Basal differentiation and expression status of SOX2 and KLF4 in basal layers are prognostic factors for disease-specific survival in oral squamous cell carcinoma.

BACKGROUND: Basal differentiation in oral squamous cell carcinoma is usually detected at invasive sites. However, its significance as a prognostic value has been poorly investigated. METHODS: COL17 was selected as a basal differentiation marker because of its stable expression in the basal-like cells of oral squamous cell carcinoma. Sixty-five cases of oral squamous cell carcinoma were subclassified into COL17-high (30 cases) and -low (35 cases) types, and the prognostic value was analyzed by Cox regression analysis. In addition, the stem cell markers such as SOX2, KLF4, MYC as well as the stem cell-related markers BMI1, EZH2, and YAP and its paralog TAZ, were immunohistochemically analyzed. Their prognostic values were investigated along with their COL17 status by Cox regression analysis. RESULTS: No significant difference was observed between the COL17-high and -low groups in the disease-specific survival and recurrence-free survival in oral squamous cell carcinoma. When the COL17-high and -low categories were combined with the SOX2, KLF4, EZH2, or YAP/TAZ status in the basal layers, together with gender and age as covariates, the hazard ratios reached 3.3, 3.7, 2.8, and 3.1, respectively. In addition, multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, showed a significantly poor prognosis for disease-specific survival. CONCLUSION: Based on the relatively high hazard ratios, it is indicated that basal differentiation and the expression status of SOX2 and KLF4 in the basal layers are prognostic factors for oral squamous cell carcinoma.

Relationship between dietary fiber to carbohydrate ratio and mortality risk in US adults: NHANES 2007-2018.

BACKGROUND AND AIMS: The evidence is inconsistent regarding associations between relative proportions of macronutrient intake and disease risk, potentially due to limitations in accounting for differential effects of simple sugars and dietary fiber, grouped as "carbohydrates." We examined the association between the ratio of dietary fiber to carbohydrate intake (FC-R) measure, the relative proportion of macronutrients, and mortality risk in a nationally representative sample of U.S. adults. METHODS AND RESULTS: We performed a retrospective cohort study, using data from the National Health and Nutrition Examination Survey in 2007-2018 and linked mortality data among 15,789 adults aged ≥40 years. We categorized participants into three groups by tertile cutpoints of FC-R, and by percent calories from carbohydrate (<45 %, 45-65 %, and >65 %). Cox proportional hazards regression was performed to estimate hazard ratios (HR) for all-cause mortality with 95 % confidence intervals (95 % CI), adjusting for demographic, health history, and lifestyle factors. During a median follow-up of 6.5 years, 2044 deaths were observed. Compared to the low FC-R group, higher FC-R groups showed a reduction in mortality risk after adjusting for potential confounders (high vs low: HR = 0.71, 95 % CI = 0.62-0.83). The association persisted in those consuming 45-65 % and >65 % of calories from carbohydrate, while the association was attenuated in those with <45 % of calories from carbohydrate. Percent calories from carbohydrate showed no association with mortality risk. CONCLUSION: Higher FC-R was associated with lower all-cause mortality risk in adults with moderate to high levels of percent calories from carbohydrate. Mechanisms of the association warrant further investigation.

Examination of age-related changes in the submandibular glands of male mice.

Salivary gland hypofunction adversely affects the oral environment and daily life by causing dry mouth (xerostomia). Senescence-related atrophy of salivary gland tissues is one cause of xerostomia, and it is particularly common among the elderly. However, the underlying mechanism is poorly understood, and no treatment has been established. Therefore, we examined age-related changes in senescence-associated secretory phenotype (SASP) factors, which regulate stemness and cellular senescence, in mouse submandibular glands. We analyzed the submandibular glands of 6-week-old (young group, n = 6) and 82-week-old mice (aged group, n = 6). We performed salivary flow rate measurements, histological analysis including immunohistochemistry, and quantitative real-time PCR. The salivary flow rate was significantly lower in the aged group than in the young group. In addition, immunostaining and quantitative real-time PCR illustrated that aquaporin-5 and α-amylase expressions were significantly decreased in aged mice, indicating salivary gland hypofunction. c-Kit and cytokeratin 5 expressions were also significantly decreased in this group, suggesting that the regenerative abilities of the submandibular glands were reduced because of decreased stem and progenitor cell counts. Furthermore, the levels of p16INK4a and p21 (the senescence markers) and TGF-ß1 and IL-6 (SASP factors) were significantly increased in mice, suggesting that senescence had been promoted. The decreased numbers of stem and progenitor cells and increased levels of SASP factors might be associated with age-related changes in mouse submandibular glands. These results might facilitate the development of treatments for senescence-related submandibular gland hypofunction.

