Search

Background: Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients. Methods: Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR. Results: Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864–0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%. Conclusions: DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients. [ABSTRACT FROM AUTHOR]

The objective of this study was to clarify the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma with additional copies of MALT1. In this multicenter retrospective study, we enrolled 145 patients with gastric MALT lymphoma who underwent fluorescence in situ hybridization (FISH) analysis to detect t(11;18) translocation. The patient cohort was divided into three groups: Group A (n = 87), comprising individuals devoid of the t(11;18) translocation or extra MALT1 copies; Group B (n = 27), encompassing patients characterized by the presence of the t(11;18) translocation; and Group C (n = 31), including patients with extra MALT1 copies. The clinical outcomes in each cohort were collected. Over the course of a mean follow-up of 8.5 ± 4.2 years, one patient died of progressive MALT lymphoma, while 15 patients died due to etiologies unrelated to lymphoma. The progression or relapse of MALT lymphoma was observed in 11 patients: three in Group A, two in Group B, and six in Group C. In Groups A, B, and C, the 10-year overall survival rates were 82.5%, 93.8%, and 86.4%, respectively, and the 10-year event-free survival rates were 96.1%, 96.0%, and 82.9%, respectively. The event-free survival rate in Group C was significantly lower than that in Group A. However, no differences were observed in the 10-year event-free survival rates among individuals limited to stage I or II1 disease (equivalent to excluding patients with stage IV disease in this study, as there were no patients with stage II2), with rates of 98.6%, 95.8%, and 92.3% for Groups A, B, and C, respectively. In conclusion, the presence of extra copies of MALT1 was identified as an inferior prognostic determinant of event-free survival. Consequently, trisomy/tetrasomy 18 may serve as an indicator of progression and refractoriness to therapeutic intervention in patients with gastric MALT lymphoma, particularly stage IV gastric MALT lymphoma. [ABSTRACT FROM AUTHOR]

Background: Sessile serrated lesions (SSLs) are precursors of colon cancer, especially in cases of large, right colon. However, they are difficult to not only detect, but only clarify the margin of the lesion, which can lead to the poor endoscopic treatment outcomes. Aims: This study evaluated the usefulness of acetic acid spray with narrow-band imaging (A-NBI) for the better visualization of the margin of SSLs. Methods: From January 2013 to March 2022, patients with superficial elevated polyps suspected of being SSLs ≥ 10 mm with an endoscopic diagnosis that had been endoscopically resected at Hiroshima City Hiroshima Citizens Hospital were enrolled. Endoscopic images with white-light imaging (WLI), narrow-band imaging (NBI), indigo-carmine (IC), and A-NBI were recorded in each lesion and were randomly arranged and assessed by 10 endoscopists. We compared the visibility score (1 to 4) and color differences (ΔE) between inside and outside of the lesions among WLI, NBI, IC, and A-NBI. Results: Forty-one lesions in 33 cases were included, and a total of 164 images were evaluated. As for the visibility score, most of the lesions were scored as 1 or 2 on WLI, whereas most were scored 4 on A-NBI. The median ΔE of A-NBI was also significantly higher than that of WLI, NBI, or IC (20.5 vs. 8.3 vs. 8.2 vs. 12.3, P < 0.01). A significant correlation was observed between the color difference and visibility score (r = 0.53, P < 0.01). Conclusions: A-NBI may be a useful modality for identifying the margin of SSLs. [ABSTRACT FROM AUTHOR]

Patients with primary intestinal follicular lymphoma are often followed-up without a specific treatment, and this approach is called the "watch-and-wait approach." However, the long-term outcomes of this patient group have not been sufficiently investigated. We enrolled patients with primary intestinal follicular lymphoma who were diagnosed before 2016 and managed with the watch-and-wait approach in 20 institutions. We retrospectively investigated the overall, disease-specific, and event-free survival rates as well as the rate of spontaneous regression. Among the 248 patients with follicular lymphoma with gastrointestinal involvement, 124 had localized disease (stage I or II1). We analyzed the data of 73 patients who were managed using the watch-and-wait approach. During the mean follow-up period of 8.3 years, the follicular lymphoma had spontaneously resolved in 16.4% of the patients. The 5-year and 10-year overall survival rates were 92.9% and 87.1%, respectively. With disease progression (n = 7), initiation of therapy (n = 7), and histologic transformation to aggressive lymphoma (n = 0) defined as events, the 5-year and 10-year event-free survival rates were 91.1% and 86.9%, respectively. No patient died of progressive lymphoma. Thus, both 5-year and 10-year disease-specific survival rates were 100%. In conclusion, an indolent long-term clinical course was confirmed in the patients with primary intestinal follicular lymphoma. The watch-and-wait strategy is a reasonable approach for the initial management of these patients. [ABSTRACT FROM AUTHOR]

