Xinyu Bi

A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway

Tumor-initiating cell (TIC) is a subpopulation of cells in tumors that are responsible for tumor initiation and progression. Recent studies indicate that hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in hepatocellular carcinoma (HCC). In this study, we found that Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited malignant growth of HCICs. Icaritin decreased the proportion of EpCAM-positive (a HCICs marker) cells, suppressed tumorsphere formation in vitro and tumor formation in vivo. We also found that Icaritin reduced expression of Interleukin-6 Receptors (IL-6Rs), attenuated both constitutive and IL-6-induced phosphorylation of Janus-activated kinases 2 (Jak2) and Signal transducer and activator of transcription 3 (Stat3), and inhibited Stat3 downstream genes, such as Bmi-1 and Oct4. The inhibitory activity of Icaritin in HCICs was augmented by siRNA-mediated silencing of Stat3 but attenuated by constitutive activation of Stat3. Taken together, our results indicate that Icaritin is able to inhibit malignant growth of HCICs and suggest that Icaritin may be developed into a novel therapeutic agent for effective treatment of HCC.

Recent advances in the ARiD family: focusing on roles in human cancer

The human AT-rich interaction domain (ARID) family contains seven subfamilies and 15 members characterized by having an ARID. Members of the ARID family have the ability to regulate transcription and are involved in cell differentiation and proliferation. Accumulating evidence suggests that ARID family members are involved in cancer-related signaling pathways, highly mutated or differentially expressed in tumor tissues, and act as predictive factors for cancer prognosis or therapeutic outcome. Here we review the molecular biology and clinical studies concerned with the role played by the ARID family in cancer. This may contribute to our understanding of the initiation and progression of cancer from a novel point of view, as well as providing potential targets for cancer therapy.

Transurethral electrochemical treatment of benign prostatic hyperplasia.

OBJECTIVE To study the mechanism and feasibility of transurethral electrochemical therapy for the treatment of benign prostatic hyperplasia (BPH). METHODS Between March 1998 and March 2000, specifically designed devices and catheters for electrochemical therapy were applied to 6 prostate specimens obtained by suprapubic prostatectomy in order to treat BPH patients with urinary retention for whom surgery was contraindicated. Sixteen patients (with a mean age of 77.3 years old) underwent electrical treatment totaling 160-220 coulombs under topical urethral anesthesia for 68-132 min. The catheters remained inside the patient for 7-10 d. RESULTS Irreversible destructive changes occurred within cathodal tissue, while carbonization occurred within anodic tissue. The radius of tissue change was 7-8 mm and 1-2 mm, respectively. In vivo trial: 11 (69%) patients could be weaned off the catheters with satisfactory urination. Three months after therapy, the mean international prostate symptom score (IPSS) was 14.5, mean peak flow rate was 10.5 ml/s, and mean residual urine was 39 ml. No serious complications were observed. CONCLUSION Transurethral electrochemical treatment is potentially a minimally invasive alternative for treatment of BPH, especially for elderly patients at high risk.

Systematic review of resecting primary tumor in MNETs patients with unresectable liver metastases

Background Treatment for midgut neuroendocrine tumor patients with unresectable liver metastasis has long been a controversial issue. This system review aims to summarize existing evidence concerning the value of primary tumor resection in this group of patients. Results 8 cohort studies were identified for qualitative analysis. None of them strictly met with the inclusion criteria and meta-analysis was impossible. There was a tendency towards better overall survival for the primary tumor resected group in all 8 studies, in which 6 demonstrated significant difference. Progression free survival to liver disease was prolonged and less patients died of liver failure in the resected group. Methods MEDLINE, EMBASE and CENTRAL were searched until 2016/7/4 for relevant studies, with primary outcome being overall survival, and secondary outcome being progression free survival, cause of death and symptom relief. Conclusions Current evidence supports resection of primary tumor for midgut neuroendocrine tumor patients with liver metastases, but randomized controlled trials are required to reach a final conclusion.