Studies on the antifungal effects of Hinokitiol on Candida albicans: inhibition of germ tube formation and synergistic pharmacological effects of miconazole.

One of the goals of oral healthcare management is to manage dry mouth. Thus, moisturizers containing antimicrobial ingredients, such as hinokitiol (HT), are applied to the oral mucosa after oral care. In this study, we investigated the preventive effect of HT against the growth of Candida albicans (C. al) and its synergistic effect when combined with miconazole (MCZ), an oral treatment for candidiasis. As the concentration of HT increased, the length and percentage of germ tubes (GT) decreased. Larger inhibition circles were observed for MCZ concentrations of 2.0 and 4.0 µg/disc compared to the HT medium without HT. The increased inhibitory effect was observed in both aerobic and anaerobic cultures. This suggests that the production of reactive oxygen species (ROS) by C. al cells increased with the combination of HT and MCZ. The length and percentage of GT increased, whereas the amount of ROS decreased when ROS scavengers were used in combination with the drug. HT led to morphological changes that inhibited the GT associated with pathogenic C. al, exhibited a complementary action against MCZ, and showed a possible association with hydrogen peroxide and superhydroxy anion radicals. These effects suggest that HT is a promising candidate for inhibiting C. al. In conclusion, HT demonstrated a prophylactic effect by inhibiting C. al and a synergistic effect with MCZ, a drug used to treat oral candidiasis. HT may also be useful for suppressing the onset and reducing the severity of oral candidiasis.

Chronic active Epstein-Bar virus infection complicated by pulmonary artery hypertension.

Chronic active Epstein-Bar virus infection (CAEBV) is known to cause various symptoms. Although pulmonary artery hypertension (PAH) has been reported as a cardiovascular complication of CAEBV, the mechanisms of PAH and the effects of treatment have not been fully elucidated. We experienced 4 adult patients with CAEBV complicated by PAH. All of them received treatment for PAH with a vasodilator followed by chemotherapy with or without allogeneic hematopoietic cell transplantation for CAEBV. In all of these patients, the transtricuspid pressure gradient improved under treatment with vasodilator, and further improvement was observed under treatment for CAEBV in 3 patients. Autopsy was performed in 2 patients, which revealed EBER-positive cells and a change in the pulmonary artery at each stage in the pathology. In conclusion, EBV-infected cells can cause vasculitis and finally PAH. However, PAH complicated with CAEBV can be improved by PAH medication and treatment of CAEBV.

Successful living donor liver transplantation for liver failure due to maternal T cell engraftment following cord blood transplantation in X-linked severe combined immunodeficiency disease: Case report.

Maternal T cells from perinatal transplacental passage have been identified in up to 40% of patients with severe combined immunodeficiency (SCID). Although engrafted maternal T cells sometimes injure newborn tissue, liver failure due to maternal T cells has not been reported. We rescued a boy with X-linked SCID who developed liver failure due to engrafted maternal T cell invasion following living donor liver transplantation (LDLT) following unrelated umbilical cord blood transplantation (UCBT). After developing respiratory failure 3 weeks postpartum, he was diagnosed with X-linked SCID. Pathological findings showed maternal T cells engrafted in his liver and hepatic fibrosis gradually progressed. He underwent UCBT at 6 months, but hepatic function did not recover and liver failure progressed. Therefore, he underwent LDLT using an S2 monosegment graft at age 1.3 years. The patient had a leak at the Roux-en-Y anastomosis, which was repaired. Despite occasional episodes of pneumonia and otitis media, he is generally doing well 6 years after LDLT with continued immunosuppression agents. In conclusion, the combination of hematopoietic stem cell transplantation (HSCT) and liver transplantation may be efficacious, and HSCT should precede liver transplantation for children with X-linked SCID and liver failure.

