Survivin/BIRC5 as a novel molecular effector at the crossroads of glucose metabolism and radioresistance in head and neck squamous cell carcinoma.

BACKGROUND: Metabolic reprogramming and abnormal glucose metabolism are hallmarks of head and neck squamous cell carcinoma (HNSCC). Certain oncogenes can promote cancer-related metabolic changes, but understanding their crosstalk in HNSCC biology and treatment is essential for identifying predictive biomarkers and developing target therapies. METHODS: We assessed the value of survivin/BIRC5 as a radioresistance factor potentially modulated by glucose for predicting therapeutic sensitivity and prognosis of HNSCC in a cohort of 32 patients. Additionally, we conducted in vitro experiments to explore the role of survivin/BIRC5 in glucose metabolism concerning radiation response. RESULTS: Tumoral BIRC5 expression is associated with serum glucose and predicts locoregional disease-free survival and lower BIRC5 mRNA levels are associated with better outcomes. Upregulation of BIRC5 by radiation depends on glucose levels and provokes a pro-tumoral and radioresistant phenotype in surviving cells. CONCLUSIONS: Survivin/BIRC5 might be independently associated with the risk of recurrence in patients with HNSCC.

Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma.

INTRODUCTION: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils × monocytes × platelets)/lymphocytes, has been proposed as a prognostic biomarker in different tumour models. The aim of this study is to analyse the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Retrospective study of 1187 patients with HNSCC treated at our centre between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. RESULTS: PIV value was significantly associated with toxic consumption (0.001), tumour location (0.0001), tumour extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category I: PIV < 136.3 (n = 118, 9.9%), category II: PIV 136.3-451.1 (n = 594, 50.0%), category III: PIV 451.1-1,141.2 (n = 357, 30.1%), and category IV: PIV > 1141.2 (n = 118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumour extension, or location of the primary tumour. The PIV category was and independent prognostic factor of disease-specific survival in a multivariable study. CONCLUSIONS: PIV is a prognostic biomarker in patients with HNSCC.

External validation of the GETTEC algorithm for elective neck dissection in patients candidates for salvage total laryngectomy.

OBJECTIVE: To perform an external validation of the algorithm for elective treatment of the lymph node areas proposed by GETTEC for patients candidates to salvage total laryngectomy after radiotherapy. This algorithm is based on the initial lymph node status, local extension of the recurrence and time to recurrence. MATERIAL AND METHODS: Retrospective study performed in 151 patients treated with salvage total laryngectomy without clinical or radiological evidence of regional involvement at the time of diagnosis of recurrence (rcN0). The percentage of patients with occult lymph node metastases was calculated according to the algorithm proposed by GETTEC. RESULTS: A total of 14.6 % (n = 22) of the patients had occult lymph node metastases. Patients with locally advanced recurrences (rcT4) had a higher risk of occult lymph node metastases. There were no significant differences in the risk of occult lymph node metastases according to initial lymph node status or time to recurrence. When applying the algorithm proposed by GETTEC, there were no significant differences in the percentage of occult lymph node metastases between the group of patients who were candidates for follow-up (14.4 %) and those candidates for elective neck dissection (14.9 %) (P = 0.940). According to our results, patients who were candidates for an elective neck dissection were those with tumors located in the supraglottis or rcT4 glottic tumors. CONCLUSION: Our results do not validate the algorithm proposed by GETTEC for the management of the lymph nodes in rcN0 patients who are candidates for salvage total laryngectomy after radiotherapy.

Results of surgical treatment of lymph node metastases in patients with cutaneous squamous cell carcinoma of the head and neck.

INTRODUCTION: Out of all cutaneous squamous cell carcinomas originating in the head and neck (HNCSCC), 2-4% are associated with parotid or cervical lymph node metastasis. The aim of this study is to analyse the prognostic factors of patients with HNCSCC with lymph node involvement treated surgically. Additionally, we aim to compare the prognostic capacity of the classification of these patients according to the 8th edition of the TNM, and an alternative classification proposed by O'Brien et al. PATIENTS AND METHODS: Retrospective review of 65 patients with HNCSCC with lymph node metastasis treated surgically during the period 2000-2020. RESULTS: During the study period we carried out 13 neck dissections and 52 parotidectomies + neck dissection in patients with lymph node metastases from a HNCSCC. The great majority of patients (89.2%) received post-operative radiotherapy. The 5 year disease-specific survival was 69.9%, and the overall survival it was 42.8%. The classification proposed by O'Brien et al., based on the parotid or cervical location of the lymph node metastases, and the size and number of the metastatic lymph nodes, had a better prognostic capacity than the TNM classification. CONCLUSIONS: The surgical treatment of lymph node metastases in patients with HNCSCC achieved a high disease control. The classification based on the location, size and number of lymph node metastases proposed by O'Brien et al had better prognostic capacity than the TNM classification.

