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

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

Estudio inmunohistoquímico comparativo de la glicosilación del epitelio normal del cuello uterino y sus lesiones asociadas y su relación con la expresión de las proteinas PCNA, P53, y el gen E6 del HPV-16

Tesis Univ. Complutense de MadridDepto. de Medicina Legal, Psiquiatría y PatologíaFac. de MedicinaTRUEpu

GFAP and alpha1a-AR staining and nuclear morphometry of oligodendrogliomas by confocal microscopy and image analysis: useful parameters for predicting survival in oligodendrogliomas

Abstract Objective This study attempts to evaluate the GFAP and alpha1a-AR staining and morphometrical nuclear features of oligodendrogliomas and their prognostic implications as compared to present histopathology classification and their survival outcome. Study design Surgical specimens from 24 patients with oligodendrogliomas during the period 1981–2000 were included. These cases were classified into two groups defined by the grade of the neoplasm: Group I: oligodendrogliomas grade II; Group II: oligodendrogliomas grade III and two groups based on the outcome status: Group of the alive cases and group of the death cases. Death rate for the groups were obtained by patients' charts. Descriptive statistics were used to examine the groups with respect to the morphometrical nuclear variables; area, perimeter, aspect, axes (major and minor), diameters (max, mean and min.), radius (max. and min.) margination, ratio of perimeter-area, roundness and sizes (length and width). In addition, an immunofluorescence method for GFAP and 1a-AR were performed and their area, density and intensity of staining were analyzed. Results Semiautomated quantitative morphometrical results showed that the variables of nuclear area (GII 48.87 μm2 vs. GIII 43.45 μm2 p-value = 0.02), aspect (GII 1.39 vs. GIII 1.55 p-value = 0.03), axis minor (GII 6.66 μm vs. GIII 6.01 μm p-value = 0.003), diameter minor (GII 5.93 μm vs. GIII 5.27 μm p-value = 0.002), radius minor (GII 2.64 μm vs. GIII 2.25 μm p-value = 0,003), perimeter-area (GII 0.0007 vs. GIII 0.0006 p-value = 0.04), size width (GII 6.60 μm vs. GIII 5.96 μm p-value = 0,003), and density of alpha1a-AR staining (GII 121.38 vs. GIII 146.03 p-value = 0.05) were statistically significant in regard of grade; and that the sum of density of GFAP (p-value = 0.01) and the intensity of alpha1a-AR (p-value = 0.01) were statistically significant in predicting survival. Conclusion These results suggest that some nuclear morphometrical features and the GFAP and alpha1a-AR immunofluorescence staining may be useful parameters for predicting survival in oligodendrogliomas.</p

Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study

Background: Surgical strategies are being adapted to face the COVID-19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods: The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results: Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X-ray plus molecular testing (PCR) being the commonest (19\ub78 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6\ub76 and 2\ub74 per cent respectively before, but 23\ub77 and 5\ub73 per cent, during the pandemic (both P < 0\ub7001). One-third changed their approach from laparoscopic to open surgery owing to the popular (but evidence-lacking) advice from expert groups during the initial phase of the pandemic. No agreement on how to filter surgical smoke plume during laparoscopy was identified. There was an overall reduction in the number of patients admitted with appendicitis and one-third felt that patients who did present had more severe appendicitis than they usually observe. Conclusion: Conservative management of mild appendicitis has been possible during the pandemic. The fact that some surgeons switched to open appendicectomy may reflect the poor guidelines that emanated in the early phase of SARS-CoV-2

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications