Second primary carcinoma arising on a flap: a new primary or a relapse?

BACKGROUND AND AIM: Free flaps or pedicle flaps are the mainstay of cancer surgery in the head and neck area. However, their long-term sequelae are still poorly understood. Among these, the development of a secondary primary tumor on a flap is a rare and uncertain reported event.   Methods: A computer-aided systematic literature search was performed by using the PubMed, EMBASE and Cochrane Library databases. A systematic review of the literature, following the PRISMA checklist, was carried out with the aim of analyzing all the citations reporting this second primary, with attention to risk factors, behavior, etiological causes.   Results: Overall, 27 cases of second primary squamous cell carcinoma arising on a pedicle or free flap were identified. In addition, other three cases were discussed.   Conclusions: Persistent exposure to oral stimuli such saliva, oral microbiome, smoke or a colonization by the adjacent mucosa were considered as a possible cause of second primary carcinoma. Although rare, a new neoplasm onset should know and considered as a new concept in the follow-up of patients undergoing reconstruction with free or pedicle flaps.

Machine learning in laryngeal cancer: A pilot study to predict oncological outcomes and the role of adverse features.

BACKGROUND: Laryngeal carcinoma (LC) remains a significant economic and emotional problem to the healthcare system and severe social morbidity. New tools as Machine Learning could allow clinicians to develop accurate and reproducible treatments. METHODS: This study aims to evaluate the performance of a ML-algorithm in predicting 1- and 3-year overall survival (OS) in a cohort of patients surgical treated for LC. Moreover, the impact of different adverse features on prognosis will be investigated. Data was collected on oncological FU of 132 patients. A retrospective review was performed to create a dataset of 23 variables for each patient. RESULTS: The decision-tree algorithm is highly effective in predicting the prognosis, with a 95% accuracy in predicting the 1-year survival and 82.5% in 3-year survival; The measured AUC area is 0.886 at 1-year Test and 0.871 at 3-years Test. The measured AUC area is 0.917 at 1-year Training set and 0.964 at 3-years Training set. Factors that affected 1yOS are: LNR, type of surgery, and subsite. The most significant variables at 3yOS are: number of metastasis, perineural invasion and Grading. CONCLUSIONS: The integration of ML in medical practices could revolutionize our approach on cancer pathology.

Trans oral robotic surgery for oropharyngeal cancer: A multi institutional experience.

OBJECTIVES: Trans Oral Robotic Surgery (TORS) has proved to be a safe and feasible treatment for oropharyngeal squamous cell carcinoma (OPSCC). The aim of this study is to analyse oncological outcomes of OPSCC patients treated with TORS. MATERIALS AND METHODS: This study involved 139 patients with OPSCC, treated with TORS between 2008 and 2020. Clinicopathological characteristics, treatment details and oncological outcomes were evaluated retrospectively. RESULTS: The management strategies included TORS alone in 42.5%, TORS-RT in 25.2% and TORS-CRT in 30.9%. The ENE was noted in 28.8% of neck dissections. In 19 patients clinically classified as unknown primaries, the primary was found in 73.7%. Rates of local, regional relapses and distant metastasis were 8.6%, 7.2%, and 6.5%, respectively. The 5 year- Overall Survival and Disease Free Survival were 69.6% and 71.3%, respectively. CONCLUSION: TORS fits well in the modern management of OPSCC. Although definitive CRT remains a milestone, TORS is proving to be a valid and safe treatment option. The choice of the therapeutic strategy requires evaluation by a multidisciplinary team.

Treatment of oropharyngeal squamous cell carcinoma: Is swallowing quality better after TORS or RT?

BACKGROUND AND PURPOSE: To answer an important question regarding the long-term morbidity of two oncological equivalent treatment for oropharyngeal squamous cell carcinoma (OPSCC), namely a comparison of swallowing function results between patients treated with trans-oral robotic surgery (TORS) versus patients treated with radiotherapy (RT). MATERIALS AND METHODS: Studies included patients with OPSCC treated with TORS or RT. Articles reporting complete data on MD Anderson Dysphagia Inventory (MDADI) and comparing the two treatments (TORS vs RT) were included in the meta-analysis. Swallowing assessed with MDADI was the primary outcome, the evaluation with instrumental methods was the secondary aim. RESULTS: Included studies provided a total of 196 OPSCC primarily treated with TORS vs 283 OPSCC primarily treated with RT. The mean difference in MDADI score at the longest follow-up was not significantly different between TORS and RT group (mean difference [MD] -0.52; 95% CI -4.53-3.48; p = 0.80). After treatment, mean composite MDADI scores demonstrated a slight impairment in both groups without reaching a statistical difference compared to the baseline status. DIGEST score and Yale score showed a significantly worse function in both treatment groups at 12-month follow-up compared to baseline status. CONCLUSION: The meta-analysis demonstrates that up-front TORS (+- adjuvant therapy) and up-front RT (+- CT) appear to be equivalent treatments in functional outcomes in T1-T2, N0-2 OPSCC, however, both treatments cause impaired swallowing ability. Clinicians should have a holistic approach and work with patients to develop an individualized nutrition plan and swallowing rehabilitation protocol from diagnosis to post-treatment surveillance.

The T-shaped FST pharyngoplasty step-by-step closure technique.

Pharyngocutaneous fistula is one of the most common and serious complications associated with total laryngectomy. Numerous studies tried to evaluate causative and predisposing factors associated with this complication, but data are considerably variable and there is still no international consensus. Incidence rate varies considerably between studies, with reported rates from 3% to 65%. This 4K video presents our T-shaped four-step technique (FST) for closing the pharyngeal mucosa after total laryngectomy in a step-by-step manner. All sutures were performed by braided absorbable 3/0 26 mm 1/2c (Vicryl plus 3.0; Ethicon, Somerville, NJ, USA). Recordings were performed using a Karl Storz 4K 3D VITOM® exoscope (Karl Storz SE & Co. KG, Tuttlingen, Germany). We have been described this technique through a high-definition video, showing each step, and tips from the authors. Our T-shaped pharyngoplasty closure technique can be divided into four steps: 1. "Key Stitches"; 2. "Area Refinement Stitches"; 3. "Modified Connell Suture"; 4. "Modified Purse String Suture." Our T-shaped FST closure technique proved to be an effective and reproducible method, which we feel could be the preferred choice for primary pharyngoplasty closure.

An unusual approach for a cervical mass: sternotomy for the treatment of a giant cervico-thoracic lipoma.

BACKGROUND AND AIM: Lipoma is a benign mesenchymal tumor. It is a very common tumor and in 13% of cases occurs in head and neck. Giant lipomas are extraordinary and cervical involvement with mediastinal extension is an exceedingly rare presentation. Only a few cases of thoracic extension are reported in literature. METHODS: We describe the case of a 62-years-old man with a giant cervico-mediastinic lipoma which required a combined approach through cervicotomy and sternotomy to ensure surgical radicality. Differential diagnoses could be thymolipoma, liposarcoma or familiar lipomatosis. RESULTS: The mass was removed en-bloc with thymus and locoregional lymph nodes. The patient recovered uneventfully. CONCLUSIONS: The aim of this report is to discuss potential pitfalls of differential diagnosis and implementation of the therapeutic treatment. Focus on the relevance of performing fluorescence in situ hybridization (FISH) for MDM2 amplification is reported, a necessary technique for the differential diagnosis. (www.actabiomedica.it).

Cell-Free Human Papillomavirus-DNA for Monitoring Treatment Response of Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

