Abstract:As no postoperative scar is left on the anterior neck area, endoscopic surgery via breast approach has been increasingly preferred by thyroid cancer patients, especially by young female patients. How to realize central compartment dissection (CCD) with a standardized endoscopic technique and extend its use in primary-level hospitals are urgent problems to be solved. Here, the authors, using bilateral areolar approach as an example, introduce the procedures of endoscopic CCD used by the surgical team led by WANG Ping in the Second Affiliated Hospital of Zhejiang University.

Abstract:The incidence of thyroid cancer is growing larger each year. However, the development of diagnostic and treatment programs in this field has been severely constrained for quite a long time, due to the lack of clinical registry data based on Chinese population. Therefore, the postoperative follow-up and clinical study of thyroid cancer have drawn increasing attention from Chinese scholars in recent years. Despite the large population base and abundant clinical cases in China, the cancer registry work has been proceeding slowly and coverage of the population is still low, especially the long-term follow-up study of thyroid cancer is greatly problematic under the weak basic conditions. The authors analyze the current status of cancer registry and the difficulties in follow-up and investigative work for thyroid cancer in China, based on reference to advanced cancer registry and follow-up models in foreign countries combined with personal experience in clinical practice and basic research.

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Objective: To investigate reasons for reoperation of papillary thyroid carcinoma (PTC) patients and the influential factors. Methods: The clinical data of 279 PTC patients undergoing reoperation from January 2007 to June 2016 were retrospectively analyzed. Results: Of the 297 patients, thyroid remnant cancer recurrence occurred in 156 cases (55.9%) and lymph node metastases occurred in 215 cases (77.1%), and the latter included central lymph node metastasis in 135 cases (48.4%) and lateral lymph node metastasis in 151 cases (54.1%). Statistical analyses showed that female gender and age≥45 years were independent risk factors for thyroid remnant cancer recurrence (both P<0.05); no central lymph node dissection (CND) and initial operation performed at a county-level hospital were independent risk factors for central lymph node metastasis (both P<0.05); male gender and total/near total thyroidectomy (TT/NTT) and CDN used as an initial procedure were independent risk factors for lateral lymph node metastasis (all P<0.05). The median recurrence time from the first operation was 33 months for patients undergoing the first operation at a hospital specialized in thyroid treatments, and they mainly had lateral lymph node metastasis (26.8%) and central lymph node metastasis (42.9%); it was 24 months in a province-level hospital, and they mainly had central lymph node metastasis (32.8%) and thyroid remnant cancer recurrence (29.9%); it was 24 and 12 months in a district- or prefecture-level and county-level hospital, and they mainly had thyroid remnant cancer recurrence of 36.7% and 45.9%, respectively. After reoperation, follow-up was obtained in 158 patients for 10 to 123 month, and of them, one case (0.4%) died, permanent hoarseness occurred in 7 cases (4.4%), permanent hypocalcemia occurred in 19 cases (12.0%), dedifferentiation after 131I therapy occurred in 9 cases (5.7%) and recurrence occurred in 22 cases (13.9%). Conclusion: Non-specialized operation and improper procedure are main reasons for increased postoperative thyroid remnant cancer recurrence and lymph node metastases and thereby reoperation in PTC. Lobectomy or TT/NTT plus ipsilateral or bilateral CND and/or combined with LND may effectively reduce the recurrence rates. The incidences of permanent surgical complications and dedifferentiation are higher after reoperation, so appropriate treatment should be taken in the initial treatment to reduce the risk of recurrence.

Abstract:Objective: To investigate the experience and efficacy of endoscopic radical operation via bilateral areolar approach in treatment of papillary thyroid microcarcinoma. Methods: The clinical data of 23 patients undergoing endoscopic radical operation for papillary thyroid microcarcinoma via bilateral areolar approach between January 2015 and January 2017 were analyzed retrospectively. All patients had a solitary thyroid nodule, with tumor size ≤1.0 cm. None of the patients had cervical lymph node metastasis. Of the patients, 18 cases were female and 5 cases were male, with an average age of 37.13 years. Results: Radical thyriodectomy was successfully performed in all the patients, without any open conversion. No reoperation due to complications was required. The average operative time was 183.83 (155–221) min, time for postoperative drainage tube was 2.17 (2–3) d, and length of postoperative hospital stay was 2.39 (2–5) d, respectively. After surgery, mild choking when drinking fluids occurred in one case, which recovered within one week; varying degrees of subcutaneous emphysema occurred in 6 cases and, in all the cases, it was spontaneously absorbed within one week. No tumor recurrence, or lymph node and distal metastasis were found on regular follow-up to date. All patients showed minimal scar and good cosmetic results in postoperative follow-up observation. Conclusion: Endoscopic radical operation for papillary thyroid microcarcinoma via bilateral areolar approach is an effective, safe and feasible procedure, with favorable cosmetic results.

