Tuberculous peritonitis after conservative treatment for acute perforated appendicitis: a case report.

BACKGROUND: Interval appendectomy is widely recommended for patients with abscesses due to perforated appendicitis. A concomitant malignancy-related problem was reported after conservative treatment of acute appendicitis with abscess, but perforated appendicitis-associated tuberculous peritonitis was never reported. CASE PRESENTATION: A 67-year-old male patient with a laryngeal cancer history presented to our hospital with an acute appendicitis-associated ileal abscess. He was scheduled for an interval appendectomy after conservative treatment. Fortunately, the symptoms subsided, and the patient was discharged for a later scheduled appendectomy. However, after 3 months, he was readmitted to our hospital with fever and abdominal pain, and emergency surgery was performed, which was suspected to be peritonitis. Intraoperative results revealed numerous white nodules in the abdominal cavity. The condition was diagnosed as tuberculous peritonitis based on macroscopic results, later pathological findings, and positive T-SPOT.TB. The antituberculosis medications were effective, and the patient recovered and was discharged from the hospital 8 days thereafter. CONCLUSION: Patients, particularly those immunocompromised, may develop tuberculous peritonitis after conservative treatment for acute perforated appendicitis.

Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small cell lung cancer in a real-world setting (OSI-FACT-EP).

OBJECTIVES: Osimertinib is the primary treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer. However, evidence of the outcomes of osimertinib treatment in patients over 75 years of age in the real-world setting is limited. MATERIALS AND METHODS: This retrospective study analyzed the data of 538 patients (203 elderly and 335 non-elderly) with EGFR mutation-positive lung cancer in whom osimertinib was initiated as first-line treatment between August 2018 and December 2019. Patients over 75 years of age were classified as elderly. The data cut-off date was February 28, 2022. RESULTS: The progression-free survival (PFS) did not significantly differ between the elderly and non-elderly groups [elderly group: median PFS, 16.9 months (95 % confidence interval (CI), 14.3-20.2); non-elderly group: median PFS, 22.1 months (95 % CI: 19.5-26.3); hazard ratio (HR) for the elderly against the non-elderly: 1.21 (95 % CI: 0.98-1.50), p = 0.079]. However, the time to treatment failure (TTF) was significantly shorter in the elderly than in the non-elderly [elderly group: median TTF, 14.0 months (95 % CI: 0.98-1.50); non-elderly group: median TTF, 21.8 months (95 % CI: 18.2-24.6); HR for the elderly against the non-elderly: 1.46 (95 % CI: 1.20-1.77), p < 0.001]. Furthermore, the rate of treatment discontinuation because of adverse events was 28.6 % in the elderly and 14.9 % in the non-elderly (p < 0.001). Among patients who discontinued treatment, the conversion rate to second-line treatment was 39.6 % in the elderly and 72.8 % in the non-elderly. In addition, the median overall survival was 30 months (95 % CI: 25.8-37.7) in the elderly and not reached (NR) (95 % CI: NR-NR) in the non-elderly (p < 0.001). CONCLUSION: In a real-world clinical setting, elderly patients receiving osimertinib as first-line treatment should be aware of the frequent inability to transition to second-line treatment due to adverse events.

Safety and efficacy of osimertinib rechallenge or continuation after pneumonitis: A multicentre retrospective cohort study.

INTRODUCTION: Although osimertinib is a standard first-line treatment for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, the incidence rate of pneumonitis associated with osimertinib is high. However, there are few reports about the safety and efficacy of osimertinib rechallenge after the development of pneumonitis. METHODS: We conducted a retrospective multicentre cohort study of consecutive patients who developed pneumonitis associated with osimertinib as a first-line and received osimertinib rechallenge. The primary outcome was the incidence rate of any grade pneumonitis after osimertinib rechallenge. The secondary outcome was treatment efficacy in patients after osimertinib rechallenge. RESULTS: In total, 33 patients who received osimertinib rechallenge were included. Of them, 26 patients had grade 1, 6 patients had grade 2, and 1 patient had grade 3 initial pneumonitis. The median follow-up period after the osimertinib rechallenge was 16.9 months (interquartile range, 11.1-21.3 months). After the start of osimertinib rechallenge, five patients (15%) experienced mild relapsed pneumonitis. Three of the five patients had similar imaging patterns for initial and relapsed pneumonitis. No significant differences in characteristics were observed between patients with and without relapsed pneumonitis. The median progression-free survival after osimertinib rechallenge was not achieved (95% confidence interval: 10.3 months - not reached). CONCLUSION: Osimertinib rechallenge was feasible and effective for patients who developed initial pneumonitis associated with first-line osimertinib therapy. Osimertinib might be considered a treatment option even after the development of mild initial pneumonitis.

