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記述言語：英語   出版者・発行元：Hepatology Research  

Aim: In hepatocellular carcinoma (HCC), molecularly targeted therapies have been the major focus of recent research. In this study, we evaluated the clinical and biological roles of tumor necrosis factor superfamily 4 (TNFSF4), an inflammatory cytokine, as a therapeutic target in HCC. Methods: Using a bioinformatics approach, we identified TNFSF4 as a candidate driver in HCC and assessed the prognostic significance of TNFSF4. Its biological role in HCC was clarified through in vitro experiments, such as cell cycle/colony formation assays, using TNFSF4-overexpressing HCC cells. Moreover, a candidate repositioned drug was identified from public drug sensitivity data, and its antitumor effects and mechanisms were examined both in vitro and in vivo. Results: Analysis of The Cancer Genome Atlas datasets for HCC revealed that TNFSF4 was overexpressed in HCC cells owing to increased DNA copy numbers. Additionally, high TNFSF4 expression was significantly associated with poorer prognosis. Immunohistochemical staining showed that TNFSF4 was overexpressed in the cytoplasm of tumor cells. In vitro analysis showed that TNFSF4 overexpression promoted the G<inf>1</inf>/S transition in the cell cycle, stimulated proliferation, and increased phosphoinositol-3-kinase (PI3K) phosphorylation, resulting in p21 downregulation and enhanced Rb phosphorylation. In bioinformatics-based drug repositioning analysis, fluspirilene, a typical antipsychotic agent, was identified as a repositioned drug that inhibited HCC growth through cyclin D1 suppression, downstream of TNFSF4. Conclusions: TNFSF4 was a candidate driver and a prognostic biomarker, promoting HCC progression by activating the PI3K/Akt signaling pathway. Furthermore, fluspirilene may have applications as a repositioned drug for HCC with high TNFSF4 expression.

DOI： 10.1111/hepr.70135

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PubMed

記述言語：英語   出版者・発行元：Surgery Today  

Purpose: Lynch syndrome (LS), the most common hereditary colorectal cancer (CRC), is caused by germline mutations in mismatch repair (MMR) genes, resulting in microsatellite instability-high (MSI-H) tumors. Lynch-like syndrome (LL) exhibits MSI-H and MMR deficiency, but lacks identifiable germline MMR mutations. Although LS/LL CRCs share clinical and molecular features, they are distinct from sporadic MSI-H (SM) CRCs, emphasizing the need for refined molecular classification. This study investigated the somatic alterations that distinguish LS/LL CRC from SM CRC. Methods: Whole-exome sequencing (WES) was performed on 49 LS/LL CRC and 96 SM CRC samples. Tumor-normal paired data were analyzed using GATK and MuTect2 to detect somatic variants. Mutation frequencies were compared using Fisher’s exact test (p < 0.005). Logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate the discriminatory performance. Results: We identified 11 gene regions that were significantly enriched in LS/LL CRC, including KRAS, ITGB3BP, CLEC16A, ARHGEF28, PIK3CA, and RBM26. A variant panel based on these alterations showed an area under the curve (AUC) of 0.85 and an Akaike information criterion of 129.81. Conclusions: These findings support the utility of LS/LL-specific somatic variants in stratifying MSI-H CRCs and identifying hereditary cases for personalized management.

DOI： 10.1007/s00595-025-03212-w

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DOI： 10.1016/j.annonc.2025.10.143

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記述言語：英語   出版者・発行元：Clinical Journal of Gastroenterology  

Esophageal squamous cell carcinoma confined to the depth of the T1a-epithelium and lamina propria mucosa rarely exhibits lymph node and distant organ metastases; therefore, the recommended therapy for such cases is endoscopic resection. Furthermore, once esophageal squamous cell carcinoma recurs after curative treatment, including endoscopic mucosal dissection, a unified treatment method cannot be established, because recurrence patterns vary from case to case. Herein, we present an unusual case of metachronous locoregional and subclavian lymph-node recurrence following repeated radical endoscopic submucosal dissection of the superficial esophageal squamous cell carcinoma judged as T1a-LPM with deep subepithelial stromal invasion. The patient was treated using a multidisciplinary approach, leading to a cancer-free status. Although recurrent lymph-node metastasis after curative endoscopic submucosal dissection for pT1a-LPM esophageal squamous cell carcinoma is rare, it is possible. A comprehensive and detailed analysis of the risk factors of recurrence after endoscopic resection for pT1a-LPM cases is required, and appropriate follow-up strategies and stratified adjuvant therapies should be selected for high-risk patients.

DOI： 10.1007/s12328-025-02206-y

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

記述言語：英語   出版者・発行元：Journal of Surgical Oncology  

Background: Remnant gastric cancer (RGC) is associated with higher surgical difficulty and poorer long-term outcomes than primary gastric cancer. However, the impact of postoperative complications on prognosis in RGC remains unclear. Methods: This retrospective, multicenter cohort study included 126 patients who underwent curative surgery for RGC across five institutions between 2007 and 2024. Postoperative complications were evaluated using the Clavien–Dindo (CD) classification. Patients were stratified into two groups based on the presence of severe complications (CD grade ≥ 3a). Logistic regression analysis was used to identify risk factors for complications, and Cox proportional hazards models were applied to determine prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Results: Severe postoperative complications occurred in 15.9% of patients. Multivariate analysis identified smoking (OR = 8.28, p = 0.0048), operative time ≥ 300 min (OR = 3.52, p = 0.0448), and blood transfusion (OR = 4.82, p = 0.0380) as independent risk factors for severe complications. Kaplan–Meier analysis demonstrated significantly poorer 5-year OS (32.0% vs. 65.6%, p = 0.002) and RFS (33.6% vs. 64.3%, p < 0.001) in patients with CD grade ≥ 3a complications. CD grade ≥ 3a and pathological Stage II or higher were independent prognostic factors for both OS and RFS. Conclusions: Severe postoperative complications are associated with poor long-term outcomes in patients undergoing curative surgery for RGC. Identifying and mitigating modifiable risk factors, such as smoking and operative invasiveness, may help improve surgical and oncological outcomes in this challenging population.

DOI： 10.1002/jso.70094

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記述言語：英語   出版者・発行元：World Journal of Surgery  

Background: Remnant gastric cancer (RGC) is known to have a poorer prognosis compared to primary gastric cancer. Inflammation-based prognostic scores (IBPSs), which reflect systemic inflammation and nutritional status, have recently emerged as useful prognostic markers in various malignancies. However, their significance in RGC remains unclear due to the rarity of the disease and the limited number of cases available at single institutions. Methods: We conducted a retrospective multicenter study of 135 patients who underwent surgery for RGC between 2013 and 2024 at Kyushu University and four affiliated hospitals. After excluding nine patients with synchronous malignancies or noncurative resections, 126 patients were included in the final analysis. Associations between IBPSs—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), and prognostic nutritional index (PNI)—and both short- and long-term outcomes were evaluated. Results: Receiver operating characteristic (ROC) analysis determined optimal cutoff values for each IBPS. Kaplan–Meier analysis revealed that PLR ≥ 195 and PNI < 43.5 were significantly associated with poorer overall survival (OS) (P = 0.008 and P < 0.001, respectively). Multivariate analysis identified PLR ≥ 195 and PNI < 43.5 as independent predictors of poor OS and recurrence-free survival (RFS). Additionally, PLR ≥ 260 was identified as an independent risk factor for postoperative complications (P = 0.047). Conclusion: PLR and PNI are independent prognostic markers for both OS and RFS in patients undergoing curative surgery for RGC. Elevated PLR also predicts postoperative complications, highlighting its potential role in perioperative risk stratification.

DOI： 10.1002/wjs.70111

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

記述言語：英語   出版者・発行元：Journal of Gastroenterology  

Background: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis, which is often driven by chromosomal amplifications at 1q. Vacuolar sorting protein 45 (VPS45), a gene located on chromosome 1q, is involved in the endocytic recycling pathway; however, its role in HCC remains unclear. In this study, we aimed to investigate the functional significance of VPS45 in the progression of HCC. Methods: VPS45 expression was analyzed using public databases, clinical HCC samples, and cell lines. Functional assays, including VPS45 knockout and rescue experiments, were conducted to assess the effect on tumor progression in vitro and in vivo. The molecular mechanisms underlying VPS45 function, particularly its role in β1 integrin recycling and FAK-AKT signaling activation, were also explored. Results: VPS45 expression was significantly elevated in HCC owing to DNA copy number amplification and correlated with poor prognosis. Moreover, VPS45 knockout suppressed cell proliferation, migration, and invasion, while promoting apoptosis. VPS45 interacted with syntaxin16 and rabenosyn-5 to facilitate the recycling of β1 integrin to the cell membrane, thereby activating FAK-AKT signaling, which promotes oncogenic phenotypes. In xenograft models, VPS45 knockout significantly suppressed tumor growth, further supporting its role in HCC progression. Conclusions: VPS45 is a key oncogene in HCC that promotes tumor progression by enhancing β1 integrin recycling and activating FAK-AKT signaling. Given its strong association with poor prognosis and tumor malignancy, VPS45 may serve as a promising prognostic biomarker and a potential therapeutic target for HCC.

