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IMPORTANCE: Multifocality is common in papillary thyroid carcinoma (PTC), but it is unclear whether multifocal tumors are associated with tumor recurrence or cancer-specific survival. OBJECTIVE: To compare tumor recurrence rates in patients with multifocal vs unifocal PTCs. DATA SOURCES: We searched PubMed, SCOPUS, Web of Science Core Collection, and Cochrane Database of Systematic Reviews for pertinent studies published in English from inception to June 30, 2020. STUDY SELECTION: The search strategy yielded 26 studies that compared tumor recurrence in patients with multifocal vs unifocal PTC. DATA EXTRACTION AND SYNTHESIS: Data was extracted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Characteristics of study populations and hazard ratio (HR) of multifocality were independently extracted by 2 investigators. MAIN OUTCOMES AND MEASURES: The primary outcome was tumor recurrence and the secondary outcome was cancer-specific survival. Subgroup analysis of the primary outcome was based on primary tumor size, number of tumor foci, and patient age. RESULTS: Among 26 studies with a total of 33 976 patients, recurrence rates were significantly higher in patients with multifocal PTC than in those with unifocal PTC (pooled HR, 1.81; 95% CI, 1.52–2.14). Cancer-specific survival was comparable between the groups (HR, 1.19; 95% CI, 0.85–1.68). In subgroup analyses, the HRs of multifocality for recurrence were associated with primary tumor size (HRs for PTC ≤1 cm and >1 cm were 1.81 and 1.90, respectively), number of tumor foci (HRs for 2 foci and ≥3 foci were 1.45 and 1.95, respectively), and patient age (HRs for pediatric and adult patients were 3.19 and 1.89, respectively). CONCLUSIONS AND RELEVANCE: This systematic review with meta-analysis found that multifocality was significantly associated with an increased risk of recurrence in patients with PTC, while cancer-specific survival showed no difference. Differences in tumor size, number of tumor foci, and patient age should be considered when interpreting the multifocality and the risk of recurrence.

Background: There is ongoing debate about whether or not robot-assisted thyroidectomy is appropriate for modified radical neck dissection (MRND). The purpose of this study was to compare the surgical outcomes of robot-assisted MRND with those of a conventional open procedure. Methods: One hundred and forty-five patients who underwent total thyroidectomy, bilateral central neck dissection, and MRND (robotic, n= 28; open, n= 117) at our institution from June 2011 to June 2015 were enrolled in the study. The surgical completeness and complication rates in the robotic and open groups were retrospectively compared after 1:3 propensity score matching for age, sex, body mass index, tumor size, and extrathyroidal extension. Results: The complication rates, including transient or permanent hypoparathyroidism and recurrent laryngeal nerve palsy, were comparable between the study groups (p > 0.05). The operating time was significantly longer in the robotic group than in the open group (p < 0.001). There was no significant difference in the number of retrieved lymph nodes, metastatic lymph nodes, or stimulated serum thyroglobulin level between the two groups (p = 0.733, p = 0.663, and p = 0.285, respectively). Conclusions: The surgical outcomes, including complication and completeness rates, were comparable between robot-assisted MRND using a bilateral axillary breast approach and conventional open surgery. Robot-assisted MRND can be recommended as an alternative to a conventional open procedure for thyroidectomy.

Bilateral axillo-breast approach robotic thyroidectomy (BABA RT) is an excellent surgical method, being oncologically safe and with anatomic views similar to those of open surgery. BABA RT, however, requires training and a learning curve for proficiency. We evaluated the educational effectiveness of a surgical training model for BABA RT, comparing objective BABA scores with scores on the da Vinci Skills Simulator (dVSS). Medical students, surgical residents, and surgical fellows performed structured tasks with the BABA training model and dVSS under the same conditions. All tasks were videotaped. BABA scores were compared with dVSS scores and with objective evaluation scores (GEARS and OSATS). Eight medical students, ten surgical residents, and eight surgical fellows participated in this study. The educational effect of BABA training improved from one to two (p< 0.001), two to three (p= 0.003), and one to three (p< 0.001) procedures. Statistically significant differences were found when students were compared with residents (p= 0.025) and fellows (p< 0.001) in the BABA training model, and between students and fellows (p= 0.004) in dVSS. BABA scores showed similar distribution patterns in the three groups to GEARS and OSATS scores (p< 0.001 each). The BABA training model is an excellent educational tool for surgical residents and surgical fellows to learn and practice BABA RT. Assessment by BABA score yielded objective results comparable to those of traditional scoring methodologies.

