Since its approval by FDA in 2001, capsule endoscopy revolutionized the study of small bowel. One of the main limitations of its diffusion has been the high cost. More recently, a new videocapsule system (OMOM CE) has been developed in China and obtained the CE mark. Its cost is approximately half that of other capsule systems. However, there are few studies regarding the clinical experience with this new videocapsule system and none of them has been performed in the western world. Among the limitations of capsule endoscopy, there is also one linked to the diagnostic yield. The rapid transit of the device in the proximal segments implies a high risk of false negatives; an indirect confirmation of this limit is offered by the poor ability to identify the papilla of Vater. In addition, recent studies show that in patients with obscure gastrointestinal bleeding, the negative outcome of capsule endoscopy is correlated to a significant risk of recurrence of anemia in the short term, as well as the presence of small bowel lesions documented by a second capsule endoscopy. It was recently approved the use of a new device called "CapsoCam" (CapsoVision, Inc. Saratoga) characterized by four side cameras that offer a panoramic view of 360 degrees, instead of the front to 160°. Two recent pilot studies showed comparable safety profiles and diagnostic yield with the more standardized capsule. Namely, side vision has made possible a clear visualization of the papilla in 70% of cases. The aim of our study is to evaluate the feasibility and diagnostic yield of these two new devices, which first may allow a reduction in costs. Moreover, their complementary use could lead to a recovery diagnostic in patients with false negative results in an initial investigation.

MATERIALI E METODI: Tra il 2012 e il 2013, abbiamo analizzato in uno studio prospettico i dati di 48 pazienti sottoposti a ThuLEP con approccio autodidatta. I pazienti sono stati rivalutati a 3, 6, 12 e 24 mesi con la valutazione del PSA, il residuo post-minzionale (RPM), l'uroflussometria (Qmax), l'ecografia transrettale e questionari validati (IPSS: international prostate symptom score e QoL: quality of life) RISULTATI: Il volume medio della prostata è di 63 ± 5,3 ml. Il tempo operatorio medio è stato di 127,58 ± 28.50 minuti. Il peso medio del tessuto asportato è stato di 30,40 ± 13,90 gr. A 6 mesi dopo l'intervento l'RPM medio è diminuito da 165,13 ± 80,15 ml a 7,78 ± 29.19 ml, mentre il Qmax medio è aumentato da 5.75 ± 1.67ml / s a 18.1 ± 5.27 ml / s. I valori medi dei IPSS e QoL hanno dimostrato un progressivo miglioramento: da 19.15 (IQR: 2-31) e 4 (IQR: 1-6) nel preoperatorio a 6.04 (IQR: 1-20) e 1.13 (IQR: 1-4), rispettivamente. Durante la curva di apprendimento si è assistito ad un progressivo aumento del peso del tessuto enucleato e ad una progressiva riduzione del tempo di ospedalizzazione e di cateterismo. Tra le principali complicanze ricordiamo un tasso di incontinenza transitoria del 12,5% a 3 mesi e del 2.1% a 12 mesi. CONCLUSIONI: ThuLEP rappresenta una tecnica chirurgica efficace, sicura e riproducibile indipendentemente dalle dimensioni della prostata. I nostri dati suggeriscono che la ThuLEP offre un miglioramento significativo dei parametri funzionali comparabili con le tecniche tradizionali, nonostante una lunga curva di apprendimento. / MATERIALS AND METHODS: Between 2012 and 2013, we prospectively analyzed the data of the first 48 patients who underwent Thulium Laser enucleation of the prostate (ThuLEP). Patients were reassessed at 3, 6, 12 and 24 months with evaluation of the PSA, post-void volume (PVR), uroflowmetry (Qmax), transrectal ultrasonography and validated questionaires (IPSS: International Prostate Symptom Score and QoL: Quality of Life). RESULTS: The mean volume of the prostate was 63 ± 5.3 ml. The mean operative time was 127.58 ± 28.50 minutes. The mean weight of the removed tissue was 30.40 ± 13.90 gr. At 6 month follow up, the mean PVR decreased from 165.13 ± 80.15 ml to 7.78 ± 29.19 ml, while the mean Qmax flow rate increased from 5.75 ± 1.67 ml/s to 18.1 ± 5:27 ml/s. The mean IPSS and QoL showed a steady improvement from 19.15 (IQR: 2-31) and 4 (IQR: 1-6) preoperatively to 6.04 (IQR: 1-20) and 1.13 (IQR: 1-4) respectively. During the learning curve, the weight of the enucleated tissue, the time of hospital stay and the catheter time improved significantly. The main complications included transient stress incontinence (12.5% ​​at 3 months and 2.1% at 12 months). CONCLUSIONS: ThuLEP is an effective, safe and reproducible surgical technique, regardless of the prostate size. Our data suggest that ThuLEP offers a significant improvement in functional outcomes comparable with traditional techniques despite a long learning curve.

