Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects.

Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- and NK-cell activity and stimulates IFNγ production. The activity of IL18 is naturally blocked by a high-affinity endogenous binding protein (IL18BP). IL18BP is induced in the tumor microenvironment (TME) in response to IFNγ upregulation in a negative feedback mechanism. In this study, we found that IL18 is upregulated in the TME compared with the periphery across multiple human tumors and most of it is bound to IL18BP. Bound IL18 levels were largely above the amount required for T-cell activation in vitro, implying that releasing IL18 in the TME could lead to potent T-cell activation. To restore the activity of endogenous IL18, we generated COM503, a high-affinity anti-IL18BP that blocks the IL18BP:IL18 interaction and displaces precomplexed IL18, thereby enhancing T- and NK-cell activation. In vivo, administration of a surrogate anti-IL18BP, either alone or in combination with anti-PD-L1, resulted in significant tumor growth inhibition and increased survival across multiple mouse tumor models. Moreover, the anti-IL18BP induced pronounced TME-localized immune modulation including an increase in polyfunctional nonexhausted T- and NK-cell numbers and activation. In contrast, no increase in inflammatory cytokines and lymphocyte numbers or activation state was observed in serum and spleen. Taken together, blocking IL18BP using an Ab is a promising approach to harness cytokine biology for the treatment of cancer.

Extended cervical approach for retrosternal multinodular goiter.

Objective: Partial or total sternotomy is required for 10% of retrosternal goiter. This study reviewed our experience with an extended cervicotomic approach as an alternative surgical solution for retrosternal goiter. Methods: A retrospective study was performed on patients who underwent partial or total thyroidectomy for retrosternal goiter between 2014 and 2019 at a tertiary medical centre. Data on clinical, radiologic, and pathologic factors were analysed. Peri- and postoperative outcomes were compared between extended and standard cervical approaches to predict the need for an extended cervical approach. Results: The cohort included 265 patients, of whom 245 (92.4%) were treated by standard thyroidectomy. In 17 (6.4%), the standard approach proved insufficient, and the horizontal incision was extended to a T-shape to improve access. The remaining 3 patients required a sternotomy. Use of the extended cervical approach was significantly associated with clinical features such as male gender, diabetes, high body mass index and postoperative hypocalcaemia. Conclusions: The extended cervicotomic approach is an alternative surgical solution for retrosternal goiter, with no increased risk of significant post-operative complications.

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, 2024.

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.

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.

The Value of Computed Tomography in Recurrent Laryngeal Cancer Following Organ Preservation Therapy.

AIM: This study aims to assess the accuracy of computed tomography (CT) in detecting recurrent laryngeal tumors after failed chemoradiation therapy (CRT). BACKGROUND: Local recurrence of laryngeal tumors following CRT has been reported in approximately 25%, yet it is often difficult to detect. METHODS: Ten patients with laryngeal cancer who failed CRT and subsequently underwent salvage total laryngectomy were included. The laryngeal subsites involved in the tumor were identified based on postoperative pathology. The corresponding preoperative CT scans were selected for review by seven experts (head-and-neck surgeons or radiologists) who scored the extent of tumor spread on each scan on a 5-point scale, from no tumor detected to clearly visible tumor. RESULTS: The rates of high tumor detectability (scores 4-5) varied according to laryngeal subsite, from 75% in the glottic region, to 45% in the subglottic region, and to 19% in the supraglottic region (P=0.01). The detectability rates were higher on scans performed 2 years or more after CRT. CONCLUSION: The CT evaluation of laryngeal cancer after CRT has limited value, particularly in the epiglottis and subglottis.

Long-term complications associated with the management of sinonasal malignancies: a single center experience.

