Genetically driven CD39 expression shapes human tumor-infiltrating CD8+ T-cell functions.

In our study, we investigated the role of CD39 on tumor-infiltrating CD8+ T lymphocytes (CD8+ TILs) in colorectal, head and neck and pancreatic cancers. Partially confirming recent observations correlating the CD39 expression with T-cell exhaustion, we demonstrated a divergent functional activity in CD39+ CD8+ TILs. On the one hand, CD39+ CD8+ TILs (as compared to their CD39- counterparts) produced significantly lower IFN-γ and IL-2 amounts, expressed higher PD-1, and inversely correlated with perforin and granzyme B expression. On the other, they displayed a significantly higher proliferative capacity ex vivo that was inversely correlated with the PD-1 expression. Therefore, CD39+ CD8+ TILs, including those co-expressing the CD103 (a marker of T resident memory [TRM] cells), were defined as partially dysfunctional T cells that correlate with tumor patients with initial progression stages. Interestingly, our results identified for the first time a single nucleotide polymorphism (SNP rs10748643 A>G), as a genetic factor associated with CD39 expression in CD8+ TILs. Finally, we demonstrated that compounds inhibiting CD39-related ATPases improved CD39+ CD8+ T-cell effector function ex vivo, and that CD39+ CD8+ TILs displayed effective suppression function in vitro. Overall these data suggest that the SNP analysis may represent a suitable predictor of CD39+ CD8+ T-cell expression in cancer patients, and propose the modulation of CD39 as a new strategy to restore partially exhausted CD8+ TILs.

Endoscopy-Assisted Intraoral Removal of Elongated Styloid Process: Mini-Invasive Surgical Treatment of Eagle Syndrome.

The aim of this work is to illustrate a transoral mini-invasive approach to safely remove elongated styloid process in Eagle syndrome. A 34-year-old Asian male came to our center referring pharyngeal and cervical pain on the right side on swallowing and opening the mouth. Computed tomography showed elongation of the right styloid process. Surgical removal was performed through endoscopy-assisted intraoral approach using a pituitary curette to perform dissection and piezosurgery for the osteotomy. Surgical intervention was completed in 25 minutes. Postoperative period was uneventful except for transient (12 hours) right facial palsy that resolved spontaneously. Two months after surgery, patient referred resolution of symptoms. This technique is easy to perform and permits to obtain good result with reduction of surgical time and with low risk of complication.

Maxillo-Mandibular Reconstruction in Pediatric Patients: How To Do It?

Maxillo-mandibular reconstruction in pediatric patients involves particular functional and cosmetic implications. Attention is required for the craniofacial growth over time, involvement of the permanent dentition, facial symmetry, and donor site morbidity. Our aim is to identify the best reconstructive options for maxilla-mandibular defects in children (<18 years) based on our experience with 25 pediatric patients. We believe that reconstruction has to be performed at the same time as resection in pediatric patients. Local flaps should be reserved for cases of maxillary defects because of malignant neoplasms, which ultimately have poor prognosis. In cases of large mandibular defects, radiotherapy is eventually required. When the condition of the soft tissues is poor (because of previous surgery, etc), free flaps potentially represent the best options. Nevertheless, in patients younger than 5 years old (with no damaged tissues), reconstruction with rib grafts should be performed, and the use of titanium plates should be reserved for very select cases (such as temporary reconstruction in toddlers).

Giant "Panfacial" Chordoma Involving Skull Base With Intracranial Invasion.

Chordomas are rare, low-grade, primary malignant bone tumor arising from primitive notochord remnants of the axial skeleton. They rarely occur in an extraosseus craniofacial location such as nasopharynx, nasal septum, paranasal sinuses, and orbits. We report here an extreme case of "panfacial" chordoma involving middle and anterior skull base with intracranial invasion, which reached considerable size because of a delay in diagnosis and treatment. In this case, a wide surgical excision was performed to improve quality of life.

Extranodal follicular dendritic cell sarcoma of the tonsil: An extremely rare clinical entity.

Follicular dentritic cell sarcomatous neoplasms originate from dendritic cells contained within the lymph nodes. In extranodal location, these neoplasms, are rare clinical entities, and even more so, their location in the head-neck region is extremely rare. Only 17 cases of primary dendritic cell sarcoma of the tonsil are reported in the literature at present. Being such a rare entity, histopathological diagnosis can be complex and requires great expertise and proper immunohistochemical analysis [1]. We present a case of a 48-year-old young man diagnosed with follicular dendritic cell sarcoma of the tonsil who underwent, probably for the first time in the literature, transoral robotic surgical resection.

Surgical management of enophthalmos in Duane syndrome.

Duane syndrome is a congenital disorder of eye movement characterized by partial or absent development of the sixth cranial nerve nucleus and/or the sixth nerve itself. Patients often undergo procedures, both surgical and nonsurgical, to correct ocular misalignment and improve the resulting visual problems. We present a case report of a 49-year-old woman with left-sided Duane syndrome who underwent aesthetic surgical correction of enophthalmos.

Exploring the Role of NCX1 and NCX3 in an In Vitro Model of Metabolism Impairment: Potential Neuroprotective Targets for Alzheimer's Disease.

Alzheimer's disease (AD) is a widespread neurodegenerative disorder, affecting a large number of elderly individuals worldwide. Mitochondrial dysfunction, metabolic alterations, and oxidative stress are regarded as cooperating drivers of the progression of AD. In particular, metabolic impairment amplifies the production of reactive oxygen species (ROS), resulting in detrimental alterations to intracellular Ca2+ regulatory processes. The Na+/Ca2+ exchanger (NCX) proteins are key pathophysiological determinants of Ca2+ and Na+ homeostasis, operating at both the plasma membrane and mitochondria levels. Our study aimed to explore the role of NCX1 and NCX3 in retinoic acid (RA) differentiated SH-SY5Y cells treated with glyceraldehyde (GA), to induce impairment of the default glucose metabolism that typically precedes Aß deposition or Tau protein phosphorylation in AD. By using an RNA interference-mediated approach to silence either NCX1 or NCX3 expression, we found that, in GA-treated cells, the knocking-down of NCX3 ameliorated cell viability, increased the intracellular ATP production, and reduced the oxidative damage. Remarkably, NCX3 silencing also prevented the enhancement of Aß and pTau levels and normalized the GA-induced decrease in NCX reverse-mode activity. By contrast, the knocking-down of NCX1 was totally ineffective in preventing GA-induced cytotoxicity except for the increase in ATP synthesis. These findings indicate that NCX3 and NCX1 may differently influence the evolution of AD pathology fostered by glucose metabolic dysfunction, thus providing a potential target for preventing AD.

Malignant trichilemmal carcinoma misdiagnosed with parotid gland malignant tumor.

Malignat proliferating trichilemmal tumor (MPTT) are rare tumors usually presenting in photo-exposed areas, especially on the face, scalp, neck,and dorsal part of the hand. Differential diagnosis include squamous cell carcinoma, basal-cell carcinoma, keratoacanthoma and malignant nodular melanoma, so that only incisional biopsy can lead to pre-operative diagnosis. We present case MPTT misdiagnosed with parotid gland malignant tumor that underwent radical surgical excision and adijuvant radiotherapy.

Surgical treatment of nasal non-melanoma skin cancer using full-thickness skin graft: can antiplatelet therapy be related to a better result?

AIM: The aim of this retrospective study is to evaluate if antiplatelet therapy in elderly patients undergoing surgical excision of nasal non-melanoma skin cancer and contemporary reconstruction with full-thickness skin graft can be related to a better vitality of the graft and consequently improved aesthetic result. MATERIALS AND METHODS: Patients affected by BCC or SCC of the nose that underwent surgical excision and contemporary reconstruction with full-thickness skin graft were divided into two groups according to antiplatelet therapy. Medications were performed 7 and 15 days after surgery. To asses engraftment, we clinically evaluated the percentage of vital flap recognizing 3 different results: less than 20%, between 20% and 80%, and more than 80% of vital surface. Finally, patients were asked to express a subjective evaluation of the aesthetic result using a numeric scale ranging from 1 to 10. Statistical analyses were performed with SPSS 15.0 for Windows. RESULTS: Twenty-four of the 36 eligible patients took antiplatelet therapy (Group 1). Statistical analysis was very close to demonstrate a significant difference between the two groups after the first evaluation (X2= 3.6; p-value = 0.0578) and it showed a clear significant difference between the two groups after the second evaluation (X2 = 13.5692 e p-value = 0.0002). The average value of the subjective evaluation conducted only on 32 of 36 patients, was 9.12. Any significant difference was observed between the two groups (p-value >0.1). CONCLUSIONS: Our preliminary results seem to suggest that antiplatelet therapy in elderly patients with non-melanoma skin cancer of the nose treated with surgical excision and contemporary reconstruction with fill-thickness skin graft could favor the graft vitality with low risk of bleeding. Further studies will be useful to determinate if antiplatelet drugs can be prescribed in the perioperative period to selected patients presenting risk factors for wound healing to increase the chances of engraftment. KEY WORDS: Antiplatelet Therapy, Non Melanoma Skin Cancer, Skin Graft.