Prognosis of patients with hepatocellular carcinoma and hypersplenism after surgery: a single-center experience from the People's Republic of China

Purpose As prognosis of patients with hepatocellular carcinoma (HCC) and hypersplenism is rarely reported, this study examined prognostic factors for patients who underwent surgery for this condition. Patients and methods This study retrospectively analyzed prognostic factors in 181 consecutive HCC patients using univariate and multivariate analyses, as well as subgroup analyses for disease-free survival (DFS) and overall survival (OS) of two groups: one group who received splenectomies (Sp) and one group who did not (non-Sp). Results 1, 3, and 5 year OS rates were 88.4%, 67.1%, and 52.8%, respectively; corresponding DFS rates were 67.0%, 43.8%, and 31.6%, respectively. Age ≥55 years old, cigarette smoking, tumor size ≥5 cm, microvascular invasion, and Child-Pugh grade B (versus A) correlated significantly with OS (P<0.05). Interestingly, in patients with tumor lymph node metastasis (TNM) stage I disease, DFS of the Sp-group (median DFS, 24.1 months; n=34) was significantly lower than that of the non-Sp group (median DFS, 62.1 months; n=74), P=0.034; whereas at TNM stage II, OS of the Sp-group (median OS, 79.1 months; n=21) was significantly better than that of the non-Sp group (median OS, 23.3 months; n=30), P=0.018. Conclusion Hepatectomy without concomitant splenectomy can contribute to improved DFS of TNM stage I HCC patients with hypersplenism, whereas simultaneous hepatectomy and splenectomy can prolong OS for patients at TNM stage II.

Should surgery be conducted for small nonfunctioning pancreatic neuroendocrine tumors: a systematic review

Background The incidence of nonfunctioning pancreatic neuroendocrine tumors smaller than 2cm has increased remarkably in the last two decades. Controversies exist regarding whether surgery should be conducted for this group of tumors. Methods MEDLINE, EMBASE and CENTRAL were search until 2017/01/17. Studies with comparative results between operation and observation group were included. Primary outcomes were overall survival and disease specific survival. Secondary outcomes were disease progression and surgical death and complications. Results 6 studies with a total of 1861 patients were identified. No randomized controlled trials were found. Survival rate was high (97-100%) and no patients died because of the disease in 5 of the 6 studies, with no difference between operation and observation group. Disease progression was compared in 3 of the 6 studies. 2 studies reported minimal disease progression (0-3.5%) and no significant difference between operation and observation group. Perioperative deaths were rare (0-3%), but complications were common (33-46%). None of the 46 patients who crossed over form observation to operation group had disease recurrence after resection. Conclusion Small NF-PNETs without distant metastasis, lymph node metastasis and local invasion on imaging studies can be observed without increase in death and disease progression.

Simultaneous hepatic resection benefits patients with synchronous colorectal cancer liver metastases

Objective The safety of the simultaneous resection of synchronous colorectal cancer liver metastases (SCRLM) is still being debated. However, this simultaneous operative approach is more commonly adopted at present than in the past. Therefore, we compared simultaneous hepatic resection with delayed hepatic resection in this study. Methods All patients with SCRLM diagnosed before initial treatment between January 2009 and September 2013 were retrospectively included in our study. Short-term and long-term outcomes were compared in patients who underwent simultaneous colorectal and hepatic resection and those treated by delayed hepatectomy. Results Among the 73 patients diagnosed with SCRLM, simultaneous colorectal and hepatic resection was performed in 60 patients (82.2%), while delayed hepatic resection was performed in 13 patients (17.8%). The mortality rate was zero. The postoperative complication rate after delayed resection was higher than, but not significantly different from, that after simultaneous resection (46% vs. 23%, P=0.166). The duration of operating time (240 vs. 420 min, P<0.05) and postoperative hospital stay time (11 vs. 18 days, P<0.05) were shorter in the simultaneous resection group. After the initial treatments were given, the 1-, 2-, and 3-year survival rates in the simultaneous resection group were 77%, 59%, and 53%, respectively, whereas those in the delayed resection group were 67%, 42%, and 10%, respectively. The 5-year survival rate in the simultaneous resection group was 23%; overall survival differed significantly between the two groups (P=0.037). Median disease-free survival (DFS) times were 19.1 months in the simultaneous resection group and 8.8 months in the delayed resection group. DFS differed significantly between the two groups. Conclusions Simultaneous colorectal and hepatic resection is safe and exhibits advantages in the long-time survival of patients.

