Neck Metastasis Research Articles

Lateral lymph node metastasis in papillary thyroid cancer: Is there a difference between PTC and PTMC?

Papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) are generally characterized as less invasive forms of thyroid cancer with favorable prognosis. However, once lateral cervical lymph node metastasis takes place, the prognosis may be significantly impacted. The purpose of this study was to evaluate whether there is a difference in the pattern of lateral lymph node metastasis between PTC and PTMC. A retrospective analysis was performed for PTC and PTMC patients that underwent central area dissection and unilateral lateral neck lymph node dissection (II-V area) between January 2020 and December 2021. Compared with PTMC group, the PTC group exhibited higher incidence of capsule invasion, extrathyroid invasion and lymphatic vessel invasion. Both the number and rate of central lymph nodes metastasis were elevated in the PTC group. While the number of lateral cervical lymph node metastasis was higher, the metastasis rate did not demonstrate significant difference. No significant differences were identified in the lymph node metastasis patterns between the 2 groups. The determination of the extent of lateral neck lymph node dissection solely based on the tumor size may be unreliable, as PTC and PTMC showed no difference in the number and pattern of lateral neck metastasis. Additional clinical data are warranted to reinforce this conclusion. For patients categorized as unilateral, bilateral, or contralateral cervical lymph node metastasis (including level I, II, III, IV, or V) or retropharyngeal lymph node metastasis who require unilateral lateral neck dissection, the size of the primary tumor may not need to be a central consideration when assessing and deciding the extent of lateral neck dissection.

Occult neck metastasis in salvage laryngectomy: a road map for super-selective neck dissection.

This study aimed to solve the debate over the role and extent of neck dissection to treat any occult nodal metastasis in patients undergoing salvage laryngectomy for recurrent and/or residual squamous cell carcinoma of larynx. This was a retrospective study over a time frame of 6 years (2016-2022) of 74 patients who underwent bilateral neck dissection and salvage laryngectomy for recurrent or persistent disease with N0 neck. We calculated the incidence of occult nodal metastasis in ipsilateral and contralateral neck. Incidence of ipsilateral neck disease was calculated as 8.11 per cent and it was 0 per cent in contralateral neck. Regarding ipsilateral nodal level distribution, level II was the highest at 6.76 per cent, followed by level III at 5.41 per cent. There was 0 per cent metastasis in levels IV and IIb. In patients undergoing salvage laryngectomy with N0 neck, ipsilateral super selective neck dissection is considered a convenient and oncologically safe option to treat the neck.

Decoding the Enigma: Harnessing HPV Testing for the Precision Care in Carcinoma Unknown Primary with Secondary Metastasis to the Neck in North Indian Population Undergoing TORS for Primary Identification.

To assess the exact role of high-risk HPV testing in patients of carcinoma unknown primary with secondary metastasis to the neck who underwent TORS and neck dissection for identification of the primary site. A prospective study was carried out at a tertiary care centre over one year. Patients with unilateral neck swelling, which was cytologically proven squamous cell carcinoma neck metastasis, were included in the study. After clinicopathological evaluation, they underwent TORS-assisted ipsilateral radical tonsillectomy, tongue base mucosal wedge biopsy for primary site identification, and ipsilateral neck dissection. They underwent HPV RNA ISH from the tonsil, the base of the tongue and blood. They also underwent HPV DNA testing from the blood. P16 was done in the base of tongue, tonsil, and lymph node specimens. In the study cohort of 18 patients who underwent ipsilateral radical tonsillectomy, mucosal tongue base wedge biopsy and neck dissection, p16 positivity was isolated in 5.56%, 0% and 2.78% of patients, respectively. (n = 1/18, 0/18, 5/18). Interestingly, HPV E7 mRNA expression was absent in the tonsil /base of tongue specimens, but metastatic lymph nodes displayed expression in 11.11%. HPV DNA was undetected in all analysed tissues and patients' blood. In the Indian subcontinent, it is not essential to do detailed high-risk HPV analysis in cases of carcinoma unknown primary with secondary metastasis to the neck.

Patterns of cervical lymph node involvement in mono-focal papillary thyroid carcinoma patients with different capsular status: A multi-center analysis

ObjectiveThe characteristics of cervical lymph node involvement in papillary thyroid carcinoma (PTC) patients with different degree of capsular invasion remains unclear, especially for those with mono-focal lesion who have traditionally been considered as low neck metastasis risk subgroup. Study designRetrospective cohort study. SettingThree academic teaching hospital. MethodsA total of 1276 mono-focal PTC patients were retrospectively analyzed. ResultsMono-focal PTC patients with extrathyroidal extension (ETE) showed significantly higher central lymph node metastasis (CLNM) rate than those without. For patients with no gross ETE (gETE), those with minimal ETE (mETE) also showed more commonly CLNM than those with encapsulated lesions. However, the lateral lymph node metastasis (LLNM) rates of patients with mETE and encapsulated tumors were comparable, both lower than that of patients with gETE. Age ≥40, male, and MTD ≥0.5 cm were identified as independent risk factors of CLNM for those with encapsulated tumors and were enrolled for creating a prediction model. In terms of LLNM, only MTD ≥1.0 cm was confirmed as independent risk factors of LLNM for patients with positive gETE. ConclusionsThe presence and degree of ETE may have different effects on the risk of central and lateral lymph node metastasis. gETE demonstrates a strong correlation with both CLNM and LLNM while mETE is only associated with CLNM in mono-focal PTC patients. A comprehensive model is established in the aim of predicting neck involvement according to the capsular status and the corresponding stratified risk factors, which may aid clinical decision-making for the management of neck regions.

Prognostic factors of oral squamous cell carcinoma: the importance of recurrence and pTNM stage

BackgroundOral squamous cell carcinoma has a poor prognosis. Therefore, prognostic factors are important to increase the survival rate. This study assessed the survival rate and the prognostic factors for survival of patients with oral squamous cell carcinoma.MethodThis study included 168 patients who underwent surgery for oral squamous cell carcinoma between January 2006 and December 2021. The survival rate was analyzed with overall survival and disease-specific survival. The patient’s age, sex, pTNM stage, primary sites (lip, tongue, mouth of floor, mandibular gingiva, maxillary gingiva, mandibular vestibule, maxillary vestibule, retromolar trigone, palate, buccal mucosa, primary intra-osseous site), smoking and alcohol drinking habits, depth of invasion, perineural and lymphovascular invasion, cell differentiation, and postoperative radiotherapy were evaluated to analyze risk factors. Kaplan–Meier methods were used to estimate the survival rates. Cox regression methods were used to investigate the main independent predictors of survival in univariable and multivariable analysis.ResultsSixty-eight patients died of oral squamous cell carcinoma during follow-up periods. Their overall survival for 5 years was 51.2%, and the disease-specific survival was 59.2%. In univariable analysis, seven factors which are neck metastasis, depth of invasion, cell differentiation, lymphovascular invasion, postoperative radiotherapy, pTNM stage, and recurrence were significantly associated with survival. In multivariable analysis, pTNM stage and recurrence were significantly associated with survival.ConclusionIn patients with oral squamous cell carcinoma, pTNM stage and recurrence were significant prognostic factors. Neck metastasis, depth of invasion, cell differentiation, lymphovascular invasion, and postoperative radiotherapy were also prognostic factors. These factors serve as markers for obtaining prognosis information in oral squamous cell carcinoma.

An Unknown Foreign laryngeal Object: an exotic complication of skull base osteoradionecrosis

BackgroundOsteoradionecrosis (ORN) of the skull base is a rare complication after head and neck radiation with a broad variety of subsequent complications.MethodsA 68-year-old woman with a complex oncological history (right-sided sphenoid meningioma; left-sided neck metastasis of a Cancer of Unknown Primary—CUP) was admitted with a right-sided epi—/ oropharyngeal mass and severe pain exacerbations for further evaluation. CT scan revealed an advanced ORN of the skull base with subsequent abruption of the ventral part of the clivus. This dislocated part of the clivus wedged in the oropharynx for 48 h and then moved towards the larynx, resulting in dyspnea and almost complete airway obstruction.ResultsDue to the dangerous airway situation, an urgent exploration and removal of the dislocated clivus was necessary. After a potential cervical spine instability was ruled out, the patient’s airway was initially secured with an awake tracheotomy and the clivus was removed transorally. The tracheostomy tube was removed during the ongoing inpatient stay, and the patient was discharged with significant pain relief.ConclusionsThe present case illustrates an orphan complication of skull base ORN resulting in a major airway emergency situation.

Revisiting Feeding Tube Utilization in Oropharynx Cancer: 6-Year Prospective Registry Analysis.

Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients. Retrospective analysis of prospective cohort from 2015 to 2021. Single-institution NCI-Designated Comprehensive Cancer Center. With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during transoral robotic surgery (TORS). Tube duration was censored at last disease-free follow-up. Multivariate regression was performed for G-tube placement (odds ratio [OR] [95% confidence interval [CI]) and removal (Cox hazard ratio, hazard ratio [HR] [95% CI]). Of 924 patients, most had stage I to II (81%), p16+ (89%), node-positive (88%) disease. Median follow-up was 2.6 years (interquartile range 1.5-3.9). Most (91%) received radiation/chemoradiation, and 16% received TORS. G-tube rate was 27% (5% after TORS). G-tube risk was increased with chemoradiation (OR 2.78 [1.87-4.22]) and decreased with TORS (OR 0.31 [0.15-0.57]) and PSSHN-Diet score ≥60 (OR 0.26 [0.15-0.45]). G-tube removal probability over time was lower for T3 to T4 tumors (HR 0.52 [0.38-0.71]) and higher for PSSHN-Diet score ≥60 (HR 1.65 [1.03-2.66]). In this modern cohort of patients treated for OPC, 27% received G-tubes-50% less than institutional rates 10 years ago. Patients with preserved baseline swallowing and/or those eligible for TORS may have lower G-tube risk and duration.

Occult metastasis is no burden factor in oral squamous cell carcinoma patients when adhering to a standardized approach in neck dissection

ObjectivesManagement of the neck in patients with oral squamous cell carcinoma (OSCC) is pivotal to oncologic control and survival. However, there is controversy regarding necessity of neck dissection (ND) in patients with clinically node-negative neck. We aimed to assess risk factors for occult metastasis and to explore whether the presence of occult lymph node metastases (LNMs) has an impact on recurrence and survival.Material and methodsA retrospective cohort study was performed including patients with primary OSCC who underwent radical tumor resection and ND in a high-volume center adhering to the prevailing German guideline. The ND was performed according to a standardized approach.ResultsFour hundred twenty-one patients with primary surgically treated OSCC were included. The incidence of occult metastasis was 14.49%. A pathological T stage > 1 (multivariate analysis, odds ratio (OR) 3.958, p = 0.042) and the presence of extranodal extension in LNMs (multivariate analysis, OR 0.287, p = 0.020) were identified as independent risk factors for occult metastasis. When comparing patients with and without occult metastasis, there were no significant differences in terms of progression-free survival (log-rank, p = 0.297) and overall survival (log-rank, p = 0.320). There were no cases of ipsilateral neck recurrence. One patient developed contralateral neck metastasis; however, he initially presented with a unilateral pT1 pN0 tumor.ConclusionsOverall, our findings suggest that conducting a standardized approach in ND should be applied in terms of management of the neck in order to maintain survival rates and to prevent neck recurrence in OSCC patients.Clinical relevance.None of the risk factors for occult metastasis can be reliably assessed preoperatively. Although elective ND does not guarantee the complete prevention of neck recurrence, it increases the likelihood of either timely removal of micrometastases or strengthens the justification for adjuvant therapy. Consequently, this approach leads to improvements in clinical outcomes.

The Role of Trans Oral Robotic Surgery in the Carcinoma of Unknown Primary: A New Evidence in the Horizon?

The detection of the primary site in Carcinoma of Unknown Primary (CUP) is a challenging task which can significantly alter the course of management and also prognosis. Various modalities have been assessed with varying sensitivity and specificity. Imaging and cytological diagnosis have formed a key part of the diagnostic algorithm of CUP. Trans Oral Robotic Surgery offers the advantage of being both diagnostic as well as therapeutic with promising sensitivity and specificity and can form an integral part in the management of CUP. A prospective study was carried out at a tertiary care centre over a period of one year. Patients with unilateral neck swelling which was histopathologically proven squamous cell carcinoma neck metastasis were included in the study. They were evaluated with endoscopy and radiology according to the standard algorithm. When these failed to detect the primary, the patients underwent ipsilateral radical tonsillectomy and tongue base mucosal wedge biopsy via TORS. Post-operative histopathological examination was done on the resected specimens to detect the primary site. Transoral Robotic Surgery was able to localise primary in 50% of the patients enrolled in the study. Out of the primary site identified by TORS; 55.56% were located in the tonsil and 44.4% in the tongue base. TORS can offer promising detection rates of the occult primary in CUP and should form an integral part of the diagnostic algorithm.

Exploring the Role of Circulating Tumor Cells in Contralateral Neck Metastasis

Background: The management of neck nodes in oral cavity cancers discernibly depends on the approach adopted for the primary tumor. There are abundant literature and consensus guidelines established for ipsilateral neck metastasis in small lateralized oral cavity cancers. However, the literature on the mechanism of contralateral neck metastasis and their management in recurrent settings is sparse. The current analysis aims at elucidating the role of circulating tumor cells (CTCs) in contralateral neck metastasis and the incidence of the same. Materials and Methods: We performed a retrospective cohort study to include all the patients with recurrent ipsilateral oral cavity squamous cell carcinoma who underwent treatment between January 2016 and October 2021. Various parameters were analyzed, and the data were curated to arrive at a conclusion. Results: The analysis of several parameters, including demographics of the patient, tumor site, individual tumor, lymph node, metastasis (TNM) category, depth of invasion (DOI), extra-nodal extension (ENE) status, CTCs, adjuvant treatment received after first surgery followed by TNM category, DOI, worst pattern of invasion, ENE, type of neck dissection, histological grading of tumor, perineural invasion, lymphovascular invasion, nodal yield, and number of nodes positive in the contralateral neck were studied in detail. Conclusion: The study showed a significant correlation between contralateral neck metastasis and CTCs.

Selective adjuvant radiation therapy for distant lymph node metastasis in patients with stage 4B epithelial ovarian cancer: a case series

Although the efficacy of surgery followed by taxane- and platinum-based systemic chemotherapy has been clearly demonstrated in the standard first-line treatment of epithelial ovarian cancer, the role of radiation therapy for distant lymph node metastasis in patients with epithelial ovarian cancer is not well-established due to a lack of reported studies. We identified four patients who underwent selective adjuvant radiation therapy for neck and para-aortic lymph node lesions after primary debulking surgery between 2020 and 2022, followed by platinum-based chemotherapy for stage 4B high-grade serous ovarian cancer. Through a retrospective review of medical records, we analyzed patient clinicopathologic features, treatment course, and imaging findings. The median age was 49.25 years (range, 46–54 years). All patients had the International Federation of Gynecology and Obstetrics stage 4B disease. Following primary debulking surgery, all patients received weekly paclitaxel-carboplatin chemotherapy and maintenance treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. All patients received selective adjuvant radiation therapy for neck and para-aortic lymph node metastasis before PARP inhibitor maintenance. The median follow-up time was 36.75 months (range, 19–45 months). All patients achieved a complete response. None of the patients experienced disease recurrence or died during the follow-up period. The management of distant lymph node metastasis in patients with epithelial ovarian cancer remains a matter of debate. Selective adjuvant radiation therapy in first-line treatment for ovarian cancer appears to be a feasible approach with maintenance therapy for stage 4B epithelial ovarian cancer.

Bilateral axillo-breast approach (BABA) robotic neck dissection for papillary thyroid carcinomas

Papillary thyroid carcinoma (PTC), the most commonly diagnosed thyroid malignancy, frequently presents with lymph node metastases. Effective management of metastatic lymph nodes is crucial due to the disease's high recurrence rates. Herein, we present our approach to robotic thyroidectomy and central/lateral neck node dissection, which has shown comparable oncologic outcomes, reduced complications, and improved cosmetic results compared to open surgeries. We detail the surgical procedure, from patient positioning and flap dissection, through central and lateral neck dissection, to closure. The BABA robotic modified radical neck dissection (MRND) is primarily recommended for patients with well-differentiated thyroid carcinoma, predominantly PTC, presenting with suspected or pathologically confirmed lateral neck metastasis. We also discuss the application of the da Vinci robot settings in performing precise procedures and preserving critical anatomical structures. This comprehensive review provides insights into the effectiveness of BABA robotic thyroid surgery and central/lateral neck node dissection in managing PTC.

Effectiveness and tolerance of electrochemotherapy as palliative therapy for patients with head and neck cancer and malignant melanoma and its relation to early skin reaction

ObjectivesTo evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). Methodsprospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n=13), papillary thyroid carcinoma (n=4), adenoid cystic carcinoma of parotid gland (n=1) or malignant melanoma (n=37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. ResultsOverall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p= 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p= 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p= 0.86). ConclusionsElectrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. Level of evidenceIII.

Elective parotidectomy and neck dissection are not beneficial in cutaneous squamous cell carcinoma of the head

ObjectiveCutaneous Squamous Cell Carcinoma (cSCC), a tumor with a significantly increasing incidence, is mostly diagnosed in the head region, where tumors have a worse prognosis and a higher risk of metastases. The presence of metastases reduces specific five-year survival from 99% to 50%. As the risk of occult metastases does not exceed 10%, elective dissection of the tributary parotid and neck lymph nodes is not recommended. MethodsWe retrospectively analyzed a group of 12 patients with cSCC of the head after elective dissections of regional (parotid and cervical) nodes by means of superficial parotidectomy and selective neck dissection. ResultsWe diagnosed occult metastases neither in the cervical nor parotid nodes in any patient. None were diagnosed as a regional recurrence during the follow-up period. ConclucionOur negative opinion on elective parotidectomy and neck dissection in cSCC of the head is in agreement with the majority of published studies. These elective procedures are not indicated even for tumors showing the presence of known (clinical and histological) risk factors for lymphogenic spread, as their positive predictive value is too low. Elective parotidectomy is individually considered as safe deep surgical margin. If elective parotidectomy is planned it should include only the superficial lobe. Completion parotidectomy and elective neck dissection are done in rare cases of histologically confirmed parotid metastasis in the parotid specimen. Preoperatively diagnosed parotid metastases without neck involvement are sent for total parotidectomy and elective selective neck dissection. Cases of clinically evident neck metastasis with no parotid involvement, are referred for comprehensive neck dissection and elective superficial parotidectomy. The treatment of concurrent parotid and cervical metastases includes total conservative parotidectomy and comprehensive neck dissection. Level of evidenceHow common is the problem?Step 4 (Case-series)Is this diagnostic or monitoring test accurate? (Diagnosis)Step 4 (poor or non-independent reference standard)What will happen if we do not add a therapy? (Prognosis)Step 4 (Case-series)Does this intervention help? (Treatment Benefits)Step 4 (Case-series)What are the COMMON harms? (Treatment Harms)Step 4 (Case-series)What are the RARE harms? (Treatment Harms)Step 4 (Case-series)Is this (early detection) test worthwhile? (Screening)Step 4 (Case-series)

CR5/CCL5 axis is linked to a poor outcome, and inhibition reduces metastasis in oral squamous cell carcinoma.

The CCR5/CCL5 axis is essential for interactions between malignant cells and microenvironment components, promoting tumor progression in oral squamous cell carcinoma (OSCC). This study aims to evaluate the association of CCL5 and CCR5 with the behavior of oral cancer and assess the therapeutic potential of a CCR5 antagonist. A retrospective study to analyze CCR5 and CCL5 expression on paraffin-embedded tissues was performed. In cell lines, rhCCL5 was added to induce CCR5-related pathways, and Maraviroc and shRNA against CCR5 were used to neutralize the receptor. Finally, an in vivo murine orthotopic xenograft model of tongue cancer was used to evaluate Maraviroc as an oncologic therapy. After 15days, the mice were killed, and the primary tumors and cervical lymph nodes were analyzed. The expression of CCR5 was associated with clinical stage and metastasis, and CCL5 was related to overall survival. Adding rhCCL5 induced cell proliferation, while shRNA and Maraviroc reduced it in a dose-dependent manner. Maraviroc treatment also increased apoptosis and modified cytoskeletal organization. In vivo, Maraviroc reduced neck metastasis. The effects of CCR5 antagonists in OSCC have been poorly studied, and this study reports in vitro and in vivo evidence for the effects of Maraviroc in OSCC. Our results suggest that the CCR5/CCL5 axis plays a role in oral cancer behavior, and that its inhibition is a promising new therapy alternative.

Glomangiosarcoma-like Anaplastic Transformation in Papillary Thyroid Carcinoma: A Novel Form of Heterologous Differentiation and a Systematic Review of Heterologous Element Prevalence.

Anaplastic thyroid carcinoma (ATC) demonstrates a wide variety of morphologies and is characteristically associated with a differentiated thyroid carcinoma component. Heterologous differentiation is a rare, potentially challenging phenomenon in ATC, mostly observed as osteosarcomatous or chondrosarcomatous differentiation. We now describe a novel 'glomangiosarcoma-like' differentiation, review our archival experience from two institutions (UPMC, CC), and perform a systematic review for the prevalence of heterologous elements in ATC. The patient is a 57-year-old female who presented with 4.5cm left thyroid, and 3.4cm neck masses. Histologically, the thyroid demonstrated a differentiated high grade papillary thyroid carcinoma, tall cell and hobnail/micropapillary subtypes transitioning into an anaplastic component with spindled to ovoid cells with hemangiopericytoma-like vasculature showing CD34 positivity, variable muscle marker expression and pericellular lace-like type IV collagen deposition. The neck mass consisted solely of the latter morphology. Targeted next-generation sequencing was performed on high grade DTC and adjacent ATC from the thyroid as well as ATC from the neck metastasis. All three components shared BRAFV600E, TERT promoter, and PIK3CA mutations confirming a clonal origin. Archival (UPMC: n = 150, CC: n = 74) and literature review showed no prior examples. Systematic review and meta-analysis of prevalence showed a baseline pooled prevalence (generalized linear mixed model) of heterologous elements of any type to be 1.6% (95% confidence interval: 1.0-2.6%) for studies where this was specifically addressed. ATC with glomangiosarcoma-like heterologous differentiation is a rarity among an already rare morphologic category with unique diagnostic pitfalls.

Investigating the Role of MK2 in Head and Neck Squamous Cell Carcinoma Growth, Metastasis and STING Pathway Activation

Our prior work demonstrated that inhibition of MAPKAPK2 (MK2) can enhance radiation (RT)-mediated in vivo head and neck squamous cell carcinoma (HNSCC) tumor control and survival in preclinical immune incompetent models. The cytosolic DNA sensor cyclic GMP-AMP synthetase (cGAS) and its downstream adaptor protein, stimulator of interferon genes (STING), are conserved proteins within the innate immune signaling pathways and are important for mediating host defense against microbial infection and can play a role in anti-cancer immunity. We hypothesized that loss of MK2 enhances radiation-induced cGAS-STING pathway activation leading to improved tumor control and survival. MK2 shRNA knockdown human (Tu167, CAL27) and MK2 Cas9/CRISPR knockout (KO) syngeneic murine (Ly2, MLM3) HNSCC cell lines were treated with 10 Gy irradiation. Micronuclei were quantitated by DAPI-immunofluorescence (IF). Protein changes in cGAS-STING were evaluated by immunoblot. Inflammatory cytokine production including Type I IFNβ1 were evaluated by RT-qPCR. Ly2 and MLM3 cells were orthotopically or flank engrafted into immune competent mice (Balb/c, C57Bl/6, respectively) for animal tumor control-survival studies. Tumor immune cell infiltrate was examined using FACS and immunohistochemistry. Selected drug studies using the MK2 inhibitor, ATI-450, were performed with RT. Loss of MK2 in HNSCC (Tu167, CAL27, Ly2, MLM3) treated with RT led to a significant increase in micronuclei formation compared to control cells. MK2-enhanced micronuclei generation following RT could be inhibited with the actin filament polymerization inhibitor, cytochalasin B. RT treatment of MK2 shRNA cells led to increased cGAS and phospho-STING levels compared to either treatment alone. IFNβ1 levels were significantly higher in HNSCC cell lines treated with RT and with MK2 inhibited by an MK2 inhibitor (ATI-450) or genetic reduction compared to either treatment alone. In-vivo implantation of MLM3 cells into C57Bl/6 comparing control vs MK2 KO tumors treated with ±8 Gy RT demonstrated improved mouse survival favoring RT+MK2 KO over RT, MK2 KO or parental (63, 58, 58.5, 35 days, respectively). FACS analysis of MLM3 WT v KO tumors 3 days post RT showed an overall increase in the number of CD3/CD8 T-cells infiltrating into the tumor in all groups except for parental tumors. Further analysis demonstrated that loss of MK2 reversed CD8 T-cell exhaustion and when combined with radiotherapy led to increased CD8 T-cell activation. Furthermore, activated CD4 and CD8 T cells were reduced in WT+RT cells compared to WT tumors whereas no reduction was seen in the KO or KO+RT. HNSCC tumor MK2 inhibition enhances RT-mediated micronuclei formation and subsequent cGAS-STING-IFNβ1 levels. Loss of HNSCC MK2 leads to increased CD4-CD8 T-cell infiltration into the tumor and this effect is enhanced following RT. Targeting tumor MK2 may facilitate improved tumor control.

Evaluation of the quality of neck dissection in patients with oral cavity squamous cell carcinoma

Oral cavity squamous cell carcinoma is one of the leading localizations in the structure of head and neck cancers in the Russian federation and in the world. Neck metastases are the key criterion which influence to survival, recurrence, and distant metastases in patients with oral squamous cell carcinoma. Neck dissection is a main step in the surgical treatment of oral squamous cell carcinoma. This literature review analyzes data on possible methods for assessing the quality of neck dissection in squamous cell carcinoma of the oral cavity. Evaluation criteria can be conditionally divided into prognostic (lymph node extracapsular extension, the size of the largest neck metastasis, lymph node yield, lymph node ratio, metastasis topography) and qualitative (lymph node yield, lymph node ratio). Nowadays, there are some prognostic factors of surgical specimen after neck dissection which we use in clinical practice except for lymph node yield, lymph node ratio. This paper analyzes the criteria for an objective assessment of the quality of the operation “neck dissection”. The clinical and prognostic significance of these parametrs is considered.

Prevalence of Occult Central Lymph Node Metastasis by Tumor Size in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

While papillary thyroid carcinoma (PTC) is associated with high occult central neck metastasis (CNM) rates, prophylactic central neck dissection (pCND) is controversial. This meta-analysis aims to look at the occult CNM rate according to tumor size. A literature search was conducted in PubMed from inception to April 2023. Inclusion criteria were primary studies that determined occult CNM rates in cN0 PTC by tumor size. Heterogeneity, influential case diagnostics, and proportion data were evaluated with Cochran's Q-test, Baujat plots and Forest plots, respectively. Fifty-two studies were included in this meta-analysis. The findings demonstrated an occult CNM rate of 30.3% for tumors ≤ 5 mm, 32.7% for tumors ≤ 1 cm, 46.0% for tumors between 1 and 2 cm, 43.1% for tumors between 2 and 4 cm, and 61.2% for tumors > 4 cm. The heterogeneity of each study group was high, though no publication bias was noted. While there was a trend towards increased occult CNM rates with larger tumors, comparisons between different size cutoffs varied in significance. This comprehensive review affirms that occult CNM is high and that an ipsilateral pCND can be justified in all PTC patients for accurate differentiation between Stage I and Stage II disease and its clinical implications.

Clinical value of dual-energy CT for predicting occult metastasis in central neck lymph nodes of papillary thyroid carcinoma.

To predict the probability of occult lymph node metastasis (OLNM) in the central cervical by analyzing the dual-energy computed tomography (DECT) parameters derived from papillary thyroid carcinoma (PTC). Data were retrospectively collected from patients with pathologically confirmed PTC who underwent arterial and venous phases of enhanced DECT with concurrent central neck lymph node dissection (CLND). Three clinical features, three shape-related features, and twenty-six DECT-derived parameters were measured. The univariate and multivariate analyses were applied to select the relevant parameters and develop the nomogram. A total 140 cases with negative diagnosis of cervical central lymph node metastases by preoperative evaluation were included, among which 88 patients with metastasis (OLNM +) and 52 patients without metastasis (OLNM -) were finally confirmed by pathology.(1) Anteroposterior/transverse diameter ratio (A/T) derived from the PTC focus had significant difference between the OLNM + and OLNM - groups (p < 0.05). (2) In the arterial phase, iodine concentration (ICarterial), normalized iodine concentration (NICarterial), effective atomic number (Zeff-arterial), electron density (EDarterial), and slope of energy curve (karterial) from PTC focus showed significant difference (all p < 0.05) between the two groups. In the venous phase, only the CT value under the 40keV (HU40keVvenous) had differences (p < 0.05). (3) The nomogram was produced to predict the probability of OLNM, and the AUC, sensitivity, and specificity in the training and test cohort were 0.830, 75.0%, 76.9%, and 0.829, 65.9%, 84.6%, respectively. DECT parameters combined with shape-related feature derived from PTC might be used as predictors of OLNM in the central neck. Preoperative imaging evaluation combining shape-related features and dual-energy CT parameters could serve as a reference to discern occult lymph node metastasis in central neck during the surgically planning of papillary thyroid carcinoma. • Papillary thyroid carcinoma (PTC) patients may have occult lymph node metastasis (OLNM) in the central neck, which is extremely difficult to find by preoperative imaging examination. • Dual-energy CT quantitative evaluation has higher accuracy than conventional CT and can predicting OLNM in the central neck of PTC. • Dual-energy CT quantitative parameters and morphology of PTC can serve as a useful tool in predicting OLNM in the central neck, and as a guide for personalized treatment.