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Background: The majority of colorectal malignancies are primary tumors. Secondary tumors are rare, and colorectal metastasis from endometrial carcinoma is exceptionally uncommon. We report a case of serous endometrial carcinoma that metastasized to the sigmoid colon, initially presenting as a primary colon carcinoma due to bowel obstruction., Case Presentation: A 79-year-old woman presented with abdominal distention and constipation. Five years earlier, she had undergone an open total hysterectomy with bilateral salpingo-oophorectomy for endometrial serous carcinoma. A colonoscopy revealed stenosis encircling the entire sigmoid colon. Abdominal computed tomography demonstrated irregular wall thickening in the sigmoid colon with enhanced regional lymph node enlargement and upstream bowel dilatation. Peritoneal dissemination in the pelvis was also noted. To relieve the obstruction, two self-expanding metal stents were inserted. Subsequently, due to the presumed diagnosis of sigmoid colon carcinoma with peritoneal dissemination, an open left hemicolectomy with resection of the peritoneal dissemination was performed. Histopathological examination identified the colon tumor and peritoneal dissemination as metastatic serous endometrial carcinoma. Immunohistochemical studies showed the tumor cells were negative for CK7, CK20, and CDX2. No chemotherapy was administered, and 6 months post-operation, no recurrence was observed., Conclusions: Metastasis of endometrial carcinoma to the colon is extremely rare. Diagnosing a colon tumor as a metastasis from endometrial carcinoma is challenging during preoperative examinations. Therefore, in patients with a history of endometrial carcinoma, the possibility that the primary site might be the uterus should be considered., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethics approval and consent to participate: The ethics committee of our institution approved all procedures used in this study. Consent for publication: Written informed consent was obtained from the patient for publication of this case report., (© 2024. The Author(s).)

Background: Primary solitary fibrous tumors (SFTs) of the gallbladder are rare. Here, we report the case of a patient who underwent surgical treatment for a primary SFT originating in the gallbladder., Case Presentation: A 48-mm gallbladder tumor was detected in a 70-year-old man using abdominal ultrasonography at a primary hospital, and he was subsequently referred to our department. A 50-mm enhanced tumor in the gallbladder was identified using computed tomography. Magnetic resonance imaging revealed a smooth-marginated tumor with hyperintensity on T2-weighted imaging. 18F-Fluorodeoxyglucose positron emission tomography confirmed high-level fluorodeoxyglucose uptake in the gallbladder tumor in the early phase without increasing uptake in the later phase. Surgical resection was planned to evaluate the tumor diagnosis. Initially, we performed open cholecystectomy with wedge resection of the gallbladder bed. Intraoperative pathological examination suggested gallbladder cancer; therefore, we performed radical surgery, including resection of the common bile duct, extended radical lymphadenectomy, and choledochojejunostomy. Ultimately, the final pathological examination revealed an SFT originating from the gallbladder with a negative surgical margin. Postoperatively, the patient developed bile leakage that was treated with tube drainage. The patient recovered satisfactorily and was discharged on postoperative day 20. At 24 months postoperatively, the patient was in good general condition without recurrence., Conclusions: We report a rare case of a primary SFT originating in the gallbladder. Clinicians should be aware that SFT can be found in the gallbladder, and when it is difficult to make a preoperative diagnosis, surgical treatment should be considered., Competing Interests: Declarations Ethics approval and consent to participate All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Consent for publication Informed consent was obtained from the patient for being included in the study. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background Recent guidelines recommend dual antiplatelet therapy (DAPT) for six months following percutaneous coronary intervention (PCI) in patients with chronic coronary disease, as unexpected hospitalization can trigger DAPT discontinuation. This study evaluated the predictive factors for unexpected hospitalization within six months after PCI in patients with chronic coronary disease. Methods This prospective multicenter study included 412 patients who underwent PCI for chronic coronary disease. Unexpected hospitalization was defined as a prolonged hospital stay, unscheduled readmission, and all-cause mortality. The predictive factors for unexpected hospitalization within six months post-PCI were evaluated using the Cox regression model. Results The rate of unexpected hospitalization 6 months after PCI was 10.8%±1.5%. Unexpected hospitalizations due to bleeding events accounted for 12.1% (n=5/41), whereas non-bleeding readmissions accounted for 87.9% (n=36/41). A multivariable analysis revealed that the number of Academic Research Consortium for High Bleeding Risk (ARC-HBR) major criteria met [adjusted hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.05-2.29; P=0.026], body weight (adjusted HR, 2.44; 95% CI 1.33-4.49; P=0.004), and presence of diabetes mellitus (adjusted HR, 1.94; 95% CI 1.09-3.47; P=0.025) were independent risk factors for unexpected hospitalization. Among the major ARC-HBR criteria, oral anticoagulant use (adjusted HR, 2.39; 95% CI, 1.14-5.02, P=0.021) and active malignancy (adjusted HR, 3.85; 95% CI, 1.47-10.05; P=0.006) were significantly associated with unexpected hospitalization after adjusting for a low body weight and diabetes mellitus. Conclusions The majority of unexpected hospitalizations after PCI in patients with chronic coronary disease are attributed to non-bleeding causes. The assessment using major ARC-HBR criteria in these patients not only addresses bleeding risks but also underscores its predictive value in conjunction with a low body weight and diabetes mellitus for the prediction of unexpected hospitalization.

Introduction: Moderately differentiated neuroendocrine tumors of the larynx are rare malignant tumors that arise from the submucosa of the larynx, for which surgery is the first-line treatment., Presentation of Case: We report a case of moderately differentiated neuroendocrine tumor of the larynx, in which the patient, a 74-year-old man, experienced long-term palliation but an unfortunate outcome of death owing to metastasis. Laryngeal endoscopic examination revealed an elevated submucosal lesion on the laryngeal surface of the epiglottis. Computed tomography and magnetic resonance imaging showed a tumor-like lesion demonstrating a contrasting effect in the submucosa of the epiglottis. A biopsy revealed a moderately differentiated neuroendocrine tumor (formerly called an atypical carcinoid), and a horizontal partial laryngectomy was performed. The patient had a good postoperative course; however, three years and ten months after surgery, he experienced recurrence in the upper gastrointestinal tract and carcinoid syndrome and died four years and three months after the surgery., Discussion: The prognosis of laryngeal neuroendocrine tumors remains poor. In this case, local control was possible without irradiation because the resection margins were negative on pathological examination. This case report has been reported in line with the SCARE Criteria., Conclusion: Long-term follow-up of this type of tumor is necessary, as distant metastasis is likely to affect prognosis. In addition to surgery, effective adjuvant therapies, including molecular targeted therapies, should be established., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In 2023, the Japan Pancreas Society (JPS) published the new eighth edition of the Japanese classification of pancreatic carcinoma. We present here an excerpted version in English, based on the latest edition. The major changes in this revision are as follows: In the eighth edition of the Union for International Cancer Control (UICC), the T category was changed to be based on tumor size; however, the eighth edition of the Japanese classification retains the previous T category based on local invasion factors. Lymph nodes have been renamed, and regional lymph nodes have been defined by location. Peritoneal cytology, which was not previously included in distant metastasis (M), has now been included in the M category. Moreover, significant additions have been made regarding the pathological diagnosis of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) and criteria for histological assessment of the effects after chemotherapy and radiation therapy. Although this classification is aimed at carcinoma originating in the pancreas, not in the bile duct or duodenum, if the differentiation of the primary organ is difficult, this classification should be applied. It is also desirable to describe tumors other than carcinoma and metastatic tumors to the pancreas in accordance with this classification., (© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

To date, only a few studies have assessed the dietary preferences, lifestyle habits, and risk factors of patients with acute myocardial infarction. This study aimed to investigate the dietary preferences and lifestyle habits of these patients to reflect on the implementation of an effective comprehensive diet therapy in the future.In total, 117 patients who were admitted to Fukuoka University Nishijin Hospital due to acute myocardial infarction from April 2014 to January 2020 were enrolled. Test values, dietary preferences, and lifestyle habits as well as specificity were investigated in patients aged < 70 years (n = 62) and ≥ 70 years (n = 55).Of the patients < 70 years of age, 56.5% preferred high-fat foods and 29.0% preferred high-salt foods, whereas of the patients ≥ 70 years of age, 41.8% preferred high-sugar foods and 32.7% preferred high-salt foods (P < 0.01). The percentages of patients who tended to eat out and drink were 60.7% and 34.2%, respectively. The percentage of patients with a smoking habit was 31.6%.Since improved lipid levels are an important target in nutritional guidance, we should consider adjusting the diet and guiding patients to stop drinking and smoking among young people and reducing sugar and salt intake in the elderly.

Cor triatriatum sinister (CTS) is a relatively rare congenital condition characterized by an abnormal septum dividing the left atrium, morphologically presenting as three atria. Although most individuals with heart failure related to CTS undergo surgical treatment in childhood, those with larger fenestrations may remain asymptomatic until they reach an age where surgery is less viable, presenting treatment challenges. In our case study, we report on an elderly woman who declined all invasive treatments and developed heart failure due to severe functional mitral valve regurgitation triggered by atrial fibrillation. She opted for conservative treatment after a comprehensive evaluation of her condition using transesophageal echocardiography, cardiac magnetic resonance imaging, and right-heart catheterization. This multimodal evaluation highlights the importance of accurate diagnostic approaches and tailored treatments for elderly patients with CTS., Competing Interests: No conflict of interest., (© The Author(s) 2024. Published by Oxford University Press.)

A 50-year-old man was diagnosed with type 1 autoimmune pancreatitis (AIP) following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and a histopathological examination. After six months of untreated follow-up, the serum IgG4 level decreased, and the diffuse pancreatic enlargement improved; however, a pancreatic head mass became apparent. EUS-FNA of this mass revealed pancreatic ductal adenocarcinoma (PDAC) with IgG4-positive plasma cells. In addition, the resected specimen revealed PDAC, without any features of AIP. After pancreatoduodenectomy, AIP did not recur. The development of AIP in this case could be related to paraneoplastic syndrome.

Background: The annual administration of the influenza vaccine is the most effective method for preventing influenza. We have evaluated the effectiveness of the inactivated influenza vaccine in children aged 6 months to 15 years across the seasons from 2013/2014 to 2022/2023. This study aims to investigate the effectiveness of the inactivated influenza vaccine in the 2023/2024 season, the first year following the easing of strict COVID-19 measures, and possibly the last season when only the inactivated vaccine is available on the market., Methods: Adjusted vaccine effectiveness for the 2023/2024 season was assessed using a test-negative case-control design, with results based on polymerase chain reaction and rapid influenza diagnostic tests. Vaccine effectiveness was calculated by influenza type and patient hospitalization/outpatient status., Results: A total of 1832 children were recruited. The inactivated influenza vaccine was effective in preventing both symptomatic influenza A and B in both inpatient and outpatient settings. Overall vaccine effectiveness for influenza A was 51% (95% confidence interval [CI], 23%-69%, n = 930) in inpatient settings and 54% (95%CI, 27%-71%, n = 559) in outpatient settings. For influenza B, effectiveness was 60% (95%CI, 22%-79%, n = 859) in inpatient settings and 56% (95%CI, 26%-74%, n = 558) in outpatient settings. Analysis suggested that administering two doses enhanced effectiveness specifically against influenza B., Conclusions: This is the first study to demonstrate influenza vaccine effectiveness in children after the relaxation of strict COVID-19 measures in Japan (2023/2024). We recommend the current inactivated vaccine for preventing both influenza A and B in children, with consideration for the potential use of two doses to enhance effectiveness against influenza B., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masayoshi Shinjoh (Shinjo) reports a relationship with MSD KK that includes: speaking and lecture fees. Masayoshi Shinjoh (Shinjo) reports a relationship with Meiji Seika Pharma Co Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh (Shinjo) reports a relationship with Mitsubishi Tanabe Pharma Corporation that includes: speaking and lecture fees. Masayoshi Shinjoh (Shinjo) reports a relationship with KM Biologics Co Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh (Shinjo) reports a relationship with Shionogi and Co Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh (Shinjo) reports a relationship with DAIICHI SANKYO COMPANY, LIMITED that includes: speaking and lecture fees. Masayoshi Shinjoh (Shinjo) reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory and speaking and lecture fees. Masayoshi Shinjoh (Shinjo) reports a relationship with Pfizer Japan Inc. that includes: consulting or advisory. Masayoshi Shinjoh (Shinjo) reports a relationship with Janssen Pharmaceutical KK that includes: consulting or advisory. Masayoshi Shinjoh (Shinjo) reports a relationship with Astellas Pharma Inc. that includes: consulting or advisory. This work was supported by JSPS KAKENHI, Japan (Grant Number JP20K10546). Outside this study, the corresponding author received Health Labour Sciences Research Grant, Japan (2024). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Granulomatous mastitis (GM), a benign inflammatory disease of the breast, often mimics breast cancer on presentation. We present a case of GM during pregnancy manifesting as a breast mass, sudden onset of plantar pain, and erythema nodosum (EN). A 31-year-old pregnant Japanese woman, gravida 2, para 1, was referred to our hospital with severe plantar pain on both soles, causing difficulty walking. This pain worsened and EN appeared on both lower legs, followed by a left breast mass. Ultrasound findings suggested malignancy; however, aspiration biopsy confirmed GM. Her arthritis and EN resolved 2 days after commencing oral prednisolone and her walking improved. EN with/without arthritis is commonly associated with GM, especially during pregnancy. The described manifestations with a breast mass are suggestive of this diagnosis., (© 2024 Japan Society of Obstetrics and Gynecology.)

Introduction: Obesity impairs patients' quality of life (QoL). Laparoscopic sleeve gastrectomy (LSG) is a common procedure for patients with severe obesity; however, studies reporting changes in obesity-related QoL are limited. The aim of this study was to assess changes in obesity-related QoL and food tolerance in the early postoperative period., Methods: We included 20 consecutive patients who underwent LSG between May 2021 and July 2023. We evaluated changes in obesity-related QoL 6 months after surgery using an obesity and weight loss QoL questionnaire (OWLQOL) and a weight related symptom measure (WRSM). Additionally, we assessed eating satisfaction and food tolerance after surgery., Results: The percentages of total weight loss and excess weight loss were 28.5% and 79.1%, respectively. OWLQOL scores and WRSM changed from 36.5 to 73.0 points and from 44.0 to 15.0 points (p = .007, .007), respectively. The food tolerance score decreased from 25 to 21.2 points (p < .001), while eating satisfaction showed no significant change (p = .25)., Conclusion: Obesity-related QoL is enhanced even in the early postoperative period, without sacrificing eating satisfaction. The findings of this study may provide valuable insights for patients when considering LSG., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Although bosutinib is generally safe and effective, drug-related toxicities (DRTs) such as diarrhea or increased transaminase levels often lead to treatment discontinuation. To clarify whether a lower initial dose of bosutinib (i.e., starting at 200 mg) would reduce rates of discontinuation due to DRTs, we conducted a phase 2 study of BOsutinib Gradual Increase (BOGI trial, UMIN 000032282) as a second/third-line treatment for chronic myeloid leukemia (CML). Between February 4, 2019 and May 24, 2022, 35 patients were enrolled. The rate of bosutinib discontinuation at 12 months was 25.7% vs. 35.9% in a historical control study (Japanese phase 1/2 study) (p = 0.102). The rate of bosutinib discontinuation due to DRTs was significantly lower, at 11.4% vs. 28.2% (p = 0.015). The incidence of grade 3/4 transaminase elevation was 20% vs. 29% (p = 0.427), while the incidence of diarrhea was 3% vs. 25% (p = 0.009). The median dose intensity of bosutinib was higher (391.7 mg/day vs. 353.9 mg/day). Pharmacokinetic analysis of bosutinib showed that patients who achieved a major molecular response tended to have high trough concentrations. Thus, a low initial dose of bosutinib followed by dose escalation reduced discontinuation due to severe DRTs while maintaining high dose intensity and efficacy., (© 2024. The Author(s).)

