Background
Surgery of tongue tumors includes different procedures ranging from mucosal resection to complex combined resection. Numerous terms have been used to describe such procedures, but there is ...no consensus between the terminology and the extent of resection.
Methods and Results
We searched the medical literature and found a lack of published information. We undertook to describe a new classification of surgical procedures for tongue tumor resection. We based it upon the surgical anatomy of the tongue and the spread of the cancer. We posited that there were five major types of glossectomy embracing all the methods of tongue cancer resection. This classification was reviewed and endorsed by an international team of experts.
Conclusion
We propose a more precise classification than that currently in practice, thereby bringing clarity and consistency to the terminology, facilitating shared communication between surgeons, comparison between published research, and ultimately improving surgical practice and patient care.
UBC9, the sole E2-conjugating enzyme required for SUMOylation, is a key regulator of essential cellular functions and, as such, is frequently altered in cancers. Along these lines, we recently ...reported that its expression gradually increases during early stages of human papillomavirus (HPV)-mediated cervical lesions transformation. However, a better understanding of how UBC9 is exploited by transforming viral oncoproteins is still needed. In the present study, we show that in human samples HPV drives UBC9 up-regulation also in very early steps of head and neck tumorigenesis, pointing to the important role for UBC9 in the HPV-mediated carcinogenic program. Moreover, using HPV-infected pre-cancerous tissues and primary human keratinocytes as the natural host of the virus, we investigate the pathological meaning and the cellular mechanisms responsible for UBC9 de-regulation in an oncoviral context. Our results show that UBC9 overexpression is promoted by transforming viral proteins to increase host cells' resistance to apoptosis. In addition, ultrastuctural, pharmacological and genetic approaches crucially unveil that UBC9 is physiologically targeted by autophagy in human cells. However, the presence of HPV E6/E7 oncoproteins negatively impacts the autophagic process through selective inhibition of autophagosome-lysosome fusion, finally leading to p53 dependent UBC9 accumulation during viral-induced cellular transformation. Therefore, our study elucidates how UBC9 is manipulated by HPV oncoproteins, details the physiological mechanism by which UBC9 is degraded in cells, and identifies how HPV E6/E7 impact on autophagy. These findings point to UBC9 and autophagy as novel hallmarks of HPV oncogenesis, and open innovative avenues towards the treatment of HPV-related malignancies.
Oral cancer is a heterogeneous disease that develops through a complex, multi-step process. Precision medicine should help to better understand its molecular basis, integrate traditional ...classifications and have a positive impact on cancer management. To apply this information in clinical practice, we need to define its histology and identify biomarkers expressed by the tumour that provide useful information for planning tailored treatment. The most reliable information currently derives from evaluation of biomarkers on post-operative samples. To plan personalised treatment, oncologists need to assess these markers on biopsy samples. We reviewed the recent literature and identified 6 of 184 publications that compared markers measured on biopsy and post-operative samples or assessed their predictivity for the development of lymph node metastases. Data from these studies suggest that markers measured on biopsy samples can provide useful indications for tailoring treatments. However, due to their heterogeneity and low level of evidence, these results need to be confirmed by clinical studies on a large population to standardise and validate biomarkers in biopsies and to assess their reliability in other diagnostic mini-invasive procedures such as radiomics and liquid biopsy.
Literature on the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy is limited, especially for non-oropharyngeal tumours. Within the context of the HPV-AHEAD study, we aimed ...to assess the prognostic value of different tests or test algorithms judging HPV carcinogenicity in HNC and factors related to HPV positivity at the European Institute of Oncology. We conducted a retrospective cohort study (2000-2010) on a total of 696 primary HNC patients. Formalin-fixed, paraffin-embedded cancer tissues were studied. All HPV-DNA-positive and a random sample of HPV-DNA-negative cases were subjected to HPV-E6*I mRNA detection and p16
staining. Multivariate models were used to assess for factors associated with HPV positivity and proportional hazards for survival and recurrence. The percentage of HPV-driven cases (considering HPV-E6*I mRNA positivity) was 1.8, 2.2, and 40.4% for oral cavity (OC), laryngeal (LC), and oropharyngeal (OPC) cases, respectively. The estimates were similar for HPV-DNA/p16
double positivity. Being a non-smoker or former smoker or diagnosed at more recent calendar periods were associated with HPV-E6*I mRNA positivity only in OPC. Being younger was associated with HPV-E6*I mRNA positivity in LC. HPV-driven OPC, but not HPV-driven OC and LC, showed better 5 year overall and disease-free survival. Our data show that HPV prevalence in OPC was much higher than in OC and LC and observed to increase in most recent years. Moreover, HPV positivity conferred better prognosis only in OPC. Novel insights on the role of HPV in HNC in Italy are provided, with possible implications in the clinical management of these patients.
Abstract Purpose Dysphagia is a debilitating complication in head and neck cancer patients (HNCPs) that may cause a high mortality rate for aspiration pneumonia. The aims of this paper were to ...summarize the normal swallowing mechanism focusing on its anatomo-physiology, to review the relevant literature in order to identify the main causes of dysphagia in HNCPs and to develop recommendations to be adopted for radiation oncology patients. The chemotherapy and surgery considerations on this topic were reported in recommendations only when they were supposed to increase the adverse effects of radiotherapy on dysphagia. Materials and methods The review of literature was focused on studies reporting dysphagia as a pre-treatment evaluation and as cancer and cancer therapy related side-effects, respectively. Relevant literature through the primary literature search and by articles identified in references was considered. The members of the group discussed the results and elaborated recommendations according to the Oxford CRBM levels of evidence and recommendations. The recommendations were revised by external Radiation Oncology, Ear Nose and Throat (ENT), Medical Oncology and Speech Language Pathology (SLP) experts. Results Recommendations on pre-treatment assessment and on patients submitted to radiotherapy were given. The effects of concurrent therapies (i.e. surgery or chemotherapy) were taken into account. Conclusions In HNCPs treatment, disease control has to be considered in tandem with functional impact on swallowing function. SLPs should be included in a multidisciplinary approach to head and neck cancer.