Simkania negevensis is a bacterium belonging to the order Chlamydiales but with certain biological characteristics different from those of chlamydia, according to which it was classified in the family Simkaniaceae. It is widespread in the environment, due to its ability to survive in amoebae also in phase cystic, for which it was hypothesized a possible transmission after contact with water in which they are present amoebae. So far it is known its role in diseases of the lower respiratory tract, such as childhood bronchiolitis and pneumonia in adults of the community, following its transmission through infected aerosols. A recent American study showed, by PCR, a high prevalence of S. negevensis in patients with lung transplant than other transplant recipients, assuming an association between the presence of the bacterium in these patients, and transplant rejection, were more frequent in lung transplant recipients infected compared to uninfected. There are no data so far analyzed in Italy relative to the population of dialysis and kidney transplant recipients relative to simkania negevensis why this study was undertaken in order to start a specific location and evaluate the scientific implications. Because its ability to assume persistent forms of infection, which may lead to a prolonged inflammatory response, Simkania negevensis, similar to other persistent bacteria or viruses, may be ivolved in pathologic complication. Sn may be a factor in graft rejection in mmunesuppressed lung transplant recipients, and further studies are planned to explore the posible association of Sn infections with various in vivo pathologies.

Il carcinoma squamoso orale (CSO) è spesso preceduto da lesioni definite potenzialmente maligne tra cui la leucoplachia e il lichen ma una diagnosi precoce avviene ancora oggi in meno della metà dei casi. Inoltre spesso un paziente trattato per CSO svilupperà secondi tumori. Scopo del lavoro di ricerca è stato: 1) Studiare, mediante metodica di next generation sequencing, lo stato di metilazione di un gruppo di geni a partire da prelievi brushing del cavo orale al fine di identificare CSO o lesioni ad alto rischio di trasformazione maligna. 2) Valurare la relazione esistente tra sovraespressione di p16INK4A e presenza di HPV in 35 pazienti affetti da lichen 3) Valutare la presenza di marker istopatologici predittivi di comparsa di seconde manifestazioni tumorali 4) valutare la relazione clonale tra tumore primitivo e metastasi linfonodale in 8 pazienti mediante 2 metodiche di clonalità differenti: l’analisi di mtDNA e delle mutazioni del gene TP53. I risultati hanno mostrato: 1) i geni ZAP70 e GP1BB hanno presentato un alterato stato di metilazione rispettivamente nel 100% e nel 90,9% di CSO e lesioni ad alto rischio, mentre non sono risultati metilati nei controlli sani; ipotizzando un ruolo come potenziali marcatori per la diagnosi precoce nel CSO. 2)Una sovraespressione di p16INK4A è risultata in 26/35 pazienti affetti da lichen ma HPV-DNA è stato identificato in soli 4 campioni. Nessuna relazione sembra essere tra sovraespressione di p16INK4A e virus HPV. 3)L’invasione perineurale è risultato un marker predittivo della comparsa di recidiva locale e metastasi linfonodale, mentre lo stato dei margini chirurgici si è rilevato un fattore predittivo per la comparsa di secondi tumori primitivi 4) Un totale accordo nei risultati c’è stato tra analisi di mtDNA e analisi di TP53 e le due metodiche hanno identificato la presenza di 4 metastasi linfonodali non clonalmente correlate al tumore primitivo. / Oral Squamous Cell Carcinoma (OSCC) is often preceded by Potentially Malignant Lesions, Leukoplakia and Lichen Planus (LP), but still today is usually diagnosed in advanced stage. Additionally patients treated for OSCC have a good chance to develop a second primary OSCC. The purpose of the research was: 1) to assess, by bisulfite Next Generation Sequencing, the methylation status of a list of candidate genes obtained from oral brushing specimens to early detect OSCC using non-invasive procedures. 