Enhanced cancer cell proliferation and aggressive phenotype counterbalance in breast cancer with high BRCA1 gene expression.

PURPOSE: While comprehensive research exists on the mutation of the DNA repair gene BRCA1, limited information is available regarding the clinical significance of BRCA1 gene expression. Given that cancer cell proliferation is aggrevated by DNA repair, we hypothesized that high BRCA1 gene expression breast cancer (BC) might be linked with aggressive tumor biology and poor clinical outcomes. METHODS: The cohorts: The Cancer Genome Atlas (TCGA, n = 1069), METABRIC (n = 1903), and SCAN-B (n = 3273) were utilzed to obtain data of 6245 BC patients. RESULTS: BC patients without BRCA1 mutation exhibited higher BRCA1 expression, which was associated with DNA repair functionality. However, no such correlation was observed with BRCA2 expression. The association of high BRCA1 expression with cancer cell proliferation was evidenced by significant enrichment of cell proliferation-related gene sets, higher histological grade, and proliferation score. Furthermore, increased levels of homologous recombination deficiency, intratumoral heterogeneity, and altered fractions were associated with high BRCA1 expression. Moreover, BC with high BRCA1 expression exhibited reduced infiltration of dendritic cells and CD8 T-cells, while showing increased infiltration of Th1 cells. Surprisingly, BRCA1 expression was not associated with the survival of BC irrespective of the subtypes. Conversely, BC with low BRCA1 expression enriched cancer aggravating pathway gene sets, such as Cancer Stem Cell-related signaling (NOTCH and HEDGEHOG), Angiogenesis, Epithelial-Mesenchymal Transition, Inflammatory Response, and TGF-beta signaling. CONCLUSION: Despite being linked to heightened proliferation of cancer cells and unassertive phenotype, BRCA1 expression did not show any association with survival in BC.

Association between preoperative cortical magnetic susceptibility and postoperative changes in the cerebral blood flow on cognitive improvement following carotid endarterectomy.

INTRODUCTION: While patients who experience improved cognition following carotid endarterectomy (CEA) typically demonstrate restored brain perfusion after the procedure, it is worth noting that less than 50% of patients in whom postoperative cerebral blood flow (CBF) restoration is achieved actually show improved cognition after postoperatively. This suggests that factors beyond the mere restoration of CBF may play a role in postoperative cognitive improvement. Increased iron deposition in the cerebral cortex may cause neural damage, and quantitative susceptibility mapping (QSM) obtained using magnetic resonance imaging (MRI) quantifies magnetic susceptibility in the cerebral cortex, allowing for the assessment of iron deposition in vivo. The purpose of the present study was to determine whether preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA. METHODS: Brain MRI with a three-dimensional gradient echo sequence was preoperatively performed in 53 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%), and QSM with brain surface correction and vein removal was obtained. Cortical magnetic susceptibility was measured in the cerebral hemisphere ipsilateral to surgery on QSM. Preoperatively and at two months after the surgery, brain perfusion single-photon emission computed tomography (SPECT) and neuropsychological assessments were conducted. Using these collected data, we evaluated alterations in CBF within the affected hemisphere and assessed cognitive improvements following the operation. RESULTS: A logistic regression analysis showed that a postoperative greater increase in CBF (95% confidence interval [CI], 1.06-1.90; p = 0.0186) and preoperative lower cortical magnetic susceptibility (95% CI, 0.03-0.74; p = 0.0201) were significantly associated with postoperatively improved cognition. Although sensitivity, specificity, and positive- and negative-predictive values with the cutoff value lying closest to the upper left corner of a receiver operating characteristic curve for the prediction of postoperatively improved cognition did not differ between postoperative changes in CBF and preoperative cortical magnetic susceptibility, the specificity and the positive-predictive value were significantly greater for the combination of postoperative changes in CBF and preoperative cortical magnetic susceptibility (specificity, 95% CI, 93-100%; positive-predictive value 95% CI, 68-100%) than for the former parameter alone (specificity, 95% CI, 63-88%; positive-predictive value 95% CI, 20-64%). CONCLUSION: Preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA.

Assessment of magnetic field interactions and heating for cerebral aneurysm flow diverters during 7T MRI.

Flow diverters (FDs) are utilized for a wide range of aneurysms, but show safety issues such as adverse interactions with static magnetic fields (displacement force and torque) and radiofrequency-induced heating during magnetic resonance imaging (MRI). The present study aimed to assess these adverse interactions in a 7-tesla (7T) static magnetic field and radiofrequency-induced heating during a 7T MRI for two types of FD. Displacement force and magnetically induced torque were assessed using the deflection angle method and low friction surface method, respectively. To assess heating, each FD was set in a phantom filled with gelled-saline mixed with polyacrylic acid and underwent a 7T MRI using a three-dimensional fast spin echo method. Displacement force and magnetically induced torque in the 7T static magnetic field were undetectable, and radiofrequency-induced heating during 7T MRI remained ≤ 0.6 °C for both types of FD, suggesting that magnetic field interactions and heating on FDs during a 7T MRI are acceptable from a safety perspective.

Which factors influence the decision to perform Hartmann's reversal in various causative disease situations? A retrospective cohort study between 2006 and 2021.

AIM: Our aim was to investigate the predictive factors for Hartmann's reversal and to describe the differences in the rates and timings of Hartmann's reversal for various causative diseases. METHOD: In this multicentre retrospective cohort study patients who underwent Hartmann's procedure (HP) between 2006 and 2018 were enrolled. To describe the demographic patterns of Hartmann's reversal through to 2021, we analysed the cumulative incidence rate of Hartmann's reversal over time based on the Kaplan-Meier failure estimate. Multivariable Cox proportional hazard analysis was performed with cluster-adjusted robust standard errors to calculate hazard ratios (HRs) for the assessment of variables associated with colostomy reversal. RESULTS: Of 250 patients who underwent the index HP and survived to discharge, 112 (45%) underwent subsequent Hartmann's reversal (36% for malignant and 51% for benign disease). The causative diseases with the highest probability of colostomy reversal were trauma (85%) and diverticular disease (73%). Conversely, colostomy reversal was performed in only 16% for colonic volvulus and 17% for bowel ischaemia. Home discharge after index HP (HR 5.22, 95% CI 3.31-8.23) and a higher body mass index (HR 1.03, 95% CI 1.01-1.04) were associated with a higher probability of Hartmann's reversal, whereas older age, malignant disease and a history of cardiovascular and psychoneurological diseases were independently associated with a lower probability of colostomy reversal. CONCLUSION: The probability and timing of Hartmann's reversal varied considerably with the surgical indications for colostomy creation. Our results could help surgeons counsel patients and their families regarding stoma closure surgery to set realistic expectations.

Prediction of cerebral hyperperfusion following carotid endarterectomy using intravoxel incoherent motion magnetic resonance imaging.

OBJECTIVES: One of the risk factors for cerebral hyperperfusion following carotid endarterectomy (CEA) is a chronic reduction in cerebral perfusion pressure due to internal carotid artery (ICA) stenosis, which is clinically detected as increased cerebral blood volume (CBV). The perfusion fraction (f) is one of the intra-voxel incoherent motion (IVIM) parameters obtained using magnetic resonance (MR) imaging that theoretically reflects CBV. The present study aimed to determine whether preoperative IVIM-f on MR imaging predicts development of cerebral hyperperfusion following CEA. MATERIALS AND METHODS: Sixty-eight patients with unilateral ICA stenosis (≥ 70%) underwent preoperative diffusion-weighted 3-T MR imaging, and IVIM-f maps were generated from these data. Quantitative brain perfusion single-photon emission computed tomography (SPECT) was performed before and immediately after CEA. Regions-of-interest (ROIs) were automatically placed in the bilateral middle cerebral artery territories in all images using a three-dimensional stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on IVIM-f maps. RESULTS: Nine patients (13%) exhibited postoperative hyperperfusion (cerebral blood flow increases of ≥ 100% compared with preoperative values in the ROIs on brain perfusion SPECT). Only high IVIM-f ratios were significantly associated with the occurrence of postoperative hyperperfusion (95% confidence interval, 253.8-6774.2; p = 0.0031) on logistic regression analysis. The sensitivity, specificity, and positive and negative predictive values of the IVIM-f ratio to predict the occurrence of postoperative hyperperfusion were 100%, 81%, 45%, and 100%, respectively. CONCLUSIONS: Preoperative IVIM-f on MR imaging can predict development of cerebral hyperperfusion following CEA.

