Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein that regulates alternative splicing and primarily acts as a splicing repressor. Previous studies have shown that PTBP1 is closely linked to cancer metabolism through regulation by miR-133b and miR-124, which inhibit PTBP1 expression and modulate the splicing of the pyruvate kinase muscle (PKM) gene. Increased PTBP1 expression promotes PKM2 production and enhances glycolysis-dependent metabolism, a hallmark of cancer known as the Warburg effect. Clinical and experimental analyses were conducted to investigate the role of PTBP1 in breast cancer (BC). In silico investigations using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets revealed a significant association between PTBP1 overexpression and poor prognosis. In vitro, PTBP1 knockdown in BC cell lines (MCF7, SK-BR-3, and MDA-MB-231) increased PKM1 expression and the PKM1/PKM2 ratio, leading to reduced cell proliferation. ATP production increased in MCF7 and SK-BR-3 cells, but not in MDA-MB-231. Although NADH levels were elevated in MCF7 and MDA-MB-231 cells, lactate accumulation was most prominent in MDA-MB-231 cells. qRT-PCR analysis of surgical BC specimens confirmed significantly higher PTBP1 expression in tumour tissues than in adjacent normal breast tissues, with expression positively correlating with tumour grade. These findings collectively demonstrate that PTBP1 is overexpressed in BC and drives cancer-specific metabolic reprogramming associated with the Warburg effect. Therefore, PTBP1 may act as an oncogenic regulator of breast cancer metabolism and serve as a potential therapeutic target.

Radiofrequency ablation (RFA) is a minimally invasive technique employed in the management of small breast tumors. RFA involves the delivery of a high-frequency current through a needle electrode under ultrasound guidance. In Japan, RFA has been covered by insurance since 2023 as a localized treatment option for early-stage breast cancers. We retrospectively analyzed the data of patients who underwent RFA at our institution between February 2016 and March 2025. Breast density was classified into four categories based on the Breast Imaging Reporting and Data System. Associations between breast density and RFA parameters, including ablation temperature, time, and impedance, were evaluated. A total of 50 breasts in 49 female patients were treated with RFA. The mean peak ablation temperature recorded after the cooling break was 81.0 ± 8.0 °C. Increased breast density was significantly associated with high temperatures. The mean ablation time until break was 446 ± 139 s, indicating a trend toward prolonged durations in cases involving denser breast tissue. The mean initial and final impedance values were 208 ± 72.3 Ω and 161 ± 66.5 Ω, respectively. Fat-rich breasts exhibited significantly higher impedance values at both time points. Fatty breast tissue is associated with higher impedance, lower peak temperatures, and shorter ablation times, potentially resulting in insufficient ablation. Breast density should be considered when planning RFA to ensure optimal treatment efficacy.

OBJECTIVE:To evaluate the impact of a rapid testing workflow for obtaining BRCA genomic test results prior to surgery and multidisciplinary collaboration on surgical treatment selection. METHODS:Among 190 breast cancer patients who underwent BRCA genomic test from January 2021 to December 2023, 161 cases were analyzed after excluding cases with missing data and those undergoing companion diagnostic testing. The study period was divided into an early phase(35 cases)and a late phase(61 cases), and a retrospective comparison was conducted to evaluate the timing of testing, the duration from initial presentation to surgery, and surgical procedure selection. RESULTS:The preoperative testing rate increased from 45.5% to 72.6%, and the average number of days from initial visit to test results decreased from 24.4 days to 15.9 days. Among the 16 BRCA-positive patients, 87.5% chose mastectomy(including 25% contralateral prophylactic mastectomy), and 79.1% of the 43 BRCA-negative patients eligible for breast-conserving surgery opted for breast-conserving surgery. CONCLUSION:A rapid diagnostic workflow and multidisciplinary collaboration are effective strategies for providing genetic information preoperatively and enabling personalized surgical treatment.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

Invasion is more likely to occur in gastric cancer affecting larger areas. Poorly differentiated adenocarcinoma tends to invade deep. The cardiac region prefers submucosal invasion because the submucosa is coarser than the other regions. A 75-year-old man presented with a chief complaint of abdominal discomfort and weight loss. Esophagogastroduodenoscopy revealed an irregular ulcerative lesion with partial redness of the upper body and lesser curve of the stomach. A continuous shallow depressed lesion invaded the abdominal esophagus by approximately 40 mm. Poorly differentiated adenocarcinomas (por, sig) were observed on biopsy. Grossly, the cancer appeared to extend into the muscle layer; however, we could not confirm invasion into the muscle layer in our biopsy tissue. We diagnosed the lesion as a superficial spreading type of advanced gastric cancer and performed a total gastrectomy, D2-lymph node dissection (spleen preservation), Roux-en-Y reconstruction, and cholecystectomy. Postoperative histopathological examination revealed extensive infiltration of poorly differentiated adenocarcinoma (90 mm × 55 mm), and all were intramucosal lesions. The final pathological diagnosis was T1a, N0, M0, and Stage IA. The postoperative course was uneventful and the patient was discharged on postoperative day (POD) 11. Five years have passed since the operation, and the patient is alive without recurrence. We encountered a case of gastric carcinoma in which poorly differentiated adenocarcinomas expanded extensively. All lesions were intramucosal.

