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Background- Early repolarization pattern is a common ECG finding characterized by J-point elevation and QRS notching or slurring in the inferior and/or lateral leads, yet little is known about its incidence and long-term prognosis in Asian populations. Methods and Results- We reviewed all the ECG records of the 5976 atomic-bomb survivors who were examined at least once during our biennial health examination in Nagasaki, Japan, between July 1958 and December 2004. We defined early repolarization pattern as >=0.1-mV elevation of the J point or ST segment, with notching or slurring in at least 2 inferior and/or lateral leads. We assessed unexpected, cardiac, and all-cause death risk by Cox analysis. We identified 1429 early repolarization pattern cases (779 incident cases) during follow-up, yielding a positive rate of 23.9% and an incidence rate of 715 per 100 000 person-years. Early repolarization pattern had an elevated risk of unexpected death (hazard ratio, 1.83; 95% confidence interval, 1.12 to 2.97; P=0.02) and a decreased risk of cardiac (hazard ratio, 0.75; 95% confidence interval, 0.60 to 0.93; P<0.01) and all-cause (hazard ratio, 0.85; 95% confidence interval, 0.78 to 0.93; P<0.01) death. In addition, both slurring and notching were related to higher risk of unexpected death (hazard ratio, 2.09; 95% confidence interval, 1.06 to 4.12; P=0.03), as was early repolarization pattern manifestation in both inferior and lateral leads (hazard ratio, 2.50; 95% confidence interval, 1.29 to 4.83; P<0.01). Conclusions- Early repolarization pattern is associated with an elevated risk of unexpected death and a decreased risk of cardiac and all-cause death. Specific early repolarization pattern morphologies and location are associated with an adverse prognosis. [ABSTRACT FROM AUTHOR]

Background: Teicoplanin is used to treat serious Gram-positive bacterial infections. However, the optimal trough concentrations for pediatric patients remain unclear owing to the lack of monitoring guidelines. This study aimed to determine the optimal teicoplanin trough concentration for treating Gram-positive bacterial infections in children., Methods: A systematic review was conducted using 4 databases. Stepwise cutoffs within the range of 10-30 mcg/mL were used for efficacy and safety. Studies were included if they reported treatment success rates and/or all-cause mortality, nephrotoxicity, hepatotoxicity, and thrombocytopenia according to the trough concentration., Results: The meta-analysis included 12 studies involving 830 pediatric patients. Teicoplanin cutoff values of 10, 15, 20, and 30 mcg/mL were reported in 9, 8, 9, and 2 studies, respectively. Trough concentrations <10 mcg/mL significantly reduced the treatment success rate, with an odds ratio of 0.07 and a 95% confidence interval ranging from 0.01 to 0.40. The overall treatment success rate was 50.0% versus 95.7% observed at concentrations ≥10 mcg/mL. However, no significant difference was observed at the 15-, 20-, and 30-mcg/mL cutoffs, when compared with lower concentrations. Trough concentrations <20 mcg/mL were associated with a decreased risk of nephrotoxicity (odds ratio = 0.21; 95% confidence interval, 0.08-0.55). However, hepatotoxicity and thrombocytopenia showed no significant associations with trough concentration ranges between 10 and 30 mcg/mL., Conclusions: Although further prospective studies are required for validation, the authors' findings suggest that 10- to 20-mcg/mL teicoplanin is the optimal trough concentration for enhanced clinical success and reduced toxicity in pediatric patients., Competing Interests: K. Matsumoto received grant support funding from Meiji Seika Pharma Co., Ltd., and Sumitomo Pharma Co., Ltd., and speaker honoraria from Meiji Seika Pharma Co., Ltd. The other authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe population-level utilization of fertility-sparing surgery and outcome of reproductive-aged patients with early epithelial ovarian cancer who underwent fertility-sparing surgery in the United States., Methods: This retrospective study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study included 3,027 patients younger than age 50 years with stage I epithelial ovarian cancer receiving primary surgical therapy from 2007 to 2020. Fertility-sparing surgery was defined as preservation of one ovary and the uterus for unilateral lesion and preservation of the uterus for bilateral lesions. Temporal trend of fertility-sparing surgery was assessed with linear segmented regression with log-transformation. Overall survival associated with fertility-sparing surgery was assessed with Cox proportional hazard regression model., Results: A total of 534 patients (17.6%) underwent fertility-sparing surgery. At the cohort level, the utilization of fertility-sparing surgery was 13.4% in 2007 and 21.8% in 2020 ( P for trend=.009). Non-Hispanic White individuals (2.8-fold), those with high-grade serous histology (2.2-fold), and individuals with stage IC disease (2.3-fold) had a more than twofold increase in fertility-sparing surgery utilization during the study period (all P for trend<.05). After controlling for the measured clinicopathologic characteristics, patients who received fertility-sparing surgery had overall survival comparable with that of patients who had nonsparing surgery (5-year rates 93.6% vs 92.1%, adjusted hazard ratio 0.87, 95% CI, 0.57-1.35). This survival association was consistent in high-grade serous (5-year rates 92.9% vs 92.4%), low-grade serous (100% vs 92.2%), clear cell (97.5% vs 86.1%), mucinous (92.1% vs 86.6%), low-grade endometrioid (95.7% vs 97.7%), and mixed (93.3% vs 83.7%) histology (all P >.05). In high-grade endometrioid tumor, fertility-sparing surgery was associated with decreased overall survival (5-year rates 71.9% vs 93.8%, adjusted hazard ratio 2.90, 95% CI, 1.09-7.67). Among bilateral ovarian lesions, fertility-sparing surgery was not associated with overall survival (5-year rates 95.8% vs 92.5%, P =.364). Among 41,914 patients who had epithelial ovarian cancer with any age and stage, those younger than age 50 years with stage I disease increased from 8.6% to 10.9% during the study period ( P for trend=.002)., Conclusion: Nearly one in five reproductive-aged patients with stage I epithelial ovarian cancer underwent fertility-sparing surgery in recent years in the United States. More than 90% of reproductive-aged patients with stage I epithelial ovarian cancer who underwent fertility-sparing surgery were alive at the 5-year timepoint, except for those with high-grade endometrioid tumors., Competing Interests: Financial Disclosure Maximilian Klar reports being a consultant for AstraZeneca, CooperSurgical, and KLS Martin. Lynda D. Roman reports being a consultant for Cardiff Oncology and Nutcracker, and she has participated in the Steering Committee for the Global Coalition of Adaptive Research. Jason D. Wright reports being a consultant and receiving a research grant from Merck and royalties from UpToDate. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess population-level trends, characteristics, and outcomes of high-grade serous tubo-ovarian carcinoma in the United States., Methods: This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 27,811 patients diagnosed with high-grade serous tubo-ovarian carcinoma from 2004 to 2020. The exposure was the primary cancer site (ovary or fallopian tube). Main outcome measures were temporal trends, clinical characteristics, and overall survival associated with primary cancer site assessed in multivariable analysis., Results: The study population comprised 23,967 diagnoses of high-grade serous ovarian carcinoma and 3,844 diagnoses of high-grade serous fallopian tubal carcinoma. The proportion of diagnoses of high-grade serous fallopian tubal carcinoma increased from 365 of 7,305 (5.0%) in 2004-2008 to 1,742 of 6,663 (26.1%) in 2017-2020. This increase was independent in a multivariable analysis (adjusted odds ratio [aOR] vs 2004-2008, 2.28 [95% CI, 1.98-2.62], 3.27 [95% CI, 2.86-3.74], and 6.65 [95% CI, 5.84-7.57] for 2009-2012, 2013-2016, and 2017-2020, respectively). This increase in high-grade serous fallopian tubal carcinoma was seen across age groups (4.3-5.8% to 22.7-28.3%) and across racial and ethnic groups (4.1-6.0% to 21.9-27.5%) (all P for trend <.001). Among the cases of tumors smaller than 1.5 cm, the increase was particularly high (16.9-67.6%, P for trend <.001). Primary-site tumors in the high-grade serous fallopian tubal carcinoma group were more likely to be smaller than 1.5 cm (aOR 8.26, 95% CI, 7.35-9.28) and unilateral (aOR 7.22, 95% CI, 6.54-7.96) compared with those in high-grade serous ovarian carcinoma. At the cohort level, the diagnosis shift to high-grade serous fallopian tubal carcinoma was associated with narrowing differences in survival over time between the two malignancy groups: adjusted hazard ratio 0.84 (95% CI, 0.74-0.96), 0.91 (95% CI, 0.82-1.01), 1.01 (95% CI, 0.92-1.12), and 1.12 (95% CI, 0.98-1.29) for 2004-2008, 2009-2012, 2013-2016, and 2017-2020, respectively., Conclusion: This population-based assessment suggests that diagnoses of high-grade serous tubo-ovarian carcinoma in the United States have been rapidly shifting from high-grade serous ovarian to fallopian tubal carcinoma in recent years, particularly in cases of smaller, unilateral tumors., Competing Interests: Financial Disclosure Jason D. Wright has been a consultant and received a research grant from Merck and royalties from UpToDate. Lynda D. Roman has been a consultant for Cardiff Oncology and Nutcracker. She participates in the Steering Committee for the Global Coalition of Adaptive Research. Maximilian Klar has been a consultant for AstraZeneca, CooperSurgical, and KLS Martin. Anil K. Sood has been a consultant for AstraZeneca, Kiyatec, Merck, GlaxoSmithKline, ImmunoGen, Iylon, and Onxeo, and is a shareholder in BioPath. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

In this cross-sectional study including 1,722,479 women who underwent laparoscopic cholecystectomy between January 2016 and December 2019 identified in the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample, the prevalence rate of gynecologic diagnoses was 11.3 per 1,000. Among presumed elective laparoscopic cholecystectomy, the highest performance rate of concurrent gynecologic procedure per gynecologic diagnosis was laparoscopic adnexectomy among patients with benign ovarian tumor (652/1,000 diagnoses), followed by laparoscopic adnexectomy for endometrioma (386/1,000 diagnoses) and cervical conization for cervical carcinoma in situ (304/1,000 diagnoses). The measured surgical morbidity rates for patients who had concurrent gynecologic surgery and those who did not were 2.8 per 1,000 and 1.9 per 1,000, respectively (adjusted odds ratio 1.39, 95% CI 0.75-2.59). These results suggest that minimally invasive gynecologic surgeries are being performed at the time of outpatient laparoscopic cholecystectomy in the United States., Competing Interests: Financial Disclosure Jason D. Wright reports his institution received a research grant from Merck, he received royalties from UpToDate, and he received payment from the American College of Obstetricians and Gynecologists. Maximilian Klar has been a consultant for CooperSurgical and KLS Martin; Lynda D. Roman has been a consultant for Cardiff Oncology and received payment from Nutcracker Therapeutics and participates in the Steering Committee for the Global Coalition of Adaptive Research. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

In this cross-sectional study examining 211,708 patients with a diagnosis of uterine prolapse who underwent hysterectomy between 2016 and 2019 identified in the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample, co-diagnosis of gynecologic malignancy was reported in 2,398 (1.1%) patients, and they were less likely to receive reconstructive surgery at hysterectomy (odds ratio [OR] 0.90, 95% CI 0.84-0.96). This absence of reconstructive surgery was most pronounced among patients with complete uterine prolapse and gynecologic malignancy (OR 0.68, 95% CI 0.57-0.81). The association was also consistent in coexisting gynecologic premalignancy (n=3,357 [1.6%]). In conclusion, this national-level assessment suggests that patients with uterine prolapse and coexisting gynecologic malignancy or premalignancy may be less likely to receive reconstructive surgery for pelvic floor dysfunction at hysterectomy., Competing Interests: Financial Disclosure Lynda D. Roman reports participation in the Steering Committee in the Global Coalition for Adaptive Research. She has been a consultant for Cardiff Oncology and Nutcracker Therapeutics. Jason D. Wright reports research grant was paid to his institution from Merck, and he received royalties from UpToDate. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study analyzes national trends in the management of uncomplicated appendicitis during pregnancy, comparing outcomes for nonoperative management (NOM) and appendectomy., Background: In the nonpregnant population, several randomized controlled trials demonstrated noninferiority of NOM compared with appendectomy for acute uncomplicated appendicitis. However, it remains unclear whether these findings are generalizable to pregnant patients., Methods: The National Inpatient Sample was queried for pregnant women diagnosed with acute uncomplicated appendicitis from January 2003 to September 2015. Patients were categorized by treatment: NOM, laparoscopic appendectomy (LA), and open appendectomy. A quasi-experimental analysis with interrupted time series examined the relationship between the year of admission and the likelihood of receiving NOM. Multivariable logistic regression analyses were used to evaluate the association between treatment strategy and patient outcomes., Results: A total of 33,120 women satisfied the inclusion criteria. Respectively, 1070 (3.2%), 18,736 (56.6%), and 13,314 (40.2%) underwent NOM, LA, and open appendectomy. The NOM rate significantly increased between 2006 and 2015, with an annual increase of 13.9% (95% CI, 8.5-19.4, P <0.001). Compared with LA, NOM was significantly associated with higher rates of preterm abortion (odds ratio [OR]: 3.057, 95% CI, 2.210-4.229, P <0.001) and preterm labor/delivery (OR: 3.186, 95% CI, 2.326-4.365, P <0.001). Each day of delay to appendectomy was associated with significantly greater rates of preterm abortion (OR: 1.210, 95% CI, 1.123-1.303, P <0.001)., Conclusions: Although NOM has been increasing as a treatment for pregnant patients with uncomplicated appendicitis, compared with LA, it is associated with worse clinical outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Advances in cancer treatment have resulted in increased attention toward potential cardiac complications, especially following treatment for esophageal cancer, which is associated with a risk of coronary artery disease. As the heart is directly irradiated during radiotherapy, coronary artery calcification (CAC) may progress in the short term. Therefore, we aimed to investigate the characteristics of patients with esophageal cancer that predispose them to coronary artery disease, CAC progression on PET-computed tomography and the associated factors, and the impact of CAC progression on clinical outcomes., Methods: We retrospectively screened 517 consecutive patients who received radiation therapy for esophageal cancer from our institutional cancer treatment database between May 2007 and August 2019. CAC scores were analyzed clinically for 187 patients who remained by exclusion criteria., Results: A significant increase in the Agatston score was observed in all patients (1 year: P  = 0.001*, 2 years: P  < 0.001*). Specifically for patients receiving middle-lower chest irradiation (1 year: P  = 0.001*, 2 years: P  < 0.001*) and those with CAC at baseline (1 year: P  = 0.001*, 2 years: P  < 0.001*), a significant increase in the Agatston score was observed. There was a trend for a difference in all-cause mortality between patients who had irradiation of the middle-lower chest ( P  = 0.053) and those who did not., Conclusion: CAC can progress within 2 years after the initiation of radiotherapy to the middle or lower chest for esophageal cancer, particularly in patients with detectable CAC before radiotherapy initiation., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia., Methods: The MarketScan Database was used to identify patients aged 18-50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed., Results: A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 ( P =.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 ( P <.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8-39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5-30.0%) of those treated with progestin-releasing IUD ( P <.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6-13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1-16.6%) of those treated with progestin-releasing IUD ( P =.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD., Conclusion: The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy., Competing Interests: Financial Disclosure Yukio Suzuki reports receiving payment from The Japan Society for Menopause and Women's Health (JMWH Bayer Grant 2022) and from Honjo (JMSA Scholarship 2022). They received a Honjo-JMSA Scholarship and a JMWH Bayer Grant from the Japan Society for Menopause and Women's Health. Jason D. Wright has received royalties from UpToDate and research support from Merck. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To perform a cost-effectiveness analysis to examine the utility and effectiveness of OS performed at the time of elective cholecystectomy [laparoscopic cholecystectomy (LAP-CHOL)]., Summary Background Data: OS has been adopted as a strategy to reduce the risk of ovarian cancer in women undergoing hysterectomy and tubal sterilization, although the procedure is rarely performed as a risk reducing strategy during other abdominopelvic procedures., Methods: A decision model was created to examine women 40, 50, and 60 years of age undergoing LAP-CHOL with or without OS. The lifetime risk of ovarian cancer was assumed to be 1.17%, 1.09%, and 0.92% for women age 40, 50, and 60 years, respectively. OS was estimated to provide a 65% reduction in the risk of ovarian cancer and to require 30 additional minutes of operative time. We estimated the cost, quality-adjusted life-years, ovarian cancer cases and deaths prevented with OS., Results: The additional cost of OS at LAP-CHOL ranged from $1898 to 1978. In a cohort of 5000 women, OS reduced the number of ovarian cancer cases by 39, 36, and 30 cases and deaths by 12, 14, and 16 in the age 40-, 50-, and 60-year-old cohorts, respectively. OS during LAP-CHOL was cost-effective, with incremental cost-effectiveness ratio of $11,162 to 26,463 in the 3 age models. In a probabilistic sensitivity analysis, incremental cost-effectiveness ratio for OS were less than $100,000 per quality-adjusted life-years in 90.5% or more of 1000 simulations., Conclusions: OS at the time of LAP-CHOL may be a cost-effective strategy to prevent ovarian cancer among average risk women., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma., Background: Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown., Methods: Patients who underwent major hepatectomy for perihilar cholan-giocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed., Results: A total of 4230 complications occurred in the 484 study patients (CDC grade I, n = 27; II, n = 132; IlIa, n = 290; IIIb, n = 4; IVa, n = 21; IVb, n = 1; and V, n = 9). The trajectory was categorized into 3 patterns: mild (n = 209), moderate (n = 235), and severe (n = 40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P<0.001). The cutoff values of the CCI on postoperative days 1, 4, and 7 for predicting a severe morbidity course were 15.0, 28.5, and 40.6 with areas under the curves of 0.780, 0.924, and 0.984, respectively., Conclusions: The CCI could depict the chronological increase in the overall morbidity burden, categorized into 3 patterns. Early CCI potentially predicted sequential progression to serious outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypertrophic scars and keloids tend to cause serious functional and cosmetic impediments to patients. As these scars are not life threatening, many patients do not seek proper treatment. Thus, educating physicians and patients regarding these scars is important. The authors aimed to develop an algorithm for a scar screening system and compare the accuracy of the system with that of physicians. This algorithm was designed to involve health care providers and patients., Methods: Digital images were obtained from