Triple-negative breast cancer (TNBC) is a heterogenous disease. For personalized medicine, it is essential to identify and classify tumor subtypes to develop effective therapeutic strategies. Although gene expression profiling has identified several TNBC subtypes, classification of these tumors remains complex. Most TNBCs exhibit an aggressive phenotype, but some rare types have a favorable clinical course. In this review, we summarize the classification and characteristics related to the various TNBC subtypes, including the rare types. Therapeutic methods that are suitable for each subtype are also discussed. Of the intrinsic breast cancer subtypes identified by gene expression analysis, the basal-like subtype specifically displayed decreased expression of an estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) cluster. We also present results that characterize the TNBC and basal-like phenotypes. TNBC may be categorized into four major classes : basal-like, immune-enriched, mesenchymal, and luminal androgen receptor. Therapeutic strategies for each subtype have been proposed along with newly approved targeted therapies for TNBC, such as immune checkpoint inhibitors. Understanding the classification of TNBC based on gene expression profiling in association with clinicopathological factors will facilitate accurate pathological diagnosis and effective treatment selection. J. Med. Invest. 68 : 213-219, August, 2021

The incidence rate of pulmonary nontuberculous mycobacterial disease (PNTMD) in Japan is the highest among major industrialized nations. Although the typical clinical course and radiological manifestations of PNTMD are different from those of pulmonary tuberculosis (TB), confusion about these mycobacterial diseases leads to a diagnostic pitfall. Diagnostic challenges include the coexistence of Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM), false positives for NTM in MTB nucleic acid amplification tests, microbial substitution, and abnormal radiological manifestations caused by NTM. Features of extrapulmonary NTM diseases, such as pleurisy, vertebral osteomyelitis, and disseminated disease, are different from the corresponding tuberculous diseases. Moreover, the immunological background of the patient (status of human immunodeficiency virus infection with or without antiviral therapy, continuation or discontinuation of immunosuppressive therapy, use of immune checkpoint inhibitor, pregnancy and delivery, etc.) influences the pathophysiology of mycobacterial diseases. This review describes the varying clinical presentations of NTM disease with emphasis on the differences from TB. J. Med. Invest. 68 : 220-227, August, 2021

The metabolic effects of androgens and their underlying mechanisms in females have been revealed by recent studies. An excess of androgens can have adverse effects on feeding behavior and metabolic functions and induce metabolic disorders / diseases, such as obesity, insulin resistance, and diabetes, in women and experimental animals of reproductive age. Interestingly, these effects of androgens are not observed in ovariectomized animals, indicating that their effects might be dependent on the estrogen milieu. Central and peripheral mechanisms, such as alterations in the activity of hypothalamic factors, reductions in energy expenditure, skeletal muscle insulin resistance, and β-cell dysfunction, might be related to these androgens’ effects. J. Med. Invest. 68 : 228-231, August, 2021

Objective : This study analysed Vincristine-induced peripheral neuropathy (VIPN) risk factors in Acute Lymphoblastic Leukaemia (ALL) children. Method : This cross-sectional study design was performed at Dr. Soetomo Hospital, Surabaya, Indonesia, from August to October 2019. It included ALL children, aged 4–18 years, undergoing the 2013 or 2018 ALL Indonesian Protocol of Chemotherapy, with a cumulative vincristine dose ≥ 12 mg / m2. VIPN diagnosis is based on complaints, the Total Neuropathy Score Pediatric Vincristine (TNS-PV), and nerve conduction studies (NCS). The examined risk factors were sex, age, ALL classification, nutritional status, impaired liver function, and cumulative vincristine dose. Results : There were 52 ALL children : median age 7 years, 59.6% boys, 59.6% ALL standard risk, 44.2% experienced impaired liver function at initial ALL diagnosis. Based on a single parameter for diagnosis, 26.9% had VIPN based on complaints, 76.9% had it based on the TNS-PV, and 100% had it based on NCS. VIPN was diagnosed in 25% of children, with predominantly motor impairment and located in lower extremities. Impaired liver function is a risk factor for VIPN in ALL children (p = 0.046, prevalence ratio (PR) 2.84). Conclusion : Impaired liver function is a significant risk factor for VIPN in ALL children. J. Med. Invest. 68 : 232-237, August, 2021

Peripherally derived steroids affect steroid production in the brain via the blood–brain barrier. However, steroid concentrations are lower in the cerebrospinal fluid than those in the blood, indicating restricted influx of steroids because of their metabolization by choroid plexus (CP) epithelial cells. Here, we analyzed the gene expression of steroidogenic enzymes [cholesterol side-chain cleavage enzyme (P450scc), 17α-hydroxylase/C17-C20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase (Cyp19a1), and 5α-reductase type 1 (5α-R1)]. These genes were expressed to a lesser extent in the CP than in the testis and to a similar extent in the cerebral cortex. However, P450scc levels were higher in the CP than in the cerebral cortex, whereas Cyp19a1 levels showed the opposite trend. We also evaluated the effects of orchiectomy and testosterone on the expression of these genes. P450c17 and 5α-R1 levels were unaffected by orchiectomy, whereas P450scc and 3β-HSD levels were increased and decreased, respectively. Cyp19a1 expression increased upon testosterone treatment, whereas that of 17β-HSD decreased upon orchiectomy or administration of testosterone. Immunohistochemistry analysis revealed that 17β-HSD was expressed in the cytoplasm of CP epithelial cells. These results indicate that CP epithelial cells synthesize and convert the certain types of steroids to contribute to the homeostasis of steroids in the brain. J. Med. Invest. 68 : 238-243, August, 2021

