Assessing Symptomatic Hypocalcemia Risk After Total Thyroidectomy: A Prospective Study.

Introduction The most common postoperative complication of total thyroidectomy is hypocalcemia, usually monitored using serum parathyroid hormone and calcium values. Objective To identify the most accurate predictors of hypocalcemia, construct a risk assesment algorithm and analyze the impact of using several calcium correction formulas in practice. Methods A prospective, single-center, non-randomized longitudinal cohort study on 205 patients undergoing total thyroidectomy. Parathyroid hormone, serum, and ionized calcium were sampled post-surgery, with the presence of symptomatic or laboratory-verified asymptomatic hypocalcemia designated as primary outcome measures. Results Parathyroid hormone sampled on the first postoperative day was the most sensitive predictor of symptomatic hypocalcemia development (sensitivity 80.22%, cut-off value ≤2.03 pmol/L). A combination of serum calcium and parathyroid concentration sampled on the first postoperative day predicted the development of hypocalcemia during recovery with the highest sensitivity and specificity (94% sensitivity, cut-off ≤2.1 mmol/L, and 89% specificity, cut-off ≤1.55 pmol/L, respectively). The use of algorithms and correction formulas did not improve the accuracy of predicting symptomatic or asymptomatic hypocalcemia. Conclusions The most sensitive predictor of symptomatic hypocalcemia present on the fifth postoperative day was PTH sampled on the first postoperative day. The need for algorithms and correction formulas is limited.

In search of new stratification strategies: tissue proteomic profiling of papillary thyroid microcarcinoma in patients with localized disease and lateral neck metastases.

INTRODUCTION: Papillary thyroid carcinomas (PTC) are the most common thyroid malignancies that are often diagnosed as microcarcinomas when the tumor is less than one centimetre in diameter. Currently, there are no valid stratification strategies that would reliably assess the risk of lateral neck metastases and optimize surgical treatment. MATERIALS AND METHODS: Aiming to find potential tissue biomarkers of metastatic potential, we conducted a cross-sectional proteomic pilot study on formalin-fixed paraffin-embedded tissues of metastatic (N = 10) and non-metastatic (N = 10) papillary thyroid microcarcinoma patients. Samples were analysed individually using liquid chromatography/mass spectrometry, and the differentially expressed proteins (DEP) were functionally annotated. RESULTS: We identified five overexpressed DEPs in the metastatic group (EPB41L2, CSE1L, GLIPR2, FGA and FGG) with a known association to tumour biology. Using bioinformatic-based tools, we found markedly different profiles of significantly enriched biological processes between the two groups. CONCLUSIONS: The identified DEPs might have a role as potential tissue biomarkers for PTC metastases. However, further prospective research is needed to confirm our findings.

Sex- and Site-Related Significance in Cutaneous Head and Neck Melanoma.

Cutaneous head and neck melanoma is a separate subgroup of cutaneous melanoma that has a worse prognosis than other primary sites. The aim of this article is to examine the significance of sex and site of primary lesion as additional risk factors. Primary localization distribution and metastatic disease in the neck in a retrospective cohort of 159 patients with cutaneous head and neck malignant melanoma were analyzed. Men develop primary melanoma more frequently than women in the left peripheral head and neck regions (P = .0364), as well as clinically visible and occult metastatic disease in the left side of the neck (P = .0138). Patients with clinically occult regional metastatic disease showed a significantly poorer survival rate than the rest of the group that underwent elective neck dissections (P = .0270). Left-sided disease in male patients may be an additional risk factor in cutaneous head and neck melanoma. Performing elective neck dissections in high-risk patients might identify patients with occult metastatic disease and worse prognosis but does not offer any significant therapeutic benefit.

Identifying early postoperative serum parathyroid hormone levels as predictors of hypocalcaemia after total thyroidectomy: A prospective non-randomized study.

OBJECTIVE: There is no clear cut-off value of serum parathyroid hormone (PTH) or calcium in which patients are at risk for hypocalcemia after total thyroidectomy. We evaluated the usefulness of serum calcium and PTH concentration measurements after total thyroidectomy in predicting late-occurring hypocalcemia. DESIGN: A prospective, single-center, non-randomized longitudinal cohort study of 143 patients undergoing thyroidectomy between August 2019 and December 2019 with serum calcium and PTH levels sampled 1 h after surgery and on the first and fifth postoperative day. Hypocalcemia was defined as serum calcium levels < 2.14 mmol/L regardless of clinical symptoms. Normal PTH range was 1.6-6.9 pmol/L. MEASUREMENTS: The primary outcome measure was presence of hypocalcemia on the first and fifth postoperative day, analyzed by a logistic regression model. The PTH cut-off value for prediction of hypocalcemia was identified using a ROC curve comparing all three time points using the Youden J index. RESULTS: Out of 143 patients, 52 (36.4%) had hypocalcemia on the fifth postoperative day. Advanced age, concomitant neck dissection and serum PTH levels < 2.9 pmol/L 1 h after surgery and on the first postoperative surgery day were associated with a high risk of hypocalcemia on the first and fifth postoperative day and need for higher doses of calcium supplements (P < 0.0001, AUC 0.748, 95% CI 0.669-0.817, with 76.92% sensitivity and 71.43% specificity). CONCLUSION: Serum PTH level measured immediately postoperatively and on the first postoperative day is a reliable predictor of postoperative hypocalcemia with important clinical implications.

