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Background: Evaluating multiple biomarkers including human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR) status, programed death-ligand 1 (PD-L1), and claudin 18.2 (CLDN18.2) is essential for selecting appropriate first-line therapy of metastatic gastroesophageal adenocarcinoma (mGEA). However, this can be challenging if tumor tissue amount is limited and may cause delays in the initiation of chemotherapy. Therefore, we assessed the feasibility of multiple biomarkers testing in routine clinical practice. Materials and methods: We reviewed the medical records of treatment-naïve patients with mGEA who underwent prospective multiple biomarkers testing between April 2022 and October 2023 in our institution. Eight biomarker status including HER2, MMR, PD-L1, CLDN18.2, Epstein–Barr virus, fibroblast growth factor receptor 2, epidermal growth factor receptor and mesenchymal epithelial transition expressions were simultaneously examined using biopsy or surgical specimens. Results: A total of 203 patients with mGEA were analyzed. Most patients underwent gastroendoscopy and tumor biopsy shortly after referral to our institution. Biomarkers testing was successfully completed on the first attempt in 198 patients (97.5%). With additional steps including additional biopsy or asking remaining tumor samples from the referring hospital, the biomarker results were eventually available in all cases. The median turnaround time from sample collection to reporting results was 7 days. Consequently, 178 patients (87.7%) could receive first-line treatment after obtaining the biomarker status. Conclusions: Multiple biomarkers testing for patients with mGEA was feasible in clinical practice. Establishment of a testing infrastructure based on the collaboration with multiple departments is essential for implementing biomarker-driven precision treatment.

Background: Although the common treatment strategy for localized gastric cancer in Japan is gastrectomy followed by adjuvant chemotherapy, several randomized studies in non-Japanese populations have established perioperative chemotherapy as the standard treatment of localized gastric or gastroesophageal junction adenocarcinoma. Therefore, we have implemented this strategy in our institution. Patients and methods: We retrospectively reviewed the medical records of patients with resectable gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma who had received perioperative FLOT (5-fluorouracil plus docetaxel plus oxaliplatin plus leucovorin) from February 2020 to February 2023. Results: In this study, a total of 91 patients were analyzed, with a median age of 70 years (range: 29-82). At the time of diagnosis, 83 patients (91.2%) had T3 or higher-grade primary lesions, and 85 (93.4%) had lymph node metastasis. A total of 10 patients had resection before completing four cycles of preoperative chemotherapy, and 77 of 91 (84.6%) completed four cycles with 74 of them receiving radical resection. Among the 84 patients who had radical resection after FLOT, 82 (97.6%) achieved R0 resection, including 8 (9.5%) with a pathological complete response. After resection, 60 patients (65.9%) received at least one cycle of post-operative FLOT, and 47 (51.6%) completed eight cycles of FLOT treatment. Chemotherapy-related adverse events of grade 3 or higher occurred during the pre- and post-operative FLOT in 60 patients (65.9%), including leukopenia (30.8%), neutropenia (50.5%), febrile neutropenia (5.5%), and anorexia (7.7%). No treatment-related deaths occurred. Conclusions: These findings were comparable to those in the pivotal FLOT 4 trial, suggesting acceptable feasibility of the FLOT regimen in Japanese clinical practice.

Abstract The prognosis of osteosarcoma (OS) has remained stagnant over the past two decades, requiring the exploration of new therapeutic targets. Cytokines, arising from tumor-associated macrophages (TAMs), a major component of the tumor microenvironment (TME), have garnered attention owing to their impact on tumor growth, invasion, metastasis, and resistance to chemotherapy. Nonetheless, the precise functional role of TAMs in OS progression requires further investigation. In this study, we investigated the interaction between OS and TAMs, as well as the contribution of TAM-produced cytokines to OS advancement. TAMs were observed to be more prevalent in lung metastases compared with that in primary tumors, suggesting their potential support for OS progression. To simulate the TME, OS and TAMs were co-cultured, and the cytokines resulting from this co-culture could stimulate OS proliferation, migration, and invasion. A detailed investigation of cytokines in the co-culture conditioned medium (CM) revealed a substantial increase in IL-8, establishing it as a pivotal cytokine in the process of enhancing OS proliferation, migration, and invasion through the focal adhesion kinase (FAK) pathway. In an in vivo model, co-culture CM promoted OS proliferation and lung metastasis, effects that were mitigated by anti-IL-8 antibodies. Collectively, IL-8, generated within the TME formed by OS and TAMs, accelerates OS proliferation and metastasis via the FAK pathway, thereby positioning IL-8 as a potential novel therapeutic target in OS.

