Clinical outcomes and challenges of surgical extirpation for carotid body paraganglioma in South Korea: a single-center retrospective study.

BACKGROUND: Carotid body paraganglioma (CBP) is a rare, highly vascularized, and slow-growing neuroendocrine tumor. Surgical resection is the definitive treatment for CBP, however, it remains challenging due to the tumor's proximity to critical blood vessels and cervical cranial nerves. This study aimed to document the characteristics of CBP and examine the clinical outcomes of patients following surgical extirpation of CBP. METHODS: This is a single-center retrospective review analyzed patients who underwent CBP extirpation. We examined the patient demographics, preoperative clinical features, tumor characteristics, levels of catecholamines and their metabolites in the serum and urine. Surgeries were performed by one vascular surgeon with follow-ups at 1,3,6 months and yearly thereafter. Logistic regression analysis was conducted to identify risk factors associated with the occurrence of either permanent or temporary cervival cranial nerve palsy (CNP). RESULTS: From September 2020 to February 2023, this study examined 21 cases of CBP removal surgeries that were carried out in 19 patients. The mean age of the patients was 38.9 ± 10.9 years and the percentage of males was 57.1% (n = 12). The most common preoperative clinical feature was painless neck mass (n = 12; 57.1%). Complete resection was achieved in 20 cases; excluding one case with pathologically proven sclerosing paraganglioma. Vascular procedures were performed in four cases (ECA resection, n = 2; primary repair of ICA tear without carotid shunting, n = 1; and ICA patch angioplasty with carotid shunting, n = 1). Temporary cranial neurologic complications, specifically aspiration and hoarseness occurred in four (19.0%), and three (14.3%) cases, respectively. Hoarseness associated with permanent CNP persisted for more than 6 months in two cases (9.5%). No recurrence or mortality was observed during the follow-up period. CONCLUSIONS: Surgical resection is the primay treatment approach for CBP; however, it poses risks of vascular or cervical CNP. The intraoperative estimated blood loss was the only identified risk factor for CNP.

Impact of Serum Albumin Levels and Body Mass Index on Outcomes of Open Abdominal Aortic Aneurysm Repair in Korean Population.

BACKGROUND: Although obese patients seem to be susceptible to chronic diseases, obesity paradox has been observed in the field of vascular surgery, in which many previous studies have reported that overweight patients have good postoperative outcomes and underweight patients have poor postoperative outcomes. The purpose of our study is to evaluate the impact of body mass index (BMI) and serum albumin levels, which are evaluated as indicators of nutritional status, on outcomes of open abdominal aortic aneurysm (AAA) repair. METHODS: We reviewed the vascular surgery database of a single tertiary referral center for all patients who underwent open AAA repair due to degenerative etiology from 1996 to 2021. To analyze the effect of BMI, patients were classified into 4 groups according to the Asian-Pacific classification of BMI: underweight (UW) (<18.5 kg/m2), normal weight (NW) (18.5-22.9 kg/m2), overweight (OW) (23-24.9 kg/m2), and obese (OB) (≥25 kg/m2). The χ2, Fisher's exact, and Kruskal-Wallis tests were used to compare demographics, comorbidities, radiologic findings, surgical details, and 1-year mortality rates between the 4 groups. We also compared the preoperative serum albumin levels of each group to assess nutritional status indirectly. Cox's proportional hazards model was performed to determine factors associated with mortality. A Kaplan-Meier survival analysis was performed, and the differences were analyzed by a log-rank test. We did not perform an analysis for 30-day mortality because cases of 30-day mortality in UW patients were rare due to the unbalanced distribution of the number of patients in the 4 groups. RESULTS: Among a total of 678 patients, 22 were classified as UW (3.2%), 200 as NW (29.5%), 183 as OW (27.1%), and 273 as OB (40.1%). The median age was 70 (64-75) years and 577 of 678 (85.1%) patients were male gender. Higher serum albumin level was associated with decreased 1-year mortality (hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.15-0.63; P = 0.001). UW patients had a higher 1-year mortality rate than NW patients (HR, 3.67; 95% CI, 1.02-13.18; P = 0.046). OB patients had a lower overall mortality rate than NW patients (HR, 0.73; 95% CI, 0.53-1; P = 0.05). CONCLUSIONS: Low BMI (<18.5 kg/m2) and low serum albumin level were associated with poor 1-year survival after elective open AAA repair. These patients also need more careful preoperative intervention, like weight gain or nutritional support, for better outcomes. The obesity paradox existed in our study; high BMI (≥25 kg/m2) was associated with better overall survival after elective open AAA repair.

