Preoperative assessment of lymph node metastasis in endometrial cancer: A Korean Gynecologic Oncology Group study.

BACKGROUND: Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed. METHODS: Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low-risk patients: 1) endometrioid-type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para-aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV). RESULTS: From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low-risk group. Fifty-three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low-risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%. CONCLUSIONS: The low-risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263-272. © 2016 American Cancer Society.

Survival impact based on the thoroughness of pelvic lymphadenectomy in intermediate- or high-risk groups of endometrioid-type endometrial cancer: A multi-center retrospective cohort analysis.

OBJECTIVE: To investigate whether the number of lymph nodes obtained during lymphadenectomy affects the survival of patients with intermediate- or high-risk endometrioid-type endometrial cancer. METHODS: A total of 476 patients who were diagnosed with FIGO stage IB to IIIC2 endometrioid adenocarcinoma through surgical staging, including hysterectomy and pelvic lymphadenectomy with or without paraaortic lymphadenectomy between 2000 and 2013 were retrospectively enrolled from four tertiary centers in Korea. Sentinel lymph node mapping was not performed in any patient. The number of nodes obtained and positive nodes, was extracted from pathologic report. RESULTS: Paraaortic lymphadenectomy was performed in 298 (62.6%) patients and 164 (34.4%) had stage IIIC disease. The isolated paraaortic lymph node metastasis rate decreased as the number of pelvic nodes obtained increased. In the total study population, an increase of negative pelvic and paraaortic nodes was associated with improved recurrence-free survival (RFS) and overall survival (OS) independent of other prognostic factors. In the node-positive group, an increase of negative pelvic nodes was an independent prognostic factor for RFS [hazard ratio (HR), 0.946; 95% confidence interval (CI), 0.906-0.988] and OS [HR, 0.907; 95% CI, 0.849-0.968]. In stage IIIC2 patients, 14 or less negative pelvic nodes was associated with poor RFS and OS. CONCLUSIONS: Removing as many pelvic nodes as possible is required to warrant accurate nodal staging and improve survival in patients with intermediate- or high-risk endometrial cancer. Sentinel lymph node mapping can be a resolution to minimize lymph node dissection without compromising staging accuracy.

Advances and Concepts in Cervical Cancer Trials: A Road Map for the Future.

OBJECTIVE: Cervical cancer is responsible for more than a quarter of a million deaths globally each year, mostly in developing countries, making therapeutic advances in all health care settings a top priority. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaboration of leading national research groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representation from the GCIG groups and selected large sites in low- and middle-income countries. METHODS: The focus was to develop a consensus on several concepts for future clinical trials, which would be developed and promoted by the GCIG and launched with major international participation. The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps in need of new evidence, validating control arms for present and future clinical trials and identifying national and international barriers for studies of cervix cancers. The second half of the meeting was concerned with achieving consensus on a path forward. RESULTS AND CONCLUSIONS: There were 5 principal outcomes as follows: first, a proposal to expand fertility-preserving options with neoadjuvant chemotherapy; second, validation of the assessment of sentinel lymph nodes using minimally invasive surgery with an emphasis on identification and management of low-volume metastasis, such as isolated tumor cells and micrometastasis; third, evaluation of hypofractionation for palliative and curative radiation under the umbrella of the GCIG Cervix Cancer Research Network; fourth, adding to the advances in antiangiogenesis therapy in the setting of metastatic disease; and fifth, developing a maintenance study among women at high risk of relapse. The latter 2 systemic interventions could study PI3K (phosphatidylinositol-3-kinase) inhibitors, immunotherapy, anti-human papillomavirus approaches, or novel antiangiogenic agents/combinations.

Use of complex surgical procedures, patterns of tumor spread, and CA-125 predicts a risk of incomplete cytoreduction: a Korean Gynecologic Oncology Group study (KGOG-3022).

OBJECTIVES: We aimed to develop a risk model to predict a risk of suboptimal cytoreduction in primary surgery of ovarian cancer. METHODS: The clinical records and computed tomography (CT) data of 358 patients with stages II-IV epithelial ovarian cancer were reviewed. Tumor spread patterns identified by principal component analysis, CA-125, and a newly developed surgical skill index were integrated into a logistic model along with other variables. Internal validation was performed using bootstrapped re-sampling and calibration was assessed by goodness-of-fit test. RESULTS: Among the 358 patients, optimal cytoreduction, which was defined as no residual tumor, was achieved in 145 patients (40.5%). The surgical capacity of an individual institution was estimated by a surgical skill index, which was the frequency of complex surgeries in patients with advanced disease. In a multivariate model, two distinctive CT patterns of tumor spread (diffuse spread pattern and upper abdominal extension pattern), a surgical skill index, and serum CA-125 independently predicted a risk of suboptimal cytoreduction (P=0.006, P=0.013, P=0.031, and P=0.001, respectively). The model showed a C-statistic of .73 (95% confidence interval .67 to .79), which was significantly higher than tumor stage or ascites. Rigorous internal validation by bootstrapped re-sampling successfully confirmed the model. CONCLUSIONS: We identified two distinct tumor spread patterns of ovarian cancer, which can be integrated to improve a prediction model. Our model may be useful in patient referral or clinical trials for patient stratification.

Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial.

BACKGROUND: Intraperitoneal chemotherapy has been shown to be effective at reducing mortality for patients with advanced epithelial ovarian cancer but is not widely used in practice. METHODS: We performed the Intraperitoneal Therapy for Ovarian Cancer with Carboplatin (iPocc) trial as an open-label, international, multi-institutional, randomized phase 2/3 clinical trial in women with newly diagnosed epithelial ovarian cancer who underwent laparotomy or laparoscopy. All patients received intravenous paclitaxel (80 mg/m2 on days 1, 8, and 15 of a 21-day cycle). In addition, patients in the control group received intravenous carboplatin (dose-dense intravenous paclitaxel plus intravenous carboplatin [dd-TCiv]), whereas patients in the experimental group received dose-dense intravenous paclitaxel plus intraperitoneal carboplatin (dd-TCip). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response, treatment completion rate, and incidence of adverse events (AEs). RESULTS: Among 655 patients randomized to treatment, median (95% confidence interval [CI]) PFS was 20.7 (18.1 to 22.8) months for dd-TCiv (n=328) and 23.5 (20.5 to 26.9) months for dd-TCip (n=327; hazard ratio, 0.83; 95% CI, 0.69 to 0.99; P=0.04). The PFS benefit with dd-TCip was consistent in patients with different baseline characteristics, stage, size of residual tumor, age, and performance status. The treatment completion rates were 68.3 and 59.9% in the dd-TCiv and dd-TCip groups, respectively. The incidence of intraperitoneal catheter-related AEs in the dd-TCip group was 10.1%; there were no such AEs in the dd-TCiv group. CONCLUSIONS: In the first-line treatment of advanced epithelial ovarian cancer, intraperitoneal carboplatin resulted in a modest prolongation of PFS when given with dose-dense weekly paclitaxel regardless of residual tumor size, with no impact on noncatheter-related toxicities. (Funded by the Japan Agency for Medical Research and Development, and others; Japan Registry of Clinical Trials number, jRCTs031180141.)

Risk of metastatic ovarian involvement in nongynecologic malignancies.

OBJECTIVE: The objectives were to evaluate the risk of malignant adnexal tumors in women with nongynecologic malignancies and to identify variables associated with the risk of malignant adnexal tumors. METHODS: The eligibility criteria included the diagnosis of a nongynecologic malignancy and adnexal tumors, which were resected or subjected to biopsy at our institute between 1999 and 2010. The risk of malignant adnexal tumors was assessed by dividing the number of patients with metastatic tumors to the adnexa or primary adnexal cancers by the total number of patients. The association of clinicopathologic variables with the risk of malignant adnexal tumors was evaluated using the Fisher exact test and binary logistic regression analysis. In patients with metastatic tumors to the adnexa, the association of clinicopathologic variables with overall survival after adnexal surgery was examined using the log-rank test. RESULTS: In 166 patients with adnexal tumors, 41 benign tumors, 113 metastatic tumors to the adnexa, and 12 primary adnexal cancers were diagnosed. Age older than 46 years, a tumor type associated with a high risk for malignant adnexal tumors, and bilateral tumors significantly increased the risk of malignant adnexal tumors. The overall survival of the patients with stomach cancer was significantly worse than the patients with colorectal or breast cancers. CONCLUSION: One hundred twenty-five of the 166 patients with nongynecologic malignancies who had adnexal tumors managed surgically were shown to have malignant tumors, and most of the tumors were metastatic from primary sites. The risk of malignant adnexal tumors was associated with age, nongynecologic malignancy, and bilaterality.

Efficacy of fibrin sealant in reducing hemorrhage after a loop electrosurgical excision procedure.

