Longterm peripheral baroreflex and chemoreflex function after bilateral eversion carotid endarterectomy

Introduction The “eversion” technique for carotid endarterectomy (e-CEA), that involves the transection of the internal carotid artery at the carotid bulb and its eversion over the atherosclerotic plaque, has been associated with an increased risk of postoperative hypertension possibly due to a direct iatrogenic damage to the carotid sinus fibers. The aim of this study is to assess the long-term effect of the e-CEA on arterial baroreflex and peripheral chemoreflex function in humans. Methods A retrospective review was conducted on a prospectively compiled computerized database of 3128 CEAs performed on 2617 patients at our Center between January 2001 and March 2006. During this period, a total of 292 patients who had bilateral carotid stenosis ≥70% at the time of the first admission underwent staged bilateral CEAs. Of these, 93 patients had staged bilateral e-CEAs, 126 staged bilateral s- CEAs and 73 had different procedures on each carotid. CEAs were performed with either the eversion or the standard technique with routine Dacron patching in all cases. The study inclusion criteria were bilateral CEA with the same technique on both sides and an uneventful postoperative course after both procedures. We decided to enroll patients submitted to bilateral e-CEA to eliminate the background noise from contralateral carotid sinus fibers. Exclusion criteria were: age >70 years, diabetes mellitus, chronic pulmonary disease, symptomatic ischemic cardiac disease or medical therapy with b-blockers, cardiac arrhythmia, permanent neurologic deficits or an abnormal preoperative cerebral CT scan, carotid restenosis and previous neck or chest surgery or irradiation. Young and aged-matched healthy subjects were also recruited as controls. Patients were assessed by the 4 standard cardiovascular reflex tests, including Lying-to-standing, Orthostatic hypotension, Deep breathing, and Valsalva Maneuver. Indirect autonomic parameters were assessed with a non-invasive approach based on spectral analysis of EKG RR interval, systolic arterial pressure, and respiration variability, performed with an ad hoc software. From the analysis of these parameters the software provides the estimates of spontaneous baroreflex sensitivity (BRS). The ventilatory response to hypoxia was assessed in patients and controls by means of classic rebreathing tests. Results A total of 29 patients (16 males, age 62.4±8.0 years) were enrolled. Overall, 13 patients had undergone bilateral e-CEA (44.8%) and 16 bilateral s-CEA (55.2%) with a mean interval between the procedures of 62±56 days. No patient showed signs or symptoms of autonomic dysfunction, including labile hypertension, tachycardia, palpitations, headache, inappropriate diaphoresis, pallor or flushing. The results of standard cardiovascular autonomic tests showed no evidence of autonomic dysfunction in any of the enrolled patients. At spectral analysis, a residual baroreflex performance was shown in both patient groups, though reduced, as expected, compared to young controls. Notably, baroreflex function was better maintained in e-CEA, compared to standard CEA. (BRS at rest: young controls 19.93 ± 2.45 msec/mmHg; age-matched controls 7.75 ± 1.24; e-CEA 13.85 ± 5.14; s-CEA 4.93 ± 1.15; ANOVA P=0.001; BRS at stand: young controls 7.83 ± 0.66; age-matched controls 3.71 ± 0.35; e-CEA 7.04 ± 1.99; s-CEA 3.57 ± 1.20; ANOVA P=0.001). In all subjects ventilation (VÝ E) and oximetry data fitted a linear regression model with r values > 0.8. Oneway analysis of variance showed a significantly higher slope both for ΔVE/ΔSaO2 in controls compared with both patient groups which were not different from each other (-1.37 ± 0.33 compared with -0.33±0.08 and -0.29 ±0.13 l/min/%SaO2, p<0.05, Fig.). Similar results were observed for and ΔVE/ΔPetO2 (-0.20 ± 0.1 versus -0.01 ± 0.0 and -0.07 ± 0.02 l/min/mmHg, p<0.05). A regression model using treatment, age, baseline FiCO2 and minimum SaO2 achieved showed only treatment as a significant factor in explaining the variance in minute ventilation (R2= 25%). Conclusions Overall, we demonstrated that bilateral e-CEA does not imply a carotid sinus denervation. As a result of some expected degree of iatrogenic damage, such performance was lower than that of controls. Interestingly though, baroreflex performance appeared better maintained in e-CEA than in s-CEA. This may be related to the changes in the elastic properties of the carotid sinus vascular wall, as the patch is more rigid than the endarterectomized carotid wall that remains in the e-CEA. These data confirmed the safety of CEA irrespective of the surgical technique and have relevant clinical implication in the assessment of the frequent hemodynamic disturbances associated with carotid angioplasty stenting.

