Laryngeal Tumors Research Articles

Open Partial Laryngectomies: History of Laryngeal Cancer Surgery.

Historically, surgery was the first-choice therapy for early, intermediate and advanced laryngeal squamous cell carcinoma (LSCC). Partial laryngeal surgery has evolved in recent decades and was influenced by many historic events and the development of new technologies. Partial laryngectomies may be performed by open, endoscopic or transoral robotic approaches. In this historic paper, we describe the evolution of open partial laryngectomy techniques, indications and surgical outcomes. Since the first partial laryngectomy in 1788, many U.S., U.K. and European surgeons, including Henry Sands, Jacob da Silva Solis-Cohen and Theodor Billroth, performed this surgical procedure under local anesthesia for tuberculosis, cancer or syphilis. Partial laryngectomy gained reputation in the medical community in 1888 due to the laryngeal cancer and death of the prince of Prussia, Frederick III. Frederick III’s death represented the turning point in the history of partial laryngectomies, calling attention to the importance of semiotics, biopsy and early diagnosis in laryngeal cancers. Hemi-laryngectomy was indicated/proposed for lateral laryngeal tumors, while thyrotomy was indicated for cancers of the middle part of the vocal fold. The second landmark in the history of partial laryngectomies was the discovery of cocaine, novocaine and adrenaline and the related development of local anesthetic techniques, which, together with the epidemiological and hygienic advances of the 19th century, allowed for better perioperative outcomes. General anesthesia was introduced in the second part of the 20th century and further improved the surgical outcomes. The diagnosis of laryngeal cancer was improved with the development of X-rays and direct laryngoscopies. The 20th century was characterized by the development and improvement of vertical partial laryngectomy procedures and the development of horizontal partial laryngectomies for both supraglottic and glottic regions. The history and the evolution of these techniques are discussed in the present historical paper.

Laryngeal malignancies - epidemiological data and particularities of the cases diagnosed in Western Romania (October 2016-July 2020).

In the last decade, the incidence and mortality associated with laryngeal malignancies has experienced an unfavorable evolution in Romania, in terms of this pathology the country that has become the leader, among the European Union (EU)-27 countries. The aim of the present retrospective study was to analyze the epidemiological data regarding laryngeal cancer and histopathological (HP) particularities in patients diagnosed in Western Romania. Within three years and 10 months (during October 2016-July 2020) in Ear, Nose and Throat (ENT) Clinic of Timişoara Municipal Emergency Clinical Hospital, 194 patients with laryngeal neoplasms (LN) were diagnosed. Most of the patients were male (93.8%), from Timiş County, mainly and the neighboring Counties of Caraş-Severin, Hunedoara, Mehedinţi and Arad. Patient's average age (both sexes) was 62.6 years, with a range from 38 to 84 years and the highest percentages in the 60+ age group (48%). Regarding smoker status, the main cause of the development of the LN, 93.9% of patients were active ones. Regarding localization [International Classification of Diseases 11th Revision (ICD-11)], about 69% were malignant neoplasm of glottis (C32.0), followed by supraglottis (C32.1), larynx-unspecified (C32.9), and subglottis (C32.2). From the HP point of view, several types of tumors were identified, most of which were non-keratinized and keratinized squamous cell carcinomas (about 90%). In addition, there were identified types of verrucous carcinoma, acantholytic carcinoma, squamous papilloma, a possible pleomorphic sarcoma, and pyogenic granuloma. The data presented in this study highlight the growing incidence of LN, which mainly affect men, at an increasingly young age. It is imperative to involve specialists from nutrition, general medicine, ENT, dentistry to start awareness programs and to develop prevention protocols.

Surgical treatment of papillary thyroid carcinoma involving larynx and trachea

Objective: To evaluate the efficacy of surgical treatment of papillary thyroid carcinoma (PTC) involving larynx and trachea. Methods: A total of 1 436 cases of thyroid malignant tumors were admitted to the Department of Otolaryngology, Qilu Hospital of Shandong University from 2004 to 2019, including 110 cases of PTC involving larynx and trachea, and of which 105 cases with complete follow-up data were retrospectively analyzed. There were 42 males and 63 females, with a male/female ratio of 1∶1.5, aged from 28 to 81 years. All lesions involved trachea, including 11 cases involving both trachea and larynx. Of those 83 cases underwent laryngeal and airway wall tumor excision, and 22 cases underwent radical tumor excision plus laryngeal and trachea repair. Extubation rate was analyzed and the postoperative survival curve of patients was analyzed by Kaplan-Meier method. Results: Among 105 cases, 16 cases underwent tracheotomy and 12 cases were successfully extubated. The overall 3- 5- and 10-year survival rates were 100.0%, 86.4% and 72.5%, and the disease-free survival rates were 93.1%, 81.6% and 57.7%, respectively. There was significant difference in survival curve between the two groups (χ2=4.21, P=0.040). The 5-year and 10-year survival rates were 94.6% and 77.3% in laryngeal and tracheal tumor exclusion group, and 85.7% and 51.4% in the radical tumor resection group. There was no significant difference in the survival curves between the two groups (χ2=3.50, P=0.061). Conclusion: PTC patients with laryngeal and tracheal involvement can achieve long survival and good quality of life through reasonable surgical treatment.

684P Liquid biopsy for detection of molecular residual disease and recurrence in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) remains a substantial health burden. Early relapse and recurrent metastasis are some of the primary reasons for the poor prognosis. The recent advent of personalised assays capable to detect circulating tumour DNA (ctDNA) has enabled detection of molecular residual disease and recurrence following curative therapy. We conducted LIONESS, a single-centre prospective cohort study to assess ctDNA in plasma and saliva from HNSCC patients (Stage I-IVb) receiving primary surgery with curative intent. Samples were collected pre- and postoperatively and during clinical follow-up. Whole exome sequencing was performed on formalin-fixed paraffin-embedded tumour tissue to a median depth of 250x. Tumour-specific variants for personalised assay design (RaDaR, Inivata) were selected to analyse serial samples for evidence of molecular residual disease. Based on staging computer tomography images, tumour volumes were correlated to ctDNA and clinical parameters. In 348 longitudinal plasma samples from 46 patients analysed to date, ctDNA was detected to levels ranging from 10.8% variant allele fraction (eVAF) to as low as 0.0005%. ctDNA was detected in 10/10 cases with confirmed clinical recurrences with lead times up to 265 days. ctDNA was also detected in baseline saliva samples from patients with tumours of various anatomical locations. This included a case with two synchronous tumours, one pT4a laryngeal tumour and a second pT1 tumour of the floor of the mouth. Postoperative plasma ctDNA detection originating from the laryngeal tumour was observed 108 days ahead of clinical recurrence. Plasma ctDNA from the small pT1 tumour was not detected preoperatively and remained undetected throughout the patient’s course of management, however, ctDNA was detected at a baseline saliva sample. Work is ongoing for analysis of the full cohort of plasma and saliva samples, which will be presented at the congress. The use of ctDNA measurements in this HNSCC patient cohort has significant potential to guide treatment decisions and improve disease outcome. In future, ctDNA analysis with subsequent ctDNA-guided treatment may reduce morbidity for HNSCC patients.

1031 Survival Outcomes for Larynx-Preserving Therapy Compared to Total Laryngectomy in Advanced Laryngeal Tumour: A North-East of Scotland Cohort

Abstract Aim Advanced laryngeal tumours (stage III and IV) management remains uncertain. This study aims to investigate whether choice of organ-preservation treatment (radiotherapy or radiochemotherapy) or surgical intervention (total laryngectomy with/without adjuvant therapy) affects survival in the North-east of Scotland cohort. Method Laryngeal cancer data was prospectively collected and maintained at a tertiary care centre at NHS Grampian Scotland. This data was retrospectively analysed for overall and disease specific survival. Death from laryngeal cancer was recorded from death certificates. Statistical analysis with Cox regression was used to estimate hazard ratios for sex, smoking status, age, staging, tumour site, and treatment choice in the advanced laryngeal cancer cohort. Results A total of 311 laryngeal cancer patients were identified. 49 patients were stage III and of which 35 (71%) received organ-preserving treatment and 14(29%) underwent total laryngectomy. The corresponding numbers for 65 stage IV patients were 13 (20%) and 52 (80%) respectively. On cox regression for overall survival, reduced survival was associated (p<0.05) with choice of organ preservation and stage IV disease, fully adjusted HRs (95%CI) were 2.57 (1.42–4.66) and 3.00(1.08–8.34) respectively. For disease specific survival, no variables were found to be significant. Median follow up time from date of diagnosis to death was 1.56 years. Conclusions Organ preserving intervention was associated with a worsened overall survival in the advanced laryngeal cancer cohort. This study suggests that primary surgical intervention remains a key element in the treatment of advanced laryngeal cancer and future bigger cohort studies may be needed to evaluate this relationship.

Awake videolaryngoscopic orotracheal intubation in patients with laryngeal tumour using the C-MAC D-Blade.

ABSTRACTBackground and Aims:This study assessed the applicability of C-MAC videolaryngoscope (VL) D-blade for awake intubation in patients with laryngeal tumour. The primary study objective was to determine the rate of successful intubation in the first attempt. The other parameters recorded were number of attempts required for intubation, duration of different stages of intubation, haemodynamics, ease of intubation and patient comfort on visual analogue scale (VAS) postoperatively.Methods:Thirty patients were studied. Patients were sedated with dexmedetomidine and fentanyl as a slow bolus (over 20 min) and Ramsay sedation score was assessed. Topicalisation of the oropharynx, tonsillar pillars and base of the tongue was done with lignocaine 10% spray. Four ml of 4% lignocaine using MADgic atomiser was used for anaesthetising the glottis and the tracheal lumen.Results:Successful intubation was achieved in 86.6% patients in first attempt and 13.3% in two attempts. Total time for all intubations was less than 30 seconds. Fremantle score was F-1-C-MAC D-blade (easy intubation with full view) in 60% patients, while 23.3% had F-2-C-MAC D-blade (full view and either required more than one attempt or a modified technique), 13.3% had P-1-C-MAC D-blade (partial view with easy intubation) and 3.3% had P-2-C-MAC D-blade (partial view and required more than one attempt or a modified technique). The VAS score for anaesthesiologist’s ease and for patient’s experience was 85.83 ± 7.20 and 86.66 ± 14.46, respectively.Conclusion:C-MAC VL D-blade-assisted awake intubation is an effective and safe method to manage the airway of patients with laryngeal tumour once adequate topicalisation is ensured before the procedure.

Solitary Extramedullary Plasmacytoma of the Larynx and Secondary Laryngeal Involvement in Plasma Cell Myeloma: Single-Centre Retrospective Analysis and Systematic Literature Review.

The involvement of the larynx in plasma cell myeloma (PCM) may manifest as solitary extramedullary plasmacytoma of the larynx (sEMP-L) or as infiltration of the larynx during newly diagnosed or relapsed systemic disease with bone marrow involvement (plasma cell myeloma with laryngeal involvement, PCM-L). To increase knowledge about these rare conditions, we performed a retrospective analysis along with a comprehensive literature review of cases of sEMP-L or PCM-L. Six patients (two sEMP-L and four PCM-L) were identified in our tertiary laryngological centre from 2009 to 2021, constituting 0.88% of all malignant laryngeal tumours. The literature search yielded 187 cases, including 152 sEMP-L and 35 sPCM-L. A comparison of baseline characteristics between sEMP-L and PCM-L performed in the combined cohort of cases from literature review and retrospective analysis revealed that patients with sEMP-L were younger (56 vs. 64 years, p ≤ 0.001) and presented less commonly with thyroid or cricoid cartilage involvement (2.2% vs. 30.8%, p ≤ 0.001). The prognosis of sEMP-L was better than PCM-L (overall survival 86% vs. 55% at 5 years, p = 0.002). Analysis of potential factors that could influence progression-free survival (PFS) in the group of sEMP-L revealed that male sex and cartilage involvement negatively affected PFS in univariate analyses, while only cartilage involvement retained statistical significance in multivariate analysis (HR = 19.94, p = 0.024). In conclusion, PCM with laryngeal involvement is sporadic. Secondary involvement of the larynx during PCM might be more common than sEMP-L and is associated with worse survival. The involvement of cartilage adversely influences the outcome of sEMP-L.

A Case of Intubation Using Airway Scope Instead of Fiberoptic Bronchoscope for a Patient with a Laryngeal Tumor on the Vocal Fold

A Case of Intubation Using Airway Scope Instead of Fiberoptic Bronchoscope for a Patient with a Laryngeal Tumor on the Vocal Fold

Increased expression of ST2 on regulatory T cells is associated with cancer associated fibroblast-derived IL-33 in laryngeal cancer

Interleukin (IL)− 33 plays an essential role in regulatory T cell (Treg)-mediated immunosuppression in cancers and underlies the crosstalk between Tregs and the tumor microenvironment. However, the phenotypic characteristics of subset Tregs modulated by IL-33 and its association with the tumor microenvironment are not fully understood. This study aimed to examine the expression of ST2, the receptor of IL-33, on Tregs in tumors and to evaluate their association with cancer associated fibroblasts (CAFs) and reciprocal influences on the prognosis of laryngeal cancer. Our results showed that increased numbers of Tregs were found in laryngeal tumor tissues. Tregs in stromal IL-33-positive tumor tissues demonstrated significantly higher expression of ST2 than those in IL-33- or adjacent nontumor tissues. ST2-expressing Tregs exhibited upregulation of Ki67 and CTLA4 compared with their ST2- negative counterparts. Furthermore, IL-33 in the tumor microenvironment was mainly derived from fibroblasts. ST2 expression on Tregs was correlated with the number of IL-33-positive CAFs. High ST2 expression on Tregs, combined high ST2 on Tregs and the presence of IL-33 expressing CAFs was associated with worse survival outcomes in laryngeal cancer. This study indicated that increased expression of ST2 on Tregs is associated with microenvironmental IL-33 signaling derived from CAFs in laryngeal cancer, unraveling the special role of Tregs and fibroblasts in modulating IL-33/ST2 involved immune-evasive tumor microenvironment.

Functional Implications of Oral Papillomatosis

The papillomatous lesion has a number of implications that destabilize the normal functioning of the stomatognathic system, but also it has psychological implications. A patient with a papilloma located in an area of maximum visibility tends to be less exposed in public, to reduce socialization, to feel embarrassed. Oral papilloma affects the masticatory function, phonation, but also aesthetics. Understanding how local immunity works in patients diagnosed with oral papilloma is essential. Local immunity influences the evolution of the papillomatous oral lesion. Toll-like receptors are extremely important in the immune process of oral papilloma. Toll-like receptors can be used as indicators of lesion progression. A reduced expression of these receptors in the focus of the lesion is suggestive of pathological progress. It is also emphasized that in the oral cavity we find a well-represented local immune system which cells have an immune role and whose expression influences the evolution of the disease. The most incriminating factor in the occurrence of oral papilloma is HPV infection. The persistent inflammatory process produced by the HPV virus stimulates the development of oral, pharyngeal, laryngeal neoplasms. The HPV virus acts as a direct inducer in the process of transforming the benign lesion into a malignant lesion. Macrophages play an important role in the malignancy potential induced by the HPV virus. Macrophages are activated by increasing the metabolic rate and fighting tumor cells.

Etiological Aspects of Hoarseness of Voice Among Patients Attending in A Tertiary Care Hospital

Hoarseness of voice is much frequent in recent times and it alters the normal quality of voice Objective: To understand and assess the etiological factors of hoarseness. Methods: A Non-randomized, longitudinal and cross-sectional study was conducted in the ENT Head & Neck Surgery, Lady Reading Hospital Peshawar and Al Nafees Medical College and Hospital, Islamabad for six months duration from September 2021 to February 2022. All subjects with a history of hoarseness underwent routine specific clinical evaluation to establish diagnosis. The simple manual analysis was applied for final outcomes assessment with percentage and frequency using SPSS 21.0. Results: Participants enrolled were 150, amongst them, the patients of 21-30 and 31-40 years of age suffered from hoarseness. Likewise, 98 (72%) were males, 52 (28%) were females with a M: F proportion of 1.45: 1. According to the distribution, the utmost communal etiology observed in this study was acute laryngitis (30%), trailed by acid peptic laryngitis in 25.3%, laryngeal neoplasms in 8.7% and other includes laryngeal tuberculosis, intubation granuloma, and very rarely trauma. Conclusions: There was an etiological variability of hoarseness, varies from simple laryngitis to malignant neoplasms. For this reason, it is significant not to overlook hoarseness and a thorough examination, investigation and proper history should be taken

Evolution and Recent Advances in MIS in Head and Neck Cancers: A Comprehensive Review

Minimally invasive approaches like Endoscopic and Robotics in head and neck cancers has got a wide area of application in managing Oral cavity, pharyngeal, hypopharyngeal, Laryngeal tumours, Sinus & Base of skull tumours and Thyroid &Parathyroid tumours. Transoral approaches allow easy access to these secluded sites and removal of tumours with minimal complications. Till today surgery has remained the only curative modality in head and neck cancer. With the availability of Endoscopy, laparoscopy and Robotic systems patients requiring major surgeries for small tumours can now be offered surgery with limited human resources, good aesthetic& cosmetic outcome with better patient compliance. The MIS is still a grey area of head and neck surgeries so we like to have a comprehensive review on the evolution and recent advances in MIS.

