Detection and Real-Time Surgical Assessment of Colorectal Liver Metastases Using Near-Infrared Fluorescence Imaging during Laparoscopic and Robotic-Assisted Resections.

BACKGROUND: The European Association of Endoscopic Surgery (EAES) recommends, with strong evidence, the use of indocyanine green (ICG) fluorescence imaging combined with intraoperative ultrasound (IOUS) to improve identification of superficial liver tumors. This study reports the use of ICG for the detection of colorectal liver metastases (CRLMs) during minimally invasive liver resection. METHODS: A single-center consecutive series of minimally invasive (laparoscopic and robotic) hepatic resections for CRLMs was prospectively evaluated (April 2019 and October 2023). RESULTS: A total of 25 patients were enrolled-11 undergoing laparoscopic and 14 undergoing robotic procedures. The median age was 65 (range 50-85) years. Fifty CRLMs were detected: twenty superficial, eight exophytic, seven shallow (<8 mm from the hepatic surface), and fifteen deep (>10 mm from the hepatic surface) lesions. The detection rates of CRLMs through preoperative imaging, laparoscopic ultrasound (LUS), ICG fluorescence, and combined modalities (ICG and LUS) were 88%, 90%, 68%, and 100%, respectively. ICG fluorescence staining allowed us to detect five small additional superficial lesions (not identified with other preoperative/intraoperative techniques). However, two lesions were false positive fluorescence accumulations. All rim fluorescence pattern lesions were CRLMs. ICG fluorescence was used as a real-time guide to assess surgical margins during parenchymal-sparing liver resections. All patients with integrity of the fluorescent rim around the CRLM displayed a radical resection during histopathological analysis. Four patients (8%) with a protruding rim or residual rim patterns had positive resection margins. CONCLUSIONS: ICG fluorescence imaging can be integrated with other conventional intraoperative imaging techniques to optimize intraoperative staging. Rim fluorescence proved to be a valid indicator of the resection margins: by removing the entire fluorescent area, a tumor-negative resection (R0) is achieved.

Cognitive trajectories after surgery: Guideline hints for assessment and treatment.

Elderly patients who undergo major surgery (not-neurosurgical) under general anaesthesia frequently complain about cognitive difficulties, especially during the first weeks after surgical "trauma". Although recovery usually occurs within a month, about one out of four patients develops full-blown postoperative Neurocognitive disorders (NCD) which compromise quality of life or daily autonomy. Mild/Major NCD affect approximately 10% of patients from three months to one year after major surgery. Neuroinflammation has emerged to have a critical role in the postoperative NCDs pathogenesis, through microglial activation and the release of pro-inflammatory cytokines which increase blood-brain-barrier permeability, enhance movement of leukocytes into the central nervous system (CNS) and favour the neuronal damage. Moreover, pre-existing Mild Cognitive Impairment, alcohol or drugs consumption, depression and other factors, together with several intraoperative and post-operative sequelae, can exacerbate the severity and duration of NCDs. In this context it is crucial rely on current progresses in serum and CSF biomarker analysis to frame neuroinflammation levels, along with establishing standard protocol for neuropsychological assessment (with specific set of tools) and to apply cognitive training or neuromodulation techniques to reduce the incidence of postoperative NCDs when required. It is recommended to identify those patients who would need such preventive intervention early, by including them in pre-operative and post-operative comprehensive evaluation and prevent the development of a full-blown dementia after surgery. This contribution reports all the recent progresses in the NCDs diagnostic classification, pathogenesis discoveries and possible treatments, with the aim to systematize current evidences and provide guidelines for multidisciplinary care.

Early outcomes of "low-risk" patients undergoing lung resection assessed by cardiopulmonary exercise testing: Single-institution experience.

Objective: Cardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO2peak). Patients with VO2peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing. Methods: Retrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period. Results: A total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO2peak above target for safe surgery. Conclusions: Postoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO2peak in identifying higher risk patients, even in this subgroup.

Sirolimus treatment for paediatric head and neck lymphatic malformations: a systematic review.

