The INMSG Survey on the Loss of Signal Management on the First Side During Planned Bilateral Thyroid Surgery.

BACKGROUND: The aim of this study is to describe the management and associated follow-up strategies adopted by thyroid surgeons with different surgical volumes when loss of signal (LOS) occurred on the first side of planned bilateral thyroid surgery, and to further define the consensus on intraoperative neuromonitoring (IONM) applications. METHODS: The International Neural Monitoring Study Group (INMSG) web-based survey was sent to 950 thyroid surgeons worldwide. The survey included information on the participants, IONM team/equipment/procedure, intraoperative/postoperative management of LOS, and management of LOS on the first side of thyroidectomy for benign and malignant disease. RESULTS: Out of 950, 318 (33.5%) respondents completed the survey. Subgroup analyses were performed based on thyroid surgery volume: <50 cases/year (n = 108, 34%); 50 to 100 cases/year (n = 69, 22%); and >100 cases/year (n = 141, 44.3%). High-volume surgeons were significantly (P < .05) more likely to perform the standard procedures (L1-V1-R1-S1-S2-R2-V2-L2), to differentiate true/false LOS, and to verify the LOS lesion/injury type. When LOS occurs, most surgeons arrange otolaryngologists or speech consultation. When first-side LOS occurs, not all respondents decided to perform stage contralateral surgery, especially for malignant patients with severe disease (eg, extrathyroid invasion and poorly differentiated thyroid cancer). CONCLUSIONS: Respondents felt that IONM was optimized when conducted under a collaborative team-based approach, and completed IONM standard procedures and management algorithm for LOS, especially those with high volume. In cases of first-site LOS, surgeons can determine the optimal management of disease-related, patient-related, and surgical factors. Surgeons need additional education on LOS management standards and guidelines to master their decision-making process involving the application of IONM.

Thermal Ablation for Benign Thyroid Nodules and Papillary Thyroid Microcarcinoma.

Ultrasound-guided minimally invasive thermoablative (MIT) therapies are a therapeutic option for selected patients with large, hypoenhancing, benign thyroid nodules that cause compression disorders or aesthetic discomfort. MIT, which does not require general anaesthesia, causes thermal necrosis of the treated nodule, which is reduced in size by 50 % without functional consequences, and is indicated for patients who are not too young or in the presence of anaesthesia-related risk factors or recurrence following thyroidectomy or refusal of surgery. For the above indications, MIT complements surgery but does not replace it; it must always be performed in centres and by surgeons with proven technical skills and clinical experience. Subject to appropriate informed consent, the treatment is short-duration, well-tolerated by the patient, safe, and non-invasive. It does not require anaesthesia and complications are rare and transient. MIT, and in particular laser-based procedures (TAL), can also be effective and safe for the treatment of potentially destructible papillary microcarcinoma, as shown by the limited but sufficient literature, including the most recent guidelines, which consider it to be a therapeutic alternative that requires a better understanding of its efficacy and safety.

Critically evaluated key points on hereditary medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) accounts for only 3% of all thyroid carcinomas: 75% as sporadic MTC (sMTC) and 25% as hereditary MTC (hMTC) in the context of multiple endocrine neoplasia type 2 (MEN2). Early diagnosis is possible by determining the tumour marker calcitonin (Ctn) when clarifying nodular goitre and by detecting the mutation in the proto-oncogene RET in the MEN2 families. If the Ctn level is only slightly elevated, up to 30 pg/ml in women and up to 60 pg/ml in men, follow-up checks are advisable. At higher levels, surgery should be considered; at a level of > 100 pg/ml, surgery is always advisable. The treatment of choice is total thyroidectomy, possibly with central lymphadenectomy. In the early stage, cure is possible with adequate surgery; in the late stage, treatment with tyrosine kinase inhibitors is an option. RET A mutation analysis should be performed on all patients with MTC. During follow-up, a biochemical distinction is made between: healed (Ctn not measurably low), biochemically incomplete (Ctn increased without tumour detection) and structural tumour detection (metastases on imaging). After MTC surgery, the following results should be available for classification in follow-up care: (i) histology, Ctn immunohistology if necessary, (ii) classification according to the pTNM scheme, (iii) the result of the RET analysis for categorisation into the hereditary or sporadic variant and (iiii) the postoperative Ctn value. Tumour progression is determined by assessing the Ctn doubling time and the RECIST criteria on imaging. In most cases, "active surveillance" is possible. In the case of progression and symptoms, the following applies: local (palliative surgery, radiotherapy) before systemic (tyrosine kinase inhibitors).

Extra-nuclear TERT counteracts oxidative stress and promotes progression in papillary thyroid carcinoma.

The reactivation of TERT is associated with poor outcome in papillary thyroid cancer (PTC). Extra-telomeric functions of TERT were reported, with a protective role against oxidative stress (OS). The aim of the present study was to explore the extra-nuclear TERT localization in PTC and its role in cancer progression. TERT nuclear export under OS were analyzed in K1 PTC cell line. We investigated the role of different TERT localizations using specific TERT constructs that limit its localization to the nucleus or to the mitochondria. The effect of SRC kinase inhibitor PP2, which reduces TERT nuclear export, was investigated as well. Moreover, TERT localization was analyzed in 39 PTC tissues and correlated with the genetic profile and the level of OS, DNA damage and apoptosis in the tumors and with the clinical characteristics of the patients. We demonstrated that TERT is exported from the nucleus in response to OS induced either from H2O2 or the BRAF inhibitor PLX4720. We proved that extra-nuclear TERT reduces mitochondrial OS and induces mitochondrial fragmentation. Moreover, limiting mitochondrial TERT localization reduced proliferation, migration, AKT phosphorylation and glycolysis and increased DNA damage and p21 expression. Finally, in PTC tissues the fraction of mitochondrial/nuclear TERT resulted inversely correlated with OS and p21 expression and associated with tumor persistence. In conclusion, our data indicate that extra-nuclear TERT is involved in reducing the effect of excessive OS, thus promoting cancer cell survival. Extra-nuclear TERT may thus represent a marker of cancer progression and a possible therapeutic target in PTC.

The risk factors for postoperative temporary vocal cord paralysis after thyroid cancer surgery: an observational retrospective cohort study.

OBJECTIVE: To analyze the potential factors influencing new-onset postoperative transient vocal cord paralysis (VCP) in thyroid cancer patients. METHODS: Case information of 8340 thyroid cancer patients hospitalized at China-Japan Union Hospital of Jilin University, Jilin Province, China, in the Thyroid Surgery Department from January 2018 to December 2020 was collected retrospectively and analyzed. The possible influencing factors were analyzed using a χ2 test, rank-sum test, and multiple logistic regression analysis. A nomogram was used to construct the clinical prediction model that was validated in the validation set by receiver operating characteristic, calibration curves, and Decision curve analysis. RESULTS: The strengthening the reporting of cohort, cross-sectional, and case-control studies in surgery (STROCSS) guideline was followed to conduct a retrospective cohort study. A total of 8340 patients, including 1817 (21.8%) men and 6523 (78.2%) women, were enrolled in this study. The rate of temporary VCP was 3.6% (308/8340). Based on the results of postoperative laryngoscopy, the patients were divided into VCP group and non-VCP group. Comparative analysis between the groups revealed that potential factors associated with postoperative transient VCP were tumor location on the dorsal side of the gland ( P =0.042), ultrasound showing a maximum nodal diameter >1 cm ( P =0.002), multifocal carcinoma ( P <0.001), invasion of surrounding tissue ( P =0.005), lymph node metastases in the central compartment ( P =0.034), lateral cervical lymph node metastasis ( P <0.001), and prolonged operation ( P <0.001). A multiple logistic regression analysis showed that the independent risk factors in postoperative transient VCP were T stage (OR=1.411, P =0.013, 95% CI: 1.075-1.853), multifocal carcinoma (OR=1.532, P =0.013, 95% CI: 1.095-2.144), and duration of surgery (OR=1.009, P <0.001, 95% CI: 1.006-1.012). Finally, a clinical prediction model was established via a nomogram and was validated in the validation set, although its diagnostic efficacy needs to be improved further. CONCLUSION: High T stage, multifocal carcinoma, and prolonged operation time may be independent risk factors for the occurrence of postoperative transient VCP in patients undergoing initial surgery for thyroid cancer.

Noticeable effect of lower baseline amplitude on the predictive accuracy of intraoperative amplitude changes for postoperative vocal cord palsy: a prospective cohort study.

