The mismatch repair (MMR) system has a major role in the detection and correction of DNA replication errors, resulting from DNA polymerase slippage or nucleotides misincorporation. Specific ...inherited/acquired alterations or epigenetic inactivation of MMR genes are associated with microsatellite instability (MSI): the loss of crucial function in repairing DNA alterations can promote carcinogenesis by favoring the accumulation of thousands of mutations in a broad spectrum of different anatomic sites such as colon, stomach, prostate, esophagus, endometrium, lung and head and neck. Recent extensive data suggest that tumor mutational burden strongly correlates with a clinical response to immunotherapy using checkpoint inhibitors and this response is influenced by MMR deficiency in a wide range of human solid cancers. In this context, few data about this crucial point are available for head and neck cancer (HNC). In this review, we discuss the role of MMR alterations and the resulting MSI in HNC pathogenesis. Furthermore, by summarizing the clinical available data on how they influence the progression of precancerous lesions and the risk of recurrence or second primary tumors, we want to define the current role of MSI in the management of HNC. Finally, we analyze the complex interaction between cancer cells and the immune system addressing the data now available about a potential correlation between microsatellite instability and immunotherapy response in HNC.
Head and neck (HN) cancer, which mainly presents in the form of squamous cell carcinoma, was the seventh most common cancer worldwide in 2018, with approximately 890,000 new cases and 450,000 deaths .......
Objectives
Swallowing and voice dysfunctions are common side effects following head-and-neck squamous-cell carcinoma (HNSCC) treatment. Our aim was to analyze the relationships between quality of ...life, swallowing, and phonatory problems in patients with an advanced-stage HNSCC and to prospectively evaluate the effects of a prophylactic swallowing program.
Methods
First, we retrospectively studied 60 advanced HNSCC patients treated with exclusive or adjuvant radiotherapy/chemoradiotherapy (RT/CRT). Subjects were classified according to general and clinical–therapeutic features. Outcome measures included EORTC QLQ-C30, EORTC QLQ-H&N35, Dysphagia Handicap Index (DHI), M.D.Anderson Dysphagia Inventory (MDADI), and Voice Handicap Index (VHI). Then, we conducted a prospective evaluation of a prophylactic swallowing counselling in 12 consecutive advanced-stage HNSCC patients by a two-arm case–control analysis. These patients were treated with exclusive or adjuvant RT/CRT.
Results
71% of the retrospective population studied reported swallowing dysfunction as a major side effect. No differences were detected in the severity of dysphagia or dysphonia according to type of treatment or staging of the primary tumour, while hypopharyngeal and laryngeal cancer patients showed significantly better swallowing ability and better QoL compared to oral cavity and oropharyngeal localisation (
p
< 0.05). In addition, a relevant correlation between swallowing and voice problems emerged (
p
< 0.05). In the prospective part, while no statistical correlation was evident before the start of RT/CRT in the experimental group compared to the control one, the former showed better performances at MDADI (
p
= 0.006) and DHI (
p
= 0.002) test 3 months after its end.
Conclusion
Dysphagia is both an acute-and-long-term side effect which greatly affects QoL of HNSCC patients undergoing multimodality treatment. Our data show that a prophylactic swallowing program could actually produce a beneficial effect on patients’ outcomes.
Level of evidence
1b and 2b.
As Guest Editors, we are very delighted to see the reprint of our Special Issue, “Head and Neck Surgery: Clinical Updates and Perspectives", which is published in the Otolaryngology section of the ...Journal of Clinical Medicine. These papers are the joint effort of many excellent colleagues who have devoted their lives and careers to the exciting field of Otorhinolaryngology. As both clinicians and surgeons, we are actively advancing the diagnosis and management of the myriad of conditions affecting the head and neck region. Unprecedented discoveries in the field of genetics and molecular biology are always integrated with sound knowledge of the intricate anatomy of our discipline, while technological advancements now permit us to provide tailored and minimally invasive treatments for our patients. We wish to thank all the authors who contributed to this publication and we hope you enjoy reading it.
Pharyngocutaneous fistula (PCF) is a frequent complication after total laryngectomy, with an incidence of up to 65%. Many conservative or invasive approaches are available and the choice among them ...is usually made on a case-by-case basis. The aim of the present review is to critically summarize the available evidence of the effectiveness of the non-surgical management of PCF.
A systematic review and a meta-analysis of the literature were conducted, according to the PRISMA guidelines. Studies investigating botulinum toxin therapy, scopolamine transdermal patch, hyperbaric oxygen therapy (HBOT), and negative pressure wound therapy (NPWT) were assessed. Complete fistula closure after the initiation of non-surgical treatment was the main outcome.
