Clinicopathological and molecular characterisation of ‘multiple-classifier’ endometrial carcinomas

Endometrial carcinoma (EC) molecular classification based on four molecular subclasses identified in The Cancer Genome Atlas (TCGA) has gained relevance in recent years due to its prognostic utility and potential to predict benefit from adjuvant treatment. While most ECs can be classified based on a single classifier (POLE exonuclease domain mutations – POLEmut, MMR deficiency – MMRd, p53 abnormal – p53abn), a small but clinically relevant group of tumours harbour more than one molecular classifying feature and are referred to as ‘multiple-classifier’ ECs. We aimed to describe the clinicopathological and molecular features of multiple-classifier ECs with abnormal p53 (p53abn). Within a cohort of 3518 molecularly profiled ECs, 107 (3%) tumours displayed p53abn in addition to another classifier(s), including 64 with MMRd (MMRd–p53abn), 31 with POLEmut (POLEmut–p53abn), and 12 with all three aberrations (MMRd–POLEmut–p53abn). MMRd–p53abn ECs and POLEmut–p53abn ECs were mostly grade 3 endometrioid ECs, early stage, and frequently showed morphological features characteristic of MMRd or POLEmut ECs. 18/28 (60%) MMRd–p53abn ECs and 7/15 (46.7%) POLEmut–p53abn ECs showed subclonal p53 overexpression, suggesting that TP53 mutation was a secondary event acquired during tumour progression. Hierarchical clustering of TCGA ECs by single nucleotide variant (SNV) type and somatic copy number alterations (SCNAs) revealed that MMRd–p53abn tumours mostly clustered with single-classifier MMRd tumours (20/23) rather than single-classifier p53abn tumours (3/23), while POLEmut–p53abn tumours mostly clustered with single-classifier POLEmut tumours (12/13) and seldom with single-classifier p53abn tumours (1/13) (both p ≤ 0.001, chi-squared test). Finally, the clinical outcome of patients with MMRd–p53abn and POLEmut–p53abn ECs [stage I 5-year recurrence-free survival (RFS) of 92.2% and 94.1%, respectively] was significantly different from single-classifier p53abn EC (stage I RFS 70.8%, p = 0.024 and p = 0.050, respectively). Our results support the classification of MMRd–p53abn EC as MMRd and POLEmut–p53abn EC as POLEmut. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

A modified technique to perform para-aortic lymphadenectomy up to the renal vein

ObjectiveTo investigate the safety and feasibility of our modified technique to perform lymph node excision up to the renal vein in cases of gynecological cancer.Materials and methods87 patients with endometrial or ovarian neoplasms underwent laparoscopic para-aortic lymphadenectomy (LPAL) up to the left renal vein were enrolled prospectively. During surgery, the surgeon was positioned to the right side of the patient and an additional trocar was introduced into the upper right abdomen. The laparoscopic video screen was placed to the side of the patient's head. Three-fan retractor forceps were used to hold up the duodenum and small bowel. The rest of the procedure was the same as conventional LPAL.ResultsThe median operating time for LPAL was 72 min (range: 40–115 min) and the median estimated blood loss was 45 ml (range: 15–1000 mL). There were two cases of intra-operative vascular injury. The median number of retrieved para-aortic lymph nodes (PALNs) was 18 (range: 10–37). Of the 87 patients, 11 patients had positive PALNs. None of the cases required laparotomy.ConclusionOur findings demonstrate that our modified LPAL technique is feasible, reproducible, can achieve good exposure and reduces surgical difficulty.     

腹腔镜直肠癌前切除术肠系膜下动脉不同结扎平面对患者预后的影响

目的分析腹腔镜直肠癌前切除术中肠系膜下动脉不同结扎平面对患者预后的影响。 方法选取2007年6月至2014年6月间青岛市市立医院收治的行腹腔镜直肠癌前切除术136例患者为研究对象，根据肠系膜下动脉不同的结扎平面，分为保留左结肠动脉的低位结扎组（LL组）76例和不保留左结肠动脉的高位结扎组（HL组）60例。比较两组患者围手术期指标，随访并评价两组的预后。 结果两组手术时间、术中出血量、术后肛门排气时间、淋巴结清扫总数和第253组淋巴结清扫个数差异无统计学意义（t=6.109、4.339、8.386、0.233、0.198，P=0.318、0.416、0.512、0.821、0.669）；LL组术后吻合口瘘的发生率明显低于HL组（χ²=5.186，P=0.029）。HL组术后3、5年总体生存率分别为80.00%和73.33%，LL组分别为77.63%和72.37%，两组比较差异无统计学意义（χ²=1.536、2.156，P=0.863、0.698）。 结论腹腔镜直肠癌前切除术中肠系膜下动脉不同结扎平面可获得相近的淋巴结清扫效果，保留左结肠动脉的低位结扎平面术后吻合口瘘的发生率更低，其他围手术期指标没有差异，联合第三站中央淋巴结清扫值得应用推广。     

