Lymphadenectomy in clinically early epithelial ovarian cancer and survival analysis (LILAC): a Gynecologic Oncology Research Investigators Collaboration (GORILLA-3002) retrospective study.

OBJECTIVE: This study aimed to evaluate the therapeutic role of lymphadenectomy in patients surgically treated for clinically early-stage epithelial ovarian cancer (EOC). METHODS: This retrospective, multicenter study included patients with clinically early-stage EOC based on preoperative abdominal-pelvic computed tomography or magnetic resonance imaging findings between 2007 and 2021. Oncologic outcomes and perioperative complications were compared between the lymphadenectomy and non-lymphadenectomy groups. Independent prognostic factors were determined using Cox regression analysis. Disease-free survival (DFS) was the primary outcome. Overall survival (OS) and perioperative outcomes were the secondary outcomes. RESULTS: In total, 586 patients (lymphadenectomy group, n=453 [77.3%]; non-lymphadenectomy groups, n=133 [22.7%]) were eligible. After surgical staging, upstaging was identified based on the presence of lymph node metastasis in 14 (3.1%) of 453 patients. No significant difference was found in the 5-year DFS (88.9% vs. 83.4%, p=0.203) and 5-year OS (97.2% vs. 97.7%, p=0.895) between the two groups. Using multivariable analysis, lymphadenectomy was not significantly associated with DFS or OS. However, using subgroup analysis, the lymphadenectomy group with serous histology had higher 5-year DFS rates than did the non-lymphadenectomy group (86.5% vs. 74.4%, p=0.048; adjusted hazard ratio=0.281; 95% confidence interval=0.107-0.735; p=0.010). The lymphadenectomy group had longer operating time (p<0.001), higher estimated blood loss (p<0.001), and higher perioperative complication rate (p=0.004) than did the non-lymphadenectomy group. CONCLUSION: In patients with clinically early-stage EOC with serous histology, lymphadenectomy was associated with survival benefits. Considering its potential harm, lymphadenectomy should be performed according to histologic subtype and subsequent chemotherapy in patients with clinically early-stage EOC. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0007309.

Determination of ovarian transposition through prediction of postoperative adjuvant therapy in young patients with early stage cervical cancer undergoing surgery: a Korean multicenter retrospective study (KGOG 1042).

OBJECTIVE: We aimed to predict the risk of postoperative adjuvant therapy using preoperative variables in young patients with early stage cervical cancer. The predicted risk can guide whether ovarian transposition should be performed during surgery. METHODS: In total, 886 patients with stage IB1-IIA cervical cancer aged 20-45 years who underwent modified radical or radical hysterectomy between January 2000 and December 2008 were included. Preoperative variables, preoperative laboratory findings, International Federation of Gynaecology and Obstetrics stage, tumor size, and pathological variables were collected. Patients with high risk factors or those who met the Sedlis criteria were considered adjuvant therapy risk (+); others were considered adjuvant therapy risk (-). A decision-tree model using preoperative variables was constructed to predict the risk of adjuvant therapy. RESULTS: Of 886 patients, 362 were adjuvant therapy risk (+) (40.9%). The decision-tree model with four distinct adjuvant therapy risks using tumor size and age were generated. Specifically, patients with tumor size ≤2.45 cm had low risk (49/367; 13.4%), those with tumor size ≤3.85 cm and >2.45 cm had moderate risk (136/314; 43.3%), those with tumor size >3.85 cm and age ≤39.5 years had high risk (92/109; 84.4%), and those with tumor size >3.85 cm and age >39.5 years had the highest risk (85/96; 88.5%). CONCLUSION: The risk of postoperative adjuvant therapy in young patients with early stage cervical cancer can be predicted using preoperative variables. We can decide whether ovarian transposition should be performed using the predicted risk.

Minimally Invasive Sacrohysteropexy Versus Vaginal Hysterectomy With Uterosacral Ligament Suspension for Pelvic Organ Prolapse: A Prospective Randomized Non-Inferiority Trial.

STUDY OBJECTIVE: To investigate whether minimally invasive Sacrohysteropexy (SH) is non-inferior to vaginal hysterectomy (VH) with uterosacral ligament suspension (USLS) in women with symptomatic uterovaginal prolapse. DESIGN: Prospective, randomized, non-inferiority study. SETTING: Tertiary university-based hospital. PATIENTS: A total of 146 patients with uterovaginal prolapse between July 2016 and August 2019. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to either laparoscopic or robotic SH surgery or VH with USLS surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome was prolapse recurrence at 1 year after surgery, defined as prolapse ≥ stage 2 evaluated using the pelvic organ prolapse quantification system, bothersome vaginal bulge symptoms, or retreatment for prolapse. The secondary outcomes included operation time, estimated blood loss, hospital stay, operation-related complications, pain intensity, quality of life, and activities of daily living. Of 146 women who underwent randomization, 73 in the SH group and 73 in the VH with USLS group were analyzed. SH was non-inferior for recurrence compared with VH with USLS (16.4% vs 15.8%, 95% confidence interval: -13.0% to 14.2%). Operating duration and transvaginal length were significantly longer in the SH group, while there were no significant differences in the estimated blood loss, length of hospital stay, or postoperative complication rates. Although perioperative pain intensity was greater from 1 week to 1 month in the SH group, the quality of life and activities of daily living did not differ between the groups throughout postoperative year 1. CONCLUSION: Laparoscopic or robotic SH was non-inferior to VH with USLS for the recurrence of pelvic organ prolapse at the 1-year follow-up.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology consensus statement.

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.

Changes in proteinuria and the associated risks of ischemic heart disease, acute myocardial infarction, and angina pectoris in Korean population.

OBJECTIVES: Proteinuria is widely used to predict cardiovascular risk. However, there is insufficient evidence to predict how changes in proteinuria may affect the incidence of cardiovascular disease. METHODS: The study included 265,236 Korean adults who underwent health checkups in 2003-2004 and 2007-2008. They were categorized into 4 groups based on changes in proteinuria (negative: negative → negative; resolved: proteinuria ≥1+ → negative; incident: negative → proteinuria ≥1+; persistent: proteinuria ≥1+ → proteinuria ≥1+). We conducted 6 years of follow-up to identify the risks of developing ischemic heart disease (IHD), acute myocardial infarction (AMI), and angina pectoris according to changes in proteinuria. A multivariate Cox proportional-hazards model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident IHD, AMI, and angina pectoris. RESULTS: The IHD risk (expressed as HR [95% CI]) was the highest for persistent proteinuria, followed in descending order by incident and resolved proteinuria, compared with negative proteinuria (negative: reference, resolved: 1.211 [95% CI, 1.104 to 1.329], incident: 1.288 [95% CI, 1.184 to 1.400], and persistent: 1.578 [95% CI, 1.324 to 1.881]). The same pattern was associated with AMI (negative: reference, resolved: 1.401 [95% CI, 1.048 to 1.872], incident: 1.606 [95% CI, 1.268 to 2.035], and persistent: 2.069 [95% CI, 1.281 to 3.342]) and angina pectoris (negative: reference, resolved: 1.184 [95% CI, 1.065 to 1.316], incident: 1.275 [95% CI, 1.160 to 1.401], and persistent: 1.554 [95% CI, 1.272 to 1.899]). CONCLUSIONS: Experiencing proteinuria increased the risks of IHD, AMI, and angina pectoris even after proteinuria resolved.

Changes in smoking status, amount of smoking and their relation to the risk of microvascular complications in men with diabetes mellitus.