Tumori primitivi multipli del polmone. Profilo clinico e biologico in pazienti affetti da neoplasie polmonari multiple. Analisi di elementi clinici e marcatori biologici come possibili fattori di differenziazione dei tumori polmonari multipli

Background: MPLC represents a diagnostic challenge. Topic of the discussion is how to distinguish these patients as a metastatic or a multifocal disease. While in case of the different histology there are less doubt on the opposite in case of same histology is mandatory to investigate on other clinical features to rule out this question. Matherials and Methods: A retrospective review identified all patients treated surgically for a presumed diagnosis of SPLC. Pre-operative staging was obtained with Total CT scan and fluoro-deoxy positron emission tomography and mediastinoscopy. Patients with nodes interest or extra-thoracic location were excluded from this study. Epidermal growth factor receptor (EGFR) expression with complete immunohistochemical analisis was evaluated. Survival was estimated using Kaplan-Meyer method, and clinical features were estimated using a long-rank test or Cox proportional hazards model for categorical and continuous variable, respectively. Results: According to American College Chest Physician, 18 patients underwent to surgical resection for a diagnosis of MPLC. Of these, 8 patients had 3 or more nodules while 10 patients had less than 3 nodules. Pathologic examination demonstrated that 13/18(70%) of patients with multiple histological types was Adenocarcinoma, 2/18(10%) Squamous carcinoma, 2/18(10%) large cell carcinoma and 1/18(5%) Adenosquamosu carcinoma. Expression of EGFR has been evaluated in all nodules: in 7 patients of 18 (38%) the percentage of expression of each nodule resulted different. Conclusions: MPLC represent a multifocal disease where interactions of clinical informations with biological studies reinforce the diagnosis. EGFR could contribute to differentiate the nodules. However, further researches are necessary to validate this hypothesis.

Stereotactict body radiotherapy (SBRT)

Purpose: evaluation and comparison of volumetric modulated RapidarcTM radiotherapy (RA-IMRT) vs linac based Stereotactic body radiotherapy (SBRT) in the salvage treatment of isolated lymph node recurrences in patients affected by gynaecological cancer. Materials and Methods From January 2010 to September 2011, 15 patients affected by isolated lymph nodes recurrence of gynaecological cancer underwent salvage radiotherapy after conventional imaging staging with CT and 18-FDG-PET/CT. Two different radiotherapy techniques were used in this study: RA-IMRT (RapidarcTM implemented radiotherapy Varian Medical System, Palo Alto, CA, USA) or SBRT (BrainLAB, Feldkirchen, Germany). Five patients underwent CT scan and all patients underwent 18FDG-PET/CT for pre-treatment evaluation and staging. The mean total dose delivered was 54.3 Gy (range 50-60 Gy with conventional fractionation and 27.4 Gy (range 12-40 Gy hypofractionation) for RA-IMRT and SBRT respectively. The mean number of fractions was 27.6 fractions (range 25-31) and 3-4 fractions , the mean overall treatment duration was 40.5 days (range 36-45) and 6.5 days (range 5-8 days) for RA-IMRT and SBRT respectively. Results: At the time of the analysis, October 2011, the overall survival was 92.3 % (80% for RA-IMRT and 100% for SBRT). Six patients are alive with no evidence of disease and also six patients are alive with clinically evident disease in other sites (40% and 50% patients RA-IMRT vs SBRT respectively, one patient died for systemic progression of disease and two patient were not evaluable at this time. Conclusions: Our preliminary results showed that, the use of RA-IMRT and SBRT are an excellent local therapy for isolated lymph nodes recurrences of gynaecological cancer with a good toxicity profile and local control rate, even if any long term survivors would be expected. New treatment modalities like Cyberknife are also being implemented.