症例は25歳の女性で，腹痛，下痢で近医を受診し，潰瘍性大腸炎と診断された．プレドニゾロン投与により炎症は寛解したが，4か月後に再燃した．同時期に妊娠が判明したため当院紹介となった．全大腸型・Matts grade 4であり，インフリキシマブ・顆粒球除去療法で効果が得られなかったため，手術適応と判断した．妊娠14週で母児の安全保持のため，3期分割手術を計画し，腹腔鏡下結腸亜全摘・回腸ストマ造設・S状結腸盲端腹壁固定を施行した．その後，妊娠41週・2,665 gで正常分娩を経て，出産後3か月で腹腔鏡下残存大腸全摘・回腸囊－肛門吻合・回腸ストマ再造設を施行，さらに半年後に回腸ストマを閉鎖した．今回，麻酔科と相談して腹腔鏡手術を選択し，安全な妊娠の継続のため手技を工夫した症例であり報告する．

若年女性に好発する線維腺腫のなかで急速に増大するものがあり，そのような巨大若年性線維腺腫は比較的稀な疾患である．症例は12歳と13歳女児．どちらも左乳房腫大を自覚し受診し，超音波検査にて最大12cmの境界明瞭な腫瘤，最大９cm大の同様の腫瘤を認めた．ともに針生検を施行し線維腺腫の診断に至るも，葉状腫瘍の可能性があること，左右差が著明であることから腫瘍摘出術を行った．病理組織学的所見はともに線維腺腫であり悪性所見は認めなかった．過去33年間の報告によると，15歳以下の線維腺腫症例は34例，15歳以下の葉状腫瘍は10例認めた．過去の文献では女性ホルモンの関与やKi-67陽性例の腫瘍増大を示唆されていたが，本症例ではともにER陰性，PgR陰性であり，Ki-67値は低値であった．本症例では術後経過良好であり再発なく整容性の改善も得られた．発生頻度も考慮し小児乳腺腫瘍の手術は腫瘍摘出術の施行とし，乳腺組織を可能な限り温存することが重要であると考えられた．

