Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells.

Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.

Endotension Following Endovascular Aneurysm Repair: Retrospective Review of Treatment and Clinical Outcome.

Purpose: : Endotension is a rare late complication characterized by an increase in sac size without any type of endoleak following endovascular aortic aneurysm repair (EVAR). Due to its rarity, few studies have demonstrated the mechanism behind and the management of endotension. In this study, we aimed to better understand the treatment and the long-term outcome of endotension in a single-center cohort. Materials and Methods: : This study was designed for a retrospective review of the patients diagnosed with endotension between January 2006 and December 2017. The study patients were categorized into two groups (primary versus secondary) based on the presence of any type of endoleak before the diagnosis of endotension. We collected data related to endotension treatment, intraoperative findings, and long-term outcomes. Results: : In a cohort of 15 patients diagnosed with endotension following EVAR, eight were classified into the primary endotension (PE) group without prior endoleak, and seven exhibited secondary endotension (SE). Among the eight PE patients, endovascular intervention for a preemptive purpose was conducted in six patients; however, three (50%) showed continuous sac expansion and finally received open conversion. Overall, eight patients (five in PE and three in SE) underwent open conversion, and one (12.5%) presented with an undetected endoleak during the operative findings. Postoperative morbidity was observed in three patients with no operative mortality. Conclusion: : Endotension can be managed initially through simple observation for changes on serial images, along with preemptive endovascular intervention. However, surgical intervention should be considered for patients with specific indications including continuous aneurysm sac enlargement, presence of symptoms, suspicions of migration of stent-graft with endoleak, and infection.

Mitochondrial fission enhances IL-6-induced metastatic potential in ovarian cancer via ERK1/2 activation.

Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin-6 (IL-6), a pro-inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL-6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL-6 on ovarian cancer cell lines (SKOV3 and PA-1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, and IL-6R in metastatic ovarian cancer tissues. Additionally, IL-6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p-Drp1(S637) to the active form p-Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL-6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL-6-induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL-6-induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient-derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL-6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.

Effects of abdominal aortic aneurysm on long-term survival in lung cancer patients.

The major causes of death in patients with abdominal aortic aneurysm (AAA) are cardiovascular disease and cancer. The purpose of this study was to evaluate the effect of AAA on long-term survival in lung cancer patients. All patient data with degenerative type AAA and lung cancer over 50 years of age during the period 2009 to 2018 was collected retrospectively from a National Health Insurance Service (NHIS) administrative database and matched to lung cancer patients without AAA by age, sex, metastasis, and other comorbidities. Mortality rate was compared between the groups. A total of 956 AAA patients who could be matched with patients without AAA were included, and 3824 patients in the matched group were used for comparison. Patients with AAA showed higher risk of death compared with the matched cohort (adjusted hazard ratio (HR) 1.14, 95% confidence interval (CI) 1.06-1.23, p < 0.001). When compared to a matched group of untreated AAA patients, patients with of history of AAA exhibited a significantly increased risk of overall mortality [HR (95%CI) 1.219 (1.113-1.335), p < .001, adjusted HR (95% CI) 1.177 (1.073-1.291), p = .001]. By contrast, mortality risk of AAA patients treated either by endovascular abdominal aortic repair or open surgical repair was not significantly different from that of the matched group (p = 0.079 and p = 0.625, respectively). The mortality risk was significantly higher when AAA was present in lung cancer patients, especially in patients with unrepaired AAA, suggesting the need for continuous cardiovascular risk management.

Treatment Outcomes of Patients With Ruptured Abdominal Aortic Aneurysms.

