Abstract
Background
Preserving parathyroid glands during thyroidectomy remains challenging, particularly in remote-access procedures. Mitoxantrone hydrochloride injection (MHI) is a local lymphotropic tracer that may improve intraoperative discrimination of parathyroid glands during gasless unilateral axillary endoscopic thyroidectomy (GUAET), but evidence remains limited. We evaluated whether intraoperative MHI was associated with a lower rate of incidental parathyroidectomy (IP) during GUAET and described parathyroid autotransplantation (PAT) as a separate management outcome.
Methods
We performed a single-center retrospective cohort study of consecutive patients who underwent GUAET at a tertiary referral center in China between July 2020 and May 2024. Patients who received intraoperative MHI were compared with patients who underwent the same procedure without MHI. The primary outcome was IP. Secondary outcomes included PAT, short-term biochemical hypoparathyroidism [parathyroid hormone (PTH) <15 pg/mL], hypocalcemia (calcium <2.11 mmol/L), lymph node metrics, and postoperative symptoms. Nearest-neighbor 1:2 propensity score matching without replacement was performed using a 0.25-standard deviation caliper.
Results
The study included 129 patients (31 in the MHI group and 98 in the control group). Propensity score matching yielded 93 patients (31 MHI and 62 controls). In the matched cohort, MHI was associated with a lower rate of IP [4/31 (12.9%) vs. 24/62 (38.7%); odds ratio (OR), 0.235; 95% confidence interval (CI), 0.073–0.754; P=0.02] and a higher rate of PAT [15/31 (48.4%) vs. 3/62 (4.8%); OR, 18.438; 95% CI, 4.746–71.630; P<0.001]. Rates of postoperative day 1 and month 1 hypoparathyroidism and hypocalcemia were similar between groups. Lymph node yield, positive lymph node counts, and postoperative symptom rates were also comparable.
Conclusions
During GUAET, intraoperative MHI was associated with fewer IPs and more frequent PAT after propensity score matching. No clear differences were observed in short-term biochemical recovery, lymph node metrics, or postoperative symptoms.
Keywords: Gasless unilateral axillary endoscopic thyroidectomy (GUAET), incidental parathyroidectomy (IP), mitoxantrone hydrochloride injection (MHI), parathyroid autotransplantation (PAT), thyroid cancer
Highlight box.
Key findings
• In gasless unilateral axillary endoscopic thyroidectomy (GUAET), intraoperative mitoxantrone hydrochloride injection (MHI) was associated with a lower rate of incidental parathyroidectomy and more frequent parathyroid autotransplantation after propensity score matching, but short-term biochemical outcomes, lymph node metrics, and postoperative symptoms were similar between groups.
What is known and what is new?
• Adjuncts such as indocyanine green, nanocarbon, and near-infrared autofluorescence can assist with parathyroid identification, but each has equipment, workflow, or interpretation limitations.
• This study provides propensity score-matched, real-world evidence that MHI, an equipment-free lymphotropic tracer, may reduce incidental parathyroidectomy during GUAET.
What is the implication, and what should change now?
• This study addresses a practical intraoperative adjunct for minimally invasive thyroid surgery.
• Because this was a small retrospective single-center study with short follow-up and no gland-level classification of autotransplantation, prospective multicenter validation is still needed before routine adoption can be recommended.
Introduction
Thyroid cancer is the most common endocrine malignancy worldwide, with an estimated 44,020 new cases and 2,290 deaths expected in the United States in 2025 alone (1). From the 1980s to the 2010s, its incidence rose steadily while mortality remained largely stable, reflecting advances in the detection of thyroid cancer (1-4). In recent years, incidence rates have begun to decline modestly (~0.8% annually) (5).
With advances in diagnostics, further emphasis is needed on surgical optimization, complication prevention, and long-term follow-up (6).
Thyroidectomy remains the cornerstone of treatment for patients with papillary thyroid carcinoma, but the procedure carries a persistent risk of parathyroid injury (7). In one retrospective study of 1,030 total thyroidectomies, transient hypoparathyroidism occurred in 28.2% and permanent hypoparathyroidism in 2.6% of patients (8). Remote-access approaches such as gasless unilateral axillary endoscopic thyroidectomy (GUAET) aim to preserve oncologic adequacy while avoiding a visible cervical scar (9-16). Unlike carbon dioxide (CO2)-insufflated approaches, GUAET avoids CO2-related risks, including hypercapnia, subcutaneous emphysema, gas embolism, and hemodynamic or metabolic effects (16,17). However, the altered viewing angle and the small size and variable location of the parathyroid glands can still make parathyroid gland identification difficult during endoscopic dissection.
