Feasibility and Tolerability of Lenvatinib, Plus PD-1 Blockades for Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study.

Objective: Lenvatinib was the standard first-line therapy for patients with unresectable HCC. PD-1 blockades demonstrated promising efficacy for patients with previously-treated HCC. Therefore, this study was to investigate the feasibility and tolerability of lenvatinib plus PD-1 blockades for patients with unresectable HCC retrospectively. Methods: A total of 37 patients with unresectable HCC who received lenvatinib plus PD-1 blockades in first-line setting were included in this study retrospectively. Efficacy of the patients was evaluated with the change of target lesion using mRECIST criteria per investigator and all the subjects were followed up regularly. Adverse reactions were collected and documented. Exploratory analysis between prognosis and baseline characteristics was performed using log rank test and multivariate analysis were performed using Cox regression analysis. Results: The best overall response of the 37 patients suggested that complete response was observed in one patient, partial response was noted in 11 patients, stable disease was noted in 16 patients and 9 patients had progressive disease, which yielded an objective response rate (ORR) of 32.4% (95%CI: 18.0-49.8) and a disease control rate (DCR) of 75.7% (95%CI: 58.8-88.2). Furthermore, the median progression-free survival (PFS) of the 37 patients with advanced HCC was 8.3 months (95%CI: 3.34-13.26). And the median overall survival (OS) was 17.8 months (95%CI: 7.19-28.41). In addition, the median duration of response (DoR) in 12 patients with response was 9.6 months (95%CI: 3.03-16.17). Furthermore, adverse reactions that were attributed to the combination administration were detected in 36 patients (97.3%), among whom a total of 22 patients (59.5%) were observed of the grade ≥3 adverse reactions. And the most common adverse reactions were hypertension, fatigue, nausea and vomiting, and hepatotoxicity. Conclusion: Lenvatinib plus PD-1 blockades demonstrated promising anticancer activity and acceptable toxicity for patients with unresectable HCC. And the conclusion should be validated in prospective clinical trials subsequently.

Appleby operation for carcinoma of the body and tail of the pancreas.

AIMS: The aim of this study is to evaluate the therapeutic efficacy of Appleby operation for carcinoma of the body and tail of pancreas. MATERIALS AND METHODS: From March 2010 to February 2015, Appleby operation was performed in 17 patients with carcinoma of the body and tail of pancreas. The values of fasting plasma blood, body weight (BW), visual analog pain intensity scale (VAS score), and the quality of life indices were evaluated before and 1 day, 1, 2, 6 weeks after surgery. Survival time, tumor recurrence time, hospitalization time, and treatment-related complications were analyzed. RESULTS: There was no hospital mortality. Pancreatic fistula and diarrhea were major and most frequent. The rate of morbidity in general was 47.1%. After operation, all of the patients were completely pain-free. The VAS score decreased more after surgery comparing with before (83.2 ± 8.5 vs. 1.9 ± 3.6, P < 0.05). After operation, patients gained more than their preoperative BW with a mean increment of (4.1 ± 1.3 kg) (68.1 ± 4.3 vs. 64.0 ± 6.7, P < 0.05). A significant rise of the overall quality of life index was observed after surgery (93.8 ± 9.7 vs. 68.6 ± 6.7, P < 0.05). The 1-, 2-, 3-, and 5-year recurrence rates were 22.9%, 58.9%, 72.6%, and 72.6%, respectively. The 1-, 2-, 3-, and 5-year survival rates after operation were 80.4%, 54.2%, 32.5%, and 16.3%, respectively. CONCLUSIONS: Appleby operation is both safe and effective with regard to pain relief and improvement of overall quality of life. Appleby operation can also achieve a high survival rate and a long overall survival time.

Possible Molecular Markers for the Diagnosis of Pancreatic Ductal Adenocarcinoma.