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) is a serious complication of abdominal aortic aneurysm associated with high operative mortality and morbidity rates. The present study evaluated the perioperative and long-term outcomes of Korean patients with rAAA based on national health insurance claims data. METHODS: The National Health Insurance Service (NHIS) database was searched retrospectively to identify patients with rAAA who underwent endovascular aneurysm repair (EVAR) and open surgical repair (OSR) from 2009 to 2018. Perioperative (≤ 30 days), early postoperative (≤ 3 month), and long-term (> 3 month) survival, reinterventions, and complications were assessed. RESULTS: The search identified 1,034 patients with rAAA, including 594 who underwent EVAR and 440 who underwent OSR. When the study period was divided into two, the total numbers of patients with rAAA, patients who underwent EVAR, and octogenarians were higher during the second half. The perioperative mortality rate was 29.8% in the EVAR and 35.0% in the OSR group (P = 0.028). Hartmann's procedure for bowel infarction was performed more frequently in the OSR than in the EVAR group (adjusted odds ratio, 6.28; 95% confidence interval [CI], 2.33-21.84; P = 0.001), but other complication rates did not differ significantly. All-cause mortality during the entire observation period did not differ significantly in the EVAR and OSR groups (adjusted hazard ratio, 1.17; 95% CI, 0.98-1.41; P = 0.087). Abdominal aortic aneurysm-related reintervention rate was significantly lower in the OSR group (adjusted hazard ratio, 0.31; 95% CI, 0.14-0.70; P = 0.005). CONCLUSION: Although EVAR showed somewhat superior perioperative outcomes for rAAA, the long-term outcomes of EVAR after excluding initial 3 months were significantly worse than OSR. When anatomically feasible for both treatments, the perioperative mortality risk and reasonable prospects of long-term survival should be considered in rAAA.

Technical Tips for Performing Suprahepatic Vena Cava Tumor Thrombectomy in Renal Cell Carcinoma without Using Cardiopulmonary Bypass.

Radical nephrectomy with tumor thrombectomy for advanced renal cell carcinoma is an oncologically relevant approach that can achieve long-term survival even in the presence of distant metastases. However, the surgical techniques pose significant challenges. The objective of this clinical review was to present technical recommendations for tumor thrombectomy in the vena cava to facilitate surgical treatment. Transesophageal echocardiography is required to prepare for this procedure. Cardiopulmonary bypass should be considered when the tumor thrombus has invaded the cardiac chamber and clamping is not feasible because of the inability to milk the intracardiac chamber thrombus in the caudal direction. Prior to performing a cavotomy, it is crucial to clamp the contralateral renal vein and infrarenal and suprahepatic inferior vena cava (IVC). If the suprahepatic IVC is separated from the surrounding tissue, it can be gently pulled down toward the patient's leg until the lower margin of the atrium becomes visible. Subsequently, the tumor thrombus should be carefully pulled downward to a position where it can be clamped. Implementing the Pringle maneuver to reduce blood flow from the hepatic veins to the IVC during IVC cavotomy is simpler than clamping the hepatic veins. Sequential clamping is a two-stage method of dividing thrombectomy by clamping the IVC twice, first suprahepatically and then midretrohepatically. This sequential clamping technique helps minimize hypotension status and the Pringle maneuver time compared to single clamping. Additionally, a spiral cavotomy can decrease the degree of primary closure narrowing. The oncological prognoses of patients can be improved by incorporating these technical recommendations.

An Epidemiologic Study of the Incidence and Mortality of Abdominal Aortic Aneurysms in Koreans Aged ≥50 Years from 2009 to 2018 Based on a National Database.

Large-scale population studies of the incidence of and mortality from abdominal aortic aneurysm (AAA) are needed to develop healthcare policies and priorities. The aim of this study was to estimate the incidence of AAA and the all-cause mortality from it among Koreans aged ≥50 years from 2009 to 2018 using data from the Korean National Health Insurance System Database. The crude and standardized incidence and all-cause mortality of the disease among patients with unruptured AAA were calculated. A total of 73,933 AAA patients were identified. The overall incidence of AAA in adults ≥50 years during the study period was 37.5 per 100,000 population (49.7 per 100,000 in men and 26.8 per 100,000 in women), with an increase from 32.33 per 100,000 persons in 2009 to 46.85 per 100,000 in 2018. The crude all-cause mortality rate of patients with untreated AAA was 21.26/100 person-years in 2009 and 8.87/100 person-years in 2018, with decreasing trends observed both in men and women. This nationwide study showed that the incidence of AAA in Koreans aged ≥50 years in 2018 was 63.40 per 100,000 in men and 32.07 per 100,000 in women. The overall rates were 0.06% and 0.03%, respectively, with an increasing trend. Mortality has decreased in both treated and untreated patients. The observed increase in incidence suggests a rising burden of AAA in the Korean population, particularly among men. The decreasing mortality rates may indicate improvements in the management and treatment of AAA over the study period.

Treatment of abdominal aortic aneurysms in Korea: a nationwide study.

