Abstract:

Thyroid cancer is a common endocrine tumor. In recent years, several advances have been made in the field of molecular biology and tumorigenic mechanisms of thyroid carcinomas, and targeted therapy research will provide new ideas for treating thyroid carcinoma. In this paper, the authors address the research progress of targeted therapy for thyroid carcinomas and includes the aspects of thyroid carcinoma stem cells, miRNA, and the microenvironment of thyroid cancer.

Abstract:

Objective: To investigate the clinical features as well as diagnosis and treatment strategies of differentiated thyroid microcarcinoma (TMC). Methods: The clinical data of 138 patients with differentiated TMC confirmed by surgical and pathological findings from January 2007 to December 2013 were reviewed, and were comparatively analyzed with the data of 29 patients with benign thyroid nodules who during the same period of time underwent surgery with the suspicion of thyroid cancer. Results: Of the 138 TMC patients, 131 cases were papillary TMC, 5 cases were follicular TMC, and 2 cases were mixed TMC; 49 cases were complicated with nodular goiter, 5 cases with nodular goiter and Hashimoto’s thyroiditis, 7 cases with Hashimoto’s thyroiditis, and 2 cases with hyperthyroidism. In TMC patients, the malignancy diagnostic rate by TI-RADS classification, and the incidence of gravel-like calcification and malignancy diagnostic rate by contrast-enhanced ultrasound were all significantly higher than those that in BTN patients (all P<0.05). All the TMC patients underwent intraoperative rapid pathological assessment, 84 cases underwent ipsilateral thyroidectomy, 46 cases underwent ipsilateral thyroidectomy plus contralateral partial thyroidectomy, 5 cases underwent bilateral total thyroidectomy, and 3 cases underwent ipsilateral thyroidectomy plus contralateral subtotal thyroidectomy; 85 cases received central lymph node dissection and 3 cases had additional ipsilateral functional neck dissection. All the TMC patients were prescribed lifelong thyroxine therapy after surgery. Conclusion: High-resolution ultrasound combined with TI-RADS or contrast-enhanced ultrasound can improve the detection rate of TMC. Well-differentiated papillary thyroid cancer and high calcification rate is frequently seen in TMC, and ipsilateral thyroidectomy plus isthmectomy with simultaneous central cervical lymph node dissection is the major surgical procedure for TMC.

Abstract:Objective: To evaluate the significance of prophylactic central lymph node dissection in determining the tumor stage and risk stratification of recurrence for cN0 differentiated thyroid carcinoma (DTC). Methods: The clinicopathologoic data of 95 patients with cN0 DTC admitted from March to July 2014 undergoing thyroidectomy with prophylactic central lymph node dissection were retrospectively analyzed. Results: Among the 95 patients who underwent prophylactic central lymph node dissection, central cervical lymph node metastases was found in 43 cases (45.3%), and of them, TNM stage was increased in 10 cases (10.5%) (I to III stage in 8 cases, and II to III stage in 2), and risk stratification of recurrence was elevated in 39 cases (41.1%). Conclusion: Prophylactic central lymph node dissection can improve the accuracy of classification of TNM stage and risk stratification of recurrence in patients with cN0 DTC, and thereby be helpful in postoperative treatment planning.

Abstract:Objective: To investigate the application value of carbon nanoparticle tracer in radical neck dissection for thyroid cancer. Methods: Eighty patients with thyroid cancer admitted during January 2013 to May 2014 were equally randomized into study group and control group. Patients in study group underwent ipsilateral level VI lymph node dissection according to scope of black-stained lymph nodes after the intrathyroid injection of carbon nanoparticles during operation, while those in control group underwent routine ipsilateral level VI lymph node dissection. The number of dissected lymph nodes and metastatic lymph nodes as well as the incidence of parathyroid injury between the two groups were compared. Results: The total number of dissected lymph nodes was 461 (441 black-stained lymph nodes) in study group, and was 272 in control group; the number of lymph nodes with tumor metastasis was 197 in study group, and 106 in control group, and both above parameters had statistical difference between the two groups (both P<0.05). There was no significant difference between study group and control group in lymphatic metastasis rate (42.73% vs. 38.97%, P>0.05). No parathyroid tissue was found in pathological examination and no postoperative hypocalcemia occurred in study group, while parathyroid tissue was found in 5 cases and postoperative hypocalcemia occurred in 5 cases in control group, however, the incidence of parathyroid injury did not reach statistical significance (P=0.055). Conclusion: Using carbon nanoparticles in radical neck dissection for thyroid cancer can clearly show the level VI lymph nodes, and thereby help in complete lymph node dissection, and meanwhile, it does not stain the parathyroid tissue, so it can avoid the inadvertent dissection of the parathyroid glands.