Incidental parathyroidectomy (IP) and devascularization may lead to transient or permanent hypoparathyroidism, which can substantially impair quality of life (18). Accordingly, techniques that improve intraoperative recognition and preservation of parathyroid glands remain clinically important. Several adjuncts have been explored, including indocyanine green (ICG) fluorescence, nanocarbon, and near-infrared autofluorescence (19-21). Autofluorescence offers label-free identification, and ICG may assist with perfusion assessment. However, both approaches require dedicated imaging systems and may complicate intraoperative workflow (19,22-25). Nanocarbon can facilitate visual contrast and lymph node mapping, but irreversible staining or tracer spillage may hinder fine dissection (26-28).
Mitoxantrone hydrochloride injection (MHI) is a lymphotropic tracer that stains thyroid lymphatic drainage and may increase the visual contrast between draining lymphatic tissue and unstained parathyroid glands (29). Although mitoxantrone is also recognized as a systemic antineoplastic agent, the tracer formulation used in thyroid surgery is administered locally in small intrathyroidal volumes rather than intravenously (29,30). Prior studies have suggested that MHI can reduce inadvertent parathyroid resection during open or more extensive thyroid procedures, but evidence for GUAET remains limited (27,31,32).
We therefore conducted a retrospective cohort study to evaluate whether intraoperative MHI was associated with a lower IP rate during GUAET. Parathyroid autotransplantation (PAT) was analyzed separately as an intraoperative management outcome. We also examined short-term biochemical recovery, lymph node metrics, and postoperative symptoms. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0292/rc).
Methods
Study design and ethics
This single-center retrospective cohort study included consecutive patients who underwent GUAET at Peking Union Medical College Hospital, a tertiary academic center in China, between July 2020 and May 2024. All procedures were performed by the same dedicated GUAET surgical team using a standardized operative technique. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval was obtained from the Institutional Review Board of the Ethics Committee of Peking Union Medical College Hospital (approval No. I-24PJ1796; approved on August 27, 2024), and the requirement for informed consent was waived because of the retrospective design.
Patients
Inclusion criteria for patients were (I) no prior thyroid surgery; (II) preoperative ultrasonography and fine-needle aspiration confirming or strongly suggesting papillary thyroid carcinoma; (III) GUAET for unilateral thyroid lobectomy. Exclusion criteria were: (I) abnormal preoperative parathyroid hormone (PTH) or known parathyroid disorder; (II) incomplete records. A total of 129 patients met the study criteria; 31 received intraoperative MHI, and 98 served as controls.
Surgical procedure and MHI protocol
All patients underwent GUAET to remove the thyroid lobe on the affected side. GUAET was performed through a 3-cm axillary incision with external retraction to establish the operative field, as previously described (33). After MHI was adopted in our institutional protocol, all consecutive eligible cases underwent intraoperative lymphatic mapping with MHI (China Resources Sanjiu Pharmaceutical Co., Ltd., Shenzhen, China; National Medical Products Administration approval H20210025, 2 mL:10 mg) (27,32).
After thyroid exposure, MHI was injected into the thyroid parenchyma at 2 to 3 sites. The injected volume was 0.05 to 0.1 mL per point, and the total injected volume did not exceed 0.6 mL. Because the formulation concentration was 10 mg/2 mL, the maximum total intraoperative tracer dose was 3 mg, administered locally into the thyroid rather than intravenously. Dissection proceeded after approximately 5 minutes to allow lymphatic migration of the tracer. The device used for injection is shown in Figure S1. The operative field after staining is shown in Figure S2.
Outcomes
The primary outcome was IP, defined as histologic identification of parathyroid tissue in the thyroidectomy specimen. Secondary outcomes were PAT, short-term biochemical hypoparathyroidism (PTH <15 pg/mL), and hypocalcemia (serum calcium <2.11 mmol/L) measured preoperatively, on postoperative day 1 (POD1), and at postoperative month 1 (POM1); lymph node yield and positivity; and postoperative symptoms, including pharyngalgia, hoarseness, aspiration when drinking, cough, perioral and acral paresthesia, reduced vocal pitch, nausea, abdominal discomfort, and fever.
Propensity score matching and statistical analysis
To reduce confounding by baseline differences, propensity scores for receiving MHI were estimated using penalized logistic regression. Preoperative covariates entered into the model were sex, age category (<18, 18–45, >45 years), body mass index category (<18.5, 18.5–23.9, ≥24 kg/m2), number of tumors, surgical side, preoperative PTH level, and preoperative calcium level. Final pathologic diagnosis and TNM stage were summarized descriptively but were not entered into the propensity model because they were postoperative variables and were not part of treatment assignment at the time of surgery.
Nearest-neighbor 1:2 matching without replacement was performed using a caliper width of 0.25 standard deviations (SD) of the logit of the propensity score, and observations outside the region of common support were discarded. Covariate balance was assessed using standardized mean differences (SMD), with |SMD| <0.10 considered desirable, and was visualized with Love plots (Figure S3).
Continuous variables were summarized as mean ± SD and compared with non-parametric tests for independent samples; categorical variables were compared using Fisher’s exact tests. Binary outcomes are presented as n/N (percentage) alongside odds ratios (OR) and 95% confidence intervals (CI). Two-tailed P values less than 0.05 were considered statistically significant. Missing data were analyzed using an available-case approach. Analyses were performed in R v4.3.2 and SPSS v30.0. The R packages MatchIt, glmnet, cobalt, tableone, splines, dplyr, and tidyr were used.
Results
Cohort and propensity score matching
Among the 129 included patients, 31 received intraoperative MHI, and 98 did not. Propensity score matching yielded a matched cohort of 93 patients, including all 31 patients in the MHI group and 62 controls. After matching, most baseline characteristics were balanced, although small residual imbalances remained for body mass index category, preoperative PTH, and preoperative calcium (Table 1, Figure S3).
Table 1. Baseline characteristics before and after propensity score matching.
| Characteristics | Before PSM | After PSM | ||||
|---|---|---|---|---|---|---|
| MHI (N=31) | Control (N=98) | P value | MHI (N=31) | Control (N=62) | P value | |
| Age (years) | 0.36 | 0.44 | ||||
| <18 | 0 (0.0) | 1 (1.0) | 0 (0.0) | 1 (1.7) | ||
| 18–45 | 28 (90.3) | 94 (95.9) | 28 (90.3) | 59 (95.2) | ||
| >45 | 3 (9.7) | 3 (3.1) | 3 (9.7) | 2 (3.2) | ||
| Female | 31 (100) | 91 (92.9) | 0.20 | 31 (100) | 59 (95.2) | 0.55 |
| BMI (kg/m2) | 0.21 | 0.11 | ||||
| <18.5 | 2 (6.5) | 11 (11.2) | 2 (6.5) | 6 (9.7) | ||
| 18.5–23.9 | 20 (64.5) | 72 (73.5) | 20 (64.5) | 49 (79.0) | ||
| ≥24 | 9 (29.0) | 15 (15.3) | 9 (29.0) | 7 (11.3) | ||
| Side | 0.53 | >0.99 | ||||
| Left | 11 (35.5) | 43 (43.9) | 11 (35.5) | 23 (37.1) | ||
| Right | 20 (64.5) | 55 (56.1) | 20 (64.5) | 39 (62.9) | ||
| Number of tumors | 0.32 | 0.33 | ||||
| 1 | 29 (93.5) | 83 (84.7) | 29 (93.5) | 52 (83.9) | ||
| 2 | 1 (3.2) | 12 (12.2) | 1 (3.2) | 8 (12.9) | ||
| 3 | 1 (3.2) | 3 (3.1) | 1 (3.2) | 2 (3.2) | ||
| Pathology | >0.99 | >0.99 | ||||
| Papillary carcinoma | 31 (100) | 97 (99.0) | 31 (100) | 61 (98.4) | ||
| Other | 0 (0.0) | 1 (1.0) | 0 (0.0) | 1 (1.6) | ||
| T | >0.99 | 0.44 | ||||
| 1a | 27 (87.1) | 83 (84.7) | 27 (87.1) | 50 (80.6) | ||
| 1b | 3 (9.7) | 12 (12.2) | 3 (9.7) | 11 (17.7) | ||
| 2 | 1 (3.2) | 2 (2.0) | 1 (3.2) | 1 (1.6) | ||
| 4a | 0 (0.0) | 1 (1.0) | 0 (0.0) | 0 (0.0) | ||
| N | 0.66 | 0.27 | ||||
| 0 | 21 (67.7) | 56 (57.1) | 21 (67.7) | 33 (53.2) | ||
| 1a | 10 (32.3) | 40 (40.8) | 10 (32.3) | 29 (46.8) | ||
| X | 0 (0.0) | 2 (2.0) | 0 (0.0) | 0 (0.0) | ||
| M | >0.99 | >0.99 | ||||
| 0 | 31 (100) | 98 (100) | 31 (100) | 62 (100) | ||
| TNM stage | >0.99 | >0.99 | ||||
| 1 | 31 (100) | 97 (99.0) | 31 (100) | 61 (98.4) | ||
| 4 | 0 (0.0) | 1 (1.0) | 0 (0.0) | 1 (1.6) | ||
Data are presented as n (%). BMI, body mass index; MHI, mitoxantrone hydrochloride injection; PSM, propensity score matching.
Impact of intraoperative MHI on parathyroid gland preservation
In the matched cohort, MHI was associated with a significantly lower rate of IP than the control strategy [4/31 (12.9%) vs. 24/62 (38.7%); OR, 0.235; 95% CI, 0.073–0.754; P=0.02] (Table 2). MHI was also associated with a higher rate of PAT [15/31 (48.4%) vs. 3/62 (4.8%); OR, 18.438; 95% CI, 4.746–71.630; P<0.001]. Altogether, MHI displays a role in both reducing inadvertent excisions and improving intraoperative decision-making for PAT (Table 2). Because the operative records did not systematically distinguish salvage autotransplantation after inadvertent excision from transplantation of a gland judged ischemic in situ, the PAT difference should not be interpreted as direct evidence of superior parathyroid preservation or function. PAT is better viewed as an intraoperative management outcome that may reflect changes in surgeon decision-making after improved gland visualization.
Table 2. Intraoperative parathyroid management outcomes before and after propensity score matching.
| Management | Before PSM | After PSM | ||||||
|---|---|---|---|---|---|---|---|---|
| MHI (N=31) | Control (N=98) | OR (95% CI) | P value | MHI (N=31) | Control (N=62) | OR (95% CI) | P value | |
| IP | 4 (12.9) | 32 (32.7) | 0.306 (0.099–0.948) | 0.04 | 4 (12.9) | 24 (38.7) | 0.235 (0.073–0.754) | 0.02 |
| PAT | 15 (48.4) | 4 (4.1) | 22.031 (6.480–74.900) | <0.001 | 15 (48.4) | 3 (4.8) | 18.438 (4.746–71.630) | <0.001 |
Data are presented as n (%), unless otherwise indicated. PAT was analyzed as an intraoperative management outcome and should not be interpreted as unequivocal evidence of superior preservation. CI, confidence interval; IP, incidental parathyroidectomy; MHI, mitoxantrone hydrochloride injection; OR, odds ratio; PAT, parathyroid autotransplantation; PSM, propensity score matching.
Despite the difference in intraoperative parathyroid-related outcomes, short-term biochemical recovery was similar between groups. In the matched cohort, the rate of POD1 hypoparathyroidism was 5/31 (16.1%) in the MHI group and 6/62 (9.7%) in the control group (P=0.50), while the rate of POD1 hypocalcemia was 1/31 (3.2%) and 7/62 (11.3%), respectively (P=0.26) (Table 3). By POM1, no patient in either group had biochemical hypoparathyroidism, and only one control patient had hypocalcemia.
Table 3. Biochemical parathyroid hormone and calcium outcomes before and after propensity score matching.
| Outcomes | Before PSM | After PSM | ||||
|---|---|---|---|---|---|---|
| MHI | Control | P value | MHI | Control | P value | |
| Preoperative hypo-PTH | 0/31 (0.0) | 0/95 (0.0) | >0.99 | 0/31 (0.0) | 0/62 (0.0) | >0.99 |
| POD1 hypo-PTH | 5/31 (16.1) | 7/94 (7.4) | 0.17 | 5/31 (16.1) | 6/62 (9.7) | 0.50 |
| POM1 hypo-PTH | 0/31 (0.0) | 0/95 (0.0) | >0.99 | 0/31 (0.0) | 0/62 (0.0) | >0.99 |
| Preoperative hypo-Ca | 0/31 (0.0) | 1/98 (1.0) | >0.99 | 0/31 (0.0) | 1/62 (1.6) | >0.99 |
| POD1 hypo-Ca | 1/31 (3.2) | 10/95 (10.5) | 0.29 | 1/31 (3.2) | 7/62 (11.3) | 0.26 |
| POM1 hypo-Ca | 0/31 (0.0) | 1/95 (1.1) | >0.99 | 0/31 (0.0) | 1/62 (1.6) | >0.99 |
Data are presented as n/N (%); denominators vary owing to missing laboratory values. Ca, calcium; MHI, mitoxantrone hydrochloride injection; POD1, postoperative day 1; POM1, postoperative month 1; PSM, propensity score matching; PTH, parathyroid hormone.
Lymph node outcomes
Lymph node metrics were comparable between the matched groups (Table 4). Mean detected lymph node counts were 6.61±4.014 in the MHI group and 7.42±4.252 in the control group (P=0.36). The mean number of positive nodes per patient (0.81±1.327 vs. 1.53±2.708; P=0.20) and the proportion of positive nodes (11.3% vs. 17.5%; P=0.21) were also similar.
Table 4. Lymph node outcomes before and after propensity score matching.
| Outcomes | Before PSM | After PSM | ||||
|---|---|---|---|---|---|---|
| MHI (N=31) | Control (N=98) | P value | MHI (N=31) | Control (N=62) | P value | |
| Detected LN | 6.61±4.014 | 6.94±4.247 | 0.65 | 6.61±4.014 | 7.42±4.252 | 0.36 |
| Number of positive LN | 0.81±1.327 | 1.21±2.391 | 0.49 | 0.81±1.327 | 1.53±2.708 | 0.20 |
| Proportion of positive LN | 0.113±0.184 | 0.144±0.214 | 0.46 | 0.113±0.184 | 0.175±0.237 | 0.21 |
Data are presented as mean ± standard deviation. LN, lymph node; MHI, mitoxantrone hydrochloride injection; PSM, propensity score matching.
Postoperative symptoms
To further assess the safety of intraoperative MHI, postoperative complications, including pharyngalgia, hoarseness, aspiration upon drinking, cough, perioral and acral paresthesia, reduced vocal pitch, nausea, abdominal discomfort, and fever were evaluated. Postoperative symptoms were infrequent and did not differ significantly between groups (Table 5). No signal suggested increased early postoperative morbidity after use of the tracer, although the study was not designed as a formal safety analysis.
Table 5. Postoperative symptoms before and after propensity score matching.
| Symptoms | Before PSM | After PSM | ||||
|---|---|---|---|---|---|---|
| MHI (N=31) | Control (N=98) | P value | MHI (N=31) | Control (N=62) | P value | |
| Pharyngalgia | 5 (16.1) | 5 (5.1) | 0.06 | 5 (16.1) | 4 (6.5) | 0.15 |
| Hoarseness | 0 (0.0) | 1 (1.0) | >0.99 | 0 (0.0) | 0 (0.0) | >0.99 |
| Aspiration upon drinking | 0 (0.0) | 1 (1.0) | >0.99 | 0 (0.0) | 0 (0.0) | >0.99 |
| Cough | 0 (0.0) | 2 (2.0) | >0.99 | 0 (0.0) | 0 (0.0) | >0.99 |
| Perioral and acral paresthesia | 3 (9.7) | 3 (3.1) | 0.15 | 3 (9.7) | 2 (3.2) | 0.33 |
| Reduced vocal pitch | 0 (0.0) | 0 (0.0) | >0.99 | 0 (0.0) | 0 (0.0) | >0.99 |
| Nausea | 0 (0.0) | 0 (0.0) | >0.99 | 0 (0.0) | 0 (0.0) | >0.99 |
| Abdominal discomfort | 0 (0.0) | 0 (0.0) | >0.99 | 0 (0.0) | 0 (0.0) | >0.99 |
| Fever | 2 (6.5) | 1 (1.0) | 0.14 | 2 (6.5) | 0 (0.0) | 0.11 |
Data are presented as n (%). MHI, mitoxantrone hydrochloride injection; PSM, propensity score matching.
Discussion
In this propensity score-matched retrospective cohort study of GUAET, intraoperative MHI was associated with fewer IPs and more frequent PAT, whereas short-term biochemical outcomes, lymph node metrics, and postoperative symptoms were similar between groups. The reduction in IP indicates improved preservation of parathyroid tissue, although whether this translates to clinically meaningful benefit remains uncertain. By contrast, the higher PAT rate should be regarded as a change in intraoperative management rather than as proof of improved gland function.
The present findings are directionally consistent with previous reports suggesting that MHI can improve intraoperative recognition of parathyroid glands during thyroid surgery (27,31,32). Alternative adjuncts merit comparison. Adjuncts such as ICG and nanocarbon are often used to aid parathyroid identification and can enhance parathyroid gland preservation in gasless transaxillary endoscopic thyroidectomy, but both methods face limitations (34). While ICG and near-infrared autofluorescence allow real-time assessment of parathyroid perfusion, they require specialized equipment and show variable reliability (19,22-25). Nanocarbon facilitates lymph node mapping, but it is irreversible and can obscure fine dissections (26-28). By contrast, MHI is a visible lymphotropic tracer that does not require fluorescence equipment, although it does not directly measure gland perfusion (27,31,32). Given that mitoxantrone has long been recognized as a cytotoxic agent when administered systemically, the concern about its safety remains. In the present study, however, MHI was used as a local intrathyroidal tracer in a total volume of no more than 0.6 mL (3 mg total), rather than as intravenous chemotherapy. Early postoperative symptom rates were similar between groups, and previously published phase I/pharmacokinetic and clinical tracing studies have suggested acceptable short-term safety with local tracer-dose use (29,30). Nonetheless, our retrospective dataset was not designed for formal drug-safety assessment, and rare or delayed adverse events cannot be excluded.
