Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis, and is one of the leading causes of cancer-related deaths worldwide. Recently, the development of therapeutic drugs via novel mechanisms of action, involving molecular-targeted drugs and immune checkpoint inhibitors, has progressed in the field of HCC. However, the recurrence rate remains high, and further improvement of the prognosis of patients with HCC is urgently needed. Cancer stem cells (CSCs) are a promising target for further development of novel anti-cancer drugs because they are reportedly involved in tumor initiation, maintenance, recurrence, and resistance to conventional therapies. Although several studies have already been conducted, the functions and roles of CSCs in the development and progression of tumors remain to be elucidated. In this review article, we will clarify the fundamental knowledge of CSCs necessary for the understanding of CSCs and will outline so-far identified markers specific to liver CSCs and the pathological and therapeutic implications of CSCs in HCC.

Background The hypopharynx is a closed space that is difficult to observe. The modified Killian’s (MK) method was introduced to obtain wider exposure. However, this method requires keeping the head forward during the examination. Postural maintenance might be problematic. To use the MK method safely for a thorough endoscopic examination, we introduced a new body immobilization device. The aim of this study was to evaluate the effectiveness of this body immobilization device.

Methods Twenty-five patients underwent transnasal laryngoscopy using the MK method with the immobilization device. This device consists of a board to place the chest and a shaft. We classified hypopharynx visualization using a 5-point scale, in various combinations of head torsion, Valsalva maneuver, and MK position. Furthermore, we classified the feasibility of the MK method for 54 patients. Age, BMI, and performance status were evaluated by MK position feasibility class.

Results The MK method with the body immobilization device was completed in all patients. It was significantly associated with higher hypopharyngeal visibility score. BMI and performance status were significantly associated with MK method feasibility. There were no significant differences in hypopharynx visualization scores with versus without this device for the patients that could maintain the MK position on their own.

Conclusion For patients with poor nutrition or poor ability to perform activities of daily living, it was difficult to maintain the MK position. Thus, this immobilization device might be useful to complete the MK method and provide accurate detection of hypopharyngeal lesions in these patients.

Background Maintaining physical activity is important for older adults. “Self-care agency” is the ability to perform self-care, which is defined as people following their own will, managing themselves, and maintaining activities. We investigated the relationship among physical activity and self-care agency, demographic factors and physical condition in older adults.

Methods Self-care agency was assessed by using the Self-Care Agency Questionnaire developed for Japanese patients with chronic diseases. Among 175 older adults aged 65 years or older living in a rural area, responses from 83 who performed physical activities were analyzed. Correspondence analysis was conducted to characterize demographic factors and self-care agency.

Results A higher proportion of women than men were engaged in physical activity. Irrespective of age and sex, many of the participants performed stretching exercises, walking, radio exercises, TV exercises, and participated in community circles. Participants who engaged in physical activities had significantly higher self-care agency scores than inactive participants. Among the active participants, the self-care agency score was significantly higher for women than men (P = .04) and was also significantly higher for participants aged ≥ 75 years compared to those aged < 75 years. Individuals with a high self-care agency tended to participate in local programs and perform brief physical activities at home.

Conclusion Physically active older adults demonstrated high self-care agency. Their activities were easily carried out in their daily lives, with activities varying by age and sex. Support from community health experts is needed to promote suitable physical activity among older adults tailored for age and sex, especially among older adults who have low self-care agency.

Background Fragile X syndrome (FXS) is a well-known X-linked disorder clinically characterized by intellectual disability and autistic features. However, diagnosed Japanese FXS cases have been fewer than expected, and clinical features of Japanese FXS patients remain unknown.

Methods We evaluated the clinical features of Japanese FXS patients using the results of a questionnaire-based survey.

Results We presented the characteristics of seven patients aged 6 to 20 years. Long face and large ears were observed in five of seven patients. Macrocephaly was observed in four of five patients. The meaningful word was first seen at a certain time point between 18 and 72 months (median = 60 months). Developmental quotient or intellectual quotient ranged between 20 and 48 (median = 29). Behavioral disorders were seen in all patients (autistic spectrum disorder in six patients, hyperactivity in five patients). Five patients were diagnosed by polymerase chain reaction analysis, and two patients were diagnosed by the cytogenetic study. All physicians ordered FXS genetic testing for suspicious cases because of clinical manifestations.

Conclusion In the present study, a long face, large ears, macrocephaly, autistic spectrum disorder, and hyperactivity were observed in almost cases, and these characteristics might be common features in Japanese FXS patients. Our finding indicated the importance of clinical manifestations to diagnosis FXS. However, the sample size of the present study is small, and these features are also seen to patients with other disorders. We consider that genetic testing for FXS should be performed on a wider range of intellectually disabled cases.

Background An increasing number of adolescents are experiencing social maladjustment. This development may be due to serious conflicts regarding psychological independence. This study aimed to elucidate factors that influence psychological independence in adolescents and to clarify the relationship among coaching-based support from significant others, adolescent self-esteem, and adolescent psychological independence, in order to help prevent and treat social maladjustment in adolescents.

Methods A total of 1814 students in all years at 2 universities and 1 junior college in A Prefecture, Japan, completed an anonymous self-administered questionnaire. The questionnaire asked about the participants’ attributes, support relationships, psychological independence, and self-esteem. Coaching-based support was assessed by the Accelerate your Coaching Effectiveness scale; psychological independence by the Psychological Jiritsu Scale; and self-esteem by the Rosenberg Self-Esteem Scale.

Results Gender, grade, major, current living situation were found to influence psychological independence of adolescents. The most significant others who had the most influence on psychological independence were mothers, fathers, and friends for male adolescents, and mothers, friends, and fathers for female adolescents, in that order. In female, coaching-based support from significant others increased their self-esteem and promoted all the sub-scales of psychological independence. In male, coaching-based support boosted their self-esteem and promoted the following sub-scales; “future orientation”, “appropriate human relations”, “value judgment and execution”, “responsibility”, and “social perspective”, except for “self-control”.

Conclusion We believe that coaching-based support from significant others can effectively help adolescents build their self-esteem and can promote their psychological independence.

Background The purpose of this study was to elucidate the factors which affect the achievement of clinical nursing competency.

Methods A survey was conducted on 717 nurses using an anonymous self-administered questionnaire. Their clinical nursing competency was assessed using the Clinical Nursing Competence Self-Assessment Scale (CNCSS). This study examined the factors affecting clinical nursing competency using regression analyses. A simple regression analysis was performed with the CNCSS as the objective variable. A multiple regression analysis was performed using the items for which the relationship was clarified as explanatory variables.

Results The factors affecting the “basic nursing competency” were age, ease of taking time off, workplace with a clear vision, and good interpersonal relationships. The factors affecting the “competency in providing assistance commensurate with the patient’s health status” were total years of experience, workplace with a clear vision, ease of taking time off, and use of acquired certifications. The factors affecting the “coordinating care environment and teamwork” were total years of experience, workplace with a clear vision, use of acquired certifications, and ease of taking time off. The factors affecting the “ability for professional growth in nursing practice” were use of acquired certifications, workplace with a clear vision, total years of experience, and ease of taking time off.

Conclusion For improvement of clinical nursing competency, the factors elucidated to be necessary were accumulation of experience as a nurse, a clear vision of goals, and a work environment with good interpersonal relationships and ease of getting days off. The way nurses make their nursing practice experience meaningful contributed toward their growth as nurses. It is important to train nurses through basic education and continued education with awareness of achievement and improvement of clinical nursing competency. Basic education should promote the ability to make clinical training experience meaningful and continuing education should enable nurses to continue to grow independently through reflection.

Background Insulin and insulin-like growth factor (IGF) signaling plays an important role in prenatal and postnatal growth and glucose metabolism. Both small-for-gestational age (SGA) and preterm infants have abnormal growth and glucose metabolism. However, the underlying mechanism remains unknown. Recently, we showed that term SGA infants have abnormal insulin/IGF signaling in cord blood. In this study, we examined whether preterm infants show similar aberrations in cord blood insulin/IGF signaling.

