Background: Prognostic assessment after preoperative systemic therapy (PST) plays a vital role in determining treatment in breast cancer patients. Many researchers have sought to develop a system to quantitate residual tumor and its correlation with prognosis after PST. This retrospective study validated the CPS + EG staging system and Neo-Bioscore in a single center in China. Methods: Data from patients with non-metastatic primary breast cancer who were treated with PST and surgery from Jan. 2008 to Dec. 2014 at the Breast Disease Center of Peking University First Hospital, China, were reviewed. DFS, DSS and OS were calculated using the K-M curve and AUC. Multivariate analysis was used for a Cox proportional hazards model. All calculations were performed with SAS 9.4. Results: A total of 403 patients were enrolled in this study. The median follow-up period was 45 (range 11-107) months. The five-year DFS, DSS and OS rates were 86.4%, 91.2% and 90.5%, respectively. The CS, PS, CPS + EG staging system and Neo-Bioscore stratified patients according to DFS, DSS, and OS after PST, with all P values < 0.0001. The CPS + EG staging system and Neo-Bioscore stratified prognosis after PST better than CS. HER2-positive patients without trastuzumab treatment had obviously worse DFS and OS than other subgroups with different HER2 statuses that scored a 3 in the Neo-Bioscore system. Conclusions: The CPS + EG staging system and Neo-Bioscore can improve prognostic prediction in non-pCR breast cancer patients after PST and, provided unfavorable prognostic factors such as insufficient treatment are incorporated, will have broader clinical applicability. (C) 2018 Elsevier Ltd. All rights reserved.

OBJECTIVE:This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness.METHODS:Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined.RESULTS:TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells.CONCLUSION:TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

OBJECTIVE:To investigate the relationship between Ki67 expression and tumor response to neoadjuvant chemotherapy with anthracyclines plus taxanes in breast cancer. METHODS:From January 2008 to June 2009, 129 patients with primary breast invasive ductal cancer received neoadjuvant chemotherapy with anthracyclines plus taxanes. The expression of Ki67 in the tumor tissues was determined by using immunohistochemistry with core needle biopsy specimens prior to the chemotherapy. The tumor response to the chemotherapy was evaluated by dynamic enhanced MRI based on RECIST2000 criteria, pathologic response was assessed according to Miller-Payne grading system, and the clinical comprehensive response was evaluated based on MRI combined with pathologic response. RESULTS:Dynamic enhanced MRI classified 87 cases (67.4%) as effective. According to the Miller-Payne grading system, 99 cases (76.7%) were ranged effective. One hundred and ten cases (85.5%) were recognized as clinically comprehensive effective. The effective rates of neoadjuvant chemotherapy in patients with a Ki67 expression >10% evaluated by the above-mentioned three standards were 73.2%, 81.4% and 89.7%, respectively; and those in patients with a Ki67 expression < or = 10% were 50.0%, 62.5% and 71.9%, respectively. Compared with patients with a Ki67 expression < or = 10%, the patients with a Ki67 expression >10% had better response rates determined by all the three standards (P values were 0.020, 0.030 and 0.010, respectively). The Ki67 expression in the tumor tissue was linearly correlated with clinically comprehensive response on the Linear-Linear association analysis. CONCLUSIONS:There is a statistic association between Ki67 expression and tumor response to the neoadjuvant chemotherapy with anthracyclines plus taxanes in breast cancer, and the patients with a higher expression of Ki67 has a better tumor response to the chemotherapy.

BACKGROUND:Adjuvant chemotherapy has become an important component of standard therapy for breast cancer. However, until now, there have been few reports on the surgical site infections (SSI) after breast cancer surgery, specially after adjuvant chemotherapy. To study the risk factors of SSI of breast cancer, we analyzed patients diagnosed with breast cancer and treated with surgery.METHODS:Fifty-five patients diagnosed with breast cancer and received breast conserving or modified radical operations in our hospital during January 2008 to March 2008 were selected. Factors (patients' age, body mass index (BMI), diabetes mellitus, no or administered adjuvant chemotherapy, with or without onset of myelosuppression and the degree, surgical approaches, duration of operation, postoperative drainage duration and total drainage volume) associated with SSI were retrospectively reviewed and statistically analyzed by single factor analysis.RESULTS:Five patients suffered SSI (5/55, 9.1%); nineteen receiving adjuvant chemotherapy experienced Grade III + myelosuppression, among which 4 had SSI; only 1 out of the remaining 36 patients without adjuvant chemotherapy had SSI. The difference between the two groups was significant (P = 0.043). The incidence of SSI in patients with post-operative drainage tube indwelling longer than 10 days was 5/21, whereas no SSI occurred in that less than 10 days (P = 0.009). In our study, there was no significant difference in other associated factors.CONCLUSIONS:Concurrent Grade III + myelosuppression after adjuvant chemotherapy is an important risk factor of SSI in breast cancer and needs further study. No SSI was detected with indwelling time of post operative drainage less than 10 days.