Successful use of C-MAC® video laryngoscope for unexpected severe airway narrowing during anesthesia induction in a patient with a moderate-sized laryngeal tumor

Successful use of C-MAC^® video laryngoscope for unexpected severe airway narrowing during anesthesia induction in a patient with a moderate-sized laryngeal tumor

Abstract 2693: The vitamin D3 metabolite, 24R,25(OH)3D3 is differentially tumorigenic in ER+ and ER- laryngeal cancer cells in vitro

Abstract Due to the high vitamin D3 levels associated with improved prognosis (but not incidence) in post-menopausal breast cancer patients with ER+ tumors, vitamin D3 supplementation has been used as potential therapeutics. 24R,25(OH)2D3, an active metabolite of vitamin D3, is known to protect cartilage cells through a membrane-initiated, p53-mediated pathway, suggesting that 24R,25(OH)2D3 may affect cancer cells through a similar mechanism. Our lab has shown that the effect of 24R,25(OH)2D3 on breast cancer cell growth is highly dependent on the expression levels of ERα isoforms, specifically ERα66. Understanding the mechanisms by which 24R,25(OH)2D3 affects tumor growth in breast cancer will aid in determining its therapeutic potential in another estrogen responsive cancer, laryngeal cancer. The goal of this study was to examine the effects of 24R,25(OH)2D3 on proliferation, apoptosis, and epithelial to mesenchymal transition (EMT) in laryngeal cancer cell lines. To assess the effect of 24R,25(OH)2D3 on cell growth, UM-SCC-12 (ERα66+) and UM-SCC-11A (ERα66-) cell lines were cultured on 96 well plates until 80% confluence. Cells were serum starved for 24 hours pretreatment and then treated with full media containing either vehicle, or 24R,25(OH)2D3 (10-9M, 10-8M, or 10-7M) for 15 minutes, at which time the media were replaced with fresh media. After 20 hours, cells were harvested for proliferation by EDU assay. For other experiments cells were treated with either vehicle, or 24R,25(OH)2D3 (10-9M, 10-8M, or 10-7M) for 15 minutes and after 24 hours, cells were assessed for apoptosis (TUNEL, P53) and metastasis (OPG/RANKL). 12 hours after treatment, cells were harvested for PCR and examined for gene expression of apoptotic markers (BAX, BCL2) and various metastatic markers (SNAI1, ERBB2). 24R,25(OH)2D3 decreased proliferation in ERα66- cells (UM-SCC-11A) with the 10-7M dosage. It also increased apoptotic markers (TUNEL, P53, BAX/BCL2 expression). EMT and metastatic markers (ERBB2, SNAI1 expression) as well as bone metastatic markers (OPG/RANKL) were reduced. Conversely, in ERα66+ cells (UM-SCC-12) 24R,25(OH)2D3 had the opposite effect, increasing proliferation with 10-7M 24R,25(OH)2D3 treatment as well as decreasing DNA fragmentation (TUNEL). Treatment with 24R,25(OH)2D3 increased total P53 content and had no effect on EMT, BAX/BCL2 or other metastatic markers (SNAI1, ERBB2, OPG, RANKL). These data show that 24R,25(OH)2D3 is functionally active in laryngeal cancer tumor regulation. Contrary to results shown in breast cancer in which 24R,25(OH)2D3 was pro-tumorigenic in ERα66- cells, 24R,25(OH)2D3 was anti-tumorigenic in ERα66- laryngeal cancer cells. While this difference may be a result of a difference in other aspects of the two ERα66- cell lines, these results provide evidence of the therapeutic potential of 24R,25(OH)2D3 in laryngeal cancer and its ERα66 dependent effect. Citation Format: Cydney D. Dennis, David Joshua Cohen, Barbara D. Boyan, Zvi Schwartz. The vitamin D3 metabolite, 24R,25(OH)3D3 is differentially tumorigenic in ER+ and ER- laryngeal cancer cells in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2693.

Induction chemotherapy using carboplatin and paclitaxel followed by hypofractionated radiation therapy in locally advanced hypopharyngeal and laryngeal squamous cell cancer.

e18039 Background: Head and neck cancer (HNC) is one of the most common cancers in Pakistan due to excessive use of chewable tobacco. Locoregional control is not optimum due to advanced stage at presentation and suboptimal cancer treatment facilities. Innovations in treatment schedules are of utmost importance to tackle the problem of overburden of patients and shortage of resources for radiation therapy in the country. The aim of the study is to assess the efficacy of induction chemotherapy with carboplatin and paclitaxel (CP) followed by hypofractionated radiotherapy (HRT) in patients with locally advanced laryngeal and hypopharyngeal cancers. Methods: A total of 68 patients with biopsy proven HNC were included. Patients having primary tumor in larynx (35) and hypopharynx (33) with TNM stage III to IVB were selected. The patients were planned for three cycles of CP every three weeks in a dose of AUC = 5 and 175 mg/m² on day 1 of each cycle respectively. After three cycles of chemotherapy, patients were planned for hypofractionated radiotherapy (HRT). A total of 55 Gray (Gy) was planned with 2.75 Gy per fraction and five fractions a week. Spinal cord dose was limited to 33 Gy. Response Evaluation Criteria in Solid Tumor (RECIST) was used to assess various response rates using computed tomography (CT) six weeks after completion of HRT. Patients were followed for a median of 27.4 months to assess disease free survival (DFS) and overall survival (OS). Results: 61 patients (90%) were available for assessment. Others were excluded due to inability to complete the planned treatment. Eight patients (12%) showed disease progression during treatment and were switched to other form of treatment. Seven patients (10%) showed grade 3 mucosal toxicity and needed treatment interruption. Thirteen patients (19%) showed hematological related grade 1-2 toxicity. The complete response (CR) was seen in 18 (35%), partial response (PR) in 27 (52%) and stable disease SD in 7 (13%) patients. Three year DFS and OS were 45% and 58% respectively. Mean and median DFS (year) were 3.67±0.13 (95% confidence interval [CI] 3.19-3.94) and 4.24±0.43 (CI 3.46-4.52) respectively. Mean and median OS (year) were 3.89±0.11 (CI 3.72-4.15) and 4.12±0.23 (CI 3.87-4.38) respectively. Conclusions: Induction CP followed by HRT is a reasonable in locally advanced laryngeal and hypopharyngeal cancer. A larger phase III randomized trial will be better to define its role before routinely recommending this schedule in these patients.

SECURITY AND FEASIBILITY STUDY OF AWAKE AIRWAY SURGICAL PROCEDURES

TYPE: Abstract TOPIC: Cardiothoracic Surgery PURPOSE: The objective is to show the secure and feasibility of local and regional management under awake anesthesia and spontaneous respiration in different airway pathologies to get a diagnosis and relieve in some cases of life-threatening disease. METHODS: Prospective clinical feasibility study for patients with upper tracheal pathology were managed with local anesthetics like spray lidocaine 10% and neural blockade by topicalization. Alternatively, we use 10 ml syringe with lidocaine 2% (n=3). All patients were taken to the operating room as an emergency procedure. The principal biochemical aspect for the emergency was CO2 retention. RESULTS: Thirty-three consecutive patients admitted to the emergency room with tracheal stenosis (n=18), laryngeal and tracheal tumors (n=7), fixed tracheostomy cannula with granuloma (n = 5), obstruction with foreign body (n=2) and tracheitis (n=1) were enrolled. There were 9 women (27.3%) and 24 men (72.7%), with mean age range from 33 to 67 years old. The time of the anesthetic procedure was average 5 minutes, with no complications and a safe management. Operations included pneumatic sequential dilatation, emergency tracheostomy, tracheoplasty and tracheal biopsy. CONCLUSIONS: Our work demonstrates the complete safety of the protocol with adequate local anesthesia that allows to perform procedures in different pathologies of the airway keeping the patient secure, awake and in most of the cases ensuring an ambulatory management. CLINICAL IMPLICATIONS: In high-risk patients where oral intubation can be difficult, impossible and is not an option because of the risk to collapse due to the airway pathology, an alternative is an awake and tubeless upper airway surgery. DISCLOSURE: Nothing to declare. KEYWORD: tracheal surgery

