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Ion-transfer reactions of alkyl and perfluoroalkyl carboxylate ions (CH 3 (CH 2 ) n-2 COO - with n = 8-12 and CF 3 (CF 2 ) n-2 COO - with n = 3-9) were investigated at the polarized Cl-(CH 2 ) m -Cl with m = 2, 4, 6, and 8 (O) | water (W) interface to evaluate the effects of n and m on the solvation energy of the ions, as well as on their methylene and terminal groups. These ions exhibited reversible or quasi-reversible voltammetric waves due to their transfer across the O | W interfaces, enabling the determination of formal potentials and formal Gibbs transfer energies from O to W, Δ G tr,O → W 0 ' . The Δ G tr,O → W 0 ' values for CH 3 (CH 2 ) n-2 COO - and CF 3 (CF 2 ) n-2 COO - increased linearly with n, allowing the estimation of Δ G tr,O → W 0 ' for methylene and difluoromethylene groups, Δ G tr,O → W 0 ' (CH 2 ) and Δ G tr,O → W 0 ' (CF 2 ), and for their terminal groups, Δ G tr,O → W 0 ' (COO -  + CH 3 ) and Δ G tr,O → W 0 ' (COO -  + CF 3 ). Whereas the Δ G tr,O → W 0 ' (CH 2 ) and Δ G tr,O → W 0 ' (CF 2 ) hardly changed with the variation in m, the Δ G tr,O → W 0 ' (COO -  + CH 3 ) and Δ G tr,O → W 0 ' (COO -  + CF 3 ) decreased noticeably. These results suggest that the solvation energy for ions in Cl-(CH 2 ) m -Cl increases with m, regardless of hydrophilic or lipophilic nature of the ions. Based on these findings, the advantage of using Cl-(CH 2 ) m -Cl with a large m as a non-aqueous solvent for ion-transfer voltammetry was discussed., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Purpose: To retrospectively evaluate the diagnostic potential of magnetic resonance imaging (MRI)-based features and radiomics analysis (RA)-based features for discriminating ovarian clear cell carcinoma (CCC) from endometrioid carcinoma (EC)., Materials and Methods: Thirty-five patients with 40 ECs and 42 patients with 43 CCCs who underwent pretherapeutic MRI examinations between 2011 and 2022 were enrolled. MRI-based features of the two groups were compared. RA-based features were extracted from the whole tumor volume on T2-weighted images (T2WI), contrast-enhanced T1-weighted images (cT1WI), and apparent diffusion coefficient (ADC) maps. The least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation method was performed to select features. Logistic regression analysis was conducted to construct the discriminating models. Receiver operating characteristic curve (ROC) analyses were performed to predict CCC., Results: Four features with the highest absolute value of the LASSO algorithm were selected for the MRI-based, RA-based, and combined models: the ADC value, absence of thickening of the uterine endometrium, absence of peritoneal dissemination, and growth pattern of the solid component for the MRI-based model; Gray-Level Run Length Matrix (GLRLM) Long Run Low Gray-Level Emphasis (LRLGLE) on T2WI, spherical disproportion and Gray-Level Size Zone Matrix (GLSZM), Large Zone High Gray-Level Emphasis (LZHGE) on cT1WI, and GLSZM Normalized Gray-Level Nonuniformity (NGLN) on ADC map for the RA-based model; and the ADC value, spherical disproportion and GLSZM_LZHGE on cT1WI, and GLSZM_NGLN on ADC map for the combined model. Area under the ROC curves of those models were 0.895, 0.910, and 0.956. The diagnostic performance of the combined model was significantly superior (p = 0.02) to that of the MRI-based model. No significant differences were observed between the combined and RA-based models., Conclusion: Conventional MRI-based analysis can effectively distinguish CCC from EC. The combination of RA-based features with MRI-based features may assist in differentiating between the two diseases., (© 2024. The Author(s).)

To investigate the prevalence of and factors associated with sarcopenia in Japanese patients with rheumatoid arthritis (RA). We analyzed a cross-section of patients with RA participating in the Institute of Rheumatology Rheumatoid Arthritis cohort survey in 2021. Participants completed self-administered questionnaires, including a 5-item sarcopenia screening index (SARC-F). Patients with a SARC-F score of 4 or higher were categorized as having sarcopenia. Among 2416 Japanese patients with RA (2113 women and 303 men; mean age 63.9 years), 341 (14.1%) patients were categorized as having sarcopenia. In a multivariable analysis of patients of all ages, age, body mass index (BMI), disease duration, history of fracture, patient pain on a visual analog scale (VAS), patient or physician global assessments based on VAS, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), biologic disease-modifying antirheumatic drugs (bDMARDs), and corticosteroids were significantly (P < 0.05) associated with sarcopenia. Disease duration, patient global assessments based on VAS, and use of NSAIDs and bDMARDs were significantly associated with sarcopenia among the patients aged < 65 years, whereas age, female sex, BMI, disease duration, history of fracture, patient pain VAS and global assessments based on VAS, and use of bDMARDs and corticosteroids were significantly associated with sarcopenia in patients aged ≥ 65 years. In Japanese patients with RA, age, BMI, disease duration, history of fracture, patient pain VAS and global assessments based on VAS, and use of NSAIDs, bDMARDs, and corticosteroids were associated with sarcopenia. Among older patients with RA, female sex was additionally associated with sarcopenia. Key Points • To our knowledge, this is the first report showing factors associated with sarcopenia in Japanese patients with rheumatoid arthritis using a large cohort database. • Age, BMI, disease duration, history of fracture, patient pain on a visual analog scale, and use of nonsteroidal anti-inflammatory drugs, biologic disease-modifying antirheumatic drugs, and corticosteroids were associated with sarcopenia in Japanese patients with rheumatoid arthritis. Limited to elderly patients, female sex was also associated with sarcopenia., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Despite their high success rates, peri-implantitis can affect the stability and function of dental implants. Various treatment modalities have been investigated for the treatment of peri-implantitis to achieve re-osseointegration. An electronic literature search was performed supplemented by a manual search to identify studies published until January 2022. Articles that evaluated re-osseointegration in peri-implantitis sites in animal models following laser therapy or antimicrobial photodynamic therapy (aPDT) were included. Case reports, case series, systematic reviews, and letters to the editor were excluded. Risk of bias and GRADE assessment were followed to evaluate the quality of the evidence. Six studies out of 26 articles identified on electronic search were included in this review. The studies included animal studies conducted on canine models. Four out of six studies reported a higher degree of re-osseointegration following treatment of implants with laser therapy. The findings suggest that laser decontamination shows potential in enhancing re-osseointegration, particularly with the Er: YAG laser, which effectively decontaminated implant surfaces. However, conflicting outcomes and limitations in the evidence quality warrant caution in drawing definitive conclusions. Based on the limited available evidence, laser therapy may show a higher degree of re-osseointegration of implants than mechanical debridement., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC., Patients and Methods: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery., Results: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16)., Conclusions: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC., (© 2023. Society of Surgical Oncology.)

