Quality of life following lobectomy versus total thyroidectomy is significantly related to hypothyroidism.

OBJECTIVE: The aim of the present study was to investigate the differences in quality of life (QOL) following complete or partial thyroidectomy and with regard to thyroid hormone replacement (LT4) therapy. STUDY DESIGN: Patients who underwent thyroidectomy were asked to complete the validated thyroid-specific ThyPRO QOL questionnaire at least 6 months following surgery. SETTING: Tertiary medical center. METHODS: Thyroid specific QOL questionnaire analysis. RESULTS: A total of 190 patients completed the ThyPRO questionnaire. Of them 89 patients had complete thyroidectomy and 101 patients had unilateral thyroid lobectomy. The total thyroidectomy group had significantly worse overall QOL self-assessment score than the lobectomy patients (p < 0.0001). Patients receiving LT4 therapy regardless of the extent of surgery, reported worse QOL compared to patients not receiving LT4. CONCLUSIONS: Quality of life following thyroid surgery is significantly related to hypothyroidism and the requirement for LT4 therapy, rather to the extent of surgery. The best QOL was reported in patients treated with lobectomy who did not require LT4 therapy.

Retrospective analysis of the role of intra-operative parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism: a single center experience over 2 decades.

PURPOSE: Role of intra-operative parathyroid hormone (IOPTH) monitoring during parathyroidectomy for primary hyperparathyroidism (PHPT) has long been debated. Our main goal was to investigate the cure rates of parathyroidectomy for primary hyperparathyroidism with and without IOPTH monitoring. Our secondary goal was to investigate if operating room time can be saved when IOPTH monitoring is not used. METHODS: A retrospective analysis of patients who underwent parathyroidectomy for PHPT due to a single adenoma between 2004 and 2019 was performed. Cure rates and operating room time were compared. RESULTS: 423 patients were included. IOPTH was used in 248 patients (59%). Four patients were not cured, two from each group, with no significant difference between the groups (98.8% vs. 99.1%, p = 0.725). Surgery time was significantly longer in the IOPTH group, p < 0.001. CONCLUSIONS: There is no advantage for using IOPTH during parathyroidectomy in suitable clinical settings. The procedure may be safely performed without IOPTH while achieving non-inferior success rates and reducing operative time.

Characterization of Fanconi Anemia Patients with Head and Neck Squamous Cell Carcinoma: Israel Fanconi Registry.

BACKGROUND: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response. OBJECTIVES: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry. METHODS: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts. RESULTS: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5-57) months. CONCLUSIONS: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.

Prophylactic central neck dissection has no advantage in patients with metastatic papillary thyroid cancer to the lateral neck.

BACKGROUND: Papillary thyroid cancer (PTC) usually metastasizes via lymphatic channels in a sequential fashion, first to the central compartment, followed by the lateral neck. PTC patients diagnosed with lateral neck disease (N1b) without proof for central involvement traditionally undergo prophylactic central neck dissection (pCND). However, substantial evidence on outcomes to support this approach is lacking. MATERIALS AND METHODS: We conducted a dual center retrospective study to compare the rate of central neck recurrence between N1b PTC patients undergoing pCND and those spared pCND. All patients diagnosed with N1b PTC who underwent total thyroidectomy and lateral neck dissections with or without pCND between January 1998 and December 2015 were included in this study. The rates of central neck recurrences were compared between the groups. RESULTS: The 111 patients who met the inclusion criteria were 44 females (39.6%) and 67 males (60.4%), with a mean age of 50.2 ± 17.7 years, and a mean follow-up of 10.2 ± 5.3 years. Sixty patients (54.1%) underwent a pCND and 51 patients (45.9%) did not (non-pCND). During follow-up, 18 patients (16.2%) had level VI recurrences, 13 in the pCND group and 5 in the non-pCND group. Cox-regression models with propensity scoring did not reveal any inclination or an advantage for performing pCND. CONCLUSION: The present study demonstrated no advantage in performing pCND to prevent central neck recurrence among PTC patients with lateral neck involvement only. These findings question the need for pCND in patients without clinical evidence of central neck disease.

