Language：English   Publisher：Annals of Surgical Oncology  

Background: The ratio of the fecal short-chain fatty acid (SCFA) to lactic acid concentrations (APB-L ratio) is a useful indicator for the healthiness of the intestinal microenvironment. A recent study indicated that the low APB-L ratio can be a predictor of postoperative infectious complications (POICs) in patients undergoing pancreaticoduodenectomy. However, the predictive power of the APB-L ratio in other highly invasive surgeries, such as esophagectomy, is still unclear. This study investigated whether the APB-L ratio can be a sensitive predictor of POICs in patients undergoing esohpagectomy. Methods: A total of 129 patients undergoing esohpagectomy with gastric conduit reconstruction were included in this study. Preoperative fecal samples were analyzed for SCFA and lactic acid concentrations. The associations between clinical characteristics, POICs, and the APB-L ratio were analyzed. Preoperative and intraoperative risk factors for POICs were explored via multivariate logistic regression analysis. Results: Postoperative infectious complications were observed in 34 patients (26%), including surgical site infections in 18 patients (14%). A low APB-L ratio was significantly associated with higher POICs and surgical site infections risk (both p < 0.05). A low APB-L ratio was identified as an independent risk factor for POICs, with an odds ratio of 3.62 (95% confidence interval, 1.44–9.10, p = 0.006). Conclusions: The APB-L ratio measured with preoperative fecal organic acid concentrations is useful to assess the risk of POICs for esohpagectomy. The results also imply the importance of maintaining a healthy intestinal metabolism (thus high APB-L ratio) to reduce POICs before highly invasive surgery.

DOI： 10.1245/s10434-025-17347-0

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Language：English   Publisher：Anticancer Research  

Background/Aim: Total neoadjuvant therapy (TNT) is promising in reducing distant metastasis and facilitating nonoperative management (NOM) in locally advanced rectal cancer. However, concerns arise regarding the quality of total mesorectal excision (TME) and local regrowth after NOM. This study investigated the feasibility of a response-guided strategy centered on induction chemotherapy to enhance patient selection and outcomes. Patients and Methods: From 2020 to 2023, patients with clinical Stage II/III lower rectal cancer, located within 10 cm from the anal verge, were enrolled. Induction chemotherapy used either an oxaliplatin-based doublet or triplet regimen over three months. Long-course chemoradiotherapy was administered selectively based on multidisciplinary evaluations, targeting either NOM or minimizing local recurrence for patients with mesorectal fascia (MRF) involvement. Results: Eighteen consecutive patients were enrolled. At first restaging, 39% (seven patients) achieved a complete or near-complete response. Consequently, five patients underwent NOM after chemoradiotherapy, achieving a 100% TME-free survival rate. R0 resections were successful in all 13 surgical cases, including two patients with residual tumor who underwent TNT and one patient with MRF involvement even after TNT, as well as 10 patients without MRF involvement treated solely with induction chemotherapy, omitting chemoradiotherapy. Conclusion: Induction chemotherapy effectively filters suitable candidates for NOM in locally advanced rectal cancer, suggesting a potential to omit routine radiotherapy. This approach highlights personalized treatment strategies and aims to enhance patients' quality of life by reducing unnecessary surgeries and preserving rectal function.

DOI： 10.21873/anticanres.17700

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DOI： 10.1245/s10434-025-17556-7

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Language：English   Publisher：Anticancer Research  

Background/Aim: Available data on the immune profiles of regional lymph nodes in individuals with esophageal squamous cell carcinoma (ESCC) are limited. This study investigated the immune profiles of proximal regional lymph nodes (PLNs) and evaluated the association between PLNs and the outcomes of patients with ESCC. Patients and Methods: This study included 39 patients with ESCC who underwent subtotal esophagectomy with three-field lymph node dissection. The immune profiles of tumor-infiltrating lymphocytes and PLNs were evaluated through immunohistochemistry. Furthermore, the impact of this immune profile on long-term outcomes was analyzed. Results: Cox proportional-hazards analysis for overall survival revealed that ypT ≥3 [hazard ratio (HR)=8.91; 95% confidence interval (CI)=1.59-49.8] and high FOXP3 status in PLNs (HR=4.29; 95%CI=1.06-17.4) are significant independent prognostic factors. Meanwhile, analysis of disease-free survival (DFS) revealed that ypT ≥3 (HR=5.52; 95%CI=1.15-26.6) and ypN ≥1 (HR=7.74; 95%CI=1.58-37.9) are independent prognostic factors. Furthermore, high FOXP3 status in PLNs was associated with low DFS rate, although the association was not statistically significant (HR=1.70; 95%CI=0.58-5.02). Conclusion: High FOXP3 status in PLNs is associated with poor prognosis in patients with ESCC.

