Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Objective:To examine the effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstruction.Methods:Data was collected from 185 patients underwent immediate DIEP reconstruction during November 2006 to March 2020 Department of Breast Surgery, Fudan University Shanghai Cancer Center. All the patients were female, aging (43.0±7.8) years (range: 29 to 61 years). The series included with a total of 187 flaps (2 bilateral, 183 unilateral). Included patients were divided into 2 groups: immediate DIEP reconstruction requring or not requring post-mastectomy radiation therapy (71 cases (71 flaps) in PMRT group, 114 cases (116 flaps) in control group). The aesthetic outcome were measured by Kroll score system and compared between the groups by t test. The complications included partial flap loss, minor necrosis were analyzed between the groups by χ 2 test, while the influence of the other correlation factors on complication occurrence was analyzed by Logistic analysis. Results:The controll groups showed better aesthetic results (2.21±0.55 vs. 2.47±0.82, t=-2.593, P=0.010). Complication rate in PMRT group was higher than that in control group (19.7% (15/71) vs. 4.2% (4/116), χ2=15.079, P<0.01). The complication rate was not correlated with age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy. Conclusions:Correlation was observed between adjuvant radiotherapy and post-operative complication of the DIEP flap. However, the complication occurrence and aesthetic results remain in the acceptable range. The other factors such as age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy should not be considered as prognosis factor of post-operative complication of the DIEP flap.

Objective:To examine the effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstruction.Methods:Data was collected from 185 patients underwent immediate DIEP reconstruction during November 2006 to March 2020 Department of Breast Surgery, Fudan University Shanghai Cancer Center. All the patients were female, aging (43.0±7.8) years (range: 29 to 61 years). The series included with a total of 187 flaps (2 bilateral, 183 unilateral). Included patients were divided into 2 groups: immediate DIEP reconstruction requring or not requring post-mastectomy radiation therapy (71 cases (71 flaps) in PMRT group, 114 cases (116 flaps) in control group). The aesthetic outcome were measured by Kroll score system and compared between the groups by t test. The complications included partial flap loss, minor necrosis were analyzed between the groups by χ 2 test, while the influence of the other correlation factors on complication occurrence was analyzed by Logistic analysis. Results:The controll groups showed better aesthetic results (2.21±0.55 vs. 2.47±0.82, t=-2.593, P=0.010). Complication rate in PMRT group was higher than that in control group (19.7% (15/71) vs. 4.2% (4/116), χ2=15.079, P<0.01). The complication rate was not correlated with age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy. Conclusions:Correlation was observed between adjuvant radiotherapy and post-operative complication of the DIEP flap. However, the complication occurrence and aesthetic results remain in the acceptable range. The other factors such as age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy should not be considered as prognosis factor of post-operative complication of the DIEP flap.

Background and purpose: Many factors have impacts on the surgery approach of breast cancer. The purpose of this study was to analyze the influence factors of breast reconstruction for patients with breast cancer, focusing on the relationship between travel distance and breast reconstruction. Methods: Retrospective review of all female breast cancer patients staging 0-Ⅱ who underwent unilateral or bilateral mastectomy with or without breast reconstruction at Fudan University Shanghai Cancer Center from 1999 to 2015 was conducted in the study. Analysis of travel distance and breast reconstruction rate was performed. Results: Non-Shanghai patients have higher breast reconstruction rate after mastectomy compared with Shanghai patients (6.1％ vs 4.5％, P＜0.001). Travel distance may have an influence on the breast reconstruction rate (P=0.035). Univariate regression analysis showed that the increase of travel distance was the predictor of breast reconstruction, and that the increase of age or body mass index (BMI), or the later TNM stage had a negative correlation with breast reconstruction (P＜0.001). Multiple regression analysis demonstrated that the increase of age or BMI, or the later TNM stage was the independent predictor of the refusal of breast reconstruction (P＜0.001), but travel distance was not (P＞0.05). No significant correlation between the travel distance and breast reconstruction types was indicated. Negative correlation was observed between age and travel distance (P＜0.001). Conclusion: Age, BMI and tumor stage are the main influence factors of breast reconstruction, while travel distance shows a linear correlation with it.