Abstract:Objective: To investigate the efficacy of concomitant I131 therapy following selective neck dissection in treatment of thyroid cancer (TC) and its influence on the salivary gland function of patients. Methods: Sixty TC patients admitted from January 2009 to September 2013 were selected, and were equally randomized into control group and observational group. Patients in control group underwent conventional thyroidectomy, while those in observational group received additional selective neck dissection and I131 therapy, and this group was further equally divided into high- (3 500 mBq) and low-dose (1 000 mBq) subgroup according to the I131 intake. The treatment efficacy, parameters for salivary gland function and postoperative survival of the patients were analyzed. Results: The initial ablation rate and overall effective rate in observational group were significantly higher than those in control group (both P<0.05); all parameters of salivary gland function in control group were better than those in low-dose subgroup, and in the latter were better than those in high-dose subgroup (all P<0.05). The 5-year survival rate showed no difference between high- and low-dose subgroup of observational group, but both were higher than that in control group (both P<0.05). Conclusion: Concomitant I131 therapy following selective neck dissection can effectively improve the surgical efficacy and prognosis in TC patients, and although it exerts adverse effects on salivary gland function, the symptoms caused by low dose treatment are mild and are within the acceptable limits for the patients.

Abstract:Objective: To evaluate the feasibility of natural orifice translumenal endoscopic (NOTES) surgery through the oral vestibule for benign thyroid disease. Methods: From October 2013 to September 2014, 6 patients with benign nodular thyroid disease underwent NOTES surgery through the oral vestibule. Three patients had a solitary right thyroid nodule, and 3 patients had a solitary left thyroid nodule; the nodule was cystic in one case, solid in 4 cases, and mixed in one case. The diameters of the nodules ranged from 1 to 4 cm. One patient was diagnosed as thyroid adenoma and 5 patients were diagnosed as nodular goiter before operation. Results: NOTES thyroidectomy through the oral vestibule was performed successfully in the 6 patients, with an average operative time of 122 (100–150) min and average intraoperative blood loss of 30 (10–40) mL. Of the patients, 5 cases underwent unilateral partial thyroidectomy, one case underwent unilateral subtotal thyroidectomy, and none required open conversion. Postoperative pathological examination revealed thyroid adenoma in one case and nodular goiter in 5 cases. No severe complications such as nerve or parathyroid injury occurred after operation. The average length of hospital stay was 8.2 (8–10) d, and there was no local recurrence during the follow-up period of 3 to 13 months. Conclusion: NOTES thyroidectomy through the oral vestibule for benign thyroid disease is feasible, and has a hidden incision and satisfactory cosmetic results.

Abstract:Objective: To evaluate the safety and effectiveness of delayed-immediate breast reconstruction after radical mastectomy. Methods: The clinical data of 100 randomly selected patients undergoing delayed-immediate breast reconstruction after modified radical mastectomy from October 2010 to October 2013 were retrospectively analyzed. In the reconstruction methods among the 100 patients, latissimus dorsi musculocutaneous flap plus expander implant (LD+expander) was performed in 39 cases, pectoralis major muscle combined with acellular dermal matrix plus expander implant (ADM+expander) was performed in 6 cases, and direct expander implant was performed in 55 cases. Results: In the entire group, both subjective and objective satisfactory rates were 92.0%. The excellent and good rate of postoperative subjective and objective satisfaction in patients undergoing LD+expander implant was 84.6% and 89.7%, was 60% and 65.5% in patients undergoing direct expander implant, and was both 100.0% in patients undergoing ADM+expander implant, respectively. Statistical analysis showed (those undergoing ADM+expander implant were not included due to the small number of cases) that both degrees in subjective and objective satisfaction in patients undergoing LD+expander implant were higher than those in patients receiving direct expander implant (both P<0.05). Conclusion: Using LD+expander implant for delayed-immediate breast reconstruction after radical mastectomy offers a better patients’ satisfaction, with less cost than that of ADM+expander implant, so it is recommended as first option.

