Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial.

PURPOSE: Alhough antiangiogenic agents are the bedrock of treatment for radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), novel antiangiogenic agents with optimized features like greater target-binding affinities and more favorable pharmacokinetics profile are needed. This phase II randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of anlotinib, a multikinase inhibitor, for RAIR-DTC. PATIENTS AND METHODS: Patients (ages between 18 and 70 years) with pathologically confirmed locally advanced or metastatic RAIR-DTC were enrolled and randomly received 12 mg anlotinib once daily or placebo on day 1 to 14 every 3 weeks. Patients on placebo were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and safety. RESULTS: Between September 2015 and August 2018, 76 and 37 patients randomly received anlotinib and placebo, respectively. Patients receiving anlotinib had a significantly longer median PFS [40.5 months, 95% confidence interval (CI), 28.3-not estimable (NE) versus placebo 8.4 months, 95% CI, 5.6-13.8; HR = 0.21, 95% CI, 0.12-0.37, P < 0.001], meeting the primary endpoint. OS was still immature, with a trend of benefit with anlotinib (HR = 0.57, 95% CI, 0.29-1.12). All patients in the anlotinib group experienced adverse events (AE); 8 (10.5%) discontinued treatment due to AEs. CONCLUSIONS: Anlotinib demonstrated promising efficacy and favorable tolerance in the treatment of locally advanced or metastatic RAIR-DTC, supporting further research to establish its role in the treatment of this serious disease.

Anlotinib in patients with medullary thyroid carcinoma with negative prognostic factors: A sub-analysis based on the ALTER01031 study.

Background: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer; however, it accounted for 13.4% of the disease-specific mortalities. ALTER01031 (NCT02586350) was a randomised, placebo-controlled phase 2b trial that evaluated the efficacy and safety of anlotinib in locally advanced or metastatic MTC. This post hoc analysis aimed to evaluate the efficacy and safety of anlotinib in older patients and those with bone metastases using ALTER01031. Methods: In ALTER01031, anlotinib significantly prolonged the median progression-free survival (PFS) from 11.1 months to 20.7 months compared with placebo in the whole population. Patients who were older (≥ 50 years) or had bone metastases were selected. PFS and overall survival (OS) were estimated and compared between patients receiving anlotinib or placebo in each subgroup. A sub-analysis of tumour response and safety was also performed. Results: Patients with older age or bone metastases experienced rapid disease progression as the median PFS was 6.8 months and 7.0 months respectively in the placebo group. Anlotinib significantly improved the median PFS to 17.5 months (P = 0.002) and 20.7 months (P = 0.029) with hazard ratio (HR) of 0.31 (95% CI, 0.15-0.68) and 0.44 (95% CI, 0.20-0.94) compared with placebo. Significant benefit in OS was observed in patients with older age after a longer follow-up (HR = 0.47 [95% CI, 0.22-0.99], P = 0.041). The safety profile of these subgroups was similar to that of the entire population. Conclusion: This sub-analysis demonstrated significant survival benefits and favourable safety of anlotinib in patients with MTC who had old age or bone metastases, supporting the feasibility of anlotinib in these patients.

Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial.

PURPOSE: Medullary thyroid cancer (MTC) accounts for about 2% of all thyroid cancer, but has a relatively poor prognosis compared with differentiated thyroid cancer. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This multicenter, randomized, double-blind, placebo-controlled phase IIB study (ALTER 01031 and NCT02586350) was conducted to investigate the efficacy and safety of anlotinib in MTC. PATIENTS AND METHODS: Patients with histopathologically confirmed, unresectable locally advanced or metastatic MTC were enrolled and randomly assigned in a 2:1 ratio to receive anlotinib (12 mg once daily from day 1 to 14 every 3 weeks) or placebo. Patients in placebo group were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: Ninety-one patients were enrolled. At data cutoff date, the median PFS was significantly prolonged in the anlotinib group than in the placebo group (20.7 months vs. 11.1 months, P = 0.029; HR, 0.53; 95% confidence interval, 0.30-0.95). The ORR of anlotinib treatment was 48.4%. The incidence of treatment-related adverse events (TRAE) was 100% and 89.7% in the anlotinib and placebo groups, respectively. The most common TRAEs of all grades in the anlotinib group were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%), and hypertriglyceridemia (48.4%). CONCLUSIONS: Anlotinib demonstrates its efficacy and safety in this phase IIB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.

