Prevention of post-sphincterotomy bleeding by proton pump inhibitor: A randomized controlled trial.

OBJECTIVE: Post-endoscopic sphincterotomy (EST) bleeding is one of the most frequent complications of endoscopic retrograde cholangiopancreatography (ERCP). Although the use of proton pump inhibitors (PPIs) reduces the risk of peptic ulcer bleeding, their role in preventing EST bleeding has not been evaluated. This study aimed to assess the use of pre-emptive PPIs in patients undergoing EST. METHODS: This was an investigator-initiated, open-label, randomized study. Consecutive patients scheduled to undergo ERCP and EST were enrolled after excluding those who had previous EST or used acid-suppression agents. Eligible patients were randomized to receive either PPI or standard care. The PPI group received intravenous esomeprazole 4 h before the EST and then every 12 h for 1 day, followed by high-dose oral esomeprazole for 10 days. All patients were followed up for 30 days. The primary outcome was the proportion of patients with combined immediate and delayed overt post-EST bleeding. RESULTS: Altogether 125 patients (60 in the PPI arm and 65 in the standard care arm) who had undergone EST were analyzed. Immediate bleeding was noted in nine (15.0%) patients in the PPI group and four (6.2%) in the standard care group (P = 0.14). Overt delayed post-EST bleeding was seen in two (3.3%) and five (7.7%) patients in PPI and standard care arms, respectively (P = 0.44). There were no significant differences in other outcomes, including a decrease in hemoglobin of >20 g/L, the need for blood transfusion, length of hospital stay and 30-day mortality. CONCLUSION: Pre-emptive PPI did not reduce the risk of post-EST bleeding.

Acute pancreatitis induced by transarterial chemoembolization: a single-center experience of over 1500 cases.

BACKGROUND: Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma. METHODS: A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications. RESULTS: Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post-chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication. CONCLUSIONS: Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved.

Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma.

BACKGROUND: Advanced inoperable hepatocellular carcinoma (HCC) conferring a grave prognosis may benefit from yttrium-90 ((90)Y) radioembolization. METHODS: Thirty patients with advanced inoperable HCC including those with any lesion >8 cm in maximal diameter or multiple bi-lobar lesions (totally more than five lesions), or portal vein thrombosis treated with radioembolization were reviewed. Treatment efficacy and safety were evaluated. Univariate and multivariate analyses were performed for identifying potential prognostic factors. RESULTS: After a median follow-up of 18.3 months, the response rate was 30.0%, and the disease control rate was 50.0%. Median overall progression-free survival (PFS) and overall survival (OS) were 3.3 months and 13.2 months, respectively. Longer median PFS was noted in those who had transarterial chemoembolization before radioembolization (7.3 months vs 3.1 months; P=0.021) and duration of alfafeto protein (AFP) response ≥6 months (11.8 months vs 3.0 months; P<0.001). Longer median OS was also revealed in those without portal vein thrombosis (17.1 months vs 4.4 months; P=0.015) and those whose duration of AFP response was ≥6 months (21.2 months vs 8.6 months; P=0.001). Seventeen patients (56.7%) developed treatment-related complications including five (16.7%) grade 3 events. Multivariate analysis revealed that treatment responders (P=0.001) and duration of AFP response ≥6 months (P=0.006) were prognostic of PFS, whereas the absence of portal vein invasion (P=0.025), treatment responders (P=0.010), and duration of AFP response ≥6 months (P=0.001) were prognostic of OS. CONCLUSION: (90)Y radioembolization is an alternative treatment with a promising outcome for poor-risk advanced inoperable HCC.

A preclinical study on the combination therapy of everolimus and transarterial chemoembolization in hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is commonly used for the treatment of locally advanced hepatocellular carcinoma (HCC) by its dual effects of chemotherapy and ischemic hypoxia. However, one of the side effects of TACE is the introduction of hypoxic condition, which in turn activates hypoxia-induced survival pathways and enhances VEGF-induced neovascularization by stabilizing HIF-1α expression. Herein, the preclinical therapeutic efficacy of the combined treatment of everolimus, a novel mTOR inhibitor and TACE for the treatment of HCC was investigated. The MHCC-97L cells were used for the study of the effect of combined treatment on cell proliferation and cellular apoptosis. HUVEC cells were used for the study on tube formation under different treatments. Inhibitions on the Akt/mTOR pathways were also studied. Finally, the effect on tumor growth was further study using an in vivo orthotopic model. The results demonstrated that everolimus enhanced the therapeutic efficacy of TACE in inhibiting cell proliferation, promoting apoptosis and inhibiting tube formation of endothelial cells by blocking the Akt/mTOR signaling pathway in vitro and inhibiting tumor growth and neoangiogenesis in vivo. Based on this preclinical study, the potential of combining everolimus with TACE was guaranteed which suggested the use of the combination therapy in the clinical treatment of advanced HCC patients.

Lyso-thermosensitive liposomal doxorubicin: an adjuvant to increase the cure rate of radiofrequency ablation in liver cancer.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. No more than 30% of HCC patients are considered suitable for curative treatment because of tumor size and severity of liver impairment, among other factors. Radiofrequency ablation (RFA) monotherapy can cure small (<3 cm) HCC tumors. An adjuvant that interacts synergistically with RFA might enable curative therapy for many HCC patients with lesions >3 cm. Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of the heat-enhanced cytotoxic doxorubicin within a heat-activated liposome. LTLD is infused intravenously prior to RFA. When heated to >39.5°C, LTLD releases doxorubicin in high concentrations into the tumor and the tumor margins. The RFA plus LTLD combination has shown a statistically significant dose-response effect for time to treatment failure in a Phase I trial in which most subjects (62.5%) had tumors >3 cm. RFA plus LTLD is currently being evaluated in a 600-patient randomized, double-blind, dummy-controlled trial.

A protein-based set of reference markers for liver tissues and hepatocellular carcinoma.

BACKGROUND: During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify "housekeeping" markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression. METHODS: A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers. RESULTS: The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples. CONCLUSION: Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference moieties for normalisation of gene and protein expression in clinical research employing human hepatic tissues.

Is radiofrequency ablation the treatment of choice for patients with small hepatocellular carcinoma?

Liver resection is widely considered the mainstay of curative therapy for small hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) was initially developed as a treatment for small HCC in patients with considerable cirrhosis and inadequate liver function reserve for liver resection. However, in some centers, RFA is now used for small HCC, as an alternative to liver resection or even as the preferred treatment. This Practice Point commentary discusses the findings and limitations of a retrospective cohort study by Livraghi et al. that analyzed the outcomes of a group of patients with small, single HCC who underwent treatment with RFA. The authors reported a low major complication rate and a local complete response rate similar to that after resection. This commentary highlights the issues to consider when interpreting and generalizing these results, in particular that these findings need to be interpreted in the light of studies that suggest a high rate of local recurrence and incomplete histopathological response after RFA of small HCC.