Trans-oral robotic surgery for the management of oropharyngeal carcinomas: A 9-year institutional experience

Trans-oral robotic surgery (TORS) has changed surgical management of patients with oropharyngeal squamous cell carcinomas (OPSCC). In this study we present surgical and oncologic outcomes of patients with oropharyngeal squamous cell carcinomas, treated using TORS, with and without an adjuvant therapy. Sixty patients with oropharyngeal squamous cell carcinomas treated with TORS between January 2008 and December 2017 have been retrospectively evaluated considering clinicopathologic features, disease characteristics, adjuvant treatments and oncological outcomes. TORS was performed for OPSCC to the base of tongue in 41.7%, tonsils in 46.7%, soft palate and posterior pharyngeal wall in 3.3% and 5%, respectively. Neck dissection was performed in 43.3% of patients. Management strategies included surgery alone in 30%, TORS and adjuvant radiotherapy in 33.3%, and TORS plus adjuvant chemotherapy in 36.7%. The 5-year overall survival of the total group was 77.6%, the 5-year disease-free survival rate was 85.2%, and the 5-year local recurrence-free survival rate was 90.6%. Finally, in selected patients TORS appears to yield similar oncologic outcomes and functional outcomes to traditional techniques and non-operative treatment with a possible benefit on long-term quality of life. The future offers exciting opportunities to combine TORS and radiotherapy in unique ways. However, further research is urgently needed to clarify the indications for adjuvant therapy following TORS resections

Transcriptional induction of the heat shock protein B8 mediates the clearance of misfolded proteins responsible for motor neuron diseases

Neurodegenerative diseases (NDs) are often associated with the presence of misfolded protein inclusions. The chaperone HSPB8 is upregulated in mice, the human brain and muscle structures affected during NDs progression. HSPB8 exerts a potent pro-degradative activity on several misfolded proteins responsible for familial NDs forms. Here, we demonstrated that HSPB8 also counteracts accumulation of aberrantly localized misfolded forms of TDP-43 and its 25 KDa fragment involved in most sporadic cases of Amyotrophic Lateral Sclerosis (sALS) and of Fronto Lateral Temporal Dementia (FLTD). HSPB8 acts with BAG3 and the HSP70/HSC70-CHIP complex enhancing the autophagic removal of misfolded proteins. We performed a high-through put screening (HTS) to find small molecules capable of inducing HSPB8 in neurons for therapeutic purposes. We identified two compounds, colchicine and doxorubicin, that robustly up-regulated HSPB8 expression. Both colchicine and doxorubicin increased the expression of the master regulator of autophagy TFEB, the autophagy linker p62/SQSTM1 and the autophagosome component LC3. In line, both drugs counteracted the accumulation of TDP-43 and TDP-25 misfolded species responsible for motoneuronal death in sALS. Thus, analogs of colchicine and doxorubicin able to induce HSPB8 and with better safety and tolerability may result beneficial in NDs models

Temperature measurement of fragment emitting systems in Au+Au 35 MeV/nucleon collisions

We report on the results of experiments performed to investigate the Au1Au 35 MeV/nucleon reaction. The reaction products generated in the disassembly of the unique source formed in central collisions and those coming from the decay of the quasiprojectile in peripheral and midperipheral ones ~five different impact parameters! were identified through a careful data selection based on the study of energy and angular distributions. The excitation energies of the fragment sources have been extracted through a calorimetric method and by means of a comparison with model calculations. The nuclear temperatures of these decaying systems have been measured from the relative isotopic abundances and, also for central collisions, from the relative populations of excited states. The temperatures of the quasiprojectile disassembling systems are slowly increasing going towards smaller impact parameter. The relationship between temperature and excitation energy seems to be almost independent of the characteristics of the emitting source. The extracted caloric curve shows a slow monotonic increase with increasing excitation energy. A comparison with data derived from Au fragmentation at much higher incident energies is discussed. @S0556-2813~98!04408-2

La difesa del suolo in mabito montano: le sistemazioni idraulico-forestali sono ancora una risposta adeguata ?

L’Italia è costantemente afflitta da catastrofi di origine idrogeologica, nell’immediato seguito delle quali molti avanzano prontamente ricette e soluzioni “definitive” per poi dimenticarsene altrettanto rapidamente. Le Sistemazioni Idraulico-Forestali (SIF) da oltre un secolo hanno giocato e continuano a giocare un ruolo fondamentale per garantire la sicurezza dei territori montani e collinari, ma in molte parti del nostro Paese ciò sembra essere stato dimenticato. Nella memoria gli Autori si pongono la domanda se le SIF siano davvero ancora attuali ed indispensabili in una società che è profondamente mutata rispetto ai decenni che le hanno viste protagoniste. La risposta che danno è positiva ed anzi evidenziano come le SIF possano essere oggi uno stimolo per tutti coloro che si occupano della difesa idrogeologica, in quanto portatrici di un messaggio semplice ed al contempo chiaro: integralità, gradualità, continuità ed economicità degli interventi

A novel approach emphasising intra-operative superficial margin enhancement of head-neck tumours with narrow-band imaging in transoral robotic surgery

The primary goal of surgical oncology is to obtain a tumour resection with disease-free margins. Transoral robotic surgery (TORS) for surgical treatment of head-neck cancer is commensurate with standard treatments. However, the likelihood of positive margins after TORS is up to 20.2% in a recent US survey. The aim of this study is to evaluate the efficacy and the feasibility of narrow-band imaging (NBI) during TORS in order to improve the ability to achieve disease-free margins during tumour excision. The present study was conducted at the ENT, Head- Neck Surgery and Oral Surgery Unit, Department of Special Surgery, Morgagni Pierantoni Hospital, Azienda USL Romagna. From March 2008 to January 2015, 333 TORS were carried out for malignant and benign diseases. For the present study, we retrospectively evaluated 58 biopsy-proven squamous cell carcinoma patients who underwent TORS procedures. Patients were divided into 2 groups: (1) 32 who underwent TORS and intra-operative NBI evaluation (NBI-TORS); (2) 21 who underwent TORS with standard intra-operative white-light imaging (WLITORS). Frozen section analysis of margins on surgical specimens showed a higher rate of negative superficial lateral margins in the NBI-TORS group compared with the WLI-TORS group (87.9% vs. 57.9%, respectively, p = 0.02). The sensitivity and specificity of intra-operative use of NBI, respectively, were 72.5% and 66.7% with a negative predictive value of 87.9%. Tumour margin enhancement provided by NBI associated with magnification and 3-dimensional view of the surgical field might increase the capability to achieve an oncologically-safe resection in challenging anatomical areas where minimal curative resection is strongly recommended for function preservation

MUTYH-associated polyposis (MAP), the syndrome implicating base excision repair in inherited predisposition to colorectal tumors

In 2002, Al-Tassan and co-workers described for the first time a recessive form of inherited polyposis associated with germline mutations of MUTYH, a gene encoding a base excision repair (BER) protein that counteracts the DNA damage induced by the oxidative stress. MUTYH-associated polyposis (MAP) is now a well-defined cancer susceptibility syndrome, showing peculiar molecular features that characterize disease progression. However, some aspects of MAP, including diagnostic criteria, genotype-phenotype correlations, pathogenicity of variants, as well as relationships between BER and other DNA repair pathways, are still poorly understood. A deeper knowledge of the MUTYH expression pattern is likely to refine our understanding of the protein role and, finally, to improve guidances for identifying and handling MAP patients