Risultati funzionali a lungo termine dopo sutura o plicatura del diaframma

Obbiettivo. Analizzare la funzionalità polmonare e diaframmatica dopo interventi di plicatura del diaframma con rete di rinforzo peri-costale eseguiti per relaxatio e riparazione di ernia transdiaframmatica cronica mediante riduzione e sutura diretta. Metodi. Dal 1996 al 2010, 10 pazienti con relaxatio unilaterale del diaframma e 6 pazienti con ernia transdiaframmatica cronica misconosciuta sono stati sottoposti a chirurgia elettiva. Gli accertamenti preoperatori e al follow-up di 12 mesi includevano prove di funzionalità respiratoria, misura della pressione massimale inspiratoria alla bocca in clino e ortostatismo, emogasanlisi, TC del torace e dispnea score. Risultati. I pazienti dei due gruppi non differivano in termini di funzionalità respiratoria preoperatoria nè di complicanze postoperatorie; al follow-up a 12 mesi il gruppo Eventrazione mostrava un significativo aumento del FEV1% (+18,2 – p<0.001), FVC% (+12,8 – p<0.001), DLCO% (+6,84 – p=0,04) e pO2 (+9,8 mmHg – p<0.001). Al contrario nrl gruppo Ernia solo il miglioramento della pO2 era significativo (+8.3 – p=0.04). Sebbene la massima pressione inspiratoria (PImax) fosse aumentata in entrambi i gruppi al follow-up, i pazienti operati per ernia mostravano un miglioramento limitato con persistente caduta significativa della PImax dall’ortostatismo al clinostatismo (p<0.001). Il Transitional dyspnoea score è stato concordante con tali miglioramenti pur senza differenze significative tra i due gruppi. La TC del torace ha evidenziato una sopraelevazione dell’emidiaframma suturato, senza recidiva di ernia, mentre i pazienti sottoposti a plicatura hanno mantenuto l’ipercorrezione. Conclusioni. L’utilizzo di un rinforzo protesico è sicuro e sembra assicurare risultati funzionali migliori a distanza in termini di flussi respiratori e di movimento paradosso del diaframma (valutato mediante PImax). Lacerazioni estese del diaframma coinvolgenti le branche principali di suddivisione del nervo frenico si associano verosimilmente a una relaxatio che può quindi ridurre il guadagno funzionale a lungo termine se non adeguatamente trattata mediante l’utilizzo di un rinforzo protesico.

Ricostruzione mandibolare con tecnologia CAD-CAM

L’obbiettivo di una ricostruzione micro vascolare di mandibola è quello di assicurare al paziente il miglior risultato estetico e funzionale auspicabile. Ciò può essere conseguito utilizzando il lembo microvascolare di perone/cresta iliaca e una placca ricostruttiva in titanio che funga da guida nella fase di modellamento del lembo per ricreare un contorno parabolico il più possibile simile al profilo mandibolare originario del paziente. Il modellamento manuale ed artigianale intraoperatorio di una placca ricostruttiva è operatore dipendente ed anche in mani molto abili o ricorrendo a modelli anatomici stereolitografici non sempre risulta preciso quanto voluto e spesso non porta ai risultati postoperatori attesi e desiderati. Obbiettivo del nostro studio è stato pertanto, sfruttando le moderne tecnologie CAD-CAM, la produzione di placche ricostruttive “custom -made” progettate direttamente al computer ricreanti il profilo osseo originale del paziente.

Studio sulla perfusione di fegato e milza in animali non convenzionali mediante ecografia e tomografia computerizzata (TC) con mezzo di contrasto