Changes in periventricular anastomosis after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic moyamoya disease.

Periventricular anastomosis in moyamoya disease (MMD) is an unusual angiographic finding that arises from perforating arteries such as the lenticulostriate artery (LSA), thalamic artery (THA), and anterior choroidal artery (AChA). This anastomosis is associated with increased hemorrhagic risk in MMD and can be corrected by direct revascularization surgery. The present supplementary analysis on a prospective cohort aimed to elucidate changes in periventricular anastomosis after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD. Twenty-two patients with misery perfusion in the symptomatic cerebral hemisphere who underwent indirect revascularization surgery alone also underwent six-vessel cerebral angiography via arterial catheterization before and at 6 months after surgery. Before surgery, two patients (9%) had positive periventricular anastomosis from the LSA and another (5%) from the AChA; all three of these periventricular anastomoses regressed after surgery, but these changes were not statistically significant (p = 0.0833). The degree of formation of collateral vessels from the LSA significantly decreased after surgery (p = 0.0143), but the degree of collateral vessels from the THA or AChA did not differ between pre- and postoperative conditions. Eight patients with postoperative regression of the collateral vessels from any perforating artery exhibited postoperative rich collateral flow from indirect revascularization. Periventricular anastomosis tended to regress after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD. Collateral vessels formed from the LSA likely regressed after indirect revascularization surgery alone for such patients, but those vessels from the THA or AChA seldom changed.

Delayed development of cerebral atrophy after cerebral hyperperfusion following arterial bypass for adult patients with ischemic moyamoya disease: supplementary analysis of a 5-year prospective cohort.

BACKGROUND: Adult patients with moyamoya disease (MMD) occasionally exhibit cerebral hyperperfusion after arterial bypass surgery, leading to persistent cognitive decline. The present supplementary analysis of a prospective 5-year cohort study aimed to determine whether cerebral hyperperfusion after arterial bypass surgery for adult patients with misery perfusion due to ischemic MMD causes cerebral atrophy, and whether the development of cerebral atrophy is related to persistent cognitive decline. METHODS: In total, 31 patients who underwent arterial bypass surgery also underwent fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and neuropsychological testing before surgery and at the end of a 5-year follow-up. The development of cerebral hyperperfusion and hyperperfusion syndrome after surgery was defined based on brain perfusion single-photon emission computed tomography (SPECT) findings and clinical symptoms. Univariate and multivariate logistic regression analyses of factors related to the development of cerebral atrophy on FLAIR MRI or cognitive decline on neuropsychological testing at the end of the 5-year follow-up were performed. RESULTS: Eleven patients (35%) developed cerebral atrophy in the frontal lobe where the superficial temporal artery was anastomosed. Cerebral hyperperfusion on brain perfusion SPECT (odds ratio [OR], 50.6; p = 0.0008) or cerebral hyperperfusion syndrome (OR, 41.8; p = 0.0026) was independently associated with the development of cerebral atrophy, and cerebral atrophy development was significantly associated with cognitive decline (OR, 47.7; p = 0.0010). CONCLUSIONS: Cerebral hyperperfusion after arterial bypass surgery for adult patients with misery perfusion due to ischemic MMD can cause cerebral atrophy related to persistent cognitive decline.

Long-term outcomes, including the survival rate and period to death, in patients over 80 years old after ruptured cerebral aneurysm clipping.

