Comparisons of in-hospital fee and surgical outcomes between robot-assisted, laparoscopic, and open radical cystectomy: a Japanese nationwide study.

OBJECTIVE: To evaluate in-hospital fees and surgical outcomes of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC) using a Japanese nationwide database. METHODS: All data were obtained from the Diagnosis Procedure Combination database between April 2020 and March 2022. Basic characteristics and perioperative indicators, including in-hospital fees, were compared among the RARC, LRC and ORC groups. Propensity score-matched comparisons were performed to assess the differences between RARC and ORC. RESULTS: During the study period, 2931, 1311 and 2435 cases of RARC, LRC and ORC were identified, respectively. The RARC group had the lowest in-hospital fee (median: 2.38 million yen), the shortest hospital stay (26 days) and the lowest blood transfusion rate (29.5%), as well as the lowest complication rate (20.9%), despite having the longest anesthesia time (569 min) among the three groups (all P < 0.01). The outcomes of LRC were comparable with those of RARC, and the differences in these indicators between the RARC and ORC groups were greater than those between the RARC and LRC groups. In propensity score-matched comparisons between the RARC and ORC groups, the differences in the indicators remained significant (all P < 0.01), with an ~50 000 yen difference in in-hospital fees. CONCLUSIONS: RARC and LRC were considered to be more cost-effective surgeries than ORC due to their superior surgical outcomes and comparable surgical fees in Japan. The widespread adoption of RARC and LRC is expected to bring economic benefits to Japanese society.

Relationship between the cholesterol and triglyceride content of lipoprotein subclasses and carotid intima-media thickness: A cross-sectional population-based study.

BACKGROUND: The association between lipoprotein subclasses and carotid intima-media thickness (cIMT) progression has yet to be fully evaluated. We assessed which lipoprotein subclasses were associated with maximum cIMT levels in the general population. METHODS: In this study, cholesterol and triglyceride content of 20 lipoprotein subclasses were analyzed using gel permeation high-performance liquid chromatography (GP-HPLC) in 864 Japanese women and men (mean age 57 y, free of chronic liver or kidney diseases and off lipid-lowering, hormone replacement, or adrenocorticosteroid medications). Univariate and multivariate regression analyses and univariate and partial correlation analyses were performed to examine the relationships between lipoprotein subclasses and maximum cIMT levels. RESULTS: After adjusting for age, sex, systolic blood pressure, smoking, diabetes, and anti-hypertensive agents, elevated low-density lipoprotein (LDL)-2 and -3 cholesterol (particle diameter 25.5 nm and 23.0 nm, respectively; medium and small LDL) were associated with higher maximum cIMT levels in both women and men (all p for trend < 0.05). These associations were significant even after participants taking anti-diabetic or anti-hypertensive agents were excluded. No significant associations were found between any triglyceride subclasses and maximum cIMT levels. CONCLUSIONS: Smaller LDL particle cholesterol values are the most atherogenic lipoprotein parameter.

Surgical outcomes of robot-assisted radical cystectomy in octogenarian or older patients: A Japanese nationwide study.

OBJECTIVE: To evaluate the surgical outcomes of robot-assisted radical cystectomy (RARC) in octogenarian or older patients based on a Japanese nationwide database. METHODS: The diagnosis procedure combination database was used to extract the data on radical cystectomy cases. Surgical outcomes of RARC in octogenarian or older patients (older group) were initially compared to those of patients younger than 80 years (younger group). Then, the surgical outcomes of RARC in the older group were compared to those of open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) in the same age group. RESULTS: Between 2018 and 2021, 478 RARC cases in the older group and 2257 RARC cases in the younger group were identified. In the older group, ileal conduit, neobladder, and other urinary diversions were carried out in 352 (73.6%), 22 (4.6%), and 104 (21.8%) patients, respectively. In the older group, when compared with the younger group, the complication rate (24.9%), blood transfusion rate (41.4%), and in-hospital mortality (1.4%) were equivalent, while significantly shorter anesthesia time and longer length of stay were observed in the older group (521.0 ± 140.4 min vs. 595.1 ± 141.71 min, p < 0.01, and 32.9 ± 16.8 days vs. 30.6 ± 17.8 days, p = 0.01, respectively). In the comparison of the surgical outcomes of older patients receiving RARC to those receiving ORC (n = 746) and LRC (n = 375), the RARC group had the lowest complication rate and the shortest length of stay, while the shortest anesthesia time was noted in the ORC group. CONCLUSION: The feasibility of RARC for octogenarian or older patients was demonstrated by the nationwide database study.