Background : The C-reactive protein (CRP)–albumin ratio (CAR) was reported as a prognostic factor of resectable hepatocellular carcinoma. The aim of this study was to analyse the significance of CAR in resectable pancreatic cancer. Patients and Methods : 163 patients with curative resection for pancreatic cancer were enrolled in this retrospective study. Cases of non-curative resection were excluded. The CAR was calculated with the preoperative plasma CRP and albumin values, with a cut-off value of 0.06, as calculated in a previous report. Results : Patients in the low CAR group had significantly better overall survival (OS) and disease-free survival (DFS) compared with the high CAR group (P < 0.05). On multivariate analysis, for high CAR, CA19-9 > 300 U / ml and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. High CAR was significantly associated with advanced T stage. Conclusion : The CAR might be a prognostic factor for patients with resectable pancreatic cancer. J. Med. Invest. 68 : 244-248, August, 2021

An intervention study was conducted to investigate the effects of daily 1,000-IU vitamin D-fortified milk intake on skeletal muscle mass, power, physical function and nutrition status in 26 healthy people and 8 older adults living in a nursing home. The serum 25-hydroxyvitamin D [25(OH)D] level was 13.4 ± 0.8 ng / mL and it markedly increased to 29.6 ± 0.9 ng / mL after daily 1000-IU vitamin D-fortified milk intake for 6 months. Handgrip strength (kg) also significantly increased in the 21-50 years and total groups, and male subjects, and the timed up and go test significantly improved in the 21-50 years and total groups, and female subjects after 6-month vitamin D intake. However, there were no significant differences between baseline and post-treatment in the Barthel Index (BI), walking speed (m / sec) or skeletal muscle mass (kg, % of BW, kg / m2). Therefore, the present study suggested that vitamin D-fortified milk intake is effective at improving muscle strength and physical function in Japanese, although further studies are needed, particularly for older adults. J. Med. Invest. 68 : 249-255, August, 2021

 Background : Surgical site infection (SSI) is an adverse event that places a major burden on patients and staff. In this study, we examined the occurrence of SSI and the characteristics of patients referred to the SSI team after colorectal surgery. Methods : In total, 955 patients underwent colorectal surgery at our hospital from 2014 to 2019. Of these 955 patients, 516 received therapeutic support by the SSI team from 2017 to 2019. All patients were evaluated using an SSI surveillance sheet, and we checked for reports of SSI once a month. Each attending physician performed SSI prophylaxis (use of new instruments before wound irrigation and closure). Results : SSI occurred in 80 (8.4%) patients. The incidence of SSI and the incidence of surface SSI were higher in the patients who did not receive intervention by the SSI team than in the patients who did. Organ / space SSI occurred in 18 patients. Among patients with surface SSI, Enterococcus was the most commonly detected bacteria. Among the 18 patients with organ / space SSI, 5 developed anastomotic leakage and 4 developed intra-abdominal abscesses. Conclusions : An SSI team for prevention and treatment of infection may contribute to reduction of SSI. J. Med. Invest. 68 : 256-259, August, 2021

Background : Although platinum-combination chemotherapy is widely used to treat advanced non-small cell lung cancer (NSCLC), not all elderly patients benefit from this regimen. In this retrospective study, we aimed to evaluate whether the Glasgow Prognostic Score (GPS), an indicator of systemic inflammation and malnutrition, could predict the tolerability and efficacy of platinum-combination chemotherapy among elderly patients with NSCLC. Methods : The eligibility criteria included patients aged ≥ 70 years with NSCLC treated with first-line platinum-combination chemotherapy at Shimane University Hospital between January 2015 and December 2018. Results : Thirty-two patients with NSCLC (median age, 74 years) were included. The GPS scores were 0–1 for 19 patients and 2 for 13 patients. Four chemotherapy cycles were completed by 57.9% and 30.8% of patients in the GPS 0–1 and GPS 2 groups, respectively. The GPS 0–1 group experienced better outcomes than the GPS 2 group (response rate : 26% vs. 15%, P = 0.67 ; median progression-free survival : 4.1 vs. 2.1 months, P = 0.0026 ; median overall survival : 22.8 vs. 9.6 months, P = 0.0092). Conclusions : Platinum-combination chemotherapy demonstrated promising efficacy among elderly NSCLC patients with a GPS 0–1. Therefore, GPS may be crucial in determining whether treatments recommended for younger patients are suitable for older patients with NSCLC. J. Med. Invest. 68 : 260-264, August, 2021

The aim of this study was to clarify the relationship between maternal mental status and social supports during pregnancy and until one month after childbirth in order to evaluate the actual situation in a local city. A survey was conducted on 78 pregnant women who completed the CES-D (depression score), STAI (anxiety score) and Social Support Scale. Data were collected four times : during the second trimester, the third trimester, postpartum hospitalization, and 1 month after childbirth. The CES-D and STAI scores were initially high during pregnancy and decreased during the postpartum period. The Social Support Scale score, however, was initially low during pregnancy and increased during the postpartum period. The CES-D and STAI scores was significantly and negatively correlated with The Social Support Scale score during all four time periods. Participants ≧ 35 years of age scored lower on The Social Support Scale than did participants < 35 years of age in the second trimester, third trimester, and 1 month after childbirth. These findings should assist with the implementation of a comprehensive support center and may be useful for a local city in Japan. J. Med. Invest. 68 : 265-270, August, 2021

The purpose of this study was to clarify characteristics of psychiatric nurses’ observation techniques for psychopathological symptoms. The subjects were 21 psychiatric nurses and 20 nursing students who had finished their practicum in psychiatric nursing. Using a non-contact eye-tracking analysis system, we compared quantitatively their radial motion while they were observing psychopathological symptoms of a schizophrenia simulation patient. The radial motion of them was recorded while they were observing a video of a simulated patient presenting psychopathological symptoms, and the recording was analyzed by the eye-tracking system. The investigator set the important observation areas and determined the sum of the fixation time and the number of fixations in the areas. Differences between psychiatric nurses and nursing students were tested using the Mann-Whitney U-test. The results revealed a significant difference in observation of the upper limbs area with a median of 7147.90 msec for nurses group and a median of 2447.54 msec for students group (U = 98.00, p = 0.01). The finding suggests that nurses tend to pay more attention to patient’s upper limbs to be cautious about possible violence and to find agitation caused by psychopathological symptoms, extrapyramidal adverse effects, and scars caused by self-mutilation. J. Med. Invest. 68 : 271-275, August, 2021

Objective : In the present study, an attempt was made to evaluate the acoustic characteristics of voice in pediatric patients with vocal nodules using acoustic analysis of voice. Methods : Thirty-five pediatric patients with vocal nodules and 32 control children without dysphonia were enrolled in this study. Their voice samples were analyzed using the Multi-Dimensional Voice Program. Acoustic parameters of voice, such as pitch period perturbation quotient (PPQ), amplitude perturbation quotient (APQ), and noise-to-harmonic ratio (NHR), were measured. Results : In phonation at a loudness of over 80 dBA, the PPQ, APQ, and NHR values of the voice significantly increased in children with vocal nodules than in the control children without dysphonia. The sensitivities and specificities of PPQ, APQ, and NHR for prediction of vocal nodules in children were 62.86% and 84.38%, 74.29% and 75.00%, and 31.43% and 93.75%, respectively. Discussion : The present findings suggest that vocal nodules affect vocal fold vibration, resulting in impaired control of pitch and loudness leading to increased noise components. NHR could be used to evaluate the efficacy of treatment, such as voice rehabilitation, in pediatric patients with vocal nodules because of its high specificity for prediction of vocal nodules in children. J. Med. Invest. 68 : 276-279, August, 2021

The administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK), and His59-Lys60 (HK) from β-lactoglobulin C variant, which is specific to Jersey cow milk, has been shown to prevent and/or restore the age-dependent atrophy and functional decline of salivary glands by affecting gene expression in elderly rats. In this study, we investigated the effect of Jersey cow defatted milk on salivary volume and composition in elderly persons. Participants (aged 85 to 98, n = 8) were administered defatted dry milk from Jersey cows twice a day for 4 weeks. Before and after 4 weeks from the start of drinking, saliva was collected and weighed. Salivary cystatin S and amylase levels were analyzed by Western blotting. To assess the effect of Jersey cow defatted milk on taste perception, questionnaires were used. Salivary volume after oral administration of 40 g of Jersey cow defatted dry milk daily for 4 weeks was 1.8 times higher than that before administration. Salivary cystatin S and amylase levels significantly increased after administration of Jersey cow defatted dry milk. Moreover, all participants who had taste impairment reported improved taste perception after administration. The administration of Jersey cow defatted dry milk increased salivary volume and changed the composition of saliva in elderly persons. Furthermore, it improved taste perception. J. Med. Invest. 68 : 280-285, August, 2021

