Evaluation of prognostic potential of ß-catenin and L1CAM expression according to endometrial cancer risk group.

OBJECTIVE: We investigate the prognostic role of ß-catenin and L1 neuronal cell-adhesion molecule (L1CAM) according to risk groups in endometrial carcinomas (EC). METHODS: A total of 335 EC patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer. We evaluated the expression of ß-catenin and L1CAM using immunohistochemistry, and their association with clinicopathological characteristics and survival. RESULTS: The expressions of ß-catenin and L1CAM were observed in 10.4% of all patients, respectively, and showed mutually exclusive pattern. While ß-catenin expression was associated with endometrioid histology (p = 0.035) and low tumor grade (p = 0.045), L1CAM expression was associated with non-endometrioid histology (p < 0.001), high tumor grade (p < 0.001), lymphovascular space invasion (p = 0.006), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.001). ß-catenin expression was most frequent in the no specific molecular (NSMP) group (26/35, 74.3%), followed by the DNA polymerase-ε-mutated (POLE-mut) (6/35, 17.1%), and mismatch repair-deficiency (dMMR) (3/35, 8.6%). L1CAM expression was most frequent in the p53-abnormal group (22/35, 62.9%), followed by the NSMP (6/35, 17.1%), dMMR (4/35, 11.4%), and POLE-mut (3/35, 8.6%). Although both markers did not show statistical significance in multivariate analysis for both progression-free survival (PFS) and overall survival in entire cohort, ß-catenin positivity was identified as the sole factor associated with worse PFS in the high-intermediate risk subgroup (p = 0.001). CONCLUSION: The expression of nuclear ß-catenin may serve as a potential biomarker for predicting recurrence and guiding therapeutic strategies in high-intermediate risk EC patients.

A differential diagnosis between uterine leiomyoma and leiomyosarcoma using transcriptome analysis.

BACKGROUND: The objective of this study was to estimate the accuracy of transcriptome-based classifier in differential diagnosis of uterine leiomyoma and leiomyosarcoma. We manually selected 114 normal uterine tissue and 31 leiomyosarcoma samples from publicly available transcriptome data in UCSC Xena as training/validation sets. We developed pre-processing procedure and gene selection method to sensitively find genes of larger variance in leiomyosarcoma than normal uterine tissues. Through our method, 17 genes were selected to build transcriptome-based classifier. The prediction accuracies of deep feedforward neural network (DNN), support vector machine (SVM), random forest (RF), and gradient boosting (GB) models were examined. We interpret the biological functionality of selected genes via network-based analysis using GeneMANIA. To validate the performance of trained model, we additionally collected 35 clinical samples of leiomyosarcoma and leiomyoma as a test set (18 + 17 as 1st and 2nd test sets). RESULTS: We discovered genes expressed in a highly variable way in leiomyosarcoma while these genes are expressed in a conserved way in normal uterine samples. These genes were mainly associated with DNA replication. As gene selection and model training were made in leiomyosarcoma and uterine normal tissue, proving discriminant of ability between leiomyosarcoma and leiomyoma is necessary. Thus, further validation of trained model was conducted in newly collected clinical samples of leiomyosarcoma and leiomyoma. The DNN classifier performed sensitivity 0.88, 0.77 (8/9, 7/9) while the specificity 1.0 (8/8, 8/8) in two test data set supporting that the selected genes in conjunction with DNN classifier are well discriminating the difference between leiomyosarcoma and leiomyoma in clinical sample. CONCLUSION: The transcriptome-based classifier accurately distinguished uterine leiomyosarcoma from leiomyoma. Our method can be helpful in clinical practice through the biopsy of sample in advance of surgery. Identification of leiomyosarcoma let the doctor avoid of laparoscopic surgery, thus it minimizes un-wanted tumor spread.

Survival outcomes of laparoscopic versus open radical hysterectomy in early cervical cancer with incidentally identified high-risk factors.

OBJECTIVE: Previously, we suggested that patients with cervical cancer (CC) with tumors ≤2 cm on preoperative magnetic resonance imaging (MRI) are safe candidates for laparoscopic radical hysterectomy (LRH). Here, we aim to investigate whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors; lymph node metastasis (LNM) or parametrial invasion (PMI). METHODS: We identified patients with 2009 FIGO stage IB1 CC who underwent Type C LRH or open radical hysterectomy (ORH) at three tertiary hospitals between 2000 and 2019. Those with a tumor ≤2 cm on preoperative MRI who were not suspicious of LNM or PMI preoperatively were included, while those who were indicated to receive adjuvant treatment but did not actually receive it were excluded. Survival outcomes were compared between the LRH and ORH groups in the overall population, then narrowed down to those with LNM, and then to those with PMI. RESULTS: In total, 498 patients were included: 299 in the LRH group and 199 in the ORH group. The LRH and ORH groups showed similar 3-year progression-free survival (PFS) (94.0% vs. 93.6%; P = 0.615) and 5-year overall survival (OS) rates (97.2% vs. 96.8%; P = 0.439). On pathologic examination, 49 (9.8%) and 16 (3.2%) patients had LNM and PMI, respectively, and 10 (2.0%) had both. In the LNM subgroup, 5-year PFS rate was not significantly different between the LRH and ORH groups (73.2% vs. 91.7%; P = 0.169). In the PMI subgroup, no difference in PFS was observed between the two groups (P = 0.893). CONCLUSIONS: LRH might not deteriorate recurrence and mortality rates in CC patients with tumors ≤2 cm when adjuvant treatment is appropriately administered, even if pathologic LNM and PMI are incidentally identified.

Preoperative education on realistic expectations improves the satisfaction of patients with central sensitization after total knee arthroplasty: a randomized-controlled trial.

PURPOSE: The aim of this study was to investigate whether an additional module on realistic expectations following total knee arthroplasty (TKA) would lead to a higher proportion of satisfied patients compared to existing preoperative education. METHODS: This was a single-center, randomized-controlled trial. A total of 172 patients who were scheduled for TKA between September 2020 and October 2021 were enrolled. Patients were randomized to receive either only standard preoperative education, or an additional module on realistic expectations following TKA. The primary outcome was patient satisfaction. Secondary outcomes were Short Form-36, Western Ontario and McMaster Universities Osteoarthritis Index, crepitus score, and range of motion. Subgroup analysis was performed based on central sensitization inventory (CSI) score stratification. Assessment was performed at the 3-month, 6-month, and > 1-year follow-up. RESULTS: At more than 1 year, 65/78 (83.3%) patients in the intervention group and 52/80 (65.0%) patients in the control group were satisfied (P = 0.03). The mean satisfaction score was measured as 4.2 ± 0.9 in the intervention and 3.9 ± 0.9 in the control at > 1 year (P = 0.01). There were significant differences in Short Form-36 physical and mental component summary scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and stiffness scores at 6 months (P = 0.02, P = 0.02, P = 0.04, P = 0.04). The frequency of satisfaction and mean satisfaction score in the top 25 percentile CSI group were 15/16 (93.8%) and 4.6 ± 0.6 in those who received intervention and 12/19 (63.2%) and 3.8 ± 0.8 in those who did not (P = 0.01, P = 0.01). CONCLUSIONS: Thorough preoperative education on realistic expectations following TKA showed effects on WOMAC pain and satisfaction at > 1 year after surgery. It was more prominent in the group with a higher CSI score at > 1-year follow-up. LEVEL OF EVIDENCE: Level I.

Graft impingement increases anterior cruciate ligament graft signal more than acute graft bending angle: magnetic resonance imaging-based study in outside-in anterior cruciate ligament reconstruction.

