Non-Invasive Tools in Perioperative Stroke Risk Assessment for Asymptomatic Carotid Artery Stenosis with a Focus on the Circle of Willis.

This review aims to explore advancements in perioperative ischemic stroke risk estimation for asymptomatic patients with significant carotid artery stenosis, focusing on Circle of Willis (CoW) morphology based on the CTA or MR diagnostic imaging in the current preoperative diagnostic algorithm. Functional transcranial Doppler (fTCD), near-infrared spectroscopy (NIRS), and optical coherence tomography angiography (OCTA) are discussed in the context of evaluating cerebrovascular reserve capacity and collateral vascular systems, particularly the CoW. These non-invasive diagnostic tools provide additional valuable insights into the cerebral perfusion status. They support biomedical modeling as the gold standard for the prediction of the potential impact of carotid artery stenosis on the hemodynamic changes of cerebral perfusion. Intraoperative risk assessment strategies, including selective shunting, are explored with a focus on CoW variations and their implications for perioperative ischemic stroke and cognitive function decline. By synthesizing these insights, this review underscores the potential of non-invasive diagnostic methods to support clinical decision making and improve asymptomatic patient outcomes by reducing the risk of perioperative ischemic neurological events and preventing further cognitive decline.

Impaired cerebrovascular reactivity correlates with reduced retinal vessel density in patients with carotid artery stenosis: Cross-sectional, single center study.

BACKGROUND: The cerebral and retinal circulation systems are developmentally, anatomically, and physiologically interconnected. Thus, we hypothesized that hypoperfusion due to atherosclerotic stenosis of the internal carotid artery (ICA) can result in disturbances of both cerebral and retinal microcirculations. We aimed to characterize parameters indicating cerebrovascular reactivity (CVR) and retinal microvascular density in patients with ICA stenosis, and assess if there is correlation between them. METHODS: In this cross-sectional study the middle cerebral artery (MCA) blood flow velocity was measured by transcranial Doppler (TCD) and, simultaneously, continuous non-invasive arterial blood pressure measurement was performed on the radial artery by applanation tonometry. CVR was assessed based on the response to the common carotid artery compression (CCC) test. The transient hyperemic response ratio (THRR) and cerebral arterial resistance transient hyperemic response ratio (CAR-THRR) were calculated. Optical coherence tomography angiography (OCTA) was used to determine vessel density (VD) on the papilla whole image for all (VDP-WIall) and for small vessels (VDP-WIsmall). The same was done in the peripapillary region: all (VDPPall), and small (VDPPsmall) vessels. The VD of superficial (VDMspf) and deep (VDMdeep) macula was also determined. Significance was accepted when p<0.05. RESULTS: Twenty-four ICA stenotic patients were evaluated. Both CVR and retinal VD were characterized. There was a significant, negative correlation between CAR-THRR (median = -0.40) and VDPPsmall vessels (median = 52%), as well as between VDPPall vessels (median = 58%), and similar correlation between CAR-THRR and VDP-WIsmall (median = 49.5%) and between VDP-WIall (median = 55%). CONCLUSION: The significant correlation between impaired cerebrovascular reactivity and retinal vessel density in patients with ICA stenosis suggests a common mechanism of action. We propose that the combined use of these diagnostic tools (TCD and OCTA) helps to better identify patients with increased ischemic or other cerebrovascular risks.

Assessment of cerebral autoregulatory function and inter-hemispheric blood flow in older adults with internal carotid artery stenosis using transcranial Doppler sonography-based measurement of transient hyperemic response after carotid artery compression.