Purpose: To establish whether gastrectomy for early gastric cancer (EGC) in elderly patients is related to poor survival. Methods: The subjects of this retrospective study were patients aged ≥ 75 years with primary stage IA EGC, who underwent curative resection with endoscopic submucosal dissection (ESD) or surgery. Results: We analyzed data on 365 patients who underwent ESD and 170 patients who underwent surgery. Overall survival (OS) was not significantly different for the ESD group vs. the surgery group (5-year cumulative rates, 81.5% vs. 79.7%; log-rank test, P = 0.506). Multivariate analysis revealed that treatments; namely, ESD or surgery, were not associated with OS (hazard ratio 1.09, 95% confidence interval 0.77–1.51). Similar results were observed even in the subgroups with worse conditions, such as age > 80 years, Eastern Cooperative Oncology Group performance status 2–3, Charlson comorbidity index ≥ 2, and prognostic nutritional index ≤ 46.7. Using propensity score matching, we selected 88 pairs of patients who underwent ESD or surgery with baseline characteristics matched and found that OS was not different between the two groups (log-rank test, P = 0.829). Conclusion: OS was comparable for elderly patients who underwent ESD and those who underwent surgery for EGC. Surgical invasiveness did not worsen the prognosis, even for elderly patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Serum glycans are known to be good markers for the early diagnosis and prognostic prediction in many cancers. The aims of this study were to reveal the serum glycan changes comprehensively during the process of carcinogenesis from colorectal adenoma (CRA) to colorectal cancer (CRC) and to evaluate the usefulness of the glycan profiles as clinical markers for CRC. Methods: Serum samples were obtained from 80 histologically proven CRC and 36 CRA cases. The levels of glycans in the serum were examined with a comprehensive, quantitative, high‐throughput unique glycome analysis, and their diagnostic and prognostic abilities were evaluated. Results: Among 34 stably detected glycans, nine were differentially expressed between CRC and CRA. Serum levels of hybrid type glycans were increased in patients with CRC compared with those with CRA (P < 0.001), and both hybrid‐type and multi‐antennary glycans were significantly increased in advanced cancer cases. The glycan, m/z 1914, showed the highest diagnostic value among the decreased glycans, whereas m/z 1708 showed the highest among the increased glycans. The glycan ratio m/z 1708/1914 showed a higher area under the receiver operating characteristic curve (0.889) than any other single glycan or conventional tumor marker, such as carcinoembryonic antigen (0.766, P = 0.040) and carbohydrate antigen 19‐9 (0.615, P < 0.001). High m/z 1708/1914 was also correlated with an advanced cancer stage and short overall survival. Conclusion: Serum glycans, especially the m/z 1708/1914 ratio, were useful for the diagnosis, staging, and prognosis prediction of CRC. [ABSTRACT FROM AUTHOR]

Background: Little is known about the association between immune-related adverse events (irAEs) and the efficacy and survival outcomes of nivolumab in patients with advanced gastric cancer (AGC). Objective: The present study examined the association between irAEs and the prognosis of patients with AGC treated with nivolumab. Patients and Methods: From July 2017 to November 2020, patients who had been diagnosed with advanced unresected gastric cancer and treated with nivolumab at our institution were included in this analysis. We compared the clinical and survival outcomes between the irAE and non-irAE groups. We also evaluated the factors associated with better survival in patients treated with nivolumab. Results: A total of 52 patients were included in the present study, and irAEs were observed in 13 (25%). Among the patients with measurable lesions (n = 29), the disease control rates were significantly higher in the irAE group than in the non-irAE group (88 vs. 24%; P = 0.0033). At the 8- and 12-week landmark analyses, the median overall survival (OS) in the irAE group was significantly longer than that in the non-irAE group, whereas the median progression-free survival was comparable between the groups. A multivariate analysis by Cox proportional hazard regression at the 8-week landmark revealed that the development of irAEs (hazard ratio 0.18; 95% confidence interval 0.0099–0.86) alone was positively associated with a longer OS. Conclusions: The development of irAEs might be associated with survival outcomes with nivolumab treatment in patients with AGC. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) for gastric neoplasms is a useful treatment globally. However, postoperative bleeding after gastric ESD is a serious, and sometimes life-threatening complication in patients receiving antithrombotic drugs, because antithrombotic drugs are considered to increase the risk of postoperative bleeding after gastric ESD. In contrast, withdrawal of antithrombotic drugs during the perioperative period increases the risk of thrombotic complications. Guidelines for the management of antithrombotic drugs during the periendoscopic period have been published by different countries, and recent guidelines place greater emphasis on the risk of thromboembolism with the discontinuation of antithrombotic drugs than on the risk of bleeding with the continuation of antithrombotic drugs. Several studies have reported on the validity of these guidelines, and clinical evidence is being established. Most studies reported that gastric ESD under continuation of aspirin or cilostazol did not increase the risk of bleeding, whereas heparin replacement was strongly associated with a higher risk of bleeding. However, the data regarding some clinical issues about the management of antithrombotic drugs, such as the safety of gastric ESD under continuation of thienopyridine, administration of multiple antithrombotic drugs including dual antiplatelet and anticoagulants (warfarin and direct oral anticoagulant), and effective prophylactic methods for postoperative bleeding after gastric ESD are lacking. Larger clinical data are needed to resolve the remaining issues in the future. [ABSTRACT FROM AUTHOR]

