Objective: There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib,a novel multitargeted receptor tyrosine kinase inhibitor, has previously shown antitumor activity in phase Ⅱ studies of patients with advanced MTC. This study was to evaluate the efficacy and the safety of vandetanib on advanced MTC. Methods: This study was an open, international multi-center phase Ⅲ clinical trial and the study number was NCT01298323. The single-center study was a sub-group analysis of the international study, which was conducted on 9 pathologically confirmed advanced MTC patients by Cancer Hospital Chinese Academy of Medical Sciences between March 2012 and October 2017. Vandetanib (300 mg) was orally administered daily till death or withdrawal. The efficacy was evaluated according to RECIST criteria and the adverse events were evaluated according to NCI criteria. Results: The objective response rate was 3/9,and the disease control rate was 4/9. The median progression-free survival was 44 months. All patients who had the elevated levels of calcitonin (CTN) and carcino-embryonic antigen (CEA) before treatment began to show the decreases in the level of CTN and CEA after 3 months and later showed again the increases in the levels of both tumor markers with tumor progression. By ROC curve analysis, CTN was of statistically significance(P<0.05, 95%CI 0.558-0.834), but CEA was not(P>0.05). Adverse events were generally mild (grade 1 or 2),including hypertension (9 cases),skin rash (9 cases), and diarrhea (6 cases). Two patients developed grade 3 elevation of serum glutamate pyruvate transaminase and one patient developed grade 3 elevation of drug-related bowel disease. No grade 4 drug-related adverse event occurred. Conclusions Vandetanib is effective and well tolerated for patients with locally advanced or metastatic MTC who have no chance for surgery. This indicates the increase of CTN is clinically relevant to disease progression, but the number of patients are extremely low, and, therefore further research is needed. Long-term use of vandetanib may cause resistance.

Leukocyte differentiation antigens (LDAs) play important roles in the immune system, by serving as surface markers and participating in multiple biological activities, such as recognizing pathogens, mediating membrane signals, interacting with other cells or systems, and regulating cell differentiation and activation. Data mining is a powerful tool used to identify novel LDAs from whole genome. LRRC25 (leucine rich repeat-containing 25) was predicted to have a role in the function of myeloid cells by a large-scale "omics" data analysis. Further experimental validation showed that LRRC25 is highly expressed in primary myeloid cells, such as granulocytes and monocytes, and lowly/intermediately expressed in B cells, but not in T cells and almost all NK cells. It was down-regulated in multiple acute myeloid leukemia (AML) cell lines and bone marrow cells of AML patients and up-regulated after all-trans retinoic acid (ATRA)-mediated granulocytic differentiation in AML cell lines and acute promyelocytic leukemia (APL; AML-M3, FAB classification) cells. Localization analysis showed that LRRC25 is a type I transmembrane molecule. Although ectopic LRRC25 did not promote spontaneous differentiation of NB4 cells, knockdown of LRRC25 by siRNA or shRNA and knockout of LRRC25 by the CRISPR-Cas9 system attenuated ATRA-induced terminal granulocytic differentiation, and restoration of LRRC25 in knockout cells could rescue ATRA-induced granulocytic differentiation. Therefore, LRRC25, a potential leukocyte differentiation antigen, is a key regulator of ATRA-induced granulocytic differentiation.
Antigens, Differentiation ; immunology ; metabolism ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Granulocytes ; cytology ; drug effects ; immunology ; metabolism ; Humans ; Leukocytes ; cytology ; drug effects ; immunology ; metabolism ; Membrane Proteins ; antagonists & inhibitors ; immunology ; metabolism ; RNA, Small Interfering ; pharmacology ; Tretinoin ; pharmacology

Objective: To investigate the value of jugulo-omohyoid lymph nodes (JOHLN) in predicting occult lateral cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC). Methods: The clinicopathological data of 136 out of 2 100 PTC patients, who had a high risk of lateral neck lymph node metastasis and treated by us from January 2010 to December 2015, were retrospectively analyzed. Super selective neck dissection (SSND, level Ⅲ and Ⅳ)was performed and JOHLNs were sent for frozen section in all the 136 cases. The clinicopathological data was analyzed and the significance of JOHLN in predicting lateral cervical LNM was calculated using the SPSS software package. Results: Of the 136 patients, total thyroidectomy was performed in 76 cases (55.9%) and unilateral lobectomy plus isthmus was performed in the other 60 cases (44.1%). SSND was performed in 72 patients (52.9%), level Ⅱ-Ⅳ dissection in 15 (11.0%), and level Ⅱ-Ⅴ dissection in 49 (36.0%). According to the pathological results, 38 patients were pN0(27.9%), 18 (13.2%) were pN1a and 80 (58.8%) were pN1b. The lymph node metastasis(LNM) rates at level Ⅱ-Ⅵ were 19.9%, 43.4%, 42.6%, 2.9%, and 59.6%, respectively. The sensitivity, specificity and accuracy of JOHLN in predicting lateral neck metastasis were 58.8%, 62.9%, and 76.7%, respectively. The rates for predicting level Ⅱ metastasis were 81.5%, 43.2%, and 59.4%, respectively. None of the patients died in the follow-up. Only 1 recurrence was found in level Ⅱ and regional control was achieved after level Ⅱ and Ⅴ dissection. Conclusions JOHLN has a high accuracy for predicting lateral cervical lymph node metastasis and high sensitivity for level Ⅱ metastasis. For patients with high risk of lateral cervival metastasis, super-selective neck dissection including level Ⅲ and Ⅳ can confirm the stage and reduce the risk of reoperation. Dissection for level Ⅱ, Ⅲ, and Ⅳ is recommended.