Pelizaeus-Merzbacher disease (PMD, currently known as hypomyelinating leukodystrophy type 1 [HLD1]) is a hereditary hypomyelinating and/or demyelinating disease associated with the proteolipid protein 1 (plp1) gene in the central nervous system (CNS). One of the major causes of this condition is incomplete or defective oligodendroglial cell myelin sheath formation triggered by endoplasmic reticulum (ER) stress and subsequent unfolded protein response (UPR). The HLD1-associated Ala-243-to-Val mutation (p.Ala243Val) of PLP1 is widely recognized to trigger defective oligodendroglial cell morphological differentiation, primarily due to ER stress. We have previously reported that knockdown of Rab7B (also known as Rab42), a small GTP/GDP-binding protein involved in intracellular vesicle trafficking around the lysosome, can recover chemical ER stress-induced incomplete cell shapes in the FBD-102b cell line, a model of oligodendroglial cell morphological differentiation. Here, we present findings indicating that incomplete cell shapes induced by PLP1 p.Ala243Val can be restored by knockdown of Rab7B using the clustered regularly interspaced short palindromic repeats (CRISPR) and CasRx (also known as Cas13d) system. Also, the knockdown promoted the trafficking of PLP1 p.Ala243Val to lysosome-associated membrane protein 1 (LAMP1)-positive organelles. These results highlight the unique role of Rab7B knockdown in modulating oligodendroglial cell morphological changes and potentially facilitating the transport of mutated PLP1 to LAMP1-positive organelles, suggesting its potential as a therapeutic target for alleviating HLD1 phenotypes, at least in part, at the molecular and cellular levels., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objectives: The objective of this study was to investigate spontaneous neural regeneration and functional recovery after resection of various lengths of the hypoglossal (XII) nerve in adult rats., Methods: Twelve weeks after XII nerve resection at lengths ranging from 0.0 to 15.8 mm, the tongue deviation angle of rats was measured to evaluate the severity of paralysis; thereafter, the XII neurons in the XII nucleus were labeled with Fluoro-Gold (FG), which was injected into the tongue to visualize regenerated XII neurons re-innervating the tongue muscles., Results: In the XII nerve-resected rats, the regenerative rates, that is, the percentage of the total number of FG-positive neurons on the injured side relative to that on the uninjured side, were divided into two groups; the regenerative rates were more than 77% and less than 6%, respectively. Upon comparing the two groups, the boundary resection length was approximately 10.0 mm. Moreover, the former and latter groups demonstrated tongue deviation angles less than or greater than 15°, respectively., Conclusions: The critical nerve gap length for spontaneous neural regeneration was approximately 10.0 mm in XII nerve-resected adult rats, and nerve regeneration occurred in both morphological and functional aspects after resection at less than the critical length., Competing Interests: Declaration of competing interest All authors are required to disclose any COI within the period of 12 months prior to the submission of any manuscript in the subject matter of which any company, entity, or organization has an interest., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Background: Approximately 10-20 % of individuals develop a recrudescent or persistent fever after intravenous immunoglobulin (IVIG) infusion for the initial treatment of Kawasaki disease. The aim of this study was to evaluate the efficacy and safety of the initial IVIG treatment of Kawasaki disease based on duration of infusion., Methods: This retrospective, single-center study included 53 patients with Kawasaki disease who were initially treated with 2 g/kg of IVIG by means of a single infusion from June 2018 to August 2019. We classified patients into two groups based on the duration of the infusion: the 12-h group and the 24-h group. We compared the treatment response of the primary IVIG and its adverse events using the Mann-Whitney U test and Fisher's exact or Chi-square tests., Results: There were no significant differences in the response to initial IVIG treatment between the two groups. The duration from treatment onset to defervescence was shorter in the 12-h group than the 24-h group (7 h vs. 12 h, respectively, p = 0.07); however, this was not significant. There were no significant between-group differences regarding adverse events., Conclusion: We concluded that the initial 12-h IVIG treatment was comparable to the 24-h treatment in terms of efficacy and safety. This will enable physicians to feel confident about pursuing a shorter course of treatment with similar results as conventional treatment and decide on administering additional therapy to their patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None, (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Extracellular fatty acids (FAs) play an important role in regulating cellular functions such as cell proliferation, survival, and migration. The effects of oleic acid (OA) on cancer cells vary depending on the cell type. Our prior study showed that two distinct ovarian cancer cell lines, RMG-1 and HNOA, proliferate in response to OA, but they differ with respect to glucose utilization. Here, we aimed to elucidate the mechanism(s) by which OA stimulates proliferation of RMG-1 cells. We found that OA stimulates RMG-1 proliferation by activating the FA transporter CD36. OA also increases uptake of glucose and glutamine, which subsequently activate the pentose phosphate pathway (PPP) and glutamine metabolism, respectively. Given that ribose 5-phosphate derived from the PPP is utilized for glutamine metabolism and the subsequent de novo nucleotide synthesis, our findings suggest that OA affects the PPP associated with Gln metabolism, rather than glycolysis associated with glutaminolysis; this leads ultimately to activation of DNA synthesis, which is required for cell proliferation. This selective activation by OA contrasts with the mechanisms observed in HNOA cells, in which OA-induced cell proliferation is driven by transcriptional regulation of the GLUT gene. The diverse responses of cancer cells to OA may be attributed to distinct mechanisms of OA reception and/or different metabolic pathways activated by OA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Small GTP-binding proteins of the Rab family regulate intracellular vesicle trafficking across many aspects of the transport system. Among these, Rab9 is recognized for its role in controlling the transport system not only around the trans-Golgi network but also around the late endosome. However, the specific functions across different cell types and tissues remain unclear. Here, for the first time, we report that Rab9 negatively regulates morphological changes in the FBD-102b cell line, an oligodendroglial precursor cell line undergoing morphological differentiation. The knockdown of Rab9 led to an increase in cell shape alterations characterized by widespread membrane extensions. These changes were accompanied by increased expression levels of oligodendroglial cell differentiation and myelination marker proteins. Notably, the knockdown of Rab9 was capable of recovering defective cell morphological changes induced by tunicamycin, an inducer of endoplasmic reticulum (ER) stress, which is one of the major causes of oligodendroglial cell diseases such as Pelizaeus-Merzbacher disease (PMD, currently known as hypomyelinating leukodystrophy type 1 [HLD1]). In addition, Rab9 knockdown recovered levels of ER stress marker proteins and differentiation markers. Similar results were obtained in the cases of dithiothreitol (DTT), another chemical ER stress inducer, as well as HLD1-associated proteolipid protein 1 (PLP1) mutant protein. These results indicate a unique role for Rab9 in oligodendroglial cell morphological changes, suggesting its potential as a therapeutic target for mitigating diseases such as HLD1 at the molecular and cellular levels.

Well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC) are distinct entities with different biological behavior. However, difficult cases showing equivocal morphology have been reported in some organs. Herein, we report a case of primary hepatic neuroendocrine neoplasm (NEN) with ambiguous histopathological features admixed with conventional hepatocellular carcinoma (HCC). A 70-year-old man with untreated chronic hepatitis B underwent left medial sectionectomy because of two incidental liver masses. On pathological examination, one of the resected tumors had intermingling NEN and HCC components. The NEN component consisted of relatively uniform tumor cells proliferating in trabecular, cord-like, or solid patterns with peripheral nuclear palisading. The tumor cells were immunopositive for synaptophysin, chromogranin A, cluster of differentiation 56 (CD56), and focally hepatocyte paraffin 1. p53 showed wild-type expression. The Ki-67 labeling index was 27% at the hot spot. Eleven months after the surgery, he died of a cerebral hemorrhage without evidence of recurrent liver cancer. The intermediate degree of differentiation and the modest proliferative activity can challenge the distinction between NEC and NET G3. While the coexisting HCC indicates NEC rather than NET in a pathogenetic viewpoint, such ambiguous tumor may not be as aggressive as typical NECs., (© 2024. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Purpose: Laparoscopic sleeve gastrectomy (LSG) drastically affects body composition. However, studies focusing on the association between the changes in the pre-and postoperative muscle mass and postoperative results are limited. We evaluated the association between changes in the muscle mass and weight loss and fat reduction., Methods: This retrospective study included 29 consecutive patients who underwent both LSG and a bioelectrical impedance analysis (BIA) consecutively. We investigated changes in the body composition on the BIA and visceral fat area (VFA) on computed tomography and correlational changes in muscle mass with weight loss and fat reduction., Results: The total weight loss (%TWL) 12 months after surgery was 30.9%. The VFAs pre- and postoperatively were 224 and 71.0 cm 2 , respectively. The fat mass (FM), percentage of FM, appendicular skeletal muscle mass (ASM), and skeletal muscle mass index (SMI) decreased from pre- to postoperatively (54.8 vs. 32.2 kg; 49.0 vs. 41.2%, 26.7 vs. 23.9 kg, 9.24 vs. 8.27, respectively), whereas the percentage of ASM (%ASM) increased (22.1 vs. 28.0%). The rate of change in %ASM positively correlated with weight loss and fat reduction (%TWL, rs = 0.65; %VFA loss, rs = 0.62)., Conclusion: The rate of change in %ASM was positively correlated with weight loss and fat reduction., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

