Results of salvage neck dissection after chemoradiation in locally advanced head and neck squamous cell carcinoma.

PURPOSE: Salvage surgery is mandatory when regional persistence/recurrence after chemoradiation. The aim of this study is to describe the outcomes of salvage surgery. METHODS: A retrospective study was conducted in patients with locally advanced head and neck squamous cell carcinoma that were primarily treated with chemorradiation and underwent salvage neck dissection (ND) with suspected recurrent/persistent nodal disease. All patients had a response evaluation at 12 weeks through clinical examination and computed tomography-positron emission tomography. Decision for ND was taken in case of suspected persistence or if there was suspicion of recurrence, histologically confirmed. RESULTS: There were 40 patients included. 32/40 (80%) ND were done because of confirmed/suspected persistence and 8/40 (20%) were done because of recurrences. Persistence was confirmed histologically in 14/32 (43.8%) cases and recurrence in 6/8 (75%) cases. Median survival from diagnosis was 39 months (95% CI 28.162-49.838). Significant differences were observed between patients who had viable tumour cells in the sample and those who did not, but the differences were only significant when only deaths due to tumour progression were considered (p = 0.014). 14/32 (43.8%) patients with suspected or confirmed persistence developed a recurrence after the ND and 3/8 (37.5%) patients with suspected or confirmed recurrence developed a new recurrence. New recurrences were more frequent in cases that had viable tumor in the specimen. CONCLUSIONS: Patients with nodal persistence/recurrence have a poor prognosis, even after salvage surgery. However, in a substantial number of patients the disease is controlled after ND, so it should be offer to these patients.

Closing of large pharyngostomes with free flaps and proposal of a new classification.

PURPOSE: Large pharyngocutaneous fistulas or pharyngostomes are difficult complications to solve, which generate high morbidity and mortality, a poor quality of life and an increase in health costs. Its management must be comprehensive according to general, local and regional factors. We review our experience in treating these pharyngostomes with free flaps. METHODS: Retrospective study analyzing the results of the reconstruction of 50 patients using free flaps during the period 1991-2019. We exclude patients who required free-flap reconstruction due to primary tumor or those who resolved in other ways. The different types of reconstruction were classified into three types. RESULTS: The 86% (43) were men, and the mean age was 57 years (25-76). In 48% (24/50) the flaps performed were anterolateral thigh (ALT), in 24% (12/50) forearm, in 22% (11/50) parascapular, in 4% (2/50) jejunum and in 2% (1/50) ulnar. A salivary by-pass was placed in 74% (37/50) of the cases. Four cases (8%) presented flap necrosis and two patients died due to treatment. In 86% (43/50) there was some type of complication and 34% (17/50) required surgical revision. 94% (45/48) were able to reintroduce oral feeding. CONCLUSION: According to our experience, we proposed a regardless size classification: type 1 when only a mucous closure (pharynx) are required (6%), type 2 exclusively skin for cutaneous coverage (10%) and mixed type 3 (mucous and skin) (84%). The treatment of large pharyngostomes with free flaps, despite its complexity, is in our experience the best option for its management.

Lectin-like transcript 1 (LLT1) expression is associated with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma.

The interaction of lectin-like transcript 1 (LLT1) with CD161 inhibits Natural Killer cell activation. Overexpression of LLT1 contributes to the immunosuppressive properties of tumor cells. However, there are little data about LLT1 expression in human solid tumors. The objective of this paper is to investigate the relationship between LLT1 expression with the clinicopathologic features and its impact on the prognosis of head and neck cutaneous squamous cell carcinoma (cSCC). LLT1 expression was analyzed on paraffin-embedded tissue samples obtained from 100 patients with cSCC by immunohistochemistry. The estimator of Fine and Gray was used to estimate the cumulative incidence curves for relapse. Proportional Hazard models and Hazard ratios (HRs) were used for studying the risk of tumor relapse and mortality. LLT1 strong expression was a significant risk factor for nodal metastasis with crude and adjusted ratios (HRs) of 3.40 (95% CI 1.39-9.28) and 3.25 (95% CI 1.15-9.16); and for cSCC specific death of 6.17 (95% CI 1.79-21.2) and 6.10 (95% CI 1.45-25.7). Strong LLT1 expression is an independent predictor of nodal metastasis and poor disease-specific survival and it might be helpful for risk stratification of patients with cSCC.

Ethical issues in non-intervention trials for thyroid cancer.