The absence of a clear difference in early postoperative PTH and calcium outcomes should be interpreted cautiously. All patients in this cohort underwent unilateral thyroidectomy, and preserved contralateral parathyroid function may have limited our ability to detect short-term biochemical differences. In this setting, a lower IP rate may still be clinically relevant even when early laboratory values normalize. Evidence regarding the functional benefit of PAT remains mixed (35-40). A cohort study with 501 patients demonstrated that selective PAT can prevent permanent hypoparathyroidism after total thyroidectomy (37). Although PAT has previously been recommended for devascularized parathyroid glands (38), several studies have yielded opposing results. In a cohort of 1,157 patients who underwent surgical intervention for Graves’ disease, PAT was associated with early postoperative hypocalcemia (39). Furthermore, a meta-analysis of 8,182 patients demonstrated that PAT does not significantly reduce the rate of permanent hypoparathyroidism (40). PAT can represent salvage of a gland that has been inadvertently removed or nearly devascularized. However, it can also reflect a lower intraoperative threshold to remove and transplant a gland in situations where in situ preservation might otherwise have been feasible. Because the retrospective operative records did not reliably distinguish ex vivo salvage of inadvertently removed glands from autotransplantation of glands judged intraoperatively to be ischemic in situ, the predominant mechanism underlying PAT could not be determined. Thus, the role of PAT merits further study, especially regarding its impact on long-term function after thyroidectomy.
Several limitations should be acknowledged. First, the study was retrospective and nonrandomized, which leaves room for measured and unmeasured confounding. Generalizability may be limited by the retrospective single-center design and potential institution-specific surgical practices. Second, MHI was introduced later during the study period. Consequently, the observed associations may partly reflect era effects. Although propensity score methods were used to reduce measured confounding, residual confounding related to time-dependent practice evolution cannot be excluded. Third, the MHI sample was small (n=31), and residual imbalance remained after matching for several variables. Fourth, follow-up was limited to 1 month for biochemical outcomes, precluding evaluation of permanent hypoparathyroidism, long-term voice outcomes, and durable oncologic safety. Consequently, our findings should be interpreted as reflecting only early postoperative outcomes rather than sustained functional or oncologic benefit. Fifth, we could not distinguish ex vivo salvage after inadvertent excision from transplantation of a gland judged devascularized in situ. This limitation substantially restricts interpretation of the PAT findings. The observed increase in PAT should not be interpreted as evidence of better functional preservation and may instead reflect altered intraoperative decision-making. Finally, adverse events specifically attributable to MHI were not systematically collected, limiting assessment of rare or delayed tracer-related toxicity.
Conclusions
In GUAET, intraoperative MHI was associated with a lower rate of IP and a higher rate of PAT after propensity score matching, without clear differences in short-term biochemical outcomes. The IP finding is the most clinically relevant result, although whether this translates into improved long-term parathyroid function remains uncertain. The PAT difference should be interpreted cautiously because the indication for autotransplantation was not classified.
Supplementary
The article’s supplementary files as
Acknowledgments
The authors used ChatGPT (OpenAI) exclusively for language polishing and grammatical editing. No AI tool was used for data analysis, data interpretation, or the generation of scientific conclusions. All final content was reviewed and approved by the authors.
