Shaving Papillary Thyroid Carcinoma Involving Functioning Recurrent Laryngeal Nerve: Safety of Incomplete Tumor Resection and Nerve Sparing.

BACKGROUND: Whether to sacrifice or spare the recurrent laryngeal nerve (RLN) when papillary thyroid carcinoma (PTC) involves a functioning RLN remains controversial. Oncological outcomes after shaving PTC with gross remnant on the RLN have been rarely reported. The objective of this study was to evaluate the oncological outcomes of patients who underwent shaving of a PTC from the RLN, leaving a gross residual tumor with the intent of vocal function preservation. METHODS: A retrospective, cohort study was conducted in 47 patients who were determined to have PTC invasion of the RLN via intraoperative inspection and underwent tumor shaving with macroscopic remnant (R2 resection) less than 1 cm in length and 4 mm in thickness. Median follow-up period was 93 (range, 60-215) months. The primary endpoint was the recurrence-free survival and the progression-free survival. Secondary endpoints were biochemical outcomes (serum thyroglobulin) and vocal cord function. RESULTS: Of the 47 patients, five (10.6%) patients showed recurrence (central neck, 3; lateral neck, 2) without death or distant metastasis. The RLN was resected along with the tumor in one (2.1%) patient who presented with progression of the residual tumor. Postoperative temporary vocal cord paralysis occurred in six (12.8%) patients without permanent cases. The final nonstimulated serum thyroglobulin was 0.7 ± 1.8 ng/ml. CONCLUSIONS: Shaving a tumor from a RLN with gross residual disease may be considered an alternative strategy to preserve vocal function when complete tumor resection with nerve preservation is impossible in patients with PTC invading a functioning RLN.

Application of Adhesive Skin Electrode for Intraoperative Neuromonitoring During Enucleation of a Cervical Vagal Schwannoma.

BACKGROUND: No reports on applying adhesive skin electrodes for intraoperative nerve monitoring (IONM) of the vagus nerve during schwannoma enucleation have been reported in the literature. METHODS: A 45-year-old patient was referred to our institution with a 2.2 cm mass in the left lateral neck, suspected to be a vagal nerve schwannoma. A pair of surface electrodes were attached to the lateral margin of the thyroid cartilage. After exposing the tumor, the authors selected the incision site avoiding the expected course of the vagus nerve fibers after mapping on the surface of the tumor. RESULTS: Postoperative vocal cord function was intact, without aspiration or dysphagia. CONCLUSIONS: The authors report the successful use of skin electrodes for IONM of the vagus nerve during cervical vagal schwannoma removal, suggesting the feasibility of applying these electrodes for IONM of neck surgeries other than those associated with the thyroid or parathyroid glands.

Detectable depth of unexposed parathyroid glands using near-infrared autofluorescence imaging in thyroid surgery.

Background: Near-infrared light can penetrate the fat or connective tissues overlying the parathyroid gland (PG), enabling early localization of the PG by near-infrared autofluorescence (NIRAF) imaging. However, the depth at which the PG can be detected has not been reported. In this study, we investigated the detectable depth of unexposed PGs using NIRAF during thyroidectomy. Materials and methods: Fifty-one unexposed PGs from 30 consecutive thyroidectomy patients, mapped by an experienced surgeon (K.D. Lee) with the use of NIRAF imaging, were included. For NIRAF detection of PGs, a lab-built camera imaging system was used. Detectable depths of the unexposed PGs were measured using a Vernier caliper. The NIRAF images were classified as faint or bright depending on whether a novice could successfully interpret the image as showing the PG. Data on variables that may affect detectable depth and NIRAF intensity were collected. Results: Detectable depth ranged between 0.35 and 3.05 mm, with a mean of 1.23 ± 0.73 mm. The average NIRAF intensity of unexposed PGs was 3.13 au. After dissection of the overlying tissue, the intensity of the exposed PG increased to 4.88 au (p < 0.001). No difference in NIRAF intensity between fat-covered (3.27 ± 0.90 au) and connective tissue-covered PGs (3.00 ± 1.23 au) was observed (p = 0.369). PGs covered by fat tissue (depth: 1.77 ± 0.67 mm) were found at deeper locations than those covered by connective tissue (depth: 0.70 ± 0.21 mm) (p < 0.001). The brightness of images of the faint group (2.14 ± 0.48 au) was on average 1.24 au lower than that of the bright group (3.38 ± 1.04 au) (p = 0.001). A novice successfully localized 80.4% of the unexposed PGs. Other variables did not significantly affect detectable depth. Conclusion: Unexposed PGs could be mapped using NIRAF imaging at a maximum depth of 3.05 mm and an average depth of 1.23 mm. A novice was able to localize the PGs before they were visible to the naked eye at a high rate. These results can be used as reference data for localization of unexposed PGs in thyroid surgery.

Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review From the American Head and Neck Society Endocrine Surgery Section.

Importance: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery. Observation: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery. Conclusions and Relevance: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.

Use of fluorescence imaging and indocyanine green during thyroid and parathyroid surgery: Results of an intercontinental, multidisciplinary Delphi survey.

BACKGROUND: In recent years, fluorescence imaging-relying both on parathyroid gland autofluorescence under near-infrared light and angiography using the fluorescent dye indocyanine green-has been used to reduce risk of iatrogenic parathyroid injury during thyroid and parathyroid resections, but no published guidelines exist regarding its use. In this study, orchestrated by the International Society for Fluorescence Guided Surgery, areas of consensus and nonconsensus were examined among international experts to facilitate future drafting of such guidelines. METHODS: A 2-round, online Delphi survey was conducted of 10 international experts in fluorescence imaging use during endocrine surgery, asking them to vote on 75 statements divided into 5 modules: 1 = patient preparation and contraindications to fluorescence imaging (n = 11 statements); 2 = technical logistics (n = 16); 3 = indications (n = 21); 4 = potential advantages and disadvantages of fluorescence imaging (n = 20); and 5 = training and research (n = 7). Several methodological steps were taken to minimize voter bias. RESULTS: Overall, parathyroid autofluorescence was considered better than indocyanine green angiography for localizing parathyroid glands, whereas indocyanine green angiography was deemed superior assessing parathyroid perfusion. Additional surgical scenarios where indocyanine green angiography was thought to facilitate surgery are (1) when >1 parathyroid gland requires resection; (2) during redo surgeries, (3) facilitating parathyroid autoimplantation; and (4) for the predissection visualization of abnormal glands. Both parathyroid autofluorescence and indocyanine green angiography can be used during the same procedure and employing the same imaging equipment. However, further research is needed to optimize the dose and timing of indocyanine green administration. CONCLUSION: Though further research remains necessary, using fluorescence imaging appears to have uses during thyroid and parathyroid surgery.

Near-Infrared Autofluorescence Imaging May Reduce Temporary Hypoparathyroidism in Patients Undergoing Total Thyroidectomy and Central Neck Dissection.

Background: Near-infrared autofluorescence (NIRAF) imaging is known to reduce the incidence of post-thyroidectomy hypocalcemia. However, there are no studies on how much NIRAF imaging affects the serum parathyroid hormone (PTH) level after surgery. We investigated the changes of the serum PTH level and ionized calcium (iCa.) in patients undergoing total thyroidectomy with central neck dissection (CND). Materials and Methods: This retrospective study with historical control enrolled 542 patients who underwent total thyroidectomy with CND. Patients were divided into two groups: the NIRAF group (261 patients) and the control group (281 patients). PTH and iCa. levels were measured at the hospital stay, 1, 3, and 6 months after surgery. In addition, the number of identified parathyroid glands (PGs), autotransplanted PGs, and the inadvertent resection rate of PGs was evaluated. Results: The incidence of postoperative hypoparathyroidism (PTH <15 pg/mL) was significantly lower in the NIRAF group during the hospitalization (88 patients: 33.7% vs. 131 patients: 46.6%; p = 0.002) and at 1 month postoperatively (23 patients: 8.8% vs. 53 patients: 18.9%; p = 0.001). There was no difference in the permanent hypoparathyroidism rate (6 months after surgery) between the NIRAF group and the control group (4.2% vs. 4.6%; p = 0.816). There was no difference in the incidence of hypocalcemia (iCa. <1.09 mmol/L) (during hospitalization: 6.5% vs. 10.0%; 1 month: 2.3% vs. 2.5%; 3 months: 0.8% vs. 0.7%; 6 months after surgery: 1.1% vs. 1.1%) between the two groups. The number of inadvertently resected PGs was significantly lower in the NIRAF group (18:6.9% vs. 36:12.8%; p = 0.021). Conclusions: These results suggest that NIRAF imaging may reduce temporary hypoparathyroidism and the risk of inadvertent resection of PGs in patients undergoing total thyroidectomy with CND.

Five-year follow-up results of thermal ablation for low-risk papillary thyroid microcarcinomas: systematic review and meta-analysis.

