Possible role of ALDH1 and CD44 in lip carcinogenesis.

BACKGROUND: Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

High-dose-rate brachytherapy at 3 Gy per fraction for lip carcinoma: Treatment outcomes and toxicity at 5-years.

PURPOSE: Low-dose-rate brachytherapy (LDR-BT) is a well-established treatment for lip cancer. High-dose-rate (HDR)-BT is a promising alternative to LDR-BT, but data are limited. In this context, we retrospectively evaluated treatment outcomes in a series of patients who underwent HDR-BT for lip carcinoma between 2003 and 2021. MATERIALS AND METHODS: A total of 32 patients were included in this study, with a median age of 73.5 years (range, 61 - 88). The indications for HDR-BT were as follows: primary treatment (n = 17), adjuvant treatment (n = 3), and recurrent disease after surgery (n = 12). The prescribed dose was 18 fractions of 3 Gy administered twice daily. RESULTS: At a median followup of 45 months (range, 12 -232), the 5-year local recurrence-free interval was 96.9% (95% CI: 90.9-100%), the disease-free interval was 85% (95% CI: 70.9-99.1), and 5-year overall survival was 64.7% (95% CI: 44.7-84.8). Eleven patients died, all on age related comorbidities. Acute toxicity manifested as G1 dry desquamation in 6 patients (18.8%), G2 erythema in 10 patients (31.2%) and G3 confluent moist desquamation in 16 patients (50%). Late complications included G1 fibrosis (100% of cases). G1 and G2 depigmentation was observed in 8 (25%) and 6 (18%) patients, G1 telangiectasia occurred in 5 patients (16%). CONCLUSIONS: These data support the use of HDR-BT for lip cancer. The dose and fractionation schedule used in this study (18 fractions x 3 Gy twice daily) seems to be effective and safe.

Interstitial Brachytherapy for Lip Cancer: Technical Aspects to Individualize Treatment Approach and Optimize Outcomes.

Primary radiation therapy using interstitial brachytherapy (IBT) provides excellent local tumor control for early-stage squamous cell carcinoma of the lip. Technical aspects of treatment are important to optimize outcomes. In this report, we discuss patient selection criteria, procedural details, and dosimetric considerations for performing IBT for cancers of the lip. Catheters are inserted across the length of tumor entering and exiting approximately 5 mm beyond the palpable tumor extent. A custom mouthpiece is fabricated to facilitate normal tissue sparing. Patients undergo computed tomography imaging, the gross tumor volume is contoured based on physical examination and computed tomography findings, and an individualized brachytherapy plan is generated with the goals of achieving gross tumor volume D90% ≥ 90% and minimizing V150%. Ten patients with primary (n = 8) or recurrent (n = 2) cancers of the lip who received high-dose-rate lip IBT using 2.0- to 2.5-week treatment regimens are described (median prescription: 47.6 Gy in 14 fractions of 3.4 Gy). Local tumor control was 100%. There were no cases of acute grade ≥4 or late grade ≥2 toxicity, and cosmesis scores were graded as good to excellent in all patients. IBT represents an excellent treatment option for patients with lip squamous cell carcinoma. With careful attention to technical considerations furthered described in the present report, high rates of tumor control, low rates of toxicity, and favorable esthetic and functional outcomes can be achieved with IBT for lip cancer.

Custom-made radiotherapy prosthesis for external and internal radiotherapy in a patient with lip cancer.

Definitive radiotherapy is an effective treatment for early-stage lip cancer. The goal of radiotherapy is to irradiate the cancer site effectively while protecting healthy surrounding tissue from the adverse effects of radiation. To this end, radiotherapy prostheses have been widely and effectively used. A maxillofacial prosthodontist working in collaboration with a radiation oncologist can create a custom-made radiotherapy prosthesis that minimizes adverse effects. This report demonstrates the successful use of spacers in external beam radiotherapy and brachytherapy in consideration of the patient's radiation therapy treatment plan and wearing conditions, ensuring adequate availability and preventing radiation-related complications.

Laser Therapy for the Treatment of Actinic Cheilitis: A Systematic Review.

