Background Mild parkinsonian signs are important clinical symptoms related to the decline of motor and cognitive functions. We aimed to identify predictors for the incidence of mild parkinsonian signs in older Japanese by conducting an 8-year longitudinal community-based cohort study.

Methods Participants aged 65 years or older, living in Ama-cho, a rural island town in western Japan, underwent a baseline assessment of motor function, cognitive function, depression score, the Pittsburgh Sleep Quality Index (PSQI), the Tanner questionnaire, and cerebral white matter lesions on brain magnetic resonance imaging from 2008 to 2010, and then underwent a follow-up neurological examination from 2016 to 2017. Mild parkinsonian signs were defined according to a modified Unified Parkinson’s Disease Rating Scale score.

Results Of the 316 participants without mild parkinsonian signs at baseline, 94 presented with incident mild parkinsonian signs at follow-up. In addition to an absence of exercise habits, a higher score on the Tanner questionnaire, PSQI, and deep white-matter hyperintensity Fazekas scores were significant independent predictors for incidence of mild parkinsonian signs.

Conclusion We suggest multiple factors related to incidence of mild parkinsonian signs. Vascular lesions and sleep disorders are associated with a pathogenesis of mild parkinsonian signs, the Tanner questionnaire is useful for early detection of subclinical mild parkinsonian signs, and exercise has a possibility of being associated with preventing onset of mild parkinsonian signs.

Background The prognostic value of combination of C-reactive protein and prealbumin (CRP/PAlb) in esophageal cancer remains unclear.

Methods We enrolled 167 esophageal cancer patients who underwent curative esophagectomy. Univariate and multivariate analyses were performed to determine the prognostic significance of various markers, including CRP-to-albumin (CRP/Alb) ratio, modified Glasgow prognostic score, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index.

Results Receiver operating characteristic analysis revealed the optimal cut-off value of each inflammatory factor, and CRP/PAlb ratio had the greatest discriminative power in predicting recurrence-free survival (RFS) among the examined measures (AUC 0.668). The 5-year overall survival and RFS rates were significantly lower in patients with high CRP/PAlb ratio than in those with low CRP/PAlb ratio (P < 0.001, P = 0.001, respectively). In the univariate analysis, RFS was significantly worse in patients with low BMI, T2 or deeper tumor invasion, positive lymph node metastasis, positive venous invasion, high CRP/PAlb ratio, high CRP/Alb ratio, high NLR, and high LMR. Multivariate analysis revealed that CRP/PAlb, but not CRP/Alb, was an independent prognostic factor along with lymph node metastasis.

Conclusion CRP/PAlb ratio was useful for predicting the prognosis of esophageal cancer patients.

Background This study attempted to clarify issues regarding difficulties in school life perceived by professional training college students and educational support systems for students including possible developmental disabilities.

Methods We surveyed 953 students enrolled at 9 professional training colleges in Japan by using an anonymous self-administered questionnaire to investigate difficulties during school life, help-seeking preferences, and self-esteem. Difficulties were investigated by using the Self-Cognitive Difficulties Scale, help-seeking preferences were assessed with the Help-Seeking Preferences Scale, and self-esteem was assessed by the Rosenberg Self-Esteem Scale. We also investigated the relationship between the Self-Cognitive Difficulties Scale and the sources of advice used by students.

Results Responses were obtained from 863 students, and those of 775 students were considered to be valid. In terms of learning scenarios, 271 students (35.0%) responded that written examinations caused the most difficulties. The Rosenberg Self-Esteem Scale and Help-Seeking Preferences Scale were negatively correlated with the Self-Cognitive Difficulties Scale. With respect to the relationship between sub-factors of the Self-Cognitive Difficulties Scale and sources of advice, the students who asked specialists for advice had significantly higher scores for the factors of interpersonal relationships and reading/writing, as well as significantly higher scores for impulsivity and learning-related difficulties. The students who asked their previous high school teachers for advice had significantly higher scores for inattention and reading/writing. Furthermore, the students who asked senior students in the same department for advice had a significantly higher score for learning-related difficulties.