BACKGROUND We aimed to identify pivotal genes and pathways involved in pancreatic ductal adenocarcinoma (PDAC), and explore possible molecular markers for the early diagnosis of the disease. MATERIAL AND METHODS The array data of GSE74629, including 34 PDAC samples and 16 healthy samples, was downloaded from GEO (Gene Expression Omnibus) database. Then, the DEGs (differentially expressed genes) in PDAC samples were compared with healthy samples using limma (linear models for microarray). Gene functional interaction networks were analyzed with Cytoscape and ReactomeFIViz. PPI networks were constructed with Cytoscape software. In addition, PPI (protein-protein interaction) network clustering modules were analyzed with ClusterONE, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses for modules were performed. RESULTS A total of 630 upregulated and 1,002 downregulated DEGs were identified in PDAC samples compared with healthy samples. Some ribosomal protein genes with higher average correlation in module 0 were enriched in the ribosome pathway. NUP107 (nucleoporin 107 kDa) and NUP160 (nucleoporin 160 kDa) were enriched in module 3. HNRNPU (heterogeneous nuclear ribonucleoprotein U) with higher average correlation in module 8 was enriched in the spliceosome pathway. The ribosome pathway and the spliceosome pathway were significantly enriched in cluster 1 and cluster 2, respectively. CONCLUSIONS Ribosomal protein genes Nup170, Nup160, and HNRNPU, and the ribosome pathway as well as the spliceosome pathway may play important roles in PDAC progression. In addition, ribosomal protein genes Nup170, Nup160, and HNRNPU may be used as possible molecular markers for the early diagnosis of the disease.

Primary Closure Following Laparoscopic Common Bile Duct Exploration Combined with Intraoperative Choledochoscopy and D-J Tube Drainage for Treating Choledocholithiasis.

BACKGROUND This study aimed to assess the clinical short-term results of a primary closure following laparoscopic common bile duct exploration (LCBDE) combined with intraoperative choledochoscopy and D-J tube drainage for choledocholithiasis treatment. MATERIAL AND METHODS Twenty-five patients (14 women and 11 men) who underwent LCBDE with primary duct closure and D-J tube drainage for choledocholithiasis were retrospectively enrolled. The D-J tube (4.7F×14 cm) was removed using a duodenoscope if there was no bile leakage. Before discharge, patients were examined for blood amylase. After discharge or D-J tube removal, all patients were routinely assessed for complications. RESULTS Mean operating time was 135±46 min (range, 78-195 min). Mean intraoperative blood loss was 71±24 mL (range, 25-110 mL). Total hospital stay was 6-9 days (mean, 8.04±1.37 days). Two patients experienced intraoperative bile leakage, which was stopped with re-suturing. None of these patients experienced postoperative bile leaks. Three patients had slight elevation of serum amylase before discharge but without pancreatitis signs. The successful clearance rate of stones was 100%. During 1-year follow-up, no recurrence or severe complications occurred. CONCLUSIONS A primary closure following LCBDE combined with intraoperative choledochoscopy and D-J tube drainage is safe and feasible for choledocholithiasis treatment.

miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated mTOR/STAT3/AKT pathway in hepatocellular carcinoma.

MicroRNAs (miRNAs) have been reported to play critical roles in tumor progression including hepatocellular carcinoma (HCC). Thus, the underlying mechanisms need further investigation. Previous study reported that loss of miR-345 expression indicated a poor prognosis of HCC patients. This study evaluated whether loss of miR-345 could promote the tumor metastasis and epithelial-mesenchymal-transition (EMT) of HCC by targeting interferon regulatory factor 1 (IRF1)-mediated mTOR/STAT3/AKT signaling. Underexpression of miR-345 was identified in 65 cases of human HCC compared to matched tumor-adjacent tissues by qRT-PCR. Moreover, we found that reduced expression of mi-345 was observed in HCC cell lines. The restoration of miR-345 inhibited cell migration and invasion in HCCLM3 cells, while its loss facilitated the cell mobility of HepG2 cells. Furthermore, miR-345 over-expression reduced lung metastases of HCC cells in nude mice. Notably, miR-345 overexpression prohibited, while its knockdown enhanced the EMT process of HCC cell lines in vitro. Bioinformatics software predicted that IRF1 was a direct target of miR-345. We then observed the negative regulation of miR-345 on IRF1 protein expression and the direct binding between them was further verified by dual-luciferase assays in HCC cells. In addition, over-expression of IRF1 mRNA was inversely correlated with the level of miR-345 in HCC specimens. Restoration of IRF1 resulted in promoted EMT and cell mobility in miR-345 overexpressing HCCLM3 cells. It was found that mTOR/STAT3/AKT pathway and its downstream targets including Slug, Snail and Twist may be involved in IRF1 mediated EMT process. In conclusion, miR-345 acts as an inhibitor of EMT process in HCC cells by targeting IRF1 and this study highlights the potential effects of miR-345 on prognosis and treatment of HCC.