Calcitonin-negative medullary thyroid carcinoma(CNMTC)is a rare subtype of medullary thyroid carcinoma,characterized by normal serum calcitonin levels,which often leads to misdiagnosis or missed diagnosis.The pathogenesis of CNMTC remains unclear and may involve impaired secretion mechanisms or assay-related false negatives.Diagnostic approaches include ultrasound-guided fine needle aspiration cytology,serum CEA and ProGRP measurements,and RET gene testing.Surgical resection remains the mainstay of treatment,while neoadjuvant therapy may be considered in selected cases.This review summarizes recent advances in the understanding,diagnosis,treatment,and prognosis of CNMTC,aiming to provide clinical guidance for better management of this challenging condition.

Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.

Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.

Calcitonin-negative medullary thyroid carcinoma(CNMTC)is a rare subtype of medullary thyroid carcinoma,characterized by normal serum calcitonin levels,which often leads to misdiagnosis or missed diagnosis.The pathogenesis of CNMTC remains unclear and may involve impaired secretion mechanisms or assay-related false negatives.Diagnostic approaches include ultrasound-guided fine needle aspiration cytology,serum CEA and ProGRP measurements,and RET gene testing.Surgical resection remains the mainstay of treatment,while neoadjuvant therapy may be considered in selected cases.This review summarizes recent advances in the understanding,diagnosis,treatment,and prognosis of CNMTC,aiming to provide clinical guidance for better management of this challenging condition.

Objective:To investigate the efficacy and prognosis of different surgical approaches in sporadic medullary thyroid carcinoma.Methods:A retrospective analysis was conducted on 101 patients with sporadic medullary thyroid carcinoma (MTC) who underwent surgical treatment at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, from Feb. 2009 to Nov. 2023. The patients included 36 males and 75 females, with a male-to-female ratio of 1:2.1. The median age of the patients was 47 years old, with an age range of 21 to 72 years old. The study divided participants into two groups based on their surgical methods: an observation group (78 cases) and a control group (23 cases). The observation group received surgical methods in accordance with expert consensus, while the control group did not. The study compared the efficacy and prognosis of the two groups.Results:Statistical differences were found between the two groups in terms of stage II and III in TNM staging, intraoperative frozen pathological findings, number of lymph node resections in the central group, number of lymph node metastases in the central group, number of lymph node resections in the lateral cervical region, postoperative follow-up time, and five-year postoperative serum procalcitonin (Ctn) levels ( P<0.05) .Both groups of patients obtained a significant decrease in Ctn after surgical treatment. In the observation group, Ctn was at the remission level in 57 cases (73.1%), at the stable level in 13 cases (16.7%), and at the progression level in 8 cases (10.2%), while in the control group, Ctn was at the remission level in 20 cases (86.9%), at the progression level in 3 cases (13.1%), and there were no patients at the stable level after the operation.One patient (1.3 per cent) in the observation group had a recurrence after surgery; Two patients (8.7 per cent) in the control group had a recurrence. Conclusions:Standardised and thorough surgery can maximise the clearance of metastatic lymph nodes, effectively reduce the recurrence rate, achieve better efficacy, and improve the long-term prognosis of patients without increasing the risk of surgery and postoperative complications.

In recent years, clinical applications of robotic thyroid surgery have been gradually promoted with the continuous improvement of the da Vinci robotic surgical system. Unlike traditional open surgery, robotic thyroid surgery mainly adopts remote access, which has many advantages, such as magnified high-definition 3D view and hand vibration stabilization. The rates and causes of postoperative complications differ due to different approaches, view angles, and operation sequences. This paper presents the literature on both transoral and bilateral areolar axillary approaches in robotic thyroid surgery, focusing on five common complications under both approaches, including laryngeal recurrent nerve injury and hypoparathyroidism, to provide theoretical support for the standardization of robotic thyroid surgery.

Objective:To investigate the clinical effectiveness of da Vinci robotics in thyroid surgery.Methods:304 cases of robotic thyroid surgery performed by the same experienced surgeon at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University during the period from Apr. 3, 2020 to Nov. 5, 2021 were prospectively included, and the operation time, operation type, postoperative drainage, postoperative hospital stay, total number of lymph node dissection and number of positive lymph nodes, operation complications, and postoperative pain level of all patients were counted. The learning curve was plotted by applying the moving average method, divided into the initial stage and the mature stage, and the differences in surgical outcomes and surgical complications between the two stages were compared. SPSS 23.0 was applied for statistical analysis, and t-test and Mann-Whitney U test were used for comparison of measurement data, and χ2 test was used for comparison of count data. Result:All surgeries were completed successfully without conversion to open cases, including 29 males and 275 females, with a mean age of (33.8±8.9) years and a range of 27-41 years. The mean body mass index (BMI) was (22.9±3.6) kg/m 2 and a range of 20.5-25.4 kg/m 2. The median operative time was 140 min, the median postoperative drainage was 52.5 ml, and the median postoperative hospital stay was 3 days. The mean number of lymph nodes cleared was 4.4±3.5, and the mean number of positive lymph nodes was 0.9±1.7. The incidence of postoperative transient laryngeal nerve (RLN) injury was 3.3%, and the incidence of transient hypoparathyroidism was 0.7%. A significant decrease in operative time occurred after the 26th case and subsequently stabilized. Compared with the initial stage of the learning curve, the mature stage had a shorter operative time (146.0±36.5 vs 198.7±56.7 min, P<0.001) , a lower incidence of temporary RLN injury (2.5% vs 11.5%, P<0.05) , and a lower percentage of benign tumor surgery (12.2% vs 26.9%, P<0.05) . Conclusion:The application of robotic technology in thyroid surgery is safe and reliable, and its successful implementation should follow a corresponding learning curve, from easy to difficult, with different surgical approaches selected according to the patient’s condition, wishes, and the operator’s technical level.