Google Images (Google LLC, Mountain View, Calif.), open access repositories, and patients in the authors' hospital. After preprocessing, 3768 images were uploaded to the Google Cloud AutoML Vision platform and labeled with one of the four diagnoses: immature scars, mature scars, hypertrophic scars, and keloid. A consensus label for each image was compared with the label provided by physicians., Results: For all diagnoses, the average precision (positive predictive value) of the algorithm was 80.7 percent, the average recall (sensitivity) was 71 percent, and the area under the curve was 0.846. The algorithm afforded 77 correct diagnoses with an accuracy of 77 percent. Conversely, the average physician accuracy was 68.7 percent. The Cohen kappa coefficient of the algorithm was 0.69, while that of the physicians was 0.59., Conclusions: The authors developed a computer vision algorithm that can diagnose four scar types using automated machine learning. Future iterations of this algorithm, with more comprehensive accuracy, can be embedded in telehealth and digital imaging platforms used by patients and primary doctors. The scar screening system with machine learning may be a valuable support tool for physicians and patients., Clinical Question/level of Evidence: Diagnostic, II., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Objective: To evaluate the impact of complications on long-term survival in patients with perihilar cholangiocarcinoma., Background: Surgical resection for perihilar cholangiocarcinoma is vulnerable to postoperative complications. The prognostic impact of complications in patients with this disease is unknown., Methods: The medical records of patients who underwent curative-intent hepatectomy for perihilar cholangiocarcinoma between 2010 and 2017 were reviewed retrospectively. The comprehensive complication index (CCI) was calculated based on all postoperative complications, which were graded by the Clavien-Dindo classification (CDC). Patients were divided into high and low CCI groups by the median score, and survival was compared between the 2 groups., Results: Excluding 8 patients who died in hospital, 369 patients were analyzed. The CDC grade was I in 20 (5.4%), II in 108 (29.3%), III in 224 (60.7%), and IV in 17 (4.6%) patients. The CCI increased with increasing CDC grade; the median was 42.9 (range, 15.0-98.9). Overall survival differed significantly between the high (n = 187) and low (n = 182) CCI groups (41.2% vs 47.9% at 5 years; P = 0.041). However, multivariable analyses demonstrated that traditional clinicopathological factors were independent predictors of survival and that the dichotomized CCI was not. In addition, the CCI score as a continuous variable was not an independent prognostic factor for overall survival in the multivariable analyses (hazard ratio per 1 CCI score: 1.00, 95% confidence interval: 0.99-1.01, P = 0.775)., Conclusions: Cumulative postoperative complications after resection of perihilar cholangiocarcinoma only moderately deteriorate long-term survival, and should not be an argument to deny surgery in this high-risk population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In Helicobacter pylori-driven gastric cancer, mucosal colonization induces chronic inflammation that may variably progress to cancer. Prospective studies of circulating inflammation-related proteins have suggested weak associations with gastric cancer risk. To assess potential utility as a screening tool in clinical settings, we examined circulating levels of a wide range of key inflammation molecules for associations with early-stage gastric cancer., Methods: We used pretreatment EDTA plasma from 239 individuals with early-stage noncardia gastric cancer (203 stage I and 36 stage II) and 256 age-frequency-matched H. pylori-seropositive cancer-free controls within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 92 biomarkers were measured by proximity extension assays using Olink's Proseek Immuno-oncology Panel. Odds ratios (ORs) for association with gastric cancer risk were calculated for quantiles (two to four categories) of each biomarker from unconditional logistic regression models, adjusted for age, sex, smoking and alcohol consumption. Two-sided P values <0.05 were considered as significant. The false discovery rate (FDR) was used to correct for multiple comparisons., Results: Of 83 evaluable biomarkers, lower levels of TNFRSF12A (per quartile OR, 0.82; nominal P-trend = 0.02) and ADGRG1 (per quartile OR, 0.84; nominal P-trend = 0.03) were associated with early-stage gastric cancer but were not statistically significant after FDR correction., Conclusion: Our study did not identify any inflammation-related biomarkers that may be useful for early disease detection. To date, this is the first assessment of circulating inflammation-related proteins in early-stage gastric cancer. Given the complex inflammation processes preceding malignant transformation, further investigation of other biomarkers is warranted., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine trends, characteristics, and oncologic outcomes of sentinel lymph node biopsy for early endometrial cancer., Methods: This observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program by examining 83,139 women with endometrial cancer who underwent primary hysterectomy with nodal evaluation for T1 disease from 2003 to 2018. Primary outcome measures were the temporal trends in utilization of sentinel lymph node biopsy and patient characteristics associated with sentinel lymph node biopsy use, assessed by multivariable binary logistic regression models. Secondary outcome measure was endometrial cancer-specific mortality associated with sentinel lymph node biopsy, assessed by propensity score inverse probability of treatment weighting., Results: The utilization of sentinel lymph node biopsy increased from 0.2 to 29.7% from 2005 to 2018 (P<.001). The uptake was higher for women with endometrioid (0.3-31.6% between 2005 and 2018) compared with nonendometrioid (0.6-21.0% between 2006 and 2018) histologic subtypes (both P<.001). In a multivariable analysis, more recent year surgery, endometrioid histology, well-differentiated tumors, T1a disease, and smaller tumor size were independently associated with sentinel lymph node biopsy use (P<.05). Performance of sentinel lymph node biopsy was not associated with increased endometrial cancer-specific mortality compared with lymphadenectomy for endometrioid tumors (subdistribution hazard ratio [HR] 0.96, 95% CI 0.82-1.13) or nonendometrioid tumors (subdistribution HR 0.85, 95% CI 0.69-1.04). For low-risk endometrial cancer, the increase in sentinel lymph node biopsy resulted in a 15.3 percentage-point (1.4-fold) increase in surgical nodal evaluation by 2018 (expected vs observed rates, 37.8 vs 53.1%)., Conclusion: The landscape of surgical nodal evaluation is shifting from lymphadenectomy to sentinel lymph node biopsy