Trends of radical cystectomy and comparisons of surgical outcomes among surgical approaches focusing on robot-assisted radical cystectomy: A Japanese nationwide database study.

OBJECTIVE: To clarify the trends in radical cystectomy and to compare surgical outcomes among surgical approaches focusing on robot-assisted radical cystectomy based on a Japanese nationwide database. METHODS: The Diagnosis Procedure Combination database was used to extract data on radical cystectomy cases. Trends in open radical cystectomy, laparoscopic radical cystectomy, minimum incision endoscopic radical cystectomy, and robot-assisted radical cystectomy between April 2012 and March 2021 were evaluated. Basic characteristics and peri-operative indicators were compared among the four groups. Propensity score matching was applied to assess the differences between open radical cystectomy and robot-assisted radical cystectomy. RESULTS: During the study period, a decreasing number of open radical cystectomies and an increasing number of minimally invasive radical cystectomies were shown in the total cohort of 28 345 cases. The number of robot-assisted radical cystectomies rapidly increased after government approval in 2018. Minimally invasive radical cystectomies, including robot-assisted radical cystectomies, had a significantly lower complication rate, a shorter length of stay, and a lower blood transfusion rate, but a longer anesthesia time than open radical cystectomies. In the propensity score matching analysis comparing the surgical outcomes of robot-assisted radical cystectomy and open radical cystectomy, similar results were demonstrated, and blood transfusion rates were equivalent. CONCLUSION: For the past decade, the number of minimally invasive radical cystectomies has steadily increased without compromised surgical outcomes, except for anesthesia time. Robot-assisted radical cystectomies in particular rapidly became widespread in Japan after government approval in 2018 and became a standard surgery within the first 3 years.

Trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval in Japan: A nationwide database study from 2016 to 2018.

OBJECTIVES: To evaluate the trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval for this type of procedure in April 2016. METHODS: This nationwide retrospective study included 3722 received robot-assisted partial nephrectomy cases carried out from April 2016 to March 2018 in 124 participating institutions. The institutions were divided into lower- and higher-volume institutions according to the median of 19 robot-assisted partial nephrectomy cases during the study period. Surgical outcomes between 616 cases from lower-volume institutions and 3106 cases from higher-volume institutions were compared using propensity score matching. RESULTS: During the study period, both the number of robot-assisted partial nephrectomy surgeries and the number of institutions in which the surgery was carried out steadily increased. Overall, the median anesthesia time was 217 min, the median postoperative length of stay was 9 days, and the proportion of blood transfusions, complications and readmissions were 0.8%, 5.1% and 1.0%, respectively. There were no significant differences in anesthesia time, incidence of blood transfusions, and complication rates between the lower-volume and higher-volume institutions. However, a slightly, but significantly, longer postoperative length of stay and a lower incidence of readmission were observed in lower-volume institutions both before and after propensity score matching. CONCLUSIONS: Robot-assisted partial nephrectomy has become widespread during the initial 2-year period after government approval with an acceptable safety profile, regardless of the institutional caseloads. This technique has become a standard of care for stage 1 renal cancer patients in Japan.

Relationships between Smoking Status, Cardiovascular Risk Factors, and Lipoproteins in a Large Japanese Population.

