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Steroids are often administered at the time of transcatheter arterial chemoembolization (TACE), a standard treatment of hepatocellular carcinoma (HCC), with the expectation of preventing postembolization syndrome. Here we investigated the precise effects of steroids on TACE. We prospectively enrolled 144 HCC patients from 10 hospitals who underwent TACE. Three hospitals used steroids (steroid group, n=77) and the rest did not routinely use steroids (control group, n=67). The occurrence of adverse events and the algetic degree at 1-5 days post-treatment were compared between the groups. Fever (grades 0-2) after TACE was significantly less in the steroid group (56/21/0) compared to the control group (35/29/3, p=0.005, Cochran-Armitage test for trend). The suppressive effect of steroids against fever was prominent in females (p=0.001). Vomiting (G0/G1/ G2-) was also less frequent in the steroid group (70/5/2) versus the control group (53/10/3), but not significantly (p=0.106). The algetic degree and the grade of hematological adverse events, including hyperglycemia, did not differ between the groups. We conclude that the administration of steroids was useful for the prevention of adverse events after TACE in patients with HCC.

Objective Previous studies have reported that nadir oxygen delivery during cardiopulmonary bypass is associated with the occurrence of postoperative acute kidney injury (AKI). However, these measurements only considered the bottom point of the oxygen delivery (DO2) but did not consider the duration of DO2. We aimed to examine whether the time–dose response of DO2 during cardiopulmonary bypass can be used to estimate the risk for postoperative AKI. Methods We evaluated 112 patients who underwent cardiac surgeries with cardiopulmonary bypass. We analyzed the perfusion parameters recorded every 20 seconds. To obtain time–dose response of DO2 index (DO2i), the area under the curve was calculated as below the 300 mL/min/m2 threshold, which accounts for depth and duration of cumulative oxygen debt. In addition, the cumulative time below DO2i 300 mL/min/m2 was also calculated. Receiver operating characteristic analysis, univariate regression analysis, and multivariate regression analysis were used to evaluate associations between perioperative variables and postoperative AKI. Results Patients who developed AKI had larger area under the curve below the 300 mL/min/m2 threshold (1581 vs 632; P Conclusions The time–dose response of DO2i during cardiopulmonary bypass is a better indicator than nadir DO2i in evaluating AKI risk. Maintaining DO2i levels >300 mL/min/m2 may result in decreased risk for postoperative AKI.

Transcatheter arterial chemoembolization (TACE) is often performed before radiofrequency ablation (RFA) for the treatment of early-stage hepatocellular carcinoma (HCC). TACE prior to RFA can expand the ablated area and reduce the tumor size, facilitating complete ablation. However, the factors correlated with size reduction remain uncertain. The aim of this study was to identify the factors associated with size reduction by TACE and develop a formula to predict the reduction rate. A total of 100 HCC patients treated with TACE followed by RFA at least 20 days later were enrolled. The tumor size was measured at the time of TACE and RFA, and correlations between the reduction rate and 13 clinical factors were examined. A formula to predict the reduction rate was built using the factors obtained by the analysis. Reduction in the tumor size was observed in 69 nodules, and the median reduction rate was 16.2%. A multivariate regression analysis revealed that a large tumor size (p< 0.01) and a long interval between the therapies (p= 0.01) were factors for a high tumor reduction rate, with tumor size more strongly related to the degree of reduction. A size reduction of more than 10% can be expected by waiting 20 days after TACE when the size of the tumor at TACE is over 25 mm in diameter. The tumor size

Background We aimed to determine expression patterns of cardiac stem cells in the left atrium (LA) tissue from patients with atrial fibrillation. Methods LA appendages were obtained during open-heart surgery and processed for explant cell culture and tissue analysis ( n = 319). The total number of grown cells and c-kit positive cells were analyzed by flow cytometry after 4 weeks of culture. The remaining tissue was used for Masson's trichrome staining to determine the area of the fibrosis. Results The diameter of the LA, as measured by echocardiography, was significantly larger in the AF group than in the sinus rhythm group. Reverse transcription polymerase chain reaction analysis revealed higher expression of collagen in the AF group and an increase in the expression of basic fibrosis growth factor and transforming growth factor-2 and -3. Masson's trichrome staining showed progression of fibrosis in the AF tissue. In addition, the expression of apoptosis-related genes were significantly higher in AF group. There was no difference in the expression of connexin-40 between groups, while the expression of connexin-43 was decreased and that of connexin-45 was increased in the AF group. The total numbers of grown cells as well as c-kit positive cells after 4 weeks of cardiac tissue culture were significantly lower in the AF group. Conclusion Progression of remodeling in LA tissue was observed in AF patients. The number of c-kit positive cells cultured from LA appendages was reduced in AF patients, suggesting impairments in self-renewal.

Background and Aim Few reports describe the endoscopic double-stenting procedure for malignant biliary and duodenal obstructions. We evaluated the clinical outcomes from double stenting, and analyzed the risk factors for biliary stent dysfunction following double stenting. Methods Eighty-one patients who underwent endoscopic double stenting for malignant biliary and duodenal obstructions were retrospectively analyzed. We determined the stent dysfunction rate and the biliary stent dysfunction risk factors, and analyzed the endoscopic reintervention results. Results Overall survival time and survival time following double stenting were 365 (38–1673) days and 73 (20–954) days, respectively. After double stenting, the 3-month and 6-month duodenal stent dysfunction rates were 14% and 41%, respectively. Reintervention technical success rate was 100% (10/10), and mean gastric outlet obstruction scoring system scores improved from 0.7 to 2.4 points (P < 0.001). The 3-month and 6-month biliary stent dysfunction rates were 26% and 41%, respectively. The reintervention technical and clinical success rates were 95% (20/21) and 81% (17/21), respectively. Risk factors for biliary stent dysfunction following double stenting were events associated with duodenal stent dysfunction (odds ratio [OR], 11.1; 95% confidence interval [CI], 2.09–87.4; P = 0.0044) and the biliary stent end's location (OR, 6.93; 95% CI, 1.37–40.2; P = 0.0019). Conclusions Some patients had stent dysfunction irrespective of the survival period after double stenting. Endoscopic reintervention was technically feasible and clinically effective even after double stenting. Duodenal stent dysfunction and biliary stent end's location were risk factors for biliary stent dysfunction.

