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PurposeThis study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent gynecologic cancers according to MMR/MSI status.Materials and MethodsWe conducted a multi-center retrospective review on the patients who were diagnosed with gynecologic cancers between 2015 and 2020. Their clinicopathologic information, results of immunohistochemistry staining for MLH1/MSH2/MSH6/PMS2 and MSI analysis, tumor response to treatment with ICIs were investigated.ResultsAmong 1,093 patients included in the analysis, MMRd/MSI-H was most frequent in endometrial/uterine cancers (34.8%, 164/471), followed by ovarian, tubal, and peritoneal cancers (12.8%, 54/422) and cervical cancer (11.3%, 21/186). When assessed by histology without regard for cancer types, the frequency of MMRd/MSI-H was 11.0% (38/345) in high-grade serous adenocarcinoma, 38.6% (117/303) in endometrioid adenocarcinoma, and 30.2% (16/53) in carcinosarcoma. A total of 114 patients were treated with ICIs at least once. The objective response rate (ORR) was 21.6% (8/37) in cervical cancer, 4.7% (2/43) in ovarian cancer, and 25.8% (8/31) in endometrial/uterine cancers. Univariate regression analysis identified MMRd/MSI-H as the only significant factor associated with the ORR (28.9% [11/38] vs. 11.8% [9/76]; odds ratio, 3.033; 95% confidence interval, 1.129–8.144; p=0.028).ConclusionThe frequency of MMRd/MSI-H is moderate to high in gynecologic cancers in the Korean population. MMRd/MSI-H could be effective predictive biomarkers in gynecologic cancers of any type.

The aim of this study was to develop an 18F-FDG PET/CT-based model to predict complete cytoreduction during primary cytoreductive surgery (CRS) for ovarian cancer (OC).We retrospectively identified patients with stage III-IV OC who underwent primary CRS between June 2013 and February 2020 at 2 tertiary centers. Patients from each hospital were assigned to training and test sets. The abdominal cavity was divided into 3 sections, and data for the PET/CT-derived parameters were collected through image analysis. Various prediction models were constructed by combining clinicopathologic characteristics and PET/CT-derived parameters. The performance of the model with the highest area under the receiver operating characteristic curve (AUC) was externally validated.The training and test sets included 159 and 166 patients, respectively. The median age of patients in the test set was 55 years; 72.3% of them had stage III tumors, and 65.4% underwent complete cytoreduction. Metabolic tumor volume, total lesion glycolysis, and the number of metastatic lesions above the upper margin of the renal vein (area A) were selected among the PET/CT parameters. The best predictive multivariable model consisted of CA-125 (750 or ≥750 IU/mL), number of metastatic lesions (2 or ≥2), and metabolic tumor volume of area A, predicting complete cytoreduction with an AUC of 0.768. The model was validated using a test set. Its predictive performance yielded an AUC of 0.771.We successfully developed and validated a preoperative model to predict complete cytoreduction in advanced OC. This model can facilitate patient selection for primary CRS in clinical practice.

This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method.OCCC patients with platinum-sensitive recurrence that received secondary treatment at five institutions between July 2007 and June 2021 were included. Patient characteristics and survival outcomes were compared according to the use of bevacizumab (BEV) during second-line chemotherapy and secondary cytoreductive surgery (CRS).138 patients were included. The BEV (n = 36) and non-BEV (n = 102) groups had similar initial FIGO stages and proportions of secondary CRS. The BEV group showed improved progression-free survival (PFS; median, 15.4 vs. 7.5 months; P = 0.042) and overall survival (OS; P = 0.043) compared to the non-BEV group. In multivariate analyses, BEV was identified as an independent prognostic factor for PFS (adjusted hazard ratio [aHR], 0.571; 95% confidence interval [CI], 0.354-0.921; P = 0.022) and OS (aHR, 0.435; 95%CI, 0.195-0.970; P = 0.042). The secondary CRS group (n = 42) had early-stage disease at diagnosis more frequently (P = 0.009) and multi-site metastasis (P0.001) at recurrence less frequently than the no surgery group (n = 96). The secondary CRS group showed significantly better PFS (median, 33.7 vs. 7.2 months; P0.001) and OS (P0.001). Secondary CRS was associated with a significantly improved PFS (aHR, 0.297; 95% CI, 0.183-0.481; P0.001) and OS (aHR, 0.276; 95% CI, 0.133-0.576; P = 0.001). The BEV and non-BEV groups showed similar PFS and OS among the patients who underwent secondary CRS. In contrast, the BEV group showed improved PFS and OS among patients who did not undergo surgery.The use of BEV during second-line chemotherapy and secondary CRS may improve PFS and OS in patients with platinum-sensitive relapsed OCCC. Further prospective studies are warranted.