The authors thank the clinical staff who contributed to perioperative care for the patients included in this study.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of the Ethics Committee of Peking Union Medical College Hospital (approval No. I-24PJ1796), and the requirement for informed consent was waived because of the retrospective design.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0292/rc
Funding: This work was supported by the National Natural Science Foundation of China (No. 31971069).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0292/coif). The authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0292/dss
References
- 1. Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025. CA Cancer J Clin 2025;75:10-45.. 10.3322/caac.21871 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Chen DW, Haymart MR. Unravelling the rise in thyroid cancer incidence and addressing overdiagnosis. Nat Rev Endocrinol 2026;22:10-20.. 10.1038/s41574-025-01168-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Vigneri R, Malandrino P, Russo M. Is Thyroid Cancer Increasing in Incidence and Aggressiveness?. J Clin Endocrinol Metab 2020;105:dgaa223.. 10.1210/clinem/dgaa223 [DOI] [PubMed] [Google Scholar]
- 4.Dunlap Q, Davies L. Differentiated Thyroid Cancer Incidence. In: Randolph GW, editor. Surgery of the Thyroid and Parathyroid Glands. 3rd ed. Elsevier; 2021:174-80.e2. [Google Scholar]
- 5.Cancer Stat Facts: Thyroid Cancer. In: Cancer Stat Facts. National Cancer Institute, National Cancer Institute. 2025. Accessed 20th, September 2025. Available online: https://seer.cancer.gov/statfacts/html/thyro.html#:~:text=In%202025%2C%20it%20is%20estimated%20that%20there%20will,die%20of%20this%20disease.%20Who%20Gets%20This%20Cancer%3F
- 6. Scheller B, Culié D, Poissonnet G, et al. Recent Advances in the Surgical Management of Thyroid Cancer. Curr Oncol 2023;30:4787-804.. 10.3390/curroncol30050361 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Papaleontiou M, Hughes DT, Guo C, et al. Population-Based Assessment of Complications Following Surgery for Thyroid Cancer. J Clin Endocrinol Metab 2017;102:2543-51.. 10.1210/jc.2017-00255 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Cho JN, Park WS, Min SY. Predictors and risk factors of hypoparathyroidism after total thyroidectomy. Int J Surg 2016;34:47-52.. 10.1016/j.ijsu.2016.08.019 [DOI] [PubMed] [Google Scholar]
- 9. Zhang P, Zhang HW, Han XD, et al. Meta-analysis of comparison between minimally invasive video-assisted thyroidectomy and conventional thyroidectomy. Eur Rev Med Pharmacol Sci 2015;19:1381-7. [PubMed] [Google Scholar]
- 10. Duek I, Duek OS, Fliss DM. Minimally Invasive Approaches for Thyroid Surgery-Pitfalls and Promises. Curr Oncol Rep 2020;22:77.. 10.1007/s11912-020-00939-2 [DOI] [PubMed] [Google Scholar]
- 11. Russell JO, Noureldine SI, Al Khadem MG, et al. Minimally invasive and remote-access thyroid surgery in the era of the 2015 American Thyroid Association guidelines. Laryngoscope Investig Otolaryngol 2016;1:175-9.. 10.1002/lio2.36 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. de Vries LH, Aykan D, Lodewijk L, et al. Outcomes of Minimally Invasive Thyroid Surgery - A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2021;12:719397.. 10.3389/fendo.2021.719397 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Jantharapattana K, Maethasith J. Transaxillary gasless endoscopic thyroidectomy versus conventional open thyroidectomy: a randomized study. Eur Arch Otorhinolaryngol 2017;274:495-500.. 10.1007/s00405-016-4242-8 [DOI] [PubMed] [Google Scholar]
- 14. Lu Q, Zhu X, Wang P, et al. Comparisons of different approaches and incisions of thyroid surgery and selection strategy. Front Endocrinol (Lausanne) 2023;14:1166820.. 10.3389/fendo.2023.1166820 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Zheng X, Wang X, Wei T. Gasless Endoscopic Thyroidectomy via the Trans-Axillary Approach. J Vis Exp 2023. [DOI] [PubMed]
- 16. Cheng X, Ding X, Wang S, et al. Progress in gasless endoscopic thyroidectomy. Front Endocrinol (Lausanne) 2024;15:1466837.. 10.3389/fendo.2024.1466837 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Meng K, Xin Y, Tan Z, et al. Key points of surgical anatomy for endoscopic thyroidectomy via a gasless unilateral axillary approach. Langenbecks Arch Surg 2024;409:294.. 10.1007/s00423-024-03473-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Almquist M, Ivarsson K, Nordenström E, et al. Mortality in patients with permanent hypoparathyroidism after total thyroidectomy. Br J Surg 2018;105:1313-8.. 10.1002/bjs.10843 [DOI] [PubMed] [Google Scholar]
- 19. Javed A, Alburaiki A, Sharma N, et al. Utilisation of Near Infrared Autofluorescence in Parathyroid Identification During Thyroidectomy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Clin Otolaryngol 2025;50:609-18.. 10.1111/coa.14313 [DOI] [PubMed] [Google Scholar]