Purpose: Although endovascular aneurysm repair (EVAR) has been shown to be superior to open surgical repair (OSR) for abdominal aortic aneurysm (AAA) treatment, no large-scale studies in the Korean population have compared outcomes and costs. Methods: The National Health Insurance Service database in Korea was screened to identify AAA patients treated with EVAR or OSR from 2008 to 2019. Perioperative, early postoperative, and long-term survival were compared, as were reinterventions and complications. Patients were followed-up through 2020. Results: Of the 13,631 patients identified, 2,935 underwent OSR and 10,696 underwent EVAR. Perioperative mortality rate was lower in the EVAR group (4.2% vs. 8.0%, P < 0.001) even after excluding patients with ruptured AAA (2.7% vs. 3.3%, P = 0.003). However, long-term mortality rate per 100 person-years was significantly higher in the EVAR than in the OSR group (9.0 vs. 6.4, P < 0.001), and all-cause mortality was lower in the OSR group (hazard ratio, 0.9; 95% confidence interval, 0.87-0.97, P = 0.008). EVAR had a higher AAA-related reintervention rate per 100 person-years (1.75 vs. 0.52), and AAA-related reintervention costs were almost 10-fold higher with EVAR (US dollar [USD] 6,153,463) than with OSR (USD 624,216). Conclusion: While EVAR may have short-term advantages, OSR may provide better long-term outcomes and cost-effectiveness for AAA treatment in the Korean population, under the medical expense system in Korea.

Clinical outcomes of in situ graft reconstruction in treating infected abdominal aortic stent grafts following endovascular aortic aneurysm repair: a single-center experience.

Purpose: This study aimed to review our experience with the explantation of infected endovascular aneurysm repair (EVAR) grafts. Methods: This single-center, retrospective, observational study analyzed the data of 12 consecutive patients who underwent infected aortic stent graft explantation following EVAR between January 1, 2010 and December 31, 2019, of which 11 underwent in situ graft reconstruction following graft removal. The presentation symptoms, infection route, original pathology of abdominal aortic aneurysms (AAA), graft materials, and clinical outcomes were analyzed. Results: Six patients underwent total explantation, whereas 5 underwent removal of only the fabric portions. For in situ reconstructions, prosthetic grafts and banked allografts were used in 8 and 3 patients, respectively. Four mechanisms of graft infection were noted in 11 patients: 4 had bacteremia from systemic infections, 3 had persistent infections following EVAR of primary infected AAA, 3 had ascending infections from adjacent abscesses, and 1 had an aneurysm sac erosion resulting in an aortoenteric fistula. No infection-related postoperative complications or reinfections occurred during the mean 65.27-month (standard deviation, ±52.51) follow-up period. One patient died postoperatively because of the rupture of the proximal aortic wall pseudoaneurysm that had occurred during forceful bare stent removal. Conclusion: Regardless of graft material, in situ graft reconstruction is safe for interposition in treating an infected aortic stent graft following EVAR. In our experience, the residual bare stent is no longer a risk factor for reinfection. Therefore, it is important not to injure the proximal aortic wall when removing the bare stent by force.

Synthetic RNA Therapeutics in Cancer.

Recent advances in the RNA delivery system have facilitated the development of a separate field of RNA therapeutics, with modalities including mRNA, microRNA (miRNA), antisense oligonucleotide (ASO), small interfering RNA, and circular (circRNA) that have been incorporated into oncology research. The main advantages of the RNA-based modalities are high flexibility in designing RNA and rapid production for clinical screening. It is challenging to eliminate tumors by tackling a single target in cancer. In the era of precision medicine, RNA-based therapeutic approaches potentially constitute suitable platforms for targeting heterogeneous tumors that possess multiple sub-clonal cancer cell populations. In this review, we discussed how synthetic coding and non-coding RNAs, such as mRNA, miRNA, ASO, and circRNA, can be applied in the development of therapeutics. SIGNIFICANCE STATEMENT: With development of vaccines against coronavirus, RNA-based therapeutics have received attention. Here, the authors discuss different types of RNA-based therapeutics potentially effective against tumor that are highly heterogeneous giving rise to resistance and relapses to the conventional therapeutics. Moreover, this study summarized recent findings suggesting combination approaches of RNA therapeutics and cancer immunotherapy.

Metabolic Syndrome as a Risk Factor of Endometrial Cancer: A Nationwide Population-Based Cohort Study of 2.8 Million Women in South Korea.