Purpose: To evaluate the anticancer effects of cabozantinib, temozolomide, and their combination in uterine sarcoma cell lines and mouse xenograft models. Experimental Design: Human uterine sarcoma cell lines (SK-LMS-1, SK-UT-1, MES-SA, and SKN) were used to evaluate the anticancer activity of cabozantinib, temozolomide, and their combination. The optimal dose of each drug was determined by MTT assay. Cell proliferation and apoptosis were assessed 48 and 72 hours after the drug treatments. The tumor weights were measured in an SK-LMS-1 xenograft mouse model and a patient-derived xenograft (PDX) model of leiomyosarcoma treated with cabozantinib, temozolomide, or both. Results: Given individually, cabozantinib and temozolomide each significantly decreased the growth and viability of cells. This inhibitory effect was more pronounced when cabozantinib (0.50 μmol/L) and temozolomide (0.25 or 0.50 mmol/L) were co-administered (P < 0.05). The combination of the drugs also significantly increased apoptosis in all cells. Moreover, this effect was consistently observed in patient-derived leiomyosarcoma cells. In vivo studies with SK-LMS-1 cell xenografts and the PDX model with leiomyosarcoma demonstrated that combined treatment with cabozantinib (5 mg/kg/d, per os administration) and temozolomide (5 mg/kg/d, per os administration) synergistically decreased tumor growth (both P < 0.05). Conclusions: The addition of cabozantinib to temozolomide offers synergistic anticancer effects in uterine sarcoma cell lines and xenograft mouse models, including PDX. These results warrant further investigation in a clinical trial.

Supplementary Data from Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma

Supplementary Figure from Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma

Supplementary Table from Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma

Purpose:To evaluate the anticancer effects of cabozantinib, temozolomide, and their combination in uterine sarcoma cell lines and mouse xenograft models.Experimental Design:Human uterine sarcoma cell lines (SK-LMS-1, SK-UT-1, MES-SA, and SKN) were used to evaluate the anticancer activity of cabozantinib, temozolomide, and their combination. The optimal dose of each drug was determined by MTT assay. Cell proliferation and apoptosis were assessed 48 and 72 hours after the drug treatments. The tumor weights were measured in an SK-LMS-1 xenograft mouse model and a patient-derived xenograft (PDX) model of leiomyosarcoma treated with cabozantinib, temozolomide, or both.Results:Given individually, cabozantinib and temozolomide each significantly decreased the growth and viability of cells. This inhibitory effect was more pronounced when cabozantinib (0.50 μmol/L) and temozolomide (0.25 or 0.50 mmol/L) were co-administered (P < 0.05). The combination of the drugs also significantly increased apoptosis in all cells. Moreover, this effect was consistently observed in patient-derived leiomyosarcoma cells. In vivo studies with SK-LMS-1 cell xenografts and the PDX model with leiomyosarcoma demonstrated that combined treatment with cabozantinib (5 mg/kg/d, per os administration) and temozolomide (5 mg/kg/d, per os administration) synergistically decreased tumor growth (both P < 0.05).Conclusions:The addition of cabozantinib to temozolomide offers synergistic anticancer effects in uterine sarcoma cell lines and xenograft mouse models, including PDX. These results warrant further investigation in a clinical trial.

To investigate the effectiveness and safety of pembrolizumab and lenvatinib (PEMBRO+LEN) for recurrent endometrial cancer (EC) in a real-world setting.This multicenter retrospective cohort study included patients with recurrent EC who received PEMBRO+LEN between March 2020 and May 2021 at three tertiary hospitals in Korea. We summarized patient characteristics and evaluated the response rates, survival outcomes, and treatment-related adverse events (AEs).In total, 48 patients were included in the study. The median age of the patients was 62.5 (range, 42-78) years. The most common histologic subtype was endometrioid adenocarcinoma (43.8%), followed by serous adenocarcinoma (25.0%). Most patients (91.7%) had mismatch repair-proficient tumors. Patients received PEMBRO+LEN for a median of 4.5 cycles, during which the best objective response rate and disease control rate were 23.8% (95% CI, 11.9-38.1) and 76.2% (95% CI, 61.9-88.1), respectively. Overall, 56.2% of patients experienced LEN dose reduction once or more and 16.7% experienced LEN interruption. The most common treatment-related AEs were fatigue (18.8%), hypertension (16.7%), and hypothyroidism (14.6%). Total of 8 patients (16.7%) discontinued LEN during the treatment because of treatment-related AEs. Serum CA-125 level was the only prognostic factor for progression-free survival (adjusted hazard ratio, 4.41; 95% confidence interval, 1.19-16.36; p = 0.03).In our real-world study, Korean patients with recurrent EC who received PEMBRO+LEN showed lower treatment response rate and similar treatment discontinuation rate, compared to clinical trials.