Background. PCNSL is mainly treated with HD-MTX-based chemotherapy with or without WBRT. However, As WBRT is associated with delayed neurotoxicity leading to dementia in the elderly, many institutes reported benefits of intensive chemotherapy or high-dose chemotherapy with ASCT. We investigated whether treatment with HD-MTX and rituximab, followed by continued-maintenance HD-MTX monotherapy (3.5g / m2), improves overall survival (OS). Methods. In this retrospective, single-center trial 52 immunocompetent patients with newly diagnosed PCNSL were included. All were treated between January 2005 and December 2017. The controls were 18 patients who, between 2005 and 2011, had received 3 cycles of HD-MTX and then adjuvant treatment with WBRT. In 2011 we started HD-MTX continued-maintenance therapy to treat 34 PCNSL patients. In the induction phase, these patients received HD-MTX every 14 days until a complete response (CR) was observed. When CR was obtained, maintenance therapy with HD-MTX (3.5g / m2) was delivered every three months. Results. In 3-year overall survival (OS) there was a statistically significant difference between the two groups [controls : 33.1% (95%, CI 12.4 - 55.7%) ; maintenance group : 74.9% (95%, CI 55.6 - 86.7%) (p < 0.02)]. Conclusion : The induction of HD-MTX based chemotherapy followed by continued-maintenance HD-MTX monotherapy improved OS compared with chemoradiotherapy consisting of HD-MTX followed by WBRT. J. Med. Invest. 68 : 286-291, August, 2021

Background : Our previous studies demonstrated that the intrarenal renin-angiotensin system (RAS) status was activated in pediatric patients with chronic glomerulonephritis. In the present study, we tested the hypothesis that angiotensin-converting enzyme 2 (ACE2) expression in the kidney is associated with the development of pediatric IgA nephropathy. Methods : We analyzed urinary ACE2 levels and ACE2 expression in the kidney tissues of pediatric patients with IgA nephropathy treated with RAS blockade. Paired tests were used to analyze changes from the first to the second biopsy. Results : Urinary ACE2 levels were significantly decreased after RAS blockade treatment, accompanied by decreased ACE2 expression levels in kidney tissues, urinary protein levels and mesangial hypercellularity scores. Urinary ACE2 levels at the first biopsy were positively correlated with the ACE2 expression levels. Conclusions : These data suggest that urinary ACE2 is associated with ACE2 expression in the diseased kidney, which correlates with the pathogenesis of IgA nephropathy in pediatric patients. J. Med. Invest. 68 : 292-296, August, 2021

Spasticity is the major cause of disabilities in stroke-survivors. Botulinum neurotoxin (BoNT) injections have been used to reduce the muscle tone in those patients, but its efficacy in functional outcome is not well delineated. We have studied the effect of a robot (Hybrid-Assisted Limb or HAL™) designed for assisting the elbow flexion and extension in those who underwent BoNT injections with reduced muscle tone. We enrolled 15 post stroke patients who had BoNT injections for more than 12 months. They were measured for active ROM (range of motion) with video recordings before and after the use of HAL for 40 minutes. Active ROM was measured by a rater who were blinded as to the use of the robot. Significant increase of active ROM was observed immediately after the use of HAL, and the effect was maintained for another 12 months by repeating the sessions. It is suggested from present study that the combined use of BoNT and robotics is effective efficacious for regaining the active function of the upper limb in stroke survivors. J. Med. Invest. 68 : 297-301, August, 2021

Introduction : Cystatin C (CysC) is biomarker for early detection of acute kidney injury (AKI). However, there is limited evidence in decompensated cirrhotic patients without AKI at admission. This study aimed to assess CysC as a predictor of 90-day mortality. Methods : Decompensated cirrhotic patients without AKI were prospectively enrolled. CysC and creatinine were measured within 24 hours of admission and compared between patients with in-hospital complications (AKI, hepatorenal syndrome (HRS), acute-on-chronic liver failure (ACLF)) vs. those without, and survivors vs. non-survivors. The AUROC and cut-off point of CysC in predicting 90-day mortality were determined. Results : Of 137 decompensated cirrhotic patients, 46 without AKI at admission were included (58.7% male, age 60.8 ± 11.2years, MELD 13.1 ± 5.1, ChildA / B / C 43.5% / 39.1% / 17.4%). The mean CysC level tended to be higher in patients with ACLF (1.52 ± 0.60 vs. 1.11 ± 0.28, p = 0.05), and significantly higher in non-survivors than survivors (1.61 ± 0.53 vs. 1.08 ± 0.28, p = 0.013). The 90-day mortality rate was 21.7%. After adjusting with age and bacterial infection on admission, CysC level  ≥ 1.25 mg / L was significantly associated with 90-day mortality. The CysC cut-off level  ≥ 1.25 mg / L provided 80% sensitivity and 75% specificity for predicting 90-day mortality. Conclusion : Plasma CysC within 24 hours could be used as a predictor for 90-day mortality and development of ACLF in decompensated cirrhotic patients. J. Med. Invest. 68 : 302-308, August, 2021