BACKGROUND/AIMS: We examined the association of fibrin sealant use with post-operative hemorrhage in patients who underwent a loop electrosurgical excision procedure (LEEP). METHODS: We retrospectively collected clinicopathologic data of 344 patients who underwent LEEP at our institute between 2007 and 2009. We defined hemorrhage which occurred between 1 and 30 days after LEEP and required electrocautery to achieve hemostasis as severe secondary hemorrhage (SSH). We determined whether or not the use of fibrin sealant during LEEP was associated with a decreased occurrence of SSH. In addition, we examined the associations of other clinicopathologic variables with SSH and fibrin sealant use. RESULTS: SSH occurred in 6 of 200 patients (3%) with fibrin sealant and in 12 of 144 patients (8%) without fibrin sealant. Based on univariate analysis, the use of fibrin sealant was associated with SSH (p = 0.028). However, age, surgeons and pathologic diagnosis were not associated with SSH. Based on multivariate analysis, the use of fibrin sealant was associated with less SSH (p = 0.033, OR = 0.328, 95% CI 0.117-0.917). CONCLUSION: Fibrin sealant use reduces the incidence of severe post-operative hemorrhage after LEEP.

Detection of recurrence by 18F-FDG PET in patients with endometrial cancer showing no evidence of disease.

This study assessed the feasibility of F-18-fluorodeoxyglucose positron-emission tomography ((18)F-FDG PET) in the post-therapy surveillance for patients with endometrial cancer showing no evidence of disease (NED). From April 1997 to June 2007, 127 patients with endometrial cancer showing NED were performed (18)F-FDG PET scan. The feasibility of (18)F-FDG PET for the early detection of recurrence in patients with endometrial cancer was evaluated retrospectively. Of the 127 patients, 32 patients showed positive lesions on (18)F-FDG PET scan. Nineteen (19/127 cases, 15%) of them were confirmed to have a recurrence clinically or histologically. The sensitivity, specificity and positive and negative predictive value of (18)F-FDG PET for detecting recurrences in patients with endometrial cancer were 100%, 88%, 59% and 100%, respectively. In conclusion, (18)F-FDG PET may be a useful method for the post-therapy surveillance in patients with endometrial cancer.

An extremely rare elderly case of proximal epithelioid sarcoma of the vulva: case report with a review of literatures.

We experienced an extremely rare case of proximal epithelioid sarcoma (PES) of the vulva in a 77-year-old woman. After history taking and physical examination, the patient was tentatively diagnosed as having Bartholin's cyst in the right labium. Based on histopathological and immunohistochemical (IHC) findings, however, a final diagnosis of PES of the vulva was made. After receiving CyberKnife treatment, the patient survived but with recurrent episodes and poor prognosis. In conclusion, our case indicates that patients with PES of the vulva should be appropriately managed with radiotherapy after a differential diagnosis based on histopathological and IHC findings.

Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial.

PURPOSE: A phase II study (ClinicalTrials.gov identifier: NCT00628251) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. PATIENTS AND METHODS: In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician's choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. RESULTS: Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. CONCLUSION: Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.

Ovarian preservation during the surgical treatment of early stage endometrial cancer: a nation-wide study conducted by the Korean Gynecologic Oncology Group.

OBJECTIVES: The objective of this study was to determine whether ovarian preservation is feasible in younger endometrial cancer patients. METHODS: Endometrial cancer patients who underwent ovary-saving surgery were recruited from the tumor registries of 14 tertiary hospitals under the influence of the Korean Gynecologic Oncology Group (KGOG). Information regarding patient age, preoperative and intraoperative evaluations, pathologic reports, and follow-up results was abstracted from medical records. RESULTS: One hundred and seventy five patients were eligible for this study. Mean patient age at the time of surgery was 38.5+/-8.3 years (range 25-57). Ovary-preserving surgery was performed in 101 (57.7%) patients who desired to preserve their ovaries, incidentally in 69 (39.4%) patients with preoperative diagnoses other than endometrial carcinoma, and in 5 patients (2.9%) with unknown reasons. Median duration of follow-up was 55.0 months (range 6.2-180.0 months). Recurrence free survival and overall survival rates were 94.3 and 93.3%, respectively. Seven of the 175 (4.0%) patients had documented recurrence, and no recurrences were observed in stage I patients with endometrioid histology. All 7 recurrences had risk factors that could have reasonably explained recurrence, namely, non-endometrioid histology (4/7), deep myometrial invasion (5/7), cervical stromal invasion (4/7), and inadequate adjuvant treatment (4/7). No metachronous ovarian malignancy occurred during follow-up. Ten (5.8%) deaths occurred during follow-up; five resulted from disease recurrence, and 5 from non-disease related causes. CONCLUSION: Our findings suggest that ovarian preservation does not adversely impact the recurrence of early stage endometrial cancer.