BACKGROUND: Smoking is a definite risk factor for macrovascular complications in diabetes mellitus (DM). However, the effect of smoking on microvascular complications is inconclusive. METHOD: Study participants were 26,673 diabetic men who received health check-up both in 2003-2004 and 2009, excluding women. Assessing smoking status (never, quitting and current) at 2003-2004 and 2009, changes in smoking status were categorised into 7 groups (never - never, never - quitting, never - current, quitting-quitting, quitting-current, current-quitting and current-current). Smoking amount was categorised into never, light (0-10 pack years), moderate (10-20 pack years), and heavy smoking (>20 pack years) based on 2009 data. They were followed-up until 2013 to identify incident microvascular complications. We calculated the adjusted hazard ratios (HR) and 95% confidence interval (CI) (adjusted HR [95% CI]) for incident microvascular complications according to changes in smoking status and smoking amount. RESULTS: Current-quitting (1.271 [1.050-1.538]), current-current (1.243 [1.070-1.444]) and heavy smoking (1.238 [1.078-1.422]) were associated with an increased risk of overall microvascular complications. The risk of nephropathy increased in current-current smoking (1.429 [1.098-1.860]) and heavy smoking (1.357 [1.061-1.734]). An increased risk of neuropathy was observed in current-quitting smoking (1.360 [1.076-1.719]), current-current smoking (1.237 [1.025-1.492]) and heavy smoking (1.246 [1.048-1.481]). However, we couldn't see the interpretable findings for the association between smoking and retinopathy. CONCLUSIONS: Lasting and heavy smoking increases the risk of microvascular complications, including nephropathy and neuropathy. Quitting smoking and reducing smoking amount are imperative in preventing microvascular complications in DM patients.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001).

BACKGROUND: To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. RESULTS: Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). CONCLUSIONS: The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.

The risk of gastric cancer according to changes in smoking status among Korean men.

OBJECTIVES: Smoking is a risk factor for gastric cancer. Studies have shown that the risk of gastric cancer can vary by smoking status and smoking amount at a single point in time. However, few data have been reported about the effect of changes in smoking status over time on the risk of gastric cancer. METHODS: This study collected data from the National Health Insurance Corporation in Korea on 97,700 Korean men without gastric cancer who underwent health check-ups from 2002 to 2013. The smoking status (never smoked, quit smoking, and currently smoking) of study participants was assessed in 2003-2004 and 2009, and the results were categorized into 7 groups: never-never, never-quit, never-current, quit-quit, quit-current, current-quit, and current-current. Participants were followed until 2013 to identify incident gastric cancer. A multivariate Cox proportional hazard model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident gastric cancer according to changes in smoking status and smoking amount (pack-years). RESULTS: Compared with group 1 (never-never), participants currently smoking in 2009 (never-current, quit-current, and current-current) had higher HRs for gastric cancer (never-quit: 1.077; 95% CI, 0.887 to 1.306, never-current: 1.347; 95% CI, 0.983 to1.846, quit-quit: 1.086; 95% CI, 0.863 to 1.366, quit-current: 1.538; 95% CI, 1.042 to 2.269, current-quit: 1.339; 95% CI, 1.077 to 1.666, and current-current: 1.589; 95% CI, 1.355 to 1.864, respectively). The risk for gastric cancer was highest in heavy smokers, followed by moderate smokers. CONCLUSIONS: In all categories of smoking status, current smoking was associated with the highest risk of gastric cancer. Heavy smoking was associated with an increased risk of gastric cancer, even in former smokers.

Cosmesis and feasibility of transvaginal natural orifice Specimen extraction (NOSE) for large organ specimen: a prospective pilot study.

BACKGROUND: This study aimed to evaluate cosmetic outcomes and feasibility of transvaginal natural orifice specimen extraction (NOSE) in patients who underwent laparoscopic or robotic surgery for the treatment of benign or malignant diseases of the kidney, liver, stomach, adrenal gland, and bladder. METHODS: This prospective study was conducted at a tertiary hospital between March 2015 and May 2020. The main outcome was cosmetic outcomes of scars assessed using the Patient and Observer Scar Assessment Scale (POSAS) 1 and 8 weeks after surgery. The secondary outcomes were postoperative pain, operating time, and complications. Sexual function was assessed using the Female Sexual Function Index (FSFI) questionnaire 6 months after surgery in 17 patients who were sexually active at the time of surgery. RESULTS: A total of 38 transvaginal NOSE procedures were performed for the extraction of 33 kidneys, 2 livers, 1 stomach, 1 adrenal gland, and 1 bladder. Observers rated pigmentation and relief scores as most deviant from normal skin (2.9 ± 1.7, 3.0 ± 2.1 at postoperative 1 week; 3.6 ± 1.9, 3.5 ± 2.2 at postoperative 8 weeks, respectively), but the overall scores of each item were low. The patients' overall satisfaction with postoperative scars was high, and the mean scores for pain and itching were low, with significant improvement from the first week to the eighth week (P = 0.014 and P = 0.006, respectively). Patients also reported low scores on vaginal assessment items, indicating better symptoms, and bleeding improved significantly between the two time points (P = 0.001). Postoperative pain was reduced from moderate during the first 24 h after surgery to mild after 24 h. The mean operative time of the transvaginal NOSE procedure was 28.3 ± 13.3 min. No postoperative complications were associated with the procedure. The mean FSFI total score was 21.2 ± 8.7 (cutoff score for dysfunction is 21), with higher scores indicating better sexual functioning. CONCLUSION: Transvaginal NOSE seems to be a feasible procedure with promising cosmetic benefits, for patients who undergo minimally invasive surgery for large organs including the kidney, liver, stomach, adrenal gland, and bladder. A prospective randomized clinical trial is needed to provide solid evidence to support transvaginal NOSE. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05113134).

The association between changes in proteinuria and the risk of cerebral infarction in the Korean population.

BACKGROUND: Proteinuria is a risk factor for cerebral infarction. It is known that proteinuria can change over time. However, published data is scarce for the association between changes in proteinuria and the risk of cerebral infarction. METHOD: Study participants were 276,861 Koreans who were assessed for urine dipstick proteinuria both in 2003-2004 and 2007-2008. They were categorized into four groups by changes in proteinuria over 4 years (negative: negative â†’ negative, resolved: proteinuria ≥ 1+ → negative, incident: negative â†’ proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1 + ). We used multivariate adjusted Cox-proportional hazard model in calculating the adjusted hazard ratios (HR) and 95% confidence interval (CI) for cerebral infarction until 2013 according to changes in proteinuria. RESULT: Adjusted HR and 95% CI for cerebral infarction significantly increased in order of persistent, incident, and resolved proteinuria, compared with negative proteinuria (negative: reference, resolved: 1.166 [1.009-1.347], incident: 1.345 [1.188-1.522], and persistent: 1.443 [1.089-1.912]). In gender subgroup analysis, men showed the more clear association between changes in proteinuria and the risk of cerebral infarction (negative: reference, resolved: 1.284 [1.057-1.560], incident: 1.351 [1.149-1.589], and persistent: 1.428 [1.014-2.012]). CONCLUSION: All types of proteinuria changes were associated with the increased risk of cerebral infarction, even in participants with once manifested but vanishing proteinuria.

Change in smoking status and its relation to the risk of gastroduodenal ulcer in Korean men.

