Incidence and prognostic values of lymph node metastasis in operable hepatocellular carcinoma and evaluation of routine complete lymphadenectomy

Sun, Hui‐Chuan; Zhuang, Peng–Yuan; Qin, Lun–Xiu; Ye, Qing–Hai; Wang, Lu; Ren, Ning; Zhang, Jubo; Qian, Yongbing; Lu, Lu; Fan, Jia; Tang, Zhao–You

doi:10.1002/jso.20772

Cited by 87 publications

(71 citation statements)

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“…3,4,6,9 Although the incidence of lymph node metastasis (LNM) in operable HCC is as low as 1.7% to 7.5%, 10,11 lymph node (LN) status is a definite prognostic factor in HCC and leads to generally dismal survival rates. 11,12 In our previous report we found that the development of LNM was related to higher T classification. 12 Furthermore, Uenishi et al 3 found that patients with HCC with CK19 expression had LNM.…”

mentioning

confidence: 87%

“…11,12 In our previous report we found that the development of LNM was related to higher T classification. 12 Furthermore, Uenishi et al 3 found that patients with HCC with CK19 expression had LNM. Likewise, we postulated that HCC with LNM can also be classified by the presence of CK19 expression, namely, positive with ICC-like differentiation and negative with higher T classification.…”

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confidence: 87%

“…Abnormally enlarged LNs on computed tomography (CT) scan or B ultrasound warranted careful intraoperative detection, and the diagnosis of LNM was predominantly established by the intraoperative detection and pathologic diagnosis of node species from either lymphadenectomy or biopsy. 12 All 47 patients with LNM belonged to stage IIIB according to AJCC/UICC tumor staging system (6th ed.). 14 Therefore, to stratify the patients with each T category, the T classification of AJCC/UICC tumor staging were adopted.…”

Section: Patients Diagnosis and Treatment Protocolmentioning

confidence: 99%

“…12 Briefly, the indications for hepatectomy were that the main tumor was technically resectable, no cancerous thrombi were present in the main trunk of the portal vein, and no distant metastasis to other organs; enlarged LNs localized in the hepatic hilum and pancreatic head based on a preoperative CT scan was not a contraindication to resection. Lymphadenectomy was conducted according to the intraoperative resectability of enlarged LNs, whereas incisional or aspiration biopsy of LNs in some rigid circumstances was performed to obtain a postoperative histologic diagnosis and avoid any further operation risks.…”

Section: Patients Diagnosis and Treatment Protocolmentioning

confidence: 99%

“…In addition to CK19 and OV-6 expression, the factors related to LNM development in our previously reported retrospective analysis 12 and this study, such as Edmondson grade, as well as AJCC/ UICC T classification, 14 which presented larger tumors, more satellite lesions, and vascular invasion, were included in the binary regression analysis. Furthermore, we found CK19 expression (odds ratio [OR], 5.170, 95% confidence interval [CI], 1.840-14.528, P 5 .002) and AJCC/UICC T classification (OR, 1.879, 95% CI, 1.236-2.857, P 5 .003) were independent risk factors for LNM.…”

Section: Ck19 Expression and Tumor Classification Were 2 Risk Factorsmentioning

confidence: 99%

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Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor

Zhuang

Zhang

Zhu

et al. 2008

Cancer

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Microwave radiation was used as the sole heating source to achieve liquefaction of Central European hardwoods, with glycols and organic acid anhydrides, using phosphoric acid as the acid catalyst. Pulsed microwaves of 300–700 W power were applied for 5–20 min. The efficiency of liquefaction increased with higher microwave power, longer radiation time, and higher phosphoric acid addition. With minor amounts of added acid it was possible to achieve complete liquefaction in 20 min. The method was tested for different hardwood types, with a series of glycols and anhydrides, and was found to be generally applicable. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101:1051–1056, 2006

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confidence: 87%

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confidence: 87%

Section: Patients Diagnosis and Treatment Protocolmentioning

confidence: 99%

Section: Patients Diagnosis and Treatment Protocolmentioning

confidence: 99%

Section: Ck19 Expression and Tumor Classification Were 2 Risk Factorsmentioning

confidence: 99%

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Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor

Zhuang

Zhang

Zhu

et al. 2008

Cancer

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Expression and prognostic significance of placental growth factor in hepatocellular carcinoma and peritumoral liver tissue

Zhu

Zhuang

et al. 2011

Intl Journal of Cancer

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Vascular endothelial growth factor‐targeted therapy is a promising treatment for hepatocellular carcinoma (HCC), but its clinical benefit is often accompanied by acquired resistance. In animal studies, antiplacental growth factor therapy is effective with less resistance. The role of placental growth factor (PlGF) in the progression of HCC is not clear. In our study, we used immunohistochemistry in tissue microarrays to investigate PlGF expression in tumor and peritumoral liver tissues from 105 patients with HCC. Intratumoral and peritumoral PlGF mRNA expression was analyzed in another cohort of 37 patients. Peritumoral PlGF expression was significantly higher than intratumoral PlGF expression (p < 0.001). Intratumoral PlGF expression was not associated with patients' overall survival (OS) or time to recurrence (TTR). However, peritumoral PlGF expression, which was associated with tumor size, presence of intrahepatic metastasis, TNM stage and Barcelona Clinic Liver Cancer stage, was an independent risk factor for OS (p = 0.026) and TTR (p = 0.041). The prognostic value of peritumoral PlGF expression was further validated in a validation cohort (n = 394). We inferred that the elevation of PlGF in peritumoral liver might be induced by hypoxia. We found that peritumoral PlGF expression was associated with hypoxia‐inducible factor‐1α (p = 0.017). PlGF expression was elevated in L02, a hepatic cell line, under hypoxic conditions in vitro. These findings indicate that high peritumoral PlGF expression is associated with tumor recurrence and survival after resection of HCC. PlGF could be a target of adjuvant therapy and deserves further investigations.

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Aryl hydrocarbon receptor nuclear translocator is associated with tumor growth and progression of hepatocellular carcinoma

Yang

et al. 2011

Intl Journal of Cancer

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bHLH/PAS proteins play important roles in tumor progression. Lost or reduced expression of single-minded homolog 2 (SIM) as well as aryl hydrocarbon receptor repressor (AHRR) has been observed in cancerous human tissues. Here, we investigated the role of aryl hydrocarbon receptor nuclear translocator (ARNT), another bHLH/PAS protein, in hepatocellular carcinoma (HCC). Using tissue microarray and immunohistochemistry, we found that intratumoral ARNT was inversely correlated with time to recurrence and overall survival of HCC patients after resection. Knockdown of ARNT in HepG2, HCCLM3 and HCCLM6 cells significantly shortened cell doubling time, increased S-phase cell populations and accelerated in vivo HCCLM6 growth and metastasis. After ARNT expression was rescued, prolonged cell doubling time and decreased S-phase cell populations were observed in HepG2, HCCLM3 and HCCLM6 cells. And, HCCLM6 growth and metastasis in vivo were remarkably inhibited. Screening by quantitative reverse-transcription PCR and PCR arrays revealed that cyclin E1, CDK2, Fos and Jun were negatively regulated by ARNT, whereas CDKN1C, CNKN2A, CDKN2B, MAPK11 and MAPK14 were positively regulated in HCC. According to the results of immunoprecipitation assay, both ARNT/ARNT and ARNT/AHRR complexes were clearly formed in HCCLM6 xenograft with increased ARNT expression. In summary, ARNT is an important regulator of HCC growth and metastasis and could be a promising prognostic candidate in HCC patients.Hepatocellular carcinoma (HCC) is the third leading cause of cancer death in the world and the second in China.1,2 The long-term prognosis of HCC patients after hepatectomy still remains a challenge, largely due to its high recurrence rate and metastasis.3 The molecular mechanisms of HCC progression need be further investigated for new insights and interventions against metastatic recurrence.Aryl hydrocarbon receptor nuclear translocator (ARNT), also known as hypoxia-induced factor-1b (HIF-1b), is one of the most important nuclear transcription factors within the basic helix-loop-helix/Per-ARNT-SIM (bHLH/PAS) superfamily. It is widely expressed in human cells, including hepatocytes. When responding to different extracellular stimuli, ARNT can form a heterodimeric complex with aryl hydrocarbon receptor (AHR), hypoxia-inducible factor-1a (HIF-1a) and its homologous factors (HIF-2a, HIF-3a), or with singleminded homolog 2 (SIM) to mediate various biological actions, such as hypoxia reaction, xenobiotic metabolism, teratogenesis, immunosuppression 4 and embryonic development.5 However, its onco-biological function is still unclear. Several prototypes of bHLH/PAS factors have been identified as being involved in tumor progression. HIF-1a promotes tumor progression and metastasis via its regulation of cancerous glycolysis, 6 proliferation, apoptosis 7 and angiogenesis.8 AHR appears to be a regulator of cell proliferation, albeit growth-inhibitory and promoting roles in MCF-7 and HepG2 cells, respectively, are observed.9 SIM is frequently lost or reduced in...

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Incidence and prognostic values of lymph node metastasis in operable hepatocellular carcinoma and evaluation of routine complete lymphadenectomy

Cited by 87 publications

References 24 publications

Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor

Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor

Expression and prognostic significance of placental growth factor in hepatocellular carcinoma and peritumoral liver tissue

Aryl hydrocarbon receptor nuclear translocator is associated with tumor growth and progression of hepatocellular carcinoma

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