Oral bisphosphonates-associated osteonecrosis in rheumatoid arthritis

Adverse effects associated with the use of bisphosphonates are infrequent and consist of pyrexia, renal function impairment, and hypocalcemia. Bisphosphonates-associated osteonecrosis of the jaws is an uncommon but potentially serious complication of intravenous bisphosphonate therapy in cancer patients. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate, is uncertain and warrants careful monitoring. Oral bisphosphonates-associated osteonecrosis can occur in patients with rheumatoid arthritis. We report a case of mandibular osteonecrosis in a patient who received alendronate for 3.8 years. The pathology improved after bisphosphonate therapy discontinuation and sequestrectomy. To our knowledge there are only three cases published in the literature relating bisphosphonates-associated osteonecrosis of the jaws in patients with rheumatoid arthritis. All the cases published, including our case, have reported association between methotrexate, prednisone and alendronate sodium (Fosamax®) therapy. Corticosteroid therapy and dental surgery could increase the risk of developing bisphosphonates-associated osteonecrosis of the jaws in these patients

Survival Outcomes in T3 Laryngeal Cancers: Primary Total Laryngectomy vs. Concurrent Chemoradiation or Radiation Therapy-A Meta-Analysis

Background: The management of cT3 laryngeal cancers remains controversial, with studies recommending surgical or non-surgical approaches. Despite the many papers that have been published on the subject, there is a lack of studies showing which treatment has better results in terms of survival. Objective: To determine the difference in survival outcomes following total laryngectomy (TL), concurrent chemoradiation (CRT) or radiation therapy (RT) alone in T3 laryngeal cancers. Methods: Search of PubMed, Scopus, and Google Scholar databases from 1995 to 2023 employing specific keywords and Boolean operators to retrieve relevant articles. Statistical analysis was conducted using a random-effects model, and heterogeneity was evaluated using the Q-test and I2 statistic. Funnel plot asymmetry was assessed using rank correlation and regression tests. Results: The qualitative data synthesis comprised 10,940 patients from 16 included studies. TL was performed in 2149 (19.4%), CRT in 6723 (61.5%), RT in 295 (2.7%), while non-surgical treatment was not specified in 1773 (16.2%) patients. The pooled 2-year overall survival (OS) rates were TL = 73%, CRT = 74.7%, RT = 57.9%, 3-year OS rates were TL = 64.3%, CRT = 62.9%, RT = 52.4%, and 5-year OS rates were TL = 54.2%, CRT = 52.7%, RT = 40.8%. There was a significant heterogeneity in the included studies. There was no statistically significant difference in 2-year OS (logOR= -0.88 (95% confidence interval (CI): -1.99 to 0.23), p = 0.12), 3-year OS (logOR = -0.6 (95% CI: -1.34 to 0.15), p = 0.11), and 5-year OS (logOR = -0.54 (95% CI: -1.29 to 0.21), p = 0.16) between TL and CRT. Instead, there was significant difference in 2-year OS (logOR= -1.2383 (95% CI: -2.1679 to -0.3087), p = 0.009), 3-year OS (-1.1262 (95% CI: -1.6166 to -0.6358), p < 0.001), and 5-year OS (-0.99 (95% CI: -1.44 to -0.53)), p < 0.001) between TL and RT alone. Conclusions and Significance: TL followed with adjuvant (chemo)radiation on indication and CRT with salvage surgery in reserve appear to have similar OS outcomes. Both resulted in better OS outcomes compared to RT alone in the treatment of T3 laryngeal cancers. If patients are unfit for chemotherapy, making CRT impossible, surgery may become the choice of treatment

Neck Surgery for Non-Well Differentiated Thyroid Malignancies: Variations in Strategy According to Histopathology

Lymph node metastases in non-well differentiated thyroid cancer (non-WDTC) are common, both in the central compartment (levels VI and VII) and in the lateral neck (Levels II to V). Nodal metastases negatively affect prognosis and should be treated to maximize locoregional control while minimizing morbidity. In non-WDTC, the rate of nodal involvement is variable and depends on the histology of the tumor. For medullary thyroid carcinomas, poorly differentiated thyroid carcinomas, and anaplastic thyroid carcinomas, the high frequency of lymph node metastases makes central compartment dissection generally necessary. In mucoepidermoid carcinomas, malignant peripheral nerve sheath tumors, sarcomas, and malignant thyroid teratomas or thyroblastomas, central compartment dissection is less often necessary, as clinical lymphnode involvement is less common. We aim to summarize the medical literature and the opinions of several experts from different parts of the world on the current philosophy for managing the neck in less common types of thyroid cancer

De-escalation studies in HPV-positive oropharyngeal cancer:How should we proceed?

Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group. (www.IHNSG.com)</p

Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review

Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. Methods: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. Results: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4–23.4) and 8.0% (95% CI 2.7–13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0–6.1%), 2.0% (95% CI 0.9–3.1) and 0.4% (95% CI 0–1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0–1.3). Conclusions: The incidence of occult lymph node metastasis is higher in supraglottic and T3–4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors

Lymph Node Metastases from Non-Melanoma Skin Cancer of the Head and Neck

Non-melanoma skin cancer (NMSC) represents the most common malignancy in the world, comprising exceedingly common lesions such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) and rare lesions such as Merkel cell carcinoma. Risk factors are widely recognized and include ultraviolet (UV) light exposure, radiation exposure, immunosuppression, and many others. As a whole, survival and functional outcomes are favorable, but each histopathological subtype of NMSC behaves differently. Treatment regimens for the primary site usually include wide surgical excision and neck dissection in cases of clinically involved metastatic lymph nodes. The elective management of draining nodal basins, however, is a contested topic. Nearly all subtypes, excluding BCC, have a significant risk of lymphatic metastases, and have been studied with regard to sentinel lymph node biopsy (SLNB) and elective neck dissection. To date, no studies have definitively established a true single standard of care, as exists for melanoma, for any of the NMSCs. As a result, the authors have sought to summarize the current literature and identify indications and management options for the management of the cervical lymphatics for each major subtype of NMSC. Further research remains critically necessary in order to develop complete treatment algorithms

Survival Outcomes in T3 Laryngeal Cancers: Primary Total Laryngectomy vs. Concurrent Chemoradiation or Radiation Therapy—A Meta-Analysis †

Background: The management of cT3 laryngeal cancers remains controversial, with studies recommending surgical or non-surgical approaches. Despite the many papers that have been published on the subject, there is a lack of studies showing which treatment has better results in terms of survival. Objective: To determine the difference in survival outcomes following total laryngectomy (TL), concurrent chemoradiation (CRT) or radiation therapy (RT) alone in T3 laryngeal cancers. Methods: Search of PubMed, Scopus, and Google Scholar databases from 1995 to 2023 employing specific keywords and Boolean operators to retrieve relevant articles. Statistical analysis was conducted using a random-effects model, and heterogeneity was evaluated using the Q-test and I2 statistic. Funnel plot asymmetry was assessed using rank correlation and regression tests. Results: The qualitative data synthesis comprised 10,940 patients from 16 included studies. TL was performed in 2149 (19.4%), CRT in 6723 (61.5%), RT in 295 (2.7%), while non-surgical treatment was not specified in 1773 (16.2%) patients. The pooled 2-year overall survival (OS) rates were TL = 73%, CRT = 74.7%, RT = 57.9%, 3-year OS rates were TL = 64.3%, CRT = 62.9%, RT = 52.4%, and 5-year OS rates were TL = 54.2%, CRT = 52.7%, RT = 40.8%. There was a significant heterogeneity in the included studies. There was no statistically significant difference in 2-year OS (logOR= −0.88 (95% confidence interval (CI): −1.99 to 0.23), p = 0.12), 3-year OS (logOR = −0.6 (95% CI: −1.34 to 0.15), p = 0.11), and 5-year OS (logOR = −0.54 (95% CI: −1.29 to 0.21), p = 0.16) between TL and CRT. Instead, there was significant difference in 2-year OS (logOR= −1.2383 (95% CI: −2.1679 to −0.3087), p = 0.009), 3-year OS (−1.1262 (95% CI: −1.6166 to −0.6358), p < 0.001), and 5-year OS (−0.99 (95% CI: −1.44 to −0.53)), p < 0.001) between TL and RT alone. Conclusions and Significance: TL followed with adjuvant (chemo)radiation on indication and CRT with salvage surgery in reserve appear to have similar OS outcomes. Both resulted in better OS outcomes compared to RT alone in the treatment of T3 laryngeal cancers. If patients are unfit for chemotherapy, making CRT impossible, surgery may become the choice of treatment

Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers

[Objective]: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules.[Design]: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively.[Methods]: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique.[Results]: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98).[Conclusions]: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology.[Significance statement]: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.Peer reviewe

Cervical lymph node metastasis in adenoid cystic carcinoma of the larynx: a collective international review

Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991-2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended

Cervical lymph node metastasis in high-grade transformation of head and neck adenoid cystic carcinoma: a collective international review

Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation