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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. [ABSTRACT FROM AUTHOR]

Background: Depression is frequently associated with unsuccessful smoking cessation., Objective: In this study, we investigated the impact of depression history on smoking cessation success in a clinical setting., Methods: This retrospective study included 726 patients who visited our smoking cessation clinic between January 1, 2001, and December 31, 2018. Kaplan-Meier analyses and Cox proportional hazards regression models were used to perform univariate and multivariate analyses of smoking cessation success factors., Results: Among the 726 patients, 76 had a history of depression and demonstrated significantly lower 12-week quit rate compared to those without (33.6% vs. 69.6%, p < .001). Multivariate Cox analysis revealed a significant association between abstinence rate and history of depression (hazard ratio 2.251, 95% CI 1.505-3.315, p < .001), history of schizophrenia (hazard ratio 2.716, 95% CI 1.427-4.840, p = .003), and Fagerström Nicotine Dependence Test scores (hazard ratio 1.519, 95% CI 1.053-2.197, p = .025)., Conclusions: Our findings suggested that a history of depression is a significant prognostic factor for smoking cessation, underscoring the need for targeted interventions for patients with a history of depression. The findings of this study are subject to potential selection bias due to recruitment from a single hospital, which may limit the generalizability of our results. This study highlights the necessity for novel, specialized smoking cessation therapies to support patients with a history of depression in their cessation journey.

Background: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC)., Methods: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified., Results: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03)., Conclusion: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Left sinus of Valsalva aneurysms are extremely rare. Concomitant aortic valve regurgitation is a comorbidity in this pathology. This case report summarizes successful surgical treatment with aortic root replacement with a modified Bentall procedure in a 49-year-old female patient who had an unruptured huge left sinus of Valsalva aneurysm with severe aortic valve regurgitation. The intraoperative assessment showed severe adhesion between the left main trunk of the coronary artery and the left sinus of Valsalva aneurysm, and meticulous adhesion detachment was required., (© 2023 The Author(s). Published by The Texas Heart Institute®.)

Limb ischemia caused by tumor embolus is rare. In this study, we report the case of a 77-year-old woman who suffered from acute ischemic limb. Computed tomography showed a tumor in the right bronchus invading the left atrium. The tumor fragments scattered resulting in the occlusion of the right iliac artery. The excluded embolus was revealed as a squamous cell carcinoma. Regarding the popliteal venous thrombus, Trousseau's syndrome was complicated. The patient was discharged without any complications. We believe that advanced lung cancer is a differential diagnosis of acute ischemic limbs and that successful limb rescue contributed to a patient's quality of life., Competing Interests: Disclosure StatementAll authors have no conflicts of interest., (© 2022 The Editorial Committee of Annals of Vascular Diseases.)

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., Competing Interests: No potential conflict of interest relevant to this article was reported.

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 (DO 2 ) but did not consider the duration of DO 2 . We aimed to examine whether the time-dose response of DO 2 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 DO 2 index (DO 2 i), the area under the curve was calculated as below the 300 mL/min/m 2 threshold, which accounts for depth and duration of cumulative oxygen debt. In addition, the cumulative time below DO 2 i 300 mL/min/m 2 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/m 2 threshold (1581 vs 632; P < .01) and cumulative time below DO 2 i 300 mL/min/m 2 (34.7 vs 15.3 minutes; P < .01). Nadir DO 2 i was not significantly different between the non-AKI and AKI groups (263.4 vs 247.0 mL/min/m 2 ; P = .291)., Conclusions: The time-dose response of DO 2 i during cardiopulmonary bypass is a better indicator than nadir DO 2 i in evaluating AKI risk. Maintaining DO 2 i levels >300 mL/min/m 2 may result in decreased risk for postoperative AKI., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Low flow (LF; i.e., reduced left ventricular stroke volume index <35 mL/m 2 ) can occur with severe aortic stenosis (AS). However, few studies have investigated the effects of LF on early and late outcomes after aortic valve replacement (AVR) for severe AS.Methods and Results:In all, 285 severe AS patients undergoing isolated AVR at Juntendo University Hospital between August 2002 and August 2015 were enrolled in the study. In this cohort, 52 patients (18%) had LF. Compared with patients with normal flow (NF) severe AS, early postoperative mortality (9.6% vs. 1.2%; P=0.006), gastrointestinal complications (5.7% vs. 0.8%; P=0.04), and the duration of the intensive care unit (ICU) stay (81.7 vs. 35.3 h; P=0.02) were increased in LF patients with severe AS. LF was an independent predictor of early mortality (Model A, odds ratio [OR] 6.81, P=0.01; Model B, OR 6.69, P=0.01) and composite complications (Model A, OR 2.44, P=0.02). In propensity score-matched comparisons, early mortality (12.8% vs. 0%; P=0.02), composite complications (28.2% vs. 10.2%; P=0.04), and duration of ICU stay (97.4 vs. 22.1 h; P=0.006) were significantly increased in LF than NF patients., Conclusions: LF, as an important independent risk factor for postoperative mortality and morbidity, should be included in risk stratification and assessment in severe AS patients.