Integrated proteogenomic characterization of glioblastoma evolution.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinoma.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. FINDINGS: RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. INTERPRETATION: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. FUNDING: This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research.

Ruptured Pancreaticoduodenal Artery Aneurysm in a Patient With Celiac Artery Dissection: A Case Report.

Unlike other visceral artery aneurysms, pancreaticoduodenal artery aneurysms (PDAAs) should be treated regardless of their size. There are no reports on PDAA associated with celiac artery (CA) dissection. We, here, report the case of a patient with a ruptured PDAA with concomitant CA dissection. A 44-year-old Korean man presented to the emergency room of another hospital 29 days ago due to a sudden onset of abdominal pain. Contrast-enhanced abdominal computed tomography (CT) revealed a large right retroperitoneal hematoma and CA dissection. Subsequently, aortography revealed no specific bleeding focus. He underwent conservative treatment for 16 days, including a transfusion, and then was referred to us. His abdominal CT angiography revealed a diminishing retroperitoneal hematoma, a 7 mm × 8 mm PDAA at the anterior inferior pancreaticoduodenal artery aneurysm (PDA), and CA dissection. Selective celiac angiography revealed sluggish and diminished blood flow to the true lumen of the CA, and the hepatic, gastroduodenal, and splenic arteries were supplied by collaterals arising from the superior mesenteric artery (SMA). We performed elective coil embolization of the anterior PDA using the right femoral approach.We believe that postprocedural surveillance is required after CA dissection because of the potential risk of recurrent PDAA. Additionally, we suggest that hidden PDAA rupture should be considered for spontaneous retroperitoneal bleeding.

The Impact of age and outcomes of high-risk patients on carotid revascularization.

OBJECTIVES: To validate the accuracy of high-risk criteria for carotid endarterectomy (CEA) and analyze the correlation between age and outcome of CEA and carotid artery stenting (CAS) in risk groups. METHODS: We reviewed a prospectively managed vascular surgery database in a single tertiary referral center, and 2482 internal carotid arteries (ICAs) had undergone carotid revascularization from November 1994 to December 2021. To validate high-risk criteria for CEA, patients were classified as high risk (Hr) and normal risk (Nr). Subgroup analysis was performed with patients older or younger than 75 years to investigate the relationship between age and outcome in each group. Primary endpoints were 30-day outcomes including stroke, death, stroke/death, myocardial infraction (MI), and major adverse cardiovascular events (MACEs). RESULTS: A total of 2345 ICAs in 2256 patients were enrolled. The number of patients in the Hr group was 543 (24%) and the number in the Nr group was 1713 (76%). CEA and CAS were performed on 1384 (61%) and 872 (39%) patients, respectively. The 30-day stroke/death rate was higher with CAS than CEA in both the Hr (1.1% vs. 3.9%, p = 0.032) and Nr (1.2% vs. 6.9%, p < 0.001) groups. In unmatched logistic regression analysis of the Nr group (n = 1778), the rate of 30-day stroke/death (OR, 5.575; 95% CI, 2.922-10.636; p < 0.001) was higher for CAS than CEA. In propensity score matching of the Nr group, the rate of 30-day stroke/death (OR, 5.165; 95% CI, 2.391-11.155; p < 0.001) was also higher for CAS than CEA. In the age <75 subgroup of the Hr group (n = 428), CAS was associated with higher 30-day stroke/death (OR, 14.089; 95% CI, 1.314-151.036; p = 0.029). In the age ≥75 subgroup of the Hr (n = 139), there was no difference in 30-day stroke/death between CEA and CAS. In the age <75 subgroup of the Nr group (n = 1318), 30-day stroke/death (OR, 6.300; 95% CI, 2.797-14.193; p < 0.001) was higher in CAS. In the age ≥75 subgroup of the Nr group (n = 460), 30-day stroke/death (OR, 6.468; 95% CI, 1.862-22.471; p = 0.003) was higher in CAS. CONCLUSIONS: In patients older than 75 years in the Hr group, there were relatively poor 30-day treatment outcomes in both CEA and CAS. Alternative treatment is needed that can expect better outcomes in older high-risk patients. In the Nr group, CEA has a significant benefit compared with CAS, and CEA should be recommended more to these patients.