Il presente studio rappresenta la prima applicazione della tecnica CEUS in alcune delle più diffuse specie non convenzionali, nonché la prima nei rettili. In particolare è stata investigata la perfusione di fegato e milza in 10 conigli, 10 furetti e il fegato in 8 iguane. Per quanto riguarda i mammiferi, la tecnica è risultata di facile attuazione e i risultati ottenuti erano equiparabili a quelli documentati per i piccoli animali. Maggiore variabilità si è messa in evidenza a livello splenico in entrambe le specie e nel coniglio rispetto al furetto. Nelle iguane è stata necessaria una modifica del protocollo a seguito dei tempi più lunghi delle fasi di wash in e di wash out. Le curve ottenute erano caratterizzate da picchi più bassi e TTP più lunghi, con wash out incompleto anche dopo 10 minuti di indagine. Nelle iguane l’indagine del fegato è stata approfondita grazie all’esecuzione di TC dinamiche con MDC, studio pioneristico per quanto riguarda la medicina dei rettili. L’esecuzione è avvenuta senza problemi in anestesia generale. Diffusione del MDC e conseguenti variazione di HU a livello aortico e epatico sono state considerate contemporaneamente, con costruzione di curve HU-tempo piuttosto ripetibili, entrambe caratterizzate da un wash in rapido, un picco, particolarmente alto a livello aortico, e da una fase di wash out più lento, anche qui incompleto dopo i 600 secondi di indagine. Una certa variabilità è stata notata in tre individui, risultato attendibile conseguentemente alla forte dipendenza da fattori intriseci ed estrinseci del metabolismo e della funzionalità epatica dei rettili. L’intero protocollo è stato applicato in un furetto e due iguane patologiche, al fine di evidenziare le potenzialità cliniche delle tecniche. Sebbene il numero esiguo di casi non permetta di trarre conclusioni a questo riguardo, l’ultimo capitolo della tesi vuole essere uno spunto per studi futuri.

Diversity of the proximal femur in humans: morphological variations of the head-neck junction

The proximal femur is a high-diversity region of the human skeleton, especially at the anterior junction between head and neck, where various bony morphologies have been recognized since mid nineteenth century. Classical literature on this topic is chaotic and contradictory, making almost impossible the comparison of data from different researches. Starting from an extensive bibliographic review, the first standardized method to score these traits has been created. This method allows representing both the anatomical diversity of the region already described in literature and a part of variability not considered before, giving few and univocal definitions and allowing to collect comparable data. The method has been applied to three identified and five archaeological European skeletal collections, with the aim of investigating the distribution of these features by sex, age and side, in different places and time periods. It has also been applied to 3D digital reconstructions of femurs from CT scan files of coxo-femoral joints from fresh cadavers. In addition to the osseous traits described in the standardized method, the presence and frequency of some features known as herniation pits have been scored both on bones and on CT scans. The various osseous traits of the proximal femur are present at similar frequencies in skeletal samples from different countries and different historical periods, even if with clear local differentiation. Some of the features examined show significant trends related to their distribution by gender and age. Some hypotheses are proposed about the etiology of these morphologies and their possible implication with the acquisition of bipedalism in Humans. It is therefore highlighted the possible relation of some of these traits with the development of disorders of the hip joint. Moreover, it is not recommended the use of any of these features as a specific activity-related marker.

The vulnerable carotid plaque. Identification of endothelial markers predictive of plaque weakness, rupture predisposition and neoangiogenesis

Background. Neoangiogenesis is crucial in plaque progression and instability. Previous data from our group demonstrated that intra-plaque neovessels show both a Nestin+/WT+ and a Nestin+/WT1- phenotype, the latter being correlated with complications and plaque instability. Aims. The aims of the present thesis are: (i) to confirm our previous results on Nestin/WT1 phenotype in a larger series of carotid atheromatous plaques, (ii) to evaluate the relationship between the Nestin+/WT1- neoangiogenesis phenotype and plaque morphology, (iii) to evaluate the relationship between the immunohistochemical and histopathological characteristics and the clinical instability of the plaques. Materials and Methods. Seventy-three patients (53 males, 20 females, mean age 71 years) were consecutively enrolled. Symptoms, brain CT scan, 14 histological variables, including intraplaque hemorrhage and diffuse calcifications, were collected. Immunohistochemistry for CD34, Nestin and WT1 was performed. RT-PCR was performed to evaluate Nestin and WT1 mRNA (including 5 healthy arteries as controls). Results. Diffusely calcified plaques (13 out of 73) were found predominantly in females (P=0.017), with a significantly lower incidence of symptoms (TIA/stroke) and brain focal lesions (P=0.019 and P=0.013 respectively) than not-calcified plaques, but with the same incidence of intraplaque complications (P=0.156). Accordingly, both calcified and not calcified plaques showed similar mean densities of positivity for CD34, Nestin and WT1. The density of Nestin and WT1 correlated with the occurrence of intra-plaque hemorrhage in all cases, while the density of CD34 correlated only in not-calcified plaques. Conclusions. We confirmed that the Nestin+/WT1- phenotype characterizes the neovessels of instable plaques, regardless the real amount of CD34-positive neoangiogenesis. The calcified plaques show the same incidence of histological complications, albeit they do not influence symptomatology and plaque vulnerability. Female patients show a much higher incidence of not-complicated or calcified plaques, receiving de facto a sort of protection compared to male patients.

