[Current trend of breast cancer neoadjuvant treatment in China: a cross-sectional study].

Objective: To investigate the current trend of breast cancer neoadjuvant therapy and provide reference for the improvement of breast cancer clinical guideline in the future. Methods: Questionnaires of cross-sectional survey were sent to 110 hospitals (breast cancer surgery quantity surpassing 200) between July 2018 and September 2018. The stages and subtypes, therapeutic regimen, treatment assession, operation choice and preforming of patients underwent neoadjuvant therapy were recorded. Results: Neoadjuvant treatment has been performed in all of the 110 hospitals. The total number of breast patients underwent neoadjuvant therapy was about 14 550 (17.0% in surgical patients) in 2017. For all of the neoadjuvant patients, the proportion of stageⅡ patients was less than 30% in 81 hospitals, and the proportion of stage Ⅲ was more than 50% in 84 hospitals. The numbers of estrogen receptor (ER) (+ )/human epidermal growth factor receptor-2 (HER-2) (-), ER (-)/HER-2 (+ ) and triple negative subtype breast cancer patients were 3 550 (24.4%), 6 024 (41.4%) and 4 991 (34.3%), respectively. Patient's scruples of relatively delayed operation and weak will of breast conservation after neoadjuvant therapy were the majority reasons for neoadjuvant therapy restriction. Anthracycline followed by taxane was the most usual neoadjuvant therapeutic regimens in 53.6% hospitals, and anthracycline plus taxane was the first choice in 42.7% hospitals. Chemotherapy with targeting therapy was recommended to HER-2 positive neoadjuvant patients in 80.9% hospitals. To assess treatment outcome of neoadjuvant treatment, 42.7% hospitals used MRI in more than 50% patients while the usage rate of MRI was less than 20% in 37.3% hospitals. The proportions of hospital using repeat-marking, tattoo and metal clip as the first method to identify the primary tumor region and lymph nodes were 60.0%, 29.1% and 10.9%, respectively. Breast-conservation rate after neoadjuvant therapy was less than 20% in 87.3% hospitals. Conclusions: Neoadjuvant therapy for breast cancer is widely performed in most hospitals in China, while the proportion of neoadjuvant treatment in patients with operable breast cancer is still low. Meanwhile, the idea of achieving de-escalation operation through neoadjuvant treatment is not promoted and the therapeutic evaluation method of neoadjuvant treatment needs further studies to improve.

[A single-center retrospective study on axillary evaluation in 1 557 breast ductal carcinoma in situ patients between 2006 and 2016].

Objectives: To examine the influence factors on axillary evaluation in ductal carcinoma in situ (DCIS) patients, and the prognosis of different choices of axillary evaluation in a single-center retrospective study. Methods: Totally 1 557 DCIS patients admitted in Department of Breast Surgery, Fudan University Shanghai Cancer Center from January 2006 to November 2016 were retrospectively enrolled. All patients were female. The median age was 49 years (range: 21 to 85 years). Surgical methods included modified radical mastectomy, simple mastectomy (with or without axillary evaluation) and breast conservation surgery (with or without axillary evaluation). Axillary evaluation included axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). T tests, χ(2) test and Logistic regression analysis was used to analyze influence factors on axillary evaluation, respectively. Kaplan-Meier curve and Log-rank analysis were used to evaluate recurrence-free survival (RFS) and loco-regional recurrence-free survival (LRRFS) in patients with different surgical methods. Results: Among the 1 557 DCIS patients, there were 1 226 cases received axillary evaluation, while 331 cases not received axillary evaluation. Patients were separated into 3 groups by different axillary evaluation choices: SLNB group (957 cases, 61.46%), ALND group (197 cases, 12.65%) and no evaluation group (403 cases, 25.88%). The patients in SLNB group increased significantly (P=0.000), from 3.85% (60/1 557) in 2006 to 75.19% (1 170/1 557) in 2016. The independent influence factors of receiving axillary evaluation were high nuclear grade (OR=3.191, 95%CI: 1.722 to 5.912, P=0.001) and tumor size>15 mm (OR=1.698, 95%CI: 1.120 to 2.573, P=0.012). Also, patients received breast conservation surgery were more likely to refuse axillary evaluation (OR=0.155, 95%CI: 0.103 to 0.233, P=0.000). There were no significant differences in RFS and LRRFS in patients with different axillary evaluation choices. Conclusions: The investigation in trends and influence factors of different axillary evaluation choices provided basis on surgical precision medicine in DCIS patients. Patients received SLNB increased significantly. The independent influence factors of axillary evaluation were nuclear grade, tumor size and surgical methods. There was no significant differences in prognosis among the groups receiving different axillary evaluations.