Objective To investigate the association between transforming growth factor β3 gene(TGFβ3) CA repeat variant and nonsyndromic cleft lip with or without cleft palate(nsCL/P) in Chinese newborns.Methods TGFβ3 CA variant was detected using PCR-SSCP for DNA samples from 170 triads with nsCL/P affected children.We performed the Transmission/disequilibrium test(TDT),Haplotype-Based Haplotype Relative Risk(HHRR) and the family-based association study(FBAT) to test the associations between this variant and risk of nsCL/P.Results Although no significant distortion of A allele at TGFβ3 CA variant in nsCL/P families was found using TDT(OR=1.38,95 %CI 0.93~2.06) and HHRR(OR=1.31,95 %CI 0.93~1.84) analysis(P0.05),a significant association was detected between the TGFβ3 CA variant and their risk of having nsCL/P under FBAT models.Conclusion TGFβ3 CA variant may be a risk factor for nsCL/P in Chinese newborns,but further research is warranted with a larger sample size.

OBJECTIVE:To evaluate the role of breast B ultrasonography and magnetic resonance imaging in assessing the tumor response to neoadjuvant chemotherapy in breast cancer.METHODS:Eighty-five patients with breast cancer diagnosed by core needle biopsy received neoadjuvant chemotherapy entered this prospective study. Breast B ultrasonography and dynamic enhanced MRI was performed before chemotherapy induction, after the second course and the fourth course of chemotherapy prior to the surgery. Clinical evaluation was made through the tumor reduction measured by B ultrasonography and MRI, based on the response evaluation criteria in solid tumors (RECIST).RESULTS:Measured by dynamic enhanced MRI, 56 patients got partial response (PR), 27 got stable disease (SD) and 2 got progressive disease (PD), none complete response (CR). Measured by B ultrasonography, 52 patients got PR, 31 got SD, 2 got PD, no CR. Residual tumor size after chemotherapy on MRI correlated well with post-operative pathologic findings (r = 0.783, P < 0.05), and B ultrasonography correlated moderately with microscopic findings (r = 0.576, P < 0.001).CONCLUSION:Dynamic enhanced MRI is a reliable method to evaluate tumor response to neoadjuvant chemotherapy in breast cancer.

Objective To determine the factors associated with hypospadias in male births in some areas of China. Methods The data was obtained from records of birth defects surveillance system in 27 cities and counties in Jiangsu, Zhejiang and Hebei Provinces in China during January 1, 1993 and December 31, 2000. The study population included all male live births,fetal deaths and still births with gestational age of 20 or more weeks. Results The results of univariate analysis were: living in southern areas or urban areas, the maternal occupation were not farmers or workers in a township factory, the education of the mother were higher than senior middle school, the paternal occupation were not farmers or workers in a township factory, twins or triplets, low birthweight, small for gestational age and preterm were the factors associated with the prevalence of hypospdias in male births (P0.05). The results after adjusted the confounding effect with multivariate logistic model were: living in southern areas (OR=2.051,95 % CI:1.296-3.248), small for gestation age (OR=20.338,95 % CI:13.667-30.265) and preterm (OR=2.710,95 % CI:1.817-4.042) were the factors associated with the prevalence of hypospdias in male births. Conclusions More researches need to focus on the etiology and prevention of hypospadias in southern area in China, and small for gestation age and preterm may share the cauases with hypospadias.

