To evaluate the diagnostic accuracy of the second edition Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) in predicting the risk of malignancy (ROM) in parotid tumors, through correlation with final histopathological diagnoses in a large consecutive single-center surgical series. A retrospective study was conducted on 249 consecutive patients who underwent parotid surgery between June 2017 and March 2024 in a tertiary referral center. Preoperative fine-needle aspiration cytology (FNAC) results were classified according to the MSRSGC. Diagnostic performance metrics were calculated, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic concordance. Cytological findings were correlated with definitive histopathology to calculate ROM, risk of high-grade malignancy (ROM-HG), and risk of neoplasia (RON). Multivariate logistic regression was performed to identify preoperative predictors of malignancy. FNAC showed high accuracy in diagnosing pleomorphic adenoma and Warthin tumor. Sensitivity for malignancy detection was 68

BackgroundPatients with head and neck cancer undergoing high-dose cisplatin chemotherapy combined with radiotherapy are particularly at risk of developing nephrotoxicity. While Acute Kidney Injury risk is well established, the role of subclinical renal impairment and its potential interplay with nutritional status remains poorly defined. We aim to evaluate how body composition pre-treatment can predict the onset of Acute Kidney Disease.Materials and methodsWe conducted a prospective, monocentric, observational study involving 110 patients with locally advanced HNC treated with concurrent cisplatin (≥200 mg/m²) and radiotherapy. Patients were treated either in a definitive or postoperative adjuvant setting, according to institutional clinical practice. Baseline body composition was assessed by bioelectrical impedance analysis (BIA). Renal function and biochemical data were collected at three time points across 21 days. Variables associated with AKD were identified via univariate analysis (Mann–Whitney U test), followed by multivariate logistic regression for independent predictors.ResultsAKD developed in 20% of patients during treatment. Those who developed AKD exhibited a significantly higher median increase in serum creatinine compared to non-AKD patients (Δcreatinine: 0.48 vs. 0.04 mg/dL, p < 0.001). Low body cell mass normalized for height (BCM/kg/m) emerged as a significant independent predictor of AKD (OR = 1.29, p = 0.04). A trend toward association was also observed for leukocyte count and platelet levels. Other nutritional indicators (BMI, phase angle, SMI) did not show a significant association. Importantly, all patients completed radiotherapy and reached the target cisplatin dose.ConclusionsA trend toward an association between low lymphocyte count and reduced muscle mass with AKD development suggests that pre-treatment nutritional and immunological status may influence nephrotoxicity risk. Bioimpedance-derived metrics may provide a non-invasive, reproducible method to identify high-risk patients.

INTRODUCTION:Major salivary gland carcinomas (MSGCs) are rare, heterogeneous malignancies with high recurrence rates. Recurrent-metastatic (RM) MSGCs frequently represent a clinical challenge due to their unpredictable behavior and the absence of established prognostic markers for the disease course of relapsed disease. MATERIALS AND METHODS:This multicenter retrospective study, involving 10 tertiary centers worldwide, included patients affected by loco-regional and/or distant relapse after surgery with curative intent. The study aimed to analyze residual survival (recurrent-metastatic survival, RMS) and identify key prognostic factors to support personalized treatment strategies, especially for exclusive loco-regional and distant recurrences. RESULTS:Among 212 patients, the median disease-free interval (DFI) after the initial treatment was 14 months, with a 1-year RMS of 58.1% (95% CI, 51.6-65.6%). Longer DFI (>30 months), adenoid cystic carcinoma histology, loco-regional recurrence rather than failure at distance, and absence of nodal metastasis (pN0) at initial diagnosis were significantly associated with a better residual overall survival. In patients with exclusive loco-regional recurrence, independent positive prognostic factors included DFI, salvage surgery, primary low-grade tumor, and lower pT classification. In contrast, for patients with exclusive distant metastasis, longer DFI (>30 months) and the type of intervention (metastasectomy for oligometastatic disease) were independent prognosticators. CONCLUSION:Disease-free interval is a key prognostic factor for the residual overall survival after a recurrence event. Primary tumor characteristics were associated with survival outcomes in the loco-regional recurrent setting, but not if the recurrence is at distance. Whenever feasible, salvage surgery for loco-regional recurrence and metastasectomy for oligometastatic disease may be considered in highly selected patients.

