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The aim of this study was to investigate the injuries in Japanese collegiate sepak takraw players. We primarily focused on hamstring strain injury (HSI), and investigated the associated physical characteristics. The study included 77 Japanese collegiate sepak takraw players who were interviewed; data were collected regarding injuries sustained by them during the game within the past year. The hip range of motion (ROM) was measured. The total number of injuries was 48 in a year. The rate of HSI was the highest (31.3 %) among all the injuries. All HSIs occurred in the dominant leg because of the sunback spike. Using the Mann-Whitney U test, significant differences in age and sport-related experience were observed between the injured group and uninjured group. Upon using logistic regression analy sis, the presence of a HSI was found to be associated with the sport-related experience (adjusted odds ratio [OR], 0.30; 95 % confidence interval [CI], 0.12-0.77) and the hip extension ROM (adjusted OR, 0.81; 95 % CI, 0.66-0.99) after adjusting for sex, sport-related experience, and the hip ROM. HSI is the most common injury in Japanese collegiate sepak takraw players. Short sport-related experience and small hip extension ROM are related with the occurrence of HSI. [ABSTRACT FROM AUTHOR]

Several studies have shown a higher prevalence of radiological abnormalities among gymnasts. However, the types of radiological abnormalities associated with low back pain (LB) have not been clarified. The hypothesis was that significant relationships between radiological abnormalities and LB may be revealed by discriminating between the types of MRI abnormalities while considering confounding factors. The subjects were 104 Japanese collegiate gymnasts (men, 70; women, 34). The presence of LB was evaluated using the questionnaire developed by Osaka City University (OCU Test). Magnetic resonance imaging (MRI) abnormalities were evaluated using T1- and T2-weighted MRI. The prevalence of more than 1 MRI abnormality in gymnasts was 47.1 % (49/104). The chi-square test showed that the incidence of lumbar disc degeneration (LDDG) and limbus vertebra was significantly greater in gymnasts with LB than in gymnasts without LB. By using logistic regression analysis to analyze the concomitant environmental variables, only LDDG (odds ratio, 2.70; 95 % confidence interval, 1.10-6.66) was selected as a statistically significant variable accounting for LB. In conclusion, LDDG is a predictor for LB in Japanese collegiate gymnasts. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the relationship between disc degeneration (DD) and physical characteristics in male collegiate rubber baseball players. Physical characteristics of 61 rubber baseball players, such as range of motion, joint flexibility, and muscle tightness, were analyzed. DD was evaluated using T2-weighted magnetic resonance images. The degree of degeneration was classified into 5 grades according to the Pfirrmann classification, and the presence of grade 3 or higher was considered to represent degeneration. According to this evaluation, we assigned all players to 2 groups, the DD group (n = 21) and the non-DD group (n = 40). The results showed that weight, body mass index (BMI), and the range of motion of the thoracolumbar region during left rotation were significantly higher in the DD group than the non-DD group (p<0.05). In conclusion, we considered that the relative weight, BMI and increased range of motion of the thoracolumbar region during left rotation have effect on DD in male collegiate rubber baseball players. [ABSTRACT FROM AUTHOR]

We investigated the risk factors of abdominis muscle strain (AMS) in male university badminton players. Twenty-nine male badminton players were studied during medical check-ups, and were classified into the AMS group(n=7)or control group(n=22). Muscle tightness tests and the range of motion (ROM) of the hip, knee and ankle joint were measured to identify risk factors of AMS. The results showed that the average of the heel to buttocks distance (HBD) in the AMS group was significantly higher than that in the control group (p <0.01). On the other hand, the knee flexion was significantly lower in the AMS group than that in the control group(p<0.01). The ankle extension was significantly lower in the AMS group than that in the control group (p<0.05). In conclusion, we suggest that the tightness of the quadriceps (HBD), and the limitation of knee flexion/ ankle extension may be important risk factors of AMS. [ABSTRACT FROM AUTHOR]

This study aims to investigate the risk factors of Achilles tendonitis in collegiate female volleyball players. Twenty-four university female volleyball players were classified into two groups : the Achilles tendonitis group (Group A, n=7) and the asymptomatic group (Group B, n=17). Physical characteristics (Looseness test, Tightness test, range of motion, and height of foot arch) were measured to identify risk factors of Achilles tendonitis. The results showed that 6 out of 7 players in Group A were attackers and 1 was a receiver in position. Achilles tendonitis of the 6 attackers was unilateral (right side)and the 1 receiver was bilateral. The foot arch was significantly higher in Group A than that in Group B (p<0.01). We conclude that unilateral Achilles tendonitis of the 6 attackers (all right side)was thought to be caused by the right Achilles tendon being subjected to great load at the time of take off in a spike-jump. In addition, our finding revealed that high arch of the foot would be an important risk factor of Achilles tendonitis in female collegiate volleyball players. [ABSTRACT FROM AUTHOR]

We investigated risk factors of hamstring muscle strain injury in female university soccer players. Fifty-two female soccer players were measured during medical check-ups, and were classified into 12 legs with injury and 92 legs without injury. The range of motion (ROM) of the hip joint and muscle tightness tests were measured to identify risk factors of hamstring muscle strain injury. The results showed that the average range of hip external rotation in the hamstring muscle strain injury group was significantly higher than that in the control (p<0.05). In addition, heel to buttocks distance, which is one of the quadriceps muscle tightness tests, also showed significant difference (p<0.05). In conclusion, we suggest that the hip external rotation and the tightness of the quadriceps (HBD) are important risk factors of hamstring muscle strain injury. [ABSTRACT FROM AUTHOR]

This study investigated the risk factors of jumper's knee in male university volleyball players. Twenty-nine male university volleyball players underwent medical check-ups, and were classified into 12 knees with patellar tendinitis (Group A) and 46 knees without patellar tendinitis (Group B). Physical characteristics (range of motion, tightness test)were measured to identify the risk factors of jumper's knee. The average range of hip flexion was significantly lower in Group A than in Group B (p<0.01). Furthermore, the average Straight Leg Raising (SLR) of the Tightness test was significantly lower in Group A than in Group B (p<0.01). Our findings indicated that restriction of hip flexion and tightness of the hamstring(SLR)are important risk factors related to jumper's knee, in addition to the findings in a previous report that jumper's knee may be caused by tightness of the quadriceps. [ABSTRACT FROM AUTHOR]

Femoral stress fracture, which is a comparatively rare injury, was examined for its features and treatment. Fourteen cases were analyzed (3 cases in the femoral neck and 11 cases in the femoral shaft) from May 2002 to September 2005. The period until consulting a physician from onset was 4 days to 3 months. The rest period was 1 month to 3 months, and it was possible to return to all games at 2.5~4.5 months after symptom. The areas of pain varied, and in 3 cases the fracture site was different from the pain area. So it was difficult to specify the fracture site from the pain area. In 8 cases, the fracture site was 1/3 the proximal medial area in the femoral shaft, a common area of femoral stress fracture. It is useful to take oblique X rays pictures because those pictures often describe the stress fracture area. [ABSTRACT FROM AUTHOR]

A study was conducted regarding the peak onset of disease using 95,414 people who were new out patients of our department during the period from 1980 to 2002. The study included Sever disease, Sinding-Larsen-Johansson disease, Osgood Schlatter disease, Osteochondritis dissecans, Avulsion fracture of the pelvis, and Stress fracture, which are sports disorders incurred during periods of growth. Each disorder has a specific onset period, and it was found that the most affected age correlated with the growth curve. [ABSTRACT FROM AUTHOR]

We investigated the sports injuries of 71,953 cases dealt with by our out-patient clinic from 1980 to 2000. (Male: 46,442 cases / Female: 25,511 cases) The most frequent age of injury occurrence was 16 years (7,491 cases). The next highest was 19 years of age and the 3rd highest was 17 years of age. The most common sport was basketball(7,177 cases). The next most common sports were soccer, baseball, track & field, and volleyball. The most common injury was internal derangement (6,714 cases) followed by low back pain, ligament injury of the ankle, anterior cruciate ligament injury of the knee, and lumbar disc herniation. According to the investigation, this tendency continued throughout the past 20 years. [ABSTRACT FROM AUTHOR]

Muscle contusion injury is one of the major traumas in sports. The aim of this study is to identify convenient indices for judgment of the severity and prediction of recovery time in quadriceps thigh muscle contusion injuries. The 16 cases treated in our hospital were assessed according to 6 indices, the term for returning to games after an injury, age, injured site, knee flexion angle (within three days after injury and at one week after injury) and ability to play following injury. Stepwise multiple regression analysis showed that the term for returning to games was related to the knee flexion angle at one week after injury (R² = 0.427). The stepwise multiple regression analysis also demonstrated that knee flexion angle at one week after injury was related to the site of the injury and the ability to play following injury (R² = 0.736). In conclusion, this study found that in severe cases of thigh muscle injury, the knee flexion angle at one week after injury, the injured site and ability to play following injury all provide valuable information for precise prediction of the length of the recovery term before returning to games. [ABSTRACT FROM AUTHOR]

A boy aged 14 years old had suffered from pain in his right elbow for three years. There was no definite cause of his elbow pain. Since he began playing tennis one year ago, his elbow pain gradually increased with a snapping phenomenon. At his first visit to our hospital, his right elbow joint represented 10° at the valgus with the full range of active motion. While extending his elbow from full flexion and flexing it from full extension in the position of the pronated forearm, snapping and pain were evident in the radio-humeral joint. Movable restiform body was palpable surrounding the radial head. The plain X-rays as well as MRI revealed no abnormal findings. Conservative treatment, such as injection of steroid with 1% lidocaine into the joint, did not relieve his symptoms. At the surgery, meniscus-like tissue connected to the annular ligament was found between the capitellum and radial head. This tissue was impacted into the radio-humeral joint in the position of the extended elbow and was then emerging with snapping in the 130° flexed position. Snapping elbow is a rare condition. In this case, the meniscus-like tissue connected to the annular ligament caused the snapping phenomenon and pain. When conservative treatment is not effective, surgery should be considered. [ABSTRACT FROM AUTHOR]

Abstract Background Although muscle dysfunction caused by unfamiliar lengthening contraction is one of most important issues in sports medicine, there is little known about the molecular events on regeneration process. The purpose of this study was to investigate the temporal and spatial expression patterns of myogenin, myoD, pax7, and myostatin after acute lengthening contraction (LC)-induced injury in the rat hindlimb. Methods We employed our originally developed device with LC in rat gastrocnemius muscle (n = 24). Male Wistar rats were anesthetized with isoflurane (aspiration rate, 450 ml/min, concentration, 2.0%). The triceps surae muscle of the right hindlimb was then electrically stimulated with forced isokinetic dorsi-flexion (180°/sec and from 0 to 45°). Tissue contents of myoD, myogenin, pax7, myostatin were measured by western blotting and localizations of myoD and pax7 was measured by immunohistochemistry. After measuring isometric tetanic torque, a single bout of LC was performed in vivo. Results The torque was significantly decreased on days 2 and 5 as compared to the pre-treatment value, and recovered by day 7. The content of myoD and pax7 showed significant increases on day 2. Myogenin showed an increase from day 2 to 5. Myostatin on days 5 and 7 were significantly increased. Immunohistochemical analysis showed that myoD-positive/pax7-positive cells increased on day 2, suggesting that activated satellite cells play a role in the destruction and the early recovery phases. Conclusion We, thus, conclude that myogenic events associate with torque recovery after LC-induced injury.