OBJECTIVE: This study aimed to identify the long-term outcomes, including the survival rate, period to death, causes of death, and predictors of poor outcomes, in patients aged over 80 years who underwent surgical clipping for a ruptured anterior circulation aneurysm. MATERIALS AND METHODS: In this retrospective observational study, the medical records of patients from April 1, 1994, to June 30, 2019, were evaluated. All patients underwent surgical clipping within 72 h of subarachnoid hemorrhage (SAH) onset. Information on the patient, SAH, and outcomes were collected. RESULTS: The mean hospitalization and long-term follow-up periods for all patients were 54.5 days and 53.3 months, respectively. The period to death was significantly shorter in patients with modified Rankin scale (mRS) of 4-5 than for those with an mRS of 0-3 at discharge (p=0.001). The Kaplan-Meier method using the log-rank test demonstrated that patients with an mRS of 4-5 at discharge had a significantly lower survival rate compared to those with an mRS of 0-3 at discharge (p<0.05). Univariate analysis revealed that the proportion of patients with Hunt and Hess grade and presence of surgical complications were significantly larger in the group with an mRS of 4-5 than in that with an mRS of 0-3 at discharge (p=0.0013 and 0.011, respectively). Multivariate analysis demonstrated that presence of surgical complications was the only independent predictor of poor outcomes (p=0.043, odds ratio [OR] 7.937, 95% confidence interval [CI] 1.061-59.38). The Kaplan-Meier method using the log-rank test demonstrated that patients with surgical complications had a significantly lower survival rate compared to those with no surgical complications (p<0.05). CONCLUSIONS: Especially in patients aged over 80 years, those with H-H grade 2 and a good clinical condition can be candidates for surgical clipping, whereas avoiding surgical complications is essential for achieving good outcomes.

Outcomes of Medical Management Alone for Adult Patients with Cerebral Misery Perfusion Due to Ischemic Moyamoya Disease.

OBJECTIVES: Although revascularization surgery is recommended for adult patients with moyamoya disease (MMD) who present with ischemic symptoms due to hemodynamic compromise, the clinical course of such patients who are treated with medical management alone remains unclear. Here, we report outcomes of adult patients with cerebral misery perfusion due to ischemic MMD who received medical management alone. MATERIALS AND METHODS: We prospectively followed up patients who showed misery perfusion in the symptomatic cerebral hemisphere on 15O gas positron emission tomography (PET) and received strict medical management alone after refusing revascularization surgery. RESULTS: Of 57 patients who showed symptomatic misery perfusion on 15O gas PET, three (5%) were included into the present study. Two of these patients suffered further ischemic events at 7 and 8 months after inclusion, after which, their modified Rankin disability scale scores deteriorated. In the remaining patient, fatal intracerebral hemorrhage developed at 10 months after inclusion. CONCLUSIONS: These findings suggest that receiving medical management alone is associated with considerably poor outcomes for adult patients with cerebral misery perfusion due to ischemic MMD.

De Novo Cerebral Microbleeds and Cognitive Decline in Cerebral Hyperperfusion After Direct Revascularization for Adult Moyamoya Disease.

OBJECTIVES: Adult patients with moyamoya disease (MMD) occasionally develop cognitive decline due to cerebral hyperperfusion following direct revascularization surgery. However, how the hyperperfusion phenomenon contributes to declines in cognitive function remains unclear. The present supplementary analysis of a prospective study aimed to determine whether cerebral hyperperfusion following direct revascularization surgery for adult MMD with ischemic presentation and misery perfusion leads to development of de novo cerebral microbleeds (CMBs) and whether postoperative cognitive decline is related to these CMBs. MATERIALS AND METHODS: In total, 32 patients who underwent direct revascularization surgery also underwent T2*-weighted magnetic resonance imaging (T2*WI) and neuropsychological testing before and 2 months after surgery. Development of cerebral hyperperfusion and hyperperfusion syndrome following surgery was defined based on brain perfusion single-photon emission computed tomography (SPECT) findings and clinical symptoms. RESULTS: Cerebral hyperperfusion on brain perfusion SPECT (95% confidence interval [CI], 1.1-10.8; p = 0.0175) or cerebral hyperperfusion syndrome (95%CI, 1.3-15.3; p = 0.0029) was significantly associated with postoperatively increased CMBs on T2*WI. Postoperatively increased CMBs were significantly associated with postoperative cognitive decline (95%CI, 1.8-20.4, p = 0.0041). For patients with cerebral hyperperfusion on brain perfusion SPECT, the incidence of postoperative cognitive decline was significantly greater in patients with than in those without postoperatively increased CMBs (p = 0.0294). CONCLUSIONS: Cerebral hyperperfusion following direct revascularization surgery for adult MMD with ischemic presentation and misery perfusion contributes to the development of de novo CMBs and postoperative cognitive decline is related to these CMBs.

Comparison of Subjective and Objective Assessments on Improvement in Gait Function after Carotid Endarterectomy.