Leukotriene B4 receptor 1 exacerbates inflammation following myocardial infarction.

Leukotriene B4 receptor 1 (BLT1), a high-affinity G-protein-coupled receptor for leukotriene B4 (LTB4 ), is expressed on various inflammatory cells and plays critical roles in several inflammatory diseases. In myocardial infarction (MI), various inflammatory cells are known to be recruited to the infarcted area, but the function of BLT1 in MI is poorly understood. Here, we investigated the role of BLT1 in MI and the therapeutic effect of a BLT1 antagonist, ONO-4057, on MI. Mice with infarcted hearts showed increased BLT1 expression and LTB4 levels. BLT1-knockout mice with infarcted hearts exhibited attenuated leukocyte infiltration, proinflammatory cytokine production, and cell death, which led to reduced mortality and improved cardiac function after MI. Bone-marrow transplantation studies showed that BLT1 expressed on bone marrow-derived cells was responsible for the exacerbation of inflammation in infarcted hearts. Furthermore, ONO-4057 administration attenuated the inflammatory responses in hearts surgically treated for MI, which resulted in reduced mortality and improved cardiac function after MI. Our study demonstrated that BLT1 contributes to excessive inflammation after MI and could represent a new therapeutic target for MI.

Optimal Contact Concentration of Paclitaxel in the Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test for Human Oral Squamous Cell Carcinoma and Evaluation of Combination with Cetuximab.

OBJECTIVE: A combination of the taxane anticancer drug paclitaxel (PTX) and molecular target drug cetuximab (cMab) is effective for the treatment of head and neck squamous cell carcinoma (HNSCC). However, its use is associated with serious side effects, such as neuropathy and myelosuppression. In addition, it is administered regardless of patient sensitivity because biomarkers indicating its efficacy are unavailable. Therefore, we investigated the usefulness of setting the indicated contact concentration of PTX and predicted the antitumor effect of combined contact with cMab using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). METHOD: Twelve human oral squamous cell carcinoma (OSCC) cell lines (i.e., SAS, HSC-2, HSC-3, HSC-4, OSC-19, OSC-20, KON, HO-1-N-1, HO-1-u-1, SAT, SCC-4, and Nialym) were used. Using the CD-DST, we calculated the optimal contact concentration of the cells with PTX based on the clinical response rate of HNSCC and evaluated the combined contact with cMab. Furthermore, nude mice were treated with standalone PTX and PTX + cMab, and the results were compared with those of the CD-DST. RESULTS: Based on the CD-DST, 0.1 µg/mL was the optimal contact concentration of PTX, to which the cells showed dose-dependent sensitivity. Moreover, the CD-DST method was used to evaluate the antitumor effects on OSCC even when PTX was used in combination with cMab. The antitumor effects in the CD-DST and nude mice were correlated (p < 0.05). CONCLUSION: The CD-DST results suggested that it was possible to predict the clinical effects of single-contact PTX and the enhancing effect of cMab + PTX.

Awareness of Complications of Dental Treatment in Patients Treated with Drugs Affecting the Immune System : A Nationwide Questionnaire Survey of Dental Practitioners in Japan.

The aim of this study was to investigate the awareness and experience, among dental practitioners, of adverse events resulting from dental treatment of patients undergoing therapy with drugs that affect the immune system [angiogenesis inhibitors, biological agents, immunosuppressants, and disease-modifying anti-rheumatic drugs (DMARDs)]. For this purpose, a nationwide questionnaire survey was conducted. Questionnaires were sent to 2,050 dentists, of which 206 (10.1%) were completed and returned. The results showed that most dentists were aware of complications associated with dental treatment of patients treated with drugs that affect the immune system, and about half had actually experienced such complications. Delayed wound healing, osteonecrosis of the jaw (ONJ), and postoperative infections were reported. Whereas approximately 50% of dentists did not discontinue the drugs during dental treatment, about 18% did. During temporary drug discontinuation, some patients experienced aggravation of the primary disease, such as worsening of rheumatism, growth of tumors, and rejection reactions of transplanted organs. As for medical cooperation, only less than half of the dentists were asked for oral hygiene management by a physician prior to starting the drug treatment. Prospective studies are needed because evidence for dental treatments in patients treated with these drugs remains limited.

