Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare distinct subtype of precursor lesions of biliary carcinoma. IPNB is considered to originate from luminal biliary epithelial cells, typically displays mucin-hypersecretion or a papillary growth pattern, and results in cystic dilatation[1]. IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts, and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma. IPNBs have similar phenotypic changes in the occurrence and development of all subtypes, and the prognosis is significantly better than that of traditional (non-papillary) cholangiocarcinoma. AIM: To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment. METHODS: Invasive IPNB, invasive intraductal papillary mucinous neoplasm of the pancreas (IPMN), and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Annual percentage changes (APCs) in the incidence and incidence-based (IB) mortality were calculated. We identified the independent predictors of overall survival (OS) and cancer-specific survival (CSS) in individuals with invasive IPNB. RESULTS: The incidence and IB mortality of invasive IPNB showed sustained decreases, with an APC of -4.5% (95%CI: -5.1% to -3.8%) and -3.3% (95%CI: -4.1% to -2.6%) (P < 0.001), respectively. Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma. Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma. A total of 1635 individuals with invasive IPNB were included in our prognosis analysis. The most common tumor sites were the pancreaticobiliary ampulla (47.9%) and perihilar tract (36.7%), but the mucin-related subtype of invasive IPNB was the main type, intrahepatically (approximately 90%). In the univariate and multivariate Cox regression analysis, age, tumor site, grade and stage, subtype, surgery, and chemotherapy were associated with OS and CSS (P < 0.05). CONCLUSION: Incidence and IB mortality of invasive IPNB trended steadily downward. The heterogeneity of IPNB comprises site and the tumor's mucin-producing status.

Simple cholecystectomy is an adequate treatment for grade I T1bN0M0 gallbladder carcinoma: Evidence from 528 patients.

BACKGROUND: T1b gallbladder carcinoma (GBC) is defined as a tumor that invades the perimuscular connective tissue without extension beyond the serosa or into the liver. However, controversy still exists over whether patients with T1b GBC should undergo cholecystectomy alone or radical GBC resection. AIM: To explore the optimal surgical approach in patients with T1b gallbladder cancer of different pathological grades. METHODS: Patients with T1bN0M0 GBC who underwent surgical treatment between 2000 and 2017 were included in the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method and log-rank test were used to analyze the overall survival (OS) and disease-specific survival (DSS) of patients with T1b GBC of different pathological grades. Cox regression analysis was used to identify independent predictors of mortality and explore the selection of surgical methods in patients with T1b GBC of different pathological grades and their relationship with prognosis. RESULTS: Of the 528 patients diagnosed with T1bN0M0 GBC, 346 underwent simple cholecystectomy (SC) (65.5%), 131 underwent SC with lymph node resection (SC + LN) (24.8%), and 51 underwent radical cholecystectomy (RC) (9.7%). Without considering the pathological grade, both the OS (P < 0.001) and DSS (P = 0.003) of T1b GBC patients who underwent SC (10-year OS: 27.8%, 10-year DSS: 55.1%) alone were significantly lower than those of patients who underwent SC + LN (10-year OS: 35.5%, 10-year DSS: 66.3%) or RC (10-year OS: 50.3%, 10-year DSS: 75.9%). Analysis of T1b GBC according to pathological classification revealed no significant difference in OS and DSS between different types of procedures in patients with grade I T1b GBC. In patients with grade II T1b GBC, obvious survival improvement was observed in the OS (P = 0.002) and DSS (P = 0.039) of those who underwent SC + LN (10-year OS: 34.6%, 10-year DSS: 61.3%) or RC (10-year OS: 50.5%, 10-year DSS: 78.8%) compared with those who received SC (10-year OS: 28.1%, 10-year DSS: 58.3%). Among patients with grade III or IV T1b GBC, SC + LN (10-year OS: 48.5%, 10-year DSS: 72.2%), and RC (10-year OS: 80%, 10-year DSS: 80%) benefited OS (P = 0.005) and DSS (P = 0.009) far more than SC (10-year OS: 20.1%, 10-year DSS: 38.1%) alone. CONCLUSION: Simple cholecystectomy may be an adequate treatment for grade I T1b GBC, whereas more extensive surgery is optimal for grades II-IV T1b GBC.