Abstract:Objective: To evaluate the feasibility of using indocyanine green (ICG) fluorescence technique in sentinel lymph node biopsy (SLNB) for breast cancer. Methods: Sixty-eight breast cancer patients admitted between November 2010 and February 2012 were selected. Of the patients, 36 cases underwent SLNB with ICG fluorescence navigation (ICG group), while 32 cases underwent SLNB using methylene blue as a tracer (dye group). All patients received level I and II axillary dissection after the SLNB. Results: The baseline clinical data between the two groups had no statistical difference (all P>0.05), and were comparable. The detection rate of sentinel lymph nodes (SLNs) was 97.2% (35/36) in ICG group and 81.3% (26/32) in dye group, and the former was significantly higher than the latter (P<0.05). There was no significant difference in false-negative rate and mean number of excised SLNs between the two groups (both P>0.05). Conclusion: The detection rate of using ICG fluorescence navigation SLNB for breast cancer is higher than that of dye tracer, and it can be used as an alternative option for radioactive or dye tracer.

Abstract:Objective: To compare the detection rate and accuracy of subareolar versus peritumoral tracer injection for location of sentinel lymph nodes (SLNs) in breast carcinoma. Methods: The literature regarding subareolar compared to peritumoral tracer injection for location of SLNs in breast cancer was collected by searching the national and international databases. After data extraction, statistical analysis was performed by using Metadisc 1.4 softeware. Results: Seven studies were finally included involving 1 350 patients. In the 794 patients undergoing subareolar injection, SLNs were detected in 747 cases, and the detection rate was 94.08%, while in the 556 patients undergoing peritumoral injection, SLNs were detected in 506 cases, and the detection rate was 91.01%, which in the former was significantly higher than that in the latter (P=0.031). For subareolar and peritumoral injection, the pooled sensitivity for was 0.962 (95% CI=0.929–0.983) and 0.937 (95% CI=0.890–0.968), specificity was 1.000 (95% CI=0.988–1.000) and 1.000 (95% CI=0.988–1.000), and area under curve of SROC was 0.983 3 and 0.956 3, respectively. Conclusion: For location of SLNs in breast cancer, the detection rate of subareolar injection is higher than that of peritumoral injection, but both methods have relatively high accuracy.

Abstract:Objective: To systematically evaluate the efficacy of use of pseudomonas aeruginosa (PA) preparation in treatment of breast cancer. Methods: The randomized controlled trials (RCTs) concerning the use of PA preparation in treatment of breast cancer were collected by searching the national and international databases, and the time period of search ranged from inception of each database until November 2014. After literature screening, data extraction and quality assessment, Meta-analysis was performed by Revman 5.1.2 software. Results: Nine RCTs were finally included. The results of Meta-analysis showed that combined use of PA preparation with conventional treatment significantly increased the complete response rate (OR=2.22), total response rate (OR=6.73), Karnofsky score (MD=9.79) and IL-2 level, and significantly decreased the stable disease rate (OR=0.36) and progress disease rate (OR=0.18), as well as shortened the time to disappearance of the postoperative fluid collection (MD=–7.52). Conclusion: Combined use of PA preparation can increase the efficacy of conventional chemoradiotherapy in treatment of breast cancer, but this conclusion needs further verification by more high quality studies.

Abstract:

Objective: To investigate the application value of ultrasound-guided vacuum-assisted 8-gauge Mammotome biopsy system (UVMS) in diagnosis and treatment of breast masses. Methods: The clinical data of 1 157 patients with breast masses (a total of 3 702 lesions) undergoing UVMS treatment from January 2012 to December 2013 were retrospectively analyzed. Results: All lesions were removed by UVMS. Among the 1 157 patients, 888 cases (76.75%) had no palpable mass, 831 cases (71.82%) had multiple lesions, and 245 cases (21.18%) had bilateral lesions. The average longitudinal diameter of the lesions was 11.2 (3–35) mm, the average operative time was 15 (3–90) min, the average blood loss was 8 (1–40) mL, and the length of incision ranged from 3 to 5 mm. The majority of the specimens (99.57%) were pathologically diagnosed to be benign lesions, in which fibroadenoma was the dominant one (64.61%). After operation, hematoma occurred in 53 cases, subcutaneous ecchymosis occurred in 26 cases, bloody nipple discharge in 2 cases, and no other severe complications were observed. Conclusion: The application of UVMS for removal of breast masses is simple, safe and minimally invasive, and is especially suitable for multiple and impalpable masses, but the indications should be strictly controlled.

Abstract:Objective: To investigate the feasibility and effect of resection of large benign breast tumor with an ultrasound-guided Mammotome revolve device. Methods: The clinical data of 105 patients with single breast mass (>3.0 cm) undergoing surgical treatment were retrospectively analyzed. Of the patients, 68 cases underwent ultrasound-guided Mammotome procedure (observational group), and the other 37 cases underwent traditional open surgery (controlled group). The main surgical variables between the two groups were compared. Results: There was no difference between the two groups in the baseline data such as age, disease constitution and tumor size (all P>0.05), so they were comparable. The operative time, intraoperative blood loss and incidence of postoperative complications showed no significant difference between the two groups (P>0.05), but the length of the incisions in observational group was significantly less than that in control group [(0.53±0.04) cm vs. (3.65±0.46) cm, P<0.05]. Follow-up was conducted for 1 to 12 months in the two groups of patients, no tumor recurrence occurred, and scars of different lengths were noted in patients in control group, while the scars were very small or invisible in those in observational group. Conclusion: Resection of large benign breast tumor with ultrasound-guided Mammotome revolve device is safe and feasible, and offers favorable cosmetic results, so it has applicable value in clinical practice.

Abstract:Objective: To investigate the relations of the levels of endogenous sex hormones and blood lipids with breast cancer in postmenopausal women and the feasibility of using them as predictors for breast cancer. Methods: Two-hundred and seventy-four postmenopausal women with breast cancer (breast cancer group) undergoing surgical treatment from July 2011 to June 2014, and 279 postmenopausal female patients admitted during the same period for other diseases who were excluded from breast diseases (control group) were enrolled. The levels of sex hormone and blood lipids between the two groups were compared, and the potential predictors for breast cancer were analyzed. Results: The levels of estrogens (E2) and testosterone (T) in breast cancer group were significantly higher than those in control group (both P<0.05), while levels of other sex hormones and blood lipids showed no significant difference between the two groups (all P>0.05). Stratification analysis demonstrated that the incidence of breast cancer was increased with either E2 level or T level, in which E2 level had a better sensitivity and specificity for prediction of breast cancer, and its area under curve (AUC) of the receiver operating characteristic (ROC) reached 0.730 (95% CI=0.649–0.811), but T level showed no significance in prediction of breast cancer. Conclusion: The E2 and T levels are associated with breast cancer in postmenopausal women, and E2 level can be used as one of the predictors of breast cancer, but has not yet become a satisfactory or excellent standard.

Abstract:Objective: To systematically evaluate the diagnostic value of detection of hypoxia-inducible factor 1α (HIF-1α) expression in male breast cancer patients through Meta-analysis. Methods: The case-control studies concerning relationship between HIF-1α and male breast cancer were collected by searching the national and international databases, and the time period of search ranged from February 2006 to June 2014. Meta-analysis was performed on the results of the eligible studies by RevMan 5.1 software. Results: A total of 6 studies were selected, involving 475 male patients in case group and 256 female patients in control group. Results of Meta-analysis showed that the positive rate of HIF-1α expression in male breast cancer patients was significant higher than that in female patients with breast cancer (OR=1.29, 95% CI=0.93–1.79); results of heterogeneity tests showed no statistical heterogeneity among the studies (χ2=7.61, P=0.18, I2=34%); pooled result showed that the difference had no statistical significance (Z=1.54, P>0.05); publication bias analysis demonstrated the authenticity of this Meta-analysis. Conclusion: Detection of HIF-1α expression level has certain diagnostic value for early breast cancer in male patients, and it can be used as one of the reference indexes. However, the above conclusion still needs verification by high-quality and large-scale studies due to the limitation in quality and sample size of the included studies.

