Recapitulation of pharmacogenomic data reveals that invalidation of SULF2 enhance sorafenib susceptibility in liver cancer.

Gene mutations play critical roles during cancer development and progression, and therefore represent targets for precision medicine. Here we recapitulated the pharmacogenomic data to delineate novel candidates for actionable mutations and therapeutic target drugs. As a proof-of-concept, we demonstrated that the loss-of-function of SULF2 by mutation (N491K) or inhibition enhanced sorafenib sensitivity in liver cancer cells and in vivo mouse models. This effect was mediated by deregulation of EGFR signaling and downstream expression of LCN2. We also report that the liver cancer patients non-responding to sorafenib treatment exhibit higher expression of SULF2 and LCN2. In conclusion, we suggest that SULF2 plays a key role in sorafenib susceptibility and resistance in liver cancer via deregulation of LCN2. Diagnostic or therapeutic targeting of SULF2 (e.g., OKN-007) and/or LCN2 can be a novel precision strategy for sorafenib treatment in cancer patients.

Identification of Caveolin-1 as an Invasion-Associated Gene in Liver Cancer Cells Using Dendron-Coated DNA Microarrays.

The conventional gene expression profiling approaches have been replaced with DNA microarrays with exhibiting a powerful high-throughput capacity. Most solid surfaces of DNA microarrays contain such a high area density of functional groups to immobilize capture DNAs to the surface that the hybridization of capture DNAs with cDNA can be hindered, resulting in low intensity and reproducibility. Since our previous works showed that the 9-acid dendron was able to increase the hybridization efficiency, we aimed to demonstrate the feasibility of 9-acid dendron-coated glass slides as an advanced microarray platform for gene expression profiling. The 9-acid dendron-coated DNA microarray could reproducibly obtain the expression levels of 2800 human cancer-associated genes in the two liver cancer lines: Hep3B and SK-Hep1. Among the differentially expressed genes, Caveolin-1 (Cav-1) was identified as the most highly up-regulated gene in invasive SK-Hep1 in comparison to non-motile Hep3B. The overexpression of Cav-1 in Hep3B promoted the cell invasion, whereas its knockdown in SK-Hep1 suppressed the invasive feature, which confirms that the overexpression of Cav-1 is closely associated with cell invasion of liver carcinoma. Collectively, the 9-acid dendron-coated surface could successfully detect the transcript levels of cells, demonstrating its feasible potential to identify the candidate genes for further functional studies or diagnosis of diseases.

SIRT6 Depletion Suppresses Tumor Growth by Promoting Cellular Senescence Induced by DNA Damage in HCC.

The role of Sirtuin 6 (SIRT6) as a tumor suppressor or oncogene in liver cancer remains controversial. Thus, we identified the specific role of SIRT6 in the progression of hepatocellular carcinoma (HCC). SIRT6 expression was significantly higher in HCC cell lines and HCC tissues from 138 patients than in an immortalized hepatocyte cell line, THLE-2 and non-tumor tissues, respectively. SIRT6 knockdown by shRNA suppressed the growth of HCC cells and inhibited HCC tumor growth in vivo. In addition, SIRT6 silencing significantly prevented the growth of HCC cell lines by inducing cellular senescence in the p16/Rb- and p53/p21-pathway independent manners. Microarray analysis revealed that the expression of genes involved in nucleosome assembly was apparently altered in SIRT6-depleted Hep3B cells. SIRT6 knockdown promoted G2/M phase arrest and downregulation of genes encoding histone variants associated with nucleosome assembly, which could be attributed to DNA damage. Taken together, our findings suggest that SIRT6 acts as a tumor promoter by preventing DNA damage and cellular senescence, indicating that SIRT6 represents a potential therapeutic target for the treatment of HCC.

Effects of Nei-Guan (P6) Acupressure Wristband: On Nausea, Vomiting, and Retching in Women After Thyroidectomy.

