Objective: Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. Methods: This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). Results: Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. Conclusion This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Abdominal aortic aneurysm (AAA) is a chronic dilation of the aorta with a tendency to enlarge and eventually rupture, which constitutes a major cause of cardiovascular mortality.Although T-cell infiltrates have been observed in AAA, the cellular, phenotypic, and functional characteristics of these tissue-infiltrating T cells are not fully understood. Here, we investigated the proportional changes of T-cell subsets—including CD4 + T cells, CD8 + T cells, and γδ T cells—and their effector functions in AAAs. We found that Vδ2 + T cells were presented at a higher frequency in aortic aneurysmal tissue compared to normal aortic tissue and PBMCs from patients with AAA. In contrast, no differences were observed in the frequencies of CD4 + , CD8 + , and Vδ1 + T cells. Moreover, we observed that the Vδ2 +T cells from AAA tissue displayed immunophenotypes indicative of CCR5 + non-exhausted effector memory cells, with a decreased proportion of CD16 + cells. Finally, we found that these Vδ2 + T cells were the main source of IL-17A in abdominal aortic aneurysmal tissue. In conclusion, our results suggest that increased Vδ2 + T cells that robustly produce IL-17A in aortic aneurysmal tissue may contribute to AAA pathogenesis and progression.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

METHODS: The efficiency of electroporation-based delivery of AsCpf1/mRNA and AsCpf1/RNP to target exon 3 of leukemia inhibitory factor (Lif) into mouse zygotes was evaluated. Embryos that developed to the two-cell stage after zygote electroporation were transferred into the oviducts of surrogate mothers to produce AsCpf1-mediated LIF KO mice. The genome editing efficiency of blastocysts and pups was tested using the T7E1 assay and/or DNA sequencing. Congenital abnormalities and reproductive phenotypes in LIF KO mice produced by electroporation with AsCpf1/RNP were examined. RESULTS: Survival and two-cell development of electroporated zygotes were comparable between the AsCpf1/mRNA and AsCpf1/RNP groups, whereas genome editing efficiency was relatively higher in the AsCpf1/RNP group (13.3% vs 18.1% at blastocyst and 33.3% vs 45.5% at offspring), respectively. Two mouse lines with a frameshift mutation in exon 3 of the Lif gene were established from the AsCpf1/RNP group. All congenital abnormalities of LIF KO mice produced by AsCpf1/RNP electroporation were observed. AsCpf1-mediated LIF KO mice showed postnatal growth retardation and implantation failure, both of which are major phenotypes of LIF KO mice generated by conventional gene targeting. CONCLUSION Electroporation of AsCpf1/RNP at the zygote stage is an efficient genome editing method to produce KO mice.

METHODS: The efficiency of electroporation-based delivery of AsCpf1/mRNA and AsCpf1/RNP to target exon 3 of leukemia inhibitory factor (Lif) into mouse zygotes was evaluated. Embryos that developed to the two-cell stage after zygote electroporation were transferred into the oviducts of surrogate mothers to produce AsCpf1-mediated LIF KO mice. The genome editing efficiency of blastocysts and pups was tested using the T7E1 assay and/or DNA sequencing. Congenital abnormalities and reproductive phenotypes in LIF KO mice produced by electroporation with AsCpf1/RNP were examined. RESULTS: Survival and two-cell development of electroporated zygotes were comparable between the AsCpf1/mRNA and AsCpf1/RNP groups, whereas genome editing efficiency was relatively higher in the AsCpf1/RNP group (13.3% vs 18.1% at blastocyst and 33.3% vs 45.5% at offspring), respectively. Two mouse lines with a frameshift mutation in exon 3 of the Lif gene were established from the AsCpf1/RNP group. All congenital abnormalities of LIF KO mice produced by AsCpf1/RNP electroporation were observed. AsCpf1-mediated LIF KO mice showed postnatal growth retardation and implantation failure, both of which are major phenotypes of LIF KO mice generated by conventional gene targeting. CONCLUSION Electroporation of AsCpf1/RNP at the zygote stage is an efficient genome editing method to produce KO mice.

PURPOSE: The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility. MATERIALS AND METHODS: In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting. CONCLUSION: Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.
Demography ; Drug Therapy ; Fallopian Tubes* ; Female ; Humans ; Ovarian Neoplasms ; Reproducibility of Results

BACKGROUND: A single-arm phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in the treatment of advanced-stage ovarian cancer has begun in Korea. We hypothesized that adding durvalumab (anti-programmed death-ligand 1 antibody) and tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4 antibody) to chemotherapy in treating this cancer can increase progression-free survival (PFS) with minimal effects on safety. METHODS: During treatment, serial biopsies will be performed on pre-treatment, at interval debulking surgery and progression to identify immune biomarkers and changes in the tumor microenvironment. Patients with histologically confirmed stage IIIC/IV epithelial ovarian cancer are offered durvalumab, tremelimumab plus chemotherapy for neoadjuvant chemotherapy and durvalumab plus chemotherapy for adjuvant chemotherapy. Twenty-four patients will be included from four Korean institutions within 1 year. The primary endpoint is a 12-month PFS rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03899610
Biomarkers ; Biopsy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Therapy ; Humans ; Immunotherapy ; Korea ; Ovarian Neoplasms ; Tumor Microenvironment

Gastric cancer patients with acute disseminated intravascular coagulation experiences a rare but severe complication resulting in a dismal prognosis. We report a case of advanced gastric cancer complicated with disseminated intravascular coagulation with intractable tumor bleeding which was successfully treated with chemotherapy consisting of 5-fluorouracil and oxaliplatin. The patient was a 63-year-old man who complained of abdominal pain, melena, and dyspnea on 24 November 2010. We diagnosed stage IV gastric cancer complicated by disseminated intravascular coagulation. Gastric tumor bleeding was not controlled after procedures were repeated three times using gastrofiberscopy. With the patient's consent, we selected the 5-fluorouracil and oxaliplatin combination chemotherapy for treatment. After one cycle of 5-fluorouracil and oxaliplatin therapy, symptoms of bleeding improved and the disseminated intravascular coagulation process was successfully controlled. The primary tumor and multiple metastatic bone lesions were remarkably shrunken and metabolically remitted after eight cycles of chemotherapy. In spite of progression, systemic chemotherapy is effective in disease control; further, the patient gained the longest survival time among cases of gastric cancer with disseminated intravascular coagulation.
Abdominal Pain ; Disseminated Intravascular Coagulation ; Drug Therapy, Combination ; Dyspnea ; Fluorouracil ; Hemorrhage ; Humans ; Melena ; Organoplatinum Compounds ; Prognosis ; Stomach Neoplasms

OBJECTIVE: This study was conducted to compare the perioperative outcomes in patients with symptomatic uterine myoma who underwent laparoscopic (LM) or laparoscopically assisted myomectomy (LAM). METHODS: A total of 207 patients with myoma underwent LM or LAM in Samsung Medical Center between October 2006 and March 2010. Of them, 121 patients with LM and 50 with LAM met the inclusion criteria and were compared for the perioperative outcomes. RESULTS: The operation time was significantly shorter in the LAM group than in the LM group (111 min versus 139 min; p<.001, respectively). Estimated blood loss was significantly higher in the LAM group (p<.001). Intraoperative, early postoperative complications, hospitalization days and postoperative analgesics use were similar between the 2 study groups. CONCLUSION: LM and LAM is comparable in the perioperative outcomes in patients with symptomatic uterine myoma.
Analgesics ; Female ; Hospitalization ; Humans ; Laparoscopy ; Lipopolysaccharides ; Myoma ; Postoperative Complications