for early endometrial cancer in the United States, with no indication of a negative effect on cancer-specific survival., Competing Interests: Financial Disclosure Koji Matsuo reports receiving travel expense for investigator meeting attendance expense from VBL Therapeutics. Lynda D. Roman reports receiving funding from Quantgene, Inc. and AXDEV. Jason D. Wright received royalties from UpToDate for writing/review of chapters related to cervical dysplasia, human papillomavirus, and cervical cancer. He served as a consultant for Clovis Oncology and participated in their advisory board (March 2019). He performed medicolegal review of malpractice cases related to delayed diagnosis of gynecologic cancer and intraoperative complications during gynecologic surgery. He is currently serving on the SGO Board of Directors (no monetary compensation), from 2019 to 2022. He conducted epidemiologic research trials examining patterns of care for ovarian, uterine, and cervical cancer for Merck. Lastly, he also has performed analysis of and provided education on clinical trials data for Otsuka Pharmacovigilance. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the effects of intraoperative ovarian capsule rupture on progression-free survival and overall survival in women who are undergoing surgery for early-stage ovarian cancer., Data Sources: MEDLINE using PubMed, EMBASE (Elsevier), ClinicalTrials.gov, and Scopus (Elsevier) were searched from inception until August 11, 2020., Methods of Study Selection: High-quality studies reporting survival outcomes comparing ovarian capsule rupture to no capsule rupture among patients with early-stage epithelial ovarian cancer who underwent surgical management were abstracted. Study quality was assessed with the Newcastle-Ottawa Scale, and studies with scores of at least 7 points were included., Tabulation, Integration, and Results: The data were extracted independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between ovarian capsule rupture and oncologic outcomes. Seventeen studies met all the criteria for inclusion in the meta-analysis. Twelve thousand seven hundred fifty-six (62.6%) patients did not have capsule rupture and had disease confined to the ovary on final pathology; 5,532 (33.7%) patients had intraoperative capsule rupture of an otherwise early-stage ovarian cancer. Patients with intraoperative capsule rupture had worse progression-free survival (hazard ratio [HR] 1.92, 95% CI 1.34-2.76, P<.001), with moderate heterogeneity (I2=41%, P=.07) when compared with those without capsule rupture. Pooled results from these studies showed a worse overall survival (HR 1.48, 95% CI 1.15-1.91, P=.003), with moderate heterogeneity (I2=53%, P=.02) when compared with patients without intraoperative capsule rupture. This remained significant in a series of sensitivity analyses., Conclusion: This systematic review and meta-analysis of high-quality observational studies shows that intraoperative ovarian capsule rupture results in decreased progression-free survival and overall survival in women with early-stage ovarian cancer who are undergoing initial surgical management., Systematic Review Registration: PROSPERO, CRD42021216561., Competing Interests: Financial Disclosure Dr. Hou has served as a consultant for Foundation Medicine. Dr. Tergas reports money was paid to her from Auro Vaccines. Dr. Matsuo received an honorarium from Chugai and investigator meeting attendance expense from VBL Therapeutics outside this study. Dr. Wright has served as a consultant for Clovis Oncology, received royalties from UpToDate, and received research support from Merck. The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Gastric varices can be present in up to 20% of patients with portal hypertension. However, a varix of the left gastroepiploic vein (LGV) is extremely rare. Surgery is required if bleeding occurs; thus, precise diagnosis is crucial. We present a successful case of preoperative diagnosis intraabdominal varix of the LGV using three-dimensional-computed tomography angiography (3D-CTA) followed by laparoscopic resection. This is the first report of a case with variant LGV. Our study demonstrates the efficacies of 3D-CTA and laparoscopic surgery for the diagnosis and safe resection of the intraabdominal varix, respectively., Patient Concerns: A 74-year-old woman was referred to our department with a tumor in the abdominal cavity. On physical examination, no lumps were palpable in the upper abdomen., Diagnosis: The enhanced CT was revealed that the tumor was not enhanced in the early phase, but in the equilibrium phase. Moreover, 3D-CTA clearly revealed that the tumor was being supplied by the LGV. Thus, it was diagnosed as a variant of the LGV., Interventions: Surgical resection was performed laparoscopically as per the guidance of preoperative 3D-CTA findings. During surgery, a dark tumor was found along the gastroepiploic vessels, supplied by the LGV. The tumor was resected safely based on the preoperative information., Outcomes: Histopathological examination of the tumor showed accumulation of various vessels, but no malignant cells. Therefore, we made a final diagnosis of the tumor as an LGV varix. For follow-up, an annual CT examination was performed and after 3 years postoperation, no recurrence was observed., Conclusions: In the present case, we have achieved a successful preoperative diagnosis using 3D-CTA, and resection was safely accomplished using laparoscopy guided by preoperative anatomical information. This is the first report of an LGV variant. Appropriate management is crucial because bleeding is a catastrophic event. Therefore, imaging procedures such as 3D-CTA for diagnosis, followed by safe resection by laparoscopic surgery, are effective tools for the treatment of epiploic vein varices., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow., Subjects and Methods: This was an open-labeled clinical trial in which 30 adult CADASIL patients received lomerizine at 10 mg/d. Numbers of symptomatic strokes during the 2 years after the start of lomerizine administration were compared with those in the 2 years before its initiation. The effect of lomerizine on preventing strokes was evaluated based on the incidence rate ratio (IR) calculated with the Mantel-Haenszel method., Results: When including all 30 patients (analysis 1), the IR was less than 1 (0.46; 95% confidence interval [CI], 0.19-1.12) but did not reach significance. To evaluate the effect of lomerizine on secondary prevention, subgroups of 15 patients with stroke episodes occurring any time before lomerizine administration (analysis 2) and 10 patients with stroke episodes during the 2 years before lomerizine administration (analysis 3) were analyzed. The IR values were 0.33 (95% CI, 0.12-0.94) in analysis 2 and 0.17 (95% CI, 0.04-0.67) in analysis 3., Conclusions: Our results suggest the effect of lomerizine on preventing secondary stroke in CADASIL patients.