Objective: The 2023 International Federation of Gynecology and Obstetrics classification with molecular classification shows superior discriminatory ability compared to staging systems lacking molecular data. However, the accuracy of endometrial biopsy data in molecular classification remains uncertain. This study aimed to assess the concordance of molecular classifications between preoperative biopsy and hysterectomy to predict prognosis before surgical staging., Methods: Endometrial biopsies and corresponding hysterectomy specimens were collected at the National Cancer Center Hospital between 2012 and 2023. Immunohistochemistry for p53 and mismatch repair (MMR) proteins and next-generation sequencing of all exons of polymerase epsilon (POLE) were performed. Given the limited number of POLE mut cases in prior studies, we prepared a POLE mut-enriched cohort. Cohen's kappa estimates were used to determine concordance for molecular and clinicopathological subgroup assignments., Results: Among 70 patients classified into four molecular subtype groups, 33 exhibited POLE mutations, 15 showed loss of MMR protein expression, 13 had p53-abnormality, and 9 had no specific molecular profile. Concordance between biopsy and hysterectomy specimens was 100% (κ = 1.000). In contrast, histological types and grades between biopsy and surgical specimens showed moderate and substantial agreement (κ = 0.420 and κ = 0.780, respectively)., Conclusions: Molecular subtypes were completely consistent with those derived from surgical specimens, demonstrating high concordance between preoperative and postoperative molecular classifications. This suggests that endometrial biopsies could reliably predict prognosis. Future studies should investigate how biopsy-based molecular profiling influences treatment planning and patient outcomes., Competing Interests: Declaration of competing interest The authors state that there are no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The prognosis of gynecological malignancies has improved with the recent advent of molecularly targeted drugs and immune checkpoint inhibitors. However, these drugs are expensive and contribute to the increasing costs of medical care., Methods: The Japanese Clinical Oncology Group (JCOG) Health Economics Committee conducted a questionnaire survey of JCOG-affiliated facilities from July 2021 to June 2022 to assess the prevalence of high-cost regimens., Results: A total of 57 affiliated facilities were surveyed regarding standard regimens for advanced ovarian and cervical cancers for gynecological malignancies. Responses were obtained from 39 facilities (68.4%) regarding ovarian cancer and 37 (64.9%) concerning cervical cancer, with respective case counts of 854 and 163. For ovarian cancer, 505 of 854 patients (59.1%) were treated with regimens that included PARP inhibitors, costing >500 000 Japanese yen monthly, while 111 patients (13.0%) received treatments that included bevacizumab, with costs exceeding 200 000 Japanese yen monthly. These costs are ~20 and ~10 times higher than those of the conventional regimens, respectively. For cervical cancer, 79 patients (48.4%) were treated with bevacizumab regimens costing >200 000 Japanese yen per month, ~10 times the cost of conventional treatments., Conclusions: In this survey, >70% of patients with ovarian cancer were treated with regimens that included poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors or bevacizumab; ~50% of patients with cervical cancer were treated with regimens containing bevacizumab. These treatments were ~10 and ~20 times more expensive than conventional regimens, respectively. These findings can inform future health economics studies, particularly in assessing cost-effectiveness and related matters., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The clinical features of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese patients with endometrial cancer (EC) were examined by evaluating the prevalence and prognostic factors of LS and sporadic MMRd in patients with EC. Targeted sequencing of five LS susceptibility genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) was carried out in 443 patients with EC who were pathologically diagnosed with EC at the National Cancer Center Hospital between 2011 and 2018. Pathogenic variants in these genes were detected in 16 patients (3.7%). Immunohistochemistry for MMR proteins was undertaken in 337 of the 433 (77.9%) EC patients, and 91 patients (27.0%) showed absent expression of at least one MMR protein. The 13 cases of LS with MMR protein loss (93.8%) showed a favorable prognosis with a 5-year overall survival (OS) rate of 100%, although there was no statistically significant difference between this group and the sporadic MMRd group (p = 0.27). In the MMRd without LS group, the 5-year OS rate was significantly worse in seven patients with an aberrant p53 expression pattern than in those with p53 WT (53.6% vs. 93.9%, log-rank test; p = 0.0016). These results suggest that p53 abnormalities and pathogenic germline variants in MMR genes could be potential biomarkers for the molecular classification of EC with MMRd., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Peutz-Jeghers syndrome (PJS) is associated with female genital lesions, such as cervical gastric-type adenocarcinoma and lobular endocervical glandular hyperplasia (LEGH). However, ovarian mucinous borderline tumors (OMBT) with atypical LEGH-like histology have not been described. The patient was a 60-year-old female with PJS clinically diagnosed at 23 years old with gastrointestinal polyposis. Abdominal distension was noted, and computed tomography scan revealed bilateral breast masses, multiple lung nodules, and a multicystic ovarian tumor. A needle biopsy revealed invasive ductal carcinoma of the breast. For the ovarian tumor, simple hysterectomy and bilateral salpingo-oophorectomy were performed. The left ovarian tumor was 25 × 20 × 12 cm in size and a multicystic tumor containing yellowish mucus without a solid part. Histologically, the cyst wall was covered with mucus cells with focal mild-to-moderate cellular atypia, forming