Surufatinib in Chinese Patients with Locally Advanced or Metastatic Differentiated Thyroid Cancer and Medullary Thyroid Cancer: A Multicenter, Open-Label, Phase II Trial.

Background: Thyroid cancer is the most common endocrine tumor with an increasing incidence. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Surufatinib targets multiple kinases (vascular endothelial growth factor receptors, fibroblast growth factor receptor-1, and colony-stimulating factor-1 receptor) involved in tumor angiogenesis and tumor immune evasion. Surufatinib has demonstrated promising antitumor activity in various advanced solid tumors. This study aimed to determine the objective response rate (ORR) of surufatinib in patients with locally advanced or distant metastatic differentiated thyroid cancer (DTC) or medullary thyroid cancer (MTC). Methods: This Phase II open-label study by Simon's two-stage design was conducted at 10 sites across China. Patients with radioiodine (RAI)-refractory DTC with locally advanced disease or distant metastasis (DTC1 group); patients who received limited initial surgery and then developed locally advanced unresectable recurrences and were not considered candidates for RAI therapy due to residual normal thyroid tissue (DTC2 group); or patients with MTC with locally advanced disease or distant metastasis (MTC group) were enrolled. A total of 59 patients were enrolled (26 in DTC1, 6 in DTC2, and 27 in MTC) and received 300 mg surufatinib daily in 28-day cycles. The primary endpoint was ORR as determined by the investigators. Results: Overall ORR was 23.2% [95% confidence interval, CI 12.98-36.42]: 21.7% in the DTC1 cohort, 33.3% in the DTC2 cohort, and 22.2% in the MTC cohort. Forty-nine patients achieved disease control (87.5% [CI 75.93-94.82]): 87.0% in the DTC1 cohort, 83.3% in the DTC2 cohort, and 88.9% in the MTC cohort. Median time to response was 59.0 days, and 59.0, 85.5, and 59.0 days in the DTC1, DTC2, and MTC cohorts. Overall median progression-free survival was 11.1 months [CI 5.98-16.69]; 11.1 months in DTC1 and MTC cohorts, while the DTC2 cohort had not reached the median at the data cutoff. The most common treatment-emergent adverse events grade ≥3 were hypertension (20.3%), proteinuria (11.9%), and then elevated blood pressure, hypertriglyceridemia, and pulmonary inflammation (5.1% each). Conclusions: Surufatinib demonstrated promising efficacy with a tolerable and manageable safety profile for patients with locally advanced or metastatic MTC, RAI-refractory DTC, or locally advanced unresectable recurrences unable to receive RAI.

Predictors of Occult Lymph Node Metastasis and Prognosis in Patients with cN0 T1-T2 Supraglottic Laryngeal Carcinoma: A Retrospective Study.

BACKGROUND: This work aimed to explore the predictors of lymph node metastasis (LNM) and analyze the prognosis of patients with clinically node-negative (cN0) T1-T2 supraglottic laryngeal carcinoma (SGLC). METHODS: Data for 130 patients with cN0 T1-T2 SGLC who initially underwent surgery were retrospectively reviewed. Occult LNM incidence, relevant factors, and prognosis were analyzed. RESULTS: Of the 130 patients with cN0 T1-T2 SGLC, 21 (16.2%) had occult LNM. Based on univariate and multivariable regression analyses, male sex and poor tumor differentiation predicted the incidence of occult LNM. The incidence of occult LNM was 20.9% in males and 5.1% in females (p = 0.035). Patients with poorly differentiated tumors had a higher incidence of occult LNM (42.9%) than patients with well-differentiated (10.3%) and moderately differentiated tumors (14.3%; p < 0.05). Thirteen patients (10%) had cervical recurrence, and all had T2 tumors (p = 0.02). The 5-year disease-specific survival rates were 70 and 90% for patients with and without LNM, respectively (p = 0.000). CONCLUSIONS: Sex and tumor differentiation are potential predictors of occult nodal disease. Female patients with cN0 T1-T2 SGLC are less likely than male patients to have neck metastasis. Poorly differentiated tumors are associated with the frequency of neck metastasis, and selective neck dissection is strongly recommended for these tumors.

Anlotinib for the Treatment of Patients with Locally Advanced or Metastatic Medullary Thyroid Cancer.

BACKGROUND: The prognosis of advanced or metastatic medullary thyroid carcinoma (MTC) is poor, and there are few therapeutic options. Anlotinib has previously shown promising antitumor activity on MTC in preclinical models and a Phase I study. This Phase II clinical trial was devised to confirm the antitumor activity of anlotinib in patients with advanced or metastatic MTC. METHODS: Patients with unresectable locally advanced or metastatic MTC received once daily oral anlotinib 12 mg, two weeks on/one week off, until disease progression, death, unacceptable toxicity, or withdrawal of consent for any reason. The dose was adjusted on the basis of observed toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Fifty-eight patients received anlotinib treatment. The primary endpoint PFS has not yet been reached at the time of analysis. On the basis of investigator assessments, 56.9% of patients experienced a partial response. PFS rate at 48 weeks was 85.5%. Forty-five patients had a ≥50% decrease in serum calcitonin concentration from baseline. The most common adverse events were hand-foot syndrome, hypertriglyceridemia, cholesterol elevation, fatigue, and proteinuria. CONCLUSIONS: Anlotinib demonstrated a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic MTC.

Familial Nonmedullary Thyroid Carcinoma: A Retrospective Analysis of 117 Families.

BACKGROUND: The first and most important step in characterizing familial nonmedullary thyroid carcinoma (NMTC) is to distinguish the true familial patients, which is the prerequisite for all accurate analyses. This study aimed to investigate whether patients from families with ≥3 first-degree relatives affected with NMTC have different characteristics than patients from families with only two affected members, and to compare these patients with those with sporadic disease. METHODS:: We analyzed the clinicopathological features and prognosis of 209 familial and 1120 sporadic cases of NMTC. Familial patients were further divided into two subgroups: families with two affected members and families with ≥3 affected members. RESULTS:: The familial group had a significantly higher risk of bilateral growth, multifocality, extrathyroidal extension, and lateral lymph node metastasis than the sporadic group (P < 0.05). These main features were also different between the group with ≥3 affected members and the sporadic group. The only difference between the two affected members' group and the sporadic group was incidence of multifocality (P < 0.05). The probability of disease recurrence in patients from families with ≥3 affected members was significantly higher than that in sporadic cases (14.46% vs. 5.27%; P = 0.001), while the probability in patients from families with two affected members was similar to that in sporadic patients (6.35% vs. 5.27%; P = 0.610). The Kaplan-Meier survival analysis showed a statistically significant difference in disease-free survival between the two subgroups (85.54% vs. 93.65%; P = 0.045). CONCLUSIONS:: Patients from families with ≥3 members affected by NMTC have more aggressive features and a worse prognosis than those from families with only two affected members. Patients from families with ≥3 affected first-degree relatives may be considered to have true familial NMTC.

Efficacy of Superselective Neck Dissection in Detecting Metastasis in Patients with cN0 Papillary Thyroid Carcinoma at High Risk of Lateral Neck Metastasis.

Background Material and Methods Results Conclusions.

[Analysis of risk factors for bleeding after thyroid surgery].

OBJECTIVE: To identify risk factors for bleeding after thyroid surgery, and discuss the potential relevance between the bleeding timing and sources. METHODS: A total of 2568 cases that underwent thyroid operation from June 2012 to June 2013 were collected and analysed retrospectively the risk factors for postoperative bleeding by Cox and the potential relevance between the bleeding timing and sources. RESULTS: Among 2568 patients, 40 patients occurred postoperative bleeding Indentified risk factors were extent resection (P=0.0435) and surgeon (P=0.0071). Thyroid bed and strap muscles/sternocleidomastoid were the most common sources of bleeding after surgery within 6 hours; while thyroid bed was the most common source of bleeding after surgery between 6 and 8 h; wound errhysis was the most common source during 8-24 h after the operation; thyroid bed and strap muscles/sternocleidomastoid were the most common sources within 24 h after thgroid surgery. CONCLUSIONS: Bleeding after thyroid surgery is a rare but potentially life-threatening complication, and the extent of resection and the surgeon are risk factors. Thyroid bed and strap muscles/sternocleidomastoid are the most common sources of bleeding after surgery within 24 hours.

Risk factors for and occurrence of postoperative cervical hematoma after thyroid surgery: A single-institution study based on 5156 cases from the past 2 years.

BACKGROUND: The occurrence of and risk factors for postoperative cervical hematoma remain unclear. METHODS: We conducted a retrospective analysis of 5156 patients treated at a single institution. RESULTS: The occurrence of postoperative cervical hematoma was 0.85% (44 of 5156 patients). The multivariate analysis showed that male sex, benign pathology, hypertension, and previous thyroid surgery are individual risk factors with odds ratios of 1.906, 2.004, 7.962, and 4.407, respectively. The majority (88.7%) of hematomas occurred within 12 hours after surgery. Obvious bleeding points were detected in 28 cases (73.6%) during reexploration, surface of the strap muscle, superior thyroid vessel, and end of the recurrent laryngeal nerve were the most frequent bleeding sources. CONCLUSION: Hematoma often occurs within 12 hours after thyroid surgery. Hypertension, previous thyroid surgery, male sex, and benign pathology may increase the risk of hematoma.

Prevention and Treatment of Life-Threatening Bleeding After Thyroid Surgery.

BACKGROUND Few reports have discussed life- threatening bleeding that occurs postoperatively in patients who have undergone thyroid surgery. In this article, we discuss the causes, treatment measures, and possible ways of preventing this severe complication. MATERIAL AND METHODS From Jan 2002 to Dec 2014 we retrospectively analyzed 7 patients who developed life-threatening bleeding after undergoing thyroid surgery at our center. RESULTS Among the group of 7 patients, there was 1 case of superior thyroid artery hemorrhage (STAH), 5 cases of carotid blowout syndrome (CBS), and 1 case of tracheo-innominate fistula (TIF). The STAH was caused by unreliable ligation. All the cases of CBS and TIF were caused by surgical wound infection. Six patients were transferred to the operating room immediately; open surgical treatment was performed on these 6 patients. Out of these 6 patients, 1 patient did not survive the operation, and hemorrhage was successfully controlled in 3 patients. The remaining 2 patients again experienced bleeding even after undergoing open surgery. Only 1 patient developed long-term neurological complications. CONCLUSIONS Infection is the most common cause of life-threatening bleeding that occurs postoperatively in some patients who have undergone thyroid surgery. Early surgical intervention can save the lives of these patients without causing any severe neurological complications.

[Cervical lymph node metastasis in medullary thyroid carcinoma].

OBJECTIVE: To study the patterns of cervical lymph node metastasis of medullary thyroid carcinoma. METHODS: Ninety-one patients with medullary thyroid carcinoma first treated between January 1999 and October 2014 were analyzed retrospectively. Of 91 patients, 39 cases presented with clinical negative node (cN0) and 52 cases with clinical positive node (cN+). Central compartment dissection was performed in all cases. Lateral neck dissection was performed in 52 cN+ cases (71 sides). All neck dissection specimens were obtained and analyzed for lymph node (LN) involvement with respect to neck levels. The distribution of LN with metastasis was studied in cN+ patients and the following factors were used to study the predictive value of central compartment LN metastasis: sex, age, family history, tumor size, bilateral tumor, multifocality of the tumor, extracapsular spread, and remote metastasis. Univariate analysis with the χ(2) test was used to analyze the statistical correlation between central compartment LN metastasis and other clinical factors. Multiple logistic regression analysis was used to identify the factors related to central compartment metastasis. RESULTS: Neck and bilateral neck metastasis rates were 73.6%, 19.8% respectively. Metastasis rates in central compartment and superior mediastinal region were 68.1% and 27.5% respectively. The central compartment metastasis rate was 33.3% in cN0 patients and 94.2% in cN+ patients. The superior mediastinal metastasis rate was 2.6% in cN0 patients and 46.2% in cN+ patients. Extracapsular spread was an independent predictive factor for central compartment metastasis (χ(2)=15.592, P=0.000, OR=12.876). The incidences of LN metastases at level II, III, IV, V were 62.9%,84.5%,83.1%,50.0% in cN+ patient, respectively. Multi-sites were involved. The possibility of lateral neck metastasis was higher when preoperative value of calcitonin was higher than 300 ng/L (66.7% vs 28.6%, χ(2)=5.771, P=0.016). CONCLUSIONS: Cervical lymph node metastasis of medullary thyroid carcinoma is higher. Central compartment dissection is necessary in cN0 patients with extracapsular spread. Neck dissection from level II to level VII was necessary in cN+ patients. Preoperative value of calcitonin maybe can predict the lateral neck metastasis incidence.

Long-term outcomes of observation for clinically negative central compartment lymph nodes in papillary thyroid carcinoma.

The treatment strategy for clinically negative lymph nodes of papillary thyroid carcinoma is controversial. We report the long-term outcomes of a series of cases treated with thyroidectomy without prophylactic central neck dissection. We reviewed 1,397 cases with papillary thyroid carcinoma treated at our institution between 1991 and 2000. One hundred and seventy-two newly diagnosed cases underwent observation for cN0 central neck lymph nodes. Regional recurrence of the ipsilateral side including central compartment and the lateral neck which needs reoperation was considered as key point for analysis. With a mean follow-up of 96.4 months (34-204 months), the overall 10-year disease-specific and recurrence-free survival rates were 99 and 86 %, respectively. The recurrence and reoperation rates of the central compartment were 3 % (5/172) and 4 % (7/172), respectively. Univariate analysis showed that extrathyroidal extension was associated with regional recurrence (99 vs. 82 %; p = 0.002). Central compartment observation is safe in cN0 cases with papillary thyroid carcinoma, particularly in those without extrathyroidal extension.

[Clinical role of BRAF V600E mutation testing in thyroid nodules].

OBJECTIVE: To evaluate the clinical role of BRAF V600E mutation testing in fine-needle aspirates (FNA) of thyroid nodules. METHODS: This study included 83 nodules in 80 patients who underwent FNA from March 2013 to September 2013. Cytological specimens were collected and BRAF exon 15 was examined by polymerase chain reaction (PCR). DNA sequencing and analysis were performed. Diagnostic performances of cytology and cytology with BRAF V600E mutation analysis were compared according to postoperative pathological diagnosis. The relation of BRAF V600E mutation with clinical factors including sex and age of patients, tumor size, lymph node metastasis, multifocality, and AJCC stage were analyzed. RESULTS: Of 83 nodules, 33 nodules were clinically observed, and 48 nodules underwent surgery, and suggestions of surgery were refused in 2 nodules. Among 48 nodules with surgery, BRAF V600E mutation was found in 25 nodules with histologic confirmation of papillary thyroid carcinoma after thyroidectomy, 13 of the 25 nodules were cytologically diagnosed as carcinoma and 12 were indeterminate. Among the 23 BRAF V600E negative noodles, 5 were cytologically diagnosed as carcinoma, 2 were benign, and 16 were indeterminate; 15 nodules were histologic confirmation of papillary thyroid carcinoma after thyroidectomy, 1 nodule was medullary thyroid carcinoma, and 7 nodules were benign. Biomolecular analysis significantly increased cytology sensitivity for papillary thyroid carcinoma from 43.9% to 73.2% (P < 0.05). Direct DNA sequencing showed that the presence of BRAF V600E mutation was 62.5% in 40 thyroid papillary nodules. There were 16 BRAF-positive nodules (80.0%) among 20 papillary thyroid nodules with extrathyroidal extension, however there were 9 BRAF-negative nodules (45.0%) among 20 papillary thyroid nodules without extrathyroidal extension. Univariate analysis indicated the BRAF V600E mutation was associated with extrathyroidal extension (χ² = 5.227, P = 0.022), but not with sex, age, tumor size, lymph node metastasis, multifocality and AJCC stage. CONCLUSION: BRAF V600E mutation analysis can significantly improve FNA diagnostic accuracy and maybe useful for prediction of high-risk of thyroid carcinoma.

Minimally-invasive endoscopically-assisted neck dissection for lateral cervical metastases of thyroid papillary carcinoma.

Traditional open operations for lateral neck dissection in patients with papillary thyroid carcinoma leave an unsightly scar. We report complete lateral neck dissection and thyroidectomy for papillary thyroid carcinoma using an endoscopically-assisted approach through a small incision, and evaluate its feasibility and safety. Between March 2010 and January 2013, 6 patients with no definite metastases to the lymph nodes at levels II-IV, and 20 with definite metastases to the lymph nodes at levels II-V were selected. Thyroidectomy, dissection of the central compartment (level VI), and ipsilateral level II-IV and II-V neck dissections were done through a small incision in the neck. The steps of endoscopic lateral neck dissection were similar to those of conventional operations. The mean operating time for the whole procedure was 3.57 hours (range 2.5 - 5.0). It was successful in all patients and there were no serious complications or serious blood loss. A total of 21 patients had lymph node metastases in the central and lateral zones. The mean yield of lymph nodes was 38.6 (range 16-61). There was no evidence of residual or recurrent disease at follow-up, and the cosmetic result was excellent. Minimally invasive, video-assisted comprehensive neck dissection for metastatic papillary thyroid carcinoma is feasible and safe, and has excellent cosmetic results. Further studies with a larger number of patients and long-term follow-up are needed to verify its oncological validity.

Pattern of Failure in Surgically Treated Patients with Cervical Esophageal Squamous Cell Carcinoma.

OBJECTIVE: The aim of this study was to analyze the pattern of failure in patients who have undergone surgical resection for cervical esophageal squamous cell carcinoma. STUDY DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND METHODS: Sixty-two patients who had undergone surgical resection of cervical esophageal squamous cell carcinoma from January 2001 through April 2012. Sites of failure were documented. RESULTS: Twenty-nine patients had developed treatment failure. Of the 29 patients, 14, 13, and 14 had developed local failure, regional failure, and distant metastasis, respectively. Of the 13 regional failures, the images of 2 patients were lost. The other 11 regional failures included left lateral nodal disease at level II (n = 2), level III (n = 4), and level IV (n = 7); right lateral nodal disease at level II (n = 2), level III (n = 3), and level IV (n = 3); and level VI (n = 4). The overall 2-year local failure-free survival rate and regional failure-free survival rates were 79.6% and 58.6% (P = .04) for patients with stage II disease and 79.6% and 59.6% (P = .054) for patients with stage III disease, respectively. CONCLUSIONS: The pattern of failure of cervical esophageal squamous cell carcinoma is characterized by early locoregional failure, especially in patients with stage III disease.

[Clinical features of familial non-medullary thyroid cancer patients].

OBJECTIVE: To analyze the clinical features of familial non-medullary thyroid cancers, and to discuss their management. METHODS: Sixty thyroid cancer patients with familial non-medullary thyroid cancer (FNMTC) history during Sep. 2003 to Sep. 2012 were collected as study group, and another 60 sporadic thyroid cancer patients were randomly chosen as control. We compared the differences of their clinical features. RESULTS: All the patients were diagnosed as thyroid papillary carcinoma. The study group included 40 female and 20 male patients. There were 16 cases in stage T1, 37 in stage T3, and 7 in stage T4. The patients were 21-66-year old ( median age 42-years). The control group included 49 female and 11 male patients. The patients were 24- to 78-year old, and the median age was 45.5 years. 43.3% of the patients in the study group and 18.3% of the patients in the control group had bilateral carcinomas (P = 0.003). There were multifocal lesions in 53.3% of the patients in the study group and 35.0% of the control group, local invasion in 73.3% of the patients in the study group and 55.0% of the control group, and coexisting benign thyroid diseases in 81.7% of the patients of the study group and 50.0% of the control group (P < 0.05 for all). There were cervical lymph node metastases in 60.0% of the patients in the study group and 38.3% in the control group (P = 0.018). In the study group, 32 cases were of parent-offspring type and 28 cases of sibling type. Among the parent-offspring type patients, the median onset age of the first generation offsprings was 58 years, and that of the second generation offsprings was 32 years (P < 0.001). CONCLUSIONS: Familial nonmedullary thyroid cancer, especially in parent-offspring type patients, is more aggressive than sporadic nonmedullary thyroid cancer, and often involves bilateral lobes, has multifocality, and combines with benign thyroid diseases. We recommend a total thyroidectomy for treatment, and to screen all the family members >20 years old, with ultrasonography for early diagnosis and treatment.

[Preliminary study of patterns of level IIb lymph node metastasis in papillary thyroid carcinoma].

OBJECTIVE: To evaluate the factors related to level IIb lymph node(LN) metastasis in papillary thyroid carcinoma (PTC). Method The medical records of 63 PTC patients were reviewed. The patients underwent neck dissection (ND) between January 2011 and December 2012, who were determined with pathologically lateral cervical LN metastasis. A total of 67 ND specimens were obtained and analyzed for LN involvement with respect to neck levels. The relation of level IIb LN metastasis with clinical factors, including age and sex of patients, tumor size, location, multifocality, extracapsular spread (ECS) and stage of primary PTC, coexistence of lymphocytic thyroiditis, distribution of metastasis LN in different levels, fusion and extracapsular invasion of LN were analyzed with univariate analysis and χ(2) test. SPSS 14.0 software was used to analyze the data. RESULTS: Of 63 patients, 41 patients revealed thyroid tumor maximum diameter more than 1 centimeter, 26 patients with tumor located in the upper 1/3 thyroid lobe, 39 patients with multiplicity of thyroid tumor and 54 patients with ECS, 54 patients with pathological T3/T4a stage, 15 patients with coexisting lymphocytic thyroiditis. Among the 67 ND specimens, 12 specimens (17.9%) showed level IIb LN metastasis and the incidences of LN metastasis at level IIa, III, IV, V, VI, IIa+III, III+IV, and IIa+III+IV were 56.7%, 86.6%, 68.7%, 22.4%, 86.6%, 52.2%, 55.2%, 37.3%, respectively. Of the 38 ND specimens with level IIa LN metastases, 10 were positive in level IIb(26.3%). But of 29 ND specimens without level IIa LN metastases, only 2 were positive in level IIb. A univariate analysis revealed that level IIa LN metastasis was a significant predictive factor for level IIb LN metastasis (χ(2) = 4.219, P = 0.040). CONCLUSION: The incidence of LN metastasis to level IIb is low in PTC, which is less when level IIa is not involved.

Identification of human tissue kallikrein 6 as a potential marker of laryngeal cancer based on the relevant secretory/releasing protein database.

OBJECTIVE: This study was aimed to create a large-scale laryngeal cancer relevant secretory/releasing protein database and further discover candidate biomarkers. METHODS: Primary tissue cultures were established using tumor tissues and matched normal mucosal tissues collected from four laryngeal cancer patients. Serum-free conditioned medium (CM) samples were collected. These samples were then sequentially processed by SDS-PAGE separation, trypsin digestion, and LC-MS/MS analysis. The candidates in the database were validated by ELISA using plasma samples from laryngeal cancer patients, benign patients, and healthy individuals. RESULTS: Combining MS data from the tumor tissues and normal tissues, 982 proteins were identified in total; extracellular proteins and cell surface proteins accounted for 15.0% and 4.3%, respectively. According to stringent criteria, 49 proteins were selected as candidates worthy of further validation. Of these, human tissue kallikrein 6 (KLK6) was verified. The level of KLK6 was significantly increased in the plasma samples from the cancer cohort compared to the benign and healthy cohorts and moreover showed a slight decrease in the postoperative plasma samples in comparison to the preoperative plasma samples. CONCLUSIONS: This laryngeal cancer-derived protein database provides a promising repository of candidate blood biomarkers for laryngeal cancer. The diagnostic potential of KLK6 deserves further investigation.

[Factors related to central lymph node metastasis in different subregions for unilateral papillary thyroid carcinoma with clinical N0 stage].

OBJECTIVE: To study clinicopathologic factors related to central lymph node (CLN) metastasis in different subregions for unilateral papillary thyroid carcinoma (PTC) with clinical N0. METHODS: A total of 145 PTC cases with clinical N0 treated in the same group of the department of head and neck surgery, Cancer Hospital, Chinese Academy of Medical Science between Jan. 2011 and Jan. 2014 was analysed retrospectively. Clinicopathologic factors related to CLN metastasis in different subregions were analyzed, including sex, age, tumor size, extrathyroidal extension, and multifocal tumor. RESULTS: CLN metastases existed in 57.9% (84/145) cases and the incidences of ipsilateral paratracheal, pretracheal, and prelaryngeal metastasis were 53.8%, 24.1% and 11.3% respectively. Right paratracheal lymph node metastasis occurred in anterior (17/38, 44.7%) and posterior (12/38, 31.6%) to the recurrent laryngeal nerve. Multivariate analysis indicated that extrathyroidal extension (OR = 4.49, 95%CI 1.80-11.20, P = 0.001) and tumor size (OR = 2.17, 95%CI 1.06-4.45, P = 0.034) were independent risk factors for ipsilateral paratracheal CLN metastasis; ipsilateral paratracheal CLN metastasis (OR = 2.12, 95%CI 0.08-4.60, P = 0.003) was an independent risk factor for pretracheal CLN metastasis. CONCLUSIONS: A high risk of CLN metastasis especially ipsilateral paratracheal metastasis exists in DTC with clinical N0. Ipsilateral paratracheal, pretracheal and prelaryngeal CLN dissection should be conducted when maximum tumor diameter more than 1 cm or extrathyroidal extension. CLN anterior and posterior to the recurrent larygeal nerve should be removed simultaneously when the ipsilateral paratracheal CLN metastasis at right side. Total thyroidectomy and contralateral paratracheal CLN dissection should be conciderded in multifocal tumor.