The appearance of breast cancer metastases on dry bone: Implications for forensic anthropology

Breast carcinoma is a major cause of morbidity and mortality in women. The study of bone pathologies presents considerable potential in anthropology, paleopathology, forensic science and medicine. In this paper, we present and discuss metastatic lesions found in the skeletons of known individuals from the CAL Milano Cemetery Skeletal Collection, clinically diagnosed with breast cancer during life. Fourteen skeletons from a contemporary and identified collection were macroscopically studied and metastases were identified by comparison with clinical literature. As a result, bone metastases were observed in 43% of the study sample. They were located most commonly on the ribs (28.1%), pelvic girdle (19.8%), vertebrae (15.6%), skull (15.6%), scapulae (10.2%) as well as proximal segment of the femora (8.4%) and humeri (2.4%) respectively, favoring sites of high vascularization. The majority of the lesions were osteolytic, although osteoblastic and mixed metastases did occur. Osteolytic metastases appear as coalescent porosity or round to oval perforating lesions on bones with denticulated margins and pitted surrounding bone, whereas osteoblastic metastases thickened the existing trabecula (spongiosclerosis). Mixed metastases were perforating lytic lesions exposing the osteoblastic activity in the underlying trabecular bone. These results, consistent with the data from the literature, strengthen the diagnostic criteria for metastases and illustrate the aspect of bone metastases in breast carcinoma.     

Transjugular Renal Biopsy Bleeding Risk and Diagnostic Yield: A Systematic Review

This study aimed to better define the safety and efficacy of transjugular renal biopsy (TJRB) based on published studies. Seventeen published articles were included (1,321 biopsies). Complications were classified as major if they resulted in blood transfusion or additional invasive procedures. All other bleeding complications were considered minor. Diagnostic tissue was obtained in 1,193 procedures (90.3%). The total incidence of bleeding complications among 15 articles with complete data was 202 of 892 procedures (22.6%): 162 (18.2%) minor and 40 (4.5 %) major. These results show that TJRB is a feasible procedure for obtaining renal tissue for diagnosis and that most complications are self-limiting.     

Can EGFR mutation status be reliably determined in pre‐operative needle biopsies from adenocarcinomas of the lung?

The identification of EGFR mutations in non‐small‐cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre‐operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro‐dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre‐operative, cytological specimens. Several (18.4%) analyses of the pre‐operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra‐tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre‐operative biopsies for EGFR mutation analysis.     

卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能和骨密度的影响分析

目的探究卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能、骨密度的影响。方法92例成人癫痫患者作为研究对象,随机分为左乙拉西坦组与卡马西平组,各46例。左乙拉西坦组采用左乙拉西坦治疗,卡马西平组采用卡马西平治疗。比较两组患者治疗前及治疗6个月后认知功能[语言智商(VIQ)、操作智商(PIQ)、总智商(FIQ)]评分、骨密度(腰椎、股骨大转子、股骨颈)变化情况。结果治疗6个月后,两组患者VIQ、PIQ、FIQ评分均较治疗前显著提升,且左乙拉西坦组患者VIQ评分(101.2±3.1)分、PIQ评分(108.1±2.3)分、FIQ评分(105.2±1.8)分均明显高于卡马西平组的(95.1±2.8)、(94.1±2.0)、(93.5±1.6)分,差异有统计学意义(P<0.05)。治疗6个月后,卡马西平组患者腰椎、股骨大转子、股骨颈骨密度均较治疗前显著下降,且明显低于卡马西平组,差异有统计学意义(P<0.05);左乙拉西坦组治疗6个月后腰椎、股骨大转子、股骨颈骨密度与治疗前比较差异无统计学意义(P>0.05)。结论左乙拉西坦与卡马西平治疗成人癫痫,左乙拉西坦更能明显提升患者认知功能,且对患者骨密度无影响。     

Molecular profiling of ctDNA in pancreatic cancer: Opportunities and challenges for clinical application

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised.