Safety and efficacy of anlotinib combined with taxane and lobaplatin in neoadjuvant treatment of clinical stage II/III triple-negative breast cancer in China (the neoALTAL trial): a single-arm, phase 2 trial.

Background: Anlotinib is a new type of tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1/2/3, platelet-derived growth factor receptors α/ß, and fibroblast growth factor receptors 1-4 and c-Kit, with a broad spectrum of inhibitory effects on tumor angiogenesis and growth. It has been proven effective in HER2-negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients with TNBC. Methods: Patients with clinical stage II/III TNBC were treated with 5 cycles of anlotinib (12 mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 ,d1, q3w or nab-paclitaxel 125 mg/m2, d1 and d8, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0) and the secondary endpoints include breast pCR (bpCR), axillary pCR (apCR), residual cancer burden (RCB), objective response rate (ORR), survival, and safety. Exploratory endpoints were efficacy biomarkers based on Fudan University Shanghai Cancer Center Immunohistochemical (FUSCC IHC) classification for TNBC and next-generation sequencing (NGS) of DNA from tumor tissue and blood samples of patients with 425-gene panel. This trial is registered with www.chictr.org.cn (ChiCTR2100043027). Findings: From Jan 2021 to Aug 2022, 48 patients were assessed and 45 were enrolled. All patients received at least one dose of study treatment and underwent surgery. The median age was 48.5 years (SD: 8.7), 71% were nodal involved, and 20% had stage III. In the intention-to-treat population, 26 out of 45 patients achieved pCR (57.8%; 90% CI, 44.5%-70.3%), and 39 achieved residual cancer burden class 0-I (86.7%; 95% CI, 73.2%-94.9%). The bpCR and apCR rate were 64.4% (29/45) and 71.9% (23/32), respectively. No recurrence or metastasis occurred during the short-term follow-up. Based on the FUSCC IHC-based subtypes, the pCR rates were 68.8% (11/16) for immunomodulatory subtype, 58.3% (7/12) for basal-like immune-suppressed subtype and 33.3% (4/12) for luminal androgen receptor subtype, respectively. NGS revealed that the pCR were 77% (10/13) and 50% (14/28) in MYC-amplified and wild-type patients, respectively, and 78% (7/9) and 53% (17/32) in gBRCA1/2-mutated and wild-type patients, respectively. The median follow-up time of the study was 14.9 months (95% CI: 13.5-16.3 months). There was no disease progression or death during neoadjuvant therapy. No deaths occurred during postoperative follow-up. In the safety population (N = 45), Grade 3 or 4 treatment emergent adverse events occurred in 29 patients (64%), and the most common events were neutropenia (38%), leukopenia (27%), thrombocytopenia (25%), anemia (13%), and hypertension (13%), respectively. Interpretation: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and encouraging antitumor activity for patients with clinical stage II/III TNBC. Funding: Chongqing Talents Project, Chongqing Key Project of Technology Innovation and Application Development and Chongqing Outstanding Youth Natural Science Foundation.

Patient-reported outcomes of mesh in minimally invasive (laparoscopic/robot-assisted) immediate subpectoral prosthesis breast reconstruction: a retrospective study.