Mucoepidermoid carcinoma (MEC) is a rare cancer typically affects salivary glands. The development of MEC in the context of the thyroglossal duct is a rare finding. We describe the clinical manifestation, histopathological results, and treatment strategy of a 72-year-old woman who was diagnosed with intermediate-grade MEC originating from ectopic salivary gland tissue within a thyroglossal duct remnant.

Enhanced Recovery After Surgery (ERAS) pathways safely reduce length of stay (LOS) and resource use in many surgical fields, but their economic impact in thyroidectomy within the Italian National Health Service (SSN) is unclear, particularly under Diagnosis-Related Group (DRG) rules that penalize early discharge. A decision-analytic model compared an ERAS-inspired thyroidectomy pathway—same-day discharge after hemithyroidectomy and 24-hour discharge after total thyroidectomy—with a conventional DRG-driven pathway based on ≥2 postoperative inpatient days. The analysis adopted a hospital/provider perspective over 30 days, using data from a high-volume endocrine surgery unit and contemporary ERAS literature. Outcomes included LOS, postoperative complications, 30-day readmissions, direct hospital costs, and contribution margin under current SSN tariffs (including early-discharge penalties) and under a neutral reimbursement scenario. In hemithyroidectomy (400 cases/year), ERAS reduced mean LOS from 2.6 to 0.33 days (–2.27 days; p<0.001), freeing 908 bed-days annually and lowering variable costs by €1,332 per patient, without increasing complications or readmissions. Despite a 30

BACKGROUND:To evaluate the impact of near-infrared autofluorescence on both postoperative parathyroid function and the learning curve of surgeons performing total thyroidectomy. METHODS:We conducted a retrospective case-control study including 335 adult patients undergoing total thyroidectomy for primary thyroid disease (181 with intraoperative near-infrared autofluorescence guidance [near-infrared autofluorescence positive] and 154 under conventional standard approach [near-infrared autofluorescence negative]). Primary endpoints were transient hypocalcemia, transient hypoparathyroidism, and parathyroid gland identification rate. To specifically explore learning dynamics, we evaluated the influence of near-infrared autofluorescence on the surgeons' performance over time, comparing outcomes and parathyroid gland identification rate across 2 consecutive near-infrared autofluorescence utilization periods. Multivariate logistic regression was used to identify independent predictors of postoperative parathyroid gland dysfunction. RESULTS:Near-infrared autofluorescence significantly increased parathyroid gland identification rate (90.7% vs 70.5%) and was associated with lower rates of transient hypocalcemia (46.3% vs 60.2%, P = .011) and transient hypoparathyroidism (45.5% vs 57.7%, P = .041). On multivariate analysis, near-infrared autofluorescence remained an independent protective factor for transient hypocalcemia (odds ratio, 0.554; P = .009) and transient hypoparathyroidism (odds ratio, 0.606; P = .040). Along the near-infrared autofluorescence adoption timeline, parathyroid gland identification rate under white-light visualization progressively improved, suggesting a possible perceptual calibration effect that may contribute to shortening the learning curve for parathyroid gland-sparing thyroidectomy. Finally, short-term postoperative calcium levels were significantly higher in the near-infrared autofluorescence-positive group. CONCLUSION:Near-infrared autofluorescence improves intraoperative parathyroid gland identification and reduces early postoperative parathyroid dysfunction after total thyroidectomy. Beyond its technical utility, fluorescence guidance may act as an educational scaffold, potentially enhancing visual discrimination of parathyroid tissue. Whether near-infrared autofluorescence independently accelerates the surgical learning curve remains to be confirmed in prospective, surgeon-stratified studies.