Effects of the prevention of medication-related osteonecrosis of the jaw by local administration of a dental pulp stem cell-conditioned medium to the rat tooth extraction socket.

The onset of osteonecrosis of the jaw, which is a side effect of bisphosphonates, often develops after tooth extraction; measures for its prevention have not yet been established. While treatment with systemic administration of bone marrow stem cell-derived conditioned medium for medication-related osteonecrosis of the jaw (MRONJ) has been reported, its preventive effects have not been clarified yet, and the high degree of invasiveness of bone marrow fluid collection remains an issue. Therefore, we created a rat model of MRONJ using BP zoledronic acid, used a dental pulp stem cell-conditioned medium (DPSC-CM), which can be collected relatively easily, and locally applied it to the tooth extraction socket with atelocollagen and gelatin sponges. The preventive effect on the onset of MRONJ was subsequently examined. The results demonstrated that the bone exposure width of the extraction socket was reduced, and the mucosal covering was promoted in the atelocollagen + DPSC-CM group as compared with the other groups. Furthermore, histological results indicated a decrease in the number of empty bone lacunae, whereas immunohistochemical staining revealed the presence of many vascular endothelial growth factor (VEGF)-positive cells. Moreover, the results of the investigation of the sustained release of atelocollagen using VEGF indicated the release of VEGF over time. Our results suggest that local administration of DPSC-CM using atelocollagen may be a useful method for the prevention of MRONJ triggered by tooth extraction.

The diagnosis and treatment of hereditary angioedema patients in Japan: A patient reported outcome survey.

BACKGROUND: The rate at which patients are accurately diagnosed with hereditary angioedema (HAE), as well as diagnosed patients access to modern treatments differs greatly among countries. Moreover, the severity and burden of HAE on patients have been reported mostly on the basis of physician-reported surveys. To gain insight into the real-world conditions of patients with HAE through a patient-reported survey in Japan and identify any unmet needs. METHODS: A questionnaire was distributed to 121 patients with HAE via a Japanese HAE patient organization during 2016-2017. Responses were collected from 70 patients (57.9%) and subjected to analysis. RESULTS: The average periods from the initial appearance of symptoms (e.g. edema) to a HAE diagnosis was 15.6 years (min-max, 0-53). Patients visited an average of 4.6 different departments until receiving a definitive diagnosis. The average age at the first visit was 25.6 years (3-73) and at diagnosis 32.8 years (0-73). Patients reported an average of 15.7 (0-100) attacks per year, but only 53.1% of attacks were treated. The days of hospitalization due to severe attacks was 14.3 (0-200) before diagnosis, but these declined to 4.3 (0-50) after diagnosis. In the treatment for attacks, 82% of the patients were treated with the plasma-derived C1 inhibitor concentrate, and 69% of the patients reported experiencing a therapeutic effect. CONCLUSIONS: There is a long gap between first attack and diagnosis of HAE, and the number of non-treated attacks is high in Japan. Steps are needed to improve the diagnostic and treatment environments to address these issues.

[A case of gastric hamartomatous inverted polyp (GHIP), preoperatively diagnosed based on EUS findings].