Objective: The aim of this study was to review the long-term complications associated with treatment of patients with sinonasal malignancies (SNMs) and risk factors for these complications. Methods: A retrospective analysis of all patients treated for SNMs at a tertiary care center between 2001 and 2018. A total of 77 patients were included. The primary outcome measure was post-treatment long-term complications. Results: Overall, long-term complications were identified in 41 patients (53%), and the most common were sinonasal (22 patients, 29%) and orbital/ocular-related (18 patients, 23%). In a multivariate regression analysis, irradiation was the only significant predictor of long-term complications (p = 0.001, OR = 18.86, CI = 3.31-107.6). No association was observed between long-term complications and tumour stage, surgical modality, or radiation dose/modality. Mean radiation dose ≥ 50 Gy to the optic nerve was associated with grade ≥ 3 visual acuity impairment (100% vs 3%; p = 0.006). Radiation therapy for disease recurrence was associated with additional long-term complications (56% vs 11%; p = 0.04). Conclusions: Treatment of SNMs has substantial long-term complications, which are significantly associated with radiation therapy.

The Predictors of Persistent Posttracheostomy Tracheocutaneous Fistula and Successful Surgical Closure.

OBJECTIVE: Persistent tracheocutaneous fistula is a well-described complication of prolonged tracheostomy, with a prevalence of about 70% when decannulation is performed after more than 16 weeks. Predictors of its occurrence and outcome of treatment in adults remain unclear. The aim of the study was to describe our experience with the treatment of persistent posttracheostomy tracheocutaneous fistula in adults and to investigate factors associated with its formation and with the success of surgical closure. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary medical center. METHODS: Patients who underwent open-approach tracheostomy between 2000 and 2020 were identified by database review. Data on background, need for surgical closure, and the surgical outcome was collected from the medical files and analyzed statistically between groups. RESULTS: Of 516 patients identified, 127 with sufficient long-term follow-up data were included in the study. Compared to patients whose fistula closed spontaneously (n = 85), patients who required surgical closure (n = 42) had significantly higher rates of smoking, laryngeal or thyroid malignancy, and airway obstruction as the indication for tracheostomy, on both univariate and multivariate analysis. In a comparison of patients with successful (n = 29) or failed (n = 11) surgical closure, factors significantly associated with failure were prior radiotherapy and lower preoperative albumin level, on univariate analysis. CONCLUSION: Smoking, thyroid or laryngeal malignancy, and airway obstruction indication are risk factors for persistent posttracheostomy tracheocutaneous fistula. Patients should be closely followed after tracheostomy and referred for surgery if the fistula fails to close. Before surgery, careful evaluation of the patient's nutritional status and consideration of prior radiation treatment is mandatory.

Cutaneous Squamous Cell Carcinoma in Immunocompromised Patients-A Comparison between Different Immunomodulating Conditions.