Computed tomography features of acinar cell carcinoma of the pancreas

PurposeTo report the computed tomography (CT) features of pancreatic acinar cell carcinoma (ACC) and identify CT features that may help discriminate between pancreatic ACC and pancreatic ductal adenocarcinoma (PDA).Materials and methodsThe CT examinations of 20 patients (13 men, 7 women; mean age, 66.5 ± 10.7 [SD] years; range: 51–88 years) with 20 histopathologically proven pancreatic ACC were reviewed. CT images were analyzed qualitatively and quantitatively and compared to those obtained in 20 patients with PDA. Comparisons were performed using univariate analysis with a conditional logistic regression model.ResultsPancreatic ACC presented as an enhancing (20/20; 100%), oval (15/20; 75%), well-delineated (14/20; 70%) and purely solid (13/20; 65%) pancreatic mass with a mean diameter of 52.6 ± 28.0 (SD) mm (range: 24–120 mm) in association with visible lymph nodes (14/20; 70%). At univariate analysis, well-defined margins (Odds ratio [OR], 7.00; P = 0.005), nondilated bile ducts (OR, 9.00; P = 0.007), visible lymph nodes (OR, 4.33; P = 0.028) and adjacent organ involvement (OR, 5.67; P = 0.02) were the most discriminating CT features to differentiate pancreatic ACC from PDA. When present, lymph nodes were larger in patients with pancreatic ACC (14 ± 4.8 [SD]; range: 7–25 mm) than in those with PDA (8.8 ± 4.1 [SD]; range: 5–15 mm) (P = 0.039).ConclusionOn CT, pancreatic ACC presents as an enhancing, predominantly oval and purely solid pancreatic mass that most frequently present with no bile duct dilatation, no visible lymph nodes, no adjacent organ involvement and larger visible lymph nodes compared to PDA.     

Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy

Background/Aim: The Glutathione S-transferases (GSTs) are important carcinogen-metabolizing enzymes. Polymorphisms involved in these enzymes can modulate the development and treatment of head and neck cancer. To investigate the association of GSTs polymorphisms with head and neck cancer and risk factors, clinical-pathological features, and survival time of the patients treated with chemotherapy and/or radiotherapy. Methods: The GST gene polymorphisms were evaluated in 197 cases and 514 controls by PCR-RFLP-Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Results: The GSTP-313 was associated with a decreased risk for HNSCC (p=0.050). The GSTP1 haplotype analysis revealed a higher frequency of the AC and AT haplotypes in the case group than in the control group (p=0.013 and p=0.019, respectively), and the opposite for G-C haplotype (p = 0.015). Yet, the different combinations between the genotypes were associated with an increased risk of cancer. The study showed no association between the polymorphisms and primary tumor site, clinical-pathological characteristics, treatment (chemotherapy and/or radiotherapy) and survival time of the patients. Conclusion: The GST polymorphisms combination showed an increased risk for carcinogenesis, and studies with larger casuistry can contribute to the clarification of the role in individual patient differences for the response to chemotherapy and/or radiotherapy and identify biomarkers of susceptibility.     

中性粒细胞与淋巴细胞比值及血小板与淋巴细胞比值变化在直肠癌新辅助治疗中的意义

目的探讨新辅助治疗前后中性粒细胞与淋巴细胞比值(NLR)及血小板与淋巴细胞比值(PLR)变化在直肠癌新辅助治疗中的意义。方法回顾性分析2013年11月至2015年1月山西省肿瘤医院收治的86例接受新辅助治疗的直肠癌患者资料,分析新辅助治疗前后NLR、PLR变化与患者临床病理特征及疗效的关系。结果86例患者治疗后NLR、PLR升高均为43例。直肠癌患者新辅助治疗前后的NLR及PLR变化与患者年龄、性别、TNM分期、淋巴结转移及癌结节数量、肿瘤长径均无关(均P>0.05),肿瘤与肛门距离<6 cm者治疗后NLR、PLR升高者比例均高于≥6 cm者[60.00%(30/50)比36.11%(13/36),χ^2=4.778,P=0.029;64.00%(32/50)比30.56%(11/36),χ^2=9.364,P=0.002];体质量指数≥28 kg/m2者治疗后NLR、PLR升高者比例均高于<28 kg/m2者[81.82%(9/11)比45.33%(34/75),χ^2=5.108,P=0.024;90.91%(10/11)比44.00%(33/75),χ^2=8.444,P=0.004]。治疗后NLR降低组患者的缓解率高于NLR升高组[72.09%(31/43)比51.16%(31/43),χ^2=3.983,P=0.046],而治疗前后PLR变化与患者新辅助治疗效果无关(P>0.05)。结论直肠癌患者新辅助治疗前后NLR变化与其疗效相关。     

MiRNA let-7a对人喉鳞癌细胞增殖的抑制作用CSCD

目的探讨miRNA let-7a调控高迁移率族蛋白2(HMGA2)对人喉鳞癌细胞株TU212增殖的影响。方法合成let-7a模拟体(let-7a mimics)并采用阳离子脂质体法瞬时转染入喉癌TU212细胞,裸鼠皮下注射TU212细胞,构建裸鼠移植瘤模型。RT-qPCR和Western blot法分别检测转染后TU212细胞及移植瘤内let-7a和HMGA2的表达。结果在过表达let-7a的喉癌TU212细胞中,HMGA2的转录和翻译水平下调,细胞增殖能力降低。体外成瘤实验证实,与let-7a NC组和空白对照组相比,转染let-7a mimics的喉癌细胞TU212成瘤组织的质量和体积均显著下降;let-7a过表达的TU212成瘤组织中HMGA2的mRNA和蛋白水平均明显下调。结论let-7a能显著抑制HMGA2的mRNA和蛋白表达,进而显著抑制喉癌细胞的增殖。