Drug-Related Pneumonitis Induced by Osimertinib as First-Line Treatment for Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Real-World Setting.

BACKGROUND: Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data currently are lacking. RESEARCH QUESTION: What is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest CT scans and clinical information during osimertinib exposure were collected until June 2020. The primary end point was DRP incidence identified through central review. RESULTS: A total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) had a diagnosis of DRP (all grades), and 21 patients (4.6%) had a diagnosis of grade 3 or more DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT scan patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and nonspecific interstitial pneumonia were found in 30, 21, 18, 9, and two patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio, 1.72; 95% CI, 1.01-2.89; P = .046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not affect treatment efficacy negatively. INTERPRETATION: For osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features.

Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT).

BACKGROUND: Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient. METHODS: We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS). RESULTS: The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2.82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P < 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), ≥50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%). CONCLUSION: During initial treatment with osimertinib, PD-L1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation.

Clinical outcomes and predictive value of programmed cell death-ligand 1 expression in response to anti-programmed cell death 1/ligand 1 antibodies in non-small cell lung cancer patients with performance status 2 or greater.

BACKGROUND: Anti-programmed cell death protein-1/ligand-1 (anti-PD-1/PD-L1) therapy is promising for patients with non-small-cell lung cancer (NSCLC); however, clinical trials have focused on patients with a performance status (PS) 0 or 1. This study aimed to evaluate the clinical outcomes and correlation between PD-L1 expression status and tumor response to anti-PD-1/PD-L1 therapy among NSCLC patients with poor PS (i.e., PS ≥ 2). METHODS: In total, 130 patients with NSCLC and PS ≥ 2 treated with anti-PD-1/PD-L1 monotherapy at 12 institutions between January 2016 and August 2019 were retrospectively reviewed. PD-L1 expression status was divided into four groups: < 1%, 1-49%, ≥ 50%, and unknown. RESULTS: The objective response rate and PS improvement rate were 23 and 21% and were higher in the PD-L1 ≥ 50% group than in other groups (P < 0.01). Median progression-free survival (PFS) was 62 days and was longer in the PD-L1 ≥ 50% group than in other groups (P = 0.03). Multivariate analyses revealed that PD-L1 expression is significantly associated with prolonged PFS (PD-L1 < 1%; reference; 1-49%, hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04-0.99, P = 0.05; ≥ 50%, HR 0.12, 95% CI 0.02-0.71, P = 0.02; unknown, HR 0.30, 95% CI 0.08-1.22, P = 0.09). CONCLUSIONS: NSCLC patients with poor PS and PD-L1 ≥ 50% are expected to benefit from anti-PD-1/PD-L1 therapy, despite a modest overall response among NSCLC patients with poor PS. Accordingly, PD-L1 expression provides useful information regarding decision-making for anti-PD-1/PD-L1 therapy even in these populations.

Upfront Cranial Radiotherapy Followed by Erlotinib Positively Affects Clinical Outcomes of Epidermal Growth Factor Receptor-mutant Non-small Cell Lung Cancer With Brain Metastases.