AIMS: Smoking is a major risk factor for cardiovascular disease (CVD), a leading cause of death and disability. Other CVD risk factors include age, gender, hypertension, diabetes, increased low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C). Our goal was to assess relationships between smoking status and CVD risk factors, with a focus on direct LDL-C, HDL-C, triglycerides (TG) and small dense LDL-C (sdLDL-C). METHODS: A total of 34,497 Japanese men and women, mean age 51 years, had their CVD risk factors including fasting serum total cholesterol, TG, HDL-C, sdLDL-C, and direct LDL-C assessed. One-way ANOVA and multiple linear regression analyses were carried to assess the interrelationships of these parameters with smoking. RESULTS: In both men and women, current smokers had significantly (p＜0.001) higher median TG (+19.6%, +16.9%) and sdLDL-C levels (+12.7%, +4.2%) levels, and significantly (p＜0.001) lower HDL-C levels (-7.3%, -4.3%) than non-smokers. They were also significantly (p＜0.05) more likely to have TG values ＞150 mg/dL (+56.8%, +116.3%), sdLDL-C ＞40.1 mg/dL (+28.8%, +44.9%), and HDL-C ＜40 mg/dL (+89.8%, +114.3%). Ex-smokers generally had lipid values that were intermediate between non-smokers and current smokers. Multivariate analysis confirmed the significance of these relationships. CONCLUSION: Our data indicate that current cigarette smoking is associated with increased TG and sdLDL-C levels, as well as decreased HDL-C levels. Furthermore, smoking effect on lipid profiles remain after cessation. These data provide further justification for smoking cessation.

Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression.

AIM: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan. METHODS: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression. RESULTS: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C ＜100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend=0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population. CONCLUSIONS: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

Direct Versus Calculated LDL Cholesterol and C-Reactive Protein in Cardiovascular Disease Risk Assessment in the Framingham Offspring Study.

BACKGROUND: Increases in circulating LDL cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) concentrations are significant risk factors for cardiovascular disease (CVD). We assessed direct LDL-C and hsCRP concentrations compared to standard risk factors in the Framingham Offspring Study. METHODS: We used stored frozen plasma samples (-80 °C) obtained after an overnight fast from 3147 male and female participants (mean age, 58 years) free of CVD at cycle 6 of the Framingham Offspring Study. Overall, 677 participants (21.5%) had a CVD end point over a median of 16.0 years of follow-up. Total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), direct LDL-C (Denka Seiken and Kyowa Medex methods), and hsCRP (Dade Behring method) concentrations were measured by automated analysis. LDL-C was also calculated by both the Friedewald and Martin methods. RESULTS: Considering all CVD outcomes on univariate analysis, significant factors included standard risk factors (age, hypertension, HDL-C, hypertension treatment, sex, diabetes, smoking, and TC concentration) and nonstandard risk factors (non-HDL-C, direct LDL-C and calculated LDL-C, TG, and hsCRP concentrations). On multivariate analysis, only the Denka Seiken direct LDL-C and the Dade Behring hsCRP were still significant on Cox regression analysis and improved the net risk reclassification index, but with modest effects. Discordance analysis confirmed the benefit of the Denka Seiken direct LDL-C method for prospective hard CVD endpoints (new-onset myocardial infarction, stroke, and/or CVD death). CONCLUSIONS: Our data indicate that the Denka Seiken direct LDL-C and Dade Behring hsCRP measurements add significant, but modest, information about CVD risk, compared to standard risk factors and/or calculated LDL-C.

[Atherosclerosis (hypertension)].

Many studies have shown that atherosclerosis is an inflammatory disease. Therefore biomarkers reflecting the magnitude of inflammation can be also a good marker for atherosclerosis. Clinical studies have shown that high sensitive C reactive protein (hsCRP) is one of a promising biomarker for presence or progression of atherosclerosis. Markers for dyslipidemia, diabetes, hypertension, and injury of endothelium and smooth muscle cells also have links to atherosclerosis. Regarding hypertension, microalbuminuria and cystatin C levels show the degree of future risk for atherosclerosis. Atherosclerosis is pathologically so complicated that no single biomarker can be perfect and it is essential for every clinician to use several appropriate biomarkers together to diagnose the disease.

