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This study investigated whether an intestinal epithelial culture method can be applied to mouse and human esophageal cultures. The esophagi harvested from 1-day-old mice and adult humans were maintained in collagen gels. A commercially available culture medium for human embryonic stem cells was used for the human esophageal culture. We discovered that the intestinal epithelial culture method can be successfully applied to both mouse and human esophageal cultures. The long-term cultured esophageal organoids were rod-like luminal structures lined with myofibroblasts. We discovered that regeneration of the esophageal mucosal surface can be almost completely achieved in vitro, and the advantage of this method is that organoid cultures may be generated using host-derived fibroblasts as a niche. This method is a promising tool for mouse and human research in intestinal biology, carcinogenesis, and regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Metabolic tumor activity using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) was believed to have a predictive value for patient outcome in malignancies. The objective of the current study was to assess the prognostic effectiveness of the highest standardized uptake value (SUV) in the primary or regional area (peak SUV) and the number of PET-positive lymph nodes in esophageal cancer. Methods: The authors retrospectively reviewed their experience with 184 consecutive esophageal cancer patients imaged preoperatively using FDG-PET scanning. Results: The median peak SUV was 4.5 (range, 1.4-21.9). The survival curve was analyzed using the median peak SUV as the cutoff value. Comparison of each group and clinicopathologic characteristics revealed significant associations between peak SUV and each of the following factors: tumor status (P < .001), lymph node status (P < .001), metastatic status (P < .05), stage of disease (P < .001), number of PET-positive lymph nodes (P < .001), and the number of histologically positive lymph nodes (P < .001). The 5-year overall survival (OS) rate for patients having FDG uptake with a peak SUV > or =4.5 was 47% and that for patients with a peak SUV <4.5 was 76% (P < .0001). On multivariate survival analysis using the Cox proportional hazards model, peak SUV and the number of PET-positive lymph nodes were found to be independent predictive factors for OS. The number of PET-positive lymph nodes was a single prognostic factor predicting both disease-free survival and OS. Conclusions: Pretreatment PET cannot only potentially diagnose the extent of disease, but also may be predictive of patient survival after esophageal cancer resection. [ABSTRACT FROM AUTHOR]

A sensitive enzyme immunoassay method (EIA) for an anticancer drug, aclacinomycin A (ACM), has been developed. With a double-antibody technique, ACM at a concentration as low as 100 pg/tube can be detected. An antibody to ACM was obtained by immunizing rabbits with an antigen prepared by coupling ACM with mercaptosuccinylated bovine serum albumin via N-maleoyl aminobutyric acid (MABA) as a coupling agent. Enzyme labeling of ACM was performed with beta-D-galactosidase (beta-Gal; EC 3.2.1.23) via m-maleoyl benzoic acid (MBA). The standard curve of the assay was linear on a logit-log plot over a concentration range of 30 pg to 10 ng. The antibody detected ACM and its metabolites, MA144 M1 (M1), MA144 N1 (N1), MA144 S1 (S1), and aklavin (T1) equally well, but was only minimally reactive with aklavinone (D1) and 7-deoxyaklavinone (C1), thus suggesting that this EIA can detect the total amounts of ACM and its biologically active glycosides among metabolites of ACM. This EIA is practically free from interference by any other anticancer drugs. Using this assay, serum levels of ACM equivalents can be determined accurately after administration of the drug to rats at a single dose of 10 mg/kg. Since ACM is now undergoing clinical trial, the EIA of the drug will be a valuable tool in clinical pharmacological studies. [ABSTRACT FROM AUTHOR]

Background: There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers., Methods: This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases., Results: CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p < 0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b., Conclusions: The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS., (© 2024. Society of Surgical Oncology.)