The purpose of the present study was to determine whether objective gait test scores obtained using a tri-axial accelerometer can detect subjective improvement in gait as determined by the patient after carotid endarterectomy (CEA). Each patient undergoing CEA for ipsilateral internal carotid artery stenosis determined whether their gait was subjectively improved at six months after CEA when compared with preoperatively. Gait testing using a tri-axial accelerometer was also performed preoperatively and six months postoperatively. Twelve (15%) of 79 patients reported subjectively improved gait. Areas under the receiver operating characteristic curve for differences between pre- and postoperative test values in stride time, cadence, and ground floor reaction for detecting subjectively improved gait were 0.995 (95% confidence interval (CI), 0.945-1.000), 0.958 (95%CI, 0.887-0.990), and 0.851 (95%CI, 0.753-0.921), respectively. Cut-off points for value differences in detecting subjectively improved gait were identical to mean -1.7 standard deviation (SD) for stride time, mean +1.6 SD for cadence, and mean +0.4 SD for ground floor reaction of control values from normal subjects. Objective gait test scores obtained using the tri-axial accelerometer can detect subjective gait improvements after CEA. When determining significant postoperative improvements in gait using a tri-axial accelerometer, optimal cut-off points for each test value can be defined.

Identification of the Distal End of Carotid Plaque Using 3-Dimensional Fast Spin Echo T1-Weighted Magnetic Resonance Plaque Imaging.

BACKGROUND: Complete removal of the distal end of the plaque is an important requirement in carotid endarterectomy (CEA) to avoid postoperative complication. Preoperative identification of the distal end of plaque contributes to complete plaque removal. Three-dimensional (3D) magnetic resonance (MR) plaque imaging has been widely used to evaluate carotid plaque characterization. The purpose of the present study was to determine whether preoperative 3D fast spin echo (FSE) T1-weighted MR plaque imaging could identify the distal end of carotid plaque. METHODS: This study was designed as a prospective cohort study. We examined 50 patients with cervical internal carotid artery (ICA) stenosis who underwent CEA. 3D-FSE T1-weighted MR plaque imaging of the affected carotid bifurcation was preoperatively performed using a 1.5-T scanner. Identification of the distal end of plaque (DEMRI) on MR plaque imaging was performed and the distance from the baseline (DistanceMRI) was measured. Intraoperatively, the superimposed distal end of carotid plaque (Esim) was marked on the ICA according to the measurement on MR plaque imaging. The actual distal end of plaque (DECEA) was then identified after arteriotomy and the difference (DifferenceCEA-MRI) between Esim and DECEA was measured. Contrast ratio of carotid plaque and tortuosity of the ICA were calculated using MR plaque imaging. RESULTS: Interobserver agreements in measurement of DistanceMRI were excellent (intraclass correlation coefficient, .955; 95% confidence interval, .922-.974). In 28 patients (56%), Esim was identical to DECEA. Mean DifferenceCEA-MRI was 1.32 ± 1.77 mm. DifferenceCEA-MRI was significantly greater with fibrotic plaque (4.14 ± 1.21 mm) than with lipid-rich or necrotic plaque (.43 ± .87 mm; P < .05) or hemorrhagic plaque (1.27 ± 1.64 mm; P < .05). Mean DifferenceCEA-MRI was significantly greater in the group with tortuosity of the ICA less than 120° (3.86 ± 1.77 mm) than in the group with greater than or equal to 120° but less than or equal to 150° (1.15 ± 1.51 mm; P < .05) or greater than150° (0.50 ± 1.10 mm; P < .05). No patients showed residual stenosis after surgery on postoperative MR angiography. CONCLUSIONS: Using 3D-FSE T1-weighted MR plaque imaging allowed identification of the distal end of carotid plaque and contributed to complete removal of the plaque, although it may be reduced for cases with low-signal-intensity plaque or severe tortuosity of the ICA.

Moyamoya disease in pregnancy: a systematic review.

BACKGROUND: Moyamoya disease (MMD) management during pregnancy poses a challenge to health care providers, and recommendations are outdated, vague, and controversial. We conducted a systematic review to investigate and present the available evidence. METHOD: We searched five online databases and bibliographies of relevant published original studies to identify case reports, case series, cohort studies, and reviews reporting on patients diagnosed with MMD before, during, or shortly after pregnancy. We report and analyze the respective data. RESULTS: Fifty-four relevant articles were identified. In the group of patients with MMD diagnosed prior to pregnancy, 68.7% had previously undergone bypass surgery, 64.5% delivered via cesarean section, 95.2% of mothers had good outcomes, and no bad fetal outcomes were reported. In patients first diagnosed with MMD due to a cerebrovascular accident during pregnancy, the mean gestational age on symptom onset was 28.7 weeks and 69.5% presented with cerebral hemorrhage. In this group, 57.2% received neurosurgical operative management, and 80% underwent cesarean section with 13.6% maternal mortality and 23.5% fetal demise. In patients diagnosed with MMD immediately postpartum, 46.6% suffered a cerebrovascular event within 3 days of delivery, 78.3% of which were ischemic. Only 15.3% underwent surgical hematoma evacuation and one patient (9%) expired. CONCLUSIONS: MMD may coincide with pregnancy, but there is paucity of high-quality data. It appears that MMD is not a contraindication to pregnancy, if blood pressure and ventilation are properly managed. There is no clear evidence that bypass surgery before pregnancy or cesarean mode of delivery improve outcomes.

[Development of Intracerebral Hemorrhage and Subarachnoid Hemorrhage Shortly after Cerebral Infarction Onset in an Adult Patient with Moyamoya Disease].

Here we describe the case of a patient with moyamoya disease who developed cerebral infarction followed shortly by subarachnoid hemorrhage and intracerebral hemorrhage. A 50-year-old woman presenting with sudden and transient weakness of the left lower limb was transferred to a local hospital. Magnetic resonance imaging(MRI)revealed cerebral infarction in the corpus callosum and in the bilateral frontal lobes induced by moyamoya disease. Pyramidal tract was not affected. The patient was treated with an anti-platelet agent(ozagrel sodium 160mg/day)and did not undergo intentional antihypertensive therapy. The patient's averaged blood pressure was 150/90mmHg. Six days after symptom onset, the patient's orientation deteriorated. Head computed tomography scans revealed a subarachnoid hemorrhage in the right sylvian fissure and in the bilateral frontal lobes and an intracerebral hemorrhage adjacent to the left corona radiata. In addition, MRI revealed a significant expansion of the cerebral infarction in the bilateral frontal lobes. Angiography with arterial catheterization confirmed that the patient's symptoms met diagnostic criteria of stage III moyamoya disease. Positron emission tomography revealed hemodynamic compromise in the left cerebral hemisphere. The patient underwent a superficial temporal artery-middle cerebral artery anastomosis with encephalo-duro-myo-synangiosis. The patient's postoperative course was uneventful. Postoperative T2*-weighted MRI revealed multiple microbleeds in both cerebral hemispheres.

The role of lidocaine in cancer progression and patient survival.

Since its development in 1943, lidocaine has been one of the most commonly used local anesthesia agents for surgical procedures. Lidocaine alters neuronal signal transmission by prolonging the inactivation of fast voltage-gated sodium channels in the cell membrane of neurons, which are responsible for action potential propagation. Recently, it has attracted attention due to emerging evidence suggesting its potential antitumor properties, particularly in the in vitro setting. Further, local administration of lidocaine around the tumor immediately prior to surgical removal has been shown to improve overall survival in breast cancer patients. However, the exact mechanisms driving these antitumor effects remain largely unclear. In this article, we will review the existing literature on the mechanism of lidocaine as a local anesthetic, its effects on the cancer cells and the tumor microenvironment, involved pathways, and cancer progression. Additionally, we will explore recent reports highlighting its impact on clinical outcomes in cancer patients. Taken together, there remains significant ambiguity surrounding lidocaine's functions and roles in cancer biology, particularly in perioperative setting.

CD133 expression is associated with less DNA repair, better response to chemotherapy and survival in ER-positive/HER2-negative breast cancer.