2) to yield more insights into the relationship between p16INK4A over-expression and the presence of HPV-DNA in 35 LP samples. 3) to identify the clinicopathologic parameters significantly related to a second loco-regional event in a population of 180 patients treated for primary OSCC 4) to evaluate the relationship between primary OSCC and lymph node metastasis in 8 patients using two different 2 clonality tests: mt-DNA D-loop and TP53 sequence analysis. The results showed that: 1) ZAP70 and GP1BB showed an aberrant methylation status respectively in 100% and 90,9% of OSCC and High Risk lesions, while resulted unmethylated in normal healthy donors. DNA methylation analysis of GP1BB and ZAP70 seems to be a promising non invasive tool to early detect OSCC from oral brushing specimens. 2) p16INK4A over-expression was found in 26/35 LP samples, whereas HPV was found in 4/35 lesions: 3 low-risk HPV and 1 high-risk HPV. P16INK4A overexpression is not correlated with HPV in patients with LP. 3) Perineural invasion was significantly related to lymph-node metastasis (18% vs 8%) and Local Recurrence (15% vs 5%), while the status of the surgical margin resulted an independent factor influencing Second Primary Tumor. 4) The results from mtDNA analysis showed a good agreement with results of p53 mutation analysis and revealed the presence of 4/11 neck nodal metastases not phylogenetically related respect to primary tumor.

L'intervento di connessione cavo-polmonare totale (TCPC) nei pazienti portatori di cuore univentricolare, a causa della particolare condizione emodinamica, determina un risentimento a carico di numerosi parenchimi. Scopo della ricerca è di valutare l'entità di questo danno ad un follow-up medio-lungo. Sono stati arruolati 115 pazienti, sottoposti ad intervento presso i centri di Cardiochirurgia Pediatrica di Bologna (52 pz) e Torino (63 pz). Il follow-up medio è stato di 125±2 mesi. I pazienti sono stati sottoposti ad indagine emodinamica (88 pz), test cardiopolmonare (75 pz) e Fibroscan ed ecografia epatica (47 pz). La pressione polmonare media è stata di 11.5±2.6mmHg, ed in 12 pazienti i valori di pressione polmonare erano superiori a 15mmHg. La pressione atriale media era di 6.7±2.3mmHg ed il calcolo delle resistenze vascolari polmonari indicizzate (RVP) era in media di 2±0.99 UW/m2. In 29 pazienti le RVP erano superiori a 2 UW/m2. La VO2 max in media era pari a 28±31 ml/Kg/min, 58±15 % del valore teorico. La frequenza cardiaca massima all'apice dello sforzo era di 151±22 bpm, pari al 74±17% del valore teorico. Il Fibroscan ha fornito un valore medio di 17.01 kPa (8-34.3kPa). Cinque pazienti erano in classe F2, 9 pazienti in classe F3 e 33 pazienti risultavano in classe F4. Nei pazienti con follow-up maggiore di 10 anni il valore di stiffness epatica (19.6±5.2kPa) è risultato significativamente maggiore a quello dei pazienti con follow-up minore di 10 anni (15.1±5.8kPa, p<0.01). La frequenza cardiaca massima raggiunta durante lo sforzo del test cardiopolmonare è risultata significativamente correlata alla morfologia del ventricolo unico, risultando del 67.8±14.4% del valore teorico nei pazienti portatori di ventricolo destro contro il 79.6±8.7% dei portatori di ventricolo sinistro (p=0.006). L'intervento di TCPC determina un risentimento a carico di numerosi parenchimi proporzionale alla lunghezza del follow-up, e necessita pertanto un costante monitoraggio clinico-strumentale multidisciplinare. / Single ventricle patients are treated with total cavo-pulmonary connection (TCPC) operation that, for the particular hemodynamic condition, can cause a multiorgan damage. Aim of the research is to evaluate the amount of this damage at a medium-long term follow-up. One hundred fifteen patients, operated in the Pediatric Cardiac Surgery Department of Bologna (52 pts) and Torino (63 pts), were enrolled. Mean follow-up was 125±2 months. Patients underwent hemodynamic evaluation (88 pts), cardiopulmonary exercise testing (CPET) (75 pts) and Fibroscan and hepatic echography (47 pts). Mean pulmonary artery pressure (PAP) was 11.5±2.6mmHg, and in 12 patients was more than 15mmHg. Mean atrial pressure was 6.7±2.3 mmHg and mean pulmonary vascular resistances (PVR) was 2±0.99 WU/m2. In 29 patients, PVR were more than 2 WU/m2. Mean peak VO2 was 28±31 ml/Kg/min, 58±15 % of the theoretic value. Mean peak heart rate during exercise was 151±22 bpm, 74±17% of the theoretic value. Mean hepatic stiffness evaluation at Fibroscan was 17.01 kPa (8-34.3 kPa). Five patients were in Metavir class F2, 9 in F3 e 33 in F4 class. Among patients with a longer than 10 years follow-up, hepatic stiffness evaluation was significantly higher (19.6±5.2 kPa) than in patients with shorter follow-up (15.1±5.8 kPa, p<0.01). Peak heart rate at CPET was significantly related to single ventricle morphology, resulting 67.8±14.4% of the theoretic value in right single ventricle patients and 79.6±8.7% in left single ventricle patients (p=0.006). TCPC operation cause a multiorgan damage proportional to follow-up length, and for this reason deserve a constant multidisciplinary clinico-instrumental monitoring.

La BCPA e’ ormai utilizzata routinariamente come stadio intermedio della palliazione di Fontan nel trattamento dei cuori funzionalmente univentricolari e si conferma intervento a ridotta mortalità e morbilità. La crescita delle arterie polmonari dopo BCPA è abbastanza variabile ed imprevedibile, le dimensioni indicizzate dei rami principali sembrano tendenzialmente ridotte, tranne quelle dell’arteria lobare inferiore destra, la quale beneficerebbe del flusso preferenziale della BCPA. Proprio i pazienti con arterie polmonari più piccole mostrerebbero un maggior incremento di dimensioni delle stesse dopo BPCA. Il ruolo ed i vantaggi del flusso accessorio nella BCPA sono ancora da definire; tuttavia sembrerebbe offrire vantaggi in termini di crescita delle arterie polmonari, soprattutto il ramo lobare sinistro, e di miglior outcome dopo TCPC. / BCPA has been routinely utilized as intermediate step to Fontan operation in patients with functionally single ventricle. After 40 years since its introduction still confirms good results with low complication and mortality rate. Pulmonary arteries growth after BCPA is rather variable and inconstant with a widely reported Nakata-index reduction after some months. Right lower lobe pulmonary index instead increases significantly, possibly due to preferential blood flow after BCPA. Patients with smaller pulmonary arteries at the beginning seem to benefit of a more effective pulmonary arteries growth. Accessory source of pulmonary blood flow at the BCPA still bares uncertain efficacy and benefits, even thought it seems to be associated with a better pulmonary artery growth, particularly left lower lobe, and better TCPC results.