[Current practice of implant-based breast reconstruction: results from China national practice questionnaire survey].

Objective: To explore the current clinical practice of implant-based breast reconstruction (IBBR) in China. Methods: The current survey was sponsored by Chinese Anti-Cancer Association, Committee of Breast Cancer Society and Chinese Society of Breast Surgeons. A survey was mailed to 110 hospitals in China, which have more than 200 breast cancer operations performed in 2017. The survey mainly included questions on the clinical practice of IBBR, sociodemographic and geographical factors associated with IBBR practice, reasons and concerns for selecting IBBR, type and timing of breast reconstruction, and the complications of IBBR. Data were analyzed using χ(2) test, Fisher's exact test or Kruskal-Wallis rank sum test. Results: IBBR was available in 86.4% (95/110) included hospitals. It was predominantly performed breast reconstruction surgery, the proportion of IBBR in all the breast reconstruction was 65.75% (4 296/6 534). However, the rate of IBBR in all the patients received mastectomy was only 7.06% (4 296/60 877). Among all the included hospitals, the number of implant reconstructions performed in 2017 was 24 (57.5) cases (M(Q(R)), range: 2-565 cases). Factors associated with the performance of IBBR including regional per capita gross domestic product (H=10.47, P=0.005) and annual surgery volume (H=8.30, P=0.016). The main reasons for choosing IBBR were relatively simple surgical procedure, short learning curve and short operation time. The effects of adjuvant radiotherapy on prosthesis, postoperative complications and patient satisfaction were the main concerns for implant reconstruction. Compared with delay reconstruction, a higher proportion of IBBR was observed in immediate reconstruction (83.1% vs. 62.0%, χ(2)=12.522, P=0.000). In all, 10.5% (10/95) hospitals reported more than 10% grade Ⅲ to Ⅳ capsular contracture. The incidence of infections need surgical intervention was reported between 10% and 20% by 4.2% (4/95) hospitals. Hospitals with 6% to 10% implant rupture and 6% to 15% implant removal were 1.1% (1/95) and 4.2% (4/95) respectively. Conclusions: IBBR was the most common used surgery in breast reconstruction after mastectomy. However, the proportion of IBBR in patients after mastectomy was still low. Reginal economy, surgery volume of hospitals, lack of specialty training program and the concern about complications and patient's satisfaction were the factors affecting the development of IBBR.

[Current trends of breast reconstruction after mastectomy in China: a cross-sectional study].

Objective: To investigate the current trends of breast reconstruction(BR) after mastectomy in China. Methods: A list of hospitals with more than 200 cases of breast cancer surgery per year nationwide was obtained, and 110 institutions were selected according to the geographical distribution. The research was conducted in the form of a questionnaire survey, and 92.3% (169/183) of the questions were single-choice questions. Information such as demographics of surgeons and hospitals, number of mastectomy and BR, type and timing of BR was included in the survey. Survey formal notification letter was issued by the China Anti-Cancer Association Breast Cancer Committee and Chinese College of Surgeons, Committee of Mammary Surgeons. Questionnaires were sent to the respondents of each center by email. The survey time range was from January 1, 2017 to December 31, 2017. All data were completely collected before September 7, 2018. Results: A total of 110 units participated in the survey. In total, 87.3% (96/110) of the hospitals have conducted BR surgery. The BR after mastectomy was 10.7% (6 534/61 099), among this, implant BR accounted for 65.7%(4 296/6 534), autologous BR accounted for 20.1% (1 312/6 534), and autologous combined implant BR accounted for 14.2% (927/6 534). Immediate reconstruction accounted for 67.6% (4 417/6 534) of BR, while delayed BR accounted for 32.4% (2 097/6 534). In 2017, 77.8% (35/45) of the plastic surgery departments cooperated with general surgery departments. General BR could be conducted after mastectomy accounted for 83.6% (92/110). The proportion of reconstruction was positively correlated with the gross domestic product (GDP) per capita (r=0.311, P=0.002). The one-step implant-based BR(IBBR) was the most preferred type in immediate BR. Two-step IBBR was the most preferred method in delayed BR. Hospitals that routinely evaluated aesthetics after BR accounted for 64.6% (62/96), while only 16.7% (16/96) of hospitals used patient-reported outcome measure (PROM). The most commonly used PROM tool was BREAST-Q. Conclusions: The overall BR in China is on upward trend, but gap between China and the developed countries still exists. Breast surgery departments should strengthen further cooperation with plastic surgery departments. Simultaneously, the aesthetics evaluation and PROM after BR should be put a high premium.

[Incidental internal mammary lymph node biopsy in 113 cases of breast cancer undergoingfree abdominal flap breast reconstruction and its influencing factors].

Objective: The aim of the current study is to determine the clinical value of incidental internal mammary lymph node biopsy in free abdominal flap breast reconstruction using internal mammary vessels as recipient vessels and to investigate the risk factors of internal mammary lymph nodes metastasis. Methods: The clinical data of all patients who underwent free abdominal flap breast reconstruction using internal mammary vessels as recipient vessels from November 2006 to December 2015 in the Department of Breast Surgery, Fudan University Shanghai Cancer Center were reviewed in the study. The incidence of internal mammary lymph node biopsy and the rate of metastasis were analyzed. Statistical analysis was conducted to evaluate the risk factors of internal mammary lymph node metastasis. Results: A total of 113 patients met the inclusion criteria, 53 (46.9%) of whom had internal mammary lymph nodes harvested. Four of these were positive for metastatic disease, all in immediate breast reconstructions. The incidence of metastasis was 7.5% in patients who had successful internal mammary lymph node biopsies.The multi-variate Logistic regression analysis showed that invasive tumor size, tumor location and axillary lymph node metastasis were not risk factors for internal mammary lymph node metastasis (P>0.05). Conclusions: Internal mammary lymph nodes found incidentally during recipient vessel exposure may provide important information about internal mammary lymph node metastasis in free flap breast reconstruction. This approach for internal mammary lymph node biopsy reveals an appreciable success rate and is convenient in clinical practice. The size of invasive tumor and the axillary lymph node metastasis are probably associated with internal mammary lymph node positivity.

Primary presacral adenocarcinoma: a case report and review of the literature.

Primary presacral adenocarcinoma is a rare presacral lesion. We report a 36-year-old male patient with -primary presacral adenocarcinoma. The patient presented with a six-month history of sacrococcygeal pain. MRI demonstrated a 4×3 cm2, well-defined presacral mass. He underwent a parasacrococcygeal procedure with complete resection of the -tumor, which subsequent histology showed adenocarcinoma. At 15 months follow-up, he remains disease free.

Comparison of molecular analysis and touch imprint cytology for the intraoperative evaluation of sentinel lymph nodes in primary breast cancer: results of the China Breast Cancer Clinical Study Group (CBCSG) 001c trial.

BACKGROUND: To validate the clinical value of the One-Step Nucleic Acid Amplification (OSNA) Breast Cancer System for the intraoperative detection of sentinel lymph node (SLN) metastases in early-stage breast cancer patients in a Chinese population, a prospective, multicenter trial, the China Breast Cancer Clinical Study Group (CBCSG)-001c trial, was conducted. The present study focused on the prospective comparison of the performance between OSNA and touch imprint cytology (TIC). METHODS: The retrieved SLNs were divided into sections. Alternate slices from the tissue blocks were subjected either to OSNA analysis or to postoperative histopathology evaluation through serial sectioning. TIC was performed on every sample surface of each tissue block and was used by the surgeon to determine whether to perform an immediate ALND. RESULTS: A total of 552 patients qualified for the analysis. The sensitivity, specificity, and overall accuracy of OSNA were 87.8%, 89.6%, and 88.4%, respectively, on a per-patient basis compared with those of TIC, which were 81.3%, 96.9%, and 92.0%, respectively. OSNA detected more micrometastasis-involved nodes than TIC (52.8% vs. 25.0%; p = 0.029) on a per-node basis. Tissue allocation bias (TAB) was the main cause of discordant results. The performance of TIC varied significantly among the institutes, while the performance of OSNA was steady. CONCLUSIONS: Both OSNA and TIC can serve as qualified intraoperative assessments of SLNs. For institutes lacking the support of experienced cytopathologists, OSNA can be the first choice for the intraoperative assessment. In addition, OSNA can be applied as a complement to histopathology assessment. However, the results of the present study do not support the routine application of OSNA in the entire SLNs in place of pathology with serial sectioning.