BACKGROUND AND AIM: Smoking is associated with the increased risk of gastroduodenal ulcer. However, although smoking status can vary over time, most of studies have analyzed this association with smoking status at a single point of time. We analyzed the risk of gastroduodenal ulcer according to change in smoking status for more than 5 years. METHODS: Study participants were 43 380 Korean adults free of gastroduodenal ulcer who received health check-up between 2002 and 2013. Through evaluating their smoking status (never, quitter, and current) at 2003-2004 and 2009, they were categorized them into seven groups (never-never, never-quitter, never-current, quitter-quitter, quitter-current, current-quitter, and current-current) and monitored until 2013 to identify incident gastroduodenal ulcer. Cox-proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% confidence interval (CI) for incident gastroduodenal ulcer according to changes in smoking status and smoking amount. RESULTS: Compared with never-never group (reference), other groups had the significantly increased adjusted HRs and 95% CI for gastroduodenal ulcer. In particular, participants with current smoking (never-current, quitter-current, and current-current) had the relatively higher HRs than other groups (never-quitter: 1.200 [1.070-1.346], never-current: 1.375 [1.156-1.636], quitter-quitter: 1.149 [1.010-1.306], quitter-current: 1.325 [1.058-1.660], current-quitter: 1.344 [1.188-1.519], and current-current: 1.379 [1.256-1.513]). Heavy smoker had the highest risk for gastroduodenal ulcer, followed by moderate and light smoker. CONCLUSION: People who ever experienced smoking had increased risk of gastroduodenal ulcer. Out of smoking status, current smoking is more associated with the increased risk of gastroduodenal ulcer than past smoking.

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.

Gastrointestinal/genitourinary perforation and fistula formation with or without bevacizumab in patients with previously irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators Collaboration (GORILLA) group (GORILLA-1001).

BACKGROUND: This study aims to evaluate the incidence of and identify risk factors for gastrointestinal (GI) and genitourinary (GU) fistula or perforation formation with or without bevacizumab in patients with recurrent cervical cancer who underwent pelvic radiation therapy (RT). METHODS: Medical records of patients with recurrent cervical cancer who previously underwent pelvic RT between 2007 and 2020 were retrospectively reviewed. Clinicopathological factors were compared between groups that are stratified according to: 1) fistula/perforation (+) versus (-); and 2) bevacizumab plus conventional chemotherapy (BC) versus chemotherapy alone (C). Univariate and multivariate regression analyses were performed to identify risk factors for fistula/perforation. Overall survival (OS) was compared between the different groups. RESULTS: Of 219 participants, fistula/perforation of any grade occurred in 36 patients (16.4%); 27 fistulas and 9 perforations. Bevacizumab was more frequently used in Bevacizumab was more frequently used ( +) group than fistula/perforation (-) group (p = 0.015). Multivariate analysis showed that bevacizumab administration was the only independent risk factor for fistula or perforation (HR, 3.27; 95% CI, 1.18-9.10; P = 0.023). F/P was observed more frequently in women receiving BC (n = 144) than those receiving C (n = 75) (20.8% vs. 8.0%; P = 0.019). During median follow-up of 33.7 months (1.2-185.6 months), no significant OS difference was observed between fistula/perforation ( +) vs. (-) (hazards ratio [HR], 1.78; median 84.2 months [95% CI, 59.3-109.0] vs. 129.5 months [95% CI, 114.1-144.9]; P = 0.065) or BC vs. C (HR, 1.03; median 119.8 months [95% CI, 97.3-142.3] vs. 115.7 months [95% CI, 96.0-135.4]; P = 0.928). CONCLUSIONS: This study suggests that incorporation of bevacizumab in chemotherapy regimens for treating recurrent cervical cancer in patients who underwent pelvic RT incurs considerable risk for GI/GU fistula or perforation. There were no other independent risk factors for developing GI/GU fistula or perforation in this study population.

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.

The association of pancreatic cancer incidence with smoking status and smoking amount in Korean men.

