UNASSIGNED: Nodal involvement in squamous cell carcinoma is an important feature directly associated with the poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC). There are no clear cut indicators available currently to identify the lymph node metastases and overall prognosis in HNSCC. Thus, the current study was conducted to correlate the immunoexpression of cytokeratins (CK) 8, 10, and 14 with lymph node metastases and tumour differentiation in patients with HNSCC.
UNASSIGNED: The study population included 61 retrospective cases of HNSCC with lymph node metastases (n = 31) and without lymph node metastases (n = 30). Expression of CK 8, 10, and 14 was assessed by immunohistochemical staining procedure. Using Pearson\'s Chi-square test and Spearman\'s correlation coefficient, the correlation of these markers with lymph node metastases and tumour differentiation was statistically analysed.
UNASSIGNED: The expression of CKs in HNSCC cases was higher than in controls. In nodal metastasis cases, CK 8 expression was noted in >50% of the tumour cells at the invasive tumour front (ITF) (P value 0.008), and in cases without nodal metastasis, <1% or negative expression was noted. CK 10 expression gradually decreased as the tumour grade increased. Association of CK 10 expression and tumour differentiation exhibited statistically significant results (P value 0.03). CK 14 expression was noted in the entire epithelium and at the ITF, strongly in most cases; however, CK 14 did not correlate with the lymph node metastasis and tumour differentiation as well.
UNASSIGNED: We found a strong correlation of CK 8 expression with nodal metastasis in HNSCC, and it can be utilised as a reliable prognostic indicator.

BACKGROUND: Among oral diseases, oral cancer is the primary cause of death and poses a serious health risk. Primary tumor (T) - regional lymph node (N) - distant metastasis (M) comprising (TNM) staging is crucial for planning treatment strategies for patients with oral squamous cell carcinoma (OSCC).
OBJECTIVE: This study evaluated the predictive accuracy of clinical TNM staging of OSCC to histopathological staging (pTNM) in an institutional setting.
METHODS: Fifty-four consecutive histologically confirmed, surgically treated OSCC cases were evaluated for TNM staging. The study compared the clinical staging at the time of surgery with the pathological staging obtained from excisional biopsy reports. Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) was used for the data compilation and descriptive analysis. The chi-square test, analysis of variance (ANOVA), and Tukey\'s Honest Significant Difference (HSD) posthoc test were used to compare the data for statistical significance with p value <0.05 using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 23.0, Armonk, NY).
RESULTS: The alveolar mucosa (n=22, 40.74%) was the most frequently occurring site, followed by the tongue (n=17, 31.48%). Out of the 54 included cases, based on clinical tumor size, there were T1 (n=6), T2 (n=13), T3 (n=13), T4a (n=16) and T4b (n=6). T2 tumors were usually upstaged (n=7) while T4a (n=8) tumors were most often downstaged. T4a (n=8) had the best concordance between clinical and histopathological staging, followed by T2, T3, and T1. In nodal status, N1 showed the most variation. The chi-squared test showed statistical significance for tumor size comparison (p <0.001) and nodal status comparison (p=0.002). ANOVA test did not show any statistical significance. Tukey\'s HSD posthoc test showed statistical significance (p=0.034) for N0 and N1 status. The highest concordance was shown by N0 and N1 followed by N2b.
CONCLUSIONS: Preoperative radiological and clinical assessments are essential for deciding on a patient\'s course of treatment. However, not all patients may require radiographs to determine tumor size or nodal status assessment. Accurate diagnosis is vital for the treatment planning of OSCC.

OBJECTIVE: Adjuvant radiation therapy (ART) for cutaneous squamous cell carcinoma is recommended based on a number of wide-ranging clinicopathologic features, which encompass a broad array of patients. The 40-gene expression profile (GEP) test classifies cutaneous squamous cell carcinoma tumors into low (class 1), higher (class 2A), or highest (class 2B) risk of nodal and/or distant metastasis. This study\'s hypotheses are as follows: (1) local recurrence is associated with metastatic disease progression and (2) 40-GEP, by identifying high risk for metastasis, could predict a metastasis-specific benefit from ART.
METHODS: Samples were obtained from 920 patients (ART-untreated: 496 class 1, 335 class 2A, and 33 class 2B; ART-treated: 11 class 1, 35 class 2A, and 10 class 2B) who were matched on clinical risk factors and stratified by ART status to create 49 matched patient strata. To control for the variety of characteristics and treatment selection bias, randomly sampled pairs of matched ART and non-ART patients comprising 10,000 resampled cohorts were each analyzed for 5-year metastasis-free survival and predicted time to metastatic event.
RESULTS: Of 96 patients experiencing local recurrence, 56.3% experienced metastasis; of those experiencing both, 88.9% experienced local recurrence before (75.9%) or concurrently (13.0%) with metastasis. After matching for clinicopathologic risk, median 5-year disease progression rates for resampled cohorts demonstrated approximately 50% improvement for class 2B ART-treated compared with ART-untreated cohorts. ART-treated class 2B cohorts had a 5-fold delay in predicted time to metastatic event and deceleration of disease progression compared with ART-untreated cohorts (Kolmogorov-Smirnov test, P < .01); this was not observed for patients with class 1 or 2A cSCC (P > .05 for each). No risk factor or staging system combined with ART status identified groups that would benefit from ART as well as 40-GEP.
CONCLUSIONS: Forty-GEP identifies patients at the highest risk of nodal/distant metastasis who may derive the greatest benefit from ART, as well as patients who may have clinical indications for ART but are at low risk of metastasis. Compared with current guidelines, 40-GEP could provide greater specificity concerning the benefit of ART in individual patients.

