Abstract:Breast cancer, as the most common malignant tumor globally, has been a hotspot of research for many years. In 2023, significant progress was made in clinical research on breast cancer in both local and systemic treatments. In terms of local treatment, evaluating axillary tumor burden and selecting appropriate treatment methods have been the focus of research. The SOUND study found that sentinel lymph node biopsy (SLNB) and axillary surgery had similar 5-year distant metastasis-free survival rates for patients with early-stage breast cancer who were negative for axillary lymph nodes on preoperative axillary ultrasound, avoiding SLNB when preoperative ultrasound screening results for axillary lymph nodes were clear. The SENOMAC study provided evidence supporting the possibility of not performing axillary lymph node dissection (ALND) for patients with low-burden sentinel lymph nodes. The OPBC05 study indicated that ALND did not improve long-term survival in patients with residual isolated tumor cells (ITCs) after neoadjuvant therapy, suggesting the feasibility of exemption from ALND. The NSABP B-51 study showed that regional lymph node irradiation (RNI) for axillary lymph node-negative patients after neoadjuvant chemotherapy (NAC) did not significantly improve the primary study endpoint. These studies emphasized the importance of personalized treatment regimens, providing important guidance for the surgical and subsequent treatment of breast cancer. In terms of systemic treatment, early-stage hormone receptor-positive [HR(+)] breast cancer treatment mainly relies on surgery, radiotherapy, and postoperative adjuvant endocrine therapy. However, approximately 30% of intermediate- to high-risk patients still face the risk of recurrence and metastasis. The MonarchE and NATALEE studies confirmed the effectiveness of CDK4/6 inhibitors in early-stage HR(+)/human epidermal growth factor receptor 2-negtive [HER-2(-)] breast cancer patients. In addition, studies on immunotherapy, such as the KEYNOTE-756 and CheckMate 7FL trials, explored the potential of PD-1 monoclonal antibodies combined with NAC in increasing the rate of pathological complete response (pCR) and reducing the risk of recurrence in high-risk patients. Standard treatment for advanced HR(+) breast cancer has evolved from single-agent endocrine therapy to combined therapy with CDK4/6 inhibitors, but resistance remains an issue. New drugs such as ADC drugs and PI3K/Akt/mTOR inhibitors are being explored to provide more treatment options. The TROPiCS-02 and TROPION-Breast01 studies validated the efficacy of TROP2-targeted ADC drugs in treating resistant HR(+)/HER-2(-) advanced breast cancer patients. Meanwhile, the INAVO 120 and Capitello-291 studies highlighted the potential of PI3K/Akt/mTOR signaling pathway inhibitors in improving treatment outcomes, especially for patients with PIK3CA mutations. In the treatment of early HER-2(+) breast cancer, the PHERGain study demonstrated the effectiveness of ¹⁸F-FDG PET/CT-based de-escalated chemotherapy adjusted according to pCR in neoadjuvant therapy for early HER-2(+) breast cancer. The APTneo study found that the addition of atezolizumab to chemotherapy had limited impact on increasing the pCR rate in neoadjuvant therapy, requiring further research to optimize efficacy and safety. Regarding advanced HER-2(+) breast cancer, the PHILA and HER2CLIMB-02 studies demonstrated the effectiveness of TKI drugs in first-line and second-line treatment. The DESTINY-Breast series of studies proved the efficacy and good safety profile of trastuzumab deruxtecan (T-DXd) in patients with HER-2(+) metastatic breast cancer across all age groups, with significant efficacy in patients with treated/stable and untreated/active brain metastases. Research on early triple-negative breast cancer (TNBC) focuses on the combination of immunotherapy and chemotherapy. The KEYNOTE-522 study showed that neoadjuvant therapy with chemotherapy plus pembrolizumab significantly increased pCR rates and event-free survival rates, and FDA and EMA have approved its use in the treatment of high-risk early-stage TNBC. However, the IMpassion030 study suggested that postoperative adjuvant immunotherapy may not be an effective option for all early-stage TNBC patients. For advanced TNBC, the KEYLYNK-009 study results showed that the combination of pembrolizumab and PARP inhibitors with chemotherapy did not significantly improve prognosis compared to pembrolizumab plus chemotherapy, but in patients with tBRCA mutations, this combination therapy significantly improved median progression-free survival (PFS), indicating its potential as first-line maintenance therapy for this patient population. The results of the BEGONIA study indicated that the combination therapy of Dato-DXd and durvalumab showed high response rates and longer PFS, potentially providing new treatment options for patients with advanced TNBC. In summary, research in the field of breast cancer treatment in 2023 has not only made breakthroughs in treatment methods but also innovated treatment concepts, bringing new hope to breast cancer patients.

Abstract:Breast cancer is the most common malignant tumor among women worldwide, with liver metastasis being a major cause of high mortality rate. With advancements in surgical techniques, particularly laparoscopic and minimally invasive surgeries, surgical treatment has become an important component of the comprehensive treatment strategy for breast cancer liver metastasis (BCLM). However, a longitudinal and cross-sectional analysis of domestic and international research reveals differences in surgical treatment practices for BCLM across regions. International studies tend to focus on technological innovations and improvements in therapeutic efficacy, while domestic research emphasizes optimizing surgical methods, exploring emerging treatment technologies, and the potential of integrating traditional Chinese and Western medicine. These differences reflect the diversity in medical resources, technological levels, and treatment philosophies across regions. Past studies on the surgical treatment of BCLM mainly relied on retrospective analyses, which often varied in quality and had significant discrepancies in results, thus limiting their credibility. In light of this, recent years have seen a shift towards prospective studies in both international and domestic research, signaling a move towards higher quality standards and broader impact in BCLM surgical treatment research. In China, the scale of research in this field remains insufficient, necessitating an expansion of research scope to synchronize with international standards and ensure more reliable and representative outcomes. Future research should focus on a deeper understanding of the biological mechanisms of BCLM and further application of technologies such as liquid biopsy, molecular typing, and genetic testing to provide more precise and personalized treatment plans for BCLM patients. Additionally, improving surgical precision and safety, as well as enhancing the accessibility of surgical treatment through networks and telemedicine, are key directions for future development. Despite the numerous challenges in the surgical treatment of BCLM, advancements in technology and multidisciplinary collaboration are expected to bring better survival rates and quality of life for BCLM patients. Continued exploration of new treatment methods is essential to further improve the treatment efficacy and prognosis for BCLM patients.

Abstract:Background and Aims In recent years, the implementation of endoscopic nipple-sparing mastectomy (NSM) with prosthetic breast reconstruction has increased. Various approaches for endoscopic surgery exist, with the axillary and lateral approaches being the most common. However, comparative studies on the surgical outcomes of these two approaches are limited. Therefore, this study was performed to compare the efficacy of endoscopic NSM with prosthetic reconstruction via the axillary and lateral approaches, providing clinical references for selecting the appropriate endoscopic surgical approach.Methods The clinical data of 152 breast cancer patients who underwent endoscopic NSM with prosthetic breast reconstruction from January 2016 to October 2022 in the Department of Breast and Thyroid Surgery of the First Affiliated Hospital of the Army Medical University were retrospectively collected. The patients were divided into the axillary approach group (78 cases) and the lateral approach group (74 cases) based on the surgical approach. Relevant clinical variables were compared between the two groups.Results There was no statistically significant difference in baseline data between the two groups (all P>0.05). The lateral approach group had a shorter operative time (211.50 min vs. 250.00 min, P<0.001) and less drainage volume (300.50 mL vs. 504.50 mL, P<0.001) compared to the axillary approach group. The axillary approach group had a significantly higher proportion of prepectoral prosthetic breast reconstruction compared to the lateral approach group (24.4% vs. 6.8%, P=0.003). There were no statistically significant differences between the two groups in intraoperative blood loss, postoperative drainage time, postoperative hematoma, infection, seroma, nipple-areola or skin flap necrosis, or capsular contracture rates (all P>0.05). Six-month postoperative follow-up showed no significant differences between the two groups in breast shape, quality of life, and postoperative satisfaction (axillary approach: 91.0% vs. lateral approach: 91.9%) (all P>0.05). Additionally, there were no significant differences in distant metastasis, local recurrence, or overall survival rates between the two groups (all P>0.05).Conclusion Both the axillary and lateral approaches for NSM with prosthetic breast reconstruction are safe and effective, with no differences in aesthetic outcomes. The axillary approach is suitable for prepectoral prosthetic implantation, while the lateral approach is simpler, shortens operation time, preserves the pectoral fascia, and allows for subpectoral prosthetic implantation without the need for a reinforcement mesh.

Abstract:Background and Aims Novel anti-human epidermal growth factor receptor 2 antibody-drug conjugates (ADCs) have provided new treatment options for breast cancer patients, including those with low HER-2 expression. However, the differences in clinicopathologic characteristics, molecular features, and prognosis between breast cancer patients with low HER-2 expression and those with zero HER-2 expression are still unclear. Therefore, this study was conducted to compare the survival prognosis, clinicopathologic characteristics, and molecular features of breast cancer patients with low HER-2 expression and zero HER-2 expression, in order to further elucidate the molecular characteristics of low HER-2 expression breast cancer and to more accurately identify the population that may benefit from ADC drugs.Methods The data of 1 245 patients with stage Ⅰ-Ⅲ early primary invasive breast cancer who underwent surgical treatment in Xiangya Hospital of Central South University from January 2011 to December 2015 were retrospectively analyzed. The differences in clinicopathologic characteristics among patients with different levels of HER-2 expression (zero expression, low expression, overexpression) were compared. The differences in overall survival (OS) and disease-free survival (DFS) were analyzed, and independent prognostic factors were identified. Molecular characteristics and immune microenvironment differences between low HER-2 expression and zero HER-2 expression breast cancer patients were compared using data from the TCGA database.Results Among the 1 245 patients, 395 (31.73%) had zero HER-2 expression, 562 (45.14%) had low HER-2 expression, and 288 (23.13%) had HER-2 overexpression. Compared to patients with zero HER-2 expression, those with low HER-2 expression had higher lymph node stage, a higher proportion of hormone receptor (HR) positivity, more axillary lymph node metastases, and lower Ki-67 level (all P<0.05). Survival analysis showed that both OS and DFS were significantly lower in patients with HER-2 overexpression compared to those with zero HER-2 expression and low HER-2 expression (all P<0.05); there were no significant differences in OS and DFS between zero HER-2 expression and low HER-2 expression patients, either overall or stratified by lymph node status or HR status (all P>0.05). Multivariate Cox risk model results indicated that age and axillary lymph node metastasis were independent risk factors for OS, while age, ER status, HER-2 expression level, and axillary lymph node metastasis were independent risk factors for DFS (all P<0.05). In terms of molecular characteristics, there were no significant differences in molecular mutation burden between low HER-2 expression and zero HER-2 expression breast cancer, but there were some differences in immune infiltration, with zero HER-2 expression breast cancer exhibiting a more active anti-tumor immune response.Conclusion There are certain differences in the pathological characteristics of low HER-2 expression and zero HER-2 expression breast cancer, but the prognostic outcomes are similar. The molecular characteristics of low HER-2 expression breast cancer are heterogeneous, but do not show significant specificity compared to HER-2 0 expression breast cancer. Therefore, the results of this study do not support the classification of low HER-2 expression as a new molecular subtype of breast cancer.

Abstract:Background and Aims The prognostic value of surgical intervention in patients with de novo metastatic breast cancer (dnMBC) has long been controversial. Some patients may benefit from local surgical treatment, but there is currently no effective method to identify those who would benefit from surgery. Therefore, this study was conducted to analyze the relationship between local surgery and prognosis in dnMBC patients, construct a prognostic prediction model, and determine the potential beneficiary group.Methods Data of pathologically diagnosed dnMBC cases from 2010 to 2019 were obtained from the SEER database. Patients were divided into surgery and non-surgery groups based on whether they received surgery on the primary breast lesion. Propensity score matching (1∶1) was used to balance baseline characteristics between the two groups. The matched cases were randomly split into training and validation sets in a 7∶3 ratio. A multivariate Cox proportional hazards model was employed to analyze independent prognostic factors for breast cancer-specific survival (BCSS) and to construct a prediction model. The model's discrimination, calibration, and clinical utility were evaluated using the C-index, time-dependent area under the curve (AUC), calibration curves, and decision curve analysis (DCA) in both the training and validation sets. Prognostic risk scores were calculated based on the prediction model, and patients were categorized into low, intermediate, and high-risk groups. The relationship between surgical treatment and prognosis in each risk group was analyzed using the Kaplan-Meier method.Results After matching, 2 034 patients were included in the analysis, with a median age of 56 (48-63) years. The training set comprised 1 441 cases, and the validation set comprised 593 cases. The median follow-up was 27 (11-48) months, during which 963 breast cancer-related deaths (47.35%) occurred. The estimated 3-year BCSS rates for surgery and non-surgery patients were 53.7% (95% CI=50.3%-57.3%) and 63.1% (95% CI=59.9%-66.5%), respectively. Survival analysis showed that surgery significantly improved BCSS in dnMBC patients (HR=0.72, 95% CI=0.63-0.82, P<0.001). Multivariate Cox model analysis indicated that race, histological grade, tumor T stage, brain metastasis, lung metastasis, bone metastasis, liver metastasis, hormone receptor status, HER-2 status, local surgery, and chemotherapy were independent prognostic factors (all P<0.05). A prognostic prediction model was constructed based on these independent prognostic factors, and the model was validated in both the training and validation sets. The validation results showed that the C-index was 0.707 (95% CI=0.685-0.728) and 0.705 (95% CI=0.672-0.738), respectively; the time-dependent AUC values were all between 0.7 and 0.8; the 1-, 2-, and 3-year calibration curves in both sets indicated a high concordance between predicted and actual survival rates; DCA demonstrated a good clinical net benefit of the prediction model. According to the prediction model, patients were divided into low, medium, and high-risk groups. Survival analysis revealed that surgery improved BCSS in the low-risk group (training set: P<0.000 1; validation set: P=0.003 8), while no improvement in prognosis was observed in the medium and high-risk groups.Conclusion The prognostic prediction model developed based on the clinicopathologic characteristics of dnMBC patients can stratify patients and assess the potential benefit of local surgery. This model requires further validation and optimization in prospective studies.

Abstract:With the advancements in endoscopic techniques, endoscopic thyroid surgery has become widely utilized. Currently, common approaches for endoscopic thyroid surgery include breast, oral vestibular, and transaxillary approach. Among them, endoscopic thyroidectomy by a gasless unilateral axillary approach has been highly recognized by many thyroid surgeons. This technique can meet patients' cosmetic needs while utilizing the natural space between neck muscles for operation to achieve the goal of minimally invasive surgery. Although the transaxillary gasless endoscopic thyroidectomy has become increasingly mature and standardized, several challenges need to be directly addressed in contralateral treatment of bilateral lobectomy during performing gasless unilateral axillary approach-endoscopic total thyroidectomy (GUA-ETT), such as avoiding tracheal obstruction, smoothly exposing the contralateral recurrent laryngeal nerve, and ensuring thorough clearance of contralateral central lymph nodes. In the authors' center, an improved three-step method for contralateral treatment and contralateral central lymph node dissection after unilateral thyroidectomy is proposed. To help thyroid surgeons master this technique, here, the authors provide a thorough explanation and sharing of the surgical methods, technical characteristics, operative techniques and nuances, as well as operative key points, difficulties, and operative experiences of the improved three-step method for contralateral treatment in GUA-ETT.