BACKGROUND: Although there is increasing interest in minimally invasive prosthesis breast reconstruction (PBR), whether meshes application in minimally invasive PBR can improve complications and cosmetic effects remains controversial. The author retrospectively analyzed postoperative complications and evaluated patient-reported quality-of-life outcomes in minimally invasive PBR with and without mesh. METHODS: This study enrolled patients who underwent minimally invasive nipple-sparing mastectomy (NSM) followed by PBR. We used the TiLOOP bra for the mesh-assisted procedure. Patient demographics and postoperative complications data were compared between the procedures. Patient-reported outcomes were evaluated with the Breast-Q. RESULTS: A total of 158 patients underwent 160 minimally invasive NSM-PBR (with mesh, n = 64; without, n = 94). Postoperative complications were comparable in the mesh-assisted (5 [7.7%]) and non-mesh-assisted (5 [5.3%]) groups (p = 0.533). The most common complication in non-mesh-assisted group was infection, with four (4.2%) cases. In mesh-assisted group, implant exposure occurred in two (3.1%) patients. Removal of prosthesis was uncommon, with two (3.1%) and three (3.2%) cases in the mesh-assisted and non-mesh groups, respectively (p = 0.977). The BREAST-Q questionnaire was completed by 52 (81.3%) patients in the mesh-assisted group and 68 (72.3%) in the non-mesh-assisted group. Comparing the non-mesh group, patients in mesh-assisted group had improved scores on the BREAST-Q Satisfaction with breast (66.0) (p < 0.05), Physical Well-being (80.0), and Sexual Well-being (56.0). CONCLUSIONS: Mesh-assisted minimally invasive NSM-PBR has good aesthetic outcomes and high patient satisfaction. There were no significant differences in complication rates between the mesh-assisted and non-mesh-assisted groups.

A multicenter single-arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

The objective of this multicenter, single-arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy-THPy) in the treatment of patients with stage II-III HER2-positive breast cancer. The present study enrolled patients with stage II-III HER2-positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21-day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention-to-treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7-75.8%), while the objective response rate was 89.1%. In the post-hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy-THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II-III HER2-positive breast cancer.

Prospective cohort study of parathyroid function and quality of life after total thyroidectomy for thyroid cancer: robotic surgery vs. open surgery.

OBJECTIVE: To compare robot-assisted thyroidectomy (RT) and open thyroidectomy (OT) through a prospective cohort study focusing on the rate of postoperative hypoparathyroidism, efficacy, and quality of life (QoL). SUMMARY BACKGROUND DATA: Hypoparathyroidism is a frequent complication after thyroidectomy. Reducing the risk of hypoparathyroidism after total thyroidectomy is a crucial and difficult task for thyroid surgeons. METHODS: We prospectively enroled 306 patients with papillary thyroid carcinoma into an RT group and OT group. The former used "super-meticulous" capsular dissection) and the latter used traditional meticulous capsular dissection. Patients were evaluated by scales [Short Form (SF)-36, Visual Impairment Scale (VIS), Swallowing Impairment Scale (SIS), Neck Impairment Scale (NIS), Scar questionnaire (SCAR-Q)]. RESULTS: The rates of transient hypoparathyroidism, permanent hypoparathyroidism, and transient hypocalcemia after surgery in the OT group and RT group were significantly different ( P <0.001). SIS and VIS scores in the two groups were significantly different ( P <0.001). SF-36 showed significant differences ( P <0.001) in the subsections of "physiological function", "body pain", "general health", "vitality", "social function", "role emotional", and "mental health" between the two groups. SCAR-Q showed that the length and appearance of scars showed significant differences between the two groups. CONCLUSIONS: RT with Super-meticulous capsular dissection can protect parathyroid function and improve postoperative QoL, and could be a new option for robot-assisted surgery against thyroid cancer.

PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

BACKGROUND: Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. METHODS: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. RESULTS: Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (Padjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827-0.997) was achieved in the integrated model. CONCLUSIONS: Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.

Association of Long-term Oncologic Prognosis With Minimal Access Breast Surgery vs Conventional Breast Surgery.

Importance: Minimal access breast surgery (MABS) has been used in breast cancer management. However, long-term prognostic data associated with MABS vs conventional breast surgery (CBS) are lacking. Objective: To investigate long-term therapeutic outcomes associated with MABS vs CBS for breast cancer management. Design, Setting, and Participants: In this single-center retrospective cohort study, 9184 individuals were assessed for inclusion. After exclusions, 2412 adult female individuals were included who were diagnosed with stage 0 to III breast cancer, underwent unilateral breast surgery between January 2004 and December 2017, and had no distant metastasis or history of severe underlying disease. Propensity score matching was performed to minimize selection bias. Data were analyzed from January 1, 2004, to December 31, 2019. Exposures: MABS or CBS. Main Outcomes and Measures: Data on demographic and tumor characteristics and long-term outcomes were collected and analyzed. Results: This study included 2412 patients (100% female; median [IQR] age, 44 [40-49] years). Of these, 603 patients underwent MABS (endoscopic, endoscopy-assisted, or robot-assisted procedures in 289, 302, and 12 patients, respectively) and 1809 patients underwent CBS. The median follow-up time was 84 months (93 in the MABS group and 80 months in the CBS group). Intergroup differences were not significant for the following parameters: 10-year local recurrence-free survival (93.3% vs 96.3%; hazard ratio [HR], 1.39; 95% CI, 0.86-2.27; P = .18), regional recurrence-free survival (95.5% vs 96.7%; HR, 1.38; 95% CI, 0.81-2.36; P = .23), and distant metastasis-free survival (81.0% vs 82.0%; HR, 0.95; 95% CI, 0.74-1.23; P = .72). The 5-, 10-, and 15-year disease-free survival rates in the MABS group were 85.9%, 72.6%, and 69.1%, respectively. The corresponding rates in the CBS group were 85.0%, 76.6%, and 70.7%. The intergroup differences were not significant (HR, 1.07; 95% CI, 0.86-1.31; P = .55). The 5-, 10-, and 15-year overall survival rates in the MABS group were 92.0%, 83.7%, and 83.0%, respectively. The corresponding rates in the CBS group were 93.6%, 88.7%, and 81.0%. The intergroup differences were not significant (HR, 1.29; 95% CI, 0.97-1.72; P = .09). Post hoc subgroup analysis showed no significant intergroup differences in disease-free survival. Conclusions and Relevance: In this cohort study, long-term outcomes following MABS were not significantly different from those following CBS in patients with early-stage breast cancer. MABS may be a safe and feasible alternative in this patient population.

Safety and Feasibility of Minimally Invasive (Laparoscopic/Robotic-Assisted) Nipple-Sparing Mastectomy Combined with Prosthesis Breast Reconstruction in Breast Cancer: A Single-Center Retrospective Study.

BACKGROUND: Minimally invasive (robotic or laparoscopic-assisted) nipple-sparing mastectomy combined with prosthesis breast reconstruction (NSM-PBR) is associated with smaller scars and greater patient satisfaction. However, the oncological safety of minimally invasive NSM-PBR remains controversial. PATIENTS AND METHODS: This was a retrospective study of patients with breast cancer who underwent breast reconstruction between 1 January 2006 and 20 February 2021. Demographic and clinicopathological characteristics, operation information, postoperative complications, and survival outcomes were analyzed. RESULTS: In all, 292 patients underwent minimally invasive NSM-PBR and 205 underwent open NSM-PBR for breast cancer. In the minimally invasive NSM-PBR group, 268 (91.8%) patients underwent laparoscopy and 24 (8.2%) patients underwent robot-assisted NSM-PBR. Mean operation time in the minimally invasive NSM-PBR group was significantly longer than that in the open NSM-PBR group (P = 0.023). Mean intraoperative blood loss was significantly less in the minimally invasive NSM-PBR group (P < 0.05). There was no significant between-group difference in total complications. Similarly, there were no significant between-group differences in overall survival, recurrence-free survival, and local recurrence rate (P = 0.450, P = 0.613, and P = 0.679, respectively). CONCLUSIONS: The complication, recurrence, and mortality rates in minimally invasive NSM-PBR group were comparable to those in open NSM-PBR group. Our preliminary results are encouraging and suggest that minimally invasive NSM-PBR affords good cosmetic results and its oncological safety is comparable to that of open surgery.

A Prospective Self-Controlled Study of Indocyanine Green, Radioisotope, and Methylene Blue for Combined Imaging of Axillary Sentinel Lymph Nodes in Breast Cancer.

PURPOSE: This self-controlled study aimed to clarify whether indocyanine green (ICG) could be an alternative tracer in the absence of radioisotope (RI) for combined imaging of axillary sentinel lymph node (SLN) in breast cancer. METHODS: Primary breast cancer, clinically axillary node-negative patients (n = 182) were prospectively enrolled from March 2015 to November 2020. ICG, methylene blue (MB), and RI were used to perform axillary sentinel lymph node biopsy (SLNB). The main observation index was the positivity of ICG + MB vs. RI + MB in axillary SLNB; the secondary observation indicators were the axillary SLN detection rate, mean number of axillary SLNs detected, mean number of metastatic axillary SLNs detected, and safety. RESULTS: All 182 patients had axillary SLNs; a total of 925 axillary SLNs were detected. Pathological examination confirmed metastatic axillary SLN in 42 patients (total of 79 metastatic SLNs). Positivity, detection rate of SLNs, detection rate of metastatic SLNs, and the number of metastatic SLNs detected were comparable with RI+MB and ICG+MB (p > 0.05). The mean number of axillary SLNs detected was significantly higher with ICG+MB than with RI+MB (4.99 ± 2.42 vs. 4.02 ± 2.33, p < 0.001). No tracer-related adverse events occurred. CONCLUSIONS: ICG appears to be a safe and effective axillary SLN tracer, and a feasible alternative to RI in combined imaging for axillary SLN of breast cancer.

Unilateral axilla-bilateral areola approach for thyroidectomy by da Vinci robot vs. open surgery in thyroid cancer: a retrospective observational study.

BACKGROUND: To compare the efficacy and safety of unilateral axilla-bilateral areola (UABA) approach for robot-assisted thyroidectomy with conventional open surgery in thyroid cancer patients. METHODS: The clinicopathological features and surgical outcomes of 194 thyroid cancer patients treated by robotic surgery using the UABA approach and 217 patients treated by open surgery in our department from January 2017 to August 2018 were analysed and compared. RESULTS: The operation time was longer in the robotic group than in the open surgery group. The patients' satisfaction with neck appearance was higher in the robotic group than in the open surgery group (91.2% vs. 21.6%, P<0.01). After total thyroidectomy and central lymph node dissection, the incidence of postoperative transient hypoparathyroidism and postoperative permanent hypoparathyroidism in the open surgery group was 29.7% (44/148) and 6.8% (10/148), higher than that [17.9% (27/151) and 2.0% (3/151)] in the robotic group (P<0.05 respectively). No significant difference was observed in the number of dissected lymph nodes or postoperative serum thyroglobulin (TG) levels or incidence of transient or permanent hoarseness of voice between the two groups. No recurrence or metastasis was found. CONCLUSIONS: Compared with open surgery, UABA robotic surgery preserved the neck appearance and effectively reduced hypoparathyroidism by super-meticulous capsular dissection (SMCD).

Neoadjuvant Pyrotinib plus Trastuzumab and Chemotherapy for Stage I-III HER2-Positive Breast Cancer: A Phase II Clinical Trial.

LESSONS LEARNED: This is the first trial to explore the neoadjuvant therapy of pyrotinib in HER2-positive operable and locally advanced breast cancer, in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab. Results primarily showed that pyrotinib in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab was effective and safe in HER2-positive operable and locally advanced breast cancer. A subsequent randomized controlled trial is still warranted to confirm these results. BACKGROUND: The efficacy and safety of neoadjuvant therapy of pyrotinib, a new irreversible tyrosine kinase inhibitor (TKI), was first estimated in patients with HER2-positive breast cancer in this phase II study, in combination with trastuzumab and chemotherapy. METHODS: Between February 19, 2019, and November 20, 2019, 20 female Chinese patients with stage I-III HER2-positive breast cancer were assigned to receive eight cycles of neoadjuvant pyrotinib (P) in combination with four cycles of epirubicin (E) and cyclophosphamide (C) followed by four cycles of docetaxel (T) and trastuzumab (H), once every 3 weeks, referred to as P + EC-TH. RESULTS: A total of 19 patients completed the therapy and final surgery. The total pathological complete response (tpCR) rate was 73.7% (95% confidence interval [CI], 48.8-90.9), and no recurrence or metastasis occurred during the short-term follow-up period. The objective response rate (ORR) was 100% (95% CI, 82.4-100). The most common adverse events (AEs) were diarrhea and leukopenia in 18 of 20 patients (90%), but no grade 5 AEs were reported. CONCLUSION: This study showed that in HER2-positive operable or locally advanced breast cancer, the tpCR rate of P + EC-TH neoadjuvant therapy was about twice as high as that of EC-TH neoadjuvant therapy reported in other trials, with tolerable side effects.

Long Non-coding Wilms Tumor 1 Antisense RNA in the Development and Progression of Malignant Tumors.

A growing number of studies have shown that long non-coding RNAs (lncRNAs) play an important role in tumor development and progression and are key molecules affecting tumor progression. The lncRNA Wilms tumor 1 antisense RNA (WT1-AS) is specifically expressed in various malignant tumors. In particular, WT1-AS expression is upregulated in colon cancer and breast cancer but is significantly downregulated in cervical cancer, liver cancer, and kidney cancer. The level of WT1-AS expression is closely related to the size, stage, and patient survival rate of these cancers. In this article, we review the modes of action, expression, function, and mechanisms of WT1-AS in different tumors to provide new targets for tumor diagnosis and treatment.

Less micrometastatic risk related to circulating tumor cells after endoscopic breast cancer surgery compared to open surgery.

BACKGROUND: Increase of circulating tumor cells (CTCs) has been found after surgery for various carcinomas but not confirmed for breast cancer, and whether endoscopic surgery confers identical effect to CTCs as open surgery did is not clear. The present study aimed to investigate whether CTCs increase after surgery and whether there is a difference between open surgery and endoscopic surgery. METHODS: Pre- and postoperative peripheral blood (5 mL) obtained from 110 female patients with operable breast cancer (53 underwent endoscopic surgery, 57 underwent open radical mastectomy). Quantitative real-time reverse transcription-PCR was done to detect cytokeratin 19 mRNA-positive CTC. CTC detection rate, cell number and the increase after surgery (named micrometastasis) were compared between the two groups. RESULTS: In the open group, CTC positive rate before and after surgery were 22.81 and 33.33%; median CTC number before and after surgery were 0.21 and 0.43 and 17 patients (29.82%) had increased micrometastatic risk. In the endoscopic group, CTC positive rate before and after surgery were 24.53 and 28.30%; median CTC number before and after surgery were 0.27 and 0.36, and 8 patients (15.09%) had increased micrometastatic risk. There was a suggestive higher postoperative CTC detection rate and CTC number and a significant increased postoperation micrometastatic risk was observed in the open group compared to the endoscopic group (OR = 3.19, 95%CI: 1.05-9.65) after adjustment for clinicopathologic characteristics. DISCUSSION: CTC tends to increase in breast cancer patients after surgery, and the micrometastatic risk was higher for open surgery compared to endoscopic surgery. TRIAL REGISTRATION: This study was prospectively registered at Chinese Clinical Trial Register (ChiCTR-OCH-10000859, 24 April 2010).

Unilateral Axilla-Bilateral Areola Approach for Thyroidectomy by da Vinci Robot: 500 Cases Treated by the Same Surgeon.