Objective: To investigate the value of secondary cervical lymph node dissection in papillary thyroid carcinoma (PTC). Methods: PTC patients with recurrence re-operated in a previously dissected area at our hospital during 2000-2016 were included in this analysis. Patients were divided according to the operative interval of 6 months. The level and number of lymph node metastasis and the number of lymph node dissection were analyzed to calculate the ratio of lymph node metastasis. Results: A total of 336 PTC patients received 360 side lateral cervical lymph nodes dissection. The ratio of recurrence in unilateral lateral neck is 92.9%(312/336). The ratio of recurrence in multiple levels (more than two regions) were 47.5% (171/360). The recurrence ratio of level Ⅱ, Ⅲ, Ⅳ and Ⅴ were 55.6%(200/360), 44.2%(159/360), 59.7%(215/360) and 10.3%(37/360), respectively. Lymph node metastases were inclined to level Ⅱ (33.6%) and Ⅳ (35.8%). The mean number of lymph node dissection and metastasis in the group of operative interval ≤ 6 months was 26.56 per case and 4.37 per case, respectively. The mean number of lymph node dissection and metastasis in the group of operative interval >6 months was 16.80 per case and 3.20 per case, respectively. The number of lymph node dissection and metastasis between these two groups were significantly different (P=0.001, P<0.001). Conclusions Lymph node metastasis of PTC patients with secondary cervical lymph node dissection are inclined to level Ⅱ and level Ⅳ. Moreover, multi-level metastasis is not rare. Level Ⅱ and level Ⅳ require more attention in the first operation. Most of the patients undergo reoperation because of residual lymph nodes from the previous treatment. Normalization and completeness of the initial dissection are particularly important to PTC patients.

Objective: To evaluate the efficacy and safety of the application of dye-tattooing under ultrasound guidance in preoperative localization of neck recurrences from thyroid cancer. Methods: Between October 2014 to September 2016, 25 patients with 34 lesions were enrolled. There were 22 cases of papillary thyroid carcinoma and three cases of medullary thyroid carcinoma, all of which could not be detected by computed tomography. Surgeons located the recurrent lesions using dye-tattooing under ultrasound guidance along with radiologist three days before the operation. Results: All lesions were successfully located (100%), 32 of which were located directly and two of which were located indirectly. Postoperative pathological examination confirmed 25 metastases of papillary thyroid carcinoma, two metastases of medullary thyroid carcinoma, and seven cases of false positives. The accuracy of ultrasound diagnosis was 79.4%. After 15 months of follow-up, neither tumor residual nor recurrences was detected according to imaging tests. Conclusions Dye-tattooing under ultrasound guidance represents a reliable and safe method for localization of neck recurrences from thyroid cancer. The cooperation between experienced surgeons and radiologists will be crucial to successful location.

Objective To analyse the clinical features and treatment strategies of papillary thyroid carcinoma(PTC) coexistent with lymphocytic thyroiditis (LT).Methods A total of 292 patients including 25 males and 267 females with LT and thyroid nodules treated in the department of head and neck surgery between Sep 2011 and Sep 2014 was analysed retrospectively and divided into two groups according to pathological results,of them 262 patients,with a median age of 47 years old,were LT with PTC and 30 patients,with a median age of 54 years old,were LT with benign nodules.Among 262 patients having LT with PTC,259 were diagnosed as having malignant or suspicious malignant nodules and 3 having benign nodules with ultrasound before surgery,98 cases were considered multifocal malignant nodules by preoperative ultrasound,and 112 cases were positive in cervical lymph nodes,including bilateral positive in 37 cases.Of 30 patients having LT with benign nodules,14 were diagnosed malignant or suspicious malignant nodules and 16 benign nodules.Results The mean age in 262 patients with PTC was less significantly than that in 30 patients with benign nodules (P ＜ 0.05).Ultrasound showed a high proportion of calcification and microcalcification in patients with PTC (34％) compared to patients with benign nodules (13 ％) (P ＜ O.05).There were not significant differences in the mean levels of serum thyroid stimulating hormone(TSH) (2.80 vs 2.99 mU/L,P =0.233),thyroglobulin(TG) (27.14 vs 18.60 μg/L,P =0.747),and anti-thyroglobulin antibodies (ATG) (417.3 vs 378.7 U/ml,P =0.834) between patients with PTC and those with benign nodules.In patients with PTC,multifocal tumor accounted for 42％.The central and lateral lymph node metastasis rates were respectively 50％ and 24％,and the occult metastasis rate of lateral neck lymph node was 16％.Univariate analysis showed that age less than 45 years old,multifocal tumor,tumor diameter more than or equal to 2cm and extrathyroidal extension were associated with central lymph node metastasis (P ＜ 0.05),but not with lateral neck metastasis.Multivariate analysis showed a closed correlation only between the lymph node metastases in central and lateral neck levels (P ＜ 0.05).Conclusions Calcification and microcalcification have the same importance in the ultrasonic diagnosis for PTC in patients with LT.Total thyroidectomy and prophylactic central lymph node should be a choice for LT with PTC.Lymph node metastasis in level Ⅵ indicates the possibility of lateral cervical lymph node metastasis in the patients having LT with PTC.

