Blood Markers Predicting Clinically Occult Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.

INTRODUCTION: The presence of cervical lymph node metastases is an unfavorable prognostic factor in head and neck squamous cell carcinoma (HNSCC) and a potential cause of treatment failure. Occult lymph node metastasis occurs in approximately 15-20% of HNSCC patients with a clinically negative neck (cN0), greatly impacting on their prognosis. The present study aimed to investigate the role of pre-treatment peripheral blood markers in predicting clinically occult cervical lymph node metastasis. METHODS: This multicenter, retrospective study was performed in a cohort of 472 patients diagnosed with cN0 HNSCC who underwent up-front surgery. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated from available blood parameters. RESULTS: Oro-hypopharyngeal and oral cancers, locally advanced stage, moderately (G2), and poorly (G3) differentiated grade were associated with an increased risk of pathological lymph node involvement. NLR, LMR, PLR, SIM, and SII were significantly associated at multivariable analysis. NLR >2.12 was the most reliable at predicting occult lymph node metastasis (OR = 5.22; 95% CI: 2.14-12.75). We describe a predictive score integrating cancer site, local stage, and NLR which is effective at predicting positive lymph node pathological status. CONCLUSIONS: The present study provides evidence that pre-treatment peripheral blood markers, in particular NLR, represent reliable predictors of clinically occult cervical lymph node metastasis in cN0 HNSCC. Therefore, the present study provides a novel useful predictive score for directing the elective management of the neck in patients with cN0 HNSCC.

Different inflammatory blood markers correlate with specific outcomes in incident HPV-negative head and neck squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. METHODS: This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. RESULTS: The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients' survival was found for SIM (10-year OS = 53.2% for SIM < 1.40 and 40.9% for SIM ≥ 2.46; c-index = 0.569) and LMR (10-year OS = 60.4% for LMR ≥ 3.76 and 40.5% for LMR < 2.92; c-index = 0.568). While LMR showed the strongest association with local failure (HR = 2.16; 95% CI:1.22-3.84), PLR showed the strongest association with regional (HR = 1.98; 95% CI:1.24-3.15) and distant failure (HR = 1.67; 95% CI:1.08-2.58). CONCLUSION: Different inflammatory blood markers may be useful to identify patients at risk of local, regional, or distant recurrences who may benefit from treatment intensification or intensive surveillance programs.

Civilian penetrating neck trauma at a level I trauma centre: A five-year retrospective case note review.

OBJECTIVES: To report the experience of civilian penetrating neck trauma (PNT) at a UK level I trauma centre, propose an initial management algorithm and assess the degree of correlation between clinical signs of injury, operative findings and radiological reports. DESIGN: Retrospective case note review. SETTING: UK level I trauma centre April 2012-November 2017. PARTICIPANTS: Three hundred ten cases of PNT were drawn from electronic patient records. Data were extracted on hard and soft signs of vascular or aerodigestive tract injury, clinical management, radiological imaging and patient outcomes. MAIN OUTCOME MEASURES: Patient demographics, mechanism of injury, morbidity and mortality. The correlation between clinical signs, and radiological reports to internal injury on surgical exploration. RESULTS: Two hundred seventy-one (87.4%) male and 39 (13.6%) female patients with a mean age of 36 years (16-87) were identified. The most common causes of injury were assault 171 (55.2%) and deliberate self-harm 118 (38%). A knife was the most common instrument 240 (77.4%). Past psychiatric history was noted in 119 (38.4%), and 60 (19.4%) were intoxicated. 50% were definitively managed in theatre with a negative exploration rate of 38%, and 50% were managed in ED. Pre-operative radiological reports correlated with operative reports in 62% of cases with venous injury the most common positive and negative finding. Multivariate correlation was r = 0.89, p = 0.045, between hard signs plus positive radiology findings and internal injury on neck exploration. CONCLUSIONS: Management of PNT by clinical and radiological signs is safe and effective, and can be streamlined by a decision-making algorithm as proposed here.

Diagnostic RET genetic testing in 1,058 index patients: A UK centre perspective.

