肿瘤坏死因子α调控MPO的分泌在子痫前期发病中的作用

子痫前期(PE)是引起全球孕产妇及新生儿发病率和死亡率升高的妊娠特发性疾病。目前其病因尚未完全明确,单一生物标志物也很难预测其变化。PE患者经积极治疗病情无好转或进行性恶化时,终止妊娠是其唯一有效的治疗措施。学者认为血管内皮细胞损伤是PE的主要发病机制。近年研究发现,PE患者血浆中肿瘤坏死因子α(TNF-α)的异常表达参与疾病的发生和发展。TNF-α与相关受体结合后,可活化丝裂原活化蛋白激酶(MAPK)信号通路导致下游靶蛋白髓过氧化物酶(MPO)水平上调。中性粒细胞过度活化后释放MPO,其表达水平增高是血管内皮细胞损伤的关键因素。综述TNF-α调控MPO的相关机制在PE发病中作用的研究进展。     

Adrenal tumors of different types with or without tumor thrombus invading the inferior vena cava: An evaluation of 33 cases

Background and objectivesAdrenal tumors with/out tumor thrombus (TT) in the inferior vena cava (IVC) pose a challenge to the surgeon due to the potential of massive hemorrhage and tumor thromboembolism. We report our experience in managing different types of adrenal tumors.MethodsFrom 11/1996–5/2015, 33 patients underwent resection of adrenal tumors with/without TT/IVC in 8 and 25 patients, respectively. Transplant-based (TB) techniques were utilized to resect the tumors. Intra-operative as estimated blood loss (EBL) and cardiopulmonary bypass (CPB) use; post-operative as length of hospital stay (LOS); and actuarial survival outcomes were recorded.ResultsMedian EBL was 200 cc (10-8,000), tumor size was 9.0 cm (4–25), and LOS was 7days (5–60). Adrenocortical carcinoma (ACC,11/33) was the commonest type. Three ACC/level IV TT/IVC underwent CPB to extract TT from the right atrium(n = 1), right atrium and right ventricle(n = 1), and right atrium and right pulmonary artery(n = 1), respectively. A complete resection of the adrenal tumors was achieved in all patients, and no deaths were observed in the immediate postoperative period. With a median follow-up of 60 (range: 18–120) months, 4/11 ACC patients have died of their disease. Actuarial survival for ACC patients at 60 months was 57.1 ± 16.4%.ConclusionsAn aggressive surgical approach is the only hope for curing large adrenal tumors with/without TT/IVC. TB techniques provide excellent exposure to the retroperitoneal space and safe removal of large adrenal masses.     

Percutaneous Radiofrequency Ablation of Appendicular Skeleton Chondroblastoma—an Experience from a Tertiary Care Cancer Center

PurposeTo evaluate safety and long-term efficacy of radiofrequency (RF) ablation in treatment of chondroblastoma.Materials and MethodsThis retrospective analysis comprised 27 consecutive patients with histopathologically proven chondroblastoma treated by RF ablation. The tumors were located in the proximal humerus (n = 6), proximal tibia (n = 8), proximal femur (n = 6), distal femur (n = 5), acromion process (n = 1), and lunate (n = 1). In 19 patients (70.3%), the tumor was in the weight-bearing area of the bone. Clinical response was assessed by comparing pain scores and functional assessment by Musculoskeletal Tumor Society (MSTS) score before and after ablation. Patients were followed for a minimum of 1 year to rule out complications and recurrence.ResultsTechnical success rate was 100%. Mean pain score before the procedure was 7.34 (range, 7–9); all patients experienced a reduction in pain, with 25 (92.6%) patients reporting complete pain relief at 6 weeks. Mean MSTS score before the procedure was 15.4, whereas mean MSTS score at 6 weeks after the procedure was 28.6, suggesting significant functional improvement (P < .0001). Two patients developed osteonecrosis and collapse of the treated bone. There were no recurrences.ConclusionsPercutaneous RF ablation is a safe and effective option for treating chondroblastoma of the appendicular skeleton.     

Clinical and pathological predictors of recurrence in breast cancer patients achieving pathological complete response to neoadjuvant chemotherapy

IntroductionDespite the excellent prognosis associated with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), some patients still develop recurrence. Here, we investigated the outcomes of breast cancer patients with pCR, as well as the clinical and pathological predictors of cancer recurrence in these patients.Materials and methodsOf the 1599 breast cancer patients treated with NAC, we evaluated 394 patients who achieved pCR between January 2007 and December 2016. pCR was defined as no evidence of invasive cancer in breast. Residual in situ ductal and axillary lymph node diseases were not considered. We analyzed the outcomes using the Kaplan–Meier method. We assessed the association of clinical and pathological predictors with cancer recurrence using the cox proportional hazards regression model.ResultsThe median follow-up time was 63 months. The 5-year disease-free survival rate was 92.3%. Cancer recurrence was observed in 28 patients (7.1%): local recurrence 8 patients (2.0%), visceral metastasis 10 patients (2.5%), and brain metastasis 10 patients (2.5%). Brain metastases were found in patients with HER2 type breast cancer. The significant predictors of cancer recurrence were HER2 positivity (p = 0.04), clinical tumor size (p < 0.01), and lymph node metastasis (p < 0.01) before NAC on univariate analysis and only lymph node metastasis on multivariate analysis.ConclusionPatients achieving pCR to NAC showed excellent outcomes. Advanced clinical stage, large tumor size, presence of lymph node metastasis, and HER2 positivity before NAC were identified as significant predictors of cancer recurrence. Residual in situ ductal and lymph node diseases after NAC were not significant predictors.     

SCC、CEA、NSE联合检测在肺癌临床诊断中的应用

目的探讨鳞状细胞癌相关抗原(SCC)、癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)联合检测应用于肺癌诊断中的实际价值。方法选择90例肺癌患者作为研究组,同期90例体检健康者作为对照组,两组研究对象均接受CEA、SCC和NSE检查。比较两组研究对象SCC、CEA、NSE水平;研究组不同病理分型患者SCC、CEA、NSE水平。结果研究组SCC、CEA、NSE水平分别为(1.95±0.17)、(22.64±3.65)、(22.00±6.14)ng/ml,均高于对照组的(0.14±0.03)、(1.22±0.97)、(8.32±1.17)ng/ml,差异具有统计学意义(P<0.05)。鳞癌患者SCC水平高于腺癌、小细胞肺癌患者,腺癌患者CEA水平高于鳞癌、小细胞肺癌患者,小细胞肺癌患者NSE水平高于鳞癌、腺癌患者,差异具有统计学意义(P<0.05)。结论应用SCC、CEA、NSE等肿瘤标志物联合检测可为临床诊断肺癌病情、明确病理分型等提供可靠依据。     

Multinodular and Vacuolating Neuronal Tumor of the Cerebrum (MVNT): A case series and review of the literature

Background and purposeMultinodular and Vacuolating Neuronal Tumor of the cerebrum (MVNT) is a benign –seizure associated– lesion affecting mostly adults. This new entity has been included in the 2016 World Health Organization classification of tumors of the central nervous system.Its pathologic hallmark consist of a subcortical cluster of nodular lesions located on the subcortical white matter.We aim to report a series of cases of presumed MVNT observed in our institution and review the literature.Materials and methodsIn this retrospective study, a search was performed on our hospital information system. Sixteen cases were included. Demographic, clinical and radiological features were detailed in a table.All patients had an MRI acquired either on a 1.5 or a 3 Tesla scanner. Sequences performed included T1, T2, GRE/SWI, T2 FLAIR and DWI. Gadolinium enhanced T1-WI wer available in 11 patients and follow-up MRI were available in 7 patients.ResultsPatient ages ranged from 16 to 77 years (mean 42 years). Seizure and non-focal headache were by far the most common neurological complaints for which MRI was requested. All lesions consisted of clusters of multiple, discrete, round or ovoid, intra-axial, FLAIR and T2-WI hyperintense nodules. Follow-up MRI scans showed no changes between studies.ConclusionsMVNT is a benign, stable lesion that exhibits a typical radiological pattern that most of the times sufficed to arrive to a diagnosis, without the need of pathological confirmation. We confirm that our demographic, clinical and radiological findings are in accordance with those published in international literature.     

Endoscopic ultrasound may be used to deliver gene expression signatures using digital mRNA detection methods to immunophenotype pancreatic ductal adenocarcinoma to facilitate personalized immunotherapy

Background & objectivesBiomarkers are increasingly required to molecularly characterize pancreatic ductal adenocarcinoma (PDAC) subgroup populations, to determine who may benefit from immune based targeted therapy. We evaluated the feasibility of gene expression signature detection and the respective landscape of specific tumor infiltrating lymphocytes (TILs), cancer/testis (CT) antigens, and immune checkpoints for possible future personalized immunotherapy eligibility.MethodsDedicated digital mRNA oncologic immune profiling of 770 genes using a Nanostring nCounter® PanCancer Immune Profiling Panel was performed using archived endoscopic ultrasound fine needle biopsy (EUS FNB) PDAC specimens as a case series in a tertiary care setting.ResultsThe spectrum of mRNA gene expression within the tumor specimens revealed that 44.8%, 10.0% and 50.7% of evaluated genes had a ≥ 2-fold increase, a ≤ 2-fold reduction or between <2 and >2 change of mRNA expression, when compared to normal controls. The corresponding landscape of TILs, CT antigens, and immune checkpoints highlighted several possibilities that could potentially be amenable to targeted personalized immunotherapy. This includes members of the Tumor Associated Macrophage family (CD68, CXCL5, and MARCO), members of the CT antigen family (PRAME, TTK and PBK) and the “second generation” checkpoints TIM3 and BTLA.ConclusionsOur study represents the ability to successfully perform digital mRNA expression profile analyses to immunophenotype PDAC EUS FNB specimens by evaluating the expression of >730 genes within the tumor immune microenvironment. This may facilitate the search for novel therapeutic targets, offering the opportunity to go beyond immune monotherapy, but perhaps to use combined immunomodulatory agents.     

Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.