Oncological results of salvage treatment in patients with oropharynx carcinoma treated with radiotherapy.

OBJECTIVE: To evaluate the possibilities of salvage after local recurrence in patients with oropharyngeal carcinomas treated with radiotherapy, and to analyse the prognostic factors related to the final control of the disease. METHODS: Retrospective study of 596 patients with oropharyngeal carcinoma treated with radiotherapy during the period 1991-2018. RESULTS: One hundred and eighty-one patients (30.4%) had a local recurrence. Of the patients with a local recurrence, 51 (28.2%) were treated with salvage surgery. Variables that were associated with the patient not receiving salvage surgery were age greater than 75 years, tumour location in the posterior hypopharyngeal wall, an initial tumour extent cT4, and a recurrence-free interval of less than 6 months. Five-year specific survival of patients treated with salvage surgery was 19.1% (95% CI: 7.3%-30.9%). Variables that were related to specific survival were extent of recurrence and status of resection margins. Final tumour control was not achieved in any of the patients with extensive recurrence (rpT3-4, n = 25) or positive resection margins (n = 22). CONCLUSION: Patients with oropharyngeal carcinomas treated with radiotherapy with local tumour recurrence have a limited prognosis. Most patients (71.8%) were not considered candidates for salvage surgery. The 5-year specific survival of patients treated with salvage surgery was 19.1%.

Host-related indexes in head and neck cancer.

PURPOSE OF REVIEW: Peripheral blood host-related indexes have been widely studied in cancer patients. Several authors have shown the prognostic capacity of these indexes in head and neck cancer. Therefore, there has been an increasing interest in this topic recently. RECENT FINDINGS: The main variables analyzed and used to create these host-related indexes are peripheral blood leukocytes - including neutrophils, monocytes and lymphocytes - albumin and hemoglobin levels. Other factors with proven prognostic capacity in some studies are: platelets, C-reactive protein, and BMI. Among all the combined indexes, the neutrophil-to-lymphocyte ratio has been the most accepted and used worldwide. Nonetheless, there are other indexes which group multiple of these factors that have shown better prognostic capacity, and are promising in the near future. SUMMARY: Host-related indexes are ideal biomarkers to be used on our daily-basis. There is enough evidence to start considering them when assessing patients with head and neck cancer.

Facial nerve palsy following parotid gland surgery: A machine learning prediction outcome approach.

Introduction: Machine learning (ML)-based facial nerve injury (FNI) forecasting grounded on multicentric data has not been released up to now. Three distinct ML models, random forest (RF), K-nearest neighbor, and artificial neural network (ANN), for the prediction of FNI were evaluated in this mode. Methods: A retrospective, longitudinal, multicentric study was performed, including patients who went through parotid gland surgery for benign tumors at three different university hospitals. Results: Seven hundred and thirty-six patients were included. The most compelling aspects related to risk escalation of FNI were as follows: (1) location, in the mid-portion of the gland, near to or above the main trunk of the facial nerve and at the top part, over the frontal or the orbital branch of the facial nerve; (2) tumor volume in the anteroposterior axis; (3) the necessity to simultaneously dissect more than one level; and (4) the requirement of an extended resection compared to a lesser extended resection. By contrast, in accordance with the ML analysis, the size of the tumor (>3 cm), as well as gender and age did not result in a determining favor in relation to the risk of FNI. Discussion: The findings of this research conclude that ML models such as RF and ANN may serve evidence-based predictions from multicentric data regarding the risk of FNI. Conclusion: Along with the advent of ML technology, an improvement of the information regarding the potential risks of FNI associated with patients before each procedure may be achieved with the implementation of clinical, radiological, histological, and/or cytological data.

Predictive capacity of FAT1 transcriptional expression in patients with head and neck squamous cell carcinomas treated with radiotherapy.

