Reliability and outcomes of lymph nodes biopsy in cT1-cT2 N0 supraglottic laryngeal squamous cell carcinoma.

BACKGROUND: In oral and oropharyngeal squamous cell carcinoma (SCC), sentinel node biopsy (SNB) was described as a reliable and reproductive alternative to elective neck dissection for the staging of clinical N0 T1-T2 patients. The SNB technique in supraglottic laryngeal SCC was successfully described in small series. The aim of this study is to analyze retrospectively the results of SNB technique in supraglottic SCC in CHU Godinne, to determine if the technique is reliable and may be proposed in a future multicentral prospective trial. METHODS: The study involved a retrospective analysis of 39 patients who underwent surgery between 2003 and 2019 at CHU Godinne. All patients presented with clinical N0 neck status. The SNB procedure included general anesthesia, 99-technetium colloid peritumoral injection, and lymphoscintigraphy. The hand-held gamma probe was utilized for SNB after tumoral resection during the same operating session. Out of 39 patients, 36 underwent SNB as the sole staging tool, while 3 patients received SNB in combination with elective neck dissection. Primary outcome was the 2-years neck recurrence-free survival (RFS). Secondary outcomes were the 2- and 5-years disease-specific survival (DSS). Additionally, sensitivity and negative predictive value (NPV) of the SNB technique were analyzed. RESULTS: Sentinel nodes were successfully identified in all 39 patients. An average of 4 nodes excised per patient. Positives SN were detected in 23% (9 in 39) cases, leading to subsequent selective neck dissection. Two cases of neck recurrence were observed, both considered as false negatives, occurring after an average of 3.5 months. Th median follow-up period was 48 months with a 2-year RFS of 95%. Sensitivity and NPV of the SNB technique were found to be 82% and 94%, respectively. Two and five years DSS were 84% and 71.7%, respectively. CONCLUSIONS: The results suggest that SNB in T1-T2 supraglottic SCC is a feasible and reliable technique for managing the neck in N0 early-stage patients. However, to establish its oncological equivalence with selective node dissection, further prospective and comparative studies are warranted. The findings of this study underscore the importance of ongoing research in refining and validating the role of SNB in the management of supraglottic SCC, potentially paving the way for more widespread adoption in clinical practice.

Aggressive recurrent respiratory papillomatosis: A series of five consecutive patients successfully treated with adjuvant intravenous bevacizumab. A single Belgian academic center experience.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a currently incurable benign neoplasm caused by human papilloma virus (HPV) infection. It usually reduces voice, respiratory, and general quality of life, and is sometimes life-threatening. Patients usually need repeated operations. The use of adjuvant bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A, has been described in several case reports, with a good efficacy and safety profile. METHODS: We report the cases of five patients with aggressive RRP who were treated with adjuvant systemic bevacizumab in a single Belgian tertiary center. RESULTS: A complete response was achieved in four patients after a median of 4.5 months, and a partial response in one. In all cases, the number of surgeries was drastically reduced, and quality of life improved. Toxicity was easily managed. CONCLUSIONS: Systemic bevacizumab seems to be an effective and safe adjuvant treatment for aggressive RRP.

Evaluation of the impact of deep neuromuscular blockade on surgical conditions for laryngeal microsurgery with High Frequency Jet Ventilation. A comparison with no block during intravenous general anesthesia with topical lidocaine.

OBJECTIVE: Laryngeal transoral surgery classically requires a neuromuscular block (NMB) to facilitate tracheal intubation and to improve surgical conditions. However, the short duration of most procedures and the potential complications of residual NMB lead to consider a no block approach. The hypothesis that intravenous anesthesia (remifentanil and propofol infusions) without NMB but including glottis topical lidocaine anesthesia would allow clinically acceptable laryngeal exposure and good surgical conditions was tested in the specific context of procedures undergone with High Frequency Jet Ventilation (HFJV). STUDY DESIGN: A prospective randomized clinical comparison. METHODS: 66 consenting patients were planned to receive 0.6 mg·kg-1 rocuronium or saline at random. The outcome measurements included the time and conditions to complete suspended laryngoscopy, and the surgical conditions rated by the surgeon. Any vocal cord movement or coughing was recorded. Data were compared using a Wilcoxon rank-sum test for numerical variables and chi-square test for categorical ones. Treatment failure was defined as an impossible laryngoscopy or a grade 4 surgical field occurring at any time during surgery and was compared to its null theoretical value by a general z-test. An interim analysis after completion of 50% patients was performed using Pocock boundaries at 0.0294 significance levels. RESULTS: A significant failure rate occurred in the non paralysed group (27%, p < 0.001). No coughing and no vocal cords movement occurred in the NMB group. Poorer surgical conditions were obtained without NMB (p = 0.011). CONCLUSION: Inducing a deep NMB ensured improved conditions during direct laryngeal microsurgery with HFJV.