Abstract:Objective: To seek the circulating miRNAs that can be used as sensitive biomarkers of breast cancer. Methods: Firstly, the expression levels of six candidate miRNAs (miR-9, miR-335, miR-205, miR-10b, miR-125b, and miR-34a) in blood circulation of 80 breast cancer patients and 80 healthy control subjects were measured by qRT-PCR, to screen out the miRNAs that changed significantly. Then, in another population of 80 breast cancer patients and 80 healthy control subjects, the miRNAs that were screened out were verified, and their diagnostic accuracy for breast cancer were analyzed through the area under the curve (AUC) of receiver operating characteristics (ROC) curve, which were also compared with that of A15-3. Results: Both screening and verification showed that the circulating level of miR-9 was increased while the circulating levels of miR-335 and miR-205 were decreased significantly in breast cancer patients compared with healthy controls (all P<0.05). The AUC of miR-9, miR-335 and miR-205 for diagnosis of breast cancer was 0.859 (95% CI=0.814–0.911), 0.920 (95% CI=0.885–0.959) and 0.899 (95% CI=0.861–0.939) respectively, and the AUC value of the combined detection of the three miRNAs (0.924, 95% CI=0.895–0.953) was significantly higher than that of CA15-3 (0.874, 95% CI=0.834–0.914) (P<0.05). Conclusion: Circulating miR-9, miR-335 and miR-205 are sensitive biomarkers for breast cancer, and their combined detection may help improve the diagnostic accuracy of breast cancer.

Abstract:Objective: To investigate the alteration of CD4+CD25+Foxp3+ regulartory T cells (hereinafter abbreviated as Foxp3+ Tregs) in breast cancer patients and its significance. Methods: Forty patients with breast cancer and 32 patients with benign breast tumors were enrolled. The levels of Foxp3+ Tregs, CD8+CD28+ T cells and NK cells in peripheral blood of the patients were measured by flow cytometry, and the Foxp3 protein and mRNA expressions in breast lesions were determined by Western blot and RT-PCR, respectively. Results: The ratio of Foxp3+ Tregs was significantly higher, while the ratios of both CD8+CD28+ T cells and NK cells in peripheral blood were significantly lower in breast cancer patients than those in patients with benign breast tumor (all P<0.05), and there was a negative correlation between the level of Foxp3+ Tregs and either the level of CD8+CD28+ T cells or NK cells in peripheral blood of breast cancer patients (r=–0.631, r=–0.578, both P<0.05); the peripheral blood level of Foxp3+ Tregs in breast cancer patients was significantly decreased after operation compared with the level before operation (P<0.05). Either protein or mRNA level of Foxp3 in breast cancer tissue was significantly higher than that in benign breast tumor tissue (both P<0.05). Conclusion: Foxp3+ Treg and its molecular marker Foxp3 are increased in breast cancer patients, which may probably contribute to the tumor immunosuppression through inhibition of CD8+CD28+ T and NK cells.

Abstract:Objective: To investigate the expression of the new microtubule-binding protein NuSAP in breast cancer tissue and its clinical significance. Methods: Fifty specimens of breast cancer tissue together with 37 specimens of the adjacent normal breast tissue (>5 cm away from the tumor) and 20 breast specimens of benign disease were collected. The expressions of protein and mRNA in these tissues were detected by immunohistochemical staining and real-time quantitative PCR, respectively. The relations of NuSAP expression with clinicopathologic characteristics of breast cancer patients were analyzed. Results: Both NuSAP protein and mRNA expression levels in breast cancer tissue were significantly higher than those in adjacent normal breast tissue and breast tissue from benign disease (all P<0.05); both NuSAP protein and mRNA expression levels were significantly increased in breast cancer tissues with axillary lymph node metastasis and positive HER-2 expression (all P<0.05), while they were irrelevant to age, menopausal status, and expressions of ER, PR and Ki-67 (all P>0.05). Conclusion: NuSAP expression is increased in breast cancer tissue, which may be closely associated with the occurrence, development and progression of breast cancer.