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., Competing Interests: No potential conflict of interest relevant to this article was reported.

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.

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].

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 < 0.05] in the total population, whereas low albumin concentration was the only independent predictor for RRT in patients with preserved renal function (OR 0.062, p < 0.0001). When creatinine levels were below 1.5 mg/dL, the predictive power of hypoalbuminemia for RRT requirement overwhelmed that of creatinine or BNP levels. Older age, preoperative elevated creatinine and BNP levels were associated with a requirement for RRT following off-pump CABG. In patients with preserved renal function, hypoalbuminemia was most significantly related to the RRT requirement.

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.

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 (p <0.0001 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, p <0.05 for all). A subgroup of patients with relatively preserved renal function before surgery (creatinine <1.12 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, p <0.0001). 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

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.

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.

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.

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., (Copyright © 2012 UICC.)

Background: Measurement of objective response to chemotherapy using imaging modalities is sometimes difficult in pancreatic cancer (PC). We aimed to verify whether monitoring of serum tumor markers (TMs), namely carcinoembryonic antigen, CA19-9, DUPAN-2, SPan-1, can facilitate earlier confirmation of treatment failure., Methods: Monitoring of serum TMs and computed tomography were performed every 4 weeks until progression of disease in 90 patients with PC undergoing gemcitabine therapy. In Group A (January 2006-October 2007), we analyzed the fluctuation rates of TMs with high pretreatment positive rates, and defined the criteria of progressive disease under TM monitoring (TM-PD). In Group B (November 2007-October 2008), we calculated the time to progression (TTP) under this TM-PD criteria, which was compared with the TTP under the RECIST criteria., Results: CA19-9 and SPan-1 had the highest pretreatment positive rates: 83% and 90%, respectively. In Group A (CA19-9, n = 38; SPan-1, n = 36), TM-PD criteria were defined as follows: fluctuation rates were ≥25% for a month or ≥10% for 2 consecutive months in CA19-9, and ≥10% for a month in SPan-1. In Group B (CA19-9, n = 18; SPan-1, n = 17), under these criteria, one-month earlier confirmation of treatment failure was feasible in 61% by CA19-9 and 59% by SPan-1. Furthermore, the combination could facilitate this determination in 72% (35/49), significantly better than CA19-9 alone (P = 0.004)., Conclusion: Monitoring of serum CA19-9 and SPan-1 is helpful for earlier confirmation of treatment failure during gemcitabine therapy in PC., (Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to evaluate clinical risk factors and assess the impact of the Society of Thoracic Surgeons (STS) scores on outcomes after contemporary aortic valve replacement (AVR) for aortic stenosis (AS)., Methods: We retrospectively analyzed the data from 209 consecutive patients with AS (mean 69 ± 9 years) who underwent AVR. The outcomes measured included operative mortality, postoperative complications, postoperative prolonged length of stay (PLOS), discharge to nonhome location, and mid-term mortality., Results: Operative mortality was 3.8%, and five-year survival was 88.6 ± 2.8%. Multivariable analysis revealed preoperative New York Heart Association (NYHA) class as a significant predictor of both operative mortality (p = 0.03; odds ratio [OR]: 8.5) and mid-term mortality (p = 0.02; OR: 10.5). NYHA class also emerged as an independent predictor for postoperative complications (p = 0.002; OR: 5.8) and PLOS (p = 0.01; OR: 2.5). Other preoperative independent predictors included dialysis for PLOS (p = 0.04; OR: 2.9), age (p = 0.03; OR: 1.1), and left ventricular ejection fraction (EF; p = 0.03; OR: 0.9) for nonhome discharge, and EF for mid-term mortality (p = 0.01; OR: 0.9). The mean STS-PROM (predicted risk of mortality) was 4.6% ± 6.1%, and thus, the observed-to-expected (O/E) ratio of operative mortality in our series was 0.82., Conclusions: Advanced NYHA class, older age, dialysis, and lower EF are significant independent preoperative risk factors for early and mid-term results of AVR for AS. Consideration of these predictors should be used to identify high-risk patients requiring AVR for AS., (© 2012 Wiley Periodicals, Inc.)