Il tumore del polmone e una delle neoplasie più diagnosticate dal 1985 e rimane ancora oggi la causa più frequente di morte cancro-correlata nel mondo. Una resezione polmonare anatomica completa continua ad essere il cardine della terapia per il tumore non a piccole cellule. Perdite aeree prolungate (PAL) sono la più comune complicanza dopo una chirurgia polmonare e sono state riportate con un’incidenza compresa tra il 3-26%, simile sia nelle resezioni polmonari per via toracotomica sia in quelle per via toracoscopica. Fattori di rischio descritti sono scissure interlobari incomplete, patologie polmonari sottostanti (come enfisema, fibrosi, tubercolosi o neoplasie), aderenze pleuriche, pazienti anziani (>75 anni) e bassa capacita di diffusione. Lo sviluppo di strumentazione all’avanguardia e di nuove tecniche chirurgiche ha contribuito a ridurre l’incidenza di queste complicanze. Considerando l’alto impatto clinico e socio-economico di queste problematiche, e stata inoltre sviluppata una varietà di complementari naturali e materiali sintetici molti utili nella gestione delle perdite aeree. / Lung cancer is one of the most diagnosed cancer in 1985 and still remains the most common cause of cancer-related death in the world. A full anatomical lung resection remains the mainstay of therapy for non-small cell cancer. Prolonged air leak (PAL) are the most common complication following a lung surgery and were reported with an incidence of between 3-26%, similar in both pulmonary resection by thoracotomy and in those thoracoscopic. Risk factors described are incomplete interlobar fissures, lung diseases underlying (such as emphysema, fibrosis, tuberculosis or malignancy), pleural adhesions, elderly patients (> 75 years) and low capacity to spread. The development of modern equipment and new surgical techniques has helped to reduce the incidence of these complications. Considering the high clinical impact and socio-economic problems of these, and was also developed a variety of complementary natural and synthetic materials useful in the management of many air leak.

Animal models have been relevant to study the molecular mechanisms of cancer and to develop new antitumor agents. Anyway, the huge divergence in mouse and human evolution made difficult the translation of the gained achievements in preclinical mouse based studies. The generation of clinically relevant murine models requires their humanization both concerning the creation of transgenic models and the generation of humanized mice in which to engraft a functional human immune system, and reproduce the physiological effects and molecular mechanisms of growth and metastasization of human tumors. In particular, the availability of genotypically stable immunodepressed mice able to accept tumor injection and allow human tumor growth and metastasization would be important to develop anti-tumor and anti-metastatic strategies. Recently, Rag2-/-;gammac-/- mice, double knockout for genes involved in lymphocyte differentiation, had been developed (CIEA, Central Institute for Experimental Animals, Kawasaki, Japan). Studies of human sarcoma metastasization in Rag2-/-; gammac-/- mice (lacking B, T and NK functionality) revealed their high metastatic efficiency and allowed the expression of human metastatic phenotypes not detectable in the conventionally used nude murine model. In vitro analysis to investigate the molecular mechanisms involved in the specific pattern of human sarcomas metastasization revealed the importance of liver-produced growth and motility factors, in particular the insulin-like growth factors (IGFs). The involvement of this growth factor was then demonstrated in vivo through inhibition of IGF signalling pathway. Due to the high growth and metastatic propensity of tumor cells, Rag2-/-;gammac-/- mice were used as model to investigate the metastatic behavior of rhabdomyosarcoma cells engineered to improve the differentiation. It has been recently shown that this immunodeficient model can be reconstituted with a human immune system through the injection of human cord blood progenitor cells. The work illustrated in this thesis revealed that the injection of different human progenitor cells (CD34+ or CD133+) showed peculiar engraftment and differentiation abilities. Experiments of cell vaccination were performed to investigate the functionality of the engrafted human immune system and the induction of specific human immune responses. Results from such experiments will allow to collect informations about human immune responses activated during cell vaccination and to define the best reconstitution and experimental conditions to create a humanized model in which to study, in a preclinical setting, immunological antitumor strategies.