Clinicopathologic characteristics of malignant germ cell tumors in the ovaries of Korean women: a Korean Gynecologic Oncology Group Study.

From January 1995 to December 2000, medical records of 196 patients were collected from 14 hospitals nationwide and were reviewed retrospectively. We evaluated the clinicopathologic characteristics of malignant germ cell tumors in the ovaries of South Korean women and determined the prognostic factors affecting recurrence. The mean patient age was 23.8 years (range, 4-63 years), and the median follow-up period was 67 months (range, 1-128 months). The distribution of the International Federation of Gynecology and Obstetrics stage was as follows: 128 cases (65.3%) in stage I, 27 cases (13.8%) in stage II, 39 cases (19.9%) in stage III, and 2 cases (1.0%) in stage IV. Histologically, immature teratoma was the most common tumor type (n = 68), followed by dysgerminoma (n = 54), endodermal sinus tumor (n = 38), mixed form (n = 24), and choriocarcinoma (n = 12). A fertility-sparing operation was performed in 134 patients, staging operation in 43 patients, and hysterectomy and bilateral salpingo-oophorectomy in 19 patients. Postoperative chemotherapy was administered in 166 patients, and the most common regimen was bleomycin, etoposide, and cisplatin (n = 120). Recurrence was observed in 13 patients (6.8%) and was influenced by the stage of the tumor and patient age (>40 years). The 5-year survival rate was 96.7%. During the follow-up period, 20 patients had 22 pregnancies that resulted in 17 normal deliveries at term and 5 abortions. The results of this study demonstrate that most malignant germ cell tumors of the ovary in Korean women are detected in the early stage and have excellent survival outcomes with conservative operation and platinum-based chemotherapy.

Adenocarcinoma arising from the respiratory ciliated epithelium in a benign cystic teratoma of the ovary.

Benign cystic teratoma of the ovary (BCTO) is the most common benign ovarian tumor, accounting for 15-20% of all ovarian tumors. It is usually diagnosed in the third and fourth decades of life. Malignant transformation is rare, occurring in approximately 1-2% of reported cases, with squamous cell carcinoma being the most common form. Adenocarcinoma arising from mature cystic teratoma is extremely rare. We present the patient with a BCTO, where a malignant transformation of respiratory ciliated epithelium resulted in well differentiated adenocarcinoma. Although respiratory epithelium is often found in BCTOs, adenocarcinoma arising from this cell type is uncommon. To our knowledge, this is the fourth reported case of adenocarcinoma arising from the respiratory epithelium of a BCTO.

Prognostic significance of pretreatment lymphocyte percentage and age at diagnosis in patients with locally advanced cervical cancer treated with definite radiotherapy.

OBJECTIVE: This study aimed to evaluate the prognostic impact of age at diagnosis, and pretreatment hematologic markers, including lymphocyte percentage and the neutrophil-to-lymphocyte ratio (NLR), in patients with locally advanced cervical cancer (LACC) treated with definitive radiotherapy (RT). METHODS: A total of 392 patients with LACC (stage IIb to IVa) treated with cisplatin-based concurrent chemoradiotherapy or RT alone between 2001 and 2012 were retrospectively enrolled. Clinical data and pretreatment complete blood counts were extracted from electronic medical records of the patients, and analyzed. Treatment outcomes, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Low lymphocyte percentage and a high NLR were associated with younger age, advanced stage, larger tumor size, lymph nodes metastasis, and treatment failure. The cut-off value for lymphocyte percentage and NLR was determined using a receiver operating characteristic curve. In univariate analysis, low lymphocyte percentage (≤24%) was associated with poor PFS and OS, while high NLR (>2.8) was significantly associated only with PFS. In multivariate analysis, both lymphocyte percentage (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.40-0.85; P=0.005) and NLR (HR, 1.55; 95% CI, 1.07-2.25; P=0.022) had independent prognostic value for PFS. Compared to younger patients (age ≤50 years), older patients (age >60 years) had a lower risk of death. CONCLUSION: Although the lymphocyte percentage did not remain significant in multivariate analysis for OS, it was predictive of PFS and OS. Thus, lymphocyte percentage is a simple hematologic parameter with a significant prognostic value in patients with LACC treated with definitive RT.