Purpose: To describe a technique suitable for treating severely angulated (>75°) necks during endovascular aneurysm repair using the Endurant stent-graft. Technique: In the push-up technique, the suprarenal stent is released early to fix the proximal stent-graft in place so that each stent in the neck can be deployed individually without displacing the device upward. It is important to push the delivery system up after each stent deployment to allow the fabric between the stents to fold up circumferentially. By doing so, there is minimal upward force applied to the suprarenal stent. Because the stents expand along the angulated neck while catching blood flow, this anatomical deployment is feasible, with hardly any change to the proximal neck shape after stent-graft implantation. Conclusion: The push-up technique and anatomical deployment with the Endurant stent-graft system are effective and safe methods for treating aneurysms with severely angulated necks.

Objective Oxidative stress is associated with the progression of chronic liver disease. Non-alcoholic fatty liver disease (NAFLD) is also an oxidative stress-related disease. However, the oxidative/anti-oxidative balance has not been fully characterized in NAFLD. The objective of the present study was to investigate the balance between oxidative stress and the anti-oxidative activity in NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC). Patients We recruited 69 patients with histologically proven NAFLD without HCC (NAFLD; n=58), and with NASH-related HCC (NASH-HCC; n=11). The 58 NAFLD patients included patients with non-alcoholic fatty liver (NAFL; n=14) and NASH (n=44). Methods The serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY) were determined and then used to calculate the oxidative index. The correlations among such factors as ROM, OXY, oxidative index, and clinical characteristics were investigated. Results In NAFLD, ROM positively correlated with the body mass index (BMI), hemoglobin A1c (HbA1c), C-reactive protein (CRP), and the histological grade or inflammatory scores, while only high HbA1c and CRP levels were significant factors that correlated with a higher ROM according to a multivariate analysis. OXY positively correlated with the platelet counts, albumin, and creatinine levels, while negatively correlating with age. However, it improved after treatment intervention. The oxidative index positively correlated with BMI, CRP, and HbA1c. The NASH-HCC patients exhibited a lower OXY than the NASH patients, probably due to the effects of aging. Conclusion Oxidative stress correlated with the levels of NASH activity markers, while the anti-oxidative function was preserved in younger patients as well as in patients with a well-preserved liver function. The NASH-HCC patients tended to be older and exhibited a diminished anti-oxidative function.

Following the publication of this article, we realize that there were some errors in the manuscript. Details of the experiments describing the gene silencing of RUNX3 with small interfering RNA (siRNA) were erroneously included in this paper, and all references to siRNA should have been deleted from the manuscript prior to publication. In the subsection entitled 'Cell lines and cell culture' on page 2577, the left‑hand column, the text should have indicated that the human HCC cell lines Hep3B and Huh7 were obtained from the American Type Culture Collection (ATCC; Manassas, VA, USA), whereas HLF cells were obtained from the Japanese Cancer Resources Bank (Tokyo, Japan). Lastly, an error was made in describing the calculation of the IC50 values, which did not correlate with the data shown in Fig. 2. Therefore, the subsection entitled 'Ectopic RUNX3 protein expression suppresses cell growth...' should have been entitled 'Ectopic RUNX3 protein expression increases 5‑FU and CDDP sensitivity', and the text herein should have read as follows: We analyzed the effects of RUNX3 on chemosensitivity in the RUNX3‑ or CAT (mock)‑transfected Hep3B and Huh7 cells. RUNX3 expression enhanced 5‑FU sensitivity in both cell lines; the cell viability with 5‑FU (100 nM) decreased from 66.3±4.6 to 34.3±5.0%, and from 71.0±4.7% to 27.0±5.5% in the Hep3B and Huh7 cells, respectively (Fig. 2A). RUNX3 expression also enhanced CDDP sensitivity in both cell lines; the cell viability with CDDP (100 nM) decreased from 58.7±2.6% to 25.7±4.9%, and from 67.7±4.1% to 25.7±7.5% in the Hep3B and Huh7 cells, respectively (Fig. 2B). We sincerely apologize for these errors and oversights, which have not affected any of the overall conclusions reported in the study, and regret any inconvenience they may have caused. [the original article was published in the Oncology Reports 35: 2576-2582, 2016; DOI: 10.3892/or.2016.4681].

According to recent advances in operative techniques, an increasing number of patients with liver dysfunction have been subjected to cardiac surgery. Model of End-Stage Liver Disease (MELD and MELD-XI) scores allow risk stratification of patients undergoing cardiac and non-cardiac surgeries.We retrospectively analyzed 1856 consecutive patients (69.3% male, mean 66.8 ± 12.2 years) undergoing cardiac surgery between 2008 and 2013 at our institution.The mean values of MELD/MELD-XI scores obtained from the total cohort were 9.7 ± 4.6/11.9 ± 4.8. Patients with high MELD/MELD-XI scores (12) were older, more anemic, and had lower left ventricular ejection fraction than those with low scores (all p0.0001). High scores were associated with longer hospitalization (36.8 ± 33.0 vs. 23.6 ± 21.5 days for MELD, 36.7 ± 34.0 vs. 23.5 ± 21.0 days for MELD-XI, both p0.0001) and higher in-hospital all-cause mortality (6.6% vs. 1.0% for MELD, 7.7% vs. 0.7% for MELD-XI). Atrial fibrillation occurred more frequently in the high MELD group, but this difference was not found for MELD-XI. MELD/MELD-XI could predict mortality with a sensitivity of 64.3%/60.0% and specificity of 79.1%/85.3%. Comparison of AUC values among MELD scores, individual MELD components, and Child-Turcotte-Pugh (CTP) classification showed that the predictive strength of MELD scores for mortality was stronger than individual parameters or CTP classification (AUC: 0.7702 for MELD, 0.7655 for MELD-XI, 0.5799 for CTP classification with pairwise p0.0001 and p=0.0002 vs. MELD and MELD-XI, respectively).Assessment of liver dysfunction using the MELD scores can be useful for predicting postoperative morbidity and mortality, which may allow additional risk stratification in patients undergoing cardiac surgery.