LEGH-like architectures. The glandular cells were immunohistochemically positive for MUC5AC, MUC6 (focal), HIK1083 (focal), and HNF4α. Stromal invasion was not observed. Cervical lesions were not observed. The final pathological diagnosis was OMBT showing atypical LEGH morphology. Targeted sequencing of nontumor tissues revealed the germline STK11 p.F354L variant. Six months later, peritoneal dissemination of adenocarcinoma showing features similar to those of the ovarian tumor was observed, and the patient died of the disease. In summary, we report a case of OMBT with an atypical LEGH-like appearance in a patient with germline STK11 p.F354L variant. This case provides us with unresolved questions regarding the pathogenicity of this STK11 variant and the malignant potential of OMBT with this unusual morphology., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Molecular classification was introduced in endometrial cancer staging following the transition of the International Federation of Gynecology and Obstetrics (FIGO) 2008 to FIGO2023. In the early stages, p53 abnormal endometrial carcinoma with myometrial involvement was upstaged to stage IIC m , in addition to the downstaging of POLE mutation endometrial cancer to stage IA m . This study compared the goodness of fit and discriminatory ability of FIGO2008, FIGO2023 without molecular classification (FIGO2023), and FIGO2023 with molecular classification (FIGO2023 m ); no study has been externally validated to date., Methods: The study included 265 patients who underwent initial surgery at the National Cancer Center Hospital between 1997 and 2019 and were pathologically diagnosed with endometrial cancer. The three classification systems were compared using Harrell's concordance index (C-index), Akaike information criterion (AIC), and time-dependent receiver operating characteristic (ROC) curves. A higher C-index score and a lower AIC value indicated a more accurate model., Results: Among the three classification systems, FIGO2023 m had the lowest AIC value (FIGO2023 m : 455.925; FIGO2023: 459.162; FIGO2008: 457.901), highest C-index (FIGO2023 m : 0.768; FIGO2023: 0.743; FIGO2008: 0.740), and superior time-dependent ROC curves within 1 year after surgical resection. In the stage IIIC, patients with p53 abnormalities had considerably lower 5-year overall survival than those with a p53 wild-type pattern (24.3% vs. 83.7%, p = 0.0005)., Conclusions: FIGO2023 m had the best discriminatory ability compared with FIGO2008 and FIGO2023. Even in advanced stages, p53 status was a poor prognostic factor. When feasible, molecular subtypes can be added to the staging criteria to allow better prognostic prediction in all stages., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although cervical cancer is often characterized as preventable, its incidence continues to increase in low- and middle-income countries, underscoring the need to develop novel therapeutics for this disease.This study assessed the distribution of fusion genes across cancer types and used an RNA-based classification to divide cervical cancer patients with a poor prognosis into subgroups., Material and Methods: RNA sequencing of 116 patients with cervical cancer was conducted. Fusion genes were extracted using StarFusion program. To identify a high-risk group for recurrence, 65 patients who received postoperative adjuvant therapy were subjected to non-negative matrix factorization to identify differentially expressed genes between recurrent and nonrecurrent groups., Results: We identified three cases with FGFR3-TACC3 and one with GOPC-ROS1 fusion genes as potential targets. A search of publicly available data from cBioPortal (21,789 cases) and the Center for Cancer Genomics and Advanced Therapeutics (32,608 cases) showed that the FGFR3 fusion is present in 1.5% and 0.6% of patients with cervical cancer, respectively. The frequency of the FGFR3 fusion gene was higher in cervical cancer than in other cancers, regardless of ethnicity. Non-negative matrix factorization identified that the patients were classified into four Basis groups. Pathway enrichment analysis identified more extracellular matrix kinetics dysregulation in Basis 3 and more immune system dysregulation in Basis 4 than in the good prognosis group. CIBERSORT analysis showed that the fraction of M1 macrophages was lower in the poor prognosis group than in the good prognosis group., Conclusions: The distribution of FGFR fusion genes in patients with cervical cancer was determined by RNA-based analysis and used to classify patients into clinically relevant subgroups., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: We investigated the utility of a molecular classifier tool and genetic alterations for predicting prognosis in Japanese patients with endometrial cancer., Methods: A total of 1029 patients with endometrial cancer from two independent cohorts were classified into four molecular subtype groups. The primary and secondary endpoints were relapse-free survival (RFS) and overall survival (OS), respectively., Results: Among the 265 patients who underwent initial surgery, classified according to immunohistochemistry, patients with DNA polymerase epsilon exonuclease domain mutation had an excellent prognosis (RFS and OS), patients with no specific molecular profile (NSMP) and mismatch repair protein deficiency had an intermediate prognosis, and those with protein 53 abnormal expression (p53abn) had the worst prognosis (P < 0.001). In the NSMP group, mutant KRAS and wild-type ARID1A were associated with significantly poorer 5-year RFS (41.2%) than other genomic characteristics (P < 0.001). The distribution of the subtypes differed significantly between patients with recurrence/progression and classified by sequencing (n = 764) and patients who underwent initial surgery (P < 0.001). Among patients with recurrence/progression, 51.4% had the opportunity to receive molecular targeted therapy., Conclusions: A molecular classifier is a useful tool for determining prognosis and eligibility for molecularly targeted therapy in patients with endometrial cancer., (© 2023. The Author(s).)