ACTIVE MIDDLE EAR VIBRANT SOUNDBRIDGE SOUND IMPLANT.

The Vibrant Soundbridge represents a new approach to hearing improvement in the form of active implantable middle ear hearing device. Unlike conventional acoustic hearing aids, which increase the volume of sound that goes to the eardrum, the Vibrant Soundbridge bypasses the ear canal and eardrum by directly vibrating the small bones in the middle ear. Because of its design, no portion of the device is placed in the ear canal itself. The Vibrant Soundbridge has been approved by the FDA as a safe and effective treatment option for adults with moderate to severe sensorineural, conductive or mixed hearing losses who desire an alternative to the acoustic hearing aids, for better hearing. The paper presents a review of the active middle ear implant Vibrant Soundbridge, which has been also implanted at the Department of Otorhinolaryngology and Head and Neck Surgery, Sestre milosrdnice University Hospital Center, which is the Referral Center for Cochlear Implantation and Surgery of Hearing Impairment and Deafness of the Ministry of Health, Republic of Croatia.

Tumor tissue hnRNP M and HSP 90α as potential predictors of disease-specific mortality in patients with early-stage cutaneous head and neck melanoma: A proteomics-based study.

BACKGROUND: Breslow tumor thickness and mitotic rate are standardly used for risk stratification of patients with malignant melanoma. However, their prognostic value is relatively limited and a need for improved prognostication has been advocated. We aimed to screen the tumor tissue proteome in a search for potentially useful prognostic factors in early-stage cutaneous head and neck melanoma. METHODOLOGY AND FINDINGS: Proteomic profiles of archival formalin-fixed tissue samples of 31 patients (age 23-90 years) with early-stage head and neck cutaneous malignant melanoma (American Joint Committee on Cancer, AJCC, stage I/II) were determined and expression intensities were compared to those of melanocytic nevi, yielding ratios used in data analysis. Medical charts were retrospectively reviewed to determine time elapsed since diagnosis to disease-specific death or censoring. In a multivariate recursive partitioning analysis (as per AJCC guidelines), higher expression levels of heterogeneous nuclear ribonucleoprotein M (hnRNP M) [n = 18, HR = 1.94 vs. the entire cohort; HR = 5.95 (95%CI 2.43-14.5) for "high" vs. "low" (n = 13)] and of heat shock protein 90 alpha (HSP 90α) [n = 17, HR = 2.09 vs. the entire cohort; HR = 4.59 (95%CI 1.87-11.2) for "high" vs. "low" (n = 14)] were each independently strongly associated with higher mortality (accounting for clinical and standard pathohistological features). Higher Breslow thickness and mitotic rate were associated with higher mortality only when proteomic data were disregarded. CONCLUSIONS AND SIGNIFICANCE: Data suggest that tumor tissue expression of hnRNP M and/or of HSP 90α deserve further investigation and clinical validation as potential novel risk stratification aids in patients with stage I-II cutaneous head and neck malignant melanoma.

RET EXPRESSION AND ITS CORRELATION WITH CLINICOPATHOLOGIC DATA IN PAPILLARY THYROID CARCINOMA.

- The purpose of this study was to analyze the possible prognostic value of RET mutation in papillary thyroid carcinoma and its incidence in the past few decades in our population, due to the increasing incidence of papillary thyroid carcinoma. The present study included 180 patients operated for papillary thyroid carcinoma. The clinical and histopathologic characteristics were analyzed. Paraffin sections of the selected histologic slides were cut again and immunohistochemically stained by the Clone 3F8 P (HIER) from Novocastra (Vision Bio Systems Europe, Newcastle upon Tyne, UK) monoclonal antibody to RET oncoprotein. Univariate analysis indicated sex (p=0.01), histologic subtype (p=0.075) and capsular invasion (p=0.010) to be statistically significant predictors of lymph node metastases, whereas age (p=0.796), tumor size (p=0.556) and intraglandular dissemination (p=0.131) showed no such correlation. The presence of RET mutation (p=0.704) was not a statistically significant predictor of the tumor metastasizing potential. RET mutation (p=0.500) showed no statistically significant correlation with papillary thyroid carcinoma classifed into prognostic groups according to clinicopathologic features either. RET mutation was detected in 30% of 180 papillary thyroid carcinomas. This is the first large study demonstrating that RET mutation incidence in papillary thyroid carcinoma in Croatian population is consistent with the classic distribution of sporadic cases, despite the increased prevalence of papillary thyroid carcinoma in the past few decades.