PURPOSE: In this study, the relationship between patient-specific geometric factors and tunnel placement in graft impingement was identified by using magnetic resonance imaging (MRI) signal intensity of anterior cruciate ligament (ACL) grafts. METHODS: Ninety-two patients, who were treated between 2014 and 2020, were included retrospectively. These patients underwent primary remnant-preserving outside-in ACL reconstruction (ACLR) and were followed up with postoperative MRI at least one year after surgery. Plain radiographs and computed tomography (CT) were used to analyze tibial and femoral tunnel positions. Postoperative MRI was performed, at 32.8 ± 17.5 months after surgery, to evaluate the graft signal intensity, the ACL/posterior cruciate ligament (PCL) ratio (APR), ACL/muscle ratio (AMR), tunnel positions, and graft impingement. Clinical and stability outcomes were analyzed using the International Knee Documentation Committee (IKDC) subjective and objective scores, Lysholm scores, and side-to-side differences (SS-D). RESULTS: The mean APR and AMR of the proximal third of the grafts were significantly lower than those of the middle third of the grafts (p = 0.017 and p = 0.045, respectively). Multivariate regression analysis showed that there was a negative association between the mean APR and AMR of entire intra-articular ACL graft and the distance from the anterior end of the intercondylar roof to the center of the tibial tunnel in the sagittal plane (p < 0.001 and p < 0.001, respectively) and the notch width index (p < 0.001 and p = 0.002, respectively). No significant correlations were found between tunneling and geometric factors, and clinical scores or SS-D. CONCLUSIONS: Graft impingement on the anterior tibial tunnel relative to the end of the intercondylar roof and narrow notch was a more significant contributing factor on increased signal intensities of the ACL graft, compared with the acute femoral bending angle in remnant-preserving outside-in ACLR. Therefore, surgeons should focus on intercondylar notch anatomy during tibial tunnel placement to avoid roof impingement. LEVEL OF EVIDENCE: Level III.

Longitudinal changes in shoulder arthroplasty stratified by age groups, types of surgical facilities, and geographical regions in Korea from 2010 to 2020.

BACKGROUND: Shoulder arthroplasty (SA), including hemiarthroplasty, reverse and anatomical total SA (TSA), improves quality of life by reducing shoulder pain and restoring function in patients not only with irreparable rotator cuff tears and/or cuff tear arthropathy but also with osteoarthritis posttraumatic arthritis, proximal humeral fractures, etc. Given the rapid developments in artificial joints and improvements in postoperative outcomes, the number of SA surgeries is increasing worldwide. Therefore, we investigated changes in trends over time in Korea. METHODS: We analyzed the longitudinal changes in the incidence of SA including anatomic and reverse TSA, hemiarthroplasty, and shoulder revision arthroplasty (SRA) by changes in the Korean age profile, surgical facilities, and geographical regions using the Korean Health Insurance Review and Assessment Service database from 2010 to 2020. Data were also collected from the National Health Insurance Service and the Korean Statistical Information Service. RESULTS: From 2010 to 2020, the TSA rate per 1,000,000 person-years increased from 10.571 to 101.372 (time trend = 1.252; 95% CI 1.233-1.271, P < .001). The shoulder hemiarthroplasty (SH) rate per 1,000,000 person-years decreased from 6.414 to 3.685 (time trend = 0.933; 95% CI 0.907-0.960, P < .001). The SRA rate per 1,000,000 person-years increased from 0.792 to 2.315; the increase was significant (time trend = 1.133; 95% CI 1.101-1.166, P < .001). DISCUSSION: Overall, TSA and SRA are increasing and SH is decreasing. For both total TSA and SRA, steep increases are evident in the numbers of patients in their 70s and older than 80 years. The SH trend is decreasing regardless of differences in age groups, surgical facilities, and geographical regions. SRA is preferentially performed in Seoul.

HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP.

The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.

Clinical relevance of roll-back replacement of ultra congruent total knee arthroplasty: comparison of mid-term outcomes with posterior stabilizing design.