Abstract:Objective: To evaluate the value of anteroposterior to transverse diameter ratio (A/T) of the thyroid nodule greater than or equal to 1 in diagnosis of its benign and malignant nature. Methods: The studies published before July 2017 evaluating the value of thyroid nodule’s A/T≥1 in diagnosis of malignant lesion were collected through searching several national and international databases. After screening for inclusion criteria, data extraction and quality assessment, the data were analyzed with Meta-DiSc 1.4 statistical software. The heterogeneity among the included studies was assessed, and the pooled effect estimates of thyroid nodule’s A/T≥1 in diagnosing its malignant nature in the included studies were calculated, which included the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the area under the curve (AUC) of summary receive operating characteristic curve and Q* index. The stability of results of the overall pooled estimates of the included studies was validated by sensitivity analysis, and the sources of heterogeneity among the included studies were analyzed. The publication bias caused by the results of the included studies was evaluated by drawing the Deek’s funnel plot. Results: A total of 13 studies were included, involving 11 243 nodules that included 9 227 benign nodules and 2 016 malignant nodules. The quality of 13 studies was uneven, and there was a heterogeneity caused by non-threshold effect among the included studies (r=0.352, P=0.239). The overall pooled sensitivity, specificity, PLR, NLR, DOR, AUC and Q* index of the included studies of thyroid nodule’s A/T≥1 for diagnosing malignant nodule were 0.31 (95% CI=0.29–0.33), 0.50 (95% CI=0.49–0.51), 1.32 (95% CI=0.81–2.14), 0.85 (95% CI= 0.73–0.99), 1.51 (95% CI=0.77–2.90), 0.538 9 and 0.529 2, respectively. The results of the overall pooled estimates of included studies were stable, and the research methods, racial differences and whether by blind design might be sources of the heterogeneity of the studies. The Deek’s funnel plot showed an asymmetrical distribution of the results, indicating that there was a publication bias caused by the results of the included studies. Conclusion: Thyroid nodule’s A/T≥1 has certain value in differential diagnosis of benign and malignant thyroid nodules. However, its sensitivity and specificity are low, so combined judgment with other imaging signs is necessary.

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Objective: To investigate the clinicopathologic features of multifocal papillary thyroid microcarcinoma (PTMC) and the significance of prophylactic central neck dissection. Methods: The clinical data of 270 PTMC patients treated in the Department of Thyroid Surgery, Xiangya Hospital from July 2013 to December 2016 were reviewed. The differences in clinicopathologic factors between patients with multifocal PTMC and unifocal PTMC were compared, and the risk factors for central lymph node metastasis of multifocal PTMC were determined. Results: Among the 270 PTMC patients, multifocal PTMC was found in 120 cases (44.4%). In patients with multifocal PTMC, the proportion of male cases and the incidences of central lymph node metastasis and capsular invasion were significantly increased compared with patients with unifocal PTMC (both P<0.05). In multifocal PTMC patients, the maximum tumor diameter (5–10 mm vs.<5 mm), and the presence or absence of capsular invasion had significant impact on incidence of central lymph node metastasis (both P<0.05), while the lesion number (2 vs. ≥3) and distribution (unilateral lesion vs. bilateral lesion) showed no significant influence on incidence of central lymph nodes metastasis (both P>0.05). Conclusion: Compared to unifocal PTMC, multifocal PTMC has relatively poor clinicopathologic features and an increased risk of central lymph node metastasis. Prophylactic central lymph node dissection is necessary for multifocal PTMC patients, especially for those who have relatively large tumors and tumors with capsular invasion.