Background Graft-versus-host disease (GVHD) is a common complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Endoscopic biopsy can provide a definitive diagnosis, but the optimal endoscopic approach for diagnosis remains uncertain. This study evaluated whether ileocolonoscopic imaging can predict acute GVHD severity after allo-HSCT. Methods Consecutive patients who underwent allo-HSCT were referred to our institution, and those diagnosed with acute GVHD by pathology were included in this retrospective study. Results Fifty-one of 261 patients who underwent ileocolonoscopy were suspected to have acute intestinal GVHD. We performed univariate and multivariate conditional logistic regression with stepwise variable selection; villous atrophy in the terminal ileum remained a statistically significant predictor of GVHD severity (odds ratio, 4.69; 95% confidence interval, 1.07–20.60, P = 0.04). Patients were classified into three groups based on ileal endoscopic findings in the terminal ileum: group S, GVHD with severe villous atrophy; group M, mild atrophy; and group N, no atrophy. Compared with patients in groups M and N, those in group S had significant clinical GVHD at diagnosis (P = 0.03). In group S, three of four, compared with five of 13 patients in groups M and N, required the addition of second-line agents (P = 0.02). Conclusions This study showed that severe atrophy of the terminal ileum predicts severe clinical GVHD that is likely to be refractory to steroid treatment. Thus, the severity of terminal ileum atrophy may serve as a tool in predicting clinically severe GVHD. Trial registration Trial Registration Number UMIN 000022805, Registration date July 1, 2016.

BACKGROUND Low flow (LF; i.e., reduced left ventricular stroke volume index

Background Bleeding after endoscopic submucosal dissection (ESD) in antithrombotic drug users is still one of the important issues to be solved. We performed scheduled second-look endoscopy (SLE) 5 days after ESD, when the resumption of antithrombotic agents is assumed to have achieved a steady state, rather than on the day after ESD. We investigated bleeding incidence and the status of ulcers. Methods A total of 299 lesions in 299 patients subjected to ESD for gastric neoplasms were enrolled. A double dose of proton pump inhibitors was administered after ESD. SLE was planned 5 days after ESD. Post-ESD bleeding occurring before SLE was defined as early phase post-ESD bleeding, whereas bleeding after SLE was defined as later phase post-ESD bleeding. Forrest IIa and IIb ulcers are defined as high-risk ulcers requiring prophylactic hemostasis. We investigated risk factors for post-ESD bleeding, particularly focusing on the use of antithrombotic agents and the presence of high-risk ulcers requiring prophylactic hemostasis during SLE. Results Under a double dose of proton pump inhibitors, early phase post-ESD bleeding occurred in 2.3% of non-users (5/218) and 6.2% of users of antithrombotic agents (5/81). High-risk ulcers were found in 19.0% of the cases during scheduled SLE (55/289). Later phase bleeding occurred in 5.5% of cases [2.8% of non-users (6/213) and 13.2% of users of antithrombotic agents (10/76)]. Cox regression analysis revealed that the risk factor for post-ESD bleeding was antithrombotic treatment (HR: 3.56; 95% CI: 1.63–8.02, p = 0.002) alone. Among patients with high-risk ulcers, a statistically significant increase in bleeding was observed in the later phase in patients under antithrombotic therapy, compared to those not receiving any antithrombotic agents (p = 0.001). Conclusions Antithrombotic treatment is a risk factor for post-ESD bleeding despite SLE being scheduled 5 days after ESD. Later phase post-ESD bleeding was observed in 13.2% of the patients under antithrombotic treatment even after prophylactic hemostasis for high-risk ulcers. Trial registration This study was registered in the UMIN Clinical Trials Registry System (000023306). Retrospectively registered on 23rd July 2016.

Aortic root operations are established procedures for patients with aortic root aneurysms, however there is a little insight for comparative long-term outcomes among different types of anatomical abnormalities and procedures. In this study, we sought to compare the results of patients with aortic abnormalities undergoing different procedures. From January 2008 to March 2017, a total of 105 patients without aortic dissection were performed the elective aortic root surgery. Patients with bicuspid aortic valve had enlarged annulus, and those with Marfan syndrome had enlarged Valsalva without enlarged annulus. Bentall operation with mechanical valve or bioprothetic valve was performed for patients with enlarged annulus and/or abnormal aortic cusp, and David operations for patients with normal cusps. This comparative study showed that these different procedures according to our policy were associated with reduced cardiac mortality and valve-related complications. The results suggest David procedure is the treatment of choice for young patients with aortic root aneurysm and normal aortic cusps, however, careful patient selection is paramount.

Renal dysfunction is a major adverse event after cardiovascular surgery. Therefore, the preoperative prediction of which patients will require renal replacement therapy (RRT) after cardiac surgery is an important issue. In the present study, 1,822 consecutive patients who underwent cardiovascular surgery from 2008 and 2013 at a single institution were reviewed. Patients who were already receiving long-term hemodialysis before surgery (n = 134) were excluded. The remaining 1,688 patients were separated into 2 groups: those requiring postoperative RRT and those without RRT requirement. A total of 128 patients (7.6%) required RRT. Patients requiring RRT had greater perioperative blood loss, longer intubation time, and longer hospital stays (p0.0001 for all). Multivariate analysis revealed that cardiopulmonary bypass use, preoperative body surface area, the left ventricular ejection fraction, serum albumin, and creatinine were independent risk factors for postoperative RRT (odds ratios 2.435, 0.204, 0.976, 0.556, and 5.394, 95% confidence intervals 1.471 to 4.140, 0.054 to 0.841, 0.962 to 1.025, 0.363 to 0.860, and 3.671 to 8.223, respectively, p0.05 for all). A subgroup of patients with relatively preserved renal function before surgery (creatinine1.12 mg/dl, a cut-off value for RRT requirement obtained from receiver-operating characteristic curve analysis [area under the curve 0.74748, sensitivity 60.2%, specificity 85.0%]) showed that preoperative serum albumin concentration was most significantly associated with postoperative RRT requirement (odds ratio 0.048, 95% confidence interval 0.023 to 0.095, p0.0001). In conclusion, cardiopulmonary bypass use, preoperative renal impairment as reflected by elevated creatinine level, small body size, a low left ventricular ejection fraction, and hypoalbuminemia were associated with a requirement for postoperative RRT. In patients with preserved renal function, hypoalbuminemia was most significantly related to requirement for RRT.