Identificazione di markers morfologici e sierologici di vulnerabilità della placca carotidea

Introduzione: L’indicazione alla rivascolarizzazione carotidea è comunemente posta in base alla percentuale di stenosi, alla presenza di sintomi neurologici ed alle condizioni cliniche del paziente. Una placca ad elevato potenziale embolico viene definita “vulnerabile”; la sua caratterizzazione, tuttavia, non è universalmente accettata ai fini della rivascolarizzazione. Lo scopo dello studio è indagare il ruolo del mezzo di contrasto ecografico (CEUS) nell’identificazione della placca carotidea vulnerabile. Materiali e Metodi: I pazienti sottoposti a endoarterectomia carotidea, sono stati valutati mediante TC cerebrale preoperatoria e CEUS. Le microbolle di contrasto rilevate nella placca, indicative di neovascolarizzazione, sono state quantificate in dB-E ed istologicamente valutate per cinque caratteristiche: (densità dei microvasi, spessore del cappuccio fibroso, estensione delle calcificazioni, infiltrato infiammatorio e core lipidico) il valore da 1 a 5, ottenuto in cieco, indica in grado di vulnerabilità della placca. L'ANOVA test, il test di Fisher e t Student sono stati usati per correlare le caratteristiche dei pazienti ed istologiche col valore di dB-E. Risultati: Di 22 pazienti (range 2-7.8, media 4.85 ±1.9 SD) vi era un numero più alto di sintomatici (7.40 ± 0.5) rispetto agli asintomatici (3.5 ± 1.4) (p = 0.002). Un più alto valore di dB-E si associava con la presenza di un sottile cappuccino fibroso (<200 µm, 5.96±1.5 vs. 3 ± 1,p = 0.01) ed un maggiore infiltrato infiammatorio (3.2 ± 0.9 vs. 6.4 ± 1.2, p = 0.03). Placche con vulnerabilità 5 si associavano ad un valore più alto di dB-E rispetto alle placche con vulnerabilità 1 (7.6 ± 0.2 vs. 2.5 ± 0.6, rispettivamente, p=0.001). Preoperatoriamente, le lesioni emboliche ipsilaterali alla TC, correlavano con un più alto valore di dB-E (5.96±1.5 vs. 3.0±1.0, p=0.01). Conclusioni: Il valore di dB-E alla CEUS indica l’estensione della neovascolarizzazione della placca carotidea e può essere utilizzato come marker di vulnerabilità della placca.

La permanence du picaresque dans la littérature contemporaine

La problématique critique autour de la permanence du picaresque à l’époque contemporaine révèle, à partir des années soixante, une controverse qui n’est pas parvenue à en donner une vision homogène. L’oscillation entre une conception historique close et une conception a-historique ouverte ne permet pas de saisir les données essentielles d’une présence très riche et qui n’a pas du tout disparu. Pour le démontrer, on a pris en considération deux ensembles d’œuvres des XXe et XXIe siècles qui présentent un caractère bien distinct : d’un côté, un corpus restreint, composé par des réécritures ou des adaptations des textes canoniques espagnols ; de l’autre, un deuxième corpus plus riche en termes quantitatifs, qui ne représente pas forcement une réélaboration du canon du genre picaresque. Pour aborder l’analyse du corpus, on a évidemment essayé d’identifier des caractéristiques spécifiques qui ont survécu, tout en subissant parfois des transformations, au cours des XXe et XXIe siècles : plus particulièrement, on a pris en considération le narrateur, le motif de la naissance ignoble, la marginalisation du héros et son statut dynamique, aussi bien que la conclusion du récit. D’une tel analyse, il émerge en définitive que la réactivation du genre picaresque ne se borne pas à une réécriture contemporaine, mais aussi qu’il constitue un genre dont la survivance ne peut être mise en question, et dont la diffusion est assez ample. L’analyse d’une telle permanence dans la littérature contemporaine permet de comprendre que ce genre n’est pas lié exclusivement à une société particulière et à un moment historique précis, mais qu’il relève d’une structure plus profonde qui réussit à s’incarner, au cours de l’histoire, dans l’écriture et dans la tradition littéraire.