After the application of selection criteria, a total of seven articles and 27 patients were included in the present review. All the eligible studies were descriptive case series, while only one article used a standard group as a comparison. The mean age was 63.3 and 14 patients (51.9%) had previously received RT. The reported comorbidities were diabetes, ischemic heart disease, hypertension, dyslipidemia, COPD, and atrial fibrillation. With a mean healing time of 25.0 days, the overall success rate was 92.6%.
Non-surgical treatment of PCF is only based on the experience of small series. Although success rates seem promising, the absence of properly designed comparative studies does not allow us, at present, to identify ideal candidates for these non-invasive management strategies for PCF.
Tumor extension and metastatic cervical lymph nodes' (LNs) number and dimensions are major prognostic factors in patients with oral squamous cell carcinoma (OSCC). Radiomics-based models are being ...integrated into clinical practice in the prediction of LN status prior to surgery in order to optimize the treatment, yet their value is still debated.
A systematic review of the literature was conducted according to the PRISMA guideline. Baseline study characteristics, and methodological items were extracted and summarized.
A total of 10 retrospective studies were included into the present study, each of them exploiting a single imaging modality. Data from a cohort of 1489 patients were analyzed: the highest AUC value was 99.5%, ACC ranges from 68% to 97.5%, and sensibility and specificity were over 0.65 and 0.70, respectively.
Radiomics may be a noninvasive tool to predict occult LN metastases (LNM) in OSCC patients prior to treatment; further prospective studies are warranted to create a reproducible and reliable method for the detection of LNM in OSCC.
Objectives:
Laryngeal squamous cell carcinoma (LSCC) can involve different anatomic subunits with peculiar surgical and prognostic implications. Despite conflicting outcomes for the same stage of ...disease, the current staging system considers different lesions in a single cluster. The aim of this study was to critically discuss clinical and pathologic staging of primary and recurrent advanced LSCC in order to define current staging pitfalls that impede a precise and tailored treatment strategy.
Methods:
Thirty patients who underwent total laryngectomy in the past 3 years for primary and recurrent advanced squamous cell LSCC were analyzed, comparing endoscopic, imaging, and pathologic findings. Involvement of the different laryngeal subunits, vocal-fold motility, and spreading pattern of the tumor were blindly analyzed. The diagnostic accuracy and differences between clinicoradiologic and pathologic findings were studied with standard statistical analysis.
Results:
Discordant staging was performed in 10% of patients, and thyroid and arytenoid cartilage were the major diagnostic pitfalls. Microscopic arytenoid involvement was significantly more present in case of vocal-fold fixation (P = .028). Upstaging was influenced by paraglottic and pre-epiglottic space cancer involvement, posterior commissure, subglottic region, arytenoid cartilage, and penetration of thyroid cartilage; on the contrary, involvement of the inner cortex or extralaryngeal spread tended to be down-staged. Radiation-failed tumors less frequently involved the posterior third of the paraglottic space (P = .022) and showed a significantly worse pattern of invasion (P < .001).
Conclusions:
Even with the most recent technologies, 1 in 10 patients with advanced LSCC in this case series was differently staged on clinical examination, with cartilage involvement representing the main diagnostic pitfall.
(1) Background: The treatment of recurrent early glottic cancer (rEGC) remains challenging. We wanted to investigate how the oncological outcomes are affected by the initial and recurrent stages, in ...order to propose our newly developed Same-Up-Down (SUD) staging system. (2) Methods: In our cohort of 258 rEGC patients, we retrospectively assessed the prognostic performances of the rTNM (the TNM staging system for recurrence), CLRSS, CLRSS-2, and SUD staging systems by univariate and multivariate Cox analysis, comparing their predictive capability using Harrell's C-index. (3) Results: The SUD classification satisfactorily predicted both overall survival (
= 0.022) and second-recurrence-free survival (
= 0.024, as same + down vs. upstage) in our cohort. It also outperformed the other three systems in terms of prediction of survival, with an improvement of 1.52%, 1.18%, and 3.96% in the predictive capacity of overall survival, disease-specific survival, and second-recurrence-free survival, respectively. (4) Conclusions: The SUD staging system can efficiently predict survival in rEGC patients, whose prognosis heavily depends on both the initial and recurrent locoregional extension.
The novel coronavirus SARS-CoV-2 enters into the human body mainly through the ACE2 + TMPRSS2+ nasal epithelial cells. The initial host response to this pathogen occurs in a peculiar immune ...microenvironment that, starting from the Nasopharynx-Associated Lymphoid Tissue (NALT) system, is the product of a long evolutionary process that is aimed to first recognize exogenous airborne agents. In the present work, we want to critically review the latest molecular and cellular findings on the mucosal response to SARS-CoV-2 in the nasal cavity and in NALT, and to analyze its impact in the subsequent course of COVID-19. Finally, we want to explore the possibility that the regulation of the systemic inflammatory network against the virus can be modulated starting from the initial phases of the nasal and nasopharyngeal response and this may have several clinical and epidemiological implications starting from a mucosal vaccine development.
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