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.     

A diagnostically‐challenging case of melanoma ex blue nevus with comprehensive molecular analysis,including the 23‐gene expression signature (myPath melanoma)

Melanoma ex blue nevus (MEBN) is a rare, aggressive, and potentially lethal neoplasm. Distinguishing MEBN from an atypical cellular blue nevus can be very challenging. We report a diagnostically difficult case of MEBN with lymph node metastases, in which single nucleotide polymorphism array and fluorescence in situ hybridization were used to arrive at the correct diagnosis. It was also analyzed by the recently‐introduced proprietary 23‐gene expression signature test. To the best of our knowledge, this is the second reported case of MEBN analyzed by the 23‐gene expression signature, which provided a false‐negative result. More studies are needed to assess the sensitivity and specificity of this test in various melanocytic proliferations.     

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.     

Targeting glycosylated antigens on cancer cells using siglec-7/9-based CAR T-cells

Chimeric antigen receptor (CAR) T-cells treatment demonstrate the increasing and powerful potential of immunotherapeutic strategies, as seen mainly for hematological malignancies. Still, efficient CAR-T cell approaches for the treatment of a broader spectrum of tumors are needed. It has been shown that cancer cells can implement strategies to evade immune response that include the expression of inhibitory ligands, such as hypersialylated proteins (sialoglycans) on their surface. These may be recognized by sialic acid-binding immunoglobulin-type lectins (siglecs) which are surface receptors found primarily on immune cells. In this regard, siglec-7 and -9 are found on immune cells, such as natural killer cells, T-cells, and dendritic cells and they can promote immune suppression when binding to sialic acids expressed on target cells. In the present study, we hypothesized that it is possible to use genetically engineered T-cells expressing siglec-based CARs, enabling them to recognize and eliminate tumor cells, in a non-histocompatibility complex molecule restricted way. Thus, we genetically modified human T-cells with different chimeric receptors based on the exodomain of human siglec-7 and -9 molecules and selected optimal receptors. We then assessed their antitumor activity in vitro demonstrating the recognition of cell lines from different histologies. These results were confirmed in a tumor xenograft model exemplifying the potential of the present approach. Overall, this study demonstrates the benefit of targeting cancer-associated glycosylation patterns using CAR based on native immune receptors and expressed in human primary T-cells.     

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling

Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.     

Treatment of generalized infantile myofibromatosis with sorafenib and imatinib: A case report

Infantile myofibromatosis (IM) is characterized by solitary musculoskeletal nodules presenting during infancy but can manifest as multiple lesions with visceral involvement. Multicentric IM with visceral involvement carries a high risk of mortality and there is no consensus on treatment. We present a case of a patient with multicentric IM and pulmonary involvement who progressed on several chemotherapeutic regimens and subsequently had a complete response to sorafenib and later imatinib. This report describes the novel use of sorafenib and imatinib to treat generalized IM and the role of continued tyrosine kinase inhibitor therapy to maintain remission.