BACKGROUND/AIM: The optimal treatment strategy for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) has not yet been fully determined. The aim of this study was to investigate the optimal management of EGFR-mutant NSCLC patients with BM. PATIENTS AND METHODS: A multicenter retrospective study was performed on the clinical outcomes of 81 advanced/recurrent EGFR-mutant NSCLC patients with BM treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) (gefitinib n=52 or erlotinib n=29). RESULTS: Among the 81 patients, 30 patients received upfront cranial radiotherapy (CRT) and 51 did not. The multivariate cox analyses revealed that the use of erlotinib and upfront CRT were independent predictive factors for overall survival (OS) (erlotinib: HR 0.21; 95% CI, 0.10-0.48; p<0.001; upfront CRT: HR 0.42; 95% CI, 0.20-0.88; p=0.022). CONCLUSION: Erlotinib and upfront CRT were associated with a favorable prognosis among EGFR-mutant NSCLC patients with BM. Upfront CRT followed by erlotinib may be an appropriate initial management approach for EGFR-mutant NSCLC patients with BM.

Sonocatalytic injury of cancer cells attached on the surface of a nickel-titanium dioxide alloy plate.

The present study demonstrates ultrasound-induced cell injury using a nickel-titanium dioxide (Ni-TiO2) alloy plate as a sonocatalyst and a cell culture surface. Ultrasound irradiation of cell-free Ni-TiO2 alloy plates with 1 MHz ultrasound at 0.5 W/cm(2) for 30s led to an increased generation of hydroxyl (OH) radicals compared to nickel-titanium (Ni-Ti) control alloy plates with and without ultrasound irradiation. When human breast cancer cells (MCF-7 cells) cultured on the Ni-TiO2 alloy plates were irradiated with 1 MHz ultrasound at 0.5 W/cm(2) for 30s and then incubated for 48 h, cell density on the alloy plate was reduced to approximately 50% of the controls on the Ni-Ti alloy plates with and without ultrasound irradiation. These results indicate the injury of MCF-7 cells following sonocatalytic OH radical generation by Ni-TiO2. Further experiments demonstrated cell shrinkage and chromatin condensation after ultrasound irradiation of MCF-7 cells attached on the Ni-TiO2 alloy plates, indicating induction of apoptosis.

Moths produce extremely quiet ultrasonic courtship songs by rubbing specialized scales.

Insects have evolved a marked diversity of mechanisms to produce loud conspicuous sounds for efficient communication. However, the risk of eavesdropping by competitors and predators is high. Here, we describe a mechanism for producing extremely low-intensity ultrasonic songs (46 dB sound pressure level at 1 cm) adapted for private sexual communication in the Asian corn borer moth, Ostrinia furnacalis. During courtship, the male rubs specialized scales on the wing against those on the thorax to produce the songs, with the wing membrane underlying the scales possibly acting as a sound resonator. The male's song suppresses the escape behavior of the female, thereby increasing his mating success. Our discovery of extremely low-intensity ultrasonic communication may point to a whole undiscovered world of private communication, using "quiet" ultrasound.

[A case of advanced colon cancer with metastases to both the Virchow's and the paraaortic lymph nodes that achieved complete long-term response with levofolinate.5-FU therapy].

A 48-year-old woman presented with a tumor in the supra-clavicular fossa. Under a diagnosis of advanced ileocecal colon cancer with metastases to Virchow's and the paraaortic lymph nodes, ileocecal resection was performed. After surgery, the patient was given 5-FU infused continuously at 500 mg/body per day, and levofolinate was dripped intravenously at 100 mg/body over 2 hours for 5 successive days per week. Two cycles were repeated each week. She was then intravenously given weekly modulation chemotherapy consisting of 125 mg/body levofolinate and 500 mg/body of 5-FU for about 5 months on an outpatient basis. Furthermore, the same administration schedule was continued bi-weekly for 1 year and 4 months. As a result, the enlarged paraaortic lymph nodes had completely disappeared by 5 months after administration of levofolinate.5-FU. The Virchow's lymph node metastasis has not been palpable for 11 months. Throughout the period of treatment, there were no severe side effects and as of this writing, no sign of recurrence for 3 years after surgery. A high quality of life has been maintained. In conclusion, this case seems significant from the viewpoint of the complete long-term response to a moderate dose of levofolinate.5-FU therapy and the long duration of administration, which was tolerable with few side effects. Moreover, we identified the presence of TS and DPD using immunohistochemical staining techniques, when both primary tumor and regional lymph nodes were all negative for the stain test. It was suggested that this cancer especially would responded to 5-FU chemotherapy.