To investigate the relationship between quantitative tracheal geometry and clinical course among various types of vascular ring and to identify factors correlating with symptom presentation. Patients with vascular ring diagnosed between April 2010 and December 2022 were included. All the patients were classified as type 1 (complete double aortic arch); type 2 (incomplete double aortic arch); type 3 (circumflex aorta); type 4 (right aortic arch and aberrant left subclavian artery with a left retroesophageal diverticulum of Kommerell); or type 5 (mirror-imaged right aortic arch with retroesophageal aortic diverticulum). Their clinical characteristics and quantitative variables on computed tomography (CT) were compared. Of the 50 patients enrolled, those with type 1 tended to have a smaller luminal tracheal diameter at the level of the ring. The median symptom-free survival time was shortest in this group (16.0 days [95% confidence interval (CI): 9.4-51.0]), followed by type 3 (138.0 days [95% CI: 0.0-851.4]). Type 1 (hazard ratio [HR]: 9.0; 95% CI: 2.3-35.0; P = 0.001), type 3 (HR: 4.2; 95% CI: 1.4-13.2; P = 0.013), and the percentage of tracheal narrowing in the anteroposterior projection (HR: 0.87; 95% CI: 0.78-0.96; P = 0.008) were significantly associated with symptom presentation in the time-dependent course. The aortic arch encircling the entire circumference in type 1 and high-pressure vasculature in front of the vertebral body in types 1 and 3 may contribute to raising the risk of symptom presentation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Sarcopenia is a prognostic predictor in emergency surgery. However, there are no reports on the relationship between osteopenia and in-hospital mortality. This study clarified the effect of preoperative osteosarcopenia on patients with gastrointestinal perforation after emergency surgery., Methods: We included 216 patients with gastrointestinal perforations who underwent emergency surgery between January 2013 and December 2022. Osteopenia was evaluated by measuring the pixel density in the mid-vertebral core of the 11th thoracic vertebra. Sarcopenia was evaluated by measuring the area of the psoas muscle at the level of the third lumbar vertebra. Osteosarcopenia is defined as the combination of osteopenia and sarcopenia., Results: Osteosarcomas were identified in 42 patients. Among patients with osteosarcopenia, older and female patients and those with an American Society of Anesthesiologists Physical Status of ≥ 3 were significantly more common, and the body mass index, hemoglobin value, and albumin level were significantly lower in these patients than in patients without osteosarcopenia. Furthermore, the osteosarcopenia group presented with more postoperative complications than patients without osteosarcopenia (P < 0.01). In the multivariate analysis, age ≥ 74 years old (P = 0.04) and osteosarcopenia (P = 0.04) were independent and significant predictors of in-hospital mortality., Conclusion: Preoperative osteosarcopenia is a risk factor of in-hospital mortality in patients with gastrointestinal perforation after emergency surgery., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Systemic inflammatory response markers are reported to be prognostic for patients with cancer. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index has been established as an immuno-nutritional scoring system. The aim of this study was to clarify the impact of the preoperative CALLY index on the outcome of patients undergoing gastrectomy for gastric cancer., Methods: We analyzed the data of 826 patients who underwent gastrectomy for stage I, II, or III gastric cancer between 2010 and 2017. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 10 4 )., Results: The cut-off of the CALLY index was 2. The 147 patients with a preoperative CALLY index < 2 had significantly worse overall survival (OS) and relapse-free survival (RFS) than those with a CALLY index ≥ 2 (P < 0.01, P < 0.01, respectively). Multivariate analysis identified that a CALLY index < 2 (P = 0.02), intraoperative blood loss (P < 0.01), and stage II or III disease (P < 0.01) were independent and significant predictors of worse RFS. A CALLY index < 2 (P = 0.01), intraoperative blood loss (P < 0.01), postoperative complications (P = 0.02), and stage II or III disease (P < 0.01) were independent and significant predictors of worse OS., Conclusion: The preoperative CALLY index was independently associated with a poor prognosis for patients after gastrectomy for gastric cancer., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Methotrexate (MTX) may induce immunosuppression and facilitate the onset of lymphoproliferative disorders (LPD). Most cases of MTX-LPD occur in patients with rheumatoid arthritis; the incidence is high in Japan. Vitreoretinal lymphoma (VRL) is a rare non-Hodgkin's lymphoma that can masquerade as steroid-resistant chronic uveitis, leading to fatal diagnostic delay. A 68-year-old woman exhibited optic disc swelling and retinal vasculitis causing floaters in the right eye. She was undergoing long-term MTX treatment for rheumatoid arthritis; she previously had been diagnosed with MTX-LPD, which regressed upon discontinuation of MTX. Steroid therapy was ineffective for optic disc swelling and retinal vasculitis; her best-corrected visual acuity decreased to 20/400. Vitreous biopsy revealed VRL, which was successfully treated with high-dose MTX-based systemic chemotherapy and intravitreal injections of MTX. To our knowledge, this is the first case report of VRL in a patient with an autoimmune disease who have a history of MTX-LPD.