OBJECTIVES: Confidence in long-term treatment results of thermal ablation for papillary thyroid microcarcinoma (PTMC) is required in comparison with active surveillance. The objective of this meta-analysis is to report 5-year follow-up results of thermal ablation for PTMC. METHODS: Ovid MEDLINE and EMBASE databases were searched through May 30, 2020, for studies reporting outcomes in patients with PTMC treated with thermal ablation and followed up for at least 5 years. Data were extracted and methodological quality was assessed independently by two radiologists according to the PRISMA guidelines. RESULTS: Three studies, involving 207 patients with 219 PTMCs, met the inclusion criteria through database searches. None of these patients experienced local tumor recurrence, lymph node metastasis, or distant metastasis or underwent delayed surgery during a mean pooled 67.8-month follow-up. Five new tumors appeared in the remaining thyroid gland of four patients, with four of these tumors successfully treated by repeat thermal ablation. The pooled mean major complication rate was 1.2%, with no patient experiencing life-threatening or delayed complications. CONCLUSIONS: Thermal ablation is an excellent local tumor control method in patients with low-risk PTMC, with low major complication rates at 5 years. KEY POINTS: • No local tumor recurrence, lymph node metastasis, or distant metastasis was noted by thermal ablation during follow-up of 5 years and none underwent delayed surgery. • The pooled mean major complication rate was 1.2%.

Long-Term Follow-Up Results of Ultrasound-Guided Radiofrequency Ablation for Low-Risk Papillary Thyroid Microcarcinoma: More Than 5-Year Follow-Up for 84 Tumors.

Background: Despite reports describing favorable short-term results for thermal ablation of thyroid cancer, there remains a need to evaluate long-term results because of its indolent characteristics. The purpose of this study was to evaluate the long-term efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) over a follow-up period of more than five years. Methods: From a cohort of patients under surveillance after US-guided RFA for primary low-risk PTMC, those with a record of follow-up data of more than five years were selected for this study. Before RFA, all patients underwent US and computed tomography to evaluate the PTMC and the presence of neck metastasis. RFA was performed using thyroid-dedicated electrodes. Follow-up US was performed 6 and 12 months after initial RFA, and then every 12 months. The status of ablated tumors was evaluated according to volume reduction, local tumor progression, newly developed cancers, lymph node (LN) or distant metastasis, and delayed surgery during follow-up. Complications during the procedure and follow-up period were evaluated. Results: A total of 84 nodules from 74 patients were included in this study. All patients tolerated RFA, and the mean follow-up duration was 72 months. After RFA, complete disappearance rates of 98.8% and 100% were achieved at 24 and 60-month follow-up, respectively. Additional ablations were performed in 13 of 84 tumors. The mean number of RFA sessions was 1.2. There were four newly developed cancers in three patients, and these were also treated with RFA and completely disappeared. During the follow-up period, there was no local tumor progression, no LN or distant metastasis, and no patients underwent delayed surgery. The major complication rate was 1.4% (1/74), and there was no delayed complication or procedure-related death. Conclusions: RFA is effective for treating low-risk PTMC patients, without occurrence of local tumor progression, LN or distant metastasis, delayed complications, procedure-related death, or delayed surgery over more than five years of follow-up.

Erratum: US-Guided Radiofrequency Ablation for Low-Risk Papillary Thyroid Microcarcinoma: Efficacy and Safety in a Large Population.

This corrects the article on p. 1653 in vol. 20, PMID: 31854153.

Fabrication and biological activity of polycaprolactone/phlorotannin endotracheal tube to prevent tracheal stenosis: An in vitro and in vivo study.

Prolonged endotracheal intubation is the most common cause of tracheal stenosis, which may lead to serious airway obstruction. Development of an endotracheal tube coated with biomaterials that exhibit anti-inflammatory or anti-fibrogenic effects may prevent tracheal stenosis. This study demonstrates that an endotracheal tube coated with phlorotannin, which is present in extracts of the brown alga Ecklonia cava, can prevent tracheal stenosis in a rabbit model. An in vitro study shows that phlorotannin inhibits proliferation of human tracheal fibroblasts treated with transforming growth factor ß1. Phlorotannin-coated endotracheal tubes show steady release of phlorotannin for up to 7 days, and removal of the tube 1 week after insertion reveals a reduction in both fibrogenesis and thickening of tracheal submucosa. Western blot analysis of tracheal tissues after removal of the phlorotannin-coated tube shows decreased protein expression levels of phenotypic markers of fibrosis such as collagen type I and α-smooth muscle actin. The ability of phlorotannin-coated endotracheal tube to prevent tracheal stenosis caused by endotracheal intubation indicates that phlorotannin may be considered as a candidate biomaterial for coating the cuff of endotracheal tubes to prevent tracheal stenosis.