Intrahepatic bile duct exploration lithotomy is a useful adjunctive hepatectomy method for bilateral primary hepatolithiasis: an eight-year experience at a single centre.

BACKGROUND: To evaluate the perioperative and long-term results of intrahepatic bile duct exploration lithotomy (IHBDIL) combined with hepatectomy for patients with complicated bilateral primary hepatolithiasis. METHODS: A study was conducted involving 56 patients with complicated bilateral primary hepatolithiasis who underwent IHBDIL combined with hepatectomy at our hospital from January 2006 to December 2014. The perioperative and long-term outcomes that were retrospectively analysed included the stone clearance rate, operative morbidity and mortality, and stone recurrence rate. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded. RESULTS: In all 56 patients, hepatic duct stones were located in the bilateral IHBD. The surgical method was IHBDIL combined with hepatectomy. Postoperative complications occurred in 15 patients (26.8%), 14 patients responded to conservative management, and there was 1 case of postoperative mortality because of hepatic failure. The overall initial success rate of stone clearance was 85.7%, and the final clearance rate was 92.9% following postoperative choledochoscopic lithotripsy. The stone recurrence rate was 13.5%, and the occurrence of postoperative cholangitis was 10.9% during the follow-up period. CONCLUSION: IHBDIL combined with hepatectomy is a safe, effective, and promising treatment for patients with complicated bilateral primary hepatolithiasis. The perioperative and long-term outcomes are satisfactory for complicated bilateral primary hepatolithiasis.

Bleeding risk in cancer patients treated with sorafenib: A meta-analysis of randomized controlled trials.

OBJECTIVE: Sorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase inhibitor, has become a cornerstone in the treatment of various malignancies. However, concerns have arisen regarding the risk of hemorrhage with sorafenib use. Nevertheless, the contribution of sorafenib to hemorrhage and the underlying risk factors remains unclear. MATERIALS AND METHODS: We performed a meta-analysis to determine the incidence and risk of hemorrhage associated with sorafenib treatment. Multiple databases were searched to identify relevant studies. The analysis included randomized controlled trials (RCTs) that directly compared cancer patients treated with or without sorafenib. Statistical analyses were conducted to determine the overall incidence, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effect models. RESULTS: Ten RCTs involving 4720 patients were included in the analysis. Overall, the incidence rates of all- and high-grade hemorrhage in patients receiving sorafenib were 9.89% (95% CI: 8.73-11.18%) and 2.86% (95% CI: 2.25-3.63%), respectively. Sorafenib treatment increased the risk of all-grade hemorrhage in patients compared to control treatment (RR: 1.99; 95% CI: 1.59-2.49; P < 0.00001), but did not increase the incidence of high-grade hemorrhage (RR: 1.42; 95% CI: 0.95-2.12; P = 0.09). Subgroup analysis showed no significant increase in the risk of hemorrhage between patients with various malignancies or concurrent treatment. No evidence of publication bias was observed. CONCLUSION: In patients with malignancy, sorafenib treatment combined with standard treatment significantly increases the risk of low-grade hemorrhagic events.

Effectiveness of hepatic parenchyma lithotomy of hepatolithiasis: A single-center experience.

To investigate the clinical significance of hepatic parenchyma incision by lithotomy near the second hepatic portal area for the treatment of complex hepatolithiasis.A retrospective study was conducted with 35 patients who had complicated hepatolithiasis in our hospital from January 2008 to December 2013, who underwent hepatic parenchyma incision by lithotomy near the second hepatic portal area. The perioperative and long-term outcomes included the stone clearance rate, operative morbidity and mortality, and the stone recurrence rate. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded from the study.All patients with hepatic duct stones were mainly located at S2, S4, and S8 regions. Surgical methods included were hepatic parenchyma incision by lithotomy near the second hepatic portal area, or by combined partial hepatectomy. The mean follow-up period was 51 months. One patient died during hospitalization. The surgical morbidity was 17.6%, stone clearance rate was 88.2%, and final clearance rate was 94.1% followed by postoperative choledochoscopic lithotripsy. The stone recurrence rate was 15.6% and the occurrence of postoperative cholangitis was 11.8% during the follow-up period.Hepatic parenchyma incision by lithotomy near the second hepatic portal area is safe with satisfactory short and long-term outcome results for complicated hepatolithiasis.

