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The combined endoscopic endonasal, transethmoidal, transcribriform approach with endoscope-assisted supraorbital craniotomy is a minimally invasive approach that can be used as an alternative to the classic transcranial, transfacial, or combined craniofacial approaches to lesions of the anterior cranial fossa. This approach is best used for lesions that extend anteriorly to the frontal sinus, laterally beyond the lamina papyracea, and inferiorly into the ethmoid sinus. This chapter details the approach as well as closure of the combined endoscopic endonasal, transethmoidal, transcribriform approach with endoscope-assisted supraorbital craniotomy.
Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour proven by microscopic examination in the absence of any substantial treatment. This paper presents the case of an older woman whose advanced-stage tonsillar squamous cell carcinoma was noted to have spontaneously regressed at seven months.
A 66-year-old woman presented with a 4-month history of dysphagia and odynophagia in September 2020. An exophytic tumour was seen on the right tonsil; this was diagnosed radiologically and histologically as a squamous cell carcinoma of the tonsils, with tumour–node–metastasis staging of T4aN0M0. The patient received best supportive care. Seven months later, the oropharyngeal lesion had disappeared, with no treatment. Subsequent computed tomography imaging showed radiological resolution of the previously noted right-sided oropharyngeal lesion.
Several mechanisms of spontaneous regression are discussed. Further studies should review this case in conjunction with other reports of spontaneous tumour regressions, to elucidate underlying mechanisms.
Head and neck cancer (HNC) accounts for 5% of all new cancer cases and most were locally advanced. Positron emission tomography/computed tomography (PET/CT) in radiotherapy practice in locally advanced head and neck squamous cell carcinoma (HNSCC) is being used in staging and proper contouring. Proper staging is essential for accurate treatment decision.
This is a prospective phase II study conducted as a single institute centre to evaluate the role of PET/CT-treatment in staging, contouring and response evaluation of 30 patients with locally advanced HNSCC in contrast to CT scan. Our cases did not undergo radical surgery for the primary tumour, and biopsy was taken with PET/CT post-treatment to evaluate response.
Median age of patients was 49·4 years (minimum age of 32 years and maximum of 68 years). Males were predominant 22 (73·3%). Nasopharynx was the predominant site 16/30 (53·3%). PET/CT changed the overall staging in 40% of the patients (upstaged in 36·7% and downstaged in 3·3%). Gross tumour volume (GTV) of PET/CT was smaller in 23 patients (76·7%) and larger in 5 (16·7%) than the GTV of conventional CT, whereas GTV of lymph nodes of PET/CT was larger in 20 patients (67·7%) and smaller in 4 (13·3%). PET/CT study detected bone metastasis in two nasopharyngeal carcinoma patients and two cases of 2nd primary tumours which were not detected using conventional CT. The Cox-regression model showed that the median standardised uptake volume (SUV) of the initial tumour had been a dependent predictor of death in patients with HNSCC (p-value = 0·033) where the risk of death was 0·725 times among patients with high SUV of the initial tumour. Consequently, the size of GTV of the tumour was significant in the prediction of death (p = 0·018).
18F-FDG-PET/CT is useful for staging, radiotherapy delineation as well as aiding proper decision making, in addition to assessment of treatment response in HNSCC patients.
Coronavirus disease 2019 was declared a pandemic on 11th March 2020. All non-urgent surgical procedures have been postponed indefinitely. The British Association of Head and Neck Oncology state that only those with treatable head and neck cancer unsuitable for alternative treatment should undergo surgery. This paper details our management of a patient who tested positive for severe acute respiratory syndrome coronavirus-2 days before curative surgery for laryngeal cancer.
By following British Association of Head and Neck Oncology guidance, a 49-year-old male scheduled for total laryngectomy and bilateral neck dissection for a T3 transglottic squamous cell cancer was pre-operatively identified as an asymptomatic carrier of severe acute respiratory syndrome coronavirus-2. Following 14-day isolation and laboratory proven viral clearance, he underwent successful major surgery. He was managed throughout the peri- and post-operative phases without complications or adverse effects on staff.
With careful planning, previous coronavirus disease 2019 positive status should not prevent an individual from undergoing successful total laryngectomy and bilateral neck dissection in a safe and timely manner during the pandemic.
To report our experience of diagnosis, investigation and management in patients who had undergone laryngectomy secondary to previous squamous cell carcinoma, who were subsequently infected with severe acute respiratory syndrome coronavirus-2 during the coronavirus disease 2019 pandemic.
Four post-laryngectomy patients with laboratory-proven severe acute respiratory syndrome coronavirus-2 infection were admitted to our institution from 1 March to 1 May 2020. All patients displayed symptoms of coronavirus disease 2019 and underwent investigations, including swab and serum sampling, and chest X-ray where indicated. All were managed conservatively on dedicated coronavirus disease 2019 wards and were discharged without the requirement of higher level care.
It is hypothesised that laryngectomy may offer a protective effect against severe or critical disease in severe acute respiratory syndrome coronavirus-2 infection. We hope sharing our experience will aid all practitioners in the management of this, often intimidating, cohort of patients.
This paper presents a case of an isolated pituitary fossa metastasis on a background of a previously treated tonsillar squamous cell carcinoma.
A 64-year-old male, diagnosed with a primary p16-negative squamous cell carcinoma in the right tonsil, was treated with a course of chemoradiotherapy with curative intent. Positron emission tomography/computed tomography, performed at six months post-treatment, revealed a good local response and no distant metastases. The patient was placed on routine follow up at two-monthly intervals. Two months into follow up, he presented with a right-sided oculomotor nerve palsy and partial Horner's syndrome. Imaging and biopsy revealed a pituitary fossa metastasis (p16-negative squamous cell carcinoma), and a further positron emission tomography/computed tomography visualised this lesion. He was deemed unsuitable for further intervention and underwent palliative radiotherapy for symptom control.
This case represents the first reported isolated pituitary fossa metastasis from a tonsillar squamous cell carcinoma. A high degree of clinical suspicion is recommended, along with a low threshold for biopsy and a cautioned use of positron emission tomography/computed tomography, when investigating such patients.
Human immunodeficiency virus infected patients have a three-fold increased risk of head and neck squamous cell carcinoma. The British HIV Association recommends human immunodeficiency virus testing in all new diagnoses of head and neck squamous cell carcinoma.
This observational study aimed to examine the current routine practice of human immunodeficiency virus testing in patients with newly diagnosed head and neck squamous cell carcinoma, and to address the importance of this test in promoting the early diagnosis and treatment of human immunodeficiency virus.
All head and neck cancer multidisciplinary teams in England were questioned on their protocol for human immunodeficiency virus testing in new diagnoses of head and neck squamous cell carcinoma.
Only 1 out of 30 hospitals leading head and neck multidisciplinary teams (3.3 per cent) routinely offered human immunodeficiency virus testing in this high-risk patient group.
This observational study highlights that head and neck specialists are not aware of, and are consequently not complying with, routine human immunodeficiency virus testing as recommended by the British HIV Association guidelines.
There has been little reported on the transoral reconstructive options following salvage transoral robotic surgery. This paper describes the facial artery musculomucosal flap as a method to introduce vascularised tissue to a previously irradiated resection bed.
A facial artery musculomucosal flap was used to reconstruct the lateral pharyngeal wall in 13 patients undergoing salvage transoral robotic surgery for oropharyngeal squamous cell carcinoma. Outcomes recorded include flap and donor site complications, length of stay, and swallowing and speech outcomes.
There were no immediate or late flap complications, or cases of delayed wound healing in this series. There were two facial artery musculomucosal related complications requiring surgical management: one bleed from the facial artery musculomucosal donor site and one minor surgical revision. Healing of the flap onto the resection bed was successful in all cases.
