Evaluation of microembolic signals on carotid ultrasound during pulmonary vein isolation with high-power short-duration and cryoballoon ablations: When and where do bubble and solid emboli arise?

INTRODUCTION: The underlying risks of asymptomatic embolization during high-power short-duration (HPSD) ablation for atrial fibrillation remain unclear. We aimed to evaluate microembolic signals (MESs) during HPSD ablation with power settings of 50 and 90 W in comparison with those during cryoballoon (CB) ablation using a novel carotid ultrasound-Doppler system that classifies solid and air bubble signals using real-time monitoring. METHODS AND RESULTS: Forty-seven patients underwent HPSD ablation using radiofrequency (RF), and 13 underwent CB ablation. MESs were evaluated using a novel pastable soft ultrasound probe equipped with a carotid ultrasound during pulmonary vein isolation. We compared the detailed MESs and their timing between RF and CB ablations. The number of MESs and solid signals were significantly higher in the RF group than in CB group (209 ± 229 vs. 79 ± 32, p = .047, and 83 ± 89 vs. 28 ± 17, p = .032, respectively). In RF ablation, the number of MESs, solid, and bubble signals per ablation point, or per second, was significantly higher at 90 W than at 50 W ablation. The MESs, solid, and bubble signals were detected more frequently in the bottom and anterior walls of the left pulmonary vein (LPV) ablation. In contrast, many MESs were observed before the first CB application and decreased chronologically as the procedure progressed. Signals were more prevalent during the CB interval rather than during the freezing time. Among the 28 patients, 4 exhibited a high-intensity area on postbrain magnetic resonance imaging (MRI). The MRI-positive group showed a trend of larger signal sizes than did the MRI-negative group. CONCLUSION: The number of MESs was higher in the HPSD RF group than in the CB group, with this risk being more pronounced in the 90 W ablation group. The primary detection site was the anterior wall of the LPV in RF and the first interval in CB ablation.

Clinical Outcomes and Predictors of All-Cause Mortality After Complex High-Risk and Indicated Revascularization Using Percutaneous Coronary Intervention.

The concept of complex and high-risk indicated procedures using percutaneous coronary intervention (CHIP-PCI) has recently been defined. However, few studies have investigated the prognosis of patients after CHIP-PCI. We enrolled 322 consecutive patients who underwent CHIP-PCI. CHIP-PCI was defined as a procedure satisfying at least one criterion each for both patient and procedure characteristics, as follows: patient characteristics [age ≥ 75 years old, low left ventricular ejection fraction (LVEF), diabetes mellitus, acute coronary syndrome, previous coronary artery bypass surgery, peripheral arterial disease, severe chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and severe valvular disease] and procedure characteristics [unprotected left main disease, degenerated saphenous or radial artery grafts, severely calcified lesions, last patent conduit, chronic total occlusions, multivessel disease, and use of mechanical circulatory support]. On Kaplan-Meier analysis, 1-, 2-, and 3-year survival rates following CHIP-PCI was 93.8%, 89.2%, and 85.4%, respectively. Moreover, on Cox multivariate hazard analysis, age (≥ 75 years old) (hazard ratio: 4.01, 95% confidence interval: 1.92-8.38, P < 0.01), COPD (hazard ratio: 2.95, 95% confidence interval: 1.38-6.32, P < 0.01), low LVEF (hazard ratio: 3.35, 95% confidence interval: 1.55-7.22, P < 0.01), severe CKD (hazard ratio: 3.02, 95% confidence interval: 1.44-6.36, P < 0.01), and use of mechanical circulatory support (hazard ratio: 5.97, 95% confidence interval: 2.72-13.10, P < 0.01) remained significant predictors of mortality. In conclusion, we revealed the clinical outcomes after CHIP-PCI. The presence of advanced age, COPD, low LVEF, severe CKD, and mechanical circulatory support use might lead to worse clinical outcomes.

Preoperative prediction of malignancy and surgical treatment strategy in appendiceal tumors: multicenter review of 51 consecutive cases.