OBJECTIVES: Our study examined the dose-response relationship between smoking amounts (pack-years) and the risk of developing pancreatic cancer in Korean men. METHODS: Of 125,743 participants who underwent medical health checkups in 2009, 121,408 were included in the final analysis and observed for the development of pancreatic cancer. We evaluated the associations between smoking amounts and incident pancreatic cancer in 4 groups classified by pack-year amounts. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of incident pancreatic cancer by comparing groups 2 (<20 pack-year smokers), 3 (20-≤40 pack-year smokers), and 4 (>40 pack-year smokers) with group 1 (never smokers). RESULTS: During 527,974.5 person-years of follow-up, 245 incident cases of pancreatic cancer developed between 2009 and 2013. The multivariate-adjusted HRs (95% CIs) for incident pancreatic cancer in groups 2, 3, and 4 were 1.05 (0.76 to 1.45), 1.28 (0.91 to 1.80), and 1.57 (1.00 to 2.46), respectively (p for trend=0.025). The HR (95% CI) of former smokers showed a dose-response relationship in the unadjusted model, but did not show a statistically significant association in the multivariate-adjusted model. The HR (95% CI) of current smokers showed a dose-response relationship in both the unadjusted (p for trend=0.020) and multivariate-adjusted models (p for trend=0.050). CONCLUSIONS: The risk of developing pancreatic cancer was higher in current smokers status than in former smokers among Korean men, indicating that smoking cessation may have a protective effect.

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.

Development and validation of a prediction model for bothersome stress urinary incontinence after prolapse surgery: A retrospective cohort study.

OBJECTIVE: To develop and validate a prediction model for bothersome stress urinary incontinence after prolapse surgery and to compare it with an existing clinical prediction model (CUPIDO model). DESIGN: Retrospective cohort study. SETTING: Two tertiary hospitals in South Korea. POPULATION: A total of 1142 patients who underwent prolapse surgery with or without a concomitant midurethral sling. METHODS: To construct a prediction model, we performed logistic regression using both exhaustive and stepwise variable selection, validating the model both internally and externally. MAIN OUTCOME MEASURES: Bothersome stress urinary incontinence defined as the presence of bothersome symptoms of stress urinary incontinence and/or subsequent continence procedure one year after surgery. RESULTS: Postoperative bothersome stress urinary incontinence occurred in 10% of patients. A model containing six predictors (age, diabetes mellitus, subjective urinary incontinence, prolapse reduction stress test result, type of prolapse surgery, and a concomitant midurethral sling) showed excellent performance for predicting bothersome stress urinary incontinence (area under the curve 0.74, 95% confidence interval 0.62-0.86) and outperformed the CUPIDO model (area under the curve 0.63, 95% confidence interval 0.49-0.76; DeLong's test P = 0.014). CONCLUSIONS: This prediction model might be a useful tool to guide patient decision making regarding a concomitant continence procedure at the time of prolapse surgery. The predictive value of this model needs to be validated further in cohorts with different characteristics. TWEETABLE ABSTRACT: The proposed prediction model for bothersome stress urinary incontinence after prolapse surgery outperforms an existing model.

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.

Radicicol Inhibits Chikungunya Virus Replication by Targeting Nonstructural Protein 2.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a debilitating febrile illness characterized by persistent muscle and joint pain. The widespread distribution of transmission-competent vectors, Aedes species mosquitoes, indicates the potential risk of large-scale epidemics with high attack rates that can severely impact public health globally. Despite this, currently, there are no antivirals available for the treatment of CHIKV infections. Thus, we aimed to identify potential drug candidates by screening a chemical library using a cytopathic effect-based high-throughput screening assay. As a result, we identified radicicol, a heat shock protein 90 (Hsp90) inhibitor that effectively suppressed CHIKV replication by blocking the synthesis of both positive- and negative-strand viral RNA as well as expression of viral proteins. Interestingly, selection for viral drug-resistant variants and mutational studies revealed nonstructural protein 2 (nsP2) as a putative molecular target of radicicol. Moreover, coimmunoprecipitation and in silico modeling analyses determined that G641D mutation in the methyltransferase (MT)-like domain of nsP2 is essential for its interaction with cytoplasmic Hsp90ß chaperone. Our findings collectively support the potential application of radicicol as an anti-CHIKV agent. The detailed study of the underlying mechanism of action further contributes to our understanding of virus-host interactions for novel therapeutics against CHIKV infection.