- 20. Takahashi T, Sa SJD, Oya R, et al. Parathyroid near-infrared autofluorescence differently benefits depending on the surgeon's skill for preventing from hypoparathyroidism after total thyroidectomy: A systematic review and meta-analysis. PLoS One 2025;20:e0321310.. 10.1371/journal.pone.0321310 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Michaelsen SH, Døssing H, Gerke O, et al. Combined near-infrared autofluorescence and preresection indocyanine green angiography for parathyroid gland preservation during thyroid surgery: A clinical controlled trial. Surgery 2025;187:109623.. 10.1016/j.surg.2025.109623 [DOI] [PubMed] [Google Scholar]
- 22. Lang BH, Wong CK, Hung HT, et al. Indocyanine green fluorescence angiography for quantitative evaluation of in situ parathyroid gland perfusion and function after total thyroidectomy. Surgery 2017;161:87-95.. 10.1016/j.surg.2016.03.037 [DOI] [PubMed] [Google Scholar]
- 23. Vidal Fortuny J, Belfontali V, Sadowski SM, et al. Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery. Br J Surg 2016;103:537-43.. 10.1002/bjs.10101 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Razavi AC, Ibraheem K, Haddad A, et al. Efficacy of indocyanine green fluorescence in predicting parathyroid vascularization during thyroid surgery. Head Neck 2019;41:3276-81.. 10.1002/hed.25837 [DOI] [PubMed] [Google Scholar]
- 25. . [Google Scholar]
- 26. Shi C, Tian B, Li S, et al. Enhanced identification and functional protective role of carbon nanoparticles on parathyroid in thyroid cancer surgery: A retrospective Chinese population study. Medicine (Baltimore) 2016;95:e5148.. 10.1097/MD.0000000000005148 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Chen S, Hou X, Hua S, et al. Mitoxantrone hydrochloride injection for tracing helps to decrease parathyroid gland resection and increase lymph node yield in thyroid cancer surgery: a randomized clinical trial. Am J Cancer Res 2022;12:4439-47. [PMC free article] [PubMed] [Google Scholar]
- 28. Xue S, Ren P, Wang P, et al. Short and Long-Term Potential Role of Carbon Nanoparticles in Total Thyroidectomy with Central Lymph Node Dissection. Sci Rep 2018;8:11936.. 10.1038/s41598-018-30299-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Jiao D, Yang B, Chen J, et al. Efficacy and Safety of Mitoxantrone Hydrochloride Injection for Tracing Axillary Sentinel Nodes in Breast Cancer: A Self-Controlled Clinical Trial. Front Oncol 2022;12:914057.. 10.3389/fonc.2022.914057 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. . [Google Scholar]
- 31. Cheng Y, Zhang S, Liu ZW, et al. Application of mitoxantrone hydrochloride in lymph node imaging during radical thyroidectomy. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2024;59:1064-71. [Article in Chinese].. 10.3760/cma.j.cn115330-20240518-00287 [DOI] [PubMed] [Google Scholar]
- 32. Cheng X, Chen L, Zang H, et al. The clinical application of mitoxantrone hydrochloride tracing in endoscopic radical resection of thyroid carcinoma. Sci Rep 2025;15:23352.. 10.1038/s41598-025-07289-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Xu S, Yang Z, Guo Q, et al. Surgical Steps of Gasless Transaxillary Endoscopic Thyroidectomy: From A to Z. J Oncol 2022;2022:2037400.. 10.1155/2022/2037400 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Ye Z, Wu K, Hu Z, et al. Nanocarbon or indocyanine green: Which is superior for gasless transaxillary endoscopic thyroidectomy to protect the parathyroid gland?. Front Surg 2022;9:1035840.. 10.3389/fsurg.2022.1035840 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Wei T, Li Z, Jin J, et al. Autotransplantation of Inferior Parathyroid glands during central neck dissection for papillary thyroid carcinoma: a retrospective cohort study. Int J Surg 2014;12:1286-90.. 10.1016/j.ijsu.2014.11.001 [DOI] [PubMed] [Google Scholar]
- 36. Zhang Q, Qu KP, Wang ZS, et al. Clinical application of parathyroid autotransplantation in endoscopic radical resection of thyroid carcinoma. Front Oncol 2022;12:942488.. 10.3389/fonc.2022.942488 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Sun H, Gao L, Xiao G, et al. Selective parathyroid autotransplantation prevent permanent hypoparathyroidism after total thyroidectomy with central neck dissection. Front Surg 2025;12:1565581.. 10.3389/fsurg.2025.1565581 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg 2016;151:959-68.. 10.1001/jamasurg.2016.2310 [DOI] [PubMed] [Google Scholar]
- 39. Hallgrimsson P, Nordenström E, Almquist M, et al. Risk factors for medically treated hypocalcemia after surgery for Graves' disease: a Swedish multicenter study of 1,157 patients. World J Surg 2012;36:1933-42.. 10.1007/s00268-012-1574-4 [DOI] [PubMed] [Google Scholar]
- 40. Koimtzis G, Stefanopoulos L, Geropoulos G, et al. The outcomes of parathyroid gland autotransplantation during thyroid surgery: a systematic review, meta-analysis and trial sequential analysis. Endocrine 2025;87:27-38.. 10.1007/s12020-024-04011-y [DOI] [PubMed] [Google Scholar]