Background and Aim: Several factors, including proangiogenic cytokines, have been reported as predictive markers for the treatment effect of sorafenib in patients with hepatocellular carcinoma (HCC); however, most of them were determined based on one‐time measurements before treatment. Methods: We consecutively recruited 80 advanced HCC patients who were treated with sorafenib prospectively. Serum levels of eight proangiogenic cytokines and the appearance of adverse events were monitored periodically, and their correlations with the prognoses of the patients were evaluated. Results: Among six significant risk factors for overall survival in univariate analyses, high angiopoietin‐2 (hazard ratio, 2.06), high hepatocyte growth factor (hazard ratio, 2.08), and poor performance status before the treatment (hazard ratio, 2.48) were determined as independent risk factors. In addition, high angiopoietin‐2 at the time of progressive disease was a marker of short post‐progression survival (hazard ratio, 4.27). However, there was no significant variable that predicted short progression‐free survival except the presence of hepatitis B virus surface antigen. Conclusions: Predictions of overall survival and post‐progression survival were possible by periodically measuring serum proangiogenic cytokines, especially angiopoietin‐2, in patients with HCC treated with sorafenib. [ABSTRACT FROM AUTHOR]

Background/Aims: The role of an undifferentiated component in submucosal invasion and submucosal invasion depth (SID) for lymph node metastasis (LNM) of early gastric cancer (EGC) with deep submucosal invasion (SID ≥500 μm from the muscularis mucosa) after endoscopic submucosal dissection (ESD) has not been fully understood. This study aimed to clarify the risk factors (RFs), including these factors, for LNM in such patients. Methods: We enrolled 513 patients who underwent radical surgery after ESD for EGC with deep submucosal invasion. We evaluated RFs for LNM, including an undifferentiated component in submucosal invasion and the SID, which was subdivided into 500–999, 1,000–1,499, 1,500–1,999, and ≥2,000 µm. Results: LNM was detected in 7.6% of patients. Multivariate analysis revealed that an undifferentiated component in submucosal invasion (OR 2.22), in addition to tumor size >30 mm (OR 2.51) and lymphatic invasion (OR 3.07), were the independent RFs for LNM. However, the SID was not significantly associated with LNM. Conclusion: An undifferentiated component in submucosal invasion was one of the RFs for LNM, in contrast to SID, in patients who underwent ESD for EGC with deep submucosal invasion. This insight would be helpful in managing such patients. [ABSTRACT FROM AUTHOR]

Background: The molecular pathogenesis of non-alcoholic steatohepatitis (NASH) is not well defined. The objective of the present study was to identify disease progression-related cytokines and investigate the molecular pathogenesis of such changes in NASH. Methods: A study population of 20 non-alcoholic fatty liver (NAFL) and 59 NASH patients diagnosed by liver biopsy and 15 healthy volunteers was recruited. The serum pro- and anti-inflammatory cytokines were measured by a multiple enzyme-linked immunosorbent assay. The hepatic mRNA expressions of cytokines were measured by real-time PCR. A monocyte cell line was stimulated with Toll-like receptor (TLR) ligand under a high glucose and insulin condition, and cellular cytokine mRNA expression was quantified. Results: One group of cytokines was higher in NAFL and NASH than in controls, while another group was higher in NASH than in NAFL and controls. The NASH-specific second group included interleukin (IL)-15 and interferon-γ-inducible protein (IP)-10. In particular, IP-10 was higher in NAFL than in controls and higher in NASH than in NAFL and controls. The sensitivity to diagnose NASH was 90%, with specificity of 50%. Insulin resistance reflecting a high glucose and insulin condition resulted in higher IP-10 mRNA expression in the monocyte cell line only with concomitant TLR-2 stimulation. Conclusions: IP-10 is a sensitive marker of the need for liver biopsy. Insulin resistance with bacteria-related TLR-2 stimulation might induce IP-10 production from monocytes. Insulin resistance and intestinal barrier function should be intensively controlled to prevent progression from NAFL to NASH. [ABSTRACT FROM AUTHOR]