Aquaporin 3 (AQP3) serves as a water and glycerol transporter facilitating epithelial cell hydration. Recently, the involvement of AQP3 in cancers has been reported. However, the immunohistochemical expression of AQP3 in carcinomas remains controversial. We hypothesized that differences in aquaporin 3 antigen recognition (AQP3 AR) may influence their expressions. Thus, our study aimed to assess the immunostaining patterns of 3 AQP3 AR sites in oral squamous cell carcinoma (OSCC) and to compare the adjacent areas of high-grade epithelial dysplasia (HG-ED) and normal oral mucosa (NOM). The study group included formalin-fixed OSCC samples (n=51) with adjacent regions of HG-ED (n=12) and NOM (n=51). The tissues were stained with anti-AQP3 antibodies (AR sites at amino acid (AA) 250-C terminus, AA180-228, and N terminus AA1-80) by immunohistochemistry. Our results showed that strong membranous immunostaining was observed for AQP3 AR sites at the AA250-C terminus and AA180-228 in all the samples for NOM and weak AQP3 immunostaining for both the AR sites in all the 12 samples for HG-ED. The invasive front of OSCC samples showed that AQP3 AR at the AA250-C terminus decreased in 42/51 samples (82.4%) and AA180-228 in 47/51 samples (92.2%). Conversely, in the AQP3 AR site at N terminus AA1-80, all samples of the NOM showed negative or slightly positive staining in the cytoplasm of the lower layers. AQP3 expression was increased in 12/12 cases (100%) and 46/51 cases (90.2%) in the HG-ED and invasive front of OSCC, respectively. AQP3 may be used as a biomarker for detecting malignant transformations. AQP3 AR site differences influence their immunohistochemical expression in OSCC.

Objective: To create a simple, objective model to predict the presence of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN), which can be easily applied in daily practice and, importantly, adopted for any lesion types., Background: No predictive model for malignant IPMN has been widely applied in clinical practice., Methods: The clinical details of 466 patients with IPMN who underwent pancreatic resection at 3 hospitals were retrospectively analyzed for model development. Then, the model was validated in 664 surgically resected patients at 8 hospitals in Japan.In the preoperative examination, endoscopic ultrasonography (EUS) was considered to be essential to observe mural nodules in both the model development and external validation sets. Malignant IPMNs were defined as those with high-grade dysplasia and associated invasive carcinoma., Results: Of the 466 patients, 258 (55%) had malignant IPMNs (158 high-grade dysplasia, 100 invasive carcinoma), and 208 (45%) had benign IPMNs. Logistic regression analysis resulted in 3 variables (mural nodule size, main pancreatic duct diameter, and cyst size) being selected to construct the model. The area under the receiver operating characteristic curve (AUC) for the model was 0.763. In external validation sets, the pathological diagnosis was malignant and benign IPMN in 351 (53%) and 313 (47%) cases, respectively. For the external validation, the malignancy prediction ability of the model corresponded to an AUC of 0.725., Conclusion: This predictive model provides important information for physicians and patients in assessing an individual's risk for malignancy and may help to identify patients who need surgery.

The incidence of breast cancer among Japanese women is substantially increasing. This study evaluated the effects of reproductive and lifestyle factors with respect to breast cancer overall and separately among pre- and postmenopausal women using data from the Three-Prefecture Cohort Study of Japan.A total of 33,410 women aged 40 to 79 years completed a self-administered questionnaire, which included items about menstrual and reproductive history and other lifestyle factors. The follow-up period was from 1984 to 1992 in Miyagi and 1985 to 2000 in Aichi Prefectures. We used Cox proportional hazards regression models to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) after adjusting for confounding factors.After 9.8 mean years of follow-up, 287 cases of breast cancer were recorded. In the overall analysis, later menarche (≥16 years) and parity were significantly associated with a decreased risk of breast cancer, with HRs of 0.69 (95% CI 0.48-0.99) and 0.72 (95% CI 0.52-0.99), respectively. Further, there was a significant decline in the risk of breast cancer with increasing number of birth among parous women (P for trend = .010). On the contrary, a family history of breast cancer in the mother was significantly associated with an increased risk of breast cancer (HR 3.22, 95% CI 1.52-6.84). Analyses based on menopausal status at baseline indicated that height (≥160 cm) and weight (≥65 kg) were significantly associated with an increased risk of postmenopausal breast cancer, with HRs of 1.34 (95% CI 0.72-2.50) and 3.13 (95% CI 1.75-5.60), respectively. Risk associated with BMI significantly differs by menopausal status.Our findings suggest the important role of reproductive factors in the development of breast cancer in Japanese women; however, body mass index (BMI) may have different effects on breast cancer in Japanese women compared with western women.

Objective: To examine the incidence and prognostic effects of intraoperative capsule rupture and to assess the effectiveness of postoperative chemotherapy for intraoperative tumor rupture in apparent stage I epithelial ovarian cancer., Methods: This is a society-based retrospective observational study in Japan that examined 15,163 women with stage IA-IC1 epithelial ovarian cancer who underwent primary surgical treatment between 2002 and 2015. Associations between intraoperative capsule rupture and cause-specific survival, and between postoperative chemotherapy and cause-specific survival among intraoperatively ruptured cases were examined by histology type (clear cell n=6,107, endometrioid n=3,910, mucinous n=3,382, and serous n=1,764)., Results: Clear cell histology had the highest risk of intraoperative capsule rupture (57.3%), followed by endometrioid (48.8%), serous (41.8%), and mucinous (32.0%) histologies (P<.001). On multivariable analysis, clear cell type exhibited the largest effect of intraoperative capsule rupture on cause-specific survival (adjusted hazard ratio [HR] 1.99, 95% CI 1.45-2.75), followed by serous (adjusted HR, 1.61, 95% CI 0.84-3.11), mucinous (adjusted HR 1.28, 95% CI 0.79-2.09), and endometrioid (adjusted HR, 1.14, 95% CI 0.64-2.01) tumors. Postoperative chemotherapy for intraoperatively ruptured cases did not improve cause-specific survival in any histologic types in multivariable analysis: clear cell, adjusted HR 0.86, 95% CI 0.56-1.31; serous, adjusted HR 1.08, 95% CI 0.42-2.74; mucinous, adjusted HR 1.11, 95% CI 0.55-2.27; and endometrioid, adjusted HR 2.81, 95% CI 0.85-9.30 (all, P>.05). In the cohort-level analysis of ruptured cases (n=7,227), postoperative chemotherapy use has significantly decreased in mucinous (16.3% relative decrease), endometrioid (13.1% relative decrease), and clear cell (9.3% relative decrease) (all, P<.05); but, the cohort-level 5-year cause-specific survival rate did not change over time (all, P>.05)., Conclusion: Among apparent stage I epithelial ovarian cancer, the clear cell type possesses a disproportionally high risk of capsule rupture during adnexectomy and is associated with the most adverse effect on survival. A decrease in the use of postoperative chemotherapy for intraoperatively ruptured cases in Japan is likely the result of increasing awareness of the absence of survival benefits.

Objective: To examine the prognostic performance of the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) cervical cancer staging schema., Methods: We used the National Cancer Database to identify women with cervical cancer diagnosed from 2004 to 2015. Using clinical and pathologic data, each patient's stage was classified using three staging schemas: American Joint Committee on Cancer 7th edition, FIGO 2009 and FIGO 2018. The FIGO 2018 revised staging classifies stage IB tumors into three substages based on tumor size (IB1-IB3) and classifies patients with positive lymph nodes (pathologically or clinically detected) as stage IIIC1 (positive pelvic nodes) or IIIC2 (positive para-aortic nodes). Five-year survival rates were estimated for each stage grouping. We sought to determine whether the 2018 FIGO staging system was able to offer improved 5-year survival rate differentiation compared with older staging schemas., Results: A total of 62,212 women were identified. The classification of stage IB tumors into three substages improved discriminatory ability. Five-year survival in the FIGO 2018 schema was 91.6% (95% CI 90.4-92.6%) for stage IB1 tumors, 83.3% (95% CI 81.8-84.8%) for stage IB2 neoplasms, and 76.1% (95% CI 74.3-77.8%) for IB3 lesions. In contrast, for women with stage III tumors, higher FIGO staging was not consistently associated with worse 5-year survival rates: stage IIIA (40.7%, 95 CI 37.1-44.3%), stage IIIB (41.4%; 95% CI 39.9-42.9%), stage IIIC1 (positive pelvic nodes) was 60.8% (95% CI 58.7-62.8%) and stage IIIC2 37.5% (95% CI 33.3-41.7%)., Conclusion: The FIGO 2018 staging schema provides improved discriminatory ability for women with stage IB tumors; however, classification of all women with positive lymph nodes into a single stage results in a very heterogeneous group of patients with highly variable survival rates.

Objective: To examine the association between surgical volume and survival of women with early-stage cervical cancer who underwent radical hysterectomy., Methods: This is a nationwide multicenter retrospective study examining consecutive women with clinical stage IB1-IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy from 2004 to 2008 (N=5,964). The surgical volume per site over the 5-year period was defined as low-volume (fewer than 32 surgeries, 46 [39.7%] institutions, n=649 [10.9%]), mid-volume (32-104 surgeries, 60 [51.7%] institutions, n=3,662 [61.4%]), and high-volume (105 surgeries or more, 10 [8.6%] institutions, n=1,653 [27.7%]). Surgical volume-specific survival was examined with multivariable analysis and propensity score matching., Results: The median number of surgeries per site was 44 (interquartile range, 17-65). The 5-year disease-free survival rates among stage IB1-IIB disease were 77.2%, 79.9%, and 84.5% for low-, mid-, and high-volume groups, respectively. On multivariable analysis, women in high-volume centers had a decreased risk of recurrence (adjusted hazard ratio [HR] 0.69, 95% CI 0.58-0.82, P<.001) and all-cause mortality (adjusted HR 0.73, 95% CI 0.59-0.90, P=.003) compared with those in mid-volume centers. Specifically, women in high-volume centers had a decreased risk of local recurrence (adjusted HR 0.62, 95% CI 0.49-0.78, P<.001) but not distant recurrence (adjusted HR 0.85, 95% CI 0.67-1.06, P=.142) compared with those in mid-volume centers. Among 1,700 women with clinical stage IB1 disease treated with surgery alone, surgery at high-volume centers was associated with a decreased risk of recurrence (adjusted HR 0.45, 95% CI 0.25-0.79, P=.006) and all-cause mortality (adjusted HR 0.29, 95% CI 0.11-0.76, P=.013) compared with surgery at mid-volume centers on multivariable analysis. After propensity score matching, surgery at high-volume centers remained an independent prognostic factor for decreased recurrence (adjusted HR 0.69, 95% CI 0.57-0.84, P<.001) and all-cause mortality (adjusted HR 0.75, 95% CI 0.59-0.95, P=.016) compared with surgery at mid- and low-volume centers on multivariable analysis., Conclusion: Hospital volume for radical hysterectomy may be a prognostic factor for early-stage cervical cancer. Surgery at high-volume centers is associated with decreased local recurrence risk and improved survival.

Purpose: Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results., Methods: We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study., Results: We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples., Conclusions: We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

Rationale: Liposarcoma (LPS) is a rare malignant soft-tissue tumor. Management of LPS is relatively difficult, because there are no characteristic symptoms, or biomarkers, nor any established effective treatment. Hence, the report of the accumulation of each LPS case is necessary. We experienced an extremely rare case of torsion caused by a primary small bowel mesentery LPS., Patient's Concern: A 70-year-old male consulted our hospital with the complaints of abdominal pain and sudden vomiting., Diagnosis: No lump could be palpated, and tumor markers tested were within normal limits. However, computed tomography revealed an intestinal obstruction caused by torsion of the small bowel due to an LPS tumor., Interventions: After decompression of the intestinal obstruction by use of an ileus tube, surgical treatment was performed with rapidity., Outcome: The torsion was found to be caused by the tumor that originated from the small bowel mesentery. The tumor was resected along with a portion of the small bowel. The growth of adipose tissues of various sizes and containing atypical cells was detected by histopathological examination. Also, immunohistochemical examination resulted in positive immuno-reactions for MDM2, CDK4, and p16INK4, which indicated the tumor to be a de-differentiated LPS. The patient was discharged on postoperative day 14 without any complications, and no recurrence of the tumor was observed at 5 years after the operation., Lessons: LPS should be considered in differential diagnosis of bowel torsion, and careful management is required because of the high possibility of recurrence. Patients should be followed carefully for at least 5 years, and further accumulation of data will be required in order to establish the appropriate management of LPS.