BACKGROUND: Immunosuppression is strongly associated with an increased risk of developing cutaneous squamous cell carcinoma (cSCC). Studies on solid organ transplant recipients (SOTR) and chronic lymphocytic leukemia (CLL) patients have already demonstrated higher rates of aggressive cSCC tumors in these populations compared to immunocompetent controls. Studies on other immunosuppressed patient groups are scarce. This study was aimed at assessing the effects of different immunomodulating conditions on patients diagnosed with cSCC. We sought to compare the clinical features, treatments, and survival rates among the different study groups, as well as outcomes to those of immunocompetent controls with cSCC. METHODS: A retrospective analysis of 465 cSCC patients, both immunosuppressed (IS) and immunocompetent controls. Etiologies for immunosuppression included SOTR, CLL, chronic kidney disease (CKD), psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). RESULTS: Compared to the control group, IS patients demonstrated several significant differences. These include higher rates of positive resection margins, higher recurrence rates, and multiple SCC tumors. Patients in the IS group, who were also given immunomodulating agents, demonstrated even lower survival rates. Cox regression analysis demonstrated statistically significant decreased overall survival (OS) rates for IS patients compared to the controls (OR = 1.9, p = 0.031). SOTR patients tend to have multiple cSCC tumors (35%), with the highest number of primary tumors compared to controls (2.54 tumors per patient on average, p < 0.001), but also compared to all other IS groups. The average SCC lesion size in the SOTR group was the smallest, measuring at 13.5 mm, compared to the control group and all other IS groups. Decreased survival rates were seen on Cox regression analysis compared to controls (HR = 2.4, p = 0.001), but also to all other IS groups. CLL patients also had the highest rates of positive margins compared to controls (36% vs. 9%, p < 0.01) and to all other IS groups. They were also most likely to get adjuvant or definitive oncological treatments, either radiotherapy or chemotherapy, compared to controls (36% vs. 15%, p = 0.02) and to other IS groups. Patients in the CKD group demonstrated the highest rates for multiple cSCC (OR = 4.7, p = 0.001) and the worst rates of survival on Cox regression analysis (HR = 3.2, p = 0.001). Both rheumatoid arthritis and psoriasis patients demonstrated the shortest disease-free survival rates (2.9y ± 1.1, 2.3y ± 0.7, respectively), compared to controls (4.1y ± 2.8) and to all other IS groups. CONCLUSIONS: Among cSCC patients, immunosuppression due to SOTR, CLL, CKD, RA, and psoriasis is associated with worse outcomes compared to controls and other IS groups. These patients should be regarded as high-risk for developing aggressive cSCC tumors. This study is the first to assess and compare cSCC outcomes among multiple IS patient groups.

A Comparison of Outcomes in Medullary Thyroid Carcinoma Patients With and Without a Preoperative Diagnosis: A Multicenter Retrospective Cohort Study.

Background: Cytological limitations pose a challenge to preoperative diagnosis of medullary thyroid carcinoma (MTC) and therefore, a significant subset of patients is only diagnosed postoperatively. The objective of this study was to investigate the impact of knowledge of a preoperative MTC diagnosis on disease management and outcomes. Methods: Multicenter, retrospective, cohort study of MTC patients treated in Israel from January 2000 to June 2021. We compared cohorts of patients according to the presence or absence of a preoperative MTC diagnosis. Results: Ninety-four patients with histologically confirmed MTC were included (mean age 56.2 ± 14.3 years, 43% males). Fifty-three patients (56%) had a preoperative MTC diagnosis (preop-Dx group), and 41 (44%) were confirmed only postoperatively (no-Dx group). The extent of surgical resection, including completion procedures, was as follows: total thyroidectomy in 83% versus 100% (p = 0.002), central lymph node dissection (LND) in 46% versus 98% (p < 0.001), ipsilateral lateral LND in 36% versus 79% (p < 0.001), and contralateral lateral LND in 17% versus 28% (NS), in the no-Dx versus the preop-Dx group, respectively. Pathology confirmed a smaller median tumor size of 16 ± 17.4 mm versus 23 ± 14.0 mm (p = 0.09), a higher proportion of micro-MTC (size ≤10 mm) 32% versus 15% (p = 0.03), and a higher rate of co-occurrence of follicular cell-derived carcinoma 24% versus 4% (p = 0.003), in the no-Dx compared to the preop-Dx group, respectively. The rates of extrathyroidal and extranodal tumor extension were not significantly different between the groups. At the last follow-up, the biochemical cure was attained in 55% [CI 0.38-0.71] compared to 64% [CI 0.50-0.77] of the no-Dx and the preop-Dx group, respectively (p = 0.41). After the exclusion of patients with micro-MTC, biochemical cure was more commonly achieved in the preop-Dx group (33% [CI 0.14-0.52] vs. 62% [CI 0.46-0.77], p = 0.04). Preop-Dx patients had improved overall survival compared to the no-Dx group (log-rank p = 0.04) over a median follow-up of 82 months (interquartile range [IQR] 30-153). Conclusions: Preoperatively, the diagnosis of MTC is often missed. An accurate preoperative diagnosis of MTC may enable guideline-concordant surgical treatment and ultimately contribute to an overall survival benefit in MTC patients.