Stromal cell-derived factor-1 (SDF-1) expression is associated with cancer progression, as a biomarker of prognosis. We clarified the significance of SDF-1 expression on chemoradiotherapy (CRT) resistance and prognosis in advanced lower rectal cancer patients. We evaluated 98 patients with advanced lower rectal cancer who underwent preoperative CRT. All patients received 40 Gy of radiation therapy, with concurrent chemotherapy containing fluorinated pyrimidines, followed by surgical resection. SDF-1 expression in surgical specimens was examined by immunohistochemistry. We divided the patients into SDF-1-positive- (n = 52) and SDF-1-negative groups (n = 46) and compared the clinicopathological factors and survival rates. The SDF-1-positive group was more resistant to CRT than the SDF-1-negative group (non-responder rate, 63.5% vs. 47.8%, respectively ; p = 0.12). Overall survival (OS) in the SDF-1 positive group was significantly poorer vs. the SDF-1-negative group (5-year OS, 73.4% vs. 88.0%, respectively ; p = 0.02), and disease-free survival (DFS) was worse (5-year DFS, 61.0% vs. 74.1%, respectively ; p = 0.07). Multivariate analysis confirmed that SDF-1 expression was a significant independent prognostic predictor of OS (p = 0.04). SDF-1 expression after preoperative CRT is significantly associated with a poor prognosis in advanced lower rectal cancer patients and is a promising biomarker. J. Med. Invest. 68 : 309-314, August, 2021

We previously showed that chemotherapy-induced dysgeusia was associated with lingual taste receptor gene expression, and monosodium glutamate (MSG) improved dysgeusia by upregulating taste 1 receptor 3(T1R3) gene expression. In recent years, decreased taste sensitivity has also been reported in some young people, and these are partly due to their disordered eating habits. From these background, we investigated the effects of MSG supplementation on taste receptor expression and dietary intake in healthy females. Fifteen young healthy volunteers were enrolled for the present crossover study and divided in two groups (dietary supplementation with MSG at 2.7 g / day or 0.27 g / day). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative PCR analysis. Food intake was assessed by food frequency questionnaire (FFQg), and body composition was measured using Omron HBF-701. T1R3 expression levels in the tongue and taste sensitivity increased significantly in participants who consumed <10 g of MSG daily, whereas no alteration was observed in participants who consumed >10 g of MSG daily. Furthermore, protein, fat, and carbohydrate (PFC) balance and salt and sugar intake improved by MSG supplementation. In conclusion, MSG supplementation increased T1R3 expression in the tongue and improved dietary balance. J. Med. Invest. 68 : 315-320, August, 2021

Many hypotheses underlie the pathogenesis of preeclampsia. This study aims to evaluate Neutrophil gelatinase-associated lipocalin (a marker of immune hypothesis) and Neutrophil / Lymphocyte ratio (a marker of inflammation) in the diagnosis of preeclampsia and its severity and to determine the correlation between them.

Study design : This randomized case-control study involved 132 pregnant women ; 88 were diagnosed with PE (divided into non-severe and severe groups), and 44 healthy pregnant women as a control group. Results : The mean serum level of NGL was significantly higher in PE (535.37 ± 158.61 ng / ml for severe PE, 522.5 ± 106.3 ng / ml for non-severe PE, and 161.96 ± 17.48 ng / ml for the control group). The ROC Curve NGL criteria of more than 204.4 ng / ml showed 100% sensitivity and specificity in both severe and non-severe cases versus control. The N / L ratio showed a significant difference (5.81 ± 5.24 for severe PE, 4.1 ± 3.41 for non-severe PE, and 3.89 ± 1.79 for the control group), but the ROC curve criterion was not significant. Both showed a non-significant positive correlation. Conclusion : NGL is an excellent diagnostic factor, whereas N / L might have lower diagnostic performance compared with NGL. Both are related independently to the pathophysiology of PE. J. Med. Invest. 68 : 321-325, August, 2021

Purpose : To evaluate the efficacy of the direct grasping technique using pean forceps under fluoroscopic guidance for ureteral stent replacement in women. Methods : Between April 2018 and September 2020, 28 female patients underwent ureteral stent replacements at our facility, and 184 stent replacement procedures were performed. A total of 127 stents were replaced using pean forceps under fluoroscopic guidance (pean forceps group), and 57 stents were replaced using the cystoscope (cystoscopy group). Clinical characteristics and surgical outcomes were compared between the groups. Results : All stents were successfully replaced. There was a statistically significant difference in the procedure time between the two groups (median [interquartile range], pean forceps group : 10.8 [8.2–13.9] minutes vs. cystoscopy group : 15.8 [11.1–20.9] minutes, P < 0.001). There were no intraoperative complications in either group and no difference in the incidence of postoperative complications (pean forceps group : 1.6% vs. cystoscopy group : 1.8%, P = 1.000). Fluoroscopy time was longer in the pean forceps group, although this difference was not statistically significant (pean forceps group : 38.9 [22.6–60.1] seconds vs. cystoscopy group : 33.0 [20.0–48.9] seconds, P = 0.0558). Conclusion : The direct grasping technique using pean forceps under fluoroscopy may be a beneficial alternative to cystoscopy for ureteral stent replacement in women. J. Med. Invest. 68 : 326-329, August, 2021

