BACKGROUND:First-line chemotherapy with maintenance therapy is expected to be well-tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). This study evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab (Bev) as maintenance therapy for mCRC, omitting both oxaliplatin and fluoropyrimidines. MATERIALS AND METHODS:Patients with untreated mCRC initially received induction chemotherapy with fluoropyrimidine, oxaliplatin plus bevacizumab for 3-4 months. After achieving stable disease or better on imaging, 52 patients transitioned to maintenance therapy with TAS+Bev: TAS-102 (35 mg/m2, twice daily on days 1-5 and 8-12) plus Bev (5.0 mg/kg on Days 1 and 15, intravenously). Progression-free survival 1 (PFS1), defined as the time from the start of maintenance therapy to disease progression or death, was evaluated as the primary endpoint. RESULTS:The median cumulative dose of oxaliplatin during induction was 529 mg/m2. Median PFS1 during TAS+Bev maintenance was 8.7 months (95% CI: 5.5-12.3). The response rate and disease control rate during maintenance were 59.6% and 94.2%, respectively. Oxaliplatin reintroduction was feasible in 53.8% (28/52) of patient with a median total first-line chemotherapy duration was 16.2 months (95% CI: 14.5-20.6). Safety outcomes, including dose intensity and adverse events, were acceptable. CONCLUSION:This strategy of switching to first-line maintenance therapy with TAS+Bev demonstrated promising efficacy and safety. This strategy effectively avoided cumulative neurotoxicity, preserved quality of life and enabled reintroduction of oxaliplatin, suggesting it may represent a promising alternative strategy for patients ineligible for prolonged oxaliplatin-based treatment. Overall survival analysis is currently ongoing. [UMIN Trial ID: UMIN000031317].

BACKGROUND:The relationship between the radiographic portal vein-superior mesenteric vein (PV-SMV) involvement and pathological PV-SMV (pPV) invasion has been established in upfront surgery cases of pancreatic cancer (PC); however, evidence remains limited for patients receiving neoadjuvant therapy (NAT). This study aimed to evaluate the association of radiographic findings with pPV invasion in patients treated with NAT, and to examine whether this association differs between patients treated with neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT). METHODS:We retrospectively analyzed patients with PC whose tumors contacted the PV-SMV on radiographic imaging before or after NAT. The relationship between radiographic findings and pPV invasion was evaluated in subgroups defined by pre- and post-NAT imaging findings. RESULTS:Tumor size, PV-SMV contact length, and contact angle were significantly reduced in post-NAT imaging. Radiographic PV-SMV involvement showed limited association with pPV invasion in the entire cohort. The overall pPV invasion rate was 15% and did not differ between the NAC and NACRT groups (17% vs. 13%, p = 0.790). Among patients with a pre-NAT tumor size of < 20 mm, the pPV invasion rate was significantly lower in the NACRT group than in the NAC group (29% vs. 0%, p = 0.007). This difference was not observed in patients with a pre-NAT tumor size ≥ 20 mm (12% vs. 19%, p = 0.438). Across other radiographic classifications, pPV invasion rates remained comparable between treatment groups. CONCLUSIONS:The association of radiographic findings with pPV invasion differs between patients treated with NAC and NACRT in patients with small tumors.

Although a low skeletal muscle mass index (SMI) leads to poor overall survival (OS) after gastrectomy in patients with gastric cancer, the cutoff value that predicts long-term survival in patients with normal SMI remains unclear. This study aimed to determine the cutoff SMI value for predicting OS in patients with normal SMI. This multicenter retrospective cohort study included patients with normal SMI who underwent radical gastrectomy for pStage I–III primary gastric cancer between January 2011 and December 2016. The patients were randomly divided at a 6:4 ratio into a training set, which examined the cutoff values for SMI, and a validation set, which validated the cutoff values. Patients were classified into high and low SMI groups according to the cutoff values. We compared OS between the high- and low-SMI groups using log-rank test and identified prognostic factors using Cox proportional hazards regression analysis. Of the 2516 patients, 1389 (55.2

Mediastinoscopic esophagectomy for thoracic esophageal cancer may reduce pulmonary morbidity; however, upper mediastinal lymphadenectomy, particularly along the left recurrent laryngeal nerve (station 106recL), remains technically challenging. We developed a transhiatal-dominant mediastinoscopic subtotal esophagectomy using the da Vinci SP system for both the abdominal and cervical phases. After completing lower and mid-mediastinal lymphadenectomy while preserving the mediastinal pleura, transhiatal dissection is advanced beyond the carina into the upper mediastinum to perform 106recL lymphadenectomy along the left recurrent laryngeal nerve from its turning point beneath the aortic arch. The cervical phase is limited to confirming and completing the cranial 106recL dissection. Two patients had no postoperative morbidity, and bilateral vocal fold mobility was confirmed by laryngoscopy on postoperative day 3. Transhiatal/cervical console times were 180/71 and 200/45 min, respectively, and postoperative hospital stay was 13 days in both cases. This transhiatal-dominant, dual-phase da Vinci SP approach appears feasible for thoracic esophageal cancer.

