Patterns of lymph node metastasis in level IIB and contralateral level VI for papillary thyroid carcinoma with pN1b and safety of low collar extended incision for neck dissection in level II.

OBJECTIVE: To explore relevant clinical factors of level IIB and contralateral level VI lymph node metastasis and evaluate the safety of low-collar extended incision (LCEI) for lymph node dissection in level II for papillary thyroid carcinoma (PTC) with pN1b. METHOD: A retrospective analysis was performed on 218 patients with PTC with pN1b who were treated surgically in the Head and Neck Surgery Center of Sichuan Cancer Hospital from September 2021 to May 2022. Data on age, sex, body mass index (BMI), tumor location, maximum tumor diameter, multifocality, Braf gene, T staging, surgical incision style, and lymph node metastasis in each cervical subregion were collected. The chi-square test was used for comparative analysis of relevant factors. All statistical analyses were completed by SPSS 24 software. RESULT: Each subgroup on sex, age, BMI, multifocality, tumor location, extrathyroidal extension, Braf gene, and lymphatic metastasis in level III, level IV, and level V had no significant difference in the positive rate of lymph node metastasis in level IIB (P > 0.05). In contrast, patients with bilateral lateral cervical lymphatic metastasis were more likely to have level IIB lymphatic metastasis than those with unilateral lateral cervical lymphatic metastasis, with a statistically significant difference (P = 0.000). In addition, lymph node metastasis in level IIA was significantly associated with lymph node metastasis in level IIB (P = 0.001). After multivariate analysis, lymph node metastasis in level IIA was independently associated with lymph node metastasis in level IIB (P = 0.010). The LCEI group had a similar lymphatic metastasis number and lymphatic metastasis rate in both level IIA and level IIB as the L-shaped incision group (P > 0.05). There were 86 patients with ipsilateral central lymphatic metastasis (78.2%). Patients with contralateral central lymphatic metastasis accounted for 56.4%. The contralateral central lymphatic metastasis rate was not correlated with age, BMI, multifocality, tumor invasion, or ipsilateral central lymphatic metastasis, and there was no significant difference (P > 0.05). The contralateral central lymphatic metastasis in males was slightly higher than that in females, and the difference was statistically significant (68.2% vs. 48.5%, P = 0.041). CONCLUSION: Lymphatic metastasis in level IIA was an independent predictor of lymphatic metastasis in level IIB. When bilateral lateral cervical lymphatic metastasis or lymph node metastasis of level IIA is found, lymph node dissection in level IIB is strongly recommended. When unilateral lateral cervical lymphatic metastasis and lymphatic metastasis in level IIA are negative, lymph node dissection in level IIB may be performed as appropriate on the premise of no damage to the accessory nerve. LCEI is safe and effective for lymph node dissection in level II. When the tumor is located in the unilateral lobe, attention should be given to contralateral central lymph node dissection because of the high lymphatic metastasis rate.

Construction of a system for head and neck tumor traceless resection with non-inflatable transaxillary total endoscopic surgery.

Radical cure and functional preservation of tumors are the fundamental goals of surgical treatment of head and neck tumors, and the preservation of good aesthetics is a higher pursuit on this basis. Fully hiding the surgical incision and reducing the visibility of scars are important goals of cosmetic surgery. Using complete endoscopy for the head and neck is an effective method. CO2-free transaxillary total endoscopic surgery is a method with many advantages, which has been widely used in the resection of thyroid tumors, but for other parts and types of tumors in the head and neck, this surgical method is rarely used. The research team expanded its application scope and applied it to submandibular gland tumor resection and other head and neck surgeries for the first time. Through this exploration, it improved traction devices such as retractors, strictly limited the surgical indications, analyzed and summarized the key points, steps and methods of surgery, and built a treatment system for head and neck tumor surgery under complete endoscopy using the non-inflatable transaxillary approach. In this article, we introduce the system and select typical cases to share.

Resection of Second, Third, and Fourth Branchial Cleft Anomalies with Recurrent or Repeated Neck Infection Using the Selective Neck Dissection Technique.

