Chlorin E6-Curcumin-Mediated Photodynamic Therapy Promotes an Anti-Photoaging Effect in UVB-Irradiated Fibroblasts.

Skin photoaging due to ultraviolet B (UVB) exposure generates reactive oxygen species (ROS) that increase matrix metalloproteinase (MMP). Chlorin e6-photodynamic therapy (Ce6-PDT), in addition to being the first-line treatment for malignancies, has been shown to lessen skin photoaging, while curcumin is well known for reducing the deleterious effects of ROS. In the current study, PDT with three novel Ce6-curcumin derivatives, a combination of Ce6 and curcumin with various linkers, including propane-1,3-diamine for Ce6-propane-curcumin; hexane-1,6-diamine for Ce6-hexane-curcumin; and 3,3'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(propan-1-amine) for Ce6-dipolyethylene glycol (diPEG)-curcumin, were studied for regulation of UVB-induced photoaging on human skin fibroblast (Hs68) and mouse embryonic fibroblast (BALB/c 3T3) cells. We assessed the antiphotoaging effects of Ce6-curcumin derivatives on cell viability, antioxidant activity, the mechanism of matrix metalloproteinase-1 and 2 (MMP-2) expression, and collagen synthesis in UVB-irradiated in vitro models. All three Ce6-curcumin derivatives were found to be non-phototoxic in the neutral red uptake phototoxicity test. We found that Ce6-hexane-curcumin-PDT and Ce6-propane-curcumin-associated PDT exhibited less cytotoxicity in Hs68 and BALB/c 3T3 fibroblast cell lines compared to Ce6-diPEG-curcumin-PDT. Ce6-diPEG-curcumin and Ce6-propane-curcumin-associated PDT showed superior antioxidant activity in Hs68 cell lines. Further, in UVB-irradiated in vitro models, the Ce6-diPEG-curcumin-PDT greatly attenuated the expression levels of MMP-1 and MMP-2 by blocking mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1), and tumor necrosis factor-α (NF-κB) signaling. Moreover, Ce6-diPEG-curcumin effectively inhibited inflammatory molecules, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, while accelerating collagen synthesis. These results demonstrate that Ce6-diPEG-curcumin may be a potential therapy for treating skin photoaging.

Pathological findings and long-term prognosis in Korean BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy.

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.

Outcomes and prognostic factors of surgically treated extramammary Paget's disease of the vulva.

OBJECTIVE: Extramammary Paget's disease (EMPD) of the vulva is a rare disease which predominantly presents in postmenopausal Caucasian women. As yet, no studies on Asian female patients with EMPD have been performed. This study aimed to identify the clinical features of patients with vulvar EMPD in Korea, and to evaluate the risk factors of recurrence and postoperative complications in surgically treated EMPD. METHODS: We retrospectively reviewed 47 patients with vulvar EMPD who underwent wide local excision or radical vulvectomy. The clinical data and surgical and oncological outcomes following surgery were extracted from medical records and analyzed. Univariate and multivariate analyses for predicting recurrence and postoperative complications were performed. RESULTS: 21.3% of patients had complications after surgery, and wound dehiscence was the most common. 14.9% of patients experienced recurrence, and the median interval to recurrence from initial treatment was 69 (range 33-169) months. Vulvar lesions larger than 40 mm was the independent risk factor of postoperative complications (odds ratio [OR]=7.259; 95% confidence interval [CI]=1.545-34.100; p=0.012). Surgical margin status was not associated with recurrence in surgically treated vulvar EMPD patients (OR=0.83; 95% CI=0.16-4.19; p=1.000). CONCLUSION: Positive surgical margin is a frequent finding in the patients with vulvar EMPD, but disease recurrence is not related with surgical margin status. Since EMPD is a slow growing tumor, a surveillance period longer than 5 years is required.

Effect of Photodynamic Therapy with Chlorin e6 on Canine Tumors.

This work aims to prepare pure Chlorin e6 (Ce6) and establish Ce6-mediated photodynamic therapy (Ce6-PDT) as a better therapy option for canine tumors as well as mouse tumor models. Five dogs suffering from various cancers were treated with Ce6-PDT from one to several times. After receiving the Ce6 (2.5 mg/kg) for 3 h, tumors were illuminated superficially or interstitially with 660 nm light. Two dogs underwent Ce6-guided fluorescence imaging by photodynamic diagnosis (PDD). Cell proliferation and apoptosis were detected by the 4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and western blot assay, respectively. Ce6-PDT efficacy was also determined using melanoma and pancreatic cancer mouse models. Two veterinary patients with mammary carcinoma and histiocytic sarcoma had their tumors significantly diminished and showed improved health after receiving Ce6-PDT. Moreover, in the cases of canine tumors, the adjunctive use of Ce6-PDD revealed cancers that were not visible with white light viewing and provided a visual contrast from surrounding tissues. Also, in vivo, Ce6-PDT remarkably reduced melanoma and pancreatic tumors in the mouse model. These findings could pave the way for a better understanding of the underlying processes of Ce6-PDT, making it an effective and safe candidate for use in human and veterinary applications to abolish various cancers.

DeepCNAP: A Deep Learning Approach for Continuous Noninvasive Arterial Blood Pressure Monitoring Using Photoplethysmography.

Arterial blood pressure (ABP) monitoring may permit the early diagnosis and management of cardiovascular disease (CVD); however, existing methods for measuring ABP outside the clinic use inconvenient cuff sphygmomanometry, or do not estimate continuous ABP waveforms. This study proposes a novel deep learning model DeepCNAP for estimating continuous BP waveform from a noninvasively measured photoplethysmography (PPG) signal in real-time. DeepCNAP was designed through the combination of deep convolutional networks and self-attention. The proposed method was constructed via 10-fold cross-validation based on the MIMIC database (the number of subjects = 942, recording time = 374.43 hours). The performance of DeepCNAP was evaluated from two perspectives: estimating ABP from PPG and classifying hemodynamically unstable events (i.e., hypertension, prehypertension, hypotension, and the normal state). The mean absolute errors of the BP estimates were 3.40 ± 4.36 mmHg for systolic BP, 1.75 ± 2.25 mmHg for diastolic BP, and 3.23 ± 2.21 mmHg for the BP waveform, indicating that DeepCNAP satisfies the standards of both the British Hypertension Society (BHS) and the Association for the Advancement of Medical Instrumentation (AAMI). From the estimated BP, hypertension, prehypertension, hypotension, and the normal state were classified with 99.44, 97.58, 92.23, and 94.64% accuracy, respectively. DeepCNAP enables feasible real-time estimation of invasively measured ABP from noninvasive PPG. With its noninvasive nature, high accuracy, and clinical relevance, the proposed model could be valuable in general wards at hospitals and for wearable devices in daily life.

Intracranial Densitometry-Augmented Machine Learning Enhances the Prognostic Value of Brain CT in Pediatric Patients With Traumatic Brain Injury: A Retrospective Pilot Study.

Background: The inter- and intrarater variability of conventional computed tomography (CT) classification systems for evaluating the extent of ischemic-edematous insult following traumatic brain injury (TBI) may hinder the robustness of TBI prognostic models. Objective: This study aimed to employ fully automated quantitative densitometric CT parameters and a cutting-edge machine learning algorithm to construct a robust prognostic model for pediatric TBI. Methods: Fifty-eight pediatric patients with TBI who underwent brain CT were retrospectively analyzed. Intracranial densitometric information was derived from the supratentorial region as a distribution representing the proportion of Hounsfield units. Furthermore, a machine learning-based prognostic model based on gradient boosting (i.e., CatBoost) was constructed with leave-one-out cross-validation. At discharge, the outcome was assessed dichotomously with the Glasgow Outcome Scale (favorability: 1-3 vs. 4-5). In-hospital mortality, length of stay (>1 week), and need for surgery were further evaluated as alternative TBI outcome measures. Results: Densitometric parameters indicating reduced brain density due to subtle global ischemic changes were significantly different among the TBI outcome groups, except for need for surgery. The skewed intracranial densitometry of the unfavorable outcome became more distinguishable in the follow-up CT within 48 h. The prognostic model augmented by intracranial densitometric information achieved adequate AUCs for various outcome measures [favorability = 0.83 (95% CI: 0.72-0.94), in-hospital mortality = 0.91 (95% CI: 0.82-1.00), length of stay = 0.83 (95% CI: 0.72-0.94), and need for surgery = 0.71 (95% CI: 0.56-0.86)], and this model showed enhanced performance compared to the conventional CRASH-CT model. Conclusion: Densitometric parameters indicative of global ischemic changes during the acute phase of TBI are predictive of a worse outcome in pediatric patients. The robustness and predictive capacity of conventional TBI prognostic models might be significantly enhanced by incorporating densitometric parameters and machine learning techniques.