PPAR signaling pathway may be an important predictor of breast cancer response to neoadjuvant chemotherapy.

PURPOSE: Neoadjuvant chemotherapy for advanced breast cancer may improve the radicality for a subset of patients, but others may suffer from severe adverse drug reactions without any benefit. To predict the responses to chemotherapy, we performed a phase II trial of neoadjuvant chemotherapy using a weekly PCb [paclitaxel (Taxol) plus carboplatin] regimen for stage II/III breast cancer and assessed the correlation between baseline gene expression and the tumor response to treatment. METHODS: A total of 61 patients with stage II-III breast cancer were included and administered four cycles of preoperative PCb. We performed a gene expression analysis using Affymetrix HG-U133 Plus 2.0 GeneChip arrays in 31 breast cancer tissues. Differentially expressed genes (DEGs) were identified by the significance analysis of microarrays (SAM) program using a false discovery rate of 0.05. The Functional Annotation Tool in the DAVID Bioinformatics Resources was used to perform the gene functional enrichment analysis. The other 30 patients (15 pCR and 15 non-pCR patients) were available as an independent validation set to test the selected DEGs by quantitative real-time PCR analysis (qRT-PCR). RESULTS: By analyzing six pathological complete response (pCR) patients and 25 patients with non-pCR, 300 probes (231 genes) were identified as differentially expressed between pCR and residual disease by the SAM program when the fold change was >2. The gene functional enrichment analysis revealed 15 prominent gene categories that were different between pCR and non-pCR patients, most notably the genes involved in the peroxisome proliferator-activated receptor (PPAR), DNA repair and ER signal pathways and in the immune-related gene cluster. The qRT-PCR analysis results for the genes in the PPAR pathway (LPL, SORBS1, PLTP, SCD5, MMP1 and CSTA) in independent validation set were consistent with the results from the microarray data analysis. CONCLUSION: In the present study, we identified a number of gene categories pertinent to the therapeutic response. We believe that the PPAR pathway may be an important predictor of genes that are involved in the chemotherapy response.

Systematic review and meta-analysis of randomized controlled trials comparing stapled haemorrhoidopexy with conventional haemorrhoidectomy.

BACKGROUND: This paper compares stapled haemorrhoidopexy with conventional haemorrhoidectomy for the treatment of haemorrhoids. METHODS: An electronic literature search was undertaken to identify primary studies and systematic reviews. Results on efficacy and safety were analysed. A meta-analysis was conducted to examine long-term outcomes. RESULTS: Twenty-nine randomized clinical trials recruiting 2056 patients were identified. Meta-analysis showed that stapled haemorrhoidopexy was less painful than conventional haemorrhoidectomy. Stapled haemorrhoidopexy required a shorter inpatient stay (weighted mean difference (WMD) -0.95 (95 per cent confidence interval (c.i.) -1.32 to -0.59) days; P < 0.001) and operating time (WMD -11.42 (95 per cent c.i. -18.26 to -4.59) min; P = 0.001). It was also associated with a faster return to normal activities (WMD -11.75 (95 per cent c.i. -21.42 to -2.08) days; P = 0.017). No significant difference was noted between the two techniques in terms of the total incidence of complications. Stapled haemorrhoidopexy was associated with a higher rate of recurrent disease (relative risk 2.29 (95 per cent c.i. 1.57 to 3.33); P < 0.001). CONCLUSION: Stapled haemorrhoidopexy offers some short-term benefits over conventional operation but the total complication rates are similar for both techniques. Stapled haemorrhoidopexy is associated with a higher rate of recurrent disease.

Suppression of telomerase activity and cytokine messenger RNA levels in acute myelogenous leukemia cells in vivo in patients by amifostine and interleukin 4.

High levels of telomerase activity and high rates of cell proliferation are associated with a poor prognosis in acute myelogenous leukemia. Furthermore, cytokine production by leukemia cells is believed to play an important role in determining the proliferative characteristics of leukemia. The in vivo effects of two noncytotoxic agents on these parameters were determined in 33 acute myelogenous leukemia patients. Three daily doses of interleukin (IL) 4 or a single dose of amifostine reduced telomerase activity in the leukemia marrow cells in 7 of 9 and 11 of 13 patients, respectively. The administration of a single dose of amifostine resulted in a reduction in tumor necrosis factor alpha and IL-6 transcript levels in the marrow cells of 10 of 13 and 12 of 13 patients in which these transcripts were present. The administration of only three doses of IL-4 or a single dose of amifostine has a significant effect on leukemia cell parameters, which are believed to have a significant impact on the in vivo biology of the disease and on its response to remission induction therapy.