It is unclear whether near-infrared (NIR) light-induced indocyanine green (ICG) fluorescence can effectively identify, and thus permit the preservation of, parathyroid glands in bilateral axillo-breast approach (BABA) robotic thyroidectomy. This case–control study with a prospectively recruited consecutive series and a retrospectively selected control group assessed the usefulness of ICG with Firefly(R) technology to identify the parathyroid glands intraoperatively during BABA robotic thyroidectomy. All consecutive patients (N= 22) who were scheduled to undergo BABA robotic thyroidectomy for papillary thyroid carcinoma in December 2013–August 2015 and met the study eligibility criteria were recruited prospectively. ICG fluorescence was used with the Firefly system (NIR illuminator: 805 nm; filter: 825 nm) integrated in the da Vinci Si robot system to identify the lower parathyroid glands. Parathyroid hormone levels were recorded on postoperative days 0, 1, 2, and 14. Propensity score matching was used to identify an age-, gender-, tumor size-, and operation type-matched group of control patients who underwent BABA robotic thyroidectomy without the Firefly system. The two groups were compared in terms of parathyroid-related outcomes. ICG fluorescence-mediated identification of the parathyroid and thyroid glands required on average (range) 203 ± 89 (125–331) and 207 ± 112 (130–356) s, respectively. The mean (range) fluorescence duration in these glands was 20.8 ± 6.0 (16.6–35.8) and 20.1 ± 7.3 (15.5–33.8) min, respectively. The ICG group had a significantly lower rate of incidental parathyroidectomy than the control group (0 vs. 15.9%, P= 0.048). ICG with NIR light may feasibly and safely identify the parathyroid glands in BABA robotic thyroidectomy.

The purpose of this study was to assess the relationship between vitamin D receptor gene (VDR) expression and prognostic factors in papillary thyroid cancer (PTC). mRNA sequencing and somatic mutation data from The Cancer Genome Atlas (TCGA) were analyzed. VDRmRNA expression was compared to clinicopathologic variables by linear regression. Tree-based classification was applied to find cutoff and patients were split into low and high VDRgroup. Logistic regression, Kaplan–Meier analysis, differentially expressed gene (DEG) test and pathway analysis were performed to assess the differences between two VDRgroups. VDRmRNA expression was elevated in PTC than that in normal thyroid tissue. VDRexpressions were high in classic and tall-cell variant PTC and lateral neck node metastasis was present. High VDRgroup was also associated with classic and tall cell subtype, AJCC stage IV and lower recurrence-free survival. DEG test reveals that 545 genes were upregulated in high VDRgroup. Thyroid cancer-related pathways were enriched in high VDRgroup in pathway analyses. VDRmRNA overexpression was correlated with worse prognostic factors such as subtypes of papillary thyroid carcinoma that are known to be worse prognosis, lateral neck node metastasis, advanced stage and recurrence-free survival.