Unhealthy vascular aging promotes atherogenesis, which may lead to significant internal carotid artery stenosis (CAS) in 5 to 7.5% of older adults. The pathogenic factors that promote accelerated vascular aging and CAS also affect the downstream portion of the cerebral microcirculation in these patients. Primary treatments of significant CAS are eversion endarterectomy or endarterectomy with patch plasty. Factors that determine adequate hemodynamic compensation and thereby the clinical consequences of CAS as well as medical and surgical complications of carotid reconstruction surgery likely involve the anatomy of the circle of Willis (CoW), the magnitude of compensatory inter-hemispheric blood flow, and the effectiveness of cerebral microcirculatory blood flow autoregulation. This study aimed to test two hypotheses based on this theory. First, we hypothesized that patients with symptomatic and asymptomatic CAS would exhibit differences in autoregulatory function and inter-hemispheric blood flow. Second, we predicted that anatomically compromised CoW would associate with impaired inter-hemispheric blood flow compensation. We enrolled older adults with symptomatic or asymptomatic internal CAS (>70% NASCET criteria; n = 46) and assessed CoW integrity by CT angiography. We evaluated transient hyperemic responses in the middle cerebral arteries (MCA) after common carotid artery compression (CCC; 10 s) by transcranial Doppler sonography (TCD). We compared parameters reflecting autoregulatory function (e.g., transient hyperemic response ratio [THRR], return to baseline time [RTB], changes of vascular resistance) and inter-hemispheric blood flow (residual blood flow velocity). Our findings revealed that CAS was associated with impaired cerebral vascular reactivity. However, we did not observe significant differences in autoregulatory function or inter-hemispheric blood flow between patients with symptomatic and asymptomatic CAS. Moreover, anatomically compromised CoW did not significantly affect these parameters. Notably, we observed an inverse correlation between RTB and THRR, and 49% of CAS patients exhibited a delayed THRR, which associated with decreased inter-hemispheric blood flow. Future studies should investigate how TCD-based evaluation of autoregulatory function and inter-hemispheric blood flow can be used to optimize surgical techniques and patient selection for internal carotid artery revascularization.

The Effect of Circle of Willis Morphology on Retinal Blood Flow in Patients with Carotid Stenosis Measured by Optical Coherence Tomography Angiography.

The Circle of Willis (CoW) is the main collateral system, and its morphological variants are more common in patients who have severe carotid artery stenosis. Earlier data suggest that optical coherence tomography angiography (OCTA) may help to assess the changes in cerebral vascular perfusion by imaging the retinal blood flow. In this single-center prospective clinical study, patients scheduled for carotid endarterectomy (CEA) underwent preoperative computed tomography angiography (CTA) of the extra- and intracranial cerebral circulation. OCTA imaging was performed one week before surgery and postoperatively one month later. The patients were divided into two subgroups based on CTA evaluation of CoW: compromised CoW or non-compromised CoW (containing hypoplastic and normal segments). The effect of the patient's age, OCTA scan quality (SQ), CoW morphology, laterality, and surgery on superficial capillary vessel density (VD) in the macula were assessed in multivariable regression models using linear mixed models. We found that VD significantly decreased with aging (-0.12%; 95%CI: -0.07--0.15; p < 0.001) and was significantly higher in patients with non-compromised CoW morphology (by 0.87% 95%CI (0.26-1.50); p = 0.005). After CEA, retinal blood flow significantly improved by 0.71% (95%CI: 0.18-1.25; p = 0.01). These results suggest that in the case of carotid artery occlusion, patients with non-compromised CoW have more preserved ocular blood flow than subjects with compromised CoW due to remodeling of the intra-orbital blood flow. Measuring the retinal blood flow might be used as a relevant and sensitive indicator of collateral cerebrovascular circulation.

A Propensity-Matched Comparison of Ischemic Brain Lesions on Postprocedural MRI in Endovascular versus Open Carotid Artery Reconstruction.

(1) Study purpose: The aim of our prospective single-center, matched case-control study was to compare the number and volume of acute ischemic brain lesions following carotid endarterectomy (CEA) versus carotid artery stenting (CAS) using a propensity-matched design. (2) Methods: Carotid bifurcation plaques were analyzed by using VascuCAP software on CT angiography (CTA) images. The number and volume of acute and chronic ischemic brain lesions were assessed on MRI scans taken 12-48 h after the procedures. Propensity score-based matching was performed at a 1:1 ratio to compare the ischemic lesions on postinterventional MR. (3) Results: A total of 107 patients (CAS, N = 33; CEA, N = 74) were included in the study. There were significant differences in smoking (p = 0.003), total calcification plaque volume (p = 0.004), and lengths of the lesion (p = 0.045) between the CAS and CEA groups. Propensity score matching resulted in 21 matched pairs of patients. Acute ischemic brain lesions were detected in ten patients (47.6%) of the matched CAS group and in three patients (14.2%) in the matched CEA group (p = 0.02). The volume of acute ischemic brain lesions was significantly larger (p = 0.04) in the CAS group than in the CEA group. New ischemic brain lesions were not associated with neurological symptoms in either group. (4) Conclusions: Procedure-related new acute ischemic brain lesions occurred significantly more frequently in the propensity-matched CAS group.