TYPE II HYPOPHARYNGEAL DEFECT RECONSTRUCTION - A SINGLE INSTITUTION EXPERIENCE.

- There are several options for hypopharyngeal reconstruction depending on defect size. Reconstructive options include primary closure, local flaps, regional axial flaps or regional intestinal flaps, and free flap transfer with skin or intestinal free flaps. The preferred method of reconstruction should minimize early postoperative complications that prolong hospital stay and/or become life threatening, ensure early restoration of function and decrease donor site morbidity. The purpose of this study was to evaluate functional outcomes of different flap reconstruction methods in type II hypopharyngeal defects. In this non-randomized retrospective cohort study, data on 31 (27 male and four female) patients were collected over a 10-year period of single institution type II hypopharyngeal defect reconstructions. The following measures of functional outcome were extracted from patient medical histories: postoperative complications (flap failure, fistula formation, donor site related complications), hospital stay in days and swallowing function after 14 days, 1 month and 6 months. There were nine patients in the radial forearm free flap (RFFF) reconstruction group, seven in the jejunum reconstruction group, and 15 in the gastric tube reconstruction group. In the RFFF group, three patients experienced flap failure; in the jejunal transfer group, no donor site morbidity was observed; whereas three patients from the gastric tube reconstruction group had minor abdominal skin wound dehiscence. Out of the 3 different reconstructive methods, RFFF was most likely to fail. The mean duration of hospital stay was 22.6 days, being shortest in the RFFF group. There were no significant differences in early postoperative swallowing function among the groups. The choice of flap used for hypopharynx reconstruction should be driven by donor site factors and functional outcomes. When assessing type II hypopharyngeal defect reconstruction results, the findings of this study suggest that free jejunal flaps and gastric tubes offer superior functional results in comparison with RFFFs.

Cyclin D1, Ret and P27 Expression in Papillary Thyroid Microcarcinoma

Th e aim of the study was to determine the influence of RET, p27 and cyclin D1 on regional lymph node metastases in papillary microcarcinoma. The analysis included 70 patients with papillary thyroid microcarcinoma that underwent surgery at Split University Hospital Center between 1999 and 2001. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue by the RET, p27 and cyclin D1 antibodies. Quantification was based on the intensity and distribution of nuclear staining, dividing tumors into those that showed expression (expressors) and those that showed no expression (non-expressors). Univariate analysis using χ²-test and Fisher exact test was performed with the level of statistical significance set at p<0.05. There was no statistically significant difference in the incidence of metastases according to the expression or non-expression of RET mutation (χ²-test: p=0.459; Fisher exact test: p=0.672). Among 25 cases with cyclin D1 expression, 6 had metastases, whereas only 2 of 45 cases with no cyclin D expression had metastases (χ²-test: p=0.014; Fisher exact test: p=0.021), indicating that the expression of cyclin D1 is not crucial for the development of metastases in lymph nodes. In contrast, analysis of p27 expression showed it to be significantly associated with lymph node metastasis because 3 of 45 patients with p27 expression had metastases, indicating a statistically significant correlation between p27 expression and lymph node metastases (χ²-test: p=0.093; Fisher exact test: p=0.124). This study confirmed the importance of the evaluation of RET, p27 and cyclin D1 expression and demonstrated the validity of their application in the assessment of microcarcinoma behavior.

A Rare Case of Recurrent Mucoepidermoid Carcinoma of the Nasal Vestibule.

We report a rare case of a large recurrent mucoepidermoid carcinoma (RMEC) in an 81-year-old female smoker, which has originated in the right nasal vestibule. The recurrent tumour was inadequately treated for 6 years. It was a slow-growing tumour for 3 years and then began to enlarge at a higher pace. In the next three years it has covered a large part of the face. The patient had refused any medical treatment. The tumour caused breathing and swallowing difficulties. Because of the profuse bleeding from the tumour, the patient underwent emergency surgery. Surgical treatment consisted of rhinectomy and resection of the central upper lip and part of the right cheek. The facial defect was reconstructed immediately. Recovery from surgery was fast with no complications. Postoperative Multislice Computed Tomography scan showed no metastases so the patient did not receive any chemotherapy or radiotherapy. During a 2.5 years' follow-up period there was no recurrence of the disease.

Significance of intraoperative findings in revision tympanomastoidectomy.