Preoperative predictors of difficult oropharyngeal exposure for transoral robotic surgery: The Pharyngoscore.

BACKGROUND: Insufficient exposure may require termination of procedure in transoral robotic surgery (TORS). The aim of study was to develop a "Pharyngoscore" to quantify the risk of difficult oropharyngeal exposure (DOE) before TORS. METHODS: Three-hundred six patients undergoing any surgical procedure at one Academic Hospital were prospectively enrolled. Oropharynx was exposed with Feyh-Kastenbauer retractor. Exposure was evaluated by direct and endoscopic visualization of the four oropharyngeal subsites. Preoperative clinical/anthropometric parameters were studied in good oropharyngeal exposure and DOE groups. Logistic regression was performed to explore association between clinical/anthropometric parameters and DOE. Statistically significant parameters at multivariate analysis were incorporated into a nomogram. RESULTS: Sixty-five (21.2%) subjects were characterized by DOE. Variables associated with DOE at univariate analysis were male (p = 0.031), modified Mallampati Class (MMC) ≥ III (p < 0.001), smaller interincisor gap (p < 0.001), and larger neck circumference (p = 0.006). MMC, interincisor gap, and neck circumference were significant at multivariate analysis and were presented with a nomogram for creating the Pharyngoscore. CONCLUSIONS: The Pharyngoscore is a promising tool for calculating DOE probability before TORS.

Transoral robotic surgery hypopharyngectomy (TORSH): feasibility and outcomes.

PURPOSE: With the development of minimal invasive procedure, trans-oral robotic surgery (TORS) is expanding in the field of ENT. Most reviews focus on oropharyngeal and laryngeal (supra-glottic) localization. We report here the feasibility and outcomes of TORS hypopharyngectomy (TORSH) for selected patients with hypopharyngeal tumor. METHODS: Between September 2009 and July 2017, 22 patients, retrospectively included, underwent TORSH with curative intent. RESULTS: From 22 successful hypopharyngectomy, no conversion to open procedure was needed. Three patients (13%) presented a post-operative bleeding and were managed by surgical revision. No fistula was encountered. The 3-year overall survival and disease-specific survival rates were 54 and 92%, respectively. Patients started oral feeding after an average of 7 days. Naso-gastric feeding tubes were removed after a median period of 16 days. Two patients (9%) needed a transient gastrostomy (< 1 year). Three patients (13%) received a transient tracheostomy (< 2 months). Median hospitalization stay was 13 days. CONCLUSIONS: TORSH is a safe technique. Patients' outcomes are favorable and the post-operative morbidity is reduced compared to open neck approach. Hospitalization length and safe swallowing time are reduced.

Prognostic impact of tumor growth velocity in head and neck squamous cell carcinoma treated by radiotherapy: A pilot study.

BACKGROUND: When a patient is seen with a newly diagnosed oropharyngeal squamous cell carcinoma, it remains unclear to the treating physicians how fast the tumor growth rate is. METHODS: From patients with oropharynx squamous cell carcinoma treated by radiotherapy, the investigators selected comparable diagnostic CT-scan (DiCT) and radiotherapy planning CT-scan (RtCT). Tumor and pathological lymph node volumes were measured in order to calculate tumor progression. RESULTS: From the selection of 19 patients, the mean absolute tumor progression rate was 0.23 ± 0.2 cm3 /d and mean relative progression rate was 1.84 ± 1.64%/d. Mean tumor doubling time is 286 days (range 7-1282 days), demonstrating a wide range of tumor growth pattern. Significant tumor progression (>20%) between DiCT and RtCT was shown in 73% of patients, and 53% of the patients were seen a tumor progression of >50% within a mean waiting time of 42.1 days. Kaplan-Meier curves showed a non-significative link between fast progression tumors (>1%/d) and higher risk of recurrence (HR: 2.2; P = .23). CONCLUSIONS: Tumor progression can be assessed based on DiCT and RtCT. Treatment delay should be avoided at all cost. Different growth patterns were evidenced. For the fast-growing tumors subgroup, pejorative clinical outcomes were suggested. Prospective studies are needed to confirm a link between fast-growing tumors and higher risk for recurrence.

Transoral Robotic Surgery Total Laryngectomy.