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.

We determined the factors associated with the expression of c-kit in the heart and the proliferation of c-kit-positive (c-kitpos) cardiac stem cells among the outgrowth cells cultured from human cardiac explants.Samples of the right atrium (RA), left atrium (LA), and left ventricle obtained from patients during open-heart surgery were processed for cell culture of outgrowth cells and tissue analysis. The total number of growing cells and the population of c-kitpos cells were measured and compared with c-kit expression in native tissues and characteristics of the patients according to the region of the heart.We analyzed 452 samples from 334 patients. Atrial fibrillation (AF) in the patients reduced the number of outgrowth cells from the RA and LA, and aging was a co-factor for the LA. The c-kitpos population from the RA was associated with serum brain natriuretic peptide (BNP). C-kit expression in native tissue was also associated with BNP expression. However, we observed no relationship in expression between outgrowth cells and native tissue. In addition, the RA tissue provided the highest number of c-kitpos cells, and the left ventricle provided the lowest.C-kit was weakly expressed in response to damage. In addition, no correlation between outgrowth cells and native tissue was found for c-kit expression.

The case is reported of a 79-year-old female who received a patch augmentation of the tricuspid anterior and septal leaflets with a resected left atrial wall to address recurrent tricuspid regurgitation, including tricuspid valve tethering. The patient was admitted to the authors' hospital for chronic heart failure with paravalvular leakage after aortic valve replacement and recurrent severe tricuspid regurgitation. She had undergone two previous cardiac surgeries. Re-tricuspid repair required an augmentation of the tricuspid valve leaflets in addition to tricuspid annuloplasty. As the autologous pericardium was unsuitable for a patch due to thickened and stiffened changes, the decision was taken to use a left atrial wall resected to reduce the size of giant left atrium, which was thin and easy to handle. This is the first report of tricuspid leaflet augmentation using a patch derived from the left atrial wall, which is a useful method in patients where pericardium is not available.

A woman in her 50s was admitted to our hospital because of multiple tumors detected in her liver. She was diagnosed with combined hepatocellular cholangiocarcinoma using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biopsy of the liver tumors. We judged the tumors to be unresectable because they were found in both lobes of the liver, with a tumor thrombus being found in the main left portal vein. The pathological findings showed that the tumors exhibited characteristics of hepatocellular carcinoma. Therefore, sorafenib was administered;however, 6 months later, the disease progressed. Consequently, she received second-line chemotherapy with a one-shot intra-arterial injection of cisplatin, but this too was ineffective, and her general condition worsened. As hence, we changed the regimen to 5-fluorouracil continuous infusion and consecutive low dose cisplatin (LFP) therapy. After one cycle of chemotherapy with LFP, Gd-EOB-DTPA-enhanced MRI showed markedly decreased sizes and numbers of tumors. To date, she has completed six cycles of LFP therapy, and almost all her tumors are no longer visible on MRI. She has recovered to a good state and has achieved long-term survival. Thus, this case indicates that although LFP therapy is generally selected for cases of advanced hepatocellular carcinoma, it also appears to be effective for long-term disease control in cases of hepatocellular cholangiocarcinoma.

Background: The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear. Methods: The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy. Results: A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41–0.56; P

The aim of this study was to evaluate the histologic diagnosis of hypovascular hepatic lesions showing hypointensity on hepatobiliary phase images of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI (EOB-MRI). In 38 patients with hepatocellular carcinoma (HCC) after curative treatments and 18 patients with liver cirrhosis, 105 hypovascular nodules that were hypointense at the hepatobiliary phase of EOB-MRI were biopsied and the clinical usefulness of these EOB-MRI findings for the diagnosis of HCC was examined. Of the 105 nodules (median diameter = 12mm), 78 (74.3%), 11 (10.5%), and 16 (15.2%) were diagnosed as HCC, dysplastic, and non-neoplastic, respectively. The positive predictive value (PPV) of hypointensity at the hepatobiliary phase of EOB-MRI for the diagnosis of HCC increased to 77-90% when combined with the following factors: washout appearance on the delayed phase of triple-phase CT, hyperintensity in diffusion-weighted image of MRI, or the appearance of a hypoechoic part in ultrasonography. PPV increased to 100% when all 3 factors were positive. A relatively large proportion of hypovascular lesions that showed hypo-intensity in the hepatobiliary phase were confirmed to be HCC, and the accuracy of HCC increased when combined with other imaging findings.

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.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.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).Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously.

Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed.Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice.REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6).Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC.Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching.About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (30 mm, hazard ratio = 1.685, P = 0.043), high des-γ-carboxyprothrombin (100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group.RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.

Cardiopulmonary bypass usage provokes a systemic inflammatory response resulting in deterioration of renal function. However, risk factors for requiring renal replacement therapy (RRT) following off-pump coronary artery bypass graft surgery (CABG) have not yet been fully elucidated. We reviewed 718 consecutive patients undergoing elective off-pump CABG at our institution, excluding patients on chronic hemodialysis preoperatively. Sub-analysis of patients with preserved renal function, defined as a creatinine level below a cut-off value of 1.12 mg/dL (obtained by receiver operating characteristic curve), was also performed. Of the 718 patients, 41 (5.7 %) required RRT. There were 556 patients (77.4 %) with preserved renal function preoperatively, and 13 (2.4 %) of these required postoperative RRT. Multivariate analysis revealed that age (years) and preoperative serum creatinine (mg/dL) and brain natriuretic peptide (BNP) levels (pg/dL) were associated with RRT [odds ratios (OR) 1.052, 95 % confidence interval (CI) 9.064 and 1.001, respectively, all p

Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelial-mesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC.