Abstract:Objective: To investigate the skip lateral lymph node metastasis (lateral cervical lymph node metastasis without central lymph node metastasis) in papillary thyroid carcinoma (PTC) and the influential factors. Methods: The clinical data of 177 PTC patients with confirmed lateral cervical lymph metastasis by postoperative pathology in Fujian Province Hospital from January 2014 to December 2015 were reviewed (all patients underwent operation for the first time). The relations of clinicopathologic features of the patients with skip lateral lymph node metastasis, and the influential factors for skip lateral lymph node metastasis were analyzed. Results: Skip metastasis was found in 29 cases (16.4%) of the 177 patients with lateral cervical lymph node metastasis. Univariate analysis showed that skip lateral lymph node metastasis in PTC was significantly related to primary tumor size≤10 mm and the primary tumor location involving the superior pole of the thyroid gland (χ2=8.645, P=0.003; χ2=4.267, P=0.039), while it was irrelevant to age, gender, lesion number, lesion distribution, tumor invasion, tumor stage, and concomitant Hashimoto disease (all P>0.05); both the detected number and positive number of lgmph nodes in both central compartment and lateral neck in patients with skip lateral lymph node metastasis were significantly less than those in patients without skip lateral lymph node metastasis (all P<0.05). Logistic regression analysis revealed that the primary tumor size≤10 mm (OR=3.499, 95% CI=1.509–8.110, P=0.004) and the primary tumor location involving the superior pole of the thyroid gland (OR=0.397, 95% CI=0.171–0.924, P=0.032) were independent influencing factors for skip lateral lymph node metastasis. Conclusion: The primary tumor size≤10 mm and the primary tumor involving the superior pole of the thyroid gland are independent influencing factors for skip lateral lymph node metastasis in PTC.

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Objective: To investigate the clinical, ultrasonic and pathologic characteristic as well as treatment and outcomes of primary squamous cell carcinoma of thyroid (SCCT). Methods: The clinical presentations, ultrasonic features, pathologic findings and results of comprehensive treatment of 7 primary SCCT patients admitted from January 2010 to December 2015 were retrospectively analyzed. Results: The 7 primary SCCT patients accounted for 0.96% (7/728) of the total number of thyroid cancer patients admitted during the same period, of whom, 3 cases were male and 4 cases were female, with an average age of 62.7 years. All patients had palpable neck mass that was associated with dyspnea in 4 cases, hoarseness in 2 cases and dysphagia in one case. All lesions in ultrasonographic images presented as irregular mixed echogenic solid mass, with thyroid capsule penetration in 5 lesions, microcalcification in 2 lesions and suspicious cervical lymph nodes in 4 lesions. Five patients underwent surgical treatment (thyroidectomy with neck dissection in 2 cases, wide local excision in 2 cases, and palliative resection with prophylactic tracheostomy in one case), and 2 patients underwent coarse needle biopsy only. All cases were confirmed as SCCT by pathology, which was combined with nodular goiter in 3 cases and with papillary thyroid carcinoma in 2 cases, and the immunohisochemical staining for P63 was positive in all cases. Of the 5 patients undergoing surgical treatment, 4 cases had postoperative radiotherapy or radiotherapy plus chemotherapy, and one case did not receive comprehensive therapy; 2 patients undergoing coarse needle biopsy only received radiotherapy or radiotherapy plus chemotherapy. Only one patient who underwent thyroidectomy with neck dissection plus postoperative radiotherapy survived more than one year, and all the remaining patients died within half a year. Conclusion: Primary SCCT is a highly malignant tumor with rapid progress and poor prognosis. Its clinical manifestations and ultrasound imaging have certain characteristics that may help the preoperative diagnosis. Immunohistochemical staining is important for its differential diagnosis, and aggresive comprehensive treatment may improve the prognosis of the patients.

Abstract:Objective: To investigate the association between the single nucleotide polymorphisms (SNPs) of rs2279744 locus in the promoter region of mouse double minute 2 homolog (MDM2) gene and risk of breast cancer. Methods: Case-control studies regarding the association between the SNPs of MDM2 rs2279744 locus and risk of breast cancer were collected by searching several national and international databases. The eligible studies were screened out according to the criteria. Meta-analysis was performed following data extraction, and the sensitivity and publication bias were also analyzed. Results: Twenty-eight case-control studies were included, with 11 804 breast cancer patients in case group and 152 09 subjects in control group. The results of Meta-analysis showed that there were significant differences in mutant genotype and wild genotype (TG/GG vs. TT) as well as in alleles (G vs. T) in the overall population (OR=1.15, 95% CI=1.06–1.24, P<0.001; OR=1.12, 95% CI=1.05–1.18, P<0.001); subgroup analysis divided by different continents reveal that those differences only found in Asia’s population (TG/GG vs. TT: OR=1.34, 95% CI=1.15–1.57, P<0.001 by random effects model, OR=1.34, 95% CI=1.20–1.50, P<0.001 by fixed effect model; G vs. T: OR=1.21, 95% CI=1.09–1.35, P=0.001 by random effects model). The sensitivity analyses and Egger’s tests verified the reliable conclusions and no obvious publication biases. Conclusion: Asian individuals with mutant genotype homozygote (GG) and heterozygous (TG) in MDM2 rs2279744 locus have a higher risk of breast cancer than those with wild genotype (TT). Mutations in MDM2 rs2279744 locus are closely associated with the risk of breast cancer in Asians.

