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.

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.

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.

Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer.

Fluid accumulation in the abdominal cavity is commonly found in advanced-stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single-cell RNA sequencing (scRNA-seq) of ascites cells from five patients with ovarian cancer, we identified seven cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype-specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand-receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long-term survival patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.

Increasing serum gamma-glutamyltransferase level accompanies a rapid increase in the incidence of endometrial cancer in Korea: A nationwide cohort study.

OBJECTIVE: This study aimed to determine the association of serum GGT levels with the risk of developing endometrial cancer. Women's obesity and menopausal status were also taken into account in our analysis. METHODS: We used a nationwide cohort to examine the association between serum GGT levels and endometrial cancer development in Korean women. Data were retrieved from the Korean National Health Insurance Service (NHIS) healthcare system. Women aged over 19 years who participated in the Korea National Health Screening Examination in 2009 and were not diagnosed with endometrial cancer 1-year post-examination were included in our study (n = 2,736,588). RESULTS: Obese (BMI, ≥25 kg/m2) women with increased GGT levels were at high risk of endometrial cancer (HR = 1.415, 95% CI: 1.236-1.621). Interestingly, in pre-menopausal women, high GGT level (Q4) was associated with the increased endometrial cancer risk only for obese women (HR = 1.482, 95% CI: 1.205-1.821). In post-menopausal women, only a high GGT level (Q4) was also associated with the increased cancer risk for obese women (HR = 1.313, 95% CI: 1.096-1.573). We observed a significant association between high GGT levels and increased risk of endometrial cancer in pre-menopausal women with abdominal obesity (WC, ≥85 cm) (HR = 1.647, 95% CI: 1.218-2.227). CONCLUSIONS: Increased GGT level is an independent risk factor of endometrial cancer, especially for post-menopausal women and obese pre-menopausal women. These results may suggest that serum GGT levels might be useful in the risk stratification of endometrial cancer. Adopting a healthy lifestyle for lowering serum GGT level is warranted, especially for women with a higher risk of developing endometrial cancer.

Impact of Chronic Kidney Disease Under Nephrology Care on Outcomes of Carotid Endarterectomy.

OBJECTIVE: This study aimed to investigate the impact of chronic kidney disease (CKD) and the delivery of nephrology care on outcomes of carotid endarterectomy (CEA). METHODS: This was a single centre, retrospective observational study. Between January 2007 and December 2014, 675 CEAs performed on 613 patients were stratified by pre-operative estimated glomerular filtration rate (eGFR) values (CKD [eGFR < 60 mL/min/1.73m2] and non-CKD [eGFR ≥ 60 mL/min/1.73m2] groups) for retrospective analysis. The study outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as fatal or non-fatal stroke, myocardial infarction, or all cause mortality, during the peri-operative period and within four years after CEA. RESULTS: The CKD group consisted of 112 CEAs (16.6%), and the non-CKD group consisted of 563 CEAs (83.4%). The MACE incidence was higher among patients with CKD compared with non-CKD patients during the peri-operative period (4.5% vs. 1.8%; p = .086) and within four years after CEA (17.9% vs. 11.5%; p = .066), with a non-statistically significant trend. In a subgroup analysis of patients with CKD under nephrology care (63/112, 56.3%; with better controlled risk factors and tighter medical surveillance by a nephrologist), patients with CKD without nephrology care (49/112, 43.8%), and non-CKD patients, the risk of both peri-operative (4.1% vs. 0.4%; p = .037) and four year post-operative (20.4% vs. 7.3%; p = .004) all cause mortality was statistically significantly higher among patients with CKD without nephrology care compared with non-CKD patients. However, there were no statistically significant differences between patients with CKD who received nephrology care and non-CKD patients in peri-operative and four year post-operative MACE occurrence, both in terms of the composite MACE outcome and the individual MACE components. CONCLUSION: Despite the higher risk of peri-operative and four year MACE after CEA among patients with CKD, and the statistically significantly higher peri-operative and four year post-operative all cause mortality rates among patients with CKD without nephrology care, patients with CKD under nephrology care had similar outcomes to non-CKD patients.

