Intratumor heterogeneity in colorectal cancer: Distribution of tumor suppressor gene variants with regard to patient lymph node status.

Intratumor heterogeneity (ITH) results from accumulation of somatic mutations in the fractions of successive cancer cell generations. We aimed to use deep sequencing to investigate ITH in colorectal tumors with particular emphasis on variants in oncogenes (ONC) and tumor suppressor genes (TSG). Samples were collected from 16 patients with colorectal cancer and negative or positive lymph node status (n = 8 each). We deep-sequenced a panel of 56 cancer-related genes in the central and peripheral locations of T3 size primary tumors and healthy mucosa. The central region of T3 tumors has a different frequency profile and composition of genetic variants. This mutation profile is capable of independently discriminating patients with different lymph node status (p = 0.028) in the central region. We noted an increasing number of mutations outside of the central region of the tumor and a higher number of mutations in tumors from node-positive patients. Unexpectedly, in the healthy mucosa, we identified somatic mutations with variant allele frequencies, characteristic not only of heterozygotes and homozygotes but also of other discrete peaks (e.g., around 10%, 20%), suggestive of clonal expansion of certain mutant alleles. We found differences in the distribution of variant allele frequencies in TSGs when comparing node-negative and node-positive tumors (p = 0.029), as well as central and peripheral regions (p = 0.00399). TSGs may play an important role in the escape of the tumor toward metastatic colonization.

Impact of autofluorescence for detection of parathyroid glands during thyroidectomy on postoperative parathyroid hormone levels: parallel multicentre randomized clinical trial.

BACKGROUND: Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. METHODS: This parallel multicentre RCT investigated the use of Fluobeam® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery. RESULTS: Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam® LX was reported. CONCLUSION: The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients. Registration number: NCT04509011 (http://www.clinicaltrials.gov).

Current approach to surgical management of hyperthyroidism.

Hyperthyroidism is a set of disorders that involve excess synthesis and secretion of thyroid hormones by the thyroid gland, which leads to thyrotoxicosis. The most common forms of hyperthyroidism include diffuse toxic goiter (Graves' disease), toxic multinodular goiter (Plummer disease), and a solitary toxic adenoma. The most reliable screening measure of thyroid function is the thyroid-stimulating hormone (TSH) level. Options for treatment of hyperthyroidism include: antithyroid drugs, radioactive iodine therapy (the preferred treatment of hyperthyroidism among US thyroid specialists), or thyroidectomy. Massive thyroid enlargement with compressive symptoms, a suspicious nodule, Graves' orbitopathy, and patient preference are indications for surgical treatment of thyrotoxicosis. This paper reviews the current literature and controversies on the surgical approach to the management of hyperthyroidism.

Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery: A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents.

BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

Volume, outcomes, and quality standards in thyroid surgery: an evidence-based analysis-European Society of Endocrine Surgeons (ESES) positional statement.

INTRODUCTION: Continuous efforts in surgical speciality aim to improve outcome. Therefore, correlation of volume and outcome, developing subspecialization, and identification of reliable parameters to identify and measure quality in surgery gain increasing attention in the surgical community as well as in public health care systems, and by health care providers. The need to investigate these correlations in the area of endocrine surgery was identified by ESES, and thyroid surgery was chosen for this analysis of the prevalent literature with regard to outcome and volume. MATERIALS AND METHODS: A literature search that is detailed below about correlation between volume and outcome in thyroid surgery was performed and assessed from an evidence-based perspective. Following presentation and live data discussion, a revised final positional statement was presented and consented by the ESES assembly. RESULTS: There is a lack of prospective randomized controlled studies for all items representing quality parameters of thyroid surgery using uniform definitions. Therefore, evidence levels are low and recommendation grades are based mainly on expert and peer evaluation of the prevalent data. CONCLUSION: In thyroid surgery a volume and outcome relationship exists with respect to the prevalence of complications. Besides volume, cumulative experience is expected to improve outcomes. In accordance with global data, a case load of < 25 thyroidectomies per surgeon per year appears to identify a low-volume surgeon, while > 50 thyroidectomies per surgeon per year identify a high-volume surgeon. A center with a case load of > 100 thyroidectomies per year is considered high-volume. Thyroid cancer and autoimmune thyroid disease predict an increased risk of surgical morbidity and should be operated by high-volume surgeons. Oncological results of thyroid cancer surgery are significantly better when performed by high-volume surgeons.