The genus Claviceps (Clavicipitaceae) is famous for producing ergot alkaloids (EAs) in sclerotia. EAs can cause ergotism, resulting in convulsions and necrosis when ingested, making these compounds a serious concern for food safety. Agroclavine (2), a typical Clavine-type EA, is a causative agent of ergotism and is listed as a compound to be monitored by the European Food Safety Authority. Clavine-type EAs are known to cause cytotoxicity, but the mechanism has not been elucidated. We performed annexin V and PI double-staining followed by flow cytometric analysis to detect apoptosis in HepG2 and PANC-1 cells after exposure to Clavine-type EAs. Clavine-type EAs reduced cell viability and induced apoptosis in both cell lines. We then performed LC-MS analysis of EAs from 41 sclerotia samples of Claviceps collected in Japan. 24 out of 41 sclerotia extracts include peptide-type EAs (ergosine/inine: 4/4', ergotamine: 5, ergocornine/inine: 6/6', α-ergocryptine/inine: 8/8', and ergocristine/inine: 9/9') and 19 sclerotia extracts among 24 sclerotia detected peptide type EAs include Clavine-type EAs (pyroclavine: 1, agroclavine: 2, festuclavine: 3) by LC-MS. We then performed a metabolomic analysis of the EAs in the sclerotia using principal component analysis (PCA). The PCA score plots calculated for EAs suggested the existence of four groups with different EA production patterns. One of the groups was formed by the contribution of Clavine-type EAs. These results suggest that Clavine-type EAs are a family of compounds requiring attention in food safety and livestock production in Japan., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Antibody drugs that target amyloid β (Aβ) are considered possible treatments for Alzheimer's disease; however, most have been dropped from clinical trials. We hypothesized that administration route for antiAβ antibody (AntiAβ) might affect its therapeutic potential and thus compared delivery of antibodies to the brain and their effect on cognitive dysfunction and amyloid disposition via intravenous (i.v.) and intranasal routes with and without the cell-penetrating peptide, L-penetratin. We demonstrated that intranasal administration with L-penetratin more efficiently delivered human immunoglobulin G (IgG), a model molecule for AntiAβ, to the brain compared with i.v. injection. We found that multiple intranasal treatments with Alexa 594-labeled AntiAβ (A594-AntiAβ) with L-penetratin significantly improved learning by mice with aged amyloid precursor protein (APP) knock-in (App KI mice). Further, intranasal administration of A594-AntiAβ increased the amount of soluble Aβ (1-42) in the brain, suggesting suppression of Aβ aggregation in insoluble form and involvement of activated microglia in Aβ clearance. Thus, administration route may be critical for efficient delivery of AntiAβ to the brain, and the nose-to-brain delivery with L-penetratin can maximize its therapeutic efficacy., (© 2022. Controlled Release Society.)