Background: A positive relationship was reported between metabolic syndrome and the risk of endometrial cancer. Studies on the relationship between metabolic syndrome and endometrial cancer have been mainly conducted in post-menopausal women. We aimed to investigate the risk of endometrial cancer according to metabolic syndrome and menopausal status using the Korean nationwide population-based cohort. Methods: We enrolled 2,824,107 adults (endometrial cancer group; N = 5,604 and control group; N= 2,818,503) from the Korean National Health Insurance Service checkup database from January 1 to December 31, 2009. The median follow-up duration was 8.37 years. Metabolic syndrome was diagnosed as having at least three of the following five components: abdominal obesity, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate endometrial cancer risk. Results: The endometrial cancer risk was higher in the metabolic syndrome group than that in the non-metabolic syndrome group (HR, 1.362; 95% CI, 1.281-1.449). The association between metabolic syndrome and endometrial cancer risk was significant in the premenopausal subgroup (HR, 1.543; 95% CI, 1.39-1.713) and postmenopausal subgroup (HR, 1.306; 95% CI, 1.213-1.407). The incidence of endometrial cancer was more closely related to metabolic syndrome components in the pre-menopausal subgroup than those in the post-menopausal subgroup (for waist circumference, blood pressure, triglycerides and high-density lipoprotein cholesterol, all p for interaction <0.0001 respectively, and for fasting blood glucose, p for interaction 0.0188). The incidence of endometrial cancer positively correlated with the number of metabolic syndrome components (log-rank p <0.0001). Conclusion: Our large population-based cohort study in Korean women suggests that metabolic syndrome and its accumulated components may be risk factors for endometrial cancer, particularly in the pre-menopausal women.

Wnt/ß-Catenin Inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer.

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/ß-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/ß-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/ß-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of ß-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/ß-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.

Prohibitin 1 interacts with p53 in the regulation of mitochondrial dynamics and chemoresistance in gynecologic cancers.

BACKGROUND: Mitochondrial dynamics (e.g. fission/fusion) play an important role in controlling chemoresistance in representative gynecologic malignancies, ovarian and cervical cancer. Processing the long form of Optic atrophy (L-Opa)1 is a distinctive character of mitochondrial fragmentation, associated with chemosensitivity. Here, we examined the role of prohibitin (Phb)1 in increasing L-Opa1 processing via the regulating mitochondrial protease, Oma1 and its direct interaction with p-p53 (ser15) and pro-apoptotic Bcl-2 antagonist/killer (Bak) 1 in the signaling axis and if this phenomenon is associated with prognosis of patients. METHODS: We compared Cisplatin (CDDP)-induced response of mitochondrial dynamics, molecular interaction among p-p53 (ser15)-Phb1-Bak, and chemoresponsiveness in paired chemosensitive and chemoresistant gynecologic cancer cells (ovarian and cervical cancer cell lines) using western blot, immunoprecipitation, sea horse, and immunofluorescence. Translational strategy with proximity ligation assessment in phb1-p-p53 (ser15) in human ovarian tumor sections further confirmed in vitro finding, associated with clinical outcome. RESULTS: We report that: (1) Knock-down of Phb1 prevents Cisplatin (cis-diamine-dichloroplatinum; CDDP) -induced changes in mitochondrial fragmentation and Oma1 mediated cleavage, and Opa1 processing; (2) In response to CDDP, Phb1 facilitates the p-p53 (ser15)-Phb1-Bak interaction in mitochondria in chemosensitive gynecologic cancer cells but not in chemoresistant cells; (3) Akt overexpression results in suppressed p-p53(Ser15)-Phb1 interaction and dysregulated mitochondrial dynamics, and (4) Consistent with in vitro findings, proximity ligation assessment (PLA) in human ovarian tumor sections demonstrated that p-p53(ser15)-Phb1-Bak interaction in mitochondria is associated with better chemoresponsiveness and clinical outcome of patients. Determining the molecular mechanisms by which Phb1 facilitates mitochondrial fragmentation and interacts with p53 may advance the current understanding of chemoresistance and pathogenesis of gynecologic cancer. CONCLUSION: Determining the key molecular mechanisms by which Phb1 facilitates the formation of p-p53 (ser15)-Bak-Phb1 and its involvement in the regulation of mitochondrial dynamics and apoptosis may ultimately contribute to the current understanding of molecular and cellular basis of chemoresistance in this gynecologic cancer.

Aortoiliac diameter and length in a healthy cohort.