Conclusion Our results suggested that professional training college students with a high Self-Cognitive Difficulties Scale score are more likely to choose a specialist as the source of advice. When providing educational support to professional training college students, it is important to consider the possibility that their sources of advice might differ depending on their individual self-perceived difficulty characteristics.

Background Patients with non-demented Parkinson’s disease (PD) sometime have mild cognitive impairment (MCI), and mild cognitive impairment in Parkinson’s disease (PD-MCI) may convert to Parkinson’s disease with dementia (PDD) within several years. Cognitive impairment also occurs in the early stages of the disease, gradually progressing to lower quality of life and instrumental activities of daily living. It is important to elucidate the predictors of progression from PD-MCI to PDD via longitudinal studies.

Methods This was a single center, case-control study. We analysed data from 49 patients with PD-MCI diagnosed as level I using the Movement Disorder Society PD-MCI criteria at baseline who had completed 1.5 years of follow-up. We defined patients who progressed to PDD as patients with progressive PD-MCI and patients who did not progress to PDD as patients with non-progressive PD-MCI. Depression, apathy, sleep disorders, constipation, light-headedness, hallucinations, impulse control disorders (ICDs) and impulsive–compulsive behaviors (ICBs) at baseline were statistically analysed as predictors of progression.

Results Of the 49 PD-MCI patients, 33 did not convert to PDD (non-progressive PD-MCI), and 16 converted to PDD (progressive PD-MCI). The Mini-Mental State Examination (MMSE) score, light-headedness and ICDs were elucidated as predictors of progressive PD-MCI via a multivariate logistic regression model. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each item were MMSE score, OR 0.324, 95% CI 0.119–0.882, P = 0.027; light-headedness, OR 27.665, 95% CI 2.263–338.185, P= 0.009; and ICDs, OR 53.451, 95% CI 2.298–291.085, P = 0.010.

Conclusion Cognitive function, ICDs and light-headedness may be risk factors for the development of PDD in PD-MCI patients.

Background Trichinellosis is a serious zoonosis with a worldwide distribution. Fecund adult worms in the intestine release newborn larvae (NBL) that enter the general circulation from 4 days post infection (dpi). Alternatively activated macrophages in the peritoneal cavities and the diaphragms in Trichinella spiralis infected mice have been reported. However, a role of newborn larvae is poorly understood.

Methods The total numbers of peritoneal macrophages in mice infected with 500 muscle-stage larvae were counted during early infection and then total RNA was extracted. Peritoneal macrophages from uninfected C57BL/6 mice were incubated with IL-4 or LPS as a control, or co-cultured with live NBL, and peritoneal macrophages were obtained from mice injected with live or frozen dead NBL into peritoneal cavity. Total RNA was extracted from these macrophages. Two types of gene expression, classical and alternative activation, were examined in the macrophages and diaphragms of the infected mice using semi-quantitative reverse transcription-PCR.

Results The number of peritoneal macrophages in T. spiralis infected mice increased significantly. mRNA peak expression of alternative activation markers, Ym1 and arginase-1 (Arg1), was confirmed in the peritoneal macrophages and in diaphragm of mice around 15 dpi, while mRNA expression of classical activation markers, TNFα, IP-10, and iNOS was not detected. Injection of live NBL into the peritoneal cavities induced mRNA expression of Ym1 and Arg1 in the peritoneal macrophages of mice 9 dpi. However, dead NBL did not induce such gene expression. Alternative activation was not detected in the peritoneal macrophages co-cultured with NBL in vitro.

Conclusion Gene expression of alternative activation makers, Ym1 and Arg1, was confirmed in the peritoneal macrophages and diaphragms of mice infected with T. spiralis. However, gene expression of classical activation markers was not detected. Live NBL induced an alternative activation of peritoneal macrophages in vivo, but not in vitro.