BACKGROUND: Postoperative nausea and vomiting (PONV) after thyroidectomy is a common health problem in the recovery room. OBJECTIVE: The aim of this study is to examine the effect of the Nei-Guan (P6) acupressure wristband for PONV among patients undergoing thyroidectomy. METHODS: Sixty Korean female participants were assigned to 1 of 3 groups (n = 20 each). The control group received usual care without the wristband. The placebo group received usual nursing care plus a wristband at the non-P6 site. The treatment group received usual care plus a wristband at the P6 acupoint 30 minutes before anesthesia; the wristband was removed before leaving the recovery room. Data were collected at 3 periods: in the recovery room and at 6 and 24 hours after surgery. RESULTS: The nausea scores of the treatment group were significantly lower than the scores of the placebo or control groups in the recovery room (F = 6.229, P = .044). There were no significant differences in vomiting or retching among the groups. CONCLUSIONS: The P6 stimulation with wristband suppressed nausea right after thyroidectomy in the recovery room but did not suppress subsequent vomiting or retching. IMPLICATION FOR PRACTICE: The findings indicate that P6 acupressure has the short-term effect of relieving nausea but not vomiting and retching. Use of P6 wristband holds promise and suggests the need for further testing in a larger randomized clinical trial. Identifying other acupoints is recommended to achieve successful management of PONV.

Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition.

We identified the specific role of vaccinia-related kinase 1 (VRK1) in the progression of hepatocellular carcinoma (HCC) and evaluated its therapeutic and prognostic potential. VRK1 levels were significantly higher in HCC cell lines than a normal hepatic cell line, and were higher in HCC than non-tumor tissue. VRK1 knockdown inhibited the proliferation of SK-Hep1, SH-J1 and Hep3B cells; moreover, depletion of VRK1 suppressed HCC tumor growth in vivo. We also showed that VRK1 knockdown increased the number of G1 arrested cells by decreasing cyclin D1 and p-Rb while upregulating p21 and p27, and that VRK1 depletion downregulated phosphorylation of CREB, a transcription factor regulating CCND1. Additionally, we found that luteolin, a VRK1 inhibitor, suppressed HCC growth in vitro and in vivo, and that the aberrant VRK1 expression correlated with poor prognostic features of HCC. High levels of VRK1 were associated with shorter overall and disease-free survival and higher recurrence rates. Taken together, our findings suggest VRK1 may act as a tumor promoter by controlling the level of cell cycle regulators associated with G1/S transition and could potentially serve as a therapeutic target and/or prognostic biomarker for HCC.

AROS Is a Significant Biomarker for Tumor Aggressiveness in Non-cirrhotic Hepatocellular Carcinoma.

Despite a low risk of liver failure and preserved liver function, non-cirrhotic hepatocellular carcinoma (HCC) has a poor prognosis. In the current study, we evaluated an active regulator of SIRT1 (AROS) as a prognostic biomarker in non-cirrhotic HCC. mRNA levels of AROS were measured in tumor and non-tumor tissues obtained from 283 non-cirrhotic HCC patients. AROS expression was exclusively up-regulated in recurrent tissues from the non-cirrhotic HCC patients (P = 0.015) and also in tumor tissues irrespective of tumor stage (P < 0.001) or BCLC stage (P < 0.001). High mRNA levels of AROS were statistically significantly associated with tumor stage (P < 0.001), BCLC stage (P = 0.007), alpha fetoprotein (AFP) level (P = 0.013), microvascular invasion (P = 0.001), tumor size (P = 0.036), and portal vein invasion (P = 0.005). Kaplan-Meir curve analysis demonstrated that HCC patients with higher AROS levels had shorter disease-free survival (DFS) in both the short-term (P < 0.001) and long-term (P = 0.005) compared to those with low AROS. Cox regression analysis demonstrated that AROS is a significant predictor for DFS along with large tumor size, tumor multiplicity, vascular invasion, and poor tumor differentiation, which are the known prognostic factors. In conclusion, AROS is a significant biomarker for tumor aggressiveness in non-cirrhotic hepatocellular carcinoma.

Chronic passive venous congestion drives hepatic fibrogenesis via sinusoidal thrombosis and mechanical forces.