Background: Interval appendectomy or non-operative management is commonly performed for complicated appendicitis in adult patients. However, these treatments are still controversial because the incidence rate of appendiceal tumors recognized after interval appendectomy is reportedly higher than that after emergency appendectomy. Thus, this study aimed to compare the appendiceal tumor rates between uncomplicated and complicated appendicitis., Methods: This study was a retrospective review of patients with appendicitis who underwent surgical removal at a single institution over 7.5 years. The primary objective was the comparison of the incidence rate of appendiceal tumors using propensity score matching, and the secondary objective was the same comparison among older patients, defined as patients aged ≥ 60 years., Results: A total of 1277 patients were included. Of these patients, 297 (23.3%) were preoperatively diagnosed with complicated appendicitis. Moreover, 22 (1.7%) patients, including 14 cases of complicated appendicitis and 8 cases of uncomplicated appendicitis, were diagnosed with appendiceal tumors based on pathological examination. No significant difference was found in the incidence rate of appendiceal tumors between the two groups after matching for patients' background, including age, sex, and history of appendicitis by propensity score matching (P = 0.073). However, among patients aged ≥ 60 years, the incidence of appendiceal tumors was significantly higher in complicated than in uncomplicated appendicitis (P = 0.006)., Conclusions: Although the overall risk of appendiceal tumors did not differ between complicated and uncomplicated appendicitis when analyzed by the propensity score matching, in older patients aged ≥ 60 years, the risk increased among those with complicated appendicitis. Therefore, although the incidence is low, complicated appendicitis, particularly, among older patients, should be examined carefully and be performed IA when unusual findings exist., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Internal hernia (IH) is one of the critical complications after gastrectomy with Roux-en-Y reconstruction, which can be prevented by closing mesenteric defects. However, only few studies have investigated the incidence of IH after laparoscopic total gastrectomy (LTG) with Roux-en-Y reconstruction for gastric cancer till date. This study aimed to assess the efficacy of defect closure for the prevention of IH after LTG., Methods: This multicenter, retrospective cohort study collected data from 714 gastric cancer patients who underwent LTG with Rou-en-Y reconstruction between 2010 and 2016 in 13 hospitals. We evaluated the incidence of postoperative IH by comparing closure and non-closure groups of Petersen's defect, jejunojejunostomy mesenteric defect, and transverse mesenteric defect., Results: The closure group for Petersen's defect included 609 cases, while the non-closure group included 105 cases. The incidence of postoperative IH in the closure group for Petersen's defect was significantly lower than it was in the non-closure group (0.5% vs. 4.8%, p < 0.001). The closure group for jejunojejunostomy mesenteric defect included 641 cases, while the non-closure group included 73 cases. The incidence of postoperative IH in the closure group of jejunojejunostomy mesenteric defect was significantly lower than that in the non-closure group (0.8% vs. 4.1%, p = 0.004). Out of 714 patients, 41 underwent retro-colic reconstruction. No patients in the transverse mesenteric defect group developed IH., Conclusion: Mesenteric defect closure after LTG with Roux-en-Y reconstruction may reduce postoperative IH incidence. Endoscopic surgeons should take great care to prevent IH by closing mesenteric defects., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The diversity of child social skills development is not well detected among Asian countries. Culturally validated assessments are needed for practitioners to evaluate child social skills. This study tested the measurement invariance of the Social Skill Scale (SSS) across Japanese and Chinese samples and explored country differences in child social skills development. The SSS utilizes a widely used factor structure (assertion, self-control, and cooperation subdomains) and has established Japanese and Chinese versions. We conducted investigations with an identical process and materials with different language versions, collecting data from 931 Japanese kindergarten children (M age  = 4.35, SD age  = 1.07; 53.6% boys) and from 1130 Chinese kindergarten children (M age  = 4.47, SD age  = 1.00; 52.3% boys). We used multiple confirmatory factor analysis to test measurement invariance of the SSS and established the validity, reliability, and scalar measurement invariance for the first-order factor structure of the SSS across the two country samples. We also examined country differences on the associations between demographics, parenting practice, and child social skills development. We found that, compared to the Chinese sample, cooperation skills significantly increased more with age among the Japanese sample. However, spanking was negatively related to self-control skills development in both countries. Our findings contribute to the demonstration of the diversity of child social skills development and have important implications for assessing and developing child social skills using culture-specific strategies., Competing Interests: Conflict of InterestThe contributing authors have no potential conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Laser ablation-ICP-mass spectrometer (LA-ICPMS) now becomes one of the most principal analytical technique for mapping analysis for major to trace elements in rocks, minerals, functional materials, or biological tissue samples. In this study, imaging analysis was conducted with coupling of small volume cell and off-set laser ablation protocol to improve the spatial resolution. Combination of newly designed small volume cell and in-torch gas mixing protocols provides faster washout time of the signals (about 0.8 s for reducing 238 U being one part in a hundred, 1% level). This is very important to improve the spatial resolution in a direction of laser scanning. Moreover, combination of small distances between the laser-line scan (laser pitch distance) and preferential and total ablation of only biological tissue samples placed on glass substrate results in laser ablation of smaller areas than the size of laser ablation pit (shaving ablation). With the shaving ablation, laser-line scanning with narrower-band width (e.g., 2 µm) can be achieved even by the laser beam of 8 µm diameter. To demonstrate the practical usage of the present technique, imaging analysis of Gd-ethylenediamine tetra-methylene phosphonic acid-doped mouse bone was conducted. Preferential distribution of Gd at the edge of the apatite cell was more clearly identified by the present technique. Combination of the shorter washout system setup and the shaving ablation protocol enables us to improve the spatial resolution of the elemental imaging obtained with the LA-ICPMS technique., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: Minimally invasive esophagectomy (MIE) is increasingly performed to expect lower complication rate compared to open esophagectomy. Studies of minimally invasive Ivor Lewis esophagectomy (MIILE) with circular staplers have reported better outcomes compared to MIE with cervical anastomosis, but frequent anastomotic complications have also been reported. MIILE with linear staplers is a promising alternative, but the long-term functional and oncological outcomes are uncertain., Methods: To evaluate the functional and oncological outcomes of MIILE with linear stapled anastomosis, a retrospective cohort study was performed in 104 patients who underwent MIILE with linear stapled anastomosis for esophageal malignant tumors. The primary endpoints were the overall complication and anastomotic leak rates. The secondary endpoints were late complications, overall and disease-free survival, and nutritional status at 6 and 12 months after MIILE., Results: Anastomotic leak occurred in 4 patients (3.8%). The short-term complication rate of grade IIIb or higher was 6.7%. During a median 57-month follow-up period, anastomotic stricture occurred in one patient, 7 required hiatal hernia repair, and 2 underwent conduit revision surgery. The 5-year overall survival and disease-free survival rates were 69.3% and 59.5%, respectively. Status of reflux esophagitis at the time of most recent evaluation was grade N/A/B/C/D in 52/10/10/13/8 among 93 patients who had follow-up endoscopy. The mean body weight loss at 6 and 12 months after MIILE was 11.3 and 11.8% with maintenance of the serum albumin level., Conclusions: MIILE with linear stapled anastomosis is a safe procedure with a low anastomotic complication rate and favorable long-term functional and survival outcomes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to evaluate the prevalence of, and the factors associated with, frailty in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires, which included the 5-item frailty screening index. Patients were classified as frail, prefrail, or robust based on the 5 components of the frailty screening index. Logistic regression analyses were used to evaluate associations between clinical variables and frailty. Among 3,290 Japanese patients with RA (86.7% female, mean age 62.4 years) who participated this frailty study, 549 (16.7%) patients were categorized as frailty, 2,063 (62.7%) as prefrailty, and 678 (20.6%) as robust. In multivariable models, body mass index (BMI) ≥ 25 kg/m 2 (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.41 to 2.47), BMI < 18.5 kg/m 2 (OR 1.31, 95% CI 1.00 to 1.71), disease activity scores in 28 joints (DAS28) (OR 1.32, 95% CI 1.18 to 1.47), Japanese version of Health Assessment Questionnaire disability index (J-HAQ) (OR 1.26, 95% CI 1.04 to 1.52), the European Quality of Life-5 Dimensions (EQ-5D) (OR 0.80, 95% CI 0.74 to 0.85), non-steroidal anti-inflammatory drug (NSAID) use (OR 1.59, 95% CI 1.23 to 1.98), and methotrexate (MTX) use (OR 0.75, 95% CI 0.60 to 0.94) were significantly (P < 0.05) associated with frailty. BMI (both overweight and underweight), DAS28, J-HAQ, EQ-5D, NSAID use, and MTX nonuse appear to be associated with frailty in Japanese patients with RA. Key Points • This is the largest study showing the prevalence and the associated factors of frailty in patients with RA. • Maintaining normal BMI appears to be important for preventing frailty in patients with RA. • We confirmed the significant associations of frailty with high disease activity, high degree of disability, and poor health related QOL in Japanese patients with RA. • NSAID use and MTX nonuse were associated with the frailty in Japanese patients with RA, which could be explained by patients' background., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: Preoperative loss of skeletal muscle mass, defined as sarcopenia, has been reported to be associated with higher incidence of complications following esophagectomy in patients with esophageal cancer. Although skeletal muscle loss promotes disability and reduced quality of life (QOL), only a few studies have focused on changes in skeletal muscle mass after surgery. This prospective cohort study aimed to evaluate the chronological changes in skeletal muscle mass after minimally invasive esophagectomy (MIE)., Methods: Patients with esophageal cancer scheduled to undergo MIE at our institution were prospectively registered. Skeletal muscle mass was evaluated before and 2, 6, 12, and 24 months after surgery. The effects of preoperative sarcopenia on surgical outcomes and chronological changes in skeletal muscle mass were evaluated., Results: Among the 71 eligible preoperative patients, 29 (40.8%) were diagnosed with sarcopenia. Patients with sarcopenia had significantly higher incidences of total (79.3% vs 52.4%, p = 0.026) and gastrointestinal (37.9% vs 11.9%, p = 0.019) complications and a significantly longer length of hospital stay (31 vs 23 days, p = 0.005) than those without sarcopenia. The median skeletal muscle mass index (kg/m 2 ) was 7.09 before surgery, which decreased to 6.46 two months after surgery (- 7.2%, P < 0.01). Thereafter, values of 6.90, 6.86, and 7.06 were reported at 6, 12, and 24 months after surgery, respectively., Conclusion: Patients with preoperative sarcopenia developed more postoperative complications than those without it. Additionally, patients experienced a decrease in skeletal muscle mass during the early postoperative period following MIE. Further research on perioperative countermeasures to prevent skeletal muscle loss during the early postoperative period and to prevent postoperative complications is necessary for patients undergoing MIE., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The chromosomal locations of a new class of Revolver transposon-like elements were analyzed by using FISH method on the metaphase chromosome in somatic cell division of the rye cultivar Petkus. First, the Revolver standard element probe λ2 was weakly hybridized throughout the rye chromosome, and comparatively large interstitial signals spotted with a dot shape were detected together with several telomeric regions. The dot shape interstitial signal was stably detected at one site on Chromosome (Chr) 1R (middle part of the interstitial region of the short arm), three sites on Chr 2R (distal part of the interstitial region and adjacent to the centromere on the short arm, middle part of the interstitial region of the long arm), and two sites on Chr 5R (middle part of the interstitial region and adjacent to the centromere on the long arm). The Revolver λ2 probe was effective for identification of 1R, 2R, and 5R chromosomes. On the other hand, Revolver nonautonomous element-specific L626-BARE-100 probe was strongly distributed throughout the rye chromosomes, and considerable numbers and diverse lengths of transcripts were detected by RT-PCR. Although the standard elements were found in localized clusters, the nonautonomous elements tended to be dispersed throughout the genome. Clustered nature of Revolver is a significantly rare case in genomics., (© 2021. Institute of Plant Genetics, Polish Academy of Sciences, Poznan.)