Methods A total of 41 preterm cord blood samples were collected. Blood glucose, insulin, IGF-1, and C-peptide concentrations were measured, and mRNA expression of IGF1R, INSR, IRS1, IRS2, and SLC2A4 (i.e., GLUT4) was analyzed by quantitative reverse-transcription PCR.

Results This study included 34 appropriate-for-gestational age (AGA) and 7 SGA preterm neonates. No hyperinsulinemia or any differences in IGF1R or INSR mRNA expression were detected between the two groups. However, GLUT4 mRNA levels were increased in preterm SGA. Moreover, the expression level in hypoglycemic preterm SGA was significantly higher than that in hypoglycemic preterm AGA. IRS2 mRNA expression did not show a statistically significant difference between preterm SGA and AGA neonates.

Conclusion SGA preterm birth does not induce hyperinsulinemia; however, it modifies insulin/IGF signaling components such as GLUT4 in umbilical cord blood. Our study suggests that prematurity or adaptation to malnutrition alters the insulin/IGF signaling pathway.

Background In this study, we developed and tested the validity and reliability of the 12-item Rest and Recreation Quality Scale (RRQ-Scale) for Workers as a new scale capable of conveniently assessing the quality of workers’ days off, that is, their rest and recreation.

Methods Participants included 756 employees (694 men, 62 women, mean age ± SD= 44.7 ± 13.5, age range = 18–81) of 26 manufacturing-related companies located in Oita Prefecture, Japan. We analyzed the factorial validity of the scale’s score distribution and its criterion-related validity and reliability (Cronbach’s coefficient α), compared to MOS 36-Item Short-Form Health Survey version 2.0 (SF-36v2) and the generalized self-efficacy scale. Participants responded to the 12 questions on 4-point scales; these were summed to calculate the total score (score range: 12–48 points).

Results The smallest and largest mean ± SD of the questions were 2.53 ± 0.89 and 3.21 ± 0.74, respectively, which are within the possible score range (1–4, implying the absence of floor and ceiling effects). A confirmatory factor analysis indicated that the goodness of fit of the higher-order factor analysis model was satisfactory (GFI = 0.955), confirming factorial validity. In addition, consistent with the theoretical predictions, the total score exhibited statistically significant positive correlations with the components of the SF-36v2; physical component summary (PCS): rs = 0.193, P < 0.001, mental component summary (MCS): rs = 0.369, P < 0.001, and role/social Component Summary (RCS): rs = 0.115, P = 0.002. This confirmed criterion-related validity. Further, the overall reliability of the scale was high; α = 0.877.

Conclusion In sum, the score distribution, validity, and reliability of the RRQ-Scale for workers were good, indicating a high degree of practicality.

Background In order to find out the factors associated with the large disparities in COVID-19 mortality rates by country, we conducted an ecological study by linking existing statistics. In Japan, a large variation was observed in between geographical areas when assessing mortality. We performed a regional correlation analysis to find factors related to regional mortality.

Methods This study design was an ecologic study. A multiple regression analysis was performed with COVID-19 mortality rates of different countries as the dependent variable together with various health care and economic factors. We calculated the cumulative mortality rate as of June 30, 2020. For the regional correlation analysis of Japan, 47 prefectures were divided into nine regions. The factors examined were health care and tourism. Data for 33 Organization for Economic Co-operation and Development (OECD) countries were analyzed. In Japan’s regional analysis, the whole country was classified into nine regions.

Results Factors related to mortality were the incidence of Kawasaki disease (KD), number of computed tomographies (CTs), and alcohol consumption. Mortality was low in countries with high incidence of KD and high number of CTs, as well as in countries with high alcohol consumption. In European countries, high smoking prevalence and a high Gini coefficient were positively related to high mortality. According to a regional analysis in Japan, mortality was related to proportion of population in the densely inhabited districts, the number of foreign visitors per capita, and the number of Chinese visitors per capita.

Conclusion Low mortality in East Asia was associated with specific disease morbidity (KD), alcohol consumption, and CT numbers. It was suggested that the mortality gap in Japan was related to the number of foreign tourists and the proportion of population in the densely inhabited districts.