Radiation Exposure Reduction by Digital Variance Angiography in Lower Limb Angiography: A Randomized Controlled Trial.

BACKGROUND: digital variance angiography (DVA) provides higher image quality than digital subtraction angiography (DSA). This study investigates whether the quality reserve of DVA allows for radiation dose reduction during lower limb angiography (LLA), and compares the performance of two DVA algorithms. METHODS: this prospective block-randomized controlled study enrolled 114 peripheral arterial disease patients undergoing LLA into normal dose (ND, 1.2 µGy/frame, n = 57) or low-dose (LD, 0.36 µGy/frame, n = 57) groups. DSA images were generated in both groups, DVA1 and DVA2 images were generated in the LD group. Total and DSA-related radiation dose area product (DAP) were analyzed. Image quality was assessed on a 5-grade Likert scale by six readers. RESULTS: the total and DSA-related DAP were reduced by 38% and 61% in the LD group. The overall visual evaluation scores (median (IQR)) of LD-DSA (3.50 (1.17)) were significantly lower than the ND-DSA scores (3.83 (1.00), p < 0.001). There was no difference between ND-DSA and LD-DVA1 (3.83 (1.17)), but the LD-DVA2 scores were significantly higher (4.00 (0.83), p < 0.01). The difference between LD-DVA2 and LD-DVA1 was also significant (p < 0.001). CONCLUSIONS: DVA significantly reduced the total and DSA-related radiation dose in LLA, without affecting the image quality. LD-DVA2 images outperformed LD-DVA1, therefore DVA2 might be especially beneficial in lower limb interventions.

Imaging retinal microvascular manifestations of carotid artery disease in older adults: from diagnosis of ocular complications to understanding microvascular contributions to cognitive impairment.

Carotid artery stenosis (CAS) is a consequence of systemic atherosclerotic disease affecting the aging populations of the Western world. CAS is frequently associated with cognitive impairment. However, the mechanisms contributing to the development of vascular cognitive impairment (VCI) associated with CAS are multifaceted and not fully understood. In addition to embolization and decreased blood flow due to the atherosclerotic lesion in the carotid artery, microcirculatory dysfunction in the cerebral circulation also plays a critical role in CAS-related VCI. To better understand the microvascular contributions to cognitive decline associated with CAS and evaluate microvascular protective effects of therapeutic interventions, it is essential to examine the structural and functional changes of the microvessels in the central nervous system (CNS). However, there are some limitations of in vivo brain vascular imaging modalities. The retinal microvasculature provides a unique opportunity to study pathogenesis of cerebral small vessel disease and VCI, because the cerebral circulation and the retinal circulation share similar anatomy, physiology and embryology. Similar microvascular pathologies may manifest in the brain and the retina, thus ocular examination can be used as a noninvasive screening tool to investigate pathological changes in the CNS associated with CAS. In this review, ocular signs of CAS and the retinal manifestations of CAS-associated microvascular dysfunction are discussed. The advantages and limitation of methods that are capable of imaging the ocular circulation (including funduscopy, fluorescein angiography, Doppler sonography, optical coherence tomography [OCT] and optical coherence tomography angiography [OCTA]) are discussed. The potential use of dynamic retinal vessel analysis (DVA), which allows for direct visualization of neurovascular coupling responses in the CNS, for understanding microvascular contributions to cognitive decline in CAS patients is also considered.

Treatment and Predictors of Recurrent Internal Carotid Artery In-Stent Restenosis.

PURPOSE: We aimed to examine the effectiveness of different therapeutic options for and to identify the possible risk factors of recurrent internal carotid artery (ICA) in-stent restenosis (ISR). METHODS: Forty-six ICA ISRs, which were reintervened at least once, were retrospectively analyzed regarding clinical and imaging characteristics, as well as invasive treatment type (percutaneous transluminal angioplasty [PTA] with a plain balloon, PTA with a drug-eluting balloon [DEB], re-stenting) used. RESULTS: The median follow-up was 29.5 months (IQR, 8.5-52.8 months) in patients who underwent reintervention for ICA ISR. Stent occlusion occurred in 3 patients (6.5%). One ISR recurrence was noted in 10 patients (21.7%); reintervention was carried out in 7 cases (7/10 [70%]; PTA, N = 5; PTA with a DEB, N = 1; re-stenting, N = 1), while 3 patients (3/10; 30%) received best medical treatment. Two ISR recurrences were observed in 3 patients (6.5%); all of them underwent reintervention (PTA, N = 1; PTA with a DEB, N = 2). Three ISR recurrences were seen in 1 patient (2.2%), who was treated with PTA. No recurrence was observed in those patients, who had DEB treatment. Multiple logistic regression analysis revealed statin therapy to be a protective factor against recurrent ISR (OR, 0.17; 95% CI, 0.03-0.84; P = .029). CONCLUSION: Our study suggests that PTA with a DEB is the most effective for the treatment of recurrent ISR, and confirms the importance of statin use in patients who have had a carotid reintervention.

Differences in guidelines for patients with carotid artery stenosis in some European countries / A nyaki veroér-szukületes betegek ellátási irányelveinek különbségei Európa különbözo országaiban.

Összefoglaló. A tudomány jelenlegi állása szerint - csoportok összehasonlítására épülo matematikai-statisztikai eszközökkel - a leginkább hatékonynak és hatásosnak vélt kezelési módszerek szisztematikus elemzése mentén, a bizonyítékokon alapuló irányelveken nyugvó gyógyító munkát tekintjük követendonek. A nyaki veroérszukület ellátása esetén az utóbbi években elkészült mind a hazai, mind az európai irányelv, mindemellett a társszakmák irányelveiben is megjelentek kezelési javaslatok. Közleményünkben összehasonlítottuk a témában publikált magyar, angol, német és olasz nyelvu, valamint az európai társaságok által kiadott irányelveket. Az irányelvek alapelveikben hasonlóak, formailag és tartalmilag azonban jelentos (idonként egymásnak ellentmondani látszó) különbségeket találhatunk. Az ellentmondások három leggyakoribb oka: 1) az egyes irányelvek által kituzött célok különbözosége, 2) az aszimptomatikus és szimptomatikus betegcsoport definíciói, valamint 3) az eltéro evidenciaszintek. Az irányelvek összevetése alapján a tünetes, szignifikáns nyaki veroérszukületek sebészi ellátása evidenciának tekintheto. A szimptomatikus nyaki veroérszukület a definíció szerint ellenoldali cerebralis ischaemia okozta, tranziens vagy definitív plegia, paresis, aphasia és az azonos oldali arteria centralis retinae embolisatiója miatti amaurosis fugax. A tünetmentes nyaki veroérszukületek ellátása tekintetében az európai és a nemzeti irányelvek nem azonosak, ezen esetek terápiás döntése egyéni mérlegelést igényel. Tünetmentes, 70%-os stenosis esetén vascularteam-konzílium javasolt. Orv Hetil. 2020; 161(51): 2139-2145. Summary. The correct practice is the one that is proven to be the most effective based on systematic statistical analyses of different treatment methods, and is applied according to evidence-based principles. In recent years, not only has the European Society of Vascular Surgery created a guideline about the management of supra-aortic steno-occlusive disease, but some nations' vascular surgical societies and related disciplines have also developed their own guidance. In this paper, the guidelines by the European societies on the clinical care of patients with carotid artery luminal narrowing is compared to national guidelines published in Hungarian, English, German, and Italian. Although the fundamental points of the guidelines are similar, there are some important differences among them both in presentation and in content; as a result, they sometimes appear to be contradictory. The three main sources of inconsistency are the various goals, the discrepancy in the definition of symptomatic and asymptomatic carotid artery stenosis, and the bias arising from the use of distinct evidence levels. A comparison of guidelines suggests that the treatment of symptomatic significant carotid artery stenosis with surgery can be considered evidence. Symptomatic carotid artery stenosis is defined as transient or definite plegia, paresis, aphasia due to cerebral ischemia, and monocular blindness caused by embolism in the central retinal artery. However, in the case of asymptomatic 70% or greater carotid artery stenosis, the guidelines are quite heterogeneous, and these patients require individual consideration and a vascular team decision is recommended. Orv Hetil. 2020; 161(51): 2139-2145.

Open repair of abdominal aortic aneurysms in patients with horseshoe kidney / Nyitott hasi aortaaneurysma-mutétek patkóvese fennállása esetén.

Összefoglaló. A patkóvese a vese leggyakrabban eloforduló fejlodési rendellenességeinek egyike. Hasi aortaaneurysmával való együttes elofordulása kifejezetten ritka (a hasi aortaaneurysmás esetek 0,12%-a). Az elso esetben egy 64 éves férfi akut alsó végtagi panaszokkal került felvételre. A CT-angiográfia patkóvesét és thrombotizált infrarenalis aortaaneurysmát igazolt. Az akut mutét során a hasi aortaaneurysma resectióját és aortobifemoralis bypassmutétet végeztünk a patkóvese ishmusának megtartásával. A második esetben hasi panaszokat okozó, mindkét arteria iliaca communisra ráterjedo infrarenalis aortaaneurysma esetén végeztünk aortobiiliacalis rekonstrukciót. Az aneurysma elott elhelyezkedo isthmus tervezetten szétválasztásra került, a poláris veseartériát visszaültettük. A tünetes hasi aortaaneurysma abszolút mutéti indikációt képez. A preoperatív CT- vagy MR-angiográfia kulcsfontosságú mind a mutéti indikáció felállítása, mind pedig a mutét megtervezése szempontjából. A beavatkozás elott pontos képet kell kapnia az érsebésznek az aorta anatómiája mellett a patkóvese vérellátásáról és a húgyúti rendszerrol. Az érsebészeti rekonstrukció esetén a transperitonealis feltárás - foleg akut mutét esetén - több elonnyel rendelkezik, mint a retroperitonealis feltárás. Orv Hetil. 2020; 161(46): 1966-1971. Summary. Horseshoe kidney is one of the most common congenital disorders of the kidney. The simultaneous incidence of horseshoe kidney and abdominal aneurysm is very low (0.12% of all cases of abdominal aortic aneurysm). In the first case, a 64-year-old male patient was admitted with acute lower limb ischaemia. CT-angiography revealed an occluded aortic aneurysm. During the emergency operation, the abdominal aneurysm was resected and an aortobifemoral bypass procedure was performed sparing the kidney's isthmus. In the second case, the abdominal complaints were caused by an infrarenal abdominal aneurysm that involved both common iliac arteries. Aortobiiliac reconstruction was performed with planned separation of the kidney isthmus and reimplantation of the accessory renal artery. Symptomatic abdominal aortic aneurysm is an urgent indication for reconstruction. The preoperative CT- or MR-angiography play a key role in the indication and planning of the reconstruction. It is highly important for the vascular surgeon to have a clear picture of the blood supply of the horseshoe kidney and the urinary tract along with the anatomy of the aorta before the operation. The transperitoneal approach has several advantages over the retroperitoneal approach during vascular reconstruction surgery. Orv Hetil. 2020; 161(46): 1966-1971.

[Management of extracranial carotid artery aneurysm]. / Extracranialis carotis aneurysmák korszeru kezelése.

Introduction: Aneurysm of the extracranial carotid artery is a rare condition and there is a diversity in the etiology. The proper treatment could be a real challenge for the surgeons. Aim: Analysis of perioperative and long term results of invasive treatment for carotid artery aneurysm. Method: A retrospective review was conducted of patients who had open or endovascular surgery due to carotid artery aneurysm through the last 13 years at the Department of Vascular Surgery of the Semmelweis University and at the Department of Surgery of the University of Szeged. Medical history, characteristics of the aneurysms, therapy and the follow-up results were reviewed. Results: Over the study period, 25 interventions were performed due to carotid artery aneurysm. There were 10 men and 15 women with a mean age of 57.8 ± 15.15 years. Seventeen patients (68%) were symptomatic. The mean aneurysm diameter was 26.8 ± 11.25 mm. The underlying etiology was atherosclerosis in eleven (44%), prior carotid endarterectomy in four (16%), infection in four (16%) and other cause (connective tissue disease, dissection, trauma) in six (24%) cases. Nineteen patients underwent open surgery, six underwent endovascular treatment. Death within 30 days was documented in one (4%) case. The mean postoperative hospital stay was 4.52 ± 2.38 days. Three (12%) patients required reintervention postoperatively. Peripheral nerve injuries were detected in four (16%) patients, all after open surgery. No stroke was documented within 30 days. The mean follow-up was 41.2 ± 38.54 months. Five (24%) deaths were not related to the carotid artery disease. One patient had stroke, one had transient ischaemic attack (TIA), and in two cases asymptomatic internal carotid artery occlusion was described. Conclusion: Both open surgery and endovascular intervention can be safely applied in the treatment of carotid artery aneurysm. Considering the variable etiology and rarity, we recommend to perform the interventions in vascular surgery centres. Orv Hetil. 2019; 160(21): 815-821.

[Endovascular treatment of blunt thoracic aortic injuries]. / Tompa trauma okozta mellkasi aortasérülések endovascularis ellátása.

INTRODUCTION: A new era has begun in the last two decades with the advent of endovascular methods in the therapy of blunt thoracic aorta injuries. Our experiences with the endovascular interventions of blunt aortic trauma in the Cardiovascular Center of Semmelweis University are summarised here. METHODS: We included those patients who underwent endovascular intervention due to blunt aortic trauma in a university hospital between 1998 and 2014. The statistical analysis was performed with the use of Excel. RESULTS: 41 patients were selected from our database. There were 34 males, the average age was 47 years (±17 years). Among the 41 patients 15 underwent an acute procedure (12 ruptures) and 26 patients received delayed treatment (in 4 cases due to growing of the pseudoaneurysm). There was only one early postoperative death. Late mortality was 22.5% and 7.5% was related to the aortic injury. CONCLUSION: Our late mortality and complication rates were similar to other studies, which reinforces international experiences. In the cases when delayed treatment is feasible, the patient can be stabilized and the CTA images can be analyzed for precise stentgraft planning. The treatment of blunt thoracic aorta injured patients should take place in specialized centers capable of such endovascular interventions.

Unusual Open Surgical Repair of a Type IB Endoleak and a Giant Symptomatic Aortic Aneurysm following Stent Grafting for Type B Aortic Dissection.

Treatment of type IB endoleak after thoracic endovascular aortic repair (TEVAR) for post-dissection aortic aneurysm usually includes attempts of endovascular interventions using coils or plugs to occlude the false lumen or placement of a distal fenestrated endograft. Open conversion usually requires deep hypothermia and circulatory arrest with the associated increased mortality and complications. We present a case of a young patient with a 90 mm descending thoracic aneurysm caused by a chronic type B aortic dissection. A type II endoleak after TEVAR was successfully treated with left subclavian artery transposition. The patient had a rapidly increasing aortic aneurysm with a persistent type IB endoleak in spite of placement of an Amplatzer plug into the false lumen of the dissection. He developed progressive acute compression of the main stem bronchi by the aneurysm sac and his dyspnea worsened by an acute pulmonary embolism treated with anticoagulation. Adequate oxygenation could only be achieved with mechanical ventilation using a double-lumen endobronchial tube. A left thoracotomy was performed and the type IB endoleak was treated with bending of the distal aorta around the stent graft with a Dacron graft sleeve. Aortic clamping and circulatory support devices were avoided. The sac of the aneurysm was opened, a giant hematoma was evacuated, and aneurysmorrhaphy was performed to cover the stent graft. There was no residual endoleak and the bronchi were decompressed. The patient recovered after prolonged hospitalization and he was discharged home in good condition 24 days after admission. He returned to his normal activities and is asymptomatic 5 months later. Computed tomographic angiography showed decreased aneurysm sac, no evidence of endoleak, no residual pulmonary embolus, and no bronchial compression.

[Open treatment of abdominal compartment syndrome after contained aortic aneurysm rupture]. / Fedett aortaaneurysma-ruptura miatt kialakult hasi compartmentsyndroma nyitott kezelése.

UNLABELLED: For the first time in Hungary, a patient with abdominal compartment syndrome after contained aortic aneurysm rupture was treated successfully implementing open abdomen treatment with vacuum-assisted wound closure (V.A.C.) and delayed abdominal wall closure with mesh. CASE REPORT: Contained aortic aneurysm rupture was diagnosed by CT angiography in a 59-year-old patient. After the acute reconstruction of the ruptured aorta (by an open procedure with aorto-aortic Dacron interposition) during the closure of the abdominal cavity the patient could not be effectively ventilated due to high intra-abdominal pressure caused by the severe oedema of the abdominal wall and the hematoma in the retroperitoneal space. In this situation, we decided upon open abdominal treatment using V.A.C. After regular changes of V.A.C. the abdomen was closed with DualMesh and three weeks later the patient was discharged home in good condition. CONCLUSION: In our case, abdominal closure was not implemented after the reconstruction of the ruptured aortic aneurysm due to the extensive oedema. The complications of abdominal compartment syndrome were prevented with the open treatment. Based on our experience and on the results of the international literature we highly recommend open abdominal treatment with V.A.C. in case of abdominal compartment syndrome.