Abstract:Objective: To compare the difference in biological behaviors between two types of tumor stem cells derived from human Luminal A and HER-2-positive breast cancer. Methods: Primary breast cancer cells were isolated from specimens of Luminal A and HER-2-positive breast cancer tissues and cultured, and then the mammospheres (MSs) were obtained, which were highly enriched in tumor stem cells. MSs were dissociated into single cells (mammospheres-derived cells, MSDCs) by trypsin digestion, and then the proliferative and regenerative abilities in vitro, the proportions of ALDH1+ cell population, and the tumor formation abilities after inoculation into NOD/SCID mice were compared between MSDCs from the two types of breast cancer. Results: MSs formed in the primary cultured breast cancer cells either isolated from Luminal A or HER-2-positive breast cancer tissue. However, in HER-2-positive breast cancer, the MSs formation time was shorter and their volume was larger than those in Luminal A breast cancer. The proliferative and regenerative abilities in MSDCs from HER-2-positive breast cancer were significantly higher than those in MSDCs from Luminal A breast cancer either cultured in serum-free medium or medium containing serum, and the proportion of ALDH1+ cell population in the former was significantly higher than that in the latter (all P<0.05). The tumor formation ability of MSDCs from HER-2-positive breast cancer was stronger than that of MSDCs from Luminal A breast cancer in NOD/SCID mice. Conclusion: The tumor stem cells isolated from Luminal A and HER-2-positive breast cancer have significantly different biological behaviors. So the two types of breast cancer may originate from different tumor stem cells.

Abstract:Objective: To investigate the miR-26b expression and its influence on the biological behaviors in breast cancer cells. Methods: The differences of miR-26b expressions in normal breast cell line MCF-10A and breast cancer cell line MCF-7 were compared. Using untreated MCF-7 cells as blank control, the changes in miR-26b expression, abilities of proliferation, migration and invasion, and Foxf2 mRNA and protein expressions in MCF-7 cells after transfection with miR-26b mimics (miR-26b) group or empty plasmid (negative control group) were determined. The influence of miR-26b on transcriptional activity of Foxf2 in MCF-7 cells was determined by dual-luciferase reporter assay system. Results: The miR-26b expression level in MCF-7 cells was significantly lower than that in MCF-10A cells (P<0.05). In miR-26b group compared with the blank control group or negative control group, the miR-26b expression level was significantly increased, the abilities of proliferation, migration and invasion were significantly decreased, and the mRNA and protein expression levels of Foxf2 were significantly down-regulated (all P<0.05). The transcriptional activity of Foxf2-3'UTR was significantly inhibited in MCF-7 cells after miR-26b mimics transfection (P<0.05). Conclusion: MiR-26b expression is decreased in breast cancer cells, increasing its expression can suppress the malignant biological behaviors of breast cancer cells, and the mechanism may be related to its down-regulating Foxf2 expression.

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Objective: To investigate the value of using pectoralis major fascia in the immediate breast reconstruction following mastectomy for breast cancer. Methods: The clinical data of 18 patients with early breast cancer undergoing subcutaneous mastectomy with nipple-areola complex preservation and immediate breast reconstruction between May 2014 and September 2016 were retrospectively analyzed. All patients received breast reconstruction with prosthesis covered and wrapped by the pectoralis major muscle and its fascia, namely, firstly, the pectoralis major fascia was detached from the pectoralis major muscle, with a direction from the parasternal and infraclavicular region toward the lateral region, and then the prosthesis was implanted between the pectoralis major and minor muscles, and finally, the lateral border of the pectoralis major muscle was sutured to the detached pectoralis major fascia for firmly wrapping the prosthesis. Results: Breast reconstruction was successfully performed in all the 18 patients. During the follow-up period of 12 to 40 months, no recurrence or metastasis occurred in any of the patients, all reconstructed breasts displayed a natural shape and acceptable symmetry, no displacement or contracture of the breast prosthesis was noted, and the postoperative appearance good rate was 100%. Conclusion: For some early breast cancer patients, subcutaneous mastectomy with nipple-areola complex preservation plus immediate breast reconstruction using pectoralis major muscle and its fascia covering and wrapping the prosthesis is simple and easy to perform, with excellent cosmetic effect and few complications.