INTRODUCTION: The outcomes of total knee arthroplasty (TKA) remain controversial, and we do not know which factors are important for successful outcomes. This study aimed to compare the mid-term outcomes of different conceptual designs by evaluating the radiological and clinical outcomes. MATERIALS AND METHODS: A total of 478 total knee arthroplasties (TKAs) were enrolled and allocated into groups I [posterior stabilizing (PS) with anterior referencing (AR)], II [PS with posterior referencing (PR), and III [ultra-congruent (UC) TKA)]. Preoperative findings, last follow-up clinical outcomes, and final follow-up radiological and indirect assessments of the femoral rollback were compared between the groups. RESULTS: The mean follow-up period was 72.6 ± 12.9 months. The tourniquet was used samely applied to every group. Flexion contracture was significantly larger in group III than in groups I and II (3.3 ± 2.7, p < 0.001), and further flexion was significantly smaller in group III (130.0° ± 2.7°, p < 0.001). Among the radiological parameters, posterior osteophyte formation was the most common in group III (67.8%). The rollback distance was significantly smaller in group III than in groups I and II (p < 0.001). The active deep flexion angle was affected by the posterior condylar offset (PCO) ratio, and the contact point changed the distance (p < 0.05). CONCLUSION: PS TKAs showed better ROMs than UC TKAs; however, no differences were noted in the clinical outcome scales. The flexion angle was affected by the PCOR and rollback at both PS and UC TKAs. However, rollback negatively affected the flexion angle during UC TKAs. An inappropriate femoral rollback was identified, and femoral osteophyte formation was determined to be the most prominent in UC TKAs. Level of evidence Level III comparative study.

Bevacizumab versus PARP-inhibitors in women with newly diagnosed ovarian cancer: a network meta-analysis.

BACKGROUND: In women with newly diagnosed ovarian cancer, bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) exhibit improved progression-free survival (PFS) when administered concurrent with chemotherapy and/or maintenance therapy, but no study has directly compared their effects. Therefore, this study aimed to compare the efficacy and safety of bevacizumab and PARPi in women with newly diagnosed ovarian cancer using a network meta-analysis. METHODS: PubMed, Medline, and Embase databases were searched, and five randomized trials assessing PFS in women with newly diagnosed ovarian cancer treated with either bevacizumab, PARPi, or placebo or no additional agent (controls) were identified. PFS was compared in the overall population with ovarian cancer, women with a BRCA1/2 mutation (BRCAm) and women with homologous-recombination deficiency (HRD). Adverse events (grade ≥ 3) were compared in all populations of the included studies. RESULTS: PARPi improved PFS significantly more than bevacizumab in women with a BRCAm (HR 0.47; 95% CI 0.36-0.60) and with HRD (HR 0.66; 95% CI 0.50-0.87). However, in the overall population with ovarian cancer, no significant difference in PFS was observed between women treated with PARPi and those treated with bevacizumab. PARPi exhibited the highest surface under the cumulative ranking probabilities value as the most effective treatment for PFS (PARPi vs. bevacizumab: 98% vs. 52% in the overall population with ovarian cancer; 100% vs. 50% in women with BRCAm; 100% vs. 50% in women with HRD). For adverse events, the risk of all treatments was similar. However, PARPi had a higher adverse risk than the control group (relative risk 2.14; 95% CI 1.40-3.26). CONCLUSIONS: In women with newly diagnosed ovarian cancer, PARPi might be more effective in terms of PFS compared to bevacizumab. The risk of serious adverse events was similar for PARPi and bevacizumab.

Open versus minimally invasive radical hysterectomy for early cervical cancer: A two-center retrospective cohort study with pathologic review of usual-type adenocarcinoma and adenosquamous carcinoma.

OBJECTIVE: To compare survival outcomes of minimally invasive surgery (MIS) and open surgery for radical hysterectomy (RH) in early cervical cancer patients with histologic subtypes of usual-type adenocarcinoma and adenosquamous carcinoma. METHODS: From two centers' cervical cancer cohorts, patients with 2009 FIGO stage IB1-IB2 who underwent RH between 2007 and 2020 were retrospectively identified. Patients with usual-type adenocarcinoma and adenosquamous carcinoma were included in the analysis after pathologic review according to the updated World Health Organization Classification of Tumors. Clinicopathologic characteristics and survival outcomes were compared in terms of open surgery or MIS. RESULTS: This study included 161 patients. No significant differences were noted in overall survival (OS; P = 0.241) and disease-free survival (DFS; P = 0.156) between patients with usual-type adenocarcinoma (n = 136) and those with adenosquamous carcinoma (n = 25). MIS RH group (n = 99) had a significantly smaller tumor size (P < 0.001), lesser pathologic parametrial invasion (P = 0.001), and lesser lymph node metastasis (P < 0.001) than open RH group (n = 62). MIS and open RH groups showed similar OS (P = 0.201) and 3-year DFS rate (87.9% vs. 75.1%; P = 0.184). In multivariate analysis, worse DFS was not associated with MIS (P = 0.589) but was associated with pathologic parametrial invasion (adjusted HR, 3.41; 95% CI, 1.25-9.29; P = 0.016). Consistent results were observed among patients with usual-type adenocarcinoma; MIS was not associated with worse DFS. CONCLUSIONS: Comparable survival outcomes were found for MIS and open RH in early-stage cervical usual-type adenocarcinoma and adenosquamous carcinoma. Although MIS RH was not a poor prognostic factor, pathologic parametrial invasion was significantly associated with worse DFS in cervical usual-type adenocarcinoma and adenosquamous carcinoma.