Abstract:With the development and popularization of endoscopic thyroidectomy, this surgical approach is increasingly accepted by more medical centers and patients. However, due to its relatively narrow operating space compared to laparoscopy and thoracoscopy, as well as issues such as the shared space between the lens and the surgical instruments manipulated by the primary surgeon, mutual interference, and limited visibility, it often becomes a challenging aspect of the surgery. To address this issue, the authors, from the perspective of the camera-holding assistant, introduce the concept of scene-based guidance. This is achieved by standardizing the key points of operation and quality control for camera-holding assistant during gasless axillary endoscopic thyroidectomy in three parts. The first part standardizes preoperative preparation and the division of the operating area of the camera-holding assistant. The second part outlines the key points of endoscope operation: "YAN GUAN LIU LU, SAN GE PING MIAN, JIN TUI ZHAN ZHUAN" a twelve-character quality control mantra for the camera holding. The third part focuses on the quality control of the endoscopic view field in three progressively deeper levels: dividing the surgical area into the recurrent laryngeal nerve area, the upper pole of the thyroid area, and the pre-tracheal area, thereby standardizing the key points and visual guidance for the camera-holding assistant in different scenarios. Through camera-holding skills and quality control, the surgical field is more fully and clearly visible, visual guidance is smoother, mutual interference between the lens and instruments is reduced, the average number of lens wipes or soaks during surgery is significantly reduced, and even secondary wiping of the lens during surgery is unnecessary, ensuring continuous operation and saving surgical time. Here, the authors elaborate on the above points, operation techniques, and details

Abstract:Background and Aims The application of robotic surgery systems in thyroid surgery has effectively promoted the development of minimally invasive thyroid surgery. Currently, the most commonly used system is the Da Vinci robotic surgical system. However, its high equipment cost limits the widespread adoption of robotic thyroid surgery. Therefore, this study was performed to investigate the safety and efficacy of the domestically manufactured robotic surgical system in the treatment of thyroid cancer, so as to provide reference for its clinical application. Methods The clinical data of 211 patients with thyroid papillary carcinoma who underwent thyroidectomy at the Department of Thyroid and Breast Surgery, the 960th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from May 2023 to October 2023 were retrospectively analyzed. Among them, 42 patients underwent robotic surgery with the Tumai ^? robotic surgical system (domestic robot group), and 169 patients underwent surgery with the Da Vinci robotic system (Da Vinci robot group). After balancing the baseline data of the two groups of patients using propensity score matching (PSM), the surgical and postoperative outcomes of the two groups were compared. Results All surgeries were successfully completed, and there were no conversions to open surgery in either group. Before PSM, there was a statistical difference in gender between the two groups ( P<0.05). After 1∶1 PSM, 41 patients were included in each group, and there were no statistically significant differences in baseline data between the two groups (all P>0.05). Compared with the Da Vinci robot group, the domestic robot group had significantly longer average total operative time, assistant preparation time, and surgeon operation time (193.68 min vs. 138.85 min, P=0.00; 43.32 min vs. 37.9 min, P=0.00; 150.37 min vs. 100.95 min, P=0.00), and a reduced number of lymph node dissection (10.41 vs. 8.32, P=0.03). There were no significant differences between the two groups in the number of lymph node metastases, postoperative drainage volume, postoperative drainage time, postoperative hospital stays, incidence of postoperative complications, pain score, cosmetic satisfaction results, and primary surgeon evaluation (all P>0.05). Conclusion The domestically manufactured robotic surgical system is safe and effective in the treatment of selective thyroid cancer patients, providing a new option for patients

Abstract:Background and Aims Methylene blue hydrochloride injection (MHI) for tracing is a new type of tracer approved by the National Medical Products Administration for use in thyroid cancer. There are few related reports at present, leaving significant research gap. Therefore, this study compared the effects of MHI and carbon nanoparticles as tracers on lymph node dissection and parathyroid protection in robot-assisted thyroid cancer surgery, so as to provide new tracer options for clinical work.Methods Using a prospective, randomized controlled design, patients undergoing da Vinci robot-assisted total thyroidectomy in the Department of Thyroid and Breast Surgery, the 960th Hospital of the People's Liberation Army were enrolled between June 2022 to June 2023. Grouping was done using a random number table. Patients receiving MHI were included in the study group, and patients receiving carbon nanoparticles were included in the control group. The number and tracing rate of level Ⅵ lymph nodes in the two groups were recorded and compared. The total number and positive number of level Ⅵ (± lateral neck) lymph node dissections, preoperative and postoperative 1-d and 6-month levels of blood calcium and parathyroid hormone (PTH), rate of inadvertent parathyroidectomy, incidence of hypoparathyroidism, incidence of temporary hypocalcemia after surgery, and whether there were residual marks at the injection site on the skin after surgery were analyzed to compare the differences in the effects of the two tracers.Results A total of 99 patients were included in this study, with 7 lost to follow-up. Finally, 92 patients completed the trial, with 46 in each group. There were no significant differences in general conditions between the two groups (all P>0.05). The lymph node tracing rates in the Ⅵ region were 97.1% (95% CI=95.7-98.5) in the study group and 96.4% (95% CI=94.9-97.8) in the control group, with no significant difference between the groups (P>0.05). The difference in the lymph node tracing rate in the Ⅵ region between the two groups was 0.7% (95% CI=1.2%-2.8%), and the Ⅵ region lymph node tracing rate in the study group was non-inferior to that in the control group (95% CI lower limit ≥-10%). The total number of lymph nodes detected in the Ⅵ region was 557 and 630 in the study and control groups, respectively (Z=-0.388, P=0.698), and the number of positive lymph nodes detected was 125 and 92, respectively (Z=-1.443, P=0.149). There were no statistically significant differences in preoperative and postoperative 1-d and 6-month PTH and blood calcium levels between the two groups (all P>0.05). Inadvertent parathyroidectomy occurred in one case in the study group and 4 cases in the control group, with no significant difference between the groups (P>0.05). There was no significant difference in the incidence of transient hypoparathyroidism after surgery between the two groups (P>0.05), but the incidence of transient hypocalcemia in the study group was lower than that in the control group (P<0.05). There was no permanent hypoparathyroidism in the study group, while one case occurred in the control group. One patient in each group had residual marks on the skin after surgery. During the 6-month follow-up, the marks had disappeared in the study group patient but remained in the control group patient. There were no cases of recurrence during the follow-up period.Conclusion In da Vinci robot-assisted thyroid cancer surgery, the use of MHI for tracing can achieve lymphatic tracing and parathyroid protection effects similar to those of carbon nanoparticles suspension injection.

