Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C Hepatocellular Carcinoma Undergoing Hepatic Resection.

[Background]Although the prevalence of non-B non-C hepatocellular carcinoma (NBNC HCC) has increased, its clinicopathologic characteristics remain unclear. [Methods]We retrospectively analyzed 518 HCC patients who underwent hepatic resection. Hepatitis B surface antigen- and hepatitis C antibody-negative patients were categorized into the NBNC HCC group (n = 145); others were categorized into the hepatitis B or C HCC (BC HCC) group (n = 373). We subdivided the etiologies of NBNC HCC according to alcohol intake and presence of steatosis. [Results]NBNC HCC was associated with nonalcoholic fatty liver disease (NAFLD) (13.1 %), fatty liver disease with moderate alcohol intake (9.0 %), alcoholic liver disease (ALD) (29.7 %), cryptogenic disease (44.1 %), and other known etiologies (4.1 %). The prevalence of obesity, diabetes mellitus, and hypertension was higher and hepatic function was better in the NBNC HCC group, which had significantly larger tumors than the BC HCC group. The entire NBNC HCC group displayed similar overall and disease-free survival as the BC HCC group. Among the subdivisions, NAFLD-associated HCC patients had significantly better disease-free survival than ALD-associated HCC and BC HCC patients. Microvascular invasion (hazard ratio [HR] 2.30; 95 % confidence interval [CI] 1.33–3.96) and steatosis area <5 % of noncancerous region (HR 2.13; 95 % CI 1.21–3.93) were associated with disease-free survival in NBNC HCC patients. [Conclusions]The prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients, NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of steatosis in hepatic parenchyma had a significant impact on disease-free survival in NBNC HCC patients

Paleoclimatic and paleoceanographic records through Marine Isotope Stage 19 at the Chiba composite section, central Japan: A key reference for the EarlyeMiddle Pleistocene Subseries boundary

Marine Isotope Stage (MIS) 19 is an important analogue for the present interglacial because of its similar orbital configuration, especially the phasing of the obliquity maximum to precession minimum. However, sedimentary records suitable for capturing both terrestrial and marine environmental changes are limited, and thus the climatic forcing mechanisms for MIS 19 are still largely unknown. The Chiba composite section, east-central Japanese archipelago, is a continuous and expanded marine sedimentary succession well suited to capture terrestrial and marine environmental changes through MIS 19. In this study, a detailed oxygen isotope chronology is established from late MIS 20 to early MIS 18, supported by a U-Pb zircon age and the presence of the Matuyama–Brunhes boundary. New pollen, marine microfossil, and planktonic foraminiferal δ18O and Mg/Ca paleotemperature records reveal the complex interplay of climatic influences. Our pollen data suggest that the duration of full interglacial conditions during MIS 19 extends from 785.0 to 775.1 ka (9.9 kyr), which offers an important natural baseline in predicting the duration of the present interglacial. A Younger Dryas-type cooling event is present during Termination IX, suggesting that such events are linked to this orbital configuration. Millennial- to multi-millennial-scale variations in our δ18O and Mg/Ca records imply that the Subarctic Front fluctuated in the northwestern Pacific Ocean during late MIS 19, probably in response to East Asian winter monsoon variability. The climatic setting at this time appears to be related to less severe summer insolation minima at 65˚N and/or high winter insolation at 50˚N. Our records do not support a recently hypothesized direct coupling between variations in the geomagnetic field intensity and global/regional climate change. Our highly resolved paleoclimatic and paleoceanographic records, coupled with a well-defined Matuyama–Brunhes boundary (772.9 ka; duration 1.9 kyr), establish the Chiba composite section as an exceptional climatic and chronological reference section for the Early–Middle Pleistocene boundary.ArticleQuaternary Science Reviews 191: 406-430(2018)journal articl

Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K‐RAS status for unresectable colorectal liver metastasis (BECK study): Long‐term results of survival

[Background/Purpose]To investigate the long‐term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. [Methods]Recurrence and survival data with long‐term follow‐up were analyzed in the cohort of a multi‐institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). [Results]A total of 22/12 patients with K‐RAS wild‐type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left‐sided primary tumors than in right‐sided tumors (75.0% vs 30.0%, P = .022). The median follow‐up was 72.6 months. The 5‐year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5‐year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow‐up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5‐year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1‐4). [Conclusions]Conversion hepatectomy achieved a similar long‐term survival to the results of previous studies in initially resectable patients, although many of them experienced several post‐hepatectomy recurrences. Left‐sided primary was found to be the predictor for conversion hepatectomy

Integrating Statistical Predictions and Experimental Verifications for Enhancing Protein-Chemical Interaction Predictions in Virtual Screening

Predictions of interactions between target proteins and potential leads are of great benefit in the drug discovery process. We present a comprehensively applicable statistical prediction method for interactions between any proteins and chemical compounds, which requires only protein sequence data and chemical structure data and utilizes the statistical learning method of support vector machines. In order to realize reasonable comprehensive predictions which can involve many false positives, we propose two approaches for reduction of false positives: (i) efficient use of multiple statistical prediction models in the framework of two-layer SVM and (ii) reasonable design of the negative data to construct statistical prediction models. In two-layer SVM, outputs produced by the first-layer SVM models, which are constructed with different negative samples and reflect different aspects of classifications, are utilized as inputs to the second-layer SVM. In order to design negative data which produce fewer false positive predictions, we iteratively construct SVM models or classification boundaries from positive and tentative negative samples and select additional negative sample candidates according to pre-determined rules. Moreover, in order to fully utilize the advantages of statistical learning methods, we propose a strategy to effectively feedback experimental results to computational predictions with consideration of biological effects of interest. We show the usefulness of our approach in predicting potential ligands binding to human androgen receptors from more than 19 million chemical compounds and verifying these predictions by in vitro binding. Moreover, we utilize this experimental validation as feedback to enhance subsequent computational predictions, and experimentally validate these predictions again. This efficient procedure of the iteration of the in silico prediction and in vitro or in vivo experimental verifications with the sufficient feedback enabled us to identify novel ligand candidates which were distant from known ligands in the chemical space