Objective: To examine survival outcomes of women with recurrent cervical cancer who received salvage chemotherapy with modified dose-dense paclitaxel (MDDP) monotherapy (paclitaxel 80 mg/m, administered on day 1, 8, and 15 without day 22)., Materials and Methods: A retrospective study was conducted to evaluate cause-specific survival after the first recurrence (SAR) of women with recurrent cervical cancer diagnosed between 2006 and 2014. Pooled analyses were performed to examine SAR in women who received MDDP monotherapy (n=17) for any treatment line, compared with those who received salvage chemotherapy with paclitaxel-doublet (n=18) and nonpaclitaxel regimens (n=52)., Results: In the whole cohort, median SAR was 13.7 months including 63 (72.4%) events. MDDP monotherapy regimen was most commonly used in the second-line setting (35.3%) followed by the third/fourth lines (both, 23.5%). Among the women who received MDDP regimen, there were 6 (35.3%) women who received ≥6 cycles; there was 1 (5.9%) women who discontinued the regimen due to adverse effects (grade 3 transaminitis); regimen postponement was seen in 2 (1.4%) of 140 total cycles; and the response rate after the sixth cycle of this regimen was 29.4% (1 complete and 4 partial responses). On univariate analysis, MDDP usage had the highest 2-year SAR rate (MDDP 54.1%, paclitaxel-doublet 43.6%, and nonpaclitaxel regimens 28.1%; Ptrend=0.044). On multivariate analysis, MDDP monotherapy remained an independent prognostic factor for improved SAR compared with the nonpaclitaxel regimen (adjusted-hazard ratio, 0.50; 95% confidence interval, 0.26-0.95; P=0.036)., Conclusion: Our results suggested that MDDP monotherapy is a tolerable and relatively effective regimen for recurrent cervical cancer.

We have previously shown that HOMER2 (Homer scaffolding protein 2), a protein coding gene, was highly expressed in low grade (LG) endometrioid adenocarcinoma (EAC) of the uterus. The role of HOMER2 in endometrial cancer (EC) is widely unknown; therefore, the aim of this study was to determine the expression and the predictive value of HOMER2 protein expression in series of patients with EC. HOMER2 protein expression was detected on paraffin-embedded tissues from 336 cases using immunohistochemistry (IHC). Tumours were categorised in two groups; group 1 (EAC, FIGO grade 1 and 2; n = 191) and group 2 (all other subtypes including grade 3 EAC; n = 145). Statistical analysis was performed to evaluate associations between HOMER2 protein expression and pathological parameters (histological type, grade, stage, lymphovascular invasion, myometrial depth of invasion) and patient outcome [progression-free survival (PFS) and cancer-specific survival (CSS)]. HOMER2 was significantly overexpressed in group 1 compared to group 2 cancers (67% versus 30%; p < 0.001) and with low tumour grade (p < 0.001). In group 1, HOMER2 overexpression was an independent prognostic factor for improved CSS (adjusted-hazard ratio 0.28; 95% confidence interval 0.08-0.96; p = 0.042). HOMER2 expression was not associated with survival in group 2 (p > 0.05). This is the first study of HOMER2 protein expression in EC. We speculate that HOMER2 may be involved in tumourigenesis of endometrioid uterine tumours and suggest that HOMER2 should be studied further for potential clinical and therapeutic applications., (Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Rationale: Liposarcoma (LPS) is a relatively rare malignant soft tissue tumor. Management of LPS including diagnosis is difficult, because it has no characteristic symptoms and no established effective treatment. Herein we reported an extremely rare case of intussusception induced by primary small bowel LPS., Patient's Concern: A-84-year-old male was a consult to our Emergency Department with symptoms of a terrible general fatigue, abdominal pain, and vomiting., Diagnosis: Abdominal ultrasonography and computed tomography (CT) revealed probable intussusception., Interventions: After decompression by insertion of an ileus tube, surgery was performed., Outcomes: The ileum and mesentery of the small intestine had invaginated into the colon. There was no evidence of metastases in the intraabdominal space. The Hutchinson maneuver could not release the invagination, and so ileocecal resection with lymph node dissection was performed. Histopathological examination showed evidence of the growth of spindle-shaped cells. Also, immunohistochemical examination indicated the tumor to be a de-differentiated LPS. The patient was discharged on postoperative day 19 without any complications; and no recurrence of the tumor was observed at 16 months post operation., Lessons: LPS should be considered in the differential diagnosis of adult intussusception, and careful management should be required, including observation, after surgery.

Tobacco smoking is one of the main risk factors for gastric cancer, but the magnitude of the association estimated by conventional systematic reviews and meta-analyses might be inaccurate, due to heterogeneous reporting of data and publication bias. We aimed to quantify the combined impact of publication-related biases, and heterogeneity in data analysis or presentation, in the summary estimates obtained from conventional meta-analyses. We compared results from individual participant data pooled-analyses, including the studies in the Stomach Cancer Pooling (StoP) Project, with conventional meta-analyses carried out using only data available in previously published reports from the same studies. From the 23 studies in the StoP Project, 20 had published reports with information on smoking and gastric cancer, but only six had specific data for gastric cardia cancer and seven had data on the daily number of cigarettes smoked. Compared to the results obtained with the StoP database, conventional meta-analyses overvalued the relation between ever smoking (summary odds ratios ranging from 7% higher for all studies to 22% higher for the risk of gastric cardia cancer) and yielded less precise summary estimates (SE ≤2.4 times higher). Additionally, funnel plot asymmetry and corresponding hypotheses tests were suggestive of publication bias. Conventional meta-analyses and individual participant data pooled-analyses reached similar conclusions on the direction of the association between smoking and gastric cancer. However, published data tended to overestimate the magnitude of the effects, possibly due to publication biases and limited the analyses by different levels of exposure or cancer subtypes.