Treatment results of carotid endarterectomy and carotid artery stenting for patients with radiation-induced carotid stenosis.

Purpose: Exposure to ionizing radiation over the head and neck accelerates atherosclerotic changes in the carotid arteries. Owing to the characteristics of radiation-induced carotid stenosis (RICS), the results regarding the optimal revascularization method for RICS vary. This study compared treatment outcomes between carotid endarterectomy (CEA) and carotid artery stenting (CAS) in RICS. Methods: This was a single-center retrospective review of consecutive patients who underwent CEA or CAS for carotid stenosis. RICS was defined as carotid stenosis (>50%) with the prior neck irradiation for cancer treatment on either side. For the analyses, demographics, comorbid conditions, carotid lesion characteristics based on imaging studies, surgical complications, neurologic outcomes, and mortality during the follow-up period were reviewed. To compare CEA and CAS results in RICS, a 1:1 propensity score matching was applied. Results: Between November 1994 and June 2021, 43 patients with RICS and 2,407 patients with non-RICS underwent carotid revascularization with CEA or CAS. RICS had fewer atherosclerotic risk factors and more frequent severe carotid stenosis and contralateral carotid occlusions than non-RICS. CAS was more commonly performed than CEA (22.9% vs. 77.1%) for RICS due to more frequent unfavorable carotid anatomy (0 vs. 16.2%). Procedure-related complications were more common in the CEA than in the CAS. However, there was no significant difference in neurologic outcomes and restenosis rates between CEA and CAS in RICS. Conclusion: Considering its lesion characteristics and cumulative incidence, RICS requires more attention than non-RICS. Although CAS has broader indications for RICS, CEA has shown acceptable results if selectively performed.

Targeted Inhibition of O-Linked ß-N-Acetylglucosamine Transferase as a Promising Therapeutic Strategy to Restore Chemosensitivity and Attenuate Aggressive Tumor Traits in Chemoresistant Urothelial Carcinoma of the Bladder.

Acquisition of acquired chemoresistance during treatment cycles in urothelial carcinoma of the bladder (UCB) is the major cause of death through enhancing the risk of cancer progression and metastasis. Elevated glucose flux through the abnormal upregulation of O-linked ß-N-acetylglucosamine (O-GlcNAc) transferase (OGT) controls key signaling and metabolic pathways regulating diverse cancer cell phenotypes. This study showed that OGT expression levels in two human UCB cell models with acquired resistance to gemcitabine and paclitaxel were significantly upregulated compared with those in parental cells. Reducing hyper-O-GlcNAcylation by OGT knockdown (KD) markedly facilitated chemosensitivity to the corresponding chemotherapeutics in both cells, and combination treatment with OGT-KD showed more severe growth defects in chemoresistant sublines. We subsequently verified the suppressive effects of OGT-KD monotherapy on cell migration/invasion in vitro and xenograft tumor growth in vivo in chemoresistant UCB cells. Transcriptome analysis of these cells revealed 97 upregulated genes, which were enriched in multiple oncogenic pathways. Our final choice of suspected OGT glycosylation substrate was VCAN, S1PR3, PDGFRB, and PRKCG, the knockdown of which induced cell growth defects. These findings demonstrate the vital role of dysregulated OGT activity and hyper-O-GlcNAcylation in modulating treatment failure and tumor aggression in chemoresistant UCB.

Ethylene oxide burn in a chemical plant worker: a case report.

BACKGROUND: Ethylene oxide is a chemical agent that is widely used for the sterilization of medical equipment and the manufacture of chemicals. Although ethylene oxide burns are frequent and can be severe, many workers are unaware of their risks. CASE PRESENTATION: A 45-year-old man presented with painful exudative lesions on the right foot after working with ethylene oxide solution in a chemical plant. The patient stated that the solution had percolated through his shoe and he had not washed the solution off for 5 hours. Symptoms, including pain and erythema, appeared after a delay of more than 12 hours from the time of initial exposure. The skin of his right foot was irrigated with saline and covered with a wet dressing and topical antibiotics in the emergency department. The patient was followed up for 4 weeks at an outpatient clinic. CONCLUSIONS: Ethylene oxide causes skin irritation, dermatitis, and burns in severe cases. Since skin reactions can be delayed for more than 12 hours after exposure, it is important to remove contaminated shoes and clothing immediately and wash the exposed area even in the absence of symptoms. It is also necessary to provide the appropriate protective equipment and educate workers on the dangers of ethylene oxide.

