Head and neck osteosarcoma—the ongoing challenge about reconstruction and dental rehabilitation

Head and Neck osteosarcoma is an uncommon disease. Hitherto, the treatment is surgical resection and survival is influenced by the presence of free margins. However, the dimension of the resection may represent a hurdle for an adequate Quality of Life (QOL). Maxillofacial district is a narrow space where the function, esthetics and patient’s relational skills fit together like the gears of a clock. The functional results depend on the type of reconstruction and prosthetic rehabilitation that are both important to guarantee a good aesthetic result and finally increase the patient’s self-esteem. This study aims to report our experience about head and neck (HN) osteosarcoma focusing the attention on reconstructive and dental-rehabilitative problems. It is a retrospective study all patients were surgically treated in our department. Subjects with histological diagnosis of HN osteosarcoma, treated between 2005 and 2017 were included. The demographic characteristics, surgical treatment, eventually secondary reconstruction and prosthetic rehabilitation, performed in the same department, have been collected. The QOL was assessed through the EORTC QLQ-H&N35 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35) questionnaire. Fifteen patients were enrolled, eight received a free flap microsurgical reconstruction. Dental rehabilitation was performed in five cases and a mobile prosthesis was always delivered. Eighteen implants were inserted in fibula bones for three patients; highly porous implants were use

Treg/Tcon Immunotherapy and High Dose Marrow Irradiation Ensure Full Control of Leukemia Relapse in Haploidentical Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most powerful therapy for patients with high risk of relapse. In spite of that, no matter the donor source or conditioning regimen used, leukemia relapse is still the leading cause of HSCT failure. In HLA-haploidentical HSCT, we recently applied a clinical protocol consisting of total body irradiation (TBI)-based conditioning regimen and a peripheral blood CD34+ cell graft combined with the adoptive transfer of naturally occurring regulatory T cells (Tregs) and conventional T cells (Tcons). No post-transplant pharmacologic GvHD prophylaxis was given. Such protocol was associated with low GvHD and relapse rate (Martelli et al., Blood 2014). To further reduce leukemia relapse in Treg/Tcon-based haploidentical HSCT (Treg/Tcon haplo-HSCT) we used high dose hyper-fractionated TBI (HF-TBI) in the conditioning regimen. We also extended Treg/Tcon haplo-HSCT to patients that are unfit (because of previous comorbidities) and/or too old to withstand high intensity regimens. In these patients the extra-hematologic toxicity of irradiation was reduced with the use of targeted total marrow and lymph node irradiation (TMLI). 40 patients with high risk acute leukemia (36 AML, 4 ALL) received Treg/Tcon haplo-HSCT. All but 3 patients were transplanted in complete remission. 12 younger patients (median age: 28, range: 20-43) received HF-TBI, while 28 older or unfit patients (59, 40-70) received TMLI in the conditioning regimen. HF-TBI (14.4 Gy) was administered in 12 fractions, 3 times a day for 4 days. TMLI was administered by means of Helical Tomotherapy HI-ART (9 fractions, 2 times a day for 4.5 days). Irradiation was followed by chemotherapy with Thiotepa, Fludarabine, and Cyclophosphamide. 2 × 106/kg freshly isolated CD4+CD25+FOXP3+ Tregs were transferred 4 days before the infusion of 1 × 106/kg Tcons and a mega-dose of CD34+ hematopoietic stem cells. No post-transplant pharmacologic GvHD prophylaxis was given. 38/40 patients engrafted. 12 (31%) developed aGvHD grade ³2 (10 are alive and off-therapy). 6 (16%) died because of transplant related complications (2 because of aGvHD, 2 infections, 1 veno-occlusive disease, 1 intracranial hemorrhage). Strikingly, despite the high risk diseases, no patient relapsed after a median follow up of 13 months (range 1-36, Fig. A). Further, only 1 patient developed cGvHD. Thus, cGvHD/Leukemia-free survival was 82% (Fig. B). Treg adoptive transfer allows for the safe infusion of an otherwise lethal dose of donor alloreactive Tcons in the absence of any other form of immune suppression. Our results demonstrate that the potent graft versus leukemia effect of Treg/Tcon adoptive transfer was boosted by high dose marrow irradiation. Thus, this study proves that the right combination of haploidentical Treg/Tcon immunotherapy plus a powerful conditioning regimen can fully eradicate leukemia

???Pull-through??? Resection for Total and Subtotal Glossectomy Involving the Posterior Third of Tongue

The lower lip-splitting incision associated with different types of mandibulotomy, in order to obtain wide access to total or subtotal glossectomy, is described. In those cases, high rates of functional and aesthetic deficit and postoperative morbidity (more in cases of patients in which adjuvant radiotherapy has been performed) are described. We present our experience in the treatment of patients undergoing total or subtotal glossectomy and contemporary reconstruction with flaps, and without lip-splitting incision and mandibulotomy. Materials and Methods: Data about patients affected by malignant tumors requiring total or subtotal (posterior third of the tongue) resection that were treated at our department from January 2004 to December 2014 were retrospectively reviewed. Data evaluated included: T and N stage, resection margins, operation time, and post-operative complications, such as fistula and flap necrosis. Results: 41 patients were identified. In two cases microscopic infiltration of one margin was found (R1); in one case a close margin was identified. In 26 cases reconstruction was performed using free flaps, and in the remaining cases a pectoralis major flap was used. In three cases postoperative complications were observed. Discussion and conclusions: In theory, lip-splitting and mandible discontinuity could allow for increased access and tumor visualization, and could facilitate flap positioning. Nevertheless, in our experience, it is not necessary in the case of total or subtotal glossectomy

Design and synthesis of high affinity compounds for the Hsp60 expression control in carcinogenic processes

First observed in cells exposed to high temperatures, Heat shock proteins (Hsps) are nowadays considered the most important cell “chaperone” complexes over-­expressed in response to a number of cell stress stimuli.1 The chaperone activity is the main function of the eukaryotic Heat shock protein 60 kDa (Hsp60), involved in the capture and refold of unfolded or misfolded proteins. Additional roles in signal transduction,2 senescence activation3 and apoptosis4 have been ascribed to cytosolic Hsp60. During the carcinogenIc process, in vivo studies demonstrated increased levels of human Hsp60 in several organs, such as uterine exocervix,5 large bowel,6 and prostate.6 In this context, our study aims to elucidate the structural details of the interaction between Hsp60 and novel designed antagonists able to specifically block this chaperonine. A preliminary virtual screening of 24 million molecules, available in the Zinc database, was carried out on the ATP-­binding site of a bacterial Hsp60 monomer, the coordinates of which were taken from Protein Data Bank (ID: 1WE3), figure 1. Compounds with high affinity were further refined by other in silico protocols previously and successfully applied by us in the study of several biological targets.7The analysis of virtual screening results highlights the N-­{5-­[1H-­imidazol-­4-­yl-­methyl)-­ amino]-­benzofuran-­3-­yl}-­benzamides of type 1 as interesting series for the inhibition of Hsp60 ATP-­binding site. Selected compounds were prepared in excellent yields, following appropriate synthetic pathways. All compounds are currently tested in order to proof they potential anticancer activity as modulator of Hsp60 function in tumor cells

Intraconal tumor-like mass as first manifestation of IgG4-related disease

A great variety of tumors and tumor-like lesions can involve the orbit. Benign and malignant neoplasms, inflammatory diseases, vascular and congenital lesions take part of this heterogeneous group that creates many challenges for diagnosis, management, and treatment. Obviously, symptoms and clinical history are fundamental to establish a differential diagnosis, and imaging is mandatory to distinguish between lesions that have similar clinical presentations in most cases. With this report, the authors highlight the diagnostic difficulties and the importance to include not only tumors but also vascular inflammatory process into the differential diagnosis of this unilateral orbital lesion type

Facial Palsy: The Right Time for the Right Choice

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Tobacco, alcohol and family history of cancer as risk factors of oral squamous cell carcinoma: case-control retrospective study

The aim of the study is to observe retrospectively the correlation between Oral Squamous Cell Carcinoma (OSCC) and risk factors; including tobacco, alcohol and Family History of Cancer (FHC). A total of 478 patients were included retrospectively from the database of the Department of Oral Sciences and Maxillofacial Surgery, Sapienza University of Rome. A Test Group (TG) consisted of 239 patients with a confirmed diagnosis of OSCC. A Control Group (CG) consisted of 239 patients without history and/or diagnosis of oral cancer. The logistic regression models were used to calculate the adjusted Odd Ratios (ORs) associated with alcohol, tobacco and FHC; including the General Family History of Cancer (GFHC) and Family History of Head and Neck Cancer (FHHNC) and their 95% Confidence Intervals (CI). The high rate of tobacco consumption was associated with an OR of 1.035 (95% CI 1.001–1.070) and a statistical significance (p = 0.041). Drinker patients showed a significant risk of developing OSCC (p = 0.05) and the OR was 1.035 (95% CI 1.010–1.061). The GFHC was associated with a marginal risk of OSCC with an OR of 1.095 (95% CI 0.953–1.259), without significance (p = 0.199). The FHHNC showed a notable risk increase with an OR of 1.871 (95% CI 0.902–3.882), without significance (p = 0.092). Alcohol and tobacco may be associated with an increase in the risk of OSCC