[Risk factors of malignancy in patients with fine needle aspiration biopsy results interpreted as "suspicious for follicular neoplasm"].

OBJECTIVE: Introduction: Approximately 10% of fine needle aspiration biopsy (FNAB) of thyroid nodules may be verified as "suspicious for follicular neoplasm"; this category involves follicular adenoma, follicular carcinoma, follicular variants of papillary carcinoma and subclass "suspicious for Hurthle cell neoplasm". At present, there is no diagnostic tool to discriminate between follicular adenoma and cancer. Most patients are required surgery to exclude malignant process. The aim: To define factors correlating with risk of malignancy in patients with FNAB of thyroid focal lesions and nodules verified as Bethesda tier IV. PATIENTS AND METHODS: Materials and Methods: In this study 110 consecutive patients were included. All patients were operated because of FNAB result "suspicious for follicular neoplasm" of thyroid gland at a single institution from January 2016 until March 2020. From this set, six specific categories were defined and the clinical records for patients were collected: sex, age, presence of oxyphilic cells, diameter of the tumour, presence of Hashimoto disease, aggregate amount of clinical and ultrasonographic features of malignancy according to ATA. RESULTS: Results: In 18 patients (16,3%) thyroid cancer occurred. Most frequent subtype turned out to be papillary cancer (66,6%). In group of benign lesion (92 patients) predominance of follicular adenoma was disclosed - (49%). Age, gender, tumour diameter, aggregate amount of clinical and ultrasonografic factors, presence of Hashimoto disease and fine needle aspiration biopsy result suspicious for Hurthle cell neoplasm did not correspond to increased risk of malignancy. CONCLUSION: Conclusions: In patients with FNAB results classified as Bethesda tier IV there are no reliable clinical features associated with low risk of malignancy and surgery should be consider in every case as most appropriate manner to exclude thyroid cancer .

[The impact of elective central lymph node dissection on postoperative pathological staging and surgical complication rate in patients with results of fine needle spiration biopsy suspicious for follicular neoplasm of thyroid].

OBJECTIVE: Introduction: Follicular-patterned lesions of the thyroid are common; these include follicular adenoma, follicular cancer and follicular variant of papillary cancer. At present, preoperative discrimination between follicular adenoma and follicular cancer is infeasible and most patients require surgery to confirm diagnosis. The aim: To assess the impact of elective central lymph node dissection on postoperative pathological staging and early surgical complication rate in patients operated for suspicion for follicular neoplasm or suspicion for oxyphilic neoplasm of thyroid. PATIENTS AND METHODS: Materials and Methods: Eighty consecutive patients operated between 2016-2018 in Third Department of General Surgery UJCM because of suspicious for follicular neoplasm of the thyroid were included into the study. Inclusion criteria were: the result of fine needle aspiration biopsy " suspicious for follicular/oxyphilic neoplasm", absence of invasive neoplasm features as follows infiltration of surrounding tissue or lymph nodes/distant metastases, informed consent. In all patients elective central lymph node dissection was performed. Surgical early postoperative complications were reported and the rate was compared between the study group and the control group consisting of patients operated on in the same period for benign nodular goitre. RESULTS: Results: In 10 (12,5%) patients thyroid cancer was diagnosed, including 8 (80%) patients with papillary cancer and 2 (20%) patients with follicular cancer. The most common benign lesion was follicular adenoma diagnosed in 42 (60%) patients. There were 129 lymph nodes dissected (mean 1.6 lymph node per 1 patient), all lymph nodes were clear of cancer cells. In 26 patients there were no lymph nodes in postoperative preparation. Metastatic lymph nodes were not identified in any patients of the study group with final diagnosis of thyroid cancer. No significant differences were identified in prevalence of early postoperative complications among the study group and the control group patients: unilateral recurrent laryngeal nerve (RLN) palsy 3.4% vs. 1.49%; p= 0,08), hypocalcemia (5% vs. 5.4%; p=0.86), postoperative hemorrhage (1.25% vs. 0.44; p=0.29). CONCLUSION: Conclusions: Elective central lymph node dissection at experienced surgical hands does not improve postoperative pathological staging and is not associated with higher risk of early postoperative complications.

