer and gallstones vs patients with gallstones without cancer, we associated exposure to aflatoxin (based on plasma level of AFB1–lysine) with gallbladder cancer. Gallbladder cancer does not appear associate with the R249S mutation in TP53. If aflatoxin is a cause of gallbladder cancer, it may have accounted for up to 22% of the gallbladder cancers in Shanghai, China during the study period, and could account for an even higher proportion in high-risk areas. If our findings are verified, reducing aflatoxin exposure might reduce the incidence of gallbladder cancer.

Most gallbladder cancer (GBC) cases arise in the context of gallstones, which cause inflammation, but few gallstone patients develop GBC. We explored inflammation/immune-related markers measured in bile and serum in GBC cases compared to gallstone patients to better understand how inflammatory patterns in these two conditions differ. We measured 65 immune-related markers in serum and bile from 41 GBC cases and 127 gallstone patients from Shanghai, China, and calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GBC versus gallstones. We then focused on the markers that were significantly elevated in bile and serum to replicate in serum from 35 GBC cases and 31 gallstone controls from Chile. Comparing the highest versus lowest quantile, 15 markers (23%) were elevated in both serum and bile from GBC versus gallstone patients in the Shanghai study (p<0.05). The strongest OR was for CXCL8 (interleukin-8) in serum (96.8, 95% CI: 11.9–790.2). Of these 15 markers, 6 were also significantly elevated in serum from Chile (CCL20, C-reactive protein, CXCL8, CXCL10, resistin, serum amyloid A). Pooled ORs from Shanghai and Chile for these 6 markers ranged from 7.2 (95% CI: 2.8–18.4) for CXCL10 to 58.2 (95% CI: 12.4–273.0) for CXCL8. GBC is associated with inflammation above and beyond that generated by gallstones alone. This local inflammatory process is reflected systemically. Future longitudinal studies are needed to identify the key players in cancer development, which may guide translational efforts to identify individuals at high risk of developing GBC.

Self-assembly is a process that operates over a vast range of length and time scales. Microfluidic technology has been proven to be a powerful tool to manipulate micro- and nano-scale substrates with precise control over size and speed using various fluidic materials and properties. In this review, we discuss the current status of microfluidic technology in manipulating fluid dynamics and interfacial phenomena which influence self-assembly process and resulted structures. The self-assembled materials/structures were summarized and discussed as the sequence of the objective size at the micro-, nano- and molecular scale. Overall, microfluidics is becoming a useful tool to manipulate various fluids regarding to physical and chemical properties, being inherently suitable for self-assembly process control.