DOI： 10.1007/s00535-025-02278-0

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記述言語：英語   出版者・発行元：Cancer Science  

Polarity genes form intracellular protein complexes that establish epithelial cell polarity and homeostasis for various normal cellular functions. Partitioning Defective 6B (PARD6B), a polarity gene, functions as a scaffold node for the Par protein complex. However, its contribution to colon cancer is not well understood. In this study, we showed that PARD6B regulates tumor progression in colorectal cancer (CRC). PARD6B is located on chromosome 20, which is frequently amplified in CRC, and its expression in CRC correlates with DNA copy number amplification, including enhancer regions. Immunohistochemistry and single-cell analyses also showed that PARD6B expression was significantly higher in cancer cells. Furthermore, unlike other polarity gene groups comprising the Par complex, PARD6B mRNA expression was the only independent poor prognostic factor. In vitro and in vivo experiments revealed that PARD6B positively regulates cell proliferation and cell cycle progression. In silico analysis also showed that PARD6B expression positively regulated MYC expression, a pathway believed to be associated. Additional in silico and in vitro analyses supported the hypothesis that PARD6B regulates miR-34c, which directly targets and represses MYC expression. Pan-cancer analysis indicated that PARD6B is highly expressed in gastrointestinal tumors, including CRC, and that high PARD6B mRNA expression is a poor prognostic factor in other cancer types. In summary, highly expressed PARD6B can promote CRC growth by upregulating MYC expression while suppressing miR-34c expression, making PARD6B a potential prognostic biomarker and therapeutic target for CRC.

DOI： 10.1111/cas.70119

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記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

DOI： 10.1245/s10434-025-17242-8

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記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. The progression of HCC involves complex molecular mechanisms, including chromosomal amplification and alterations in pre-mRNA splicing. In this study, we investigated sodium channel modifier 1 (SCNM1), a component of the minor spliceosome, as a potential oncogenic driver of HCC. Methods: We analyzed SCNM1 expression and its relationship with clinical outcomes using The Cancer Genome Atlas and GSE14520 datasets and patient samples. Functional assays, including realtime-quantitative polymerase chain reaction, Western blotting, colony formation, and apoptosis analyses, were performed to elucidate the role of SCNM1 in HCC progression. We also evaluated the correlations between SCNM1 and its downstream targets DERL2 and BAG6. Results: Because of DNA copy number gain and arm-level amplification of chromosome 1q, SCNM1 expression was significantly elevated in HCC tissues. High SCNM1 expression correlated with poor prognosis and was identified as an independent prognostic factor. Via its splicing activity, SCNM1 promotes tumor growth, suppresses apoptosis, and regulates the expressions of DERL2 and BAG6, which contribute to cancer cell survival by facilitating protein degradation and suppressing apoptosis. Overexpression of SCNM1 is observed in multiple cancer types, suggesting a broad oncogenic role. Conclusions: Sodium channel modifier 1 plays a critical role in HCC progression by regulating the key pathways involved in tumor proliferation and survival. Its restricted expression in specific cancer types and influence on the minor spliceosome highlights its potential as a cancer-specific therapeutic target. Further research on SCNM1-targeted therapies may provide innovative strategies for treating HCC and other cancers.

DOI： 10.1245/s10434-025-17108-z

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記述言語：英語   出版者・発行元：Journal of Gastroenterology  

Background: Intracellular calcium (Ca²⁺) signaling regulates key cancer processes. Research findings suggest that the SEC61 complex, involved in protein translocation, contributes to calcium leakage from the endoplasmic reticulum. However, the mechanism by which SEC61 Translocon Subunit Gamma (SEC61G), a component of this complex, influences colorectal cancer (CRC) progression remains unclear. Methods: Bioinformatics analysis was performed using The Cancer Genome Atlas data sets to identify candidate genes on chromosome 7p, examine their association with DNA copy number amplification. In addition, SEC61G expression in CRC cells and tissues was validated using reverse-transcription quantitative polymerase chain reaction and immunohistochemistry. Moreover, in vitro and in vivo experiments were performed to investigate the effects of SEC61G overexpression and knockdown on CRC cell proliferation. Furthermore, publicly available single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) data were used to validate the role of SEC61G in CRC. Results: SEC61G was significantly upregulated in CRC tissues and was correlated with poor prognosis in patients with CRC. SEC61G overexpression enhanced cell proliferation and activated the EGFR pathway, promoting cell cycle progression from the G1 to S phase. In addition, SEC61G overexpression increased cytosolic Ca²⁺ levels, which activated EGFR signaling via calmodulin. Moreover, analyses of scRNA-seq and ST-seq data confirmed that SEC61G expression was higher in tumor epithelial cells and that it was co-expressed with EGFR pathway-related genes. Conclusions: SEC61G promotes CRC progression by regulating cytosolic Ca²⁺ concentration, EGFR activation, and cell cycle progression, highlighting its potential as a prognostic biomarker and therapeutic target in CRC.