Accuracy, predictability and prognostic implications of fine-needle aspiration biopsy for parotid gland tumours: A retrospective case series.

OBJECTIVE: To evaluate the precision and utility of fine-needle aspiration (FNA) in differentiating between benign and malignant parotid tumours, and the implications of FNA results on management and outcomes. DESIGN: Retrospective case series. SETTING: Tertiary medical centre. PARTICIPANTS: All adults who underwent preoperative FNA, followed by postoperative histological examination, between 1986 and 2014. MAIN OUTCOME MEASURES: Differences in clinical management and outcomes of patients with parotid masses in light of FNA results. RESULTS: We analysed 505 samples from 485 patients. According to histopathological results, preoperative FNA successfully identified benign tumours in 89% of the cases (362/405) and only 59% of malignant tumours (59/100). Overall sensitivity and specificity of FNA in distinguishing between different subtypes of benign lesions were 80% and 99%, respectively, whereas positive predictive value (PPV) and negative predictive value (NPV) were 85% and 98%. Moreover, malignant lesions subtyping had high false-positive and false-negative rates with sensitivity, specificity, PPV and NPV of 44%, 100%, 75% and 99%, respectively. Additionally, when FNA falsely classified malignant tumours as benign, surgeries were inappropriately delayed and the durations of surgeries and hospitalisations were shorter, compared to true malignant FNA results. Interestingly, survival was not affected in falsely benign lesions that were mostly low-grade, conversely non-diagnostic FNA for malignant tumours resulted in decreased survival. CONCLUSIONS: Our findings highlight the limitations of FNA as a decision-making tool in preoperative evaluation of parotid masses. Clinicians should take into account that FNA is inaccurate for identifying specific subtypes of malignant lesions, which may eventually delay treatment and influence outcome.

Is the Risk to Develop Osteoradionecrosis of the Jaws Following IMRT for Head and Neck Cancer Related to Co-Factors?

Background and Objectives: Determine the contribution of coexisting factors to the risk to develop Osteoradionecrosis (ORN) of the jaws among patients who have received radiotherapy by intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC) between 2013 and 2016, in a single medical center. Materials and Methods: The records of all patients treated with IMRT for HNC between 2013 and 2016 in The Davidoff Center for the treatment and Research of Cancer in Rabin Medical Center-Beilinson hospital, Petah-Tikva, Israel were screened. Patients who have received a minimum mean dose of 40 Gy to the oral cavity entered the research and their medical records were retrospectively reviewed. Collected background data included: age, gender, smoking, diabetes mellitus (DM), ASA score, mean and maximal radiation doses (Gy), and diseases characteristics including histological diagnosis, primary tumor site, and disease stage. Results: A total of 1232 patients were surveyed. Out of all screened patients, 93 received a minimum mean dose of 40 Gy to the oral cavity. Out of the 93 patients, 7 (7.52%) developed ORN (ORN+) and 86 did not develop ORN (ORN-). Tumor type in all seven patients in the ORN+ group was Squamous Cell Carcinoma (SCC). In three out of those seven patients (42.9%), the tumor was located in the mandible. Conclusions: within the limits of the relatively small cohort in the current study, we suggest that the development of ORN due to Radiation therapy (RT) with IMRT is related significantly only to the location of a tumor in the mandible. Other co-factors do not significantly increase the risk to develop ORN when RT is delivered via IMRT.

[THE USE OF ROBOTICS IN HEAD AND NECK SURGERY - THE EXPERIENCE OF RABIN MEDICAL CENTER].