Serum Human Epididymis Protein 4 as a Prognostic Marker in Cervical Cancer.

OBJECTIVES: The objective is to evaluate the prognostic value of serum human epididymis protein 4 (HE4) as a tumor marker in patients with cervical cancer. METHODS: Sixty-seven patients with cervical cancer treated at Seoul National University Bundang Hospital from September 2014 to May 2018 were retrospectively reviewed. Serum HE4 levels were measured by immunoassay before starting primary treatment. A mean serum HE4 level of 72.6 pmol/L was used to divide the patients into low and high HE4 groups. Patient characteristics, clinicopathological variables, and survival outcomes were compared between the two groups. RESULTS: The low and high HE4 groups included 55 (82.1%) and 12 (17.9%) patients at diagnosis, respectively. Higher HE4 levels were significantly associated with older age at diagnosis (age <50: .0% vs age ≥50: 100.0%; P = .002), menopause (premenopause: 8.3% vs postmenopause: 91.7%; P = .009), higher FIGO stage (stage I-II: 33.3% vs III-IV: 66.7%; P = .017), large tumor size (<4.0 cm: 41.7% vs ≥4.0 cm: 58.3%; P = .029), positive lymph node metastasis (negative: 41.7% vs positive: 58.3%; P = .049), and involvement of the parametrium (negative: 25.0% vs positive: 75.0%; P = .002). Higher HE4 level was a predictive factor for worse overall survival but not for progression-free survival. Elevated HE4 levels were not independent factors for the prediction of either overall survival or progression-free survival. Subgroup analysis by histological type revealed similar results for patients with squamous cell carcinoma. CONCLUSIONS: High levels of HE4 expression correlated with poor overall survival, indicating that elevated HE4 levels are associated with a poor prognosis for patients with cervical cancer.

Efficacy and safety of skin-adhesive low-level light therapy for overactive bladder: a Phase III study.

INTRODUCTION AND HYPOTHESIS: Overactive bladder (OAB) is a common condition that remains challenging to treat. We hypothesized that skin-adhesive low-level light therapy (LLLT) would be an effective treatment for OAB caused by bladder muscle contraction. Accordingly, we aimed to evaluate the efficacy and safety of an LLLT device for the treatment of OAB. METHODS: This prospective, randomized, double-blind, placebo-controlled, multicenter trial included patients with a clinical diagnosis of OAB who were treated at either of two university hospitals. Patients were instructed to apply an LLLT device (Color DNA-WSF) or a sham device at home three times daily for 12 weeks. The primary outcome was the change in the mean daily number of urge urinary incontinence (UUI) episodes between baseline and 12 weeks. The secondary outcomes were the mean changes in incontinence, voiding, and nocturia episodes from baseline and the likelihood of achieving a > 50% reduction in UUI and incontinence episodes after 12 weeks. All patients completed the Overactive Bladder Symptom Score (OABSS), Urogenital Distress Inventory-6 (UDI-6), and Impact Urinary Incontinence-7 (IIQ-7) questionnaires. Safety parameters included treatment-emergent adverse events. RESULTS: Compared with those in the sham group, the numbers of UUI and urinary incontinence episodes in the LLLT group were significantly decreased at week 12 (UUI, (-1.0 ± 1.7 vs. -0.4 ± 2.5, P = 0.003; urinary incontinence, -1.1 ± 1.9 vs. -0.5 ± 2.9, P=0.002). Furthermore, the OABSS, UDI-6, and IIQ-7 scores at week 12 tended to be better in the LLLT group than in the sham group. The incidence of device-related treatment-emergent adverse events was similar between groups. CONCLUSIONS: LLLT may be clinically useful and safe for the treatment of OAB.

