Evaluation of LMR, NLR and PLR as predictors of malignancy in indeterminate thyroid nodules.

OBJECTIVE: Thyroid nodules with indeterminate cytology represent 20% of all thyroid nodules. Inflammation plays an important role in cancer. Lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are independent prognostic scores in numerous cancers, although no study has documented their role in cytology indeterminate nodules. The aim of this study is to evaluate the role of LMR, NLR and PLR values as predictors of malignancy in patients with cytology indeterminate nodules. METHODS: This retrospective study analysed data from 298 patients with indeterminate thyroid nodule. Anatomopathological and haematological data were analysed, dividing the population into two groups. LMR, NLR and PLR values were determined using ROC curve and data were analysed using independent samples t-test, test of proportions, Fisher's exact test and univariate and multivariate logistic regression. RESULTS: We found that a baseline LMR value ≥ 4.09 was indicative of benignity of indeterminate nodule. The probability of malignancy in patients with LMR < 4.09 was 26 times higher than patients with a LMR value ≥ 4.09. CONCLUSIONS: This study showed that only LMR has shown a concrete probability to find a thyroid cancer in patients with indeterminate nodules. Further studies are necessary to implement tailored treatment.

Clinical significance of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio and prognostic nutritional index in low-risk differentiated thyroid carcinoma.

OBJECTIVE: Inflammation and nutritional status play an important role in the prognosis of cancer. Lymphocyte-to monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI) are independent prognostic scores in numerous cancers. However, any study showed their prognostic role in low-risk differentiated thyroid carcinoma (DTC). We aimed to clarify and identify the prognostic value of inflammation indices in low-risk DTC patients. METHODS: We analysed data from 116 patients, dividing the population into two groups, according to AJCC staging system (8th edition). The LMR, NLR, PLR and PNI cut-off value were determined using receiver operating characteristic (ROC) curve. Disease-free survival (DFS) was calculated with Kaplan-Meyer and Log-Rank tests and the risk of recurrence was calculated with univariate and multivariate Cox regression. Statistical significance was p < 0.05. RESULTS: We found a baseline NLR value ≥ 1.750 (75% sensitivity, 40.2% specificity) and a baseline LMR value of 3.83 (66.7% sensitivity, 48.9% specificity). Overall DFS was 74.995 ± 3.236 with a p value of 0.678. NLR showed a hazard ratio for recurrence with almost twice the risk of recurrence (Adjusted Hazard Ratio /HRA): 1.828, p-value = 0.019). CONCLUSIONS: NLR can be considered a prognostic score with twice the risk of recurrence in low-risk DTC patients with NLR < 1.750.

The Human Microbiota in Endocrinology: Implications for Pathophysiology, Treatment, and Prognosis in Thyroid Diseases.

The human microbiota is an integral component in the maintenance of health and of the immune system. Microbiome-wide association studies have found numerous diseases associated to dysbiosis. Studies are needed to move beyond correlations and begin to address causation. Autoimmune thyroid diseases (ATD) are one of the most common organ-specific autoimmune disorders with an increasing prevalence, higher than 5% worldwide. Most frequent manifestations of ATD are Hashimoto's thyroiditis and Graves' disease. The exact etiology of ATD remains unknown. Until now it is not clear whether bacterial infections can trigger ATD or modulate the efficacy of treatment and prognosis. The aim of our review is to characterize the microbiota and in ATD and to evaluate the impact of dysbiosis on treatment and prognosis. Moreover, variation of gut microbiome has been associated with thyroid cancer and benign nodules. Here we will characterize the microbioma in benign thyroid nodules, and papillary thyroid cancer to evaluate their implications in the pathophysiology and progression.

Dynamic transperineal ultrasonography correlates with prolonged pudendal nerve latency in female with fecal incontinence.

The pelvic floor is a complex anatomical entity and its neuromuscular assessment is evaluated through debated neurophysiological tests. An innovative approach is the study of pelvic floor through dynamic transperineal ultrasound (DTU). The aim of this study is to evaluate DTU sensitivity in recognizing patients with fecal incontinence and to evaluate its concordance with the results of the motor latency studied via pudendal nerve terminal motor latency (PNTML). Female patients affected by FI addressed to our center of coloproctology were prospectively assessed. After a coloproctological evaluation, comprising the PNTML assessment to identify pudendal neuropathy, patients were addressed to DTU to determine anterior and posterior displacement of puborectalis muscle by a blinded coloproctologist. In order to compare the data, a cohort of female healthy volunteers was enrolled. Sixty-eight subjects (34 patients and 34 healthy volunteers) were enrolled. The sensitivities of anterior displacement, posterior displacement and either anterior or posterior displacement in determining the fecal incontinence were 82%, 67% and 91%, respectively. A further high correlation of either anterior or posterior displacement with PTNML was also noted (88%). DTU is an indirect, painless and reproducible method for the identification of the pelvic floor neuromuscular integrity. Its findings seem to highly correlate with FI symptoms and with PNTML results. In the near future, after larger comparative studies, DTU would be considered a potential reliable non-invasive and feasible indirect procedure in the identification of fecal incontinence by pudendal neuropathy. Trial registration number is NCT03933683.