INTRODUCTION: In recent years, minimally invasive surgeries have been undergoing a revolution with the development of robotic assisted surgery. Due to the anatomical region in which many operations are carried out, in small spaces through natural orifices in the body such as the mouth, the nose or the ear, as well as the esthetic discomfort caused by external scars in the head and neck, the use of robotic assisted surgery in the field of head and neck surgery is gaining momentum and is being implemented more and more in Israel and around the globe. Most of the operations currently performed in otolaryngology are carried out through the oral cavity or through distant and camouflaged skin cuts. In this article we will review the new applications and technologies in the field of surgical robotics in otolaryngology - head and neck surgeries, as well as summarize the experience of the Department of Otorhinolaryngology and Head and Neck Surgery at the Rabin Medical Center in robot assisted surgeries.

Quantitative self-assembly prediction yields targeted nanomedicines.

Development of targeted nanoparticle drug carriers often requires complex synthetic schemes involving both supramolecular self-assembly and chemical modification. These processes are generally difficult to predict, execute, and control. We describe herein a targeted drug delivery system that is accurately and quantitatively predicted to self-assemble into nanoparticles based on the molecular structures of precursor molecules, which are the drugs themselves. The drugs assemble with the aid of sulfated indocyanines into particles with ultrahigh drug loadings of up to 90%. We devised quantitative structure-nanoparticle assembly prediction (QSNAP) models to identify and validate electrotopological molecular descriptors as highly predictive indicators of nano-assembly and nanoparticle size. The resulting nanoparticles selectively targeted kinase inhibitors to caveolin-1-expressing human colon cancer and autochthonous liver cancer models to yield striking therapeutic effects while avoiding pERK inhibition in healthy skin. This finding enables the computational design of nanomedicines based on quantitative models for drug payload selection.

Cetuximab intensifies cisplatin-induced testicular toxicity.

Epidermal growth factor receptor (EGFR) has proliferative properties in the testis. Cetuximab, an anti-EGFR, is administered together with chemotherapy to patients with various types of cancer. This studies aim was to investigate the effect of cetuximab on testicular function. Adult male mice were injected with cetuximab (10 mg/kg), cisplatin (8 mg/kg) or a combination of both, and killed one week or one month later. The doses were chosen by human equivalent dose calculation. Testicular function was evaluated by epididymal-spermatozoa total motile count and sperm motility, weights of testes and epididymides, and the level of anti-Müllerian hormone (AMH) in the serum. Immunohistochemistry was performed to examine germ cell proliferation (Ki-67), apoptosis (Terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labelling), reserve (DAZL-Deleted in azoospermia-like, Promyelocytic leukaemia zinc-finger), blood vessels (CD34) and Sertoli cells (GATA-4). Administration of cetuximab alone increased testicular apoptosis and decreased epididymal-spermatozoa total motile count over time. When added to cisplatin, cetuximab exacerbated most of the recorded testicular parameters, compared with the effect of cisplatin alone, including testis and epididymis weights, epididymal-spermatozoa total motile count, AMH concentration, meiosis and apoptosis. In conclusion, cetuximab has only a mild effect on testicular reserve, but when added to cisplatin, it exacerbates cisplatin-induced testicular toxicity.

Recurrent pleomorphic adenoma of the parotid gland: Institutional experience and review of the literature.

BACKGROUND: Recurrent pleomorphic adenoma (PA) of the parotid gland is a challenging surgical issue with controversy regarding management and long term outcome. METHODS: All patients who were operated for recurrent PA of the parotid gland between the years 1991 and 2013 were reviewed. Patient demographics, clinicopathologic variables, and operative details were collected retrospectively. RESULTS: A total of 22 patients were operated for recurrent PA of the parotid gland. Mean interval between recurrences was 7 and 6 years for first recurrence and second recurrence, accordingly. Second recurrence was significantly influenced by younger age at initial treatment (P = 0.009). Only two patients (9%) with a recurrence developed facial nerve paralysis following surgery. Adjuvant radiotherapy was given to nine patients with no evidence of disease progression or recurrence. There were no cases of malignant transformation. CONCLUSIONS: Recurrent PA of the parotid gland tends to occur in long intervals in a multifocal pattern. Adjuvant radiotherapy could be suggested as an alternative for surgery. J. Surg. Oncol. 2016;114:714-718. © 2016 Wiley Periodicals, Inc.

Hearing loss patterns after cochlear implantation via the round window in an animal model.

PURPOSE: The mechanism and the type of hearing loss induced by cochlear implants are mostly unknown. Therefore, this study evaluated the impact and type of hearing loss induced by each stage of cochlear implantation surgery in an animal model. STUDY DESIGN: Original basic research animal study. SETTING: The study was conducted in a tertiary, university-affiliated medical center in accordance with the guidelines of the Institutional Animal Care and Use Committee. SUBJECTS AND METHODS: Cochlear implant electrode array was inserted via the round window membrane in 17 ears of 9 adult-size fat sand rats. In 7 ears of 5 additional animals round window incision only was performed, followed by patching with a small piece of periosteum (control). Hearing thresholds to air (AC) and bone conduction (BC), clicks, 1 kHz and 6 kHz tone bursts were measured by auditory brainstem evoked potential, before, during each stage of surgery and one week post-operatively. In addition, inner ear histology was performed. RESULTS: The degree of hearing loss increased significantly from baseline throughout the stages of cochlear implantation surgery and up to one week after (p<0.0001). In both operated groups, the greatest deterioration was noted after round window incision. Overall, threshold shift to air-conduction clicks, reached 61 dB SPL and the bone conduction threshold deteriorated by 19 dB SPL only. Similar losses were found for 1-kHz and 6-kHz frequencies. The hearing loss was not associated with significant changes in inner ear histology. CONCLUSIONS: Hearing loss following cochlear implantation in normal hearing animals is progressive and of mixed type, but mainly conductive. Changes in the inner-ear mechanism are most likely responsible for the conductive hearing loss.

Proposal for anatomical classification of the superior pole in thyroid surgery.

OBJECTIVE: To propose a distinct anatomical classification for the superior thyroid pole that may serve as a surgical landmark and could help reduce complications in thyroid surgery. MATERIALS AND METHODS: A comprehensive anatomical study based on existing literature and surgical observations. RESULTS: The proposed superior pole classification is based on two parameters that closely interact: one is the shape of the superior pole and the other is the structure of the vascular pedicle of the superior pole. We have come up with three distinct types of superior thyroid pole anatomical structure that may be predictive of the risk for both hemorrhage and nerve injury. CONCLUSIONS: Superior pole classification may serve as a guiding tool during thyroid surgery in order to reduce complications such as bleeding and injury to the external branch of the superior laryngeal nerve.

Analysis of failure following transoral laser surgery for early glottic cancer.

This study aimed at clarifying further the clinical behavior of early glottic cancer following transoral laser surgery and to determine, using retrospective analysis, whether the site of tumor involvement along the vocal fold has prognostic significance. The study included all patients treated with transoral laser surgery, for early glottic cancer (T1/T2N0M0) between May 1998 and January 2012 in a university affiliated tertiary care medical center. Data on demographics, site and extent of disease, treatment and outcome were collected and analyzed. Patients with insufficient data and/or follow-up of <2 years were excluded from the study. One-hundred and twenty-one patients were eligible for the study. Mean follow up time was 6.7 years (range 2-12 years). Overall recurrence rate following primary transoral laser surgery was 16.5 %. Histological grade was associated with higher recurrence rate (p = 0.008). Anterior commissure involvement was associated with reduced disease-free survival and tumors extending to the middle third of the true vocal fold were associated with lower recurrence rate. As per the results, anterior extension of glottic tumors is associated with higher recurrence rate compared to middle vocal fold extension, presumably due to earlier detection, better visualization and different biological behavior pattern of middle vocal fold tumors. Patients with higher grade tumors should be closely monitored for disease recurrence.