Objective To analyze the risk factors of delayed breast cellulitis(DBC) after breast conserving surgery in breast cancer.Methods The clinical data of 152 patients received breast conserving surgery during January 2001 to December 2006 in Breast Disease Center of Peking University First Hospital were analyzed retrospectively.All the patients were identified by the accepted criteria: diffuse breast erythema,edema,tenderness,and warmth occurring 3 months after definitive surgery and 3 weeks after radiotherapy.Forteen patients were diagnosed DBC.Results The incidence of DBC in the group was 9.2%(14/152).The median time to onset of DBC was 6.2 months after breast conserving surgery.Primary tumor T stage,upper outer quadrant tumor,15 axillary lymph nodes removed and the breast hematoma/seroma after surgery,were significantly associated with DBC.Age,diabetes,neoadjuvant chemotherapy,positive axillary lymph nodes metastasis were not the factors associated with DBC.Conclusion Lymphatic drainage damaged by surgery procedures and radiotherapy maybe the most important factors contributed to the onset of DBC.

1 病历简介 例1 女性,55岁.因"左乳头血性溢液20d"于2006-02-23入院.查体:双侧乳房未及肿物.双腋窝未及肿大淋巴结.既往患高血压病,2型糖尿病,剖宫产术后,胆囊切除术后.已绝经,月经、婚育史无特殊.否认乳腺癌、卵巢癌家族史.

1 病历简介 病人女,58岁.主因"发现右腋下肿物2周"于2007年5月21日入院.查体:右腋窝4cm×5cm肿物,无红肿,质硬,活动好,无压痛,与皮肤无粘连.双侧乳腺触诊弥漫性增厚,左侧腋窝及双侧锁骨上未触及肿大淋巴结.月经、婚育史无特殊,否认乳腺癌、卵巢癌家族病史.

BACKGROUND:There are no large randomized trials of the effect of folic acid dosing regimens on blood folate and homocysteine concentrations.OBJECTIVE:We aimed to evaluate the changes in folate and homocysteine concentrations in response to different folic acid doses and to withdrawal in young women not exposed to other sources of folic acid.DESIGN:Women (n = 1108) were randomly assigned to 1 of 6 intervention groups for which daily intakes of folic acid for 6 mo were 100 microg 1 time/d, 25 microg 4 times/d, 400 microg 1 time/d, 100 microg 4 times/d, 4000 microg 1 time/d, or 4000 microg 1 time/wk. Plasma and red blood cell folate and homocysteine concentrations were measured at baseline; at 1, 3, and 6 mo; and 3 mo after the discontinuation of folic acid.RESULTS:Folate and homocysteine concentrations were not different at baseline between the groups who had the same daily intake of folic acid as a single dose or multiple doses (P = 0.058). Plasma folate concentrations plateaued at 3 mo with 108% (95% CI: 97.7%, 120%), 259% (95% CI: 240%, 279%), 460% (95% CI: 417%, 503%), and 142% (95% CI: 123%, 162%) observed increases for the folic acid groups receiving 100, 400, and 4000 microg/d and 4000 microg/wk, respectively. The rate of reduction in folate concentrations during the 3 mo after cessation of folic acid was dose-dependent-higher intakes were associated with faster reductions.CONCLUSIONS:Changes in folate and homocysteine concentrations were unaffected by different dosing schedules. After folic acid cessation, blood folate declined rapidly, which indicated that the intervention-enhanced folate status was rapidly diminished.

OBJECTIVE:To study the association between transforming growth factor alpha gene (TGFalpha) TaqI variant and nonsyndromic cleft lip with or without cleft palate (nsCL/P) in Chinese population.METHODS:TGFalpha TaqI variant was detected using polymerase chain reaction-restriction fragment length polymorphism for DNA samples of the 149 triads with nsCL/P affected child. We performed the Transmission/disequilibrium test and the family-based association study (FBAT) to identify the associations between this variant and risk of nsCL/P.RESULTS:Significant distortion of C2 allele at TGFalpha TaqI locus in nsCL/P groups (P > 0.05) was not found. In the family-based association test, C2 allele and offspring C2C1 genotype was not found to be significantly associated with an increase risk of nsCL/P (P > 0.05).CONCLUSION:Our findings did not suggest an association between offspring TGFalpha TaqI variant and the increased risk of nsCL/P in Chinese population.