Risk factors for and prognosis of carboplatin-related hypersensitivity in patients with epithelial ovarian cancer.

PURPOSE: We aimed to identify the predictive risk factors for carboplatin-related hypersensitive reactions (HRs) and investigate their impact on survival outcomes in patients with epithelial ovarian cancer (EOC). METHODS: This retrospective study included 222 patients with EOC who received carboplatin infusion between July 2016 and November 2019. We compared the clinicopathologic characteristics and survival outcomes between carboplatin-related hypersensitivity and non-hypersensitivity groups. Hypersensitivity data were classified using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, categorizing grades from 1 to 5 as mild/moderate/severe/life-threatening/death. Multiple logistic regression analysis was used to analyze risk factors of HRs. The Cox proportional hazard regression model was used to determine the factors of being significantly associated with overall survival. RESULTS: Of the 222 patients, eight exhibited HRs (incidence rate, 3.6%). All HRs were of grade 3 or 4 (life-threatening). In all cases, a desensitization protocol was followed. Advanced stage (III or IV) (P = 0.022), previous history of carboplatin use (P < 0.001), and recurrent ovarian cancer (P = 0.001) were significantly associated with HR to carboplatin. Multivariate logistic analysis showed that a previous history of carboplatin was the only independent risk factor for carboplatin-related hypersensitivity (OR, 20.19; 95% CI 1.22 - 3034.10; P = 0.034). However, HR to carboplatin did not influence the overall survival (P = 0.526). CONCLUSION: In EOC patients, prior use of carboplatin was an independent risk factor for carboplatin-related HRs; HRs to carboplatin did not influence the overall survival. Clinicians should not underestimate the possibility risk of carboplatin HSRs when re-administrating carboplatin in EOC patients.

Risk Factor and Treatment of Vaginal Intraepithelial Neoplasia After Hysterectomy for Cervical Intraepithelial Neoplasia.

OBJECTIVES: The aim of the study were to identify the risk factors for recurrent vaginal intraepithelial neoplasia (VaIN)1+ and to evaluate the efficacy of laser vaporization in patients who underwent hysterectomy for the treatment of cervical intraepithelial neoplasia (CIN). METHODS: Medical records of 374 women who underwent hysterectomy for the treatment of CIN were retrospectively reviewed. Recurrence was defined as VaIN1+ diagnosis by colposcopy-directed biopsy. RESULTS: Among 374 patients, 36 (9.6%) had VaIN1+ during a median follow-up of 32 (0-193) months: 13 (3.5%) had VaIN1, 6 (1.6%) VaIN2, 15 (4.0%) VaIN3, and 2 (0.5%) invasive cancer. Multivariate analysis showed that age of greater than 50 years was the only independent risk factor for VaIN1+ recurrence (odds ratio, 3.359; 95% CI, 1.60-7.07; p = .001). Among the 34 patients with VaIN, 21 (61.8%) were treated with laser vaporization and 11 (32.3%) were observed without treatment. Time to second recurrence was longer in the VaIN treated by laser vaporization group than that in the observation group (mean time to subsequent recurrence, 128.7 [95% CI, 101.4-156.0] vs. 41.8 [15.7-67.9] months; p = .003). Moreover, laser vaporization (hazard ratio, 0.125; 95% CI, 0.03-0.59; p = .009) was the only independent good prognostic factor for the second VaIN1+ recurrence. CONCLUSIONS: Patients older than 50 years who underwent hysterectomy for the treatment of CIN might be highly at risk of VaIN1+. Laser vaporization is the only independent prognostic factor that might prevent the second VaIN1+ recurrence.

The voiding VAS score is a simple and useful method for predicting POUR after laparoscopy for benign gynaecologic diseases: a pilot study.