Actinic cheilitis (AC) is a chronic inflammation of the lip considered an oral, potentially malignant disorder associated with an increased risk of lip squamous cell carcinoma (SCC) development. Controversies surrounding current therapeutic modalities of AC are under debate, and the implications of laser treatment have not been specifically investigated through a systematic review design. The present study aims to evaluate the degree of evidence of laser for the treatment of AC in terms of efficacy and safety. We searched for primary-level studies published before January 2022 through MEDLINE/PubMed, Embase, Web of Science, Scopus and CENTRAL, with no limitation in publication language or date. We evaluated the methodological quality and risk of bias of the studies included using the updated Cochrane Collaboration's tool for assessing risk of bias (RoB-2). Twenty studies (512 patients) met our eligibility criteria. Laser therapy showed a complete clearance of AC in 92.5% patients, with a maximum recurrence rate of 21.43%, and a very low frequency of malignant transformation to SCC (detected in only 3/20 studies analyzed). In addition, cosmetic outcomes and patient satisfaction were described as excellent. In conclusion, our findings indicate that laser therapy is a high efficacy approach to AC.

Terapia fotodinámica con luz de día en el tratamiento de la queilitis actínica / Actinic Cheilitis Treated With Daylight Photodynamic Therapy

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Risk of squamous cell carcinoma of the lip and cutaneous melanoma in older Australians using hydrochlorothiazide: A population-based case-control study.

Recent European and US studies reported increased risks of skin cancers associated with hydrochlorothiazide (HCTZ) treatment. Our study aimed to determine the risk of lip cancer and malignant melanoma among Australians prescribed HCTZ. We conducted a case-control study nested within a population of veterans residing in New South Wales in 2004-2015, using Australian Department of Veterans' Affairs data linked with cancer registrations, hospitalisation and prescription dispensings. Among DVA healthcare card holders 65 years and older, we identified incident cases of squamous cell carcinoma of the lip and of cutaneous melanoma, each matched with up to 20 controls through risk-set sampling. We estimated odds ratios (ORs) associating HCTZ use with each cancer using conditional logistic regression, adjusting for predefined confounders. For lip cancer (45 cases), ever-use of HCTZ yielded an OR of 2.6 (95% CI: 1.4-5.0) and high HCTZ use (≥25 000 mg) an OR of 4.7 (95% CI: 1.6-13.7). For cutaneous melanoma (659 cases), ever-use of HCTZ resulted in an OR of 1.2 (95% CI 1.0-1.5) and high HCTZ use in an OR of 1.2 (95% CI: 0.8-1.8). Our findings align with risk estimates from previous studies and provide further evidence that HCTZ's photosensitising properties may promote carcinogenesis in sun-exposed tissues.

Infantile hemangioma of the upper lip and enamel hypoplasia: Two case reports.

Segmental infantile hemangiomas related to PHACE syndrome have recently been associated with enamel hypoplasia. We present two cases of solitary, localized upper lip infantile hemangioma with enamel hypoplasia of deciduous teeth.

Immunoexpression of glucocorticoid receptor alpha (GRα) isoform and apoptotic proteins (Bcl-2 and Bax) in actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: Actinic cheilitis (AC) is a potentially malignant disorder that can progress to squamous cell carcinoma (SCC), but this process is not fully understood. This study evaluated the immunoexpression of glucocorticoid receptor alpha (GRα) isoform and apoptotic proteins (Bcl-2 and Bax) in AC and lower lip SCC (LLSCC). METHODS: Twenty-two AC and 44 LLSCCs (22 with regional nodal metastasis and 22 without metastasis) were selected. The percentages of nuclear (GRα) and cytoplasmic (GRα, Bcl-2, and Bax) staining in epithelial cells were assessed and correlated with clinical (tumor size/extent and clinical stage) and histopathological parameters (risk of malignant transformation for AC and histopathological grade of malignancy for LLSCCs). RESULTS: Expression of GRα was observed in all cases studied, with relatively high median percentages of positive staining. When compared to AC, LLSCCs exhibited lower nuclear expression and higher cytoplasmic expression of GRα (P < 0.05). Regarding clinicopathological parameters, significant differences were only found for cytoplasmic expression of GRα according to the histopathological grade of LLSCCs (P = 0.036). Higher expression of Bax compared to Bcl-2 was observed in AC and LLSCCs (P < 0.05). In LLSCCs, there was a positive correlation between nuclear and cytoplasmic expressions of GRα (P = 0.006). CONCLUSION: Reduced nuclear translocation and increased cytoplasmic expression of GRα may be important events in lip carcinogenesis but are not involved in the progression of LLSCC. The role of GRα in lip cancer development does not seem to be primarily related to modulations in the expression of Bcl-2 or Bax.