BACKGROUND: To explore the effect of lower baseline amplitude on its predictive accuracy of postoperative vocal cord paralysis (VCP) in monitored thyroid surgery. MATERIALS AND METHODS: Clinical and electrophysiological data were collected during thyroid surgeries performed between November and December 2021 at China-Japan Union Hospital. Univariate/multivariate regression analysis were applied to these data to examine a possible correlation. A receiver operating characteristic curve was used to evaluate predictive efficacy. RESULTS: A total of 631 nerves-at-risk (NAR) were identified in 460 patients who were divided into two groups according to postoperative development of VCP. The VCP group included a higher percentage of NAR with V1<1000 (68.2 vs. 40.7%, respectively; P =0.014) and NAR with R1<1400 (77.3 vs. 47.0%, respectively; P =0.005) compared with the non-VCP group. Multivariate regression analysis further identified V1<1000 [odds ratio (OR)=2.688, P =0.038], R1<1400 (OR=3.484, P =0.018) as independent risk factors for postoperative temporary VCP. The receiver operating characteristic curve showed the AUC value of V signal decline for predicting VCP was 0.87. The diagnostic efficiency of R signal decline reached as high as 0.973. A multivariate logistic regression analysis identified independent risk factors for V1<1000 and these included: higher BMI (OR=1.072, P =0.013), hypertension (OR=1.816, P =0.015), smoking (OR=1.814, P =0.031), and male sex (OR=2.016, P =0.027). CONCLUSION: In our cohort, lower baseline amplitude was an independent risk factor for developing transient postoperative VCP. It also affected the predictive efficacy of intraoperative amplitude changes on VCP. Higher BMI, hypertension, smoking, and male sex may also be closely associated with lower initial amplitude. Thus, maintaining a higher initial amplitude is critical for patient safety during thyroid surgery.

Complication and conversion outcomes in transoral endoscopic thyroidectomy vestibular approach (TOETVA): a retrospective multicenter propensity score-matched cohort study.

Transoral endoscopic thyroidectomy with vestibular approach (TOETVA) is a scarless thyroid surgery used as an alternative to open conventional surgery. Our aim was to investigate possible risk factors for complications and conversion during TOETVA. The study was conducted internationally by centres from Turkiye, the Republic of Korea, Italy, and Peru. A total of 406 patients who underwent TOETVA and were ≥ 18 years of age were included in the study. Demographic, pre-, intra-, and postoperative data were collected and compared between the groups with/without complication/conversion to identify possible predictors of complication/conversion. Subsequently, patients with complication/conversion were matched by the hospital, age, sex, and American Society of Anesthesiologists classification score using a propensity score (PSM) of 1:3 to eliminate confounding differences. Results were reported for the un-matched and matched groups. Complications occurred in 11 (2.7%) patients. High body mass index (26.4 ± 3.4 vs. 23.3 ± 3.7, p = 0.007), larger tumor size (1.7 ± 1.3 cm. vs. 1.1 ± 1.0 cm, p = 0.012), larger thyroid volume (20.0 ± 9.2 vs. 12.8 ± 8.5, p = 0.007) and long operation time (127.8 ± 45.0 min. vs. 97.7 ± 38.5 min., p = 0.008) were significantly associated with complications in un-matched analyses. Older age (42.7 ± 8.0 vs. 34.9 ± 9.2, p = 0.023), high BMI (26.7 ± 3.2 vs. 23.3 ± 3.7, p = 0.012), and longer operation time (160.1 ± 54.1 min. vs. 97.4 ± 37.8, p = 0.001) were significantly related to conversion in un-matched analyses. However, significance was lost after PSM for both complication and conversion. The data from this study conducted on TOETVA cases do not suggest a risk factor for complications and conversion with PSM.

Relationships between serum levels of vitamins and papillary thyroid cancer: a single center case-control study.

Background: Vitamins are involved in various human physiological and biochemical mechanisms due to their antioxidant properties and their ability to enhance the immune response. Deficiency of some serum vitamins has been reported to be associated with an increased risk of developing cancer, including thyroid cancer. However, medical literature dealing with cholecalciferol supplementation was not able to show the potential of this intervention in cancer prevention. The aim of this paper is to highlight the association between lower serum vitamins levels and papillary thyroid cancer occurrence. Methods: This case-control study was conducted between September 2018 and October 2019. Cases were defined as patients with histologically diagnosed papillary thyroid cancer who underwent thyroidectomy were retrospectively recruited and serum levels of various vitamins were assessed by examining their relationships with clinical, pathological and molecular data (n=51). Controls matched on sex and thyroid surgery were randomly selected from the same population (n=49). Results: In this study, serum concentrations of vitamins A and E in neoplastic patients were significantly lower than in controls (1.40 vs. 1.78, P<0.003 and 23.9 vs. 29.1, P<0.003, respectively). Serum concentrations of vitamin D and methylmalonic acid were borderline significantly low (15.6 vs. 17.9, P=0.06 and 100.3 vs. 110.4, P=0.055, respectively), while homocysteine was statistically similar in the two groups. Furthermore, serum vitamin levels were compared with the pathological characteristics of cancer patients, and vitamin D concentrations were significantly lower in BRAF-positive than in BRAF-negative neoplastic patients (8.2 vs. 16.0, P=0.021). On the other hand, no significant differences were observed in the correlation between serum levels of vitamins and other pathological characteristics, in particular with regard to lymph node metastases. Conclusions: In conclusion, albeit with the analysis of a limited sample, this study highlighted the phenomenon that deficiencies in vitamins A and E can be associated with a higher frequency of occurrence of papillary thyroid cancer.

Laparoscopic vs Open Treatment for Gastric and Non-Gastric Gastrointestinal Stromal Tumors: a Two-Center Experience.

We retrospectively reviewed the medical records of 109 patients who underwent curative laparoscopic or open resection for different types of gastrointestinal stromal tumors (GIST). Only primary GIST patients who did not receive preoperative chemotherapy or oral imatinib treatment were included in the analysis. We divided the patients into 2 groups according to the surgical approach:a laparoscopic group (LAP) and a laparotomic group (OPEN). Our aim was to confirm the feasibility and safety of laparoscopic surgery for GISTs that differed in size and location, and to assess its long-term oncologic outcome in terms of overall survival (OS) and disease-free survival (DFS). Furthermore, we performed a surgical short-term outcome analysis. The two groups did not differ with respect to age at operation, gender, BMI or comorbidities. Even the NIH and AFIP risk classifications were not significantly different between the two groups. Furthermore, in our analysis, there was no significant difference in mean tumor size or location between the two groups. Wedge resection was the most frequently performed procedure. The conversion rate was 7.8%. The operative time was 194.75 (60- 350) min for the open group and 181.70 (57-480) min for the laparoscopic group. Our data clearly indicated that the long-term oncologic outcome and DFS of laparoscopic resection were not inferior to those of traditional open operations and laparoscopic resection was still feasible in cases with large tumors: the median size of the tumor was 4.5 cm (3-25) and the tumor was larger than 4.5 cm in 47.7% of the cases in the LAP group. With regard to short-term outcomes, our study demonstrated that the LAP group had fewer complications, faster gastrointestinal recovery, reduced use of analgesic drugs and shorter postoperative hospital stay (each p<0.05). In conclusion, our experience confirms that GISTs are very uncommon cancers for which the prognosis is closely related to size, localization and class of risk. In light of our clinical data, laparoscopic resection for gastric and non-gastric GISTs is a safe, feasible and oncologically correct procedure. The most important advantage of this technique is that it ensures a better postoperative outcome compared with open surgery, without worsening the prognosis.

A Feasible Technique for Transoral Endoscopic Thyroidectomy Through Vestibular Access Using a Single-port Technique: A Video Vignette in Cadaver Dissection.

BACKGROUND: The aim of this study was to evaluate the safety and feasibility of a single-port system for transoral endoscopic thyroidectomy with vestibular access (TOETVA). MATERIALS AND METHODS: Two embalmed human cadavers were used to test the single-port technique. After positioning, a median vestibular incision was made. Adipose tissue was dissected through the mentum with a Kelly clamp to reach the subplatysmal level. The Keyport Single Port System (Richard Wolf) was then inserted. After port placement, flexible endoscopic dissectors and a 5-mm endoscope were advanced. After removing the dissectors, we inserted the ArtiSential laparoscopic instruments. We also used a 3-port TOETVA on another human cadaver to compare the results with those of the single-port surgery. RESULTS: In the first cadaver, skin tension was observed during trocar insertion and dissection. Trocar insertion resulted in skin perforation in the submental area. In the second cadaver, the single-port trocar was successfully inserted despite the significant skin tension. However, the trocar did not allow the necessary surgical maneuvers to proceed with subsequent surgical steps and create a working space. Postprocedural anatomic dissection revealed that the distal branches of the mental nerve were related to the trocar passage. CONCLUSIONS: Our cadaver study demonstrated that single-port TOETVA is unsafe and not feasible with the current technology of the Keyport single-port system. This approach needs to be improved to perform this technique without injury to distal branches of the mental nerve, skin perforation, and other complications.