Transoral laser microsurgery (TLM) is a mature approach to supraglottic cancer, while transoral robotic surgery (TORS) is emerging. The present study compared these approaches.
The first 10 patients ...(2002-2005) given TLM were compared with the first 10 (2007-2011) given TORS for cT1-3 cN0-cN2c supraglottic cancer.
A feeding tube was used in four TLM and seven TORS patients. Margins were more often positive, but operating times shorter, in TORS. All 10 TORS patients are without evidence of disease, but only six TLM patients remain disease-free after much longer follow-up. TORS was considerably less uncomfortable and fatiguing for the surgeon.
TORS seems as safe and effective as TLM. Shorter TORS operating times are probably attributable to prior experience with TLM. For laryngeal exposure, length of tube placement and margin evaluability, TLM was superior; however, this may change as TORS develops and transoral robotic instruments are optimized.
Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid ...(DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer.
We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan-Meier method.
Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%.
The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases.
Several studies have shown that the thickness of tongue carcinoma is related to prognosis and to the likelihood of cervical node metastases. We investigated whether preoperative estimates of tumor ...thickness and volume, as determined from magnetic resonance imaging (MRI), correlated with histologic thickness and might therefore predict the presence of neck metastases. We assessed relationships between histologic tumor thickness and MRI tumor thickness and volume in a retrospective series of 33 patients with squamous cell carcinoma of the tongue. Thicknesses were determined by direct measurement and by considering corrections for ulceration or tumor vegetation (reconstructed thickness). Relationships between MRI thickness and the presence or absence of homolateral and contralateral nodal metastases were also investigated. We found that MRI thicknesses correlated strongly and directly with histologic tumor thicknesses, although mean MRI thicknesses were significantly greater than histologic thicknesses. MRI thicknesses were significantly greater in patients with contralateral neck involvement than in those with no neck involvement. We conclude that MRI provides an accurate and reproducible means of estimating the thickness of tongue carcinomas, paving the way for further studies on more extensive series of patients to determine whether preoperatively determined MRI thickness can reliably predict homolateral and bilateral neck involvement.
The management of patients with cervical lymph-node metastases from unknown primary site (UPS) remains a matter of discussion. This study aimed to analyze the results and prognostic factors in a ...series of patients treated with radiotherapy.
Data from 113 patients who presented with cervical lymph nodes metastases from UPS treated from 1980 to 2004 were reviewed. Eighty-seven patients (77.0%) were squamous cell carcinoma (SCC). Ninety-one patients were treated with curative and 22 with palliative intent. Fifty-nine of 113 patients (52.2%) received surgery followed by radiotherapy and 54 of 113 (47.8%) received radiotherapy alone. Radiotherapy was delivered to the neck and pharyngeal mucosa in 67 patients and to the ipsilateral or bilateral neck in 45 patients. Twenty-one patients (18.5%) also received chemotherapy.
The 5-year overall survival rates were 40.7% for the entire group and 46.6% for the SCC subgroup. The occurrence of the occult primary was observed in 23 of 113 patients (20.3%), 19 (82.6%) within the head and neck region. At multivariate analysis, treatment with curative intent and extensive irradiation of bilateral neck and pharyngeal mucosa were favorable prognostic factors for the whole series, and treatment with curative intent, extensive irradiation of bilateral neck and pharyngeal mucosa, and absence of extracapsular spread were favorable prognostic factors for the SCC subgroup.
Patients with cervical lymph node metastases from UPS have a similar prognosis to those affected by other head and neck malignancies. Curative treatment strategies including neck dissection and extensive irradiation by three-dimensional conformal radiation therapy resulted in significantly better outcomes.
The purpose of this study was to register the accuracy and reproducibility of the multidetector computed tomography (MDCT) estimate of hypopharyngeal and laryngeal tumor volumes. Eighteen consecutive ...patients with larynx or hypopharynx squamous cell carcinoma were enrolled in this prospective trial, scheduled for surgery and examined by MDCT. A total of 72 tumor volume measurements were reported by two different operators, one of them in three different sessions, using the sum-of-areas method. The results were compared with the volume calculated by surgical sampling. The mean tumor volume measured by MDCT was 5.7 +/- 9.3 ml (range 0.1-41.6). The mean volume measured from the surgical specimens was 5.6 +/- 8.6 ml (range 0.06-33.6). The level of agreement between histological and MDCT volumes was high, with a slight tendency of MDCT to overestimation, proportional to the size. The analysis of interoperator variability showed a tendency of the more expert operator to make more accurate estimates, but the differences were not significant (P = 0.62, 0.75 and 0.63). The evaluation of the three different sessions of the less expert operator revealed a good repeatability. According to our study, MDCT estimate of tumor volume is an effective, reproducible method. MDCT tends to produce more dispersed results in case of large tumors.
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