We demonstrated here that near-infrared fluorescence imaging system is a novel and reliable intraoperative technique to identify hepatic segment and subsegment for anatomical hepatic resection.
Background Preoperative imaging is widely used and extremely helpful in hepatobiliary surgery. However, transfer of preoperative data to a intraoperative situation is very difficult. Surgeons need intraoperative anatomical information using imaging data for safe and precise operation in the field of hepatobiliary surgery. We have developed a new system for mapping liver segments and cholangiograms using intraoperative indocyanine green (ICG) fluorescence under infrared light observation. Method The imaging technique for mapping liver segments and cholangiogram based on ICG fluorescence used an infrared-based navigation system. Eighty one patients with liver tumors underwent hepatectomy from 2006, January to 2009, March. In liver surgery, 1 ml of ICG was injected via the portal vein under observation by the fluorescent imaging system. Fourteen patients were underwent laparoscopic cholecystectomy for chronic cholecystitis with gallstones. In laparoscopic cholecystectomy, 5 ml of ICG was administered intravenously just before operation and the bile duct was observed using the infrared-based navigation system. Result This new technique successfully identified stained subsegments and segments of the liver in 73 of 81 patients (90.1%). Moreover, clear mapping of liver segments was obtained even against a background of liver cirrhosis. Fluorescent cholangiography clearly showed the common bile duct and cystic duct in 10 of 14 patients (71.4%). No adverse reactions to the ICG were encountered. Conclusion Application of this technique allows intraoperative identification of anatomical landmark in hepatobiliary surgery.
Aptamer-drug conjugates (ApDCs) have the potential to improve the therapeutic index of traditional chemotherapeutic agents due to their ability to deliver cytotoxic drugs specifically to cancer cells while sparing normal cells. This study reports on the conjugation of cytotoxic drugs to an aptamer previously described by our group, the pancreatic cancer RNA aptamer P19. To this end, P19 was incorporated with gemcitabine and 5-fluorouracil (5-FU), or conjugated to monomethyl auristatin E (MMAE) and derivative of maytansine 1 (DM1). The ApDCs P19-dFdCMP and P19-5FdUMP were shown to induce the phosphorylation of histone H2AX on Ser139 (γ-H2AX) and significantly inhibited cell proliferation by 51%–53% in PANC-1 and by 54%–34% in the gemcitabine-resistant pancreatic cancer cell line AsPC-1 (p ≤ 0.0001). P19-MMAE and P19-DM1 caused mitotic G2/M phase arrest and inhibited cell proliferation by up to 56% in a dose-dependent manner when compared to the control group (p ≤ 0.001). In addition, the cytotoxicity of P19-MMAE and P19-DM1 in normal cells and the control human breast cancer cell line MCF7 was minimal. These results suggest that this approach may be useful in decreasing cytotoxic side effects in non-tumoral tissue.
This technique showed the potential to improve the intraoperative identification and demarcation of tumors. Its use could potentially reduce the number of positive resection margins.
This study was approved by the Ethics Committee of Showa University (approval number: 3008) and was performed according to the guidelines of the Declaration of Helsinki.Patients. In this retrospective study, we included 125 patients who underwent liver resection for hepatocellular carcinoma (HCC, n=53) or colorectal liver metastasis (CRLM, n=72
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