Purpose: This study aimed to identify cases in which lateral lymph node (LLN) dissection (LLND) can be excluded by clarifying preoperative factors, including an evaluation of the middle rectal artery (MRA), associated with LLN metastasis., Methods: Fifty-five consecutive patients who underwent preoperative positron emission tomography-computed tomography (PET/CT) and total mesorectal excision with LLND for rectal cancer were included. We retrospectively investigated the preoperative clinical factors associated with pathological LLN (pLLN) metastasis. We analyzed the regions of pLLN metastasis using MRA., Results: pLLN metastasis occurred in 13 (23.6%) patients. According to a multivariate analysis, clinical LLN (cLLN) metastasis based on short-axis size and LLN status based on PET/CT were independent preoperative factors of pLLN metastasis. The negative predictive value (NPV) was high (97.1%) in patients evaluated as negative based on PET/CT and cLLN short-axis size. MRA was detected in 24 patients (43.6%) using contrast-enhanced CT, and there was a significant relationship between pLLN metastasis and the presence of MRA. pLLN metastasis in the internal iliac region but not in the obturator region was significantly correlated with the presence of MRA., Conclusion: Combined cLLN metastasis based on short-axis size and PET/CT showed a higher NPV, suggesting this to be a useful method for identifying cases in which LLND can be excluded., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of Interests for this article., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: The significance of reinforcement of the duodenal stump with seromuscular sutures and the effectiveness of reinforced staplers in preventing duodenal stump leakage remain unclear. We aimed to explore the importance of duodenal stump reinforcement and determine the optimal reinforcement method for preventing duodenal stump leakage., Methods: This retrospective cohort study was conducted between January 1, 2012 and December 31, 2021, with data analyzed between December 1, 2022 and September 30, 2023. This multicenter study across 57 institutes in Japan included 16,475 patients with gastric cancer who underwent radical gastrectomies. Elective open or minimally invasive (laparoscopic or robotic) gastrectomy was performed in patients with gastric cancer., Results: Duodenal stump leakage occurred in 153 (0.93%) of 16,475 patients. The proportions of males, patients aged ≥ 75 years, and ≥ pN1 were higher in patients with duodenal stump leakage than in those without duodenal stump leakage. The incidence of duodenal stump leakage was significantly lower in the group treated with reinforcement by seromuscular sutures or using reinforced stapler than in the group without reinforcement (0.72% vs. 1.19%, p = 0.002). Duodenal stump leakage incidence was also significantly lower in high-volume institutions than in low-volume institutions (0.70% vs. 1.65%, p = 0.047). The rate of duodenal stump leakage-related mortality was 7.8% (12/153). In the multivariate analysis, preoperative asthma and duodenal invasion were identified as independent preoperative risk factors for duodenal stump leakage-related mortality., Conclusions: The duodenal stump should be reinforced to prevent duodenal stump leakage after radical gastrectomy in patients with gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Objectives: This study aimed to investigate preoperative factors, including the C-reactive protein (CRP)/albumin ratio (CAR), associated with postoperative outcomes in patients with colorectal perforation who underwent emergency surgery to improve postoperative prognosis., Methods: Twenty-eight consecutive patients who underwent emergency surgery for colorectal perforations were included. We retrospectively investigated the clinical factors associated with their postoperative outcomes., Results: The median patient age was 69.5 years (range, 46.0-93.0 years); 13 patients (46.4%) were males and 15 (53.6%) were females. Colorectal cancer (8 [28.6%]) was the most common cause of colorectal perforation. Postoperative complications were diagnosed in 18 patients (64.3%), with intraabdominal abscess as the most common (6 [21.4%]). Multivariate analysis revealed that CAR (odds ratio, 1.357; 95% confidence interval, 1.056-1.743; p=0.017) was an independent risk factor for postoperative complications. A cutoff value of 4.9 was selected to predict the development of postoperative complications based on the CAR. The proportion of all postoperative complications (p=0.016), postoperative complications of Clavien-Dindo classification grade II or higher (p=0.002), and death during hospitalization (p=0.049) were significantly higher in the group of patients with CAR ≥ 4.9 than in those with CAR < 4.9. Additionally, intraabdominal abscess (p=0.049) was significantly higher in the group of patients with a non-improvement in CAR on postoperative day 3 than in those with an improvement in CAR on postoperative day 3., Conclusions: Perioperative CAR could be a predictor of perioperative complications and death and might be useful in improving the postoperative prognosis of colorectal perforations., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Introduction: This multicenter study aimed to determine whether the pretreatment prognostic nutrition index (PNI) or a change in the index after two treatment courses could be a biomarker for predicting treatment sensitivity in patients with unresectable advanced or recurrent gastric cancer treated using chemotherapy and nivolumab as the first-line treatment., Methods: This multicenter retrospective study with 104 patients was conducted at 12 institutions. PNI was calculated before treatment and after two courses of treatment in each case. We also focused on changes in PNI from the pretreatment value., Results: After two courses of chemotherapy plus nivolumab treatment, the high PNI group had significantly better rates of overall survival (OS) (p = 0.0016) and time-to-treatment failure (p = 0.0060). Low PNI was an independent prognostic factor predicting both therapeutic sensitivity to chemotherapy plus nivolumab treatment and poorer OS. Furthermore, correlation with low pretreatment PNI transitioning to high after two courses of treatment was not noted in any patient in the progressive disease group (p = 0.0075)., Conclusions: PNI is a score composed of a patient's albumin level and lymphocyte count that can be easily assessed in daily clinical practice. Evaluating it is easy for each treatment; thus, when there is a focus on its transition, PNI could be a very powerful biomarker for predicting treatment sensitivity., (© 2024 S. Karger AG, Basel.)