Background The psychological preparation factors associated with positive or negative emotions in pediatric patients with developmental disorders are not well known. We aimed to clarify which psychological preparation factors affect positive (favorable) or negative (fear) emotions toward hospitals in pediatric patients with autism spectrum disorder (ASD) or attention deficit hypertensive disorder (ADHD), using the questionnaires for the patients and guardians.

Methods The questionnaires were sent by mail via prefectural patient-family groups to pediatric patients (6 to 15 years old; diagnosed with ASD or ADHD) and their guardians living in seven prefectures in Japan. Thereafter, we statistically analyzed the associations between the background factors or psychological preparations and the patients’ positive or negative emotions toward the hospital.

Results The questionnaire results of 68 patients (age: 6–15 years; 15 = females; 53 = males) and their guardians indicated the main diagnoses for patients were ASD (n = 54) and ADHD (n = 14). Intellectual disability and hypersensitivity were positively associated with fear experiences in the hospital. In contrast, the staff’s explanations during interventions negatively associated with patients’ fear experiences. The psychological preparations performed by doctors during the medical checks were positively associated with the patient’s positive emotions toward the hospital.

Conclusion Regarding the psychological preparations for patients with ASD or ADHD, interpersonal communication with doctors and staff promotes positive emotions and reduces anxiety in the hospital.

Background We conducted a workshop-style program based on applied behavior analysis (ABA) for Japanese teachers in charge of children with developmental disabilities who had behavioral problems. Additionally, we investigated whether making and implementing behavioral intervention plans (BIPs) for participants, improved students’ behavioral problems, and the mental health of participants.

Methods The participants were 18 Japanese elementary and kindergarten teachers in charge of students with behavioral problems. The workshop comprised eight two-hour sessions of lectures and group discussions related to ABA. Achievement level was evaluated for the development and implementation of the BIP and improvement of behavioral problems. In addition, we analyzed changes in the 30-item General Health Questionnaire (GHQ-30) scores pre- and post-workshop to assess participants’ mental health. Fifteen teachers who participated in more than half of the sessions were analyzed.

Results All 15 teachers analyzed were able to perform appropriate functional behavioral assessment (FBA) and make a BIP, and 12 showed improvement in the targeted problem behaviors. Many target behaviors had avoidance functions and many antecedent strategies were behavior contracts. Adaptive behaviors incompatible with problem behaviors were selected as alternative behaviors to problem behaviors. Also, there was no aversive control over the outcome strategy. The average score for “social activity disorder” and “anxiety / caprice” in GHQ30 showed a statistically significant improvement in pre- and post-workshop.

Conclusion It was found that appropriate FAB and BIP could be created using “the strategy sheet,” in workshops based on the ABA. It was also suggested that the workshop program may in turn improve teachers’ mental health. Further study is needed on the effectiveness of the workshop program using intergroup comparison designs for more subjects.

Background Subcutaneous injection of tumescent solution, which contains local anesthetic, adrenaline, and saline, before split-thickness skin graft harvesting, shows a significant hemostatic effect. This method can reduce the initial bleeding from the donor site. The aim of this study is to assess the benefits of controlling the bleeding from donor sites by tumescent injection. A randomized, controlled trial was performed to compare the wound healing of split-thickness skin graft donor sites treated with or without tumescent injection.

Methods This randomized, controlled trial examined donor site healing days as the main measure of outcome. postoperative pain, donor site ulceration, and scar quality were evaluated as secondary outcome measures. Patients planned for split-thickness skin graft harvest were randomly assigned to receive either pre-harvest subcutaneous injection of local anesthetic, adrenaline, and saline solution (tumescent solution) (Group 1) or post-harvest application of adrenaline solution-soaked gauze to the skin graft donor sites (Group 2). Donor sites were treated with calcium alginate dressings after graft harvesting. On the 10th postoperative day, the dressings were removed and donor site healing were measured. Follow-up evaluation of scar quality was performed 6 months after surgery. Postoperative pain was evaluated on the 1st day after operating.

Results Forty-five patients (26 males; average age 61.8 years) completed the late follow-up evaluation (6 months postoperatively), with 26 patients in group 1 and 19 in group 2. There were no significant differences between the two groups in any of the outcome measures.

Conclusion Tumescent technique provides sufficient hemostasis in split skin graft donor sites, especially the initial bleeding just after graft harvesting, without any negative effects. Larger series should be studied to evaluate the effect in donor site wound healing.

Background To perform successful coil embolization of cerebral aneurysms, it is crucial to make an appropriately shaped microcatheter tip for an aneurysm and its parent artery. So far, we manually shaped a mandrel by referencing two-dimensional (2D) images of a rotation digital subtraction angiography (DSA) on a computer screen. However, this technique requires a lot of experience, and often involves trial and error. Recently, there have been increasing reports of manual mandrel shaping using a full-scale three-dimensional (3D) model of an aneurysm and its parent artery output by various types of 3D printer. We have further developed this method by producing a hollow model of an aneurysm and its parent artery with a stereolithography 3D printer and inserting a mandrel inside the model to fit and stabilize a microcatheter tip.

Methods Based on digital imaging and communications in medicine (DICOM) data obtained by rotational DSA, 3D images of an aneurysm and its parent artery were created and converted into standard triangulated language (STL) data. A hollow model was produced by extruding the STL data outward in the normal direction, and then a hole was made at the tip of the aneurysm using these STL data. We output these STL data to a stereolithography 3D printer. After cleaning and sterilizing the model, the mandrel was inserted in the direction of the parent artery through the hole made in the tip of the aneurysm and pushed in, creating the ideal mandrel shape. Twelve cases (14 aneurysms) were included in this study. A microcatheter tip was shaped by this method for patients who were scheduled to undergo coil embolization for an unruptured aneurysm.

Results In 13 of the 14 aneurysms, the microcatheter was easily guided into the aneurysms in one or two trials, the position of the microcatheter tip in the aneurysm was appropriate, and the stability during coil embolization was high.

Conclusion Our method differs from the conventional one in that a hollow model made of resin is produced with a stereolithography 3D printer and that the mandrel is shaped by inserting it retrogradely into the hollow model. Using our new method, it will be possible to shape the tip of a microcatheter suitable for safe and stable coil embolization without relying on an operator’s experience.

Background Talaporfin sodium photodynamic therapy (TS-PDT) for local failure after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma has recently been reported to be highly effective and less invasive, compared to other treatment modalities. TS-PDT was recently introduced at the Tottori University Hospital, Japan. The aim of this study is to clarify the efficacy and safety of PDT in our hospital.

Methods This was a single-center observational study. We examined eight cases of TS-PDT performed between January 2016 and December 2019. The main endpoints were local complete remission (L-CR) rate and the adverse events. In addition, age, gender, histology, tumor location, TNM stage, tumor depth, irradiation dose, and overall survival (OS) were examined.

Results The patients included 7 men and a woman, with an average age of 72.1 years (range 63–82 years). The baseline clinical stages before CRT or radiotherapy were stage I in 1, stage II in 3, stage III in 3, and stage IVA in 1 patient. The T stage on endoscopic assessment before TS-PDT was T1 in 6 patients and T2 in 2 patients. Treatment outcomes and adverse events were evaluated. There were no treatment-related deaths, and no significant adverse events occurred intraoperatively or postoperatively. The L-CR rate was 7/8 (87.5%); T1 cases had 100% (6/6) L-CR, while T2 cases had 50% (1/2). The 2-year OS rates were 87%.

Conclusion TS-PDT was observed to be safe and effective in the first eight cases of its application following its introduction in our hospital.

We report a case of subcutaneous panniculitis-like T-cell lymphoma with diffuse indurated lesions without erythema. A 27-year-old man was referred to us with a 1-month history of fever, general fatigue and indurated skin lesions. The initial examination revealed indurated skin lesions without erythema and subcutaneous tumors in the right lower abdomen, back and buttocks. Histopathology showed a panniculitis predominantly in lobular pattern, and infiltration of atypical lymphocytes in the subcutaneous tissue. Characteristically, there was rimming of individual fat cells by surrounding atypical lymphocytes. Results of laboratory examinations showed hemophagocytic syndrome (HPS). Based on these findings, we made a diagnosis of subcutaneous panniculitis-like T-cell lymphoma without erythema and subcutaneous tumors with HPS. To our knowledge, there has been no report of SPTCL with diffuse indurated lesions without erythema, tumors, or plaque, all of which are considered to be typical characteristics of SPTCL. Positron emission tomography / computed tomography (PET/CT) showed noticeable thickening of diffuse subcutaneous involvement throughout the body. Hence, PET/CT is a useful for the detection of SPTCL as well as its distribution.

Fecal impaction is the impaired excretion of a large fecal mass, and mild cases are treated by enema and osmotic laxatives. However, treatment-resistant cases need more invasive alternatives. A woman in her 60s presented with abdominal discomfort. Her abdomen was soft and without tenderness. Computed tomography revealed a large mass of feces in her sigmoid colon and no intestinal dilatation proximal to the mass. Endoscopy confirmed a fecal mass occupying the lumen. A glycerin enema, oral administration of polyethylene glycol, and enteral administration of amidotrizoic acid during colonoscopy were ineffective. We maneuvered a guidewire to form a loop at the tip of an endoscope, with which we subdivided the mass for successful removal. The patient’s abdominal discomfort disappeared immediately. Endoscopic disimpaction is far less invasive than surgery and should be considered when treating fecal impaction cases, without severe obstructive colitis, which are nonresponsive to conservative treatment.

We present a rare case of concurrent resection of pancreatic and gastric cancer in which indocyanine green (ICG) fluorescence was used to evaluate the remnant stomach. An 80-year-old man was referred with a tumor in the distal pancreas. Computed tomography showed a 25-mm mass in the pancreatic tail; endoscopic ultrasound-guided fine-needle aspiration revealed adenocarcinoma. Upper gastrointestinal endoscopy and subsequent upper gastrointestinal series revealed advanced gastric cancer in the mid-stomach. Concurrent resection of the pancreatic and gastric tumors was performed. After distal pancreatectomy and distal gastrectomy, ICG evaluation of the stomach showed fluorescence extending only 3 cm distal from the cardia. To avoid ischemic change at the remnant stomach, total gastrectomy was performed. Since remnant gastric necrosis and anastomotic leak following ischemia can lead to fatal outcomes, the use of ICG to evaluate blood supply at anastomotic sites can help determine the extent of safe resection in such cases.

Gastrointestinal stromal tumors (GISTs) originate from mesenchymal cells throughout the gastrointestinal tract. A common symptom is gastrointestinal hemorrhage; intra-abdominal hemorrhage is relatively rare. There are few reports of GIST presenting with both types of hemorrhage concurrently. A 77-year-old man was admitted to our hospital because of melena and anemia (Hb: 4.7 g/dL). Computed tomography revealed a small bowel tumor and high-density fluid in both the small intestine and the pelvic floor. We diagnosed a small intestinal tumor with concurrent gastrointestinal and intra-abdominal hemorrhage, and performed emergency surgery. The tumor arose from the small intestine and was ruptured. We found hemorrhage in the pelvic cavity and performed partial small intestine resection. Pathological findings revealed that the tumor was positive for c-Kit protein and was diagnosed as GIST. The patient was discharged from the hospital on postoperative day 9 and received imatinib 1 month postoperatively. We experienced a very rare case of ruptured GIST originating from the small intestine associated with both gastrointestinal and intra-abdominal hemorrhage. We also reviewed the relevant literature.

This study provided a telehealth program for kindergarten and nursery teachers in charge of children with, or suspected of having, developmental disabilities. We examined teacher participation, behavior intervention plans (BIP), practice, and improvement of children’s behavior. Six sessions of online lectures and two online consultations based on functional behavioral assessments (FBA) were held. All ten teachers conducted the FBA, and seven created the BIP. Additionally, six out of seven teachers recorded their children’s problem behaviors, showing improvement in the problem behavior of these children. Moreover, the non-targeted problem behaviors also showed improvement following the intervention.