PURPOSE: The study was designed to assess correlations between intraoperative findings in revision tympanomastoidectomy as predictors of cholesteatoma recurrence. MATERIALS AND METHODS: A retrospective single-institution cohort of 101 patients who underwent surgical treatment for recurrent chronic otitis media in a tertiary referral otology centre. RESULTS: Out of 101 patients, 65 had canal wall up and 36 canal wall down revision surgery. There were 35 cholesteatoma recurrences. Sites most commonly associated with recurrent disease were residual facial ridge cells in 46 (45.5%), ossicular chain sites in 46 (45.5%) patients, posterior external auditory canal wall erosions in 38 (37.6%) patients and mastoid apex recurrence in 35 (34.7%) patients. Ossicular and posterior external auditory canal wall erosion and incomplete removal of mastoid apex cells correlate well with cholesteatoma recurrence accompanied by canal wall up surgery (p=0.009). Residual mastoid apex cells, posterior external auditory canal wall erosion and presence of residual facial ridge cells were identified as the strongest positive predictors of cholesteatoma recurrence, identifying high risk patients associated with canal wall down procedures (p=0.0036). CONCLUSIONS: Correlations between intraoperative findings and cholesteatoma recurrence could improve preoperative and intraoperative planning and reduce the rates of postoperative failures1 due to mismanagement of high risk areas.

Osteoblastic Extraosseous Osteosarcoma of the Neck.

Extraosseous osteosarcoma as a primary tumor of the neck is exceedingly rare, with only a few cases reported to date. The most appropriate therapy is still under investigation. We report a case of an aggressive, right-sided, advanced-stage extraosseous osteosarcoma in a female patient. A 48-year-old woman presented with a right-sided infra-parotid mass encompassing neck regions II and III, measuring over 6 cm in craniocaudal diameter. She was initially treated by wide surgical resection. The definitive histopathologic diagnosis was osteoblastic extraosseous osteosarcoma. Computed tomography at initial presentation did not show signs of tumorous growth in other areas. The patient was treated with adjuvant chemoradiotherapy postoperatively. A local recurrence with intraspinal propagation was noted 4 months after surgery, and a second surgical attempt was made to remove the tumor. The disease recurred in the neck and spine 3 months after the second surgical procedure, and a final unsuccessful attempt at reducing the tumor mass was performed. The tumor site was reirradiated. The patient died of local disease propagation 3 months later. Extraosseous osteosarcoma of the neck is an extremely rare tumor, distinct from primary osteosarcoma of the bone, with a high rate of local recurrence and poor prognosis in advanced disease.

Therapeutic efficacy of azithromycin and acetylcysteine in chronic otitis media with effusion.

Otitis media with effusion (OME) is a common disease in childhood. There is no consensus on the optimal therapeutic option for OME. Considering the known efficacy of acetylcysteine (AC) and azithromycin (AZ) in the treatment of middle ear mucosa, the aim of the study was to assess their efficacy in the management of chronic OME. The study included 90 children with OME, both ears. They are divided into three groups of 30 children. Group 1 (AC) patients were treated with acetylcysteine per os, 3 × 100 mg, for 3 weeks; group 2 (AZ) with body weight adjusted dose of azithromycin for 3 days; and group 3 (AC + AZ) with a combination of acetylcysteine and azithromycin at doses described above. Three measurements were performed. On second measurement, tympanogram improvement was recorded in 45% of 60 ears in group I, 53.3% of 60 ears in group II, and 61.7% of 60 ears in group III. The percentage of improvement was highest in group III. Although between-group differences did not reach statistical significance, the results obtained appear to be clinically relevant. In conclusion, conservative therapy for chronic OME is reasonable. Although study results don't have a strong statistical differences and may not refer clinical improvement results suggest that this combination of drugs (antibiotics, bronchosecretolytics) can be useful in the treatment of OME.

Proton pump (H+/K+-ATPase) expression in human larynx.

OBJECTIVE: The goal of our study was to investigate and to identify the existence of proton pump in different parts of larynx. The presence of acidic content in this area is known to be connected to several laryngeal diseases. It is mostly developed by upward recurrence of acidic gastric content, but there are some signs that the acid can be produced in the larynx as well, because of the proton pump activity in laryngeal mucosa. METHODS: The study was performed on two types of specimens: (1) 50 cadaver larynges and (2) 11 surgical larynges obtained after laryngectomy. Samples were taken from supraglottis, glottis and subglottic areas and immunohistochemistry for the beta subunit of the proton pump was done. RESULTS: The presence of proton pump was proved in seromucous glands in laryngeal supraglottic area, but it was also, for the first time, found in human chondrocytes in the thyroid and epiglottic cartilage. CONCLUSION: These new findings could encourage further research that would illuminate better the etiopathogenesis not only of laryngopharyngeal reflux, but also the pathophysiology of cartilaginous disorders.