Tumor-infiltrating lymphocytes and tumor-associated macrophages as potential predictors of lymph node metastases in major salivary gland cancers.

Purpose: The purpose of this study is to define if tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) could represent potential predictors of lymph node metastases (LNM) in salivary gland cancers (SGC). Methods: A selected number of immunohistochemical markers related to TILs (CD3, CD4, CD68, and FOXP3) and TAMs (CD68 and CD163) were investigated on major salivary gland cancers. TIL and TAM densities were measured on digital images using the open-source QuPath both in the tumor interior (TI) and invasive margin (IM). Correlation with pathologic N classification and follow-up clinical data was investigated. Results: A total of 25 consecutive patients (men: 11; median age: 62.0) were included. Densities of CD3+ IM (OR = 7.7, 95% CI 1.2-51.2), CD8+ TI (OR = 7.7, 95% CI 1.2-51.2), CD8+ IM (OR = 7.7, 95% CI 1.2-51.2), FOXP3+ TI (OR = 24.0, 95% CI 2.2-255.9), CD68+ TI (OR = 7.7, 95% CI 1.2-51.2), and CD163+ IM (OR = 7.7, 95% CI 1.2 - 51.2), and the Immunoscore CD8/CD3 (OR = 1.9, 95% CI 1.1-3.4) were significantly associated with LNM (p < 0.05). CD3+ TI density was significantly associated with tumor recurrence and death (HR = 5.8, 95% CI 1.5-22.6; p < 0.05). Conclusion: A high density of specific TIL and TAM subpopulations might be correlated with a higher probability of LNM in SGC.

High-Definition 3-D Exoscope for Micro-Laryngeal Surgery: A Preliminary Clinical Experience in 41 Patients.

OBJECTIVE: The aim of this prospective clinical study is to evaluate the feasibility of the micro-laryngeal surgery (MLS) using a 3D operating exoscope (OE) in substitution to a conventional operating microscope (OM). METHODS: A total of 41 consecutive patients were included (male: 26; median age: 55.0 years; IQR: 46.0-68.0). After each procedure, the surgeon and the scrub nurse were asked to fill out a tailored questionnaire on a 3-point Likert scale (1-not acceptable, 2-acceptable, 3-good) including 12 items. RESULTS: The majority of the procedures were therapeutic (n = 31, 75.6%), while the remaining were diagnostic (n = 10, 24.4%). All surgeries were successfully completed without the support of the OM, and no complications or unwanted delays were detected. The majority of the individual items were judged "good" either by surgeons (n = 399, 81.1%) and scrub nurses (n = 287, 87.5%). The natural posture during the procedure, and the ease of use the joystick and focusing were the best-rated items by the surgeons. CONCLUSIONS: This study demonstrates the feasibility of MLS using the OE. Further comparative clinical studies are needed to clarify its real value in substitution to a conventional operating microscope and to better define advantages and disadvantages.

Present and Future of De-intensification Strategies in the Treatment of Oropharyngeal Carcinoma.

PURPOSE OF REVIEW: The treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic factor, and HPV+ OPSCC is considered a distinct pathological entity with dedicated NCCN guidelines and may deserve a more personalized therapeutic strategy. The possibility to reduce surgical invasiveness and acute and late toxicity of radiotherapy/chemotherapy has led to the new concept of de-escalation treatment strategies. In particular, several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. The aim of the present review is to systematically illustrate the current status of research in de-intensification surgical and non-surgical strategies in the treatment of the OPSCC. RECENT FINDINGS: We categorized all completed and on-going trials on the basis of the specific de-escalated treatment protocol. Several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. Considering the conflicting results reported so far by preliminary studies, it is necessary to wait for the final results of the on-going trials to better clarify which is the best de-intensified strategy and which patients would really benefit from it.

Characterization of Plasmodium falciparum Atypical Kinase PfPK7- Dependent Phosphoproteome.

PfPK7 is an "orphan" kinase displaying regions of homology to multiple protein kinase families. PfPK7 functions in regulating parasite proliferation/development as evident from the phenotype analysis of knockout parasites. Despite this regulatory role, the functions of PfPK7 in signaling pathways are not known. To better understand PfPK7-regulated phosphorylation events, we performed isobaric tag-based quantitative comparative phosphoproteomics of the schizont and segmenter stages from wild-type and pfpk7 - parasite lines. This analysis identified 3,875 phosphorylation sites on 1,047 proteins. Among these phosphorylation events, 146 proteins with 239 phosphorylation sites displayed reduction in phosphorylation in the absence of PfPK7. Further analysis of the phosphopeptides revealed three motifs whose phosphorylation was down regulated in the pfpk7 - cell line in both schizonts and segmenters. Decreased phosphorylation following loss of PfPK7 indicates that these proteins may function as direct substrates of PfPK7. We demonstrated that PfPK7 is active toward three of these potential novel substrates; however, PfPK7 did not phosphorylate many of the other proteins, suggesting that decreased phosphorylation in these proteins is an indirect effect. Our phosphoproteomics analysis is the first study to identify direct substrates of PfPK7 and reveals potential downstream or compensatory signaling pathways.