Aim Recurrence of hepatocellular carcinoma (HCC) is observed frequently, even after curative treatments. The aim of this study is to elucidate the risk factors for recurrence of HCC after radiofrequency ablation (RFA), focusing on the carcinogenic potential of the liver assessed by α-fetoprotein (AFP). Methods We enrolled 357 consecutive patients who underwent complete ablation by RFA for primary HCC (≤3 cm, ≤3 tumors) and analyzed the correlation between 17 critical parameters, including AFP and HCC recurrence. Results Recurrence was observed in 236 patients during a mean observation period of 54.3 months. Multivariate analysis revealed that multiple tumors (risk ratio [RR] = 1.70, 95% confidence interval [CI] = 1.27-2.26, P < 0.001), high AFP (>10 ng/mL, RR = 1.45, 95% CI = 1.09-1.94, P < 0.001) and high des-γ-carboxyprothrombin (>40 mAU/mL, RR = 1.52, 95% CI = 1.13-2.02, P < 0.005) were significantly correlated with recurrence. AFP was selected as a significant factor even when the cut-off level was set lower (≤5 ng/mL). The risk of recurrence increased linearly according to the increase of the lowest AFP level after RFA and the adjusted ratios relative to AFP less than 5 ng/mL were 1.56, 2.14, 2.57 and 3.13 in AFP 5-10 ng/mL, 10-20 ng/mL, 20-50 ng/mL and over 50 ng/mL, respectively. In addition, the recurrence rate was predicted by the AFP level after RFA, regardless of the level before the treatment. Conclusion AFP less than 5 ng/mL after curative RFA was an important predictor of a better prognosis and was considered to indicate the low carcinogenic potential of the non-cancerous liver. [ABSTRACT FROM AUTHOR]

Objectives The aims of this study were to determine the change in whole-serum N-glycan profile in autoimmune pancreatitis (AIP) patients and to investigate its clinical utility. Methods We collected serum from 21 AIP patients before any treatment, and from 60 healthy volunteers (HLTs). Serum glycan profile was measured by comprehensive and quantitative high-throughput glycome analysis. Results Of the 53 glycans detected, 14 were differentially expressed in AIP patients. Pathway analysis demonstrated that agalactosyl and monogalactosyl bi-antennary glycans were elevated in AIP patients. Among the 14 glycans, #3410, #3510, and #4510 showed high area under receiver operating characteristic (AUROC) values (0.955, 0.964, and 0.968 respectively) for the diagnosis of AIP. These three glycans were mainly bound to immunoglobulin G; however, their serum levels were significantly higher, even in AIP patients who showed lower serum IgG4 levels, than in HLTs. Conclusions We demonstrated, for the first time, whole-serum glycan profiles of AIP patients and showed that the levels of glycans #3410, #3510, and #4510 were increased in AIP patients. These glycans might be valuable biomarkers of AIP. [ABSTRACT FROM AUTHOR]

Aim Most of the modification of N-glycosylation reported in cancers including hepatocellular carcinoma ( HCC) were based on the examinations of a small number of patients or particular proteins. The aim of this study is to reveal changes in whole serum N-glycan profiles systematically during the process of hepatocarcinogenesis and to elucidate their clinical application. Methods We analyzed sera from 105 patients with chronic hepatitis/liver cirrhosis ( CH/ LC) and age-/sex-matched healthy volunteers ( HLT), as well as from 114 patients with HCC. Serum N-glycan profiles were measured comprehensively by a new, quantitative, high-throughput method and compared with clinical parameters. Results The total amount of N-glycan expression was significantly higher in patients with CH/ LC than in HLT; however, no differences were observed between CH/ LC and HCC patients. In HCC patients, multi-antennary glycans with fucose residues, particularly m/z 3195, were increased compared with CH/ LC patients. The expression of m/z 3195 was high, especially in patients with a high number of intrahepatic lesions (>3), large tumor size (>3 cm), macroscopic vascular invasion or metastasis. The ratio of pairs of glycans on the same path of the biosynthesis pathway ( m/z 3195/1914) showed a higher area under the receiver-operator curve of 0.810 than any other single glycan to distinguish HCC from CH/ LC. Conclusion We demonstrate the full spectrum of the alterations of serum N-glycans comprehensively in patients with liver disease, and elucidate the possible use of glycans as novel biomarkers of liver disease progression. [ABSTRACT FROM AUTHOR]

Background: Cell-free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer.Methods: The authors compared K-ras mutations detected in endoscopic ultrasound-guided fine-needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K-ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates.Results: The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3%), 22 of 75 samples (29.3%), and 6 of 75 samples (8.0%), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6%), 29 of 75 samples (38.6%), and 4 of 75 samples (5.3%), respectively. Overall, the K-ras mutation rates in tissue and ctDNA were 74.7% and 62.6%, respectively, and the concordance rate between them was 58 of 75 samples (77.3%). Survival did not appear to differ by the presence of K-ras mutations in tissue DNA, but the survival of patients with K-ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation.Conclusions: Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival. [ABSTRACT FROM AUTHOR]

Background/objectives Diagnosing the invasiveness of intraductal papillary mucinous neoplasms (IPMNs) is difficult, especially by blood test. Alterations in serum glycan profiles have been reported for several cancers, but changes in serum glycan profiles have not been investigated in patients with IPMNs. The objectives of this study were to determine the serum N -glycan profile and to investigate its clinical utility in patients with IPMNs. Methods We measured serum N -glycan profiles in 79 patients with IPMNs, including 13 invasive IPMNs, by performing comprehensive glycome analysis and assessed the relationship between N -glycan changes and clinical parameters. Results Seventy glycans were identified and their expression profiles were significantly different depending on the cyst size, the presence of an enhancing solid component, and the histological grade of the IPMN. Nine glycans were highly expressed in patients with invasive IPMNs. The glycan m/z 3195, which is a fucosylated tri-antennary glycan, had the highest diagnostic value for distinguishing invasive IPMNs from non-invasive IPMNs (area under the receiver operating characteristic curve = 0.803). Multivariate analyses revealed high levels of m/z 3195 [odds ratio (OR), 20.5; 95% confidence interval (CI) 2.60–486.4] and the presence of enhancing solid components (OR, 35.8; 95% CI, 5.39–409.6) were significant risk factors for invasive IPMNs. Conclusions We performed a comprehensive evaluation of the changes in serum N -glycan profiles in patients with IPMNs for the first time. We determined that increased expression of fucosylated complex-type glycans, especially m/z 3195, is a potential marker for invasive IPMNs. [ABSTRACT FROM AUTHOR]

Background and Aims Serum glycans have been reported to be promising diagnostic markers for many inflammatory diseases and cancers. The aims of this study were to investigate whole glycan expression in patients with non-alcoholic fatty liver diseases and to evaluate the potential use of glycan profiles as new clinical biomarkers to distinguish non-alcoholic steatohepatitis ( NASH) from simple steatosis ( SS). Methods We collected sera from 42 histologically proven NASH and 15 SS patients prior to treatment. Serum glycan profiles were measured by comprehensive, quantitative, high-throughput glycome analysis, and diagnostic values of serum glycans for NASH prediction were examined. Results Among the 41 serum glycans examined, the expression levels of 8 glycans in NASH were significantly higher than those of SS. Out of these eight glycans, three glycans ( m/z 1955, 2032, and 2584) showed high areas under the receiver operating characteristic curve (0.833, 0.863, and 0.866, respectively) for distinguishing NASH from SS. In multivariate analyses with clinical parameters and serum glycans, these three glycans were significant predictive factors for distinguishing NASH from SS. The odds ratio of m/z 1955, 2032, and 2584 were 48.5, 6.46, and 11.8, respectively. These glycans also correlated significantly with lobular inflammation, ballooning, and fibrosis, but not with steatosis. Conclusion We clearly demonstrated whole-serum glycan profiles in NASH patients, and the feasibility of serum glycans ( m/z 1955, 2032, and 2584) as new noninvasive biomarkers for distinguishing NASH from SS. [ABSTRACT FROM AUTHOR]

Background: The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients. Methods: We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT). Results: Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group ( p < 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group ( p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18 %, p < 0.01) and PVTT (45 vs. 18 %, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups ( p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively). Conclusions: CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT. [ABSTRACT FROM AUTHOR]