Background : The aim of this study is to clarify the regeneration of the CL (caudate lobe) without any reconstructions of short hepatic veins (SHVr) after LDLT (living donor liver transplantation) and compare the regeneration of the CL after right hepatectomy (Rt. Hx), as the surrogate model of extended left lobe graft (Ex LLG) with complete SHVr. Methods : Eleven Ex LLGs with CL were included in this study. SHVr was not performed in all cases. The volumetry was performed before, one month and six months after LDLT. Seven patients who underwent Rt. Hx were also included in this study as the surrogate model. Results : In Ex LLGs with CL, the regeneration rate of the large CL (> 30 ml) was worse than that of small CL (< 30 ml). In the surrogate model, the regeneration rate of the CL was not worse than other segments. However, the regeneration rate of the large CL was also worse than that of small CL even in the presence of complete SHVr. Conclusions : The regeneration of the large CL was worse than that of the small CL regardless of the presence or absence of SHVr, indicating that SHVr in Ex LLG with CL might not be necessary. J. Med. Invest. 68 : 330-333, August, 2021

Background : Appendectomy can be challenging and occasionally converted to extensive resection for complicated appendicitis. However, optimal treatment strategies can be developed using preoperative risk assessment. Thus, we aimed to investigate the preoperative predictors of extensive resection in complicated appendicitis patients undergoing surgery. Materials and methods : In total, 173 complicated appendicitis patients undergoing surgery between 2014 and 2019 were classified into the appendectomy (n = 153) or extensive resection (n = 20) groups. Clinicopathological factors and surgical outcomes were compared between groups. Results : Extensive resection was performed in 20 of 173 complicated appendicitis patients (11.5%). The rates of having defects in the wall structure at the appendix root on computed tomography images were significantly higher, and the duration from onset to surgery was significantly longer in the extensive resection group. Significant differences were found in operative duration, blood loss and postoperative hospitalization, but none in the incidence of postoperative complications between groups. Multivariate analyses showed that defects in the wall structure at the appendix root and five days or longer from onset were identified as independent predictors of extensive resection. Conclusions : Defects in the wall structure at the appendix root and five days or longer from onset predict extensive resection performance in complicated appendicitis patients. J. Med. Invest. 68 : 334-341, August, 2021

Background : Several prognostic factors were reported in pancreatic cancer. The fibrinogen–platelet ratio (FPR) was reported as a prognostic factor of resectable gastric cancer. In this report, the FPR was evaluated in patients with resectable pancreatic cancer. Methods : Between 2004 and 2019, 163 patients with curative resection for pancreatic cancer were enrolled. Cases of non-curative resection were excluded. The FPR was calculated using the preoperative plasma fibrinogen and the platelet counts and the cut-off value was determined by receiver operating characteristic (ROC) curve analysis. The patients were divided into high and low FPR groups according to this cut-off value. Results : The cut-off value of FPR was 25.2. Among age, sex, body mass index (BMI), and surgical factors including surgery type, volume of blood loss and surgery time, there was no significant difference between the two groups. Patients in the low FPR group had significantly better overall survival (OS) and relapse-free survival (RFS) compared with the high FPR group (P < 0.05). On multivariate analysis, a high FPR, CA19-9 > 300 U / ml, and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. Conclusions : The FPR might be a prognostic factor for patients with resectable pancreatic cancer. J. Med. Invest. 68 : 342-346, August, 2021

Peripheral nerve injury (PNI) after pelvic surgery is a common issue with a significant impact on patients. Autologous nerve grafting is the gold standard treatment for PNI, but this technique cannot be applied to fine nerve fibers in the pelvis. Schwann-like cell (SLC) differentiation is a novel therapeutic strategy for this clinical condition. However, the efficiency of SLC differentiation remains unsatisfactory. We modified an SLC differentiation protocol using adipose-derived stem cells (ADSCs) and folic acid. Morphology, gene expression and secretion of neurotrophic factors were examined to assess the differentiation quality and phenotypic characteristics. Our new modified protocol effectively induced a Schwann cell (SC) phenotype in ADSCs as assessed by morphology and expression of SC markers [S100 calcium-binding protein B (S100B), P < 0.01 ; p75 neurotrophic receptor (p75NTR), P < 0.05]. SLCs produced by the new protocol displayed a repair phenotype with decreased expression of ERBB2 and early growth response protein 2 (EGR2) / KROX20 (P < 0.01). Furthermore, our new protocol enhanced both mRNA expression and secretion of nerve growth factors by SLCs (P < 0.01). This protocol enhanced the SC characteristics and functions of ADSC-derived SLCs. This promising protocol requires further research and may contribute to SC-based nerve regeneration. J. Med. Invest. 68 : 347-353, August, 2021

