Oral squamous cell carcinoma of tongue: Histological risk assessment. A pilot study

Background: More than 90% of malignant tumors diagnosed in the oral cavity are Oral Squamous Cell Carcinomas (OSCC) whose preferred location is the tongue. Classically, this disease has affected men preferentially, although recent studies suggest that trends are changing and the proportion of women with OSCC is increasing. In addition, the prevalence of oral cancer is also determined by some risk factors as alcohol consumption and tobacco. Currently, the Tumor, Node, Metastasis (TNM) classification is employed to defined tumor stage and based on this guide specific treatments are established. However, 5-year-survival does not exceed 50% of cases. The objective of this study is to determine whether a histological risk pattern indicative of higher recurrence might be present in T1-T2 tumors located in the anterior two thirds of the tongue. Material and Methods: Samples from 26 patients with OSCC were analyzed and histological risk pattern of recurrent and non-recurrent tumors were compared. We have analyzed histological variables described in Anneroth and Brandwein-Gensler classifications. Additionally, we have also examined both clinical variables such as age, sex or comorbidities, as well as habits such as tobacco or alcohol consumption. Results: We found that sex (male) and keratinization degree (high or moderate) are directly related with OSCC recurrence. In fact, free illness time is lower in men and higher in those cases with minimal or no keratinization. Conclusions: Based on the variables analyzed, it has not been possible to establish a histological risk pattern that, complementary to the TNM classification, could have a predictive role in these early-stage tongue carcinoma

Expression of clec9a in the oral cancer microenvironment. A preliminary immunohistochemical pilot study

The search for treatments to improve cancer survival has led to the emergence of immunotherapy and the study of the tumour microenvironment existing in neoplasms. This preliminary study aims to understand the clinical and pathological relationship of clec9a expression in oral cancer and to explore survival models for future studies. Material and methods: Immunohistochemical study that included 26 patients with a diagnosis of oral squamous cell carcinoma (OSCC) in mobile tongue and floor of the mouth. Clinical and histopathological variables were recorded, and the biomarkers clec9a for dendritic cells and CD8 and CD4 for lymphocytes were used. Clec9a was expressed in 58% of the sample. It was more common in cases with low lymphoplasmacytic infiltration and in type 2 invasion patterns. It was significantly related to CD8 expression (p=0.055 and p=0.007). No prognostic risks were evident in the survival models studied (overall survival, disease-specific survival, disease-free survival). CLEC9A expression is present in the OSCC microenvironment and is mainly related to the presence of CD8 lymphocytes. The relationship of its expression with survival prognosis in OSCC could not be confirmed; however, this needs to be confirmed through future studies with larger sample size

Oral mucositis. Is it present in the immunotherapy of the immune checkpoint pd1/pd-l1 against oral cancer? A systematic review

Oral mucositis (OM) is a painful lesion that takes place in the mucosa of the oral cavity, usually its etiology is associated with drug therapies in cancer patients. It is presented as well-defined ulcers whose painful symptomatology sometimes implies the suspension of oncological treatment or parenteral feeding, being therefore an important adverse effect, marking the evolution of these types of therapies against cancer. The present work aim is to know the prevalence of oral mucositis in oral cancer immunotherapy compared to its prevalence in standard therapy. A protocol was developed for a systematic review following PRISMA® guidelines and a focused question (PICO) was constructed. A comprehensive literature search was conducted on electronic databases including PubMed, the SCOPUS database, the Cochrane library and the Web of Science (WOS). Six clinical trials were included that met the different inclusion criteria. In these articles, a discrepancy between the prevalence of OM in patients treated with chemotherapy and patients treated with immunotherapy related to the immune checkpoint PD-1/PD-L1 (Nivolumab and Pembrolizumab) was observed. The prevalence of oral mucositis is lower in new immunotherapy with monoclonal antibodies against oral cancer than drugs used so far (chemotherapy drugs [methotrexate, cisplatin] as well as cetuximab). However, more studies should be carried out to confirm these data

Dental implants rehabilitation in a patient with head and neck radiotherapy for osteosarcoma in the jaw. A clinical case report

A 52-year-old female patient with a diagnostic of osteosarcoma in the mandible, in which it was necessary a reconstruction with a microvascularized osteomyocutaneous fibula bone. Coadjuvant chemotherapy was scheduled. Two years later, 4 osseointegrated implants (OII) were placed in the fibula a 2 OII in the right mandible, using a splint guided surgery. The final prosthodontic consisted in a metal ceramic restoration using CAD/ CAM technology

Prognosis Value of Immunoregulatory Molecules in Oral Cancer Microenvironment: An Immunohistochemical Study

Objectives: To evaluate the relationship of the immune-checkpoint PD-1/PD-L1 with the clinical evolution of OSCC; to assess survival in OSCC based on the characteristics of TME and histologic risk score; to evaluate the clinical and histopathological relationship of OSCC with immunological TME. Material and Methods: A retrospective study was carried out on 65 samples from patients with OSCC on the floor of the mouth or tongue. Clinicopathological variables and the expression of the biomarkers PD-1, PD-L1, FoxP3, CD4, CD8, CSF1R, and p16 were recorded. The relationship of the clinical and histological variables with the expression of the biomarkers and survival was studied. Results: The univariate and multivariate analysis indicated that positive PD-1 expression was an independent protective factor for survival (overall, disease-free, disease-specific survival) and that high PD-L1 also improved survival. Poorly differentiated histological grades and metastasis were associated with a worse prognosis. Conclusions: PD-1 is a protective survival factor that is maintained independently of PD-L1 expression. High values of PD-L1 expression also improve survival. Higher expression of PD-1 is observed in smaller tumors, and higher expression of PD-L1 is more likely in women. No relationship between the tumor microenvironment and histologic risk score was found to influence the survival patterns studied in the OSCC. There is no evidence of a relationship between the histopathological features and the studied markers, although the positive PD-1 and PD-L1 cases have a lower risk of a high WPOI score, and positive PD-1 expression was associated with a lower DOIThis research was funded by the Fundación para la investigación Biomédica Hospital Universitario La Paz with the project number: EC_5474. The research has been partially funded through a predoctoral research grant awarded by the Official College of Dentists of Madrid (Madrid, Spain) with not project number associate