Abstract:Background and Aims Fine-needle aspiration cytology (FNAC) guided by ultrasound is the primary method for preoperative evaluation of thyroid nodules' benign or malignant nature. Its drawback is inadequate sampling, which may lead to misdiagnosis or missed diagnosis. Core needle biopsy (CNB) can compensate for the shortcomings of FNAC, but its disadvantages include increased pain and trauma. Therefore, this study compared the diagnostic efficacy and characteristics of FNAC and CNB to diagnose thyroid nodules, aiming to provide a reference for clinical rational selection.Methods The data of 552 patients who underwent thyroid surgery in Zhongnan Hospital of Wuhan University from November 2020 to November 2022 were retrospectively analyzed. All patients underwent preoperative ultrasound examination and subsequent FNAC and CNB. Thyroidectomy on the affected side was performed within one week after the puncture. Clinical data of patients, ultrasound characteristics of thyroid nodules, preoperative cytology, histopathology, and postoperative routine pathology results were collected. Postoperative routine pathology was used as the gold standard to analyze the diagnostic efficacy of FNAC and CNB.Results Overall, FNAC and CNB showed similar sensitivity, specificity, and accuracy in diagnosing thyroid nodules, with no statistically significant differences (88.7% vs. 91.4%, P=0.283; 90.6% vs. 97.4%, P=0.226; 85.3% vs. 89.1%, P=0.058). CNB was superior to FNAC in distinguishing between benign and malignant follicular tumors (P=0.024). When the nodule diameter was ≤2.0 cm, there was generally no difference in diagnostic efficacy between FNAC and CNB. When the nodule diameter was >2.0 cm, the sensitivity of CNB was significantly higher than that of FNAC (95.0% vs. 79.2%, P<0.01), and the combined diagnosis of both further increased the sensitivity to 99.2%. For the diagnosis of calcified nodules, cystic nodules, and nodules with rich vascularity, the sensitivity and accuracy of CNB were higher than those of FNAC (91.0% vs. 88.7%, 91.0% vs. 84.8%, 92.8% vs. 85.1%; 93.2% vs. 88.8%, 91.7% vs. 84.8%, 93.3% vs. 85.2%), with statistically significant differences except for calcified nodules (all P<0.05). For the diagnosis of avascular nodules, the sensitivity and accuracy of FNAC were higher than those of CNB (92.7% vs. 90.2%, P=0.004; 96.2% vs. 90.5%, P=0.005).Conclusion CNB and FNAC have similar diagnostic efficacy for thyroid nodules with a diameter ≤2.0 cm, but CNB has certain advantages in distinguishing follicular tumors. CNB is more effective than FNAC for thyroid nodules with a diameter >2.0 cm, calcified nodules with rich vascularity, and cystic or solid nodules. Combining FNAC and CNB examinations for nodules with the above characteristics can improve the preoperative diagnostic accuracy of thyroid nodules to a certain extent.