Effectiveness of Surgical Treatment with Complete Cyst Excision for Cystic Adventitial Disease of the Popliteal Artery.

BACKGROUND: Cystic adventitial disease is a rare, nonatherosclerotic disease that affects various arteries and veins, involving the formation of a mucinous cyst within the adventitia. The etiology of the cystic adventitial disease is currently unclear, with several hypotheses having been suggested. The purpose of this retrospective observational study was to evaluate the etiology of popliteal cystic adventitial disease based on imaging and surgical findings and to evaluate the efficacy of surgical treatment. METHODS: From April 2013 to January 2020, nine patients were diagnosed with the popliteal cystic adventitial disease and underwent surgical treatment. We performed complete resection of the cyst and the affected segment of the popliteal artery, followed by interposition with autologous reversed small saphenous vein or great saphenous vein. RESULTS: The resected adventitial cyst tissue was multilobular, filled with high-viscosity mucus. Pathologic examination of the surgical specimen revealed intramural cysts filled with gelatinous material located between the media and the adventitia, consistent with the clinical diagnosis of cystic adventitial disease. The median follow-up period was 27.5 months (range: 2-91 months). All patients underwent cyst excision with graft interposition, and the overall graft patency was 80.9 months (95% CI: 62.2-99.6 months). CONCLUSIONS: Computed tomography, magnetic resonance imaging, and surgical findings confirmed communication between the synovial cyst and arterial adventitia. It is recommended that priority be given to surgical resection and graft interposition because this can eliminate the disease's cause and reduce its recurrence.

Risk Factors for Early and Late Iliac Limb Occlusions of Stent Grafts Extending to the External Iliac Artery after Endovascular Abdominal Aneurysm Repair.

BACKGROUND: Iliac limb stent grafting to the external iliac artery (EIA) is a commonly performed procedure in various situation during endovascular abdominal aneurysm repair (EVAR). However, this procedure is associated with a risk of graft occlusion. We evaluated risk factors affecting occlusion among patients who underwent iliac limb stent-graft extension to the EIA. MATERIALS AND METHODS: We compared occluded limbs with patent limbs during the follow-up period using variables, including anatomical values, demographics, and other factors. Thereafter, we divided the occluded limbs into early and late occlusion subgroups. The main and subgroup analyses used the same variables. Survival analysis was performed to evaluate time-dependent risk factors for late limb occlusion. RESULTS: From 2007 to 2016, 766 iliac limbs from 383 patients who underwent EVAR were initially included in our analysis. Among them, 134 iliac limbs underwent limb extension to the EIA. The limb extension was a significant risk factor for occlusion (hazard ratio = 6.34, P < 0.001). Occlusion occurred in 10 patients who underwent iliac limb extension. The size of common iliac artery (CIA) was associated with occlusion. The most significant factor was iliac bifurcation diameter (patent vs. occluded limbs, 21.6 ± 7.6 vs. 27.5 ± 9.5 mm, P = 0.005). Subgroup analysis revealed that the CIAs of the early occlusion subgroup were generally more tortuous (1.16 ± 0.33 vs. 1.47 ± 0.25, P = 0.091) and longer (53 ± 24 vs. 74 ± 9, P = 0.01) than those of the patent limb group. In addition, the EIA diameters of the late occlusion subgroup were narrower than those of the patent limb group (10.9 ± 1.6 mm vs. 9.1 ± 0.8 mm, P = 0.011). Using the log-rank test, those patients with an EIA diameter narrower than 10.1 mm had a higher risk for late limb occlusion (log-rank χ2 = 5.73, P = 0.017) and the patients who did not take at least a single antiplatelet agent had a significantly higher chance of limb occlusion (log-rank χ2 = 11.029, P = 0.001). In addition, the patients who did not take a statin had a higher risk for late limb occlusion (log-rank χ2 = 7.41, P = 0.007). CONCLUSIONS: Among patients who underwent EVAR with iliac limb extension, the CIA length affected early limb occlusion and predisposed patients to vessel injury or stent-graft kinking, and there was the possibility that CIA tortuosity was associated with a higher risk. The late occlusion subgroup had narrower EIAs than the patent limb group. Appropriate antiplatelet and statin therapy is expected to play a key role in the prevention of late limb occlusion after EVAR.

Surgical Repair of Juxtarenal Abdominal Aortic Aneurysms and safety of Suprarenal Aortic Clamping.

BACKGROUND: Juxtarenal abdominal aortic aneurysm (AAA) comprises 15-20% of all AAAs and often requires open surgical repair (OSR) due to anatomical limitations associated with endovascular aneurysm repair (EVAR), particularly in the case of hostile proximal necks. This study aimed to evaluate short- and long-term outcomes of suprarenal clamping during OSR of juxtarenal AAAs and compare the outcomes of this technique with those of infrarenal clamping for AAAs. METHODS: Between January 1 2014, and December 31 2016, 289 consecutive patients aged ≥40 years underwent primary repair for infrarenal AAAs, including 141 OSRs and 148 EVARs. Of the 141 patients, 20 were excluded and totally, 121 patients were included. RESULTS: All patients had fusiform-type AAAs and were divided into infrarenal (N = 98) or suprarenal (N=23) clamp groups. The mean follow-up period was 51.4 months (95% CI: 48.6-54.2). Mean survival time was 51.4 months (95% CI: 48.6-54.2). Thirty-day mortality was 0.8%, and there was no significant difference between two groups (P > .999). Renal complication in infrarenal clamp group was 4.1% and suprarenal clamp group was 4.3% (P > .999). Old age (HR: 1.084; 95% CI: 1.025-1.147; P=.005) and high ASA score (HR: 2.361; 95% CI: 1.225-4.553; P = .010) were substantially associated with in-hospital complications. CONCLUSIONS: Although endovascular procedures for repairing juxtarenal AAAs, such as fenestrated EVAR, have been developed, surgical repair is the standard treatment for juxtarenal AAAs. Morbidity and mortality due to open surgery were not higher in the juxtarenal AAA group than in the infrarenal AAA group. Therefore, need for suprarenal clamp should not preclude OSR and also there is continued need for training in surgical exposure of juxtarenal AAA and OSR.

Outcomes of arteriovenous access among cancer patients requiring chronic haemodialysis.

BACKGROUND: There are limited data focusing specifically on the types of arteriovenous (AV) access used and outcomes of AV access among cancer patients as a consequence of cancer. We aimed to describe outcomes of AV access among cancer patients requiring chronic haemodialysis, and also to compare outcomes between patients with and without cancer. METHODS: In this single-centre, retrospective, observational cohort study, 84 patients diagnosed with cancer before AV access placement were included; we analysed outcomes of AV access among these patients and compared these outcomes with our previous results. The study endpoints were AV access patency and early failure, defined as AV access abandonment within 12 months after AV access placement. RESULTS: Various cancer types, stages, and treatments were identified in our analysis. Autologous arteriovenous fistulas (AVFs) were used for 92.9% of this study population. Using our previous results for comparison, we found no significant difference in death-censored primary (P = 0.546) and secondary (P = 0.266) patency of AV access between patients with and without cancer; however, the rate of early AVF failure was statistically significantly higher among cancer patients (25.6% vs 13.9%; P = 0.008), and the most common cause of AVF failure was patient death. The rate of early failure was significantly higher among patients with advanced-stage cancer (59.1%) than among those with early-stage cancer (12.9%) (P <  0.001). CONCLUSIONS: Although AV access patency rates were similar among patients with and without cancer in the death-censored analysis, cancer patients were more prone to early AVF failure, mainly due to cancer-associated deaths, and this consideration needs to be carefully balanced against individual patients' life expectancies, according to cancer type and stage.