Aim Recently, a relationship between platelets and cancer metastasis has been reported. The aim of this study is to elucidate the risk factors for extrahepatic metastasis ( EHM), with emphasis on association with platelets in patients, with hepatocellular carcinoma ( HCC). Methods We examined risk factors for EHM in 1613 consecutive, newly diagnosed HCC patients by logistic regression analysis (case-control study). We also examined the factors by Cox proportional hazard model in a retrospective cohort fashion in 803 patients who received non-curative treatment for HCC. Results In the case-control study, multivariate analysis revealed that high platelet counts (odds ratio [ OR] = 4.84; 95% confidence interval [ CI] = 1.29-29.54; P = 0.01), high tumor number and the presence of macroscopic vascular invasion were significantly associated with EHM. In the cohort study, EHM was diagnosed in 71 patients during the study period (mean observation time = 23.3 months). On multivariate analysis, high tumor number, high des-γ-carboxyprothrombin ( DCP) and Child- Pugh class A were significantly correlated with EHM, and the patients with high platelet counts tended to develop EHM ( OR = 1.73; 95% CI = 0.99-3.14; P = 0.055). Conclusion HCC patients with high platelet counts, as well as large numbers of tumors, high serum DCP and Child- Pugh class A, are at risk for EHM. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation ( RFA) is frequently used to treat early stage hepatocellular carcinoma. Two of the most cumbersome side-effects of the ablation procedure are intractable pain and vagotonia when deep sedation is not used. We describe local injection of anesthetic into Glisson's sheath as a new technique for overcoming these problems. Lidocaine was injected into Glisson's sheath when radiofrequency ablation of hepatocellular carcinomas, which were located adjacent to Glisson's sheath, could not be continued due to severe pain ( n = 8) or bradycardia ( n = 3). In all three patients who showed vagotonia with bradycardia during the ablations, injection of lidocaine prevented bradycardia, allowing completion of the radiofrequency ablation. Pain was reduced in all eight patients who experienced pain during ablation. No side-effects were observed during the procedures. Injection of anesthetic into Glisson's sheath is simple and effective for reducing intractable pain and vagotonia associated with RFA. [ABSTRACT FROM AUTHOR]

Aim We investigated whether continuous sorafenib administration keeps suppressing the growth of hepatocellular carcinoma ( HCC) after first progressive disease ( PD), and whether it prolongs patients' survival. Methods The size of metastatic lesions was measured in 36 patients with advanced HCC treated with sorafenib. The tumor growth rates before and after radiological PD as well as survival were compared between the patients who continued ( n = 23) and stopped ( n = 13) sorafenib at first radiological PD. Results The growth rate did not differ between before and after PD in patients who continued sorafenib, while it increased after PD in patients who stopped sorafenib at PD ( P = 0.002). Survival beyond first progression was longer in patients who continued sorafenib than in those who stopped it at PD ( P = 0.012), and this tendency was observed even when the analysis was limited to Child- Pugh class A patients ( P = 0.085). Conclusion Sorafenib administration beyond first radiological PD could continuously suppress HCC growth and may have survival benefit. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to determine the change of whole-serum N-glycan profile in ulcerative colitis (UC) patients and to investigate its clinical utility. Methods: We collected serum from 75 UC patients at the time of admission and the same number of age/sex-matched healthy volunteers. Serum glycan profile was measured by comprehensive quantitative high-throughput glycome analysis and was compared with disease activity and prognosis. Results: Out of 61 glycans detected, 24 were differentially expressed in UC patients. Pathway analysis demonstrated that highly sialylated multi-branched glycans and agalactosyl bi-antennary glycans were elevated in UC patients; in addition, the glycan ratio m/z 2378/1914, which also increased in UC, showed the highest Area under Receiver Operating Characteristic curve (0.923) for the diagnosis of UC. Highly sialylated multi-branched glycans and the glycan ratio m/z 2378/1914 were higher in the patients with total colitis, Clinical Activity Index >10, Mayo endoscopic score 3, or a steroid-refractory status. In particular, the glycan ratio m/z 2378/1914 (above median) was an independent prognostic factor for the need for an operation (hazard ratio, 2.67; 95% confidence interval, 1.04–7.84). Conclusions: Whole-serum glycan profiles revealed that the glycan ratio m/z 2378/1914 and highly sialylated multi-branched glycans increase in UC patients, and are correlated with disease activity. The glycan ratio m/z 2378/1914 was an independent predictive factor of the prognosis of UC. [ABSTRACT FROM AUTHOR]