Radiofrequency ablation (RFA) is a standard therapy for the treatment of hepatocellular carcinoma (HCC) with 3 or fewer tumors of up to 3 cm (early-stage HCC); when RFA is unsuccessful or unfeasible, transcatheter arterial chemoembolization (TACE) has often been performed. However, little information about the outcome of TACE for early-stage HCC has been reported and it is hard to decide whether to perform additional treatment following TACE in these difficult conditions. The aim of this study was to determine the risk factors for local or intrahepatic distant recurrence after TACE in early-stage HCC.Among 1,560 newly diagnosed HCC patients who were admitted to Okayama University Hospital, 43 patients with early-stage HCC who received only TACE in at least one nodule were enrolled in this study. We analyzed the risk factors for local and distant recurrence by the Cox proportional hazard model.The local recurrence rates and intrahepatic distant recurrence rates at 3 months, 6 months, and 1 year were 18.6, 33.4, and 61.8%, and 2.8, 2.8, and 34.3%, [corrected] respectively.Among 12 parameters examined as possible risk factors for recurrence, heterogeneous Lipiodol uptake (risk ratio 3.38; 95% confidence interval 1.14-10.60) and high serum des-gamma-carboxy prothrombin (DCP) (2.58; 1.03-7.14) were significantly correlated with local recurrence, and the presence of multiple tumors (10.64; 1.76-93.75) was significantly correlated with intrahepatic distant recurrence.Heterogeneous Lipiodol uptake, high serum DCP, and multiple tumors are risk factors for recurrence in patients with early-stage HCC who have undergone palliative TACE.

Treatment of chronic hepatitis C virus (HCV) infection with interferon (IFN) prevents the development of hepatocellular carcinoma (HCC). The purpose of this study was to clarify the effect of previous IFN treatment before the development of HCC on recurrence and survival in HCV-related HCC patients.Three hundred ninety-five patients who underwent curative treatment for HCV-related HCC were enrolled. Of these, 124 had received IFN treatment before the development of HCC (17 achieved sustained virological response [SVR group] and 107 did not [non-SVR group]), whereas 271 patients had never received IFN treatment (IFN-untreated group). The first and second recurrence and survival rates in these patient groups were statistically analyzed.The first HCC recurrence rate was similar among patient groups. In contrast, the second HCC recurrence rate was significantly lower in the SVR group than in the non-SVR group (p = 0.003) and the IFN-untreated group (p = 0.006). In multivariate analysis, platelet count (p = 0.033) and number of tumors (p = 0.001) were associated with the first HCC recurrence, while SVR (p = 0.002) was the only factor associated with the second HCC recurrence. The survival rate was higher in the SVR group than in non-SVR and IFN-untreated groups, and SVR to previous IFN treatment was an independent factor associated with better survival (p0.001).SVR to previous IFN treatment before the development of HCV-related HCC was associated with lower risk of the second recurrence of HCC and better survival.

SummaryBackgroundDiabetes mellitus is an independent risk factor for cardiovascular events after coronary artery bypass grafting (CABG), and hemoglobin A1c (HbA1c) is the most convenient marker for monitoring glycemic control among diabetic patients. However, few studies have reported the impact of baseline HbA1c levels on outcomes for diabetic patients after CABG. This study therefore aimed to investigate whether preoperative HbA1c levels in diabetic patients are predictive of long-term outcomes after off-pump CABG (OPCAB).Methods and resultsOf 893 patients undergoing primary isolated OPCAB at Juntendo University Hospital from July 2002 to December 2007, subjects comprised 306 diabetic patients

The aim of this study was to evaluate the effect of folate and homocysteine on colon tumorigenesis by performing colonoscopy and examining serum folate and homocysteine levels in end-stage renal disease (ESRD) patients. We performed colonoscopy in 72 ESRD patients who were undergoing hemodialysis and also measured their serum folate and homocysteine levels. Serum folate and homocysteine concentrations of the 72 ESRD patients were 6.0 ± 3.9 μg/l and 37.3 ± 25.5 μmol/l, respectively. Colorectal neoplasia was detected in 47 (65%) of the patients. Compared to a control group, ESRD patients had significantly more and larger neoplasia (P = 0.002 and 0.001, respectively). Multivariate analysis revealed that ESRD patients with lower levels of serum homocysteine had significantly more and larger neoplasia than those with higher levels (P = 0.02 and 0.03, respectively). In addition, patients with a shorter duration of hemodialysis were likely to have larger neoplasia. ESRD patients had higher than normal serum homocysteine levels. Interestingly, patients with lower homocysteine levels were likely to carry more and larger colorectal neoplasia. These results suggest that suppression of folate metabolism and an elevated serum homocysteine concentration are inversely associated with colon tumorigenesis in ESRD patients.

Objectives To examine the difference in the methylation status in normal colon mucosa between the proximal and distal colon, in relation to the correlation between the methylation status of normal mucosa and characteristics of neoplasia. Design and methods Paired biopsy specimens of normal mucosa from the proximal and distal colon of 82 patients who underwent colonoscopy were obtained. The methylation status of the promoter region of estrogen receptor 1 ( ESR1 ) and myogenic differentiation 1 ( MYOD1 ) was examined. Results Normal mucosa was more highly methylated in the distal than in the proximal colon in both ESR1 and MYOD1 loci ( p p = 0.0009, respectively). Advanced characteristics of polyps in the distal colon were frequently observed in patients with lower methylation of ESR1 in the distal colon normal mucosa. Conclusions Methylation levels in normal mucosa differ between the proximal and distal colon, and lower methylation of ESR1 in the distal colon normal mucosa may correlate with advanced features of neoplasia in the distal colon.