Jaw in a day: Osseointegration of the implants in the patient’s leg before reconstructive surgery of a maxilla with ameloblastoma. A 4-year follow-up case report

Background: To describe a clinical case of a cancer patient who underwent ablative tumor surgery, including treatment planning, surgical resection and subsequent implant rehabilitation. Case Report: A 61-year-old patient with a diagnosis of multicystic follicular ameloblastoma in the maxilla, in which it was necessary a muitidisciplinary approach and two surgical steps. In the first surgical intervention osseo-integrated implants (OII) were placed in the fibula, until their osseointegration period of 8 weeks was complete. Afterwards, in the second surgery, the micro-vascularized free fibular flap bearing the implants was transplanted into the oral cavity, in order to perform simultaneous reconstruction and early rehabilitation. The final prosthetic rehabilitation consisted in a hybrid prosthesis fabricated using CAD CAM technology. Results: The latest advances in medical research have improved our understanding of the oral cavity’s regenerative capacity after oncological treatment. This, aided by the advances in digital 3D technologies, has allowed meticulous treatment planning prior surgery. Conclusions: The functional and esthetic reconstructions described in these two case reports were made possible by coordinating multidisciplinary approaches involving dentists and oral and maxillofacial surgeons. Advances in medicine have improved understanding of the regenerative capacity of the oral region following oncologic treatment, facilitating meticulous advance planning, while advances in digital 3D technologies for planning make it possible to reduce the number of surgical sessions and the time taken for the patient to recover both the esthetics and function of the stomatognathic system

Bisphosphonate-related osteonecrosis. Application of adipose-derived stem cells in an experimental murine model

Bisphosphonate-related osteonecrosis of the jaw is a pathological condition without effective established treatment and preventive strategies. The aim of this study was to analyse the effect of adipose-derived stem cells (ASC) in an experimental murine model of osteonecrosis. 38 Wistar rats were injected intraperitoneally with zoledronic acid. After treatment, upper jaw molars were extracted. The animals were randomly assigned to one of two groups. In the control group, saline solution was applied over the alveolar sockets after the tooth extractions. In the treatment group, ASCs were applied instead of saline solution. The control and treatment groups were subdivided based on the time of euthanasia. A clinical and histological analysis was performed. The presence of osteonecrosis in alveolar bone was observed in a similar distribution in both groups. In the ASC-treated group, new bone formation was greater than in controls. In this study, application of ASCs showed greater new bone formation in an osteonecrosis-like murine model. Previous inhibited post-extraction bone remodelling could be reactivated, and these findings appeared to be secondary to implantation of ASCs

Anti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapy

Sarcoma is one of the most severe forms of pediatric cancer and current therapies -chemotherapy and surgery- fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 expression is implicated in rhabdomyosarcoma progression, so we analyzed relapses and chemotherapy-resistant rhabdomyosarcoma tumors from pediatric patients and found that they had particularly high levels of CXCR4 expression. Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells. On the other hand, activated and expanded natural killer (NKAE) cell therapy showed high cytotoxicity against sarcoma cells in vitro and completely inhibited RH30 tumor implantation in vivo. Only the combination of MDX1338 and NKAE treatments completely suppressed metastasis in mice. In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease dissemination.This work was supported in part by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI15/00973; Asociacion Espanola Contra el Cancer to AP-M; CRIS Foundation to Beat Cancer grant to JV, LF, and AE; and Patients' Support Associations Fundacion Mari Paz Jimenez Casado and La Sonrisa de Alex to MV and the research project

Tumor glómico maligno: a propósito de un caso y revisión de la literatura

Los tumores glómicos malignos son neoplasias poco frecuentes del cuerpo glómico mioarterial. Presentamos un caso de tumor glómico maligno en mano derecha en mujer de 72 años. La resonancia magnética identificó tumoración de partes blandas de predominio subcutáneo, en el segundo dedo de la mano, con áreas más profundas que contactaban con los tendones flexores del dedo, el músculo primer interóseo dorsal y los huesos subyacentes. El estudio de extensión no evidenció enfermedad macroscópica maligna. Histológicamente el tumor tenía arquitectura plexiforme. Las células tumorales estaban en íntima relación con vasos de pequeño calibre, en ocasiones con tinción PAS positiva, con morfología fusiforme y focalmente epitelioide, atipia moderada y tasa mitótica de 4 mitosis en 10 campos de gran aumento, sin identificarse mitosis atípicas ni necrosis tumoral. Con técnicas de inmunohistoquímica se observó positividad difusa para actina de músculo liso y vimentina, con marcaje célula a célula de colágeno tipo IV y negatividad para CD34, caldesmon, desmina, queratinas y S100. Realizamos escisión quirúrgica amplia con márgenes negativos y se administró radioterapia adyuvante sobre la mano, sin evidencia de recidiva tumoral tras 9 meses de seguimiento. Presentamos también una revisión de la literatura sobre tumores glómicos malignos en miembro superior, así como el diagnóstico diferencial de este tipo de lesiones cuando se localizan en la piel y el tejido celular subcutáneo