The objective of the present pilot study is to compare operative outcomes between vaginal natural orifice transluminal endoscopic surgery (vNOTES) and single-port access (SPA) adnexectomy. Subjects were patients who underwent adnexectomy for benign adnexal disease, from November 2019 to May 2021. A total of 12 patients underwent vNOTES adnexectomy, and 55 patients received SPA laparoscopic adnexectomy. All surgeries were performed by one surgeon. In order to balance the baseline characteristics of the patients, 1:2 matching was performed. The vNOTES group demonstrated a low postoperative pain score within 12 h after surgery. They also required less use of analgesic medications postoperatively. Other surgical outcomes were comparable between the two groups. This study showed that vNOTES adnexectomy has comparable surgical outcomes to SPA.

BACKGROUND/AIM Niraparib is effective against epithelial ovarian cancer (EOC), but with adverse effects. In this study, we retrospectively investigated niraparib maintenance treatment feasibility in Korean patients newly diagnosed with EOC. PATIENTS AND METHODS The medical records of 35 patients were reviewed. Data on the baseline clinical characteristics were collected, and adverse effects were described. RESULTS Sixteen patients underwent treatment suspension or dose reduction. There was no significant difference in adverse effects (A/E) due to the interval between adjuvant chemotherapy conclusion and niraparib initiation. The two groups had similar International Federation of Gynaecology and Obstetrics (FIGO) stages. The number of patients with a history of bevacizumab use was higher in the dose modification group than in the standard dose group. CONCLUSION Niraparib use must be considered in those previously treated with bevacizumab. There is a need for prospective research on lower dose (

The enhanced recovery after surgery (ERAS) refers to multimodal interventions to reduce the length of hospital stay and complications at various steps of perioperative care. It was first developed in colorectal surgery and later embraced by other surgical disciplines including gynecologic oncology. The ERAS Society recently published guidelines for gynecologic cancer surgeries to enhance patient recovery. However, limitations exist in the implementation of the guidelines in ovarian cancer patients due to the distinct characteristics of the disease. In the present review, we discuss the results that have been published in the literature to date regarding the ERAS protocols in ovarian cancer patients, and explain why more evidence needs to be specifically assessed in this type of malignancy among other gynecologic cancers.

Single-port access (SPA) laparoscopic surgery and vaginal natural orifice transluminal endoscopic surgery (vNOTES) have many advantages. The objective of the present study is to compare patient characteristics, operative details, and postoperative outcomes between the two surgical methods. Patients who were planned to undergo vNOTES or SPA laparoscopic surgery between April 2020 and June 2021 were prospectively enrolled. The surgical method was determined by a single surgeon after imaging results evaluation and a physical exam. Those who had favorable pelvic conditions without any evidence of adhesion were scheduled for vNOTES. A total of 33 patients underwent a vNOTES hysterectomy while 40 patients received a SPA laparoscopic hysterectomy. All surgeries were performed by one surgeon. The proportion of the patients who had a history of vaginal delivery was significantly higher in the vNOTES group. The operative time for port installation was significantly longer in the vNOTES group, but the total operative time was shorter compared to the SPA group. The postoperative pain scores 12 h after the operations were also significantly lower in the vNOTES group. Other surgical outcomes were comparable between the two groups. The present study demonstrated that the early operative outcomes of vNOTES hysterectomy were comparable to those of SPA hysterectomy. It also highlights the importance of adequate patient selection when determining surgical methods based on imaging results and physical examinations.

Simple Summary Recurrent patients with gynecologic cancer experience a difficult situation when using immune checkpoint inhibitors based on mismatch repair gene immunohistochemistry and microsatellite instability. Six machine learning algorithms were used to create predictive models with seven prospective features (four MMR IHC [MLH1, MSH2, MSH6, and PMS2], MSI, Age 60, and tumor size). The experimental results showed that the RF-based model performed best at predicting gynecologic cancer recurrence, with AUCs of 0.818 and 0.826 for the 5-fold cross-validation (CV) and 5-fold CV with 10 repetitions, respectively. This provides novel and baseline results of patients with recurrent gynecologic cancer using immune checkpoint inhibitors by using machine learning methods based on Lynch syndrome-related screening markers. Abstract To support the implementation of genome-based precision medicine, we developed machine learning models that predict the recurrence of patients with gynecologic cancer in using immune checkpoint inhibitors (ICI) based on clinical and pathologic characteristics, including Lynch syndrome-related screening markers such as immunohistochemistry (IHC) and microsatellite instability (MSI) tests. To accomplish our goal, we reviewed the patient demographics, clinical data, and pathological results from their medical records. Then we identified seven potential characteristics (four MMR IHC [MLH1, MSH2, MSH6, and PMS2], MSI, Age 60, and tumor size). Following that, predictive models were built based on these variables using six machine learning algorithms: logistic regression (LR), support vector machine (SVM), naive Bayes (NB), random forest (RF), gradient boosting (GB), and extreme gradient boosting (EGB) (XGBoost). The experimental results showed that the RF-based model performed best at predicting gynecologic cancer recurrence, with AUCs of 0.818 and 0.826 for the 5-fold cross-validation (CV) and 5-fold CV with 10 repetitions, respectively. This study provides novel and baseline results about predicting the recurrence of gynecologic cancer in patients using ICI by using machine learning methods based on Lynch syndrome-related screening markers.

No studies have examined the issue of intraabdominal port-site adhesion following single-port access (SPA) laparoscopic surgeries. The purpose of the present study was to investigate the clinical effects of temperature-sensitive adhesion barrier solution in preventing periumbilical adhesion in SPA laparoscopy. This was a prospective, single-arm study in which patients were given GUARDIX-SGTM after SPA laparoscopic surgery for benign gynecologic diseases. One gram of GUARDIX-SGTM was applied on the abdominal viscera just below the umbilical port site and adjacent abdominal wall prior to fascia closure. The primary endpoint was the incidence of postoperative adhesion evaluated by visceral sliding technique through transabdominal sonography after three months. Between June 2019 and March 2020, a total of 37 healthy patients without any history of previous abdominal surgery received SPA laparoscopic surgery by a single surgeon. No postoperative complications such as wound dehiscence or surgical site infection occurred during the follow-up period of three months. No postoperative adhesion around the umbilicus was noted in all 37 patients. The mean visceral movement measured by transabdominal sonography during maximal respiration was 4.9 cm (4.9 ± 1.9 cm). Using an adhesion barrier around the port site prior to fascia closure prevents postoperative adhesion in benign SPA laparoscopic gynecologic surgery.

Hematopoietic stem cells (HSCs) self-renew and generate all blood cells. Recent studies with single cell transplants and lineage tracing suggest that adult HSCs are diverse in their reconstitution and lineage potentials. However, prospective isolation of these subpopulations has remained challenging. Here, we identify Neogenin-1 (NEO1) as a unique surface marker on a fraction of mouse HSCs labeled with Hoxb5 , a specific reporter of long-term HSCs (LT-HSCs). We show that NEO1 + Hoxb5 + LT-HSCs expand with age and respond to myeloablative stress in young mice while NEO1 − Hoxb5 + LT-HSCs exhibit no significant change in number. Furthermore, NEO1 + Hoxb5 + LT-HSCs are more often in the G 2 /S cell cycle phase compared to NEO1 − Hoxb5 + LT-HSCs in both young and old bone marrow. Upon serial transplantation, NEO1 + Hoxb5 + LT-HSCs exhibit myeloid-biased differentiation and reduced reconstitution while NEO1 − Hoxb5 + LT-HSCs are lineage-balanced and stably reconstitute recipients. Gene expression analysis reveals erythroid and myeloid priming in the NEO1 + fraction and association of quiescence and self-renewal–related transcription factors with NEO1 − LT-HSCs. Finally, transplanted NEO1 + Hoxb5 + LT-HSCs rarely generate NEO1 − Hoxb5 + LT-HSCs while NEO1 − Hoxb5 + LT-HSCs repopulate both LT-HSC fractions. This supports a model in which dormant, balanced NEO1 − Hoxb5 + LT-HSCs can hierarchically precede active, myeloid-biased NEO1 + Hoxb5 + LT-HSCs.