The purpose of this study was to build a prognostic model of hepatocellular carcinoma (HCC) using time-dependent covariates to re-evaluate the prognosis at any stage of the disease. The subjects were consecutive HCC patients who were treated at our institute between 1995 and 2007. We constructed time-fixed and time-dependent prognostic models with a training group (n=336) and compared the prognostic abilities between conventional Cancer of the Liver Italian Program (CLIP) scores, Japan Integrated Staging (JIS) scores, an Okuda classification, and our prognostic models in the testing group (n=227) with the c-index. The time-dependent prognostic model consisted of main tumor size, tumor number, portal vein invasion, distant metastasis, alpha-fetoprotein, des-gamma-carboxy prothrombin (DCP), bilirubin, and albumin and the weighted scores were set for each factor depending on the hazard ratio for the prognosis. The prognostic index was determined by summing the scores. The c-index values for the CLIP scores, JIS scores, Okuda classification, and our time-dependent model were 0.741, 0.727, 0.609, and 0.870, respectively. These results indicate that our time-dependent model can estimate the prognosis of HCC more precisely than traditional time-fixed models and can be used to re-predict the prognosis of HCC.

We present the case of a patient with postinfarction ventricular septal rupture (VSR) who underwent delayed repair using a modified infarction exclusion technique. The patient was taken to the operating room 21 days after the first incidence of acute myocardial infarction because the intra-aortic balloon pump maintained a stable circulatory condition without cardiogenic shock. In our procedure, a Dacron patch was sutured to the healthy endocardium to exclude the infarcted septum, and the VSR was subsequently closed with another Dacron patch. After three years of postoperation, the patient's condition remains normal with good ventricular kinesis and no residual shunt. We describe herein a novel procedure for repairing postinfarction VSR by using two Dacron patches.

Aim: To identify specific colonoscopic findings in patients with ulcerative colitis (UC) complicated by cytomegalovirus (CMV) infection., Methods: Among UC patients who were hospitalized due to exacerbation of symptoms, colonoscopic findings were compared between 15 CMV-positive patients and 58 CMV-negative patients. CMV infection was determined by blood test for CMV antigenemia. Five aspects of mucosal changes were analyzed (loss of vascular pattern, erythema, mucosal edema, easy bleeding, and mucinous exudates) as well as five aspects of ulcerative change (wide mucosal defect, punched-out ulceration, longitudinal ulceration, irregular ulceration, and cobblestone-like appearance). Sensitivity, specificity, positive predictive value, and negative predictive value of each finding for CMV positivity were determined., Results: The sensitivity of irregular ulceration for positive CMV was 100%. The specificity of wide mucosal defect was 95%. Punched-out ulceration and longitudinal ulceration exhibited relatively high sensitivity and specificity (more than 70% for each)., Conclusion: Specific colonoscopic findings in patients with UC complicated by CMV infection were identified. These findings may facilitate the early diagnosis of CMV infection in UC patients.

Heterotopic cardiac xenotransplantation from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) swine to baboons was performed to characterize immunological reaction to the xenograft in the absence of anti-Gal antibody-mediated rejection. Eight baboons received heterotopic cardiac xenografts from GalT-KO porcine donors. All baboons were treated with chronic immunosuppressive therapy. Both histological and immunohistochemical studies were performed on biopsy and graftectomy samples. No hyperacute rejection was observed. Three baboons were euthanized or died 16 to 56 days after transplantation. The other five grafts ceased beating between days 59 and 179 (median, 78 days). All failing grafts exhibited thrombotic microangiopathy (TM) with platelet-rich fibrin thrombi in the microvasculature, myocardial ischemia and necrosis, and focal interstitial hemorrhage. TM developed in parallel with increases in immunoglobulin (IgM and IgG) and complement (C3, C4d, and C5b-9) deposition, as well as with subsequent increases in both TUNEL(+) endothelial cell death and procoagulant activation (increased expression of both tissue factor and von Willebrand factor and decreased expression of CD39). CD3(+) T-cell infiltration occurred in all grafts and weakly correlated with the development of TM. In conclusion, although the use of GalT-KO swine donors prevented hyperacute rejection and prolonged graft survival, slowly progressive humoral rejection--probably associated with non-Gal antibodies to the xenograft--and disordered thromboregulation represent major immunological barriers to long-term xenograft survival.