Primary malignant cardiac tumors rarely occur, and cardiac synovial sarcoma (SS) is especially rare among such tumors. Herein, we present the case of a 35-year-old female with primary cardiac SS treated with surgery, chemotherapy, and radiotherapy. She presented with chest symptoms and underwent imaging examinations. A cardiac tumor was suspected, and an open biopsy was performed. The pathological findings suggested cardiac SS. Next, we performed a resection, and the tumors persisted at a macroscopic level. Immunohistochemistry was negative for SS18-SSX and positive for the SSX C-terminus and cytokeratin CAM5.2, a reduction of SMARCB1/INI1 was observed, and fluorescence in situ hybridization showed positive SS18 split staining. Owing to the FNCLCC grade 3 tumor and R2 margins, adjuvant chemotherapy with ifosfamide, doxorubicin, and radiotherapy was initiated, and the patient was diagnosed with cardiac SS. The differences in patients with cardiac SS compared with general SS include male predominance, larger tumor size, and poorer prognosis. Pathological findings of immunohistochemistry and fluorescence in situ hybridization were found to be more reliable than imaging findings for a correct diagnosis. Additionally, because incomplete resection is frequently performed, adjuvant therapy, including chemotherapy and radiation therapy, may be performed. The findings indicate that multiple therapies, including surgery, chemotherapy, and radiotherapy, are essential treatment strategies for improving the prognosis of patients with cardiac SS.

Conclusion: The high success rate of endoscopic hemostasis and no difference in adverse events made the prompt resumption of antithrombotic medications after emergency endoscopy for UGIB acceptable.

Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of mesenchymal origin occurring in young adults. Based on its clinical course, it is said to have an intermediate potential. We present a case of a 59-year-old woman with AFH in the hand that was difficult to diagnose. A benign soft tissue tumor was suspected on magnetic resonance imaging, and its size and open biopsy suggested nodular fasciitis or inflammatory myofibroblastic tumor. A diagnosis of AFH was eventually made based on the analysis of the resected specimens. The characteristic findings of histopathology and immunohistochemistry in this case were relatively poor, so fluorescence in situ hybridization contributed to making the correct diagnosis. Considering its prognosis, careful follow-up was decided upon without additional surgery. Our case is a challenging one because of its atypical presentation and inconclusive imaging and histopathological findings.

Abstract Background This study aimed to evaluate the usefulness of discharge standards in outpatients undergoing sedative endoscopy by comparing the modified post-anesthetic discharge scoring system (MPADSS) and the modified Aldrete score. Methods We prospectively enrolled 376 outpatients who underwent gastrointestinal endoscopy under midazolam sedation; 181 outpatients were assessed regarding discharge after sedative endoscopy using the MPADSS (group M), and 195 patients were assessed by the modified Aldrete score (group A). The clinical characteristics, types of endoscopy, endoscopic outcomes, and anesthesia outcomes were evaluated between the two groups. We compared discharge score, recovery time, and adverse events using propensity-score matching. Results Propensity-score matching created 120 matched pairs. The proportion of patients who had a recovery time within 60 min after endoscopy was significantly higher in group A than that in group M (42.5% versus 25.0%, respectively; P 120 min of recovery time after endoscopy was significantly lower in group A than that in group M (0.0% versus 5.0%, respectively; P = 0.03). However, significantly more patients had drowsiness at discharge in group A compared with group M (19.1% versus 5.0%, respectively; P

Zinc finger E‐box binding homeobox 1 (ZEB1) has been identified as a key factor in cancer cell differentiation and metastasis, and has been well studied in the field of cancer cell biology. ZEB2 has a highly similar conformation to ZEB1, but its role in head and neck squamous cell carcinoma (HNSCC) cells is not fully understood. Here, we separately overexpressed ZEB1 and ZEB2 in C57BL/6 mouse oral cancer (MOC) cells and investigated their cellular characteristics, including E‐cadherin levels, motile properties, chemoresistance, and metastatic ability in immunocompetent mice. Both ZEB1 and ZEB2 overexpression reduced epithelial traits and converted cells to an aggressive phenotype. Surprisingly, ZEB1 overexpression increased the endogenous level of ZEB2 in MOC cells, and vice versa. The molecular mechanisms underlying these findings remain unclear. However, the in vitro anchorage‐independent growth of MOC cells overexpressing ZEB2 was considerably greater than that of MOC cells overexpressing ZEB1. These findings suggest that ZEB2, like ZEB1, has the ability to induce the differentiation of cancer cells into those with highly aggressive traits. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma (OS) is the most frequently occurring malignant bone tumor in children. Although advances in chemotherapy and surgery have gradually improved OS prognosis, no improvement has been reported over the past two decades. Recently, tumor microenvironment (TME) has attracted attention as a novel therapeutic target. The TME includes peritumoral immune cells, blood vessels, extracellular matrix, fibroblasts, lymphocytes, bone marrow-derived inflammatory cells, platelets, and signaling molecules, which create an environment that promotes tumor growth, metastasis, and anticancer drug resistance. Research on the TME is particularly important because tumor-associated macrophages (TAMs) are a major component of this microenvironment, and the interaction between tumors and TAMs contributes towards tumor aggressiveness. However, our knowledge of the interaction between OS and TAMs is limited. In this review, we aim to describe the characteristics of TAMs in the OS TME. Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. Prognosis is improving with advances in multidisciplinary treatment strategies, but the development of new anticancer agents has not, and improvement in prognosis for patients with pulmonary metastases has stalled. In recent years, the tumor microenvironment (TME) has gained attention as a therapeutic target for cancer. The immune component of OS TME consists mainly of tumor-associated macrophages (TAMs). They exhibit remarkable plasticity, and their phenotype is influenced by the TME. In general, surface markers such as CD68 and CD80 show anti-tumor effects, while CD163 and CD204 show tumor-promoting effects. Surface markers have potential value as diagnostic and prognostic biomarkers. The cytokines and chemokines produced by TAMs promote tumor growth and metastasis. However, the role of TAMs in OS remains unclear to date. In this review, we describe the role of TAMs in OS by focusing on TAM surface markers and the TAM-produced cytokines and chemokines in the TME, and by comparing their behaviors in other carcinomas. We found contrary results from different studies. These findings highlight the urgency for further research in this field to improve the stalled OS prognosis percentages. [ABSTRACT FROM AUTHOR]