Abstract:Background and Aims Currently, the commonly used endoscopic thyroidectomy approaches include the axillary approach, transthoracic breast approach, and transoral approach. Compared with other approaches, the axillary approach creates a natural space between neck muscles. It exposes the thyroid gland in the deep surface of the anterior cervical banded muscle to operate, which minimizes the impact on neck function and avoids the need for CO₂ insufflation, thus reducing the cardiovascular and cerebrovascular effects. Therefore, the axillary approach has been increasingly accepted by surgeons in recent years. However, finding the sternocleidomastoid muscle space is a major challenge in the axillary approach to endoscopic thyroidectomy. Many beginners cannot accurately locate the muscle space in this step, leading to increased surgical time and trauma. In response, our center has made certain improvements to gasless axillary endoscopic thyroidectomy to reduce difficulty finding muscle space during surgery. This study evaluated this modified approach's short-term efficacy and safety to provide a basis for its clinical application.Methods The clinical data of 46 patients with thyroid cancer treated in the Department of Thyroid and Breast Surgery, Suqian First People's Hospital, from January 2023 to May 2023, were retrospectively analyzed. Among them, 23 patients underwent improved gasless endoscopic thyroidectomy via the axillary approach (observation group), while the other 23 patients underwent conventional gasless endoscopic thyroidectomy via the axillary approach (control group). In patients in the observation group before surgery, saline was injected into the space between the sternal and clavicular attachments of the sternocleidomastoid muscle under ultrasound guidance to separate and expand the muscle space. Then, the posterior edge of the sternocleidomastoid muscle at the sternal part was sutured for positioning. After accurate entry into the muscle space, the operation was performed according to the conventional axillary approach endoscopic thyroidectomy method.Results The two groups had no significant differences in general data (all P>0.05), indicating comparability. The average operative time in the observation group was significantly shorter than that in the control group (65.6 min vs. 87.2 min, P<0.05). At the same time, there were no significant differences in intraoperative blood loss, postoperative drainage volume, number of central lymph nodes removed, and length of hospital stay between the two groups (all P>0.05). One patient in the observation group developed a subcutaneous hematoma in the axilla, which was resolved by aspiration and compression. There were no complications, such as difficulty breathing, hoarseness, numbness in the limbs, or coughing while drinking in the remaining patients. Three months after surgery, the two groups had no significant differences in neck pain score, neck injury index, and swallowing disorder index (all P>0.05). After surgery, all patients received individualized thyroid-stimulating hormone (TSH) suppression therapy with oral levothyroxine sodium tablets. During the follow-up period, none of the patients experienced recurrence or metastasis.Conclusion Preoperative ultrasound-guided suture positioning of the sternocleidomastoid muscle combined with saline injection to separate the muscle space is convenient and practical, facilitating the identification of the muscle space during surgery. This approach reduces the surgical difficulty of gasless endoscopic thyroidectomy via the axillary approach and has good clinical application value.

Abstract:Background and Aims Various neck scarless surgeries have gradually matured in recent years. Transoral endoscopic thyroidectomy via vestibular approach (TOETVA) has gained popularity among doctors and patients due to its shorter path, convenient and thorough lymph node dissection, and absence of visible scars. However, in the initial TOETVA cases the authors' team performed, some patients experienced varying degrees of chin numbness, reduced lower lip mobility, swelling and deformation, and hardening of chin scars after operation. Therefore, the team adopted a 5 mm endoscope for transoral thyroid surgery, supplemented by an axillary approach for assistance and specimen retrieval. This combined method is termed the axillary channel-assisted transoral endoscopic thyroidectomy vestibular approach (AcaTOETVA). For patients with a prominent chin bone, where establishing the oral observation channel is difficult, a 5 mm submental incision is made to create the observation channel to perform submental and axillary channel-assisted transoral endoscopic thyroidectomy vestibular approach (SaAcaTOETVA). This paper summarizes the limited cases of this surgical method to explore its feasibility, advantages, and disadvantages preliminarily.Methods The clinical data of 6 patients who underwent SaAcaTOETVA in the Breast and Thyroid Surgery Department of Wuhan First Hospital from September to November 2020 were retrospectively analyzed.Results All 6 patients completed the surgery. Among them, 3 patients underwent left thyroid lobectomy with left central lymph node dissection, 1 patient underwent right thyroid lobectomy with right central lymph node dissection, 1 patient underwent near-total right thyroid lobectomy, and 1 patient underwent near-total bilateral thyroid lobectomy. The surgery duration ranged from 100 to 155 min, intraoperative blood loss was 10 to 20 mL, and the postoperative hospital stay was 3 d. No patients experienced recurrent laryngeal nerve injury, subcutaneous hematoma, chin nerve injury, chin and lip numbness, chin swelling, hypocalcemia, swallowing difficulties, CO₂ embolism, or delayed wound healing. One patient had a small bruise on the chin due to a puncture of the operation hole, which resolved within a week. On one-month postoperative follow-up, the submental incision healed well, and when standing normally, the incisions were hidden under the chin and in the armpit, making them relatively inconspicuous. Patients were satisfied with the submental and axillary incisions, and postoperative examinations found no tumor implantation, recurrence, or metastasis.Conclusion SaAcaTOETVA is safe and feasible and is an important supplement to AcaTOETVA for specific cases. It features relatively hidden and aesthetically pleasing incisions. However, issues with the clarity of the 5 mm endoscope and the initially small working space may affect the widespread adoption of this surgical method.