Outcomes of cisplatin dosing strategies in locally advanced non-nasopharyngeal head and neck squamous cell carcinoma treated with definitive concurrent chemoradiation in a safety-net hospital.

e18064 Background: For patients with locally advanced non-nasopharyngeal head and neck squamous cell carcinoma (HNSCC) not amenable for resection, concurrent chemoradiation with cisplatin is the standard of care. Most popular dosing strategies for cisplatin include bolus dosing once every three weeks for a total of three cycles and once a week for seven cycles. Randomized studies comparing efficacy and tolerability of these dosing strategies have been conflicting. We examined how different dosing strategies affect outcomes in our institution, a safety-net hospital serving the medically underserved population in a large metropolitan area. Methods: We conducted a retrospective chart review of patients diagnosed with HNSCC from January 2015 to July 2021 in our institution. Patients with biopsy proven HNSCC with oral cavity, oropharyngeal, laryngeal, or hypopharyngeal primary tumor sites treated with definitive concurrent chemoradiation with cisplatin were included in the study. Those who received cisplatin bolus dosing were identified as Arm A and weekly dosing identified as Arm B. Primary outcome studied was 12-month event-free survival (EFS). We controlled for stage at diagnosis, age, p16 positivity, smoking status, treatment delay or premature discontinuation, and number of comorbidities. Secondary outcomes were rates of treatment delay or discontinuation, and median cisplatin dose received. To determine whether a preliminary association exists, a Pearson Chi-Square test for association of treatment type to 12-month EFS was utilized. To control for potential confounding variables the Mantel-Haenszel test was used on each confounder. Results: A total of 51 patients were included in the study, 36 (70.6%) with bolus and 15 (29.4%) with weekly cisplatin. After controlling for confounding variables listed above, there was no statistically significant association between Arm A or Arm B and 12-month EFS (p = 0.324). Delay or discontinuation rate for Arm A was 10 out of 36 patients (27.8%) and for Arm B was 5 out of 15 patients (33.3%). The difference in these rates were not statistically significant (p = 0.743). The median cisplatin dose received for Arm A was 300 mg/m2 and 280 mg/m2 for Arm B. Conclusions: In our institution, there was no difference in 12-month EFS or rates of treatment delay or discontinuation between patients who underwent definitive concurrent chemoradiation with bolus versus weekly cisplatin (p = 0.324). This has a significant impact on practical management of concurrent chemoradiation in our resource limited setting.

Pilot Investigation on p75ICD Expression in Laryngeal Squamous Cell Carcinoma.

Simple SummaryLaryngeal Squamous Cell Carcinoma (LSCC) is a squamous cancer with 2.4% new diagnoses each year, accounting for 25% of head and neck cancers, and has a high mortality rate. A deeper understanding of key mechanisms and knowledge of the putative target molecules of theranostic relevance are required. The receptor for neurotrophins p75NTR has been shown to be highly expressed in cancer stem cells (CSCs) of squamous epithelia, in LSCC as well as in other cancers. However, whether its cleavage product p75ICD expression, known to finely regulate the survival/death balance in neurons, is also a master regulator in cancer and LSCC in particular has not been directly addressed so far. To resolve this question, we performed a preliminary study using a limited number of LSCC specimens and studied p75ICD presence and expression pattern in LSCC specimens, showing that p75ICD may be a promising target in LSCC, requiring further investigation.We investigated the p75 Neurotrophin Receptor (p75NTR) expression and cleavage product p75NTR Intracellular Domain (p75ICD) as potential oncogenic and metastatic markers in human Laryngeal Squamous Cell Carcinoma (LSCC). p75NTR is highly expressed in Cancer Stem Cells (CSCs) of the laryngeal epithelia and it has been proposed as a marker for stemness, cell migration, and chemo-resistance in different squamous carcinomas. To investigate the clinical significance of p75NTR cleavage products in solid tumors, full-length and cleaved p75NTR expression was analyzed in laryngeal primary tumors from different-stage LSCC patients, diagnosed at the Policlinico Umberto I Hospital. Molecular and histological techniques were used to detect the expressions of p75NTR and p75ICD, and ATP Binding Cassette Subfamily G Member 2 (ABCG2), a CSC marker. We found regulated p75NTR cleavage during squamous epithelial tumor progression and tissue invasion. Our preliminary investigation suggests p75ICD expression and localization as possible features of tumorigenesis and metastaticity. Its co-localization with ABCG2 in squamous cells in the parenchyma invaded by the tumor formation allows us to hypothesize p75NTR and p75ICD roles in tumor invasion and CSC spreading in LSCC patients. These data might represent a starting point for a comprehensive analysis of p75NTR cleavage and of its clinical relevance as a potential molecular LSCC signature, possibly helping diagnosis, and improving prognosis and personalized therapy.