Objective: To report our experience of implementing non-invasive prenatal testing (NIPT) in a tertiary urban academic medical center in South Korea. Materials and methods: An observational retrospective study of singleton and twin pregnancies that underwent prenatal screening for fetal aneuploidy from July 2016 to April 2018 was conducted. Demographics of the study population electing NIPT versus those opting the integrated test were compared. We also assessed clinical significant factors influencing cfDNA fetal fraction in NIPT. Results: Among the 817 women who underwent serum screening tests during the study period, 490 women (60.0%) chose the integrated test while 327 women (40.0%) chose NIPT. Compared to the integrated test group, women in the NIPT group were older (mean age 34.7 ± 3.7 vs. 32.6 ± 3.4; p-value < 0.01), multiparous (47.1% vs. 39.8%; p-value = 0.046), and had higher rate of previous abortion history (28.4% vs. 21.6%; p-value = 0.033). A significant decrease in the number of invasive diagnostic tests was observed since the adoption of NIPT. The screen negative and positive rates of the integrated test group for fetal aneuploidy were 95.3% and 4.7%, respectively while those of the NIPT group were 95.9% and 1.2%, respectively. The rate of inadequate cfDNA fetal fraction was 3.0%. Low fetal fraction was associated with higher maternal age, body weight and BMI. Conclusions: The implementation of NIPT has significantly affected the practice pattern of prenatal aneuploidy screening by replacing the integrated test and decreasing invasive diagnostic tests. Keywords: Non-invasive prenatal testing (NIPT), Integrated test, Maternal serum screening, Tertiary medical center, South Korea

Purpose: Several cell-free DNA (cf-DNA) features, such as genome-wide coverage, fragment size, and fragment end motif frequency, have shown their potentials for cancer detection. In this study, we developed two independent models, GC (gross chromatin), and FEMS (fragment end motif frequency and size). Each model uses images generated from genome-wide normalized sequencing coverage and cf-DNA fragment end motif frequencies according to the different cf-DNA size profiles. Then we integrated them into a single ensemble model to improve cancer detection and multi-cancer type classification accuracy. Methods: Low depth cf-WGS data was generated from 1,396 patients (stage I: 14.9%, stage II: 35.6%, stage III: 24.9%, stage IV: 24.2%, unknown: 0.4%) with breast (n=702), liver (n=213), esophageal (n=155), ovarian (n=151), pancreatic (n=85), lung (n=53), head and neck (n=16), biliary tract (n=15), and colon cancer (n=6) and 417 healthy individuals. Samples were randomly split into training, validation, and test set stratifying cancer type and stages. Cancer types with a small number of samples ( Results: For cancer detection, the ensemble model achieved sensitivities of 85.2% [95% confidence interval (CI): 71.8% to 94.5%], 74.9% (CI: 68.0% to 88.0%), 73.2% (CI: 66.7% to 85.9%) at a specificity of 95%, 98% and 99% and the AUC value of 0.97(CI: 0.95-0.99) in the test dataset. By the cancer stages, sensitivity was 62.8% (CI: 48.8% to 83.7%) in stage I, 66.3% (CI: 57.7% to 82.7%) in stage II, 85.9% (CI: 77.5% to 94.4%) in stage III, and 76.1% (CI: 63.4% to 87.3%) in stage IV at 99% specificity. For multi-cancer classification, the overall accuracy of 85.1% (CI: 80.4% to 89.3%) was achieved including 6 cancer types. Conclusions: Highly sensitive and accurate deep learning model for cancer detection and multi-cancer classification was generated by combining different types of cf-DNA features. This result provides the opportunity for general population multi-cancer screening using various cf-DNA features. Citation Format: Tae-Rim Lee, Jin Mo Ahn, Joo Hyuk Sohn, Sook Ryun Park, Min Hwan Kim, Gun Min Kim, Ki-Byung Song, Eunsung Jun, Dongryul Oh, Jeong-Won Lee, Joseph J Noh, Young Sik Park, Sun-Young Kong, Sang Myung Woo, Bo Hyun Kim, Eui Kyu Chie, Hyun-Cheol Kang, Youn Jin Choi, Ki-Won Song, Jeong-Sik Byeon, Junnam Lee, Dasom Kim, Chang-Seok Ki, Eunhae Cho. Deep learning algorithm for multi-cancer detection and classification using cf-WGS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6371.