Background and aim The health-related quality of life (HRQOL) of patients with ulcerative colitis (UC) can be impaired because of the chronic symptoms. Although UC patients suffer from such symptoms over the long term, there have been few reports on the changes of HRQOL with disease duration. The aim of this study was to clarify these changes. Methods The HRQOL of 331 Japanese UC patients was examined using the validated Japanese version of the Inflammatory Bowel Disease Questionnaire (J-IBDQ). HRQOL and factors affecting HRQOL identified using multiple linear regression analysis were stratified by disease duration. Results Of the 15 clinical factors examined, the clinical activity index score was the strongest determinant (P

The aim of this study is to elucidate the prognostic factors and the treatment effect on survival in hepatocellular carcinoma (HCC) patients with Child C cirrhosis. Out of 3330 newly discovered HCC patients, 157 consecutive HCC individuals with Child C cirrhosis were enrolled. The prognostic factors were examined by Cox proportional hazards regression analysis and their survival was compared by propensity score-matched analysis. Multivariate analysis revealed that high serum bilirubin (3 mg dl(-1)), the presence of uncontrollable ascites, and a high platelet count (8 x 10(4) mm(-3)), so-called background liver factors, as well as multiple tumours, large tumours (3 cm), high alpha-fetoprotein (400 ng ml(-1)), and the presence of portal vein thrombus, so-called tumour factors, were factors of poor prognosis. While transcatheter arterial chemoembolisation (TACE) was a factor of good prognosis (relative risk=0.50, 95%CI=0.27-0.89, P=0.019), local ablation therapy and transcatheter arterial chemoinfusion (TAI) were not significant prognostic factors. The survival of patients who received TACE was superior to matched patients without active treatment (P=0.009); however, we did not observe survival benefit after local ablation therapy or TAI. These results suggested that tumour factors as well as background liver factors are prognostic factors of HCC even in patients with Child C cirrhosis, and selective use of TACE in these patients provides survival benefit.

Upper gastrointestinal bleeding is a major adverse event of non-steroidal anti-inflammatory drugs (NSAIDs), and co-administration of proton pump inhibitors and H2 receptor antagonists has been established as a means of preventing such an eff ect. However, the incidence of bleeding associated with NSAID-induced ulcers under conditions where such strong anti-acid agents are used for prevention has yet to be clarified. We aimed to determine the annual incidence of serious upper gastrointestinal ulcer bleeding among Japanese patients in whom NSAIDs were used in our hospital. Before commencing the study, we recommended to all the physicians in our hospital the best method for caring for NSAID users, focusing on the concomitant use of proton pump inhibitors or H2 receptor antagonists. We conducted a cohort study involving 17,270 patients for whom NSAIDs had been newly prescribed. Bleeding from gastric ulcers was observed in 8 of the 17,270 patients using NSAIDs (0.05%). The pooled incidence rate for bleeding was calculated as 2.65 (95% confidence interval, 2.56-2.74) and 1.29 (1.27-1.31) per 1,000 patient years for low-dose aspirin and non-aspirin NSAID users, respectively. None of the bleeding ulcer patients required blood transfusion or were in serious condition. In conclusion, gastric ulcer bleeding occurred in low-dose aspirin or non-aspirin NSAID users, but its incidence was low and outcomes were not serious when adequate preventive measures were taken.

Our aim is to establish the risk factors for carrying high-grade dysplasia or carcinoma by analyzing endoscopically treated adenoma cases.Patients who underwent endoscopic polypectomy at our hospitals between January 2003 and August 2004 were analyzed.A total of 889 patients (mean age: 63+/-11 years), and 1486 adenomas resected from these patients, were included in the analysis. Seventy-five adenomas (5%) from 72 patients (8%) were found to have high-grade dysplasia or carcinoma. Among patient factors, female sex [odds ratio (OR) 2.25, 95% confidence intervals (CI)=1.34-3.76], presence of multiple adenomas (OR=2.15, 95% CI=1.15-4.00), older age (OR=1.02, 95% CI=1.00-1.04), and rectal bleeding as the indication for colonoscopy (OR=2.57, 95% CI=1.34-4.92) were identified as the significant risk factors for carrying high-grade dysplasia or carcinoma using the multivariate analysis. In addition, a size ofor = 10 mm (OR=10.83, 95% CI=5.86-20.0), flat appearance (OR=3.91, 95% CI=2.20-6.95), and location on the left side of the colon (OR=1.80, 95% CI=1.03-3.13) were identified as tumor risk factors.Distinct factors were proved to be associated with high-grade dysplasia or carcinoma. These results are useful to select lesions that require immediate treatment. Moreover, female sex as a risk factor raises an interesting problem regarding the progression from adenoma to carcinoma.

Background Although the left subclavian artery (LSA) is simply covered to exclude distal aortic arch aneurysm during endovascular stent-grafting, this technique is potentially harmful. Methods and Results Between January 2001 and April 2005, 40 cases of stent-grafting were performed for distal aortic arch diseases. For all 31 elective cases, the LSA occlusion test using a balloon catheter was preoperatively performed to predict critical complications secondary to LSA coverage by a stent graft and this revealed 2 cases in which the LSA was crucial for brain circulation (6.5%). The LSA was saved by using a hand-made fenestrated stent graft without bypass-grafting to the LSA in 22 cases. Bypass-grafting to LSA was performed in 5 cases. The LSA was simply occluded in 13 cases. Hospital mortality rates for the elective and emergency cases were 3.2% and 30.0%, respectively. One elective patient had a cerebral infarction (2.5%). LSA patency was successfully maintained in all 22 cases using a fenestrated stent graft. Conclusion The LSA plays an important role in brain circulation in some patients and so a preoperative LSA occlusion test is helpful when aortic stent-grafting is proposed. Fenestrated stent graft saved the LSA in more than 50% of the present cases. (Circ J 2008; 72: 449 - 453)

BACKGROUND Off-pump coronary artery bypass grafting (OPCAB) has evolved into a standard technique in coronary artery bypass grafting. However, a detailed investigation in Japanese population undergoing OPCAB has not yet been fully elucidated. METHODS A total of 1109 consecutive patients undergoing isolated OPCAB between 2006 and 2013 at Juntendo University were reviewed. The data was evaluated in the light of previously published OPCAB-associated reports. RESULTS There were 904 male (81.5%) and a mean was 67.5 ± 9.8 years. Eight patients (0.5%) died within 30 days postoperatively or before discharge, which was equivalent to or rather better than the previously reported mortality rates, including the European System for Cardiac Operation Risk Evaluation II (2.1 ± 2.1) data. A morbidity analysis revealed that prolonged intubation (>24 h) occurred in 43 patients (3.6%), surgical site infections in 18 (1.9%), neurological complications in 13 (1.3%). A reduced preoperative left ventricular ejection fraction (less than 40%) was found to be a risk factor for early postoperative death (odds ratio 10.58, respectively, p

Background Renal failure is a serious complication after cardiac surgery, which can be caused by long-term intravenous (IV) loop diuretic use. Tolvaptan is an oral selective vasopressin-2 receptor antagonist used in patients irresponsive to loop diuretics. We investigated their renal perfusion changes using the resistive index (RI) postoperatively. Methods Serial renal RI, echocardiography, and laboratory examinations from 14 patients requiring continuous postoperative IV loop diuretics were reviewed. Eight patients received tolvaptan (Group T) and six received oral loop diuretics before the discontinuation of IV loop diuretics (Group L). The 1st data were obtained between postoperative day 0 and 2, the 2nd when patients were still under IV loop diuretic treatment, the 3rd after the initiation of tolvaptan or oral loop diuretic, and the 4th after the discontinuation of IV diuretics. Results The 2nd RI value was higher in Group T than Group L (0.77 ± 0.09 vs. 0.69 ± 0.01, p = 0.049) but significantly decreased after tolvaptan administration [0.77 ± 0.09 to 0.65 ± 0.05 (2nd to 3rd), to 0.62 ± 0.04 (to 4th), both p = 0.006], while no such changes were seen in Group L. The serum sodium and albumin levels, and echo-derived tricuspid annular plane systolic excursion increased only in Group T (134.1 ± 1.5 to 138.8 ± 3.2 mEq/L, 3.3 ± 0.3 to 3.7 ± 0.5 g/dL, 16.4 ± 3.6 to 19.7 ± 4.2 mm, all p

BACKGROUND Cerebrovascular accidents (CVA) are a major adverse event following cardiac surgery, for which atrial fibrillation (AF) is considered as a risk factor. We have recently performed left atrial appendage (LAA) surgical closure or amputation (LAAC/A), which is the main source of emboli, during open-heart surgery. METHODS AND RESULTS A prospective observational study of 1,831 consecutive patients (69.2% male, aged 66.8±12.2 years) undergoing cardiac surgery between 2009 and 2013 was performed. The incidence of postoperative CVA within 6 months in patients with and without LAAC/A was compared. We further stratified patients according to their risk of CVA using CHA2DS2-VASc score; dichotomizing low-risk (score

Objectives The objectives of this study were to examine the whole-serum N-glycan profile of patients with unresectable pancreatic cancer and to evaluate the ability of glycans to predict gemcitabine treatment efficacy and patient survival. Methods We collected serum from 52 patients with advanced pancreatic cancer before they began gemcitabine monotherapy. The serum glycan profile was measured through comprehensive quantitative high-throughput glycome analysis and compared with the treatment efficacy and patient survival. Results Of the 61 glycans detected, the serum levels of glycan 4310 (molecular weight [m/z] 1549.566), 6301 (m/z 2032.724), and 9200 (m/z 2010.692) were high in patients with a short time to tumor progression (TTP). Multivariate analysis revealed that a high glycan 9200 concentration was an independent risk factor for shorter TTP (hazard ratio, 2.11; 95% confidence interval, 1.07-4.17) and poor overall survival (hazard ratio, 2.56; 95% confidence interval, 1.08-6.19). The median TTP of patients with up-regulation of 9200 after gemcitabine treatment was shorter than for the remaining patients (91 vs 301 days; P = 0.0005). A similar relationship was observed for overall survival (median, 181 vs 561 days; P = 0.001). Conclusions Glycan 9200 is a possible biomarker predicting gemcitabine efficacy survival in patients with unresectable pancreatic cancer.

Background The aim of our study was to examine and compare the predictive value of operative mortality of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, the Society of Thoracic surgeons (STS) score, the Ambler score, and the Japan score in patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS). Methods A total of 406 patients undergoing AVR with or without coronary artery bypass grafting (CABG, n = 139) at our institution from August 2002 to December 2013 were enrolled in this cohort study. Accuracy of calibration and discrimination performance of four risk scores was assessed in the overall patient population and quartiles of each risk score. Results Operative mortality was 3.4% ( n = 14). The mean EuroSCORE II, STS score, Ambler score, and the Japan score were 3.1%, 4.9%, 5.7%, and 3.2%, respectively, giving observed-to-expected (O/E) ratio of 1.09, 0.69, 0.59, and 1.06. The C -statistics for operative mortality were 0.704 (EuroSCORE II), 0.781 (STS score), 0.709 (Ambler score), and 0.771 (Japan score). In the last quartile, the EuroSCORE II demonstrated excellent calibration (O/E ratio = 0.97) and discrimination ( C -statistic = 0.904), and the STS score (O/E ratio = 0.86, C -statistic = 0.779) and the Japan score (O/E ratio = 1.14, C -statistic = 0.80) showed reasonable correlation. However, the risk calibration by the Ambler score in the last quartile was unacceptable (O/E ratio = 0.60). Conclusions The EuroSCORE II and the Japan score showed superior ability of calibration, but the STS score and the Ambler score overestimated the risk. However, the discrimination power was similar among the four risk scores. In the last quartile of risk, the EuroSCORE II gave an excellent predictive performance.

We reviewed the histories of 144 patients who underwent heart valve replacement with the CarboMedics prosthesis from 1990 to 2000. There were 74 males and 70 females, with a mean age of 52 years, including 69 aortic valve replacements, 48 mitral valve replacements, and 27 double (aortic and mitral) valve replacements. The mean duration of follow-up was 6.5 years. Early mortality was 7.6% (11 patients). Late deaths occurred in 14 patients, including cardiac-related late deaths in 9 and valve-related deaths in 3. The survival rate including early deaths was 84.7 +/- 3.2% at 5 years and 78 +/- 4.1% at 10 years. Preoperative New York Heart Association Class IV (p = 0.0001) was found to be a significant predictor of cardiac-related late death. Freedom rate from complications at 10 years were embolism 84.7 +/- 4.2% (linearized rate 1.8% per patient year), valve thrombosis 92.7 +/- 2.7% (linearized rate 0.8% per patient year), bleeding 95.6 +/- 2.6% (linearized rate 0.4% per patient year), reoperation 85.9 +/- 4% (linearized rate 1.5% per patient year), valve endocarditis 98.7 +/- 1.3% (linearized rate 0.1% per patient year), and nonstructural dysfunction 90 +/- 3.5% (linearized rate 1% per patient year). There was no structural deterioration. The early and long-term results with the CarboMedics heart valve implantation were acceptable, but valve thrombosis remains a concern in the present study. Further investigation for optimal anticoagulation therapy is necessary to reduce the incidence of valve thrombosis as well as embolic and bleeding complications.