Single-Incision versus Multiport Robotic Myomectomy: A Propensity Score Matched Analysis of Surgical Outcomes and Surgical Tips.

We aimed to compare the perioperative outcomes of single-incision robotic myomectomy (SIRM) and multiport robotic myomectomy (MPRM) and provide surgical tips. We retrospectively analyzed the medical records of 462 patients with symptomatic leiomyoma who underwent MPRM or SIRM between March 2019 and April 2021. Demographic characteristics and surgical outcomes, including the total operative time (OT), estimated blood loss (EBL), and surgical complication rate, were compared between the two groups. Patients in the SIRM group had lower a body mass index and rate of previous pelvic surgery and were younger than those in the MPRM group. The myoma type was not different between groups; however, the MPRM group had larger, and more myomas than the SIRM group. After propensity score matching, these variables were not significantly different between the groups. The total OT, EBL, difference in hemoglobin levels, transfusion rate, and postoperative fever were not different between the groups. No postoperative complications occurred in the SIRM group. In the MPRM group, one patient needed conversion to laparotomy, and two patients had postoperative complications (umbilical incisional hernia and acute kidney injury). In conclusion, both MPRM and SIRM are feasible and effective surgical options for symptomatic myomas with cosmetic benefits and minimal risk of laparotomy conversion.

The Clinical Significance and Utility of HPV-DNA Testing in Korean Women with Atypical Glandular Cells in Cervical Pap Tests: An Analysis of 311 Cases at a Single Institution.

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2 vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1 vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions.

Prediction of Life-Threatening Intracranial Hypertension During the Acute Phase of Traumatic Brain Injury Using Machine Learning.

Intracranial hypertension (IH) following acute phase traumatic brain injury (TBI) is associated with high mortality. Objective: This study proposes a novel parameter that may identify a potentially life-threatening IH (LTH) event and designs a machine learning model to predict LTH. Continuous recordings of intracranial pressure (ICP) and arterial blood pressure (ABP) from 273 TBI patients were used as the development dataset. The pressure-time dose (PTD) and pressure reactivity index (PRx) were calculated for each IH event, and an IH event with PRx > 0 and PTD > 5 was considered an LTH event. The association between the LTH parameters accumulated over five days and mortality was analyzed. A categorical boosting (CatBoost) model was employed to predict the occurrence of a future LTH event from the onset of IH using the ABP- and ICP-related parameters. Training and validation were performed on a total of 5,938 IH events. External performance evaluation was performed in 307 IH events included in the Cerebral Haemodynamic Autoregulatory Information System (CHARIS) database. The performance of the proposed model was evaluated through the area under the receiver operating characteristic curve (AUROC). The LTH parameters were able to distinguish between the deceased and surviving patients (AUROC > 0.7, p < 0.001). The CatBoost model predicted LTH with an AUROC = 0.7 on the external test dataset. This study demonstrated that the proposed LTH prediction model has a reasonable predictive capacity for mortality. The CatBoost model anticipates whether an IH event will develop into an LTH event. The findings of this study support the usefulness of ICP monitoring.

Cerebrospinal fluid dynamics correlate with neurogenic claudication in lumbar spinal stenosis.

Neurogenic claudication is a typical manifestation of lumbar spinal stenosis (LSS). However, its pathophysiology is still unclear. The severity of clinical symptoms has been shown not to correlate with the degree of structural stenosis. Altered cerebrospinal fluid (CSF) flow has been suggested as one of the causative factors of LSS. The objectives of this study were to compare CSF dynamics at the lumbosacral level between patients with LSS and healthy controls and to investigate whether CSF dynamics parameters explain symptom severity in LSS. Phase-contrast magnetic resonance imaging (PC-MRI) was conducted to measure CSF dynamics in 18 healthy controls and 9 patients with LSS. Cephalic peak, caudal peak, and peak-to-peak CSF velocities were evaluated at the lumbosacral level in the patients and controls. The power of CSF dynamics parameters to predict symptom severity was determined using a linear regression analysis adjusted for demographic and structural variables. Significantly attenuated CSF flow velocity was observed in the patients compared with the controls. The cephalic peak, caudal peak, and peak-to-peak velocities at the lumbar level were greater in the controls than in the patients (p<0.001). The predictive power increased most when the peak-to-peak velocity was added (adjusted R2 = 0.410) to the model with age, body mass index, and the minimum anterior-posterior diameter (adjusted R2 = 0.306), and the peak-to-peak velocity was the only statistically significant variable. CSF dynamics variables showed an association with the severity of LSS symptoms, independent of structural stenosis. PC-MRI can help to further our understanding of the pathophysiology of neurogenic claudication and support the diagnosis of LSS.

Real-world experience of olaparib as maintenance therapy in BRCA-mutated recurrent ovarian cancer.

PURPOSE: The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients. METHODS: We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed. RESULTS: All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1-33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression. CONCLUSION: Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.

New Surgical Technique for Robotic Myomectomy: Continuous Locking Suture on Myoma (LSOM) Technique.

Robot-assisted laparoscopic myomectomy (RALM) has broadened the indications even in complex myomas. However, the high cost of RALM remains the main disadvantage. Therefore, a surgical technique that can reduce the cost of RALM and still has the advantages of robotic surgery is required. We propose a "locking suture on myoma (LSOM)" technique and compared the operative and perioperative outcomes of patients who underwent RALM with or without the LSOM technique. We included 337 patients who underwent RALM with (n = 160) or without (n = 177) the LSOM technique between March 2019 and August 2020. The LSOM group had low parity and gravidity, with a low rate of Cesarean sections. Myoma type was not different between the groups; however, patients in the LSOM group had larger, heavier, and higher number of myomas, although fewer patients had multiple myomas and were discharged earlier. Total operating time, estimated blood loss, pre- and postoperative hemoglobin levels, transfusion rate, and postoperative fever were not different between the two groups. In conclusion, the LSOM technique may be a viable surgical option for myomas, as it can reduce the cost of RALM by obviating the need for robotic Tenaculum forceps.

Continued medical treatment for persistent early endometrial cancer in young women.

OBJECTIVE: We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients. METHODS: We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed. RESULTS: Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p < 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001). CONCLUSIONS: Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.

Usefulness of sentinel lymph node mapping using indocyanine green and fluorescent imaging in the diagnosis of lymph node metastasis in endometrial cancer.

The lymph node status is the most important prognostic factor for endometrial cancer. This study aimed to assess whether sentinel lymph node mapping (SLNM) is applicable in endometrial cancer. A retrospective review of patients with endometrial cancer who were diagnosed and treated in Asan Medical Centre from September 2015 to December 2017 was conducted. One hundred patients underwent robotic (da Vinci®) or laparoscopic surgical treatment, including SLNM with indocyanine green (ICG) fluorescence detection using the Firefly® and NIR/ICG systems. At least one lymph node area was observed in 100% of SLNM cases. Sentinel node detection and frozen biopsy were performed in all cases, and all patients with metastasis were found on SLNM. The sensitivity and negative predictive value were both 100% in the patient-by-patient and station-by-station analyses. SLNM appears to be a feasible method to reduce the morbidity and increase the detection rate in early-stage endometrial carcinoma.What is already known on this subject? There are studies that it is safe to diagnose the possibility of lymph node metastasis through sentinel lymph node mapping in endometrial cancer.What do the results of this study add? In this study, it is shown that the accuracy of sentinel lymph node mapping is 100% accurate.What are the implications of these findings for clinical practise and/or further research? Therefore, total lymphadenectomy will not be necessary for the future.

Robot-Assisted Laparoscopic Myomectomy versus Abdominal Myomectomy for Large Myomas Sized over 10 cm or Weighing 250 g.

PURPOSE: Here, we compared the operative and perioperative outcomes between robot-assisted laparoscopic myomectomy (RALM) and abdominal myomectomy (AM) in patients with large (>10 cm) or heavy myomas (>250 g). MATERIALS AND METHODS: We included 278 patients who underwent multi-port RALM (n=126) or AM (n=151) for large or heavy myomas in a tertiary care hospital between April 2019 and June 2020. The t-test, chi-square, Bonferroni's test, and multiple linear regression were used. RESULTS: No differences were observed in age, body mass index, parity, or history of pelvic surgery between the two groups. Myoma diameters were not different (10.8±2.52 cm vs. 11.2±3.0 cm, p=0.233), but myomas were lighter in the RALM group than in the AM group (444.6±283.14 g vs. 604.68±368.35 g, respectively, p=0.001). The RALM group had a higher proportion of subserosal myomas, fewer myomas, fewer large myomas over >3 cm, lighter myomas, and longer total operating time. However, the RALM group also had shorter hospital stay and fewer short-term complications. Estimated blood loss (EBL) was not different between the two groups. The number of removed myomas was the most significant factor (coefficient=10.89, p<0.0001) affecting the EBL. CONCLUSION: RALM is a feasible myomectomy technique even for large or heavy myomas. RALM patients tend to have shorter hospital stays and fewer postoperative fevers within 48 hours. However, RALM has longer total operating time.