OBJECTIVES/HYPOTHESIS: The aim of this study was to assess the value of cell-free human papillomavirus-DNA (cfHPV-DNA) as a diagnostic test for the post-treatment surveillance of patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) through a systematic review and meta-analysis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search was conducted in three databases (MEDLINE, Embase, and Scopus) in January 2021. The population included patients with HPV-positive HNSCC. The intervention was the use of the repeated liquid biopsy with circulating HPV-DNA detection during follow-up. The outcome was to establish the value of cfHPV-DNA as a diagnostic test for the post-treatment surveillance of patients with HPV-positive HNSCC. RESULTS: Ten studies included in the meta-analysis provided a total of 457 patients with HPV-positive HNSCC. The meta-analytic study estimated the diagnostic performance of cfHPV-DNA as follows: pooled sensitivity and specificity of 0.65 (95% confidence interval [CI]: 0.40-0.84) and 0.99 (99% CI: 0.96-0.99), respectively; positive and negative likelihood ratios of 62.5 (99% CI: 22.9-170.2) and 0.05 (99% CI: 0.013-0.24), respectively; and pooled diagnostic odds ratio of 371.66 (99% CI: 60.4-2286.7). CONCLUSION: Currently, the follow-up protocol for HNSCC patients includes routine clinical evaluation and radiological imaging. Biomarkers to monitor this disease are not established. Considering its high specificity, cfHPV-DNA represents a potential confirmatory test in the case of positive positron emission tomography and computed tomography. In the near future, cfHPV-DNA could be used as a biomarker for monitoring the treatment response during the clinical trials of de-escalation therapy or immunotherapy. Larger sample sizes and the homologation of study protocols and methodology are needed to better establish its utility in the clinical practice. Laryngoscope, 132:560-568, 2022.

Microenvironmental Factors in Oral Cavity Squamous Cell Carcinoma Undergoing Surgery: Correlation with Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced MRI.

BACKGROUND: In this prospective study, we hypothesized that magnetic resonance imaging (MRI) may represent not only the tumor but also the microenvironment, reflecting the heterogeneity and microstructural complexity of neoplasms. We investigated the correlation between both diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced (DCE)-MRI with the pathological factors in oral cavity squamous cell carcinomas (OSCCs). METHODS: A total of 37 patients with newly diagnosed OSCCs underwent an MR examination on a 3T system. The diffusion coefficient (D), the kurtosis parameter (K), the transfer constants Ktrans and Kep and the volume of extravascular extracellular space ve were quantified. A histogram-based approach was proposed to investigate the associations between the imaging and the pathological factors based on the histology and immunochemistry. RESULTS: Significant differences in the DCE-MRI and DKI parameters were found in relation to the inflammatory infiltrate, tumor grading, keratinization and desmoplastic reaction. Relevant relationships emerged between tumor-infiltrating lymphocytes (TILs) and DKI, with lower D and higher K values being associated with increased TILs. CONCLUSION: Although a further investigation is needed, these findings provide a more comprehensive biological characterization of OSCCs and may contribute to a better understanding of DKI-derived parameters, whose biophysical meaning is still not well-defined.

Concurrent and Concordant Anal and Oral Human PapillomaVirus Infections Are Not Associated with Sexual Behavior in At-Risk Males.

Men who have sex with men (MSM) harbor the highest prevalence of anal and oral Human Papillomavirus (HPV) infection, particularly if HIV-infected. We investigated anal and oral HPV infections in HIV-infected and HIV-uninfected MSM, to assess concurrent (HPV detected at both sites, irrespective of the genotypes), and concordant infections (same genotype[s] detected at both sites). Matched anal and oral samples from 161 MSM (85 HIV-infected, and 76 HIV-uninfected) were tested with the Linear Array. Determinants of concurrent and concordant infections were evaluated using logistic regression. Anal infections were 4 to 7 times more frequent than oral infections in both study groups (p < 0.0001). Concurrent infections were not significantly different in HIV-infected (25.9%) and HIV-uninfected MSM (17.1%), p = 0.18. A concordant infection was found in 15 MSM (9.3%). Concordance was for one genotype in 14 individuals and for four genotypes in the remaining subject. In the overall population, only age was independently associated with a concurrent infection (AOR = 3.10, 95% CI: 1.34-7.19 for >39 vs. ≤39 years). None of the parameters of sexual behavior showed independent association with concordant infections. Among MSM, concordant anal and oral HPV infections do not seem to be explained by sexual behavior, but might derive from sequential acquisition by autoinoculation.

Antibody Persistence 6 Months Post-Vaccination with BNT162b2 among Health Care Workers.

BACKGROUND: We present immunogenicity data 6 months after the first dose of BNT162b2 in correlation with age, gender, BMI, comorbidities and previous SARS-CoV-2 infection. METHODS: An immunogenicity evaluation was carried out among health care workers (HCW) vaccinated at the Istituti Fisioterapici Ospitalieri (IFO). All HCW were asked to be vaccine by the national vaccine campaign at the beginning of 2021. Serum samples were collected on day 1 just prior to the first dose of the vaccine and on day 21 just prior to the second vaccination dose. Thereafter sera samples were collected 28, 49, 84 and 168 days after the first dose of BNT162b2. Quantitative measurement of IgG antibodies against S1/S2 antigens of SARS-CoV-2 was performed with a commercial chemiluminescent immunoassay. RESULTS: Two hundred seventy-four HWCs were analyzed, 175 women (63.9%) and 99 men (36.1%). The maximum antibody geometric mean concentration (AbGMC) was reached at T2 (299.89 AU/mL; 95% CI: 263.53-339.52) with a significant increase compared to baseline (p < 0.0001). Thereafter, a progressive decrease was observed. At T5, a median decrease of 59.6% in COVID-19 negative, and of 67.8% in COVID-19 positive individuals were identified with respect to the highest antibody response. At T1, age and previous COVID-19 were associated with differences in antibody response, while at T2 and T3 differences in immune response were associated with age, gender and previous COVID-19. At T4 and T5, only COVID-19 positive participants demonstrated a greater antibody response, whereas no other variables seemed to influence antibody levels. CONCLUSIONS: Overall our study clearly shows antibody persistence at 6 months, albeit with a certain decline. Thus, the use of this vaccine in addressing the COVID-19 pandemic is supported by our results that in turn open debate about the need for further boosts.

Multiparametric MRI Evaluation of Oropharyngeal Squamous Cell Carcinoma. A Mono-Institutional Study.

The aim of this paper is to define the pre-treatment radiological characteristics of oropharyngeal squamous cell carcinoma (OPSCC) using morphological and non-morphological magnetic resonance imaging (MRI), based on HPV status, in a single-institution cohort. In total, 100 patients affected by OPSCC were prospectively enrolled in the present study. All patients underwent 1.5T MR with standard sequences, including diffusion-weighted imaging with and intravoxel incoherent motion (IVIM-DWI) technique and a dynamic contrast-enhanced (DCE) MRI. For all patients, human papillomavirus (HPV) status was available. No statistically significant differences in the volume of primary tumors (PTs) and lymph nodes (LNs) were observed based on HPV status. When comparing the two patient groups, no significant differences were found for the PT radiologic characteristics (presence of well-defined borders, exophytic growth, ulceration, and necrosis) and LN morphology (solid/cystic/necrotic). Tumor subsite, smoking status, and alcohol intake significantly differed based on HPV status, as well as ADC and Dt values of both PTs and LNs. We detected no significant difference in DCE-MRI parameters by HPV status. Based on a multivariate logistic regression model, the combination of clinical factors, such as tumor subsite and alcohol habits, with the perfusion-free diffusion coefficient Dt of LNs, may help to accurately discriminate OPSCC by HPV status.

Early Onset of SARS-COV-2 Antibodies after First Dose of BNT162b2: Correlation with Age, Gender and BMI.

BACKGROUND: The first goal of the study was to analyse the antibody titre 21 days after the first dose of the BNT162b2 vaccine in a group of 252 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and body mass index (BMI). METHODS: Participants had a nasopharyngeal swab for SARS-CoV-2 and were assessed for the presence of SARS-CoV-2 antibodies at baseline and 21 days after the BNT162b2 priming dose. RESULTS: First dose of BNT162b2 activated immune responses in 98% of the participants. Five HWC had no increase in antibody titre 21 days after the first dose. Antibody titre was greater in young (<38 years) vs. older participants (<38 vs. 47-56 p = 0.002; <38 vs. >56 p = 0.001). Higher antibody levels were detected in underweight vs. pre-obesity group (p = 0.026) and in normal-weight vs. pre-obesity group (p = 0.007). This association was confirmed after adjusting for age (p = 0.0001) and gender (p = 0.00001). CONCLUSIONS: Our study demonstrates that a single dose of BNT162b2 activates the immune response, and being young and normal-weight correlate positively with this response. Larger specifically designed clinical trials are needed to validate these results.

Predictors of Oral Infection by Mucosal and Cutaneous Human Papillomaviruses in HIV-Infected and Uninfected Men Who Have Sex with Men of the OHMAR Study.

Mucosal Human Papillomaviruses (HPVs) play a role in the development of a subset of head and neck cancers. Cutaneous HPVs are abundantly present in the oral cavity. The determinants of these infections have not been extensively investigated. We assessed the correlates of oral infection by alpha and beta and/or gamma HPVs in HIV-infected and uninfected men who have sex with men (MSM). Oral rinse-and-gargles were collected with a mouthwash. Alpha and beta/gamma HPVs were detected using the Linear Array HPV genotyping test and a multiplex PCR combined with Luminex technology, respectively. Multiple logistic regression was performed to identify independent predictors of oral HPV infection. Overall, 193 HIV-uninfected and 117 HIV-infected MSM were enrolled. Among HIV-infected MSM, the only determinant of alpha HPV infection was the number of lifetime oral sex partners (AOR: 8.26, 95% CI: 2.26-30.16). The strongest determinant of beta/gamma HPV infection was represented by practicing condomless receptive oral sex (AOR: 10.76, 95% CI: 1.56-74.17). Age was independently associated with alpha HPV infection in HIV-uninfected MSM. Beta/gamma HPV infection was not associated with sexual behavior in these subjects. In conclusion, predictors of oral infection differ between HIV-infected and uninfected MSM, as well as between alpha and beta/gamma HPVs.

Initial observations on age, gender, BMI and hypertension in antibody responses to SARS-CoV-2 BNT162b2 vaccine.

BACKGROUND: Literature data suggests that age, gender and body mass index (BMI) could be associated with difference in immune responses to vaccines. The first goal of the study was to analyze the antibody titre seven days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCWs). The second goal was to analyze how antibody titre changes in correlation with age, gender, BMI and hypertension. METHODS: An immunogenicity evaluation was carried out among HCWs vaccinated at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy. All HCWs were asked to be vaccinated by the Italian national vaccine campaign at the beginning of 2021. 260 vaccinated HCWs were enrolled in the study. All eligible participants were assigned to receive the priming dose in two weeks' time and the booster dose exactly 21 days thereafter. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Quantitative measurements of IgG antibodies against S1/S2 antigens of SARS-CoV-2 were performed with a commercial chemiluminescent immunoassay. Presence of SARS-Cov-2 in nasopharyngeal swab was determined by commercial RT-PCR testing. FINDINGS: 248 HWCs were analyzed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7) was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p<0.0001. Multivariate linear regression analysis of AU/mL by age, gender and BMI multivariate was performed by the inclusion of covariates. This analysis demonstrated that age (p<0.0001) and gender (p = 0.038) are statistically associated with differences in antibody response after vaccination, whereas BMI and hypertension have no statistically significant association (p = 0.078 and p = 0.52 respectively). INTERPRETATION: 99.5% of HCW developed a humoral immune response and female and young participants seem to have an increased capacity to mount humoral immune responses. BMI and hypertension seem not associated with difference in immune response to the vaccine. FUNDING: None.

Airway obstruction from tracheostomy balloon cuff herniation during oral cancer removal. Emergency successfully managed and lessons learnt from device malfunction.