DOI： 10.21873/anticanres.17466

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PubMed

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407214615

CiNii Research

Language：English   Publisher：Cancer Medicine  

Purpose: A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. Methods: Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m² per day) and cisplatin (70 mg/m² per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m² per day) on days 1–5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. Results: Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. Conclusion: Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

DOI： 10.1002/cam4.6974

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Language：English   Publisher：Cancer Chemotherapy and Pharmacology  

Purpose: This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer. Methods: Preoperative DCF (docetaxel, 70 mg/m²/day, day 1; cisplatin, 70 mg/m²/day, day 1; fluorouracil, 750 mg/m²/day, days 1–5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients. Results: According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3′-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027). Conclusions: ABCC2-24C > T (rs717620), TYMS 3′-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.

DOI： 10.1007/s00280-023-04607-7

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Language：English   Publisher：Nagoya Journal of Medical Science  

In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m²) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.

DOI： 10.18999/nagjms.86.1.43

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407214373

CiNii Research

Language：English   Publisher：Cancers  

This retrospective study examined early the predictive factors for successful conversion surgery (CS) with R0 resection in patients with metastatic gastric cancer (MGC) who underwent systemic chemotherapy. This study included 204 patients diagnosed with metastatic gastric adenocarcinoma, who received chemotherapy between 2009 and 2019. Of these patients, 31 (15%) underwent CS with R0 resection. The incidence of CS with R0 resection was not affected by the volume of metastatic lesions or the presence of peritoneal metastasis. The overall survival time of the CS with R0 resection group was significantly longer than that of the non-CS group (hazard ratio, 0.12; 95% confidence interval, 0.07–0.23; p < 0.0001), with a 5 year overall survival rate of 50.2%. Multivariate analysis of 150 patients, excluding those with disease progression until the initial Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, showed that carcinoembryonic antigen > 5.0 ng/mL at the initial RECIST evaluation was an independent, significant, and unfavorable predictor of CS with R0 resection (odds ratio, 0.21; p = 0.0108), whereas systemic chemotherapy with trastuzumab for HER2-positive cancer was a favorable factor (odds ratio, 4.20; p = 0.0119). Monitoring serum carcinoembryonic antigen levels during chemotherapy may be a useful predictor of the CS implementation in patients with MGC.

DOI： 10.3390/cancers15215197

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Language：English   Publisher：Japanese Journal of Clinical Oncology  

Background: Anastomotic leakage (AL) is one of the most critical postoperative complications after subtotal esophagectomy in patients with esophageal cancer. This study attempted to develop an optimal scoring system for stratifying the risk for AL. Methods: The study included 171 patients who underwent subtotal esophagectomy for esophageal cancer followed by esophagogastrostomy in the cervical region from January 2011 to April 2021 at Nagoya University Hospital. AL was defined by radiologic or endoscopic evidence of anastomotic breakdown using some modalities. A risk scoring system for an early diagnosis of AL was established using factors determined in the multivariate analysis. A score was calculated for each patient, and the patients were classified into three categories according to the risk for AL: low-, intermediate- and high-risk. The trend of the risk for AL among the categories was evaluated. Results: Twenty-nine patients (17%) developed AL. Multivariate analysis demonstrated that sinistrous gross features of drain fluid (P < 0.001; odds ratio (OR), 10.2), radiologic air bubble sign (P < 0.001; OR, 15.0) and the level of drain amylase ≥280 U/L on postoperative Day 7 (P < 0.001; OR, 9.0) were significantly associated with AL. According to the matching number of the above three risk factors and categorization into three risk groups, the incidence of AL was 6.1% (8/131) in the low-risk group, 45.5% (15/33) in the intermediate-risk group and 85.7% (6/7) in the high-risk group (area under curve, 0.81; 95% confidence interval, 0.72-0.90). Conclusions: The present AL-risk scoring system may be useful in postoperative patient care after subtotal esophagectomy.

DOI： 10.1093/jjco/hyad072

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Language：English   Publisher：Anticancer Research  

Background/Aim: In patients with esophageal cancer, muscle loss induced by neoadjuvant therapy before esophagectomy is correlated with poor prognosis. However, little is known about the causes of muscle loss. Thus, the purpose of this retrospective study was to clarify the risk factors for muscle loss during neoadjuvant therapy. Patients and Methods: Patients with esophageal cancer who underwent neoadjuvant therapy before esophagectomy between 2009 and 2020 were investigated (n=132). The patients received either cisplatin plus 5-fluorouracil (CF); docetaxel, cisplatin plus 5-fluorouracil (DCF); or CF with radiotherapy as neoadjuvant therapy. The cross-sectional areas of the bilateral psoas muscles were measured at the level of the third lumbar vertebra using CT, before and after neoadjuvant therapy, and psoas muscle loss was calculated. The patients were divided into the high muscle loss group with 5% or more muscle loss or the low muscle loss group with less than 5% loss. Correlations between muscle loss and clinical factors were evaluated. Results: The median value of psoas muscle loss was 5.30%. Psoas muscle loss was significantly correlated with a poor 3-year overall survival rate (p=0.034). Multivariate analysis showed that the independent factors associated with muscle loss were age ≥70 years [odds ratio (OR)=2.43, p=0.022], treatment with DCF (OR=3.47, p=0.034), and a poor response to neoadjuvant therapy (OR=2.68, p=0.028). Conclusion: A regimen of DCF was a major trigger of muscle loss during neoadjuvant therapy.

DOI： 10.21873/anticanres.16278

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407213704

CiNii Research

Language：English   Publisher：Scientific Reports  

Gastric stump cancer (GSC) has distinct clinicopathological characteristics from primary gastric cancer. However, the detailed molecular and pathological characteristics of GSC remain to be clarified because of its rarity. In this study, a set of tissue microarrays from 89 GSC patients was analysed by immunohistochemistry and in situ hybridisation. Programmed death ligand 1 (PD-L1) was expressed in 98.9% of tumour-infiltrating immune cells (TIICs) and 6.7% of tumour cells (TCs). Epstein–Barr virus (EBV) was detected in 18 patients (20.2%). Overexpression of human epidermal growth factor receptor 2 and deficiency of mismatch repair (MMR) protein expression were observed in 5.6% and 1.1% of cases, respectively. Moreover, we used next-generation sequencing to determine the gene mutation profiles of a subset of the 50 most recent patients. The most frequently mutated genes were TP53 (42.0%) followed by SMAD4 (18.0%) and PTEN (16.0%), all of which are tumour suppressor genes. A high frequency of PD-L1 expression in TIICs and a high EBV infection rate suggest immune checkpoint inhibitors for treatment of GSC despite a relatively low frequency of deficient MMR gene expression. Other molecular characteristics such as PTEN and SMAD4 mutations might be considered to develop new treatment strategies.

DOI： 10.1038/s41598-021-83711-1

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Language：English   Publisher：Surgical Endoscopy  

Background: Insufficient information is available about the long-term outcomes of patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) who undergo laparoscopic transhiatal approach (LTH). Here we evaluated the oncological safety of LTH for patients with Siewert type II AEG compared with the open transhiatal approach (OTH). Methods: Subjects included 79 patients with Siewert type II AEG who underwent gastrectomy combined with lower esophagectomy from 2008 to 2018 at our institution. Overall survival (OS), recurrence-free survival (RFS), status of adjuvant chemotherapy, late-phase complications, and recurrence patterns were compared between the OTH (n = 29) and LTH groups (n = 43). Results: The median observation periods were 60 months (6–120 months) and 36 months (1–88) for the OTH and LTH groups, respectively. The 5-year OS rates were significantly different: 74% (95% CI 71–77%) and 98% (95% CI 97–99) in the OTH and LTH groups (HR 0.10, 95% CI 0.01–0.83), respectively, though the OTH group included more patients with advanced disease. After stratification, according to pathological stage to adjust for selection bias, the 5-year OS and RFS rates were longer, but not significantly different among patients in the LTH group with pStage III (HR 0.42, 95% CI 0.05–3.47; HR 0.47, 95% CI 0.10–2.12, respectively). Recurrence patterns were similar in the both groups. Conclusions: Long-term outcomes of the LTH group were not inferior to those of the OTH group, suggesting the possibility of LTH as a treatment option for selected patients with Siewert type II AEG.