BACKGROUND: To date, although most thyroid carcinoma (THCA) achieves an excellent prognosis, some patients experience a rapid progression episode, even with differentiated THCA. Nodal metastasis is an unfavorable predictor. Exploring the underlying mechanism may bring a deep insight into THCA.
METHODS: A total of 108 THCA from Chinese patients with next-generation sequencing (NGS) were recruited. It was used to explore the gene alteration spectrum of THCA and identify gene alterations related to nodal metastasis in papillary thyroid carcinoma (PTC). The Cancer Genome Atlas THCA cohort was further studied to elucidate the relationship between specific gene alterations and tumor microenvironment. A pathway enrichment analysis was used to explore the underlying mechanism.
RESULTS: Gene alteration was frequent in THCA. BRAF, RET, POLE, ATM, and BRCA1 were the five most common altered genes. RET variation was positively related to nodal metastasis in PTC. RET variation is associated with immune cell infiltration levels, including CD8 naïve, CD4 T and CD8 T cells, etc. Moreover, Step 3 and Step 4 of the cancer immunity cycle (CIC) were activated, whereas Step 6 was suppressed in PTC with RET variation. A pathway enrichment analysis showed that RET variation was associated with several immune-related pathways.
CONCLUSIONS: RET variation is positively related to nodal metastasis in Chinese PTC, and anti-tumor immune response may play a role in nodal metastasis triggered by RET variation.

(1) Background: Minimally invasive surgery (MIS) represents a feasible approach in early-stage ovarian cancer, while this question is still unsolved for advanced and recurrent disease. (2) Methods: In this retrospective, multicenter study, we present a series of 21 patients who underwent MIS for primitive or recurrent epithelial ovarian cancer (EOC) with bulky nodal metastasis and discuss surgical technique and outcomes in relation to the current literature. (3) Results: Complete cytoreduction at primary debulking surgery was obtained in 86% of cases. No complication occurred in our patients intraoperatively and only 11.1% of our patients experienced grade 2 and 3 postoperative complications. Notably, all the patients with isolated lymph nodal recurrence (ILNR) were successfully treated with a minimally invasive approach with no intra- or postoperative complications. (4) Conclusions: The results of our study are consistent with those reported in the literature, demonstrating that MIS may represent a safe approach in advanced and recurrent EOC with nodal metastasis if performed on selected patients by expert surgeons with an adequate setting and appropriate technique.

BACKGROUND: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer.
METHODS: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry.
RESULTS: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor-infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively).
CONCLUSIONS: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

Congenial neutropenia is a rare genetic disorder that puts individuals at risk of life-threatening bacterial infections early in life, and the current standard of care includes the use of colony-stimulating factors or curative intent bone marrow transplant. Cancer treatment strategies that include surgery, chemotherapy, radiation, and immunotherapy present significant challenges to an individual with a baseline immunodeficiency as seen in this condition. Evidence-based national guidelines aid physicians and patients in moving through complex cancer care regimens. However, these are altered when the intensity of the patient\'s comorbidities puts them at increased risk of developing a potentially life-threatening infection. Here, we present a patient treated for rectal carcinoma in the setting of severe congenital neutropenia.