PURPOSE: A diagnostic and treatment strategy for appendiceal tumors (ATs) has not been established. We aimed to evaluate our treatment strategy in ATs, including laparoscopic surgery (LS), and to identify preoperative malignancy predictors. METHODS: A total of 51 patients between 2011 and 2021 were retrospectively reviewed. Data, including tumor markers and imaging findings, were compared between carcinoma and non-carcinoma patients. Validity of planned operation was evaluated based on pathological diagnosis. RESULTS: Twenty-five patients were diagnosed with carcinoma, 13 with low-grade mucinous neoplasm, and 13 with other diseases. Symptoms were more commonly present in carcinoma patients than in non-carcinoma patients (68.0% vs. 23.1%, p = 0.001). Elevated CEA and CA19-9 were more frequently observed in carcinoma patients than in non-carcinoma patients (p < 0.01 and p = 0.04, respectively). Five carcinoma patients had malignancy on biopsy, compared with zero non-carcinoma patients. Significant differences were noted in the percentages of carcinoma and non-carcinoma patients with solid enhanced mass (41.7% vs. 0%, p < 0.001) and tumor wall irregularity (16.7% vs. 0%, p = 0.03) on imaging. Although the sensitivity was not high, the specificity and positive predictive value of these findings were 100%. Forty-two patients (82.4%) underwent LS as minimally invasive exploratory and/or radical operation, of whom 2 were converted to open surgery for invasion of adjacent organ. No patients had intraoperative complications or postoperative mortality. CONCLUSION: Clinical symptoms, elevated tumor markers, and worrisome features of solid enhanced mass and tumor wall irregularity on imaging can be malignancy predictors. For management of ATs, LS is feasible and useful for diagnosis and treatment.

Evaluation of the direction and extent of ice formation during cryoballoon ablation: an experimental study.

BACKGROUND: The distal hemisphere of a balloon is generally cooled during cryoapplication. However, a wide ablation area can be acquired after cryoballoon ablation. This study aimed to evaluate the extent of ice formation on two types of balloon surfaces through experimental and simulation studies. METHODS: A standard cryoballoon (SCB; Arctic Front Advance Pro, Medtronic) and novel cryoballoon (NCB; POLARx, Boston Scientific) were frozen for 240 s in 36 °C normal saline solution to observe ice formation on the balloon surface. Pieces of porcine tissue were placed between the upper and lower sides of the balloon, and the balloon was frozen in the horizontal direction for 240 s in 20 attempts (10 for SCB and NCB each). The measured areas of ice formation were evaluated and compared between the upper and lower sides of each balloon. RESULTS: Ice formation was greater on the lower side of the balloon than on the upper side. A larger area of ice formation in the tissue slab was observed on the lower side than on the upper side in both balloons, and the ice formation extended to the proximal hemisphere on the lower side of the balloon. The ice formation area in the NCB was significantly larger than that in SCB. CONCLUSIONS: Ice formation was significantly greater on the lower side of the cryoballoon than on the upper side and extended to the proximal hemisphere of the balloon, which might facilitate the acquisition of a wide ablation area on the left atrial posterior wall after cryoballoon ablation. Different ice formation after cryoballoon ablation Greater ice formation on the lower side of cryoballoon and an extensive ice formation in the proximal hemisphere, especially in novel cryoballoon.

Usefulness of the Snare Technique During Leadless Pacemaker Implantation for a Patient with a Severely Dilated Right Atrium.

We report here the case of a 92-year-old woman with atrial fibrillation bradycardia in which leadless pacemaker implantation was performed with a difficult delivery of the catheter sheath due to an extremely large right atrium. Using a snare technique with correction of the direction of the force on the catheter toward the right ventricle (RV) can result in successful delivery of the pacemaker catheter and stable placement of the pacemaker system in the RV septum. This specific snare technique has the potential to facilitate leadless pacemaker implantation safely in a severely dilated chamber of the heart, making this technique effective to use in clinical practice.

Cryoballoon ablation for atrial fibrillation without the use of a contrast medium: a combination of the intracardiac echocardiography and pressure wave monitoring guided approach.

In cryoballoon ablation (CBA), a contrast medium is commonly used to confirm balloon occlusion of the pulmonary veins (PVs). However, a contrast medium cannot always be used in patients with renal dysfunction and allergy. The present study aimed to assess the efficacy and safety of CBA without the use of a contrast medium. We retrospectively examined consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent first-time CBA. We compared the procedural results and outcomes in patients for whom a contrast medium was used (contrast group) and those from whom a contrast medium was not used (non-contrast group). In the non-contrast group, we used saline injection on the intracardiac echocardiography and pressure wave monitoring for PV occlusion. Fifty patients (200 PVs) and 22 patients (88 PVs) underwent CBA with and without a contrast medium, respectively. The success rate of PV isolation with CBA alone was 93% and 90% in the non-contrast and contrast groups, respectively (p = 0.40). The fluoroscopy time and nadir temperature were significantly lower in the non-contrast group as compared to that in the contrast group. The recurrence rate 1 year after ablation did not differ between the two groups (18% vs. 18%, p > 0.99). Furthermore, the number of reconnected PVs in patients with recurrence was significantly lower in the non-contrast group than in the contrast group (6% vs. 36%, p = 0.017). In conclusion, CBA using the intracardiac echocardiography and pressure monitoring approach without the use of a contrast medium was safe and efficient.

Clinical Significance of the Left Atrial Appendage Orifice Area.

Objective The left atrial appendage (LAA) is one of the major sources of cardiac thrombus formation. Three-dimensional transesophageal echocardiography (TEE) made it possible to perform a detailed evaluation of the LAA morphologies. This study aimed to evaluate the clinical implications of the LAA orifice area. Methods A total of 149 patients who underwent TEE without significant valvular disease were studied. The LAA orifice area was measured using three-dimensional TEE. The patients were divided into two groups according to the LAA orifice area (large LAA orifice group, ≥median value, and small LAA orifice group). The clinical characteristics and echocardiographic findings were evaluated. Results The median LAA orifice area among all patients was 4.09 cm2 (interquartile range 2.92-5.40). The large LAA orifice group were older (67.2±10.4 vs. 62.4±15.3 years, p=0.02), more often had hypertension (66.7% vs. 44.6%, p=0.007), and atrial fibrillation (70.7% vs. 39.2%, p<0.001) than the small LAA orifice group. Regarding the TEE findings, the LAA flow velocity was significantly lower (33.7±20.0 vs. 50.2±24.3, p<0.001) and spontaneous echo contrast was more often observed (21.3% vs. 8.1%, p=0.02) in the large LAA orifice group. Multivariate models demonstrated that atrial fibrillation was an independent predictor of the LAA orifice area. In the analysis of atrial fibrillation duration, the LAA orifice area tended to be larger as patients had a longer duration of atrial fibrillation. Conclusion Our findings indicated that a larger LAA orifice area was associated with the presence of atrial fibrillation and high thromboembolic risk based on TEE findings. A continuation of the atrial fibrillation rhythm might lead to the gradual expansion of the LAA orifice.

Earliest pulmonary vein potential-guided cryoballoon ablation is associated with better clinical outcomes than conventional cryoballoon ablation: A result from two randomized clinical studies.

INTRODUCTION: With regard to short-term outcome in atrial fibrillation (AF), the benefit of cryoballoon ablation (CBA) by pressing a balloon against the earliest pulmonary vein (PV) potential site during PV isolation (earliest potential [EP]-guided CBA) has been previously demonstrated. The present study aimed to evaluate the long-term outcome of the EP-guided CBA. METHODS AND RESULTS: This study included 136 patients from two randomized studies, who underwent CBA for paroxysmal AF for the first time. Patients were randomly assigned to the EP-guided and conventional CBA groups in each study. In the EP-guided CBA group, we pressed a balloon against the EP site when the time-to-isolation (TTI) after cryoapplication exceeded 60 and 45 s in the first and second studies, respectively. We compared the clinical outcomes for 1 year after the procedure between the EP-guided CBA group (68 patients) and the conventional CBA group (68 patients). The primary endpoint was the recurrence of atrial arrhythmia after ablation. No significant differences in baseline characteristics were observed between the two groups. Compared with the conventional CBA group, the EP-guided CBA group had a significantly higher success rate at TTI ≤ 90 s (98.5% vs. 90.0%, p < .001); lower touch-up rate and total cryoapplication; and shorter procedure time, and fluoroscopy time. The recurrence at 1 year after ablation was significantly lower in the EP-guided CBA group than in the conventional CBA group (6.0% vs. 19.4%; p = .019). CONCLUSIONS: The EP-guided CBA approach can facilitate the ablation procedure and achieve low recurrence at 1 year after ablation.

Disappearance pattern and the last remaining earliest pulmonary vein potential during cryoballoon ablation in predicting recurrence and conduction gap site of pulmonary veins.

Electrophysiological studies have rarely evaluated the sites prone to pulmonary vein (PV) conduction gap during cryoballoon ablation (CBA) for atrial fibrillation (AF). In addition, no studies have analyzed the sequence of PV potentials just before PV isolation during CBA for AF. Of the 238 patients who underwent first-time CBA for paroxysmal AF, 115 PVs of 29 patients who underwent repeat session due to recurrence after the procedure were retrospectively evaluated in the study. We evaluated the disappearance pattern of PV potential and PV reconnection on intracardiac electrograms and investigated whether the conduction gap site of the PV was related to the last remaining earliest PV potential (EP) and sequence pattern during the first-time CBA. Time to isolation was observed in 81 PVs during the first-time CBA. At the repeat session, PV reconnection was only observed in 22 of 81 PVs. PV potentials disappeared with sequence changes in 36 PVs and without sequence changes in 38 PVs. Multivariate analysis demonstrated that disappearance of PV potentials without change in the EP site but with delay or disappearance of other PV potentials was independently associated with PV reconnection (12/22 PVs [55%] vs. 4/59 PVs [6.8%]; odds ratio 14.4; 95% confidence interval 3.75-55.5; p < 0.001). In 19 of 22 (86%) reconnected PVs, PV conduction gap sites at repeat ablation corresponded with the last remaining EP sites during first-time CBA. In conclusion, disappearance pattern of the PV potential and the last remaining EP during the CBA can predict PV reconnection and gap site.

Impact of the clinical frailty scale on clinical outcomes and bleeding events in patients with ST-segment elevation myocardial infarction.

The Clinical Frailty Scale (CFS) is a simple tool to assess patients' frailty and may help to predict adverse outcomes in elderly patients. The aim of the present study was to examine the impact of CFS on clinical outcomes and bleeding events after successful percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI). We enrolled 266 consecutive patients with STEMI who underwent primary PCI in between January 2015 and June 2018. Patients were categorized into two groups based on the CFS stages: CFS 1-3 and CFS ≥ 4. We collected the data and evaluated the relationship between the CFS grade and the incidence of major adverse cardiovascular events (MACE) and Bleeding Academic Research Consortium 3 or 5 bleeding events. Of these patients, CFS ≥ 4 was present in 59 (22.2%). During the follow-up, 37.3% in the CFS ≥ 4 group and 8.2% in the CFS 1-3 group experienced MACE. In Kaplan-Meier analysis, the proportion of MACE-free survival for 4 years was significantly lower in the CFS ≥ 4 group (log-rank P < 0.001). Additionally, the proportion of bleeding event-free survival was significantly lower in the CFS ≥ 4 group (log-rank P < 0.001). The CFS (per 1-grade increase) remained an independent significant predictor of MACE on multivariate Cox proportional hazard analysis [hazard ratio 1.39 (95% confidence interval: 1.08 to 1.79, P = 0.01)]. In conclusion, CFS was an independent predictor of future adverse cardiac events in patients with STEMI. Therefore, the assessment of CFS is crucial in this population.

