Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time?

Precision Medicine is becoming the new paradigm in healthcare as it enables better resources allocation, treatment optimization with a potential side-effects reduction and consequent impact on quality of life and survival. This revolution is being catalyzed by liquid biopsy technologies, which provide prognostic and predictive information for advanced cancer patients, without the analytical and procedural drawbacks of tissue-biopsy. In particular, circulating tumor DNA (ctDNA) is gaining momentum as a clinically feasible option capable to capture both spatial and temporal tumor heterogeneity.Several techniques are currently available for ctDNA extraction and analysis, each with its preferential case scenarios and preanalytical implications which must be taken into consideration to effectively support clinical decision-making and to better highlight its clinical utility.Aim of this review is to summarize both analytical developments and clinical evidences to offer a comprehensive update on the deployment of ctDNA in breast cancer’s (BC) characterization and treatment.     

138例儿童颅外恶性生殖细胞肿瘤临床研究

目的:研究儿童恶性生殖细胞瘤（malignant germ cell tumor，MGCT）的临床及预后特征。方法:回顾性分析1998年1月至2016年1月上海儿童医学中心收治的初发颅外MGCT患儿138例。对患儿的临床特点、疗效及预后做综合分析。结果:按病理分期，Ⅰ期患儿5年总生存期（overall survival，OS）OS为100.00%，Ⅱ期患儿5年为94.44%，Ⅲ期5年OS为96.43%，Ⅳ期5年OS为88.73%。多因素分析显示，病理分期对生存率的影响有统计学差异（P<0.01），年龄、性别及部位对于生存率的影响无显著统计学差异。本研究中共有13例Ⅰ/Ⅱ期患儿接受手术后临床观察，有5例（38.5%）在2年内出现疾病复发进展的情况并接受化疗，目前均达到临床缓解。结论:通过以手术联合含铂类药物化疗并根据临床危险度的不同分层治疗MGCT瘤患儿，可得到较好的临床疗效。     

Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

ZBTB16: A new biomarker for primitive neuroectodermal tumor element / Ewing sarcoma

Primitive neuroectodermal tumor (PNET) traditionally encompasses two different classes of tumors with similar morphology - PNET of the peripheral nervous system (pPNET) and PNET of the central nervous system (cPNET). The latter also includes germ cell tumor-derived PNET (gPNET). There are currently no specific markers for gPNET. This study seeks to investigate the expression of ZBTB16 in PNET and other small round blue cell tumors as well as its potential diagnostic utility. Immunohistochemical expression of the ZBTB16 was studied in a total of 27 PNETs (12 pPNETs, 8 cPNETs, 3 primary testicular gPNETs, and 4 metastatic gPNETs) and 38 small round blue cell tumors. Positive expression for ZBTB16 was seen diffusely in 9/12 (75%), moderately in 2/12 (17%) and focally in 1/12 (8%) of pPNETs, diffusely in 3/7 (43%) and moderately in 4/7 (57%) of gPNETs, and diffusely in 2/8 (25%), moderately in 2/8 (25%) and focally in 4/8 (50%) of cPNETs. Whereas, all of the 38 non-PNET small round blue cell tumors were nonreactive. The results suggest that ZBTB16 is a highly sensitive and specific biomarker for both pPNET and gPNET/cPNET. ZBTB16 effectively differentiates PNETs from other small round blue cell tumor mimics, including the two most common germ cell tumor-derived somatic malignancies - rhabdomyosarcoma and nephroblastoma. Of note, compared to the expression of ZBTB16 in pPNET/Ewing sarcoma and gPNET, the expression of ZBTB16 in cPNET was more variable, which appears consistent with the heterogeneity of cPNET. The close proximity of ZBTB16 and FLI-1 genes on chromosome 11q may explain the overexpression of ZBTB16 in PNET, especially in pPNET with t(1122) translocation.     

Personalizing surgical margins in retroperitoneal sarcomas: an update

Introduction: Tumor biology, as well as completeness of surgical resection, are two important prognostic factors when treating retroperitoneal sarcoma (RPS). A frontline extended surgical approach is associated with improved local control and possibly improved survival. However, this approach has to be tailored to each histological subtype, as the patterns of growth and recurrence risks vary significantly among them.

Areas covered: We provide a review of the literature in RPS, describing the behavior of each of the five main histologic subtypes: well-differentiated liposarcoma (WDLPS), dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS), solitary fibrous tumor (SFT) and malignant peripheral nerve sheath tumor (MPNST). The prognostic factors relevant to oncologic outcomes of RPS, the role of margins and the importance of local control are discussed. Finally, a histologic specific surgical approach to RPS is provided in detail.

Expert opinion: While tumor-related factors are paramount, the only intervenable predictive factor is extent and quality of surgery. The extended surgical approach has been advocated for previously and again we describe it in more detail, tailored specifically to the tumor subtype. The aim of this approach is to maximize the possibility of achieving a complete resection through a standardized approach based on histologic behavior and site of origin.     

Plaque‐like myofibroblastic tumor,a rare entity of childhood: Possible pitfalls in differential diagnosis

Plaque‐like myofibroblastic tumor is a rare and benign pediatric soft tissue tumor. It presents as a slowly growing plaque reaching several centimeters in diameter, made up of multiple nodules. The clinical and histological features of this benign entity are similar to other fibrohistiocytic or myofibroblastic tumors occurring in childhood, so the diagnosis can be difficult. The correlation between clinical data, histopathology, and immunohistochemistry is necessary for the correct diagnosis.     

Positive HLA‐B27 and sacroiliitis is not always spondyloarthritis

A 36‐year‐old man was treated for several years with multiple agents for ankylosing spondylitis based on positive human leukocyte antigen‐B27 and sacroiliitis. He was also diagnosed with osteoporosis and hypophosphatemia. Over these years, from being an avid runner, he became dependent on a walker for ambulation. The lack of treatment response and the low phosphorus were clues that eventually led to a diagnosis of tumor‐induced osteomalacia. This case discusses the importance of not solely relying on genetic markers and sacroiliitis for diagnosing ankylosing spondylitis as other conditions can cause similar presentations.     

Histopathology of giant cell tumors of the bone: With special emphasis on fibrohistiocytic and aneurysmal bone cyst like components

Objective

The aim of this study was to define histopathological features of giant cell tumor of bone, especially accompanying fibrohistiocytic or aneurysmal bone cyst like components, in the light of our institutions experience.

改良Miccoli腔镜辅助下手术和经乳晕入路单孔法内镜下治疗甲状腺良性肿瘤效果观察

目的探讨改良Miccoli腔镜辅助下手术和经乳晕入路单孔法内镜下治疗甲状腺良性肿瘤的效果。方法对2015年8月～2017年3月我院60例甲状腺良性肿瘤患者进行筛选,依据患者意愿及要求选择手术治疗方式,对改良Miccoli组(30例)与经乳晕单孔组(30例)围术期机体创伤指标、手术指标、术后切口美容效果、术后疼痛指标等展开对比。结果两组创伤相关指标在术前均无差异(P0.05),术后WBC、TSH测验水平均上升,血钙、PTH测验水平下降,且改良Miccoli组波动幅度相较经乳晕单孔组更为轻微,差异有统计学意义(P0.05)。改良Miccoli组手术切口大小、术中出血量、术后引流总量、手术时间、住院时间指标统计均较经乳晕单孔组显著下降(P0.05),住院费用远高于经乳晕单孔组(P0.05)。改良Miccoli组患者颈部活动恢复时间相较经乳晕单孔组明显缩短,术后6 h、12 h及24 h疼痛值低于经乳晕单孔组(P0.05)。对术后1周、1个月及1年切口的美容效果比较,改良Miccoli组均较经乳晕单孔组评分高(P0.05)。改良Miccoli组并发症总发生率(10%)低于经乳晕单孔组(20%),差异有统计学意义(P0.05);总满意度(93.33%)高于经乳晕单孔组(86.67%),但差异无统计学意义(P0.05)。结论对甲状腺良性肿瘤患者予以改良Miccoli腔镜辅助手术及经乳晕入路单孔法内镜治疗,均可取得满意效果,但相对而言,前者对患者机体所造成的创伤应激更小,但费用更高,且后者手术切口位于隐秘部位,颈部无创,故临床在选择术式可充分考虑患者意愿,取更适宜术式。     

Biweekly Cetuximab Plus FOLFOX6 as First-Line Therapy in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The CEBIFOX Trial

BackgroundThe multicenter, single-arm, phase II study CEBIFOX evaluated the efficacy of a biweekly cetuximab administration in combination with FOLFOX6 as first-line therapy in KRAS (exon 2) wild-type (wt) metastatic colorectal cancer (mCRC).Patients and methodsPatients received FOLFOX6 with cetuximab (500 mg/m²) every second week. Primary endpoint was objective response rate (ORR), among others secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), and patient-reported outcome (PRO). The impact on the treatment efficacy was evaluated in explorative subgroup analyses, including extended molecular profiling and primary tumor location.ResultsIn total, 57 were included in the intention-to-treat (ITT) analyses. New RAS mutations were detected in 14.0% by post hoc next-generation sequencing analysis in 43 patients. The ORR in the all RASwt population was 70.3% with a median PFS and OS of 10.9 (95% confidence interval [CI], 9.0-12.9) and 33.8 (95% CI, 21.1-45.5) months. Grade 3-5 adverse events occurred in 66.7% of the ITT, without significant impact on the PRO. Patients with right-sided primary tumors had a reduced ORR (54.5%), and median PFS and OS (10.1 and 23.8 months). BRAF mutations were detected in 11.3%. These patients had a significantly lower ORR, and median PFS and OS. Patients with RASwt/BRAFwt tumors had a notably high median PFS and OS of 14.3 and 38.9 months.ConclusionsThis study supports the efficacy and safety of biweekly cetuximab given in combination with FOLFOX6 in patients with RASwt/BRAFwt mCRC with left-sided primary tumor. CEBIFOX is the first trial reporting the complete dataset, including extended molecular profiling and tumor location of a biweekly administered cetuximab/FOLFOX6 in mCRC. Clinical trial number: NCT01051167.