Intraoperative Neuromonitoring of Recurrent Laryngeal Nerve During Thyroidectomy with Adhesive Skin Electrodes.

BACKGROUND: Alternative methods to overcome limitations of electromyogram (EMG) tube applied for intraoperative neuromonitoring (IONM) of recurrent laryngeal nerve (RLN) during thyroidectomy have been introduced. In this study, we evaluated the feasibility of adhesive skin electrodes for IONM of RLN in patients who underwent thyroidectomy. METHODS: A total of 39 nerves at risk were prospectively enrolled in this study. Twenty-five patients with papillary thyroid carcinoma, 3 patients with follicular neoplasm, and 2 patients with Graves' disease underwent thyroidectomy. All patients were intubated with EMG tube, and two disposable pre-gelled surface electrodes were attached to skin at both upper margins of thyroid cartilage. We followed the standard procedure of IONM, and the latency (msec) and amplitude (µV) of each signal were recorded prospectively. RESULTS: Intraoperative neuromonitoring using skin adhesive electrodes was successful in all nerves at risk. Amplitudes of the signals in IONM were significantly lower compared to those from EMG tube at each step of IONM, while no significant difference was identified in latency between two methods. Four nerves at risk (10.3%) showed loss of signal (<100 µV) during the steps of IONM from EMG tube, while all nerves at risk from adhesive skin electrodes showed acceptable biphasic EMG signal. CONCLUSION: We verified the usefulness of adhesive skin electrodes for IONM of RLN during thyroidectomy. Although lower amplitude remains the major limitation of this technique, adhesive skin electrodes may be considered an alternative method for IONM during thyroidectomy.

Phase-sensitive fluorescence detector for parathyroid glands during thyroidectomy: A preliminary report.

Despite advances in medical technology, the parathyroid glands are still damaged during thyroid surgery. Our previous studies exploring methods for locating the parathyroid glands using autofluorescence have limitations, such as turning off the surgical light or requiring additional matching between the autofluorescence image and real-surgical field-of-view. We developed a probe-type parathyroid autofluorescence detector using a phase-sensitive process and optical filtering to overcome these limitations. A preliminary clinical trial was performed on eight parathyroid glands in four patients. The normalized mean signal of the normal parathyroid glands was 332% stronger than that of the thyroid, and 384%, 459% and 286% stronger than the signal of the muscle, trachea and fat, respectively. Additionally, the device also detected fluorescence from indocyanine green.

US-Guided Radiofrequency Ablation for Low-Risk Papillary Thyroid Microcarcinoma: Efficacy and Safety in a Large Population.

OBJECTIVE: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) in a large population. MATERIALS AND METHODS: Cases of 152 biopsy-proven PTMCs from 133 patients who had undergone RFA for PTMC between May 2008 and January 2017 were included in this study. All patients were either of high surgical risk or refused to undergo surgery. They were followed up for at least 6 months after initial RFA. Ultrasonography (US) and computed tomography were performed to evaluate the PTMC and the presence of neck metastasis before treatment. RFA was conducted using an internally cooled thyroid-dedicated electrode system. Follow-up US was performed at 1 week, and 2, 6, and 12 months, after the initial RFA, and then at every 6-12 months. We evaluated serial changes of ablated tumors, newly developed cancers, lymph node (LN) or distant metastasis and complications. RESULTS: Complete disappearance was found in 91.4% (139/152) of ablated tumors. Among the 13 tumors in patients who did not show complete disappearance, no tumor displayed any regrowth of the residual ablated lesion during the follow-up period. The mean follow-up period was 39 months. During the follow-up period, there were no local recurrence, no LN or distant metastasis, and no newly developed thyroid cancers. No patients were referred to surgery. The overall complication rate was 3% (4/133) of patients, including one voice change. There were no life-threatening complications or procedure-related deaths. CONCLUSION: Our results suggest that RFA is an effective and safe option for treating low-risk PTMC patients who are of high surgical risk or refuse surgery.

Video-assisted parathyroid gland mapping with autofocusing.

Preservation of the parathyroid gland (PTG) in neck endocrine surgery is important for regulating the amount of calcium in the blood and within the bones. Localization of the PTG has been attempted using various methods such as ultrasound, sestamibi, computerized tomography, magnetic resonance imaging and indocyanine green fluorescence imaging. These methods cannot be used during surgery, have high sensitivity or have PTG specificity. However, autofluorescence technique has shown high sensitivity and does not require exogenous contrast. In this study, a new optical system was designed and developed into a clinical system. The system enabled easier and faster focusing on the surgical area and high-resolution video imaging while maintaining a clear image. The system was located above the head of the surgeon. The surgeon was able to see the real-time autofluorescent image on the monitor next to the operating table at any time to locate the PTG. The PTG buried in the adipose tissue and connective tissue was located easily and accurately. The clinical trial conducted in this study consisted of 56 parathyroid cases in 26 patients. For the statistical results, the sensitivity and accuracy in this redesigned autofluorescent imaging system were 98.1% and 96.4%, respectively.