Transcutaneous laryngeal ultrasonography: a reliable, non-invasive and inexpensive preoperative method in the evaluation of vocal cords motility-a prospective multicentric analysis on a large series and a literature review.

Thyroidectomy is a largely performed intervention and its rate has sharply increased. The most feared postoperative complication is the recurrent laryngeal nerve paralysis, which is the most frequent cause of medicolegal litigations. Therefore, surgeons have introduced the preoperative evaluation of vocal cords function through laryngoscopy. Transcutaneous laryngeal ultrasonography has been proposed as a non-invasive indirect examination of vocal cords function. The aim of this study is to assess transcutaneous laryngeal ultrasonography reliability as an alternative painless and inexpensive method in the evaluation vocal folds function in patients amenable of thyroid surgery. We conducted a prospective multicentric study on patients affected by thyroid disease referred to the thyroid surgery divisions of two tertiary hospitals. All patients preoperatively underwent transcutaneous laryngeal ultrasonography and subsequently were evaluated via laryngoscopy by a blinded otolaryngologist. The ultrasonographical and laryngoscopical findings were then compared by an external blinded investigator. Our analysis on 396 patients showed an assessability rate of 96.46%, a sensitivity of 96.8%, a specificity of 95.6%, a positive predictive value of 65.2% and a negative predictive value of 99.7% in the identification of vocal cords alterations. A concordance between transcutaneous laryngeal ultrasonography and laryngoscopy of 95.7% was reported. In 14 patients (3.54%), the investigator reported a hard visualization of vocal cords through ultrasonography. Transcutaneous laryngeal ultrasonography is a valid non-invasive and painless alternative method in the assessment of vocal cords in a selected population; moreover, it could be useful in identifying patients addressable to second-level examination.

Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review.

BACKGROUND: Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described. CASE PRESENTATION: We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse. CONCLUSION: A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.

Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?

BACKGROUND: Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. METHODS: Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. RESULTS: Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8-38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. CONCLUSIONS: Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

The impact of the ultrasonic, bipolar and integrated energy devices in the adrenal gland surgery: literature review and our experience.

BACKGROUND: The gold standard approach for surgical treatment of benign and malignant adrenal lesion is considered the laparoscopic one, due to a lot of advantages compared to open approach. The rapid propagation of this surgical technique is due to the diffusion of haemostatic devices in laparoscopic adrenal surgery. The principal aim of this study is to analyze the outcome of LA using each energy modality, evaluating the eventual superiority of an instrument over the others. METHODS: A retrospective study, involving 75 consecutive patients submitted to LA by transperitoneal lateral approach from January 2013 to June 2017, was performed. Age less than 70 years old, adrenal adenomas less than 8 cm in diameter, incidentalomas < 6 cm, myelolipomas < 13 cm, adrenal metastases < 7 cm and ASA score ≤ III were the main surgical inclusion criteria. All involved patients were divided into three group, one for each energy device: group 1 - Harmonic Scalpel, group 2 - Ligasure vessel sealing system and group 3 - Thunderbeat. In each group only one device was applied for dissection and haemostasis during the whole operation. Each group consisted of 25 patients, well matched for histology, tumor size and site, gender and age. The following parameters were collected: age, gender, size of the tumor, side of the affected gland, pathology, operating time, intraoperative blood losses, hospitalization time, complication and conversion rate. RESULTS: There was no significant statistical difference between groups regarding the relationship between male/female, right site/left site, the mean age, hospitalization time and the tumor size (p > 0.05). Significant statistical difference are detectable in operation time and intraoperative blood losses. Thunderbeat, compared respectively with Ligasure and Harmonic Scalpel, is the fastest device (p < 0,001). The second faster device resulted Harmonic Scalpel, which meanly reduced the operation time compared to Ligasure (p = 0.048). intraoperative blood losses are reduced using Thunderbeat (p < 0,001) and HS (p = 0.006) compared to Ligasure, but between Thunderbeat and Harmonic Scalpel there isn't significant statistical difference (p = 0.178). CONCLUSIONS: Analyzing the results, laparoscopic adrenalectomy carried out using Thunderbeat appeared to show a statistically significant decrease in operation time and intraoperative blood losses compared with laparoscopic adrenalectomy performed using Harmonic Scalpel and Ligasure, while hospitalization time was superimposable in all groups. According to our data, a responsible use of advanced energy devices can improve surgical outcomes guarantying a cost savings and patient's satisfaction.