Background: Lumbar disk degeneration (LDD) occurs frequently in athletes. Researchers have found that LDD occurs mainly in the lower disks (L4/L5 and L5/S1) in the general and athletic populations. However, a retrospective study showed a high prevalence of LDD in the upper lumbar disks (L1/L2), especially in elite gymnasts., Purpose: To investigate the effect of competition level on the prevalence and incidence of LDD in the upper lumbar disks (L1/L2)., Study Design: Cross-sectional study; Level of evidence, 3; and cohort study; Level of evidence, 2., Methods: We conducted 2 studies to evaluate the effect of competition level on the prevalence and incidence of LDD in Japanese collegiate gymnasts. In study 1, a cross-sectional study of 298 collegiate gymnasts was conducted between 2011 and 2015. Competition levels were categorized as regional, national, and international, and T2-weighted magnetic resonance imaging (MRI) was used to evaluate LDD. Chi-square testing was applied to assess differences in the prevalence of LDD and spinal levels among the 3 competition levels. In study 2--a prospective cohort study--LDD progression and its related risk factors were investigated in 51 collegiate gymnasts. Baseline lumbar MRI scans and measurements of physical function (generalized joint laxity and finger-floor distance test) were performed in March 2014. Follow-up lumbar MRI scans were obtained 2 years later, in February 2016. Logistic regression analyses were performed to investigate the relationship between competition level and LDD progression., Results: In study 1, the prevalence of at least 1 degenerated disk in the regional, national, and international groups was 44.2% (19/43), 44.7% (98/219), and 52.8% (19/36), respectively ( P = .655). The prevalence of LDD at L1/L2 in the international group was significantly higher than that in the other 2 groups ( P = .018). In study 2, the presence of LDD at L1/L2 was associated significantly with international-level competition (adjusted odds ratio, 47.8; 95% CI, 2.75-830.50)., Conclusion: In Japanese collegiate gymnasts, competing at the international level was found to be a risk factor for LDD at L1/L2., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by a Japan Society for the Promotion of Science KAKENHI grant (16K01741). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Lymph node metastasis (LNM) is a well-established prognostic factor in endometrial cancer (EC). We aimed to construct a model that predicts LNM and prognosis using preoperative factors such as myometrial invasion (MI), enlarged lymph nodes (LNs), histological grade determined by endometrial biopsy, and serum cancer antigen 125 (CA125) level using two independent cohorts consisting of 254 EC patients. The area under the receiver operating characteristic curve (AUC) of the constructed model was 0.80 regardless of the machine learning techniques. Enlarged LNs and higher serum CA125 levels were more significant in patients with low-grade EC (LGEC) and LNM than in patients without LNM, whereas deep MI and higher CA125 levels were more significant in patients with high-grade EC (HGEC) and LNM than in patients without LNM. The predictive performance of LNM in the HGEC group was higher than that in the LGEC group (AUC = 0.84 and 0.75, respectively). Patients in the group without postoperative pathological LNM and positive LNM prediction had significantly worse relapse-free and overall survival than patients with negative LNM prediction (log-rank test, P < 0.01). This study showed that preoperative clinicopathological factors can predict LNM with high precision and detect patients with poor prognoses. Furthermore, clinicopathological factors associated with LNM were different between HGEC and LGEC patients., (© 2022. The Author(s).)