Intraoperative neuromonitoring versus visual nerve identification for prevention of recurrent laryngeal nerve injury in adults undergoing thyroid surgery.

BACKGROUND: Injuries to the recurrent inferior laryngeal nerve (RILN) remain one of the major post-operative complications after thyroid and parathyroid surgery. Damage to this nerve can result in a temporary or permanent palsy, which is associated with vocal cord paresis or paralysis. Visual identification of the RILN is a common procedure to prevent nerve injury during thyroid and parathyroid surgery. Recently, intraoperative neuromonitoring (IONM) has been introduced in order to facilitate the localisation of the nerves and to prevent their injury during surgery. IONM permits nerve identification using an electrode, where, in order to measure the nerve response, the electric field is converted to an acoustic signal. OBJECTIVES: To assess the effects of IONM versus visual nerve identification for the prevention of RILN injury in adults undergoing thyroid surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 21 August 2018. We did not apply any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing IONM nerve identification plus visual nerve identification versus visual nerve identification alone for prevention of RILN injury in adults undergoing thyroid surgery DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance. One review author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second review author checked them. For dichotomous outcomes, we calculated risk ratios (RRs) with 95% confidence intervals (CIs). For continuous outcomes, we calculated mean differences (MDs) with 95% CIs. We assessed trials for certainty of the evidence using the GRADE instrument. MAIN RESULTS: Five RCTs with 1558 participants (781 participants were randomly assigned to IONM and 777 to visual nerve identification only) met the inclusion criteria; two trials were performed in Poland and one trial each was performed in China, Korea and Turkey. Inclusion and exclusion criteria differed among trials: previous thyroid or parathyroid surgery was an exclusion criterion in three trials. In contrast, this was a specific inclusion criterion in another trial. Three trials had central neck compartment dissection or lateral neck dissection and Graves' disease as exclusion criteria. The mean duration of follow-up ranged from 6 to 12 months. The mean age of participants ranged between 41.7 years and 51.9 years.There was no firm evidence of an advantage or disadvantage comparing IONM with visual nerve identification only for permanent RILN palsy (RR 0.77, 95% CI 0.33 to 1.77; P = 0.54; 4 trials; 2895 nerves at risk; very low-certainty evidence) or transient RILN palsy (RR 0.62, 95% CI 0.35 to 1.08; P = 0.09; 4 trials; 2895 nerves at risk; very low-certainty evidence). None of the trials reported health-related quality of life. Transient hypoparathyroidism as an adverse event was not substantially different between intervention and comparator groups (RR 1.25; 95% CI 0.45 to 3.47; P = 0.66; 2 trials; 286 participants; very low-certainty evidence). Operative time was comparable between IONM and visual nerve monitoring alone (MD 5.5 minutes, 95% CI -0.7 to 11.8; P = 0.08; 3 trials; 1251 participants; very low-certainty evidence). Three of five included trials provided data on all-cause mortality: no deaths were reported. None of the trials reported socioeconomic effects. The evidence reported in this review was mostly of very low certainty, particularly because of risk of bias, a high degree of imprecision due to wide confidence intervals and substantial between-study heterogeneity. AUTHORS' CONCLUSIONS: Results from this systematic review and meta-analysis indicate that there is currently no conclusive evidence for the superiority or inferiority of IONM over visual nerve identification only on any of the outcomes measured. Well-designed, executed, analysed and reported RCTs with a larger number of participants and longer follow-up, employing the latest IONM technology and applying new surgical techniques are needed.

Training in endocrine surgery.

BACKGROUND/PURPOSE: In Europe, the Division of Endocrine Surgery (DES) determines the number of operations (thyroid, neck dissection, parathyroids, adrenals, neuroendocrine tumors of the gastro-entero-pancreatic tract (GEP-NETs)) to be required for the European Board of Surgery Qualification in (neck) endocrine surgery. However, it is the national surgical boards that determine how surgical training is delivered in their respective countries. There is a lack of knowledge on the current situation concerning the training of surgical residents and fellows with regard to (neck) endocrine surgery in Europe. METHODS: A survey was sent out to all 28 current national delegates of the DES. One questionnaire was addressing the training of surgical residents while the other was addressing the training of fellows in endocrine surgery. Particular focus was put on the numbers of operations considered appropriate. RESULTS: For most of the operations, the overall number as defined by national surgical boards matched quite well the views of the national delegates even though differences exist between countries. In addition, the current numbers required for the EBSQ exam are well within this range for thyroid and parathyroid procedures but below for neck dissections as well as operations on the adrenals and GEP-NETs. CONCLUSIONS: Training in endocrine surgery should be performed in units that perform a minimum of 100 thyroid, 50 parathyroid, 15 adrenal, and/or 10 GEP-NET operations yearly. Fellows should be expected to have been the performing surgeon of a minimum of 50 thyroid operations, 10 (central or lateral) lymph node dissections, 15 parathyroid, 5 adrenal, and 5 GEP-NET operations.

Ten-Year Follow-Up of a Randomized Clinical Trial of Total Thyroidectomy Versus Dunhill Operation Versus Bilateral Subtotal Thyroidectomy for Multinodular Non-toxic Goiter.

BACKGROUND: The aim of this study was to validate in a 10-year follow-up the initial outcomes of various thyroid resection methods for multinodular non-toxic goiter (MNG) reported in World J Surg 2010;34:1203-13. MATERIALS AND METHODS: Six hundred consenting patients with MNG were randomized to three groups of 200 patients each: total thyroidectomy (TT), Dunhill operation (DO), bilateral subtotal thyroidectomy (BST). Obligatory follow-up period of 60 months was extended up to 120 months for all the consenting patients. The primary outcome measure was the prevalence of recurrent goiter and need for revision thyroid surgery. The secondary outcome measure was the cumulative postoperative and post-revision morbidity rate. RESULTS: The primary outcomes were twice as inferior at 10 years when compared to 5-year results for DO and BST, but not for TT. Recurrent goiter was found at 10 years in 1 (0.6%) TT versus 15 (8.6%) DO versus 39 (22.4%) BST (p < 0.001), and revision thyroidectomy was necessary in 1 (0.6%) TT versus 5 (2.8%) DO versus 14 (8.0%) BST patients (p < 0.001). Any permanent morbidity at 10 years was present in 5 (2.8%) TT patients following initial surgery versus 7 (4.0%) DO and 10 (5.7%) BST patients following initial and revision thyroidectomy (nonsignificant differences). At 10 years, 23 (11.5%) TT versus 25 (12.5%) DO versus 26 (13.0%) BST patients were lost to follow-up. CONCLUSIONS: Total thyroidectomy can be considered the preferred surgical approach for patients with MNG, as it abolishes the risk of goiter recurrence and need for future revision thyroidectomy when compared to more limited thyroid resections, whereas the prevalence of permanent morbidity is not increased at experienced hands. REGISTRATION NUMBER: NCT00946894 ( http://www.clinicaltrials.gov ).

Prognostic value of intraoperative neural monitoring of the recurrent laryngeal nerve in thyroid surgery.

PURPOSE: The diagnostic accuracy of intraoperative recurrent laryngeal nerve (RLN) monitoring (IONM) remains controversial. The aim of this study was to evaluate IONM diagnostic accuracy in prognostication of postoperative nerve function in thyroid surgery. METHODS: This prospective study was conducted in 2011-2013. Five hundred consenting patients qualified for total thyroidectomy with IONM (1000 nerves at risk) using NIM 3.0 Response equipment were included. Laryngoscopy was used to evaluate and follow up RLN injury. The primary outcome was diagnostic accuracy of IONM. The receiver operating characteristics (ROC) were used for evaluation of IONM diagnostic accuracy. RESULTS: Loss of signal (LOS) occurred in 31 cases, including 25 patients with LOS and corresponding vocal fold paresis found in postoperative laryngoscopy (2.5 %), including 20 (2.0 %) temporary and 5 (0.5 %) permanent nerve lesions. The following diagnostic accuracy values were calculated for the criterion recommended by INMSG (V2 amplitude ≤ 100 µV): sensitivity 92.0 %, specificity 99.3 %, positive predictive value (PPV) 76.7 %, and negative predictive value (NPV) 99.8 %. The ROC curve analysis allowed for calculation of the most optimal criterion in prognostication of postoperative vocal fold paresis, namely, V2 amplitude ≤ 189 µV. For this criterion, PPV was 77.4 %, while NPV was 99.9 %. CONCLUSIONS: Adherence to the standardized protocol recommended by the International Neural Monitoring Study Group allows for optimizing predictive values of IONM in prognostication of postoperative RLN function. Any changes in the cutoff values for the definition of LOS only marginally improve PPV and NPV of IONM and need to be carefully assessed in multicenter studies.

Comparison of perioperative stress in patients undergoing thyroid surgery with and without neuromonitoring-a pilot study.

PURPOSE: A comprehensive psychological comparison of preoperative stress in patients scheduled for thyroidectomy with versus without intraoperative neurophysiologic monitoring (IONM) has never been reported. The aim of this study was to assess whether a planned utilization of IONM had any effect on the reduction of stress and anxiety level before and after thyroid surgery. METHODS: The outcomes of 32 patients scheduled for thyroidectomy with IONM were compared to the outcomes of a carefully matched control group of 39 patients operated on without IONM. All the patients were tested before the surgery and at 1-7 days postoperatively employing psychological self-report instruments: the Depression Anxiety Stress Scales (DASS), State-Trait Anxiety Inventory (STAI), 12-item General Health Questionnaire (GHQ), Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT H&N), and the visual analog scale (VAS). RESULTS: The examined groups were homogenous and carefully matched in terms of mental health (GHQ), the quality of life (FACT H&N), and the intensity of depression level (DASS). The IONM group showed a significantly lower level of "the state anxiety"(STAI) 1 day before the operation (p < 0.05), greater trust in the doctor (VAS) (p < 0.05), and greater confidence in the treatment method (VAS) as compared to the patients in the control group (p < 0.05), while no significant differences were found when the remaining items were compared. CONCLUSIONS: The planned use of IONM during thyroidectomy may reduce patient anxiety before surgery. However, further research in this area is necessary to confirm this preliminary finding in a larger population of patients.

Experience with intraoperative neuromonitoring of the recurrent laryngeal nerve improves surgical skills and outcomes of non-monitored thyroidectomy.

PURPOSE: Intraoperative neuromonitoring (IONM) can serve as a tool to increase skills in recurrent laryngeal nerve (RLN) identification and complete removal of thyroid tissue. The aim of this study was to validate this hypothesis. METHODS: This prospective study involved 632 patients (1161 RLNs at risk) who underwent thyroid surgery in 2011-2014. Although IONM was not used until 2012, this prospective study started on 1 January 2011. The three participating surgeons knew about the study before that date and that the rate of RLN identification would be carefully measured in total and near-total surgery. Solely, visual identification of the RLN was used throughout 2011. IONM was introduced as a training tool in 2012-2014 for the first 3 months of each year. In the remaining months, thyroid operations were performed without IONM. Outcomes of non-monitored thyroid operations were compared before (01-12/2011) vs. after (04-12/2012-2014) 3 months of exposure to IONM yearly (01-03/2012-2014). The rate of RLN identification was assessed in total and near-total thyroidectomies and in totally resected lobes in Dunhill's operation. The prevalence of RLN injury and the utilization of total thyroidectomy were evaluated. RESULTS: In 2011, the rate of successful RLN visual identification in total and near-total thyroidectomies and in totally resected lobes in Dunhill's operation was 45.71 %. After the introduction of IONM in 2012-2014, in the procedures performed without IONM, the rate was 86.66, 90.81, and 91.3 %. The prevalence of RLN injury in 2011 was 6.8 %, while in the years following the introduction of IONM, it was 3.61, 2.65, and 1.45 %. Utilization of total thyroidectomy increased from 47.9 % in 2011 to 100 % in 2014. CONCLUSIONS: Experience with IONM led to an increase in RLN identification (p < 0.0001), a decrease of RLN injury (p < 0.05), and an increase in the safe utilization of total thyroidectomy (p < 0.0001) in non-monitored thyroid operations. IONM is a valuable tool for surgical training.

The learning curve for intraoperative neuromonitoring of the recurrent laryngeal nerve in thyroid surgery.

PURPOSE: Intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) is often used in thyroid surgery. However, this procedure is complex and requires a learning period to master the technique. The aim of the study was to evaluate the learning curve for IONM. METHODS: A 3-year period (2012-2014) of working with IONM (NIM3.0, Medtronic) was prospectively analyzed with a special emphasis on comparing the initial implementation phase in 2012 (101 patients, 190 RLNs at risk) with subsequent years of IONM use in 2013 (70 patients, 124 RLNs at risk) and 2014 (65 patients, 120 RLNs at risk). RESULTS: The rate of successful IONM-assisted RLN identification increased gradually over the 3-year study period (92.11 % in 2012 vs. 95.16 % in 2013 vs. 99.16 % in 2014; p = 0.022), with a corresponding decrease in the rate of technical problems (12.87, 4.3, and 4.6 %, respectively; p = 0.039). The rate of RLN injuries tended to decrease over time: 3.68, 1.55, and 0.83 %, respectively (p = 0.220). Between 2012 and 2014, increases in the sensitivity (71.4 vs. 100 %), specificity (98 vs. 99 %), positive predictive value (62.5 vs. 75 %), negative predictive value (98 vs. 100 %), and overall accuracy of IONM (97.4 vs. 99.6 %) were observed (p = 0.049). Increasing experience with IONM resulted in more frequent utilization of total thyroidectomy (92 % in 2012 vs. 100 % in 2013-2014; p = 0.004). CONCLUSIONS: There was a sharp decrease in the number of technical problems involving equipment setup from 2012 to 2014.

The current state of intermittent intraoperative neural monitoring for prevention of recurrent laryngeal nerve injury during thyroidectomy: a PRISMA-compliant systematic review of overlapping meta-analyses.

PURPOSE: Recurrent laryngeal nerve (RLN) injury is one of the most common and detrimental complications following thyroidectomy. Intermittent intraoperative nerve monitoring (I-IONM) has been proposed to reduce prevalence of RLN injury following thyroidectomy and has gained increasing acceptance in recent years. METHODS: A comprehensive database search was performed, and data from eligible meta-analyses meeting the inclusion criteria were extracted. Transient, permanent, and overall RLN injuries were the primary outcome measures. Quality assessment via AMSTAR, heterogeneity appraisal, and selection of best evidence was performed via a Jadad algorithm. RESULTS: Eight meta-analyses met the inclusion criteria. Meta-analyses included between 6 and 23 original studies each. Via utilization of the Jadad algorithm, the selection of best evidence resulted in choosing of Pisanu et al. (Surg Res 188:152-161, 2014). Five out of eight meta-analyses demonstrated non-significant (p > 0.05) RLN injury reduction with the use of I-IONM versus nerve visualization alone. CONCLUSIONS: To date, I-IONM has not achieved a significant level of RLN injury reduction as shown by the meta-analysis conducted by Pisanu et al. (Surg Res 188:152-161, 2014). However, most recent developments of IONM technology including continuous vagal IONM and concept of staged thyroidectomy in case of loss of signal on the first side in order to prevent bilateral RLN injury may provide additional benefits which were out of the scope of this study and need to be assessed in further prospective multicenter trials.

[Giant supernumerary parathyroid adenoma as a cause of persistent primary hyperparathyroidism in a patient with a multiglandular parathyroid disease].

Despite the significant progress that has been made in recent years in parathyroid imaging, improvements in surgical techniques and availability of surgical quality control based on intraoperative parathyroid hormone levels (PTH) assay, approximately 1-5% of patients undergoing surgery have state of persistent hyperparathyroidism. The most common causes of persistent hyperparathyroidism are: limited surgical experience, a failure to recognize multiglandular parathyroid disease, ectopic parathyroid adenoma location, insufficient range of resection of diseased parathyroid glands, parathyroid capsule tearing leading to parathyromathosis, as well as parathyroid cancer. In this clinical observation the case of a 52-years old man is described who underwent surgical removal of 2 parathyroid adenomas, and within few days he was found to have persistent hypercalcemia. After completing the diagnostic imaging and biochemical work-up that patient underwent bilateral neck re-exploration with removal of ectopic giant supernumerary parathyroid adenoma (60 mm in diameter and 22.8 g in weight) which was localized in the upper part of the posterior mediastinum, resulting in stable normocalcemia afterwards.

