Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: a nationwide study.

BACKGROUND: Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. METHODS: A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 µmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival. CONCLUSION: One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.

Upregulated calcium-binding tyrosine phosphorylation-regulated protein-a/b regulates cell proliferation and apoptosis and predicts poor prognosis in hepatocellular carcinoma.

BACKGROUND: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR-a/b (combined CABYR-a and CABYR-b), in HCC remain to be established. METHODS: CABYR-a/b expression was detected in HCC tissues and cell lines by quantitative real-time polymerase chain reaction and Western blot analysis. The correlation of CABYR-a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR-a/b were also investigated using molecular biology approaches. RESULTS: The present research found that CABYR-a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR-a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR-a/b level had poorer overall survival (OS) and disease-free survival (DFS) than those with reduced CABYR-a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR-a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR-a/b downregulation suppressed cell proliferation and induced G1-phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B-cell lymphoma 2 (Bcl-2) and increasing Bcl-2-associated death promoter. CONCLUSION: Our research indicates that CABYR-a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.

Design, synthesis and antitumor activity of a novel PEG-A6-conjugated irinotecan derivative.

A novel PEG-A6-conjugated irinotecan derivative 8 was designed and synthesized as antitumor agent by the PEGylation and A6-peptide modification of irinotecan. In vivo antitumor activity screening assay revealed that 8 exhibited better in vivo antiproliferation activity than irinotecan and its previous PEG-cRGD-conjugated derivative BGC0222 in MIA PaCa-2, NCI-H446, MDA-MB-231, HT-29 and NCI-N87 xenograft models, while the tumor of one in six mice in NCI-H446 assay and the tumors of two in six mice in MIA PaCa-2 assay completely subsided and disappeared within the 21-day period of 8-treatment, indicating that 8 should be a potential antitumor agent.

Design, synthesis and pharmacological evaluation of a novel PEG-cRGD-conjugated irinotecan derivative as potential antitumor agent.

A novel PEG-cRGD-conjugated irinotecan derivative BGC0222 was designed and synthesized as antitumor agent. Antitumor activity screening assay indicated that BGC0222 exhibited better in vitro antiproliferation activity than irinotecan and NKTR-102 against HT29, MIA PaCa-2 and MCF-7 tumor cell lines, with IC50 of 1.83 ±â€¯0.09 µM, 3.95 ±â€¯0.16 µM and 0.68 ±â€¯0.04 µM, respectively, while it displayed better in vivo antiproliferation activity than irinotecan and NKTR-102 in HT-29, MIA PaCa-2, NCI-H446, U-87 MG and MDA-MB-231 xenograft models. The action mechanism of BGC0222 was then investigated by integrin-binding competition (IBC) and chick chorioallantoic membrane (CAM) angiogenesis assays, which indicated that BGC0222 may exert antitumor activity by binding to αvß3 target and consequently inducing neovascularization effect. Pharmacokinetic analysis showed that BGC0222 could slowly and steadily release irinotecan, which was subsequently metabolized into 7-ethyl-10-hydroxycamptothecin (SN-38) in the whole blood.

A near-vision chart for children aged 3-5 years old: new designs and clinical applications.

AIM: To introduce a new near-vision chart for children aged 3-5 years old and its clinical applications. METHODS: The new near-vision chart which combined the Bailey-Lovie layout with a newly devised set of symmetry symbols was designed based on Weber-Fechner law. It consists of 15 rows of symmetry symbols, corresponding to a visual acuity range from 1.3 to 0.1 logMAR. The optotypes were red against a white background and were specially shaped four basic geometric symbols: circle, square, triangle, and cross, which matched the preschool children's cognitive level. A regular geometric progression of the optotype sizes and distribution was employed to arrange in 15 lines. The progression rate of the optotype size between two lines was 1.2589 and two smaller groups of optotypes ranging from 0.7 to -0.1 logMAR were included for repetitive testing. A near visual acuity was recorded in logMAR or decimal, and the testing distance was 25 cm. RESULTS: This new near-vision chart with pediatric acuity test optotypes which consists of 4 different symbols (triangle, square, cross, and circle) met the national and international eye chart design guidelines. When performing the near visual acuity assessment in preschoolers (3-5 years old). It overcame an inability to recognize the letters of the alphabet and difficulties in designating the direction of black abstract symbols such as the tumbling 'E' or Landolt 'C', which the subjects were prone to lose interest in. Near vision may be recorded in different notations: decimal acuity and logMAR. These two notations can be easily converted each other in the new near-vision chart. The measurements of this new chart not only showed a significant correlation and a good consistency with the Chinese national standard logarithmic near-vision chart (r=0.932, P<0.01), but also indicated good test-retest reliability (89% of retest scores were within 0.1 logMAR units of the initial test score) and a high response rate. CONCLUSION: The results of this study support the validity and reliability of near visual acuity measurements using the new near-vision chart in children aged 3-5y over a wide range of visual acuities, and the new eye chart was especially suitable for the detection of amblyopia risk factors and low vision examination in children (3-5y of age). It can be applied in routine clinical practice.