The aim of this study was to identify an appropriate scoring system for predicting postoperative urinary retention (POUR) after gynaecological laparoscopic surgery for benign disease. We analysed 99 patients who underwent gynaecological laparoscopic surgery for benign disease. All patients were asked to complete self-administered questionnaires, including the International Prostate Symptom Score (IPSS), voiding visual analogue scale (VAS), and Brief Pain Inventory-Korean version. Of the 99 patients, 27 (27.3%) experienced urinary retention at least once, while 72 (72.7%) did not. The preoperative and postoperative IPSS scores were not associated with the development of POUR. However, the voiding VAS score was significantly lower in patients that developed POUR (p = .014). In conclusion, our results show that the voiding VAS score is a simple and useful method for identifying patients at risk of POUR after gynaecologic laparoscopic surgery for benign disease. IMPACT STATEMENTWhat is already known on this subject? Postoperative urinary retention (POUR) is an often underestimated complication defined as inability to void during the postoperative period despite a full bladder. Undetected POUR may lead to complications such as urinary tract infection, bladder distention, and bladder dysfunction. Routine assessment of POUR by bladder ultrasonography in all surgical patients places a larger workload on the nursing staff.What do the results of this study add? Among the self-scoring assessment tools, the voiding VAS provided the most accurate reflection of POUR in patients undergoing gynaecologic laparoscopic surgery for benign disease.What are the implications of these findings for clinical practice and/or further research? As laparoscopy is the most widely employed surgical procedure in gynaecology, our findings could have significant implications for postoperative care in daily clinical practice.

A multicentre, randomised, open-label, parallel-group Phase 2b study of belotecan versus topotecan for recurrent ovarian cancer.

BACKGROUND: This Phase 2b study compared the efficacy and toxicity of belotecan and topotecan in recurrent ovarian cancer. METHODS: Patients with platinum-sensitive recurrent or platinum-resistant recurrent ovarian cancer (PRROC) were randomised 1:1 to receive belotecan 0.5 mg/m2 or topotecan 1.5 mg/m2 for five consecutive days every 3 weeks. The primary endpoint was overall response rate (ORR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: A total of 140 (belotecan, n = 71; topotecan, n = 69) and 130 patients (belotecan, n = 66; topotecan, n = 64) were included in the intention-to-treat (ITT) and per-protocol (PP) populations. ORR did not differ significantly between the belotecan and topotecan groups (ITT, 29.6% versus 26.1%; PP, 30.3% versus 25%). Although PFS did not differ between the groups, belotecan was associated with improved OS compared with topotecan in the PP population (39.7 versus 26.6 months; P = 0.034). In particular, belotecan showed longer OS in PRROC and non-high-grade serous carcinoma (non-HGSC; PP, adjusted hazard ratios, 0.499 and 0.187; 95% confidence intervals 0.255-0.977 and 0.039-0.895). Furthermore, there were no differences in toxicities between the two groups. CONCLUSIONS: Belotecan was not inferior to topotecan in terms of overall response for recurrent ovarian cancer. CLINICAL TRIAL REGISTRATION: NCT01630018.

Incidence and risk of venous thromboembolism according to primary treatment type in women with endometrial cancer: a population-based study.

