Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

家族性甲状腺髓样癌诊断与治疗

家族性甲状腺髓样癌（FMTC）作为甲状腺髓样癌（MTC）的一个重要分型,恶性程度较高,具有早期侵犯区域淋巴结和远处转移的倾向,预后相对较差,且有发病率不断增高的趋势。近年来关于FMTC临床的诊断和治疗进展较多,血清降钙素水平检测、基因检测等诊断方法提供了更精准的术前评估与复发监测的手段;疾病早期,根治性手术治疗仍占FMTC治疗的主要地位。根据基因检测的结果,进行预防性甲状腺切除以及分子靶向治疗也得到了快速的发展和应用,使传统手术与新兴治疗方法相结合,进一步提高了FMTC的治疗效果。     

甲状腺髓样癌手术切除范围及预后影响因素研究

目的 分析甲状腺髓样癌（MTC）手术切除范围及预后影响因素。方法 回顾性分析2015年1月至2017年6月期间首诊于天津医科大学肿瘤医院MTC病人的临床资料。分析临床病理特征与中央区、侧颈区淋巴结转移及生化治愈的关系;探讨影响病人无进展生存期的危险因素。结果 77例病人,术前降钙素水平正常者5例,升高者72例。行全甲状腺切除28例,单侧腺叶切除49例。仅行中央区淋巴结清扫39例,中央区及患侧侧颈淋巴结清扫38例。MTC病人中央区淋巴结转移与性别、侵出腺叶、肿瘤直径、TNM分期、术前降钙素、降钙素水平/肿瘤直径具有相关性（P＜0.05）。侧颈淋巴结转移与年龄、TNM分期具有相关性（P＜0.05）。生化治愈率66.1%（39/59）,与中央区淋巴结转移、TNM分期、肿瘤直径、术前降钙素水平及降钙素水平/肿瘤直径具有相关性（P＜0.05）。中位随访时间35（7~69）个月。侵出腺叶、中央区淋巴结转移、淋巴结转移、淋巴结切除范围、TNM分期、术前降钙素水平和生化治愈是MTC病人无进展生存期的影响因素（P＜0.05）。结论 MTC病人建议至少行患侧腺叶切除及中央区淋巴结清扫,必要时行全甲状腺切除,根据超声、CT及降钙素水平等检查结果行预防性/治疗性侧颈淋巴结清扫。规范化的手术治疗是达到较高生化治愈率,减少复发的关键。     

股骨髓腔狭窄患者生物柄全髋关节置换

背景：亚洲人体型较小,股骨通常较短且髓腔狭窄,进行人工髋关节置换时常会遇到插入困难,目前尚无有关股骨髓腔狭窄患者进行人工关节置换的相关报道。目的：探讨股骨髓腔狭窄患者生物柄假体全髋关节置换的固定特点与临床疗效。方法：2005年5月至2009年8月,采用锥形生物柄进行全髋关节置换22例23髋,男2例2髋,女20例21髋;年龄19～56岁,平均37.6岁。股骨髓腔峡部直径7.5～8.2mm,平均7.8mm。手术采用生物型全髋关节置换假体,其中三锥度生物型股骨直柄18例,二锥度生物型股骨直柄5例。术后第1、3、6个月及1年门诊随访,以后每年随访1次,随访时采用Harris髋关节评分评估髋关节功能,X线片观察假体压配和生物学固定效果。结果：全部病例随访28～72个月,平均38.5个月。1例22mm直径股骨头术后第3天侧卧拍片摆动体位时发生股骨头前脱位,经手法复位后回纳。Harris髋关节评分由术前（46.2±6.2）分改善至术后半年（90.2±5.1）分,末次随访仍维持在（92.1±3.2）分。23髋术后均立即实现股骨柄的压配。正侧位X线片示股骨柄的髓内充填分别达94%～98%,平均96.5%和87%～94%,平均91.2%。术后3个月的X线片示均获得广泛性骨长入。结论：股骨髓腔狭窄患者适当扩髓可获得良好的临床效果,周密而严谨的术前计划可准确地预测出假体型号、位置,并能有效缩短手术时间,减少术后并发症。     

Neurotoxicity of prenatal alcohol exposure on medullary pre-B?tzinger complex neurons in neonatal rats

Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is un-known whethe...     

Differential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis

Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer of thyroid C-cells, for which few treatment options are available. We have recently reported a role for cyclin-dependent kinase 5 (CDK5) in MTC pathogenesis. We have generated a mouse model, in which MTC proliferation is induced upon conditional overexpression of the CDK5 activator, p25, in C-cells, and arrested by interrupting p25 overexpression. Here, we identify genes and proteins that are differentially expressed in proliferating versus arrested benign mouse MTC. We find that downstream target genes of the tumor suppressor, retinoblastoma protein, including genes encoding cell cycle regulators such as CDKs, cyclins and CDK inhibitors, are significantly upregulated in malignant mouse tumors in a CDK5-dependent manner. Reducing CDK5 activity in human MTC cells down-regulated these cell cycle regulators suggesting that CDK5 activity is critical for cell cycle progression and MTC proliferation. Finally, the same set of cell cycle proteins was consistently overexpressed in human sporadic MTC but not in hereditary MTC. Together these findings suggest that aberrant CDK5 activity precedes cell cycle initiation and thus may function as a tumor-promoting factor facilitating cell cycle protein expression in MTC. Targeting aberrant CDK5 or its downstream effectors may be a strategy to halt MTC tumorigenesis.     

RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D

There are no reports on the relationship between familial medullary thyroid carcinoma (FMTC) associated with cutaneous amyloidosis (CA) and RET or OSMR/IL31RA gene mutations. In this study, we investigated a Chinese family with FMTC/CA and found a recurrent RET c.2671T>G (p.S891A) mutation in six of 17 family members. Three of the six p.S891A mutation carriers presented with medullary thyroid carcinoma (MTC). Of them, three (two with and one without MTC) were diagnosed as having combined lichen/macular biphasic CA. We also identified a novel RET variant, c.1573C>T (p.R525W) in five members. Of them, three carriers had no evidence of thyroid/skin or basal serum/stimulated calcitonin abnormalities. In vitro cell proliferation assay indicated that oncogenic activity of RET p.S891A was slightly enhanced by p.R525W, whereas p.R525W alone had no effect on cell proliferation. Meanwhile, we identified a novel OSMR variant, c.1538G>A (p.G513D) in seven members. We noticed that three OSMR p.G513D carriers presenting with CA also had the RET p.S891A mutation. Our investigation indicated that the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as FMTC and CA.     

甲状腺髓样癌的外科治疗进展

甲状腺髓样癌(medullary thyroid carcinoma,MTC)为相对少见的恶性肿瘤之一,约占所有甲状腺癌的3%~5%,其组织来源为甲状腺滤泡旁细胞。MTC细胞能够产生降钙素(calcitonin)和其他具有内分泌活性的物质,其临床表现可有腹泻、潮红等类癌综合征或内分泌失调的表现,治疗上主张甲状腺全切除术,故不同于其他类型甲状腺癌。本文就MTC的外科治疗进展作一综述。