MRI for intracranial lesions has unsatisfactory signal-to-noise ratios due to BBB (Blood Brain Barrier) obstruction and the rapid metabolism of contrast agent molecules. A pH-sensitive nanosystem can cloak Gd3+ from protons in normal tissues and activate Gd3+ signals in acidic TME (tumor microenvironment). In addition, based on the theory of homologous binding between tumor cells and the membranous inheritance of the initial BBB-traversing ability of brain metastatic breast tumor cells, nanoparticles camouflaged by the U87-4T1-hybridized-membrane obtained the potential in traversing the BBB and targeting to glioma. This study aimed to construct a biocompatible TME-responsive MRI nano-contrast agent with potent BBB-traversing and tumor-targeting ability for glioma diagnosis with significantly enhanced T1WI signal intensity. PGdCa@hCCM was synthesized with an average particle size and zeta potential of 199.1 ± 24.5 nm and 23.4 ± 6 mV, respectively, which remained stable within 7 days. Camouflage by U87 cell membrane endowed nanoparticles with homologous affinity and led to stronger accumulation in U87 cells. The MFI of PGdCa@hCCM that traversed the artificial BBB model and targeted to U87 cells was significantly higher than that of PGdCa@CCM (U87 only) or PGdCa (without membrane camouflage) (p < 0.001), indicating the hybridized membranes facilitated nanoparticles crossing BBB and targeting to U87 cells. The MRI signals of PGdCa@hCCM under neutral PBS (a.u.=196.3 ± 6.9) and pH7.4 PBS (a.u.=239.8 ± 13.2) were significantly weaker than that under pH6.5 (a.u.=711.1 ± 27.8), indicating that the MRI capacity could be activated under acidic environment. The MRI signal in PGdCa@CCM (U87 only) group exhibited a signal-to-noise ratio of 14.9 ± 1.3 after 6 h, while the tumor-to-noise ratio in mice injected with PGdCa@hCCM was enhanced to 30.2 ± 5.5 after 6 h. PGdCa@hCCM was also proved to possess good biosafety and prolonged circulation time and metabolizability. In this study, an in situ activable MRI nano-contrast PGdCa@hCCM was engineered. With the substantial improvements in tumor-targeting and BBB-traversing efficiency, as well as the pH-sensitive switch on/off function, PGdCa@hCCM successfully promoted the sensitivity and accuracy in MR imaging of glioma.
STUDY QUESTION:Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER:PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY:High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION:Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS:The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE:Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA:N/A. LIMITATIONS, REASONS FOR CAUTION:Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS:Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S):This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER:N/A.
Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2-3 cm) of the initial resected lesion due to the unreachable residual cancerous cells. Here, a completely biodegradable microneedle for surgical cavity delivery glioblastoma-associated macrophages (GAMs)-activating immune nano-stimulator that mitigates glioblastoma relapse is reported. The residual tumor lesion-directed biocompatible microneedle releases the nano-stimulator and toll-like receptor 9 agonist in a controlled manner until the microneedles completely degrade over 1 week, efferently induce in situ phonotypic shifting of GAMs from anti- to pro-inflammatory and the tumor recurrence is obviously inhibited. The implantable microneedles offer a significant improvement over conventional transdermal ones, as they are 100% degradable, ensuring safe application within surgical cavities. It is also revealed that the T cells are recruited to the tumor niche as the GAMs initiate anti-tumor response and eradicate residual GBM cells. Taken together, this work provides a potential strategy for immunomodulating the postoperative tumor niche to mitigate tumor relapse in GBM patients, which may have broad applications in other malignancies with surgical intervention.