In this study, we assess the association between the occurrence of new fractures and vitamin D deficiency in Japanese patients with rheumatoid arthritis using our large IORRA cohort. The results suggest that vitamin D deficiency is a significant risk factor for new fractures in Japanese female patients over the age of 50 years with rheumatoid arthritis., Purpose: Both rheumatoid arthritis (RA) and menopause are known risk factors for the onset of osteoporosis. The occurrence of new clinical fractures in patients with RA can significantly lower quality of life. The purpose of this study was to investigate whether vitamin D deficiency in Japanese women with RA could be a risk factor for new fractures., Methods: Between 2011 and 2017, a total of 2567 female patients with RA over the age of 50 years (mean age, 65.9 years) were enrolled in a prospective observational study. Self-reported occurrences of new fractures were verified using patient medical records. Vitamin D deficiency was defined as serum 25(OH)D levels < 20 ng/mL. Cox proportional hazards models were used to analyze the independent contributions of various risk factors to the occurrence of a new fracture., Results: New clinical fractures were sustained by 205 patients in the included cases. Among them, new osteoporotic fractures were sustained by 139 patients (63 vertebral fractures and 76 non-vertebral fractures). Among all patients, the mean (SD) serum 25(OH)D level was 16.9 (5.89) ng/mL and the prevalence of vitamin D deficiency was 72.6%. A Cox proportional hazards model revealed that vitamin D deficiency was significantly associated with all new clinical fractures (hazard ratio, 1.44 [95% confidence interval 1.02‒2.05]; p = 0.0365) and all new osteoporotic fractures (hazard ratio, 1.75 [95% confidence interval 1.14‒2.69]; p = 0.0109)., Conclusion: Vitamin D deficiency is a risk factor for new fractures in Japanese female patients over the age of 50 years with RA. Screening these patients for serum 25(OH)D could potentially be seminal to reducing their risk of fractures., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Entamoeba histolytica is distributed throughout the world. Invasive amebiasis affects millions of people globally, and the associated complications cause 40,000-100,000 deaths per year. In countries where fecal-oral transmission is unusual, amebic colitis is not common, and the infection may be seen in travelers to and emigrants from endemic areas. Without adequate treatment, amebic colitis may develop into fulminant and become rapidly fatal. With the current increase in global mobility, amebic colitis should be suspected even in patients not in the endemic areas. CT plays an important role in the diagnosis of amebic colitis by demonstrating the presence of colitis with the typical involvement of the cecum and rectum. Pathological features of atypical involvement are also demonstrated. Since preoperative diagnosis can reduce the mortality associated with necrotizing colitis, radiologists need to recognize the typical as well as atypical CT findings of amebic colitis. Considering this requirement, this paper aims to describe the histopathologic features of amebic colitis and to illustrate the spectrum of corresponding CT findings.

Background: Presently, there is no consensus as to what procedure of intracorporeal esophagojejunostomy (EJS) in totally laparoscopic total gastrectomy (TLTG) is best to reduce postoperative complications. The aim of this study was to demonstrate the superiority of linear stapled reconstruction in terms of anastomotic-related complications for EJS in TLTG., Methods: We collected data on 829 consecutive gastric cancer patients who underwent TLTG reconstructed by the Roux-en-Y method with radical lymphadenectomy between January 2010 and December 2016 in 13 hospitals. The patients were divided into two groups according to reconstruction method and matched by propensity score. Postoperative EJS-related complications were compared between the linear stapler (LS) and the circular stapler (CS) groups., Results: After matching, data from 196 patients in each group were analyzed. The overall incidence of EJS-related complications was significantly lower in the LS group than in the CS group (4.1% vs. 11.7%, p = 0.008). The incidence of EJS anastomotic stenosis during the first year after surgery was significantly lower in the LS group than in the CS group (1.5% vs. 7.1%, p = 0.011). The incidence of EJS bleeding did not differ significantly between the groups, although no bleeding was observed in the LS group (0% vs. 2.0%, p = 0.123). The incidence of EJS leakage did not differ significantly between the groups (2.6% vs. 3.6%, p = 0.771)., Conclusion: The use of linear stapled reconstruction is safer than the use of circular stapled reconstruction for intracorporeal EJS in TLTG because of its lower risks of stenosis.

Background: The recurrent laryngeal nerve (RLN) lymph nodes are among the most frequently involved lymph nodes in esophageal cancer. Surgical removal of these lymph nodes is considered beneficial for postoperative prognosis, especially in patients with squamous cell carcinoma. Unfortunately, the precise surgical anatomy of the upper mediastinum is not well understood and no distinct high-resolution images are currently available., Methods: In this article, we provide a simple intuitive concept of upper mediastinal surgical anatomy that could facilitate rational anatomical lymphadenectomy of the RLN lymph nodes. The essential concept of this mesenteric excision is to mobilize mesoesophagus including RLN in an en bloc fashion and to save RLN laterally by incising visceral sheath. This is applicable identically to both right and left upper mediastinum., Results: Between January 2009 and December 2017, thoracoscopic esophagectomy with upper mediastinal lymphadenectomy for primary esophageal cancer was performed in 189 patients. Median thoracoscopic procedure time was 297 (range 205-568) min and median intraoperative blood loss was 70 ml (range unmeasurable up to 2545 ml). Median number of harvested upper mediastinal lymph nodes was 12. Postoperative complication of Clavien-Dindo classification grade III or higher events was observed in 14% of patients. RLN palsy of grade II or higher occurred in 20 patients (11%)., Conclusion: The mesoesophagus in the upper mediastinum is an anatomical unit surrounded by fibrous connective tissue containing the esophagus, trachea, tracheoesophageal vessels, lymphatic tissue, and RLNs. Thus, mesenteric excision of esophagus is defined to resect this area by sparing trachea and RLNs for rational anatomical lymphadenectomy. We believe that this concept makes upper mediastinal lymphadenectomy safer and more appropriate.

The basidiomycetous yeast Moesziomyces antarcticus (often cited as Pseudozyma antarctica), originally isolated from a sediment sample obtained from Lake Vanda in Antarctica, was asexually typified but closely related to the smut fungus Moesziomyces bullatus (Ustilaginales). We found a smut fungus on an ovary of barnyardgrass (Echinochloa crus-galli) in Japan, which had been identified as M. bullatus. The teliospores germinated and formed yeast-like colonies. Physiological and phylogenetic studies revealed that the characteristics of the yeast-like isolates coincided with those of "P. antarctica." We thus recognised the smut fungus as the teleomorph of M. antarcticus, and then emended the description of M. antarcticus based on the holomorph. The identified fungus could degrade certain biodegradable plastics and produce mannosylerythritol lipids (MELs) in similar qualities as the "P. antarctica" type strain. This discovery provides a significant bioresource, as genetically diverse M. antarcticus isolates could be obtained from the smut fungus.

Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype-phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype-phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.

Key Message: Genomic prediction accuracy within a large panel was found to be substantially higher than that previously observed in smaller populations, and also higher than QTL-based prediction. In recent years, genomic selection for wheat breeding has been widely studied, but this has typically been restricted to population sizes under 1000 individuals. To assess its efficacy in germplasm representative of commercial breeding programmes, we used a panel of 10,375 Australian wheat breeding lines to investigate the accuracy of genomic prediction for grain yield, physical grain quality and other physiological traits. To achieve this, the complete panel was phenotyped in a dedicated field trial and genotyped using a custom Axiom TM Affymetrix SNP array. A high-quality consensus map was also constructed, allowing the linkage disequilibrium present in the germplasm to be investigated. Using the complete SNP array, genomic prediction accuracies were found to be substantially higher than those previously observed in smaller populations and also more accurate compared to prediction approaches using a finite number of selected quantitative trait loci. Multi-trait genetic correlations were also assessed at an additive and residual genetic level, identifying a negative genetic correlation between grain yield and protein as well as a positive genetic correlation between grain size and test weight.