DOI： 10.1007/s00535-025-02259-3

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記述言語：英語  

DOI： 10.1007/s13691-025-00748-z

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記述言語：英語   出版者・発行元：Anticancer Research  

Background/Aim: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor survival rates. Effective molecular-targeted therapies are urgently needed. This study aimed to identify novel candidate tumor-associated genes in ESCC by analyzing chromosomal amplification regions. Materials and Methods: DNA copy number variation (CNV) and mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE). Single-cell RNA sequencing data from Gene Expression Omnibus (GEO) were analyzed using Scanpy. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded (FFPE) ESCC tissues. PDCD10 was identified as a potential tumor-associated gene, and its association with clinicopathological factors and prognostic impact was evaluated using Kaplan-Meier survival and Cox regression analyses. Pathway analysis was performed to investigate the biological processes, and drug sensitivity profiling was conducted to identify compounds whose efficacy correlated with PDCD10 expression in ESCC cell lines. Results: PDCD10, a signaling protein involved in cell proliferation and vascular development, showed significant amplification and over-expression in ESCC cases. High PDCD10 expression was associated with poor prognosis. Single-cell RNA sequencing confirmed its tumor-specific expression. GSEA revealed enrichment of mTORC1 signaling, E2F, and Myc target pathways in high PDCD10-expressing tumors. Drug sensitivity analysis identified Azelaic acid and Rebamipide as compounds whose efficacy correlated with PDCD10 expression in ESCC cell lines. Conclusion: PDCD10 could be a novel tumor-associated gene associated with tumor progression and poor prognosis in ESCC. Azelaic acid and Rebamipide are candidate therapeutic agents targeting PDCD10.

DOI： 10.21873/anticanres.17527

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

症例は46歳女性で、基礎疾患の定期的なフォローアップとして実施された腹部CTで5cmの虫垂嚢胞性腫瘍の偶発的所見が認められ、当科に紹介された。腹部症状、リンパ節腫大、明らかな遠隔転移は認めなかった。腹腔鏡下回盲部切除術を合併症や腫瘍損傷なく施行した。手術中に腹腔内に散在性病変や粘液の蓄積は認められなかった。病理組織検査では、嚢胞性粘膜腔を覆う低異型度粘液性腫瘍細胞と、粘液腫瘍細胞成分の近傍にクロモグラニンA陽性の杯細胞カルチノイドが認められた。両細胞タイプの混合は認めなかったため、衝突腫瘍が示唆された。術後補助化学療法は行わず、術後1年間再発はなかった。虫垂の衝突腫瘍に関する報告は限られていたが、本症例の二つの腫瘍タイプは異なる前駆細胞から発生した可能性が考えられた。

記述言語：英語  

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

DOI： 10.11241/jsmtmr.40.9

CiNii Research

記述言語：英語   出版者・発行元：(一社)日本外科学会  

症例は61歳男性で、53歳頃から運動後の筋力低下を自覚しており、58歳頃には頸部筋力低下が進行して頸椎カラーを必要とした。頸部、四肢近位筋、体幹筋に著明な筋力低下と筋萎縮を認めた。血液検査でクレアチニンキナーゼ(CK)高値を認め、筋炎が疑われたが、筋炎関連抗体は陰性で、ステロイドおよび免疫抑制剤は無効であった。筋生検で筋線維下のグリコーゲン沈着を認め、PHKA1遺伝子エクソン領域17塩基欠失が判明し、糖原病IXd型と診断した。以後、CK上昇時は入院管理を行っていた。今回、右鼠径部膨隆と疼痛を主訴に受診し、超音波検査で右外鼠径ヘルニアと小腸脱出を認めた。AST 33U/L、LDH 376U/L、CK 598U/L、CRP 0.61mg/dLであり、超音波検査で右鼠径部に小腸脱出を伴う外鼠径ヘルニアを認めた。TEP法による鼠径ヘルニア修復術を施行した結果、合併症はなく、術後CKは425U/Lから291U/Lへ改善し、術後7日目に退院となった。

記述言語：英語   出版者・発行元：(一社)日本外科学会  

記述言語：英語   出版者・発行元：一般社団法人 日本外科学会  

<p><b>INTRODUCTION:</b> Glycogen storage disease type IX (GSD type IX) is caused by a deficiency in phosphorylase b kinase (PHK) and is classified into hepatic (IXa–c) and muscular (IXd) subtypes. GSD type IXd leads to exercise intolerance, rhabdomyolysis, and myoglobinuria owing to impaired glycogen breakdown. It is a rare and mild metabolic disorder, with only 19 reported cases of <i>PHKA1</i> mutations. To the best of our knowledge, this is the 1st report on the perioperative management of a patient with GSD type IXd.</p><p><b>CASE PRESENTATION:</b> A 61-year-old male presented with a right inguinal hernia requiring surgical repair. He had experienced muscle weakness since the age of 53, which progressed to severe neck muscle atrophy by the age of 58. Genetic testing confirmed a <i>PHKA1</i> mutation, leading to the diagnosis of GSD type IXd. He had previously undergone multiple surgeries without any complications. Given his underlying muscle weakness, totally extraperitoneal (TEP) inguinal hernia repair was performed to minimize postoperative pain and muscle damage. Postoperative monitoring revealed no rhabdomyolysis or myoglobinuria, and the patient was discharged without complications on POD 7.</p><p><b>CONCLUSIONS:</b> We successfully managed a patient with GSD type IXd perioperatively, without complications. Although this disease can cause rhabdomyolysis, the symptoms are often mild and may remain undiagnosed. Therefore, in patients with muscle weakness or elevated creatine kinase levels, careful surgical planning and perioperative monitoring are essential.</p>

DOI： 10.70352/scrj.cr.25-0239

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記述言語：英語   出版者・発行元：一般社団法人 日本外科学会  

<p><b>INTRODUCTION:</b> Stomach-partitioning gastrojejunostomy (SPGJ) is widely performed for malignant gastric outlet obstruction; however, its utility may be limited when the obstruction is located in the distal duodenum, where digestive fluid stasis can become problematic. We devised a novel modification, termed dual-outlet stomach-partitioning gastrojejunostomy (DO-SPGJ), to address this limitation by adding a 2nd gastrojejunostomy distal to the gastric partition.</p><p><b>CASE PRESENTATION:</b> A 67-year-old man with a tumor in the 3rd portion of the duodenum was diagnosed with squamous cell carcinoma without distant metastasis. The tumor was deemed unresectable due to invasion of the superior mesenteric artery. After 2 months of systemic chemotherapy, the patient developed symptoms of gastric outlet obstruction. A laparoscopic modified SPGJ was performed, involving a standard proximal gastrojejunostomy and an additional distal anastomosis between the gastric antrum and jejunum. The postoperative course was uneventful, and oral intake was successfully resumed.</p><p><b>CONCLUSIONS:</b> This dual-anastomosis approach allows for both food bypass and drainage of digestive secretions, addressing the limitation of conventional SPGJ in cases of distal duodenal obstruction. The technique may also mitigate complications related to fluid stagnation, such as cholangitis or pancreatitis. This novel technique may represent a viable surgical option for select patients with unresectable malignant obstruction of the distal duodenum, especially when fluid stasis is a concern.</p>

DOI： 10.70352/scrj.cr.25-0483

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記述言語：英語   出版者・発行元：一般社団法人 日本外科学会  

<p><b>INTRODUCTION:</b> Duodenal adenocarcinoma (DA) is an extremely rare malignancy, accounting for less than 1% of all gastrointestinal cancers. Most cases are diagnosed at an advanced stage, making curative resection difficult and leading to a poor prognosis. Recent advances in tumor immunology have identified microsatellite instability-high (MSI-H) and deficient mismatch repair (dMMR) as predictive biomarkers for immune checkpoint inhibitors (ICIs). However, clinical evidence regarding their efficacy in DA remains limited. We report 3 cases of MSI-H/dMMR DA.</p><p><b>CASE PRESENTATION:</b> (a) Case 1: A 55-year-old woman underwent pancreaticoduodenectomy for DA and was subsequently diagnosed with Lynch syndrome. She has remained recurrence-free for 5 years and 2 months postoperatively. (b) Case 2: A 75-year-old man with locally advanced DA and impaired oral intake declined pancreaticoduodenectomy. After gastrojejunostomy, pembrolizumab was administered, achieving durable disease control for 1 year and 10 months. (c) Case 3: A 65-year-old woman with DA invading adjacent organs received neoadjuvant pembrolizumab. Following bowel obstruction, she underwent partial small intestine resection, and pathological examination revealed a complete response. She has remained recurrence-free for 3 years and 2 months.</p><p><b>CONCLUSIONS:</b> Surgical resection remains the standard treatment for DA. However, in MSI-H/dMMR cases, ICIs are expected to be effective, as observed in other gastrointestinal cancers. Pembrolizumab may represent a useful neoadjuvant option, and in patients who achieve a pathological response, nonsurgical management could also be considered.</p>