We report the case of a patient with a gastric hamartomatous inverted polyp (GHIP) and discuss the relevant literature. A 65-year-old woman was referred to our hospital because of a slow-growing pedunculated polyp measuring 30mm in diameter, present in the greater curvature of the fundic region of the stomach. It was covered with normal gastric mucosa, and the top was reddish. A biopsy specimen taken from the reddish area;it showed inflamed gastric mucosa with hyperplastic and mildly distorted foveolar glands. Abdominal contrast computed tomography showed a protruding tumor that was unevenly enhanced and contained multiple cystic lesions inside. Endoscopic ultrasonography (EUS, Olympus GIF-UCT260) showed a heterogeneous tumor with multiple anechoic or low-echoic cystic lesions, originating from the second or third layer of the stomach wall. The patient had no clinical symptoms, no family history, and no laboratory data abnormalities. Based on these findings, we diagnosed her with GHIP. As the polyp had shown an increase in size (5mm/5 years) and about 20% of GHIPs were reported to coexist with precancerous or cancerous lesions, we performed endoscopic polypectomy. The tumor was histologically characterized by submucosal growth of hypertrophic glands with cystic dilatation, accompanied by smooth muscle proliferation, branching from the bundles. Thus, the final diagnosis was GHIP. Though GHIP is a rare and basically benign polyp, the rate with gastric cancer was reported to be relatively high. EUS findings are important for the diagnosis and when GHIP is suspected, the lesion requires to be monitored closely. If there are some signs that suggest a malignancy (growth, changes in surface mucosa, etc.), endoscopic en bloc resection or surgical resection should be considered.

Exercise-induced allergic reactions on desensitization to wheat after rush oral immunotherapy.

BACKGROUND: The effect of oral immunotherapy (OIT) on wheat allergy is promising in terms of the potential to obtain desensitization; however, the frequency of exercise-induced allergic reactions on desensitization (EIARDs) and the associated risk factors remain to be determined. METHODS: Twenty-five patients underwent rush OIT for wheat allergy, and 21 achieved the full-dose intake of wheat products (5 g of wheat protein). Exercise-provocation tests were repeatedly performed after the ingestion of a full-dose wheat product. The time-course of the levels of the specific IgEs (sIgE) to wheat extract, total gliadin, deamidated gliadin, recombinant gliadin components (α/ß-, γ- and ω-5-), and glutenin (high and low molecular weight) components was analyzed using ImmunoCAP® , ELISA, or IgE immunoblotting. RESULTS: Fourteen patients (66.7%) were diagnosed as EIARD+, which remained 5 years after rush OIT in 11 patients (52.4%). There were no differences in the clinical backgrounds of the EIARD+ and EIARD- patients. However, EIARD+ patients showed significantly higher sIgE levels to all gliadin and glutenin components than EIARD- patients before OIT. The sIgE levels to each component decreased equally after 1 and 2 years of OIT. On IgE immunoblotting, sera from all patients reacted to the multiple gluten bands, and some reacted to the water-soluble bands. The intensity of all IgE-reactive bands also became equally lighter after OIT. CONCLUSIONS: EIARDs were frequently observed and remained for a long period after successful OIT for wheat allergy. None of the specific wheat components were found to contribute to EIARDs.

Biosynthetic gene cluster identification and biological activity of lucilactaene from Fusarium sp. RK97-94.

We identified the biosynthetic gene cluster for lucilactaene, a cell cycle inhibitor from a filamentous fungus Fusarium sp. RK 97-94. The luc1 knockout strain accumulated demethylated analogs, indicating the involvement of Luc1 methyltransferase in lucilactaene biosynthesis. Lucilactaene showed potent antimalarial activity. Our data suggested that methylation and ether ring formation are essential for its potent antimalarial activity.

Usefulness of Preoperative Mechanical Bowel Preparation in Patients with Colon Cancer who Undergo Elective Surgery: A Prospective Randomized Trial Using Oral Antibiotics.

BACKGROUND: To prevent surgical site infection (SSI) in colorectal surgery, the combination of mechanical bowel preparation (MBP), oral antibiotic bowel preparation (OABP), and the intravenous antibiotics have been proposed as standard treatment. We conducted an RCT comparing the incidence of SSI between MBP + OABP and OABP alone after receiving a single dose of intravenous antibiotics. METHODS: The study group comprised 254 patients who underwent elective surgery for colon cancer. Patients were randomly assigned to receive MBP + OABP and intravenous antibiotics (MBP + OABP group) or to receive OABP and intravenous antibiotics (OABP alone group). RESULTS: Overall, 125 patients in MBP + OABP group and 126 patients in OABP alone group were eligible. Incisional SSI occurred in 3 patients (2.4%) in MBP + OABP group, and 8 patients (6.3%) in the OABP-alone group. Organ/space SSI developed in 0 patients (0%) and in 4 patients (3.2%) in each group respectively. The OABP-alone group was thus not shown to be noninferior to the MBP + OABP group in the incidences of incisional SSI or organ/space SSI. Other infectious complications developed in 7 patients (5.6%) and in 6 patients (4.8%) in each group, indicating the non-inferiority of OABP alone to MBP + OABP. CONCLUSIONS: MBP combined with oral antibiotics and intravenous antibiotics remains standard in elective colon cancer surgery.

A prospective clinical study assessing the presence of exfoliated cancer cells and rectal washout including tumors in patients who receive neoadjuvant chemoradiotherapy for rectal cancer.

PURPOSE: Rectal washout is performed in rectal cancer surgery to eliminate exfoliated cancer cells. Before rectal washout, a cross-clamp should generally be placed distal to the tumor. In some patients with lower rectal cancer, however, the tumor cannot be adequately isolated. We, therefore, hypothesized that neoadjuvant chemoradiotherapy (nCRT) can decrease the number of exfoliated cancer cells even after the rectal washout including tumors. METHODS: We prospectively studied 86 patients with rectal cancer who underwent proctectomy after nCRT. A cross-clamp was applied proximal to the tumor, and the rectum was washed with 2000 mL of physiological saline solution. The initial 100 mL used to wash the rectum was collected as a pre-washout sample. After the rectum was washed with the remaining 1900 mL, the solution remaining in the rectum was collected as a post-washout sample. Cells classified as class IV or higher according to the papanicolaou classification were considered to indicate a positive diagnosis. RESULTS: The cytological diagnosis was positive in pre-washout samples in 21 patients (24%) and post-washout samples in two patients (2%). CONCLUSION: In patients with rectal cancer, nCRT may decrease the number of exfoliated cancer cells in the rectum, and rectal washout including the tumor may be oncologically acceptable.

Preventive effects of a synthetic absorbable antiadhesive film (seprafilm) on small bowel obstruction in patients who underwent elective surgery for colon cancer: A randomized controlled trial.

BACKGROUND: Seprafilm did not decrease small bowel obstruction (SBO), but significantly decreased reoperation in patients with inflammatory bowel disease. However, the preventive effect in colon cancer remains unclear. METHODS: We conducted a randomized controlled trial in patients with colon cancer. The study group comprised 345 patients with colon cancer. In the seprafilm group (n = 166), two sheets of seprafilm were inserted under a midline incision. Patients who were admitted and required decompression were considered to have SBO. RESULTS: The median follow-up was 61.9 months. Patient characteristics were well balanced. There was no significant difference in the incidence of SBO between the seprafilm group (7.8%) and the control group (10.6%) (P = .46). In patients who underwent reoperation, SBO occurred in a midline incision in one patient and at other sites in four patients in the seprafilm group as compared with two patients and five patients, respectively, in the control group. Multivariate analysis showed that only a history of laparotomy was an independent risk factor for SBO. CONCLUSIONS: Seprafilm did not decrease SBO or reoperation in colon cancer. The incidence of SBO caused by adhesion to the midline incision was relatively low as compared with that caused by adhesion to other sites.

Discovery of 2,4-diamino-5-cyanopyrimidine derivatives as protein kinase C theta inhibitors with mitigated time-dependent drug-drug interactions.

Protein kinase C theta (PKCθ) plays a critical role in T cell signaling and has therapeutic potential for T cell-mediated diseases such as transplant rejection and rheumatoid arthritis. PKCθ inhibitors have emerged as effective immunomodulative agents for the prevention of transplant rejection. We previously reported that the 2,4-diamino-5-cyanopyrimidine derivative 2 was a potent PKCθ inhibitor; however, it exhibited CYP3A4 time-dependent inhibition (TDI). Here, we report the structural modification of compound 2 into 34 focusing on mitigating CYP3A4 TDI. Compound 34 exhibited potent in vitro activity with mitigated CYP3A4 TDI and efficacy in vivo transplant model.