[HER2-positive breast cancer: available targeted agents and biomarkers for therapy response]. / HER2-pozitív emlotumorok célzott terápiájában alkalmazott szerek és a terápiás válasz elorejelzése.

In the last decade, the targeted therapy of breast cancer became part of routine clinical protocols all over the globe. Options in today's targeted therapy include hormonal therapy and the modulation of the EGFR/HER-pathway. Of the four HER receptors, HER2 is the target of currently used treatment strategies. HER2 activates multiple intracellular pathways via RAS, RAF and PI3K. We give a comprehensive summary of approved monoclonal antibodies and tyrosine kinase inhibitors acting over HER2, including trastuzumab, lapatinib and pertuzumab. We elaborate on their mechanism of action and on clinical trials behind their approval. Agents in third phase clinical studies (neratinib, afatinib) are also described. We give a brief overview of agents currently in phase I and phase II studies; these are acting over the PI3K pathway, over IGFR1 and over HSP90. Furthermore, currently validated negative biomarkers (markers predicting lack of response) in clinical use are also summarized. Finally, the major bottlenecks of clinical application including tumor heterogeneity and the high diversity of clinical studies are discussed. For a breakthrough we will need to identify new positive biomarkers of therapy response.

A meta-analysis of gene expression-based biomarkers predicting outcome after tamoxifen treatment in breast cancer.

To date, three molecular markers (ER, PR, and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Our aim was to validate new biomarker candidates predicting response to tamoxifen treatment in breast cancer by evaluating these in a meta-analysis of available transcriptomic datasets with known treatment and follow-up. Biomarker candidates were identified in Pubmed and in the 2007-2012 ASCO and 2011-2012 SABCS abstracts. Breast cancer microarray datasets of endocrine therapy-treated patients were downloaded from GEO and EGA and RNAseq datasets from TCGA. Of the biomarker candidates, only those identified or already validated in a clinical cohort were included. Relapse-free survival (RFS) up to 5 years was used as endpoint in a ROC analysis in the GEO and RNAseq datasets. In the EGA dataset, Kaplan-Meier analysis was performed for overall survival. Statistical significance was set at p < 0.005. The transcriptomic datasets included 665 GEO-based and 1,208 EGA-based patient samples. All together 68 biomarker candidates were identified. Of these, the best performing genes were PGR (AUC = 0.64, p = 2.3E-07), MAPT (AUC = 0.62, p = 7.8E-05), and SLC7A5 (AUC = 0.62, p = 9.2E-05). Further genes significantly correlated to RFS include FOS, TP53, BTG2, HOXB7, DRG1, CXCL10, and TPM4. In the RNAseq dataset, only ERBB2, EDF1, and MAPK1 reached statistical significance. We evaluated tamoxifen-resistance genes in three independent platforms and identified PGR, MAPT, and SLC7A5 as the most promising prognostic biomarkers in tamoxifen treated patients.

Improving Pathological Assessment of Breast Cancer by Employing Array-Based Transcriptome Analysis.

Breast cancer research has paved the way of personalized oncology with the introduction of hormonal therapy and the measurement of estrogen receptor as the first widely accepted clinical biomarker. The expression of another receptor-HER2/ERBB2/neu-was initially a sign of worse prognosis, but targeted therapy has granted improved outcome for these patients so that today HER2 positive patients have better prognosis than HER2 negative patients. Later, the introduction of multigene assays provided the pathologists with an unbiased assessment of the tumors' molecular fingerprint. The recent FDA approval of complete microarray pipelines has opened new possibilities for the objective classification of breast cancer samples. Here we review the applications of microarrays for determining ER and HER2 status, molecular subtypes as well as predicting prognosis and grade for breast cancer patients. An open question remains the role of single genes within such signatures. Openly available microarray datasets enable the execution of an independent cross-validation of new marker and signature candidates. In summary, we review the current state regarding clinical applications of microarrays in breast cancer molecular pathology.