The safety of robotic thyroidectomy (RT) for small-sized thyroid carcinomas has been well established. The surgical outcomes of bilateral axillo-breast approach RT for thyroid carcinomas larger than 2 cm were evaluated and compared with those of open thyroidectomy (OT). The medical records of patients who underwent total thyroidectomy or hemithyroidectomy followed by completion thyroidectomy for differentiated thyroid carcinomas measuring 2–4 cm were retrospectively reviewed. The study included 86 patients who underwent RT (n= 21) or OT (n= 65) with mean ages of 30.8 and 51.6 years, respectively. The mean tumor size was 2.8 cm in both groups. There were no significant differences between the RT and OT groups in vocal cord palsy rate (transient, 19.0 vs. 9.2 %; permanent, 0 vs. 1.5 %), postoperative hypoparathyroidism rate (transient, 19.0 vs. 33.8 %; permanent, 4.8 vs. 1.5 %), and the number of retrieved central lymph nodes in papillary thyroid carcinoma patients (6.4 ± 3.5 vs. 6.1 ± 3.9, respectively). The proportion of the patients with serum stimulated thyroglobulin level of <1.0 ng/ml at the initial radioactive iodine treatment was 64.7 % (11/17) for RT group and 66.0 % (35/53) for OT group (p= 0.920). There were three patients (1 RT and 2 OT) who had a biochemical incomplete response, and there was no case of anatomical recurrence or mortality during the median follow-up period of 40.2 months. RT is a safe and oncologically sound treatment option for differentiated thyroid carcinomas measuring 2–4 cm in a selected group of patients. The role of RT should be evaluated in correlation with technological advances and increased experience.

Surgical procedures involving the thyroid gland require identification of the parathyroid glands. Indocyanine green (ICG) is a near-infrared (NIR) fluorescent contrast agent used for a variety of procedures such as intraoperative angiography, extrahepatic cholangiography, and lymph node mapping. In this study, we used a canine model to evaluate ICG for NIR fluorescent imaging of the parathyroid gland. Three dogs were used for the study. The dogs were administered general anesthesia, and after surgical dissection, each dog received a series of intravenous ICG doses ranging from 12.5 to 100 µg/kg ICG. The excitation light source used to illuminate the operating field was a NIR laser (λ= 785 nm). Intravascular ICG fluorescence (λ= 835/45 nm) was recorded using a charge-coupled device that employed optical filtering to block ambient and laser light. Fluorescent imaging was assessed after injection of each dose of ICG. NIR fluorescent imaging visualized the parathyroid glands. The intensity curves showing the peak and plateau of fluorescence are similar regardless of the concentration of ICG. The time to peak fluorescent intensity was 50.2 ± 2.0 s after injection of ICG. Taking into consideration background fluorescent intensity, the estimated optimal dose of ICG was 18.75 µg/kg. At 106.7 ± 5.8 s, the parathyroid glands lost much of their fluorescence, although they remained sufficiently fluorescent to be distinguishable. There was a positive correlation of fluorescent intensity with ICG dose escalation up to 25 µg/kg. ICG NIR fluorescent imaging was useful in detecting the parathyroid glands of dogs. By allowing detection of parathyroid glands, the current technique shows promise for use by endocrine surgeons performing thyroidectomies.

Robotic thyroidectomy (RoT) is frequently performed due to its excellent cosmesis and recovery features. However, postoperative pain in the operating field after RoT remains a concern due to extensive tissue dissection and tension during the operation. The aim of this study was to evaluate the anterior chest pain and the effect of levobupivacaine spraying on postoperative pain control after bilateral axillo-breast approach (BABA) RoT. We randomized 55 adult patients scheduled for BABA RoT into the control group (group C, n= 27) or the levobupivacaine group (group L, n= 28). At the end of surgery, patients in groups C and L were sprayed with the same volume (30 ml) of normal saline and 0.25 % levobupivacaine, respectively, on the flap dissection area. Pain scores, the consumption of patient-controlled analgesia (PCA), and other adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Patients in group L showed lower pain scores than those of group C at 1 h (50 [0–100] vs. 80 [20–100]; p= 0.004), 6 h (30 [0–90] vs. 70 [30–90]; p< 0.001), 24 h (30 [0–80] vs. 50 [10–80]; p= 0.016) and 48 h (10 [0–80] vs. 30 [10–80]; p< 0.001) postoperatively. PCA consumption of group L was less than that of group C at 6, 24, and 48 h after surgery. There were no significant differences in postoperative nausea–vomiting, headache, or dizziness. Local anesthetic-related adverse effects were not reported. Levobupivacaine spray on the operative field at the end of BABA RoT reduced postoperative pain and PCA consumption without adverse events.

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