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).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.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.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.

Objectives: We have reviewed 260 patients who underwent initial tricuspid valve surgery for functional tricuspid valve regurgitation (TR) and analyzed independent predictors for early and late unfavorable results. Materials and methods: Between 1981 and 1998, 260 tricuspid valve operations were performed for functional TR. There were 94 males and 166 females with a mean age of 55 years. The tricuspid valve surgery procedures consisted of De Vega tricuspid annuloplasty in 240 patients, ring annuloplasty in four patients, and tricuspid valve replacement in 16 patients. The mean duration of follow-up was 7.8 years. Results: Hospital mortality was 8.9% (23 patients). Late deaths occurred in 34 patients including cardiac-related late deaths in 26 patients. The survival rates were 83 ^ 2% at 5 years and 78 ^ 3% at 10 years. Late tricuspid valve reoperation was performed on 13 patients due to residual or recurrent TR in 12 patients and thrombosed tricuspid bileaflet mechanical valve in one patient. The tricuspid valve reoperation-free survival rate was 90 ^ 2% at 5 years and 84 ^ 3% at 10 years. The only predictor of hospital mortality was preoperative highly elevated right atrial pressure (Pa 0:01). Variables predictive of cardiacrelated late death were preoperative New York Heart Association (NYHA) class IV (Pa 0:01) and poor left ventricular ejection fraction (LVEF) (Pa 0:02). Residual TR of more than grade 21 early after tricuspid annuloplasty was a significant risk factor for late tricuspid valve reoperation (Pa 0:01). Preoperative TR of grade 41 was predictive of early residual TR (Pa 0:04). Conclusions: Tricuspid valve surgery for functional TR can be performed with acceptable levels of early mortality. Cardiac-related late mortality after tricuspid surgery may be improved by earlier surgical treatment before NYHA class IV or deterioration of LVEF occurs. To prevent late tricuspid reoperation, it is important not to leave residual TR of grade 21 or more after tricuspid annuloplasty. q 2001 Elsevier Science B.V. All rights reserved.

From January 1976 to September 1994, 26 patients underwent a tricuspid valve replacement (TVR) with porcine bioprostheses (Hancock II in 19 patients, Carpentier-Edwards in 3, Hancock standard in 2, Medtronic-Intact in 1, and Liotta in 1). The mean age of these patients was 38.4 years (range, 9 to 70 years). The mean follow-up period was 6.7 years (range, 1.8 to 16.5 years). There was a complete follow-up in 100%. There were two hospital deaths and three late deaths. The actuarial survival rate at 16 years was 78.7%+/-8.6%. Five patients developed structural deterioration. Four of these 5 patients underwent re-TVR. The actuarial freedom rate from structural deterioration at 10 years was 47.1%+/-19.1%. There were no instances of thromboembolism and prosthetic valve endocarditis. Our experience indicated the major problem of the porcine bioprostheses in the tricuspid position thus to be valve durability: however, the long-term actuarial survival rate was satisfactory, including no operative morality with re-TVR due to tricuspid prosthetic structural deterioration. We therefore conclude that the choice of a porcine bioprosthesis in the tricuspid position should be considered not only for patients with isolated tricuspid valve disease, but also for the patients who have not previously received mechanical valves in the mitral or the aortic valve position.

Redo-coronary artery bypass grafting( redo-CABG) still remains a challenging operation and is associated with a significantly higher risk of morbidity and mortality when compared with primary CABG. The higher risk of redo-CABG is largely attributable to the increased technical difficulty and the greater incremental risk in redo-CABG patients. Annual reports by the Japanese Association for Thoracic Surgery in recent years reveled that the absolute and relative number of redo-CABG gradually decreased, and in-hospital mortality did not change significantly over this periods and was much higher than primary CABG. The increasing use of percutaneous coronary intervention (PCI) for previous CABG patients could be a reason for the decrease of redo-CABG, and therefore surgery of redo-CABG is becoming more limited. This paper presents the current indications, safe surgical technique, and perioperative management of redo-CABG patients, as well as the contemporary results of redo-CABG in our institution.

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.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.Median serum FST levels in HCC, liver cirrhosis, chronic hepatitis, and healthy volunteers were 1168, 1606, 1324, and 1661 pg/mL, 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).Serum FST levels are significantly associated with HCC prognosis and could represent a predictive biomarker in this disease.

The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with non-alcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases. We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC). NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients (P < 0.001 and < 0.001, respectively; log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients (P < 0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI (P = 0.028). The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients.

Minimally invasive cardiac surgery (MICS) using a small surgical incision in children provides less physical stress. However, concern about safety due to the small surgical field has been noted. Recently, the authors developed a modified MICS procedure to extend the surgical field. This report assesses the safety and benefit of this modified procedure by comparing three procedures: the modified MICS (group A), conventional MICS (group B), and traditional open heart surgery (group C). A retrospective analysis was performed with 111 pediatric patients (age, 0–9 years; weight, 5–30 kg) who underwent cardiac surgery for simple cardiac anomaly during the period 1996–2010 at Juntendo University Hospital. The modified MICS method to extend the surgical view has been performed since 2004. A skin incision within 5 cm was made below the nipple line, and the surgical field was easily moved by pulling up or down using a suture or a hemostat. The results showed no differences in terms of gender, age, weight, or aortic cross-clamp time among the groups. Analysis of variance (ANOVA) indicated significant differences in mean time before cardiopulmonary bypass (CPB), CPB time, operation time, and bleeding. According to the indices, modified MICS was similar to traditional open surgery and shorter time or lower bleeding volume than conventional MICS. No major mortality or morbidity occurred. In conclusion, the modified MICS procedure, which requires no special techniques, was as safe as conventional open heart surgery and even reduced perioperative morbidity.