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关键词： Gastric cancer   Mutation   Deep learning   Digital pathology   Formalin-fixed paraffin-embedded  

摘要： BACKGROUND Studies correlating specific genetic mutations and treatment response are ongoing to establish an effective treatment strategy for gastric cancer(GC).To facilitate this research,a cost-and time-effective method to analyze the mutational status is *** learning(DL)has been successfully applied to analyze hematoxylin and eosin(H and E)-stained tissue slide *** To test the feasibility of DL-based classifiers for the frequently occurring mutations from the H and E-stained GC tissue whole slide images(WSIs).METHODS From the GC dataset of The Cancer Genome Atlas(TCGA-STAD),wildtype/mutation classifiers for CDH1,ERBB2,KRAS,PIK3CA,and TP53 genes were trained on 360×360-pixel patches of tissue *** The area under the curve(AUC)for the receiver operating characteristic(ROC)curves ranged from 0.727 to 0.862 for the TCGA frozen WSIs and 0.661 to 0.858 for the TCGA formalin-fixed paraffin-embedded(FFPE)*** performance of the classifier can be improved by adding new FFPE WSI training dataset from our *** classifiers trained for mutation prediction in colorectal cancer completely failed to predict the mutational status in GC,indicating that DL-based mutation classifiers are incompatible between different *** This study concluded that DL could predict genetic mutations in H and E-stained tissue slides when they are trained with appropriate tissue data.

关键词： 前列腺癌   表皮生长因子受体   rs884419   基因多态性   临床病理学特征  

摘要： 背景与目的:表皮生长因子受体(epidermal growth factor receptor,EGFR)基因的高表达被证明在前列腺癌中可间接促进肿瘤细胞迁移,并与较短的无转移生存期相关。但此前对于EGFR基因的研究主要集中于机制方面,很少与临床指标建立联系。对比EGFR基因在西方国家和中国前列腺癌患者中基因型的差异,同时探讨临床病理学特征与EGFR基因多态性的相关性。方法:检测EGFR(rs884419)基因在复旦大学附属肿瘤医院2014—2019年连续收治的182例前列腺癌患者外周血白细胞DNA中的多态性情况,比较中国与西方人群基因型变异的差异,并比较基因型与临床病理学特征及基线特征的相关性。结果:与EGFR(rs884419)基因型为AA和AG的变异组患者相比,基因型为GG的正常组患者在初诊时为M1期的占比更高(65.3%vs 84.2%,P<0.05)。EGFR(rs884419)基因多态性与确诊时年龄、确诊时前列腺特异性抗原、转移负荷及Gleason评分无相关性(P>0.05)。与美国前列腺癌患者相比,EGFR(rs884419)基因的变异频率更高(20.4%vs 79.1%,P<0.05)。结论:EGFR基因型正常组患者初诊时M_(1)期占比较变异组高,提示EGFR基因的表达差异可能参与前列腺癌转移的发生、发展过程,根据基因型理论上可以预测患者初诊时的远处转移状态;同时,与西方人群相比,中国前列腺癌患者EGFR基因的变异频率较高,对确诊后治疗效果的预测效能会更高。

摘要： Purpose/Objective(s) The standard of care for rectal cancer is either long or short course radiation followed by surgery with or without adjuvant chemotherapy. Recently, total neoadjuvant therapy, an approach consisting of giving all chemotherapy and radiotherapy prior to definitive surgery, has been a promising alternative. This study aims to assess the pathologic complete response (pCR) rates among different neoadjuvant treatment regimens and determine if neoadjuvant chemotherapy improves pCR rates. Materials/Methods Electronic medical databases were queried to identify rectal cancer patients treated with neoadjuvant therapy at our institution from 2006-2019. Patients were grouped according to neoadjuvant therapy received: long-course chemoradiation (CRT), long-course chemoradiation with chemotherapy (CRT TNT), short-course radiation (SCRT), and short-course radiation with chemotherapy (SCRT TNT). Patients without follow-up data or surgical pathology reports were excluded. pCR was defined as no evidence of disease at surgery. pCR rates were determined and compared using Chi-square analysis. Results A total of 249 patients were analyzed. Table 1 shows treatment characteristics in each group. There were 200 (80.3%) patients who received CRT, 26 (10.4%) who received CRT TNT, 13 (5.2%) who received SCRT, and 10 (4%) who received SCRT TNT. Initial stage was different between groups, with metastatic patients more likely to receive SCRT TNT (P < 0.001). The median time to surgery were significantly different between groups (P < 0.001). Eleven (42.3%) and 6 (60%) patients received FOLFOX, and 13 (50%) and 4 (40%) of the patients received XELOX for CRT TNT and SCRT TNT, respectively. The remaining patients (7.7%) in the CRT TNT group received Capecitabine. For CRT, 53 (26.5%) patients achieved pCR, 3 (11.5%) in CRT TNT, 1 (7.7%) in SCRT, and 2 (20%) in SCRT TNT. None of these differences were statistically different (P  = 0.19). On univariate analysis, age (P  = 0.13), cli

关键词： 抽象绘画   病理学   著名教育家   实验装置   中国文化自信   徐诵明   流派  

摘要： 徐冬冬一直坚信建立一个画种不是最终目标,让中国文化自信地进入世界才是中国知识分子的理想与追求。“画画不是目的,问道是根本。”这是开中国抽象绘画流派之先河的画家徐冬冬的追求。年少成名从小与外祖父,著名教育家、中国病理学奠基人徐诵明先生生活在一起的徐冬冬年少时的理想是当一名水利工程师,年少气盛的他还曾因为实验装置未能获得满意的奖项而赌气“我不干了”。

摘要： Purpose/Objective(s) Total neoadjuvant therapy (TNT) including chemotherapy (chemo) and concurrent chemo and radiotherapy (RT) is a promising strategy for rectal cancer. Characterizing tumor regression during TNT represents an important area of research. We report a prospective validation study of the Magnetic Resonance Tumor Regression Grade (MR-TRG) using MRIs from NRG-GI002, a phase II trial of TNT for rectal cancer. Materials/Methods This was the a priori designed imaging biomarker study of NRG-GI002 seeking to correlate the MR-TRG with the pathologic Neoadjuvant Rectal score (NAR) and pathologic complete response (pCR). 110 patients (pts) were needed with 2 MRI's, 1 pre-TNT and 1 post. Three diagnostic radiologists independently reviewed each MRI and completed a consensus read. Radiologists’ assessment of complete response (mriCR) was tested for its positive predictive value (PPV), negative predictive value (NPV), sensitivity (sen), and specificity (spec) with pCR. Chi-squared test was used for association of mriCR and pCR, and Wilcoxon-Mann-Whitney test was used for association of MR-TRG and pCR. Spearman Rho was used for association of MR-TRG/mriCR and NAR. P -values < .05 (2-sided) were considered significant. Each reader's T-stage, N-stage, extra-mural vascular invasion (EMVI), MR-TRG score and diffusion weighted imaging (DWI) assessment was evaluated for inter-reader variability by Kappa statistics. Kappa values of agreement were interpreted as: poor, < 0.0; slight, 0.0–0.2; fair, 0.2–0.4; moderate, 0.4–0.6; substantial, 0.6–0.8; and almost perfect, 0.8–1.0. All analyses were performed using a data management and decision management software. Radiologists were blinded to pathologic data. Results A total of 126 patients, from 76 institutions, had 2 MRI's (pre-TNT and post), 3 radiologists completed 756 MRI interpretations. Of 126 patients, 29% were female (N = 37), 85% white (N = 107) and median age was 55 (24-76). Individual and consensus MR-TRG scores wer

摘要： Purpose/Objective(s) While exploring histopathological high-risk factors for squamous cell oral cancer most studies have included oral tongue as major subsite in their patient population. Buccal mucosal squamous cell carcinoma (BMSCC) being rare in developed countries is a less studied site in this regard. Hence most of the knowledge we have about high-risk factors of BMSCC is extrapolated from oral tongue carcinoma. The objective of this study was to explore inter-correlations between various pathological high-risk factors found in resected specimen of BMSCC. Materials/Methods It was a retrospective analysis in which we reviewed the final histopathology of surgical specimen of 150 patients with BMSCC who had undergone upfront surgical resection followed by adjuvant therapy. Various high-risk factors studied were pT Stage, pN Stage, depth of invasion (DOI), grade, perineural invasion (PNI), lymphovascular invasion (LVI), tumor thickness (TT), worst pattern of invasion (WPOI), and extranodal extension (ENE). Inter-correlations were performed between various pathological factors using Spearman's correlation test. Results Inter-correlation between various factors were found and shown in Table. Conclusion pT stage showed significant positive correlation with pN stage, TT, DOI, PNI, nodal deposit size and with ENE. pN stage showed significant positive correlation with pT stage, PNI, LVI, WPOI and ENE. PNI showed significant positive correlation with pT stage, pN stage, nodal deposit size, ENE, LVI, DOI, TT, WPOI. LVI showed significant positive correlation with PNI, WPOI, pN stage, nodal deposit size and ENE. DOI showed significant positive correlation with pT stage, PNI, TT. TT showed significant positive correlation with pT stage, PNI and DOI. WPOI showed significant positive correlation with pN stage, frozen section margin, PNI, LVI and ENE. ENE showed significant positive correlation with pT stage, pN stage, PNI, LVI and WPOI. Grade, configuration and margin status o

