Promotion of tumor progression and cancer stemness by MUC15 in thyroid cancer via the GPCR/ERK and integrin-FAK signaling pathways

Thyroid cancer is the fifth most common cancer diagnosed in women worldwide. Notwithstanding advancements in the prognosis and treatment of thyroid cancer, 10-20% of thyroid cancer patients develops chemotherapeutic resistance and experience relapse. According to previous reports and TCGA database, MUC15 (MUCIN 15) upregulation is highly correlated with thyroid cancer progression. However, the role of MUC15 in tumor progression and metastasis is unclear. This study aimed to investigate factors mediating cancer stemness in thyroid cancer. MUC15 plays an important role in sphere formation, as an evident from the expression of stemness markers including SOX2, KLF4, ALDH1A3, and IL6. Furthermore, ectopic expression of MUC15 activated extracellular signal-regulated kinase (ERK) signaling via G-protein-coupled receptor (GPCR)/cyclic AMP (cAMP) and integrin/focal adhesion kinase pathways. Interestingly, ectopic expression of MUC15 did not affect RAF/mitogen-activated protein kinase kinase (MEK)-mediated ERK activation. The present findings may provide novel insights into the development of diagnostic, prognostic, and therapeutic applications of MUC15 in thyroid cancer.ope

Radiomics in predicting mutation status for thyroid cancer: A preliminary study using radiomics features for predicting BRAFV600E mutations in papillary thyroid carcinoma

PURPOSE: To evaluate whether if ultrasonography (US)-based radiomics enables prediction of the presence of BRAFV600E mutations among patients diagnosed as papillary thyroid carcninoma (PTC). METHODS: From December 2015 to May 2017, 527 patients who had been treated surgically for PTC were included (training: 387, validation: 140). All patients had BRAFV600E mutation analysis performed on surgical specimen. Feature extraction was performed using preoperative US images of the 527 patients (mean size of PTC: 16.4mm±7.9, range, 10-85 mm). A Radiomics Score was generated by using the least absolute shrinkage and selection operator (LASSO) regression model. Univariable/multivariable logistic regression analysis was performed to evaluate the factors including Radiomics Score in predicting BRAFV600E mutation. Subgroup analysis including conventional PTC <20-mm (n = 389) was performed (training: 280, validation: 109). RESULTS: Of the 527 patients diagnosed with PTC, 428 (81.2%) were positive and 99 (18.8%) were negative for BRAFV600E mutation. In both total 527 cancers and 389 conventional PTC<20-mm, Radiomics Score was the single factor showing significant association to the presence of BRAFV600E mutation on multivariable analysis (all P<0.05). C-statistics for the validation set in the total cancers and the conventional PTCs<20-mm were lower than that of the training set: 0.629 (95% CI: 0.516-0.742) to 0.718 (95% CI: 0.650-0.786), and 0.567 (95% CI: 0.434-0.699) to 0.729 (95% CI: 0.632-0.826), respectively. CONCLUSION: Radiomics features extracted from US has limited value as a non-invasive biomarker for predicting the presence of BRAFV600E mutation status of PTC regardless of size.ope

Hemodynamic stability during adrenalectomy for pheochromocytoma: A case control study of posterior retroperitoneal vs lateral transperitoneal approaches

Hemodynamic stability is one of the most critical aspects of adrenal surgery for pheochromocytoma. Few articles have evaluated the hemodynamic status of patients undergoing posterior retroperitoneal adrenalectomy (PRA) for pheochromocytoma. The aim of this study is to compare the intraoperative hemodynamic parameters between lateral transperitoneal adrenalectomy (TPA) and PRA in this groups of patients.This report describes a retrospective study of 53 pheochromocytoma patients who underwent endoscopic adrenalectomy via transperitoneal (22 patients) or posterior retroperitoneal (31 patients) approaches from January 2008 to March 2015. Data from these patients were compared to investigate the differences in hemodynamic parameters between the 2 approaches.Clinical parameters at presentation were similar between the 2 groups, except for tumor size, which was larger in the TPA group. The PRA group is associated with reduced operative time, blood loss, and length of hospital stay compared to TPA even after adjusting for the tumor size. There was greater BP fluctuations and higher maximum systolic and diastolic blood pressure (BP) within the TPA group compared to PRA during univariate analysis. This was however not significant after adjusting for tumor size. There was no difference in the intraoperative inotropic support requirement between the 2 groups.PRA is associated with stable intraoperative hemodynamic status, as well as favorable perioperative outcomes compared to TPA in patients with small pheochromocytomas.ope

Hashimoto's thyroiditis and papillary thyroid cancer

The association of Hashimoto’s thyroiditis (HT) with papillary thyroid cancer (PTC) has been still under debate. Some suggest that these two are positively correlated, whereas other studies report no relationship. We performed a systematic literature review of original studies to investigate the correlation between HT and PTC. The existing data provide inconsistent evidence favoring a causal relationship between HT and PTC. The average prevalence rate of PTC in patients with HT was 1.2% in 8 fine needle aspiration (FNA) studies of 18,023 specimens and 27.6% in 8 archival thyroidectomy studies of 9884 specimens. The risk ratio of PTC in HT specimens ranged from 0.39 to 1.00 in the FNA group (average RR 0.69) in contrast to 1.15 to 4.16 from thyroidectomy studies (average RR 1.59). Population-based fine needle aspiration biopsy studies report no relationship, whereas many of the studies using thyroidectomy specimens report a positive relationship, possibly related to selection bias. Several studies identified a few biomolecular markers, including the PI3K/Akt pathway, RET/PTC gene rearrangements, p63 protein, and loss of heterozygosity of hOGG1, that are potentially involved in neoplastic transformation from HT to PTC. So far, no causal genetic linkage has been confirmed. PTC with concurrent HT is associated with female gender, young age, less aggressive disease such as small tumor size, less frequent capsular invasion and nodal metastasis, and better outcome. However, more prospective studies with long term follow-up are needed to further elucidate this relationship and prognosis. Careful observation and follow-up of HT patients is recommended, especially those with nodular variants.ope

Bone Metastases from Differentiated Thyroid Carcinomas

Purpose: Only limited information exists on the clinicopathological profiles and the treatment outcomes of bone metastases from differentiated thyroid carcinomas. Therefore the impact of treatment strategies has been inadequately investigated. The aims of this study were to evaluate the proper management and the prognostic factors that influence the long-term outcomes of patients treated for bone metastasis from differentiated thyroid carcinoma. Methods: Twenty-two cases of bone metastases out of 3,775 differentiated thyroid carcinomas treated at Yonsei University Medical Center between Jan. 1986 and Dec. 2004 were analyzed. The overall incidence of bone metastases from differentiated thyroid carcinomas in our series was 0.6%. There were 11 women and 11 men, with a mean age at the time of primary diagnosis of 51 years (25∼71 years). The mean follow-up after diagnosis of bone metastases was 83 months (1∼358 months). Results: The histological diagnoses of primary tumor were 21 and 1 papillary and follicular cancers, respectively. Metastases restricted to the skeleton alone were found in 13 patients, whereas 9 patients showed associated extraskeletal distant metastases. Seventeen patients had multiple bone metastases. In 6 patients, the bone metastases were surgically removed with intention of cure. The overall survival rates at 10 years was 44.4%. From univariate log-rank survival rates analyses, capsular invasion (P=0.0014), preoperative vocal cord palsy (P=0.0097), multiple organ involvement (P=0.024) and the impossibility of surgical treatment for skeletal metastaisis (P=0.0471) were related with a poor prognosis. Conclusion: From the results, the survival rate was shown no significantly decline in the patients with poor prognostic factors. Therefore the therapeutic options should be individualized according to the initial clinical state and the prognostic factors. Our data also suggest that surgical resection for metastatic bone lesions and postoperative adjuvant therapy should be performed to obtain better survival rates.ope

A Case of Differentiatied Thyroid Carcinoma with Internal Jugular Vein Tumor Thrombus

Differentiated thyroid carcinoma rarely shows gross angioinvasion with intraluminal tumor thrombus. Although there was no definite result of long-term survival, a vascular invasion or thrombus indicates poor prognosis. Total thyroidectomy with en block resection of involved vessels is known as the best surgical approach, and followed by postoperative radioiodine therapy. However, the effect of adjuvant external irradiation therapy remains in debate. We report a case of differentiated thyroid carcinoma with internal jugular vein tumor thrombus treated successfully by a complete surgical resection and postoperative radioiodine therapy.ope

Graves's Disease Presenting Concurrently with Thyroid Cancer

Purpose: Graves’ disease presenting concurrently with thyroid cancer is a rare condition. The clinical behaviors and the extent of surgery in this condition is still controversial. This study examined the prognostic factors influencing the long-term outcomes as well as the appropriate treatment modalities in patients with Graves’ disease presenting concurrently with thyroid cancer. Methods: Forty nine patients who underwent surgery for thyroid cancer with Graves’ disease were enrolled in this study. The outcomes of various types of surgical treatments as well as the factors associated with the long-term outcome were retrospectively analyzed. Results: There were 42 women and 7 men with a median age 39 years (15～70 years). The surgical procedures included a bilateral subtotal thyroidectomy (n=17), a bilateral total thyroidectomy (n=16), and a total and contralateral subtotal thyroidectomy (n=16). The mean follow-up period was 83 months (4～218 months) after surgery. Disease-free survival at 5 and 10 years were 97.6% and 88.9%, respectively. Univariate log-rank survival analyses revealed that the age at diagnosis, the size of the thyroid cancer, capsular invasion, multiplicity, lymph node involvement, and clinical cancer to be poor prognostic factors. However, the extent of the surgical treatment was not significant for survival. Conclusion: The prognosis is expected to be poor when thyroid cancer presenting concurrently with Graves’ disease is clinically apparent or has invaded the thyroid capsule. Patients with Graves’ disease should be screened with ultrasonography to detect thyroid cancer. A total thyroidec-tomy or completion total thyroidectomy is not necessary in patients who do not have any of the poor prognostic factors, such as incidentally detected microcarcinoma postoperatively.ope

Fibromatosis of the Neck: a Case Report and Review of the Literatures

The fibromatosis (desmoid tumor) is histologically benign fibrous neoplasm arising from the musculoaponeurotic structures through out the body, but that shows locally aggressive growth. Common anatomic sites includes the limbs, trunk and mesentery. Fibromatoses arising in the neck have been reported rarely. If the tumors are occurred in the neck, complete resection is often difficult, because of its locally infiltrative nature. Therefore radiotherapy, chemotherapy and hormonal therapy are occasionally needed to reduce local recurrence. We report herein a case of fibromatosis arising in the left supraclavicular region with infiltration to surrounding tissues, which was successfully treated by complete surgical excision and postoperative adjuvant radiotherapy.ope

Gasless Endoscopic Thyroidectomy Via an Axillary Approach

Purpose: Surgery for thyroid disease requires skin incisions that can result in postsurgical problems, such as prominent scars, adhesions and hypesthesia, as well as paresthesia of the neck. To overcome these problems we performed a gasless endoscopic thyroidectomy via an axillary approach. Methods: Between November 2001 and April 2005, 141 patients underwent a gasless endoscopic thyroidectomy via an axillary approach. The surgical outcomes were evaluated in terms of the operating time, length of hospital stay and the incidence of perioperative complications. Patient opinions were assessed using a verbal response scale at two and four months after surgery. Results: The mean operating time and length of hospital stay were 122.7±32.8 minutes and 3.4±0.9 days, respectively. No cases required either conversion to open surgery or involved significant intraoperative complications. Two months after surgery, 75 patients (53.2%) complained of hypesthesia or paresthesia in the anterior chest wall. The number of patients with such complaints (9.9%) had decreased 4 months after surgery (P＜0.001). Four months after surgery, only 4 patients (2.8%) complained of hypesthesia or paresthesia in the neck, and 10 (7.1%) complained of discomfort while swallowing. All patients were satisfied with the cosmetic results. Conclusion: A gasless endoscopic thyroidectomy via an axillary approach is feasible and safe, and provides excellent cosmetic results, with a minimal degree of postoperative complaints. This procedure provides another surgical option for the treatment of benign thyroid disease in selected patients.ope

Differentiated Thyroid Carcinoma in Patients Less than 20 Years of Age at Diagnosis: Clinicopathologic Characteristics and Prognostic Factors

Purpose: This study investigated the clinicopathological characteristics and prognostic factors in young patients with differentiated thyroid carcinoma. Methods: Among the 3,837 patients with DTC who were treated in the Department of Surgery at Yonsei University College of Medicine from March 1986 to March 2005, 71 patients were less than 20 years of age when diagnosed. The mean age was 14.9 years (range, 4～20 years). There were 59 females and 12 males with a mean follow-up period of 91.8 months (range, 14～205 months). Results: The cause specific and the progression-free survivals at 10 years were 100% and 80.3%, respectively. Eleven patients (15%) experienced a recurrence and 1 patient showed a progression of a pulmonary metastasis at diagnosis. Compared with 39 patients older than 15, 32 patients younger than 15 years of age tended to have a higher incidence of a N1b and M1 stage, and a lower progression-free survival rate. Univariate analysis revealed that an age ≤15 years, multicentricity, N1b stage, M1 stage, and bilateral radical neck dissection had a negative impact on the progression-free survival. However, multivariate analysis showed that the age at diagnosis and the M1 stage were independent prognostic factors for progression- free survival. Conclusion: Being younger 15 years and the M1 stage are the most significant prognostic factors negatively influencing the progression-free survival. The high incidence of lateral neck and lung metastasis justifies a total thyroidectomy and modified radical neck dissection, followed by postoperative 131I therapy even in patients younger than 15 years of age.ope