A new specialized visual acuity chart for amblyopic children aged 3-5 years old: development and its clinical applications.

AIM: To introduce a new specialized visual acuity chart for amblyopic children aged 3-5 years old and its clinical applications. METHODS: The new visual acuity chart and notations were designed based on Weber-Fechner law. The optotypes were red against a white background and were specially shaped four basic geometric symbols: circle, square, triangle, and cross. A regular geometric progression of the optotype sizes and distribution was employed to arrange in 14 lines. The progression rate of the optotype size between two lines was 1.2589 and the testing distance was 3m. Visual acuity score could be recorded as logMAR notation or decimal notation. Age-stratified diagnostic criteria for amblyopia established by consensus statement on diagnosis of amblyopia (2011) among members of the Strabismus and Pediatric Ophthalmology Group, Ophthalmology Society, Chinese Medical Association (SPOGOSCMA) were illustrated in the new visual acuity chart. RESULTS: When assessing visual acuity in children aged 3-5 years old, this new visual acuity chart that consists of four symmetrical shapes (triangle, square, cross, and circle) overcame an inability to recognize the letters of the alphabet and difficulties in designating the direction of black abstract symbols such as the tumbling 'E' or Landolt 'C', which the subjects were prone to lose interest in. The visual acuity score may be recorded in different notations: decimal acuity and logMAR. These two notations can be easily converted each other in the new eye chart. The measurements of this new chart not only showed a significant correlation and a good consistency with the international standard logarithmic visual acuity chart (r=0.932, P<0.01), but also indicated a high test-retest reliability (89% of retest scores were within 0.1logMAR units of the initial test score). CONCLUSION: The results of this study support the validity and reliability of distance visual acuity measurements using the new eye chart in children aged 3 to 5 years over a wide range of visual acuities, and the new eye chart is great for early detection of amblyopia. It can be applied in various clinical settings.

Primary hepatic neuroendocrine carcinoma: clinical analysis of 11 cases.

BACKGROUND: Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare, and fewer than 300 cases have been reported in the English/Chinese-language literature, therefore it is difficult to make a proper diagnosis and determine a therapeutic approach. METHODS: Eleven PHNEC patients were admitted to our hospital between January 1996 and May 2008. Laboratory examination, digestive endoscopy, B-ultrasonography, CT, MRI, or PET-CT were performed on the patients for preoperative diagnosis. All patients received liver resection. Some patients received transcatheter arterial chemoembolization (TACE), percutaneous ethanol injection treatment (PEIT), or octreotide injection when a recurrence was found. The patients' clinical data were recorded and all patients were followed up. RESULTS: The patients were confirmed pathologically as having PHNEC . Their median follow-up time was 33 months (12-107 months). All patients survived, and the longest post-operative survival time was 107 months, the longest disease-free survival time was 98 months, the 1-year survival rate was 100%, and the 1-year recurrence rate was 45.5% (5/11). CONCLUSIONS: Since PHNEC is easy to confuse with hepatocellular carcinoma, careful screening of symptoms is needed to avoid misdiagnosis. Resection is the first choice of treatment for PHNEC and provides the most favorable outcomes including long-term survival. Other treatment such as TACE and PEIT can be considered as well, especially when a tumor recurs.