After a nuclear accident, radioactive nuclides are rapidly absorbed through wounds into the body, causing serious internal radiation injury. In this study, we synthesized chitosan methacryloyl (CSMA) and graft-modified it with the broad-spectrum chelating agent diethylenetriamine pentaacetate (DTPA) to prepare a DTPA-modified chitosan hydrogel dressing (CSMA-g-DTPA). The compounds and hydrogels were examined for their physical and chemical properties and their biological safety was verified. The effectiveness of CSMA-g-DTPA dressings for early decontamination and promotion of wound healing was evaluated in vivo. The results indicated that CSMA-g-DTPA exhibits good mechanical properties and swelling behavior as well as excellent biocompatibility. In vitro experiments revealed that CSMA-g-DTPA is capable of removing uranium and strontium. In vivo experiments demonstrated that the CSMA-g-DTPA hydrogel can decontaminate radioactive Sr-89 and U-238 from rat skin wounds, prevent the absorption of Sr-89 and U-238 through the wounds and alleviate oxidative stress and inflammatory responses in the wounds, thereby promoting wound healing. Overall, the DTPA-modified chitosan hydrogel dressing has good mechanical performance, biosafety and decontamination effects on strontium and uranium. It has potential applications for emergency decontamination of wounds during the early stages of a nuclear disaster.
Purpose:To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers. Materials and Methods:In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity. Results:The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors. Conclusion:This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.
Previous postmortem and animal studies have shown decreases in the prefrontal cortex (PFC) volume and the number of glial cells in the PFC of depression. Running exercise has been shown to alleviate depressive symptoms. However, the effects of running exercise on the medial prefrontal cortex (mPFC) volume and oligodendrocytes in the mPFC of depressed patients and animals have not been investigated. To address these issues, adult male rats were subjected to chronic unpredictable stress (CUS) for 5 weeks, followed by treadmill running for 6 weeks. Then, the mPFC volume and the mPFC oligodendrocytes were investigated using stereology, immunohistochemistry, immunofluorescence and western blotting. Using a CUS paradigm that allowed for the analysis of anhedonia, we found that running exercise alleviated the deficits in sucrose preference, as well as the decrease in the mPFC volume. Meanwhile, we found that running exercise significantly increased the number of CNPase + oligodendrocytes and Olig2 + oligodendrocytes, reduced the ratio between Olig2 + /NG2 + oligodendrocytes and Olig2 + oligodendrocytes and increased myelin basic protein (MBP), CNPase and Olig2 protein expression in the mPFC of the CUS rat model. However, running exercise did not change NG2 + oligodendrocyte number in the mPFC in these rats. These results indicated that running exercise promoted the differentiation of oligodendrocytes and myelin-forming ability in the mPFC in the context of depression. These findings suggest that the beneficial effects of running exercise on mPFC volume and oligodendrocytes in mPFC might be an important structural basis for the antidepressant effects of running exercise.
Transdermal drug delivery system (TDDS) has attracted much attention in the pharmaceutical technology area. However, the current methods are difficult to ensure penetration efficiency, controllability, and safety in the dermis, so its widespread clinical use has been limited. This work proposes an ultrasound-controlled monodisperse lipid vesicles (U-CMLVs) hydrogel dressing, which combines with ultrasound to form TDDS. Using microfluidic technology, prepare size controllable U-CMLVs with high drug encapsulation efficiency and quantitative encapsulation of ultrasonic response materials, and even uniform mix them with hydrogel to prepare the required thickness of dressings. The high encapsulation efficiency can ensure sufficient dosage of the drugs and further realize the control of ultrasonic response through quantitative encapsulation of ultrasound-responsive materials. Using high frequency (5 MHz, 0.4 W cm-2 ) and low frequency (60 kHz, 1 W cm-2 ) ultrasound to control the movement and rupture of U-CMLVs, the contents not only penetrate the stratum corneum into the epidermis but also break through the bottleneck of penetration efficiency, and deep into the dermis. These findings provide the groundwork for deep, controllable, efficient, and safe drug delivery through TDDS and lay a foundation for further expanding its application.