OBJECTIVE: Diameter is currently the only screening and diagnostic criterion for asymptomatic aneurysms. Therefore, aortic and lower-extremity arterial diameter has diagnostic, therapeutic, and prognostic importance. We aimed to determine aortic and lower-extremity arterial reference diameters in a general population and compare them according to age, sex, and other characteristics. METHODS: We evaluated consecutive 3,692 patients who underwent computed tomography as part of a general health checkup from 2015-2019 in a single tertiary center. Aortic and lower-extremity arterial diameters and the most important factor related to arterial diameters were evaluated. RESULTS: The mean diameter of the abdominal aorta was 17.490 ± 2.110 mm, while that of the common iliac artery was 10.851 ± 1.689 mm. The mean diameter of the abdominal aorta was 18.377 ± 1.766 mm in men and 15.884 ± 1.694 mm in women. Significant intersex differences were observed for all mean diameters and lengths. Multilinear regression analysis showed that age, sex, and body surface area impacted mean diameters of all measured sites except aorta and common iliac artery length. Between male and female patients matched for body surface area, there were significant intersex differences for all measured sites, except for common iliac artery length. CONCLUSIONS: The mean diameter of the abdominal aorta in this healthy cohort was 17.490 ± 2.110 mm overall, 18.377 ± 1.766 mm in men, and 15.884 ± 1.694 mm in women. Arterial diameter increased with male sex, older age, and increased body surface area, and aortic diameters were larger in men than in women with the same body surface area.

Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA-based diagnostic signature in ovarian cancer.

Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers. The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites. Extracellular vesicles (EVs) are emerging as promising clinical biomarkers in liquid biopsy. Here, we aimed to investigate robust liquid biopsy-based EV miRNA biomarkers for ovarian cancer diagnosis and metastasis regulation. EVs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases. EV small RNA sequencing identified a panel of eight miRNAs (miR-1246, miR-1290, miR-483, miR-429, miR-34b-3p, miR-34c-5p, miR-145-5p, miR-449a) based on dysregulated miRNAs overlapped in the ascites and plasma subset. The ovarian cancer EV miRNA (OCEM) signature developed based on these eight miRNAs demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine). In addition, malignant ascites-derived EVs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids. Notably, miR-1246 and miR-1290 shuttled in malignant ascites-derived EVs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target RORα.

BRAFV600E Mutation Enhances Estrogen-Induced Metastatic Potential of Thyroid Cancer by Regulating the Expression of Estrogen Receptors.

BACKGRUOUND: Cross-talk between mitogen-activated protein kinase and estrogen has been reported; however, the role of BRAFV600E in the estrogen responsiveness of thyroid cancer is unknown. We elucidated the effect of BRAFV600E on the estrogen-induced increase in metastatic potential in thyroid cancer. METHODS: Using a pair of cell lines, human thyroid cell lines which harbor wild type BRAF gene (Nthy/WT) and Nthy/BRAFV600E (Nthy/V600E), the expression of estrogen receptors (ERs) and estrogen-induced metastatic phenotypes were evaluated. Susceptibility to ERα- and ERß-selective agents was evaluated to confirm differential ER expression. ESR expression was analyzed according to BRAFV600E status and age (≤50 years vs. >50 years) using The Cancer Genome Atlas (TCGA) data. RESULTS: Estradiol increased the ERα/ERß expression ratio in Nthy/V600E, whereas the decreased ERα/ERß expression ratio was found in Nthy/WT. BRAFV600E-mutated cell lines showed a higher E2-induced increase in metastatic potential, including migration, invasion, and anchorage-independent growth compared with Nthy/WT. An ERα antagonist significantly inhibited migration in Nthy/V600E cells, whereas an ERß agonist was more effective in Nthy/WT. In the BRAFV600E group, ESR1/ESR2 ratio was significantly higher in younger age group (≤50 years) compared with older age group (>50 years) by TCGA data analysis. CONCLUSION: Our data show that BRAFV600E mutation plays a crucial role in the estrogen responsiveness of thyroid cancer by regulating ER expression. Therefore, BRAFV600E might be used as a biomarker when deciding future hormone therapies based on estrogen signaling in thyroid cancer patients.

Quality-adjusted life year comparison at medium term follow-up of endovascular versus open surgical repair for abdominal aortic aneurysm in young patients.

