Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours

Wilms' tumour is one of the most common solid tumours of childhood. 11p13 (WT1 locus) and 11p15.5 (WT2 locus) are known to have genetic or epigenetic aberrations in these tumours. In Wilms' tumours, mutation of the Wilms tumour 1 (WT1) gene at the WT1 locus has been reported, and the WT2 locus, comprising the two independent imprinted domains IGF2/H19 and KIP2/LIT1, can undergo maternal deletion or alterations associated with imprinting. Although these alterations have been identified in many studies, it is still not clear how frequently combined genetic and epigenetic alterations of these loci are involved in Wilms' tumours or how these alterations occur. To answer both questions, we performed genetic and epigenetic analyses of these loci, together with an additional gene, CTNNB1, in 35 sporadic Wilms' tumours. Loss of heterozygosity of 11p15.5 and loss of imprinting of IGF2 were the most frequent genetic (29%) and epigenetic (40%) alterations in Wilms' tumours, respectively. In total, 83% of the tumours had at least one alteration at 11p15.5 and/or 11p13. One-third of the tumours had alterations at multiple loci. Our results suggest that chromosome 11p is not only genetically but also epigenetically critical for the majority of Wilms' tumours.     

康艾注射液治疗肿瘤的临床应用概况

康艾注射液目前为我国常用的抗肿瘤注射液,由人参、黄芪、苦参素组成,主要应用于原发性肝癌、肺癌、直肠癌等恶性肿瘤的治疗,获得了较好疗效。本文就其应用、药效以及安全性等研究作了综述,为安全用药提供依据。     

虚弱症临床诊治研究进展

老年人群中常见一种包括跌倒、失能、认知障碍、自主活动减少、非自主体重下降以及疲劳等系列临床症状的 综合状态,通常与特定疾病状态无关,被称为“虚弱症（frailty）”。虚弱症是营养不良的主要表现之一,又与肌肉减少症 有本质的不同,虚弱症是患者整体机能的减退,并不完全与骨骼肌的数量减少或功能减退有关。虚弱症患者的神经、肌肉、 代谢和免疫系统的生理储备下降,抗应激能力减退,其不良临床结局包括并发症增多、意外伤害（如跌倒或骨折）、残疾、 生活质量差甚至死亡等。虚弱症常见于老年人群、肿瘤、心血管和呼吸系统等疾病患者、营养不良人群等。不同报道显示 老年人群患病率为 4.0%~59.1%,且随年龄增加。虚弱症可通过核心症候群（表型）或虚弱指数进行诊断。虚弱评估可以提 供额外的有价值的预后判断指标,尽早评估并干预,对改善预后有重要意义。维持个体内在的稳态平衡比治疗某个疾病可 能获益更大,改善营养、加强锻炼、制定个体化多因素干预模式是预防虚弱症患者不良临床结局的最好方法。本文对虚弱 症的定义与诊断、流行病学、病因与病理机制以及干预措施等进行了综述。     

Analysis of time-dose factors in clinically positive neck nodes treated with irradiation alone in squamous cell carcinoma of the head and neck

This is a retrospective analysis of time-dose factors in 139 patients with 238 evaluable clinically positive lymph nodes treated with external beam radiation therapy alone to the primary lesion and neck for squamous cell carcinoma of the head and neck at the University of Florida from October 1964 through April 1980. Lymph node control by lymph node size was 8/8 (100%) for less than 1.0 cm, 51/62 (82%) for 1.0 cm, 68/82 (83%) for 1.5-2.0 cm, 24/40 (60%) for 2.5-3.0 cm, 24/38 (63%) for 3.5-6.0 cm, and 0/8 (0%) for greater than or equal to 7.0 cm. Lymph node control was also influenced by dose, overall treatment time, and fractionation schedule; these factors were interrelated and appeared to increase in importance as the size of the lymph node increased.     

Optimising faecal occult blood screening:retrospective analysis of NHS Bowel Cancer Screening data to improve the screening algorithm

Background:

Colorectal neoplasia causes bleeding, enabling detection using Faecal Occult Blood tests (FOBt). The National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) guaiac-based FOBt (gFOBt) kits contain six sample windows (or ‘spots'') and each kit returns either a positive, unclear or negative result. Test kits with five or six positive windows are termed ‘abnormal'' and the subject is referred for further investigation, usually colonoscopy. If 1–4 windows are positive, the result is initially ‘unclear'' and up to two further kits are submitted, further positivity leads to colonoscopy (‘weak positive''). If no further blood is detected, the test is deemed ‘normal'' and subjects are tested again in 2 years'' time. We studied the association between spot positivity % (SP%) and neoplasia.

Methods:

Subjects in the Southern Hub completing the first of two consecutive episodes between April 2009 and March 2011 were studied. Each episode included up to three kits and a maximum of 18 windows (spots). For each positivity combination, the percentage of positive spots out of the total number of spots completed by an individual in a single-screening episode was derived and named ‘SP%''. Fifty-five combinations of SP can occur if the position of positive/negative spots on the same test card is ignored.The proportion of individuals for whom neoplasia was identified in Episode 2 was derived for each of the 55 spot combinations. In addition, the Episode 1 spot pattern was analysed for subjects with cancer detected in Episode 2.