Feasibility and safety of fertility-sparing surgery in epithelial ovarian cancer with dense adhesion: a long-term result from a single institution.

OBJECTIVE: We investigated the feasibility and safety of fertility-sparing surgery (FSS) in patients with epithelial ovarian cancer (EOC) with dense adhesions. METHODS: Patients were divided into cases with and without dense adhesions in this retrospective study. RESULTS: Of the 95 eligible patients, 29 patients had dense adhesions. Mean age, proportion of staging procedure, distribution of histologic type, and co-presence of endometriosis were different (p=0.003, 0.033, 0.011, and 0.011, respectively). The median follow-up period was 57.8 (0.4-230.0) months. There were no differences in the rates of recurrence (21.2% vs. 20.7%, p=1.000) or death (16.7% vs. 6.9%, p=0.332) between the 2 groups. There was no difference in the pattern of recurrence or in disease-free survival (DFS) and overall survival (OS) between the 2 groups. In multivariate analysis, pretreatment cancer antigen-125 >35 U/mL and International Federation of Gynecology and Obstetrics stage IC were significant factors of worse DFS and OS, while dense adhesion was not a prognostic factor for both DFS (hazard ratio [HR]=0.9; 95% confidence interval [CI]=0.3-2.7; p=0.792) and OS (HR=0.2; 95% CI=0.1-1.8; p=0.142), nor were age, proportion of staging procedure, histologic type, and co-presence of endometriosis. Moreover, the distribution of those 2 significant prognostic factors was not different between the 2 groups. Dense adhesions were subgrouped into non-tumor and tumor associated dense adhesions for further analysis and the results were same. CONCLUSION: FSS is feasible and safe in EOC, regardless of the presence of dense adhesions.

Low value of staging in detecting extraovarian occult metastasis in mucinous borderline ovarian tumors.

OBJECTIVES: Staging procedure in borderline ovarian tumors is a topic of controversy. Upstaging in non-serous borderline ovarian tumors that are confined to the ovary is rare. The aim of this study was to assess the impact of surgical staging on clinical outcomes in mucinous borderline ovarian tumors. METHODS: This was a retrospective study conducted at the Asan Medical Center, Seoul, Korea between January 1990 and December 2015, that included 432 patients with mucinous borderline ovarian tumors and at least 6 months follow-up. These patients were divided into a 'staging group' and 'unstaged group'. The staging group referred to patients who, in addition to hysterectomy and/or adnexal surgery, underwent at least one of the following: cytology, omental biopsy/omentectomy, peritoneal biopsy, lymph node biopsy/lymphadenectomy, or appendectomy. The unstaged group referred to patients who did not undergo any staging procedure but underwent adnexal surgery (cystectomy or oophorectomy). RESULTS: Median patient age was 40 (range 9-87) years. A total of 367 patients (85%) underwent a staging procedure (staging group) and 65 (15.0%) patients did not (unstaged group). Among the staging group, 258, 4, 100, and 5 patients were FIGO stage IA, IB, IC, or II-III, respectively. Overall recurrence was confirmed in 15 patients and median time to recurrence was 13.4 (range 0.4-127.3) months. One patient was in the unstaged group and had borderline recurrence. Fourteen were in the staging group, and 11 of them had borderline and three had invasive recurrence. Extraovarian disease was found at recurrence only in two patients. There was no significant difference in recurrence-free survival (p=0.39) and in overall survival between the staging group and the unstaged group (p=0.40). In total, 16 (4.4%) of 367 patients who underwent a staging procedure were upstaged. CONCLUSION: Staging in mucinous borderline ovarian tumors may be omitted if there is no obvious evidence of gross extraovarian disease.

Comparison of Risk of Ovarian Malignancy Algorithm and cancer antigen 125 to discriminate between benign ovarian tumor and early-stage ovarian cancer according to imaging tumor subtypes.

The present study aimed to compare the accuracy of the Risk of Ovarian Malignancy Algorithm (ROMA) and cancer antigen (CA)125 to discriminate between benign ovarian tumors and early-stage ovarian cancer according to imaging tumor subtypes associated with post-operative histopathological findings. A total of 1,207 patients who were assessed using the ROMA test due to suspected early-stage ovarian cancer and underwent surgery at Asan Medical Center (Seoul, Korea) between September 2014 and March 2018 were identified. A total of 981 patients who met the inclusion criteria were included in the retrospective analysis. Among the 981 subjects, 816 had benign tumors, 90 had malignant tumors and 75 had borderline tumors. Of the patients diagnosed with ovarian cancer or borderline tumor, 47.3% were judged as high-risk by the ROMA test and 58.2% had CA125 levels of >35 U/ml. The specificity and accuracy of ROMA were higher compared with those of CA125 in pre-menopausal females. However, the superiority of the ROMA test in the identification of malignant ovarian tumors compared with CA125 was only observed in patients with endometriotic-type tumors but not in any of the other tumor subtypes. In the endometriotic type of ovarian tumor, the superiority of the ROMA test compared to CA125 was confirmed in triage of ovarian tumor. However, the sensitivity and specificity of ROMA and CA125 were similar for the other tumor types. Therefore, future development of better tumor-specific biomarkers for triage of ovarian tumor is required.

Prognostic Factors and Impact of Minimally Invasive Surgery in Early-stage Neuroendocrine Carcinoma of the Cervix.

STUDY OBJECTIVE: To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). DESIGN: Retrospective cohort study. SETTING: Asan Medical Center, Seoul, Korea. PATIENTS: Patients with International Federation of Obstetrics and Gynecology (2009) stages IB1 to IIA HG NECC. INTERVENTIONS: All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. MEASUREMENTS AND MAIN RESULTS: Between 1993 and 2017, 47 patients with International Federation of Obstetrics and Gynecology stages IB1 to IIA1 HG NECC were initially treated with RH. Clinicopathologic variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1-42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH by MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph node metastasis and resection margin involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018-4.871; p =.045 and HR, 6.494; 95% CI, 1.415-29.809; p =.016, respectively) and OS (HR, 3.236; 95% CI, 1.188-8.815; p =.022 and HR, 12.710; 95% CI, 1.128-143.152; p =.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs 72.4% log-rank p =.196, 38.9% vs 37.9% p =.975). CONCLUSION: Lymph node metastasis and resection margin involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.

Accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade of mucinous ovarian tumors.

OBJECTIVE: To determine the accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade in patients with mucinous ovarian tumors. METHODS: This study included 1,032 patients with mucinous ovarian tumors who underwent frozen section diagnosis during surgery. Sensitivity, specificity, and diagnostic accuracy of frozen section diagnosis was calculated. Univariate and multivariate regression analyses were performed to determine factors associated with diagnosis upgrade in the final pathology report. RESULTS: The sensitivity and specificity of frozen section diagnosis were 99.1% (95% confidence interval [CI]=98%-99.6%) and 82.2% (95% CI=77.9%-85.7%), respectively, for benign mucinous tumors; 74.6% (95% CI=69.1%-79.4%) and 96.7% (95% CI=95.2%-97.8%), respectively, for mucinous borderline ovarian tumors; and 72.5% (95% CI=62.9%-80.3%) and 98.8% (95% CI=97.9%-99.3%), respectively, for invasive mucinous carcinomas. The multivariate analysis revealed that mixed tumor histology (odds ratio [OR]=2.8; 95% CI=1.3-6.3; p=0.012), tumor size >12 cm (OR=2.5; 95% CI=1.5-4.3; p=0.001), multilocular tumor (OR=2.9; 95% CI=1.4-6.0; p=0.006), and presence of a solid component in the tumor (OR=3.1; 95% CI=1.8-5.1; p<0.001) were independent risk factors for final pathological diagnosis upgrade. CONCLUSIONS: Mixed tumor histology, tumor size >12 cm, multilocular tumor, and presence of a solid component in the tumor were independent risk factors for final pathological diagnosis upgrade based on frozen section diagnosis.