Malignant transformation of actinic cheilitis: A systematic review of observational studies.

The aim of the present systematic review was to determine the malignant transformation rate of actinic cheilitis (AC). A comprehensive literature search was conducted using Medline/PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, OvidSP, and Google Scholar. The inclusion criteria comprised of observational human studies involving the malignant transformation of AC and publications in English. Studies included in this review were clinical follow-up, cohort, retrospective, or prospective investigations. The search yielded 1126 articles, and after exclusion, 34 full-text articles were eligible for full-text analysis. Only one article met the inclusion criteria. Based on the included article, it was determined that the malignant transformation rate of AC to squamous cell carcinoma (SCC) was 3.07%. Excluded articles focused on the clinicopathological characteristics and treatment efficacies of AC, and no malignant transformation rate was assessed. There is a need for more clinical studies on the malignant transformation of AC, as lip cancer is a public health concern. High-risk populations, including those living in tropical regions, have excessive exposure to UV radiation, and have older aged males, fair-skinned people, and smokers should be identified to prevent AC and its malignant change. Health practitioners should facilitate early intervention to prevent the progression of AC to SCC of the lip.

Cancer incidence among merchant seafarers: an extended follow-up of a Danish cohort.

OBJECTIVES: While maritime safety generally has improved dramatically over the last century, modern seafarers are still faced with numerous occupational hazards potentially affecting their risk of chronic diseases such as cancer. The aim of this study is to offer updated information on the incidence of specific cancers among both male and female seafarers. METHODS: Using records from the Danish Seafarer Registry, all seafarers employed on Danish ships during 1986-1999 were identified, resulting in a cohort of 33 084 men and 11 209 women. Information on vital status and cancer was linked to each member of the cohort from the Danish Civil Registration System and the Danish Cancer Registry using the unique Danish personal identification number. SIRs were estimated for specific cancers using national rates. RESULTS: The overall incidence of cancer was increased for both male and female seafarers (SIR 1.19, 95% CI 1.15 to 1.23, and SIR 1.14, 95% CI 1.07 to 1.22) compared with the general population. This excess was primarily driven by increases in gastrointestinal, respiratory and genitourinary cancers. In addition, male seafarers working in areas with asbestos exposure showed significantly increased risk of mesothelioma. Finally, the male seafarers had an increased risk of lip cancer. CONCLUSIONS: The majority of cancers among seafarers continue to be lifestyle-related. However, occupational exposure to asbestos and ultraviolet radiation seems to affect the cancer pattern among the male seafarers as well.

Moesin Involvement in Oral Carcinogenesis of the Lower Lip.

BACKGROUND/AIM: This study analyzed moesin immunoexpression in 91 lip squamous cell carcinomas and its influence in patients' prognosis. MATERIALS AND METHODS: Moesin immunoexpression was evaluated at the invasive tumor front by a semi-quantitative score method. The association of moesin with the clinicopathological variables was analyzed by the Chi-square test, the survival rates were calculated by Kaplan-Meier and the survival curves compared using the log-rank test. RESULTS: The expression of moesin was strong at the invasive tumor front and weak/negative in differentiated cells such as keratin pearls. There was no association between moesin expression and the clinicopathological variables, but there was a tendency for patients with lip cancer and strong moesin expression to have lower 5- and 10-year overall and disease-free survival rates. CONCLUSION: Our results confirm the participation of moesin in oral carcinogenesis and suggest that this protein can influence the survival rates of patients with lip squamous cell carcinoma.

Cierre de grandes defectos en el labio inferior. Combinación: colgajo de Karapandzic y colgajo de deslizamiento contralateral / Closure of Large Lower Lip Defects: Combining a Karapandzic Flap and a Contralateral Sliding Flap

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Cutaneous squamous cell carcinoma of the lip: A population-based analysis.