UNLABELLED: Chronic passive hepatic congestion (congestive hepatopathy) leads to hepatic fibrosis; however, the mechanisms involved in this process are not well understood. We developed a murine experimental model of congestive hepatopathy through partial ligation of the inferior vena cava (pIVCL). C57BL/6 and transgenic mice overexpressing tissue factor pathway inhibitor (SM22α-TFPI) were subjected to pIVCL or sham. Liver and blood samples were collected and analyzed in immunohistochemical, morphometric, real-time polymerase chain reaction, and western blot assays. Hepatic fibrosis and portal pressure were significantly increased after pIVCL concurrent with hepatic stellate cell (HSC) activation. Liver stiffness, as assessed by magnetic resonance elastography, correlated with portal pressure and preceded fibrosis in our model. Hepatic sinusoidal thrombosis as evidenced by fibrin deposition was demonstrated both in mice after pIVCL as well as in humans with congestive hepatopathy. Warfarin treatment and TFPI overexpression both had a protective effect on fibrosis development and HSC activation after pIVCL. In vitro studies show that congestion stimulates HSC fibronectin (FN) fibril assembly through direct effects of thrombi as well as by virtue of mechanical strain. Pretreatment with either Mab13 or Cytochalasin-D, to inhibit ß-integrin or actin polymerization, respectively, significantly reduced fibrin and stretch-induced FN fibril assembly. CONCLUSION: Chronic hepatic congestion leads to sinusoidal thrombosis and strain, which in turn promote hepatic fibrosis. These studies mechanistically link congestive hepatopathy to hepatic fibrosis.

Influence of preoperative transcatheter arterial chemoembolization on gene expression in the HIF-1α pathway in patients with hepatocellular carcinoma.

PURPOSE: Although transcatheter arterial chemoembolization (TACE) is the most common treatment option in patients with hepatocellular carcinoma (HCC), its clinical benefits remain still controversial. Since TACE induces hypoxic necrosis in tumors, hypoxia-inducible factor 1α (HIF-1α) could critically affect biology in residual tumors after TACE treatment and subsequent prognosis. However, HIF-1α and its prognostic relevance in TACE have rarely been examined in human specimens. In the current study, we investigated the prognosis and expression of genes regulated by HIF-1α in HCC patients receiving preoperative TACE for the first time. METHODS: In total, 35 patients with HCC (10 patients undergoing preoperative TACE) were retrospectively studied. The prognostic significance of TACE was analyzed using Kaplan-Meier and Cox regression models. Protein levels of HIF-1α and mRNA levels of HIF-1α-associated genes were examined using immunohistochemistry (IHC) and real-time RT-PCR, respectively. RESULTS: Preoperative TACE was significantly associated with increased 2-year recurrence rate (80 vs. 36 %, P = 0.00402) and shorter disease-free survival (DFS) time (11.9 vs. 35.7 months, P = 0.0182). TACE was an independent prognostic factor for recurrence (P = 0.007) and poor DFS (P = 0.010) in a multivariate analysis. Immunohistochemical staining revealed in vivo activation of HIF-1α in human specimens treated with TACE. Notably, protein levels of HIF-1α were significantly increased in TACE tissues demonstrated by IHC. Transcriptional targets of HIF-1α showed mRNA expression patterns consistent with activation of HIF-1α in TACE tissues. CONCLUSIONS: Our findings collectively demonstrate that preoperative TACE confers poor prognosis in HCC patients through activation of HIF-1α.

Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging.

Sirtuins are NAD(+) -dependent deacetylases that regulate a range of cellular processes. Although diverse functions of sirtuins have been proposed, those functions of SIRT6 and SIRT7 that are mediated by their interacting proteins remain elusive. In the present study, we identified SIRT6- and SIRT7-interacting proteins, and compared their interactomes to investigate functional links. Our interactomes revealed 136 interacting proteins for SIRT6 and 233 for SIRT7 while confirming seven and 111 proteins identified previously for SIRT6 and SIRT7, respectively. Comparison of SIRT6 and SIRT7 interactomes under the same experimental conditions disclosed 111 shared proteins, implying related functional links. The interaction networks of interactomes indicated biological processes associated with DNA repair, chromatin assembly, and aging. Interactions of two highly acetylated proteins, nucleophosmin (NPM1) and nucleolin, with SIRT6 and SIRT7 were confirmed by co-immunoprecipitation. NPM1 was found to be deacetylated by both SIRT6 and SIRT7. In senescent cells, the acetylation level of NPM1 was increased in conjunction with decreased levels of SIRT6 and SIRT7, suggesting that the acetylation of NPM1 could be regulated by SIRT6 and SIRT7 in the aging process. Our comparative interactomic study of SIRT6 and SIRT7 implies important functional links to aging by their associations with interacting proteins. All MS data have been deposited in the ProteomeXchange with identifiers PXD000159 and PXD000850 (http://proteomecentral.proteomexchange.org/dataset/PXD000159, http://proteomecentral.proteomexchange.org/dataset/PXD000850).