A strategic tool to improve the study of molecular determinants of Alzheimer's disease: The role of glyceraldehyde.

Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by progressive neurodegeneration leading to severe cognitive, memory, and behavioral impairments. The onset of AD involves a complex interplay among various factors, including age, genetics, chronic inflammation, and impaired energy metabolism. Despite significant efforts, there are currently no effective therapies capable of modifying the course of AD, likely owing to an excessive focus on the amyloid hypothesis and a limited consideration of other intracellular pathways. In the present review, we emphasize the emerging concept of AD as a metabolic disease, where alterations in energy metabolism play a critical role in its development and progression. Notably, glucose metabolism impairment is associated with mitochondrial dysfunction, oxidative stress, Ca2+ dyshomeostasis, and protein misfolding, forming interconnected processes that perpetuate a detrimental self-feeding loop sustaining AD progression. Advanced glycation end products (AGEs), neurotoxic compounds that accumulate in AD, are considered an important consequence of glucose metabolism disruption, and glyceraldehyde (GA), a glycolytic intermediate, is a key contributor to AGEs formation in both neurons and astrocytes. Exploring the impact of GA-induced glucose metabolism impairment opens up exciting possibilities for creating an easy-to-handle in vitro model that recapitulates the early stage of the disease. This model holds great potential for advancing the development of novel therapeutics targeting various intracellular pathways implicated in AD pathogenesis. In conclusion, looking beyond the conventional amyloid hypothesis could lead researchers to discover promising targets for intervention, offering the possibility of addressing the existing medical gaps in AD treatment.

Lipostructure in Parry-Romberg disease.

Parry-Romberg syndrome is a disease characterized by progressive hemifacial atrophy. Multiple surgical procedures have been used to improve the facial volume and contours of patients with this disease, including alloplastic, silicone, or collagen implants; lipofilling; and pedicled or free-flap transplants. The present case describes the successful application of lipostructure to treat a woman with Parry-Romberg syndrome affecting the left side of her face.

Single-step nasal reconstruction with osteocutaneous forearm flap after total rhinectomy.

PURPOSE: Nasal defects resulting from tumor excision can be classified according to tissues involved, such as skin, cartilage, and bone. Although in the case of "simple" defects, reconstruction with loco-regional flap eventually associated with cartilage grafts can lead to satisfactory results; in the case of total or partial rhinectomy, a minimum of 3 and a maximum of 7 operations have to be performed in the current series to achieve an acceptable end result. We present the case of a total rhinectomy reconstruction in a single-step procedure with an osteocutaneous forearm free flap (RFOFF). CLINICAL REPORT: A 50-year-old man underwent total rhinectomy to excise a pathologically proven T4aN0 moderately differentiated squamous cell carcinoma of the nose; contemporary single-step reconstruction with an RFOFF was performed. Adjuvant radiotherapy was performed. RESULT: At 18 months of follow-up, the patient is free of disease and no postirradiation flap damage has been experienced; the flap notably did not appear to be bulky. CONCLUSIONS: We believe that the RFOFF is morphologically and functionally better than other flaps owing to its capability to adapt to the new environments of the nasal cavity, and to avoid, when possible, a three-dimensional reconstruction of the same.

Intramasseterin-infiltrating angiolipoma: a challenging diagnosis.