PURPOSE: This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on treatment efficacy but also on possible treatment-related adverse events, and treatment combinations with other techniques. METHODS: Search criteria were applied to MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases and included all studies published up to March 2022 reporting paediatric lymphatic malformations treated with sirolimus. We selected all original studies that included treatment outcomes. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for patient demographics, lymphatic malformation type, size or stage, site, clinical response rates, sirolimus administration route and dose, related adverse events, follow-up time, and concurrent treatments. RESULTS: Among 153 unique citations, 19 studies were considered eligible, with reported treatment data for 97 paediatric patients. Most studies (n = 9) were case reports. Clinical response was described for 89 patients, in whom 94 mild-to-moderate adverse events were reported. The most frequently administered treatment regimen was oral sirolimus 0.8 mg/m2 twice a day, with the aim of achieving a blood concentration of 10-15 ng/mL. CONCLUSION: Despite promising results for sirolimus treatment in lymphatic malformation, the efficacy and safety profile of remains unclear due to the lack of high-quality studies. Systematic reporting of known side effects, especially in younger children, should assist clinicians in minimising treatment-associated risks. At the same time, we advocate for prospective multicentre studies with minimum reporting standards to facilitate improved candidate selection.

Management and Outcome of Parathyroid Carcinoma-Induced Primary Hyperparathyroidism: A Single-Centre Experience.

BACKGROUND: Parathyroid carcinoma (PC) is the rarest endocrine cancer and an infrequent cause of primary hyperparathyroidism (PHPT), responsible for less than 1% of cases. Due to its rarity, treatment is challenging. METHODS: A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. We identified and individually described the patients affected with PC. Then, we split all patients treated for PHPT into four groups based on the cause: PC, adenoma, atypical adenoma, and hyperplasia. Patients' demographics, preoperative evaluation results, intraoperative findings, and outcomes for the PC group were compared with groups of PHPT due to benign causes. RESULTS: Eight cases of PC were identified, five males and three females. Seven cases presented with symptoms of hypercalcemia and one with a neck mass. Five underwent en bloc resections and three local excisions. Histopathological features showed capsular invasion in four patients, capsular and soft tissue invasion in three patients, and vascular invasion in one case. No patients had distant metastasis. One patient was classed as high risk based on the Schulte classification system. All patients treated for PC were alive and disease-free at a mean follow-up of 38.4 months. When compared with other PHPT patients, PC patients were more frequently male and had higher preoperative blood calcium and PTH and lower phosphate levels, larger and heavier parathyroids excised, lower postoperative calcium, and a higher rate of postoperative hypoparathyroidism. CONCLUSION: Our study highlights some aspects valuable to suspect PC and differentiate PHPT-PC from benign causes of PHPT preoperatively. Preoperative suspicion of malignancy is essential to guarantee the best course of treatment for patients. Although limited for size and follow-up, the excellent outcome of our series seems to support the value of both surgery extension and risk class according to the Schulte classification as possible prognostic factors for recurrence.

An Unusual Histology for a Lung Nodule: A Case Report of Primary Pulmonary Paraganglioma.

Introduction: Primary pulmonary paraganglioma is a rare tumor with few cases reported in literature and unspecific clinical presentation. Case Presentation: A 49-year-old woman presented to our department with an incidental finding of a pulmonary mass at chest X-ray and no associated clinical symptom. The CT scan and the FDG-PET showed mild uptake of contrast, but a definitive diagnosis was only possible after surgery through histopathological examination. Conclusion: Paragangliomas originating in the pulmonary tissue are generally non-functioning masses discovered incidentally in otherwise asymptomatic patients. Surgery appears to be the best treatment option, with only radiologic follow-up necessary afterwards.

Unexpected thymoma in a challenging case of hyperparathyroidism.

We report the case of a woman with primary hyperparathyroidism suspected of mediastinal ectopic parathyroid adenoma revealed to be a thymoma. Our aim was to focus on some possible criticisms in distinguishing between ectopic parathyroid and thymus.

Adipose-Derived Stem Cells from Fat Tissue of Breast Cancer Microenvironment Present Altered Adipogenic Differentiation Capabilities.

Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into multiple cell types, including adipocytes, osteoblasts, and chondrocytes. The role of adipose-derived stem cells (ADSCs) in cancers is significantly relevant. They seem to be involved in the promotion of tumour development and progression and relapse processes. For this reason, investigating the effects of breast cancer microenvironment on ADSCs is of high importance in order to understand the relationship between tumour cells and the surrounding stromal cells. With the current study, we aimed to investigate the specific characteristics of human ADSCs isolated from the adipose tissue of breast tumour patients. We compared ADSCs obtained from periumbilical fat (PF) of controls with ADSCs obtained from adipose tissue of breast cancer- (BC-) bearing patients. We analysed the surface antigens and the adipogenic differentiation ability of both ADSC populations. C/EBPδ expression was increased in PF and BC ADSCs induced to differentiate compared to the control while PPARγ and FABP4 expressions were enhanced only in PF ADSCs. Conversely, adiponectin expression was reduced in PF-differentiated ADSCs while it was slightly increased in differentiated BC ADSCs. By means of Oil Red O staining, we further observed an impaired differentiation capability of BC ADSCs. To investigate this aspect more in depth, we evaluated the effect of selective PPARγ activation and nutritional supplementation on the differentiation efficiency of BC ADSCs, noting that it was only with a strong differentiation stimuli that the process took place. Furthermore, we observed no response in BC ADSCs to the PPARγ inhibitor T0070907, showing an impaired activation of this receptor in adipose cells surrounding the breast cancer microenvironment. In conclusion, our study shows an impaired adipogenic differentiation capability in BC ADSCs. This suggests that the tumour microenvironment plays a key role in the modulation of the adipose microenvironment located in the surrounding tissue.

The Ribonucleic Complex HuR-MALAT1 Represses CD133 Expression and Suppresses Epithelial-Mesenchymal Transition in Breast Cancer.

Epithelial-to-mesenchymal transition (EMT) is a core process underlying cell movement during embryonic development and morphogenesis. Cancer cells hijack this developmental program to execute a multi-step cascade, leading to tumorigenesis and metastasis. CD133 (PROM1), a marker of cancer stem cells, has been shown to facilitate EMT in various cancers, but the regulatory networks controlling CD133 gene expression and function in cancer remain incompletely delineated. In this study, we show that a ribonucleoprotein complex including the long noncoding RNA MALAT1 and the RNA-binding protein HuR (ELAVL1) binds the CD133 promoter region to regulate its expression. In luminal nonmetastatic MCF-7 breast cancer cells, HuR silencing was sufficient to upregulate N-cadherin (CDH2) and CD133 along with a migratory and mesenchymal-like phenotype. Furthermore, we found that in the basal-like metastatic cell line MDA-MB-231 and primary triple-negative breast cancer tumor cells, the repressor complex was absent from the CD133-regulatory region, but was present in the MCF-7 and primary ER+ tumor cells. The absence of the complex from basal-like cells was attributed to diminished expression of MALAT1, which, when overexpressed, dampened CD133 levels. In conclusion, our findings suggest that the failure of a repressive complex to form or stabilize in breast cancer promotes CD133 upregulation and an EMT-like program, providing new mechanistic insights underlying the control of prometastatic processes. Cancer Res; 76(9); 2626-36. ©2016 AACR.

Enhanced brain release of erythropoietin, cytokines and NO during carotid clamping.

Although effective and safe, carotid endarterectomy (CEA) implies a reduced blood flow to the brain and likely an ischemia/reperfusion event. The high rate of uneventful outcomes associated with CEA suggests the activation of brain endogenous protection mechanisms aimed at limiting the possible ischemia/reperfusion damage. This study aims at assessing whether CEA triggers protective mechanisms such as brain release of erythropoietin and nitric oxide. CEA was performed in 12 patients; blood samples were withdrawn simultaneously from the surgically exposed ipsilateral jugular and leg veins before, during (2 and 40 min) and after clamp removal (2 min). Plasma antioxidant capacity, carbonylated proteins, erythropoietin, nitrates and nitrites (NOx) were determined. No changes in intraoperative EEG, peripheral and transcranial blood oxygen saturation were detectable, and no patients showed any neurologic sign after the intervention. Antioxidant capacity and protein carbonylation in plasma were unaffected. Differently, erythropoietin, VEGF, TNF-α and NOx increased during clamping in the jugular blood (2 and 40 min), while no changes were observed in the peripheral circulation. These results show that blood erythropoietin, VEGF, TNF-α, and NOx increased in the brain during uncomplicated CEA. This may represent an endogenous self-activated neuroprotective mechanism aimed at the prevention of ischemia/reperfusion damage.

Multidisciplinary approach to follicular thyroid carcinoma with giant mandibular and multiple sites metastases Case report.

UNLABELLED: Multidisciplinary approach to follicular thyroid carcinoma with giant mandibular and multiple sites metastases. Case report Metastatic tumors generally have poor prognosis, with short survival period and rarely indication to surgical treatment. In case of thyroid-differentiated cancer with distant metastases, prognosis is usually better, because of the possibility of treating metastasis by Radio Ablation by 131Iodine, after surgery. We report the case of a 65 years old woman, presenting with a giant mandibular metastasis from follicular thyroid carcinoma, originating from a cervico-mediastinal nonfunctioning goiter, with lung metastases. After the diagnostic work-up, she underwent left hemi-mandibulectomy, reconstruction by the placement of a precustomized titanium plate with condylar prosthesis and total thyroidectomy. Subsequently the Patient was treated by Radio Ablation by 131 Iodine, in four consecutive sessions. She is alive with no progression of the neoplasm after forty-six months follow-up. Even in advanced differentiated thyroid carcinoma, surgery should be taken into consideration, to treat the patient by complementary therapies and to improve the prognosis in term of survival. KEY WORDS: Advanced differentiated thyroid carcinoma, Metastatic differentiated thyroid carcinoma.

Thyroid microcarcinoma approach: a ten year experience.

AIM: To optimize thyroid microcarcinoma approach, through a retrospective examination of Authors' experience and literature review. MATERIALS: Characteristics, treatment and outcomes of patients affected with thyroid microcarcinoma were examined: among 1733 patients operated on for thyroid diseases at Endocrine Surgery Unit of San Paolo Hospital in Milan, from 2001 to 2011, 104 (6.0%) resulted affected with microcarcinoma. Twenty (19.2%) had pre-operative and 84 (80.8%) post-operative diagnosis, 11 with (N+) and 93 without (N0) lymph node metastasis. Eighty-five patients underwent total thyroidectomy, 11 (N+) total thyroidectomy with lymphoadenectomy and 8 lobectomy, 2 radicalized in thyroidectomy. All patients underwent Levo-thyroxine suppressive therapy, 25 (24.0%) 131I ablation. Differences between N0 and N+ patients were researched. RESULTS: Neither recurrences nor death at a mean follow-up of 5.6 years. Tumour was multifocal and in thyroid with no other diseases in N+, in a greater rate than in N0 patients. DISCUSSION: Microcarcinoma generally has an indolent course, but sometimes it presents with nodal metastasis. For this reason its treatment in literature is still largely debated. CONCLUSION: In cases of pre-operative diagnosis of microcarcinoma without lymph node metastasis, we propose total thyroidectomy; otherwise, total thyroidectomy with lymphoadenectomy. In cases of post-operative diagnosis, after a partial resection, only selected cases on the basis of patients' and tumour features require a completion total thyroidectomy. We propose Levo-thyroxine suppressive therapy to all patients, 131I ablation in cases of lymphatic metastasis and only in selected cases without metastasis, on the basis of patients' and tumour aspects (age, sex, histological variant, multifocality).

Erythropoietin: recent developments in the treatment of spinal cord injury.

Erythropoietin (EPO), originally identified for its critical function in regulating production and survival of erythrocytes, is a member of the type 1 cytokine superfamily. Recent studies have shown that EPO has cytoprotective effects in a wide variety of cells and tissues. Here is presented the analysis of EPO effects on spinal cord injury (SCI), considering both animal experiments concerning to mechanisms of neurodegeneration in SCI and EPO as a neuroprotective agent, and some evidences coming from ongoing clinical trials. The evidences underling that EPO could be a promising therapeutic agent in a variety of neurological insults, including trauma, are mounting. In particular, it is highlighted that administration of EPO or other recently generated EPO analogues such as asialo-EPO and carbamylated-EPO demonstrate interesting preclinical and clinical characteristics, rendering the evaluation of these tissue-protective agents imperative in human clinical trials. Moreover the demonstration of rhEPO and its analogues' broad neuroprotective effects in animal models of cord lesion and in human trial like stroke, should encourage scientists and clinicians to design clinical trials assessing the efficacy of these pharmacological compounds on SCI.

Genetic control of chemokines in severe human internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Atherosclerosis is an inflammatory disease. Chemokines and chemokine receptors are known to be involved in atherogenesis. Common single nucleotide polymorphisms (SNPs) affect transcription in response to inflammatory stimuli. The aim of this study was to evaluate the correlations between MCP-1, RANTES, SDF-1, CCR2, and CCR5 gene polymorphisms with increased risk of internal carotid artery (ICA) stenosis. METHODS: Hundred and twelve patients, consecutively recruited for ICA occlusive disease, and 282 controls were genotyped for MCP-1-2518G, RANTES-403A, CCR5Delta32, CCR2 V64I, and SDF-1-801A polymorphisms. RESULTS: The frequency of the SDF-1A allele was significantly different between cases and controls: 0.32 vs. 0.20, respectively (OR 1.81; 95% CI 1.25-2.60; p=0.007). The frequency of the RANTES-403G allele was significantly higher in patients with stenosis >70% (OR, 2.45; 95% CI 1.12-5.71; p=0.015). No significant differences were observed with the other polymorphisms. CONCLUSION: The reported results seem to correlate the polymorphisms of the genes encoding for SDF-1, RANTES with pathogenesis and progression of ICA occlusive disease. Although suggestive, these results need confirmation in prospective cross-sectional studies.

Genetic contribution to carotid vascular disease in patients with systemic lupus erythematosus.

OBJECTIVE: We investigated whether stromelysin, a candidate gene in atherogenesis, plays a role in atherogenesis of systemic lupus erythematosus (SLE), a leading cause of mortality in SLE. PATIENTS AND METHODS: A genetic study using polymorphism located in the promoter region of stromelysin was performed in 55 Italian patients with SLE. Carotid intimal-medial thickness (IMT) was evaluated by B mode ultrasonography. RESULTS: All patients with an "abnormal" (> or =0.9 mm) IMT carried at least one 6A allele, and the degree of IMT was significantly greater in patients carrying at least one 6A allele (0.63 +/- 0.22 vs 0.43 +/- 0.04 mm, 5A/6A + 6A/6A vs 5A/5A, p = 0.018). CONCLUSION: Our data show that polymorphism of stromelysin promoter may be relevant for SLE-related cardiovascular disease.

Xanthine oxido-reductase activity in ischemic human and rat intestine.

We measured time course and extent of xanthine dehydrogenase (XD) to xanthine oxidase (XO) conversion in ischemic human and rat intestine. To model normothermic no-flow ischemia, we incubated fresh biopsies for 0, 2, 4, 8 and 16h. At t = 0h, XO was less in humans than in rats (P < 0.0004), while XD was essentially the same (P = NS). After 16h incubation at 37 degrees C, there was no appreciable XD-to-XO conversion and no change in neither XO nor XD activity in human intestine. In contrast, the rat intestine had XO/(XO + XD) ratio doubled in the first 2h and then maintained that value until t = 16 h. In conclusion, no XO-to-XD conversion was appreciable after 16 h no-flow normothermic ischemia in human intestine; in contrast, XO activity in rats increased sharply after the onset of ischemia. An immunohistochemical labelling study shows that, whereas XO + XD expression in liver tissue is localised in both hepatocytes and endothelial cells, in the intestine that expression is mostly localised in epithelial cells. We conclude that XO may be considered as a major source of reactive oxygen species in rats but not in humans.

Genetic risk factor characterizes abdominal aortic aneurysm from arterial occlusive disease in human beings: CCR5 Delta 32 deletion.

OBJECTIVE: Inflammation is involved in the pathogenesis of atherosclerosis and abdominal aortic aneurysm (AAA), and chemokines are mediators of the inflammatory process. The homozygous Delta 32 deletion mutation of the gene of the chemokine receptor CCR5 is a cause of its lack in inflammatory cells. The purpose of this study was to investigate the relationship between CCR5 Delta 32 deletion mutation and AAA, peripheral arterial occlusive disease (PAOD), and carotid stenosis. METHODS: The CCR5 Delta 32 polymorphism was genotyped in 380 subjects: 70 patients operated on to treat AAA (21 ruptured AAAs, 49 elective repair), 76 patients with PAOD, 62 patients with carotid stenosis, and 172 age-matched and sex-matched healthy control subjects. Risk factors for AAA were considered. Each patient was assessed according to a diagnostic procedure tailored to symptoms at presentation. RESULTS: In patients with AAA the Delta allelic variation was significantly different compared with control subjects (P = .002; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.41-5.15). The increased presence of this allele differentiates AAA from both PAOD (P = .017; OR, 2.77; 95% CI, 1.17-6.52) and carotid stenosis (P = .01; OR, 3.47; 95% CI, 1.31-9.11). The presence in the genotype of patients with AAA of at least 1 Delta 32 allele is more frequent in ruptured AAAs than in electively repaired AAAs (genotype: OR, 4.04; 95% CI, 1.34-12.1; P = .011; allelic frequency: OR, 2.75; 95% CI, 1.07-7.07; P = .035). Among the patients, multiple regression analysis showed that the Delta 32 allele is an independent risk factor for AAA vs PAOD (OR, 3.13; 95% CI, 1.33-7.33; P = .012) and for ruptured AAAs vs electively repaired AAAs (OR, 3.52; 95% CI, 1.01-11.80; P = .045). CONCLUSIONS: CCR5 Delta 32 deletion mutation is significantly more frequent in patients with AAA than in control subjects and in both patients with PAOD and carotid stenosis, and could be a factor that differentiates AAA from PAOD, and ruptured AAAs from AAAs that can be electively repaired. CLINICAL RELEVANCE: The major threat of abdominal aortic aneurysm (AAA) is rupture, accounting for extremely high mortality. This occurrence has been correlated to aneurysm size, but it is a common observation that small AAAs can rupture and large AAAs can remain stable for many years. This study was carried out in an attempt to search for genetic markers of aneurysm rupture. Some single nucleotide polymorphisms are implicated in acceleration of transcription for enzymes involved in the inflammatory process and in extracellular matrix remodeling. An association between single nucleotide polymorphisms and aneurysm rupture could enable better selection for surgical indications in patients with small AAs and in patients at poor risk with large AAAs.