UNASSIGNED: Although large retrospective database studies have associated extranodal extension (ENE) with worse survival in several head and neck cancers, the prognostic significance of ENE in laryngeal squamous cell carcinoma (LSCC) remains unclear. Our study examines ENE and overall survival (OS) in LSCC.
UNASSIGNED: The 2006-2017 National Cancer Database was queried for patients with LSCC undergoing surgical resection and neck dissection, with or without adjuvant therapy. Kaplan-Meier and multivariable Cox regression survival analyses were implemented to identify the independent impacts of pathologic nodal (pN) classification and ENE on OS.
UNASSIGNED: Of 4208 patients satisfying inclusion criteria, 2343 (55.7%) were pN0/ENE-negative, 1059 (25.2%) were pN1-2/ENE-negative, and 806 (19.2%) were pN1-2/ENE-positive. The 5-year OS of pN0/ENE-negative, pN1-2/ENE-negative, and pN1-2/ENE-positive patients was 62.8%, 56.7%, and 32.9%, respectively (p < .001). Among pN1-2/ENE-positive patients undergoing no adjuvant therapy, adjuvant radiotherapy alone, and adjuvant chemoradiotherapy, 5-year OS was 24.1%, 30.7%, and 36.7%, respectively (p < .001). After adjusting for patient demographics, clinicopathologic features, and adjuvant therapy, ENE-positivity was associated with worse OS than ENE-negativity (adjusted hazard ratio [aHR] 1.76, 95% confidence interval [CI] 1.53-2.02, p < .001). pN1/ENE-positivity (aHR 1.82, 95% CI 1.31-2.54) and pN2/ENE-positivity (aHR 1.89, 95% CI 1.49-2.40) were associated with worse OS than pN1/ENE-negativity (p < .001). Microscopic (aHR 1.83, 95% CI 1.54-2.18) and macroscopic ENE-positivity (aHR 1.75, 95% 1.35-2.26) were associated with worse OS than ENE-negativity (p < .001).
UNASSIGNED: ENE-positivity has prognostic significance in LSCC and is associated with worse OS than ENE-negativity. pN classification did not have prognostic significance independent of ENE. ENE should be carefully considered when determining the prognosis of LSCC and selecting adjuvant therapy.
UNASSIGNED: 4.

OBJECTIVE: The prognostic value of depth of invasion (DOI) in oral squamous cell cancer carcinoma and cutaneous melanoma is well established, while there is a lack of reports investigating the role of DOI in laryngeal cancer. This study aims to explore the association of glottic cancer DOI with other established pathological risk factors and nodal metastasis and evaluate the feasibility of measuring DOI preoperatively using tomographic imaging.
METHODS: The medical records of glottic cancer patients treated between 2015 and 2020 in a single tertiary referral center were screened retrospectively. Pathologically measured DOI (pDOI) value was also reviewed and registered. Preoperative computer tomography (CT) was used to obtain the radiological DOI (rDOI) measured by two dedicated radiologists. Their inter-rated agreement was assessed and the correlation between pDOI and rDOI was calculated. pDOI association with the main pathology report features was assessed with univariable analysis. Cox univariable and multivariable models were used to explore the role of pDOI on survival.
RESULTS: Ninety-one patients had pDOI data available, of which 59 also had rDOI data. A strong concordance between the two radiologists was found (concordance correlation coefficient = 0.96); rDOI and pDOI were highly and significantly correlated (R = 0.85; p < 0.001). pDOI was significantly higher in patients with perineural invasion (PNI; p < 0.001), lymphovascular invasion (LVI; p < 0.001), and nodal metastasis (p < 0.001). pDOI was associated with disease-free survival at univariable analysis (p = 0.04) while it did not show a significant impact (p = 0.10) at multivariable analysis.
CONCLUSIONS: Glottic carcinoma DOI correlates with PNI, LVI, and nodal metastasis and it can be reliably assessed in a preoperative setting using CT imaging.
METHODS: 3 Laryngoscope, 134:3230-3237, 2024.

Oral squamous cell carcinoma (OSCC) has the highest mortality rate of any type of head and neck squamous cell carcinoma. For many eons, the clinical TNM (tumor size, nodal metastasis, and distant metastasis) classification and histological grading of malignancies have been used to predict clinical behavior, confusing it with prognosis and overall survival. This review aimed to systematically identify and evaluate the prognostic value of Broder\'s and Bryne\'s grading system for OSCC. Electronic resources such as PubMed, Cochrane Database of Systematic Reviews, Google Scholar, Scopus, and direct web searches were used to conduct a thorough search. The titles were examined to identify relevant papers, which were then reviewed for inclusion by reading the abstract. To incorporate studies published outside of the electronic database, the bibliography of all recognized papers was scanned. This review examined all research that investigated the prognostic value of Broder\'s and Bryne\'s grading systems in OSCC. The electronic database search identified 221 articles. After reading full articles, based on the titles and abstracts and after removing duplicates, six articles were screened. Finally, six articles were selected based on their ability to meet the inclusion criteria and answer the research question. All studies analyzed the competence of this histological grading system in predicting the prognosis of OSCC patients. Four studies evaluated lymph node metastasis and two studies analyzed the histological grading of OSCC. While evaluating the histological grade, we recommend the application of Bryne\'s (1992) system for grading OSCC. The standardization of a single, effective method would make it easier to compare results from various studies. This grading system yields better interobserver agreement and bears a prognostic value which may help in devising a treatment strategy for better patient outcomes.