Rotatorenmanschettenrupturen (RM-Rupturen) haben eine hohe Prävalenz in der Bevölkerung und kommen mit zunehmendem Alter gehäuft vor (Ozaki et al. 1988, Milgrom et al.1995). Die operative Rekonstruktion der RM gilt als Goldstandard der Behandlung. Unbehandelt neigen RM-Rupturen zu Progression und zu fettiger Infiltration des Muskelbauchs und zu Abnahme der Sehnenqualität (Goutallier et al. 1994). Im weiteren Verlauf droht eine Defektarthropathie mit schmerzhafter Bewegungsseinschränkung und hochgradigem Funktionsverlust der Extremität. Eine zeitgerechte Rekonstruktion der RM kann diesen Verlauf günstig beeinflussen und die Funktion des Schultergelenkes signifikant verbessern (Deutsch et al. 1997, Gladstone et al. 2007). Mit zunehmendem Funktionsanspruch, auch noch im fortgeschrittenen Alter, gewinnt die Rekonstruktion der RM zunehmend an Bedeutung (Worland et al. 1999). Die Rerupturrate der operativen Rekonstruktion ist hoch und wird je nach Autor mit bis zu 94% angegeben (Boileau et al. 2005, Galatz et al. 2004). Uneinigkeit herrscht in der Literatur über die Art der Primärrefixation der Sehne im Knochen (Bishop et al. 2006, Boileau et al. 2005, Galatz et al. 2004). Mehrere Autoren berichten, dass die Nahtankerreparatur der transossären Refixation gleichwertig bzw. überlegen ist (Reed et al., 1996, Klinger et al. 2007). Des Weiteren wird die Anzahl und das Platzierungsmuster der Nahtanker, im Hinblick auf die Primärstabilität, kontrovers diskutiert (Apreleva et al. 2002, Craft et al. 1996, Rossouw et al. 1997). 52 Ziel des Schulterchirurgen sollte es sein, eine möglichst hohe Primärfestigkeit der Rekonstruktion zu erreichen, des Weiteren sollte die Refixationsmethode die spannungsfreie Einheilung der Sehne ermöglichen, den Patienten möglichst schnell einer aktiven Rehabilitation zuführen und die Rerupturrate möglichst gering halten (Kim et al. 2005). Ziel der Arbeit war es zu zeigen, ob eine weitere Reihe Nahtanker eine höhere Primärstabilität in Abhängigkeit des verwendeten Nahtmaterials bietet. Hierzu wurden 32 frische Schafsschultern in 4 Gruppen zu je 8 Präparaten aufgeteilt. Eine vollständige RM-Ruptur wurde simuliert und anschließend wurden die Rupturen entweder mit einer Einreihen-Nahtankerversorgung (single-row-Technik) oder mit einer Zweireihen-Nahtankerversorgung (double-row-Technik) refixiert. Dabei kamen 2 verschiedene Nahtmaterialien zum Einsatz (nicht resorbierbares Polyesterfadenmaterial (Ethibond®) und nicht resorbierbares Polyethylenfadenmaterial (HiFi®) der Stärke 2.0). Die Präparate wurden in einer Zugmaschine auf ihre Zugfestigkeit getestet. Die double-row-Technik in Kombination mit nicht-resorbierbarem Polyethylenfadenmaterial (HiFi®, Gruppe IV) erzielte hierbei eine signifikant höhere Ausreißfestigkeit als die anderen Versorgungen. Mehrere Fixationspunkte der Verbindung Knochen-Faden/Naht-Sehne bei der double- row-Technik erreichen so durch eine gleichmäßige Lastverteilung eine höhere Zugfestigkeit Inwieweit diese erhöhte Primärfestigkeit eine Verbesserung des klinischen Ergebnisses und eine Reduktion der Rerupturrate erbringen kann, muss durch zukünftige klinisch-prospektive Studien validiert werden. Der Einsatz dieser kostenintensiven und operativ anspruchsvollen Methode ist unseres Erachtens nur dann gerechtfertigt, wenn die Anzahl an Revisionseingriffen hierdurch signifikant gesenkt werden kann.

No description available.