DOI： 10.70352/scrj.cr.25-0645

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記述言語：英語   出版者・発行元：(一社)日本外科学会  

記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

記述言語：英語   出版者・発行元：Cancer Science  

Considering the cost and invasiveness of monitoring postoperative minimal residual disease (MRD) of colorectal cancer (CRC) after adjuvant chemoradiotherapy (ACT), we developed a favorable approach based on methylated circulating tumor DNA to detect MRD after radical resection. Analyzing the public database, we identified the methylated promoter regions of the genes FGD5, GPC6, and MSC. Using digital polymerase chain reaction (dPCR), we termed the “amplicon of methylated sites using a specific enzyme” assay as “AMUSE.” We examined 180 and 114 pre- and postoperative serial plasma samples from 28 recurrent and 19 recurrence-free pathological stage III CRC patients, respectively. The results showed 22 AMUSE-positive of 28 recurrent patients (sensitivity, 78.6%) and 17 AMUSE-negative of 19 recurrence-free patients (specificity, 89.5%). AMUSE predicted recurrence 208 days before conventional diagnosis using radiological imaging. Regarding ACT evaluation by the reactive response, 19 AMUSE-positive patients during their second or third blood samples showed a significantly poorer prognosis than the other patients (p = 9E-04). The AMUSE assay stratified four groups by the altered patterns of tumor burden postoperatively. Interestingly, only 34.8% of cases tested AMUSE-negative during ACT treatment, indicating eligibility for ACT. The AMUSE assay addresses the clinical need for accurate MRD monitoring with universal applicability, minimal invasiveness, and cost-effectiveness, thereby enabling the timely detection of recurrences. This assay can effectively evaluate the efficacy of ACT in patients with stage III CRC following curative resection. Our study strongly recommends reevaluating the clinical application of ACT using the AMUSE assay.

DOI： 10.1111/cas.16149

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

血漿中の微量な循環腫瘍DNA(ctDNA)のメチル化を検出することによりステージIIIの大腸癌患者の術後の微小残存病変(MRD)をモニターできるか評価した。公開データベースを解析し、FGD5、GPC6、MSC遺伝子のメチル化されたプロモーター領域を同定した。デジタルPCRを用いた特異的酵素を用いたメチル化部位のアンプリコンアッセイを「AMUSE」と名付けた。病理学的ステージIIIの大腸癌再発患者28例および無再発患者19例それぞれの術前術後の連続血漿検体、180検体および114検体を調べた。その結果、再発患者28例中22例がAMUSE陽性(感度78.6%)、無再発患者19例中17例がAMUSE陰性(特異度89.5%)であった。AMUSEはX線画像診断による従来の診断より208日早く再発を予測した。反応性応答による術後補助化学放射線療法(ACT)評価に関しては、2回目または3回目の採血でAMUSE陽性の患者19例は、他の患者より有意に予後不良であった。AMUSEアッセイにより、術後の腫瘍負荷の変化パターンによって4群に層別化された。以上より、AMUSEアッセイは、正確なMRDモニタリングに対する臨床的ニーズに対応し、普遍的な適用性、最小限の侵襲性、費用対効果により、タイムリーな再発の発見を可能にすることが示唆された。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/cas.16149.

記述言語：英語  

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記述言語：日本語   出版者・発行元：(一社)日本腹部救急医学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jgh.16223.