Impact of skeletal muscle mass on clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Low skeletal muscle mass is one of the components of sarcopenia. However, the prognostic impact of skeletal muscle mass on clinical outcomes in patients after transcatheter aortic valve replacement (TAVR) remains unclear. Therefore, we assessed the impact of skeletal muscle mass on future cardiovascular events in patients undergoing TAVR. We enrolled 71 consecutive patients who underwent TAVR for symptomatic severe aortic stenosis. We applied bilateral psoas muscles as an indicator of skeletal muscle mass. Psoas muscle volumes were measured from the origin of psoas at the level of the lumbar vertebrae to its insertion in the lesser trochanter on three-dimensional computed tomography datasets. Psoas muscle mass index (PMI) was calculated as psoas muscle volume/height2 (cm3/m2). According to the median value of PMIs (79.8 and 60.0 cm3/m2 for men and women), the enrolled patients were divided into two groups. During the follow-up, 11 (31.4%) patients in low PMI group and 4 (11.1%) in high PMI group experienced major adverse cardiovascular events (MACE) defined as a composite of death from any cause, myocardial infarction, heart failure hospitalization, and stroke. The proportion of MACE-free survival was significantly lower in low PMI group (log-rank P = 0.033), mainly due to the difference of hospital readmission for congestive heart failure. On multivariate Cox proportional hazard analysis, PMI remained an independent negative predictor of MACE [hazard ratio 0.95 (95% confidence interval 0.92-0.98, P = 0.002)]. In conclusion, low skeletal muscle mass independently predicted MACE in patients undergoing TAVR.

Atypical clinical presentation of mechanical small bowel obstruction with superior mesenteric vein occlusion caused by a retained free intraperitoneal staple after laparoscopic appendectomy: A case report.

Mechanical small bowel obstruction (SBO) is a common postoperative complication, and most cases are caused by postoperative adhesions. We herein report a case of SBO with superior mesenteric vein occlusion caused by a metal staple after laparoscopic appendectomy. A 35-year-old Japanese woman presented to our department with severe upper abdominal pain and vomiting. She had undergone laparoscopic appendectomy using a linear stapler 7 years before. Abdominal CT showed mild small intestinal dilation with mesenteric edema and volvulus of the small bowel mesentery. Moreover, occlusion of the superior mesenteric vein was observed. Emergency exploratory laparoscopy revealed a strangulated SBO caused by a free unformed staple. The obstruction was released by a laparoscopic technique without bowel resection. The number of laparoscopic surgeries has recently been increasing, and complications specific to laparoscopic surgery have been recognized. All spilled and unformed staples should be removed to the greatest extent possible during laparoscopic operations.

Earliest pulmonary vein potential-guided cryoballoon ablation for atrial fibrillation.

No studies have evaluated both the time-to-isolation (TTI) and the sequence of pulmonary vein (PV) potentials in cryoballoon ablation (CBA) for atrial fibrillation (AF). This study aimed to prospectively evaluate the acute results of pulmonary vein isolation (PVI) using a novel CBA technique-the earliest potential (EP) of PV-guided CBA-in paroxysmal AF. We pressed a balloon against the earliest PV potential site during PVI when TTI could not be achieved within 60 s (EP-guided CBA group). We compared 32 patients consecutively treated by EP-guided CBA to 32 patients treated without pressing the balloon against the EP site (conventional CBA group). The cryoapplication protocol was the same, except with regard to the pressing of the balloon. All 256 PVs (EP-guided CBA group, 128 PVs; conventional CBA group, 128 PVs) were isolated successfully. The TTI observation rate was similar in both groups. Compared with conventional CBA, EP-guided CBA was associated with a lower non-success rate of TTI ≤ 90 s (9% vs. 26%; P = 0.040) and shorter left atrial dwell time (38 ± 9 vs. 46 ± 19 min; P = 0.036), total procedure time (76 ± 15 vs. 87 ± 23 min; P = 0.043), and fluoroscopy time (23 ± 8 vs. 30 ± 11 min; P = 0.006). This novel EP-guided CBA approach may help facilitate the ablation procedure.

Laparoscopic high anterior resection for triple colorectal cancers with persistent ascending and descending mesocolons: A case report.

