血清IL-6和胃蛋白酶原Ⅰ/Ⅱ比值对老年胃癌患者预后评估的价值

目的探究老年胃癌患者术前血清白细胞介素6 (IL-6)、胃蛋白酶原(PG)Ⅰ、Ⅱ及PG-Ⅰ/Ⅱ比值在患者预后评估中的意义。方法选择2016年1月—2017年1月南通大学附属海安医院收治的101例外科手术治疗的老年胃癌患者为研究对象。收集患者的临床病理资料,检测血清IL-6和PG-Ⅰ/Ⅱ水平。以全因死亡为随访终点,使用Kaplan-Meier曲线明确患者预后与各指标间的关系。结果受试者工作特征曲线提示,IL-6、PG-Ⅰ和PG-Ⅰ/Ⅱ比值在最佳切割值为10.23pg/mL、30.65μg/L和2.44时,可评估患者的预后,而PG-Ⅱ则无法评估患者的预后。与IL-6≤10.23pg/mL组相比,IL-6> 10.23pg/mL组的肿瘤细胞分化更差、TNM分期Ⅲ期比例明显升高。Kaplan-Meier曲线结果表明,IL-6> 10.23pg/mL组的中位生存期显著短于IL-6≤10.23pg/mL组(28个月vs47个月,P<0.001);PG-Ⅰ≤30.65μg/L组的中位生存期显著短于PG-Ⅰ>30.65μg/L组(34个月vs49个月,P=0.008);PG-Ⅰ/Ⅱ≤2.44组的中位生存期显著短于PG-Ⅰ/Ⅱ> 2.44组(29个月vs56个月,P=0.02)。多因素Cox回归分析表明,肿瘤分化程度、TNM分期、IL-6及PG-Ⅰ/Ⅱ比值是影响患者生存率的独立危险因素。结论术前检测IL-6及PG-Ⅰ/Ⅱ比值有助于评估老年胃癌患者的预后。     

嘌呤能受体X1与肺腺癌预后及免疫细胞浸润的相关性研究

目的：探索嘌呤能受体X1(purinergic receptor，P2RX1)与肺腺癌(LUAD)患者预后及免疫细胞浸润的相关性。方法：利用生物信息学技术分析非小细胞肺癌中P2RX1的表达及其甲基化与患者预后的关系，对P2RX1共表达基因进行富集分析并筛选核心基因。利用TIMER 2.0数据库、R软件等分析P2RX1与免疫细胞、免疫检查点、免疫基质评分等的相关性。结果：P2RX1在LUAD中表达下调，低表达P2RX1的患者预后较差(P<0.05)，且P2RX1与肿瘤纯度、分期等临床病理因素有关(P<0.05)。P2RX1的表达与肺鳞癌患者预后无明显相关。Cg06475633等P2RX1 CpG位点甲基化与患者预后相关。P2RX1共表达基因主要富集于免疫细胞活化、分化等通路和生物学进程，核心基因主要包括BTK、IKZF1等。P2RX1的表达与B细胞浸润、免疫/基质评分、PD-1、CTLA-4等多个免疫检查点显著相关(P<0.05)。结论：P2RX1有望成为LUAD诊断和免疫治疗的新靶点。     

姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义

目的:探讨姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义。方法:回顾性分析2010年1月至2016年12月7年间收治的287例发生腹膜转移的胃癌患者的临床病理资料。通过χ2检验分析评分与患者临床病理因素间的关系。通过Kaplan-Meier法绘制生存曲线，Log-rank检验比较患者生存率的差异；采用Cox比例风险回归模型对患者进行预后分析。结果:与评分中得分为2分和1分的患者相比，得分为0分的患者肿瘤侵润至T4b 期的患者较少［31%(18/58)比50.8%(63/124)、56.2%(59/105)，P=0.039］。全组患者的中位生存时间仅为8.7月。对患者进行单因素预后分析结果显示，血清白蛋白浓度（≤40 g/L），腹水，腹膜转移范围较大，肿瘤T分期较晚，评分得分较高的患者预后较差（均P＜0.05）。将上述因素纳入Cox多因素分析结果显示:评分［HR（95%CI）:1.384（1.165~1.644），P=0.000］，血清白蛋白浓度［HR（95%CI）:0.759（0.593~0.971），P=0.028］，肿瘤T分期［HR（95%CI）:1.493（1.216~1.832），P=0.000］是患者预后的独立危险因素。结论:评分对于胃癌伴腹膜转移患者的预后生存评估具有重要的临床意义。     