BACKGROUND:Nodal metastases significantly affect prognosis in oral cavity squamous cell carcinoma (OCSCC). In early-stage OCSCC (cT1-T2 cN0), management of the clinically negative neck (cN0) remains controversial. Depth of invasion (DOI) is a key determinant for END, but other histopathological parameters, such as grading, perineural invasion (PNI), lymphovascular invasion (LVI), and worst pattern of invasion (WPOI), are emerging prognostic factors. METHODS:This multicenter retrospective study analyzed 1109 patients with cT1-T2 cN0 OCSCC treated at 30 Italian hospitals since 2017. Data on histopathological parameters, tumor characteristics, and patient outcomes were collected via the REDCap platform. Simple and multivariable logistic regression models were developed to assess predictors of occult nodal metastases. RESULTS:A total of 585 patients were clinically classified as cT1 tumors (53%), 503 as cT2 (45%), and cTis (1.9%). Of the 1109 patients, 193 (28%) had occult nodal metastases, with DOI, LVI, PNI, WPOI, and grading emerging as significant predictors. A predictive model integrating these variables demonstrated superior accuracy compared to a DOI-only model (AUROC comparison, p < 0.01). CONCLUSION:This study highlights the importance of incorporating multiple histopathological parameters into risk models for occult nodal metastases, overcoming the fixed DOI as a cutoff. The proposed predictive model offers a more precise method for guiding END in early-stage OCSCC, allowing individualized risk estimation.

Background: High-dose cisplatin (≥200 mg/m2 cumulative) remains the standard of care in concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, its use is frequently limited by nephrotoxicity, including acute kidney disease (AKD). This recently described clinical renal syndrome encompasses functional alterations of the kidney lasting fewer than 3 months post-exposure. Although hydration protocols and antiemetic strategies are routinely applied to avoid reduction in oral liquid intake and to prevent dehydration that could worsen renal function, AKD continues to pose a threat to reach the therapeutic dose, to treatment completion, and long-term outcomes. Recent evidence supports the nephroprotective role of intravenous (IV) magnesium in mitigating cisplatin-induced tubular injury, yet prospective data on its impact in real-world LA-HNSCC settings remain limited. We aimed to prospectively investigate the incidence and characteristics of renal impairment, particularly AKD, in a real-world cohort of LA-HNSCC patients treated with high-dose cisplatin and standardized supportive therapy, including intravenous magnesium. Methods: We conducted a prospective observational study including 207 patients with LA- HNSCC undergoing high-dose cisplatin-based CRT (≥200 mg/m2 cumulative dose), within a standardized supportive care protocol incorporating IV magnesium. Renal function was assessed over three cycles via serum creatinine and estimated glomerular filtration rate (eGFR). AKD was defined and staged according to KDIGO criteria. Clinical and biochemical predictors of AKD were explored. Results: AKD occurred in 5.3% of patients (11/207; 95% CI 2.7–9.3), with eight events between C1→C2, 3 between C2→C3, and 0 thereafter; recovery at the next cycle was 9.1% (1/11). Among them, 57.1% were classified as stage 1. A baseline eGFR < 90 mL/min/1.73 m2 was associated with a higher AKD incidence (13.3% vs. 5.4%). Body mass index (BMI) was significantly associated with AKD in univariate analysis (p = 0.02), whereas no independent predictor emerged in multivariate analysis. Use of renin–angiotensin–aldosterone system (RAAS) inhibitors was more frequent among patients who developed AKD (p = 0.04). Renal function declined more steeply in AKD patients, with a median eGFR slope of −0.3917 mL/min/1.73 m2/day vs. −0.0483 mL/min/1.73 m2/day in those without AKD (p = 0.0005), irrespective of CKD stage. Conclusions: In a real-world cohort receiving high-dose cisplatin with structured nephroprotection including IV magnesium, AKD developed in approximately 10% of patients. Lower baseline eGFR, elevated BMI, and RAAS inhibitor use emerged as potential risk factors. These findings reinforce the importance of proactive renal monitoring and suggest a role for magnesium supplementation as an accessible strategy to enhance renal safety in curative-intent CRT.

Background: Cisplatin (CDDP) concomitant to radiotherapy (RT) is one of the main treatments for locally advanced head and neck squamocellular carcinoma (LA HNSCC); nevertheless, elderly patients are underrepresented in trials and frequently receive less intensive and suboptimal treatments, which often are unimodal, even if it is well demonstrated how chemoradiotherapy (CRT) with CDDP is superior to RT alone. We aim to analyze clinical feasibility in terms of acute toxicity and treatment adherence in patients receiving concurrent high-dose CDDP and RT with curative or adjuvant intent, comparing elderly (≥65 years) with young (<65 years) patients. Methods: This is a monocentric, observational, prospective study of consecutive LA HNSCC patients treated with high dose CDDP concomitant to RT, from January 2017 to June 2024. The primary aim is to compare the performance of elderly patients with young patients in terms treatment adherence and toxicity, while the secondary aim is to assess treatment efficacy in terms of OS and PFS endpoints. The LA HNSCC patients were selected only by treatment, so all patients who did not receive chemoradiation were excluded. No difference in terms of compliance and toxicity events >G1 in the elderly versus young population is the null hypothesis. Data were analyzed using MedCal statistical software 14.12. A p < 0.05 was considered statistically significant. Results: A total of 170 patients were included in the study, according to the selection criteria stated. Only 7 elderly (12.3%) patients received a dose < 200 mg/m2, whereas 163 patients (87.7%) received ≥ 200 mg/m2 and all elderly patients completed RT, indicating a high level of adherence and effective management of treatment protocols, in front of a comparable incidence of acute toxicity to young patients (p-value: 0.84). OS and PFS were not statistically different between elderly and young patients (p = 0.20 and p = 0.72, respectively). Conclusions: Our findings suggest the feasibility of curative oncological treatment for elderly individuals with LA HNSCC, if they are well selected and adequately supported. Future studies should focus on validating and expanding these results to improve patient care and outcomes.

Objectives:This study aims to evaluate the effectiveness and reproducibility of the submental island flap (SIF) for reconstructing defects in the parotid region after oncological surgery. The primary goals are to assess the flap's impact on patient morbidity, its overall feasibility in complex head and neck reconstructions, and its potential for consistent outcomes across different cases. Methods:A retrospective multicentric study was conducted across 6 tertiary centres in Northern Italy, reviewing cases from 2015 to 2023. Inclusion criteria encompassed adult patients undergoing parotid region reconstruction using the SIF, specifically for defects arising from parotid or associated skin tumours. Data on patient demographics, comorbidities, tumour characteristics, surgical details, flap characteristics, complications, and long-term oncological outcomes were collected and analysed. Results:The study included 30 patients with a mean age of 75.4 years, most of whom had significant comorbidities. The flap success rate was 93.3%, with minimal donor site morbidity. The aesthetic outcomes were favourable, with the flap providing a good match of colour and texture. Oncological safety was affirmed, with no nodal transfers observed. Conclusions:The SIF is a reliable and aesthetically favourable option for parotid region reconstruction, particularly in elderly patients with multiple comorbidities. Its use minimises donor site morbidity and does not require microsurgical expertise. Careful patient selection is critical to avoid complications, particularly in those with a history of submental trauma, and to not risk metastatic lymph node transfer in advanced nodal disease. The SIF allows for effective reconstruction without compromising oncological outcomes, supporting its use as a standard approach in appropriate cases.