Abstract:Background and Aims Long non-coding RNAs (lncRNAs) can indirectly regulate the transcription and degradation of downstream mRNAs by binding to microRNAs (miRNAs), thereby regulating the occurrence and development of tumors. LncRNA FOXP4-AS1 is a recently discovered tumor-related biomarker, playing different regulatory roles in different tumors. Our previous study found that FOXP4-AS1 is downregulated in papillary thyroid carcinoma (PTC) and is a tumor suppressor. In addition, bioinformatics analysis predicted that miR-507 could complementarily bind to FOXP4-AS1. Therefore, this study was conducted to explore the role and mechanism of FOXP4-AS1 in inhibiting the growth of PTC cells by regulating miR-507 and its downstream target mRNA.Methods The expression levels of miR-507 in thyroid cancer (TC) and its clinical significance were analyzed using the TCGA database. The expression levels of miR-507 in PTC cell lines (TPC-1, K1) and normal thyroid follicular epithelial cells (Nthy-ori3-1) were detected by qRT-PCR and the changes in miR-507 expression levels after overexpression and knockdown of FOXP4-AS1 were measured. The dual-luciferase reporter gene assay was used to verify the targeting relationship between FOXP4-AS1 and miR-507. miR-507 mimic and inhibitor were transfected into stable cell lines overexpressing or knockdown of FOXP4-AS1, and changes in cell function were detected by CCK-8 assay, colony formation assay, Transwell assay, scratch healing assay, and flow cytometry. Bioinformatics analysis was used to predict the downstream targets of miR-507, and qRT-PCR was used for validation.Results Analysis of the TCGA database showed that miR-507 was highly expressed in TC, and its expression level was associated with clinical pathological features such as clinical stage, T stage, and extrathyroidal infiltration (all P<0.05). qRT-PCR results showed that compared with Nthy-ori3-1 cells, miR-507 was highly expressed in both PTC cell lines, and the expression levels of miR-507 in both PTC cells changed inversely after overexpression and knockdown of FOXP4-AS1 (all P<0.05). The results of the dual-luciferase reporter gene assay showed that FOXP4-AS1 targeted and inhibited the expression of miR-507. Cell function experiments and functional recovery experiments showed that after overexpression of FOXP4-AS1, the proliferation, migration, and anti-apoptotic ability of PTC cells were significantly weakened, and these functions were restored after the addition of miR-507 mimic (all P<0.05); knockdown of FOXP4-AS1 in PTC cells resulted in a significant increase in proliferation, migration, and anti-apoptotic ability, and these functions were restored after the addition of the miR-507 inhibitor (all P<0.05). Bioinformatics prediction and GO, KEGG enrichment analysis results showed that miR-507 downstream may involve CAMK4. qRT-PCR validation results showed that the expression level of CAMK4 changed in the same direction as the expression level of FOXP4-AS1, and its expression level changed inversely with the addition of miR-507 mimic and inhibitor (all P<0.05).Conclusion FOXP4-AS1 can target miR-507, and may regulate the proliferation, migration, and apoptosis of PTC cells by inhibiting the expression level of miR-507 through a sponge mechanism. CAMK4 may be one of the downstream targets of the FOXP4-AS1/miR-507 pathway in exerting its anticancer effects.

Abstract:Type Ⅱ deiodinase (D2) is an important selenium-containing protease responsible for the outer ring deiodination of thyroxine (T₄) to form the more biologically active triiodothyronine (T₃), thereby regulating metabolism, growth and development, and energy balance in the body. D2 activity is regulated by various factors, including thyroid hormone levels, the cAMP pathway, ubiquitination, endoplasmic reticulum stress, and environmental factors. D2 is closely related to the occurrence and development of thyroid diseases and plays a crucial role in regulating cell proliferation, thus it is considered a potential cancer marker. Additionally, the Thr92Ala polymorphism of the type Ⅱ deiodinase gene (DIO2) has been confirmed as a factor related to thyroid diseases. Understanding the relationship between this polymorphism and thyroid diseases can help predict individual disease risk and provide a basis for personalized treatment. This review focuses on the regulatory mechanisms of D2 and its essential role in thyroid diseases, as well as the impact of the DIO2 Thr92Ala polymorphism on disease development, to provide a guidance for future research and clinical praxis.

Abstract:Plasma cell mastitis (PCM) is a type of non-lactational mastitis characterized by dilated mammary ducts and plasma cell infiltration as its main pathological features. The etiology of PCM remains unclear, and current treatments, including antibiotics, anti-tuberculosis drugs, hormones, and surgery, have shown limited efficacy. These treatments often result in significant physical and mental damage to female patients due to drug side effects, postoperative disfigurement, and recurrences. It is crucial to further investigate the pathogenesis of PCM to develop precise and effective treatments and reduce recurrence rates. Most scholars believe that the accumulation and leakage of fatty substances within the mammary ducts lead to chemical irritation and immune responses around the ducts, resulting in the infiltration of various inflammatory cells. The accumulation of mammary duct secretions may be related to abnormal material exchange in mammary duct epithelial cells, ultimately causing epithelial cell necrosis. Substance exchange channels facilitate the transfer of materials between cells while maintaining homeostasis in the internal environment. Recent studies indicate that these channels are closely related to inflammation and immunity. Ion channels are involved in physiological and pathological responses in the mammary gland through mechanisms such as regulating ion-water balance and initiating immune responses. The mechanosensitive ion channel Piezo1 acts as a force sensor in chronic inflammation associated with mechanical force. Exploring how mechanical injury and a firm environment induce the secretion of pro-inflammatory factors and the migration of inflammatory cells may provide insights into the local inflammatory response in PCM following trauma. Aquaporins (AQPs) dynamically regulate water and solute transport. The rapid swelling and liquefaction of local PCM lesions might result from fast water flow changes mediated by AQPs and inflammation involving both innate and adaptive immunity. Some AQPs exhibiting a glycerol transport capacity play roles in lipolysis and lipid deposition, offering insights into the accumulation of lipid-like secretions in PCM ducts. Extracellular vesicles (EVs) encapsulate and transport various biomolecules, protecting them from degradation in harsh extracellular environments and facilitating short- and long-distance communication. When carrying pro-inflammatory content, EVs can spread destructive inflammation, explaining the PCM breast accompanied by systemic inflammatory reactions such as fever, cough, and erythema nodosum of the lower limbs. PCM patients exhibit secretion accumulation in the ducts, significant ductal dilation, and extensive inflammatory cell infiltration around the ducts. Abscesses containing a large number of necrotic cells and tissue debris can lead to fistula formation if treatment is delayed and the condition persists. This paper explores the pathogenesis of PCM from the perspective of substance exchange channel disorders, including ion channels, AQPs, and EVs, aiming to provide new insights for future research on key pathological mechanisms and intervention targets in PCM.

