Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions. @*Materials and Methods@#Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients. @*Results@#We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients. @*Conclusion@#Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

The Clinical Impact of Capmatinib in the Treatment of Advanced Non–Small Cell Lung Cancer with MET Exon 14 Skipping Mutation or Gene Amplification / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non–small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification. @*Materials and Methods@#Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients’ clinical outcome were retrospectively reviewed. @*Results@#A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123). @*Conclusion@#Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.

Immunogenicity and Optimal Timing of 13-Valent Pneumococcal Conjugate Vaccination during Adjuvant Chemotherapy in Gastric and Colorectal Cancer: A Randomized Controlled Trial / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Pneumococcal vaccination (13-valent pneumococcal conjugate vaccine [PCV13]) is recommended to cancer patients undergoing systemic chemotherapy. However, the optimal time interval between vaccine administration and initiation of chemotherapy has been little studied in adult patients with solid malignancies. @*Materials and Methods@#We conducted a prospective randomized controlled trial to evaluate whether administering PCV13 on the first day of chemotherapy is non-inferior to vaccinating 2 weeks prior to chemotherapy initiation. Patients were randomly assigned to two study arms, and serum samples were collected at baseline and 4 weeks after vaccination to analyze the serologic response against Streptococcus pneumoniae using a multiplexed opsonophagocytic killingassay. @*Results@#Of the 92 patients who underwent randomization, 43 patients in arm A (vaccination 2 weeks before chemotherapy) and 44 patients in arm B (vaccination on the first day of chemotherapy) were analyzed. Immunogenicity was assessed by geometric mean and fold-increase of post-vaccination titers, seroprotection rates (percentage of patients with post-vaccination titers > 1:64), and seroconversion rates (percentage of patients with > 4-fold increase in post-vaccination titers). Serologic responses to PCV13 did not differ significantly between the two study arms according to all three types of assessments. @*Conclusion@#The overall antibody response to PCV13 is adequate in patients with gastric and colorectal cancer during adjuvant chemotherapy, and no significant difference was found when patients were vaccinated two weeks before or on the day of chemotherapy initiation.

The economic evaluation of nitrous oxide in sevoflurane anesthesia

BACKGROUND: Nitrous oxide (N2O) is much cheaper than recently introduced volatile anesthetics such as sevoflurane and desflurane, and can reduce the consumption of these anesthetics. The use of N₂O is under current debate. The purpose of this study was to evaluate economic effect of 50% N₂O during sevoflurane anesthesia in Korea. METHODS: Seventy patients were randomly allocated to Group A or Group N. Anesthesia induction was performed using propofol, rocuronium, and 3–5% of sevoflurane with air (Group A) or 50% N2O (Group N). Fresh gas flow (FGF) was 6 L/min during induction, and 3 L/min for maintenance. Mean arterial pressure (MAP), heart rate (HR), bispectral index (BIS), and minimum alveolar concentration (MAC) were recorded. The consumption of sevoflurane was measured at every 10 minutes for the first 1 hour. The economic effect was analyzed based on the payment criterion of Korean National Health Insurance Service. RESULTS: MAP, HR, BIS, and MAC showed no differences between the two groups. The sevoflurane consumptions for the first 1 hour were 39.2 ± 6.3 ml in Group A and 29.2 ± 4.9 ml in Group N (P < 0.01); and the N₂O consumption was 93.7 ± 1.5 L in Group N. The total costs of inhaled anesthetics were 16,190 (14.8 USD) and 13,062 (12.0 USD) Korean won for the first 1 hour in Groups A and N, respectively. CONCLUSIONS: Use of 50% N₂O with 3 L/min FGF reduced the sevoflurane consumption by 25% and anesthetic cost by 20% for the first 1 hour.

Classification of Colon Cancer Patients Based on the Methylation Patterns of Promoters

Diverse somatic mutations have been reported to serve as cancer drivers. Recently, it has also been reported that epigenetic regulation is closely related to cancer development. However, the effect of epigenetic changes on cancer is still elusive. In this study, we analyzed DNA methylation data on colon cancer taken from The Caner Genome Atlas. We found that several promoters were significantly hypermethylated in colon cancer patients. Through clustering analysis of differentially methylated DNA regions, we were able to define subgroups of patients and observed clinical features associated with each subgroup. In addition, we analyzed the functional ontology of aberrantly methylated genes and identified the G-protein-coupled receptor signaling pathway as one of the major pathways affected epigenetically. In conclusion, our analysis shows the possibility of characterizing the clinical features of colon cancer subgroups based on DNA methylation patterns and provides lists of important genes and pathways possibly involved in colon cancer development.

A Case of Cardiogenic Shock after Chemotherapy with 5-Fluorouracil and Leucovorin in Rectal Cancer / 대한내과학회지

A 51-year-old man with rectal adenocarcinoma was admitted to hospital for neoadjuvant concurrent chemoradiotherapy. Three days after receiving 5-fluorouracil (425 mg/m2) and leucovorin (20 mg/m2) chemotherapy, the patient complained of chest pain. The patient had no history of cardiac disease. Electrocardiography showed ST segment elevation in leads II, III, and aVF, but the cardiac enzymes were normal. Transthoracic echocardiography revealed global hypokinesia with marked systolic dysfunction (ejection fraction 21.55%) and coronary angiography showed no significant stenosis. Unfortunately, he died of cardiogenic shock, despite intensive medical treatment.

Two Cases of Neuroendocrine Carcinoma and GIST in a Patient with Neurofibromatosis Type 1 / 대한내과학회지

Patients with neurofibromatosis type 1 (NF1) are at increased risk of developing tumors throughout the gastrointestinal tract, including neuromas, gastrointestinal stromal tumors (GISTs), and periampullary somatostatin-rich carcinoids. The simultaneous occurrence of a GIST and a well-differentiated neuroendocrine carcinoma in a patient with NF1 is very rare. Here, we report two cases of the coexistence of a low-risk GIST in the jejunum with a well-differentiated neuroendocrine carcinoma in the duodenum in patients with NF1. These cases strengthen the known association of GIST with neuroendocrine carcinoma in patients with NF1.

Two Cases of Neuroendocrine Carcinoma and GIST in a Patient with Neurofibromatosis Type 1 / 대한내과학회지

Patients with neurofibromatosis type 1 (NF1) are at increased risk of developing tumors throughout the gastrointestinal tract, including neuromas, gastrointestinal stromal tumors (GISTs), and periampullary somatostatin-rich carcinoids. The simultaneous occurrence of a GIST and a well-differentiated neuroendocrine carcinoma in a patient with NF1 is very rare. Here, we report two cases of the coexistence of a low-risk GIST in the jejunum with a well-differentiated neuroendocrine carcinoma in the duodenum in patients with NF1. These cases strengthen the known association of GIST with neuroendocrine carcinoma in patients with NF1.