Obturator bypass using a ringed polytetrafluoroethylene graft for inguinal graft infection.

OBJECTIVE: Inguinal vascular graft infections are high-risk events that cannot be controlled medically but require surgical intervention. This study reviewed the long-term clinical outcomes of obturator bypass using a ringed polytetrafluoroethylene graft for inguinal graft infection. METHODS: A total of eight consecutive patients who underwent obturator bypass using a ringed polytetrafluoroethylene graft for inguinal prosthetic graft infection at a single medical center between January 2006 and October 2017 were retrospectively analyzed. The demographics, clinical characteristics, surgical procedure, and clinical outcomes were evaluated. RESULTS: There was no perioperative death; however, there were three operative complications. On the 1st and 9th postoperative day, two patients underwent hematoma evacuation in the pelvic cavity, and the other patient underwent suture reinforcement for partial dehiscence of the distal anastomosis on the 49th postoperative day. The median length of hospital stay was 14.5 (range, 7-29) days. Only one graft occlusion was observed at postoperative month 40; however, there were no ischemic symptoms. There were no limb amputations and postoperative deaths during the long-term follow-up period. There were no infections of the previous residual and obturator bypass grafts and inguinal infection during the follow-up period of 49 (range, 7-154) months. CONCLUSION: Obturator bypass for inguinal graft infection is feasible and durable with excellent long-term outcomes. However, perioperative bleeding should be taken into consideration.

Relationship of Lower-extremity Deep Venous Thrombosis Density at CT Venography to Acute Pulmonary Embolism and the Risk of Postthrombotic Syndrome.

Background Acute deep venous thrombi (DVT) have higher Hounsfield unit values than chronic (bland) thrombi at CT venography. Purpose To determine the relationship between DVT thrombus density found on CT venography images to the presence of acute pulmonary embolism (PE) and the future risk of postthrombotic syndrome (PTS) in patients with DVT. Materials and Methods In this retrospective study, patients were divided into two groups: PE with DVT group and DVT-only group. Wells scores were recorded. Thrombus density ratios were calculated (DVT thrombus Hounsfield units/surrounding vein Hounsfield units). The presence or absence of PTS was determined from the results of the Venous Insufficiency Epidemiologic and Economic Study on Quality of Life (VEINES-QOL) questionnaires given to the patients with DVT. Statistical analyses used receiver operating characteristic curves and Spearman correlation analyses. Results Eighty-six patients were included; the mean age was 60 years ± 17 (51 men; PE with DVT group, 54 patients [63%]; DVT-only group, 32 patients [37%]). The mean thrombus density ratio was significantly higher in the PE with DVT group than in the DVT-only group (53.6% ± 12.4 [standard deviation] vs 42.8% ± 11.9, respectively; P < .001). At multivariable analysis, Wells score greater than 4 (odds ratio, 12.0; 95% confidence interval [CI]: 3.0, 47; P < .001) and higher thrombus density ratio (odds ratio, 1.1; 95% CI: 1.0, 1.2; P = .001) were independent predictors of PE. The diagnostic performance for the thrombus density ratio (area under the receiver operating characteristic curve, 0.74; 95% CI: 0.63, 0.85; P < .001) may be more discriminative than that of the Wells score (area under the receiver operating characteristic curve, 0.70; 95% CI: 0.59, 0.81; P = .002) for the presence of PE. In subgroup analysis, the thrombus density ratio and VEINES-QOL score were correlated (r = 0.61; 95% CI: 0.30, 0.80; P < .001). Conclusion Deep venous thrombosis (DVT) density ratio at CT venography was associated with acute pulmonary embolism in patients with lower-extremity DVT. © RSNA, 2019 Online supplemental material is available for this article.

Comparison of outcomes after carotid endarterectomy between type 2 diabetic and non-diabetic patients with significant carotid stenosis.