The facial artery musculomucosal flap provides a suitable transoral local flap option for selected patients undergoing salvage transoral robotic surgery for oropharyngeal malignancies.
Gestational nutrition is widely recognized to affect an offspring’s future risk of lifestyle-related diseases, suggesting the involvement of epigenetic mechanisms. As folic acid (FA) is a nutrient essential for modulating DNA methylation, we sought to determine how maternal FA intake during early pregnancy might influence tumor sensitivity in an offspring. Dams were maintained on a FA-depleted (FA(−)) or normal (2 mg FA/kg; FA(+)) diet from 2 to 3 days before mating to 7 days post-conception, and their offspring were challenged with chemical tumorigenesis using 7,12-dimethylbenz[a)anthracene and phorbol 12-myristate 13-acetate for skin and 4-nitroquinoline N-oxide for tongue. In both squamous tissues, tumorigenesis was more progressive in the offspring from FA(−) than FA(+) dams. Notably, in the skin of FA(−) offspring, the expression and activity of cylindromatosis (Cyld) were decreased due to the altered DNA methylation status in its promoter region, which contributed to increased tumorigenesis coupled with inflammation in the FA(−) offspring. Thus, we conclude that maternal FA insufficiency during early pregnancy is able to promote neoplasm progression in the offspring through modulating DNA methylation, such as Cyld. Moreover, we propose, for the first time, “innate” utero nutrition as the third cause of tumorigenesis besides the known causes—hereditary predisposition and acquired environmental factors.
In Pakistan, oral cancer ranks as the most common malignancy in males and the second most common malignancy in females. Cyclooxygenase-2 has been explored as an agent of carcinogenesis in oral and other neoplasms. This study aimed to observe the expression of cyclooxygenase-2 in oral squamous cell carcinoma, and to correlate the expression with patients’ clinical features and overall and disease-free survival.
Immunohistochemistry for cyclooxygenase-2 was performed on a total of 100 oral squamous cell carcinoma formalin-fixed, paraffin-embedded blocks. Expression was correlated with patients’ clinicopathological variables and overall and disease-free survival.
Cyclooxygenase-2 was overexpressed in 55 per cent of oral squamous cell carcinoma patients. Overexpression was correlated with overall survival (p = 0.013) and disease-free survival (p = 0.001) on univariate analysis. However, on multivariate analysis, cyclooxygenase-2 was associated with only disease-free survival (p = 0.044) and not overall survival (p = 0.208).
Expression of cyclooxygenase-2 is associated with poorer overall survival and higher rates of recurrence in oral squamous cell carcinoma patients.
Cervical metastasis from an unknown primary site invariably results in pan-mucosal irradiation if a primary tumour is not identified. Transoral robotic and laser-assisted mucosectomy are valid techniques to increase diagnostic rates, but these remain restricted to certain centres. This paper describes, in detail, a technique in which mucosectomy is performed via endoscopic electrocautery.
Patients were prospectively recruited between May 2017 and June 2018. Inclusion criteria stipulated biopsy-proven metastatic cervical squamous cell carcinoma, with negative findings on magnetic resonance imaging and positron emission tomography/computed tomography, in addition to examination under anaesthetic, tonsillectomy and ‘blind’ tongue base biopsies without tumour identification, prior to mucosectomy.
Of nine patients, a mucosal primary was identified in four (44.4 per cent), for which ipsilateral intensity-modulated radiotherapy was advocated in three and completion tongue base resection in the fourth. Dysplasia was demonstrated in two further patients, which provided information relevant to radiotherapy fields and post-treatment surveillance. No surgical complications were identified.
Tongue base mucosectomy using electrocautery and conventional tonsillectomy equipment is a safe, effective technique in the identification of cervical metastasis from an unknown primary site. It expands the potential breadth of use, quickens prolonged diagnostic pathways and obviates the necessity for pan-mucosal irradiation.