PURPOSE: To explore the applied value of the selective neck dissection to treat second, third, and fourth branchial cleft anomalies with recurrent or repeated neck infections. METHOD: We made a retrospective study about 29 patients with the second, third, and fourth branchial cleft anomalies with recurrent or repeated neck infections who were treated by surgery from 2002 to 2018 in Sichuan Province Cancer Hospital. According to the characteristics of branchial cleft anomaly on embryology and anatomy, different types of selective neck dissection were chosen to remove pathological scar tissue or inflammatory tissue en bloc. RESULT: Of 29 cases, 28 had primary healing, and 1 had local infection, healing after dressing change for a long time. In 1 case, branchial cleft anomalies adhered to the internal jugular vein, which was ruptured and sutured. During the follow-up time of 12∼195 months with an average of 91.76 months, there were no recurrent cases. CONCLUSION: The selective neck dissection technique is safe and effective in the treatment of branchial cleft anomalies with recurrent or repeated neck infection.

A case report of ectopic thyroid adenoma resection by transaxillary non-inflatable endoscopic surgery.

INTRODUCTION AND IMPORTANCE: The ectopic thyroid gland is a rare disease in which abnormal migration of the embryonic thyroid germ is thought to be the basis for the formation of the ectopic thyroid gland. CASE PRESENTATION: A 37 year old female sought medical attention due to feeling a sensation of swallowing foreign objects, without any other positive symptoms such as pain or difficulty breathing. Preoperative examination revealed a nodule in the left lobe of the thyroid gland and a nodule behind the left lobe. The patient ultimately underwent non-inflatable endoscopic surgery under the axilla to completely remove the tumor located in the suprasternal fossa. Postoperative pathological examination confirmed ectopic thyroid adenoma. The patient's postoperative thyroid function was normal. CLINICAL DISCUSSION: The diagnosis of ectopic thyroid is difficult due to its highly non-specific histological characteristics and positional changes. However, clinical diagnosis and treatment should not overlook the possibility of ectopic thyroid. On the basis of completely removing the lesion, the transaxillary non-inflatable endoscopic surgery also meets the patient's minimally invasive and aesthetic needs. CONCLUSION: The diagnosis of ectopic thyroid is difficult, and through transaxillary non-inflatable endoscopic surgery, the tumor can be completely removed and the patient's aesthetic needs can be met.

Application of CT and MRI images based on artificial intelligence to predict lymph node metastases in patients with oral squamous cell carcinoma: a subgroup meta-analysis.

Background: The performance of artificial intelligence (AI) in the prediction of lymph node (LN) metastasis in patients with oral squamous cell carcinoma (OSCC) has not been quantitatively evaluated. The purpose of this study was to conduct a systematic review and meta-analysis of published data on the diagnostic performance of CT and MRI based on AI algorithms for predicting LN metastases in patients with OSCC. Methods: We searched the Embase, PubMed (Medline), Web of Science, and Cochrane databases for studies on the use of AI in predicting LN metastasis in OSCC. Binary diagnostic accuracy data were extracted to obtain the outcomes of interest, namely, the area under the curve (AUC), sensitivity, and specificity, and compared the diagnostic performance of AI with that of radiologists. Subgroup analyses were performed with regard to different types of AI algorithms and imaging modalities. Results: Fourteen eligible studies were included in the meta-analysis. The AUC, sensitivity, and specificity of the AI models for the diagnosis of LN metastases were 0.92 (95% CI 0.89-0.94), 0.79 (95% CI 0.72-0.85), and 0.90 (95% CI 0.86-0.93), respectively. Promising diagnostic performance was observed in the subgroup analyses based on algorithm types [machine learning (ML) or deep learning (DL)] and imaging modalities (CT vs. MRI). The pooled diagnostic performance of AI was significantly better than that of experienced radiologists. Discussion: In conclusion, AI based on CT and MRI imaging has good diagnostic accuracy in predicting LN metastasis in patients with OSCC and thus has the potential for clinical application. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, PROSPERO (No. CRD42024506159).

The role and mechanism of NADPH oxidase in the development and progression of thyroid carcinoma.

Thyroid cancer is the fastest increasing cancer in both men and women and is the most common endocrine cancer. Researchers have gradually intensified their research on the mechanism of thyroid cancer development. Within this realm, Oxidative stress is often believed to play a causal and contributory role in thyroid cancer development. NADPH oxidase is one of the important sources of reactive oxygen species for tumor cell growth and is involved in the biological processes of thyroid tumor cell proliferation, migration, invasion and epithelial-to-mesenchymal transition. However, the mechanism of NADPH oxidase in the pathogenesis of thyroid cancer is still not very clear at present. Clarifying the role and mechanism of NADPH oxidase in the pathogenesis of thyroid cancer will help to develop new strategies for the prevention and treatment of thyroid cancer as early as possible, and improve the survival rates of thyroid tumor patients. This article reviews the research progress on the mechanism of NADPH oxidase in thyroid cancer.

Targeting NOX4 disrupts the resistance of papillary thyroid carcinoma to chemotherapeutic drugs and lenvatinib.

Advanced differentiated thyroid cancer cells are subjected to extreme nutritional starvation which contributes to develop resistance to treatments; however, the underlying mechanism remains unclear. Cells were subjected to serum deprivation by culture in medium containing 0.5% fetal bovine serum. A CCK8 assay, cell death Detection ELISAPLUS kit, and PI staining were conducted to determine cell viability, cell apoptosis, and cell cycle, respectively. NADPH oxidase 4 (NOX4) knockdown-stable cell lines were generated by lentivirus-mediated shRNA knockdown in BCPAP cells and TPC-1 cells. Etoposide and doxorubicin, two chemotherapeutic drugs, as well as lenvatinib were utilized to determine the effect of NOX4 on drug resistance. Lenvatinib-resistant BCPAP cells (LRBCs) were established to confirm this effect. The underlining mechanisms of NOX4 under starvation were explored using western blot. Finally, GLX351322, an inhibitor targeting NOX4, was used to inhibit NOX4-derived ROS in vitro and detect its effect on drug resistance of tumor cells in vivo. NOX4 is overexpressed under serum deprivation in BCPAP or TPC-1 cells. NOX4 knockdown impairs cell viability, increases cell apoptosis, extends G1 phase during cell cycle and modulates the level of energy-associated metabolites in starved cells. When the starved cells or LRBCs are treated with chemotherapeutic drugs or Lenvatinib, NOX4 knockdown inhibits cell viability and aggravates cell apoptosis depending on NOX4-derived ROS production. Mechanistically, starvation activates TGFß1/SMAD3 signal, which mediates NOX4 upregulation. The upregulated NOX4 then triggers ERKs and PI3K/AKT pathway to influence cell apoptosis. GLX351322, a NOX4-derived ROS inhibitor, has an inhibitory effect on cell growth in vitro and the growth of BCPAP-derived even LRBCs-derived xenografts in vivo. These findings highlight NOX4 and NOX4-derived ROS as a potential therapeutic target in resistance to PTC.

[Application value of CTA combined with digital technology in the design of anterolateral thigh flap in repairing operative defect of head, neck and maxillofacial tumor resection].

Objective:To explore the value of computed tomography angiography （CTA） combined with digital technology in the vascular anatomy of the anterior thigh flap in patients with operative defects after head, neck and maxillofacial tumor operation, and in the design of preoperative and intraoperative flaps. Methods:Twenty-five cases of patients with postoperative defect after head, neck and maxillofacial tumor surgery admitted to our hospital from April 2018 to April 2019 were selected. Preoperative CTA and digital technology were used to clarify vascular anatomy and other related conditions, and the operation was carried out. Consistency analysis was applied to evaluate the value of CTA, digital technology and CTA combined digital technology in the localization of anterolateral thigh perforator flap with operative defects after head, neck and maxillofacial tumor resection, and the diagnostic efficacy of the three methods was compared. Results:The preoperative CTA examination revealed that there were 26 intermuscular perforators with a diameter greater than 0.8 mm in the flap donor site, and 17 musculocutaneous perforators with a diameter greater than 1.0 mm. During the operation, it was actually found that there were 27 intermuscular perforators with a diameter greater than 0.8 mm and 17 musculocutaneous perforators with a diameter greater than 1.0 mm. The accuracy rates of Pre-operative examination were 96.29% and 100.00%, respectively.In addition, the lateral femoral circumflex artery determined by digital technology. The starting position of the descending branch, the diameter of the vessel, the direction of the perforating vessel, and the maximum length of the pedicle that can be cut were consistent with the actual observation during the operation. All the patients in the group successfully underwent flap removal and repair. After the operation, 2 skin flaps suffered from vascular crisis, and survived under the managements of anticoagulation, lifting of restraint, and massage. The rest of the flaps survived smoothly. The patients were followed up for 3-12 months postoperatively. Twenty-four cases of skin flaps had good appearance. One case had swollen wound And the appearance of the skin flap was satisfactory after elective secondary thinning. Among the 25 patients with head and neck defects, in the perforator location examination, 18 cases were detected by CTA, with a sensitivity of 90.0%, a specificity of 60.0%, an accuracy of 84.0%, and Kappa=0.500. 19 cases was detected by digital technology, with a sensitivity of 86.36%, a specificity of 66.67%, a accuracy rate of 84.00%, and Kappa=0.412. 21 cases was detected by CTA combined with digital technology,with a sensitivity of 95.45%, a specificity of 66.67%, a accuracy of 92.00%, and Kappa=0.621. The accuracy of CTA combined with digital technology in the perforator positioning of patients with head and neck tumor defects was significantly higher than that of the single method（P<0.05）. Conclusion:CTA has good application value in the positioning of perforator in patients with head, neck and maxillofacial tumor defects. In addition, the combination of CTA and digital technology can improve the accuracy of the vascular anatomy of the anterior thighflap and the design of the preoperative and intraoperative flaps, which is beneficial to surgery clinical implementation.

Relationship between the extent of central node dissection and parathyroid function preservation in thyroid cancer surgery.

BACKGROUND: The risk and effect of hypocalcemia following surgery of different magnitudes remains unclear. Thus, we assessed whether different extents of central lymph node dissection (CLND) and status of preserved parathyroid glands can influence parathyroid function in differentiated thyroid carcinoma (DTC) patients with initial surgical resection. METHODS: Participants were categorized into 6 groups based on the extent of the surgical procedures, number of parathyroid glands preserved in situ, and parathyroid autotransplantation. The frequencies of hypocalcemia, serum calcium (Ca) levels, and parathyroid hormone (PTH) levels among the different groups were analyzed. RESULTS: The prevalence of hypocalcemia, number and status of parathyroid glands preserved in situ, and parathyroid autotransplantation were inversely related to extensive CLND (r=-0.18; P<0.05). The decrease of serum Ca and PTH was most severe on postoperative days (POD) 1-7. The incidence of hypocalcemia was higher in Group C than in Group B and A (P<0.05). The average postoperative serum Ca and PTH levels in Group C were significantly lower than group A on POD 1-7 (P<0.05). The incidence of hypocalcemia was obviously increased in Group D compared to Groups E and F (P<0.05). The mean serum Ca and PTH levels in Group D were significantly lower than in Group F (P<0.05), and the same results could be observed between Groups D and E (P<0.05). However, through parathyroid autotransplantation, there was no significant difference that could be found between Groups E and F on POD 1-7 (P>0.05). CONCLUSIONS: With the expansion of CLND scope, postoperative parathyroid function will be affected, increasing the risk of postoperative hypocalcemia. When at least 1-2 parathyroid glands were reserved in situ plus at least 1 parathyroid gland autotransplantation, there was little effect on postoperative parathyroid function.

Gasless transaxillary endoscopic thyroidectomy for unilateral low-risk thyroid cancer: Li's six-step method.

The past decade has witnessed rapid advances in gasless transaxillary endoscopic thyroidectomy (GTET) for thyroid cancer, which has become a reliable procedure with good therapeutic effectiveness, aesthetic benefits, and safety. This procedure has been widely promoted in some Asian countries; however, few studies have described the specific surgical steps for unilateral low-risk thyroid cancer. Based on a review of the literature and our own clinical experience, we introduce in detail the surgical procedure of GTET for the unilateral low-risk thyroid cancer, briefly summarized into Li's 6 steps: surgical position and incision design; creation of surgical cavities; dissection of the superior pole of the thyroid and its vessels, and identification and protection of superior laryngeal nerve; identification and protection of the superior parathyroid gland, and identification of the inferior parathyroid gland; identification and protection of the recurrent laryngeal nerve and the inferior parathyroid gland, and central neck dissection; and processing of the suspensory ligaments of thyroid gland and en bloc resection of the tumor. The six-step approach is simple to learn. The lymph nodes are dissected first, followed by resection of the primary lesion and protect important structures, which meets the principles of radical tumor treatment. It is hoped that the proposed Li's six-step method can promote the standardized, safe, and wide application in treating early thyroid cancer.

An algorithm for one-stage malignant oncologic scalp reconstruction.

BACKGROUND: Scalp reconstruction has always been a challenging problem after oncological resection. Advanced surgical techniques can reconstruct any defects, but there are a large number of patients who cannot benefit from surgery for immature strategies. The authors here describe an algorithm for selecting the best reconstructive categories and minimizing complications according to the surgical defect of scalp tumors. METHODS: A single-institution retrospective review was conducted that included 173 patients with scalp tumors treated with surgery followed by reconstruction. Patients were identified by tumor type and nature; the location of scalp defect, size, and depth; the types of reconstructions and surgical. A systematic algorithm was developed according to our findings and current literature. RESULTS: Small defects (≤4 cm2) could be closed by primary closure. Medium defects (4-30 cm2) were reconstructed by local flaps. We routinely used skin graft for significant surgical defects (30-90 cm2). And the tumor's location did not have an impact on reconstructive categories of above three types of defects. Free flaps should reconstruct very large-sized defects (>90 cm2) in frontal, temporal, and vertex locations while pedicle flaps suited for occipital defects due to its anatomic vicinity. The reconstruction algorithm of recurrent disease was like the management in primary tumors except for the medium size defect in the occipital region that was primarily reconstructed by a skin graft. Multiple free flaps reconstruction is the best possibility for total scalp resection. Free flap reconstruction is used mainly for composite resection of the scalp, calvarium, and dura. CONCLUSIONS: Successful scalp reconstruction requires careful preoperative assessment, flexible and precisely intraoperative management. The algorithm based on defect size, depth, and location can supply some degree of guidelines when considering choosing suitable reconstructive procedures.

Surgery for retrosternal goiter: cervical approach.

BACKGROUND: Retrosternal goiter refers to when the thyroid gland extends from the neck to the substernal portion, descending below the thoracic inlet into the mediastinum. It is typically accompanied by compressive symptoms, and most patients need to undergo surgery. This retrospective study set out to analyze the surgical approach to retrosternal goiter and to evaluate perioperative complications, with the aim of recommending best surgical technique. METHODS: We carried out retrospective analysis of 115 patients with retrosternal goiter treated at our center between May 4, 2011 and March 19, 2019. We analyzed patient characteristics, surgical methods, and perioperative complications using SPSS. RESULTS: Of the 115 patients in our study, 112 underwent thyroidectomy by cervical approach, with only 3 requiring an extracervical approach. The median age of the patients was 52.3 years, and the majority were female (81.74%). Most of the patients (73.91%) experienced no symptoms but were diagnosed with tracheal compression during surgery or preoperative imaging examination. Ninety-eight (85.22%) of our patients underwent preoperative evaluation of their condition by CT imaging. No obvious surgical contraindications were found before thyroid function tests. The mean operation time was 115.11 min, and the average amount of bleeding during surgery was 54.43 mL. The mean postoperative hospital stay was 5.38 days. In 109 cases (94.78%), the goiter was found to be benign, and malignancy was diagnosed in 6 patients (5.22%). Of the 112 patients who were treated with the cervical approach, 7 (6.25%) experienced recurrent laryngeal nerve palsy; 6 of these cases were transitory and 1 was permanent. The number of patients treated by cervical and extracervical approach who experienced transient hypocalcaemia was 23 (20.54%) and 2, respectively. Transient hypoparathyroidism affected 16 patients (14.29%) treated by cervical approach. Two patients had tracheomalacia phenomenon and one patient had pleural effusion after surgery. No cases experienced permanent hypocalcemia, permanent hypoparathyroidism, postoperative hematoma, tracheostomy, or death. CONCLUSIONS: Retrosternal goiter surgery is challenging for surgeons. The best surgical approach for the patient should be based on CT scan evaluation. In our study, based on preoperative CT imaging and in-operation evaluation, 50% of the tumor volume was located below the thoracic inlet and 50% of the tumor volume was located above the thoracic inlet in almost all of the patients. Both sections could be successfully removed via a cervical incision, and no obvious complications were observed during the perioperative period. With careful planning and execution before surgery and meticulous operation during surgery, most retrosternal goiters can be safely treated by cervical approach.