OBJECTIVE: The aim of our study is to demonstrate our technique for performing transoral robotic surgical total laryngectomy (TORS-TL) with the use of the da Vinci robotic system. MATERIALS AND METHODS: We provide a comprehensive description of the TORS-TL operative techniques. Two fresh-frozen human cadavers were selected after ethics approval to describe the appropriate step-by-step surgical resection. We adopted a 5-step procedure that was later applied to 2 of our patients. The first patient presented initially with a squamous cell carcinoma (SCC) in the laryngeal glottis area. A lack of clinical response to initial treatment by chemoradiotherapy led to the decision of performing salvage TL surgery. The second patient had a previous history of head and neck SCC (HNSCC); he had no recurrence of his primary tumor but suffered significantly from postoperative breathing and swallowing difficulties due to severe laryngeal incompetence. RESULTS: TORS-TL was successfully performed in all cases. The operative time for the cadavers was approximately 65 and 55 min, respectively. It was significantly longer for the patients, 210 and 235 min, respectively, despite the fact that exactly the same steps were followed throughout all procedures. There were no intra- or postoperative complications or surgical morbidity related to the use of the da Vinci system. CONCLUSION: TORS-SL for SCC was performed in a safe, reliable, and smooth manner and was shown to be successful in treating our patients. We thus believe that our step-by-step surgical technique for TORS-SL is efficient and reproducible.

The effect of voice rest on the outcome of phonosurgery for benign laryngeal lesions: preliminary results of a prospective randomized study.

OBJECTIVES: According to the literature, voice rest following phonosurgery, as recommended in clinical practice, varies between 3 and 7 days. However, up until now, no randomized trials have been published comparing voice rest of short versus long duration. METHODS: This is an ongoing prospective randomized study, comparing strict voice rest of 5 versus 10 days on the voice following phonosurgery. Thirty-one elective patients operated on for benign laryngeal lesions were randomized. They completed pre- and postoperative assessments, including perceptual voice quality (Grade, Roughness, Breathiness, Asthenia, Strain, Instability scale), Voice Handicap Index total score, and voice analysis with both acoustic and aerodynamic measurements. Additional factors such as smoking, vocal abuse, reflux, and preoperative speech therapy were also taken into account. RESULTS: Sixteen patients were randomized to follow 5 days' voice rest and 15 patients were randomized to 10 days' voice rest. Statistical analysis showed no significant differences in pre- or postoperative measurements between the 2 groups. However, multilinear regression analysis for the effect of voice rest duration on postoperative values showed a significant improvement in maximum phonation time (MPT) with 10 days' voice rest. CONCLUSIONS: Preliminary results show a benefit of prolonged voice rest (10 days' duration) on MPT.

Medialization thyroplasty for voice restoration after transoral cordectomy.

Fourteen dysphonic patients who had previously undergone total or extended cordectomy underwent medialization thyroplasty. A minimum delay of 6 months was respected to allow the spontaneous "neocord" formation, to evaluate the voice recovery achieved by speech therapy alone and to avoid an undiagnosed early recurrence. Surgery was performed under general anaesthesia, using a laryngeal mask, because undermining the fibrous tissue at the inner side of the thyroid ala is a prolonged and difficult procedure. This step was essential to ensure an easy placement of the implant and to avoid tearing the fibrous tissue, with subsequent risk of implant extrusion. Visual control of the implant implementation was obtained by flexible videoendoscopy. The Montgomery(®) implant system (Boston, Westborough, MA) was used for the majority of the cases. Hand-made modified Montgomery implants or Gore-tex(®) were used in case of extended scarring or peculiar anatomic defect. The voice assessment showed a decrease of the VHI score from 50.5 to 39.4; a decrease of G from 2.4 to 2; an increase of maximum phonation time (MPT) from 6.2 to 7.3 s; a decrease of the maximum fundamental frequency (Fo-high) from 338.7 to 242.4 Hz and a decrease of the phonation quotient from 1,144.9 to 544.9 ml/s. The lower intensity (I-low) remained unchanged, from 60 to 58 dB. Statistically significant improvement was noted only for VHI and G grading. A decrease of the voice efforts and fatigue were noticed by all the patients.

Outcomes following transoral robotic surgery: supraglottic laryngectomy.