In recent years, the increasing numbers of small, apparently indolent thyroid cancers diagnosed in the world have encouraged investigators to consider non-intervention as an alternative to surgical management. In the following pages, the prospect of a non-intervention trial for thyroid cancer is considered with attention to the ethical issues that such a trial might raise. Such a non-intervention trial is analyzed relative to 7 ethical considerations: the social or scientific value of the research, the scientific validity of the trial, the necessity of fair selection of participants, a favorable risk-benefit ratio for trial participants, independent review of the trial, informed consent, and allowing the study participants to withdraw from the trial. A non-intervention trial for thyroid cancer is also considered relative to the central concept of equipoise.

Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 1).

Head and neck cancer is one of the most frequent malignances worldwide. Despite the site-specific multimodality therapy, up to half of the patients will develop recurrence. Treatment selection based on a multidisciplinary tumor board represents the cornerstone of head and neck cancer, as it is essential for achieving the best results, not only in terms of outcome, but also in terms of organ-function preservation and quality of life. Evidence-based international and national clinical practice guidelines for head and neck cancer not always provide answers in terms of decision-making that specialists must deal with in their daily practice. This is the first Expert Consensus on the Multidisciplinary Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It offers several specific recommendations based on the available evidence and the expertise of our specialists to facilitate decision-making of all health-care specialists involved.

Histological analysis of tonsillectomies: relationship with surgical technique, post-operative pain and haemorrhage.

OBJECTIVES: There is no consensus on the optimal technique to decrease post-tonsillectomy morbidity. Histopathological analysis can estimate collateral tissue damage. This study compared histological findings for tonsils removed by cold or electrocautery dissection and their relationship with post-operative complications. METHODS: Two adult out-patient groups were included in the study: 37 who underwent cold dissection and 37 who underwent electrocautery dissection. Histological analysis was used to assess tissue damage. RESULTS: Tissue damage was significantly higher in the electrocautery dissection group (p = 0.002), as were the number of emergency department visits (p = 0.01) and the need for supplemental analgesia (p = 0.013). Patients in the cold dissection group experienced less pain (p = 0.001) and fewer secondary haemorrhage episodes. CONCLUSION: Cold dissection produces less tissue damage, which is associated with lower incidence of complications. This study suggests that cold dissection is the technique of choice for tonsillectomy.

The impact of family history on non-medullary thyroid cancer.

INTRODUCTION: Around 10% of patients with non-medullary thyroid cancer (NMTC) will have a positive family history for the disease. Although many will be sporadic, families where 3 first-degree relatives are affected can be considered to represent true familial non-medullary thyroid cancer (FNMTC). The genetic basis, impact on clinical and pathological features, and overall effect on prognosis are poorly understood. METHODS: A literature review identified articles which report on genetic, clinical, therapeutic and screening aspects of FNMTC. The results are presented to allow an understanding of the genetic basis and the impact on clinical-pathological features and prognosis in order to inform clinical decision making. RESULTS: The genetic basis of FNMTC is unknown. Despite this, significant progress has been made in identifying potential susceptibility genes. The lack of a test for FNMTC has led to a clinical definition requiring a minimum of 3 first-degree relatives to be diagnosed with NMTC. Although some have shown an association with multi-centric disease, younger age and increased rates of extra-thyroidal extension and nodal metastases, these findings are not supported by all. The impact of FNMTC is unclear with all groups reporting good outcome, and some finding an association with more aggressive disease. The role of screening remains controversial. CONCLUSION: FNMTC is rare but can be diagnosed clinically. Its impact on prognostic factors and the subsequent role in influencing management is debated. For those patients who present with otherwise low-risk differentiated thyroid cancer, FNMTC should be included in risk assessment when discussing therapeutic options.

Moving towards personalised therapy in head and neck squamous cell carcinoma through analysis of next generation sequencing data.

Personalised medicine tumour boards, which leverage genomic data to improve clinical management, are becoming standard for the treatment of many cancers. This paper is designed as a primer to assist clinicians treating head and neck squamous cell carcinoma (HNSCC) patients with an understanding of the discovery and functional impact of recurrent genetic lesions that are likely to influence the management of this disease in the near future. This manuscript integrates genetic data from publicly available array comparative genome hybridization (aCGH) and next-generation sequencing genetics databases to identify the most common molecular alterations in HNSCC. The importance of these genetic discoveries is reviewed and how they may be incorporated into clinical care decisions is discussed. Considerations for the role of genetic stratification in the clinical management of head and neck cancer are maturing rapidly and can be improved by integrating data sets. This article is meant to summarise the discoveries made using multiple genomic platforms so that the head and neck cancer care provider can apply these discoveries to improve clinical care.

Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma.

OBJECTIVE: Complement C4d-containing fragments have been proposed as diagnostic markers for lung cancer. The purpose of this study was to evaluate the presence of C4d in oropharyngeal (OPSCC) and oral (OSCC) squamous cell carcinomas. SUBJECTS AND METHODS: C4d staining was analyzed by immunohistochemistry in 244 OPSCC surgical specimens. C4d levels were quantified by ELISA in resting saliva samples from 48 patients with oral leukoplakia and 62 with OSCC. Plasma samples from 21 patients with leukoplakia and 30 with oral carcinoma were also studied. RESULTS: C4d staining in OPSCC specimens was associated with nodal invasion (P = 0.001), histopathologic grade (P = 0.014), disease stage (P = 0.040), and focal-adhesion kinase expression (P < 0.001). No association was found between C4d and prognosis. Saliva C4d levels were higher in patients with oral cancer than in subjects with leukoplakia (0.07 ± 0.07 vs 0.04 ± 0.03 µg ml(-1) , P = 0.003). The area under the ROC curve was 0.63 (95%CI: 0.55-0.71). Salivary C4d levels in stage IV patients were higher than in patients with earlier stages (P = 0.028) and correlated with tumor size (P = 0.045). Plasma C4d levels also correlated with salivary C4d levels (P = 0.041), but differences between patients with oral cancer and subjects with leukoplakia were not significant (1.26 ± 0.59 vs 1.09 ± 0.39 µg ml(-1) , P = 0.232). CONCLUSION: C4d-containing fragments are detected in oral primary tumors and are increased in saliva from patients with OSCC.

Trismus in patients with head and neck cancer: etiopathogenesis, diagnosis and management.

BACKGROUND: Trismus indicates severely restricted mouth opening of any aetiology. A mouth opening of 35 mm or less should be regarded as trismus. Aim of this study was to review the etiopathogenesis, incidence, treatment and prevention of trismus in patients with head and neck cancer. OBJECTIVE OF REVIEW: Trismus is frequently seen in patients suffering from malignant tumours of the head and neck. The reported prevalence of trismus in those patients varies considerably in the literature and ranges from 0 to 100% depending on the tumour site and extension. Trismus may worsen or remain the same over time, or the symptoms may reduce, even in the absence of treatment. When a patient presents with trismus after tumour treatment, it is important to determine whether the trismus is the result of the treatment, or is the first sign of a recurrence. Restricted mouth opening may impede inspection of the oral cavity as needed for dental care, and particularly for oncologic follow-up. CONCLUSIONS: Mouth opening after radiotherapy (RT) decreases on average by approximately 20% compared to mouth opening prior to RT. The prevalence of trismus increases with increasing doses of RT to mastication structures. The use of intensity-modulated RT seems to lower the percentage and severity of RT-induced trismus. Treatment of trismus can be conservative (with either medical or physical therapy) or surgical. Exercise therapy is the mainstay of treatment and exercise should start as soon as possible after treatment. The prevention of trismus, rather than its treatment, is the most important objective.

The relation between hypoxia-inducible factor (HIF)-1alpha expression with p53 expression and outcome in surgically treated supraglottic laryngeal cancer.

OBJECTIVE: The purpose of this study was to examine whether a relationship exists between HIF-1alpha expression and the pro-apoptotic protein p53 in supraglottic laryngeal squamous cell carcinomas (SCCs), which could provide information concerning patient prognosis. METHODS: The study population was composed of 106 previously untreated men with SCC of the supraglottic larynx. All the patients underwent surgical resection of the tumor and bilateral neck dissection. Immunohistochemical analysis of HIF-1alpha and p53 protein expression was performed in relation with clinicopathological parameters and prognosis. RESULTS: HIF-1alpha nuclear expression was detected in 71% of primary carcinomas and 55% of the paired lymph node metastases. There was a significant positive correlation between HIF-1alpha and T-classification but no associations were observed with other clinicopathological variables and with prognosis. There was no correlation between the expression of HIF-1alpha and p53. HIF-1alpha overexpression in combination with p53 immunostaining was not associated with disease recurrence or survival. CONCLUSION: The data suggest that HIF-1alpha expression does not have a prognostic value in surgically treated supraglottic laryngeal SCC, and that immunohistochemical determination of p53 does not allow improving the clinical significance of HIF-1alpha.

Distinctive clinicopathological associations of amplification of the cortactin gene at 11q13 in head and neck squamous cell carcinomas.

Amplification of the 11q13 region is a prevalent genetic alteration in head and neck squamous cell carcinoma (HNSCC). We investigated the clinical significance of cortactin (CTTN) and cyclin D1 (CCND1) amplification in both malignant transformation and tumour progression. CTTN and CCND1 amplification was analysed by differential and real-time PCR in a prospective series of laryngeal/pharyngeal carcinomas and archival premalignant tissues. CTTN mRNA and protein expression were respectively determined by real-time RT-PCR and immunohistochemistry, and correlated with gene status. Molecular alterations were associated with clinicopathological parameters and disease outcome. CTTN and CCND1 amplifications were respectively found in 75 (37%) and 90 (45%) tumours. Both correlated with advanced disease; however, only CTTN amplification was associated with recurrence and reduced disease-specific survival (p = 0.0022). Strikingly, CTTN amplification differentially influenced survival depending on tumour site (p = 0.0001 larynx versus p = 0.68 pharynx) and was an independent predictor of reduced survival in the larynx (p = 0.04). CCND1 amplification was detected in early tumourigenesis and increased with the severity of dysplasia. Importantly, CTTN amplification was only found in high-grade dysplasias that progressed to invasive carcinoma. CTTN gene status strongly correlated with mRNA and protein expression. Furthermore, CTTN overexpression correlated significantly with reduced disease-specific survival (p = 0.018). Taken together, these data indicate that CTTN may serve as a valuable biomarker to identify patients with laryngeal tumours at high risk of recurrence and poor outcome.

[Functional outcomes of transoral laser surgery of supraglottic carcinoma]. / Resultados funcionales de la laringectomía supraglótica láser.

OBJECTIVES: To analyse the functional outcome of patients with supraglottic carcinomas treated by transoral laser surgery. METHODS: The clinical records of 55 patients who underwent transoral laser surgery were reviewed. Swallowing capacity, surgical complications, requirements for tracheotomies, percentage of decannulations, laryngeal paralysis, stenosis, aspiration associated pneumonia, time to remove the nasogastric tube and postsurgical stay in hospital were the studied variables. RESULTS: 52% of the patients had a normal or within functional limits swallowing performance. 18% suffered aspiration pneumonia. 13% developed a laryngeal stenosis. 7% suffered of laryngeal palsy. 18 tracheostomies were performed, of them 10 could be reverted. The mean time to remove the nasogastric tube was 9 days. The mean hospital stay was 23 days. CONCLUSIONS: The main functional advantages of transoral laser surgery for supraglottic carcinoma, when compared with the conventional approach, are a lower incidence of temporary tracheotomies, a faster removal of the nasogastric feeding tube, and a lower incidence of pharyngocutaneous fistulas (0%).

[Orthotopic murine model of head and neck squamous cell carcinoma]. / Modelo murino ortotópico de carcinoma epidermoide de cabeza y cuello.

PURPOSE: To develop a reliable animal model able to reproduce the behavior of head and neck squamous cell carcinomas (HNSCC). This model should facilitate our understanding of the molecular mechanisms of tumorigenicity and progression of these tumors, as well as the evaluation of novel therapies. MATERIAL AND METHODS: 20 nude mice nu/nu were injected intraorally and submucosally with a cell line derived from a human squamous cell carcinoma of the glottis. RESULTS: 90% of the mice developed locally agressive squamous cell carcinomas, invading the surrounding muscle fibers and into loose connective tissue structures. All the tumors showed perineural growth. Four (22%) of the 18 mice showed bone destruction, and 22% vascular invasion. Tumor cells invaded lymphatic vessels in all the specimens, and 100% of the mice developed regional lymph node metastases. None of the animals developed haematogenous metastases. CONCLUSIONS: We present a metastasing model of HNSCC that resembles its human counterpart in many aspects.

[Efficacy of postoperative radiation therapy for squamous cell carcinoma of the head and neck: results of a prospective randomised clinical trial]. / Eficacia de la radioterapia postoperatoria en los carcinomas epidermoides de cabeza y cuello: resultados de un ensayo prospectivo aleatorizado.