Background: The outcomes of laparoscopic adhesiolysis for small bowel obstruction have generally been satisfactory over the short term. However, the long-term outcomes, including recurrence of symptoms and management of recurrence, remain controversial. This study compares the long-term outcomes of a series of laparoscopic and open surgery procedures for the treatment of small bowel obstruction., Methods: Patients who underwent adhesiolysis for small bowel obstruction at our institution between 2008 and 2015 were retrospectively reviewed. In total, 156 patients were enrolled, 78 with laparoscopic and 78 with open surgery. Propensity score matching was used to minimize the bias in patient selection. Long-term outcomes included incidence of recurrent symptoms and reoperation. In addition to the comparison of outcomes, risk factor assessment for recurrent symptoms and analysis of detailed information in patients with reoperation were performed. Statistical methods included χ 2 test, Mann-Whitney U test, Cox proportional hazards model, and Kaplan-Meier plots with log-rank comparison., Results: Laparoscopy was performed in a younger population with milder bowel dilation and less complicated etiologies. These factors were used to construct the propensity score model, which yielded a matched cohort of 52 legs in each group. Laparoscopy achieved good short-term outcomes including early recovery of gastrointestinal function, reduced incidence of complications, and shorter hospital stay. For long-term outcomes, while the overall recurrence rate did not differ between the groups (11.5 vs 7.7%), the incidence of reoperation for recurrence was significantly higher in the laparoscopically treated group (7.7 vs 0%, p = .017). The Cox proportional hazards model showed that multiple prior surgeries (≥3 times) were a risk factor for overall recurrence (hazard ratio 7.39, p = .041)., Conclusion: Laparoscopic adhesiolysis did not decrease the incidence of recurrent symptoms; rather, it was related to higher incidence of recurrent small bowel obstruction requiring surgical treatment.

The purpose of the study is to demonstrate the characteristics of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA) and risk factors for LPD among RA patients concurrently treated with methotrexate (MTX). Among patients who participated in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study in October 2010, past existence of LPD from patient's report was confirmed through medical charts. Background factors, LPD pathological findings, and the clinical courses of LPD and RA after LPD were assessed. To analyze the risk of MTX-associated LPD among RA patients concurrently treated with MTX, a nested case-control study design was used to select control patients who had received MTX but did not develop LPD by matching calendar date, sex, and age (within 5 years) at a 1:10 ratio. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for occurrence of LPD were analyzed by multivariate analysis. Forty-eight patients experienced LPD among 5757 patients, and 25 (52.1%) of those had lymphoma. LPD regressed in 60.4% of all LPD patients and 24.0% of lymphoma patients. In the 26 cases who developed LPD during MTX treatment, multivariate analysis revealed that 28-joint disease activity score (DAS28) (OR 1.57 [95% CI, 1.12-1.57]; p < 0.01) and lactate dehydrogenase (LDH) level (OR 1.01 [95% CI, 1.00-1.02]; p < 0.01), but not concomitant dose of MTX, were risk factors for LPD. Among RA patients concomitantly treated with MTX, high disease activity, but not MTX dose, was a risk factor for the occurrence of LPD.

The Notch signaling pathway is a basic cell-to-cell communication mechanism. This pathway is activated by the interaction between Notch receptors and the ligands of adjacent cells. Once activated, Notch receptors are cleaved and the intracellular domains translocate into the nucleus, where the transcription of target genes starts. In the mammalian kidney, Notch receptors are activated during nephrogenesis. Afterwards, in the mature glomeruli, the Notch pathway becomes silent. However, many researchers have reported the activation of Notch receptors in mature podocytes under pathological conditions. In this review, we discuss the role of Notch signaling in podocytes.

Amelotin (AMTN) is expressed and secreted by ameloblasts in the maturation stage of amelogenesis and persist with low levels in the junctional epithelium (JE) of erupted teeth. The purpose of this study is to investigate the transcriptional regulation of the AMTN gene by transforming growth factor beta1 (TGFβ1) in gingival epithelial (GE1) cells in the apoptosis phase. Apoptosis was evaluated by the fragmentation of chromosomal DNA and TUNEL staining. A real-time PCR was carried out to examine the AMTN mRNA levels induced by TGFβ1 and Smad3 overexpression. Transient transfection analyses were completed using the various lengths of mouse AMTN gene promoter constructs with or without TGFβ1. Chromatin immunoprecipitation (ChIP) assays were performed to investigate the Smad3 bindings to the AMTN gene promoter by TGFβ1. TGFβ1-induced apoptosis in GE1 cells were detected at 24 and 48 h by DNA fragmentation and TUNEL staining. AMTN mRNA levels increased at 6 h and reached maximum at 24 h in GE1 cells. Luciferase activities of the mouse AMTN gene promoter constructs were induced by TGFβ1. The results of the ChIP assays showed that there was an increase in Smad3 binding to Smad-binding element (SBE)#1 and SBE#2 after stimulation by TGFβ1. Immunohistochemical localization of AMTN was detected in the JE, and the AMTN protein levels in Smad3-deficient mice were decreased compared with wild-type mice. AMTN mRNA levels were induced at the initiation of apoptosis by TGFβ1, which mediated through the Smad3 bindings to SBEs in the mouse AMTN gene promoter.

Purpose: A phase II study was performed to evaluate the safety and efficacy of laparoscopic gastrectomy (LG) for gastric cancer of clinical stage II or higher., Methods: The eligibility criteria were gastric cancer of clinical stage II or higher that was amenable to potentially curative resection. Patients with prior chemotherapy, tumors requiring total gastrectomy (TG), tumors that invaded adjacent organs, and patients with bulky lymph node metastasis were included. The primary endpoint was incidence of postoperative complications of grade II or higher in the Clavien-Dindo classification. The sample size was determined to be 73, based on an expected rate of complications of 19 % and a threshold of 30 %. Gastrectomy was performed by expert surgeons who were certified by the Japan Society for Endoscopic Surgery., Results: A total of 73 patients were enrolled; 54 patients (74 %) had clinical T stage T4a/T4b, and 47 patients (64 %) were administered preoperative chemotherapy. The type of surgery was distal gastrectomy in 41 patients and TG in 31 patients. Dissection of D2 or more was performed in 62 patients (85 %). Of the 25 patients who underwent D2/D2+ TG, 15 underwent splenectomy or pancreaticosplenectomy. R0 resection was performed in 64 patients (88 %). The median number of resected lymph nodes was 56, and postoperative complications occurred in 15 patients (20.5 %), which was significantly lower than the threshold value (p = 0.039). One in-hospital death occurred (1.4 %)., Conclusion: LG for gastric cancer of clinical stage II or higher can be safely performed by experienced surgeons.

Background: The critical risk factors for surgical site infection (SSI) after laparoscopic total gastrectomy (LTG) remain unclear. We analyzed the association between body composition and SSI after LTG., Methods: We performed a retrospective study of patients with gastric cancer who underwent LTG between March 2006 and October 2014 at Kyoto University Hospital, Japan. Visceral fat area and skeletal muscle mass were assessed from preoperative computed tomography scans to define sarcopenia and obesity. Patients were classified into one of four body composition categories according to the presence or absence of sarcopenia or obesity. The incidence of SSI was compared between the four body composition categories., Results: Of the 157 eligible patients, 45 (24 %) fulfilled the criteria for sarcopenic obesity, 28 (18 %) for nonsarcopenic obesity, 52 (33 %) for sarcopenic nonobesity, and 32 (20 %) for nonsarcopenic nonobesity. Thirty-two patients developed SSI (overall incidence rate, 20 %). The incidence of SSI in each body composition category was 33, 25, 13, and 9 %, respectively (P = 0.03). Multivariate logistic regression analysis showed that only sarcopenic obesity was associated with an increased incidence of SSI (odds ratio 4.59, 95 % confidence interval 1.18-17.78, P = 0.028)., Conclusions: Sarcopenic obesity is an independent risk factor for the development of SSI after LTG.