OBJECTIVE: Diagnostic germline RET analysis is offered to all patients with a diagnosis of medullary thyroid carcinoma (MTC), or other conditions associated with multiple endocrine neoplasia type 2 (MEN2) in the United Kingdom. Here, we report the experience of a single centre's germline RET analysis over a 21-year period. DESIGN: Retrospective case-note review. PATIENTS: All index patients referred to the Exeter Genomics Laboratory for diagnostic germline RET analysis between 1997 and 2018, and unaffected family members, undergoing predictive testing. MEASUREMENTS: The rate and nature of pathogenic variant detection were recorded, as well as the indication for testing. RESULTS: 1,058 index patients and 551 unaffected family members were tested. The overall rate of pathogenic variant detection was 10.2% amongst index patients and 29% amongst unaffected family members. The commonest indication was isolated MTC, and amongst the 690 patients with isolated MTC, 68 (9.9%) were found to harbour a RET pathogenic variant. Of those with presumed sporadic MTC, 8.5% were found to harbour germline RET pathogenic variants, compared with 36.4% of those with a family history of MEN2-associated conditions. Pathogenic variants were identified in 3.6% and 0% of patients with isolated phaeochromocytoma and primary hyperparathyroidism, respectively. CONCLUSIONS: Although the detection rate of RET germline pathogenic variants in patients with presumed sporadic MTC was significant, the overall detection rate in those with MTC was lower than expected in this series. Advances in RET analysis in response to reports of new variants over the last two decades are likely to have improved the pick-up rate in recent years.

The risk of recurrence in surgically treated head and neck squamous cell carcinomas: a conditional probability approach.

BACKGROUND: Over 50% of patients with head-and-neck squamous cell carcinoma (HNSCC) experience locoregional recurrence, which is associated with poor outcome. In the course of follow-up for patients surviving primary surgery for HNSCC, one might ask: What is the probability of recurrence in one year considering that the cancer has not yet recurred to date? MATERIALS AND METHODS: To answer this question, 979 patients surgically treated for HNSCC (i.e. cancer of the oral cavity, oropharynx, hypopharynx or larynx) between March 2004 and June 2018 were enrolled in a multicenter retrospective cohort study, followed up for death and recurrence over a 5 year period. The conditional probability of recurrence in 12 months - i.e. the probability of recurrence in the next 12 months given that, to date, the patient has not recurred - was derived from the cumulative incidence function (Aalen-Johansen method). RESULTS: Overall, the probability of recurrence was the highest during the first (17.3%) and the second years (9.6%) after surgery, declining thereafter to less than 5.0% a year thereafter. The probability of recurrence was significantly higher for stage III-IV HNSCCs than for stage I-II HNSCCs in the first year after surgery (20.4% versus 10.0%; p < 0.01), but not thereafter. This difference was most pronounced for oral cavity cancers. No significant differences were observed across different tumor sites. CONCLUSION: This dynamic evaluation of recurrence risk in patients surgically treated for HNSCC provides helpful and clinically meaningful information, which can be useful to patients in planning their future life, and to clinicians in tailoring post-treatment surveillance according to a more personalized risk stratification.

Beta human papillomaviruses infection and skin carcinogenesis.

During the last decade, the worldwide incidence of keratinocyte carcinomas (KC) has increased significantly. They are now the most common malignancy, representing approximately 30% of all cancers. The role of ultraviolet (UV) radiation as a major environmental risk factor for skin cancers is well recognized. The aim of this review is to analyse the current understanding of the nature of beta-human papillomavirus (HPV) and its association with KC and explore the implications for the management and prevention of these cancers. A comprehensive review of the literature on beta-HPV and its association with KC was undertaken, the results reported in the form of a narrative review. A subgroup of HPV that infects the mucosal epithelia of the genital tract has been firmly associated with carcinogenesis. In addition, some HPV types with cutaneous tropism have been proposed to cooperate with UV in the development of KC. The first evidence for this association was reported in 1922 in patients with epidermodysplasia verruciformis (EV). Since then, epidemiological studies have highlighted the higher risk of skin cancer in patients with EV and certain cutaneous HPV types, and in vitro studies have elucidated molecular mechanisms and transforming properties of beta-HPV. Furthermore, in vivo research conducted on transgenic mice models has shown the possible role of beta-HPV in cutaneous carcinogenesis as a co-factor with UV radiation and immunosuppression. There is good evidence supporting the role of beta-HPV in the oncogenesis of KC. The high prevalence of beta-HPV in human skin and the worldwide burden of KC makes the search for an effective vaccine relevant and worthwhile.

