Clinical classification of recurrent laryngeal nerve palsy.

Background: The application of intraoperative neurophysiological monitoring (IONM) has been accepted to avoid injury of a recurrent laryngeal nerve (RLN). Loss of the neuromonitoring signal indicates nerve injury and is subdivided into segmental type and global type nerve paralysis. This study aimed to determine the course of vocal cord function recovery after definitive loss of signal (LOS) types. Methods: This retrospective study included 1,442 patients (with 2,752 nerves at risk) who had thyroidectomies between January 2018 and December 2021. Preoperative and postoperative vocal cord functions were evaluated by laryngoscopic examination. Results: LOS occurred in 168 of 1,442 (11.7%) patients and 171 of 2,748 (6.2%) nerves at risk during surgery. Of LOS nerves of benign tumors, 74.2% showed global type. In cancer cases, segmental paralysis was more common, accounting for 51.3% of LOS nerves. Of nerves with segmental LOS in cancer patients, 55.3% needed partial layer resection for RLN invasion. Intraoperative recovery was seen in 9 of 62 nerves (14.5%) with segmental LOS and 32 of 109 (29.4%) nerves with global type LOS. The vocal cord palsy rate on postoperative days (PODs) 2-3 was lower after global type nerve paralysis (63.6%) than after segmental loss (84.9%). At 6 months postoperatively, the rate of vocal cord paralysis in benign tumors was not significantly different between segmental type and global type (P=0.586). However, cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively (rate of nerve palsy: segmental 40.0% vs. global 3.4%) (P<0.001). Conclusions: The intraoperative recovery rate and early nerve recovery rate are significantly higher for patients with global LOS than for patients with segmental LOS. Cancer patients with segmental LOS significantly more often had vocal cord dysfunction than those with global LOS at 6 months postoperatively.

Role of Surgery in Patients with Stage IE Primary Thyroid MALT Lymphoma Staged by a Modified Classification System: The Tokyo Classification.

PURPOSES: To establish the appropriate staging system and assess the role of curative thyroidectomy alone (Surgery) vs. involved-site radiation therapy after open biopsy (OB-ISRT) in stage IE mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: We examined the Tokyo Classification as a modified classification. This retrospective cohort study included 256 patients with thyroid MALT lymphoma; 137 underwent standard therapy (i.e., OB-ISRT) and were enrolled for the Tokyo classification. Sixty stage IE patients with the same diagnosis were examined to compare Surgery with OB-ISRT. RESULTS: Overall survival (p = 0.0092) and relapse-free survival (0.00113) were significantly better in stage IE vs. stage IIE under the Tokyo classification. No OB-ISRT and Surgery patients died, but three OB-ISRT patients relapsed. The incidence of permanent complications was 28% in OB-ISRT (mainly dry mouth) and 0% in Surgery (p = 0.027). The number of painkiller prescription days was significantly greater in OB-ISRT (p < 0.001). During follow-up, the rate of the new appearance/change of the low-density area in the thyroid gland was significantly higher in OB-ISRT (p = 0.031). CONCLUSIONS: The Tokyo classification allows an appropriate discrimination between stages IE and IIE MALT lymphoma. Surgery can provide a good prognosis in stage IE cases; it also avoids complications, shortens painful periods during treatment, and simplifies ultrasound follow-up.

Downhill Varices in the Hypopharynx of a Patient with a Large Thyroid Tumor: A Case Report.

Downhill varices are usually caused by superior vena cava (SVC) obstruction due to bronchogenic carcinoma or mediastinal tumors. These structures exhibit retrograde blood flow and are located in the proximal esophagus. Varices in the hypopharynx resulting from mediastinal thyroid tumor are extremely rare. A 70-year-old man with a 35-year history of a growing thyroid tumor on the right side of his neck visited a local hospital. Fine-needle aspiration cytology of the tumor revealed benign goiter. Contrast-enhanced computed tomography showed a huge tumor (13 × 10 × 5 cm) in the right to left lobe of the thyroid that extended into the mediastinum. A well-enhanced mass mimicking hypopharyngeal cancer was identified in the hypopharynx. Endoscopic examination showed varices in the postcricoid region, so biopsy was contraindicated. The preoperative diagnosis was adenomatous goiter and hypopharyngeal varices caused by obstruction of the internal jugular and brachiocephalic vein by the goiter. Total thyroidectomy was performed and the hypopharyngeal varices had disappeared by the next day. The histopathological diagnosis of the thyroid tumor was poorly differentiated carcinoma. Mediastinal thyroid tumor rarely causes downhill varices due to SVC obstruction. However, signs of SVC obstruction were absent in this case, and varices were present in the hypopharynx, not in the upper esophagus. Obstructed venous flow from the thyroid plexus might circulate via the superior laryngeal vein and cause varices in the postcricoid region. When a patient with a large mediastinal tumor has a tumor-like lesion in the hypopharynx, downhill varices should be considered before scheduling a biopsy.

Learning Curve for Endoscopic Thyroidectomy Using Video-Assisted Neck Surgery: Retrospective Analysis of a Surgeon's Experience with 100 Patients.

BACKGROUND: Endoscopic thyroidectomy offers excellent cosmetic outcomes but requires some time for surgeons to become proficient. We examined the learning curve for the first 100 patients treated by a single surgeon using a subclavian approach for video-assisted neck surgery (VANS). METHODS: We retrospectively studied the records of 100 patients (99 women, 1 man; mean age, 36.2 years) with either benign or malignant thyroid disease treated between 2016 and 2020. RESULTS: Preoperative diagnosis was papillary thyroid carcinoma (PTC) in 36 cases and other (non-PTC) in 64 cases. All patients underwent lobectomy, with additional unilateral central node dissection for patients with PTC. Mean operative time was 125 min for non-PTC cases and 129 min for PTC cases (p = 0.43); blood loss was 33.8 mL and 7.6 mL, respectively (p = 0.01). Recurrent laryngeal nerve paralysis (RNP) was observed in 12 patients (12%) and hemorrhage in 2 patients (2%). In a comparison of the first 30 cases and subsequent 70 cases, no significant differences in operative time or blood loss were evident, although tumor size was significantly greater among later non-PTC cases (32.4 mm vs. 39.5 mm, p = 0.039). RNP was significantly lower in later cases (26.7% vs. 5.7%, p = 0.003). Multivariate analysis revealed that tumor size was a significant risk factor for increased blood loss, and increased experience significantly correlated with a decrease in RNP. CONCLUSIONS: In VANS, satisfactory surgical proficiency was reached after treating 30 patients.

Video-assisted neck surgery (VANS) using a gasless lifting procedure for thyroid and parathyroid diseases: "The VANS method from A to Z".

PURPOSE: To describe and evaluate our video-assisted neck surgery (VANS) method for thyroid and parathyroid diseases. METHODS: We describe in detail the VANS method for enucleation, lobectomy, total (nearly total) thyroidectomy, and lymph node dissection for malignancy and Graves' disease. In collaboration with the Japan Society of Endoscopic Surgery (JSES), we evaluated several aspects of this method. The JSES evaluated the method for working-space formation and surgical complications, whereas we examined the learning curve of the surgeons, and the cosmetic satisfaction of the patients and the degree of numbness and pain they experienced. We also asked patients who underwent conventional surgery whether they would have selected VANS had it been available. RESULTS: The working space for 81.5% of the procedures in Japan was created using the gasless lifting method. The learning curve, considering both blood loss and operating time, decreased after 30 cases. Both factors improved for tumors smaller than 5 cm in diameter. Over 60% of the patients who underwent conventional surgery stated that they would have selected VANS, had it been available. Postoperative pain was worse after conventional surgery than after VANS, but neck numbness after VANS was more frequent than expected. CONCLUSIONS: The VANS method is a feasible, safe, and cost-effective procedure with clear cosmetic advantages over conventional surgery.

The Reality of Multiple Endocrine Neoplasia Type 2B Diagnosis: Awareness of Unique Physical Appearance Is Important.

BACKGROUND: Multiple endocrine neoplasia type 2B (MEN2B) is an extremely rare syndrome mainly caused by RET918 germline mutations. MEN2B typically causes medullary thyroid carcinoma (MTC), pheochromocytoma, and unique physical characteristics including mucosal neuroma, distinctive facial appearance, and Marfanoid habitus. Most patients have abdominal symptoms such as bloating, intermittent constipation, and diarrhea. MTC is the most important determinant of mortality in patients with MEN2B. Establishing the diagnosis of MEN2B at a curative stage of MTC is crucial. CASE PRESENTATION: We have encountered four patients with MEN2B. Two were hereditary cases from the same family, and two were considered de novo cases with phenotypically normal parents. Mean age at diagnosis was 25.5 years (range, 13-39 years). Although all patients had shown mucosal neuroma on the lips and tongue, in addition to gastrointestinal symptoms from infancy, diagnoses were made from symptomatic MTC even for the hereditary patients (our index case was a 14-year-old girl, whose mother was subsequently diagnosed with advanced MTC). Genetic tests for RET mutations revealed the M918T mutation in all patients. Two patients developed pheochromocytoma, two died from distant metastases of MTC, and two received treatment for multiple metastases of MTC (one with vandetanib). CONCLUSIONS: In our patients with MEN2B, prophylactic or early thyroidectomy could not be performed. The characteristic phenotype associated with MEN2B is almost always seen prior to detection of MTC or pheochromocytoma. Knowledge about the non-endocrine manifestations of MEN2B needs to be shared among pediatricians and gastroenterologists.

Expression of MRP1 and ABCG2 is associated with adverse clinical outcomes of papillary thyroid carcinoma with a solid component.

Solid variant of papillary thyroid carcinoma (PTC) is characterized by a solid component (SC) retaining classical cytological features of PTC. Despite some controversies, PTC with SC (PTCSC) cases have poor prognosis compared with well-differentiated PTC. We investigated if cancer stem cells (CSCs) may have a role in pathogenesis of PTCSC. PTCSC tumors (n=27) were histologically represented by a mixture of papillary component (PC) and varying degrees of SC involving 10% to 85% of the tumor. Immunohistochemical expression of CSC markers ABCG2 and MRP1, and HBME1 and CK19 was compared between SC and PC within each tumor in association with clinicopathological parameters. ABCG2 and MRP1 were highly expressed in SC, whereas their expression was limited or absent in PC (P=.04 and .002, respectively). In contrast, expression of HBME1 and CK19 appeared higher in PC than in SC (P=.08 and .02, respectively). Higher expression of ABCG2 was associated with higher incidence of large-sized SC (P=.01). Higher expression of MRP1 was associated with higher incidence of lymphovascular invasion (P=.049). Higher expression of ABCG2 and MRP1, and lower expression of CK19 in SC were associated with higher tumor recurrence rate (P=.02, .01, and .02, respectively), and shorter disease-free survival (P<.001 for all the variables). Our findings indicate that the tumor cells harboring CSC-like characteristics in SC could contribute to the pathogenesis of PTCSC and might account for the poor disease prognosis.

An extended family with familial medullary thyroid carcinoma and Hirschsprung's disease.

Familial medullary thyroid carcinoma (FMTC) is an autosomal dominant inherited disease that has highly characteristic clinical features, including medullary thyroid carcinoma (MTC). Mutation of the RET proto-oncogene is known to be responsible for development of FMTC and for multiple endocrine neoplasia types 2A and 2B. Hirschsprung's disease is the most common form of structural intestinal obstructive disease in human newborns. Hirschsprung's disease is defined by the absence of neural crest-derived enteric ganglia along a variable length of the bowel that invariably involves the rectoanal junction. Co-segregation of FMTC and Hirschsprung's disease is uncommon; nevertheless, in 3 generations of 1 family, we observed 5 patients with FMTC, 2 patients with Hirschsprung's disease, and 1 patient with characteristics of both FMTC and Hirschsprung's disease. Moreover, a Cys620Ser mutation in RET was identified in 4 of the 8 patients. This mutation had both activating and inactivating effects on the RET (REarranged during Transfection) protein. There were individual differences in the penetrance of Hirschsprung's disease due to the RET mutation, but the penetrance of MTC was uniform and high. Genetic testing is important for making decisions about treatment and follow-up in families of this kind.

Identification of pathological and normal parathyroid tissue by fluorescent labeling with 5-aminolevulinic acid during endocrine neck surgery.