Objective To obtain a better understaning of the clinical features of Castleman tumor associated paraneoplastic pemphigus. Methods The clinical features and therapy of 10 cases of this disease, diagnosed in the Department of Dermatology of Peking University First Hospital were analyzed. Results Castleman tumor was shown to be the most common neoplasm associated with paraneoplastic pemphigus in China. The clinical presentations, histopathologic characteristics, CT scan findings, and immunologic features were all unique. The early diagnosis and removal of the Castleman tumor are crucial for the treatment of this tumor-associated autoimmune disease. Conclusions Because Castleman tumor is directly related to the induction of autoimmunity, early diagnosis and prompt removal of the tumor are essential to the management of this disease.

目的研究胃肠道间质瘤(gastrointestinal stromal tumors,GISTs)病理诊断特征及临床治疗方法.方法对北京大学第一医院1990年1月至2001年8月收治的GISTs进行光镜和超微结构复检,用EnVision二部法免疫组织化学方法检测波形蛋白、CD117(c-kit)、CD34等8种抗原标记物在肿瘤中的表达情况.并对其中临床资料完整的30例病人的病理特点、外科治疗及预后进行回顾性分析.结果复检确诊GISTs 87例,占同期胃肠道肿瘤的2%(87/3016),30例病人中恶性21例,良性7例,交界性2例;恶性者10例复发,复发率为47%(10/21),其中8例死亡,5年生存率为62%(13/21).结论GISTs是消化道常见的原发性间叶性肿瘤,CD117、CD34等免疫标记物配合使用可确诊;恶性GISTs单纯外科手术复发率高,预后不良.

目的 了解Castleman瘤伴发副肿瘤性天疱疮的临床特点.方法分析总结我科诊治的10例Castleman瘤伴发副肿瘤性天疱疮的临床特点和治疗方法.结果Castleman瘤为我国最常见伴发副肿瘤性天疱疮的肿瘤,其临床表现、皮损和肿瘤的病理学特点、CT及免疫学特点都较独特.肿瘤切除手术中给予静脉滴注丙种球蛋白,对降低术后呼吸道症状的出现,使患者早日康复是有益的.结论由于肿瘤直接产生抗体致病,因此早期诊断、早期切除肿瘤,是成功治疗本病的关键。

Objective To investigate the clinical characteristics and surgical treatment of retroperitoneal Castleman′s disease (CD) with paraneoplastic pemphigus (PNP).Methods The clinical symptoms, laboratory, histopathologic, CT findings and results of surgery in 7 patients were evaluated.Results All of 7 patients presented with PNP.Retroperitoneal tumors were found by CT examination and surgically removed.Castleman disease was confirmed by histopathology.Reoperation was performed to resect the recurrent tumor in one patient.The signs of PNP were dissolved completely or partially after operation.Conclusion Retroperitoneum CD with PNP are characteristic of distinctive clinical features.Surgical excision improves the mucocutanous manifestation of PNP.

OBJECTIVE:To describe the distribution of reduced folate carrier gene (RFC1)genotype and allele frequency between southern and northern, female and male Chinese population. METHOD:RFC1 (A80G) genotype was detected, using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) on 720 blood spot DNA from the normal subjects. RESULTS:The frequencies of the northern population with AA, GG and GA genotypes were 22.28%, 31.09% and 46.63%, and the frequencies of the southern population were 18.56%, 22.75% and 58.68%, respectively. Findings showed that there were significant differences between southerners and northerners in RFC1 (A80G) genotype (P < 0.01). There was no significant difference between G allele frequency of the northern (52.10%) and southern population (54.40%). The frequencies of male with RFC1 (A80G) AA, GG and GA genotype were 24.88%, 25.85% and 49.27%, and among female were 18.83%, 27.77% and 53.40%, respectively. There were no significant differences between male and female in RFC1 genotype (P > 0.05), or between G allele frequency in female (50.49%) and that in male (54.47%). CONCLUSIONS:The distribution of RFC1 genotype seemed to be consistent with neural tube defects (NTDs) while its prevalence among the northerners was higher than that of southerners, with female having a higher NTDs prevalence. This study provided genetic epidemiological data for etiological hypothesis between RFC1 and diseases relative to folate metabolism.