OBJECTIVE: To analyze the predictive capacity at the primary location of the tumor of the FAT1 transcriptional expression in patients with head and neck squamous cell carcinoma treated with radiotherapy. MATERIAL AND METHODS: We conducted a retrospective study from biopsies of the primary location of the tumor in 82 patients with head and neck squamous cell carcinoma treated with radiotherapy. The transcriptional expression of FAT1 was determined by RT-PCR. The level of FAT1 transcriptional expression was categorized according to the local control after radiotherapy using a recursive partitioning analysis. RESULTS: Elevated FAT1 transcriptional expression was associated with an increased risk of local recurrence after radiotherapy. Patients with a high expression level of FAT1 (n=18; 22.0%) had a 5-year local recurrence-free survival of 42.1% (95% CI: 18.6%-65.6%), whereas for patients with a low expression (n=64; 78.0%) it was 72.4% (95% CI: 61.5%-83.3%) (p=0.002). According to the result of a multivariate analysis, patients with a high FAT1 expression category had a 2.3-fold increased risk of local recurrence (95% CI: 1.0-5.2; p=0.043). CONCLUSIONS: Elevated FAT1 transcriptional expression was associated with a significantly increased risk of local recurrence in patients with head and neck squamous cell carcinoma treated with radiotherapy.

Relationship between transcriptional expression of pyruvate dehydrogenase and local control of disease in patients with oral cavity carcinomas.

BACKGROUND: The altered cellular metabolism is one of the hallmarks of the cancer cells, favoring the process of aerobic glycolysis, known as the Warburg effect. The pyruvate dehydrogenase (PDH) complex is one of the elements involved in this metabolic process. The present study aims to evaluate the relationship between the transcriptional expression of PDHB and the risk of local recurrence in patients with oral cavity carcinomas. METHODS: We determined the transcriptional expression of PDHB in biopsies from 41 patients with oral cavity carcinomas treated with surgery. The PDHB expression was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: During the follow-up period 13 patients (31.7%) had a local recurrence of the tumor. Considering local disease control as the dependent variable, the recursive partitioning analysis classified the patients in two categories according to high (n=16, 39.0%) or low (n=25, 61.0%) PDHB expression. Five-year local recurrence-free survival for patients with high PDHB expression was 84.8% (95% CI: 65.2-100%), and for patients with low expression it was 54.3% (95% CI: 34.3-74.2 %) (P=0.034). The results of multivariate analysis showed that patients with a low PDHB expression had a 4.90 times higher risk of local recurrence of the tumor (95% CI: 1.02-22.68, P=0.042). CONCLUSION: There is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence.

Second esophageal neoplasms after head and neck index tumor: Incidence, risk factors and prognosis.

OBJECTIVE: Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of second esophageal neoplasms. The aim of the present study is to evaluate the incidence, risk factors and prognosis of second esophageal neoplasms in patients with HNSCC. METHODS: A retrospective study of 4711 patients with index tumor in the oral cavity, oropharynx, hypopharynx or larynx between 1985 and 2020 was conducted. RESULTS: During the period analysed 149 patients (3.2%) had a second esophageal neoplasm. The incidence of second esophageal neoplasia was 0.42% per year and remained nearly constant throughout the follow-up period. According to the results of a multivariate study, the risk factors related to the appearance of second esophageal neoplasms were a history of high alcohol consumption and the location of the primary tumor in the oropharynx or hypopharynx. The 5-year disease-specific survival rate in patients with a second esophageal neoplasm, calculated from the diagnosis of this second neoplasm, was 10.5%. CONCLUSIONS: Patients with a HNSCC have an increased risk of developing of a second esophageal neoplasm. The risk factors associated with the appearance of a second esophageal neoplasm were severe alcohol consumption and the location of the primary tumor in the oropharynx or hypopharynx.

Association between maximum standarised uptake value (SUV) and local control in patients with oropharyngeal carcinoma treated with radiotherapy.

OBJECTIVE: To analyse the prognostic ability of the maximum standardised uptake value (SUVmax) on local disease control in patients with oropharyngeal carcinoma treated with radiotherapy. MATERIAL AND METHODS: Retrospective study of 105 patients with oropharyngeal carcinomas treated with radiotherapy, including chemo- and bio-radiotherapy, and who had a PET-CT scan prior to the start of treatment. RESULT: Patients with a SUVmax value higher than 17.2 at the primary tumour site had a significantly higher risk of local recurrence. The 5-year local recurrence-free survival for patients with SUVmax less than or equal to 17.2 (n = 71) was 86.5% (95% CI 78.2-94.7 %), and for patients with SUVmax greater than 17.2 (n = 34) it was 55.8% (95% CI 36.0-75.6 %) (P = 0.0001). This difference in local control was maintained regardless of patients' HPV status. Specific survival was similarly lower for patients with a SUV greater than 17.2. The 5-year specific survival for patients with SUVmax greater than 17.2 was 39.5% (95% CI: 20.6-58.3 %), significantly shorter than that of patients with SUVmax equal to or less than 17.2, which was 77.3% (95% CI: 66.9-87.6 %) (P = 0.0001). CONCLUSIONS: Patients with oropharyngeal carcinomas treated with radiotherapy with a SUVmax greater than 17.2 at the level of the primary tumour site had a significantly higher risk of local recurrence.

Results of radiotherapy in oropharyngeal carcinomas.

OBJECTIVE: To present the results of radiotherapy treatment in patients with oropharyngeal carcinomas. MATERIAL AND METHODS: Retrospective study of a cohort of 359 patients treated with radiotherapy, including chemo- and bio-radiotherapy, during the period 2000-2019. Information on human papillomavirus (HPV) status was available for 202 patients, of whom 26.2% were HPV-positive. RESULTS: Five-year local recurrence-free survival was 73.5% (95% CI: 68.8%-78.2%). The variables that were related to local disease control in a multivariate study were the local tumor extension category and the HPV status. Five-year local recurrence-free survival for patients with cT1 tumors was 90.0%, for cT2 88.0%, for cT3 70.6%, and for cT4 42.3%. Five-year local recurrence-free survival for HPV-negative tumors was 67.2% and for HPV-positive tumors 93.3%. Five-year specific-disease survival was 64.4% (95% CI: 59.1%-69.7%). Variables that were related to specific survival in a multivariate study were the patient's general condition, local and regional extent of the tumor, and HPV status. CONCLUSIONS: Five-year local recurrence-free survival of patients with oropharyngeal carcinomas treated with radiotherapy was 73.5%. Variables that were related to local control were local tumor extension and HPV status.

Exploring the Relationship between the Gut Microbiota and Ageing: A Possible Age Modulator.

The gut microbiota (GM) has been the subject of intense research in recent years. Therefore, numerous factors affecting its composition have been thoroughly examined, and with them, their function and role in the individual's systems. The gut microbiota's taxonomical composition dramatically impacts older adults' health status. In this regard, it could either extend their life expectancy via the modulation of metabolic processes and the immune system or, in the case of dysbiosis, predispose them to age-related diseases, including bowel inflammatory and musculoskeletal diseases and metabolic and neurological disorders. In general, the microbiome of the elderly tends to present taxonomic and functional changes, which can function as a target to modulate the microbiota and improve the health of this population. The GM of centenarians is unique, with the faculty-promoting metabolic pathways capable of preventing and counteracting the different processes associated with age-related diseases. The molecular mechanisms by which the microbiota can exhibit anti-ageing properties are mainly based on anti-inflammatory and antioxidant actions. This review focuses on analysing the current knowledge of gut microbiota characteristics and modifiers, its relationship with ageing, and the GM-modulating approaches to increase life expectancy.

Clinical and Virological Features of SARS-CoV-2 Variants during the Four Waves of the Pandemic in the Mexican Southeast.

We conducted a retrospective study using a population of patients who were hospitalized at Dr. Juan Graham Casasus Hospital in Villahermosa (Tabasco, Mexico) and had a positive RT-PCR test for SARS-CoV-2 between June 2020 and January 2022. We analyzed all medical records, including demographic data, SARS-CoV-2 exposure history, underlying comorbidities, symptoms, signs at admission, laboratory findings during the hospital stay, outcome, and whole-genome sequencing data. Finally, the data were analyzed in different sub-groups according to distribution during waves of the COVID-19 pandemic regarding Mexican reports from June 2020 to January 2022. Of the 200 patients who tested positive via PCR for SARS-CoV-2, only 197 had samples that could be sequenced. Of the samples, 58.9% (n = 116) were males and 41.1% (n = 81) females, with a median age of 61.7 ± 17.0 years. Comparisons between the waves of the pandemic revealed there were significant differences in the fourth wave: the age of patients was higher (p = 0.002); comorbidities such as obesity were lower (p = 0.000), while CKD was higher (p = 0.011); and hospital stays were shorter (p = 0.003). The SARS-CoV-2 sequences revealed the presence of 11 clades in the study population. Overall, we found that adult patients admitted to a third-level Mexican hospital had a wide range of clinical presentations. The current study provides evidence for the simultaneous circulation of SARS-CoV-2 variants during the four pandemic waves.

Differential characteristics of patients with squamous cell carcinoma of the head and neck with no history of tobacco or alcohol use.

OBJECTIVE: The present study aims to analyse the differential characteristics of patients with head and neck squamous cell carcinoma (HNSCC) without a history of consumption of toxic substances such as tobacco and alcohol. MATERIAL AND METHODS: We carried out a retrospective study of 4694 patients with HNSCC located in the oral cavity, oropharynx, hypopharynx or larynx treated in our centre during the period 1985-2019. RESULT: 7.7% of the patients (n = 363) did not report a history of consumption of toxic substances. The group of patients with no toxic history was older, had a higher proportion of women, a higher frequency of cases located in the oral cavity, a higher proportion of cases diagnosed in early stages, and a lower incidence of second neoplasms. The percentage of patients with no history of consumption of toxic substances increased significantly over the study period. The overall survival of patients with no history of consumption of toxic substances was significantly higher than that of patients with toxic substances use. Specific survival for patients with tumours located in the oral cavity without a history of consumption of toxic substances was significantly lower than that of patients with toxic substances use, whereas for patients with oropharyngeal carcinomas the absence of a history of consumption of toxic substances was associated with a better prognosis. CONCLUSIONS: There were differences in the epidemiological and prognostic characteristics of patients with HNSCC according to the history of consumption of toxic substances such as tobacco and alcohol.

External validation of the H-index (host index) in patients with head and neck squamous cell carcinomas.

BACKGROUND: The aim of the current study is to perform an external validation of the prognostic capacity of the H-index in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective study of 835 patients with HNSCC located in the oral cavity, oropharynx, hypopharynx, or larynx. RESULTS: When applying the cutoffs proposed in the original description of the H-index (1.5 and 3.5), we observed an orderly and significant decrease in the disease-specific survival and overall survival as H-index increased. Additionally, we were able to observe a decrease in survival as the H-index increased regardless of the location, the extension of the tumor or the type of treatment performed. CONCLUSION: We have validated the prognostic capacity of the H-index in patients with HNSCC regardless of the location of the primary tumor, the extent of the disease, or the type of treatment performed.

Is long-term screening for lung cancer justified in patients with head and neck carcinoma?

OBJECTIVE: Patients with head and neck squamous cell carcinoma (HNSCC) have a higher risk of second lung neoplasms than the general population. The aim of the present study is to evaluate the long-term incidence of second lung malignancies after the diagnosis of a HNSCC and to consider the convenience of the screening for lung cancer in these patients. MATERIAL AND METHODS: We conducted a retrospective study performed on 4954 patients with an index tumor located in the oral cavity, oropharynx, hypopharynx, or larynx during the period 1985-2017. RESULTS: During the follow-up period 469 patients (9.5%) presented a second pulmonary neoplasm. The incidence of second lung neoplasm was 1.26% per year and remained practically constant throughout the 25-year follow-up period analyzed. According to the results of a multivariate study, male patients, aged between 50 and 80 years, with a history of tobacco use, and with tumors located in the oropharynx or the supraglottis were those with the highest risk of second lung neoplasms. CONCLUSION: Patients with a HNSCC index tumor have a high risk of second neoplasms located in the lung. In order to achieve an early diagnosis of these second neoplasms, it would be advisable to establish screening protocols based on the use of low-dose lung CT, which should be maintained indefinitely during the follow-up period.

Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma.

BACKGROUND: To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC). METHODS: We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery. RESULTS: Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n = 51) was 39.2% (95% confidence interval [CI]: 25.3%-53.1%), and for patients with a low expression (n = 59), it was 63.6% (95% CI: 51.1%-76.1%) (p = 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p = 0.086). CONCLUSION: In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.

The extended SCIP flap: An anatomical and clinical study of a new SCIP flap design.

PURPOSE: We describe a variation of the superficial circumflex inguinal artery perforator (SCIP) flap, based the superficial branch of the superficial circumflex inguinal artery (SCIA) METHODS: The vascular supply of the SCIP flap was prospectively studied in 91 preoperative CT angiograms in patients undergoing reconstruction with other flaps, and verified randomly with a hand-held doppler in 20% of them. Based on the results, a new SCIP flap was designed medial and cranial to the anterosuperior iliac spine (ASIS) using the superficial branch of the SCIA. This flap was used in 39 patients to reconstruct lower limb and head and neck defects RESULTS: The superficial branch of the SCIA was found in all patients and its exit point through Hesselbach's fascia was located within a 21 mm-radius circumference drawn 18 mm medial and 17 mm distal to the ASIS in 90% of the patients. Reconstruction with this SCIP flap was successful in 92.3% of the patients. Complications were present in 17.9% of the patients CONCLUSIONS: The design of the SCIP flap can be displaced cranially to obtain a larger flap with a long and constant vascular pedicle that is based on the main trunk of the SCIA. This facilitates the reconstruction of large and complex three-dimensional defects that require thin and pliable tissue, such as those located in the head and neck or limbs. Furthermore, supramicrosurgical expertise is not required. LEVEL OF EVIDENCE: IV.