J. Dong

Quantified postsurgical small cell size CTCs and EpCAM+ circulating tumor stem cells with cytogenetic abnormalities in hepatocellular carcinoma patients determine cancer relapse

Detection of hepatocellular carcinoma circulating tumor cells performed with conventional strategies, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, as well as degradation of cytokeratins during epithelial-to-mesenchymal transition, which inevitably lead to non-negligible false negative detection of such uncapturable and invisible CTCs. A novel SE-iFISH strategy, improved for detection of HCC CTCs in this study, was applied to comprehensively detect, in situ phenotypically and karyotypically characterize hepatocellular and cholangiocarcinoma CTCs (CD45-/CD31-) in patients subjected to surgical resection. Clinical significance of diverse subtypes of CTC was systematically investigated. Existence of small cell size CTCs (≤5xa0μm of WBCs) with cytogenetic abnormality of aneuploid chromosome 8, which constituted majority of the detected CTCs in HCC patients, was demonstrated for the first time. The stemness marker EpCAM+ aneuploid circulating tumor stem cells (CTSCs), and EpCAM- small CTCs with trisomy 8, promote tumor growth. Postsurgical quantity of small triploid CTCs (≥5xa0cells/6xa0ml blood), multiploid (≥pentasomy 8) CTSCs or CTM (either one ≥xa01) significantly correlated to HCC patients poor prognosis, indicating that detection of those specific subtypes of CTCs and CTSCs in post-operative patients help predict neoplasm recurrence.

Traditional surgical planning of liver surgery is modified by 3D interactive quantitative surgical planning approach: a single-center experience with 305 patients

BACKGROUNDnDecision making and surgical planning are to achieve the precise balance of maximal removal of target lesion, maximal sparing of functional liver remnant volume, and minimal surgical invasiveness and therefore, crucial in liver surgery. The aim of this prospective study was to validate the accuracy and predictability of 3D interactive quantitative surgical planning approach (IQSP), and to evaluate the impact of IQSP on traditional surgical plans based on 2D images.nnnMETHODSnA total of 305 consecutive patients undergoing hepatectomy were included in this study. Surgical plans were created by traditional 2D approach using picture archiving and communication system (PACS) and 3D approach using IQSP respectively by two groups of physicians who did not know the surgical plans of the other group. The two surgical plans were submitted to the chief surgeon for selection before operation. The specimens were weighed. The two surgical plans were compared and analyzed retrospectively based on the operation results.nnnRESULTSnThe two surgical plans were successfully developed in all 305 patients and all the 3D IQSP surgical plans were selected as the final decision. Total 278 patients successfully underwent surgery, including 147 uncomplex hepatectomy and 131 complex hepatectomy. Twenty-seven patients were withdrawn from hepatectomy. In the uncomplex group, the two surgical plans were the same in all 147 patients and no statistically significant difference was found among 2D calculated resection volume (2D-RV), 3D IQSP calculated resection volume (IQSP-RV) and the specimen volume. In the complex group, the two surgical plans were different in 49 patients (49/131, 37.4%). According to the significance of differences, the 49 different patients were classified into three grades. No statistically significant difference was found between IQSP-RV and specimen volume. The coincidence rate of territory analysis of IQSP with operation was 92.1% (93/101) for 101 patients of anatomic hepatectomy.nnnCONCLUSIONSnThe accuracy and predictability of 3D IQSP were validated. Compared with traditional surgical planning, 3D IQSP can provide more quantitative information of anatomic structure. With the assistance of 3D IQSP, traditional surgical plans were modified to be more radical and safe.

Augmented reality technology for preoperative planning and intraoperative navigation during hepatobiliary surgery: A review of current methods

BACKGROUNDnAugmented reality (AR) technology is used to reconstruct three-dimensional (3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes.nnnDATA SOURCESnThe keywords augmented reality, liver, laparoscopic and hepatectomy were used for searching publications in the PubMed database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles.nnnRESULTSnIn general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery, which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology.nnnCONCLUSIONSnWith recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling, and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.

In situ splitting after selective partial portal vein ligation or simultaneous hepatic artery ligation promotes liver regeneration.

This study seeks to compare the impact of selective partial portal vein ligation (PPVL) or the combination of simultaneous hepatic artery ligation (PPVAL) with in situ splitting (ISS) on liver regeneration and injury. Rats were randomized into three groups; namely: selective PVL, PPVLu2009+u2009ISS and PPVALu2009+u2009ISS. The changes in hepatic hemodynamics, liver regeneration and hepatocytic injury were examined. Blood flow to the left portal branch and the microcirculation of the left median lobe after PPVL or PPVAL was significantly reduced. Liver regeneration of PPVALu2009+u2009ISS group was more pronounced than that in the PPVLu2009+u2009ISS and PVL groups at 48 and 72u2009hours as well as 7 d postoperatively. The serum biochemical markers and histopathological examination demonstrated reduced levels of liver injury in the PPVLu2009+u2009ISS group. Injury to hepatocytes was more pronounced with PPVALu2009+u2009ISS than PVL. HGF, TNF-α and IL-6 expression in the regenerated lobes in both PPVALu2009+u2009ISS and PPVLu2009+u2009ISS groups increased significantly when compared to the PVL group. We demonstrated that both PPVLu2009+u2009ISS and PPVALu2009+u2009ISS were effective and feasible means of inducing remnant liver hypertrophy and could serve as a rapid clinical application for qualified patients.

Coordinative control of G2/M phase of the cell cycle by non-coding RNAs in hepatocellular carcinoma

Objective To investigate the interaction of non-coding RNAs (ncRNAs) in hepatocellular carcinoma. Methods We compared the ncRNAs and mRNAs expression profiles of hepatocellular carcinoma and adjacent tissue by microarray and RT-PCR. The relationship between different ncRNAs and mRNA was analyzed using bioinformatics tools. A regulatory model of ncRNAs in hepatocellular carcinoma cells was developed. Results A total of 1,704 differentially expressed lncRNAs, 57 miRNAs, and 2,093 mRNAs were identified by microarray analyses. There is a co-expression relationship between two ncRNAs (miRNA-125b-2-3p and lncRNA P26302). Bioinformatics analysis demonstrated cyclin-dependent kinases 1 and CyclinA2 as potential targets of miR-125b-2-3p and Polo-like kinase 1 as potential target of lncRNAP26302. All three gene are important components in the G2/M phase of cell cycle. Subsequently real-time polymerase chain reaction (PCR) studies confirmed these microarray results. Conclusion MiR-125b-2-3p and lncRNAP26302 may affect the G2/M phase of the cell cycle through the regulation of their respective target genes. This study shows a role of ncRNAs in pathogenesis of hepatocellular carcinoma at molecular level, providing a basis for the future investigation aiming at early diagnosis and novel treatment of hepatocellular carcinoma.