Angiolipomas are benign mesenchymal tumors infrequently affecting the head and neck region, manifesting themselves as small (<4 cm), slow-growing mass that are painful or tender to palpation. Ultrasonography, fine needle aspiration biopsy, computed tomography, and magnetic resonance imaging can be used to make a diagnosis. Surgical excision is the treatment of choice in both infiltrating and noninfiltrating forms, even if liposuction can be considered in multiple forms. We describe a case of infiltrating intramasseterin angiolipoma, in which diagnosis was suspected after magnetic resonance imaging with gadolinium; then a transoral surgical excision was performed. To the best of our knowledge, only 1 other case of intramasseterin-infiltrating angiolipoma has been previously described.

Management of benign parotid tumors. What can we learn from our experience?

AIM: Parotid gland is the most common location for salivary gland tumors, more commonly pleomorphic adenoma and Warthin's tumor. Types of parotid surgery include superficial parotidectomy (SP), partial superficial parotidectomy (PSP), total conservative parotidectomy (TCP), enucleation (E), extracapsular dissection (ECD), and are related to different incidence of complications. The choice depends on tumors localization, dimension and histology. The aim was to compare complications rate such as facial and great auricular nerve impairment and Frey syndrome according to type of surgery performed. MATERIALS AND METHODS: We retrospectively review the management of 116 benign tumors of the parotid gland treated between January 2004 and January 2020 at our Department. RESULTS: Most frequent complication observed was a GAN deficiency (22.41%), permanent in 13% of cases. Post-operative facial nerve impairment was observed in 19 patients (persistent only in 1 case). Only Frey syndrome (4,31% of cases) seemed to be related to type of surgery (p<0.05) resulting more frequent in the group of patients that underwent "classical" parotidectomy, while facial nerve impairment, even if more frequent in this cases, did not statistically correlated with operative technique (p=0.054). CONCLUSIONS: Once experience is gained, in order to reduce post-operative morbidity extracapsular dissection is a reliable technique in the management of these neoplasms, even if attention has to be paid particularly in the removal of superficial masses "emerging" from the parenchyma. PSP is an alternative to SP, while CTP has to be reserved to selected cases ot tumors arising in the deep lobe. KEY WORDS: Benign tumor, Extracapsular dissection, Enucleation, Facial nerve Parotid gland, Parotidectomy, Superficial parotidectomy.

Recovery of Regular Daily Physical Activities Prevents Residual Dizziness after Canalith Repositioning Procedures.

OBJECTIVE: Residual dizziness is a disorder of unknown pathophysiology, which may occur after repositioning procedures for benign paroxysmal positional vertigo. This study evaluates the relationship between regular daily physical activity and the development of residual dizziness after treatment for benign paroxysmal positional vertigo. STUDY DESIGN: Prospective observational cohort study. SETTING: Academic university hospital. METHODS: Seventy-one patients admitted with benign paroxysmal positional vertigo involving the posterior semicircular canal were managed with Epley's procedure. Three days after successful treatment, the patients underwent a telephone interview to investigate vertigo relapse. If the patients no longer complained of vertigo, they were asked about symptoms consistent with residual dizziness. Subsequently, they were asked about the recovery of physical activities they regularly performed prior to the onset of vertigo. RESULTS: Sixty-nine patients (age: 57.79 ± 15.05) were enrolled: five (7.24%) reported vertigo relapse whereas twenty-one of sixty-four non-relapsed patients (32.81%) reported residual dizziness. A significant difference in the incidence of residual dizziness was observed considering the patients' age (p = 0.0003). Of the non-relapsed patients, 46 (71.88%) recovered their regular dynamic daily activities after treatment and 9 (19.57%) reported residual dizziness, while 12 of the 18 patients (66.67%) who did not resume daily activity reported residual symptoms (p = 0.0003). A logistic regression analysis showed a significant association between daily activity resumption and lack of residual dizziness (OR: 14.01, 95% CI limits 3.14-62.47; p = 0.001). CONCLUSIONS: Regardless of age, the resumption of regular daily physical activities is associated with a lack of residual dizziness.

Orbital lesions, an interdisciplinary pathology. The experience of the maxillo-facial surgeons.