BACKGROUND:A wide percentage (25-40%) of patients affected by head and neck squamous cell carcinoma (HNSCC) are over 70 years old, and they present with different characteristics if compared to younger patients. Elderly patients often receive less intensive, non-surgical, and non-multimodal treatments. Although age does not mean frailty, the elderly are at a higher risk of developing toxicity. In fact, several studies enrolling patients treated with cisplatin + radiotherapy (CISPLATIN + RT) or cetuximab + radiotherapy (Cet + RT) showed reduced efficacy over 65 years. METHODS:We conducted a multicenter retrospective analysis in patients with Locally Advanced HNSCC aged over 65 years, who underwent Cet-RT, diagnosed in the period between 2017 and 2024. The primary endpoint was to describe Overall Survival (OS), the secondary endpoints were Progression Free Survival (PFS) and the percentage and type of Adverse Events (AEs). Patients received a geriatric assessment using the G8 questionnaire. RESULTS:Data regarding Eighty-Two (82) patients were analyzed, median age was 74 years (range 65-84), most patients had oral cavity (26.8%) and laryngeal cancer (37.8%). Fifty-six point one (56.1%) of patients were smokers, and 17.1% reported alcohol consumption. All patients completed radiotherapy, and 80.5% of them developed AEs, which in 25.6% of cases were G3-4 toxicities. No relationship was found between G3-4 AEs and age (p = 0.596), G8score < 14 (p = 0.804), and smoking (p = 0.245)/drinking habits (p = 0.341). Median OS was 58 months, with a slightly non-significant positive trend in OS for patients who were non-smokers and those who did not develop G3-4 AEs (p = 0.786 and 0.799, respectively). Association between folliculitis and OS was statistically significant (p = 0.001). CONCLUSIONS:In elderly patients, Cet-RT represents a feasible, well-tolerated option, although further prospective studies are needed.

ABSTRACTBackgroundSupraglottic squamous cell carcinoma (SCC) is a significant portion of head and neck cancers, with the management of clinically negative necks (cN0) through selective neck dissection (SND) being debated due to potential morbidities and low metastasis rates in levels IIb and IV.MethodsThis study is a retrospective, multicenter examination of the potential feasibility of limited neck dissection (LND), including only levels IIa and III in cN0 supraglottic SCC patients. It analyzed occult metastasis rates and explored relapse occurrences alongside potential predictors of lymph node metastasis.ResultsAmong 425 patients, predominantly male (85.6%) with a mean age of 63 years, the occult metastasis rate was 28.9%, and 13.7% experienced relapses during a mean follow‐up of 52 months. Advanced clinical stage, higher grading, and other risk factors emerged as predictors of occult lymph node metastasis at level IIb.ConclusionsThe study supports LND potential feasibility for cN0 supraglottic SCC, suggesting level IIb dissection can be omitted in specific early‐stage cases to reduce morbidity without affecting outcomes.

BACKGROUND:Reconstructive surgery with flaps plays a key role in the head and neck region, but the potential toxicity of adjuvant treatment on flap are uncertain. AIM:to identify possible predictors of acute toxicity and flap failure in patients affected by head and neck cancer (HNC) who underwent surgery with flap reconstruction and adjuvant radiotherapy. MATERIALS AND METHODS:We retrospectively analyzed clinical data of 46 patients affected by locally advanced HNC, who underwent surgery with major reconstruction, followed by adjuvant treatment (radiotherapy +/- chemotherapy), between December 2005 and December 2022. RESULTS:pN status and type of flap are the only two independent predictors of severe acute toxicity (p = 0,018 and p = 0,038 respectively) but none of the variables seems influencing per se the viability of the reconstructive flap at multivariate analysis. However, radiation-induced flap fibrosis occurred most commonly in the pedicled flap group. CONCLUSIONS AND SIGNIFICANCE:This study was able to confirm the favorable integration of reconstructive flaps in advanced HNC patients, highlighting the robustness and resilience of the reconstructive flap even after adjuvant treatments. It contributes to the existing literature by identifying pN status and flap type as significant predictors of toxicity in locally advanced HNC patients undergoing adjuvant treatment.