Abstract:

Objective: To investigate the expression and clinical significance of hypoxia inducible factors 1α (HIF-1α) and glucose transporter 1 (Glut-1) in basal-like breast carcinoma (BLBC). Methods: The protein expressions of HIF-1α and Glut-1 in 95 specimens of BLBC and their adjacent breast tissue, and 708 samples of non-BLBC tissue were detected by immunohistochemical staining, and their relations with the clinicopathologic factors of BLBC were analyzed. Results: The positive expression rate of either HIF-1α or Glut-1 protein in BLBC tissue was significantly higher than that in adjacent breast tissue and non-BLBC tissue (all P<0.05), and both HIF-1α and Glut-1 protein expressions were associated with lymph node metastasis and clinical stage of BLBC (all P<0.05); there was a significantly positive correlation between HIF-1α and Glut-1 expression in BLBC tissue (r=0.368, P<0.05). Conclusion: HIF-1α and Glut-1 synchronously overexpress in BLBC tissue, which may co-participate in the occurrence and development of BLBC, and can be potentially used as a prognostic index for BLBC patients.

Abstract:Objective: To investigate the effects of thermal induction on transcriptional activity and targeting specificity of human telomerase reverse transcriptase promoter (hTERTp) modified with eight tandem repeats of consensus heat shock element (8HSE). Methods: The hTERTp was cloned from the genome of colon cancer cells by PCR amplification, and the hTERTp or hTERTp modified with 8HSE fragments were recombined into the dual luciferase reporter vector pGL4.2, which were then co-transfected with the internal control plasmid pGL4.74 (containing TK promoter) into the high hTERT expressing SW480 cells and low hTERT expressing MKN28 cells, respectively. The transcriptional activity of hTERTp in the two types of cells at the temperature of 37 ℃ and 43 ℃ were analyzed by dual-luciferase reporter assay system. Results: As identified by PCR, enzyme digestion and sequencing, the hTERTp cloning, 8HSE synthesis and plasmid vector constructions were all successful. Under the condition of 37 ℃, the transcriptional activity of the unmodified hTERTp in SW480 cells was significantly higher than that in MKN28 cells (P<0.05), while 8HSE modification exerted no enhancing effect on transcriptional activity of hTERTp, and it even inhibited the transcriptional activity of hTERTp in SW480 cells; under the condition of 43 ℃, the transcriptional activity of unmodified hTERTp in either type of cells showed no significant change (P>0.05), while compared with unmodified hTERTp, the transcriptional activity of 8HSE modified hTERTp in SW480 cells was significantly increased (P<0.05), but showed no significant change in MKN28 cells (P>0.05). Conclusion: Thermal induction has no obvious effect on transcriptional activity of hTERTp, but can significantly enhance the transcriptional activity of 8HSE modified hTERTp, which also specifically targets tumor cells with high hTERT expression.

Abstract:Cancer stem cell (CSC) theory has drawn increasing attention in recent years. The presence of CSCs in thyroid cancer has been demonstrated by previous studies. Thyroid cancer CSCs are considered to be the potential culprit of occurrence, metastasis, recurrence and drug-resistance of thyroid cancer, thus, investigation in thyroid cancer CSCs may offer great significance for diagnosis, treatment and prevention of thyroid cancer. Here, the authors address the current knowledge about the thyroid cancer CSCs.

Abstract:Hypoparathyroidism (HypoPT) is one of the most common complications after thyroid surgery. It still mainly relies on calcium supplements and activated vitamin D analogues as symptomatic treatment in clinical practice at present, which comes with many problems. Parathyroid hormone replacement therapy (PTH-RT) as a new treatment modality has increasingly been given attention, and has achieved rapid development after continuous efforts for years. The authors present the research progress in PTH-RT from the aspects of drugs for PTH-RT, drug-delivery methods and physical impacts

Abstract:Endocrine therapy is the basic treatment for patients with hormone receptor-positive breast cancer, which can significantly reduce the tumor recurrence and mortality. However, not all patients may benefit from endocrine therapy, so how to further improve the efficacy of endocrine therapy is of a great clinical significance. Carcinoma-associated fibroblasts (CAFs) are the major cellular component in the tumor stroma of breast cancer, possessing tumor-promoting characteristics distinct from those of normal fibroblasts. CAFs can change the microenvironment of the tumor cells and thereby, affect the efficacy of endocrine therapy. Recently, researches targeting CAFs have been gradually carried out, and also proved to be effective in improving the efficacy of endocrine therapy. The authors overview, in this article, the role of CAFs in endocrine therapy for breast cancer and how to improve the efficacy of endocrine therapy by targeting CAFs.