Culture-based bacterial evaluation of the appendix lumen and antibiotic susceptibility of acute appendicitis in Japan: A single-center retrospective analysis.

The question of whether to perform an appendectomy or conservative treatment for acute appendicitis can differ depending on the facility or surgeon, but antibiotic treatment is administered regardless of whether an appendectomy or conservative treatment is selected. We investigated the contemporary bacteriology for acute appendicitis and evaluated the antibiotic sensitivity of the bacteria that are currently associated with appendicitis. We retrospectively analyzed the bacterial culture results and antibiotic susceptibility of 141 patients who underwent appendicitis surgery, including the identification and antimicrobial susceptibility of the cultured bacteria within the excised appendices. Bacterial cultures were positive in 131 cases (92.9%). The most commonly isolated bacteria were Escherichia coli (90 isolates, 66.7%), followed by Enterococcus species (n = 19, 14.5%), Pseudomonas aeruginosa (n = 18, 13.7%), Streptococcus species (n = 15, 11.5%), and Klebsiella species (n = 8, 6.1%). Eight strains (8.8%) of E coli were extended-spectrum ß-lactamase producers, and ten strains (11.1%) were fluoroquinolone-resistant. Tazobactam/piperacillin and meropenem inhibited the growth of 100% of the major identified bacteria. The patients with appendicoliths had a significantly higher bacterial culture rate. Enterococcus species were frequently isolated from the patients with complicated appendicitis. For the antibiotic treatment of appendicitis, it is essential to understand the patient's microbiological profile and antibiotic susceptibilities. Research from Asian countries such as Japan can enhance our knowledge of regional antibiotic resistance patterns and inform effective treatment strategies.

Comparison of Short-term Outcomes Between Esophageal Bypass Surgery and Self-expanding Stent Insertion in Esophageal Cancer: A Propensity Score-matched Analysis Using a Large-scale Inpatient Database.

BACKGROUND: Advanced esophageal cancer is occasionally accompanied by difficulty swallowing owing to esophageal stenosis or tracheoesophageal fistula formation. Esophageal bypass surgery and stent insertion are considered feasible palliative management options. The aim of this study was to evaluate the short-term outcomes of these palliative treatments. MATERIALS AND METHODS: Patient data were obtained from a large-scale inpatient database of 42 National University Hospitals in Japan. Patients with advanced esophageal cancer who underwent esophageal bypass surgery or stent insertion between April 2016 and March 2021 were included in this study. One-to-one propensity score matching of patients who underwent bypass surgery or stent insertion was performed. The primary outcomes were time to diet resumption and length of hospital stay after surgery. The secondary outcome was the incidence of postoperative complications. RESULTS: In 43 propensity score-matched pairs, the incidence of postoperative respiratory complications was significantly higher in the bypass group than in the stent group (32.6% vs. 9.3%, P = 0.008). Postoperative length of hospital stay was longer in the bypass group than in the stent group (24 vs. 10 d, P < 0.001). Logistic regression analysis revealed that stent insertion was associated with a decreased risk of respiratory complications (odds ratio 0.077, P < 0.007). Among patients who underwent the interventions (bypass surgery or stent insertion) and subsequently underwent anticancer therapy (chemotherapy/radiotherapy) during hospitalization, the interval between the intervention and anticancer therapy was longer in the bypass group than in the stent group (25 vs. 7 d, P = 0.003). CONCLUSIONS: Esophageal stent insertion provides better short-term outcomes than bypass surgery in patients with advanced unresectable esophageal cancer.

MEK inhibitor and anti-EGFR antibody overcome sotorasib resistance signals and enhance its antitumor effect in colorectal cancer cells.

The Kirsten rat sarcoma (KRAS) oncogene was "undruggable" until sotorasib, a KRASG12C selective inhibitor, was developed with promising efficacy. However, inhibition of mutant KRAS in colorectal cancer cells (CRC) is ineffective due to feedback activation of MEK/ERK downstream of KRAS. In this study, we screened for combination therapies of simultaneous inhibition to overcome sotorasib resistance using our previously developed Mix Culture Assay. We evaluated whether there was an additive effect of sotorasib administered alone and in combination with two or three drugs: trametinib, a MEK inhibitor, and cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody. The MAPK pathway was reactivated in KRASG12C-mutated cell lines treated with sotorasib alone. Treatment with KRAS and MEK inhibitors suppressed the reactivation of the MAPK pathway, but upregulated EGFR expression. However, the addition of cetuximab to this combination suppressed EGFR reactivation. This three-drug combination therapy resulted in significant growth inhibition in vitro and in vivo. Our data suggest that reactive feedback may play a key role in the resistance signal in CRC. Simultaneously inhibiting KRAS, MEK, and EGFR is a potentially promising strategy for patients with KRASG12C-mutated CRC.