OBJECTIVES: This study aimed to compare the quality of life and cost effectiveness between endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in young patients with abdominal aortic aneurysm (AAA). DESIGN: This was a single-center, observational, and retrospective study. MATERIALS AND METHODS: A retrospective analysis was conducted of patients with AAA, who were <70 years old and underwent EVAR or OSR between January 2012 and October 2016. Only patients with aortic morphology that was suitable for EVAR were enrolled. Data on the complication rates, medical expenses, and expected quality-adjusted life years (QALYs) were collected, and the cost per QALY at three years was compared. RESULTS: Among 90 patients with aortic morphology who were eligible for EVAR, 37 and 53 patients underwent EVAR and OSR, respectively. No significant differences were observed in perioperative cardiovascular events and death between the two groups. However, during the follow-up period, patients undergoing OSR showed a significantly lower complication rate (hazard ratio [HR] = 0.11; P = .021). From the three-year cost-effectiveness analysis, the total sum of costs was significantly lower in the OSR group (P < .001) than that in the EVAR group, and the number of QALYs was superior in the OSR group (P = .013). The cost per QALY at three years was significantly lower in the OSR group than that in the EVAR group (mean: $4038 vs. $10 137; respectively; P < .001). CONCLUSIONS: OSR had lower complication rates and better cost-effectiveness than EVAR Among young patients with feasible aortic anatomy.

Cardiovascular morbidities in postoperative colorectal cancer patients.

This retrospective observational study investigated the long-term prevalence of new-onset cardiovascular disease (CVD) and the predictive role of atherosclerotic plaque in the aorta and iliac arteries for CVD in postoperative colorectal cancer (CRC) patients who received surgical treatment between 2014 and 2015. CVD included coronary or cerebrovascular diseases which required treatment and new-onset CVD included peri-and postoperatively diagnosed CVDs or aggravated CVDs that required additional treatment during follow-up. Of the 2,875 patients included in this study, the prevalence of CVD was 8.9% (255/2875) and 141 (4.9%) developed new-onset CVD. Maximum arterial stenosis in the aorta or iliac arteries occurred in 40.8 ± 18.6% of patients with new-onset CVD and 11.6 ± 13.8% of patients without new-onset CVD (p < 0.001). The mean new-onset CVD-free survival time in patients with > 30% and < 30% stenoses were 52.5 [95% confidence intervals (CIs) 50.0-54.9] and 66.5 (95% CIs 66.2-66.8) months, respectively (p < 0.001). The area under the receiver operating characteristic curve of the maximal arterial stenosis for new-onset CVD was 0.911. These results suggest that CRC patients are at risk for developing new-onset CVD, which is associated with reduced survival. Atherosclerotic burden in the aorta or both iliac arteries may help predict future CVD events.

The Prevalence of Concomitant Abdominal Aortic Aneurysm and Cancer.

Cancers and abdominal aortic aneurysms (AAA) cause substantial morbidity and mortality and commonly develop in old age. It has been previously reported that AAA patients have a high prevalence of cancers, which has raised the question of whether this is a simple collision, association or causation. Clinical trials or observational studies with sufficient power to prove this association between them were limited because of the relatively low frequency and slow disease process of both diseases. We aimed to determine whether there is a significant association between AAA and cancers using nationwide data. The patients aged > 50 years and diagnosed with AAA between 2002 and 2015, patients with heart failure (HF) and controls without an AAA or HF matched by age, sex and cardiovascular risk factors were enrolled from the national sample cohort from the National Health Insurance claims database of South Korea. The primary outcome was the prevalence rate of cancers in the participants with and without an AAA. The secondary outcome was cancer-related survival and cancer risk. Overall, 823 AAA patients (mean (standard deviation) age, 71.8 (9.4) years; 552 (67.1%) men) and matching 823 HF patients and 823 controls were identified. The prevalence of cancers was 45.2% (372/823), 41.7% (343/823) and 35.7% (294/823) in the AAA, HF and control groups, respectively; it was significantly higher in the AAA group than in the control group (p < 0.001). The risk of developing cancer was higher in the AAA patients than in the controls (adjusted odds ratio (OR), 1.52 (95% confidence interval [CI], 1.24-1.86), p < 0.001) and in the HF patients (adjusted OR, 1.37 (1.24-1.86), p = 0.006). The cancer-related death rate was 2.64 times higher (95% CI, 2.22-3.13; p < 0.001) for the AAA patients and 1.63 times higher (95% CI, 1.37-1.92; p < 0.001) for the HF patients than for the controls. The most common causes of death in the AAA patients were cancer and cardiovascular disease. There was a significantly increased risk of cancer in the AAA than in the HF and control groups. Therefore, appropriate screening algorithms might be necessary for earlier detection of both diseases to improve long-term survival.