The role of panendoscopy in the modern investigation of head and neck cancer is changing with the development of improved radiological techniques, in-office biopsy capabilities and the low rate of synchronous primary tumours. This study aimed to review the indications for panendoscopy in the investigation of newly diagnosed head and neck cancer.
A retrospective review was conducted of 186 patients with newly diagnosed head and neck cancer, between January 2014 and December 2015, at two tertiary centres.
Obtaining a tissue diagnosis was the most common indication for panendoscopy (65 per cent), followed by surgical planning including transoral robotic surgery suitability assessment (22.6 per cent), and the investigation of carcinoma of an unknown primary (11.3 per cent). Two synchronous primary tumours were identified, generating a yield of 1.1 per cent.
Panendoscopy remains integral in the assessment of transoral robotic surgery suitability. Refining indications for modern panendoscopy could reduce the need for this procedure in this cohort of patients.
To assess five-year local control and ultimate local control rates of patients treated for locally advanced T3–4 glottic carcinoma with surgery only, radiotherapy only, or surgery plus radiotherapy. Cancer-specific survival, overall survival and rates of malignancy development were also assessed.
A retrospective review was conducted on patients from 1967 to 2015, with analysis of local control, ultimate local control, overall survival and cancer-specific survival performed using Kaplan–Meier and Cox regression.
Of 169 eligible patients, the majority (59 per cent) were treated with surgery plus radiotherapy, with laryngectomy being the most common surgical procedure. Local control and ultimate local control rates were higher with surgery only (94.1 per cent) and surgery plus radiotherapy (87.9 and 86.8 per cent respectively), compared to radiotherapy only (46.8 and 52.4 per cent) (both p < 0.001). Cancer-specific survival, overall survival and malignancy development did not differ between groups.
Surgery, with or without radiotherapy, offers significantly higher five-year local control and ultimate local control for patients with advanced glottic carcinoma, compared to radiotherapy only.
To evaluate for the first time the prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in a Middle-Eastern population, and to determine associations between human papillomavirus profiles and clinicopathological characteristics.
A retrospective chart review was conducted of all patients treated for oropharyngeal squamous cell carcinoma at the Hotel Dieu de France University Hospital (Beirut, Lebanon) between January 2010 and 2016. Existing formalin-fixed paraffin-embedded tumour samples were analysed. Human papillomavirus DNA viral load and p16 expression were evaluated using polymerase chain reaction and immunohistochemistry respectively.
Thirty patients (mean age of 60 years) were included. Twenty-seven per cent of patients were p16-positive/human papillomavirus DNA positive, 53 per cent were p16-negative/human papillomavirus DNA negative and 20 per cent were p16-positive/human papillomavirus DNA negative. Human papillomavirus 16 was the most frequent subtype (75 per cent). Smoking and alcohol consumption were significantly lower in the human papillomavirus positive group compared to the human papillomavirus negative group (p = 0.049 and 0.004, respectively).
Human papillomavirus rate was lower than reported rates in Western populations. Possible explanations include differences in social and cultural behaviours.
This study associated Human Papillomavirus (HPV) infection and other clinical parameters with five-year survival of oral squamous cell carcinoma patients at a tertiary care hospital in Karachi, Pakistan.
A total of 140 patients diagnosed with oral squamous cell carcinoma were enlisted. HPV status and subtypes were established through polymerase chain reaction performed in a previously published study. Clinical data including five-year survival were obtained through institutional medical records.
Ninety-five patients (67.9 per cent) were positive for HPV. Of these, 85 patients were HPV 16 positive while 2 patients were HPV 18 positive. The mean survival time for HPV positive patients was 44.3 months, whereas survival time for HPV negative patients was 46.9 months. Univariate analysis showed that HPV status in oral squamous cell carcinoma was not a statistically significant factor in determining five-year survival rate (p = 0.386).
