Anticancer effects of thymoquinone in head and neck squamous cell carcinoma: A scoping review.

Objective: Thymoquinone (TQ), the active constituent of Nigella sativa, has been shown to have anticancer effects in head and neck squamous cell carcinoma (HNSCC). This review aims to outline the properties of TQ, the known drivers in HNSCC formation, and summarize the anticancer effects of TQ in SCC. Data Sources: Three databases (PubMed, Embase, and Google Scholar) were queried for the key words "thymoquinone squamous cell carcinoma." Review Methods: Publications that were not original research and publications that did not have full-text available for review were excluded. Results: Sixteen research articles met the inclusion criteria. Our review demonstrates that TQ-induced cytotoxicity is associated with increased expression and activity of the tumor suppressor p53, proapoptotic proteins Bax and caspases, as well as decreased expression and activity of antiapoptotic proteins Bcl-2 and Mdm2. Additionally, TQ modulates cell-survival pathways such as the PI3k/Akt pathway. TQ synergizes with therapeutics including cisplatin and radiation. Early TQ administration may prevent carcinogenesis via upregulation of antioxidant enzymes, and TQ administration in the presence of cancer can result in disease mitigation via induction of oxidative stress. Conclusion: TQ acts as an upregulator of proapoptotic pathways and downregulator of antiapoptotic pathways, modulates the oxidative stress balance in tumor development, and works synergistically alongside other chemotherapeutics to increase cytotoxicity. TQ has the potential to prevent carcinogenesis in patients who are at high-risk for SCC and adjuvant treatment for SCC patients undergoing conventional treatments. Future studies should aim to identify specific populations in which TQ's effects would be the most beneficial. Level of Evidence: Not available.

Nigella sativa oil mitigates xerostomia and preserves salivary function in radiotherapy-treated mice.

Objective: This study aimed to assess if Nigella sativa oil (NSO), a health supplement containing thymoquinone as a major component, can act as a protective agent in salivary gland stem cells following radiotherapy (RT) damage. Methods: Forty, 10-week-old, male C3H/HeJ mice were randomized to four experimental groups: sham RT + H2O gavage (control) (N = 4); 15 Gy RT + H2O gavage (N = 12); sham RT + NSO gavage (N = 12); and 15 Gy RT + NSO gavage (N = 12). Weight changes, saliva production, and salivary gland histopathologic staining were recorded for each group over the course of the experiment. Results: All mice in the sham RT + H2O gavage and sham RT + NSO gavage groups demonstrated 100% 60-day survival. RT + H2O compared to RT + NSO gavaged mice were significantly underweight by an average of 6.4 g (p < .001). Salivary output showed significant decline in RT + H2O gavaged mice at days 3 and 16, whereas salivary output in RT + NSO during these same time periods was comparable to the control. At day 60, all mice that survived recovered salivary function regardless of their treatment arm. Salivary specimens from the RT + NSO gavage group demonstrated early signs of recovery of Kr 5+ salivary gland stem cells in both submandibular and sublingual glands at day 16 with complete recovery by day 60, marked by strong histopathologic staining, whereas the RT + H2O gavage group did not recover as effectively. Conclusion: NSO may help preserve salivary function in mice treated with RT and may mitigate xerostomia by accelerating the recovery of salivary gland stem cells. Level of evidence: Not applicable.

Head & neck melanoma: A 22-year experience of recurrence following sentinel lymph node biopsy.

OBJECTIVE: To examine the clinicopathologic factors that contribute to regional and distant recurrence in intermediate to high risk head and neck melanoma patients after sentinel lymph node biopsy (SLNB). METHODS: This study is a retrospective review from an academic tertiary care center. Patients treated with SLNB for head and neck melanoma from 1997 to 2019 were reviewed and characterized by sentinel lymph node (SLN) status. Clinical variables were examined for the impact on regional and distant recurrence in SLNB-negative patients using univariable and multivariable Cox regression analysis. RESULTS: One hundred and fifty four patients were included. Of note, 127 (82.5 %) were men, and the average age was 61.3 years. Median follow-up was 68.6 weeks. Pathologic review of SLNs found 3.9% positive for metastatic melanoma; 96.1% were negative. Regional recurrence was significantly associated with tumor stage and age on multivariate analysis. A total of 4.5% of patients recurred in a previously labeled negative basin. Scalp subsite accounted for 30.5% of primary tumors and was more likely to yield a positive SLN on univariate analysis (P = .023). Tumor stage and age were significantly associated with distant metastasis on multivariable analysis (P = .026, P < .001 respectively). CONCLUSION: We report a number of prognostic trends in head and neck melanoma. SLN positivity was found more often in patients with a primary tumor of the scalp. Regional recurrence was significantly associated with age and tumor stage, whereas distant recurrence was significantly associated with tumor staging and scalp subsite. Scalp subsite was associated with an increased risk for nodal metastasis and distant recurrence. LEVEL OF EVIDENCE: 3.

Merkel Cell Carcinoma: A 28-Year Experience.

OBJECTIVE: To evaluate the management and recurrence outcomes of head and neck Merkel cell carcinoma (HN-MCC) at a single institution. STUDY DESIGN: A retrospective review of outcomes in patients with HN-MCC. SETTING: A tertiary center from May 1990 to December 2018. SUBJECTS AND METHODS: Electronic medical records of patients with HN-MCC were reviewed. RESULTS: Sixty cases were included, with 67% (40 of 60) males and a mean age of 73.3 years. Imaging had a moderate sensitivity and specificity for detection of occult disease when compared with histopathologic analysis. Forty-two percent (25 of 60) of patients underwent neck dissection, and 12% (7 of 60) had a sentinel lymph node biopsy (SLNB). There was a high rate of negative SLNB findings. The majority of patients were treated with surgery alone (29 of 60), followed by a cohort (21 of 60) treated with surgery plus adjuvant treatment, and 10 of 60 patients were treated with radiation therapy with or without chemotherapy. Recurrence-free survival was 50%, 45%, and 42% at 1, 2, and 5 years. CONCLUSIONS: We report higher recurrence rates and higher negative SLNB result rates than other studies. Our results affirm that imaging may not be a substitute for SLNB and that it had an intermediate ability to identify the occult disease. Traditional predictors, including SLNB and cervical node pathology, may not identify patients at risk for recurrence in HN-MCC. We report similar recurrence rates in patients who had treatment of the cervical nodes by radiation therapy or neck dissection as compared with those who did not receive neck treatment.