Mortality after Use of Paclitaxel-Coated Balloons Correlates with Total Cumulative Dosage of Paclitaxel in Real-World Analysis.

This study used independent, real-world, patient-level data to examine whether the dosage or frequency of paclitaxel exposure correlated with mortality during follow up. We conducted a retrospective analysis of patients treated with a drug-coated balloon (DCB) for an atherosclerotic femoropopliteal lesion from February 2013 to December 2018, excluding patients with non-atherosclerotic lesions or restenosis after DCB treatment in another hospital. We investigated the causes of death, comorbidities (including cancer status), and the initial and total cumulative dosages and frequency of paclitaxel use. To determine whether the dosage or frequency of paclitaxel exposure affected mortality during follow up, we analyzed the risk factors for all-cause death by conducting a time-dependent Cox regression analysis that considered demographics, comorbidities, lesion and procedural characteristics, and paclitaxel exposure data (dosage and frequency). Our analysis examined 225 patients (mean age 71 ± 9 years, range 38-93 years, male 81%). During a mean follow-up duration of 35 months (range 1-89 months), 56 patients (24.9%) died from cardiac disorders (16%, including acute myocardial infarction, heart failure, or sudden cardiac arrest), malignancy (14.3%), respiratory failure with pneumonia (12.5%), septic shock (12.5%), or another cause. Univariable and multivariable Cox regression analyses identified age (hazard ratio, HR, 1.057; 95% confidence interval, CI, 1019-1096; p = 0.0032), critical limb ischemia (CLI) (HR, 4135; 95% CI, 2171-7876; p < 0.0001), and the total dosage of paclitaxel (mg) (HR, 1.040; 95% CI, 1006-1074; p = 0.0210) as predictors of mortality during follow up. The subgroup analysis found that the total dosage of paclitaxel (mg) was also a predictor of mortality during follow up in the CLI group (HR, 1.046; 95% CI, 1007-1087, p = 0.0198). The estimated cut-off value of total cumulative paclitaxel dosage for predicting mortality was 12 mg as evaluated by minimum p value approach. This patient-level analysis identified the total cumulative dosage of paclitaxel as a predictor of mortality after the use of paclitaxel-coated balloons. Our results provide limited information about the potential dose-response relationship underlying paclitaxel-associated mortality concerns.

Comparable surgical outcomes of abdominal aortic aneurysm repair in patients with and without Marfan syndrome.

OBJECTIVE: Marfan syndrome (MFS) affects the cardiovascular system. Aortic root aneurysm is a pathognomonic feature of MFS; however, the abdominal aorta is rarely affected. A consensus on surveillance for the abdominal aorta in patients with MFS has not been established. In the present study, we compared the outcomes after open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) in patients with and without MFS. METHODS: We conducted a retrospective, single-center cohort study from 2003 to 2020. We reviewed and compared 28 patients with MFS and 426 patients without MFS who had undergone OSR for AAAs. The baseline characteristics, medical comorbidities, previous cardiovascular surgery, anatomic features of the AAAs, and surgical treatment outcomes were compared between the two groups. RESULTS: The patients with MFS were younger than those without MFS at the AAA diagnosis (47.2 ± 12.3 vs 70.6 ± 7.9 years; P < .001). The proportion of women was also greater for those with MFS (46.4% vs 15.7%; P < .001). The AAAs were most often located at the infrarenal aorta in both groups. However, thoracoabdominal AAAs were more often found among patients with MFS (10.7% vs 0.9%; P < .012). The proportion of symptomatic patients was lower in the MFS group (3.6% vs 21.6%; P = .022). The maximum median diameter of the AAA at surgery was smaller in the patients with MFS (52 mm vs 58 mm; P = .001). However, concomitant aortic dissection (32.1% vs 3.3%; P < .001) was more prevalent among the patients with MFS. Consequent aneurysmal changes in the iliac artery after AAA repair were more frequent in the patients with MFS (7.1% vs 0%; P = .004). No significant differences were found in 30-day or overall mortality between the patients with and without MFS during a median follow-up period of 71 months (interquartile range, 24.7-121.1 months) and 26.7 months (interquartile range, 7.4-69.5 months), respectively. CONCLUSIONS: The surgical outcomes of OSR for AAAs for patients with MFS were not significantly different from those for patients without MFS in a well-established surveillance program of MFS.