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

胃癌微创外科临床研究进展及展望（2000-2020）

目前临床研究已证实腹腔镜胃癌根治术治疗早期胃癌的安全性、可行性和有效性。基于此，第4版日本《胃癌治疗指南》推荐腹腔镜手术治疗临床Ⅰ期远端胃癌。然而，腹腔镜胃癌手术治疗进展期胃癌的有效性和安全性仍存争议。中国腹腔镜胃肠外科研究组（CLASS研究组）发起的CLASS-01研究顺利完成，提供了全球首个局部进展期胃癌腹腔镜手术安全性和疗效的前瞻性多中心证据。胃癌外科的主流方向在从“大切口和扩大化手术切除”逐渐向“微创、精准化手术”转变，以使手术安全性和病人术后生活质量最优化。     

胃癌患者根治术后腹腔灌洗液中CEA mRNA表达的临床意义

目的：探讨胃癌患者根治术后腹腔冲洗液中CEA mRNA表达情况及其临床意义。方法: 回顾性分析了2013 年1 月至2017 年12 月在南京大学医学院附属鼓楼医院接受胃癌根治切除术后进行腹腔灌洗液CEA mRNA检测的139 名患者的病历资料，并进行术后常规随访。用RT-PCR检测139 胃癌患者根治术后腹腔灌洗液中CEA mRNA表达情况。卡方检验分析腹腔灌洗液中CEA mRNA表达与临床基本特征、组织病理学资料、血液学指标及复发方式之间的关系。采用Logistic 单因素及多因素回归分析筛查影响CEA mRNA表达水平的因素。结果：139 名患者中44 名（31.7%）患者腹腔灌洗液CEA mRNA阳性。分析显示，胃癌患者腹腔灌洗液CEA mRNA阳性表达与性别、年龄、病理分级、Lauren 分型和HER2、EGFR、VEGFR等标记物间均没有明显的关联（均P>0.05），与病理类型、脉管是否侵犯、局部浸润深度、淋巴结转移程度和临床AJCC 分期有明显的关联（均P<0.05）。CEA mRNA阳性患者腹膜复发率明显高于阴性患者（P=0.012）。Logistic 单因素回归分析显示，印戒细胞癌（P=0.04，HR=2.810，95% CI: 1.050~7.520）、T 分期（P=0.016，HR=6.329，95% CI: 1.417~28.264）、N 分期（P=0.022，HR=3.068，95% CI: 1.172~8.027）、AJCC分期（P=0.016 ，HR=3.971 ，95% CI: 1.295~12.173 ）、神经侵犯（P=0.002 ，HR=6.738，95% CI: 1.995~22.757）、脉管侵犯（P<0.001，HR=16.36，95% CI: 3.85~69.512）为胃癌患者腹腔灌洗液CEA mRNA阳性表达的危险因素。Logistic 多因素回归分析显示，经过对其他因素的校正，脉管侵犯（P<0.001，HR=21.314，95% CI: 4.21~107.907）为胃癌患者腹腔灌洗液CEA mRNA阳性表达的独立危险因素。结论：胃癌腹腔灌洗CEA mRNA阳性的患者腹膜复发转移风险高且预后不良，应考虑包括腹腔局部治疗在内的更加积极的抗肿瘤治疗。     

Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

Objective: Human epidermal growth factor receptor 2 (erbb2/HER2) overexpression, has now been implicatedin advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-EastIndia and to assess the impact of various demographic and clinical parameters on HER2 positivity. Methods: A total of68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examinationfrom September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational(epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved,standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters.Results: The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantlyhigher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patientswith well differentiated histology and was more common in patients with stage II and III diseases, but neither of theassociations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours(56% versus 44%, P=0.002). Conclusion: HER2 overexpression was evident in 56% of the North-East Indian patientswith locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlatedsignificantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expressionis recommended to provide a therapeutic advantage in Indian patients.     

Can EGFR mutation status be reliably determined in pre‐operative needle biopsies from adenocarcinomas of the lung?

The identification of EGFR mutations in non‐small‐cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre‐operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro‐dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre‐operative, cytological specimens. Several (18.4%) analyses of the pre‐operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra‐tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre‐operative biopsies for EGFR mutation analysis.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.