Recently, several devices exploiting the near-infrared autofluorescence (NIR-AF) of parathyroid glands (PGs) have been developed. Nevertheless, their impact on both preserving PGs from inadvertent surgical dissection and on post-surgical hypoparathyroidism (hypoPTH) is controversial. A retrospective study of 845 patients undergoing thyroid surgery in 2 academic tertiary centres was conducted. In 291 patients, a NIR-AF device was used during surgery to identify PGs. The characteristics of the cohort were examined. The number of PGs identified during surgery, missed PGs, auto-transplants, inadvertent parathyroidectomies, as well as the occurrence of transient and permanent hypoPTH, were analysed. The use of NIR-AF device resulted in a higher identification of PGs (92

Cisplatin is a nephrotoxic agent able to damage renal function both in acute and chronic phases. Radiotherapy concomitant with cisplatin 100 mg/m2 given once every 3 weeks is the curative standard of care for locally advanced head and neck cancer. A prospective evaluation of a wide range of biochemical and anthropometrical parameters, handgrip strength, risk of malnutrition, visual analogue scale of appetite, and body composition was performed before, during, and after concomitant chemoradiotherapy in 60 consecutive patients affected by locally advanced head and neck cancer. The treatment dramatically influenced every clinical and laboratory parameter, especially regarding nutritional status despite a high protein intake. In terms of medium eGFR decay, chemoradiotherapy reduced the renal function of about 8 ml/min/1.73m2 in 6 weeks, harboring some cases of mild acute kidney injury and acute kidney disease. Furthermore, patients with eGFR < 60 mL/min/1.73m2 pre-treatment were just 3 (5

Managing postoperative complications is crucial in reconstructive surgery. Indocyanine green fluorescence video-angiography (ICGA) aids in assessing flap vascularization intraoperatively, potentially reducing complications. An ambispective study enrolled head and neck cancer patients undergoing ablative surgery with soft tissue reconstruction. An experimental arm (March 2021-May 2023) used ICGA, while a control arm (January 2017-December 2020) did not. Complications were graded by Clavien-Dindo classification. We also evaluated the effect of systemic inflammation on the sensitivity of ICGA in detecting hypoperfused areas of the flap. Complications were less frequent in the experimental arm, both overall (11.4

Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. Methods: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. Results: Associations were found between systemic inflammation markers—NLR, MLR, and PLR—and tumor microenvironment factors, such as TILs and CD8+ cell prevalence—elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. Discussion: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response’s role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. Conclusions: Future integration into cancer classification could improve risk stratification and treatment guidance.

Sentinel lymph node biopsy (SLNB) is currently considered as a viable alternative to elective neck dissection (END) for the management of cN0 oral cavity squamous cell carcinoma (OCSCC). However, some difficulties were detected in sentinel lymph node (SLN) identification in floor of mouth (FOM) and ventral tongue tumors because of the so-called “shine-through radioactivity” of the injection site, which may mask nodal hotspots in proximity. We assessed the feasibility and the potential strengths of combining 99mTc-Tilmanocept with indocyanine green (ICG) fluorescence lympho-angiography in a dedicated multimodal protocol for SLNB in T1/T2N0 oral cancer to evaluate the synergistic role of each of these two tracers in providing the appropriate sensitivity and ease of learning, even in such a critical anatomical subsite. A detailed, stepwise description of our multimodal protocol is provided, together with the presentation of its application in two cases of early-stage ventral tongue tumors. Radioactive guidance with 99mTc-Tilmanocept was used preoperatively to perform planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography and to define the nodal hotspot(s) and the surgical “roadmap”. In addition, it was used intraoperatively to pinpoint the SLN location within each nodal hotspot with high specificity but limited spatial resolution. Optical guidance with ICG injection at the tumor bed and near-infrared fluorescence imaging was then added, providing intuitive intraoperative guidance within each nodal hotspot with high spatial resolution. Our small experience with this protocol is illustrated and future perspectives are highlighted.

Head and neck cancer (HNC) represents the sixth most common neoplasm worldwide, accounting for 800,000 new cases and 400,000 deaths globally every year. The locally advanced HNC (LAHNC) requires chemotherapy with high dose cisplatin, a nephrotoxic agent able to damage renal function both in acute and chronic asset. Moreover, this necessary aggressive oncological regimen increases the rate of malnutrition, catabolism and sarcopenia in the majority of patients, making the nutritional therapy an essential cornerstone of the multidisciplinary approach in the management of LA-HNC.