Background: In Asia, adjuvant chemotherapy after gastrectomy with D2 or more extensive lymph-node dissection is standard treatment for people with pathological stage III gastric or gastro-oesophageal junction (GEJ) cancer. We aimed to assess the efficacy and safety of adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy administered in this setting., Methods: ATTRACTION-5 was a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial conducted at 96 hospitals in Japan, South Korea, Taiwan, and China. Eligible patients were aged between 20 years and 80 years with histologically confirmed pathological stage IIIA-C gastric or GEJ adenocarcinoma after gastrectomy with D2 or more extensive lymph-node dissection, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and available tumour tissue for PD-L1 expression analysis. Patients were randomly assigned (1:1) to receive either nivolumab plus chemotherapy or placebo plus chemotherapy via an interactive web-response system with block sizes of four. Investigational treatment, either nivolumab 360 mg or placebo, was administered intravenously for 30 min once every 3 weeks. Adjuvant chemotherapy was administered as either tegafur-gimeracil-oteracil (S-1) at an initial dose of 40 mg/m 2 per dose orally twice per day for 28 consecutive days, followed by 14 days off per cycle, or capecitabine plus oxaliplatin consisting of an initial dose of intravenous oxaliplatin 130 mg/m 2 for 2 h every 21 days and capecitabine 1000 mg/m 2 per dose orally twice per day for 14 consecutive days, followed by 7 days off treatment. The primary endpoint was relapse-free survival by central assessment. The intention-to-treat population, consisting of all randomly assigned patients, was used for analysis of efficacy endpoints. The safety population, defined as patients who received at least one dose of trial drug, was used for analysis of safety endpoints. This trial is registered with ClinicalTrials.gov (NCT03006705) and is closed., Findings: Between Feb 1, 2017, and Aug 15, 2019, 755 patients were randomly assigned to receive either adjuvant nivolumab plus chemotherapy (n=377) or adjuvant placebo plus chemotherapy (n=378). 267 (71%) of 377 patients in the nivolumab group and 263 (70%) of 378 patients in the placebo group were male; 110 (29%) of 377 patients in the nivolumab group and 115 (31%) of 378 patients in the placebo group were female. 745 patients received assigned treatment (371 in the nivolumab plus chemotherapy group; 374 in the placebo plus chemotherapy group), which was the safety population. Median time from first dose to data cutoff was 49·1 months (IQR 43·1-56·7). 3-year relapse-free survival was 68·4% (95% CI 63·0-73·2) in the nivolumab plus chemotherapy group and 65·3% (59·9-70·2) in the placebo plus chemotherapy group; the hazard ratio for relapse-free survival was 0·90 (95·72% CI 0·69-1·18; p=0·44). Treatment-related adverse events occurred in 366 (99%) of 371 patients in the nivolumab plus chemotherapy group and 364 (98%) of 374 patients in the placebo plus chemotherapy group. Discontinuation due to adverse events was more frequent in the nivolumab plus chemotherapy group (34 [9%] of 371 patients) than the placebo plus chemotherapy group (13 [4%] of 374 patients). The most common treatment-related adverse events were decreased appetite, nausea, diarrhoea, neutrophil count decreased, and peripheral sensory neuropathy., Interpretation: The results of this trial do not support the addition of nivolumab to postoperative adjuvant therapy for patients with untreated, locally advanced, resectable gastric or GEJ cancer., Funding: Ono Pharmaceutical and Bristol Myers Squibb., Competing Interests: Declaration of interests Y-KK is a consultant for ALX Oncology, Amgen, Blueprint Medicines, Bristol Myers Squibb, DAE HWA Pharmaceutical, Macrogenics, Novartis, Surface Oncology, and Zymeworks. MT receives honoraria from Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Intuitive Surgical, Johnson & Johnson, Eli Lilly, Medtronic, Olympus, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceuticals, and Yakult Honsha and receives institutional research funding from Ono Pharmaceutical. NB receives honoraria from Bristol Myers Squibb Japan, Daiichi Sankyo, Ono Pharmaceutical, and Taiho Pharmaceutical and receives institutional research funding from Ono Pharmaceutical and Takeda Pharmaceuticals. HCC is an employee of MDBiolab; is a consultant for Amgen, BeiGene, Bristol Myers Squibb, Celltrion, Gloria Biosciences, Eli Lilly, Merck Serono Pharmaceutical, MSD, Quintiles, Taiho Pharmaceutical, and Zymeworks; receives speakers fees from Foundation Medicine, Eli Lilly, and Merck Serono; and receives institutional research funding from Amgen, BeiGene, Bristol Myers Squibb, GlaxoSmithKline, Incyte, Eli Lilly, Merck Serono, MSD, Taiho Pharmaceutical, and Zymeworks. J-SC receives research funding from Amgen, Astellas Pharma, AstraZeneca, Janssen, Merck, MSD Oncology, Ono Pharmaceutical, Roche, Senhwa Biosciences, and TTY Biopharm. L-TC is independent director of ScinoPharm; receives honoraria from ACT Genomics, AstraZeneca, Bristol Myers Squibb, Eli Lilly, MSD, Novartis, Ono Pharmaceutical, PharmaEngine, SynCoreBio, and TTY Biopharm; is a consultant for AstraZeneca, Bristol Myers Squibb, CStone Pharmaceuticals, Ipsen Pharma, Eli Lilly, MSD, Ono Pharmaceutical, Onward Therapeutics, Taivex Therapeutics, and TTY Biopharm; receives institutional research funding from ACT Genomics, Celgene, Novartis, OBI Pharma, Pfizer, Polaris Pharmaceuticals, SynCoreBio, and TTY Biopharm; and holds patents, royalties, and other intellectual property related to anti-α-enolase monoclonal antibody from HuniLife Biotechnology. M-HR receives honoraria from AstraZeneca, Bristol Myers Squibb, DAE HWA Pharmaceutical, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Ono Pharmaceutical, and Taiho Pharmaceutical; is a consultant for AstraZeneca, Bristol Myers Squibb, DAE HWA Pharmaceutical, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Ono Pharmaceutical, and Taiho Pharmaceutical. TO receives honoraria and institutional research funding from Daiichi Sankyo. SYR is a consultant for Amgen, Astellas Pharma, AstraZeneca, Daiichi Sankyo, Eisai, Eutilex, Indivumed, LG Chem, MSD Oncology, and Ono Pharmaceutical; receives speakers fees from Amgen, AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Union Chimique Belge Japan, Eisai, Eli Lilly, and MSD Oncology; and receives research funding from Amgen (paid to their institution), ASLAN Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daichii Sankyo, Eisai, Indivumed, Eli Lilly, MSD Oncology, Roche–Genentech, Sillajen, and Zymeworks. TY receives honoraria from Bristol Myers Squibb, Johnson & Johnson, Janssen, Ono Pharmaceutical, and Taiho Pharmaceutical. MS receives honoraria from Chugai Pharmaceutical, Daiichi Sankyo, Ono Pharmaceutical, and Taiho Pharmaceutical. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The pocket-creation method (PCM) was developed to overcome the technical difficulties of endoscopic submucosal dissection (ESD), although opening the pocket remains challenging. We developed a novel technique of PCM with single-clip traction (PCM-CT), which uses a reopenable clip as a traction device to maintain stability during the procedure. No prospective study has compared the efficacy of PCM-CT and PCM. This study aimed to investigate the effectiveness of PCM-CT vs. PCM in a randomized controlled trial., Methods: This randomized controlled clinical trial was conducted at four Japanese institutions. Patients with superficial colorectal neoplastic lesions were included following Japanese guidelines for colorectal cancer. Seven moderately experienced endoscopists performed the ESD procedures using either PCM-CT or PCM., Results: 100 patients were enrolled in the study. Compared with PCM, PCM-CT achieved significantly faster mean (SD) dissection speed (21.4 [10.8] vs. 27.0 [14.5] mm2/min [95%CI 0.5 to 10.7], P = 0.03), and reduced the mean procedure time (81.8 [57.9] vs. 64.8 [47.6] minutes [95%CI -38.2 to 4.3], P = 0.12) and pocket-opening time (37.8 [33.0] vs. 30.0 [28.9] minutes [95%CI -20.2 to 4.6], P = 0.22). En bloc and R0 resection rates were not significantly different between the two groups (100% vs. 100%, P >0.99; 100% vs. 96%, P = 0.50, respectively). No significant differences were observed in adverse events between the two groups., Conclusion: ESD facilitated by the novel PCM-CT method appeared to be significantly faster than PCM. Both methods achieved high R0 resection rates., Competing Interests: H. Yamamoto: patent holder for a double-balloon endoscope and small caliber tip transparent hood produced by Fujifilm; consultant for Fujifilm; honoraria, grants, and royalties from Fujifilm. T. Morikawa, D. Nemoto, T. Kurokawa, T. Yamashina, Y. Hayashi, M. Kitamura, M. Okada, T. Takezawa, Y. Nakajima, Y. Kowazaki, H. Fukuda, T. Nomura, N. Lazaridis, N. Fukushima, and K. Sunada declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Managing heart rate (HR) is crucial for enhancing clinical prognosis in patients with heart failure (HF) and atrial fibrillation (AF). Nevertheless, the prognostic impact of HR at discharge in hospitalized HF patients remains unclear., Objectives: This study aimed to determine the HR associated with the lowest risk of death and HF in patients hospitalized with HF and AF., Methods: In this observational study, 334 persistent AF patients were analyzed from a database of 1,930 consecutive HF hospitalizations. Exclusion criteria included sinus rhythm or paroxysmal AF, cardiac pacemakers, or unrecorded HR at discharge. Participants were divided into four groups based on HR at discharge in 10 beats/min increments. The primary endpoint was a composite of death from any cause and rehospitalization due to HF. The association between resting HR and the primary endpoint was determined using Kaplan-Meier analysis and Cox proportional hazards models., Results: The median follow-up period was 389 days, with 133 patients (39.8%) reaching the primary endpoint. Kaplan-Meier analysis revealed a significantly higher primary endpoint incidence in patients with HR >81 beats/min at discharge compared to those with HR <60 beats/min (log-rank test for trend: P  = 0.039). Multivariable Cox regression analysis showed that HR >81 beats/min at discharge was associated with the primary endpoint, with a hazard ratio of 1.79 (95% CI: 1.04-3.07), compared to HR <60 beats/min., Conclusions: The findings suggest that controlling HR to less than 80 beats/min at discharge may lead to better clinical outcomes in patients with HF and persistent AF., Competing Interests: The research presented in this manuscript was conducted at Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

We present a case of BK polyomavirus (BKV) nephropathy (BKVN) after heart transplantation (HTx). The patient was a male with non-ischemic cardiomyopathy who received HTx at the age of 56 years [serum creatinine (sCre) at the time of HTx: 0.89 mg/dl]. Following 3 months of standard triple immunosuppression using tacrolimus, mycophenolate, and corticosteroid, everolimus with reduced tacrolimus therapy was introduced because of cardiac allograft vasculopathy. However, renal function gradually deteriorated. BKVN was diagnosed via positive simian virus 40 antigen staining of renal biopsy specimens 46 months after HTx (sCre: 2.48 mg/dl). Decoy cells and elevated serum BKV load were also observed. After reduction of immunosuppression and monthly low-dose intravenous immunoglobulin administration, the serum BKV load decreased and sCre plateaued while on uneventful clinical course. Since renal function is an important prognostic factor after HTx, early diagnosis and intervention are crucial for successful BKVN treatment. Urine cytology should be performed during post-transplant screening for renal dysfunction., Learning Objective: BK polyomavirus nephropathy (BKVN) is a critical issue following solid organ transplantation. However, reports regarding BKVN after heart transplantation (HTx) are sparse, possibly underestimating the significance of BKVN in HTx recipients, therefore case studies are crucial for the understanding of BKVN in HTx recipients. This case clearly demonstrated the clinical course of BKVN and highlights the important clinical implications for the diagnosis and management of BKVN in HTx recipients., Competing Interests: None., (© 2024 Japanese College of Cardiology. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Maxillary angiosarcoma, an aggressive tumor derived from vascular endothelial cells, is very rare. Recently, antivascular endothelial growth factor (VEGF) therapies have attracted considerable attention. We describe the clinical course of a patient with maxillary angiosarcoma and discuss the expression of VEGF signaling molecules assessed via immunohistological analysis. An 81-year-old man presented with an aggressive tumor in the left maxillary sinus. Biopsy revealed atypical nuclear cell proliferation, and the tumor was suspected to be a sarcoma. The maxillary malignancy was treated using a multidisciplinary approach with a combination of surgery, radiotherapy, and regional chemotherapy. Examination of the specimen obtained in the first surgery revealed maxillary angiosarcoma, found to be positive for CD31, while negative for CD34, D2-40, and factor Ⅷ. Although no pathological residual tumor was observed after the planned wide surgery, cervical lymph node and distant metastases occurred. The patient died 24 months after the first surgery. Staining revealed VEGF receptor (VEGFR) 1, VEGFR2, phosphorylated Ak strain transforming, mitogen-activated protein kinase, and signal transducer and activator of transcription 3 positivity. Although our findings do not indicate that anti-VEGF therapy is beneficial for treating maxillary angiosarcomas, we found that VEGFR signaling pathways were activated in maxillary angiosarcomas similar to angiosarcomas originating at other sites. Herein, we report a case of maxillary angiosarcoma, focused on VEGFR and signaling pathway activation. To our knowledge, this is the first report to describe VEGFR system immunostaining findings in maxillary angiosarcoma., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Systemic inflammatory response is significant prognostic indicator in patients with various diseases. The relationship between prognostic scoring systems based on the modified Glasgow Prognostic Score (mGPS) and achalasia in patients treated with laparoscopic Heller‑myotomy with Dor‑fundoplication (LHD) remains uninvestigated. This study aimed to examine the role of mGPS in patients with achalasia., Methods: 457 patients with achalasia who underwent LHD as the primary surgery between September 2005 and December 2020 were included. We divided patients into the mGPS 0 and mGPS 1 or 2 groups and compared the patients' background, pathophysiology, symptoms, surgical outcomes, and postoperative course., Results: mGPS was 0 in 379 patients and 1 or 2 in 78 patients. Preoperative vomiting and pneumonia were more common in patients with mGPS of 1 or 2. There were no differences in surgical outcomes. Postoperative upper gastrointestinal endoscopy revealed that severe esophagitis was more frequently observed in patients with mGPS of 1 or 2 (P < 0.01). The clinical success was 91% and 99% in the mGPS 0 and mGPS 1 or 2 groups, respectively (P < 0.01)., Conclusions: Although severe reflux esophagitis was more common in patients with achalasia with a high mGPS, good clinical success was obtained regardless of the preoperative mGPS., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Purpose: To clarify the diagnostic utility and formation of the Mille-feuille sign for ovarian carcinosarcoma (OCS) on MRI, and to evaluate the other MRI findings and serum markers compared to ovarian metastases from colorectal carcinoma (OMCRC)., Method: Three blinded radiologists retrospectively reviewed MR images of 12 patients with OCS, 18 with OMCRC, and 40 with primary ovarian carcinoma (POC) identified by the electronic database of radiology reports. The interobserver agreement was analyzed using Fleiss' kappa test. Their MRI characteristics and tumor markers were compared using Fisher's exact test and Mann-Whitney's U test. Receiver operating characteristic curve analyses were used to determine the cutoff points for the ADC value. This study was approved by the institutional ethics committee., Results: Interobserver agreement analysis was moderate or higher for all MRI characteristics. The frequency of Mille-feuille sign was comparable for both OCS and OMCRC groups, and predominantly higher than that of the POC group (p < 0.001, p < 0.001), respectively. Pathologically, the Mille-feuille sign in OCS reflected alternating layers of tumor cells with stroma and necrosis or intraluminal necrotic debris. Compared to OMCRC, intratumoral hemorrhage (p = 0.02), margin irregularity (p = 0.048), unilateral adnexal mass (p = 0.02), and low ADC values (p < 0.01) were more frequently observed and serum CEA levels was significantly lower (p = 0.007) in the OCS group. Under setting of the cutoff value of ADC at 0.871 × 10 -3 mm 2 /s, the discriminative ability for OCS showed 66.7% sensitivity, 94.4% specificity, and 81.0% accuracy, respectively., Conclusions: The Mille-feuille sign was seen in both OCS and OMCRC. MR findings of intratumoral hemorrhage, margin irregularity, unilateral adnexal mass, low ADC values, and low serum CEA levels can be useful in differentiating OCS from OMCRC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cancer utilizes immunosuppressive mechanisms to create a tumor microenvironment favorable for its progression. The purpose of this study is to histologically characterize the immunological properties of the tumor microenvironment of oral squamous cell carcinoma (OSCC) and identify key molecules involved in the immunological microenvironment and patient prognosis., Methods: First, overlapping differentially expressed genes (DEGs) were screened from OSCC transcriptome data in public databases. Correlation analysis of DEGs with known immune-related genes identified genes involved in the immune microenvironment of OSCC. Next, stromal patterns of tumor were classified and immunohistochemical staining was performed for immune cell markers (CD3, CD4, Foxp3, CD8, CD20, CD68, and CD163), programmed death-ligand 1 (PD-L1), and guanylate binding protein 5 (GBP5) in resected specimens obtained from 110 patients with OSCC who underwent resection. Correlations between each factor and their prognostic impact were analyzed., Results: Among the novel OSCC-specific immune-related genes screened (including ADAMDEC1, CXCL9, CXCL13, DPT, GBP5, IDO1, and PLA2G7), GBP5 was selected as the target gene. Histopathologic analysis showed that multiple T-cell subsets and CD20-positive cells were less common in the advanced stages, whereas CD163-positive cells were more common in advanced stages. The immature type in the stromal pattern category was associated with less immune cell infiltration, lower expression of PD-L1 in immune cells, lower expression of GBP5 in the stroma, and shorter overall survival and recurrence-free survival. Expression of GBP5 in the tumor and stroma correlated with immune cell infiltration of tumors and PD-L1 expression in tumor and immune cells. Patients with low tumor GBP5 expression and high stromal expression had significantly longer overall survival and recurrence-free survival., Conclusions: The stromal pattern category may reflect both invasive and immunomodulatory potentials of cancer-associated fibroblasts in OSCC. GBP5 has been suggested as a potential biomarker to predict the prognosis and therapeutic efficacy of immune checkpoint inhibitors., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The recently published WHO Reporting System for Pancreaticobiliary Cytopathology (World Health Organization [WHO] System) is an international approach to the standardized reporting of pancreaticobiliary cytopathology, updating the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System). Significant changes were made to the categorization of benign neoplasms, intraductal neoplasms, mucinous cystic neoplasms, and malignant neoplasms considered low grade. Benign neoplasms, such as serous cystadenoma, categorized as Neoplastic: benign in the PSC system, are categorized as Benign/negative for malignancy in the WHO system. Pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and gastrointestinal stromal tumor, categorized as Neoplastic: other in the PSC system, are categorized as Malignant in the WHO System in accord with their classification in the 5th edition WHO Classification of Digestive System Tumours (2019). The two new categories of Pancreaticobiliary Neoplasm Low-risk/grade and Pancreaticobiliary Neoplasm High-risk/grade are mostly limited to intraductal neoplasms and mucinous cystic neoplasms. Low-risk/grade lesions are mucinous cysts, with or without low-grade epithelial atypia. High-risk/grade lesions contain neoplastic epithelium with high-grade epithelial atypia. Correlation with clinical, imaging, and ancillary studies remains a key tenet. The sections for each entity are written to highlight key cytopathological features and cytopathological differential diagnoses with the pathologist working in low resource setting in mind. Each section also includes the most pertinent ancillary studies useful for the differential diagnosis. Sample reports are provided for each category. Finally, the book provides a separate section with risk of malignancy and management recommendations for each category to facilitate decision-making for clinicians., (© 2024 American Cancer Society.)