关键词： 甲状腺髓样癌   儿童青少年   免疫组织化学   降钙素   预后  

摘要： 背景与目的:儿童青少年甲状腺髓样癌(medullary thyroid carcinoma,MTC)少见,国内报道甚少。探讨儿童青少年MTC临床病理学特征、诊断及预后因素,以提高对其认识。方法:收集2007年1月—2021年5月在福建省肿瘤医院确诊的儿童青少年MTC共10例,对其临床特征、形态学、免疫表型、基因突变及预后进行分析。结果:散发病例6例,有家族史者4例,年龄10~20岁,平均17岁,均有血清降钙素(calcitonin,CT)和癌胚抗原(carcinoembryonic antigen,CEA)升高。9例为双侧甲状腺病变,肿瘤直径0.2~3.5 cm,中位直径1.5 cm。镜下肿瘤呈片状、巢状或梁状分布,侵袭性生长模式,伴有卫星结节病灶,部分病例可见乳头及滤泡结构,肿瘤细胞以圆形、卵圆形细胞为主,混杂有梭形/纺锤状细胞及浆样细胞,可见少量瘤巨细胞及核内假包涵体。间质不同程度纤维化/淀粉样沉积,偶见钙化和砂粒体。肿瘤细胞呈突触素(synaptophysin,Syn)、嗜铬素A(chromogranin A,CgA)、分化簇(cluster of differentiation,CD)56、CT、CEA、甲状腺转录因子-1(thyroid transcription factor-1,TTF-1)及刚果红染色阳性表达,甲状腺球蛋白(thyroglobulin,Tg)阴性。RET基因M918T突变为MTC最常见的基因改变。8例患者术后血清CT和CEA降至正常水平,随访时间27~98个月,平均为62个月,无复发、转移(生化治愈);1例患者生化未愈,且于术后第75和108个月行两次颈部转移淋巴结清扫。另外1例患者术后6个月因肿瘤死亡。该死亡病例的肿瘤细胞呈现高级别核(细胞多形、核仁明显,核分裂象>3个/10HPF),Ki-67增殖指数较高(20%),并可见大量脉管内癌栓及局灶性坏死。结论:儿童青少年MTC绝大多数为双侧甲状腺病变,双侧甲状腺全切是清除潜在隐性病灶和防止复发的最佳治疗方式。血清CT和CEA升高是其重要临床特征。高级别核、高Ki-67增殖指数、脉管内癌栓及坏死,为其重要不良预后指标。

关键词： 胃癌   MSI   HGF   临床病理学特征   预后  

摘要： 目的探究微卫星不稳定性(MSI)、肝细胞生长因子(HGF)与胃癌临床病理学特征及预后关系。方法选取石家庄市人民医院普通外科2013年12月至2018年12月收治的100例胃癌患者作为研究对象。免疫组化法检测MSI、HGF表达情况,分析两者与胃癌患者临床病理学特征关系,对患者进行随访,Kaplan-Meier生存分析患者预后生存情况,COX回归分析影响胃癌患者预后的影响因素。结果 MSI-H、MSI-L、MSS三组在肿瘤位置、肿瘤Lauren分型、TNM分期、淋巴结转移、分化程度上,比较差异有统计学意义(P<0.05);HGF表达情况与胃癌临床病理学特征均无相关(P>0.05)。spearman相关性分析显示:MSI与HGF表达呈负相关(r=-0.259,P<0.05)。Kaplan-Meier生存分析显示,MSI与MSS、HGF表达阴性与HGF表达阳性胃癌患者的生存时间比较差异有统计学意义(P<0.05)。多因素COX回归分析显示,TNM分期Ⅲ~Ⅳ期、淋巴结转移阳性、HGF表达阳性均为胃癌患者预后的危险因素,MSI为其保护因素(P<0.05)。结论 MSI、HGF表达与胃癌患者随访生存率相关密切;TNM分期Ⅲ~Ⅳ期、淋巴结转移阳性、HGF表达阳性均为胃癌患者预后的危险因素,MSI为其保护因素。