The purpose of the study was to evaluate the feasibility of laparoscopic approach versus laparotomy in endometrial cancer that extends to the cervix in the form of glandular extension and/or stromal invasion. A retrospective, single-center cohort study was conducted using data between 1995 and 2017 at an urban tertiary academic medical center. We identified patients who were diagnosed with endometrial cancer whose tumor involved the uterine cervix on final pathology. Operative and oncologic outcomes were compared between the patients who underwent minimally-invasive surgery (MIS) versus those who underwent laparotomy. A total of 282 patients with endometrial cancer were reviewed for the study. Among these patients, 76 patients underwent hysterectomy and surgical staging via MIS. There was no conversion from MIS to laparotomy. In the MIS group, shorter hospital stay (4.4 ± 2.3 days for MIS group vs. 7.1 ± 4.7 days for laparotomy group; p-value = 0.002) and less blood loss during the operations (228 mL vs. 478 mL, p-value < 0.001) were observed compared to the laparotomy group. The multivariate Cox regression analysis revealed that age at diagnosis, FIGO stage, histology grades, tumor size, lymph-vascular space invasion were independent prognostic markers for poor oncologic outcomes but the types of surgical approach (MIS vs. laparotomy) were not associated with it. The means by which colpotomy was performed (either intracorporeal or transvaginal) among the MIS group also did not affect patient survivals. Among the women with endometrial cancer that involved the uterine cervix, surgical treatment via MIS compared to laparotomy showed no difference in survival outcomes but better perioperative results. These findings support the use of MIS for these patient group.

Background: We investigated the incidence of reactive thrombocytosis after maximal cytoreductive surgery in advanced epithelial ovarian cancer and its role on survival. Methods: We retrospectively reviewed electronic medical records of patients who underwent primary cytoreductive surgery for advanced epithelial ovarian/fallopian cancer or peritoneal cancer from January 1, 2012, and December 31, 2017. In addition to known clinical prognostic factors, we analyzed the correlation serum platelet counts and prognosis at various time points including before surgery, during peri-operative period, and on each cycle of adjuvant chemotherapy.Results: 474 patients were eligible for the analysis. Median age was 54 years (18-88). 401 patients (84.6%) were FIGO stage III and 405 patients (85.4%) were serous adenocarcinoma. 79 patients (22.6%) had splenectomy and optimal cytoreduction (residual < 1 cm) was achieved at 326 patients (68.8%). A week after surgery, thrombocytosis was observed in 229 patients (48.3%) patients in the entire cohort. Especially, higher platelet counts were observed in patients with splenectomy compared with patients without splenectomy at various time points after surgery. Subgroup of patients who had persistent thrombocytosis during adjuvant chemotherapy showed poor survivals. In particular, thrombocytosis on 5th cycle of adjuvant chemotherapy showed most significant impact on overall survival (HR; 1.871, 95%CI; 1.034-3.386, p = 0.038) among various time points in multivariate analysis. In a logistic regression model, splenectomy (p < 0.001) significantly attributed to thrombocytosis on 5th cycle. Conclusion: Reactive thrombocytosis after primary cytoreductive surgery is associated with poor survival in advanced epithelial ovarian cancer, particularly when thrombocytosis was observed during adjuvant chemotherapy.

Purpose: To investigate the anti-cancer effects of tetraarsenic hexoxide (TAO, As4O6) in cervical cancer cell lines and in a series of patient-derived xenograft (PDX) mouse models. Methods: Human cervical cancer cell lines, including HeLa, SiHa and CaSki, and human umbilical vein endothelial cells (HUVECs), were used to evaluate the anti-cancer activity of TAO. Cellular proliferation, apoptosis, and enzyme-linked immunosorbent assay (ELISA) for matrix metallopeptidase 2 (MMP-2) and 9 (MMP-9) were assessed. The tumor weights of the PDXs that were given TAO were measured. The PDXs included primary squamous cell carcinoma, primary adenocarcinoma, recurrent squamous cell carcinoma, and recurrent adenocarcinoma. Results: TAO significantly decreased cellular proliferation and increased apoptosis in cervical cancer cell lines and HUVEC. The functional studies on the cytotoxicity of TAO revealed that it inhibited the activation of Akt and vascular endothelial growth factor receptor 2 (VEGFR2). It also decreased the concentrations of MMP-2 in both cervical cancer cell lines and HUVECs. Active caspase-3 and p62 were both increased by the treatment of TAO, indicating increased rates of apoptosis and decreased rates of autophagy, respectively. In vivo studies with PDXs revealed that TAO significantly decreased tumor weight for both primary squamous cell carcinoma and adenocarcinoma of the cervix. However, this anti-cancer effect was not seen in PDXs with recurrent cancers. Nevertheless, the combination of TAO with cisplatin significantly decreased tumor weight in PDX models for both primary and recurrent cancers. Conclusions: TAO exerted inhibitory effects on angiogenesis, cellular migration, and autophagy, and it showed stimulatory effects on apoptosis. Overall, it demonstrated anti-cancer effects in animal models for human cervical cancer.