High-sensitivity C-reactive protein level is an independent predictor of poor prognosis in cirrhotic patients with spontaneous bacterial peritonitis.

BACKGROUND/AIMS: The production of high-sensitivity C-reactive protein (hs-CRP) may be affected by hepatic function, and the clinical importance of hs-CRP in patients with liver cirrhosis is still not clear. The aim of this study was to evaluate the clinical implications of hs-CRP in cirrhotic patients with spontaneous bacterial peritonitis (SBP). METHODS: We retrospectively investigated 336 consecutive patients treated for SBP from 2007 to 2012. The relationship between serum hs-CRP and the result of the treatment was assessed. RESULTS: A response to antibiotics was observed in 182 patients (54.2%), and 126 patients (37.5%) died of SBP. The initial hs-CRP (odds ratio=1.061, P=0.016), coexistent hepatocellular carcinoma, and Child-Pugh (CP) score were independent prognostic factors for high in-hospital mortality. Serum hs-CRP level was also an independent predictor of lower antibiotic response rate (odds ratio=0.916, P<0.001). However, hs-CRP was negatively correlated with the CP score (r=-0.199, P<0.001) and Model for End-Stage Liver Disease score (r=-0.182, P=0.001). CONCLUSIONS: This study found that serum hs-CRP level is related to a lower response rate to antibiotics, a higher mortality rate in patients with SBP. The hs-CRP level was negatively correlated with the CP and Model for End-Stage Liver Disease scores, which suggests that the prognostic function of hs-CRP was not a surrogate for hepatic dysfunction.

Serum insulin-like growth factor-I level is an independent predictor of recurrence and survival in early hepatocellular carcinoma: a prospective cohort study.

PURPOSE: Insulin-like growth factor-I (IGF-I) reflects hepatic synthetic function and plays an important role in the development and progression of various cancers. In this study, we investigated whether pretreatment serum IGF-I levels predict time-to-recurrence (TTR) and overall survival (OS) in patients with early-stage hepatocellular carcinoma after curative treatment. EXPERIMENTAL DESIGN: Consecutive patients with hepatocellular carcinoma who had undergone surgical resection, radiofrequency ablation, or percutaneous ethanol injection as curative treatments of early hepatocellular carcinoma were included from two prospective cohorts and the training set (n = 101) and the validation set (n = 91) were established. Serum samples were collected before treatment and the levels of IGF-I and IGF-binding protein-3 (IGFBP-3) were analyzed with regard to their associations with recurrence and survival. RESULTS: In the training set, patients with low IGF-I levels showed significantly shorter TTR [median, 14.6 months; 95% confidence interval (CI), 1.8-27.5] than patients with high IGF-I levels (median, 50.8 months; 95% CI, 36.9-64.7; P < 0.001) during a median follow-up period of 52.4 months. In the multivariate analysis, low levels of IGF-I were an independent predictor of recurrence (HR, 2.49; 95% CI, 1.52-4.08; P < 0.001). Furthermore, together with high-serum α-fetoprotein and multiple tumors, low levels of IGF-I remained an independent predictor of poorer survival (HR, 8.00; 95% CI, 1.94-33.01; P = 0.004). Applied to the independent validation set, low-serum IGF-I levels maintained their prognostic value for shorter TTR and OS. CONCLUSIONS: Low-baseline IGF-I levels independently correlated with shorter TTR and poorer survival in patients with early-stage hepatocellular carcinoma after curative treatment.

Actionable gene expression-based patient stratification for molecular targeted therapy in hepatocellular carcinoma.

BACKGROUND: The effectiveness of molecular targeted agents is modest in hepatocellular carcinoma (HCC). Efficacy of molecular targeted therapies has been better in cancer patients with high expression of actionable molecules defined as cognate target molecules. However, patient stratification based on the actionable molecules dictating the effectiveness of targeted drugs has remained understudied in HCC. EXPERIMENTAL DESIGN & RESULTS: Paired tumor and non-tumoral tissues derived from a total of 130 HCC patients were studied. Real-time RT-PCR was used to analyze the mRNA expression of actionable molecules in the tissues. mRNA levels of EGFR, VEGFR2, PDGFRß, FGFR1, and mTOR were up-regulated in tumors compared to non-tumors in 35.4, 42.3, 61.5, 24.6, and 50.0% of patients, respectively. Up-regulation of EGFR was observed at early stage and tended to gradually decrease toward late stages (BCLC stage A: 41.9%; B: 30.8%; C: 17.6%). Frequency of VEGFR2 expression in tumors at stage C was lower than that in the other stages (BCLC stage A: 45.9%; B: 41.0%; C: 29.4%). PDGFRß and mTOR were observed to be up-regulated in more than 50% of tumors in all the stages whereas FGFR1 was up-regulated in only about 20% of HCC irrespective of stages. A cluster analysis of actionable gene expression revealed that HCC can be categorized into different subtypes that predict the effectiveness of molecular targeted agents and combination therapies in clinical trials. Analysis of in vitro sensitivity to sorafenib demonstrated that HCC cells with up-regulation of PDGFRß and c-Raf mRNA are more susceptible to sorafenib treatment in a dose and time-dependent manner than cells with low expression of the genes. CONCLUSIONS: mRNA expression analysis of actionable molecules could provide the rationale for new companion diagnostics-based therapeutic strategies in the treatment of HCC.

Polymorphisms near interleukin 28B gene are not associated with hepatitis B virus clearance, hepatitis B e antigen clearance and hepatocellular carcinoma occurrence.

BACKGROUND: Polymorphisms near the IL28B gene have been proposed to be strongly associated with treatment response and the rate of spontaneous clearance of hepatitis C virus infection, and treatment response of hepatitis B virus (HBV) infection. In this study, we aimed to determine whether these polymorphisms could affect natural courses of HBV infection. METHODS: Genetic variations were identified through direct DNA sequencing using TaqMan assay in 1,439 patients with past or present HBV infection. Subjects included 404 spontaneously recovered patients, 313 chronic hepatitis B (CHB) patients, 305 liver cirrhosis (LC) patients and 417 hepatocellular carcinoma (HCC) patients. Three polymorphisms near the IL28B gene, rs8099917T>G, rs12979860C>T and rs12980275A>G, were identified. Associations between these polymorphisms and HBV clearance, hepatitis B e antigen (HBeAg) clearance as well as HCC occurrence among patients were analyzed using logistic regression analyses adjusted for age and gender. RESULTS: There were no significant associations between these polymorphisms and the HBV clearance both in CHB and LC groups. Similarly, these polymorphisms showed no significant associations with HBeAg clearance and the occurrence of HCC either. DISCUSSION: No significant association was identified between polymorphisms near the IL28B gene and the natural courses of chronic HBV infection, including the HBV clearance and HCC occurrence.

BNIP3 is degraded by ULK1-dependent autophagy via MTORC1 and AMPK.

BNIP3 (BCL2/adenovirus E1B 19 kDa interacting protein 3) is an atypical BH3-only protein that is induced by hypoxia-inducible factor 1 (HIF1) under hypoxia. BNIP3 is primarily regulated at the transcriptional level. However, little is known about the underlying mechanism of BNIP3 degradation. In this study, we found that BNIP3 was downregulated when hypoxia was accompanied by amino acid starvation. The BNIP3 downregulation did not occur at the transcription level and was independent of HIF1A. BNIP3 was primarily degraded by the proteasome, but BNIP3 was subjected to both proteasomal and autophagic degradation in response to starvation. The autophagic degradation of BNIP3 was dependent on ATG7 and MAP1LC3. We determined that autophagic degradation of BNIP3 was specifically regulated by ULK1 via the MTOR-AMPK pathway. Moreover, we confirmed that BNIP3 could play a protective role in tumor cells under hypoxia, and the treatment with Torin1, an MTOR inhibitor, decreased the BNIP3 level and enhanced the death of hypoxic tumor cells.