Abstract:Thyroid cancer is one of the malignant tumors with an increasing incidence worldwide, in which, papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) occasionally exhibit superior mediastinal lymph node metastasis (SMLNM). Although this is still considered regional metastasis, it is indicative of a later stage of the disease and is prone to being misdiagnosed or undertreated. For common types of PTC and MTC, thorough dissection of the central compartment, lateral neck, and the rare superior mediastinal lymph node metastases (SMLNM) can significantly improve disease-free survival rates. Anatomically, the thyroid has an extensive lymphatic drainage network. The intrathyroidal lymphatic network connects both lobes of the gland through the isthmus, while the extrathyroidal lymphatics drain to the mediastinal lymph nodes. Currently, there is no specialized and mature classification for SMLNM in thyroid cancer, hence the classification of lung cancer is commonly used. The most common regions for thyroid cancer SMLNM are zones 2R and 2L, with zones 4R and 3a being relatively less common. The incidence of SMLNM ranges from 0.7% to 48.1%. The mediastinal lymph node metastasis rate for PTC is approximately 6% to 12%, while MTC, which more readily metastasizes to lymph nodes, has a metastasis rate of up to 18%. Clinically, SMLNM often presents without obvious symptoms and is commonly detected through imaging examinations or tumor marker tests. Ultrasound examination has difficulty detecting SMLNM. Typical features on enhanced neck and chest CT scans include enhancement, calcification, cystic changes, and invasion. Enhanced MRI, PET, and ¹³¹I scans can also assist in the diagnosis. For thyroid cancer patients with SMLNM, safe, standardized, and thorough surgery remains key to achieving good outcomes, with individualized surgical plans tailored to the specific circumstances of each patient. Surgical principles include aiming for R₀ resection in a single session whenever possible, ensuring complete dissection while maintaining surgical safety to achieve both anatomical and biochemical cures. Surgical approaches may include open neck surgery, sternotomy, endoscopic-assisted surgery, and thoracoscopic surgery. Most dissections can be completed through the cervical approach; however, extensive low-level metastasis or severe invasion of surrounding major blood vessels may require sternotomy, sometimes with endoscopic assistance and/or thoracoscopic surgery. Postoperative care should focus on avoiding complications such as major vessel tears and injuries to the trachea and esophagus. Given the complex anatomical structure of the superior mediastinum, its difficult exposure from the neck, and the high surgical risk, thyroid or head and neck surgeons often face relative unfamiliarity and challenges, necessitating multidisciplinary collaboration. Although patients with thyroid cancer metastasis to the superior mediastinum generally have a poorer prognosis, the use of individualized surgical approaches and plans, in conjunction with thoracic and cardiovascular surgeons, for complete dissection of mediastinal metastases can significantly improve patient prognosis and quality of life. This article reviews the surgical diagnosis and treatment of thyroid cancer SMLNM to provide a reference for thyroid surgeons in their clinical practice.

Abstract:In recent years, studies have found that G protein-coupled estrogen receptor (GPER), distinct from traditional nuclear receptors, is a third independent estrogen receptor that belongs to the family of seven-transmembrane G protein-coupled receptors (GPCRs). Estrogen activates G protein signaling pathways through GPER, playing important roles in normal physiology and various pathological conditions, including cancer, cardiovascular diseases, and inflammatory diseases. GPER is expressed in various immune cells and plays a role in immune responses by enhancing immune cell activity or modulating interactions between immune cells. Additionally, GPER can participate in the expression of inflammatory factor-related genes, thereby inhibiting inflammatory responses. Recent studies have further revealed that GPER is not only involved in maintaining normal immune system function, abnormal immune diseases, and inflammatory diseases but also may have important value in tumor immune regulation. The authors' research team has previously confirmed the downstream signaling pathways mediated by GPER and its biological functions in various malignant tumors, and have found that GPER may regulate tumor immunity of breast and liver cancer through energy metabolism remodeling in the tumor microenvironment, and targeting GPER in hematologic tumor immune therapy has a synergistic effect with anti-tumor drugs. Based on existing research findings, GPER participates in tumor immune processes of various cancers in diverse ways. For example, in breast cancer, GPER affects tumor immune escape by regulating the expression of immune checkpoint molecules; in liver cancer, GPER regulates the immune microenvironment and immune cell infiltration, affecting tumor immune regulation by increasing the production of cytokines and chemokines; in colorectal cancer, GPER enhances the anti-tumor activity of immune cells and promotes the cytotoxicity of immune cells; in hematologic tumors, GPER influences the "cross-talk" between different immune cells, enhancing anti-tumor immune therapy, etc. Therefore, GPER provides a new avenue for the development of immune-related diseases treatments. Although it is still in the exploratory stage, the development of GPER as a new target combined with immune checkpoint inhibitors and other drugs is full of clinical potential. This article reviews the current research progress on the immune regulatory effects of GPER, to provide a reference for related basic and clinical research.