DOI： 10.1007/s00464-020-07406-w

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Language：English   Publisher：Journal of Surgical Oncology  

Background and Objectives: The lymphatic flow around the esophagogastric junction is complicated. Therefore, it is unclear whether lymphatic invasion in the esophageal region (eLI) and in the gastric region (gLI) in patients with adenocarcinoma of the esophagogastric junction (AEG) equally affect the incidence of lymph node metastases (LNM), and consequently, survival. Methods: We retrospectively reviewed clinicopathological data of 175 patients with AEG between January 2008 and July 2017. Risk factors for LNM and impacts of eLI or gLI on survival outcomes were investigated. Results: eLI was identified in 34% of the patients (59/175). By multivariate analysis, eLI was associated with an increased risk of both mediastinal LNM (odds ratio [OR] = 2.98, 95% confidence interval [CI]: 1.26-7.05) and abdominal LNM (OR = 5.44, 95% CI: 1.95-15.20). The 5-year overall survival for patients with eLI (53%) was significantly worse than for patients without eLI (76%) (hazard ratio = 2.45, 95% CI: 1.37-10.01). gLI was not selected in either of these analyses. Conclusions: Positive eLI was strongly associated with mediastinal and abdominal LNM and worse survival in patients with AEG compared with gLI. In the histopathological examination, it seems to make sense to assess eLI and gLI separately.

DOI： 10.1002/jso.25964

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CiNii Research

Language：English   Publisher：Surgery Today  

Purpose: Lymphatic invasion (LI) is associated with lymph node metastasis (LNM) and a poor prognosis in patients with early gastric cancer (EGC). Although the impact of the LI volume on LNM has been described, no reports have assessed the impact of its depth on LNM. Methods: A total of 360 EGC patients with pathologically proven LI who underwent radical gastrectomy with lymphadenectomy between January 2005 and June 2018 at our institution were extracted from our database. Patients were divided into 2 groups: the mLI group, in which LI was limited to the muscularis mucosae (n = 34); and the smLI group, in which LI reached the submucosal region (n = 326). Clinicopathological features, including the LNM incidence, were compared between the groups. Results: LNM was recognized in 3 patients (9%) in the mLI group and 101 (31%) in the smLI group (P = 0.005). In the mLI group, LNM was not recorded in any patients who met the curative criteria of ESD other than mLI. Conclusions: LI limited to the mucosal region does not seem to be a strong indicator for LNM. When pathological findings of an endoscopic submucosal dissection specimen show only mLI as a non-curative criterion, the probability of LNM may be very low.

DOI： 10.1007/s00595-019-01913-7

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Event date： 2025.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Event date： 2025.10

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Event date： 2025.9

Language：English   Presentation type：Poster presentation  

Venue：Lotte Hotel, Seoul  

Event date： 2025.8

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Event date： 2025.7

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Event date： 2025.7

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Event date： 2025.7

Language：English   Presentation type：Symposium, workshop panel (public)  

Event date： 2025.6

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Event date： 2025.5

Language：English   Presentation type：Poster presentation  

Venue：Maritim Hotel, Amsterdam  

Event date： 2025.4

Language：Japanese   Presentation type：Poster presentation  

Event date： 2025.3

Language：English   Presentation type：Symposium, workshop panel (public)  

Event date： 2024.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2024.9

Language：English   Presentation type：Poster presentation  

Venue：Seoul   Country：Korea, Republic of  

Event date： 2024.9

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Venue：名古屋   Country：Japan  

Event date： 2024.6

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Venue：名古屋   Country：Japan  

Event date： 2024.4

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2024.2 - 2024.3

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：京都  

Event date： 2023.12

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2023.7

Language：English   Presentation type：Oral presentation (general)  

Event date： 2023.4

Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

Event date： 2023.2

Language：Japanese   Presentation type：Poster presentation  

Event date： 2022.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋   Country：Japan  

Event date： 2022.7

Language：English   Presentation type：Symposium, workshop panel (public)  

Country：Japan