BackgroundHuman malignancies are composed of heterogeneous subpopulations of cancer cells with phenotypic and functional diversity. Among them, a unique subset of cancer stem cells (CSCs) has both the capacity for self-renewal and the potential to differentiate and contribute to multiple tumor properties. As such, CSCs are promising cellular targets for effective cancer therapy. At the molecular level, hyper-activation of multiple stemness regulatory signaling pathways and downstream transcription factors play critical roles in controlling CSCs establishment and maintenance. To regulate CSC properties, these stemness pathways are controlled by post-translational modifications including, but not limited to phosphorylation, acetylation, methylation, and ubiquitination.ConclusionIn this review, we focus on E3 ubiquitin ligases and their roles and mechanisms in regulating essential hallmarks of CSCs, such as self-renewal, invasion and metastasis, metabolic reprogramming, immune evasion, and therapeutic resistance. Moreover, we discuss emerging therapeutic approaches to eliminate CSCs through targeting E3 ubiquitin ligases by chemical inhibitors and proteolysis-targeting chimera (PROTACs) which are currently under development at the discovery, preclinical, and clinical stages. Several outstanding issues such as roles for E3 ubiquitin ligases in heterogeneity and phenotypical/functional evolution of CSCs remain to be studied under pathologically and clinically relevant conditions. With the rapid application of functional genomic and proteomic approaches at single cell, spatiotemporal, and even single molecule levels, we anticipate that more specific and precise functions of E3 ubiquitin ligases will be delineated in dictating CSC properties. Rational design and proper translation of these mechanistic understandings may lead to novel therapeutic modalities for cancer procession medicine.
The therapeutic effects and application of radiotherapy are restricted to some extent due to low radiosensitivity of tumor tissues and adverse effects by excess dosage. Current radiosensitizers are confronted with problems in clinical translation because of complicated manufacture technique and high cost. In this research, we have synthesized a radiosensitizer with advantages in low cost and mass production, which could be applied to CT imaging and enhanced radiotherapy in breast cancer, namely Bi-DTPA. It not only enhanced tumor CT imaging which resulted in better therapeutic accuracy, but also realized radiotherapy sensitization by producing massive ROS and inhibit tumor proliferation, providing a sound perspective in the clinical translation of the radiosensitizer.
Objective To compare the efficacy and safety of unilateral axilla-bilateral areola approach (UABA) for robotic thyroidectomy with conventional open surgery in thyroid cancer patients. Methods We retrospectively analyzed the clinical data of 229 patients who were diagnosed with thyroid cancer and underwent total thyroidectomy plus bilateral central node dissection in the Department of Breast and Thyroid Surgery, First Affiliated Hospital of Army Medical University from January 2018 to May 2020, including 105 cases undergoing robotic surgery (robotic group) and 124 cases undergoing conventional open surgery (open group). All of them were followed up for 12 to 36 months. The hypoparathyroidism, recurrent laryngeal nerve injury, operation time, intraoperative blood loss, drainage volume within postoperative 3 days, postoperative complications and patient satisfaction with neck appearance were recorded and compared between 2 groups. Results The incidences of transient hypoparathyroidism (28.57% vs 64.52%, P=0.000) and permanent hypoparathyroidism (0 vs 5.65%, P=0.016) were significantly lower in the robot group than the open group. So was the rate of permanent recurrent laryngeal nerve injury (0 vs 5.65%, P=0.016). The patients in the robotic group obtained significantly higher satisfaction than those of the open group (100% vs 87.1%, P < 0.001). However, operation time (156.57±37.87 vs 113.98±46.03 min, P < 0.001) was longer, and drainage volume within 3 d postoperatively (141.57±43.16 vs 120.79±49.96 mL, P < 0.001) was statistically larger in the robotic group than the open group. There were no significant differences in intraoperative blood loss (50.31±23.37 vs 50.48±13.67 mL, P=0.455), number of removed lymph nodes (11.23±6.77 vs 12.97±6.77, P=0.055) and postoperative thyroglobulin level (1.01±5.36 vs 1.43±8.47 ng/mL, P=0.330) between the 2 groups. No recurrence or metastasis was observed in the 2 groups during the follow-up period. Conclusion Compared with open surgery, unilateral axilla-bilateral areola approach for robotic surgery shows similar therapeutic effect, but it can better protect the parathyroid gland and recurrent laryngeal nerve and preserve the neck appearance by super-meticulous capsular dissection.