Objective: To investigate the efficacy and safety of da Vinci robot-assisted thyroidectomy via an unilateral axilla-bilateral areola (UABA) approach. Methods: The clinical data of 500 patients undergoing robotic thyroidectomy via an UABA approach from July 2014 to April 2018 were retrospectively analyzed. All 500 patients were operated on by the same surgeon and divided into two groups by the time sequence. The efficacy and complications were compared between the two groups. Results: Robotic thyroidectomy via an UABA approach was performed successfully in 500 cases, including 196 cases of benign thyroid diseases with a lesion diameter of 3.1 ± 1.3 cm (0.4 - 8.2 cm) and 304 cases of thyroid cancer with a tumor diameter of 1.2 ± 0.7 cm (0.4 - 4.4 cm). Surgical procedures included unilateral lobectomy and total thyroidectomy with or without central lymph node dissection. Among the 500 patients, 9 (1.8%) had transient recurrent laryngeal nerve injury, 1 (0.2%) had permanent unilateral recurrent laryngeal nerve injury, 12 (2.4%) had subcutaneous hemorrhage of the trajectory area, and 6 (1.2%) had subcutaneous infection of the trajectory area after surgery. Among 239 thyroid cancer patients undergoing total thyroidectomy, 45 (18.8%) had transient hypoparathyroidism and 5 (2.1%) had permanent hypoparathyroidism. The incidence of permanent hypoparathyroidism was 1.9% (4/212) among the patients undergoing total thyroidectomy plus unilateral central lymph node dissection, and 3.7% (1/27) among the patients undergoing total thyroidectomy plus bilateral central lymph node dissection. During the follow-up of median 17 months, all patients were satisfied with postoperative appearance of the neck and no structural recurrence or metastases occurred. There was no significant difference in efficacy between the two groups (P > 0.05), while the complication rate in phase 2 was significantly lower than that in phase 1 (P < 0.05) as the surgeon became more proficient in the UABA approach. Conclusion: Robotic thyroidectomy via an UABA approach is simple, safe, and minimally invasive, suitable for radical resection of large benign tumors and early thyroid cancer and central lymph node dissection.

First report of in-situ preservation of a subcapsular parathyroid gland through super-meticulous capsular dissection during robotic radical thyroidectomy.

PURPOSE: Meticulous capsular dissection can preserve the function of the parathyroid gland in most patients, but it is difficult to identify and preserve the subcapsular parathyroid gland. We performed in-situ preservation of the subcapsular parathyroid gland during robotic radical thyroidectomy using super-meticulous capsular dissection, and evaluated its effect on postoperative parathyroid function. METHODS: A 45-year-old woman was admitted with bilateral thyroid nodules. Color Doppler ultrasound demonstrated a 7 × 7 × 6 mm hypoechoic area in the middle and inferior part of the right lobe and 3 × 3 × 3 mm hypoechoic nodule in the middle part of the left lobe. She was diagnosed with right thyroid papillary cancer by fine-needle aspiration. Robotic bilateral thyroidectomy plus right central lymph node dissection was performed. During the left thyroidectomy, we found that the left inferior parathyroid gland was just under the true capsule. Subsequently, the super-meticulous capsular dissection was performed for in-situ preservation of the parathyroid gland. RESULTS: The patient's serum parathyroid hormone concentration was 43.77 pg/ml before and 37.98 pg/ml after surgery (normal: 15-65 pg/ml). Her blood calcium level was 2.21 mmol/l before and 2.18 mol/l after surgery (normal: 2.10-2.65 mmol/l). CONCLUSIONS: The super-meticulous capsular dissection, which could cut through the true capsule to identify subcapsular parathyroid and protect its anatomic structure as well as blood supply, is recommend for in-situ preservation of subcapsular parathyroid gland during robotic radical thyroidectomy.

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Multicenter cross-sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations.