Abstract:Objective: To investigate the clinical features of neuroendocrine tumor of the breast and its diagnosis and treatment. Methods: The clinicopathologic data of three patients with neuroendocrine tumor of the breast treated in Hunan Provincial People’s Hospital from 2013 to 2017 were retrospectively analyzed. Results: All three patients were female, with age of 31 to 39 years and tumor size of 0.5 to 4.0 cm. Two cases sought medical help for breast mass, and one case for nipple discharge. All cases presented with hypoechoic mass lesion in ultrasound scan. One case underwent modified radical mastectomy, one case underwent nipple-sparing modified radical mastectomy plus primary breast prosthesis reconstruction, and one case underwent simple mastectomy. The pathologic types included solid carcinoma in two cases and small cell carcinoma in one case. Immunohistochemical staining showed chromogranin A (CgA) and synaptophysin (Syn) positive in all the three cases and neuron-specific enolase (NSE) positive in two cases. Patients were followed up for 6 to 32 months, one case died of liver metastases at 6 months after excision, and 2 cases survived with tumor free status. Conclusion: Neuroendocrine tumor of the breast is a rare and special type of breast cancer. Its clinical features and imaging characteristics are usually nonspecific. Pathological and immunohistochemical examinations are considered as gold standard for its diagnosis. The comprehensive treatment with surgical treatment is the main method. Small cell neuroendocrine breast cancer has a poor prognosis.

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Objective: To investigate the clinical efficacy of endocrinotherapy in treatment of breast cancer patients with hormone receptor (HR)-negative primary lesion and HR-positive axillary lymph node metastases. Methods: Sixty-seven breast cancer patients with HR-negative primary lesion and HR-positive axillary lymph node metastases admitted from January 2011 to January 2016 were randomly designated to observation group (33 cases) and control group (34 cases). Patients in both groups received the same chemoradiotherapy regimen, while those in observation group were additionally given administration of tamoxifen (pre-menopausal patients) or letrozole (post-menopausal patients) after chemotherapy. The recurrence/metastasis and survival rates of the two groups of patients were compared. Results: All patients were followed up for 12 to 60 months, during which time, recurrence/metastasis occurred in 13 cases and death occurred in 7 cases in observation group, and recurrence/metastasis occurred in 19 cases and death occurred in 15 cases in control group. The incidence of recurrence/metastasis of the two groups showed no significant difference (P>0.05), while the rate of death due to recurrence/metastasis was significantly lower in observation group than that in control group (P<0.05). The 1-, 3- and 5-year disease-free survival (DFS) rate was 100%, 81.8% and 72.7% in observation group and was 100%, 58.8% and 47.1% in control group respectively; the 1-, 3- and 5-year overall survival (OS) rate was 100%, 90.9% and 81.8% in observation group and was 100%, 70.6% and 58.8% in control group. Both 3- and 5-year DFS and OS in observation group were significantly higher than those in control group (all P<0.05). Conclusion: Attention should be paid to the molecular classification of primary lesion and axillary lymph node metastasis in breast cancer patients. Postoperative endocrinotherapy may improve the survival and reduce the risk of death for breast cancer patients with HR-negative primary lesion and HR-positive axillary lymph node metastases.

Abstract:Nodular goiter is a common disease in the field of general surgery, and has a high postoperative recurrence rate, which poses a challenge for following treatment. Nevertheless, standardized postoperative thyroxine treatment can effectively reduce postoperative recurrence of the nodular goiter by inhibiting the thyroid-stimulating hormone (TSH) of the patients and controlling it at a proper level after operation. Here, the authors address the progress of postoperative TSH suppressive therapy for nodular goiter patients.

Abstract:Triple-negative breast cancer (TNBC) is a subtype of breast cancer defined as the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2), and characterized by onset at a younger age and high incidence of early metastasis. TNBC does not respond to endocrine therapy targeting ER or PR and HER-2-targeted agents, and has accordingly become a challenge in clinical treatment and a hotspot in research of breast cancer. A great number of investigations have been done by scholars for finding new biomarkers of TNBC and thereby improving its clinical diagnosis and treatment. Here, the authors present the recent progress on researches concerning the biomarkers of TNBC both at home and abroad.

Abstract:

Ultrasound is one of the conventional techniques for the clinical diagnosis of breast cancer. The ultrasonic features of breast cancer are diverse, and more information is needed to ensure its early diagnosis and assessment. So, the combination of the multimodal ultrasound technologies is particularly important for the diagnosis of breast cancer. Here, the authors summarized the recent progress of multimodal ultrasound technologies, including automated breast volume scanner, elastography, contrast-enhanced ultrasound, etc. These technologies are playing important roles in the diagnosis of breast cancer and may have more promising clinical prospects in the future.