Persistent mesocolon is an embryological anomaly of the colon resulting from failure of the primitive dorsal mesocolon to fuse with the parietal peritoneum. We herein present a case of laparoscopic high anterior resection for triple colorectal cancers with persistent ascending and descending mesocolons and a right-bound inferior mesenteric artery. Preoperative 3-D CT demonstrated that the sigmoid colon had shifted to the right abdomen and was located under the ascending colon. Moreover, the inferior mesenteric artery and vein traveled toward the right abdomen accompanied by the mesentery of the descending colon. Adhesiolysis between the ascending and sigmoid colon was initially performed, and the sigmoid colon was placed in its normal position. The inferior mesenteric artery was then divided with lymph node dissection using a medial approach, and high anterior resection was completed. An understanding of the anatomical characteristics of persistent mesocolon is important to ensure safe laparoscopic surgery.

Impact of Coronary Stent Fracture on Restenotic Neointimal Tissue Characterization After Drug-Eluting Stent Implantation.

Although drug-eluting stents (DESs) reduce the rates of in-stent restenosis (ISR) and subsequent target lesion revascularization, stent fracture (SF) after DES implantation has become an important concern because of its potential association with restenosis and stent thrombosis. We aimed to assess the pathogenic impact of SF on in-stent restenotic neointimal tissue components after DES implantation. We analyzed 43 consecutive patients (14 with SF and 29 without SF) with ISR requiring revascularization after DES implantation between January 2008 and March 2014. For evaluation of in-stent tissue components, integrated backscatter intravascular ultrasound (IB-IVUS) was performed. SF was defined as complete or partial separation of stent segments observed using plain fluoroscopy or intravascular ultrasound. On volumetric IB-IVUS analyses, patients with SF had a significantly higher percentage of lipid tissue volume within the neointima and a significantly lower percentage of fibrous tissue volume than those without (37.3 ± 18.9% versus 24.9 ± 12.4%, P = 0.02, and 61.2 ± 18.3 versus 72.6 ± 12.1%, P = 0.04, respectively). Moreover, SF was positively correlated with the percentage of lipid volume on multiple linear regression analysis after adjustment for confounding factors (ß = 0.36, P = 0.03). The interval from stent implantation was similar in both groups (47.0 ± 28.7 versus 37.7 ± 33.3 months; P = 0.39). In conclusion, SF is associated with larger lipid tissue volume within the neointima after DES placement, suggesting a contribution to the development of neoatherosclerosis and vulnerable neointima. Thus SF might lead to future adverse coronary events.

Akt-dependent Girdin phosphorylation regulates repair processes after acute myocardial infarction.

Myocardial infarction is a leading cause of death, and cardiac rupture following myocardial infarction leads to extremely poor prognostic feature. A large body of evidence suggests that Akt is involved in several cardiac diseases. We previously reported that Akt-mediated Girdin phosphorylation is essential for angiogenesis and neointima formation. The role of Girdin expression and phosphorylation in myocardial infarction, however, is not understood. Therefore, we employed Girdin-deficient mice and Girdin S1416A knock-in (Girdin(SA/SA)) mice, replacing the Akt phosphorylation site with alanine, to address this question. We found that Girdin was expressed and phosphorylated in cardiac fibroblasts in vitro and that its phosphorylation was crucial for the proliferation and migration of cardiac fibroblasts. In vivo, Girdin was localized in non-cardiomyocyte interstitial cells and phosphorylated in α-smooth muscle actin-positive cells, which are likely to be cardiac myofibroblasts. In an acute myocardial infarction model, Girdin(SA/SA) suppressed the accumulation and proliferation of cardiac myofibroblasts in the infarcted area. Furthermore, lower collagen deposition in Girdin(SA/SA) mice impaired cardiac repair and resulted in increased mortality attributed to cardiac rupture. These findings suggest an important role of Girdin phosphorylation at serine 1416 in cardiac repair after acute myocardial infarction and provide insights into the complex mechanism of cardiac rupture through the Akt/Girdin-mediated regulation of cardiac myofibroblasts.

Girdin/GIV regulates transendothelial permeability by controlling VE-cadherin trafficking through the small GTPase, R-Ras.