Comparison of hypocalcemia rates between LigaSure and clamp-and-tie hemostatic technique in total thyroidectomies.

BACKGROUND: Postoperative hypocalcemia (PH) is a serious complication after total thyroidectomy. This study aimed to compare PH rates between LigaSure Small Jaw (LSJ) and clamp-and-tie hemostatic technique in patients undergoing total thyroidectomy. METHODS: Four hundred twenty patients were divided into two groups: group L (210 patients) performed with LSJ and group C (210 patients) with clamp-and-tie technique. Serum ionized calcium (iCa) was measured before and 12, 24, 48, 72 hours after surgery. PH was defined as iCa lower than 4.2 mg/dL in at least two measurements. RESULTS: There was no significant difference between groups in sex, age, extent of surgery, pathology, and the strategy of intraoperative management of parathyroid glands (PG). The PH rate was significantly lower in group L compared to group C (22.9% vs 32.4%, P = .03). CONCLUSIONS: Compared to clamp-and-tie technique, LigaSure is superior to decrease PH rate after total thyroidectomy.

Chitosan as a stabilizer and size-control agent for synthesis of porous flower-shaped palladium nanoparticles and their applications on photo-based therapies.

This study reported a newly developed green synthesis method using chitosan and vitamin C to prepare porous flower-shaped palladium nanoparticles. We found that chitosan not only worked as a stabilizer but also as a size-control agent for the synthesis of these nanoparticles. The growth model of flower-shaped palladium nanoparticles was proposed to interpret mechanistic understanding. The obtained nanoparticles showed good biocompatibility and strong near-infrared absorption. The nanoparticles were successfully demonstrated to be highly efficient for both in vitro photothermal therapy and in vitro photoacoustic imaging.

pH/Redox-Triggered Photothermal Treatment for Cancer Therapy Based on a Dual-Responsive Cationic Polymer Dot.

In the present study, a pH/redox-responsive cationic polymer dot (CD) was successfully prepared for a near-infrared (NIR)-mediated, simultaneously controllable photothermal temperature guided imaging off/on system to monitor therapeutic delivery. Carbonized disulfide cross-linked branched polyethyleneimine (bPEI) was conjugated with folic acid (FA) as a targeting moiety and partially formed an ionic complex with anionic indocyanine green (ICG) to afford a bPEI-based CD (ICG-CD). This was responsive to mild reductive (glutathione, GSH) and acidic tumor conditions, which enabled the simultaneous biodegradation of those hydrophobic and complex sites. The ICG-CD internalized readily into the cytoplasm of cancer cells by a FA receptor and cationic-mediated endocytosis in the off state, whereas if ICG-CD met intracellular GSH at high concentrations, GSH contributed partially to the recovery of fluorescence and was then internalized into acidic endosomes to induce complete restoration of fluorescence. This tumor-sensitive degradability of the CD not only facilitated ICG release in the tumor location but also allowed controllable photothermal therapy effects of nanoparticles under NIR irradiation, which resulted in improved cancer therapy. Taken together, the results indicate great potential in tumor targeting, intracellular imaging, and controllable therapeutic delivery through a fluorescence off/on assay under the pH/redox conditions of cancer cells.

Real-time localization of the parathyroid gland in surgical field using Raspberry Pi during thyroidectomy: a preliminary report.

We created an auto-para viewer, an autofluorescence imaging device, to localize the parathyroid glands during thyroidectomy using an inexpensive Raspberry Pi. A special emission filter in the auto-para viewer was designed to pass 1/100 of visible light and nearly all infrared light longer than 808 nm. With this emission filter, we simultaneously acquired an autofluorescence image of the parathyroid and a visible light image of the surrounding surgical field. The auto-para viewer displayed four times brighter autofluorescence of the parathyroid glands compared to the background tissues without operating room light. Additionally, it showed two times brighter autofluorescence than the background tissues simultaneously showing the surgical field illuminated by the visible light from the operating room light. The NOIR camera, using the auto-para viewer, could reduce the camera's exposure time so the parathyroid glands to be viewed in real-time, which is expected to prevent unintentional damage to the parathyroid gland during thyroidectomy.