Effect of Opioid Receptor Activation and Blockage on the Progression and Response to Treatment of Head and Neck Squamous Cell Carcinoma.

Recent studies suggest that opioids have a role in the progression of HNSCC mediated by mu opioid receptors (MOR), however, the effects of their activation or blockage remains unclear. Expression of MOR-1 was explored in seven HNSCC cell lines using Western blotting (WB). XTT cell proliferation and cell migration assays were performed on four selected cell lines (Cal-33, FaDu, HSC-2, and HSC-3), treated with opiate receptor agonist (morphine), antagonist (naloxone), alone and combined with cisplatin. All four selected cell lines display an increased cell proliferation and upregulation of MOR-1 when exposed to morphine. Furthermore, morphine promotes cell migration, while naloxone inhibits it. The effects on cell signaling pathways were analyzed using WB, demonstrating morphine activation of AKT and S6, key proteins in the PI3K/AKT/mTOR axis. A significant synergistic cytotoxic effect between cisplatin and naloxone in all cell lines is observed. In vivo studies of nude mice harboring HSC3 tumor treated with naloxone demonstrate a decrease in tumor volume. The synergistic cytotoxic effect between cisplatin and naloxone is observed in the in vivo studies as well. Our findings suggest that opioids may increase HNSCC cell proliferation via the activation of the PI3K/Akt/mTOR signaling pathway. Moreover, MOR blockage may chemo-sensitize HNSCC to cisplatin.

Tumor Satellites Are Associated With Poor Outcome in Patients With Oral Cancer.

OBJECTIVES: Tumor satellites are defined as islands of tumor cells completely separated from the border of the main tumor. They are believed to be a sign of aggressive disease. Our goal was to investigate the association between tumor satellites and outcome in patients with oral squamous cell carcinoma. MATERIALS AND METHODS: A retrospective analysis of all patients treated for oral squamous cell carcinoma at a university-affiliated tertiary care center between 2010 and 2018 was performed. Data collected included demographics, clinical and pathological features including tumor satellites, staging, treatment modalities, and outcomes. RESULTS: A total of 144 patients were included. The mean age of all patients was 63.5 and 50.7% were males. The mean follow-up time was 40.5 months. Seventeen patients (11.8%) had tumor satellites. These patients had a higher rate of involved margins, peri-neural invasion, lympho-vascular invasion, and extra-nodal extension. Tumor, nodal and overall classification were significantly more advanced in patients with satellites. Disease-specific and overall survival rates were significantly lower among satellites patients (28.7% vs. 59.7% and 28.7% vs. 54.9%, respectively). CONCLUSIONS: Tumor satellites are associated with several adverse features and advanced locoregional disease. Patients with satellites should be treated aggressively with a combination of surgery aimed at achieving free surgical margins and adjuvant treatment, as they have a worse prognosis compared with patients without satellites. Further prospective studies are mandatory to consolidate the importance of adjuvant treatment in these patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:336-343, 2023.

The protective effect of aspirin-induced temporary threshold shift in an animal model of cisplatin-related ototoxicity.

PURPOSE: The purpose of this study was to evaluate whether induction of temporary threshold shift (TTS) with aspirin prior to cisplatin exposure can prevent or minimize cisplatin detrimental effects on hearing. METHODS: We randomly divided BALB mice into three groups: (1) cisplatin only, (2) aspirin only, and (3) combined aspirin/cisplatin. Cisplatin was administered as a single intraperitoneal injection of 14 mg/kg. Aspirin was administered for three weeks via intraperitoneal injection of 200 mg/kg sodium salicylate, twice daily. Air conduction thresholds were recorded using Auditory Brainstem Responses (ABR). Cochleae were harvested and cochlear hair cells were counted using a scanning electron microscope (SEM). RESULTS: Aspirin-induced TTS have reached an average of 30.05±16.9 dB after 2 weeks. At 60 days, cisplatin-only treated mice experienced an average threshold shifts of 50.7 dB at 4 kHz, 35.16 dB at 8 kHz, 70 dB at 16 kHz, 53.1 dB at 32 kHz. All threshold shifts were significantly worse than for cisplatin/aspirin treated mice with TTS of 11.85 dB at 4 kHz, 3.58 dB at 8 kHz, 16.58  dB at 16 kHz, 20.41 dB at 32 kHz (p < 0.01). Cochlear cell count with SEM has shown reduction in the number of both inner and outer hair cells in the mid-turn in cisplatin treated mice. CONCLUSION: Aspirin induced TTS can protect from cisplatin-induced ototoxicity. This beneficial effect was demonstrated by auditory thresholds as well as SEM. Larger pre-clinical and clinical studies are still needed to confirm these findings.

Quality of Life Following Robotic Transaxillary Versus Conventional Hemithyroidectomy: A Comparative Analysis.

Background: Robotic technology has proven safe and effective for thyroidectomy procedures. Few studies have addressed the quality-of-life outcomes of robotic thyroidectomy compared with conventional thyroidectomy. Materials and Methods: The database of a tertiary medical center was retrospectively reviewed for all patients with thyroid disease who had undergone robotic hemithyroidectomy in 2012-2020. All patients treated by transaxillary robotic surgery and a similar number of randomly selected patients treated by conventional cervical surgery completed a standardized self-administered thyroid disease-specific quality-of-life (QOL) questionnaire (ThyPRO). Clinical data were derived from the medical files. The results were compared using mean comparison tests and multivariate logistic regression models. Results: The cohort consisted of 131 patients: 63 after robotic thyroidectomy and 68 after conventional thyroidectomy. The mean age was 38.87 ± 14.11 and 58.85 ± 14.1 years, respectively (P < .0001). The robotic hemithyroidectomy group reported better QOL outcomes in physical and mental health parameters, including decreased anxiety, depression, lower sex life impairment, and cognitive impairment scores (P < .0001). Furthermore, after adjusting for age, gender, malignancy status, and surgical approach, we found that patients undergoing robotic hemithyroidectomy had a lower probability of experiencing depressive symptoms than the conventional hemithyroidectomy group (odds ratio = 0.31; 95% confidence interval, 0.11-0.88). Of interest, no significant difference in cosmetic outcomes was found. Conclusions: Patients who underwent robotic thyroidectomy report better postoperative QOL after surgery than patients operated by the conventional approach in terms of anxiety, depression, cognitive and sex-life scores.

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.

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.

The rate of occult nodal metastasis in submandibular gland malignancies: A case series and meta-analysis.

OBJECTIVE: Submandibular gland (SMG) malignancies are exceedingly rare. Lymph node metastasis is one of the most important determinants of outcome in SMG malignancies. The aim of this study was to investigate the overall rate of occult neck nodal metastasis in SMG malignancies. STUDY DESIGN: The study design is a meta-analysis of all studies on patients with a primary SMG malignancy, without evidence of neck nodal metastasis, who underwent an elective neck dissection (END). The search strategy identified 158 papers that appeared in print from January 1980 to July 2020. All eligible patients from the Tel-Aviv Medical Center were analyzed and consolidated into a case series. A total of 12 retrospective studies that included 306 suitable patients met inclusion criteria. RESULTS: The risk for occult metastasis in primary SMG malignancies was 0.0% to 50.0%, with a fixed effect model of 19.52% (95% CI, 14.9%-24.5%). The analyzed studies included a wide range of pathologies. The most common malignancies were adenoid cystic carcinoma and mucoepidermoid carcinoma. CONCLUSIONS: The overall rate of occult neck metastasis in SMG malignancies is relatively high, and an END should be the default intervention in these cases. An END is unwarranted in tumors judged clinically to be low stage and low grade.