Internal carotid artery occlusive disease and polymorphisms of fractalkine receptor CX3CR1: a genetic risk factor.

BACKGROUND AND PURPOSE: Fractalkine (FKN), a chemokine expressed by inflamed endothelium, induces leukocyte adhesion and migration via the receptor CX3CR1. The polymorphisms V249I and T280M affect receptor expression and function. The role of FKN in atherosclerosis has been recently demonstrated. The aim of this study was to investigate a possible association between CX3CR1 polymorphisms and increased risk of internal carotid artery (ICA) occlusive disease. METHODS: We studied 108 patients consecutively recruited for ICA occlusive disease, 84 of whom underwent operation for carotid endarterectomy, and 204 subjects without ICA occlusive disease (controls). Polymorphic genotypes were determined by polymerase chain reaction and sequencing analysis. RESULTS: The adjusted odds ratio (OR) associated with the presence of the M280 (TM+MM versus TT genotype) was 0.55 (95% CI: 0.29 to 0.99; P=0.037). Therefore, this allele is associated with a reduced risk of ICA occlusive disease. No significant differences were observed in I249 distribution. The frequency of I249 allele was significantly higher in cases of hard plaques, which are considered more stable than soft ones (OR: 0.38; 95% CI: 0.13 to 1.05; P=0.037). Multiple logistic regression analysis using the common risk factors and the I249 and M280 allele variants revealed that the M280 allele was an independent risk factor for ICA stenosis (P=0.047). CONCLUSIONS: The results show that the CX3CR1 M280 is an independent genetic risk factor for ICA occlusive disease and that I249 is involved in the stability of carotid plaques. Even if obtained from a relatively limited patient series, these results might have relevant implications for treatment of ICA stenosis and possibly prevention of carotid related stroke. Further prospective cross-sectional studies are needed to confirm these results.

Vascular invasion in human breast cancer is correlated to T-->786C polymorphism of NOS3 gene.

BACKGROUND: Nitric oxide (NO) is a free radical known to be a major regulator of vascular tonus, to inhibit cell proliferation, induce apoptosis, and be a mediator of macrophage cytostatic and cytotoxic effects. Recently, NO synthesis has been reported to be elevated in different cancers and is expected to promote metastasis by maintaining a vasodilator tone in blood vessels in and around the tumour. Two different common genetic polymorphisms were found on endothelial NO synthase (NOS3) gene: Glu298Asp on exon 7 and T-->786C in the promoter region. PURPOSE: To evaluate the impact of the NOS3 polymorphisms on vascular invasion and metastasis in breast cancer patients. DESIGN: Two NOS3 gene polymorphisms (Glu298Asp and T-->786C) were genotyped in 71 patients operated for breast cancer and followed for 6-30 months (median 21). A control population of 91 age and sex matched tumour-free subjects was also genotyped for the same polymorphisms. RESULTS: The distribution of both polymorphisms was not different between cases and controls. In patients without vascular invasion, T allele frequency was significantly lower than in patients with vascular invasion (p=0.033). At the end of the follow-up, T allele frequency was found to be less frequent in the metastasis free group than normal population (0.51 vs 0.64; p=0.047). CONCLUSION: Our results suggest that T allele reduction at the NOS3 promoter region may reduce vascular invasion in breast cancer and consequently reduce metastatic spread and be a favorable prognostic factor. These results need further validation in larger studies.