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 effect. 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.

Background: The recent generation of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs has allowed investigation of the survival of GalT-KO pig organs in nonhuman primates., Methods: Heterotopic heart transplantation from GalT-KO pigs was carried out in baboons (n=8) using a human antihuman CD154 monoclonal antibody-based immunosuppressive regimen., Results: In six of the eight cases, graft survival extended to between approximately 2 and 6 months. All grafts developed thrombotic microangiopathy (TM). In particular, the clinical course of one baboon in which the graft functioned for 179 days is summarized. This baboon received aspirin (40 mg on alternate days) from day 4 in addition to heparin, which may have been a factor in the delay of onset and progression of TM and in prolonged graft survival. Maintenance therapy with anti-CD154 mAb, mycophenolate mofetil, and methylprednisolone was associated with persistently low numbers of CD3CD4 and CD3CD8 cells. Despite persisting depletion of these cells, no infectious complications occurred., Conclusions: It remains to be established whether TM is related to a very low level of natural preformed or T-cell-induced antibody deposition on the graft, inducing endothelial activation and injury, or to molecular incompatibilities in the coagulation mechanisms between pig and baboon, or to both. However, function of a pig organ in a baboon for a period approaching six months, which has not been reported previously, lends encouragement that the barriers to xenotransplantation will eventually be overcome.

Background: Xenotransplantation using pigs as source species carries a risk for the activation of latent herpesviruses from the porcine donor and potential transmission to the recipient. In pig-to-baboon xenotransplantation, activation of porcine cytomegalovirus (PCMV) has been associated with xenograft injury and an increased incidence of consumptive coagulopathy and graft loss. Activation of porcine lymphotropic herpesvirus (PLHV)-1 was not observed in pig-to-baboon solid organ xenotransplantation, but was associated with a syndrome of post-transplantation lymphoproliferative disorder (PTLD) after allogeneic stem cell transplantation in pigs., Material and Methods: Early weaning of piglets was used to try to reduce the viral burden of xenograft donors. This consisted of separating the piglets of a litter from the sow within the first 2 weeks after birth and raising them in isolation from the remaining herd., Results: We have previously demonstrated that PCMV could be excluded from source animals by early weaning of piglets. However, early weaning failed to exclude PLHV-1 from source pigs., Conclusions: This disparity between PCMV and PLHV-1 reflects differing pathogenesis of infection of these herpesviruses. New approaches will be needed to exclude PLHV-1 from pig colonies.

Hearts from alpha1,3-galactosyltransferase knockout pigs (GalT-KO, n = 8) were transplanted heterotopically into baboons using an anti-CD154 monoclonal antibody-based regimen. The elimination of the galactose-alpha1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2-6 months (median, 78 d); the predominant lesion associated with graft failure was a thrombotic microangiopathy, with resulting ischemic injury. There were no infectious complications directly related to the immunosuppressive regimen. The transplantation of hearts from GalT-KO pigs increased graft survival over previous studies.

Background: Acute humoral xenograft rejection (AHXR) is an immunologic barrier in pig-to-baboon organ transplantation (Tx). We report microvascular thrombosis and myocardial necrosis in a series of cardiac xenografts., Methods: Ten baboons underwent heterotopic heart Tx from pigs transgenic for human decay-accelerating factor. Recipients were treated with soluble Gal glycoconjugates and multiple immunosuppressive agents. Grafts were removed when palpable contractions stopped. Stained tissue sections from harvested grafts were analyzed by light and fluorescence microscopy., Results: Xenograft survival ranged from 4 to 139 (mean 37, median 27) days. Some histology was typical for AHXR (n = 4; median survival 22 days). Hemorrhage and edema were only focal in the longer-surviving grafts (n = 4, median survival 54 days). All grafts had multiple platelet-rich fibrin thrombi occluding myocardial vessels. Ischemic damage was manifested by contraction band necrosis in four grafts, myocytolysis in eight, coagulative necrosis in nine, and patchy myocyte dropout in all grafts. A notable paucity of interstitial mononuclear cells was observed in all grafts. Marked intimal thickening resembling that of allograft vasculopathy was observed in one graft. Immunofluorescence showed immunoglobulin (Ig)G and/or IgM deposition in five grafts. Multivessel C4d deposition appeared in seven grafts. Significant C3 deposition was absent., Conclusions: Cardiac xenograft survival in the pig-to-baboon model can be significantly prolonged by vigorous immunosuppressive treatment of recipient animals. Additional efforts to block humoral activation of graft endothelial cells and/or to overcome species-specific molecular coagulation pathway incompatibilities may prevent the development of microvascular thrombosis and myocardial infarction. Cardiac xenograft vasculopathy (chronic rejection) can occur with prolonged graft survival., (Copyright 2004 Blackwell Munksgaard)

Natural and elicited antipig antibodies (Abs) lead to acute humoral xenograft rejection (AHXR). Ten baboons underwent heterotopic heart transplantation (Tx) from human decay-accelerating factor (hDAF) pigs. Depletion of anti-Galalpha1, 3Gal (Gal) Abs was achieved by the infusion of a Gal glycoconjugate from day-1. Immunosuppression included induction of antithymocyte globulin, thymic irradiation, and cobra venom factor, and maintenance with a human antihuman CD154 mAb, mycophenolate mofetil, and methylprednisolone; heparin and prophylactic ganciclovir were also administered. Pig heart survival ranged from 4 to 139 (mean 37, median 27) days, with three functioning for >50 days. Graft failure (n = 8) was from classical AHXR [4], thrombotic microangiopathy [3], or intragraft thrombosis [1], with death (n = 2) from pneumonia [1], or possible drug toxicity (with features of thrombotic microangiopathy) [1]. Anti-Gal Abs (in microg/mL) were depleted by Gal glycoconjugate before graft implantation from means of 41.3 to 6.3 (IgM) and 12.4-4.6 (IgG), respectively, and at graft excision were 6.3 and 1.7 microg/mL, respectively. No elicited Abs developed, and no cellular infiltration was seen. The treatment regimen was effective in maintaining low anti-Gal Ab levels and in delaying or preventing AHXR. The combination of costimulatory blockade and heparin with Tx of a Gal-negative pig organ may prolong graft survival further.

Repeat median sternotomy is still associated with high morbidity and mortality from catastrophic hemorrhage or myocardial injury. To overcome these problems, we devised a new technique of sternal re-entry using the Kent retractor set (Takasago Ika Kogyo, Tokyo, Japan), which increases the safety of retrosternal dissection and sternal redivision.

Background and Aim of the Study: Uncertainties remain regarding the influence of several preoperative and intraoperative factors on outcome after double (simultaneous aortic and mitral) valve replacement (DVR)., Methods: Between 1981 and 1999, 132 patients (58 males, 74 females; mean age 53.8 years) underwent DVR with either aortic and mitral bileaflet mechanical valves in 81 patients, aortic tilting disk valve and mitral bileaflet valve in 36, and aortic tilting disk and mitral biological valve in 15. The mean duration of follow up was 7.6 years; cumulative follow up was 860 patient-years (pt-yr)., Results: Early mortality was 9.9% (n = 13). Late death occurred in 21 patients (linearized rate 2.4%/pt-yr; freedom rate at 10 years 77.6 +/- 5.4%) including cardiac-related death in 16 patients (linearized rate 1.9%/pt-yr; freedom rate at 10 years 86.9 +/- 4.5%) and valve-related death in 11 (linearized rate 1.3%/pt-yr; freedom rate at 10 years 87.7 +/- 4.3%). Late morbidity included 30 cases of thromboembolism (linearized rate 3.5%/pt-yr; freedom rate at 10 years 70.2 +/- 6.1%), seven bleeding (linearized rate 0.8%/pt-yr; freedom rate at 10 years 95.6 +/- 2.2%), 22 reoperations (linearized rate 2.6%/pt-yr; freedom rate at 10 years 79.4 +/- 5.1%), three prosthetic valve endocarditis, 13 structural valve deterioration, and two paravalvular leakage. Independent determinants of early and late mortality and morbidity, except for valve reoperation, were preoperative patient-related factors of NYHA class IV, left ventricular ejection fraction < or = 40%, mean right atrial pressure > or = 15 mmHg, and mean pulmonary artery wedge pressure > or = 25 mmHg. However, late valve reoperation and all valve-related complications were influenced by a valve-related factor, namely mitral bioprosthesis., Conclusion: Earlier surgical management before the development of severe heart failure, myocardial dysfunction and hemodynamic deterioration would improve the results of DVR. Mitral bioprosthesis combined with a mechanical aortic valve should be avoided as it increases the risk of reoperation.

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.