BACKGROUND: Current prophylaxes and treatments for venous thromboembolism (VTE) in women with gynecologic cancer are mainly guided by studies on solid cancers because studies in gynecologic cancer did not provide sufficient data. Large-scale studies evaluating the incidence and risk of VTE according to therapeutic modality may guide prophylaxis and treatment of VTE in gynecologic cancer. This study was performed to determine the incidence and risk of VTE according to primary treatment type in Korean women with endometrial cancer. METHODS: We selected 26,256 women newly diagnosed with endometrial cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service database. During the total follow-up period and first six months after primary treatments initiation, the incidence and risk of VTE were evaluated according to primary treatment type, that is, no treatment, surgery, radiotherapy, chemotherapy, or hormone therapy. RESULTS: VTE occurred in 136 per 10,000 women during the total follow-up period and in 54 per 10,000 women during the first six months with the highest frequency in women that underwent chemotherapy. During the first year, the monthly incidence of VTE decreased with time among women that underwent no treatment, surgery, or hormone therapy and remained unchanged in those that received radiotherapy or chemotherapy. Compared with women that received no treatment, VTE risk, especially of PE significantly increased in women that underwent chemotherapy (VTE: hazard ratio (HR), 2.334; 95% CI, 1.38-3.949; P = 0.002) (PE: HR, 2.742; 95% CI, 1.424-5.278; P = 0.003) or hormone therapy (VTE: HR, 2.073; 95% CI, 1.356-3.17; P = 0.001) (PE: HR, 2.086; 95% CI, 1.19-3.657; P = 0.01) during the total follow-up period and women that underwent only chemotherapy during the first six months (VTE: HR, 2.532; 95% CI, 1.291-4.966; P = 0.007) (PE: HR, 3.366; 95% CI, 1.496-7.576; P = 0.003). CONCLUSIONS: In this cohort study, the incidence and risk of VTE were highest in women with endometrial cancer that underwent chemotherapy as a primary treatment. Notably, the incidence of VTE decreased over time in women that received no treatment, surgery, or hormone therapy. This study can help guide therapies for prophylaxis and treatment of VTE in women with endometrial cancer.

Diagnosis and treatment of bullous pemphigoid that developed twice after total knee replacement arthroplasty: a case report.

BACKGROUND: Total knee replacement arthroplasty (TKA) is frequently performed in South Korea. Simple swelling-associated blistering around the periphery of the operative wound is a well-known adverse effect. However, in rare cases, the blisters are bullous pemphigoid (BP). CASE PRESENTATION: A 75-year-old male presented with knee pain that had not improved despite 5 years of medication. We performed TKA of the left knee, placing a Stryker posteriorly stabilized prosthesis. Three days later, blisters developed near the buttocks and thighs and, on day 10 after surgery, around the operative site. A skin biopsy revealed BP. Commencing on day 14 after surgery, prednisolone 10 mg was administered twice daily. The symptoms improved by 3 weeks after surgery and were healed at 4 months. After 1 year, we performed TKA of the right knee. On day 2 after surgery, as formerly, blisters developed on the buttocks and an immediate biopsy revealed BP. Commencing on day 3 after surgery, prednisolone 10 mg was administered twice daily. On day 10 after surgery, the blisters on the buttocks had improved and no blisters were observed at the surgical site. All symptoms had resolved by 2.5 months after surgery. CONCLUSIONS: After TKA surgery, generalized BP may develop, diagnosed via skin biopsy. A quick diagnosis is important because early treatment can prevent symptom progression and shorten treatment.

Effects of an activity tracker with feedback on physical activity in women after midline laparotomy: A randomized controlled trial.

PURPOSE: To investigate whether the use of an activity tracker with feedback increases physical activity and is safe in patients who underwent a midline laparotomy for gynecologic disorders. METHODS: Patients who were planned to undergo a midline laparotomy for gynecologic diseases wore an activity tracker at baseline and from postoperative days 1-6. Patients in the experimental arm could monitor their step counts and were encouraged to achieve the individualized step-count goal daily. In contrast, patients in the control arm did not monitor their step-counts and received the usual encouragement for ambulation. The primary endpoint was the percentage of the average step-count at postoperative days 4-5 divided by the baseline activity count. RESULTS: Seventy-three patients were randomized; 63 patients underwent a surgery and wore an activity tracker; 53 patients were evaluable for primary endpoint. The activity recovery rate was significantly higher in the experimental arm compared to the control arm (71% vs 41%, p < 0.01). However, the study arm was not significantly associated with the activity recovery rate in multivariate analysis. The brief pain inventory score, brief fatigue inventory score, day of first flatus, day of soft blend diet initiation, ileus incidence, and length of postoperative hospital stay were similar between arms. The incidence of wound dehiscence and other adverse events were similar between arms. There were no grade 3 of 4 adverse events. CONCLUSION: The use of an activity tracker with feedback is safe and may increase physical activity in patients who have undergone major gynecologic surgery.

Difluoromethylornithine Induces Apoptosis through Regulation of AP-1 Signaling via JNK Phosphorylation in Epithelial Ovarian Cancer.

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.