OBJECTIVES/HYPOTHESIS: The role of cumulative ultraviolet (UV) radiation in cutaneous squamous cell carcinoma of the lip (CSCCL) is well understood. This study seeks to evaluate overall survival as well as incidence and demographics across geographic regions, given differences in UV exposure across the United States. STUDY DESIGN: Retrospective population-based analysis. METHODS: A total of 14,901 CSCCL cases were identified as being from the West, Midwest, South, or Northeast, utilizing the Surveillance, Epidemiology, and End Results registry from 1973 to 2013. Demographics, stage of disease, and treatment modalities were compared among regions. RESULTS: Of the CSCCL cases reported, 58.3%, 24.5%, 10.8%, and 6.4% originated from the West, Midwest, South, and Northeast, respectively. Patients most commonly presented with T1 tumors (81.3%), and nodal and distant metastasis was rare for patients from all regions (3.1% and 0.3%, respectively). Patients with American Joint Committee on Cancer stage II and higher were most likely from the Northeast or South. Overall, most patients were treated with surgery monotherapy (89.5%); however, surgical monotherapy was least commonly utilized in patients in the Northeast and South. Overall 5-year disease specific survival was measured at 94.7%. CONCLUSION: Although areas of high UV index are implicated in increased morbidity and mortality due to CSCCL, this study indicates that a variety of factors play a role in CSCCL incidence and outcomes in the United States. The elderly and non-white populations were identified as poor prognostic demographic factors. Investigation detailing differences in CSCCL detection and treatment may aid in the identification of higher-risk populations. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:84-90, 2018.

DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF 59 PATIENTS WITH LIP CANCER AT A TERTIARY UNIVERSITY HOSPITAL IN TURKEY - A SINGLE-CENTER EXPERIENCE.

The aim of this study is to evaluate the general demographic and clinical features, and our treatment outcomes in our patients with lip cancers, during the last 15 years. This study was conducted as a retrospective chart-review, and included a total of 59 patients with lip cancer, who were diagnosed, treated, and followed-up at the otorhinolaryngology department of Ankara University, Faculty of Medicine, Ibn-i Sina Hospital between 2000 to 2015. 91.5% of cases were male with a mean age of 61.2 years, 39% were farmers, 87% were smoking, 40.7% had dental prosthesis and 67.8% had poor oral hygiene. 93.2% of the cases had lower-lip tumors and 72.9% had stage 1 tumors. Postoperative pathological assessments revealed well-differentiated squamous-cell carcinoma in 58.3% of cases. Neck dissection was performed in 52.5% of patients. Five-year survival rate was 96.1% and 10-yeat survival was 72.1%. Patients with and without neck dissection had similar survival rates. Lip cancers are frequent cancers, and constitute a significant health problem regarding functional and esthetic roles of the mouth region. Early-diagnosis provides effective treatment, but advanced cases require complex resection and reconstruction techniques. Neck dissection in early-diagnosed cases did not contributed to survival in our cases.

Clinicopathological study of lip cancer: a retrospective hospital-based study in Taiwan.

To evaluate the clinicopathological characteristics, high-risk lifestyle factors (HRLF: chronic exposure to sun, betel quid, alcohol, and tobacco), and prognostic factors of lip cancer. The hospital records of patients with pathologically confirmed lip squamous cell carcinoma (LSCC, n = 112) and lip basal cell carcinoma (LBCC, n = 21) were reviewed. Differences in clinicopathological characteristics between LSCC and LBCC, upper and lower lip, and status of second primary tumors were compared by chi-square test and logistic regression. The prognostic factors for LSCC were analyzed by Cox regression. Compared with LBCC patients, LSCC patients were men-predominant (p < 0.001), had younger ages at onset (p < 0.001), and higher rates of lower lips involvement (p < 0.001) and HRLFs. Patients with second primary tumors were highly associated with lower lip cancer involvement (adjusted odds ratio = 2.91, p = 0.03). Patients with lower lip cancer had more HRLFs with an increasing linear trend (p = 0.004). The poorer prognostic factors of LSCC for disease-specific survival were advanced stage III/IV [crude hazard ratio (CHR) = 11.16, p < 0.001], tumor dimension >4 cm (CHR = 8.19, p = 0.006), lymph node involvement (CHR = 11.48, p < 0.001), and recurrence (CHR = 3.96, p = 0.01); whereas for disease-free survival were moderately to poorly differentiated LSCC (CHR = 4.97, p = 0.002) and alcohol consumption (CHR = 3.13, p = 0.04). LSCC and lower lip cancer were highly associated with HRLFs.