Due to lack of systematic reviews, BRCA, DNA Repair Associated (BRCA) mutations in the Chinese population are not completely understood. The following study investigates the prevalence and type of BRCA mutations in Chinese patients with high hereditary risk of breast cancer (BC). Patients Drwere recruited from 14 cities between October 2015 and February 2016, and were selected based on family and personal medical history. BRCA mutations were analyzed by collecting blood samples from all participants. 437 BC patients were included. A total of seventy-six (17.4%) mutation carriers were identified with no geographic difference. The mutation rate in the early-onset BC patients was lower compared to family history of breast/ovarian cancer (OC), bilateral BC, male BC, BC&OC or meeting ≥2 criteria (9.2 vs. 21.7, 24.0, 22.2, 16.7 and 24.3%, respectively, P=0.007). A total of 61 mutation sites were identified (BRCA1 32, BRCA2 29) including 47.5% novel sites and extra 10 variants of uncertain significance. A total of five sites were repeated in more than one unrelated patient. A total of 11 sites were associated with hereditary breast and ovarian cancer syndrome, two of which were confirmed by family pedigrees. Compared with BRCA- patients, patients with BRCA1 mutation tended to be triple-negative BC (P<0.001), whereas patients with BRCA2 mutation were more likely to be hormone receptor positive BC (P=0.02). The present study provides a general BRCA mutation profile in the Chinese population. The prevalence of BRCA mutation in BC patients with high hereditary risk is lower compared with Western populations. Chinese mutation type is different with Western people, without obvious founder mutation.

Comparison of sentinel lymph node detection performances using blue dye in conjunction with indocyanine green or radioisotope in breast cancer patients: a prospective single-center randomized study.

OBJECTIVE: This randomized study aimed to compare the clinical efficacy between the novel dual tracer composed of indocyanine green (ICG) and blue dye (BD) and the conventional dual tracer composed of radioisotope and BD for sentinel lymph node (SLN) mapping in patients with breast cancer. METHODS: This study enrolled 471 clinically lymph node-negative patients with primary breast cancer. All patients underwent mastectomy, and those undergoing sentinel lymph node biopsy (SLNB) were randomized to receive blue dye plus radioisotope (RB group) or BD plus ICG (IB group). The detection performances on SLN identification rate, positive SLN counts, detection sensitivity, and false-negative rate were compared between the two groups. RESULTS: In the IB group, 97% (194/200) of the patients who underwent the ICG and BD dual tracer injection showed fluorescent-positive lymphatic vessels within 2-5 min. The identification rate of SLNs was comparable between the IB group (99.0%, 198/200) and the RB group (99.6%, 270/271) (P = 0.79). No significant differences were observed in the identification rate of metastatic SLNs (22.5% vs. 22.9%, P > 0.05, RB group vs. IB group, the same below), positive SLN counts (3.72 ± 2.28 vs. 3.91 ± 2.13, P > 0.05), positive metastatic SLN counts (0.38 ± 0.84 vs. 0.34 ± 0.78, P > 0.05), SLNB detection sensitivity (94.4% vs. 92.5%, P > 0.05), or false-negative rate (5.6% vs. 7.5%, P > 0.05) between the two groups. CONCLUSIONS: ICG can be used as a promising alternative tracer for radioisotope in SLN mapping, and when it is combined with BD in lymphangiography, it offers comparable detection sensitivity compared to the conventional lymphatic mapping strategies that are widely used in clinical practice.

Robot-assisted internal mammary lymph chain excision for breast cancer: A case report.

RATIONALE: Understanding the status of internal mammary lymph nodes of breast cancer is critical in the accurate staging of breast cancer and the development of accurate therapeutic regimen for selected patients. Current techniques for dissection of internal mammary lymph node biopsy involve endoscopic or Traditional thoracic surgery, An important drawback of the current techniques is the great trauma caused by them. PATIENT CONCERNS: Da Vinci robotic surgery system (Intuitive Surgical Inc. Sunnyvale, CA) was used to perform the internal mammary lymph chain excision for a breast cancer patient with left internal mammary lymph node metastasis. DIAGNOSES: Positron emission tomography-computed tomography examination and Ultrasonography examination. INTERVENTIONS: In this paper, we introduce a Robot-assisted technique for dissection of internal mammary lymph node biopsy with only 3 small trocar ports. This technique reduces the incision size and considerably reduce the trauma. OUTCOMES: The operation lasted a duration of 1.5 hours. The operation was carried out smoothly with removal of 9 internal mammary lymph nodes in total. The amount of intra operative bleeding was less than 10 ml. The patient's postoperative recovery was fast. 11-month postoperative follow-up showed that the patient recovered well after surgery, no local recurrence or distant metastasis was found, and no obvious discomfort was reported. LESSONS: Robot-assisted excision of internal mammary lymph chain in breast cancer is a safe, effective and simple operation with minimal invasion.

Endoscopic nipple sparing mastectomy with immediate implant-based reconstruction versus breast conserving surgery: a long-term study.

To evaluate the differences between endoscopic nipple sparing mastectomy (ENSM) with immediate implant-based reconstruction and breast conserving surgery(BCS) applied to early-stage breast cancer in postoperative outcomes, function, and cosmesis. we made a prospective, non-randomized study reviewed a total of 346 cases of breast cancer from January 2007 to December 2011, including 189 cases of BCS and 157 cases of ENSM. All the patients were followed up to April 2016, with a median follow-up time of 74 months. The operative time, blood loss and drainage, postoperative complications, postoperative cosmesis, local recurrence rate, disease-free survival rate and overall survival rate of the two groups were compared. we found out that the operative time of ENSM was longer than that of BCS. There was no difference in blood loss and drainage, the postoperative complications, the disease-free survival rate and overall survival rate between the two groups. In regarding to cosmesis, patients in the ENSM group were more likely to get a satisfactory postoperative breast appearance. we reached a conclusion that ENSM is a safe and effective operative method retainingadvantages of TSSM to further improve the postoperative cosmetic effect, without increasing other risks. The surgery provides a new choice for patients with early-stage breast cancer.

Evaluation of the tracing effect of carbon nanoparticle and carbon nanoparticle-epirubicin suspension in axillary lymph node dissection for breast cancer treatment.

BACKGROUND: Carbon nanoparticle suspension, using smooth carbon particles at a diameter of 21 nm added with suspending agents, is a stable suspension of carbon pellets of 150 nm in diameter. It is obviously inclined to the lymphatic system. There were some studies reporting that carbon nanoparticles are considered as superior tracers for sentinel lymph nodes because of their stability and operational feasibility. However, there were few study concerns about the potential treatment effect including tracing and local chemotherapeutic effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. METHODS: In the current study, a randomized controlled analysis was performed to investigate the potential treatment effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. A total of 90 breast cancer patients were randomly divided into three equal groups: control, tracer, and drug-load groups. The control group patients did not receive any lymphatic tracers, the tracer group patients were subcutaneously injected with 1 ml carbon nanoparticle suspension, and the drug-load group patients were injected with 3 ml carbon nanoparticle-epirubicin suspension at four separate sites around the areola 24 h before surgery. Modified radical mastectomy, endoscopic subcutaneous mammary resection plus axillary lymph node dissection, and immediate reconstruction with implants or breast-conserving surgery were performed. RESULTS: The mean number of the dissected lymph nodes per patient was significantly higher in the tracer (21.3 ± 6.1) and drug-load (19.5 ± 3.7) groups than in the control group (16.7 ± 3.4) (P < 0.05). Most lymph nodes in the former two groups were stained black (75.7 and 73.3 %, respectively), but with no significant difference between the groups. Most metastatic lymph nodes were also stained black in the tracer group (68.6 %) and drug-load group (78.1 %) and with no significant difference between the groups (P = 0.198). Microscopic examination revealed that the carbon nanoparticles were localized around or among the cancer cell masses and residues of necrotized cancer cells surrounded by fibroblastic proliferation could be found within the stained lymph nodes in the drug-load group. CONCLUSIONS: The majority of axillary lymph nodes were stained black by the suspension of carbon nanoparticles, which helped identify the lymph nodes from the surrounding tissues and avoided aggressive axillary treatment. Thus, a combination therapy of carbon nanoparticles with epirubicin could play an important role in lymphatic chemotherapy without affecting tracing. TRIAL REGISTRATION: ChiCTRTRC13003419.