INTRODUCTION: A prospective randomised clinical trial was designed to assess the usefulness of postoperative radiotherapy (RT) in terms of loco-regional control and survival in patients with surgically treated advanced (stages III to IV) head and neck squamous cell carcinoma with negative margins and without extracapsular extension in positive neck nodes. MATERIALS AND METHODS: Between 1994 and 1995, 51 patients were included in the study and 42 were considered evaluables (from which 21 received postoperative RT). A minimum follow-up of 3 years was required. RESULTS: The loco-regional recurrence rates were identical in irradiated and non-irradiated patients (15/21 cases--70%--in each group), as was the 5-year disease-specific survival (35% for both groups). The only parameter that was associated with a reduced disease-specific survival was the presence of regional lymph node metastases. CONCLUSION: Our results suggest that postoperative RT does not increase loco-regional control or survival in patients with completely resected advanced head and neck squamous cell carcinoma.

[Nasal polyposis: postoperative long term results (5 years) after endoscopic sinus surgery]. / Poliposis nasal: resultados a los 5 años tras cirugía endoscópica nasal.

The purpose of this study is to evaluate the results after endoscopic sinus surgery in cases of nasal polyposis. We include 54 patients with diffuse nasal polyposis suffering from nasal obstruction. An endoscopic sinus surgery under general anesthesia with excision of the polyposis was performed. There were no complications. The patients were followed closely and treated with local and systemic steroids. After 5 years, the 75% of these patients were free of nasal symptoms and in the 67% the mucosa appeared normal. We also review the influence of some factors (ASA triad, anosmia, allergy...) in the recurrence of the disease.

Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features.

The aim of this study was to investigate the prognostic significance of E-cadherin expression in squamous cell carcinomas of the supraglottic larynx. 101 primary carcinomas were retrospectively studied. The level of E-cadherin expression was determined by immunohistochemistry. There was a significant correlation between decreased E-cadherin expression and the presence of nodal metastases (P=0.007). T-stage (P=0.025) and histological grade (P=0.043) were also associated with nodal metastases. Multivariate analysis confirmed that these three parameters were independent predictors of nodal metastases. Decreased E-cadherin expression also correlated with an increase in recurrence rates (P=0.019). However, in multivariate analysis only pathological N-stage was significantly associated with disease-specific survival. We conclude that E-cadherin is an independent predictor of nodal metastases in supraglottic squamous cell carcinomas. Determination of E-cadherin expression levels might be useful in identifying patients with clinically negative lymph nodes who are at risk of occult metastases, allowing more effective treatment strategies to be implemented.

Variability of genetic alterations in different sites of head and neck cancer.

OBJECTIVE: Tumors arising from different sites of the head and neck area have different clinical behavior. However, most of the studies on genetic alterations in head and neck squamous cell carcinomas do not make a distinction between the sites within this area. The objective of this study is to compare the genetic alterations in three different sites of the head and neck (larynx, oropharynx, and hypopharynx). STUDY DESIGN: Prospective study. METHODS: Thirty-eight laryngeal, 29 oropharyngeal, and 37 hypopharyngeal carcinomas were studied. DNA from tumor and healthy tissue was evaluated for amplification of the oncogenes at 11q13 region (CCND1, FGF3, FGF4 and EMS1) and of the oncogenes MYC and ERBB1; for integration of the human papillomavirus (HPV) types 6b and 16; for loss of heterozygosity (LOH) at p53 and NAT2; and for the cellular DNA content. RESULTS: FGF3 and FGF4 showed a significantly higher frequency of amplification in hypopharyngeal tumors (P =.006 and P =.0002, respectively). CCND1 amplification had a nearly statistically significant (P =.072) higher frequency of amplification in hypopharyngeal tumors. Aneuploid tumors were found in a significantly lower proportion in the larynx (P =.03) compared with the other sites. For the other genetic alterations, no significant differences among the three sites were found. CONCLUSIONS: These results suggest that cancers originating from different sites in the head and neck may have different tumor biology. Therefore, they should be considered as different entities.

P53 allelic loss and outcome in patients with squamous cell carcinoma of the head and neck.

Although loss of heterozygosity (LOH) on the p53 locus is frequent in squamous cell carcinomas of the head and neck (SCCHN), controversy still remains regarding the prognostic significance of such an event. Eighty consecutive SCCHN were studied. DNA was extracted from matched sets of normal and tumour tissue and used for polymerase chain reaction amplification of microsatellite markers located in the p53 locus. LOH at the p53 locus was found in 39 (70%) of the 56 informative cases. No relationship was found between p53 LOH and age, site, T stage, N stage, disease stage, and histological differentiation. Recurrence occurred in 53% of the cases with LOH and in 58% of the cases without it (P = 0.28). Moreover, no statistically significant association was found between p53 LOH and disease-specific survival (log-rank P = 0.98). These data suggest that although LOH at the p53 locus is common in SCCHN, this finding is of little clinical significance.