Results:

During Episode 2, 284 261 subjects completed gFOBT screening and colonoscopies were performed on 3891 (1.4%) subjects. At colonoscopy, cancer was detected in 7.4% (n=286) and a further 39.8% (n=1550) had adenomas. Cancer was detected in 21.3% of subjects with an abnormal first kit (five or six positive spots) and in 5.9% of those with a weak positive test result.The proportion of cancers detected was positively correlated with SP%, with an R² correlation (linear) of 0.89. As the SP% increased from 11 to 100%, so the colorectal cancer (CRC) detection rate increased from 4 to 25%. At the lower SP%s, from 11to 25%, the CRC risk was relatively static at ∼4%. Above an SP% of 25%, every 10-percentage points increase in the SP%, was associated with an increase in cancer detection of 2.5%.

Conclusions:

This study demonstrated a strong correlation between SP% and cancer detection within the NHS BCSP. At the population level, subjects'' cancer risk ranged from 4 to 25% and correlated with the gFOBt spot pattern.Some subjects with an SP% of 11% proceed to colonoscopy, whereas others with an SP% of 22% do not. Colonoscopy on patients with four positive spots in kit 1 (SP% 22%) would, we estimate, detect cancer in ∼4% of cases and increase overall colonoscopy volume by 6%. This study also demonstrated how screening programme data could be used to guide its ongoing implementation and inform other programmes.     

A quality-adjusted survival analysis (Q-TWiST) of rituximab plus CVP vs CVP alone in first-line treatment of advanced follicular non-Hodgkin's lymphoma

Background:

To evaluate the impact of treatment on health states that affect patients'' quality of life in advanced follicular lymphoma.

Methods:

A quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TwiST) analysis was performed on data from a phase III clinical trial (Marcus et al, 2008).

Results:

Cyclophosphamide, vincristine, and prednisone plus rituximab (R-CVP)-treated patients gained a mean of 15.17 months in TWiST, 8.33 months in Q-TwiST, and 11.30 months less in disease relapse, without increase in toxicity compared with cyclophosphamide, vincristine, and prednisone (CVP)-treated patients.

Conclusion

Rituximab plus CVP-treated patients reached a significant and clinically meaningful improvement within 12 months in quality-adjusted survival compared with CVP.     

Comprehensive Clinical and Genetic Characterization of Hyperprogression Based on Volumetry in Advanced Non–Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor

IntroductionHyperprogressive disease (HPD), characterized by accelerated tumor progression, has been proposed as a new pattern of progression after immune checkpoint inhibitor (ICI) treatment. The aim of this study was to describe the characteristics of HPD and investigate its predictive markers.MethodsClinical and radiological findings of 335 patients with advanced NSCLC treated with ICI monotherapy were retrospectively analyzed. Radiological data were quantitatively and longitudinally analyzed for tumor size and volume by comparing baseline and follow-up computerized tomography results. The findings were matched with individual genomic profiles generated by deep sequencing of 380 genes.ResultsAmong 135 patients with progressive disease (PD), as assessed by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria, 48 (14.3% of all patients and 35.6% of those with PD) and 44 (13.1% of all patients and 32.6% among those with PD) were found to have HPD by volumetry (HPD_V) and assessed by RECIST 1.1 (HPD_R), respectively. Patients with HPD_V were associated with significantly inferior overall survival (OS) versus that of patients without HPD_V with PD (median OS = 4.7 months [95% confidence interval: 3.5–11.9)] versus 7.9 months [95% confidence interval: 6.0–13.5] [p = 0.004]); OS did not differ between patients without and without HPD_R. HPD_V status was an independent factor in OS. A derived neutrophil-to-lymphocyte ratio greater than 4 and lactate dehydrogenase level greater than the upper limit of normal were significantly associated with HPD_V. Moreover, we identified coinciding KRAS and serine/threonine kinase 11 gene (STK11) mutations in the cohort of patients with HPD_V (three of 16), whereas none were found in the cohort of patients without HPD_V (zero of 28).ConclusionsDefining HPD treated with ICI on the basis of volumetric measurement is more precise than is defining it on the basis of one-dimensional analysis. Pre-ICI derived neutrophil-to-lymphocyte ratio, lactate dehydrogenase level, and concurrence of STK11 and KRAS mutations could thus be used as potential biomarkers for HPD prediction.     

结直肠癌患者术前营养状况对术后生活质量影响

目的 探讨术前营养风险对胃肠肿瘤患者术后生存质量的影响,并对临床营养治疗提出合理建议。方法 通过一 项回顾性研究,选取2014 年 6 月至2016 年 6 月上海交通大学附属第六人民医院普外科新入院结直肠癌患者150 例,入院 后 24 小时内,应用NRS 2002 评估其营养状况,根据评分将患者分为两组,即研究组（存在营养风险）和对照组（无营养 风险）,比较两组患者术后并发症之间的差异,运用欧洲癌症研究与治疗组织的生命质量核心量表比较两组间生存质量差 异。结果 NRS 2002结果显示对照组86例（57%）,研究组 64例（43%）。不同营养状况患者比较,研究组患者术后感染, 吻合口瘘的发生率显著高于对照组患者。两者整体生存质量,躯体功能、认知功能、疲乏、失眠差异有统计学意义（P＜0.05）; 而角色功能、情绪功能、社会功能、恶心呕吐、疼痛、气促、食欲丧失、便秘、腹泻、经济困难差异无统计学意义（P＞0.05）。 通过多元逐步线性回归分析得出术前营养状态可以作为患者术后生活质量的独立影响因素。结论 术前存在营养风险的结直 肠癌患者,术后并发症显著增加,术后生活质量下降,应加强对术前存在营养风险患者的营养治疗。