Non-response to preoperative chemotherapy is a contraindication to hepatectomy plus radiofrequency ablation in patients with colorectal liver metastases

The long-term outcome of 228 patients with colorectal liver metastases (CRLM) who underwent preoperative chemotherapy followed by hepatectomy ± RFA were retrospectively analyzed. Stratified by chemotherapy response, patients were divided into responding (n=129) and non-responding groups (n=99). Patients who underwent hepatectomy-RFA had a greater number of metastases (median of 4 vs. 2, p=0.000), a higher incidence of bilobar involvement (66.7% vs. 49.1%, p=0.014) and longer chemotherapy cycles (median of 6 vs. 4, p=0.000). In the responding group, the median overall survival (OS) and recurrence free survival (RFS) of hepatectomy-RFA and the hepatectomy alone subgroups were comparable (38.6 months vs. 43.2 months, p=0.824; 8.2 months vs. 11.4 months, p=0.623). In the non-responding group, the median OS and RFS of patients treated with hepatectomy-RFA were significantly shorter (18.5 months vs. 34.2 months, p=0.000; 5.1 months vs. 5.9 months, p=0.002). RFA was identified as the unfavorable independent factor for both OS (HR=3.60, 95%CI=1.81-7.16, p=0.039) and RFS (HR=1.70, 95%CI=1.00-2.86, p=0.048) in non-responsive patients. Local recurrence rate after hepatectomy-RFA was higher in the non-responding group (48.1% vs. 23.6%, p=0.018). Non-response to preoperative chemotherapy may be a contraindication to hepatectomy-RFA in patients with CRLM.

Clinical features and prognostic factors of cryptogenic hepatocellular carcinoma

Background: To explore the clinical features and prognostic factors of cryptogenic hepatocellular carcinoma (cHCC). Methods: The clinical data of 59 cHCC patients who had undergone radical surgery in our center from February 1999 to December 2010 were retrospectively analyzed. Survival analysis was performed by using the Kaplan-Meier method. Univariate and multivariate regression analyses were carried out for the assessment of potential prognostic factors. Results: Among these 59 patients, there were 49 men and 10 women aged 27 to 84 years (mean: 61.4 years). Sixteen patients (27.12%) had nonalcoholic fatty liver disease (NAFLD), whereas hepatitis virus serologic markers were not completely negative in 43 patients (72.88%; non-all-negative group). All patients received radical resection in our hospital. HCC was confirmed after postoperative pathologic examinations in all these 59 patients. Pathology revealed that 34 patients also had cirrhosis, and the manifestations of cirrhosis significantly differed between all-negative group and non-all-negative group. Forty-three patients (72.88%) died within follow-up. The postoperative 3- and 5-year survival rates were 44.07% and 35.59%, respectively. The longest disease-free survival after the operation was 195 months, and the median survival time was 32 months. Multivariate analysis showed that HBcAb (+) and NAFLD were independent prognostic factors for the postoperative survival of patients with cryptogenic HCC (HR =2.558, 95% CI: 1.146–5.711, P=0.022; HR =2.067, 95% CI: 1.056–4.049, P=0.034). Conclusions: cHCC is a relatively rare disease and occurs mainly in elderly obese males. The development of cHCC is associated with NAFLD and hepatitis B virus Infection. HBcAb (+) status and NAFLD are independent prognostic factors for the postoperative survival of cHCC patients.

Primary hepatic neuroendocrine tumors: retrospective analysis of seven cases and literature review

Background: Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare. Their clinical features, diagnosis and effective treatment strategies are not well understood. Methods: We aimed to investigate them by combining retrospectively analyzing the clinical data of seven patients with PHNETs who were admitted to our hospital from April 2009 to November 2017 with literature review. Results: PHNET patients without medical history of hepatitis or liver cirrhosis presented no specific symptom, and hepatic tumor markers such as alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were all within the normal range. Imaging of PHNET patients was found to be with a dominant hypervascular hepatic mass accompanied by a lower cystic signal and a higher hemorrhagic signal area on T1-weighted magnetic resonance imaging (MRI), with rapid washout and capsular enhancement on dynamic MR imaging or computed tomography (CT) imaging and restricted diffusion on diffusion-weighted (DW)-MRI. All patients underwent preoperative and postoperative CT examination or MRI examination which identified no extrahepatic tumors. All patients underwent surgery-centered comprehensive individualized treatment. Postoperative pathology confirmed that all patients had NETs. On immunohistochemistry all of the tumors were chromogranin A (CgA) positive, six were synaptophysin (Syn) positive. At the end of the follow-up period ranging from 9 to 87 months, six patients survive without recurrence. The longest postoperative survival time and the longest disease-free survival (DFS) time were all 87 months. Conclusions: Our findings suggest PHNET patients have unique clinical characteristics. The diagnosis of PHNETs relies on pathology and imaging examination MRI or CT to exclude primary extrahepatic tumors. Surgery-centered individualized comprehensive treatment leads to a good prognosis of patients with PHNETs.