記述言語：英語   出版者・発行元：Journal of Gastroenterology and Hepatology Australia  

Background and Aim: This study aimed to clarify the prognostic value of various inflammation-based prognostic scores (IBPSs) in patients who underwent radical surgery for colorectal cancer (CRC) and to develop a novel prognostic index using IBPSs and other predictive factors. Methods: Data of 1157 patients who underwent radical surgery for CRC were reviewed. The predictive value of various IBPSs in determining the CRC prognosis was compared. A novel index score based on the IBPSs and other parameters that were associated with survival in patients with CRC was established, and its usefulness was evaluated. Results: The patients were randomly divided into the training (n = 694) and validation (n = 463) sets. Male sex (P = 0.0001), age ≥ 75 years (P < 0.0001), a carcinoembryonic antigen (CEA) level of > 5 (P = 0.0009), a C-reactive protein/albumin ratio (CAR) of ≥ 0.04 (P = 0.0033), and a prognostic nutritional index (PNI) of < 43.1 (P = 0.0004) were poor independent prognostic factors of overall survival. The novel index score was calculated based on the scores of these five prognostic factors. The Kaplan–Meier survival curves showed that the CRC patients with higher novel index scores in the training and validation datasets had poorer overall survival. Conclusions: CAR and PNI were superior to other IBPSs for predicting the prognosis of CRC patients. The novel index score established based on sex, age, CEA level, CAR, and PNI can predict the prognosis of CRC with more precise and clearer stratification than the individual parameters alone.

DOI： 10.1111/jgh.16223

Scopus

記述言語：英語   出版者・発行元：Journal of Laparoendoscopic and Advanced Surgical Techniques  

Background: This study aimed to clarify the safety and efficacy of laparoscopic surgery for colorectal perforation by comparing the clinical outcomes between laparoscopic and open emergency surgery for colorectal perforation. Materials and Methods: We retrospectively reviewed the data of 116 patients who underwent surgery for colorectal perforation. The patients were categorized into two groups: the open group included patients who underwent laparotomy, and the laparoscopic group included those who underwent laparoscopic surgery. Clinical and operative characteristics and postoperative outcomes were evaluated. Results: The open and laparoscopic groups included 67 and 49 patients, respectively. More than half of the patients in both groups developed perforation in the sigmoid colon (open, 58.2%; laparoscopic, 61.2%). The most common cause of perforation was diverticulum, followed by colorectal cancer. The mean intraoperative blood loss was significantly lower in the laparoscopic group than in the open group (70.0 mL versus 160.3 mL; P = .0290). The incidence of surgical site infection was lower in the laparoscopic group than in the open group (2.0% versus 13.4%; P = .0430). There were no significant differences in either the short- or long-term outcomes between the two groups. Univariate and multivariate analyses showed that the choice of surgical approach (open versus laparoscopic) did not affect overall survival in patients with colorectal perforation. Conclusion: The laparoscopic approach for colorectal perforation in an emergency setting can be safely performed and provides certain advantages over an open approach in suitable patients.

DOI： 10.1089/lap.2022.0423

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1089/lap.2022.0423.

記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

症例は60歳女性で、嚥下障害を主訴に当院を受診した。皮膚筋炎と乳癌の既往があった。食道内視鏡検査では、下部胸部食道に黒色色素沈着を伴う60mm大の暗褐色隆起性腫瘍を認めた。生検標本の病理組織学的検査では、楕円形の過色素性核、時折明瞭な核小体、境界の不鮮明な細胞質、メラニン色素を有する異型円形細胞を認めた。免疫組織化学染色ではヒトメラノーマブラック45とメラニンAが陽性であった。T3N0M0ステージII食道原発悪性黒色腫と診断した。根治的食道切除術を施行し、術後治療としてニボルマブ(240mg/body)を2週間毎に投与した。2コース後に両側性気胸が発生したが、胸腔ドレナージにより回復した。ニボルマブ治療を術後1年以上経過した時点でも継続し、再発なく生存した。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13691-022-00582-7.

記述言語：英語   出版者・発行元：(一社)日本外科学会  

症例は73歳男性で、内視鏡検査で食道腫瘍を指摘され精査加療目的に当院紹介となった。29年前に胃癌に対する幽門側胃切除、12年前に結腸癌に対する横行結腸切除、11年前に残胃癌に対する内視鏡下粘膜下層剥離術(ESD)を受けていた。10年前に上部胸部食道癌に対するESD、7年前に喉頭・下咽頭癌に対する内視鏡下咽喉頭切除、4年前に再発性喉頭癌に対する化学放射線療法、2年前に上部胸部食道癌に対するESD、1年前に下咽頭癌に対する経口的喉頭鏡手術を受けていた。臨床検査では異常所見はみられず、内視鏡検査で歯列弓から40cmの部位に粘膜下腫瘍に類似する表面平滑な円形病変を認め、超音波内視鏡にて第二層に低エコー性病変が検出された。組織診では肉腫を示唆する所見であったが確定診断には至らず、下部食道切除、残胃切除、空腸再建術を行った。横行結腸、残胃、膵および肝の吻合部に強固な癒着が生じていたためこれを剥離し、続いて下部食道切除術、残胃切除、食道空腸吻合術を施行した。術後の組織病理学的検査では粘膜下層に花筵状パターンを呈する多形性紡錘細胞浸潤を認め、免疫組織化学染色の結果と合わせて未分化型多形性肉腫と診断した。重篤な合併症の発症なく1ヵ月後に退院となり、その後1年、局所再発や遠隔転移なく経過している。