BACKGROUND: When performing parathyroid or thyroid surgery, surgeons must distinguish parathyroid tissue from the surrounding thyroid tissue, to preserve healthy parathyroid tissue while excising diseased thyroid tissue or to completely remove pathological parathyroid lesions. Here, we explored the feasibility of labeling the parathyroid glands for easy identification by administering 5-aminolevulinic acid (5-ALA) orally to patients undergoing endocrine neck surgery, because 5-ALA accumulates in the parathyroid and has a fluorescent metabolite, protoporphyrin IX. METHODS: Twenty-nine patients about to undergo endocrine (parathyroid or thyroid gland) neck surgery were orally given 5-ALA, a nontoxic substance that occurs naturally in the human body and has no known major side effects. During surgery, we used blue light to excite protoporphyrin IX, the fluorescent metabolite of 5-ALA, and viewed the resulting bright red fluorescence through an optical filter. RESULTS: In the majority of the patients, the parathyroid glands were defined by a clear fluorescence. In 23 patients with pathological parathyroid tissue, the fluorescence enabled us to identify and completely remove diseased parathyroid tissue. In 3 patients with thyroid disease, we were able to easily remove diseased thyroid tissue, and an accidentally removed parathyroid gland was autotransplanted during surgery. CONCLUSIONS: In all but a few cases, 5-ALA clearly labeled parathyroid tissue, allowing for its clean removal or preservation according to the purpose of the surgery. This simple, benign technique is extremely useful for identifying parathyroid tissue, whether pathological or normal, during endocrine neck surgery.

[Current progress and management in molecular targeted therapy for advanced thyroid cancer].

Surgery results in improved outcomes for most patients with thyroid cancer, but there are no effective treatment options for patients with locally advanced/metastatic medullary thyroid cancer(MTC), differentiated thyroid cancer(DTC)refractory to radioiodine therapy, or highly malignant anaplastic thyroid cancer(ATC). Recent studies have shown that tumorigenesis and dedifferentiation of thyroid cancer cells are caused by the activation of several major signaling pathways and the related molecular aberrations, as well as by angiogenesis mediated by the vascular endothelial growth factor receptor(VEGFR)and epidermal growth factor receptor(EGFR). The efficacy of using molecular targeted agents for thyroid cancer treatment is under investigation in Western countries. In April 2011, the Food and Drug Administration(FDA)approved the use of vandetanib for the treatment of advanced MTC based on the results of phase III clinical trials. At the 2013 American Society of Clinical Oncology(ASCO)meetings, investigators reported that sorafenib improved progression-free survival in patients with advanced DTC, according to a phase III trial. FDA approved the use of sorafenib for the treatment of advanced DTC in November 2013. A multicenter clinical trial for ATC is also currently underway. Further research is required in order to characterize the mechanisms of the therapeutic response, to delineate the optimal management of drug-related adverse effects, and to identify biomarkers that can predict the efficacy of therapy. A clinical trial of these novel molecular agents has just begun in Japan, but in the near future, this new treatment strategy could become standard treatment for patients with advanced thyroid cancer.

Introduction and use of video-assisted endoscopic thyroidectomy for patients in Belarus affected by the Chernobyl nuclear disaster.

INTRODUCTION: We developed video-assisted neck surgery (VANS) - a feasible, simple, and safe endoscopic thyroid procedure with cosmetic benefits - in 1998. To date, we have performed this procedure 633 times. We have also introduced the VANS method in Belarus, a country that was left contaminated by the Chernobyl nuclear disaster. METHODS: From a mass screening, nine Belarusian patients, including two with papillary carcinoma of the thyroid, were selected to undergo an operation using the VANS method, performed by a single surgeon (author Shimizu). We compared indicating factors for minimally invasive surgery, specifically the operating time and blood loss, between the Belarusian cases and the 33 most recent cases performed at our institute in Tokyo. RESULTS: The procedures in Belarus were performed under very different working conditions than in Japan. However, operating time and blood loss improved for the Belarusian cases as the surgeon gained experience in this environment; all the cosmetic outcomes were excellent. Subsequently, over a 2-year period, surgeons in Belarus performed the VANS method, with modification, for 29 cases of thyroid tumor. CONCLUSION: The VANS method is easily learned by inexperienced surgeons without major technical problems.