Nivolumab has become a standard treatment for advanced or recurrent esophageal squamous cell carcinoma (ESCC). However, reliable blood-based biomarkers predictive of response remain undefined. We investigated dynamic changes in peripheral PD-1+ CD8+ T-cell subsets during nivolumab therapy and evaluated their clinical significance. Fifty-seven patients with advanced or recurrent ESCC treated with nivolumab were enrolled in this retrospective observational study. Peripheral blood mononuclear cells were collected before treatment and at 1, 2, and 4 weeks after initiation. Flow cytometric analyses evaluated the expression of CD103, CD45RA, Tim-3, LAG-3, TIGIT, and Ki-67 among nivolumab-binding PD-1+ CD8+ T cells. Associations between immunophenotypic changes, treatment response, survival outcomes, immune-related adverse events (irAEs), and nutritional/inflammatory indices were analyzed. The objective response rate was 24.6

BACKGROUND:Squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA) are routinely monitored after definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC) in Japan, but their clinical significance remains unclear. METHODS:We analyzed data from patients with resectable ESCC treated with dCRT in the JCOG0502 and JCOG0909 trials, who underwent intensive protocolized surveillance with computed tomography (CT), esophagogastroduodenoscopy (EGD), SCC-Ag, and CEA. Tumor marker positivity was defined as exceeding the cut-off value at least once, at two consecutive measurements, or at three consecutive measurements during follow-up. Sensitivity and specificity were calculated for SCC-Ag and CEA at 0.1-ng/mL increments to determine whether any cut-off met the predefined performance criteria (sensitivity ≥60% and specificity ≥70%). RESULTS:This study included 239 patients (stage I/II/III = 147/58/34 [UICC 6th edition]), among whom 38% (91/239) experienced disease progression or recurrence. The median baseline SCC-Ag and CEA levels were 1.0 ng/mL (interquartile range [IQR], 0.8-1.5) and 2.3 ng/mL (IQR, 1.6-3.6), respectively, with a median of 16 measurements each (IQR, 8-19 for SCC-Ag; 8-20 for CEA). The highest specificities with sensitivity ≥60% were 19.6% for SCC-Ag (cut-off, 1.5 ng/mL) and 20.3% for CEA (cut-off, 2.2 ng/mL), but neither met the predefined criteria. CONCLUSIONS:In this pooled cohort of patients with resectable ESCC who underwent dCRT and intensive protocolized CT and EGD surveillance, routine SCC-Ag and CEA monitoring showed limited incremental diagnostic value. The relevance of these findings to higher-risk cohorts and less intensive surveillance settings warrants further study.

BACKGROUND Appendectomy reduces the occurrence and controls the severity of ulcerative colitis (UC); however, how it exerts these effects remains unclear. AIM To elucidate the contribution of appendix-associated immune responses in intestinal inflammation and their relevance to the effects of appendectomy in UC. METHODS This study was conducted at Graduate School of Medicine, The University of Osaka. We included patients undergoing surgery for UC and those without inflammatory bowel disease undergoing colorectal cancer surgery as controls. Appendiceal tissues were collected from both patient groups, and macroscopically normal appendices located at least 10 cm from the tumor were used as controls. Single-cell RNA sequencing, immunohistochemistry, and flow cytometry were performed. RESULTS Single-cell RNA sequencing identified T, B, plasma, innate lymphoid, and mast cells, together with other myeloid cells in appendiceal tissues. A hallmark feature of the appendices in UC was an increase in immunoglobulin G (IgG)-expressing plasma cells. Immunohistochemistry revealed significantly reduced IgG levels in the large intestines of patients with UC who had undergone an appendectomy compared with levels in those who did not undergo appendectomy. Repertoire analysis revealed an increased production of IgG antibodies bearing an integrin-binding motif at antigen-recognition sites in patients with UC. CONCLUSION The appendix is a major site of pathogenic IgG antibody production in patients with UC, providing the immunological basis for appendectomy as a treatment for UC.