BACKGROUND: We aimed to compare early and late outcomes after carotid endarterectomy (CEA) between Korean type 2 diabetic and non-diabetic patients and to investigate the impact of diabetes on the overall incidence of cardiovascular events after CEA. METHODS: We retrospectively analyzed 675 CEAs, which were performed on 613 patients with significant carotid stenosis between January 2007 and December 2014. The CEAs were divided into a type 2 diabetes mellitus (DM) group (n = 265, 39.3%) and a non-DM group (n = 410, 60.7%). The study outcomes included the incidence of major adverse events (MAEs), defined as fatal or nonfatal stroke or myocardial infarction or all-cause mortality, during the perioperative period and within 4 years after CEA. RESULTS: Patients in the DM and non-DM groups did not differ significantly in the incidence of MAEs or any of the individual MAE manifestations during the perioperative period. However, within 4 years after CEA, the difference in the MAE incidence was significantly greater in the DM group (P = 0.040). Analysis of the individual MAE manifestations indicated a significantly higher risk of stroke in the DM group (P = 0.006). Multivariate analysis indicated that diabetes was not associated with MAEs or individual MAE manifestations during the perioperative period, whereas within 4 years after CEA, diabetes was an independent risk factor for MAEs overall (hazard ratio [HR], 1.62; 95% confidence interval [CI] 1.06-2.48; P = 0.026) and stroke (HR, 2.55; 95% CI 1.20-5.41; P = 0.015) in particular. CONCLUSIONS: Diabetic patients were not at greater risk of perioperative MAEs after CEA; however, the risk of late MAE occurrence was significantly greater in these patients. Within 4 years after CEA, DM was an independent risk factor for the occurrence of MAEs overall and stroke in particular.

New predictors of aneurysm sac behavior after endovascular aortic aneurysm repair.

OBJECTIVES: This study aimed to identify new predictors of sac behavior after endovascular aortic aneurysm repair (EVAR) and to investigate whether sac behavior is associated with long-term clinical outcomes. METHODS: A total of 168 patients undergoing successful EVAR for abdominal aortic aneurysms with CTA follow-up of at least 1 year were included. Predictors of aneurysm sac behavior and its impact on long-term clinical outcomes were retrospectively analyzed. RESULTS: According to sac behavior, eligible patients were stratified into the sac regression group (n = 79, 47.0%) and the sac non-regression group (n = 89, 53.0%). Patients in the regression group were younger (p = 0.036) and more likely to take sarpogrelate hydrochloride postoperatively (p = 0.011) than those in the non-regression group. The incidence of postimplantation syndrome (PIS) was significantly higher in the regression group (p = 0.005). On multivariate analysis, sac regression was more likely to occur in those with PIS (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.07-2.64; p = 0.023) and less likely to occur in those with transient type II endoleaks (HR, 0.43; 95% CI, 0.20-0.95; p = 0.037) and higher thrombus density within the sac on follow-up CTA (HR, 0.97; 95% CI, 0.95-0.99; p = 0.013). Non-regression of the sac was associated with significantly higher rates of re-intervention during the follow-up period (p = 0.001). CONCLUSIONS: In addition to type II endoleaks, PIS and thrombus density are new predictors of aneurysm sac behavior, and sac regression is significantly associated with lower rates of re-intervention. KEY POINTS: • After endovascular aortic aneurysm repair (EVAR), patients with sac regression were younger and more likely to take sarpogrelate hydrochloride postoperatively than those with sac non-regression. • The incidence of postimplantation syndrome (PIS) was significantly higher in patients with sac regression. • In our analysis, PIS and thrombus density within the sac were newly identified predictors of aneurysm sac behavior after EVAR.

Clinical Outcomes of Surgical Resection for Leiomyosarcoma of the Inferior Vena Cava.