Objective To study anatomy of the tensor fascia latae perforator flap (TFLP flap) and explore its clini-cal application in reconstruction of head and neck defects. Methods Five fresh cadavers were prepared, and mor-phology and blood supply of TFLP flap were examined by microsurgery anatomy. During dissections, the following parameters were recorded: number and type of perforators vessels, diameter of perforators, pedicle length, diameter of the original vessels, course (infra fascia and supra fascia) ,and its position was located by anatomical landmark. Results There were 41 TFLP flap perforators in all specimen with 35 musculocutaneous perforator and 6 septocuta-neous perforator. Original vessel was ascend branch of lateral circumflex femoral artery/vein with average diameter of (3.01±0.49) mm/(3. 28±0.57) mm. The mean pedicle length was (9. 1±0.79) cm. The surface location was (4. 22± 1. 37) cm laterally and (8. 73±2.72) cm beneath to anterosuperior iliac spine. Conclusion With the characteristics of constant position, large caliber and convenient preparation, TFLP flap is useful for operation andoption in reconstruction of head/neck defects and considered as backup of anterolateral thigh flap. The disadvantage of this flap is its short vascular pedicle.

OBJECTIVE To evaluate the treatment results of perioperative radiation and conservation laryngeal surgery for advanced hypopharyngeal cancer. METHODS Forty seven patients with hypopharyngeal cancer treated with laryngeal function-sparing surgery were collected in this retrospective study. There were 3 posterior hypopharyngeal wall cancers and 44 pyriform sinus cancers. Forty four patients received preoperative irradiation,and three postoperatively. The types of surgery were:21 pyriform sinusectomies,16 pyriform sinusectomies accompanying with partial laryngectomies,and 10 partial hypopharyngectomies with near total laryngectomies. Six skin flaps and 2 jejunum flaps were used to repair the defects. RESULTS The 5 year survival rate of Ⅲ,Ⅳstage was 59 % and 50.2 % respectively and the laryngeal functions were preserved. CONCLUSION The policy of laryngeal function preservation was feasible in the treatment of locally advanced hypopharyngeal cancer. Suffice it to say that a combination of radiation and surgery was mandatory

AIM: To investigate relationship between activity of matrix metalloproteinases - 2 ( MMP - 2, 72 kD) and invasion, metastasis of breast cancer. METHODS: Useing zymography and computer software assisted analysis, the activitive levels of MMP- 2 (72 kD) in tissues from breast cancer were measeured. RESULTS: Mean activitive levels of MMP- 272 kD (13.93 + 3.60) in breast cancer were lower than those in benign disease (21.43 + 8.31), P < 0.05. There was no difference (P > 0.05) in MMP - 2 62 kD + 72 kD of benign and malignant dis ease, but MMP - 262 kD ( 13.83 + 4.53) and MMP - 262 kD/62 kD + 72 kD (0.48) respectively were significantly higher in malignant disease (P < 0.01). It was also found that MMP- 262 kD/62 kD + 72 kD were apparently higher in invasive carcinomas (0.48) and lymph node metastases (0.61), P < 0.01, respectively. CONCLUSION: These results demonstrated that a clear relationship between MMP - 2 activity and the invasion and metastasis of breast carcinoma.

AIM: To investigate relationship between activity of matrix metalloproteinases-2 ( MMP-2, 72 kD) and invasion, metastasis of breast cancer. METHODS: Useing zymography and computer software assisted analysis, the activitive levels of MMP-2 (72 kD) in tissues from breast cancer were measeured. RESULTS: Mean activitive levels of MMP-2 72 kD (13.93?3.60) in breast cancer were lower than those in benign disease (21.43?8.31), P0.05) in MMP-2 62 kD+72 kD of benign and malignant disease, but MMP-2 62 kD (13.83?4.53) and MMP-2 62 kD/62 kD+72 kD(0.48) respectively were significantly higher in malignant disease (P