Adiponectin: an independent risk factor for coronary heart disease in men in the Framingham offspring Study.

OBJECTIVE: Our aim was to determine whether plasma adiponectin levels were an independent predictor of coronary heart disease (CHD) risk. METHODS AND RESULTS: Plasma adiponectin levels were measured in 3188 male and female participants from cycle 6 of the Framingham offspring Study (mean age: 57 years in both men and women; BMI: 28.5 kg/m(2) in men and 27.3 kg/m(2) in women), using a novel fully automated assay. Plasma adiponectin levels (median [25th percentile, 75th percentile]) were significantly higher in female than in male CHD-free subjects (14.8 [10.7,20.5] µg/ml versus 9.0 [7.0,12.2] µg/ml, p<0.001). Participants were followed for a mean of 7.5 years. After adjustment for age, BMI, smoking status, systolic blood pressure, treatment for hypertension, diabetes, use of cholesterol-lowering medication, total cholesterol level, high-density lipoprotein cholesterol level, and C-reactive protein levels, a higher plasma adiponectin level was a significant predictor of lower risk of future CHD events (n=117) in men (HR 0.49, p<0.0022). A similar trend was observed in women, but was no longer significant after multivariate adjustments. CONCLUSIONS: Our data indicate that plasma adiponectin levels are an independent predictor of CHD in Caucasian men initially free of CHD.

Effects of weight loss, induced by gastric bypass surgery, on HDL remodeling in obese women.

Plasma lipoproteins and glucose homeostasis were evaluated after marked weight loss before and over 12 months following Roux-en-Y gastric-bypass (RYGBP) surgery in 19 morbidly obese women. Standard lipids, remnant-lipoprotein cholesterol (RLP-C); HDL-triglyceride (TG); apolipoproteins (apo) A-I, A-II, E, and A-I-containing HDL subpopulations; lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) mass and activity; plasma glucose and insulin levels were measured before and at 1, 3, 6, and 12 months after GBP surgery. Baseline concentrations of TG, RLP-C, glucose, and insulin were significantly higher in obese than in normal-weight, age-matched women, whereas HDL cholesterol (HDL-C), apoA-I, apoA-II, alpha-1 and alpha-2 levels were significantly lower. Over 1 year, significant decreases of body mass index, glucose, insulin, TG, RLP-C, HDL-TG, and prebeta-1 levels were observed with significant increases of HDL-C and alpha-1 levels (all P < 0.05). Changes of fat mass were correlated with those of LDL cholesterol (P = 0.018) and LCAT mass (P = 0.011), but not with CETP mass (P = 0.265). Changes of fasting plasma glucose concentrations were inversely correlated with those of CETP mass (P = 0.005) and alpha-1 level (P = 0.004). Changes of fasting plasma insulin concentrations were positively correlated with those of LCAT mass (P = 0.043) and inversely with changes of alpha-1 (P = 0.03) and alpha-2 (P = 0.05) concentrations. These results demonstrate beneficial changes in HDL remodeling following substantial weight loss induced by RYGBP surgery and that these changes are associated with improvement of glucose homeostasis in these patients.

Substitution of vegetable oil for a partially-hydrogenated fat favorably alters cardiovascular disease risk factors in moderately hypercholesterolemic postmenopausal women.