BACKGROUND: Leiomyosarcoma of the inferior vena cava (IVC) is a rare mesenchymal tumor with poor prognosis. Surgical resection is currently the only potential curative treatment. This study analyzed long-term outcomes of patients who underwent surgical resection of leiomyosarcoma of the IVC. METHODS: The charts of 12 patients who underwent surgical resection of leiomyosarcoma of the IVC from January 1999 to December 2017 at a single center were retrospectively reviewed. RESULTS: Of the 12 patients, 10 (83.3%) were women. Median age at diagnosis was 63 years (range 42-67). Leiomyosarcoma involved the middle segment of the IVC in 9 patients (75.5%) and the lower segment in 3 (25.0%). Ten patients underwent IVC resection, followed by reconstruction with polytetrafluoroethylene in 9 patients and a bovine patch in 1. Two patients underwent IVC resection followed by ligation of the IVC. Eleven patients (91.7%) underwent grossly radical resection, with 1 (8.3%) having peritoneal seeding at the first operation. After resection, 8 patients received adjuvant chemotherapy and 7 received adjuvant radiotherapy. No patient experienced regional recurrence at the resection margins of the IVC, but 9 patients (75.5%) experienced distant metastases to sites such as the lungs, liver, bones, pelvis, peritoneum, and scalp. Median follow-up was 41 months (range 6-149). Median disease-free survival (DFS) was 49 months (range 8-88), and median overall survival (OS) was 127 months (range 25-149). The 3- and 5-year DFS rates were 77.9% and 39.0%, respectively, and the 3-, 5-, and 10-year OS rates were 87.5%, 75.0%, and 56.3%, respectively. CONCLUSIONS: Although there is no established treatment for leiomyosarcoma of the IVC and metastasis after surgery is frequent, surgical resection followed by chemotherapy and/or radiotherapy can enhance long-term survival.

Effects of patient age on patency of chronic hemodialysis vascular access.

BACKGROUND: In this single-center, retrospective observational study, we assessed the long-term patency of vascular access (VA) after first VA placement to uncover independent risk factors associated with VA patency in Asian hemodialysis (HD) patients stratified by age. We also investigated factors associated with VA patency among older HD patients according to the type of VA in the overall study population. METHODS: The study period was from January 2011 to December 2013. A total of 651 chronic HD patients with confirmed first upper-extremity VA placement were enrolled, and their records were analyzed retrospectively. A total of 445 patients (68.4%) made up the nonelderly group (< 65 years), and 206 patients (31.6%) were in the elderly group (≥ 65 years). Study outcomes were defined as primary or secondary VA patency. RESULTS: Autologous arteriovenous fistula (AVF) was more common in the nonelderly group (P <  0.01). Kaplan-Meier curve survival analysis indicated that primary patency was longer in the nonelderly group (P <  0.01); secondary patency, however, was similar between groups (P = 0.37). The multivariate analysis of factors associated with primary VA patency revealed that increased age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03; P <  0.01) was associated with shorter primary patency, and AVF (HR, 0.38; 95% CI, 0.28-0.51; P <  0.01) was associated with longer primary patency. AVF (HR, 0.57; 95% CI, 0.37-0.87; P = 0.010) and diabetes mellitus (HR, 1.56; 95% CI, 1.07-2.29; P = 0.02) were independently associated with longer and shorter secondary patency periods, respectively; however, increased age was not a risk factor for decreased secondary patency. CONCLUSIONS: Increased age was associated with shorter primary patency but not secondary patency, whereas AVF placement was associated with longer primary and secondary patency. Considering the similar rates of secondary patency between groups and the superior patency of AVF compared to arteriovenous graft, a fistula-first strategy should be applied to appropriate older patients.

Resveratrol as a Tumor-Suppressive Nutraceutical Modulating Tumor Microenvironment and Malignant Behaviors of Cancer.