Value of ultrasound in detecting central compartment lymph node metastases in differentiated thyroid carcinoma.

The value of ultrasound in detecting central compartment lymph node metastasis in patients with well-differentiated thyroid carcinoma (WDTC) is unclear. Prospective patients with WDTC attending a university-affiliated tertiary medical center between July 2010 and June 2011 underwent neck ultrasound for detection of central compartment lymph node metastases prior to surgery. Central lymph node dissection was performed during the initial surgery regardless of ultrasound findings. The sensitivity and specificity of preoperative ultrasound in detecting central lymph node metastases were calculated according to the final histopathological results. Sixty-four patients met the study criteria. Twenty-four had pathologic central compartment lymph nodes according to preoperative ultrasound, 20 of which were confirmed by histological examination. One patient was found to have pathological central lymph nodes by histology which was not detected by US. Sensitivity of preoperative ultrasound was 95%, specificity 90%, and negative and positive predictive values 97 and 83%, respectively. Preoperative ultrasound may serve as an accurate and important tool for deciding the extent of surgery in WDTC.

Salivary Gland Secretory Carcinoma; Review of 13 Years World-Wide Experience and Meta-Analysis.

OBJECTIVES: Secretory Carcinoma is a malignant salivary gland tumor, initially described in 2010. This rare tumor is associated with the translocation t(12;15) (p13;q25), resulting in the fusion gene ETV6-NTRK3. Since this tumor is quite rare, most publications describe only small cohorts of patients. We aimed to investigate the clinical, pathological, and prognostic features of this newly defined malignant entity. DATA SOURCES: Pubmed, Google Scholar, and Web of Science databases. REVIEW METHODS: All published articles between 2010 and 2023 were reviewed. Search terms included the terms "Mammary Analogue Secretory Carcinoma" and "Secretory Carcinoma". All articles published in English reporting on Secretory Carcinoma of salivary glands were retrieved. RESULTS: One-hundred and 12 retrospective articles reporting a total of 674 patients were included, with 52% males and a mean age of 44.9 ± 18.9. The event rate for patients with advanced-stage disease (Stage 3/4) at presentation was 24.1% (95% CI 17.6%-31.9%, I2 = 9.2%), 14.6% for regional metastases (95% CI 10.5%-20%, I2 = 12%), and the event rate of distant metastasis was 8.4% (95% CI 5.5%-12.7%, I2 = 4.2%). Adjuvant radiotherapy was administered for 30.3% of patients (95% CI 24.1%-37.2%, I2 = 21.5%). The recurrence rate was 19% (95% CI 15.1%-23.8%, I2 = 5%). Survival outcomes showed a 17.2% death of disease rate for Secretory Carcinoma patients (95% CI 13.5%-21.8%, I2 = 7.3%). CONCLUSIONS: Secretory Carcinoma is a rare and relatively newly defined entity arising in the parotid gland most commonly. Characterized as a low-grade tumor, the majority of patients are diagnosed at an early stage, without regional or distant disease, and the prognosis is relatively good. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1716-1724, 2024.

Foregoing elective neck dissection for elderly patients with oral cavity squamous cell carcinoma.

OBJECTIVE: Elective neck dissection (END) improves outcomes among clinically node-negative patients with oral cavity squamous cell carcinoma (OCSCC). However, END is of questionable value, considering the potentially higher comorbidities and operative risks in elderly patients. METHODS: A retrospective review of all patients older than 65 years of age who were treated for OCSCC at a tertiary care centre between 2005 and 2020 was conducted. RESULTS: Fifty-three patients underwent primary tumour resection alone, and 71 had simultaneous END. Most primary tumours were located on the mobile tongue. The patients who did not undergo END had a higher mean age (81.2 vs. 75.1 years, P < 0.00001), significantly shorter surgeries, and shorter hospitalizations. Occult cervical metastases were found in 24% of the patients who underwent END. The two groups showed no significant differences in overall survival or recurrence rates. Similar results were shown in a subpopulation analysis of patients older than 75 years. CONCLUSION: Foregoing END in elderly patients with no clinical evidence of neck metastases did not result in lower survival rates or higher recurrence rates.