Robotic surgical systems are gradually being used in minimally invasive surgery with their advantages of high-definition magnified 3D images, stable surgical field and flexible operation. The change of surgical approach and the narrow operating space in robotic thyroid surgery have made it more difficult to identify and protect the laryngeal nerve, and the application of nerve monitoring has been limited. Many researchers have attempted to improve the monitoring equipment and probe placement to make intraoperative neuromonitoring techniques work well in robotic thyroid surgery. In this paper, we seek effective ways to protect the laryngeal nerve in robotic thyroid surgery, and lay the foundation for a more minimally invasive and standardized development of this technology.

Objective:To investigate the incidence and risk factors of neonatal asphyxia in twin pregnancy.Methods:This study retrospectively recruited 2 035 women with twin pregnancy and their 4 070 twin neonates in the Obstetrics and Gynecology Hospital of Fudan University from January 2010 to December 2018. There were 211 cases suffered from neonatal asphyxia (asphyxia group) and 3 859 did not (non-asphyxia group). The demographic information of the women and their newborns and the incidence of perinatal complications were compared between the two groups by two independent samples t-test and Chi-square test. Multivariate logistic regression was used to analyze the risk factors of neonatal asphyxia in twin pregnancy. Results:The age of 2 035 women was (31.8±4.4) years old (17-52 years old). The gestational age of the twins at delivery was (35.2±2.2) weeks (25-40 weeks). There were 1 330 (65.4%) premature births, including 997 (49.0%) born at ≥34 weeks. Monochorionic diamniotic twin pregnancies accounted for 22.6% (460/2 035). The total incidence of neonatal asphyxia was 5.2% (211/4 070), 5.0% (102/2 035) in the first- and 5.4% (109/2 035) in the second-born twin infants, and the three figures were all decreased with the increase of gestational age ( χ2trend=1 601.965, 549.693 and 1 089.709, all P<0.001) as well as birth weight ( χ2trend=1 273.386, 437.906 and 848.007, all P<0.001). Univariate analysis showed that the asphyxia group had smaller gestational age and lower birth weight [(34.1±2.8) vs (35.3±2.1) weeks, t=6.279; (2 113.3±565.7) vs (2 339.6±478.7) g, t=5.700], but a higher ratio of male infants [58.3% (123/211) vs 48.5% (1 878/3 859), χ2=7.704], vaginal delivery [10.4% (22/211) vs 4.5% (173/3 859), χ2=15.493], monochorionic diamniotic twins [27.5% (58/211) vs 22.3% (862/3 859), χ2=7.714], special complications related to monochorionic diamniotic twin pregnancies [8.1% (17/211) vs 2.5% (95/3 859), χ2=23.403] and fetal distress [13.7% (29/211) vs 3.8% (148/3 859), χ2=47.222] than the non-asphyxia group (all P<0.05). After adjusting for the gestational age, birth weight and gender, multivariate logistic regression found that vaginal delivery ( OR=1.748, 95% CI: 1.069-2.861), special complications related to monochorionic diamniotic twin pregnancies ( OR=3.200, 95% CI: 2.056-4.982) and fetal distress ( OR=2.017, 95% CI: 1.073-3.791) were the risk factors for asphyxia in twin neonates (all P<0.05). Conclusions:The incidence of neonatal asphyxia is high in twins with small gestational age and low birth weight. Vaginal delivery, fetal distress and special complications related to monochorionic diamniotic twin pregnancies are the high-risk factors. Clinicians should be well prepared for resuscitation when encountering neonatal asphyxia.

Objective:To evaluate the pregnancy outcomes of fetal tethered cord (TC) prenatally diagnosed by MRI.Methods:Clinical data of 38 fetuses diagnosed as having TC by MRI, including 36 singletons and two fetuses who were both one of dichorionic diamniotic twins, were retrospectively collected and analyzed in the Obstetrics and Gynecology Hospital of Fudan University from January 2015 to August 2019. According to whether conus medullaris was located above the bladder or reached the lower edge of the bladder, all cases were divided into high or low groups. Pregnancy outcomes were compared between the two groups using Fisher's exact test and Student's t-test. Results:(1) The gestational age at MRI was (25.5±4.7) weeks. Among the 38 cases, 14 (36.8%) were isolated TC, 24 (63.2%) were complicated by other anomalies. The meningocele was responsible for the most (39.5%, n=15). The results of the ultrasound were consistent with those of MRI in 24 cases (63.2%). While in the other 14 cases (36.8%), the ultrasound only showed vertebral body's abnormal morphology, after which further MRI examination revealed a tethered cord. (2) Twenty-nine women (76.3%) chose to terminate the pregnancy. One patient (2.6%) underwent fetal reduction at 23 gestational weeks (one normal twin was delivered prematurely), and one (2.6%) was lost to follow-up. Seven (18.4%) cases continued the pregnancies to delivery. The postnatal follow-up period was 8.1 months (4.0 to 54.9 months). Two infants without comorbidities showed normal growth and development. Another three cases underwent surgeries after birth, and two cases died in the neonatal period. (3) The average width of the medullary cone was (2.5±0.8) cm. There was no significant difference in the spinal cord width between the high [(2.5±0.8) cm, n=34] and low group [(2.7±1.1) cm, n=4]. Six pregnancies (17.6%) in the high group was continued to delivery, and one of the neonates died of severe hydrocephalus. One patient in the low group (1/4) was delivered, while the baby died of neonatal asphyxia. Conclusions:Fetuses with isolated TC are prone to have a good prognosis. Further study should focus on the relation between the high or low position of the conus medullaris and pregnancy outcomes.