OBJECTIVE: Tracheostomy tube cuff balloon herniation is a rare event and can determine airway obstruction. Sometimes the obstruction is not very evident but, if it is not correctly solved, can determine a severe hypoxia with patient's death. MATERIAL AND METHODS: We present a 49-year-old male patient, with cT4aN0M0 squamous cell carcinoma of the oral cavity, who was admitted to the hospital for definitive surgical resection. Due to mass an endo-oral intubation was not possible, so a surgical tracheotomy was performed. General anaesthesia was induced with Propofol (2 mg/kg) and Fentanil (1 mcg/kg) without gas. Surgery commenced via a trans-oral and trans-cervical approach, but it was halted after approximately 2 min as oximetry demonstrated a progressive fall from 98% to 78%. After confirmation of correct function of anaesthetic devices, the endotracheal cannula was tested; although surgeon deflated the tube cuff, repositioned the tube, and re-inflated the cuff, oxygen saturation did not change. So, the cannula was changed and patient's saturation increased up to normal value. RESULTS: The balloon cuff of the cannula showed a herniation, responsible of insufficient ventilation. CONCLUSIONS: Cuff herniation should be considered in case of unexpected airway obstruction, and a systematic, rapid approach to investigation and management should ensure timely identification and correction.

Evolving Profile of HPV-Driven Oropharyngeal Squamous Cell Carcinoma in a National Cancer Institute in Italy: A 10-Year Retrospective Study.

Globally, 30% of oropharyngeal carcinomas (OPSCC) are caused by Human Papillomavirus (HPV). Recently, increasing incidence trends for HPV-driven OPSCC have been reported in many countries and changes in the typical HPV-positive OPSCC patient have been recorded, with an increase in the median age and diagnoses in women. We investigated the characteristics of the OPSCC patients attending an Italian Cancer Institute from 2010 to 2019 and assessed possible changes overtime of demographic, behavioral, and clinico-pathologic variables of HPV-driven OPSCC. Overall, 339 OPSCCs were evaluated. HPV-DNA and p16 positivity were 48.7% and 55.2%, respectively, with an HPV-driven fraction (i.e., HPV-DNA+/p16+) of 48.3%. We observed a significant increase overtime in the rate of HPV-associated cases (53.7% in 2015-2019 vs. 40.3% in 2010-2014, p = 0.019). The rate of HPV-driven cases was significantly higher among women, never smokers, patients with T1-T2 tumors, and with nodal involvement. A trend was also observed toward an increase in HPV-driven OPSCCs among patients >61 years, women, former smokers, and patients with no nodal involvement in 2015-2019. Our findings consolidate the observation that HPV-associated OPSCCs are also increasing in Italy. Moreover, they suggest that the profile of the HPV-driven OPSCC patient might be changing.

Oral Infection by Mucosal and Cutaneous Human Papillomaviruses in the Men Who Have Sex with Men from the OHMAR Study.

Both mucosal and cutaneous Human Papillomaviruses (HPVs) can be detected in the oral cavity, but investigations regarding the epidemiology of cutaneous HPVs at this site are scarce. We assessed mucosal (alpha) and cutaneous (beta and gamma) HPV infection in oral samples of HIV-infected and uninfected men who have sex with men (MSM). Oral rinse-and-gargles were collected from 310 MSM. Alpha HPVs were detected using the Linear Array, whereas beta and gamma HPVs were detected using multiplex PCR and Luminex technology. An amplicon-based next-generation sequencing (NGS) protocol was applied to a subset of samples collected from 30 HIV-uninfected and 30 HIV-infected MSM. Beta HPVs were significantly more common than alpha types (53.8% vs. 23.9% for HIV-infected subjects, p < 0.0001; 50.3% vs. 17.1% for HIV-uninfected subjects, p < 0.0001). Gamma HPVs were also frequently detected (30.8% and 25.9% in HIV-infected and uninfected MSM, respectively). NGS produced 2,620,725 reads representative of 146 known HPVs (16 alpha-PVs, 53 beta-PVs, 76 gamma-PVs, one unclassified) and eight putative new HPVs, taxonomically assigned to the beta genus. The oral cavity contains a wide spectrum of HPVs, with beta types representing the predominant genus. The prevalence of beta and gamma HPVs is high even in immunorestored HIV-infected individuals. NGS confirmed the abundance of cutaneous HPVs and identified some putative novel beta HPVs. This study confirms that cutaneous HPVs are frequently present at mucosal sites and highlights that their pathological role deserves further investigation since it may not be limited to skin lesions.