Elective neck dissection in primary parotid carcinomas: A systematic review and meta-analysis.

BACKGROUND: To estimate the rate of occult cervical lymph node metastases in cN0 patients affected by primary parotid carcinomas and to scrutinize the evidence on the indication and extent of elective neck dissection in these neoplasms. METHODS: Medline, Embase, Web of Science, Cochrane Library and Scopus were searched until August 31, 2020, to identify studies reporting the use of elective neck dissection in the management of malignant parotid tumours. The PRISMA checklist was used. A single arm meta-analysis was then made to determine the pooled rate of occult lymph node metastases. Risk of bias of the included studies was assessed through the ROBINS-E tool. RESULTS: The initial search returned 20 541 articles, of which twelve met the inclusion criteria and were included in the meta-analysis. They comprised 1310 patients with parotid carcinoma, of whom 542 cN0 underwent elective neck dissection, which led to the diagnosis of lymph node metastasis (pN+/cN0) in 113 cases. Meta-analysis of the results of elective neck dissection showed an overall rate of occult metastases of 0.22 (99% CI: 0.14-0.30). Locally advanced or high-grade tumours were the commonest indications for elective neck dissection in the included studies. The most dissected lymph node levels were I-II-III, and level II was the commonest site of occult nodal metastases. CONCLUSIONS: An occult metastasis rate of 0.22 (99% CI: 0.14-0.30) represents a not negligible percentage value, which should encourage further research to outline the most appropriate elective neck management in cN0 patients with parotid carcinomas.

Advanced lung cancer inflammation index and its prognostic value in HPV-negative head and neck squamous cell carcinoma: a multicentre study.

PURPOSE: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. METHODS: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). RESULTS: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51-6.90 for PFS and HR 3.41, CI 1.47-7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31-4.51 for PFS and HR = 2.40, 95% CI: 1.19-4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone. CONCLUSIONS: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.

The role of molecular genetics in the clinical management of sporadic medullary thyroid carcinoma: A systematic review.

BACKGROUND: The significant variation in the clinical behaviour of sporadic medullary thyroid carcinoma (sMTC) causes uncertainty when planning the management of these patients. Several tumour genetic and epigenetic markers have been described, but their clinical usefulness remains unclear. The aim of this review was to evaluate the evidence for the use of molecular genetic and epigenetic profiles in the risk stratification and management of sMTC. METHODS: MEDLINE and Embase databases were searched using the MeSH terms "medullary carcinoma", "epigenetics", "molecular genetics", "microRNAs"; and free text terms "medullary carcinoma", "sporadic medullary thyroid cancer", "sMTC", "RET", "RAS" and "miR". Articles containing less than ten subjects, not focussing on sMTC, or not reporting clinical outcomes were excluded. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale. RESULTS: Twenty-three studies met the inclusion criteria, and key findings were summarized in themes according to the genetic and epigenetic markers studied. There is good evidence that somatic RET mutations predict higher rates of lymph node metastasis and persistent disease, and worse survival. There are also several good quality studies demonstrating associations between certain epigenetic markers such as tumour miR-183 and miR-375 expression and higher rates of lymph node and distant metastasis, and worse survival. CONCLUSIONS: There is a growing body of evidence that tumour genetic and epigenetic profiles can be used to risk stratify patients with sMTC. Further research should focus on the clinical applicability of these findings by investigating the possibility of tailoring management to an individual's tumour mutation profile.

Penetrating neck trauma: radiological predictors of vascular injury.