Minimal effective dose of lactic-fermented egg white on visceral fat in Japanese men: a double-blind parallel-armed pilot study.

BACKGROUND: We previously reported that the consumption of 8 g of protein per day in the form of lactic-fermented egg white (LAFEW) improves visceral fat obesity. In this study, we investigated the minimum effective intake of LAFEW for visceral fat reduction in the Japanese males with mild obesity. METHODS: Twenty-two Japanese adult males with a Body mass index (BMI) ≥24 and a waist circumference ≥ 85 cm were included in this study. The subjects were divided into three groups, that is, control group, LAFEW 6 g group, and LAFEW 8 g group. The LAFEW 6 and 8 g groups consumed 6 and 8 g, respectively, of egg white protein (EWP) in a drink at breakfast for 8 weeks, whereas the control group consumed a drink containing 8 g of milk whey protein. Body weight, body fat percentage, abdominal circumference, and visceral fat (VF) area around the navel were measured at 0 and 8 weeks after initiating the consumption. RESULTS: No changes in body weight or body fat percentage were observed in any of the groups. No significant differences between the pre- and posttreatment measurements were found in the VF area around the navel in the control group and the LAFEW 6 g group. In the LAFEW 8 g group, the VF area had decreased significantly after 8 weeks of consumption, when compared to that before consumption, and the average observed decrease (Δcm2) was 13.2 ± 4.7 cm2. Among the subjects with an initial BMI > 25, the VF area was significantly smaller in the LAFEW 8 group, when compared to the week 0 values and those in the control group. Visceral fat/subcutaneous fat values in the LAFEW 8 group were also significantly smaller than those in the control group or at week 0. CONCLUSION: The results suggested that the minimum effective intake of EWP in the LAFEW to reduce the VF area in the Japanese men is 8 g. TRIAL REGISTRATION: This clinical trial was retrospectively registered with the University hospital Medical Information Network (UMIN) Center, ( UMIN000031681 ; registered on 12/03/2018).

Optimal use of antiplatelet agents, especially aspirin, in the perioperative management of colorectal cancer patients undergoing laparoscopic colorectal resection.

BACKGROUND: Laparoscopic abdominal surgery is considered superior to open surgery. However, efficacy and safety outcomes of laparoscopic surgery in colorectal cancer (CRC) are unclear, particularly in patients undergoing antiplatelet therapy (APT). The aim of this study was to evaluate safety of antiplatelet agents, especially aspirin, in peri-operative management of patients undergoing laparoscopic colorectal resection for CRC. METHODS: A total of 578 radical laparoscopic colorectal surgeries in CRC patients performed between January 2005 and December 2015 at the Kokura Memorial Hospital were retrospectively reviewed. Patients were divided into three groups based on the risk for thromboembolism: a high-risk group receiving APT (APT-HR), a low-risk group receiving APT (APT-LR), and a low-risk group not receiving APT (non-APT). Bleeding complications (BC) and thromboembolic complications (TC) were assessed. Perioperative and outcome variables in groups receiving APT were compared with those in the non-APT group. RESULTS: APT-HR, APT-LR, and non-APT groups included 54 (9.3%), 114 (19.7%), and 410 (70.9%) patients, respectively. Blood loss during operation (p = 0.304), operative time (p = 0.956), hospitalisation after surgery (p = 0.307), and Clavien-Dindo classification of surgery-related complications (p = 0.467) were not significantly different in the three groups. Occurrence of intra-operative BC (blood loss ≥ 200 ml) (p = 0.864), post-operative BC (p = 0.630), and TC (p = 0.287) were also not significantly different in the three groups. Results of our analysis indicated that APT and non-interrupted APT were not associated with BC or TC. CONCLUSIONS: Analysis of laparoscopic colorectal resection in CRC showed that APT was not a major factor for fatal BC or TC. In patients with high thromboembolic risk, continuing aspirin may inhibit the increase in TC without increasing BC in the peri-operative period.