Objective This longitudinal study aimed to clarify the changes in the medical treatment behavior of Japanese patients with chronic diseases during the early phase of the coronavirus disease 2019 (COVID-19) pandemic and examine the factors associated with disease worsening. Methods Subjects with chronic diseases were selected from a panel survey that started at the beginning of the COVID-19 pandemic consists of 2,400 participants recruited via the Internet. Medical treatment behaviors (decrease in medical visit frequency, inability to take regular medications, and utilization of telephone/online medical care), psychological distress, and sociodemographic factors were evaluated at baseline (May 2020) and at the follow-up survey (February 2021). A worsening of chronic diseases was defined as those who answered "yes" to the question, "Has-the-condition-of-the-chronic-disease-worsened?". The factors related to the worsening of chronic diseases at follow-up were examined. Results A total of 514 participants (mean age 61.6±12.9 years) were analyzed. The percentage of participants who reported decreasing medical visit frequency was 34% at the baseline and 16.5% at follow-up, and those who reported a worsening of chronic diseases was 5.1% and 5.1%, respectively. A worsening of chronic diseases at follow-up was significantly associated with a younger age, a decreased frequency of medical visits, unemployment, a history of smoking, and psychological distress. Conclusions A decreased frequency of medical visits was observed among one-third of the participants with chronic disease in the early stage of the pandemic, and it reduced by half at follow-up. In the early stages of an emerging infectious disease pandemic, decreased regular hospital/clinic visits can lead to a worsening of chronic diseases. Those who had psychological distress, unemployment, and a history of smoking were vulnerable to a worsening chronic disease.

Background: The 2018 Osaka earthquake caused severe damage to the National Cerebral and Cardiovascular Center, and the interruption to the delivery of hospital food in particular had a significant effect on patients with left ventricular assist devices (LVAD). Methods and Results: We retrospectively assessed 10 patients who had been provided with emergency rations on the day of earthquake and the next day for breakfast. Catered foods were provided thereafter. Vitamin K content was largely reduced due to emergency rations; the prothrombin time-international normalized ratio (PT-INR) on day 2 was significantly higher than on day 1. Conclusions: Close monitoring of PT-INR and assessing vitamin K content may be important for preventing complications in patients with a LVAD during a disaster., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Purpose: Calcaneofibular ligament (CFL) injuries are harder to diagnose than anterior talofibular ligament (ATFL) ones. This study aimed to clarify the fibular attachment of the CFL and verify the bony landmark for evaluating the CFL on ultrasonography., Methods: Fifty-nine ankles were used in this anatomical study. To confirm the control function of the CFL, we performed passive movement manually using cadaveric ankles and observed the ankle positions where the CFLs were tense. Histological observation of CFL attachment of the fibula was performed using Masson's trichrome stain. The ATFL and CFL were removed, and the bone morphology of the CFL attachment and inferior fibular end was imaged using a stereomicroscope and a 3D scanner. Using ultrasonography, we evaluated the bone morphology of the fibular attachment of the CFL in short-axis images of 27 healthy adult ankles., Results: The CFL was tensed according to ankle motions: supination, maximum dorsi flexion, maximum plantar flexion, and mild plantar flexion-external rotation. Below the CFL attachment of the fibula was a slight groove between the inferior tip and the obscure tubercle of the fibula. This groove was observed in 81.5% of cases using short-axis ultrasonography., Conclusion: The CFL was tensed in various ankle positions to control the movements of the talocrural and subtalar joints. There was a slight groove at the inferior end of the fibula where the CFL coursed downward. We called it the CFL groove and proposed that it could serve as a landmark for the short-axis image of ultrasonography., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Medical care and long-term care utilization in the last year of life of frail older adults could be a key indicator of their quality of life. This study aimed to identify the medical care expenditure (MCE) trajectories in the last year of life of frail older adults by investigating the association between MCE and long-term care utilization in each trajectory., Methods: The retrospective cohort study of three municipalities in Japan included 405 decedents (median age at death, 85 years; 189 women [46.7%]) from a cohort of 1,658 frail older adults aged ≥65 years who were newly certified as support level in the long-term care insurance program from April 2012 to March 2013. This study used long-term care and medical insurance claim data from April 2012 to March 2017. The primary outcome was MCE over the 12 months preceding death. Group-based trajectory modeling was conducted to identify the MCE trajectories. A mixed-effect model was employed to examine the association between long-term care utilization and MCE in each trajectory., Results: Participants were stratified into four groups based on MCE trajectories over the 12 months preceding death as follows: rising (n = 159, 39.3%), persistently high (n = 143, 35.3%), minimal (n = 56, 13.8%), and descending (n = 47, 11.6%) groups. Home-based long-term care utilization was associated with increased MCE in the descending trajectory (coefficient, 1.48; 95% confidence interval [CI], 1.35-1.62). Facility-based long-term care utilization was associated with reduced MCE in the rising trajectory (coefficient, 0.59; 95% CI, 0.50-0.69). Both home-based (coefficient, 0.92; 95% CI, 0.85-0.99) and facility-based (coefficient; 0.53; 95% CI, 0.41-0.63) long-term care utilization were associated with reduced MCE in the persistently high trajectory., Conclusions: These findings may facilitate the integration of medical and long-term care models at the end of life in frail older adults., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Yoshiyuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A 34-year-old woman received umbilical cord blood transplantation for refractory T-cell prolymphocytic leukemia after salvage therapy with alemtuzumab. She developed right angular cheilitis on the 46th day after transplantation, which worsened after receiving systemic steroid therapy for extensive chronic graft versus host disease. The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV-resistant mutations of the herpes simplex virus type 1 (HSV-1) in the thymidine kinase domain. Foscarnet is expected to be effective against ACV-resistant HSV-1 infection. However, it could not be used because the patient developed renal dysfunction. Several viral thymidine kinase mutations related to ACV resistance were found in the patient's sample. Nevertheless, amenamevir, a helicase-primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ACV-resistant HSV infection after allo-HSCT is an rare but important complication in the era of low-dose long-term ACV prophylaxis. To date, there is no established treatment against ACV-resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV-resistant HSV infection in patients with renal failure after allo-HSCT., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Achalasia is a rare esophageal motility disorder characterized by nonrelaxation of the lower esophageal sphincter. Laparoscopic Heller myotomy (LHM) is the gold standard treatment for achalasia. Peroral endoscopic myotomy (POEM), a less invasive treatment, is performed extensively, and the selection of the intervention method remains debatable to date. In addition to the availability of extensive studies on short-term outcomes, recent studies on the long-term outcomes of LHM and POEM have shown similar clinical success after 5 y of follow-up. However, gastroesophageal reflux disease (GERD) was more common in patients who had undergone POEM than in those who had undergone LHM. Moreover, existing studies have compared treatment outcomes in various disease states. Some studies have suggested that POEM is superior to LHM for patients with type III achalasia because POEM allows for a longer myotomy. Research on treatment for sigmoid types is currently in progress. However, the long-term results comparing LHD and POEM are insufficient, and the best treatment remains controversial. Further research is needed, and treatment options should be discussed with patients and tailored to their individual needs and pathologies., Competing Interests: The authors declare no conflicts of interest for this article., (© 2024 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background: PEComa is a mesenchymal tumor that can occur in various organs including the uterus and soft tissues. PEComas are composed of perivascular epithelioid cells, and angiomyolipoma (AML), clear cell sugar tumor (CCST), and lymphangiomyomatosis (LAM) are considered lesions of the same lineage as tumors of the PEComa family. Histologically, a common PEComa shows solid or sheet-like proliferation of epithelioid cells. This is accompanied by an increase in the number of dilated blood vessels. Here, we report a case of pancreatic PEComa with marked inflammatory cell infiltration., Case Presentation: A 74-year-old male patient underwent an appendectomy for acute appendicitis. Postoperative computed tomography and magnetic resonance imaging revealed a 30 × 25 mm non-contrast-enhanced circular lesion in the tail of the pancreas. The imaging findings were consistent with a malignant tumor, and distal pancreatectomy was performed. Histologically, most area of the lesion was infiltrated with inflammatory cells. A few epithelioid cells with large, round nuclei, distinct nucleoli, and eosinophilic granular cytoplasm were observed. Spindle-shaped tumor cells were observed. Delicate and dilated blood vessels were observed around the tumor cells. Immunohistochemically, the atypical cells were positive for αSMA, Melan A, HMB-45, and TFE3. The cytological characteristics of the tumor cells and the results of immunohistochemical staining led to a diagnosis of pancreatic PEComa., Conclusions: A histological variant known as the inflammatory subtype has been defined for hepatic AML. A small number of tumor cells present with marked inflammatory cell infiltration, accounting for more than half of the lesions, and an inflammatory myofibroblastic tumor-like appearance. To our knowledge, this is the first report of pancreatic PEComa with severe inflammation. PEComa is also a generic term for tumors derived from perivascular epithelioid cells, such as AML, CCST, and LAM. Thus, this case is considered an inflammatory subtype of PEComa. It has a distinctive morphology that is not typical of PEComa. This histological phenotype should be widely recognized., (© 2024. The Author(s).)

Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed procedure in bariatric-metabolic surgery (BMS) worldwide, accounting for approximately 90% of BMS procedures in Japan. While numerous studies have reported on the safety and efficacy of LSG, gastroesophageal reflux disease (GERD) remains a major postoperative complication. Although Roux-en-Y gastric bypass (RYGB) is preferred for severe obesity with GERD, it is less suitable for Japanese patients who have a higher risk of gastric cancer due to the remnant stomach which is difficult to observe with esophago-gastro-duodenoscopy. To address de novo and exacerbation GERD after LSG, we conducted LSG with Toupet fundoplication (T-sleeve) for Japanese patients with severe obesity. In our first T-sleeve case, the patient demonstrated sufficient weight loss and improved GERD following surgery. Hence, we suggest that T-sleeve is a feasible option for Japanese patients with obesity and concurrent GERD., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Aims: Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM., Methods and Results: Fibrosis extent in 70 RV-EMB specimens of DCM diagnosis was compared with that in the whole cross-sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13-19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance-late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV-EMB correlated significantly with that in the short-axis cut of the LV of excised hearts (r = 0.82, P < 0.0001) and with a diffuse pattern of LGE (r = 0.71, P = 0.003). In a multivariate model, after adjusting for the interval between biopsy performance and heart excision, the fibrosis area ratio in RV-EMB was associated with that in LV-excised heart (regression coefficient, 0.82; 95% confidence interval, 0.68-0.95; P < 0.0001)., Conclusions: The fibrosis observed in RV-EMB positively correlated with the extent of fibrosis in the LV of excised hearts in patients with DCM. The study findings may help predict LV fibrosis, considered a prognostic factor of DCM through relatively accessible biopsy techniques., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Changing the mode of commuting from nonactive by car or motorcycle to active by walking, cycling, or public transport is expected to benefit health. However, the proportion of nonactive commuters who can change their commute mode to active forms remains unclear. The aim of this study was to determine the proportions of nonactive commuters and of those who can change their commute mode to an active form in various regions in Japan., Methods: In this descriptive study, data were used from an online survey conducted from April to May 2021. Participants included 3,000 adults (20 to 79 years), who were registered with an online survey company. Workers were asked their means of transportation to work and commuting time. Workers using a car or motorcycle for more than 1 minute for commuting were defined as nonactive commuters, and the others were defined as active commuters. Then, nonactive commuters were asked about the possibility of changing their commute mode to active commuting (0%-100%, 11 options in 10% increments). The possibility of change was classified into four groups, i.e., impossible (0%), difficult (10%-40%), probably possible (50%-90%), and possible (100%). The proportions of nonactive commuters and nonactive commuters who can transition to active commuting were described by region., Results: A total of 2,683 participants answered the survey, including 1,647 workers, of whom 1,551 were commuters. The nonactive commuters accounted for 41.4% of commuters overall. The proportion of nonactive commuters was higher in rural than in urban regions. The proportion of nonactive commuters who could change their commute mode was 32.9% of the nonactive commuters or 12.8% of all workers. Among the nonactive commuters, the proportion who could change their commute mode was higher in urban than in rural regions. Of the total workers, the proportion of nonactive commuters who could change their commute mode was higher in rural regions., Conclusion: Nonactive commuters accounted for 41.4% of all commuters. The proportion of nonactive commuters who could change their commute mode among nonactive commuters was higher in urban regions. However, in rural regions, as the proportion of nonactive commuters was high, the proportion of nonactive commuters who could change their commute mode among total workers was also high. These results suggest that some of nonactive commuters can change their commute mode from nonactive to active commuting, in rural as well as in urban regions.

A 61-year-old woman was administered 35 cycles of pembrolizumab for the treatment of recurrent endometrial cancer, achieving a complete response. She presented with asymptomatic pancreatic enlargement and elevated hepatobiliary enzymes, but amylase and lipase levels were within the normal ranges. Intrapancreatic bile duct stenosis due to pancreatic enlargement was present, mimicking autoimmune pancreatitis on computed tomography performed before the onset of clinical manifestations. A histological examination of a biopsy specimen showed lymphocyte and plasma cell infiltration with dense fibrosis in the stroma. The patient was successfully treated with oral prednisolone. There were no manifestations of recurrent pancreatitis after tapering the prednisolone dose.

A 69-year-old woman suffering with multiple myeloma developed coronavirus disease 2019 (COVID-19). Shortly after administration of remdesivir, she presented with symptoms of facial flushing, wheezing, and hypoxemia. Subsequently, thrombocytopenia and hypofibrinogenemia rapidly manifested, leading to a diagnosis of enhanced fibrinolytic-type disseminated intravascular coagulopathy (DIC). This clinical presentation was considered an immediate hypersensitivity reaction with associated coagulation abnormalities induced by remdesivir. Although remdesivir is generally considered safe and efficacious in the treatment of COVID-19, physicians should remain vigilant regarding the potential for severe adverse events associated with this medication.

Background and Aims: Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality., Methods: Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity., Results: In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C., Conclusions: Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients., (© 2024 Wiley Periodicals LLC.)