Versican enhances locomotion of astrocytoma cells and reduces cell adhesion through its G1 domain.

Versican is a large extracellular proteoglycan and is expressed in a variety of tissues including the central nervous system. A malignant astrocytoma cell line U87 with high motility expressed a higher level of versican than another malignant astrocytoma cell line U343 with lower motility. We observed that the U87 cells were less adherent to tissue culture plates than the U343 cells. To investigate the role of versican in astrocytoma cell migration, we generated recombinant products of a mini-versican construct expressed in COS-7 cells. We found that the mini-versican products enhanced astrocytoma cell migration. Furthermore, enhanced migration was promoted by the G1 domain but not the G3 domain of versican. We introduced culture medium containing products of the mini-versican, the G1, and the G3 constructs separately into the astrocytoma cell lines U87 and U343. The mini-versican and the G1 construct, but not the G3 construct, were shown to reduce astrocytoma cell adhesion. The present data suggest that versican exerts its effect on astrocytoma cell migration and adhesion through the G1 domain.

Identification of a common hyaluronan binding motif in the hyaluronan binding proteins RHAMM, CD44 and link protein.

We have previously identified two hyaluronan (HA) binding domains in the HA receptor, RHAMM, that occur near the carboxyl-terminus of this protein. We show here that these two HA binding domains are the only HA binding regions in RHAMM, and that they contribute approximately equally to the HA binding ability of this receptor. Mutation of domain II using recombinant polypeptides of RHAMM demonstrates that K423 and R431, spaced seven amino acids apart, are critical for HA binding activity. Domain I contains two sets of two basic amino acids, each spaced seven residues apart, and mutation of these basic amino acids reduced their binding to HA--Sepharose. These results predict that two basic amino acids flanking a seven amino acid stretch [hereafter called B(X7)B] are minimally required for HA binding activity. To assess whether this motif predicts HA binding in the intact RHAMM protein, we mutated all basic amino acids in domains I and II that form part of these motifs using site-directed mutagenesis and prepared fusion protein from the mutated cDNA. The altered RHAMM protein did not bind HA, confirming that the basic amino acids and their spacing are critical for binding. A specific requirement for arginine or lysine residues was identified since mutation of K430, R431 and K432 to histidine residues abolished binding. Clustering of basic amino acids either within or at either end of the motif enhanced HA binding activity while the occurrence of acidic residues between the basic amino acids reduced binding. The B(X7)B motif, in which B is either R or K and X7 contains no acidic residues and at least one basic amino acid, was found in all HA binding proteins molecularly characterized to date. Recombinant techniques were used to generate chimeric proteins containing either the B(X7)B motifs present in CD44 or link protein, with the amino-terminus of RHAMM (amino acids 1-238) that does not bind HA. All chimeric proteins containing the motif bound HA in transblot analyses. Site-directed mutations of these motifs in CD44 sequences abolished HA binding. Collectively, these results predict that the motif of B(X7)B as a minimal binding requirement for HA in RHAMM, CD44 and link protein, and occurs in all HA binding proteins described to date.

[AgNOR of gastational trophoblastic tumors and its clinical significance].

A total of 120 paraffin-embedded gestational trophoblastic tumor tissue blocks was selected and divided into 5 groups: (1) 20 cases of normal chorionic villi. (2) 40 cases of hydatidiform mole with no malignant change during a following-up period of at least two years. (3) 40 cases of hydatidiform mole which developed into invasive mole or choriocarcinoma. (4) 10 cases of invasive mole. (5) 10 cases of choriocarcinoma. Nucleolar organizer regions (NORs) was Ag-stained and AgNOR dots were counted using the Plotion's method. The result showed that there was significant difference between group 1 and group 2 (P < 0.005), group 2 and group 3 (P < 0.001), group 3 and group 4 (P < 0.05). Taking the AgNOR count 4.00 as a standard, 75% of the cases in group 2 (mean = 2.730) was below this standard. The study suggested that with the increase of malignancy of trophoblastic tumor, the AgNOR count increased correspondingly. A quantitative study of AgNOR might be a useful measure to detect the early malignant change of hydatidiform mole.