日本睡眠歯科学会口腔内装置診療ガイドライン作成委員会の活動報告

Oral appliance therapy was approved by national health insurance in Japan in 2004 and oral appliances（OAs）have since been widely used in the treatment of obstructive sleep apnea（OSA）. We herein described the process of making clinical practice guidelines by the task force of the Japanese Academy of Dental Sleep Medicine as a work report. In Japan, OAs are covered by national health insurance. In consideration of the balance between medical treatment fees and the price of technical materials, we used a single-piece（monoblock）OA that advanced the mandible forward and limited mouth opening in OSA patients in Japan. The Japanese Academy of Dental Sleep Medicine（JADSM）focused on OAs frequently used for the treatment of OSA in Japan, and considered an evaluation of their effects to benecessary. Clinical practice guidelines were developed using the Grading of Recommendations, Assessment, Development, and Evaluation（GRADE）system. We recommend OAs that advanced the mandible forward and limited mouth opening for patients with OSA.However, CPAP should be used by patients for whom it has been indicated. OAs are desirable for those who cannot use CPAP（GRADE 1B, strong recommendation/quality of evidence, “Moderate quality”）. The long-term effects and side effects, OSA severity, and comorbidities of OA therapy were not examined, which represented a limitation to the present study. In future studies, the Japanese Academy of Dental Sleep Medicine plan to update clinical practice guidelines for oral appliances used in OSA

Relationships between the Nutrition Status and Oral Measurements for Sarcopenia in Older Japanese Adults

Introduction: The purpose of the present study was to clarify the relationships between the risk of malnutrition as a preliminary stage of malnutrition and overall and oral measurements for sarcopenia in older Japanese adults. Methods: Forty-five participants (79.7 &plusmn; 6.1 years) were included in the analysis. The nutrition status of the participants was assessed using the Mini Nutritional Assessment-Short Form (MNA-SF) and classified into two groups: normal and at risk of malnutrition. Overall measurements for sarcopenia in the present study were the skeletal muscle mass index, grip strength, and walking speed, while oral measurements were the cross-sectional area of the geniohyoid muscle, tongue pressure (TP), and oral diadochokinesis. Results: MNA-SF correlated with TP (r = 0.347, p = 0.019). We observed decreases of 5.7 kPa in TP and 3.9 kg/cm2 in BMI in the at risk of malnutrition group. A multiple regression analysis of parameters contributing to the risk of malnutrition identified TP as an independent variable (&beta; = 0.913, p = 0.042). Conclusions: The present results demonstrate that the risk of malnutrition is associated with TP as an oral measurement for sarcopenia, but not overall measurements for sarcopenia. Therefore, low TP may be related with the risk of malnutrition

Spontaneous Uterine Perforation of Pyometra Presenting as Acute Abdomen

Pyometra is the accumulation of pus in the uterine cavity, and spontaneous perforation of pyometra resulting in generalized diffuse peritonitis is extremely uncommon. We report a rare case of diffuse peritonitis caused by spontaneous perforation of pyometra. A 66-year-old postmenopausal woman with diffuse abdominal pain and vomiting was admitted to our institution. She had a history of mixed connective-tissue disease and had been taking steroids for 20 years. Under a diagnosis of generalized peritonitis secondary to perforation of the gastrointestinal tract or uterus, supravaginal hysterectomy and bilateral salpingo-oophorectomy were performed. Unfortunately, wound dehiscence and infection occurred during the postoperative course, which were exacerbated by her immunocompromised state. Despite intensive care and a course of antibiotics, the patient died of multiple organ failure resulting from sepsis on the 36th postoperative day. Although correct diagnosis, early intervention, and proper treatment can reduce morbidity and mortality of spontaneous perforation of pyometra, if severe infection occurs, this disease can be life threatening for immunocompromised hosts

Laparoscopic Distal Gastrectomy is Feasible in Very Elderly Patients as Compared with Open Distal Gastrectomy

Laparoscopic gastrectomy was shown to be feasible even in elderly patients in many retrospective case-controlled studies. However, the definition of elderly differed among those studies, such as an age of 65, 70, or 75 years or older. This study was conducted to elucidate the advantages of laparoscopic distal gastrectomy (LDG) in very elderly (≥80 years) patients, and comprised 70 patients, 45 of whom underwent LDG and 25 underwent open distal gastrectomy (ODG) between 2004 and September 2016. LDG had significantly less estimated blood loss (p < .01), earlier flatus (p < .01), earlier food intake (p < .01), and shorter hospitalization (p < .01) as compared with ODG. No significant difference between LDG and ODG was found in the incidence of postoperative surgical complications (p = .40), although LDG tended to reduce overall and medical postoperative complications (p = .11 and .09, respectively). LDG might be a feasible, beneficial treatment with good short-term outcomes in very elderly patients with gastric cancer