Abstract Background Endoscopic mucosal resection (EMR) to remove colon polyps is increasingly common in patients taking antithrombotic agents. The safety of EMR with submucosal saline injection has not been clearly demonstrated in this population. Aims The present study aimed to evaluate the efficacy and safety of submucosal injection of saline–epinephrine versus hypertonic saline in colorectal EMR of patients taking antithrombotic agents. Methods This study enrolled 204 patients taking antithrombotic agents among 995 consecutive patients who underwent colonic EMR from April 2012 to March 2018 at Ureshino Medical Center. Patients were divided into two groups according to the injected solution: saline–epinephrine or hypertonic (10%) saline (n = 102 in each group). Treatment outcomes and adverse events were evaluated in each group and risk factors for immediate and post-EMR bleeding were investigated. Results There were no differences between groups in patient or polyp characteristics. The main antithrombotic agents were low-dose aspirin, warfarin, and clopidogrel. Propensity-score matching created 80 matched pairs. Adjusted comparisons between groups showed similar en bloc resection rates (95.1% with saline–epinephrine vs. 98.0% with hypertonic saline). There were no significant differences in adverse events (immediate EMR bleeding, post-EMR bleeding, perforation, or mortality) between groups. Multivariate analyses revealed that polyp size over 10 mm was associated with an increased risk of immediate EMR bleeding (odds ratio 12.1, 95% confidence interval 2.0–74.0; P = 0.001). Conclusions Two tested solutions in colorectal EMR were considered to be both safe and effective in patients taking antithrombotic agents.

Background and Aim: Elobixibat is a novel ileal bile acid transporter inhibitor. This study aimed to compare the efficacy, tolerability, and safety of the combination of elobixibat and 1 L of polyethylene glycol formulation containing ascorbic acid (PEG‐Asc) solution versus the combination of sodium picosulfate and 1‐L PEG‐Asc solution as bowel preparation for colonoscopy. Methods: This multi‐center, randomized, observer‐blinded, non‐inferiority study recruited 210 outpatients who were assigned to either the elobixibat plus 1‐L PEG‐Asc group (group A) or the sodium picosulfate plus 1‐L PEG‐Asc group (group B). The quality of the bowel cleansing level was assessed by the Boston Bowel Preparation Scale (BBPS) and compared the bowel cleansing level between the groups. Data regarding bowel preparation time, patients' tolerability, and adverse events were also analyzed. Results: Data for 196 patients (99 in group A and 97 in group B) were analyzed finally. BBPS was comparable between group A and B (8.3 ± 0.9 vs. 8.3 ± 0.7; P = 0.88). Consequently, the adequate bowel preparation rate in groups A and B was 95.0% and 99.0%, respectively (−4.0%, 95% CI −9.3 to 1.5). Bowel preparation time in group A was similar to that in group B (348.2 ± 79.8 min vs. 330.8 ± 82.5 min; P = 0.13), whereas, sleep disturbance was significantly less frequent in group A than in group B (10.2% vs. 22.7%; P = 0.02). Conclusions: The combination of elobixibat and 1‐L PEG‐Asc can be considered an alternative bowel preparation for colonoscopy considering the equivalent bowel cleansing effect and less frequent sleep disturbance. The Japan Registry of Clinical Trials (jRCTs41180026). [ABSTRACT FROM AUTHOR]

Case: A 17-year-old man experienced night pain in his right hallux. Radiographs revealed a lytic lesion in the proximal phalanx of the right hallux. Magnetic resonance imaging showed a low-signal intensity mass on T1-weighted sequences and isointense–high-signal intensity on T2-weighted sequences. We suspected a benign bone tumor such as osteoid osteoma or a bone cyst and consequently performed biopsy and surgical treatment. The lesion was filled with a whitish chalk-like substance, and pathologic examination revealed tophaceous gout. Conclusions: It can be difficult to distinguish intraosseous tophaceous gout from other diseases, including bone tumors, using imaging; hence, pathological examination may be necessary for the diagnosis. [ABSTRACT FROM AUTHOR]