Posttransplantation lymphoproliferative disorder involving the central nervous system in liver transplant recipients.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) involving the central nervous system (CNS) is a rare and serious complication associated with solid organ transplantation. We treated a case of PTLD with CNS involvement in a liver transplant recipient and reviewed the literature. METHOD: The clinicopathological features of a 53-year-old man were retrospectively analyzed. RESULTS: Metastasis of the hepatoma was preoperatively considered on the basis of clinical findings. Craniotomy was performed and PTLD was diagnosed pathologically. The patient was treated with antiviral agents, radiation therapy, and chemotherapy; the immunosuppressive medication was reduced. The patient is still alive after follow-up for 14 months. CONCLUSIONS: Definitive diagnosis of PTLD is only established on the basis of histopathologic evaluation of the tissue. Although there are several ways to manage PTLD with CNS involvement, the prognosis is still poor.

NADPH oxidase NOX4 is a glycolytic regulator through mROS-HIF1α axis in thyroid carcinomas.

The function of the NAD(P)H oxidases (NOXs) family member NOX4 is to generate reactive oxygen species (ROS), however, the molecular function of NOX4 has not been fully studied and waiting to be clarified. To elucidate the function of endogenous Nox4 in human thyroid carcinomas, papillomatosis thyroid cancer cells were used to study the cell growth by knocking down the expression of NOX4 and knocking out its functional partner p22phox/CYBA. As a result, the increasement of mitochondrial ROS(mROS) was abolished due to both knockdown of NOX4 and p22phox knockout in hypoxia, which destabilized HIF1α decreasing glycolysis and retarded cell growth. These data suggests that Nox4 is potent oncotarget due to its role in regulating glycolysis through mROS-HIF1α pathway, thereby mediating proliferation in thyroid carcinomas.

A novel synthetic compound exerts effective anti-tumour activity in vivo via the inhibition of tubulin polymerisation in A549 cells.

Microtubules are critical elements that are involved in a wide range of cellular processes, and thus, they have become an attractive target for many anticancer drugs. A novel synthesised compound, 12P, was identified as new microtubule inhibitor. This compound inhibits tubulin polymerisation through binding to the colchicine-binding site of tubulin. 12P exhibits excellent anti-proliferative activities against a panel of human cancer cell lines, with IC50 values range from 9 to 55nM. Interestingly, compound 12P also displayed equally potent cytotoxicity against several drug-resistant cell lines, and it showed high selectivity for active human umbilical vein endothelial cells (HUVECs). Further flow cytometric analysis showed that 12P induces G2/M phase arrest and apoptosis in A549 cells. Cellular studies have revealed that the induction of apoptosis by 12P was associated with a collapse of mitochondrial membrane potential (MMP), accumulation of reactive oxygen species (ROS), alterations in the expression of some cell cycle-related proteins (e.g. Cyclin B1, Cdc25c, Cdc2) and some apoptosis-related proteins (e.g. Bax, Bad, Bcl-2, Bcl-xl). Importantly, 12P significantly reduced the growth of xenograft tumours of A549 cells in vivo (tumour inhibitory rate of 12P: 84.2%), without any loss of body weight. Taken together, these in vitro and in vivo results suggested that 12P may become a promising lead compound for the development of new anticancer drugs.