Aim Des-γ-carboxyprothrombin ( DCP) is known to be increased by the use of sorafenib for the treatment of hepatocellular carcinoma ( HCC), despite its therapeutic efficacy. In addition to the tumor progression, hypoxia that impairs vitamin K uptake is known to induce DCP and this mechanism may explain DCP elevation by sorafenib. In this study, we tried to evaluate the effect of sorafenib treatment using a new marker, NX-DCP, which is specific to vitamin K absence. Methods Serum DCP and NX-DCP were measured in 50 consecutive HCC patients before and 1 week after starting sorafenib, and compared with the treatment effect using the modified Response Evaluation Criteria in Solid Tumors guidelines. Results DCP and NX-DCP increased 1.58- (median, range 0.21-28.7) and 1.20-fold (median, range 0.41-14.2) after the administration of sorafenib, respectively. The increases of both markers were less than twofold in approximately half of the patients (low-elevation group). However, 12 patients showed over twofold increase of both DCP and NX-DCP (double-elevation group), and eight patients showed over twofold increase of DCP alone ( DCP-elevation group). The disease control rate ( DCR) of the DCP-elevation group (12.5%) was significantly lower than those of the double-elevation group (75.0%, P = 0.020) and the low-elevation group (60.0%, P = 0.042). Progression-free survival ( PFS) was significantly shorter in the DCP-elevation group than in the double-elevation group ( P = 0.006) and the low-elevation group ( P = 0.001). Conclusion NX-DCP in combination with DCP could be a useful biomarker of sorafenib treatment for advanced HCC. [ABSTRACT FROM AUTHOR]

Background: Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility. Methods: Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters. Results: Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan ( m/ z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway ( m/ z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p < 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44-4.79) was higher than that of any single glycan and 1-year survival of patients with a high and low ratio was 36.9 and 69.2 %, respectively, ( p = 0.001). Conclusions: Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously. [ABSTRACT FROM AUTHOR]

Background and Aim Follistatin ( FST) is a glycoprotein expressed in most organs, which interacts with activins or other members of the transforming growth factor beta family. Recently, several reports have shown that FST regulates a variety of processes during tumor progression. Here, serum FST in patients with liver diseases was measured, and its clinical utility as a biomarker was assessed. Methods Serum was collected from 162 patients (91 hepatocellular carcinoma [ HCC], 43 liver cirrhosis, and 28 chronic hepatitis) as well as from 16 healthy volunteers. FST was quantified by enzyme-linked immunosorbent assays, and levels were compared with clinical parameters including survival of the HCC patients. Results Median serum FST levels in HCC, liver cirrhosis, chronic hepatitis, and healthy volunteers were 1168, 1606, 1324, and 1661 pg/m L, respectively, not significantly different. In HCC patients, higher serum FST was associated with greater age, hepatitis C virus antibody-negativity, large tumor size, g-glutamyl transpeptidase, des-gamma carboxyprothrombin and presence of portal vein tumor thrombus. Survival of HCC patients with high FST levels was significantly shorter than for those with low levels ( P = 0.004). Multivariate analysis revealed that in addition to large tumor size and presence of portal vein thrombus, high FST levels were independently correlated with poor prognosis (hazard ratio = 2.41, 95% confidence interval = 1.16-5.00, P = 0.02). Conclusions Serum FST levels are significantly associated with HCC prognosis and could represent a predictive biomarker in this disease. [ABSTRACT FROM AUTHOR]

Aim: Hepatocellular carcinoma (HCC) is a common clinical problem all over the world. Fucosylated hemopexin (Fuc-Hpx) is a newly reported glycoprotein for the diagnosis of HCC, however, its clinical implications are unclear. The aim of this study was to elucidate the clinical utility of Fuc-Hpx in Japanese patients with HCC. Methods: The sera from 331 HCC patients, 45 with liver cirrhosis (LC), 85 with chronic hepatitis (CH) and 22 healthy people were examined for the expression of Fuc-Hpx; the level was compared with clinical parameters as well as hemopexin (Hpx) expression. The expressions of Fuc-Hpx in 12 HCC tissues and corresponding adjacent non-cancerous liver tissues were also examined. Results: No correlation was observed between Hpx and Fuc-Hpx level. The median Fuc-Hpx levels in healthy people and CH, LC and HCC patients were 3.8, 3.7, 6.1 and 7.6 AU/mL, respectively (CH vs LC, P = 0.002; CH vs HCC, P < 0.001; LC vs HCC, P = 0.02). Multivariate analysis revealed that low albumin, low prothrombin time and the presence of HCC were significantly correlated with high Fuc-Hpx ( P = 0.013, =0.001 and <0.001, respectively). Among the HCC patients, albumin was correlated with high Fuc-Hpx; however, none of the tumor factors, such as tumor size, tumor number and tumor stage, was correlated with Fuc-Hpx level. The expression of Fuc-Hpx in cancer tissue was not different from that in non-cancerous tissue. Conclusion: Fuc-Hpx is a valuable biomarker for HCC but it might be a marker for hypercarcinogenic liver rather than a marker for tumor-bearing liver. [ABSTRACT FROM AUTHOR]