記述言語：英語   出版者・発行元：Obesity Surgery  

Purpose: Patients who have undergone bariatric surgery are at risk for gallstone formation. However, the incidence of gallstone formation after bariatric surgery has not been adequately studied in the Japanese population. We aimed to elucidate the incidence and risk factors for gallstone formation after laparoscopic sleeve gastrectomy (LSG) for Japanese patients with severe obesity. Methods: We conducted a retrospective cohort study among patients with severe obesity treated with LSG between April 2017 and June 2020 at two institutions. Patients who had received previous cholecystectomy, had preoperative gallstones, and had received postoperative prophylactic ursodeoxycholic acid were excluded. Body weight, body mass index, and blood data were collected at each follow-up visit before and after the surgery. Follow-up abdominal ultrasonography was performed 6–12 months after surgery, and the incidence of gallstones was calculated. The association between the data and gallstone formation was evaluated. Results: During the study period, we performed LSG for 98 patients. Of these, 61 cases remained by above conditions and were examined using abdominal ultrasonography over 6 months after surgery. The incidence of gallstones was 23.0% and that of symptomatic gallstones was 3.3%. Anti-Helicobacter pylori antibody seropositive and titer were the only factors that showed significant association with de novo gallstone formation after LSG. Conclusions: Anti-Helicobacter pylori antibody seropositive may be associated with de novo gallstone formation after LSG for Japanese patients with severe obesity. Graphical abstract: [Figure not available: see fulltext.]

DOI： 10.1007/s11695-022-06253-z

Web of Science

Scopus

PubMed

記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

記述言語：英語   出版者・発行元：Surgery Open Science  

Background: Inflammation-based prognostic scores have prognostic value in cancer or cardiovascular disease patients. This study evaluated the prognostic value of inflammation-based prognostic scores in colorectal perforation patients. Methods: Data of 97 patients who underwent surgery for colorectal perforation were reviewed. We calculated various inflammation-based prognostic scores and analyzed the relationship between inflammation-based prognostic score and hospital mortality due to colorectal perforation. Results: Multivariate analyses of hospital mortality revealed neutrophil–lymphocyte ratio (P = .0021), C-reactive protein/albumin ratio (P = .0224), and prognostic nutritional index (P = .0078) as independent predictive factors. The Kaplan–Meier analysis showed that patients who met all of the following parameters avoided hospital death: neutrophil–lymphocyte ratio < 30, prognostic nutritional index ≥ 27.2, age < 75 years, and perforation of the left colon. Conclusion: Neutrophil–lymphocyte ratio, C-reactive protein/albumin ratio, and prognostic nutritional index were superior to other inflammation-based prognostic scores in predicting mortality of colorectal perforation. Neutrophil–lymphocyte ratio, prognostic nutritional index, patient's age, and sidedness of the perforation site may be useful parameters to identify subgroups in which a favorable prognosis can be expected.

DOI： 10.1016/j.sopen.2022.01.003

Scopus

記述言語：英語   出版者・発行元：Jgh Open  

Background and Aim: Several inflammation-based scores have prognostic value for patients diagnosed with various cancers. However, using only a single inflammation-based prognostic score may be unreliable, as the cut-off values and relative usefulness among various inflammation-based prognostic scores vary. We established a new combined index of four inflammation-based prognostic scores, namely the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, prognostic index, and prognostic nutritional index, and assessed its usefulness to predict the prognosis of gastric cancer. Methods and Results: We reviewed the data of 635 patients who underwent surgical resection for gastric cancer. We calculated the combined index as the total value of each of the four included inflammation-based prognostic scores and analyzed the relationship between the combined index and postoperative prognosis of gastric cancer. The new combined index was represented as a value between 0 and 6 in each patient. The Kaplan–Meier survival curves showed that patients whose combined index was 0 had good long-term outcomes, while the prognosis of patients whose combined index ranged from 4 to 6 was poor. Conclusion: This new combined index was strongly associated with poor prognosis in patients who underwent surgery for gastric cancer. It is inferred that it can predict patient prognosis after surgical resection for gastric cancer with a stronger correlation and clearer stratification than a single inflammation-based prognostic score.

DOI： 10.1002/jgh3.12723

Scopus

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