Background: When the indication for surgery of highly advanced gastric cancer is considered, careful selection of the patients is important. In addition to tumor-node-metastasis factors and peritoneal lavage cytology (CY), which are important predictors of prognosis, detection of circulating tumor cells (CTCs) could be another potential marker., Methods: This study prospectively evaluated CTCs using a semi-automated immunomagnetic separation system (CellSearch) for 136 patients with advanced gastric cancer to determine the frequency of CTC positivity. For 123 patients who also had their CY evaluated, the significance of both CTC and CY, was investigated as a potential biomarker to predict progression-free survival (PFS) or to monitor the therapeutic effect., Results: In 25 patients (18.4 %), CTCs were positive. Positive CTC counts were more common for tumors with diffuse histologic type and distant metastasis. The PFS of CTC-positive patients was significantly shorter than that of CTC-negative patients (hazard ratio 2.03; P = 0.016). A multivariate analysis of 123 patients showed that CTC and CY as well as performance status and macroscopic distant metastasis were independent factors for PFS. When both CTC and CY were converted to negative values by therapeutic interventions, long-term PFS was achieved., Conclusions: Detection of CTCs was an independent predictor of a shorter PFS in advanced gastric cancer. For selecting patients who require intensive treatment, CTCs could be a valuable biomarker. The combined status of CTC and CY would be useful in selecting patients for radical surgery. Further investigation with a larger number of patients is necessary to establish the importance of CTCs.

To clarify the impact of comorbidities on treatment strategies and outcomes in patients with rheumatoid arthritis (RA) using a large observational RA cohort, the presence of comorbidities was assessed using the Charlson Comorbidity Index (CCI). Changes in medication, disease activity by Disease Activity Score-28 joint count (DAS28) over 6 months, disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), and quality of life by EuroQOL-5-Dimensions (EQ-5D) over 1 year in patients with high disease activity (DAS28 > 5.1) at baseline were assessed according to age-adjusted CCI (CCI(A)) and categorized into four groups (CCI(A) 0, 1-2, 3-4, and ≥5). Among 5,317 patients, 975 patients (18.3%) had at least one comorbidity listed by CCI. DAS28, J-HAQ, and EQ-5D increased in severity with increased CCI(A) levels. Among patients with high disease activity (n = 267), treatment with methotrexate and/or biologics and improved DAS28 scores, shown by attenuated intensity, were associated with increased CCI(A) levels. J-HAQ improved from 1.29 ± 0.31 to 0.87 ± 0.37 in 1 year in the CCI(A) 0 group. The adjusted difference (standard error) in J-HAQ at 1 year in CCI(A) 1-2, 3-4, and ≥5 groups was worse than J-HAQ in the CCI(A) 0 group by 0.32 (0.09, p < 0.001), 0.45 (0.10, p < 0.001), and 0.45 (0.15, p < 0.01), respectively. The magnitude of improvement of EQ-5D was significantly attenuated with increasing CCI(A) levels. Thus, patients with comorbidities may not experience the same degree of benefit from recent RA treatments compared with patients without comorbidities in daily practice.

To determine the prevalence of vitamin D deficiency and associations with clinical characteristics in Japanese patients with rheumatoid arthritis (RA), serum 25(OH)D levels, laboratory data, and clinical data were obtained from 4,793 patients with RA (4,075 women, 718 men, mean age 59.7 years) who participated in the Institute of Rheumatology Rheumatoid Arthritis observational cohort study in April and May of 2011. Serum vitamin D levels were evaluated using a radioimmunoassay. We defined vitamin D deficiency as <20 ng/mL and severe deficiency as <10 ng/mL. Associations of vitamin D deficiency with patient characteristics were examined using multivariate logistic regression. Among all patients, the mean (SD) serum 25(OH)D level was 16.9 ng/mL (6.1), and the prevalence of vitamin D deficiency and severe deficiency were 71.8 and 11.5%, respectively. In multivariate analysis, female gender, younger age, high Japanese version of health assessment questionnaire (HAQ) disability score, low serum total protein levels, low serum total cholesterol levels, high serum alkaline phosphate (ALP) levels, and non-steroidal anti-inflammatory drug (NSAID) use were significantly associated with vitamin D deficiency (P < 0.01). Vitamin D deficiency appears to be common in Japanese patients with RA, as previously reported for patients of other ethnicities. Female gender, younger age, high HAQ disability score, low serum levels of total protein and total cholesterol, high serum ALP levels, and NSAID use appear to be associated with vitamin D deficiency in Japanese patients with RA.

Background: Endoscopic ultrasound (EUS)-guided drainage is widely used to manage pancreatic pseudocysts. Several studies have reported the use of EUS-guided drainage for pancreatic fistula and stasis of pancreatic juice caused by stricture of the pancreatic duct after pancreatic resection., Methods: At the authors' hospital, 262 patients underwent surgery involving pancreatic resection from April 2005 to March 2010. In 90 of these patients (34%), a grade B or C postoperative pancreatic fistula developed that required additional treatment. The authors performed EUS-guided transmural drainage (EUS-TD) for six patients (2.1%) with a pancreatic fistula or dilation of the main pancreatic duct visible by EUS. Percutaneous drainage was provided for 18 patients (6.8%). The success rates for EUS-TD and percutaneous drainage were compared in a retrospective analysis., Results: In all six cases, EUS-TD was performed successfully without complications. Five of the six patients were successfully treated with only one trial of EUS-TD. The final technical success rate was 100% for both EUS-TD and percutaneous drainage. Both the short- and long-term clinical success rates for EUS-TD were 100% and those for percutaneous drainage were 61.1 and 83%, respectively. The differences in these rates were not significant (short-term success, P = 0.091 vs. long-term success, P = 0.403). However, the time to clinical success was significantly shorter with EUS-TD (5.8 days) than with percutaneous drainage (30.4 days; P = 0.0013) in the current series., Conclusions: The EUS-TD approach appears to be a safe and technically feasible alternative to percutaneous drainage and may be considered as first-line therapy for pancreatic fistulas visible by EUS.

The anal canal is an important body part clinically. However, there is no agreement about the epithelium of the anal canal, the anal transitional zone (ATZ) epithelium in particular. The aim of this study is to clarify the structure of the epithelium of the human lower rectum and anal canal. Intact rectum and anus obtained from patients who underwent surgery for rectal carcinoma were examined by light and scanning electron microscopy (LM and SEM). By LM, three types of epithelium were observed in the anal canal: simple columnar epithelium, stratified squamous epithelium, and stratified columnar epithelium. The lower rectum was composed of simple columnar epithelium. SEM findings showed stratified squamous epithelium that consisted of squamous cells with microridges, changing to simple columnar epithelium consisting of columnar cells with short microvilli at the anorectal line. LM and SEM observations in a one-to-one ratio revealed that the area of stratified columnar epithelium based on LM corresponded to the anal crypt and sinus. In conclusion, the epithelium of the human anal canal was fundamentally composed of simple columnar epithelium and stratified squamous epithelium. We found no evidence of the ATZ.