Rapamycin inhibits both motility through down-regulation of p-STAT3 (S727) by disrupting the mTORC2 assembly and peritoneal dissemination in sarcomatoid cholangiocarcinoma.

Cholangiocarcinoma (CC) is a malignant epithelium neoplasm that originates from the bile epithelium and for which there are few therapeutic strategies. The mTOR pathway involved in many cellular processes was reported to be up-regulated in various cancers. We investigated the activation of the AKT/mTOR pathway in CC cell lines with different degrees of dedifferentiation and found that rapamycin could suppress the motility and the peritoneal dissemination of sarcomatoid SCK cells. Inhibition of the mTOR pathway with rapamycin decreased significantly the number of tumor nodules and prolonged the survival rates of nude mice inoculated with sarcomatoid CC cells. Prolonged treatments with rapamycin were found to disrupt the mTORC2 assembly and to reduce the phosphorylation of STAT3 at Ser 727. Rapamycin decreased both mRNA and protein levels of MMP2 and Twist1, which are regulated by STAT3 and associated with cancer metastasis. The overexpression of STAT3 S727A lacking the phosphorylation site resulted in significantly less sensitivity to rapamycin than the overexpression of STAT3 WT. Taken together, our results suggest that rapamycin could suppress the motility of sarcomatoid CC by down-regulating p-STAT3 (S727) through the impairment of mTORC2 assembly.

REST-dependent expression of TRF2 renders non-neuronal cancer cells resistant to DNA damage during oxidative stress.

REST is a neuronal gene silencing factor ubiquitously expressed in non-neuronal tissues. REST is additionally believed to serve as a tumor suppressor in non-neuronal cancers. Conversely, recent findings on REST-dependent tumorigenesis in non-neuronal cells consistently suggest a potential role of REST as a tumor promoter. Here, we have uncovered for the first time the mechanism by which REST contributes to cancer cell survival in non-neuronal cancers. We observed abundant expression of REST in various types of non-neuronal cancer cells compared to normal tissues. The delicate roles of REST were further evaluated in HCT116 and HeLa, non-neuronal cancer cell lines expressing REST. REST silencing resulted in decreased cell survival and activation of the DNA damage response (DDR) through a decrease in the level of TRF2, a telomere-binding protein. These responses were correlated with reduced colony formation ability and accelerated telomere shortening in cancer cells upon the stable knockdown of REST. Interestingly, REST was down-regulated under oxidative stress conditions via ubiquitin proteasome system, suggesting that sustainability of REST expression is critical to determine cell survival during oxidative stress in a tumor microenvironment. Our results collectively indicate that REST-dependent TRF2 expression renders cancer cells resistant to DNA damage during oxidative stress, and mechanisms to overcome oxidative stress, such as high levels of REST or the stress-resistant REST mutants found in specific human cancers, may account for REST-dependent tumorigenesis.

Transdermal delivery of hyaluronic acid -- human growth hormone conjugate.

Hyaluronic acid (HA) is one of the major components of extracellular matrix (ECM). Keratinocyte and fibroblast are known to have HA receptors in the skin. Fibroblast also has human growth hormone (hGH) receptors. In this work, HA-hGH conjugate was developed as a receptor mediated transdermal delivery system of protein drugs. HA-hGH conjugate was synthesized by specific coupling reaction between aldehyde modified HA and the N-terminal amine group of hGH. We could confirm the proliferative effect of HA on keratinocyte and fibroblast, and the biological activity of HA-hGH conjugate in fibroblast with an elevated expression level of phosphorylated Janus kinase 2 (p-JAK2). Interestingly, fluorescence microscopy clearly visualized the dramatically enhanced penetration of HA-hGH conjugate through the dorsal skin of mice after topical treatment with FITC labeled HA-hGH conjugate. According to pharmacokinetic analysis, HA-hGH conjugate appeared to be delivered through the skin into the blood stream possibly by the receptor mediated transdermal delivery. This work confirms the feasibility of using the HA-hGH conjugate as a model system for the receptor mediated transdermal delivery of protein drugs and their further exploitation for various cosmetic and tissue engineering applications.

