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.

Background: Disruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment. Results: The Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the midcolon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such asTNF-α, IL-6, IL-1β, IL-13, and IL-4 in Lm + Pt treated SD rats. Conclusions These results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.

Background: To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX. Results: The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 pro-tein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The ­ IC50 level to DOX was lower in both primary cells ­(IC50 = 0.12 μM and 0.20 μM) as compared to the CT26 cells ­(IC50 = 0.32  μM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7–23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8–254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells. Conclusions To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALENmediated Trp53 mutant gene.

Background: In psoriasis treatment, not all body regions improve simultaneously after clinical interventions. Objective: This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans. Methods: This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis. Results: The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits. Conclusion We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment.

The deep inferior epigastric perforator (DIEP) flap has been widely used for autologous breast reconstruction after mastectomy. In the conventional surgical method, a long incision is needed at the anterior fascia of the rectus abdominis muscle to obtain sufficient pedicle length; this may increase the risk of incisional hernia. To shorten the incision, several trials have investigated the use of endoscopic/robotic devices for pedicle harvest; however, making multiple additional incisions for port insertion and operating in the intraperitoneal field were inevitable. Here, we describe the first case, in which a DIEP free flap was successfully made using the da Vinci SP model. Our findings can help surgeons perform operations in smaller fields with a single port in the extraperitoneal space. Moreover, this method is expected to lead to fewer donor-related complications and faster healing.

Background/Aims: We aim to evaluate the effects of auranofin, a known antioxidant, on hepatic steatosis, inflammation, and fibrosis, contributing to non-alcoholic steatohepatitis (NASH) development in vivo and in vitro. Methods: Transcriptome analysis of LX-2 cells was that expression patterns of genes changed by auranofin, and their related pathways were estimated. We used the gene set enrichment analysis (GSEA) program to determine the pathway involved in overall genetic change. In vitro, LX-2 and HepG2 cells were treated with transforming growth factor (TGF)-β1 and palmitic acid (PA), respectively, and the antifibrotic and antiadipogenic effect function of auranofin was evaluated. Results: Transcriptome analysis revealed that auranofin decreased the expression of 15 genes, including thrombospondin 1, endothelin 1 (ET-1), fibronectin 1, and LOX. The molecular functions of these genes are involved in collagen binding. GSEA of the overall gene expression pattern revealed that many genes increased in the reactive oxygen species pathway and decreased in the inflammatory response. Auranofin decreased nuclear factor kappa B (NF-κB) and IκBα in TGF-β1-induced LX-2 cells, thereby reducing ET-1 and fibrosis. Furthermore, increased pNRF2 in PA-induced HepG2 cells led to increased antioxidant marker expression and decreased lipid accumulation. In the bile duct ligation model mice, auranofin reduced the fibrosis area and increased the survival rate. Auranofin reduced liver fibrosis and lipid accumulation in NASH model mice fed on a Western diet. Conclusions Auranofin inhibits lipogenesis and fibrosis formation and is a proposed candidate for NASH treatment.

Rectovaginal fistula, which can arise after an injury to the vaginal canal or rectum, is a troublesome obstacle for patients’ everyday life. In most cases, it can be covered with a local flap, but previous radiation therapy increases the recurrence rate, making it especially difficult to cure. As the application of stromal vascular fraction (SVF) obtained from enzymatically digested autologous adipose tissue has become increasingly common, several reports have advocated its effectiveness for the treatment of refractory wounds. In light of the angiogenic, regenerative characteristics of SVF, it was incorporated as a treatment option in two cases of rectovaginal fistula discussed here. As described in this report, irradiated rectovaginal fistulas in rectal cancer patients were successfully treated with SVF injection, and we suggest SVF as a feasible treatment option for cases of rectovaginal fistula that would otherwise be very difficult to cure.

Background: Reconstruction after removal of a malignant tumor in the head and neck region is crucial for restoring tissue integrity, function, and aesthetics. We retrospectively analyzed patients who underwent intraoral reconstruction surgery using radial forearm free flaps (RFFF) and anterolateral thigh free flaps (ALT) at a single institution to provide more information supporting the choice of a reconstruction method after removal of head and neck cancer. Methods: The charts of 708 patients who underwent head and neck reconstruction between 1998 and 2018 at the Department of Plastic and Reconstructive Surgery at our institution were retrospectively reviewed. Patients’ age, sex, and history of radiation therapy, diabetes mellitus, and smoking were retrieved. The primary cancer site, types of defects, and complications were investigated. Results: Overall, 473 and 95 patients underwent reconstruction surgery with RFFF and ALT, respectively. RFFF was more often used in patients with cancers of the pharynx, larynx, esophagus, or tonsil, while ALT was more frequently used in patients with cancers of the mouth floor with tonsil or tongue involvement. The proportion of patients undergoing ALT increased gradually. Flap failure and donor site morbidities did not show significant differences between the two groups. Conclusions RFFF and ALT flaps resulted in similar outcomes in terms of flap survival and donor site morbidity. ALT can be an option for head and neck reconstruction surgery in patients with large and complex defects or for young patients who want to hide their donor site scars.