Purpose: CD133, a cancer stem cells (CSC) marker, has been reported to be associated with treatment resistance and worse survival in triple-negative breast cancer (BC). However, the clinical relevance of CD133 expression in ER-positive/HER2-negative (ER+/HER2-) BC, the most abundant subtype, remains unknown. Methods: The BC cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1904) and The Cancer Genome Atlas (TCGA, n = 1065) were used to obtain biological variables and gene expression data. Results: Epithelial cells were the exclusive source of CD133 gene expression in a bulk BC. CD133-high ER+/HER2- BC was associated with CD24, NOTCH1, DLL1, and ALDH1A1 gene expressions, as well as with WNT/ß-Catenin, Hedgehog, and Notchsignaling pathways, all characteristic for CSC. Consistent with a CSC phenotype, CD133-low BC was enriched with gene sets related to cell proliferation, such as G2M Checkpoint, MYC Targets V1, E2F Targets, and Ki67 gene expression. CD133-low BC was also linked with enrichment of genes related to DNA repair, such as BRCA1, E2F1, E2F4, CDK1/2. On the other hand, CD133-high tumors had proinflammatory microenvironment, higher activity of immune cells, and higher expression of genes related to inflammation and immune response. Finally, CD133-high tumors had better pathological complete response after neoadjuvant chemotherapy in GSE25066 cohort and better disease-free survival and overall survival in both TCGA and METABRIC cohorts. Conclusion: CD133-high ER+/HER2- BC was associated with CSC phenotype such as less cell proliferation and DNA repair, but also with enhanced inflammation, better response to neoadjuvant chemotherapy and better prognosis.

Higher inflammatory response in hepatocellular carcinoma is associated with immune cell infiltration and a better outcome.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) often develops from chronic liver inflammation. Inflammation within a tumor can either promote cancer progression or activate an immune response against it. This study aims to determine the clinical significance of enhanced inflammation in HCC. METHODS: Data from 655 HCC patients across four cohorts (TCGA, GSE6764, GSE76427, GSE89377) were examined. Inflammatory response was quantified using a scoring system derived from the gene set variation analysis of the "INFLAMMATORY_RESPONSE" gene set. RESULTS: A stepwise increase in inflammatory response was noted from normal liver to cirrhosis, with consistently lower levels in HCC across both GSE6764 and GSE89377 cohorts (both p < 0.001). Similar trends were observed in interferon response, pathways such as IL6/JAK/STAT3 and complement signaling, coagulation cascade, and allograft rejection (all p < 0.02). HCCs with high inflammatory response were associated with increased immune cell infiltrations (p < 0.01) and cytolytic activity (p < 0.001). Interestingly, these HCCs had reduced mutation rates, no relationship with cell proliferation, and displayed both immune responses and pro-cancerous signals including epithelial-mesenchymal transition, KRAS, and hypoxia. Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p = 0.034) and overall survival in GSE76427 (p = 0.008). CONCLUSION: HCC with higher levels of inflammatory response demonstrated increased immune cell infiltration, enhanced immune-related and other pro-cancerous-related signaling, and showed a trend toward a better patient prognosis.

Gastric cancer with enhanced myogenesis is associated with less cell proliferation, enriched epithelial-to-mesenchymal transition and angiogenesis, and poor clinical outcomes.

Gastric cancer (GC) remains a lethal disease, with over 26,000 new cases and more than 11,000 deaths annually in the US. Thus, a deeper understanding of GC biology is critical to improve survival. Myogenesis is the formation of muscle fibers, which is a mesodermal tissue. In cancer, epithelial-to-mesenchymal transition (EMT) is a known phenomenon that promotes metastasis and poor survival. Given that myogenesis produces mesenchymal cells, we hypothesized that GC with increased myogenesis is linked to aggressive tumor behaviors and less favorable outcomes. In this study, three GC patient cohorts: TCGA (n=375), GSE26253 (n=432), and GSE84437 (n=482), were analyzed. The "MYOGENESIS" set in the Hallmark collection which comprises 200 myogenesis-related genes was analyzed to perform gene set variation analysis to create a score to quantify the myogenesis activity. Our results showed that T category of AJCC cancer staging that reflects the tumor invasion to stomach wall consistently correlated with myogenesis activity in two GC cohorts. High myogenesis GC was associated with lower cell proliferation, evidenced by reduced proliferation scores, decreased Ki67 gene expression, and less enrichment of E2F Targets, G2M checkpoint, MYC Targets V1, and V2 gene sets. High myogenesis tumors showed increased stromal cells (fibroblasts and adipocytes) infiltration within the tumor microenvironment, as well as less silent and non-silent mutation rates and copy number alterations. Higher lymphocyte infiltration, leukocyte fraction, T-cell receptor richness, and B-cell receptor richness were associated with high myogenesis GC. However, infiltration of CD4 cells, T helper type 1 and 2 cells, Natural Killer cells, regulatory T cells, and plasma cells was lower, with increased infiltration of dendritic cells in high myogenesis GC. High myogenesis GC enriched EMT, Hedgehog, TGF-ß, and KRAS gene sets. Furthermore, it was associated with enhanced angiogenesis, evidenced by enrichment of Angiogenesis, Coagulation, and Hypoxia gene sets, and increased infiltration of microvascular and lymphatic endothelial cells and pericytes. High myogenesis GC consistently correlated with worse overall survival in all three cohorts, and worse disease-specific and progression-free survival in the TCGA cohort. Hence, our findings suggest that GC with enhanced myogenesis is associated with decreased cell proliferation, increased EMT and angiogenesis, and worse prognosis.