The present study was conducted to report the perioperative outcomes of single-port access (SPA) laparoscopic gynecologic surgeries with focus on the incidence of postoperative incisional hernia from our cumulative data of 2498 patients. A retrospective review was performed on the women who had received SPA surgeries from 2008 to 2018. Patient characteristics and perioperative outcomes including the incidence of postoperative incisional hernia were analyzed. There were 2498 Korean patients who received SPA surgeries for various gynecologic diseases. The median age of the patients was 40.3 ± 9.2 years, and the mean body mass index (BMI) was 22.6 ± 3.2 kg/m2. A total of 3 postoperative incisional hernia occurred during the study period. Two patients whose fascial layers were closed in running sutures developed hernias 6 and 8 months after their operations. One patient whose fascial layers were closed in interrupted sutures developed hernia 11 months after her operation. The incidence of postoperative incisional hernia following SPA surgery is low in Asian women whose BMI is relatively lower than other patient populations. Interrupted suture technique may reduce postoperative incisional hernia by providing a distinct visualization of fascial layers during closure. Detailed descriptions of our surgical techniques of closing the port incision are provided.

This study aimed to evaluate the prognostic significance of tumor regression rate according to radiation phase and histologic subtype in patients with locally advanced cervical cancer (LACC) treated with chemoradiation. We retrospectively reviewed the medical records of 398 patients with FIGO stage IIB-IVA cervical cancer treated with concurrent chemoradiotherapy (CCRT) between 2001 and 2019. Tumor response was assessed using serial magnetic resonance imaging (MRI) at three time points: pre-treatment, post-external beam radiotherapy (EBRT), and post-intracavitary radiotherapy (ICR). Tumor regression pattern according to histologic subtype and radiation phase (EBRT and ICR) was evaluated. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Of 398 patients, 44 patients had adenocarcinoma/adenosquamous carcinoma (AC/ASC) and 354 patients had squamous cell carcinoma (SCC). AC/ASC was associated with significantly worse PFS and OS than SCC (p &lt, 0.001). AC/ASC had a relatively poorer regression rate in response to EBRT than SCC (p &lt, 0.001), whereas there was no significant difference in overall tumor regression rate after completion of RT (EBRT and ICR) between the two histologic subtypes. Multivariable analysis demonstrated AC/ASC histology to be an independent prognostic factor of decreased PFS and OS. Moreover, tumor regression rate after completion of EBRT (post-EBRT tumor regression rate (EBRTregression &le, 26%) and proportion of tumor regression during EBRT to overall tumor regression (EBRTproportion &le, 40%) were independent predictors of poor survival in patients with LACC. Tumor regression pattern of LACC in response to CCRT differs according to histologic subtype. AC/ASC histology and poor tumor response to EBRT are independent prognostic factors for worse survival in patients with LACC. Further studies are needed to develop a CCRT protocol that is specialized for patients with AC/ASC.

Objectives To compare the surgical, pathological and oncological outcomes of single-port access (SPA) laparoscopy against laparotomy for large ovarian tumor (>15 cm) suspected to be a borderline ovarian tumor (BOT) on preoperative imaging. Methods A retrospective review of the patients who underwent SPA laparoscopy (SPA Group) or laparotomy (Laparotomy Group) for suspected BOT was performed. Surgical outcomes, including the rates of iatrogenic spillage of tumor contents, and oncological outcomes, such as recurrence-free survival (RFS) and overall survival (OS), were compared between the two groups. Correlation between intraoperative frozen section analysis and permanent pathology results was also assessed. Results A total of 178 patients underwent surgical treatment for suspected large BOT. Among them, 105 patients with a mean tumor diameter of 20.9 ± 6.5 cm underwent SPA laparoscopy, and the other 73 patients, with a mean tumor diameter 20.2 ± 5.9 cm, underwent laparotomy. The mean operation time did not differ between the two groups (99.1 ± 41.9 min for SPA Group vs. 107.3 ± 35.7 min for Laparotomy Group, p = 0.085). There was no difference in the occurrence of iatrogenic spillage of tumor contents between the groups either (11.4% in the SPA Group vs. 6.8% in the Laparotomy Group, p = 0.381). However, the postoperative complication rates were significantly higher in the Laparotomy Group compared with SPA Group (16.4% vs. 5.7%, p = 0.025). The surgical approach was not associated with the misdiagnosis rates of frozen section analysis (19% in the SPA Group vs. 26% in the Laparotomy Group, p = 0.484). The most common histologic type of the tumors was mucinous in both groups. Conclusion SPA laparoscopy is feasible, safe, and not inferior to laparotomy for surgical treatment of large ovarian tumors that suspected to be BOT on preoperative imaging.