Backgroud and Aim: Chronic hepatitis C virus (HCV) infection is a well known risk factor for hepatocellular carcinoma (HCC). The aim of this study is to elucidate the genetic risk of development and recurrence of HCC in patients with HCV. Methods: A total of 468 patients with HCV, including 265 with HCC were enrolled. We genotyped 88 single nucleotide polymorphisms (SNPs) in 81 genes expected to influence hepatocarcinogenesis using the iPLEX assay. Risk of HCC was clarified by stratifying patients into risk groups based on the multiplied odds ratio (MOR) for SNPs associated with HCC, and the cumulative effects on the development and recurrence of HCC were analyzed. Results: Six SNPs associated with risk of HCC were identified (OR range: 0.29-1.76). These included novel SNPs for hepatocarcinogenesis with HCV CCND2 rs1049606, RAD23B rs1805329, CEP164 rs573455, and GRP78rs430397 in addition to the known SNPs MDM2 rs2279744 and ALDH2 rs671. MOR analysis revealed that the highest risk group exerted about a 19-fold higher relative OR compared with the lowest risk group ( P = 1.08 × 10−5). Predicted 10-year HCC risk ranged from 1.7% to 96% depending on the risk group and the extent of fibrosis. Recurrence-free survival of radiofrequency ablation-treated HCC in the high risk group ( n = 53) was lower than that of low risk group ( n = 58, P = 0.038). Conclusion: Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of HCC in Japanese patients with HCV. [ABSTRACT FROM AUTHOR]

Background and Aim: Sorafenib, the first agent demonstrated to have efficacy to improve the survival of patients with advanced hepatocellular carcinoma (HCC), is an active multikinase inhibitor affecting angiogenesis and tumor proliferation. We analyzed cytokines related to angiogenesis or cell proliferation, and tried to determine their utility as biomarkers of sorafenib treatment effect for HCC. Methods: Nine serum cytokines (angiopoietin-2 [Ang-2], follistatin, granulocyte colony-stimulating factor [G-CSF], hepatocyte growth factor [HGF], interleukin-8 [IL-8], leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor) were measured in 30 HCC patients treated with sorafenib, and the effects of treatment were compared using modified Response Evaluation Criteria in Solid Tumors. Results: All but IL-8 were significantly higher at baseline in patients with progressive disease. Progression-free survival was significantly shorter in patients with high levels of Ang-2, G-CSF, HGF, and leptin, and the hazard ratios were 2.51, 6.89, 2.55, and 4.14, respectively. As the number of cytokines at a high level increased, the treatment response deteriorated. Disease progression was seen in three of 12 (25.0%) patients with zero to two high biomarkers, two of six (33.3%) patients with 3-5 high biomarkers, and 10 of 12 (83.3%) patients with six to eight high biomarkers ( P = 0.008). The prognosis of all patients with eight high biomarkers was progressive disease. Conclusion: High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC. [ABSTRACT FROM AUTHOR]

Presents a prototype of a novel television set (TV) with personal computer (PC) capability. Overview of the system; User interface of the television set; Functions of a mediator board; Conclusion.

There have been no comparative studies investigating the results of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with gastric mesenchymal tumors, including leiomyomas, leiomyosarcomas, schwannomas, and gastrointestinal stromal tumors (GISTs). We retrospectively reviewed the data of 142 patients with pathologically diagnosed gastric mesenchymal tumors treated at 11 institutions. We analyzed the correlation between the maximum standardized uptake value (SUVmax) evaluated using fluorodeoxyglucose-positron emission tomography (FDG-PET) and the tumor size. The correlation between the SUVmax and mitotic index was also investigated in GISTs. The SUVmax (mean ± standard deviation) was 0.5 ± 0.6 in very low-risk GISTs (n = 42), 2.1 ± 0.7 in low-risk GISTs (n = 26), 4.9 ± 0.8 in intermediate-risk GISTs (n = 22), 12.3 ± 0.8 in high-risk GISTs (n = 20), 1.0 ± 1.0 in leiomyomas (n = 15), 6.9 ± 1.2 in schwannomas (n = 10), and 3.5 in a leiomyosarcoma (n = 1). The SUVmax of GISTs with an undetermined risk classification was 4.2 ± 1.3 (n = 8). Linear associations were observed between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax of GISTs with a high mitotic index was significantly higher than that of GISTs with a low mitotic index (9.6 ± 7.6 vs. 2.4 ± 4.2). In conclusion, we observed positive correlations between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax also positively correlated with the mitotic index and risk grade in GISTs. Schwannomas showed a higher FDG uptake than GISTs and leiomyomas. [ABSTRACT FROM AUTHOR]