PURPOSE: Vascular injury in penetrating neck trauma predicts a poorer outcome and usually requires surgical neck exploration. Multi-detector computed tomography (MDCT) angiography is a readily available non-invasive diagnostic tool that can identify direct and indirect signs of vascular injury in stable patients. This study aims to investigate the diagnostic accuracy of radiological signs of vascular injury on MDCT, and their implications on patient management in the setting of penetrating neck trauma. METHODS: A retrospective cohort study of penetrating neck injuries (PNI) between 2012 and 2018 in a UK major trauma centre was performed. Clinical data and operative findings were compared with radiological findings on MDCT performed at the time of admission. RESULTS: 157 patients were identified with PNI in the study period, with 67 meeting inclusion criteria. The predictive value of indirect radiological signs of vascular injury alone was low, with only 12.1% of these patients having significant vascular injury found at neck exploration. However, the combined use of direct radiological signs with clinical signs resulted in a specificity of 97.7% for vascular injury. CONCLUSIONS: The use of direct and indirect radiological signs of vascular injury can increase the accuracy of diagnosis when used in conjunction with clinical signs. Combining clinical assessment and radiological investigation, specifically contrast-enhanced MDCT, improves the specificity in pre-operative assessment of potential vascular injury in PNI. MDCT is recommended in stable patients with clinical signs of vascular injury to reduce the rate of negative neck exploration.

Vaginoplasty: a modern approach: a report of 2 cases.

BACKGROUND: Split-thickness skin graft vaginoplasty is one of many methods for vaginal reconstruction. In its 130-year history it has been modified by numerous authors in attempts to improve graft viability and neovaginal function. We describe a modern approach that aims to improve outcomes and reduce complications. CASES: Two cases of split-thickness skin graft vaginoplasty are presented in which the traditional Abbé-McIndoe technique was supplemented by the combined use of vacuum-assisted closure and fibrin tissue sealant. In both cases 100% graft survival and normal neovaginal function were observed, with no recipient site complications. Both patients mobilized on postoperative day 3, and both were sexually active 4 months postoperatively. CONCLUSION: This approach has not been described previously in the literature. The impressive results seen in these cases suggest that the use of vacuum-assisted closure and fibrin tissue sealant in combination may improve graft survival and resulting neovaginal function.

Management of Parastomal Recurrence Following Total Laryngectomy.

Parastomal recurrence occurs in around 5% of patients undergoing total laryngectomy for laryngeal squamous cell carcinoma. It carries a poor prognosis which has changed little over the last 50 years, and poses a significant challenge to the head and neck surgeon. At present, surgical excision offers the only realistic chance of cure, although patients must be selected carefully following thorough work-up and in-depth multidisciplinary team discussion. This article provides a review of the literature on the management of parastomal recurrence following total laryngectomy.

Sporadic medullary thyroid cancer: a systematic review and meta-analysis of clinico-pathological and mutational characteristics predicting recurrence.

INTRODUCTION: Sporadic medullary thyroid cancer accounts for 75% of all medullary thyroid cancers and presents at a more advanced disease stage than its hereditary counterparts. Yet there is little evidence to support risk stratification of patients according to risk of recurrence. METHODS: A systematic review and meta-analysis was performed investigating clinical and pathological factors that are associated with recurrent disease in patients with medullary thyroid cancer. RESULTS: 10 studies totalling 458 patients were included in the meta-analyses. T3 and T4 disease (OR 9.33 (95% CI 2.5 - 34.82) p = 0.0009.), AJCC stage III and IV disease (OR 13.34 (95% CI 2.9 - 60.3) p = 0.0008) and the presence of nodal disease (OR 7.28 (95% CI 7.2-43.3) p = 0.03) were all associated with recurrent disease. RET mutations (OR 0.08 (95% CI -0.03-0.19) p = 0.17) and RET 918 T mutations (OR 1.77 (95% CI 0.804.0) P = 0.17) were not associated with disease recurrence. It was not possible to pool data with respect to extrathyroidal extension, extracapsular extension, peri-neural and lymphovascular invasion and RAS mutations. CONCLUSION: T3 and T4 disease, AJCC stage III and IV disease and the presence of nodal disease are associated with recurrent disease. The heterogeneous reporting of recurrence and the lack of individual patient data precludes larger scale meta-analyses. Future research in this area should involve collaboration to establish standardised definitions of disease recurrence.