There is a high prevalence of HPV positive oral squamous cell carcinoma in Pakistan; however, there is no difference in the five-year survival rate when compared to HPV negative oral squamous cell carcinoma.
To analyse the relationship of pre-operative body mass index with surgical complications and oncological outcomes in patients undergoing microvascular reconstruction for head and neck squamous cell cancer.
A retrospective review was conducted of 259 patients who underwent microvascular free flap reconstruction after head and neck ablative surgery.
Mean body mass index was 22.48 kg/m2. There were no correlations between body mass index and: flap failure (p = 0.739), flap ischaemia (p = 0.644), pharyngocutaneous fistula (p = 0.141) or wound infection (p = 0.224). The five-year disease-specific survival rate was 63 per cent. On univariate analysis, the five-year disease-specific survival rate was significantly correlated with pre-operative body mass index, based on Kaplan–Meier survival curves (p = 0.028). The five-year disease-specific survival rates in underweight, normal weight, overweight and obese groups were 47 per cent, 55 per cent, 65 per cent and 80 per cent, respectively.
Pre-operative body mass index was a useful predictor for recurrence and survival in patients who underwent microvascular reconstruction for head and neck squamous cell cancer.
Several risk factors for depression in patients with oropharyngeal cancer have been determined. However, it is unknown whether human papillomavirus associated oropharyngeal cancer, which has a distinct clinico-demographic profile, modulates this risk.
A retrospective analysis was conducted of patients with oropharyngeal cancer. These patients had completed a 10-item depression screening questionnaire before receiving treatment for their disease from 2011 to 2014. Associations between patient or disease characteristics and depression screening questionnaire results were investigated.
The study comprised 69 patients, 31 (44.9 per cent) of whom screened positive for depression. There were no significant differences in distributions of clinico-demographic or histopathological characteristics, including human papillomavirus tumour status, by depression screen result.
This population has a high risk for depression, but no obvious risk factors, including human papillomavirus tumour status, were associated with an elevated risk. This inability to risk-stratify patients by clinico-demographic or disease characteristics emphasises the importance of regular depression screening for all patients in this population.
Metastatic cutaneous squamous cell carcinoma is the most common parotid malignancy in Australasia. Prognostic indicators are not clearly defined and the extent of surgical resection required is controversial.
A retrospective analysis was conducted of 63 patients who underwent surgery for metastatic cutaneous squamous cell carcinoma of the parotid gland at a tertiary hospital over a 10-year period.
The five-year overall survival rate was 53 per cent, the disease-specific survival rate was 78 per cent and the locoregional control rate was 72 per cent. Immunosuppression and no adjuvant radiotherapy were associated with a significant reduction in disease-specific survival. None of the factors analysed had a significant effect on locoregional control rates.
More extensive surgery, including lateral temporal bone resection, may improve local control rates in cases of more advanced disease. The reduced survival of immunocompromised patients must be considered when planning their management.
This study aimed to: describe the incidence of thyroid gland involvement in advanced laryngeal cancer, analyse patterns of spread to the thyroid and elucidate predictors of thyroid involvement.
A retrospective review was performed on patients who underwent laryngectomy from 1991 to 2015 as a primary or salvage treatment for squamous cell carcinoma of the larynx, hypopharynx or base of tongue. The incidence of thyroidectomy during total laryngectomy, type of thyroidectomy, incidence of gland involvement, route of spread, and positive predictors of spread were analysed and reported.
A total of 188 patients fit the inclusion criteria. Of these, 125 (66 per cent) underwent thyroidectomy. The thyroid was involved in 10 of the 125 patients (8 per cent), 9 by direct extension and 1 by metastasis. Cartilage invasion was a predictor of thyroid gland involvement, with a positive predictive value of 26 per cent.
There is a low incidence of thyroid gland involvement in laryngeal carcinoma. Most cases of gland involvement occurred by direct extension. Thyroidectomy during laryngectomy should be considered for advanced stage tumours with cartilage invasion.