Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

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.

OBJECTIVES: The aim of this study was to develop a new prognostic classification for epithelial ovarian cancer (EOC) patients using gradient boosting (GB) and to compare the accuracy of the prognostic model with the conventional statistical method. METHODS: Information of EOC patients from Samsung Medical Center (training cohort, n=1,128) was analyzed to optimize the prognostic model using GB. The performance of the final model was externally validated with patient information from Asan Medical Center (validation cohort, n=229). The area under the curve (AUC) by the GB model was compared to that of the conventional Cox proportional hazard regression analysis (CoxPHR) model. RESULTS: In the training cohort, the AUC of the GB model for predicting second year overall survival (OS), with the highest target value, was 0.830 (95% confidence interval [CI]=0.802–0.853). In the validation cohort, the GB model also showed high AUC of 0.843 (95% CI=0.833–0.853). In comparison, the conventional CoxPHR method showed lower AUC (0.668 (95% CI=0.617–0.719) for the training cohort and 0.597 (95% CI=0.474–0.719) for the validation cohort) compared to GB. New classification according to survival probability scores of the GB model identified four distinct prognostic subgroups that showed more discriminately classified prediction than the International Federation of Gynecology and Obstetrics staging system. CONCLUSION: Our novel GB-guided classification accurately identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method. This approach would be useful for accurate estimation of individual outcomes of EOC patients.
Area Under Curve ; CA-125 Antigen ; Chungcheongnam-do ; Classification ; Cohort Studies ; Gynecology ; Humans ; Machine Learning ; Methods ; Obstetrics ; Ovarian Neoplasms ; Prognosis

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

Technical developments have made laparoendoscopic single-site (LESS) surgery increasingly more feasible for treating gynecological conditions, including cancer. However, complex surgeries such as radical hysterectomy have rarely been performed with single-port access because of technical difficulties. The majority of the difficulties are due to the inefficient retraction of tissue during dissection. Here, we report a detailed description of LESS radical hysterectomy plus pelvic lymph node dissection that was successfully performed in two patients with stage IB1 cervical cancer. We used our expertise with LESS to perform space development as much as possible before the ligaments were resected. The oncologic clearance was comparable to that of conventional laparoscopic radical hysterectomy.
Humans ; Hysterectomy* ; Ligaments ; Lymph Node Excision ; Uterine Cervical Neoplasms*

OBJECTIVE: To gain basic information regarding the biologic stability of plasma ion-implanted miniscrews and their potential clinical applications. METHODS: Sixteen plasma ion-implanted and 16 sandblasted and acid-etched (SLA) miniscrews were bilaterally inserted in the mandibles of 4 beagles (2 miniscrews of each type per quadrant). Then, 250 - 300 gm of force from Ni-Ti coil springs was applied for 2 different periods: 12 weeks on one side and 3 weeks contralaterally. Thereafter, the animals were sacrificed and mandibular specimens including the miniscrews were collected. The insertion torque and mobility were compared between the groups. The bone-implant contact and bone volume ratio were calculated within 800 microm of the miniscrews and compared between the loading periods. The number of osteoblasts was also quantified. The measurements were expressed as percentages and analyzed by independent t-tests (p < 0.05). RESULTS: No significant differences in any of the analyzed parameters were noted between the groups. CONCLUSIONS: The preliminary findings indicate that plasma ion-implanted miniscrews have similar biologic characteristics to SLA miniscrews in terms of insertion torque, mobility, bone-implant contact rate, and bone volume rate.
Animals ; Mandible ; Nickel ; Osteoblasts ; Plasma ; Population Characteristics ; Titanium ; Torque

Esophageal candidiasis is the most common disease among all candida infections of the gastrointestinal tract, and generally develops in immunocompromised patients. The prevalence of esophageal candidiasis has increased in patients undergoing antibiotic therapy, diabetes, adrenal dysfunction, alcohol intoxication, old age, esophageal injury, esophageal stasis, gastric surgery, and acid suppressive therapy. However, the overall prevalence is not higher than that of immunocompromised patients. Gastric candidiasis is uncommon because of the strong acidity of the gastric juices. The most common clinical setting for gastric candidiasis is in patients with neoplastic disease. However, there are some case reports suggesting an increase in the prevalence of gastric candidiasis after gastric ulcer therapy with surgery or acid suppressive agents. Delayed gastric emptying, increased intragastric pH, and reflux of the duodenal contents into the stomach are factors indicative of the pathophysiology of gastric candidiasis after gastric surgery. We encountered a case of aggravated esophageal candidiasis and the formation of a gastric yeast bezoar following a gastric outlet obstruction due to a duodenal stenosis. We herein report this case along with an overview of the relevant literature.
Bezoars* ; Candida ; Candidiasis* ; Constriction, Pathologic* ; Gastric Emptying ; Gastric Juice ; Gastric Outlet Obstruction* ; Gastrointestinal Tract ; Gastroparesis ; Humans ; Hydrogen-Ion Concentration ; Immunocompromised Host ; Prevalence ; Stomach ; Stomach Ulcer ; Yeasts*