Purpose: We investigated whether a 5-fluorouracil (5-FU)-resistant tumor could regain chemosensitivity after the administration of 5-aza-2′-deoxycytidine (DAC) as a demethylating agent. Methods: Human colorectal cancer cells (SW48) are characterized by the hypermethylation of proapoptotic genes. They were transplanted into 20 athymic BALB/c nu/nu mice which were randomly placed into 4 groups (1 = control; 2 = 5-FU alone; 3 = DAC alone; 4 = DAC followed by 5-FU). We evaluated the synergistic effect of DAC and 5-FU on the growth of these xenografts. Reactivation of proapoptotic genes in these cells was analyzed by methylation-specific PCR. Gene expression was determined by a quantitative reverse-transcription PCR assay. Results: Compared with the control group, relative tumor volumes were statistically significantly decreased only in group 4 mice (p = 0.006). In groups 3 and 4, p14, p16 and death-associated protein kinase (DAPK) promoter regions were demethylated and p14 gene expression was gradually increased after DAC administration. Conclusion: DAC could be a useful medicine that breaks the silencing of various genes and recovers some expressions. By pretreating with DAC at a nontoxic level, we confirmed the restoration of 5-FU chemosensitivity and apoptosis induction. The combination of demethylating agents and several cytotoxic drugs has potential in clinical practice.

Sato Y, et al. J Gastric Cancer. 2018 Aug;18:e33. https://doi.org/10.5230/jgc.2018.18.e33

Background: The incidence of esophagogastric junction cancer (EGJC) is increasing in both Western and Eastern countries. Despite this trend, a globally accepted treatment strategy remains elusive due to the tumor’s anatomical complexity and variability in clinical practice. Aim: This review aims to provide a comprehensive overview of current evidence regarding EGJC treatment, focusing on the surgical approach, extent of lymph node dissection, and perioperative therapy. Special attention is given to regional differences and the implications of recent clinical trials. Findings: Transhiatal and minimally invasive surgical approaches have demonstrated favorable safety profiles, particularly for Siewert type II tumors. Lymph node dissection strategies are increasingly tailored based on the extent of esophageal invasion. Pre- and postoperative chemotherapy and chemoradiotherapy are standard in the West, while East Asian countries are gradually adopting these approaches through trials such as RESOLVE (China) and PRODIGY (Korea). Immunotherapy has also emerged as a promising option following the CheckMate 577 trial. Conclusions: EGJC requires individualized treatment planning based on tumor characteristics and regional practices. While ongoing trials continue to inform optimal management, international collaboration and a stepwise, biomarker-informed approach will be essential to harmonize treatment strategies for this anatomically and therapeutically complex disease.

Background/Objectives: With population aging, determining appropriate surgical indications for patients aged ≥80 years with esophageal or esophagogastric junction cancer has become increasingly important. This study compared perioperative and long-term outcomes between surgically treated patients aged ≥80 years and those aged <80 years. Methods: Patients who underwent surgery for esophageal or esophagogastric junction cancer between April 2009 and April 2026 were retrospectively analyzed. Propensity score matching was performed using sex, American Society of Anesthesiologists physical status, tumor location, histological type, clinical stage, surgical procedure, and neoadjuvant chemotherapy. After matching, 40 patients were included in each group. Perioperative outcomes, postoperative complications, overall survival (OS), and disease-specific survival (DSS) were compared. Results: Operative time, blood loss, and postoperative hospital stay did not differ significantly between the groups. Patients aged ≥80 years had fewer dissected lymph nodes (26.0 vs. 48.5, p = 0.003) and a lower incidence of Clavien–Dindo grade ≥IIIa complications (17.5% vs. 40.0%, p = 0.047). The incidences of pneumonia, recurrent laryngeal nerve palsy, and anastomotic leakage did not differ significantly. The 5-year OS was lower in patients aged ≥80 years (32.9% vs. 55.3%, p = 0.006; HR, 2.31; 95% CI, 1.24–4.28), whereas 5-year DSS did not differ significantly (55.4% vs. 69.0%, p = 0.122; HR, 1.86; 95% CI, 0.84–4.12). Conclusions: Surgery may be feasible in carefully selected patients aged ≥80 years. These findings do not establish a survival advantage over non-surgical treatment. Surgical eligibility should be based on overall condition, oncological factors, and anticipated surgical invasiveness rather than chronological age alone.

Background: Immune checkpoint inhibitors (ICIs) such as pembrolizumab (Pem) have demonstrated clinical benefits in esophageal cancer. Cisplatin, 5-fluorouracil, and Pem combination (CF plus Pem) has emerged as a promising first-line regimen. However, dose reduction of cytotoxic agents is necessary in real-world practice in patients with advanced age and/or renal dysfunction. This study aimed to evaluate the real-world effectiveness and safety of CF plus Pem therapy and assess survival outcomes based on the initial dose intensity. Methods: We retrospectively analyzed patients with unresectable or recurrent esophageal cancer who received CF plus Pem between February 2022 and February 2025. Clinical data, including patient characteristics, treatment details, tumor response, adverse events, and survival outcomes, were collected and analyzed. Results: We included 54 patients (median age, 72.5 years; 74.1% male). The initial CF dose was reduced in 55.6% of the patients. The overall response and disease control rates were 55.6% and 81.5%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 18.6 and 6.5 months, respectively, with no significant differences observed among groups based on dose reduction, age, or change in treatment interval. Grade ≥ 3 adverse events occurred in 16.7% of patients, with fewer events and higher treatment continuity in the dose-reduction group. Conclusions: Thus, CF plus Pem therapy is effective and tolerable in real-world settings. Initial dose reduction does not compromise survival and supports individualized dosing strategies for esophageal cancer treatment.