Vascular permeability is regulated by intercellular junction organization of endothelial cells, the dysfunction of which is implicated in numerous pathological conditions. Molecular mechanisms of how endothelial cells regulate intercellular junction in response to extracellular signals, however, have so far remained elusive. This study identified that Girdin (also termed GIV), an Akt substrate functioning in post natal angiogenesis, was expressed in a mature endothelial monolayer, where it regulated VE-cadherin trafficking to maintain vascular integrity. Girdin depletion abrogated VEGF-induced VE-cadherin endocytosis and the disassembly of adherens junctions in a monolayer of endothelial cells, thus leading to a significant decrease in the permeability. We also showed that activated R-Ras, a member of the Ras family GTPase, known to be a master regulator of transendothelial permeability, interacts with Girdin, and facilitates the complex formation between Girdin and VE-cadherin in endothelial cells. However, the increased permeability mediated by the loss of R-Ras was rescued by Girdin depletion, thus suggesting that the interaction of Girdin with R-Ras functions in VE-cadherin trafficking pathways distinct from endocytosis. The recycling of VE-cadherin was promoted by the exogenous expression of the active mutant of R-Ras, which was attenuated in the Girdin-depleted endothelial cells. These results show that Girdin regulates transendothelial permeability in synergy with R-Ras and VE-cadherin in an endothelial monolayer.

Associations between vitamin D receptor (VDR) gene polymorphisms and colorectal cancer risk and effect modifications of dietary calcium and vitamin D in a Japanese population.

Much interest has been drawn to possible associations between vitamin D receptor (VDR) gene polymorphisms and colorectal cancer risk in conjunction with potentially protective effects of calcium and vitamin D. In a study of 685 cases of colorectal cancer and 778 community controls in Japan, we examined the associations of the FokI, BsmI, ApaI, and TaqI polymorphisms with colorectal cancer risk and effect modification by dietary calcium and vitamin D. Genotypes were determined by the PCR-RFLP method. The ApaI polymorphism seemed to be associated with a decreased risk of colorectal cancer, particularly of rectal cancer. The adjusted odds ratio of colorectal cancer for the ApaI AA and Aa genotypes combined versus the aa genotype was 0.83 (95% confidence interval [CI] 0.67-1.02), and the corresponding value for rectal cancer was 0.75 (95%CI 0.56-0.99). A decreased risk of colorectal cancer for the ApaI AA and Aa genotypes combined was more evident in individuals with high calcium intake (interaction p=0.055). The FokI polymorphism seemed to be associated with a decreased risk of colon cancer among those with high vitamin D intake (interaction p=0.09). The BsmI and TaqI polymorphisms were unrelated to colorectal cancer risk, and the null associations were not modified by calcium or vitamin D intake. In conclusion, the ApaI polymorphism may be associated with a decreased risk of colorectal cancer in Japanese, dependent on dietary calcium intake.

Sugars, sucrose and colorectal cancer risk: the Fukuoka colorectal cancer study.

OBJECTIVE: A diet high in sugars may promote colorectal carcinogenesis, but it remains uncertain whether high intake of sugars or sucrose confers increased risk of colorectal cancer. The authors investigated the associations of sugars and sucrose intake with colorectal cancer risk in a community-based case-control study in Japan. METHODS: The study subjects comprised 816 incident cases of colorectal cancer and 815 community controls. Consumption frequencies and portion sizes of 148 food and beverage items were ascertained by a computer-assisted interview. The authors used the consumption of 29 food items to estimate sugars and sucrose intake. The odds ratios of colorectal cancer risk according to intake categories were obtained using a logistic regression model with adjustment for potential confounding variables. RESULTS: Overall, intakes of sugars and sucrose were not related to colorectal cancer risk either in men or women. The association between sugars intake and colorectal cancer risk differed by smoking status and alcohol use in men, but not in women. In men, sugars intake tended to be associated with colorectal cancer risk inversely among never-smokers and positively among male ever-smokers (interaction p=0.01). Sugars intake was associated with an increased risk among men with no alcohol consumption, but was unrelated to the risk among male alcohol drinkers (interaction p=0.02). Body mass index did not modify the association with sugars intake in either men or women. CONCLUSION: Sugars intake was associated with increased risk of colorectal cancer among smokers and non-alcohol drinkers in men selectively.