Abstract Background High z number element is advanced in Computed Tomography (CT) imaging and the sensibilization of radiotherapy because of higher mass energy absorption coefficients. Bi-Diethylene triamine pentaacetic acid (Bi-DTPA), structured on Bi element, is advanced in CT imaging ability and advantages of strong water solubility, good biocompatibility, low cost and mass production. So in this study, Bi-DTPA was used in CT imaging and radiotherapy of breast cancer to explore its feasibility and effect in CT imaging of mouse breast cancer model, and whether it had sensitization radiation characteristics through radiotherapy. Methods The characterization of Bi-DTPA was detected by FT-IR, 1H-NMR and HR-MS. Compared the tumor CT imaging effect of Bi-DTPA with I 370 on 4T1 tumor bearing mouse model. The radiosensitization mechanism of Bi-DTPA was investigated by CCK-8 assay, clonogenic assay, ROS detection, DNA double strand break detection, flow cytometry for the detection of cell apoptosis, and treatment of 4T1 tumor bearing mouse model. Result The Bi-DTPA’s CT imaging signal was higher than I 370 at a safe concentration which synthesized by the one-pot method. During radiotherapy with Bi-DTPA, the viability of cells was reduced and the sensitization rate was 1.51. The level of ROS generated, DNA damage sites and the proportion of cell apoptosis was significantly higher than that in the radiotherapy group. The results of in vivo treatment showed that Bi-DTPA had better inhibitory effect on tumors. Conclusion The synthesized Bi-DTPA was advanced and applicable in CT imaging and possessed sound capacity in radiation therapy (RT) sensitization which can effectively kill tumor cells by ROS and inhibit tumor proliferation. Therefore, it has great potential in the future application of tumor integrated diagnosis and treatments.
2019 年12 月以来,以湖北省武汉市为中心,全国各省市、自治区、新疆生产建设兵团以及境外陆续出现了多例新型冠状病毒肺炎(简称新冠肺炎)患者. 该病毒潜伏期长、传染性强. 截止2020年2月26日24时,全国累计确诊患者78497例,累计死亡患者2744例,疑似患者及累计追踪到密切接触者652174例[1]. 疫情之下,陆军军医大学第一附属医院乳腺甲状腺外科全体医护人员积极响应号召,参照国家、军队以及重庆市相关政策法规及规章制度及时制定并发布了《新型冠状病毒肺炎疫情期间乳腺疾病患者诊治流程管理》[2]、《新型冠状病毒肺炎疫情下乳腺癌日间化疗病房运行管理实践》[3]等一系列乳腺疾病管理流程. 工作人员严格执行这些管理流程,基本保障了需来院手术、化疗和靶向治疗等患者的需求,实现了在科学防控的基础上最大限度保证肿瘤患者诊治的目的[4].
自2019年12月在湖北省出现首例患者以来,新型冠状病毒肺炎(简称新冠肺炎)呈现爆发性流行趋势[1-2].WHO已将本次疫情认定为国际公共卫生紧急事件[3],中国也将新冠肺炎纳入《中华人民共和国传染病防治法》规定的乙类传染病,并采取甲类传染病的预防控制措施进行防控[4].鉴于新冠肺炎传染性很强,其主要传播途径为经呼吸道飞沫和密切接触传播,多地采取了包括“封城”、“封路”在内的多种方式减少人员聚集,以切断传播途径,但同时也对人民群众的正常生活和社会生产造成了极大影响.
目的 探讨新辅助化疗对乳腺癌切除假体植入Ⅰ期乳房重建术后并发症及远期疗效的影响.方法 接受乳腺癌切除+假体植入Ⅰ期乳房重建手术的乳腺癌患者429例,其中术前接受2~8个周期新辅助化疗者236例为新辅助化疗组,直接行乳腺癌切除+假体植入Ⅰ期乳房重建术者193例为单纯手术组.比较2组手术方式、术后引流量、住院时间、术后并发症发生情况以及远期疗效.结果 新辅助化疗组101例采用腔镜辅助手术,135例行传统开放手术;单纯手术组75例采用腔镜辅助手术,118例行传统开放手术;2组手术方式比较差异无统计学意义(P>0.05).新辅助化疗组术后引流量[(284.0±79.4)mL]、术后住院时间[(5.6±1.2)d]与单纯手术组[(289.0±76.8)mL、(5.5±1.0)d]比较差异无统计学意义(P>0.05).2组术后血肿、手术区域感染、乳头乳晕及皮瓣坏死、患侧上肢水肿、包膜挛缩及假体丢失发生率比较差异均无统计学意义(P>0.05).新辅助化疗组局部复发率(2.12%)、远处转移发生率(7.63%)和病死率(3.39%)与单纯手术组(1.55%、5.70%、2.59%)比较差异均无统计学意义(P>0.05).结论 新辅助化疗对乳腺癌切除假体植入Ⅰ期乳房重建术后并发症及远期疗效无影响,在获得治疗效果的同时并未对乳房重建带来如伤口愈合不良或皮瓣坏死率增高等不利影响.
2019年12月以来,湖北省武汉市陆续发现了多例新型冠状病毒肺炎(简称新冠肺炎)患者.随着疫情的蔓延,国内各省、自治区、直辖市、新疆生产建设兵团及境外也相继发现了此类病例.该病毒潜伏期长,传染性强.2020年1月20日,中华人民共和国国家卫生健康委员会将新冠肺炎纳入《中华人民共和国传染病防治法》规定的乙类传染病,并采取甲类传染病的预防、控制措施[1].截止2020年2月5日24时,全国累计确诊病例28 018例,累计死亡病例563例,疑似病例24 702例[2].
Objective To investigate the anti-adhesion effect of anti-adhesion film in robotic thyroid cancer surgery. Methods We retrospectively analyzed the clinical data and treatment outcomes of 452 patients who underwent Da Vinci robotic surgery for thyroid cancer between January, 2016 and December, 2018.In 228 of the patients, anti-adhesion film (absorbable medical film) was placed on the trachea before thyroid resection and dissection of the lymph nodes (test group); the other 224 patients underwent identical surgical procedures but without the use of the anti-adhesion film (control group). Results The scores for swallowing discomfort were significantly lower in the test group than in the control group at 3 and 6 months after the operation.Subgroup analysis showed that in the patients receiving unilateral thyroidectomy, the scores for swallowing discomfort did not differ significantly between the 2 groups at 3, 6, and 12 months postoperatively.In patients receiving total thyroidectomy, the scores were significantly lower in the test group than in the control group at 3 months (P=0.00) and 6 months (P=0.001), and the incidence of swallowing discomfort (either mild or severe) was also significantly lower in the test group at 3 months (74.6% vs 83.6%, P=0.004) and 6 months (24.2% vs 40.9%, P=0.006) after the operation.No significant differences were found in the incidences of postoperative hoarseness and hypoparathyroidism, drainage volume, or the length of hospital stay between the 2 groups. Conclusion The use of absorbable medical film during robotic total thyroidectomy for thyroid cancer can effectively reduce neck soft tissue adhesion, lower the incidence of postoperative swallowing discomfort, and improve postoperative quality of life of the patients.