Culture-Negative Mycotic Aortic Aneurysms Probably Have a Less Severe Clinical Nature Than Culture-Positive Counterparts.

BACKGROUND: Mycotic aortic aneurysm constitutes a potentially devastating disease that necessitates prompt suspicion and diagnosis. There is no exact consensus for treatment, but removal of infected tissues and prolonged use of antimicrobials based on the identified causative microorganisms seem widely acceptable and have been similarly practiced worldwide. However, some patients still show no identified microorganisms. In this study, we sought to determine whether there are any clinical significance or differences of note in culture-negative mycotic aortic aneurysms. METHODS: Between October 2003 and August 2018, 71 patients were identified as treated for mycotic aortic aneurysms at a single tertiary institution. Review of medical records and imaging studies were completed to collect the following information: demographics, previous medical/surgical history regarding potential infection sources, laboratory and radiologic findings, clinical presentations, treatment method, and morbidity and mortality rates. For analysis, patients were categorized into two groups: the blood and/or tissue culture-positive (CP) group and the blood and/or tissue culture-negative (CN) group. The latter was further divided as CN with identified microorganism by molecular biologic methods [CN(+)] and CN with no identified microorganism [CN(-)]. RESULTS: More patients in the CP group were symptomatic than were in the CN(+) group (100% vs. 80%; P = 0.034). However, identification of causative microorganisms did not result in a difference in symptom status upon comparing the [CP + CN(+)] and [CN(-)] groups. Inflammatory markers were the most elevated in the CP group and least elevated in the CN(-) group. The aneurysm growth rate seemed slower in the CN(-) group than in the CN(+) and CP groups (1.3 vs. 3.4 vs. 9 mm/month respectively). Aneurysm rupture at initial presentation was more prevalent in the CP group (33.3%). 18F-Fluorodeoxyglucose-positron emission tomography showed increased uptake regardless of whether or not the microorganisms were identified. Early mortality and disease-specific mortality rates during the follow-up period were higher in the CP group but without statistical significance. CONCLUSIONS: Compared with the CP group, the CN groups appeared clinically less severe, and also exhibited a relatively less devastating course as exhibited by the slower aneurysm expansion rate and smaller number of ruptured aneurysms at the initial presentation.

Strategy to avoid open surgical conversion after endovascular aortic aneurysm repair for patients with infrarenal abdominal aortic aneurysm.

PURPOSE: Open surgical conversion (OSC) is the last treatment option for patients with endovascular aneurysm repair (EVAR)failure. We investigated the underlying causes of EVAR failure requiring OSC and attempted to determine strategies to avoid OSC after EVAR. METHODS: We retrospectively reviewed the database of patients who underwent OSC after EVAR from 2005 to 2018 in a single institution. Twenty-six OSCs were performed in 24 patients (median age, 74.5 years; 79.2% of males) who had undergone standard EVAR. We investigated pre-, intra-, and postoperative computed tomography or angiographic images and outcomes of the OSCs. RESULTS: Two main indications for OSC were persistent endoleak (50.0%) and endograft infection (EI) (38.5%). All 13 patients who underwent OSC due to endoleaks received EVAR outside of indications for use. Among 10 patients who underwent OSC due to EI, we found overlooked infection sources in 7 (70.0%) at the time of EVAR or during the surveillance period. OSC was performed at a median of 31.8 months (interquartile range, 9.4-69.8) after EVAR as an emergency (15.4%) or elective (84.6%) surgery. Aortic endograft was removed in 84.6% of cases (totally, 57.7%; partially, 26.9%), whereas it was preserved in 4 cases (15.4%). After 26 OSCs, 2 early deaths (7.7%) and 2 aortoenteric fistulae (7.7%) developed as major complications. CONCLUSION: OSC after EVAR was associated with relatively higher perioperative morbidity and mortality. To avoid OSC after EVAR, we recommend careful assessment of coexisting infection sources and avoidance of EVAR for patients with especially unfavorable anatomy for EVAR, particularly the in proximal neck.