Background: MicroRNA-125a (miR-125a) has been shown to function as tumor suppressive miRNA by pre-clinical in vitro studies. However, to the best of our knowledge, there is no study that investigated the clinical relevance of miR-125a in breast cancer patients. We hypothesized that miR-125a high expressing breast cancer associate with less aggressive cancer characteristics and with favorable survival outcome. Material and Methods: The clinicopathological and survival information associated with comprehensive transcriptomic data was analyzed in 2042 breast cancer patients from large publicly available databases, The Molecular Taxonomy of Breast Cancer International Consortium (METARBRIC) The Cancer Genome Atlas (TCGA), and GSE57897. The survival analysis, gene set enrichment analysis (GSEA) were conducted comparing miR-125a high expressing and low expressing tumors, divided by the median cutoff. The association between the miR-125a expression and tumor immune microenvironment was assessed by utilizing xCell. Results: The expression levels of miR-125a were lower in tumors compared with normal breast tissues in both TCGA and GSE57897 cohorts, which is in agreement with the notion that it is a tumor suppressive miRNA (p<0.001 and p<0.001, respectively). ER-positive/HER2-negative (ER+/HER2-) showed the highest miR-125a expression among the subtypes in TCGA (p<0.001). MiR-125a expression was not associated with cancer staging in any of the subtypes in neither TCGA nor METABRIC cohorts. Surprisingly, miR-125a high expressing tumors demonstrated worse disease free (DFS), disease specific (DSS), and overall survival (OS) compared with low expressing in ER+/HER2- breast cancer patients (p=0.008, p=0.005, and p=0.037) which was not the case for the other subtypes in METABRIC cohort. Interestingly, we found that miR-125a expression significantly correlated with Nottingham histological grade only in ER+/HER2- among the subtypes (p<0.001). miR-125a high tumors significantly demonstrated higher expression of MKI67, one of the most commonly used parameters for cell proliferation, correlated with miR-125a expression in ER+/HER2- and Her2-positive patients (both < p=0.02), but not in triple negative breast cancer (TNBC). Furthermore, miR-125a high expressing tumors enriched four out of five cell proliferation related gene sets in Hallmark collection, such as E2F Targets, G2M Checkpoint, Mitotic Spindle, and MYC Targets V2 in ER+/HER2- subtype, but not in TNBC. This was also the case in immune-related gene sets; interferon-alpha response and interferon-gamma response that enriched to miR-125a high tumors in ER+/HER2-, but not in TNBC. Infiltration of CD8 cells, T-helper type 1 cells, T-helper type 2 cells and M1 macrophages were all elevated in MiR-125a high ER+/HER2- subtype (all p<0.03), but none in TNBC. We found that tumor suppressive miR-125a was highly expressed in ER+/HER2- subtype, where its expression was associated with multiple clinical and molecular biological parameters of cell proliferation, as well as with both favorable and unfavorable immune response. Given its association with the survival outcome, we cannot help but speculate that miR-125a expression parallels with highly proliferative ER+/HER2- breast cancer, but its tumor suppressive effect is not enough to improve survival outcome. This study is hypothesis generating, and our results need mechanistic analyses by experimental investigations. Conclusion: MiR-125a high tumors were associated with aggressive characteristics in ER+/HER2- patients which may contribute to the worse survival outcomes. The current result support the importance of analyses of large patient cohorts to clarify the role of a miRNAs in patients. Citation Format: Yoshihisa Tokumaru, Manabu Futamura, Kohei Taniguchi, Masanori Oshi, Junichi Mase, Yoshimi Asano, Ryutaro Mori, Kazuaki Takabe, Kazuhiro Yoshida. microRNA-125a high expressing tumors enrich cell proliferation associated gene sets and associated with poor prognosis in estrogen receptor positive breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-10-04.

症例は75歳男性で，S状結腸癌に対してS状結腸切除術＋D3リンパ節郭清を施行した．病理組織学的所見ではpT3（SS），pN0，pM0，pStage Ⅱであった．S状結腸癌術後１年６カ月にCTにて膵体尾部にring enhanceを伴う腫瘍性病変を認め，転移性膵癌もしくは原発性膵癌と判断し膵体尾部切除術＋D2リンパ節郭清を行った．病理組織学的にS状結腸癌と同所見であったため膵転移と診断した．術後４年経過後，無再発生存中である．大腸癌の孤立性膵転移は比較的稀であり，十分な検討がなされていない．文献的考察を加え報告する．

INTRODUCTION:Several studies reported that skeletal muscle mass affects the clinical response and quality of life of cancer patients during chemotherapy. Here we examined the adverse events and effects of anticancer drugs on the skeletal muscle mass of patients with esophageal cancer who received biweekly docetaxel, cisplatin, and 5-fluorouracil(DCF)neoadjuvant chemotherapy in our department.SUBJECTS AND METHODS:We retrospectively analyzed 105 patients with esophageal cancer who received biweekly-DCF neoadjuvant chemotherapy in 2009-2019. The cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on computed tomography was assessed to calculate the psoas muscle index(PMI). Patients were divided into the high PMI group(high-group)and low PMI group(low-group)by cut-off value(male: 6.36 cm2/m2; female: 3.92 cm2/m2). Hematological toxicity, non-hematological toxicity, and therapeutic effect were retrospectively examined.RESULTS:Male in the high-group had significantly less ≥Grade 3 hematological toxicity than those in the low-group. Univariate and multivariate analyses showed that PMI(odds ratio: 1, p<0.05)was significantly related to decreased hematological toxicity.CONCLUSION:In preoperative chemotherapy for esophageal cancer, the incidence of hematological toxicity was significantly higher in patients with low skeletal muscle mass. Thus, skeletal muscle mass may be a marker for determining optimal anticancer drug dosage.