Phase II evaluation of CKD-602, a camptothecin analog, administered on a 5-day schedule to patients with platinum-sensitive or -resistant ovarian cancer.

BACKGROUND: To evaluate the toxicity and efficacy of a newly developed topoisomerase I inhibitor, CKD-602 in second-line therapy of ovarian cancer. METHODS: We enrolled 24 patients with recurrent ovarian cancer, of median age 54 years (range, 39-64). Eleven patients had measurable lesions on CT scan, and the other 13 had increased serum CA-125 levels. Eighteen patients had platinum-sensitive disease (minimum treatment free interval > or =6 months) and 6 had platinum-resistant disease (minimum treatment free interval <6 months). CKD-602 (0.5 mg/m(2)/day) was administered intravenously for 5 days every 3 weeks. The median number of courses per patient was 6 (range, 1 to 12). Response was evaluated by the evaluation of the size of the mass by CT scan and CA-125 response. RESULTS: The overall response rate was 45.0% (9/20), with 4 patients exhibiting partial responses and 5 patients exhibiting 75% CA-125 responses in 20 evaluable patients. Of the 9 responsive patients, 8 were platinum-sensitive (8/15, 53.3%) and 1 was platinum-resistant (1/5, 20.0%). An additional 5 patients showed stable disease, whereas 6 patients exhibited progressive lesions. Of 24 patients, the most common toxicity was hematological, with grades 3 or 4 neutropenia developing in all 24 patients (100%) and in 94 cycles (71.7%). Grade 3 thrombocytopenia developed in 4 patients (16.7%) and 6 cycles (4.6%). None of the patients experienced grades 3 and 4 gastrointestinal toxicities, including nausea, vomiting, and anorexia. CONCLUSIONS: The newly developed topoisomerase I inhibitor, CKD-602, showed activity against both platinum-sensitive and -resistant ovarian cancer, with acceptable toxicity.

Prognostic Importance of the Site of Recurrence in Patients With Metastatic Recurrent Cervical Cancer.

PURPOSE: The clinical characteristics and outcomes of patients with metastatic recurrent cervical cancer remain poorly understood. The goals of the present study were to investigate the survival outcomes according to the recurrence site in a large cohort of cervical cancer patients. METHODS AND MATERIALS: Of 1322 patients with primary cervical cancer from 2000 to 2013, 205 with recurrence after primary or adjuvant postoperative radiation were enrolled retrospectively. Aggressive salvage therapy (AST), which was defined as salvage therapy that aimed not only to relieve symptoms but also to ablate recurrent tumors by the single or combined application of surgical resection of local recurrence, metastasectomy, or metastasis-directed irradiation, followed by chemotherapy, was performed according to our institutional guidelines. The patterns of recurrence, application rate and mode of AST, and survival outcomes were evaluated retrospectively under approval from the institutional review board. RESULTS: Regarding the pattern of recurrence, distant-only (DO) recurrence was most common (59.5%), followed by combined (21.5%), central (cervix or vaginal stump; 10.7%), and pelvic (pelvic lymph nodes or pelvic side wall; 8.3%) recurrence. Two subgroups (distant lymph nodes and lung parenchyma) of the DO group demonstrated remarkably good prognosis and were categorized as type A DO; the other subgroups were labeled type B DO. Patients with type A DO recurrence constituted 36% of all recurrences and 83.8% of them received AST. The 5-year overall survival rates were significantly greater in the type A DO group than in the other groups (44.8% in the type A DO group, 12.6% in the pelvic group, and 6.8% in the type B DO group). CONCLUSIONS: We identified a patient subgroup with favorable outcomes after salvage therapy, type A DO, defined as recurrence in the distant lymph nodes only or in the lung parenchyma only. A future prospective trial is needed to investigate whether AST improves survival in this group.

Tolerogenic dendritic cells show gene expression profiles that are different from those of immunogenic dendritic cells in DBA/1 mice.