This study assessed the impact of an institutional certification system that was newly introduced by the Japanese Gastric Cancer Association on short-term surgical outcomes in patients with gastric cancer using data from the National Clinical Database. A retrospective cohort study of distal gastrectomy and total gastrectomy procedures performed between January 2020 and December 2022 was conducted. The institutions were classified into three categories: type A, type B, and non-certified institutions, in decreasing order of certification stringency. The primary outcome was the incidence of grade ≥ IIIa postoperative complications based on the Clavien–Dindo classification system. The secondary outcome was surgery-related mortality. Logistic regression with risk adjustment, estimated using generalized estimating equations, was used to account for intra-cluster correlation. There was no significant difference in the risks of distal gastrectomy-related complications across the three institution types. However, type A- (odds ratio (OR) 0.39, 95

ABSTRACT Objectives Microsatellite instability‐high (MSI‐H) or mismatch repair‐deficient (dMMR) colorectal cancer (CRC) is a distinct subtype. Although immune checkpoint inhibitors are used for advanced cases, data on its frequency and characteristics, especially in resectable Asian CRC, remain limited. This study investigated MSI‐H/dMMR frequency and features in Japanese patients to support future personalized treatment strategies. Methods This multicenter observational study included 1464 patients with pathologically confirmed primary CRC enrolled from April 2024 to March 2025 at 25 institutions affiliated with Osaka University. MSI/MMR status and clinicopathological data were extracted from a prospectively maintained database. Univariate analyses were performed to evaluate factors associated with MSI‐H/dMMR. Results Among 1464 patients, 137 (9.4%) had MSI‐H/dMMR tumors. MSI/MMR testing was conducted preoperatively in 772 patients (52.7%). MSI‐H/dMMR was more frequent in patients aged ≥ 70 years, in females (OR = 1.46, p = 0.036), and in tumors located in the cecum, ascending, or transverse colon ( p < 0.001). It was significantly less common in Stage IV disease (OR = 0.22, p < 0.001) and KRAS ‐mutant tumors (OR = 0.22, p < 0.001), but strongly associated with BRAF V600E mutation (OR = 52.41, p < 0.001), poorly differentiated adenocarcinoma (OR = 7.17, p < 0.001), and mucinous adenocarcinoma (OR = 3.10, p = 0.002). Conclusions MSI‐H/dMMR CRC accounted for 9.4% of Japanese patients, including resectable cases, and exhibited distinct clinical and molecular characteristics. These findings provide a basis for future personalized treatment strategies in this population.

Combination immune checkpoint inhibition with ipilimumab plus nivolumab (NIVO + IPI) has shown promising efficacy in advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate648 trial. However, real-world evidence regarding its safety, efficacy as first-line therapy, and host-related biomarkers relevant to immunotherapy remains limited. This multicenter retrospective study evaluated a large cohort of 111 patients with unresectable advanced or recurrent ESCC who received first-line NIVO + IPI therapy. Treatment response, treatment-related adverse events, and prognostic factors were analyzed. The objective response and disease control rates in cases with target lesions were 44.0

Risk assessment is essential for planning esophagectomy in patients with esophageal or gastro-esophageal junction (GEJ) cancers. However, previous reports using only preoperative variables (preoperative risk models) have poorly predicted postoperative anastomotic leakage. This study aimed to develop a novel risk model for anastomotic leakage using a combination of preoperative, intraoperative, and postoperative variables (perioperative risk model). Clinical data of 20,113 patients with esophageal or GEJ cancer who underwent esophagectomy followed by reconstruction between 2016 and 2019 were retrieved from the National Clinical Database (NCD), a Japanese web-based nationwide registry. Preoperative and perioperative risk models for anastomotic leakage were developed using only preoperative variable and a combination of preoperative, intraoperative, and postoperative variables within 72 h, respectively. The performance of the perioperative risk model was validated using NCD data of 5,147 esophagectomies registered in 2020. In the overall population, 11,360 (45.0

Heat-not-burn cigarettes (HNBCs) are marketed as reduced-risk combustible cigarette alternatives. However, their impact on surgical outcomes after invasive procedures, including esophagectomy, remains unclear. To evaluate the association between preoperative HNBC use and short-term outcomes after oncological esophagectomy. This retrospective cohort study utilized Japanese National Clinical Database data from patients who underwent esophagectomy for thoracic esophageal cancer between January 2019 and December 2021. The exposure was self-reported HNBC use within 1 year before surgery. The primary outcome was operative mortality. Secondary outcomes included life-threatening complications (Clavien–Dindo classification ≥ IV), anastomotic leakage, postoperative pneumonia, surgical site infection, and prolonged mechanical ventilation (≥ 48 h). Associations between HNBC use and outcomes were assessed using multilevel logistic regression models, adjusting for patient demographics, comorbidities, combustible cigarette smoking history, alcohol use, and tumor characteristics. Of 17,797 patients, 589 (3.3