Background Ultrasonography is superior to other imaging modalities for detecting salivary gland diseases. However, there have been no reports of the results of salivary gland screening with ultrasonography. In this study, the salivary glands were also observed during thyroid ultrasonography to determine the degree of salivary gland abnormalities detected by ultrasonography.

Methods This study was conducted retrospectively using medical records. It assessed the association between the following abnormal findings detected during thyroid ultrasonography and their final diagnoses: atrophy/swelling, unclear demarcation from surrounding tissues, decreased salivary gland parenchyma echo level, heterogeneity of parenchyma, hypervascularity of salivary gland parenchyma, dilatation of the ducts, and a mass within the gland.

Results Of the 908 patients who underwent thyroid ultrasonography, salivary gland abnormalities were detected in 36 (4.0%) patients. Of the 36 patients with abnormal ultrasonographic findings, 22 underwent further examination. Of the 22 patients, 16 received definitive diagnoses of salivary gland diseases.

Salivary gland disorders were considered to be absent in patients with only heterogeneity of the salivary glands observed on ultrasonography. Salivary gland disorders in all patients with further abnormal ultrasonographic findings such as atrophy/swelling, unclear boundary, or hypervascularity in addition to internal heterogeneity were confirmed by further blood examinations and imaging studies. We were able to detect autoimmune sialadenitis such as Sjögren’s syndrome and IgG4-related sialadenitis by ultrasonography in patients without obvious symptoms.

Conclusion Salivary gland screening during thyroid ultrasonography revealed abnormal findings including Sjögren’s syndrome and IgG4-related sialadenitis in about 4% of the patients. Thus, ultrasonography may also be useful for early detection of autoimmune diseases of salivary glands.

Background Dynamic computed tomography (CT) angiography is useful for evaluating of hepatic vascularity. Although vasodilators increase hepatic blood flow, the utility of dynamic CT with vasodilators is unclear. Here we investigated the utility and safety of dynamic CT with vasodilators.

Methods A prospective case-control radiographic evaluation using abdominal dynamic CT with and without vasodilator was performed at a single center between October 2015 and September 2016. We compared the CT values in Hounsfield units of the aorta; celiac artery; and common, right, and left hepatic arteries in the arterial phase and the main trunk; right and left branches of the portal vein; and right, middle, and left hepatic veins in the portal phase with and without vasodilators. The region of interest was set in each element of the liver vasculature. Four radiological technologists independently and visually compared the scores of the portal vein (P-score) and hepatic vein (V-score) on a 5-point scale with and without vasodilators.

Results The CT values of arteries and veins using vasodilators were significantly higher than those without vasodilators. With and without vasodilators, the P-scores were 3.1 ± 1.2 and 4.0 ± 1.1 (P < 0.05) and the V-scores were 3.3 ± 1.4 and 4.3 ± 1.0 (P < 0.05). Only one patient with vasodilator use had transient hypotension and recovered immediately without medication.

Conclusion Dynamic CT with vasodilators can provides better visualization of vascular structures.

Background Radical prostatectomy and radiotherapy are standard treatments for localized prostate cancer. When making decisions about treatment, it is important to not only consider medical information such as the patient’s age, performance status, and complications, but also the impact on quality of life (QOL) after treatment.

Our purpose was to compare health related quality of life (HRQOL) after robot-assisted laparoscopic radical prostatectomy (RARP) versus radiation therapy in Japanese patients with localized prostate cancer retrospectively.

Methods Patients with localized prostate cancer receiving RARP or radiotherapy at Tottori University Hospital between October 2010 and December 2014 were enrolled in a retrospective observational study with follow-up for 24 months to December 2016. The Medical Outcome Study 8-Item Short-Form Health Survey was performed before treatment and 1, 3, 6, 12, and 24 months post-treatment.

Results Complete responses to the questionnaire were obtained from 154/227 patients receiving RARP, 41/67 patients receiving intensity-modulated radiation therapy, 35/82 patients receiving low dose rate brachytherapy, and 18/28 patients given low dose rate brachytherapy plus external beam radiation therapy. The median physical component summary score of the Medical Outcome Study 8-Item Short-Form Health Survey was significantly lower at 1 month after prostatectomy than radiotherapy, but was similar for both treatments at 3 months, and was significantly higher at 6, 12 and 24 months after prostatectomy. The median mental component summary score was also significantly lower in the prostatectomy group at 1 month, but not from 3 months onwards.

Conclusion Our study suggested that HRQOL was inferior at 1 month after RARP, however, recovered at 3 months after RARP and was better than after radiotherapy at 6, 12, and 24 months.

Background There is sufficient evidence to show the mortality reduction effect of colorectal cancer (CRC) screening programs using the fecal occult blood test (FOBT). However, we see cases that are found to be advanced CRC despite yearly FOBT screening.

Methods The aim of this study was to investigate the characteristics of advanced CRC detected by a fecal immunochemical test (FIT) screening program in participants with a negative screening result the previous year, which we call “Negative advanced CRC”. A total of 109,639 participants (10.0% required colonoscopy, of whom 76.9% received one) underwent a CRC screening program using a FIT from fiscal 2009 to 2017. Negative advanced CRC was compared with advanced CRC (First advanced CRC) found at the first visit in a person who had not had a FIT screening history for more than 3 years. In addition, we compared the characteristics of Negative advanced CRC with those of interval cancer: cancer cases detected after a negative screening result and before the date of the next recommended screening.

Results A total of 339 cases of CRC (175 male: 164 female, 173 early stage: 166 advanced stage) were detected in the nine-year CRC screening period. The rate of right-sided CRCs was significantly higher in female (P < 0.01), advanced stage (P < 0.01), negative result previous year (P < 0.01), and symptom-negative (P < 0.01) participants than in each counterpart, respectively. The ratio of female (22/35; 62.9%) patients in Negative advanced CRCs tended to be high compared with that (40/83; 48.2%) in First advanced CRCs (P = 0.145). Overall, 22 (62.9%) of 35 Negative advanced CRCs and 28 (33.7%) of 83 First advanced CRCs were located in the right-sided colon, and the rate was significantly higher in Negative advanced CRCs (P < 0.01). In addition, the frequency of female patients was significantly higher in right-sided Negative advanced CRCs than in right-sided First advanced CRCs (P = 0.03).

Conclusion The characteristics of Negative advanced CRC cases (female and right-sided colon) were similar to those of interval cancer reported so far. In the future, it will be necessary to introduce a screening program that is highly sensitive to right-sided CRC.

Background C-reactive protein (CRP) levels reflect ongoing inflammation and/or tissue damage, and studies suggest that platelets play a role in tumor invasion and metastasis. P-CRP is defined as the multiplied product of serum CRP and platelet levels. Here the prognostic value of pre- and post-operative P-CRP levels in pancreatic cancer (PC) patients was assessed.

Methods This retrospective study used data from 107 consecutive PC patients who had undergone either pancreaticoduodenectomy or distal pancreatectomy. Clinicopathological parameters and pre/post-operative laboratory data derived from patient records were used for analyses. P-CRP was defined as the product of peripheral thrombocyte count (/uL) × serum CRP level (mg/dL) divided by 10⁴; the optimal P-CRP cut-off value was defined using receiver operating characteristic curves.