Purpose: It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients., Methods: We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy., Results: Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094)., Conclusions: Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The β2-adrenergic receptor (β2-AR) is a therapeutic target for circulatory agonists and exhibits oncogenic activity in several cancers. However, its role in advanced colorectal cancer (CRC) treated using chemotherapy remains unclear. We investigated the potential of β2-AR as a novel chemosensitivity marker and therapeutic target in inoperable CRC., Methods: β2-AR expression was evaluated immunohistochemically in 80 advanced or recurrent CRC cases for which untreated resected specimens were available before systemic chemotherapy implementation. We assessed the relationship among β2-AR protein expression, clinicopathological factors, therapeutic response, and prognosis. Furthermore, we evaluated the significance of β2-AR as an in vitro and in vivo therapeutic target using CRC cell lines and a CRC xenograft model treated with the β-blocker, propranolol, and other anticancer agents., Results: High tumoral β2-AR expression was associated with shorter progression-free survival and chemotherapeutic resistance in patients treated with oxaliplatin-based regimens and bevacizumab-based regimens. We found no synergistic effect between propranolol and oxaliplatin. However, combined administration of propranolol and bevacizumab induced significant tumor shrinkage in the CRC xenograft model., Conclusions: β2-AR is a possible biomarker for chemosensitivity and prognosis in advanced CRC. Repositioning existing β-blockers could be beneficial for treating CRC resistant to existing treatment regimens., (© 2024. Society of Surgical Oncology.)

Introduction: In this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors., Methods: This multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index, and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment., Results: A total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease/progressive disease group significantly increased (p = 0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased., Conclusion: The LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy., (© 2024 S. Karger AG, Basel.)

Background/aim: An increasing number of patients with complicated systemic comorbidity can undergo colorectal cancer (CRC) surgery. Such patients have a high risk of developing poor postoperative outcomes. This study aimed to identify preoperative factors, including nutritional and sarcopenia statuses, leading to poor postoperative outcomes in patients with severe systemic comorbidities., Patients and Methods: This study included 114 patients who underwent radical CRC resections and had American Society of Anesthesiologists Physical Statuses ≥3. We retrospectively analyzed the relationships between clinical factors, postoperative complications (within 28 days postoperatively and Clavien-Dindo classification grade ≥2), length of hospital stay, discharge destination, and overall survival (OS)., Results: The median patient age was 74.5 years (range=41.0-93.0 years). Thirty-six patients had postoperative complications (31.6%), and the risk factors in the multivariate analyses were rectal cancer and preoperative nutritional disorders with Prognostic Nutritional Index ≤40. In patients with nutritional disorders, the postoperative hospital stay was longer, and a higher (but not statistically significant) percentage were not discharged home. Moreover, the independent factors for OS identified in the multivariate analyses were body mass index (BMI) and hemodialysis., Conclusion: In patients with CRC and severe systemic comorbidities, those with Prognostic Nutritional Index ≤40 have a high risk of developing postoperative complications, leading to a prolonged postoperative hospital stay and possibly preventing discharge home. Additionally, among these patients, OS was poor in those with low BMI or preoperative hemodialysis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)