The need for adjuvant therapy after radical resection for patients with stage II–III thoracic esophageal squamous cell carcinoma (TESCC) who have undergone neoadjuvant chemotherapy (NAC) has not been determined. Since recurrence can occur after radical resection and since the prognosis is still poor, it is necessary to consider additional treatment strategies, including adjuvant chemotherapy. We retrospectively investigated the significance of adjuvant therapy after NAC followed by radical resection for TESCC. Between 2008 and 2018, 115 patients with clinical stage II–III underwent radical subtotal esophagectomy after neoadjuvant therapy. Among them, 62 were analyzed, excluding patients with T4 tumors and patients who had undergone R plus resection or who were receiving preoperative chemoradiotherapy. We compared patients who received adjuvant chemotherapy with those who only received observation; we examined overall survival (OS) and recurrence rates. Twenty-nine patients (46.7%) had lymph node metastasis, 12 of whom received adjuvant chemotherapy (41.3%). The recurrence rates for patients with and without lymph node metastasis were 55.1 % and 15.1%, respectively (p = 0.0022). Among patients with lymph node metastasis, there was no significant difference in the recurrence rate (p = 0.9270) or OS (p = 0.5416) based on the administration of adjuvant chemotherapy. However, in 15 patients with two or more positive lymph nodes, adjuvant chemotherapy increased OS (p = 0.0404). Adjuvant chemotherapy was associated with improved OS in clinical stage II–III TESCC patients with two or more pathological positive lymph nodes after NAC followed by radical surgery.

Aim: Many therapeutic means have emerged to treat esophageal cancer. Factors relating to nutritional status such as body weight maintenance are important to the continuation of these treatments. In this study, we investigated methods to extend the administration of diversified treatments for patients with esophageal cancer, especially regarding measures to suppress body weight loss after surgery. Methods: We retrospectively evaluated a strategy for preventing postoperative body weight loss which can hinder the continuation of treatment via a reconstruction method aimed at safety and comfort combined with postoperative dietary intake and nutritional support for esophageal cancer patients. Results: The subjects comprised 386 patients who underwent subtotal stomach reconstruction during esophageal cancer surgery performed from January 2008 to January 2021 at Gifu University Hospital. The anastomotic leakage rate was 0.5％. By administering oral nutritional supplementation under strict rules using ENSURE? H during the perioperative period, the percentage of body weight loss after 5 years could be limited to 4.78％ compared to that before treatment. Scores assessing early feeling of fullness measured using the EORTC QLQ-OES18 at postoperative months 3, 12, 24, 36, 48, and 60 were 1.7 ± 0.3, 2.0 ± 0.2, 1.2 ± 0.3, 1.3 ± 0.2, 1.5 ± 0.2, and 1.4 ± 0.1, respectively. Conclusion: Considering methods to eliminate the factors that prevent continuation of treatment may lead to sustainable treatment against esophageal cancer. Proper surgical reconstruction and nutritional management will allow maintenance of body weight and good quality of life.

Background/Aim: The frequency of detecting cancer-associated venous thromboembolism (CAT) during chemotherapy is increasing. It is not desirable to discontinue chemotherapy for CAT. In this study, we investigated the feasibility of simultaneous progression of anticoagulant and anticancer therapy, focusing on drug interactions. Patients and Methods: We retrospectively evaluated patients with gastroenterological CAT from February 2017 to December 2020 at the Gifu University Hospital. When both chemotherapy and CAT treatments using edoxaban were performed in parallel and the thrombus disappeared, patients were defined as being Keep-ACT2 (keeping anticancer therapy and anticoagulant therapy) successful. The effect and safety of treatment strategy focusing on cytochrome P450 (CYP) metabolism using edoxaban were evaluated. Results: A total of 114 patients with CAT during chemotherapy were treated with edoxaban. Keep-ACT2 was successful in 101 (88.6%) cases. Clinically relevant non-major bleeding was observed in 5 cases (4.4%). All 114 patients were using some drug affected by CYP metabolism, and the median number of affected cases was 5. Conclusion: Combined use of edoxaban for CAT may lead to sustainable therapy for gastroenterological cancer patients who are administered several drugs.

Mitochondria-eating protein (MIEAP; also known as SPATA18), a p53-downstream gene, is involved in mitochondrial quality control (MQC). Enforced MIEAP expression induces caspase-dependent cell death in vitro, and impairment of the p53/MIEAP-regulated MQC pathway is frequently observed in breast cancer (BC), resulting in poor disease-free survival (DFS). To investigate the clinical significance of MIEAP in BC, we identified 2,980 patients from two global, large-scale primary BC cohorts: the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=1,904) and the Cancer Genome Atlas (TCGA; n=1,076). We divided patients in each cohort into high and low groups based on median gene expression levels and analyzed the association between MIEAP expression and clinical outcomes. Compared with normal tumors, MIEAP expression was significantly downregulated in all patients with p53-mutant BC regardless of subtype. MIEAP expression was negatively correlated with KI67 expression. Gene set enrichment analysis demonstrated that cell cycle- and proliferation-associated gene sets were significantly enriched in MIEAP-low tumors compared to MIEAP-high tumors. Patients with MIEAP-high luminal subtype were associated with significantly longer DFS than those with MIEAP-low luminal tumors in both cohorts, whereas significantly longer overall survival was observed only in the METABRIC cohort, which has roughly double the number of samples. These results indicated that the mechanistic role of MIEAP is clinically relevant in the two independent cohorts. This is the first study to use large cohorts to demonstrate the association between MIEAP expression and survival in patients with luminal subtype BC.