Results PC patients were classified as either P-CRP^Low (< 1.782; n = 49) or P-CRP^High (≥ 1.782; n = 58), based on the cut-off value of 1.782. Univariate analysis revealed that performance status, clinical stage, pathological T and N stages, P-CRP, and carbohydrate antigen 19-9 (CA19-9) significantly affected overall survival (OS). Multivariate analysis revealed that independent risk factors for OS were pathological N stage, P-CRP, and CA19-9. Additionally, 103 PC patients for whom postoperative data were available were classified into four groups (P-CRP^Low-Down, P-CRP^Low-Up, P-CRP^High-Down and P-CRP^High-Up), based on preoperative P-CRP and postoperative trend of P-CRP, and we found that prognosis, in terms of OS, was significantly different among these groups (P = 0.012).

Conclusion Pre- and post-operative P-CRP values are a potential predictor of prognosis in PC patients.

Background Liver fibrosis progresses to decompensated liver cirrhosis, for which medical needs remain unmet. We recently developed IC-2, a small-molecule compound that suppresses Wnt/β-catenin signaling, and found that IC-2 also suppresses liver fibrosis. In this study, we performed three-step screening of newly synthesized IC-2 derivatives to identify other small-molecule compounds that suppress liver fibrosis.

Methods The screening system consisted of three steps: a cell viability assay, a transcription factor 4 (TCF4) reporter assay, and induction of α-smooth muscle actin (α-SMA) and collagen 1α1 (Col1A1) expression in response to each compound. Screening using human LX-2 hepatic stellate cells (HSCs) was performed to target HSCs, which are the driver cells of liver fibrosis.

Results In the first step, since 9b and 9b-CONH₂ at 100 μM did not have any effects on cell viability, they were omitted in the next screening. Additionally, the conditions that led to > 40% inhibition of the controls were also excluded in subsequent screening. The second step was performed under 31 conditions for 19 small-molecule compounds. Sixteen small-molecule compounds caused significant reduction of TCF4 activity relative to that of 0.1% DMSO. Of the 16 compounds, the 10 showing the greatest suppression of TCF4 activity were selected for the third step. Expressions of mRNA for α-SMA and Col1A1 were significantly reduced by seven and three small-molecule compounds, respectively. The greatest reductions in the α-SMA and Col1A1 mRNA expressions were observed in the cells treated with IC-2-F. Protein expressions of α-SMA and Col1A1 caused by IC-2-F were also comparable to those caused by IC-2.

Conclusion IC-2-F was identified as a novel deactivating small-molecule compound for HSCs in vitro. These data suggest that IC-2-F is a promising medicine for liver fibrosis.

We present the case of a 58-year-old Japanese woman with a natural killer T (NK/T)-cell lymphoma complicated by brain abscess. NK/T-cell lymphomas represent a rare type of lymphoma derived from either activated NK cells or, rarely, cytotoxic T cells. They are aggressive Epstein-Barr virus (EBV)-associated lymphomas that involve mainly the nasal cavity. Brain abscess associated with primary extranodal nasal-type NK/T-cell lymphoma is extremely uncommon: to our knowledge, this is the first reported case of this lymphoma with brain abscess as the initial clinical manifestation. Endoscopic surgery was performed for definitive diagnosis under intraoperative navigation system. Chemotherapy followed by radiotherapy was performed and was effective: 72 months later the tumor has not recurred. Recommendations of endoscopic management for diagnosis and treatment of this rare neoplasm are discussed.

We report a case of X-linked recessive ichthyosis with basal cell carcinoma. An 86-year-old man was referred to our department for evaluation of a 1-year history of an ulcer on his left leg. He had suffered from dry skin with scales on his entire body since childhood. Histopathological examination of the lower leg revealed intradermal proliferation of a solid nest of basaloid cells showing unclear palisading in the periphery. Marked hyperkeratosis and hypergranulosis were also seen in the adjacent dermis. Loss of the steroid sulfatase gene was found on chromosome X. Based on these finding, we made a diagnosis of X-linked recessive ichthyosis with basal cell carcinoma. To our knowledge, there has been no report of X-linked recessive ichthyosis with cutaneous malignancy. We discuss the risk of skin cancer in relation to ichthyosis.