Nanodrug-loaded Bifidobacterium bifidum conjugated with anti-death receptor antibody for tumor-targeted photodynamic and sonodynamic synergistic therapy

Using bacteria for tumor-targeted therapy has attracted much attention in recent years. However, how to improve the targeted delivery and cancer therapy efficacy is an important but challenging scientific issue. Herein, a drug delivery system using a probiotic as a carrier was developed for tumor-targeted photodynamic and sonodynamic synergistic therapy. In this system, chlorin e6 (Ce6) nanoparticles (NPs) were prepared and incorporated into B. bifidum, followed by the conjugation of anti-death receptor 5 antibody (anti-DR5 Ab). Interestingly, B. bifidum under 671 nm laser or ultrasound (US) irradiation could generate reactive oxygen species (ROS), and Ce6–B. bifidum–anti-DR5 Ab obtained could target hypoxic regions in tumor with high efficiency after intravenous injection. The ROS level generated by Ce6–B. bifidum–anti-DR5 Ab under both laser and US irradiation was much higher than the combined ROS generated separately using a laser and US for the same probiotics. The cytotoxicity and laryngeal tumor growth-inhibiting efficiency of Ce6–B. bifidum–anti-DR5 Ab under both laser and US irradiation were significant higher than the values obtained using laser or US irradiation alone, which demonstrated the synergistic effect on tumor growth. B. bifidum could be eliminated from the body without exerting harmful effects on mouse health. This strategy is a platform that can be extended to treat other solid tumors. Statement of significanceUsing bacteria as drug delivery carriers will show unique advantages. However, how to improve the targeted delivery efficiency and tumor inhibiting capacity is a challenging scientific issue. Herein, a delivery system using a probiotic as carrier was developed for tumor-targeted therapy. In this delivery system, chlorin e6 nanoparticles were prepared and then incorporated into living Bifidobacterium bifidum (B.bifidum), followed by the conjugation of anti-death receptor 5 antibody. This delivery system could efficiently target to mouse tumors, accumulate the hypoxic areas and inhibit the tumor growth through the photodynamic and sonodynamic synergistic effect. Our results will provide a platform for B.bifidum–mediated tumor targeted therapy.

Predictors of prolonged stay after laryngeal surgery for benign neoplasms in children

BackgroundPediatric benign laryngeal tumors can often be treated as same-day surgeries. This study identified factors associated with prolonged hospital stay in children undergoing laryngeal surgery for benign tumors. MethodsA retrospective analysis of records of pediatric patients who underwent laryngeal surgery with a post-op diagnosis of benign tumor was performed with the American College of Surgeons Pediatric National Surgery Quality Improvement Program (ACS-NSQIP-P) database (2014–2018). Clinical variables analyzed included comorbidities, total length of stay (LOS), readmission, and reoperation. Results1775 patients were identified with a mean age at time of surgery of 8.95 years (95% CI 8.76–9.14). 966 (54.4%) were males and 809 (45.6%) were females. Mean LOS was 0.22 days (95% CI 0.12–0.32). Only 128 (7.3%) patients had a LOS of one day or more. Children with a variety of comorbidities, including premature birth, oxygen support, tracheostomy, developmental delay, and cardiac risk factors, had a significantly prolonged LOS (P < .001). Additionally, younger children were significantly more likely to stay overnight (β = −0.041, P < .001). Twenty-three (1.3%) patients were readmitted, 2 (0.1%) were reintubated, and 13 (0.7%) underwent reoperation for related reasons. Despite the association of premature birth, ventilator dependence, oxygen support, tracheostomy, esophageal/GI disease, developmental delay, seizure, neuromuscular disorders, congenital malformations, and steroid use with LOS, only younger age and ventilator dependence were associated with readmission. ConclusionThis study suggests that laryngeal surgery for benign tumors is safe but recognizes that patients with comorbidities or young children may require a prolonged stay. Awareness of these implications may help guide management.