Background: The recurrent laryngeal nerve (RLN) can be injured during thyroid surgery, which can negatively affect a patient's quality of life. The impact of intraoperative anatomic variations of the RLN on nerve injury remains unclear. Objectives of this study were to (1) better understand the detailed surgical anatomic variability of the RLN with a worldwide perspective; (2) establish potential correlates between intraoperative RLN anatomy and electrophysiologic responses; and (3) use the information to minimize complications and assure accurate and safe intraoperative neuromonitoring (IONM). Methods: A large international registry database study with prospectively collected data was conducted through the International Neural Monitoring Study Group (INMSG) evaluating 1000 RLNs at risk during thyroid surgery using a specially designed online data repository. Monitored thyroid surgeries following standardized IONM guidelines were included. Cases with bulky lymphadenopathy, IONM failure, and failed RLN visualization were excluded. Systematic evaluation of the surgical anatomy of the RLN was performed using the International RLN Anatomic Classification System. In cases of loss of signal (LOS), the mechanism of neural injury was identified, and functional evaluation of the vocal cord was performed. Results: A total of 1000 nerves at risk (NARs) were evaluated from 574 patients undergoing thyroid surgery at 17 centers from 12 countries and 5 continents. A higher than expected percentage of nerves followed an abnormal intraoperative trajectory (23%). LOS was identified in 3.5% of NARs, with 34% of LOS nerves following an abnormal intraoperative trajectory. LOS was more likely in cases of abnormal nerve trajectory, fixed splayed or entrapped nerves (including at the ligament of Berry), extensive neural dissection, cases of cancer invasion, or when lateral lymph node dissection was needed. Traction injury was found to be the most common form of RLN injury and to be less recoverable than previous reports. Conclusions: Multicenter international studies enrolling diverse patient populations can help reshape our understanding of surgical anatomy during thyroid surgery. There can be significant variability in the anatomic and intraoperative characteristics of the RLN, which can impact the risk of neural injury.

Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.

Metastatic progression of tumors is driven by genetic alterations and tumor‐stroma interaction. To elucidate the mechanism underlying the oncogene‐induced gastric tumor progression, we have developed an organoid‐based model of gastric cancer from GAstric Neoplasia (GAN) mice, which express Wnt1 and the enzymes COX2 and microsomal prostaglandin E synthase 1 in the stomach. Both p53 knockout (GAN‐p53KO) organoids and KRAS^G12V‐expressing GAN‐p53KO (GAN‐KP) organoids were generated by genetic manipulation of GAN mouse‐derived tumor (GAN wild‐type [WT]) organoids. In contrast with GAN‐WT and GAN‐p53KO organoids, which manifested Wnt addiction, GAN‐KP organoids showed a Wnt‐independent phenotype and the ability to proliferate without formation of a Wnt‐regulated three‐dimensional epithelial architecture. After transplantation in syngeneic mouse stomach, GAN‐p53KO cells formed only small tumors, whereas GAN‐KP cells gave rise to invasive tumors associated with the development of hypoxia as well as to liver metastasis. Spatial transcriptomics analysis suggested that hypoxia signaling contributes to the metastatic progression of GAN‐KP tumors. In particular, such analysis identified a cluster of stromal cells located at the tumor invasive front that expressed genes related to hypoxia signaling, angiogenesis, and cell migration. These cells were also positive for phosphorylated extracellular signal‐regulated kinase (ERK), suggesting that mitogen‐activated protein kinase (MAPK) signaling promotes development of both tumor and microenvironment. The MEK (MAPK kinase) inhibitor trametinib suppressed the development of GAN‐KP gastric tumors, formation of a hypoxic microenvironment, tumor angiogenesis, and liver metastasis. Our findings therefore establish a rationale for application of trametinib to suppress metastatic progression of KRAS‐mutated gastric cancer.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its management has been a subject of ongoing debate among endocrinologists, surgeons, and oncologists. The landscape of surgical management for PTC has witnessed notable shifts. Traditionally, extensive procedures, such as prophylactic central neck dissection (CND) and lateral neck dissection (LND), were common. However, guidelines published in the last decade no longer recommend routine prophylactic LND,¹ and prophylactic CND is now considered unnecessary for low-risk PTC, as it may not benefit all patients.^2-4 The choice between total thyroidectomy and thyroid lobectomy has also evolved, with lobectomy increasingly considered a viable option in select cases. In other words, treatment decisions for patients with PTC will be assessed based on whether there is an advantage to prophylactic contralateral lobectomy. It is important to distinguish this from completion lobectomy, which is defined as the surgical removal of the contralateral remnant thyroid tissue following an initial procedure that is less than a total thyroidectomy. In contrast, prophylactic contralateral lobectomy refers to the simultaneous removal of the contralateral thyroid lobe during the initial surgery, aiming to prevent potential future recurrence.⁵