结直肠癌治疗疗效评价标准的研究进展——挑战与进步

随着抗肿瘤治疗方法的不断进步,疗效评价标准也在不断更新。从最初评价化疗药物疗效的WHO和RECIST标准,到抗血管治疗的CHOI标准和CT形态学等,以及最新的免疫治疗的疗效评价标准,每一种评价标准都是在新疗法对现有标准的挑战中被提出并完善。在此,我们按照抗肿瘤治疗类别,对相应的疗效评价标准加以综述。     

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel

BackgroundThe European Association of Urology (EAU) prognostic factor risk groups for non–muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s.ObjectiveTo update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression.Design, setting, and participantsIndividual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel.InterventionPatients underwent TURBT followed by intravesical instillations at the physician’s discretion.Outcome measurements and statistical analysisMultivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves.Results and limitationsA total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004–2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review.ConclusionsThis study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary.Patient summaryThe newly updated European Association of Urology prognostic factor risk groups for non–muscle-invasive bladder cancer provide an improved basis for recommending a patient’s treatment and follow-up schedule.     

Stage-specific gene expression during hepatocarcinogenesis in the rat

The alteration of genetic expression ubiquitously seen in both preneoplastic and neoplastic tissues has been investigated for many years in the hope that the critical molecular changes resulting in cancer can be elucidated. The alteration of the expression of specific genes has already been employed in diagnostic and even screening procedures for this disease. In the past many observations of such alterations have led to a variety of theories but not definitive generalizations. Studies of the alteration of genetic expression may now be viewed in the light of our understanding of the multistage nature of neoplastic development. This brief review describes a number of genes the expressions of which are altered during the stages of initiation and promotion, in contrast to the alteration of expression of genes during the stage of progression. The promotion stage is concerned primarily with the chronic interaction of promoting agents in the environment with the genetic apparatus of the cell, played out on the altered genetic background resulting from the stage of initiation. In contrast, the progression stage is characterized primarily by an evolving karyotypic instability resulting in continual genetic changes during this stage. On the basis of these distinctions it is possible to identify genes the altered expression of which is unique to the stage of progression. The identification of these genes and an understanding of mechanisms resulting in their altered expression will allow not only a better molecular characterization of the progression stage but also the quantitative analysis of neoplastic development in several model animal systems as well as eventually in the human.Abbreviations GSTP glutathioneS-transferase placental form - GTT -glutamyltranspeptidase - TGF transforming growth factor Dedicated to the Cancer Institute on the occasion of its 60th anniversary and to Dr. Haruo Sugano on the occasion of his 70th birthday. This work was supported in part by grants from the National Cancer Institute (CA-07175, CA-22484 and CA-45700)     

Inhibition of Periostin Expression Protects against the Development of Renal Inflammation and Fibrosis

Increased renal expression of periostin, a protein normally involved in embryonic and dental development, correlates with the decline of renal function in experimental models and patient biopsies. Because periostin has been reported to induce cell differentiation, we investigated whether it is also involved in the development of renal disease and whether blocking its abnormal expression improves renal function and/or structure. After unilateral ureteral obstruction in wild-type mice, we observed a progressive increase in the expression and synthesis of periostin in the obstructed kidney that associated with the progression of renal lesions. In contrast, mice lacking the periostin gene showed less injury-induced interstitial fibrosis and inflammation and were protected against structural alterations. This protection was associated with a preservation of the renal epithelial phenotype. In vitro, administration of TGF-β to renal epithelial cells increased the expression of periostin several-fold, leading to subsequent loss of the epithelial phenotype. Furthermore, treatment of these cells with periostin increased the expression of collagen I and stimulated the phosphorylation of FAK, p38, and ERK 42/44. In vivo delivery of antisense oligonucleotides to inhibit periostin expression protected animals from L-NAME–induced renal injury. These data strongly suggest that periostin mediates renal disease in response to TGF-β and that blocking periostin may be a promising therapeutic strategy against the development of CKD.     

幕上Ⅱ级胶质瘤预后的相关因素分析

目的 探讨幕上Ⅱ级胶质瘤预后的相关因素.方法 回顾性分析215例幕上Ⅱ级胶质瘤的临床资料,记录每个患者的无进展生存时间和总体生存时间.用Kaplan-Meier法对患者的各相关因素进行单因素分析,并采用Log-rank法检验差异的显著性,对在单因素分析中P<0.05者应用Cox回归模型进行多因素分析.结果 单因素分析结果显示:影响患者无进展生存时间和总体生存时间的因素包括年龄、首发症状、术前KPS评分、肿瘤长径、肿瘤形态、肿瘤强化程度、病理类型、手术切除程度、术后放疗(P值均<0.05).多因素分析显示:患者的年龄、术前KPS评分、肿瘤强化程度、手术切除程度和术后放疗等因素对患者的无进展生存时间和总体生存时间影响更为显著(P值均<0.05).结论 患者的年龄、术前KPS评分、肿瘤强化程度、手术切除程度和术后是否放疗等因素,是影响幕上Ⅱ级胶质瘤的预后因素.     

Radiographic progression of large joint damage in patients with rheumatoid arthritis treated with biological disease-modifying anti-rheumatic drugs

Objectives: Radiographic progression of damage to the small joints in patients with rheumatoid arthritis (RA) is well known; however, it has not been studied fully in the large joints. In this study, we looked at the prevalence of radiographic progression of large joint damage in patients with RA treated with biological disease-modifying anti-rheumatic drugs (bDMARDs).

Methods: A total of 273 large joints in the upper and lower extremities of 67 patients with RA treated with bDMARDs were investigated. Radiographs for tender and/or swollen large joints were taken at least twice during the study period (mean 18.6 months), and the progression of damage was evaluated.

Results: Progressive damage was found in 20.9% of patients and 6.2% of joints. A multivariate analysis revealed that the Larsen grade (LG) alone was a risk factor for progressive damage. The LG cutoff value was determined to be 2.5 (sensitivity: 0.529, specificity: 0.805).

Conclusions: The only factor to predict progressive damage was the LG of the joints with symptoms, and the damage must be stopped within LG II. Regular radiographic examinations for large joints should be performed in addition to routine examinations for small joints, such as the hand and foot.     

Clinical utility of whole body diffusion-weighted imaging in an immunocompetent adult with atypical cat scratch disease

BackgroundCat scratch disease (CSD) is an infectious disease caused by Bartonella henselae. CSD follows a typical course, characterized by regional lymphadenopathy. In atypical CSD, the lesions spread to systemic organs and can cause fever of unknown origin (FUO). A previous study showed the usefulness of whole-body magnetic resonance imaging (WB-MRI) with diffusion-weighted imaging (DWI) for limited areas in the diagnosis of FUO, but there are no studies on the clinical utility of whole-body DWI (WB-DWI). We herein report the case of an immunocompetent young man in whom contrast-enhanced CT-unidentifiable multiple liver abscess and osteomyelitis were successfully detected by WB-DWI. Follow-up with a liver biopsy helped confirm an atypical CSD diagnosis.Case presentationA 23-year-old previously healthy man was admitted for a 19-day history of high fever despite 3-day treatment by azithromycin. His physical examination was unremarkable and contrast-enhanced CT showed only a low attenuated area in the right lobe of the liver, indicating a cyst. WB-DWI revealed multiple nodular lesions of hypo-diffusion in the liver, spine, and pelvic region. The biopsy specimens of the liver abscess showed no evidence of tuberculosis/malignancy and the polymerase chain reaction (PCR) test of liver abscess aspirate showed positive findings for Bartonella henselae, confirming the diagnosis of CSD. He completed minocycline monotherapy for a total of 60 days without any deterioration.ConclusionsWB-DWI can be useful for the diagnosis of atypical CSD with hepatic and bone involvement, which can cause FUO in young immunocompetent adults.