The aim of the present study was to investigate the prognostic role of the pre-treatment complete blood count (CBC) profile as a predictive marker of survival, recurrence, and death in early stage squamous cell carcinoma and adenocarcinoma of the cervix. The pre-treatment CBC profiles of the patients from nine tertiary medical centers in South Korea who were treated surgically for early stage cervical cancer were reviewed. Statistical models by the Akaike&rsquo, s information criterion (AIC) were developed using CBC profiles to calculate individuals&rsquo, risk scores for clinical outcomes. A total of 1443 patients were included in the study and the median follow-up was 63.7 months with a range of 3&ndash, 183 months. Univariate analyses identified the components of CBC that were significantly related to clinical outcomes including white blood cell (WBC), hemoglobin, neutrophil, and platelet levels. The models developed using CBC profiles and the conventional clinical predictive factors provided individuals&rsquo, risk scores that were significantly better in predicting clinical outcomes than the models using the conventional clinical predictive factors alone. Pre-treatment CBC profiles including WBC, hemoglobin, neutrophil, lymphocyte, and platelet levels were found to be a potential biomarker for survival prognosis in early cervical cancer.

PURPOSE Salvage second-line chemotherapy is usually recommended for patients with advanced epithelial ovarian cancer (AEOC) who develop progressive disease (PD) after neoadjuvant chemotherapy (NAC). Herein, we investigated the role of cytoreductive surgery (CRS) for such patients. MATERIALS AND METHODS We retrospectively reviewed the medical records of 36 patients with AEOC who developed PD after receiving NAC at two tertiary academic centers with different treatment strategies between 2001 and 2016. Patients who developed PD after NAC were consistently treated with CRS at one hospital (group A; n=13) and second-line chemotherapy at another (group B; n=23). The clinical characteristics and treatment outcomes were compared between the groups. RESULTS Overall survival (OS) was longer in group A than in group B (19.4 months vs. 7.9 months; p=0.011). High-grade serous histology was associated with longer OS than non-high-grade serous types. In group A, optimal surgery resection (

Objective To report a case of vulvar epithelioid sarcoma, a rare type of tumor that has been reported in 37 cases in the English literature to date. Case report We report three cases of vulvar epithelioid sarcoma, proximal type. Wide excisions of the mass were performed with margins free of tumor in all three cases. Conclusion Due to its low incidence, there are no evidence-based diagnostic algorithms or published recommendations for treatment. Locoregional lymph node involvement, vascular invasion, tumor size larger than 2 cm, deep localization, presence of necrosis, and a high mitotic index are known as poor prognostic factors. Adjuvant radiotherapy is advisable in the presence of a high-grade tumor or positive margins. The beneficial effect of adjuvant chemotherapy is not well established. Treatment decisions should be made based on the individual case presentation and pathology evaluation.

SummaryHematopoietic stem cells (HSCs) are responsible for the generation of blood and immune cells throughout life. They have the unique ability to self-renew and generate more HSCs or differentiate into a progenitor cell in response to cell-intrinsic and -extrinsic stimuli. The balance of HSC fate commitment is critical for a healthy blood supply. Imbalances during hematopoiesis, which are frequent in aging, can result in hematological malignancies and pre-malignancies as well as increase risk of atherosclerosis. Given the importance of HSCs and their progenitors, they have been extensively characterized in genomic and transcriptomic studies. However, an understanding of protein expression within the HSC compartment and more broadly throughout hematopoiesis remains poorly understood, and it has been widely reported that the correlation between mRNA and proteins is more complicated than previously thought. Previous mouse mass spectrometry studies have focused either specifically on stem and the first early progenitor or broadly across mixed populations of stem and progenitor cells, which do not allow for cell-type specific protein resolution across stages of differentiation. Mass cytometry has been employed to characterize transcription factor expression in human HSCs and progenitors but does not apply an unbiased discovery approach. New mass spectrometry technology now allows for deep proteomic coverage with no more than 200 ng of sample input. We report here a proteomics resource characterizing protein expression in mouse adult and aged HSCs, multipotent progenitors and oligopotent progenitors, 12 cell types in total. We validated differential expression by flow cytometry analysis and immunofluorescence staining. Additionally, we investigated the relationship between mRNA and protein levels of individual genes in HSCs compared to progenitors through RNA sequencing studies and identified two proteins that appear to be uniquely regulated in the HSC compartment, Cpin1 and Adnp. In summary, this resource provides proteomic coverage of adult and aged hematopoietic stem cells and their progenitors and reveals changes in protein abundance between cell types, with potential future implications in understanding mechanisms for stem-cell maintenance, niche interactions and fate determination.