摘要： Purpose/Objective(s) VMAT, deep inspiratory breath hold (DIBH) and adaptive replanning (ART), are increasingly used for LA-NSCLC to improve conformality and reduce treatment toxicity. Yet, impact of these advanced techniques on pathologic response (PR) and local recurrence (LR) is lacking. We evaluated VMAT, DIBH and ART compared to 3D-conformal radiation therapy (3DCRT) and free breathing (FB), hypothesizing that PR and LR would be unaffected. Materials/Methods Retrospective analysis of PR and LR in patients with LA-NSCLC treated in a single academic center between 2012-2021 with platinum based chemoradiation (CRT) followed by completion resection. Radiation techniques assessed: VMAT, DIBH and ART (due to tumor shrinkage during treatment). Data collected: gender, smoking, stage, GTV, tumor histology, tumor location, dose (Gy), chemotherapy, and time interval between CRT and surgery. Endpoints: PR and LR. PR was converted to a binary variable: Major pathologic regression (MPR) (complete response or ≤10% residual tumor cells) vs. residual tumor (> 10% residual tumor cells). Pathological assessment was blinded to radiation technique. LR was determined by CT or PET-CT. Statistical analysis was by logistic regression. Results Characteristics of patients (n = 106) with LA-NSCLC were: median age: 63 (range 43-79), males: 73/106 (69%), mean radiation dose: 60.7 Gy (SD 4.6 Gy), median GTV: 115cc (range 19-448), and median time interval (CRT-surgery): 65d (range 28-424d). Radiation techniques were: 3DCRT-FB (n = 51, 48 %), VMAT-FB (n = 40, 38%), VMAT-DIBH (n = 15, 14%), and ART (n = 24, 22.6%). Overall MPR was 73/106 (68.9%). MPR was not significant for VMAT (40/55, 73%) vs. 3DCRT (33/51, 64.7%) (OR 0.7, NS) or DIBH (11/15, 73%) vs. FB (62/91, 68%) (OR-1.1, NS). MPR was significant for ART (20/24, 83%) vs. no-ART (53/82, 64.6%) (OR 3.2, P  = 0.037), never smokers (6/18, 33%) vs. smokers (65/86, 75%) (OR-0.49, P  = 0.007), GTV > 115cc (45/55, 81%) vs. GTV ≤115 cc (28/51, 55%)

摘要： Purpose/Objective(s) The therapeutic response of soft tissue sarcoma (STS) to neoadjuvant treatment has been associated with improved margin status, disease control, and survival. Given the rarity of this disease and the confounding effects of chemotherapy, this study analyzes whether the pathological necrosis rate (PN) of preoperative radiation (RT) alone is associated with improved clinical outcomes for STS. Materials/Methods An IRB retrospective review was conducted on a database of 315 patents treated at our institution between 1987 and 2015 who received neoadjuvant RT alone followed by surgical resection, of which 203 had documented PN. Time to event outcomes estimated via Kaplan-Meier included overall survival (OS), progression-free survival (PFS), time to loco-regional failure (TTLRF), and time to distant failure (TTDF). Cox regression analyses were performed to determine prognostic variables associated with clinical outcomes. Results With a median follow up of 87 months, 157 patients (77%) obtained a clear resection margin (R0). The average PN rate was 56% and 37 patients (18%) achieved a PN≥95%. PN was significantly higher for R0 (vs. R1) resection (70% vs. 45%, P  = 0.014) and achieving a PN≥95% was associated with an R0 resection (P  = 0.057). PN≥95% was associated with a 5-year non-significant benefit in TTLRF (94% vs 86%, P  = 0.274) and TTDF (70% vs 45%, P  = 0.130), which translated to a significant 5-year PFS benefit (65% vs. 45%, P  = 0.036). R0 margin status was associated with a 5-year TTLRF improvement (91% vs 80%, P  = 0.046). On multivariate analysis, PN ≥95% independently associated with PFS (HR 0.4, 95% CI 0.2-0.8, P  = 0.015), and achieving an R0 resection was independently associated with improved PFS (HR 0.5, 95% CI 0.30-0.83, P  = 0.007) and OS (HR 0.52, 95% CI 0.29-0.91, P  = 0.027). Conclusion Therapeutic response to preoperative radiation alone is associated with improved surgical margin status and clinical outcomes in STS. Achieving P