Incidental Thyroid Tissue in Sentinel Nodes From Oral Squamous Cell Carcinoma.

OBJECTIVE: Sentinel node biopsy (SNB) is a surgical staging test in which sentinel nodes (SNs) undergo intensive histological analysis. SNB diagnoses early cancer spread, but can also reveal unexpected findings within the SNs. We review cases of incidental thyroid cells (TC) found in SNs from patients with oral squamous cell carcinoma (OSCC) to assess the prevalence of TC, and the clinical significance of these. METHODS: Multicenter retrospective review of SNB performed for cT1-T2N0 OSCC. Incidental TC were identified by TTF-1 or thyroglobulin positivity. Anatomical location of nodes containing TC, TC morphology, and ongoing management/follow up of this incidental finding was recorded. Neck dissections performed during the same period were reviewed to establish the expected incidence of TC in neck nodes without serial sectioning analysis. RESULTS: 278 SNB cases were reviewed. Ten procedures detected TC in nine patients (10/278, 3.6%). During the same time period 725 neck dissections were performed, six containing TCs (6/725, 0.8%). One patient underwent SNB twice with TC identified on both occasions. Three patients had both OSCC metastasis and thyroid cells. All SNB patients with TC identified underwent thyroid USS with no primary tumours identified. Three patients underwent thyroidectomy, in all cases no primary thyroid tumour was found. CONCLUSION: Prevalence of incidental TC in SNs appears to be higher than that reported in neck dissections, these are not likely to be clinically relevant and can be managed on a conservative basis in the absence of clear metastatic features. LEVEL OF EVIDENCE: Multicentre retrospective cohort study, 3 Laryngoscope, 134:1278-1281, 2024.

Serial step sections at narrow intervals with immunohistochemistry are required for accurate histological assessment of sentinel lymph node biopsy in oral squamous cell carcinoma.

BACKGROUND: Sentinel lymph node (SLN) biopsy is an accurate staging modality in early oral squamous cell carcinoma (OSCC), but its accuracy relies on labor-intensive histopathology protocols. We sought to determine whether serial step sections with immunohistochemistry (SSSIHC) at narrow intervals of the entire SLN are required to accurately exclude metastasis. METHODS: Consecutive SLN biopsies over a 13-year period were retrospectively evaluated. If the index section was negative for carcinoma, the entire SLN was subjected to SSSIHC at 150 µm intervals. The first section level and total number of section levels to contain carcinoma were recorded. RESULTS: One hundred and eighteen SLN+ from 90 patients were included. SSSIHC upstaged the nodal status in 19.5% of patients. Metastasis was identified in 16.7% and 10.2% beyond section levels 4 and 6, respectively. Among SLNs requiring SSSIHC, 47.5% contained carcinoma in a single section level. CONCLUSION: SSSIHC of the entire SLN at 150 µm intervals are required to identify occult metastasis in OSCC.

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy.

PURPOSE: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. MATERIAL AND METHODS: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. RESULTS: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. CONCLUSION: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.

Differential effects of lithium isotopes in a ketamine-induced hyperactivity model of mania.

Sub-anesthetic doses of ketamine produce an increase in rodent ambulation that is attenuated by co-administration of naturally-occurring lithium (LiN), the drug most commonly employed in the treatment of bipolar illness. As a consequence, ketamine-induced hyperactivity has been proposed as an animal model of manic behavior. The current study employed a modified version of this model to compare the potency of LiN to that of each of its two stable isotopes - lithium-6 (Li-6) and lithium-7 (Li-7). Since Li-7 constitutes 92.4% of the parent compound it was hypothesized to produce comparable behavioral effects to that of LiN. The current study was devised to determine whether Li-6 might be more, less, or equally effective at tempering hyperactivity relative to Li-7 or to LiN in an animal model of manic behavior. Male rats were maintained on a restricted but high-incentive diet containing a daily dose of 2.0 mEq/kg of lithium (LiN), Li-6 or Li-7 for 30 days. A control group consumed a diet infused with sodium chloride (NaCl) in place of lithium to control for the salty taste of the food. On day 30, baseline testing revealed no differences in the locomotor behavior among the four treatment groups. Animals then continued their Li/NaCl diets for an additional 11 days during which every subject received a single IP injection of either ketamine (25 mg/kg) or 0.9% physiological saline. On the final four days of this regimen, locomotor activity was assessed during 60 min sessions each beginning immediately after ketamine injection. While all three lithium groups produced comparable decreases in ketamine-induced hyperactivity on the first trial, by the fourth trial Li-6 animals exhibited significantly greater and more prolonged reductions in hyperactivity compared to either Li-7 and Li. These results suggest that Li-6 may be more effective at treating mania than its parent compound.

Effects of chronic lithium exposure in a modified rodent ketamine-induced hyperactivity model of mania.

Bipolar illness is characterized by periods of "mania" - high energy, irritability, and increased psychomotor activation. While the neurobiological investigation of mania has been limited by the lack of reliable animal models, researchers have recently reported that daily subanesthetic doses of ketamine produce a lithium-reversible increase in rodent locomotor activity. Such studies have typically employed short-term (2 week) exposure to daily intraperitoneal-injected lithium and extremely brief (i.e., 5-min) open-field tests of hyperactivity. To increase the translational utility of the model, the effects of 70-days of orally administered lithium were examined on ketamine-induced hyperlocomotion during 30-min test sessions. Rats consumed 2.0 mEq/kg lithium chloride (LiCl) presented daily in a high incentive food (10 g of peanut butter). Control animals ingested peanut butter infused with an equimolar concentration of sodium chloride (NaCl). After 60 days of treatment, a 30-min baseline revealed no differences in the locomotor activity of LiCl and NaCl animals. During the next 10 days, animals received single daily supplemental injections of 25 mg/kg IP ketamine. A subset of animals was injected daily with saline and served as non-ketamine controls. Behavioral testing on the final two days of treatment confirmed that ketamine administration produced a profound increase in locomotor activity that was significantly attenuated in the LiCl group. Additionally, blood plasma levels of lithium were found to be comparable to low-moderate human therapeutic levels. These data confirm the viability and utility of ketamine-induced hyperlocomotion as a rodent model of mania.

Activation of 5-HT1B receptors in the Lateral Habenula attenuates the anxiogenic effects of cocaine.

Recent work has implicated the Lateral Habenula (LHb) in the production of anxiogenic and aversive states. It is innervated by all the major monoamine neurotransmitter systems and has projections that have been shown to modulate the activity of both dopaminergic and serotonergic brain regions. Cocaine is a stimulant drug of abuse that potentiates neurotransmission in these monoamine systems and recent research suggests that the drug's behavioral effects may be related in part to its actions within the LHb. The present research was therefore devised to test the hypothesis that alterations in serotonin (5-HT) function within the LHb can affect the behavioral response to cocaine. Male rats were fitted with intracranial guide cannula and trained to traverse a straight alleyway once a day for a 1 mg/kg i.v. injection of cocaine. Intra-LHb pretreatment with the 5-HT1B agonist CP 94,253 (0, 0.1, or 0.25 µg/side) attenuated the development of approach/avoidance "retreat" behaviors known to be a consequence of cocaine's dual rewarding (approach) and anxiogenic (avoidance) properties. This effect was reversed by co-administration of a selective 5-HT1B antagonist, NAS-181 (0.1 µg/side), demonstrating drug specificity at the 5-HT1B receptor. These data suggest that 5-HT1B signaling within the LHb contributes to the anxiogenic effects of cocaine.