Purpose : To predict local control / failure by a multiparametric approach using magnetic resonance (MR)-derived tumor morphological and functional parameters in pharynx squamous cell carcinoma (SCC) patients. Materials and Methods : Twenty-eight patients with oropharyngeal and hypopharyngeal SCCs were included in this study. Quantitative morphological parameters and intratumoral characteristics on T2-weighted images, tumor blood flow from pseudo-continuous arterial spin labeling, and tumor diffusion parameters of three diffusion models from multi-b-value diffusion-weighted imaging as well as patients’ characteristics were analyzed. The patients were divided into local control / failure groups. Univariate and multiparametric analysis were performed for the patient group division. Results : The value of morphological parameter of ‘sphericity’ and intratumoral characteristic of ‘homogeneity’ was revealed respectively significant for the prediction of the local control status in univariate analysis. Higher diagnostic performance was obtained with the sensitivity of 0.8, specificity of 0.75, positive predictive value of 0.89, negative predictive value of 0.6 and accuracy of 0.79 by multiparametric diagnostic model compared to results in the univariate analysis. Conclusion : A multiparametric analysis with MR-derived quantitative parameters may be useful to predict local control in pharynx SCC patients. J. Med. Invest. 68 : 354-361, August, 2021

Background : CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1 (PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods : A total of 105 patients who had undergone curative surgical resection for stage II / III GC at Tokushima University Hospital were included in this study. The expression of CMTM6 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results : CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS : 57.2% vs. 79.2%, respectively ; p < 0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS : 52.8% vs. 72.4%, respectively ; p < 0.05). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p < 0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p = 0.07). Conclusions : CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC. J. Med. Invest. 68 : 362-367, August, 2021

Tazobactam / piperacillin (TAZ / PIPC) is an injectable combination drug consisting of a broad-spectrum penicillin and a β-lactamase inhibitor. This antimicrobial has a wide spectrum of efficacy against both Gram-positive bacteria and anaerobes. Adverse events usually present as diarrhea or liver dysfunction ; agranulocytosis has not been reported in Japanese patients with puerperal disorders. However, we report a 32-year-old Japanese woman who received TAZ / PIPC to treat an intraperitoneal infection that developed after complications related to transvaginal delivery. Within 14 days of beginning TAZ / PIPC therapy, the patient developed agranulocytosis, indicated by a white blood cell count of 1900 cells / µL and a neutrophil count of 475 cells / µL. We discontinued TAZ / PIPC at this point and changed the antimicrobial to meropenem. Seven days later, her white blood cell count increased to 3700 cells / µL (neutrophil count : 1684 cells / µL), and the intraperitoneal infection resolved. Patients receiving TAZ / PIPC should be monitored periodically for agranulocytosis as well as for diarrhea and liver dysfunction. J. Med. Invest. 68 : 368-371, August, 2021

Background : Pyomyositis is a subacute bacterial infection of the skeletal muscles. Its most common features are fever, muscle swelling, and focal pain. There have been insufficient data regarding pyomyositis in healthy infants. Case report : A one-month-old boy presented with an impairment of his left arm movement. He was well-nourished and not under any apparent distress. His vital signs were within the normal limits but neurological examination revealed left forearm paralysis. Physical examination showed no abnormal findings in the region from the left shoulder joint to the fingertips. Considering these factors, an intracranial pathology was initially suspected. However, he developed a fever, regular tachycardia, and swelling in the left forearm. Magnetic resonance imaging revealed inflammation in the left forearm muscles. He was diagnosed with bacterial myositis and started on intravenous antibiotics. On the 17th day, he was discharged with oral antibiotic treatment, which was completed over 25 days without any sequelae nor relapse. Conclusion : Here we report the case of Japanese primary pyomyositis following one-day afebrile upper limb monoplegia in an infant. Even when infants exhibit afebrile symptoms, a bacterial infection should be suspected. J. Med. Invest. 68 : 372-375, August, 2021

Background : An accessory parotid gland (APG) is a common anatomical structure that occurs in 10%–56% of individuals. Pleomorphic adenomas are the most common benign tumors of the APG, and their ideal treatment is surgical excision, although there is a risk for aesthetic disorders and facial nerve damage due to the site of origin. Moreover, despite being benign, these tumors are known to recur. Therefore, it is necessary to achieve both reliable excision and avoidance of facial nerve damage. Case presentation : We report a case of a 49-year-old Japanese man with a mass in his left cheek. The lesion was diagnosed as a benign salivary gland tumor derived from the APG by computed tomography imaging, magnetic resonance imaging and fine needle aspiration cytology. We resected the tumor using modified high submandibular incision under the endoscopic-assisted field of view. Discussion and Conclusions : The tumor was less invasive and reliably resected using an endoscope. In surgical treatment, the endoscopic-assisted technique is very useful to achieve complete tumor resection and prevent relapse while avoiding serious complications due to surgical procedures. J. Med. Invest. 68 : 376-380, August, 2021

Multiple-system atrophy is an adult-onset progressive neurodegenerative disease affecting the central nervous system, including the spinal cord. There has been no perioperative guideline of the muscle relaxants used in multiple-system atrophy, although a recent article recommends anesthesiologists to use shorter-acting drugs at the lowest possible doses in the patients. Here, we document the first case with multiple-system atrophy undergoing surgery managed with a combination of rocuronium and sugammadex. The recovery time to the train-of-four count 2 after intravenous rocuronium 0.6 mg / kg, or the time from the start of sugammadex 2 mg / kg intravenously to the train-of-four ratio over 0.9 was prolonged in our case more than 20 and 2 minutes compared with those in healthy subjects, respectively. Neuromuscular monitoring, in addition to the careful vigilance in the perioperative period, seems mandatory in the patients. J. Med. Invest. 68 : 381-382, August, 2021