[A case of primary mucoepidermoid carcinoma arising from the common bile duct].

Mucoepidermoid carcinoma of the bile duct is an extremely rare tumor. Seventeen cases originating from intrahepatic bile duct and 2 cases from common hepatic duct have been reported in the English literature. Mucoepidermoid carcinoma arising from the common bile duct has not been previously reported. A 68 year-old man was admitted due to obstructive jaundice. Computed tomography showed a malignant tumor of the common bile duct located in the intrapancreatic segment. Filling defects of the distal common bile duct was seen on endoscopic retrograde cholangiogram. Under the impression of bile duct cancer, pylorus-preserving pancreatoduodenectomy was performed. Histologic diagnosis of the resected specimen was mucoepidermoid carcinoma of the common bile duct. After surgery, the patient received concurrent chemoradiotherapy, and planned to receive additional chemotherapy. We herein report on a first case of primary mucoepidermoid carcinoma of the common bile duct, and review the literature.

Case report: a case of light chain deposition disease involving liver and stomach with chronic hepatitis C virus infection and hepatocellular carcinoma.

Light chain deposition disease (LCDD) is a rare, plasma cell proliferative disorder characterized by mainly abnormal light chain deposition in various organs. Hepatitis C virus (HCV) is a hepatotrophic and lymphotrophic virus and significantly related to B-cell proliferation. This is a case report of systemic LCDD involving liver, stomach, bone marrow, and probably kidney, in a patient with HCV-related hepatocellular carcinoma (HCC). A 62-year-old man with chronic HCV infection who presented with a small HCC in segment 8 of the liver and nephrotic syndrome showed kappa typed immunoglobulin light chain depositions in biopsy specimens of bone marrow, stomach, and non-tumorous liver parenchyma. After treatment of the HCC with transarterial chemoembolization, antiviral therapy for chronic hepatitis C was started. The patient showed early virologic response at 12 weeks of treatment; however, antiviral therapy was discontinued due to adverse effects and he was lost to follow-up. This is the first case of LCDD involving the liver and stomach in a patient with chronic HCV infection and HCC, which may represent LCDD as a rare HCV-associated B cell proliferative disease.

[Comparison between conventional 4 L polyethylene glycol and combination of 2 L polyethylene glycol and sodium phosphate solution as colonoscopy preparation].

BACKGROUND/AIMS: Effective bowel preparation is essential for accurate diagnosis of colon disease. We investigated efficacy and safety of 2 L polyethylene glycol (PEG) solution with 90 mL sodium phosphate (NaP) solution compared with 4 L PEG method. METHODS: Between August 2009 and April 2010, 526 patients were enrolled who visited Seoul National University Bundang Hospital for colonoscopy. We allocated 249 patients to PEG 4 L group and 277 patients to PEG 2 L with NaP 90 mL group. Detailed questionnaires were performed to investigate compliance, satisfaction and preference of each method. Bowel preparation quality and segmental quality were evaluated. Success was defined as cecal intubation time less than 20 minutes without any help of supervisors. RESULTS: Both groups revealed almost the same baseline characteristics except the experience of operation. PEG 4 L group's compliance was lower than PEG 2 L with NaP 90 mL group. Success rate and cecal intubation time was not different between two groups. Overall bowel preparation quality of PEG 2 L with NaP 90 mL group was better than PEG 4 L group. Segmental bowel preparation quality of PEG 2 L with NaP 90 mL group was also better than PEG 4 L group in all segments, especially right side colon. Occurrence of hyperphosphatemia was higher in PEG 2 L with NaP 90 mL group than PEG 4 L group. However, significant adverse event was not reported. CONCLUSIONS: PEG 2 L with NaP 90 mL method seems to be more effective bowel preparation than PEG 4 L method.