Microcystic stromal tumors (MCSTs) of the ovary are rare sex cord-stromal tumors that are considered benign neoplasms because almost all cases display unilateral, localized lesions and have benign outcomes, except for one recurrent case with familial adenomatous polyposis and another initial metastatic case with a CTNNB1 mutation. We report herein a sporadic case that relapsed as intra-abdominal spread 9 years and 1 month after primary left salpingo-oophorectomy for torsion of the ovarian tumor pedicle. The tumor relapsed as multiple disseminations at the subabdominal wall, Douglas pouch, and omentum. Histologically, the tumor cells formed microcysts and infiltrated the surrounding adipose tissue, similar to the invasive implants of ovarian epithelial borderline tumors. Mutation analysis of the recurrent tumor revealed a somatic CTNNB1 p.S33Y activated missense mutation and a germline KDR p.Q472H variant. In conclusion, long-term clinical follow-up may be needed to detect any recurrence of MCST, irrespective of familial adenomatous polyposis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To identify prognostic factors in patients with grade 3 (high-grade) endometrial endometrioid carcinoma, we evaluated the spectrum of genomic alterations and examined whether previously reported molecular subtypes of endometrial carcinoma were adapted to clinical outcome prediction. Seventy-five Japanese patients with grade 3 endometrial endometrioid carcinoma, who underwent a potentially curative resection procedure between 1997 and 2018 at the National Cancer Center Hospital, were included. We classified the patients into four risk groups of the disease based on the Proactive Molecular Risk Classifier for Endometrial Cancer. Genomic alterations in PTEN, ARID1A, TP53, and PIK3CA were detected in more than 30% of the patients. Overall survival and recurrence-free survival of patients with genomic alterations in CTNNB1 were poorer than those of patients with wild-type CTNNB1 (p = 0.006 and p = 0.004, respectively). Compared with that of alterations prevalent in Caucasians, the frequency of genomic alterations in POLE and TP53 was higher in our study than in The Cancer Genome Atlas dataset (p = 0.01 and p = 0.01, respectively). The tendency for recurrence-free survival in the POLE exonuclease domain mutation group was better than that in the TP53 mutation and mismatch repair-deficient groups (p = 0.08 and p = 0.07, respectively), consistent with the Proactive Molecular Risk Classifier for Endometrial Cancer risk classifier definition. The CTNNB1 mutation is a potential novel biomarker for the prognosis of patients with grade 3 endometrial endometrioid carcinoma, and prognosis classification using Proactive Molecular Risk Classifier for Endometrial Cancer may help screen Japanese patients with the disease., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Cervical adenocarcinoma (ADC) is the second most common pathological subtype of cervical cancer after squamous cell carcinoma. It accounts for approximately 20% of cervical cancers, and the incidence has increased in the past few decades, particularly among young patients. The persistent infection of high-risk human papillomavirus (HPV) is responsible for most cervical ADC. However, almost all available in vitro models are designed to study the carcinogenesis of cervical squamous cell carcinoma. To gain better insights into molecular background of ADC, we aimed to establish an in vitro carcinogenesis model of ADC. We previously reported the establishment of an in vitro model for cervical squamous cell carcinoma by introducing defined viral and cellular oncogenes, HPV16 E6 and E7, c-MYC, and activated RAS to human cervical keratinocytes. In this study, the expression of potential lineage-specifying factors and/or SMAD4 reduction was introduced in addition to the defined four oncogenes to direct carcinogenesis toward ADC. The cell properties associated with the cell lineage were analyzed in monolayer and organoid cultures and the tumors in mouse xenografts. In the cells expressing Forkhead box A2 (FOXA2), apparent changes in cell properties were observed, such as elevated expression of columnar cell markers and decreased expression of squamous cell markers. Strikingly, the histopathology of tumors expressing FOXA2 resembled cervical ADC, proposing that FOXA2 plays a vital role in dictating the histopathology of cervical cancers., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aldehyde dehydrogenase 2 (ALDH2) catalyses aldehyde species, including alcohol metabolites, mainly in the liver. We recently observed that ALDH2 is also expressed in skeletal muscle mitochondria; thus, we hypothesize that rs671 polymorphism-promoted functional loss of ALDH2 may induce deleterious effects in human skeletal muscle. We aimed to clarify the association of the ALDH2 rs671 polymorphism with muscle phenotypes and athletic capacity in a large Japanese cohort. A total of 3,055 subjects, comprising 1,714 athletes and 1,341 healthy control subjects (non-athletes), participated in this study. Non-athletes completed a questionnaire regarding their exercise habits, and were subjected to grip strength, 30-s chair stand, and 8-ft walking tests to assess muscle function. The ALDH2 GG, GA, and AA genotypes were detected at a frequency of 56%, 37%, and 7% among athletes, and of 54%, 37%, and 9% among non-athletes, respectively. The minor allele frequency was 25% in athletes and 28% in controls. Notably, ALDH2 genotype frequencies differed significantly between athletes and non-athletes (genotype: p = 0.048, allele: p = 0.021), with the AA genotype occurring at a significantly lower frequency among mixed-event athletes compared to non-athletes (p = 0.010). Furthermore, non-athletes who harboured GG and GA genotypes exhibited better muscle strength than those who carried the AA genotype (after adjustments for age, sex, body mass index, and exercise habits). The AA genotype and A allele of the ALDH2 rs671 polymorphism were associated with a reduced athletic capacity and poorer muscle phenotypes in the analysed Japanese cohort; thus, impaired ALDH2 activity may attenuate muscle function., Competing Interests: The authors have no conflict of interest to declare., (Copyright © Biology of Sport 2021.)