Flow Diversion Effect in a Saphenous Vein Graft Aneurysm Using a Double-Layer Micromesh Stent: A Case Report.

BACKGROUND AND IMPORTANCE: A double-layer micromesh stent is designed for the treatment of carotid artery stenosis that has been reported to potentially provide a flow diversion effect. However, the actual flow diversion effect of stents remains unclear. Here, we present a case of a growing saphenous vein graft (SVG) aneurysm treated with the placement of the double-layer micromesh stent using its flow diversion effect. CLINICAL PRESENTATION: A 66-year-old woman, who underwent high-flow bypass using a SVG for a blister-like internal carotid artery aneurysm 13 years earlier at our institute, was referred to our hospital with a pulsatile cervical mass. Magnetic resonance angiography showed a 9-mm aneurysm on the left SVG, although the aneurysm was a small pouch 4 years earlier. Digital subtracted angiography demonstrated a 9.4 × 8.3-mm aneurysm from the SVG at the auricular level. Because the diameter of the graft was larger than that of the available flow diverter stents in Japan, we decided to place the double-layer micromesh stent (CASPER RX, 7 × 25 mm MicroVention) using its flow diversion effect. Computational fluid dynamics analysis before and after stent deployment showed a significant reduction in the average flow velocity and wall shear stress in the aneurysm, indicating actual flow diversion. An angiogram 2 months postoperatively showed complete obliteration of the aneurysm. CONCLUSION: Obliteration of the saphenous vein aneurysm was achieved because of the flow diversion effect of the double-layer micromesh stent. The stents might be a feasible alternative for treating cervical carotid aneurysms.

Higher Inflammatory Response in Hepatocellular Carcinoma is Associated with Immune Cell Infiltration and a Better Outcome.

Background & Aims: Hepatocellular carcinoma (HCC) often develops from chronic liver inflammation. Inflammation within a tumor can either promote cancer progression or activate an immune response against it. This study aims to determine the clinical significance of enhanced inflammation in HCC. Methods: Data from 655 HCC patients across four cohorts (TCGA, GSE6764, GSE76427, GSE89377) were examined. Inflammatory response was quantified using a scoring system derived from the gene set variation analysis of the "INFLAMMATORY_RESPONSE" gene set. Results: A stepwise increase in inflammatory response was noted from normal liver to cirrhosis, with consistently lower levels in HCC across both GSE6764 and GSE89377 cohorts (both p<0.001). Similar trends were observed in interferon response, pathways such as IL6/JAK/STAT3 and complement signaling, coagulation cascade, and allograft rejection (all p<0.02). HCCs with high inflammatory response were associated with increased immune cell infiltrations (p<0.01) and cytolytic activity (p<0.001). Interestingly, these HCCs had reduced mutation rates, no relationship with cell proliferation, and displayed both immune responses and pro-cancerous signals including epithelial-mesenchymal transition, KRAS, and hypoxia. Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008). Conclusion: HCC with higher levels of inflammatory response demonstrated increased immune cell infiltration, enhanced immune-related and other pro-cancerous-related signaling, and better patient prognosis.