Prognostic Significance of Regional Disease in Young Patients with Oral Cancer: A Comparative Study.

BACKGROUND: Regional metastases are considered the most important prognostic factor in OSCC patients. We aimed to investigate the impact of regional disease among different age groups with OSCC. METHODS: A retrospective comparison between patients 40 years old or younger, 41-69 years old, and 70 years or older treated for OSCC between 2000 and 2020 in a tertiary-care center. RESULTS: 279 patients were included. The mean age was 65 ± 17.7 and 133 were male (47.7%). Thirty-six (12.9%) were 40 years old or younger, 101 (36.2%) were 41-69 years and 142 (50.9%) were 70 years or older. Five-year overall survival and disease-specific survival (DSS) were significantly better among patients younger than 40 compared to the mid-age group and patients 70 years or older (76.7% vs. 69.4% vs.48.2%, Log-rank p < 0.001, and 76.7% vs. 75.3% vs. 46.5%, Log-rank p < 0.001, respectively). While an association between regional spread and overall survival and DSS was demonstrated among all age groups, the odds ratio (OR) for death of any cause and death of disease regarding cervical metastasis was much higher among patients younger than 40 compared with the 41-69 and 70+ age groups (death of any cause-OR = 23, p-value = 0.008, OR = 2.6, p-value = 0.026, OR = 2.4, p-value = 0.13, respectively. Death of disease-OR = 23, p-value = 0.008, OR = 2.3, p-value = 0.082, OR = 4.1, p-value = 0.001, respectively). In univariate  analysis, regional metastasis was associated with disease-free survival only among patients younger than 40 (p-value = 0.04). CONCLUSIONS: Regional metastases correspond with worse prognosis in young patients compared to older patients. These patients may benefit from a comprehensive treatment approach with close post-treatment follow-up. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2212-2220, 2024.

The Clinical Behavior and Recurrence Patterns of Oral Cavity Cancer in Oral Lichen Planus Patients.

OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory disorder involving epithelia with squamous differentiation. Although described as a potential malignant precursor, the characteristics of malignancies arising among these patients are not widely described. Our goal was to describe the patterns of disease recurrence of patients with oral cavity squamous cell carcinoma (OSCC) arising on the background of OLP. METHODS: A retrospective analysis of all surgically treated patients with OSCC at a university-affiliated tertiary care center between 2000 and 2020. RESULTS: Two hundred seventy-nine patients with OSCC treated surgically were included. Forty (14.3%) had OLP. The mean age of patients with OLP was 70.9 years compared with 64.3 years for non-OLP patients (p = 0.03). OLP patients had a significantly higher rate of disease recurrence, persistence, or multiple primary disease (70% vs. 33.9%, p < 0.001). The mean number of sequential oncologic events for each patient with recurrence was also significantly higher among OLP patients (1.86 vs. 1.36, p = 0.03), a difference explained by a higher rate of multiple primary presentations (0.71 vs. 0.28, p = 0.008). A significant difference in disease-free survival (DFS) was demonstrated between the groups as patients with OLP had a lower 5-year DFS (34.7% vs. 61.3%, log-rank p value <0.001). On multivariate analysis, OLP was significantly associated with multiple primary events (p < 0.001, Odds ratio = 7.42, 95% confidence interval 2.9-19). CONCLUSIONS: OSCC patients with OLP background demand close clinical follow-up, as multiple primary disease is significantly more common and the DFS is significantly lower among these patients. A thorough clinical evaluation for all oral cavity subsites is mandatory. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3146-3151, 2024.