OBJECTIVES/HYPOTHESIS: To describe a single center outcomes following transoral robotic surgery for supraglottic laryngectomy (TORS-SL). STUDY DESIGN: Prospective data collection. METHODS: Patient records receiving TORS-SL for squamous cell carcinoma (SCCA) with at least 12 months follow-up fit inclusion for this study. Two patients with previous SCCA were excluded. RESULTS: 18 patients (14 male, 4 female) were included in the study, having a mean follow-up time of 28.1 months (SD = 12.1). All patients had negative margins confirmed on final pathology. Nine (50%) patients received postoperative chemoradiation therapy for advanced neck disease. No (0%) patients received tracheostomy or gastrostomy tubes. There were no (0%) local recurrences, and three (16.7%) regional recurrences. Five (27.8%) patients experienced temporary postoperative complications. Overall 2-year outcomes reached 83%, 100%, and 89% for locoregional control, disease-specific survival, and overall survival respectively. CONCLUSIONS: Initial outcomes for TORS-SL are encouraging and are comparable to previously described treatment modalities. Larger studies are encouraged.

Assessment of p53 functional activity in tumor cells and histologically normal mucosa from patients with head and neck squamous cell carcinoma.

BACKGROUND: The purpose of this study was to investigate the value of p53 functional analysis of separated alleles in yeast (FASAY) as a witness of p53/p21 pathway alteration in head and neck squamous cell carcinoma (HNSCC). METHODS: The p53 transcriptional activity was prospectively analyzed in 82 newly diagnosed patients with HNSCC. FASAY and p53 immunostaining were carried out on paired tumoral and histologically normal tissues. The predictive value of FASAY for locoregional recurrence was assessed by Cox survival analysis. RESULTS: Loss of p53/p21 transcriptional activity was encountered in 88% tumoral and 18% histologically normal samples, associated with mutations (79%) and insertions/deletions (21%). The p53 overexpression underestimated p53 transcriptional abnormalities. FASAY-positive histologically normal mucosa was significantly associated with locoregional recurrence. CONCLUSION: FASAY positivity indicates field cancerization in a subgroup of patients with HNSCC, in which nonfunctional p53 was significantly associated with locoregional recurrence. This prompted us to pursue the study on the p53 functional status of normal mucosa in patients with HNSCC.

Automated cell disruption is a reliable and effective method of isolating RNA from fresh snap-frozen normal and malignant oral mucosa samples.

BACKGROUND: This study compared automated vs. manual tissue grinding in terms of RNA yield obtained from oral mucosa biopsies. METHODS: A total of 20 patients undergoing uvulectomy for sleep-related disorders and 10 patients undergoing biopsy for head and neck squamous cell carcinoma were enrolled in the study. Samples were collected, snap-frozen in liquid nitrogen, and divided into two parts of similar weight. Sample grinding was performed on one sample from each pair, either manually or using an automated cell disruptor. The performance and efficacy of each homogenization approach was compared in terms of total RNA yield (spectrophotometry, fluorometry), mRNA quantity [densitometry of specific TP53 amplicons and TP53 quantitative reverse-transcribed real-time PCR (qRT-PCR)], and mRNA quality (functional analysis of separated alleles in yeast). RESULTS: Although spectrophotometry and fluorometry results were comparable for both homogenization methods, TP53 expression values obtained by amplicon densitometry and qRT-PCR were significantly and consistently better after automated homogenization (p<0.005) for both uvula and tumor samples. Functional analysis of separated alleles in yeast results was better with the automated technique for tumor samples. CONCLUSIONS: Automated tissue homogenization appears to be a versatile, quick, and reliable method of cell disruption and is especially useful in the case of small malignant samples, which show unreliable results when processed by manual homogenization.

Preservation of RNA for functional analysis of separated alleles in yeast: comparison of snap-frozen and RNALater solid tissue storage methods.

BACKGROUND: The aim of the present study was to compare RNALater with the usual method of liquid nitrogen snap freezing as a surrogate mRNA preservation method for functional analysis of separated alleles in yeast (FASAY). METHODS: A total of 81 patients with transitional cell carcinoma of the bladder underwent fresh tissue biopsies directly transferred into RNALater and stored at room temperature or at 4 degrees C for increasing time intervals until RNA processing. From this cohort of patients, 53 paired snap-frozen and RNALater preservative-suspended tissues were obtained. Samples immediately frozen in liquid nitrogen were further stored at -80 degrees C. RESULTS: Of the 81 RNALater samples, 14 were not processed for FASAY because of RNA degradation. Of the remaining 67 samples, 15 (22%) were FASAY-positive. Identical FASAY results were found for 50 of 53 (94.4%) paired samples and the percentage of red yeast colonies was highly correlated (Cohen's kappa<0.82; p<0.00001). A single p53 missense mutation was found in each of the three discordant positive FASAY and was identical in each concordant positive sample (10/53). Storing samples in RNALater at room temperature for 3 days and at 4 degrees C for less than 1 month provided high-quality mRNA suitable for FASAY. CONCLUSIONS: Our results demonstrate that RNALater is a suitable and flexible alternative to snap freezing for FASAY analysis.