Background : Although an increase in sympathetic nerve activity is generally associated with a decrease in the photoplethysmography (PPG) amplitude, the present case study demonstrates that nociceptive stimuli, such as tracheal intubation, paradoxically induce an increase in PPG amplitude. To the best of our knowledge, this is the first study to capture an increase in the PPG amplitude in response to sympathetic nerve activation. Case presentation : A 73-year-old woman underwent open surgery. Following anesthesia induction, tracheal intubation was performed, which resulted in increased heart rate and raised blood pressure. While nociception usually decreases the PPG amplitude, the opposite was found. Conversely, the vascular stiffness K value, our research group’s unique monitoring method to quantify the strength of sympathetic activity, increased reflecting increased peripheral vascular resistance. Conclusions : We report a paradoxical case of increased PPG amplitude following tracheal intubation. It is important to note that the PPG amplitude does not always decrease with nociceptive stimuli. J. Med. Invest. 68 : 383-385, August, 2021

We report a rare case of a partial thickness tear of the supraspinatus at the musculotendinous junction in a softball catcher. Preoperative magnetic resonance images of the shoulder showed high signal intensity areas at the musculotendinous junction, along with discontinuity of the articular side of the supraspinatus. Arthroscopic examination revealed articular-side partial tear at the musculotendinous junction. The patient was able to return to playing softball 20 weeks after arthroscopic side-to-side repair. J. Med. Invest. 68 : 386-388, August, 2021

A 50-year-old woman was referred to our hospital for further examination of severe constricting pain at the right-side dominant anterior chest. She had medical history of outgrown childhood asthma and allergies to several animals. Chest auscultation revealed no wheezes, rhonchi and other crackles. Laboratory findings showed an eosinophilia and an elevation of total immunoglobulin E. The results of an electrocardiogram, a chest X-ray and a chest CT were unremarkable. A fractional exhaled nitric oxide value remarkably elevated, but the abnormalities in pulmonary function test were modest. Her chest pain was ameliorated after inhaling procaterol. Based on these findings, a diagnosis of chest tightness variant asthma was formulated, and we started treatment with inhaled corticosteroid / long acting β2 agonist. At two-weeks after treatment, her symptom markedly improved and a fractional exhaled nitric oxide value decreased, which led to a definitive diagnosis of chest tightness variant asthma. A fractional exhaled nitric oxide value further decreased to the normal range in consistent with symptom disappearance at 10-months after treatment, indicating the usefulness of fractional exhaled nitric oxide as a promising marker for the diagnosis and clinical improvement of chest tightness variant asthma. J. Med. Invest. 68 : 389-392, August, 2021

Hem-o-lok clips are commonly used for renal artery ligation in laparoscopic renal surgery. However, failure of the renal artery ligation clips is potentially fatal. A 61-year-old man underwent hand-assisted laparoscopic nephroureterectomy using a retroperitoneal approach for left ureteral carcinoma. One hour postoperatively, he was diagnosed with hemorrhagic shock. An immediate laparotomy revealed two closed, undamaged Hem-o-lok clips around the left renal artery. Pulsatile bleeding was observed, and the renal artery was immediately ligated with non-absorbable thread. We determined that the failure of the Hem-o-lok clips on the renal artery was caused by the lack of space between the two Hem-o-lok clips and the distal renal artery cuff beyond the distal clip. To prevent a potentially fatal failure of the renal artery ligation clips, one should maintain a sufficient space between the Hem-o-lok clips and an adequate distal renal artery cuff beyond the distal clip. J. Med. Invest. 68 : 393-395, August, 2021

A 76-year-old woman with a history of angina pectoris, hypertension and dyslipidemia was pointed out an abnormal opacity in the right hilar region on routine chest X-ray. Chest computed tomography showed masses in the anterior mediastinum with the invasion of the adjacent ascending aorta, right brachiocephalic vein and right pleura. Histologic examination led to a diagnosis of Masaoka stage IVa thymoma. Three courses of chemotherapy were given, but further tumor progression was seen. Thereafter, the patient was followed without aggressive treatments. One year after the initial diagnosis, she presented with dyspnea and right chest pain. Chest CT revealed right massive pleural effusion with pleural dissemination and much further progression of existing tumors. For the purpose of symptom palliation, a low dose (5 mg / day) of prednisolone was commenced, which unexpectedly led to marked alleviation of patient’s symptoms and dramatic decrease of pleural effusion. To the best of our knowledge, this is the first report of an invasive thymoma responded to low-dose corticosteroid. The present case suggests that corticosteroids, even at low doses, might be potentially effective for invasive thymoma after failure of surgery, chemotherapy and radiotherapy. J. Med. Invest. 68 : 396-399, August, 2021

Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021