We report a successful case that offered a symbolic therapeutic experience of interventional radiology and surgery collaboration for superior mesenteric artery thrombosis. A 70-year-old man presented with a chief complaint of sudden abdominal pain. Contrast-enhanced computed tomography revealed superior mesenteric artery thrombosis. Interventional radiology was performed, and thrombotic occlusion was observed in the superior mesenteric artery trunk. The abdominal pain disappeared; however, after a while, the thrombus re-formed and the abdominal pain reappeared. Thus, emergency surgery was performed. Before surgery, thrombus aspiration was performed via interventional radiology as much as possible. During surgery, when the blood flow was evaluated using fluorescence with indocyanine green, a region of markedly poor blood flow was detected in the ileum, and the area was excised. The postoperative course was favorable. In this patient, it is possible that preoperative removal of the thrombus via interventional radiology minimized the ischemic area of the intestinal tract, and blood flow evaluation using indocyanine green allowed reliable excision of only the ischemic area. We believe that our case involved a treatment that exploited the advantages of both interventional radiology and surgery using indocyanine green fluorescence.

Introduction Relapsing polychondritis is a relatively rare chronic inflammatory disease of unknown etiology. In this case the treatment for esophageal cancer may have triggered relapsing polychondritis. Case presentation A 70-year-old man complained of dysphagia and weight loss. An upper gastrointestinal endoscopy revealed type 2 advanced esophageal cancer. A subtotal esophagectomy and three-region lymph node dissection were performed after chemotherapy. One month later, the patient developed respiratory distress accompanied by wheezing, dizziness, and hearing loss. The symptoms improved within a few days. The frequency of respiratory distress increased and the patient visited our department. Pharyngeal endoscopy revealed narrowing of the glottic space and a subglottic tumor. No malignant findings were found histopathologically on the biopsy specimens, but infiltration of inflammatory cells was observed. We diagnosed relapsing polychondritis based on the histopathological findings of the pharyngeal cartilage, in addition to the osteolytic changes of the cricoid cartilage on CT. The symptoms were relieved after the administration of oral steroids. Despite tapering of the steroids, no recurrence of relapsing polychondritis occurred. There was no evidence of esophageal cancer recurrence. Conclusion Early diagnosis and treatment for relapsing polychondritis are necessary because this condition is often associated with airway lesions. Esophageal cancer treatment may trigger relapsing polychondritis.

Right-sided Zenker's diverticulum is a rare pharyngoesophageal diverticulum. The risk of intraoperative injury of the recurrent laryngeal nerve is high during transcervical diverticulectomy because this nerve presents many variations of extralaryngeal bifurcation before entry into the larynx. We present a case of right-sided Zenker's diverticulum that was safely resected with the use of intraoperative neuromonitoring to prevent right recurrent laryngeal nerve injury. A 55-year-old man complaining of chronic cough and regurgitation of ingested food was diagnosed as having right-sided Zenker's diverticulum and underwent open transcervical diverticulectomy and cricopharyngeal myotomy. The location of the right recurrent laryngeal nerve was accurately determined during dissection by intermittent stimulation using a monopolar stimulation probe of an intraoperative neuromonitoring system to avoid injury. The postoperative course was uneventful, and postoperative evaluation showed no vocal cord paralysis. Intraoperative neuromonitoring may be beneficial during transcervical diverticulectomy for right-sided Zenker's diverticulum nearby the right recurrent laryngeal nerve, which can present with many variations of extralaryngeal bifurcation.

症例は78歳の男性で，胃体部および噴門部癌があり，造影CTで肝門部および気管分岐部リンパ節転移を伴いStage IVと診断した．化学療法としてpaclitaxel+S-1療法を行い，のちにHER2陽性であることが判明しtrastuzumab+cisplatin+capecitabine療法を計17コース施行した．化学療法後の上部消化管内視鏡検査では瘢痕を認めるのみであり，転移リンパ節も著明な縮小を認めたため，幽門側胃切除術，D2+#8p・#13リンパ節郭清を施行した．術後病理組織結果では，#4dに腫瘍細胞の残存を認めたが，原発巣は組織学的CR（pathological complete response；pCR）であった．HER2陽性胃癌の術前化学療法としてtrastuzumabを含むレジメンの有用性が示唆された．