Risk for Upgrade to Malignancy After Breast Core Needle Biopsy Diagnosis of Lobular Neoplasia: A Systematic Review and Meta-Analysis

PurposeLobular neoplasia (LN) detected on breast core needle biopsy is frequently managed with surgical excision because of concern for undersampled malignancy. The authors performed a systematic review and meta-analysis to estimate the risk for upgrade to malignancy in the setting of imaging-concordant classic LN diagnosed on core biopsy.MethodsPubMed and Embase were searched for original articles published from 1998 to 2020 that reported rates of upgrade to malignancy for classic LN, including atypical lobular hyperplasia (ALH) and classic lobular carcinoma in situ (LCIS). Two reviewers extracted study data and assessed the following quality criteria: exclusion of variant LCIS, exclusion of imaging-discordant lesions, and outcome reporting for ≥70% of lesions. For studies meeting all criteria, pooled risks for upgrade to any malignancy (invasive carcinoma or ductal carcinoma in situ) and invasive malignancy for all LN, ALH, and LCIS were estimated using random-effects models.ResultsFor 65 full-text articles included in the review, the risk for upgrade to any malignancy ranged from 0% to 45%. Among the 16 studies that met all quality criteria for the meta-analysis, pooled risks for upgrade to any malignancy were 3.1% (95% confidence interval [CI], 1.8%-5.2%) for all LN, 2.5% (95% CI, 1.6%-3.9%) for ALH, and 5.8% (95% CI, 2.9%-11.3%) for LCIS. Risks for upgrade to invasive malignancy were 1.3% (95% CI, 0.7%-2.4%) for all LN, 0.4% (95% CI, 0.0%-4.2%) for ALH, and 3.5% (95% CI, 2.0%-5.9%) for LCIS.ConclusionsThe risk for upgrade to malignancy for LN found on breast biopsy is low. Imaging surveillance can likely be offered as an alternative to surgical management for LN, particularly for ALH.     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Risk communication in a patient decision aid for radiotherapy in breast cancer: How to deal with uncertainty?

Background and aimPatient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy.MethodsFirstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise.ResultsConsensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible side-effects were explained using verbal labels.ConclusionsWe developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801).     

间期细胞原位PCR检测B细胞系恶性淋巴瘤

目的：应用原位PCR技术检测B细胞系恶性淋巴瘤。方法：采用免疫球蛋白重链（IgH)基因第三互补决定区（CDR－Ⅲ）的引物，dig-11-dUTP标记物，应用直接原位PCR技术检测Ⅲ-Ⅳ级恶性淋巴瘤的间期淋巴细胞，结果：在初诊的15例恶性淋巴瘤患中，12例检测到IgH基因重排；4例临床表现呈现淋巴瘤性白血病患，治疗后骨髓完全缓解，2例间期细胞原位PCR仍显示有IgH基因重排，6个月复发，结论：间期细胞原位PCR技术能敏感、准确地检测Ⅲ级以上的恶性淋巴瘤，并帮助预测复发，为一有效的基因诊断方法。     

Changes in glial fibrillary acidic protein mRNA expression after corticospinal axotomy in the adult hamster

We examined changes in the expression of glial fibrillary acidic protein (GFAP) mRNA during Wallerian degeneration in the corticospinal system of the adult Golden hamster following axotomy. GFAP is the product of a type III intermediate filament (IF) gene that is expressed specifically in mature astrocytes. A well-studied component of a complex response termed reactive astrogliosis that occurs after various types of CNS injury is the increased production of astrocytic processes filled with GFAP-containing IFs. While increased expression of GFAP during reactive astrogliosis has been well established at the protein level, little is known about whether or not changes in GFAP mRNA levels occur after CNS injury. In the present study we used in situ hybridization methods to examine this issue. A 35S-labeled mouse GFAP cDNA probe was used for in situ hybridizations of sections of the brain stem obtained 2, 7, and 14 days after unilateral transections of the corticospinal tract in the caudal medulla. Film as well as emulsion autoradiography showed a dramatic increase in GFAP mRNA labeling associated with the degenerating corticospinal tract. GFAP mRNA levels were already dramatically increased in the injured corticospinal tract by 2 days post axotomy and remained elevated at 14 days. Interestingly, in addition to the robust increase in GFAP mRNA levels specifically associated with the degenerating tract, a diffuse increase in GFAP mRNA labeling was observed throughout the grey matter of the brain stem at 2 days post-axotomy, but not after this time. Immunoblotting and immunocytochemical experiments verified that the increased GFAP mRNA levels in the degenerating corticospinal system were accompanied by an increased expression of the protein. These results demonstrate that an increase in GFAP mRNA levels occurs during Wallerian degeneration in the CNS and suggest that increased expression of the GFAP gene is a major contributor to CNS scarring that results after direct traumatic injury.     

大黄乙醇提取物的体外抗新城疫病毒作用

目的：研究大黄乙醇提取物的抗新城疫病毒（ＮＤＶ）作用。方法：采用体外细胞培养的方法研究大黄乙醇提取物对ＮＤＶ感染的拮抗作用。结果：２０ｇ／Ｌ剂量大黄乙醇提取物对ＢＨＫ２１细胞未有任何毒性作用；０．５ｇ／Ｌ大黄对ＮＤＶ所致ＣＰＥ有明显的抑制作用；大黄可预防ＮＤＶ感染，并对ＮＤＶ的复制动力学有明显影响。结论：大黄乙醇提取物具有明显的抗ＮＤＶ作用。     

分子生物学技术新进展

分子生物技术的发展,衍生出DNA测序、DNA突变以及基因定位和克隆的各种方法.生物芯片则是当代生物技术的最新发展,它对基础研究以及在医学上对疾病分子的探索,开拓了临床新的诊断和治疗手段.该文就这些技术和发展趋势进行综述.