Background: During esophagectomy, laparoscopy can be used together with thoracoscopy, but it is not known whether a combined thoracoscopic-laparoscopic procedure is associated with fewer postoperative complications than open esophagectomy, and without compromising oncological outcome., Methods: This was a longitudinal cohort study that included 185 esophageal cancer patients, including 72 who underwent combined thoracoscopic-laparoscopic esophagectomy (TLE), 34 who underwent thoracoscopic esophagectomy (TE), and 79 who underwent open esophagectomy (OE) between January 2002 and May 2010. The main outcome measures were postoperative respiratory and overall complications. The secondary outcome was 2-year relapse-free survival (RFS)., Results: Respiratory complications occurred in 9 patients who underwent TLE, 13 who underwent TE, and 31 who underwent OE. TLE was associated with fewer respiratory complications (TLE vs. OE: odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09-0.53 and TE vs. OE: OR, 0.71; 95% CI 0.29-1.76). Overall complications occurred in 34 patients who underwent TLE, 20 who underwent TE, and 54 who underwent OE. TLE was associated with fewer overall complications (TLE vs. OE: OR, 0.47; 95% CI 0.23-0.94 and TE vs. OE: OR, 0.51; 95% CI 0.21-1.25). The 2-year RFS rates were similar among the three groups: 71.6% for TLE, 57.7% for TE, and 58.3% for OE (TLE vs. OE: hazard ratio, 0.65; 95% CI 0.35-1.20 and TE vs. OE: hazard ratio, 0.91; 95% CI 0.45-1.82)., Conclusion: Unlike TE, TLE was associated with fewer postoperative complications than was OE, with no compromise of 2-year RFS. A randomized controlled trial with longer follow-up is needed.

Background: One prerequisite for the safe stapling of anastomoses is the formation of perfectly aligned B-shaped staples. Using an animal model, this study investigated whether precompression enhances secure staple formation., Methods: A 45-mm linear stapler with a blue cartridge (staple leg length, 3.5 mm) was used on three portions each of six porcine stomachs (cardia, center, and pylorus). Staple shape and height were examined according to the precompression time (0, 1, or 5 min) before firing. The shape was classified as optimal or suboptimal, and the heights of the staples were measured individually. The completeness of the proximal staple lines also was compared with the distal lines., Results: The optimal staple rate in the 5-min group (52.7%) was significantly higher than in the 1-min group (28.7%; p<0.001) or the 0-min group (17.1%; p=0.002). The optimal staple rate in the 5-min group for the cardiac portion (mean wall thickness, 2.7 mm) reached 98.9%. However, this rate was less than 50% in the center (5.3 mm) and pylorus (4.2 mm) portions regardless of the precompression time. Compared with the root side, the top side of the cartridge had a lower optimal rate (45.3 vs. 18.7%; p<0.001). A high correlation of completeness was observed between the distal and proximal sides of the stump., Conclusions: When a linear stapling device is used, proper staple formation is correlated with intestinal wall thickness, and a sufficient amount of precompression time is effective for gaining the secure staple formation.

Background: To facilitate acceptance of laparoscopic total gastrectomy (LTG) for patients with upper gastric cancer, a simple, secure technique of reconstruction is necessary. The authors developed a new technique for intracorporeal esophagojejunal anastomosis that does not require hand sewing., Methods: From September 2006 to January 2008, 16 patients (11 men and 5 women) with gastric cancer underwent LTG at the authors' institution. Laparoscopic esophagojejunal anastomosis using the following method was attempted for all patients. The esophagus was transected while being rotated by about 45 degrees counterclockwise to make the subsequent anastomosis easier. After the Y-anastomosis was created, an endoscopic linear stapler was applied to create a side-to-side anastomosis between the left dorsal side of the esophagus and the jejunal limb. The entry hole was first closed roughly with hernia staplers. Subsequently, an endoscopic linear stapler was applied so that all hernia staplers could be removed and the closure completed., Results: Laparoscopic esophagojejunal anastomosis was successfully performed for 15 patients. Intracorporeal anastomosis failed for one patient because a nasogastric tube was caught between the jaws of an endostapler, which resulted in a conversion to open procedure. No postoperative anastomotic complications occurred., Conclusions: Using the new technique, intracorporeal linear-stapled esophagojejunal anastomosis can be performed easily and securely. This technique could become one of the standard methods for reconstruction after LTG, facilitating the acceptance of LTG as a surgical option for patients with upper gastric cancer.

Background: Lymph node dissection is a crucial procedure for curative resection of gastric cancer [1]. To avoid portal vein injury during laparoscopic extended lymph node dissection for gastric cancer, taping of the common hepatic artery and subsequent confirmation of the portal vein have been recommended [2, 3]. This taping method, however, makes laparoscopic nodal dissection technically complicated. This study introduces a novel procedure for safe and simple laparoscopic suprapancreatic nodal dissection without taping of the common hepatic artery., Methods: The authors' novel, simplified method consists of four steps: (1) dissection along the cranial edge of the pancreas from right to left, (2) dissection along the splenic artery with exposure of the left renal fascia, (3) dissection along the left gastric and the common hepatic arteries, and (4) retraction of the lymph nodes surrounding the common and proper hepatic arteries and their complete dissection from the portal vein. This procedure is reversely directed compared with conventional open gastrectomy (i.e., the nodal dissection is from left to right). For this study, the lymph node stations and groups were defined according to the 13th edition of the Japanese Classification for Gastric Carcinoma. The described procedures were performed for 58 consecutive patients with gastric cancer. The indication for this operation is primary T1/T2 gastric cancer without clinical nodal metastasis., Results: In all cases, safely extended suprapancreatic lymph node dissection was successfully accomplished using the described technique. A total of 43.5 +/- 18 lymph nodes were retrieved, including 14.4 +/- 6.3 second-tier lymph nodes. The overall number of retrieved lymph nodes in this study was similar to that reported previously [4]. Postoperative morbidity occurred at a rate of 22.3%, and the mortality rate was 0%. There was no conversion to open surgery. The mean blood loss was 127 ml (range, 0-490 ml), and the mean operative time was 289 min (range, 104-416 min) in the last 20 consecutive cases. To date, no tumor recurrence has been observed. The median postoperative observation period was 1.4 years (range, 0.4-2.4 years)., Conclusion: The described novel procedure would be sufficient and convenient for dissection of the suprapancreatic lymph nodes.

Background: Laparoscopic pancreatic surgery is rapidly evolving due to improving instrumentation and surgical techniques. The challenges confronting laparoscopic pancreaticoduodenectomy (LPD), however, are its technical difficulty and its appropriateness for oncologic treatment. This study sought to develop a novel technique for LPD in an acute porcine model and to evaluate the safety and feasibility of LPD before clinical trials are undertaken., Methods: The LPD procedure was performed in 10 pigs. Modified Child's reconstruction was performed intracorporeally. After the animals were killed, anastomotic sites were investigated by laparotomy., Results: All the animals underwent LPD. The median operation time was 5 h, with minimal blood loss. One choledochojejunostomy had a small leak., Conclusions: The study proved LPD to be technically safe and feasible in an acute porcine model. Further studies and technical advances are necessary for transition of this clinical application of LPD to humans.

Background: Osteopontin (OPN) is a secreted, integrin-binding glycophosphoprotein that has been implicated in the progression of various solid tumors. To evaluate the clinical significance of OPN in gastric carcinoma, we investigated OPN expression in resected tumors., Methods: Expression of OPN protein by gastric cancer cells was evaluated using western blot analysis. OPN messenger RNA (mRNA) expression in 18 gastric cancers was compared with that in the corresponding normal gastric epithelium by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Paraffin sections of tumors from 295 patients with gastric cancer were also investigated using immunohistochemistry., Results: All four gastric cancer cell lines analyzed using western blotting had almost the same level of OPN protein expression as the positive control (HeLa cells). OPN mRNA was upregulated in 83% (15/18) of the tumors studied. On immunohistochemical staining, 90 tumors were classified as negative (-), whereas 205 were classified as positive (1+, 2+, or 3+). The level of OPN protein expression was significantly associated with the patient's age (p = 0.04), tumor depth (p = 0.03), histological grade (p = 0.008), and hematogenous metastasis (p = 0.007). Kaplan-Meier analysis showed that OPN positivity was significantly associated with a shorter survival time (p = 0.027). Furthermore, multivariate analysis revealed that OPN positivity was an independent risk factor for hematogenous metastasis (p = 0.034)., Conclusions: The present findings suggest that increased tumor expression of OPN is an important determinant of shorter survival time and that OPN positivity may be useful for predicting the risk of hematogenous metastasis in gastric cancer patients.