目的 探讨乳腺癌术后一期假体重建患者免除乳房假体区域放射治疗对并发症及复发、转移的影响.方法 依据纳入、排除标准,选取2012年1月至2014年12月在陆军军医大学第一附属医院乳腺甲状腺外科确诊为乳腺癌,且行根治性切除加假体植入一期乳房重建术后放射治疗的95例患者进行回顾性研究.所有患者中,接受乳房假体区域加淋巴结引流区域放射治疗者56例(对照组),免除乳房假体区域放射治疗而仅接受淋巴结引流区域放射治疗者39例(试验组).每例患者经过5年以上的随访.对比分析2组患者放射治疗相关并发症(放射性皮肤损伤、放射性肺炎、包膜挛缩和假体取出),以及肿瘤局部复发和远处转移的情况.放射治疗相关并发症发生率、肿瘤局部复发率及远处转移率的比较,采用χ2检验或Fisher确切概率检验.结果 对照组56例患者中,发生5例(8.9%)放射性皮肤损伤,2例(3.6%)放射性肺炎,5例(8.9%)放射治疗引起的包膜挛缩(Ⅱ级和Ⅲ级各2例,Ⅳ级1例),共导致2例(3.6%)假体取出,而试验组39例患者中,只发生1例(2.6%)放射性皮肤损伤;2组相比,放射性皮肤损伤、放射性肺炎、放射治疗引起的包膜挛缩和假体取出发生率的差异均无统计学意义(P=0.395、0.511、0.076、0.511).对照组共有12例(21.4%,12/56)患者发生放射治疗相关并发症,试验组仅1例(2.6%,1/39)患者发生放射治疗相关并发症,2组相比,差异有统计学意义(χ2=6.926,P=0.008).中位随访66个月(范围:60~81个月),对照组发生局部复发4例(7.1%,4/56)和远处转移5例(8.9%,5/56),试验组局部复发和远处转移均为3例(7.7%,3/39),2组比较,差异均无统计学意义(P=0.999、0.999).结论 对于接受乳腺癌根治性切除术后一期假体重建的患者,免除乳腺假体区域放射治疗不影响其疗效,同时可以减少放射治疗相关并发症,改善患者术后生活质量.
背景与目的:尽管目前国内新型冠状病毒肺炎(COVID-19)疫情得到了有效的控制,但国外病例仍在持续增加,防控形势依然严峻.本研究以陆军军医大学第一附属医院乳腺外科为例,分析总结新型冠状病毒肺炎疫情期间综合性三甲医院乳腺外科运行情况,为疫情期间及后疫情时期安全、高效地开展乳腺外科工作提供有效参考和经验做法.方法:选取自2020年1月31日-2020年2月20日COVID-19流行期间陆军军医大学第一附属医院乳腺甲状腺外科收治的37例乳腺癌患者,对其临床特征、防护手段及治疗效果等病例资料进行回顾性分析.对患者的人院和术前准备、术中防护、术后康复等关键环节,以及医护人员自我防护及心理疏导进行方法总结.对专科治疗及疫情防控的效果进行随访研究.分析在后疫情时期如何提升对潜在传染病风险的认知,结合乳腺外科的诊治特点,从手术指征把握、气溶胶管理和诊室防护等多方面加强疫情防控和职业防护工作.结果:37例乳腺癌患者经排除COVID-19风险后均接受手术治疗,平均手术时间为(152.23±46.19) min,平均术中出血量为(85.23±23.47) mL,无术中输血病例.在37例乳腺癌患者中,有19例患者接受术前6~8周期新辅助治疗,其中7例术后证实为病理学完全缓解.术后2例出现持续发热,经过隔离、监测体温及对症支持治疗后恢复正常,新型冠状病毒核酸检测排除COVID-19感染可能.经跟踪随访,患者及陪护人员均无发热、咳嗽、乏力等COVID-19疑似表现,相关医护人员同样未出现疑似病例,总体防控效果较好.结论:在COVID-19疫情流行期间,在科学防控、竭力避免医患双方感染COVID-19的前提下,可结合当地疫情情况全力为乳腺癌患者提供有效治疗.应继续遵从“科学决策、人文服务”的精神,严格遵循上级下发的各类防控指南和管理规范,并依据实际完成乳腺癌患者的院前排查、术前准备、术中防护、术后康复等必要环节.严格在患者入院前及围手术期各环节遵循疫情防护规范、协调好疫情防控与专科诊治的关系,有利于最大限度地确保乳腺外科手术安全地完成,守护患者及医务人员的健康.