Anti-Cancer Effects of RAW 264.7 Cells on Prostate Cancer PC-3 Cells.

Macrophages have the potential to re-programing tumor cells in the tumor microenvironments. Thus we investigated anti-cancer effects of M1-polarized macrophages by lipopolysaccharide (LPS) on the physiological properties of human prostate cancer PC-3 cells. To identify communications with immune cells and tumor cells, we performed in-direct way by using conditioned-media (CM) and analyzed tumor properties via quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blot and flow cytometry. CM of M1-polarized macrophages induced apoptotic cell death in PC-3 cells, and it surprisingly suppressed tumor parameters including epithelial to mesenchymal transition (EMT), invasion, migration and angiogenesis. EMT specific markers, N-cadherin, snail-1, and TGF ß2 were diminished; however, E-cadherin was increased. In addition, migration markers, vimentin and CCL2 were down-regulated, and finally wound healing was also inhibited. Decreased expression of matrix metalloprotein (MMP)-9 and VEGFA might reduce the invasive and angiogenic abilities of PC-3 cells. These results suggested that co-culture with CM of M1-polarized macrophages showed higher anti-cancer effects on PC-3 cells. Thus, therapeutic targeting of macrophages toward PC-3 cells may represent a useful strategy to complement with the secreted molecules of RAW 264.7 cells as inhibitors of metastasis and anti-cancer agents.

Integrative genomic analysis of salivary duct carcinoma.

Salivary duct carcinoma (SDC) is one of the most aggressive subtypes of salivary gland cancers. Conventional chemotherapy and/or radiation have shown only limited clinical efficacy in the treatment of recurrent or metastatic SDC. Currently, clinically approved targeted-therapeutics are not generally applicable except in very limited cases, and there exists a strong need for the development of treatment against this unique tumor type. To further interrogate genomic features of SDC, we have conducted multi-omic profiling of the SDC to describe the genomic alterations prevalent in this disease. Whole-genome sequencing, whole exome-sequencing and transcriptome sequencing were performed on a discovery cohort of 10 SDC samples. Targeted genomic profiling was performed in additional 32 SDC samples to support the findings obtained from the original discovery cohort. The cancer cohort was characterized by an average mutation burden of 85 somatic exonic mutations per tumor sample. The cohort harbored a mutational signature of BRCA and APOBEC/AID. Several genes, including TP53, RB1, SMAD4, HRAS, APC, PIK3CA and GNAQ were recurrently somatically altered in SDC. A novel fusion gene, generated by genomic rearrangement, MYB-NHSL1, was also noted. Our findings represent a significant layer in the systematic understanding of potentially clinically useful genomic and molecular targets for a subset of recurrent/metastatic SDC.

Differential Diagnosis and Treatment Outcomes of Tumors at the Carotid Bifurcation.

PURPOSE: Primary tumor at the carotid bifurcation is uncommon, which includes paraganglioma, schwannoma, and lymphoma. Due to their rarity, characteristics of these tumors and problems related to their surgical treatment have not been well known. We tried to elucidate different clinical characteristics and surgical complications of these tumors. MATERIALS AND METHODS: We retrospectively reviewed 21 patients with carotid bifurcation tumor from the Vascular Surgery division of a Korean tertiary institution from 1995 to 2018. We investigated patients' demographics and clinical features, image characteristics, treatment details, and surgical outcomes. RESULTS: During the period from January 1995 to January 2018, we experienced surgical resections of 21 carotid bifurcation tumors which included 16 (76.2%) paragangliomas and 5 (23.8%) schwannomas. The most common clinical feature was a non-tender cervical mass. According to Shamblin classification, paragangliomas were classified into class II in 68.8% and class III in 25.0%. On the preoperative computed tomography images, all the paragangliomas showed characteristic splaying of the carotid bifurcation and hypervascularity of the tumors. On the contrary, all the schwannomas showed hypovascularity and splaying sign in 60%. Surgical complications related to cervical nerve injury developed in 50% and 60% of patients with Shamblin class III paraganglioma and schwannoma, respectively. During the mean follow-up period of 25 months (range, 1 to 163 months), distant metastases developed in 2 (12.5%) of paraganglioma patients. CONCLUSION: Neurologic complications were more common after surgical resection of Shamblin class III paraganglioma and schwannoma. For patients with paraganglioma, postoperative periodic follow-up examination is advised to detect distant metastasis.