Background: Invisible near-infrared (NIR) fluorescent light permits high sensitivity, real-time image-guidance during oncologic surgery without changing the look of the surgical field. In this study, we complete pre-clinical development of the technology for sentinel lymph node (SLN) mapping using a large animal model of spontaneous melanoma., Methods: Sinclair swine with spontaneous melanoma metastatic to regional lymph nodes were used because of their similarity to human melanoma. Organic lymphatic tracers tested included FDA-approved indocyanine green adsorbed non-covalently to human serum albumin (HSA), and NIR fluorophore CW800 conjugated covalently to HSA (HSA800). The inorganic/organic hybrid tracer tested was type II NIR quantum dots with an anionic coating. Primary tumors received four peri-tumoral injections of each tracer, with a fluorophore dose of 100 pmol to 1 nmol per injection. SLN mapping and image-guided resection were performed in real-time., Results: Each of the 3 lymphatic tracers was injected into n = 4 separate primary melanomas in a total of 6 animals. All 12 injections resulted in identification of the SLN(s) and their associated lymphatic channels within 1 minute in 100% of cases, despite highly pigmented skin and black fur. Hydrodynamic diameter had a profound impact on tracer behavior in vivo., Conclusions: This study completes the pre-clinical development of NIR fluorescence-guided SLN mapping and provides insight into imaging system optimization and tracer choice for future human clinical trials. The technology is likely to eliminate the need for radioactive and colored tracers, permits real-time image guidance throughout the procedure, and assists the pathologist in tissue analysis.

Vascular endothelial growth factor (VEGF) plays an essential role in the angiogenesis of growing cartilage. Although VEGF expression in cartilage vanishes in normal adults, VEGF is known to be expressed in chondrocytes of osteoarthritic (OA) cartilage. As little information is available on the VEGF expression in the cartilage of OA-like lesions of the temporomandibular joint (TMJ), VEGF expression in the condylar cartilage of TMJs of rats affected with OA was examined. To evoke OA, mechanical stress was applied by forced jaw opening for 10 or 20 days. After 20 days, marked OA-like lesions were observed in the condyle. VEGF was expressed in the chondrocytes of the mature and hypertrophic cell layers of the intermediate and posterior region of the condyle. The percentage of VEGF immunopositive chondrocytes significantly increased with the period of applied mechanical stress. Furthermore, tartrate-resistant acid phosphatase (TRAP) staining of the condylar cartilage showed significant increment of osteoclasts in the mineralized layer subjacent to the hypertrophic layer where high VEGF expression could be detected. The results suggest that VEGF plays an important role in the progression of OA.

Objective: Propofol (2,6-diisopropylphenol) is widely used for anesthetic induction as well as for chronic sedation in intensive care units. In this study, we investigated the interaction between propofol and premedications, i.e., psychotropic and antianxiety agents (diazepam, midazolam), hypnotics (thiamylal), local anesthetics (lidocaine), depolarizing muscular relaxants (vecuronium), an antihypertensive (clonidine) and an H2-receptor antagonist (cimetidine) using human liver microsomes in vitro., Methods: The interaction effects between propofol and premedications were examined using human liver microsomal preparation in vitro. The concentration of propofol was determined by HPLC with UV detection., Results: The apparent Michaelis-Menten constant (Km) and the maximal velocity of total metabolic formation (Vmax) of propofol in human liver microsomes were 123 microM and 26.1 micromol/min per milligram of mg protein, respectively. Seven premedications (diazepam, midazolam, thiamylal, lidocaine, cimetidine, vecuronium, and clonidine) did not inhibit propofol metabolism in human liver microsomes at concentrations within the therapeutic range., Conclusions: These results showed no interactions between propofol and seven premedication drugs within the therapeutic range of propofol using human liver microsomes in vitro.

It is well known that angiogenesis is essential for the replacement of cartilage by bone during skeletal growth and regeneration. To address angiogenesis of endochondral ossification in the condyle, we examined the appearance of vascular endothelial growth factor (VEGF) and its receptor Flt-1 in condylar cartilage of the growing rat. The early expression of VEGF at various sites during condylar cartilage development indicates that VEGF plays a role in the regulation of angiogenesis at each site of bone formation. From the findings of Flt-1 immunoreactivity, the VEGF produced by the chondrocytes of the hypertrophic zone should contribute to the promotion of endothelial cell proliferation and to stimulate migration and activation of osteoclasts in condylar cartilage, resulting in the invasion of these cells into the mineralized zone.

Ten healthy male volunteers were given trimethadione (TMO) 4 mg/kg and antipyrine (AP) 500 mg alone or concomitantly to determine whether the metabolism of the drugs was mediated by the same or closely related forms of cytochrome P-450. Whether administered alone or together the clearance (CL) and half-life (t 1/2) of TMO and AP were the same, and there was a good correlation between the CL and t 1/2 of TMO and AP (alone r = 0.755 and 0.623, respectively; coadministered r = 0.771 and 0.503, respectively). Excretion of AP and its main metabolite and the clearance for production of AP metabolites after AP was administered alone were not significantly different when TMO and AP were taken together. When the two drugs were administered alone or coadministered, the correlation between the CL of TMO and the excretion of 3-hydroxymethyl-3-norantipyrine (NORA) was close (alone r = 0.734, coadministered r = 0.749). The correlation between the CL of TMO and CLm of NORA when TMO and AP were given alone or concomitantly was 0.762 and 0.772, respectively. The findings suggest that TMO metabolism and the formation of NORA in healthy subjects are mediated by a closely related form(s) of the cytochrome P-450 system.

Nicotinic acetylcholine-receptor ion channels (AChR channels) were studied in bullfrog sympathetic ganglion cells cultured for 1 day to 3 weeks, using a patch clamp technique. Microsuperfusion of ACh (2-10 microM) to the ganglion cell under the whole cell clamp produced an inward current at membrane potentials negative to -60 mV, which had a fast onset and decay. This rapid ACh-induced current was accompanied by a large current fluctuation, decreased and increased in amplitude by membrane depolarization and hyperpolarization, respectively, and blocked by d-tubocurarine. Thus, this current must be induced by the nicotinic action of ACh, but not by a muscarinic effect to activate a slow cation-selective current. At depolarized levels more than -50 mV, ACh induced an additional inward current which was slow in time course, accompanied by no or decreased current fluctuation and increased in amplitude by membrane depolarization. Accordingly, this slow ACh-induced current could result from the suppression of a voltage-dependent K+ current (M-current: Brown and Adams 1980) by the muscarinic action of ACh. Fluctuation analysis of the rapid ACh-induced current at potentials negative to -50 mV revealed the elementary conductance of 14 pS and a power spectral density distribution of the double Lorentzian function which yielded the time constants of 5.4 and 62.5 ms at -60 to -80 mV. The variance of either component was independent of the mean current.