Objective To determine the clinicopathological features and prognostic differences between ductal carcinoma in situ (DCIS) and ductal carcinoma in situ with microinvasion (DCIS-MI) of breast cancer. Methods A cohort of 489 female patients with surgically diagnosed DCIS (n=240, 49.1%) and DCIS-MI (n=249, 50.9%) in our hospital from January 2004 to December 2014 were recruited in this study. Their clinicopathological data and follow-up data were collected and analyzed for the differences in clinicopathological data, molecular subtypes and prognosis between DCIS and DCIS-MI patients. Results The age of initial diagnosis was usually younger than 55 years old (60.3%) in the 2 groups. Compared with DCIS patients, DCIS-MI patients had larger tumor size (P=0.034), higher histological grade (P < 0.05), and lower ER positive rate (P < 0.05); DCIS-MI patients had lower proportion of luminal-A type (54.6% vs 63.8%, P=0.040), while higher HER-2 over-expressed type (18.1% vs 9.2%, P=0.004). Statistical differences were seen in the distribution of molecular subtypes between the groups (Chi-square=8.921, P=0.030). The 5-year disease-free survival rate was 93.75% and 93.17% respectively in the DCIS and DCIS-MI patients, with no significant difference (Log-rank, Chi-square =0.074, P=0.785). Conclusion DCIS and DCIS-MI have different clinicopathological features and molecular subtype distribution, but no significant difference in prognosis, which indicates that they may be in different stages of breast cancer progression.
The 41st San Antonio Breast Cancer Symposium was held in San Antonio, Texas, USA on December 4-8, 2018. In this article, we reviewed the key advancement in breast cancer surgery, chemotherapy, targeted therapy, immunotherapy and endocrine therapy reported in this symposium, in order to provide references for clinicians in the treatment and research of breast cancer. The 10-year follow-up data of the EORTC AMAROS study suggested that axillary radiotherapy was a safe and feasible alternative to axillary lymph node dissection for primary breast cancer patients with positive axillary lymph nodes confirmed by sentinel lymph node biopsy. The result of the phase 3 GEICAM/CIBOMA study showed that in early triple negative breast cancer patients, capecitabine administration after surgery and standard chemotherapy did not significantly improve the patients’ survival. The meta-analysis conducted by researchers in Harvard University suggested that the patients who achieve pCR after neoadjuvant chemotherapy could be exempted from conventional adjuvant chemotherapy, with no obvious effect on patients’ survival. The multi-center PEONY study conducted by Professor Shao Zhimin in China showed that for neoadjuvant therapy of early or locally advanced HER-2 positive breast cancer patients in Asia, the overall postoperative pCR rate of double-target group (pertuzumab monoclonal antibody + trastuzumab monoclonal antibody + docetaxel) was significantly higher than that of single-target group (trastuzumab monoclonal antibody + docetaxel). The KATHERINE study showed that the trastuzumab monoclonal antibody combined with maitansine conjugate was feasible in the adjuvant treatment of HER-2 positive early breast cancer. An exploratory analysis to evaluate the efficacy of immuno-biomarker subgroups in the IMpassion 130 study showed that the patients with programmed death ligand 1 positive in immunocytes significantly benefited from the treatment of atezolizumab monoclonal antibody + albumin paclitaxel. The PALLET study showed that in postmenopausal early breast cancer patients with ER positive and HER-2 negative, the neoadjuvant endocrine therapy of letrozole combined with CDK4/6 inhibitors significantly increased the inhibition rate of Ki67, but did not improve the clinical response rate. The 10-year clinical data of the AERAS study showed that the patients significantly benefited from the adjuvant endocrine therapy if the use of anastrozole was extended to 10 years. The meta-analysis of EBCTCG showed that prolonged endocrine therapy significantly reduced the overall risk of recurrence in hormone receptor-positive postmenopausal breast cancer. The TAM-01 study suggested that low-dose administration of tamoxifen could reduce the toxicity and improve the efficacy in patients with breast intraductal neoplasms. The clinicians should actively promote the clinical research of new drugs and the exploratory analysis of predictive biomarkers, take the advantages of domestic researches and learn advanced techniques and concepts overseas in order to benefit most of breast cancer patients. Key words: Breast neoplasms; Endocrine therapy; Triple negative breast cancer; Neoadjuvant therapy; Immunotherapy