We aimed to clarify the effect of aging on trabecular bone volume and trabecular bone microstructure in a rat model of Duchenne muscular dystrophy (DMD). Six rats each of wild type (WT) and DMD model at 15 weeks of age, and 4 rats each at 30 weeks of age, were analyzed by dual energy X-ray absorptiometry and by micro-CT for analysis of trabecular and cortical bone of the femur. Bone mineral density was significantly lower in the DMD group than in the WT group at both 15 and 30 weeks of age. Micro-CT showed that trabecular bone volume and number were not significantly different between the two groups at 15 weeks, but at 30 weeks both were significantly lower in the DMD group than in the WT group. Connectivity density and structure model index were not significantly different between the two groups at 15 weeks, but at 30 weeks they differed significantly. No significant differences between the WT and DMD groups in cortical thickness and cortical area were evident at both 15 and 30 weeks. In conclusion, trabecular bone volume is significantly reduced, with deteriorated microstructure, with aging in a rat model of DMD.

We aimed to uncover which rectus femoris strain injury types affect regional activation within the rectus femoris. The rectus femoris has a region-specific functional role; the proximal region of the rectus femoris contributes more than the middle and distal regions during hip flexion. Although a history of strain injury modifies the region-specific functional role within the rectus femoris, it was not obvious which rectus femoris strain injury types affect regional activation within it. We studied 12 soccer players with a history of rectus femoris strain injury. Injury data were obtained from a questionnaire survey and magnetic resonance imaging. To confirm the region-specific functional role of the rectus femoris, surface multichannel electromyographic signals were recorded. Accordingly, eight legs had a history of central tendon injury, four had a history of myofascial junction injury, and four had a healed strain injury. When the injury was limited to the central tendon, the region-specific functional role disappeared. The region-specific functional role was confirmed when the injury was outside the central part. The neuromuscular function was also inhibited when the longitudinal range of the injured region was long. Our findings suggest that a central tendon injury with a long injury length impairs regional neuromuscular activation of the rectus femoris muscle.

Acetaldehyde dehydrogenase 2 (ALDH2) is an enzyme involved in redox homeostasis as well as the detoxification process in alcohol metabolism. Nearly 8% of the world's population have an inactivating mutation in the ALDH2 gene. However, the expression patterns and specific functions of ALDH2 in skeletal muscles are still unclear. Herein, we report that ALDH2 is expressed in skeletal muscle and is localized to the mitochondrial fraction. Oxidative muscles had a higher amount of ALDH2 protein than glycolytic muscles. We next comprehensively investigated whether ALDH2 knockout in mice induces mitochondrial adaptations in gastrocnemius muscle (for example, content, enzymatic activity, respiratory function, supercomplex formation, and functional networking). We found that ALDH2 deficiency resulted in partial mitochondrial dysfunction in gastrocnemius muscle because it increased mitochondrial reactive oxygen species (ROS) emission (2',7'-dichlorofluorescein and MitoSOX oxidation rate during respiration) and the frequency of regional mitochondrial depolarization. Moreover, we determined whether ALDH2 deficiency and the related mitochondrial dysfunction trigger mitochondrial stress and quality control responses in gastrocnemius muscle (for example, mitophagy markers, dynamics, and the unfolded protein response). We found that ALDH2 deficiency upregulated the mitochondrial serine protease Omi/HtrA2 (a marker of the activation of a branch of the mitochondrial unfolded protein response). In summary, ALDH2 deficiency leads to greater mitochondrial ROS production, but homeostasis can be maintained via an appropriate stress response.