The Overwhelming Majority but not All Motor Fibers of the Bifid Recurrent Laryngeal Nerve are Located in the Anterior Extralaryngeal Branch.

BACKGROUND: Few small studies reported that motor fibers are located exclusively in the anterior branch of the bifid recurrent laryngeal nerve (RLN). The aim of this study was to investigate the location of the motor fibers to the intrinsic muscles of the larynx among the bifid RLNs, and assess the prevalence of RLN injury with respect to nerve branching in a pragmatic trial. METHODS: This was a prospective cohort study of 1250 patients who underwent total thyroidectomy with intraoperative neural monitoring. The primary outcome was the position of the motor fibers in the bifid nerves. Adduction of the vocal folds was detected by the endotracheal tube electromyography and abduction by finger palpation of muscle contraction in the posterior cricoarytenoid. The secondary outcomes were the prevalence of the RLN branching and the prevalence of RLN injury in bifid versus non-bifid nerves. RESULTS: The bifid RLNs were identified in 613/2500 (24.5%) nerves at risk, including 92 (7.4%) patients with bilateral bifurcations. The motor fibers were present exclusively in the anterior branch in 605/613 (98.7%) bifid nerves, and in both the RLN branches in 8/613 (1.3%) bifid nerves. Prevalence of RLN injury was 5.2 versus 1.6% for the bifid versus non-bifid nerves (p < 0.001), odds ratio 2.98 (95% confidence interval 1.79-4.95; p < 0.001). CONCLUSIONS: The motor fibers of the RLN are located in the anterior extralaryngeal branch in the vast majority of but not in all patients. In rare cases, the motor fibers for adduction or abduction are located in the posterior branch of the RLN. As the bifid nerves are more prone to injury than non-branched nerves, meticulous dissection is recommended to assure preservation of all the branches of the RLN during thyroidectomy.

Trends in Prevalence of Thyroid Cancer Over Three Decades: A Retrospective Cohort Study of 17,526 Surgical Patients.

INTRODUCTION: Thyroid cancer (TC) incidence has been increasing in recent years. The aim of this study was to investigate our institution-based estimates of operative volumes for TC over the last three decades. MATERIALS AND METHODS: This was a retrospective cohort study of patients undergoing thyroid surgery at our institution. Patient characteristics were reviewed in three subgroups: Group I (treated in 1981-1986), Group II (treated in 1987-2002), and Group III (treated in 2003-2012). RESULTS: TC was diagnosed in 1578/17,526 (9.0%) thyroid operations. Incidence of TC increased from 3.7% in Group I to 10.4% in Group III (p < 0.001). Incidence of papillary TC increased form 40.6% in Group I to 81.3% in Group III (p < 0.001). In the latter group, 23.5% of all papillary TCs were diagnosed in patients with Hashimoto's disease. Meanwhile, incidence of anaplastic TC decreased from 16.2% in Group I to 2.1% in Group III patients (p < 0.001). pT1 tumors were diagnosed in 8.1% Group I and 54.8% Group III (p < 0.001), whereas pT4 tumors were identified in 40.5% Group I, 2.4% Group II, and 0.84% Group III subjects (p < 0.001). pT3 tumors were found in 51.6% Group I, whereas multifocal papillary TCs were found in 15.7% Group III patients, the latter with a higher prevalence of pN1 stage (p < 0.001). CONCLUSIONS: The following trends in surgical volume for TC were identified throughout the study period: a fivefold increase of thyroid operations for TC, a threefold increase in incidence of papillary TC, and an eightfold decrease in incidence of anaplastic TC. It is of interest that a significant increase in incidence of multifocal papillary TC in young female patients with Hashimoto's disease was found over time.