Prevalence and prognostic impact of retropharyngeal lymph nodes metastases in oropharyngeal squamous cell carcinoma: Meta-analysis of published literature.

BACKGROUND: This systematic review and meta-analysis aims to estimate the prevalence and prognostic impact of retropharyngeal lymph node metastases (RLNMs) in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: This meta-analysis was conducted according to PRISMA guidelines. INCLUSION CRITERIA: studies with more than 20 patients reporting the prevalence or prognostic impact of RLNMs in OPSCC. Whenever available, data on HPV status and subsites were extracted. RESULTS: Twenty-two articles were included. The overall prevalence of RLNMs in OPSCC was 13%, with no significant differences depending on HPV status. The highest prevalence was observed for posterior pharyngeal wall SCC (24%), followed by soft palate (17%), palatine tonsil (15%), and base of tongue (8%). RLNMs were associated with a significantly higher risk of death (HR:2.54;IC95%1.89-3.41) and progression (HR:2.44;IC95%1.80-3.30). CONCLUSIONS: The prevalence of RLNMs in OPSCC was 13%, being higher in tumors of the posterior pharyngeal wall. RLNMs were associated with unfavorable outcomes.

Pretreatment High MCV as Adverse Prognostic Marker in Nonanemic Patients with Head and Neck Cancer.

OBJECTIVE: Mean corpuscular volume (MCV) has been shown in to be a reliable prognostic marker in other cancers; however, no evidence exists on its use in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the association between MCV, hemoglobin, platelet count and albumin concentration, and survival in stage III/IVA-B HNSCC treated with concurrent chemoradiotherapy. STUDY DESIGN: Retrospective cohort study. METHODS: In this multicenter retrospective study, we analyzed MCV, platelet count, hemoglobin concentration, and albumin concentration in peripheral blood samples from 260 patients with HNSCC undergoing organ preservation treatment with curative intent at the time of diagnosis. We then analyzed survival outcomes after accounting for confounders using multivariate analysis. RESULTS: After adjustment for potential confounders, patients with low hemoglobin had a 3.3-fold higher risk of death (95% confidence interval [CI]: 2.26-4.81) than those with normal hemoglobin. Patients with an elevated MCV had a 1.54-fold higher risk of death (95% CI: 1.06-2.24), independent of site, stage, and human papillomavirus status. Interestingly, the effect of MCV on overall and progression-free survival was limited to those with a normal pretreatment hemoglobin. We identified no associations between pretreatment platelet count or albumin concentration and survival. CONCLUSION: These findings suggest that pretreatment anemia and macrocytosis are independent predictors of lower overall and progression-free survival in HNSCC patients undergoing organ preservation treatment. LEVEL OF EVIDENCE: III Laryngoscope, 131:E836-E843, 2021.

Prognostic indicators in clinically node-negative malignant primary salivary tumours of the parotid: A multicentre experience.

OBJECTIVES: Nodal metastasis is an important prognosticator in primary parotid cancers. The management of the clinically node-negative neck is an area lacking consensus. This study investigates the occult nodal metastasis rate, and prognostic indicators in primary parotid cancers. MATERIALS AND METHODS: We performed a multicentre retrospective case note review of patients diagnosed and treated surgically with curative intent between 1997 and 2020. Demographic, clinic-pathological and follow-up data was recorded. RESULTS: After exclusions, 334 patients were included for analysis, with a median follow-up of 48 months. The overall rate of occult lymph node metastasis amongst patients undergoing elective neck dissection was 22.4%, with older age, high-grade and more advanced primary tumours being associated with higher rates. On multivariable analysis, age ≥ 60 years (HR = 2.69, p = 0.004), high-grade tumours (HR = 2.70, p = 0.005) and advanced primary tumours (pT3-4, HR = 2.06, p = 0.038) were associated with worse overall survival. Occult nodal metastasis on final pathology was associated with a close-to-significant reduction in regional recurrence free survival (HR = 3.18, p = 0.076). CONCLUSION: This large series confirms the significant occult lymph node metastasis rate in primary parotid cancer, and demonstrates the importance of primary histology, tumour grade and stage in predicting survival outcome. This data supports the use of elective neck dissection in patients with high-risk tumours.

TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma.

OBJECTIVE: To date, no useful prognostic biomarker exists for patients with oral squamous cell carcinoma (OCSCC), a tumour with uncertain biological behaviour and subsequent unpredictable clinical course. We aim to investigate the prognostic significance of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of telomerase reverse transcriptase (TERT) gene and the impact of TERT single nucleotide polymorphism (SNP) rs2853669 in patients surgically treated for OCSCC. METHODS: The genetic frequencies of rs2853669, -124 C>T and -146 C>T as well as the telomere length were investigated in 144 tumours and 57 normal adjacent mucosal (AM) specimens from OCSCC patients. RESULTS: Forty-five tumours harboured TERT promoter mutations (31.3%), with -124 C>T and -146 C>T accounting for 64.4% and 35.6% of the alterations respectively. Patients with -124 C>T TERT promoter mutated tumours had the shortest telomeres in the AM (p=0.016) and showed higher risk of local recurrence (hazard ratio [HR]:2.75, p=0.0143), death (HR:2.71, p=0.0079) and disease progression (HR:2.71, p=0.0024) with the effect being potentiated by the co-occurrence of T/T genotype of rs2853669. CONCLUSION: -124 C>T TERT promoter mutation as well as the T/T genotype of the rs2853669 SNP are attractive independent prognostic biomarkers in patients surgically treated for OCSCC, with the coexistence of these genetic variants showing a synergistic impact on the aggressiveness of the disease.

Prognostic value of H-index in patients surgically treated for squamous cell carcinoma of the larynx.

OBJECTIVE: Recently, a novel host-related index, the Host-index (H-index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host-related indexes This study aimed to investigate the prognostic performance of the H-index using pretreatment blood tests in patients receiving up-front surgery for SCC of the larynx. METHODS: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H-index. Their association with disease-free survival (DFS) and overall survival (OS) was measured. RESULTS: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37-96] years; 191 [82.7%] men). The median follow-up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04-1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07-2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21-3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24-4.40) and OS (aHR for death = 2.67; 95% CI: 1.51-4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H-index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65-4.79) and death (2.22; 95% CI: 1.26-3.89). CONCLUSION: In conclusion, the present study confirms the prognostic value of pretreatment H-index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. LEVEL OF EVIDENCE: III.

The impact of nodal status in major salivary gland carcinoma: A multicenter experience and proposal of a novel N-classification.

OBJECTIVES: Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma. MATERIALS AND METHODS: A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-R2. RESULTS: Intra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1-3 vs ≥ 4) and/or their maximum diameter (<20 mm vs ≥ 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-R2 indices when compared to current N-classification. CONCLUSION: All the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed.

Controversies in the surgical management of sporadic medullary thyroid carcinoma.

PURPOSE OF REVIEW: Medullary thyroid carcinoma (MTC) represents a wide spectrum of tumours with differing biology, behaviour and natural history. The only current available curative treatment is surgery in the form of thyroidectomy with or without ipsilateral or bilateral neck dissection. There is a lack of consensus in the available published guidelines on the optimum extent of initial surgery, and there is significant variation in clinical practice. This review focuses on the most recently published evidence. RECENT FINDINGS: Many patients with limited disease do not receive total thyroidectomy and central neck compartment dissection as recommended by international guidelines. Despite this, 5-year disease-specific survival is over 90% in those without distant metastases at presentation. Over 20% of patients may harbour occult lateral compartment nodal metastases, and baseline calcitonin alone (>1000 pg/ml) is not a good predictor of nodal metastasis. Although delayed lateral neck compartment dissection results in similar survival outcomes to prophylactic neck dissection for clinically node-negative patients, there is an underappreciated psychological effect of having biochemical evidence of persistent disease following limited surgery. SUMMARY: No single currently available prognostic indicator is sufficient to predict disease behaviour and evidence of occult nodal metastases. In clinically ad radiologically node-negative patients, the extent of neck dissection at initial operation, therefore, needs to be planned and executed on an individual patient basis.