Tolerogenic dendritic cells (tDCs) play an important role in inducing peripheral tolerance; however, few tDC-specific markers have been identified. The aims of this study were to examine whether tDCs show a different gene expression profile from that of immunogenic DCs and identify specific gene markers of each cell type, in DBA/1 mice. tDCs were generated by treating immature DCs (imDCs) with TNF-α and type II collagen. The gene expression profiles of mature (m)DCs and tDCs were then investigated by microarray analysis and candidate markers were validated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Supervised selection identified 75 gene signatures, 63 of which were consistently upregulated in mDCs and 12 of which were upregulated only in tDCs. Additionally, 10 genes were overexpressed or equally expressed in both tDCs and mDCs. Scin (tDC-specific genes) and Orm1, Pdlim4 and Enpp2 (mDC-specific genes) were validated by real-time qRT-PCR. Taken together, these results clearly show that tDCs and mDCs can be identified according to their expression of specific gene markers.

Analysis of immune cell populations and cytokine profiles in murine splenocytes exposed to whole-body low-dose irradiation.

PURPOSE: In contrast to high-dose therapeutic irradiation, definitive research detailing the physiological effects of low-dose irradiation is limited. Notably, the immunological response elicited after low-dose irradiation remains controversial. MATERIALS AND METHODS: Female C57BL/6 mice were whole- body-irradiated with a single or three daily fractions up to a total dose of 0.1, 1, or 10 cGy. Blood and spleen were harvested 2, 7 and 14 days after irradiation. RESULTS: The splenic CD4(+) T cell subpopulations were temporarily increased at 2 days after single or fractionated irradiation, whereas the percentage of dendritic cells (DC) and macrophages was decreased. Whereas CD8(+) T cell populations were decreased in single-dose irradiated mice at day 7, early and sustained reduction of CD8(+) T cell numbers was observed in fractionated- dose-irradiated mice from day 2 until day 14. In addition, single-dose irradiation resulted in a Th1 cytokine expression profile, whereas fractionated-dose irradiation drove a Th2 shift. Additionally, increased expression of immune-related factors was observed at early time-points with single-dose irradiation, in contrast to the dose-independent induction following fractionated-dose irradiation. CONCLUSIONS: Our results demonstrate that low-dose irradiation modulates the immune response in mice, where the sensitivity and kinetics of the induced response vary according to the dosing method.

Asian Society of Gynecologic Oncology International Workshop 2014.

The Asian Society of Gynecologic Oncology International Workshop 2014 on gynecologic oncology was held in Asan Medical Center, Seoul, Korea on the 23rd to 24th August 2014. A total of 179 participants from 17 countries participated in the workshop, and the up-to-date findings on the management of gynecologic cancers were presented and discussed. This meeting focused on the new trends in the management of cervical cancer, fertility-sparing management of gynecologic cancers, surgical management of gynecologic cancers, and recent advances in translational research on gynecologic cancers.

Detection of early recurrence with 18F-FDG PET in patients with cervical cancer.

UNLABELLED: This study investigated the feasibility of PET with (18)F-FDG to evaluate retrospectively early recurrence in patients with cervical cancer. METHODS: From September 1997 to March 2000, 249 patients with no evidence of cervical cancer after treatment were investigated with (18)F-FDG PET. (18)F-FDG PET scanning, beginning 50 min after injection of 370-555 MBq (18)F-FDG, was performed. (18)F-FDG uptake other than physiologic uptake was evaluated with the standardized uptake value and was analyzed by 2 observers who were unaware of CT or MRI data. CT or MRI and needle biopsies were performed to evaluate the positive lesions on (18)F-FDG PET, and all patients were monitored closely for 6 mo for recurrence. RESULTS: Of the 249 patients, 80 patients (32.1%) showed positive lesions with (18)F-FDG PET, and 28 patients (11.2%) were clinically or histologically confirmed as having recurrences. Eighty-two percent of recurrence was detected within 6-18 mo after diagnosis, and 89% of recurrence occurred in Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIb and stage III patients. The sensitivity and specificity of (18)F-FDG PET for detection of early recurrence were 90.3% and 76.1%, respectively. The sensitivity of (18)F-FDG PET was high in mediastinal, hilar, and scalene lymph nodes, spine, and liver; however, the sensitivity was relatively low in lung, retrovesical lymph nodes, and paraaortic lymph nodes. Three false-negative cases were detected in lung, retrovesical lymph nodes, and paraaortic lymph nodes. CONCLUSION: (18)F-FDG PET was effective in detecting early recurrences in cervical cancer patients with no evidence of disease. (18)F-FDG PET may be a useful follow-up method for cervical cancer, thereby providing the patients with early opportunities for sophisticated treatments.