AIM: The main focus of this paper was to describe our experience in the management of primary lesions involving the orbit, analyzing signs and symptoms and illustrating surgical management. MATERIAL OF STUDY: We describe our experience managing 62 consecutive patients diagnosed with orbital tumors confined to the orbital content (not involving skin or bone, with no intracranial invasion) and treated between January 2013 and December 2016. Demographic characteristics, symptoms, clinical findings, histological types and approaches have been recorded. RESULTS: We found that the most common clinical manifestations were exophthalmos/proptosis and ocular movement impairment; the most common histological types were vascular malformation and ocular adnexal lymphomas. DISCUSSION: Primary neoplasms involving orbital contents include a broad spectrum of pathologies difficult to manage without a firm diagnosis, usually histological. Different surgical accesses are described in order to perform incisional biopsy or resection of the mass. CONSCLUSION: In every case, accurate surgical planning is mandatory, in order to prevent functional and/or aesthetic complications. KEY WORDS: Blepharoplasty incision, Intraorbital neoplasia, Lateral orbital tumor, Orbitotomy, Surgical treatment, Transconjunctival approach.

Reconstruction of the mandibular symphysis: pilot study compares three different flaps.

BACKGROUND: Restoration of mandibular continuity, functionality and attempting to return to the patient's premorbid state is the ultimate goal of reconstruction. Some studies compare different flaps, but the reconstructed portions vary and there is little consensus on the best option for a particular defect. METHODS: This pilot study compares three different reconstructive options with free flaps. We will analyze the accuracy of the reconstruction, the postoperative complications related to the reconstruction, the morbidity of the donor site. This pilot study compares three different reconstructive options with free flap in the reconstruction of the mandibular symphysis: iliac crest, scapula and fibula. RESULTS: In our sample the morbidity of the donor site was overlapping, as for all three choices free from complications. In post resection edentulous patients, the fibula seems to guarantee better positioning, while in patients with residual occlusion the iliac crest seems to allow a more congruous repositioning. The fibula seems to have a superiority over the other flaps in terms of accuracy in all types of patients. CONCLUSIONS: Contrary to the most recent work on the accuracy of CAD/CAM, we have analyzed the error in the reconstruction of a specific segment and in the repositioning of the residual mandibular component without the use of guided computer programming.

Orbital bone fractures: 10 years' experience at the Rome trauma centre: retrospective analysis of 543 patients.

Orbital fractures are among the most frequent facial traumas. This study retrospectively analysed patients treated in Umberto I Hospital Trauma-Centre, Sapienza University of Rome from 1 January 2010 to 31 December 2020. The inclusion criteria were as follows: diagnosis of pure/impure orbital bone fracture, complete clinical and radiological records, and a minimum 12-month follow up. Gender, age, aetiology, fracture type, treatment, and associated complications were analysed using IBM SPSS Statistics, and p values of <0.05 were considered significant. In total, 1393 patients presented with orbital trauma, 543 of whom met the inclusion criteria and underwent surgery (394 males (72.6%) and 149 females (27.4%); mean (range) age 39.2 (7-90) years). Assault (n = 165, 30.4%) was the most common cause of trauma, followed by road traffic accidents and sports-related incidents. Diplopia was the major symptom at diagnosis (n = 183, 33.6%). Open reduction and internal fixation via a sub-eyelid approach was the preferred treatment, achieving a significant reduction in the functional changes induced by fracture (p < 0.05). Our data will aid future studies of maxillofacial traumatology and suggest that education and prevention measures could reduce the incidence of this type of trauma.

Cricoid-based extramedullary plasmocytoma.

Extramedullary plasmocytomas are solitary, vascular, soft tissue plasma cell tumors without evidence of multiple myeloma (MM) that represent approximately 1% of head and neck malignancies. Approximately one third of them disseminate to MM within 2 years from presentation. Extramedullary plasmocytomas have been reported to involve larynx in 6% to 18% of cases, most commonly affecting the epiglottis and the ventricle, followed in order by the true vocal cord, false vocal cord, aryepiglottic fold, arytenoids, and subglottis. In this report, we describe a case of plasmocytoma involving the cricoid, the left cricoaritenoid joint, and the homolateral vocal process that developed MM 1 year after primary treatment.