OBJECTIVE:To study the association between reduced folate carrier gene (RFC1) polymorphism and congenital heart defects (CHD) as well as cleft lip with or without cleft palate (CLP) and to provide epidemiological evidence on genetic markers of CHD and CLP.METHODS:RFC1 (A80G) genotype was detected using RFLP-PCR for blood DNA of the 67 triads with nonsyndromic CHD-affected child, the 82 triads with child-affected cleft lip with or without CLP and the 100 control families without child-affected birth defects. We performed a family-based association test and analyzed the interaction between RFC1 A80G genotype and maternal periconceptional supplementation of folic acid.RESULTS:Offspring of mothers who did not take folic acid had an elevated risk for CHD when comparing with offspring of mothers who did (OR = 2.68, 95% CI: 1.14 - 6.41). There was a statistical association between the risk of CHD and maternal periconceptional folic acid supplementation (chi(2) = 6.213, P < 0.05). In the family-based association test, G allele was positively associated with an increased risk for children CHD (Z = 2.140, P < 0.05) while G allele of RFC1 (A80G) polymorphism might increase the risk for CHD. Elevated risks for either CLP group were not observed between RFC1 genotype using or not using folic acid.CONCLUSION:Our findings suggested that the G allele was likely to be a genetically susceptible allele for CHD. There was possible association between offspring with GG, GA genotype and maternal periconceptional folicacid deficiency.

OBJECTIVE:To study the appropriate surgical treatment for breast ductal carcinoma in situ (DCIS).METHODS:Twenty-six such patients treated between 1992 and 2001 were retrospectively analyzed. Among them, 3 patients were treated by simple mastectomy, 23 patients by mastectomy and axillary lymph node dissection, 8 patients by chemotherapy and one patient by radiotherapy after operation. Median follow-up was 42 m (rang 12 - 112 m).RESULTS:Except 3 of these 26 patients lost in follow-up and 1 patient died from diabetes mellitus, all the other 22 patients survived over 5 years. All lymph nodes dissected from 23 patients were negative. After surgery, 3 patients developed lymph edema of the arm.CONCLUSION:DCIS, lacking the potential of metastasis, is not invasive. Conservative breast surgery without lymph node dissection is feasible for most DCIS patients.

OBJECTIVE:To describe the epidemiology of neural tube defects (NTDs) in high- and low-prevalence areas of China.METHODS:Birth defects surveillance data, collected from 1992 through 1994 was analyzed. These data were collected as part of the Sino-American cooperative project on NTDs prevention. We classified NTDs as anencephaly, encephalocele, high-level and low-level spina bifida (SB) according to location of the lesion (high vs low) and whether the defect was isolated or occurred in association with other birth defects. Rates were compared in the high-prevalence (North) region and the low-prevalence (South) region, after adjusted for classification, urban and rural, season and sex, and calculated the adjusted rate of NTDs.RESULTS:Among seven hundred and eighty-four NTDs cases in 326 874 recorded births (include in livebirth, stillbirth and fetal death with a gestational age of at least 20 weeks), the overall NTDs prevalence in the North was 5.57/1,000 births, and in the South was 0.88/1 000. There were also significant differences in the prevalence of anencephaly, encephalocele, high-level and low-level SB between North (0.97, 0.49, 2.75 and 1.11/1,000 birth) and South (0.36, 0.15, 0.21 and 0.14/1,000 birth) (P < 0.01), with adjusted prevalences in the North 3 - 7 times higher than those in the South. There were significant difference between urban (2.04) and rural areas (6.57/1,000 birth) in the North (P < 0.01), urban (0.52) and rural areas (0.95/1,000 birth) in the South (P < 0.05). Adjusted prevalence rates in the rural were 3 - 4 times higher than those of urban in the North and 1.6 - 1.9 times higher than in the South; The seasonal rate of high-level SB increased between September and November in the North (3.44/1,000 birth), while the seasonal rate of anencephaly decreased between September and November (0.18/1,000 birth) in the South. However there were no seasonal changes in other classified NTDs both in the South and North.CONCLUSIONS:The birth prevalence of NTDs in the North of China was the highest in the world. There were significant differences between the North and the South, urban and rural. There was seasonal change in high-level SB in the North, which was in accordance to the phenotype of NTDs. It was suggested that there might exist etiological heterogeneity among anecephalus, low- and high-level SB.