Background and purpose:Perioperative anesthetic management is thought to be critical to the success of free flap breast reconstruction. The purpose of this study was to discuss intraoperative fluid, hemodynamic and temperature management in patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction.Methods:From Jun. 2011 to Dec. 2015, 126 patients underwent DIEP lfap breast reconstruction. Postoperative complications were reviewed. Intraoperative fluid infusion rate was analyzed. Mean arterial blood pressure (MAP) and core temperature were measured before induction (T0), after lfap elevation but before lfap transfer (T1), 15 min after flap revascularization (T2), and at the end of surgery (T3).Results:Nine patients developed flap compromised: 7 were salvaged and 2 failed. The mean intraoperative lfuid infusion rate was (5.44±1.66) (mL?kg-1)/h. MAP at T0, T1, T2 and T3 were (87.45±8.90), (74.19±8.63), (74.60±8.71) and (79.62±7.88) mmHg, respectively. Core temperature at T0, T1, T2 and T3 were (36.69±0.14), (36.36±0.18), (36.27±0.14) and (36.21±0.15)℃, respectively. Conclusion:Standard practice focusing on intraoperative lfuid management, hemodynamic adjustment and temperature control in microsurgical reconstruction of the breast should be established to further improve free lfap outcome.

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.

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.

OBJECTIVETo evaluate the role of germline mutations of TP53 gene among a Chinese population with high risk for breast cancer.

METHODSA total of 81 BRCA-negative breast cancer probands from cancer families were analyzed using targeted capture and next-generation sequencing. Candidate mutations were verified with Sanger sequencing. Co-segregation analyses were carried out to explore the likely pathogenicity of the mutation.

RESULTSOf the 81 BRCA-negative patients, 3 exonic mutations in the TP53 gene were identified in 3 breast cancer patients. Of these, 2 mutations were previously reported and 1 was novel. One family with TP53 mutation has met the criteria for Li-Fraumeni syndrome (LFS) and accounted for 9.1% of all families who fulfilled the diagnostic criteria for LFS. Two of the carriers were diagnosed with breast cancer under the age of 30, and have accounted for 11.8% (2/17) of all very young (≤30 years) breast cancer patients in our study.

CONCLUSIONThe TP53 germline mutation is more common in Chinese population with a high risk for breast cancer than previously thought. TP53 gene mutation screening should be considered particularly for patients with a family history of LFS and very young age of onset.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; China ; DNA Mutational Analysis ; Exons ; Family Health ; Female ; Genetic Predisposition to Disease ; ethnology ; genetics ; Germ-Line Mutation ; Heterozygote ; Humans ; Li-Fraumeni Syndrome ; ethnology ; genetics ; Male ; Middle Aged ; Pedigree ; Risk Factors ; Tumor Suppressor Protein p53 ; genetics ; Young Adult

Background and purpose: BRCA1 and BRCA2 mutation carriers have a high lifetime risk of developing breast and ovarian cancer. Through genetic counseling, mutation carriers can take the appropriate measures to reduce such cancer risk. At present, almost all related studies were conducted in Caucasian, while, the studies in Chinese population were rare. This study aimed to investigate the risk of breast cancer in BRCA1 and BRCA2 mutation carriers in Chinese Han population. Methods:Twenty unrelated families with BRCA1 or BRCA2 mutations were re-viewed. Kaplan-Meier analyses were used to estimate the cumulative risks of unilateral breast cancer and contralateral breast cancer for female BRCA1 and BRCA2 mutation carriers. Results:Breast cancer risk to 70 years (penetrance) was 67.2%(sx 0.100) for BRCA1 and 76.8%(sx 0.079) for BRCA2, respectively. Different from BRCA1 mutation carriers, the cumulative incidence of breast cancer in BRCA2 mutation carriers remained increasing after 70 years, reaching 93.1%at age 80. The 10-and 20-year risk for contralateral breast cancer was 19.4%(sx 0.089) and 50.3%(sx 0.155) for BRCA1/2 mutation carriers. Conclusion:BRCA1 and BRCA2 mutation carriers in Chinese Han population have a high risk of developing breast cancer. Thus, it has great clinical signiifcance to test mutations in BRCA1/2 genes in Chinese high-risk population.