OBJECTIVE: Compared to vegetable oils in their unmodified state, partially-hydrogenated fat is associated with less favorable effects on cardiovascular disease (CVD) risk factors. Acceptable alternatives must be adjudicated. Our objective was to assess the effect of a recent commercial fat substitution, corn oil for partially-hydrogenated soybean oil. METHODS: Using a double-blind cross-over design, 30 postmenopausal women >or=50 years with LDL-cholesterol concentrations >or=120 mg/dL were randomly assigned to each of two 35-day phases; all food and beverage was provided to maintain body weight. Corn or partially-hydrogenated soybean oil was incorporated throughout the diet and contributed two-thirds of fat. Primary outcomes included fasting and non-fasting lipid, lipoprotein, apolipoprotein, and fasting high sensitivity C-reactive protein (hsCRP) concentrations; secondary outcomes included fasting small dense LDL (sdLDL)-cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, and endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities. RESULTS: Relative to the partially-hydrogenated soybean oil enriched diet, the corn oil enriched diet resulted in lower fasting total cholesterol (7%; P<0.0001), LDL-cholesterol (10%; P<0.0001), VLDL-cholesterol (7%; P=0.052), apo B (9%; P<0.0001), lipoprotein (a) [Lp(a)] (5%; P=0.024), sdLDL-cholesterol (17%; P=0.001), and RemLC (20%; P=0.007) concentrations, and no significant effect on the other outcomes. Changes in postprandial (4-h post-meal) lipid, lipoprotein and apolipoprotein concentrations were similar to the fasting state. CONCLUSION: The replacement of partially-hydrogenated soybean oil with corn oil favorably affects a range of CVD risk factors and is an appropriate option to decrease cardiovascular disease risk factors in moderately hypercholesterolemic individuals.

Hyperbaric oxygen induces basic fibroblast growth factor and hepatocyte growth factor expression, and enhances blood perfusion and muscle regeneration in mouse ischemic hind limbs.

BACKGROUND: It is not clear how hyperbaric oxygen therapy (HBO) affects ischemia-induced pathophysiological responses such as angiogenesis and skeletal muscle regeneration. In the present study the effects of HBO on the functional and morphological recovery of ischemic hind limbs, blood perfusion and the local production of angiogenic growth factors were studied in a mouse model. METHODS AND RESULTS: Mice were placed in pure oxygen under 3 atm for 1 h/day for 14 days after the removal of a segment of the left femoral artery. HBO-treated mice showed better functional recovery and greater blood flow in the ischemic hind limb than untreated mice. Histological examination revealed unatrophied muscle fibers with islands of small regenerating muscle cells only in HBO-treated mice. Regeneration of muscle was confirmed by the increase in myf5 mRNA. The amount of mRNA for vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) was slightly increased in the ischemic hind limbs. HBO eliminated the increase in VEGF mRNA. In contrast, the amount of mRNA for bFGF and HGF was further increased by HBO treatment. HBO transiently increased early growth response protein 1 (Egr-1) in the ischemic hind limbs. CONCLUSIONS: HBO accelerates the recovery of ischemic hind limbs by increasing the production of bFGF and HGF and by promoting muscle regeneration in mice.

Suppressive effects of diacylglycerol oil on postprandial hyperlipidemia in insulin resistance and glucose intolerance.

The diacylglycerol (DAG), a commonly used as a cooking oil in Japan, results in a lower elevation of serum triglyceride (TG) after ingestion compared to triacylglycerol (TAG). Postprandial hyperlipidemia (PPHL) and an increase in remnant lipoproteins (RLP) levels are risk factors for CAD, and a close relationship between PPHL and type 2 diabetes and/or insulin resistance has been reported. To evaluate the effect of DAG on PPHL in insulin resistance and glucose intolerance, 11 subjects with a normal glucose tolerance (NGT) and 14 subjects with IGT received oral fat tolerance test (OFTT) twice. They ingested emulsified test oils prepared with either DAG or TAG. In the IGT subjects, after the DAG and TAG load, the serum concentrations of TG, RLP-TG, and RLP-cholesterol increased throughout the 4-h study. The responses of these variables above baseline after the DAG load were significantly smaller than those after the TAG load (p<0.05). In contrast, in the NGT subjects, changes in these parameters were much smaller than those observed for IGT subjects. The difference in the integrated responses for serum RLP-cholesterol concentration during OFTT between DAG and TAG in all subjects can be easily explained by the integrated response of insulin rather than glucose during oral glucose tolerance test (r=0.7, p<0.01). DAG was more effective in insulin resistant and hyperinsulinemic participants regardless of glucose intolerance, and may be beneficial in reducing the extent of CAD risk in such individuals.