Tumor-suppressive effects of resveratrol have been shown in various types of cancer. However, regulation of tumor microenvironment by resveratrol is still unclear. Recent findings suggest resveratrol can potentiate its tumor-suppressive effect through modulation of the signaling pathways of cellular components (fibroblasts, macrophages and T cells). Also, studies have shown that resveratrol can suppress malignant phenotypes of cancer cells acquired in response to stresses of the tumor microenvironment, such as hypoxia, oxidative stress and inflammation. We discuss the effects of resveratrol on cancer cells in stress environment of tumors as well as interactions between cancer cells and non-cancer cells in this review.

Pro-inflammatory M1 macrophage enhances metastatic potential of ovarian cancer cells through NF-κB activation.

Obesity is a serious health problem and critically related to poor prognosis in cancer, presumably through induction of chronic inflammation. The major culprit for cancer progression in obesity is presumed to be macrophages. Accumulation of macrophages in adipose tissue due to obesity induced chronic inflammation has been observed. However, obesity-induced macrophage accumulation related to ovarian cancer progression remains unclear. So, the role of macrophage in cancer progression is needed to be further defined for therapeutic intervention. Here we determined the effect of macrophage type 1 (M1 macrophage) on ovarian cancer cells in relation to the metastasis. Ovarian cancer cell lines (PA-1, SKOV3) and monocyte-derived macrophages were used in this study. Treatment with M1 macrophage conditioned media on ovarian cancer cells increased the metastatic potential, such as migration and invasion capabilities. Interestingly, upon treatment with M1 macrophage conditioned media, nuclear translocation of NF-κB, p60, and p50, from the cytosol was enhanced together with increased transcriptional activity of the NF-κB. Pre-treatment with TPCK (NF-κB inhibitor) and NF-κB siRNA on ovarian cancer cells suppressed M1 macrophage-induced metastatic potential. Furthermore, Treatment of TNF-α on ovarian cancer cells showed NF-κB activation. Co-treatment with TNF-α inhibitor, etanercept, and M1 macrophage conditioned media on ovarian cancer cell lines reversed M1 macrophage conditioned media induced NF-κB activation. Taken together, TNF-α released from M1 macrophage increased metastatic potential in ovarian cancer cells through the activation of NF-κB signaling pathway. These results provide a new insight into the critical role of M1 macrophage in the tumor microenvironment in ovarian cancer.

Quantitative analysis of the effect of end-tidal carbon dioxide on regional cerebral oxygen saturation in patients undergoing carotid endarterectomy under general anaesthesia.

AIMS: Regional cerebral oxygen saturation (rSO2 ) is currently the most used measure in clinical practice to monitor cerebral ischaemia in patients undergoing carotid endarterectomy (CEA). Although end-tidal carbon dioxide (PET CO2 ) is known as a factor that influences rSO2 , the relationship between PET CO2 and rSO2 has not been quantitatively evaluated in patients with severe arteriosclerosis. This study aimed to evaluate the effect of PET CO2 on rSO2 in patients undergoing CEA under general anaesthesia. METHODS: The intervention to change PET CO2 was conducted between skin incision and clamping of the carotid artery. The rSO2 values were observed by changing PET CO2 in the range of 25-45 mmHg. The PET CO2 -rSO2 relationship was characterized by population analysis using a turnover model. RESULTS: In total, 1651 rSO2 data points from 30 patients were used to determine the pharmacodynamic characteristics. Hypertension (HTN) and systolic blood pressure (SBP) were significant covariates on the slope factor in the stimulatory effect of PET CO2 on rSO2 and fractional turnover rate constant (kout ), respectively. The estimates of the parameters were kout (min-1 ): 3.59 for SBP <90 mmHg and 0.491 for SBP ≥90 mmHg, slope: 0.00321 for patients with HTN and 0.00664 for patients without HTN. CONCLUSION: The presence of HTNattenuates the response of rSO2 after a change in PET CO2 . When cerebral blood flow is in a state of decline caused by a decrease in SBP to <90 mmHg, the response of rSO2 to PET CO2 is increased. It is advisable to maintain SBP >90 mmHg in patients with HTNduring CEA.