[Interferon-induced transmembrane protein 3 knock-down inhibits proliferation and invasion of hepatocellular carcinoma HepG2 cells in vitro].

OBJECTIVE: To investigate the abnormal expression of interferon-induced transmembrane protein 3 (IFITM3) in hepatocellular carcinoma (HCC) and the effect of IFITM3 knock-down on the biological behaviors of hepatocellular carcinoma HepG2 cells. METHODS: Western blot analysis and immunohistochemical staining were used to determine the expression of IFITM3 protein in 60 HCC samples and paired adjacent tissues. A small interfering RNA fragments of IFITM3 (IFITM3 siRNA) was transiently transfected into HepG2 cells and expressions of IFITM3 at mRNA and protein levels were examined by qRT-PCR and Western blotting. The changes in the proliferation of the transfected cells were determined using cell counting kit 8 (CCK8) assay, and the cell invasion and migration were tested using Transwell assay and wound-healing assay. RESULTS: Compared with the adjacent tissues, HCC tissues expressed significantly higher levels of IFITM3. In HepG2 cells, transfection with IFITM3 siRNA resulted in significant down-regulation of IFITM3 expression at both the protein and mRNA levels and obviously suppressed cell proliferation, invasion, and migration ability as compared with the cells transfected with scrambled siRNA and control cells (P<0.05). CONCLUSIONS: IFITM3, which is overexpressed in HCC, plays a vital role in the proliferation and invasion of HCC cells and may serve as a potential target for gene therapy of HCC.

Arrangements of hepatobiliary cystadenoma complicated with congenital choledochal cyst: a case report and literature review.

Hepatobiliary cystadenoma complication with congenital choledochal cyst is extremely rare and has never been reported in literatures so far.The aim of the study was to investigate the disease arrangements by analyzing the case and performing a systematic review of the literature.This case report documents the details and clear patterns of the patient. A 65-year-old woman with fever (39.2°C), nausea, vomiting, and chronic hepatitis B imaging demonstrated a left hepatic multilocular cystic mass and cystic dilated common bile duct.A regular left hemihepatectomy was performed with resection of the entire tumor and choledochal cyst.The surgical margins were negative and a final diagnosis of hepatobiliary cystadenoma complicated with congenital choledochal cyst was established. The patient had an uneventful postoperative recovery and liver function returned to normal levels.Main lessons learned from this case are: the awareness should be raised about the disease to avoid misdiagnosis; preoperative ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography play an important role in detecting the lesion; the scope and timing of the surgery should be determined, which provide the chance of cure to complete resection of the tumor.

Inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma: in vitro and in vivo studies.

OBJECTIVE: To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo, which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer. METHODS: Humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology. In this combined in vitro and in vivo study, the inhibitory effects of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on tumor growth, invasion, and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay, Tanswell assay, Hochest33258 staining, and DNA ladder analysis. The anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402 xenografts. RESULTS: Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells. And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis. Transwell assay found that the drug also inhibited the metastasis ability of tumor cells. Furthermore, anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration (92.9%), followed by As2O3-stealth nanoparticles, anti-VEGFR-2 ScFv, and As2O3 (61.4%, 58.8%, 20.5%, P<0.05). The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles group was more selectively. CONCLUSIONS: Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.

Risk of serious neutropenic events in cancer patients treated with bevacizumab: a meta-analysis.

Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancer but associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidence and relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, we searched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at the American Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 to December 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapy or biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients were included in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrile neutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95% CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31; 95% CI: 1.08-1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those who did not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly with tumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent, as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumab addition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may be dose-dependent.