Oh Kyoung Kwon

Three-dimensional gastric cancer cell culture using nanofiber scaffold for chemosensitivity test.

A three-dimensional (3D) culture of cancer cells has long been advocated as a better model of the malignant phenotype that is most closely related to tumorigenicity in vivo. To investigate the sensitivity of cancer cells to anticancer drugs, nanofiber scaffolds composed of PHBV and collagen peptide were fabricated by electrospinning. A 3D culture of cancer cells was successfully achieved by the use of nanofiber scaffolds. From the result of a chemosensitivity test, it was found that higher concentrations of anticancer drugs were required to achieve a comparable cytotoxic effect in 3D culture due to their structural architecture. These data demonstrate that the electrospun nanofiber scaffolds can provide a 3D model particularly appropriate for investigating mechanisms involved in cancer cell sensitivity to anticancer drugs.

Long-term Quality of Life After Distal Subtotal and Total Gastrectomy: Symptom- and Behavior-oriented Consequences.

Objective:This study assessed long-term quality of life (QoL) after subtotal gastrectomy (STG) and total gastrectomy (TG) by comparing groups matched by a set of patient factors at and beyond postoperative 5 years. The cause of QoL gaps based on symptomatic and behavioral consequences of surgery were investigated. Background:Survivors after STG and TG were matched by a set of patient factors (age, sex, stage, chemotherapy, and postoperative period). QoL data were obtained from 53 and 36 pairs of survivors at and beyond postoperative 5 years, respectively. Methods:The European Organization for Research and Treatment of Cancer QoL Questionnaire (QLQ)-C30 and QLQ-STO22 were used to assess QoL. QoL comparisons between STG and TG groups were made for 5-year survivors and long-term survivors. Results:Five-year survivors after TG showed significantly worse QoL in social functioning, nausea and vomiting, eating restrictions, and taste. For long-term survivors, QoL inferiority of the TG group was observed only in eating restrictions. Among 4 items constituting eating restrictions, the TG group tended to exhibit worse QoL in 2 items (enjoyable meals and social meals). Conclusions:Although 5-year survivors after TG still suffer from QoL inferiority from symptomatic and behavioral consequences of surgery, inferiority from behavioral consequences will persist even after symptomatic inferiority to STG survivors is no longer valid. Efforts to ameliorate persistent QoL inferiority in TG survivors should be directed toward restoring dietary behaviors, where TG survivors are prevented from enjoyable meals and social meals.

Quality of life in cancer survivors 5 years or more after total gastrectomy: A case-control study

INTRODUCTION This study investigated how total gastrectomy (TG), along with memories of cancer, affect the subjective wellness of survivors long after surgery. Rational approaches for effectively improving the quality of life (QoL) of these survivors were suggested. METHODS Between 2008 and 2013, QoL data of gastric cancer patients who underwent a curative TG, were obtained at 5-year postoperative follow-up visits (5-year survivors) and at visits beyond 5 years (long-term survivors). The control groups for these survivor groups were constructed from volunteers who visited our health-examination center for annual medical checkups. The Korean versions of the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the gastric cancer specific module, the EORTC QLQ-STO22, were used to assess QoL. RESULTS Five-year survivors showed worse QoL compared to the control group in role functioning, social functioning, nausea/vomiting, appetite loss, financial difficulties, reflux, eating restrictions, taste, and body image, and better QoL in the emotional and cognitive functioning scales. In long-term survivors, deterioration in QoL were still apparent in financial difficulties, reflux, and eating restrictions, while QoL differences in the remaining scales had diminished. DISCUSSION Surviving 5 years after TG does not result in living in a carefree state in terms of QoL. After 5 postoperative years, survivors still need extended care for deteriorated QoL indicators due to symptomatic, behavioral, and financial consequences of surgery. CONCLUSION While relevant clinical and institutional approaches are required for corresponding declines in QoL, such efforts must extend beyond 5 postoperative years.

Laparoscopy Assisted versus Open Distal Gastrectomy with D2 Lymph Node Dissection for Advanced Gastric Cancer: Design and Rationale of a Phase II Randomized Controlled Multicenter Trial (COACT 1001)

Purpose Laparoscopy-assisted distal gastrectomy for early gastric cancer has gained acceptance and popularity worldwide. However, laparoscopy-assisted distal gastrectomy for advanced gastric cancer is still controversial. Therefore, we propose this prospective randomized controlled multi-center trial in order to evaluate the safety and feasibility of laparoscopy assisted D2-gastrectomy for advanced stage gastric cancer. Materials and Methods Patients undergoing distal gastrectomy for advanced gastric cancer staged cT2/3/4 cN0/1/2/3a cM0 by endoscopy and computed tomography are eligible for enrollment after giving their informed consent. Patients will be randomized either to laparoscopy-assisted distal gastrectomy or open distal gastrectomy. Sample size calculation revealed that 102 patients are to be included per treatment arm. The primary endpoint is the non-compliance rate of D2 dissection; relevant secondary endpoints are three-year disease free survival, surgical and postoperative complications, hospital stay and unanimity rate of D2 dissection evaluated by reviewing the intraoperative video documentation. Discussion Oncologic safety is the major concern regarding laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Therefore, the non-compliance rate of clearing the N2 area was chosen as the most important parameter for the technical feasibility of the laparoscopic procedure. Furthermore, surgical quality will be carefully reviewed, that is, three independent experts will review the video records and score with a check list. For a long-term result, disease free survival is considered a secondary endpoint for this trial. This study will offer promising evidence of the feasibility and safety of Laparoscopy-assisted distal gastrectomy for advanced gastric cancer.Trial Registration: NCT01088204 (international), NCCCTS-09-448 (Korea).

Chronological Changes of Quality of Life in Long-Term Survivors after Gastrectomy for Gastric Cancer

Purpose A few studies have prospectively evaluated changes in quality of life (QoL) after surgery in short-term survivors; however, no prospective study has evaluated the longitudinal changes in QoL in long-terms survivors. We prospectively evaluated the chronological changes in QoL after a gastrectomy over a 5-year postoperative period in a large group of patients. Materials and Methods QoL data from the European Organization for Research and Treatment of Cancer QLQ-C30 and the QLQ-STO22 questionnaires were obtained from 254 patients who completed the entire series of QoL assessments preoperatively and at 1, 2, 3, 4, and 5 years after surgery. Results There was no statistically significant change in global health status/QoL during the 5-year postoperative period. Decreases in QoL from upper gastrointestinal symptoms including diarrhea (p < 0.001), dysphagia (p < 0.001), reflux symptoms (p=0.029), and eating restrictions (p < 0.001) were observed among the long-term survivors. Decreased physical functioning (p < 0.001), role functioning (p < 0.001), and cognitive functioning (p < 0.001), along with fatigue (p=0.045) and a poor body image (p=0.003), negatively impacted the patients’ QoL for a long time. Conclusion Management of gastrointestinal symptoms should be specifically targeted as a part of long-term patient care after a gastrectomy. Proper nutritional care will improve food intake resulting in weight gain and improved physical functioning, role functioning, and body image. In addition, patients should be encouraged to preserve self-esteem and maintain social activity.

Effect of Intravenous Ferric Carboxymaltose on Hemoglobin Response Among Patients With Acute Isovolemic Anemia Following Gastrectomy: The FAIRY Randomized Clinical Trial

Importance Acute isovolemic anemia occurs when blood loss is replaced with fluid. It is often observed after surgery and negatively influences short-term and long-term outcomes. Objective To evaluate the efficacy and safety of ferric carboxymaltose to treat acute isovolemic anemia following gastrectomy. Design, Setting, and Participants The FAIRY trial was a patient-blinded, randomized, phase 3, placebo-controlled, 12-week study conducted between February 4, 2013, and December 15, 2015, in 7 centers across the Republic of Korea. Patients with a serum hemoglobin level of 7 g/dL to less than 10 g/dL at 5 to 7 days following radical gastrectomy were included. Interventions Patients were randomized to receive a 1-time or 2-time injection of 500 mg or 1000 mg of ferric carboxymaltose according to body weight (ferric carboxymaltose group, 228 patients) or normal saline (placebo group, 226 patients). Main Outcomes and Measures The primary end point was the number of hemoglobin responders, defined as a hemoglobin increase of 2 g/dL or more from baseline, a hemoglobin level of 11 g/dL or more, or both at week 12. Secondary end points included changes in hemoglobin, ferritin, and transferrin saturation levels over time, percentage of patients requiring alternative anemia management (oral iron, transfusion, or both), and quality of life at weeks 3 and 12. Results Among 454 patients who were randomized (mean age, 61.1 years; women, 54.8%; mean baseline hemoglobin level, 9.1 g/dL), 96.3% completed the trial. At week 12, the number of hemoglobin responders was significantly greater for ferric carboxymaltose vs placebo (92.2% [200 patients] for the ferric carboxymaltose group vs 54.0% [115 patients] for the placebo group; absolute difference, 38.2% [95% CI, 33.6%-42.8%]; P = .001). Compared with the placebo group, patients in the ferric carboxymaltose group experienced significantly greater improvements in serum ferritin level (week 12: 233.3 ng/mL for the ferric carboxymaltose group vs 53.4 ng/mL for the placebo group; absolute difference, 179.9 ng/mL [95% CI, 150.2-209.5]; P = .001) and transferrin saturation level (week 12: 35.0% for the ferric carboxymaltose group vs 19.3% for the placebo group; absolute difference, 15.7% [95% CI, 13.1%-18.3%]; P = .001); but there were no significant differences in quality of life. Patients in the ferric carboxymaltose group required less alternative anemia management than patients in the placebo group (1.4% for the ferric carboxymaltose group vs 6.9% for the placebo group; absolute difference, 5.5% [95% CI, 3.3%-7.6%]; P = .006). The total rate of adverse events was higher in the ferric carboxymaltose group (15 patients [6.8%], including injection site reactions [5 patients] and urticaria [5 patients]) than the placebo group (1 patient [0.4%]), but no severe adverse events were reported in either group. Conclusion and Relevance Among adults with isovolemic anemia following radical gastrectomy, the use of ferric carboxymaltose compared with placebo was more likely to result in improved hemoglobin response at 12 weeks. Trial Registration clinicaltrials.gov Identifier: NCT01725789

Predictive Factors for Lymph Node Metastasis in Signet Ring Cell Gastric Cancer and the Feasibility of Endoscopic Submucosal Dissection

Purpose Endoscopic submucosal dissection has recently been practiced on a differentiated type of early gastric cancer. However, there is no clear evidence for endoscopic treatments of signet ring cell carcinoma. The aim of this study is to identify the predictive clinicopathological factors for lymph node metastasis in signet ring cell carcinoma for assisting endoscopic submucosal dissection trials. Materials and Methods A total of 186 patients with early signet ring cell carcinoma who underwent radical curative gastrectomy between January 2001 and September 2009 were enrolled in this study. Retrospective reviews of their medical records are being conducted. Several clinicopathologic factors were being investigated in order to identify predictive factors for lymph nodes metastasis: age, gender, tumor size, type of operation, tumor location, gross type, ulceration, Laurens classification, depth of invasion, and lymphatic invasion. Results The lymph node metastasis rate for signet ring cell carcinoma was 4.3% (n=8). Of the 186 lesions with early signet ring cell carcinoma, 91 (48.9%) tumors were larger than 15 mm in size and 40 (21.5%) showed submucosal invasions in the resection specimens. In multivariate analysis, only the lymphatic invasion (P<0.0001) showed an association with lymph node metastasis. To evaluate cutoff values for tumor sizes in the presence of lymph node metastasis, early signet ring cell carcinomas with lymphatic invasions were excluded. In the absence of lymphatic invasion, mucosal cancer with tumor sizes <15 mm had no lymph node metastasis. Conclusions Endoscopic submucosal dissection can be performed on patients with early signet ring cell carcinoma limited to the mucosa and less than 15 mm.

High level of viral microRNA-BART20-5p expression is associated with worse survival of patients with Epstein-Barr virus-associated gastric cancer

This study analyzed the relationship between several Epstein-Barr virus (EBV) microRNA (miRNA) expression profiles and the clinicopathologic features of patients with EBV-associated gastric cancer. The miRNA expression was examined in 59 tumor and 39 paired normal mucosal tissues from available formalin-fixed paraffin embedded tissue samples. The expression levels of miR-BamHI fragment A rightward transcript (BART)1-5p, miR-BART4-5p, and miR-BART20-5p were determined using a quantitative real-time polymerase chain reaction. The expression of all three analyzed EBV microRNAs was significantly higher in the tumor tissue than in the paired normal tissue (P < 0.001 for each). When the median value of the EBV microRNA expression levels was used as the cutoff point, a high BART20-5p expression was associated with worse recurrence-free survival (P = 0.034) in a multivariate analysis including age and pathologic stage. In conclusion, the expression level of BART20-5p may predict recurrence-free survival for patients with EBV-associated gastric cancer. Further studies are warranted to clarify the roles of EBV BART microRNAs in the carcinogenesis, and their potential as a biomarker and therapeutic target for EBV-associated gastric cancer.

Preparation and Evaluation of Poly(γ-glutamic acid)-Based Anti-Adhesion Membranes

Poly(γ-glutamic acid)(γ-PGA) based nanofiber sheets were prepared by using electrospinning technique to evaluate the ability of the prevention of postoperative tissue adhesion. The anti-adhesion membranes were prepared from poly(γ-glutamic acid) and PLGA with different compositions by electrospinning. Also nonsteroidal anti-inflammatory drug (ibuprofen) was incorporated during fabrication of nanofibers. Various electrospun nanofibers were characterized by the measurements of microstructure (surface morphology and fiber diameter by SEM), ATR-FTIR, water contact angle and in vivo animal study using Sprague Dawley rat model. The average diameter of nanofibers electrospun from trifluoroacetic acid (TFA) solution ranged from 300 nm to 900 nm, approximately. From in vivo animal study, it was observed that ibuprofen-incorporated γ- PGA nanofiber sheet was significantly effective in preventing tissue adhesion and inducing wound healing, probably due to the appropriate hydrophilicity of γ-PGA preventing shrinkage of the sheet and appropriate barrier property, while PLGA nanofibrous mat was dramatically contracted in in vivo due to its high hydrophobicity resulted in insufficient coverage of wound.

Nanofiber mats composed of a chitosan-poly(d,l-lactic-co-glycolic acid)-poly(ethylene oxide) blend as a postoperative anti-adhesion agent.

Postoperative tissue adhesion causes serious complications and suffering in 90% of patients after peritoneum surgery, while commercial anti-adhesion agents cannot completely prevent postoperative peritoneal adhesions. This study demonstrates electrospining of a blended solution of chitosan, poly(d,l-lactic-co-glycolic acid) (PLGA), and poly(ethylene oxide) (PEO) to fabricate a chitosan-based nanofibrous mat as a postoperative anti-adhesion agent. Rheological studies combined with scanning electron microscopy reveal that the spinnability of the chitosan-PLGA solution could be controlled by adjusting the blend ratio and concentration with average fiber diameter from 634 to 913 nm. Biodegradation of the nanofiber specimens showed accelerated hydrolysis by chitosan. Proliferation of fibroblasts and antimicrobial activity of nanofibers containing chitosan was analyzed. Abdominal defects with cecum adhesion in rats demonstrated that the blend nanofiber mats were effective in preventing tissue adhesion as a barrier (4 weeks after abdominal surgery) by coverage of exfoliated peritoneum and insufficient wound sites at the beginning of the wound healing process. Chitosan-PLGA-PEO blend nanofiber mats will provide a promising key as a postoperative anti-adhesion agent.