BackgroundWhen treating bladder cancer patients, the most significant problems usually concern cases with high-grade non-muscle-invasive carcinoma, and a better understanding of which patients would benefit from early radical cystectomy is urgently needed. The uropathology community is seeking more user-friendly approaches to distinguishing between T1 cancers exhibiting different types of clinical behavior.MethodsAfter a retrospective review, we selected a group of 314 patients who underwent transurethral resection of the bladder (TURB) and were diagnosed with high-grade urothelial carcinoma staged as T1. Three different substaging systems were applied: one was the anatomy-based T1 a/b; and two involved micrometric thresholds of either 0.5 mm of invasion (as proposed by van Rhijn et al.), or 1 mm of invasion (as proposed in the present study). Early reTUR (repeated transurethral resection) was performed in 250 patients, and the same substaging approaches were applied to cases of T1.ResultsIt proved feasible to apply the 1 mm substaging system in 100 % of cases, the van Rhijn system in 100 %, and the anatomy-based method (T1 a/b) in 72.3 % of cases. At a mean follow-up of 46 months, the recurrence-free survival rate was significantly better (p < 0.001) in the group that underwent reTUR, while none of the three substaging systems reliably predicted recurrences. The 1 mm did seem promising, however, as a threshold for predicting progression, reaching statistical significance in the Kaplan Meier estimates (p < 0.04).ConclusionOur study shows that micrometric substaging is feasible in this setting and should be extended to include any early reTUR to complete the substaging done after the first TURB. It can also provide helpful prognostic information.

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The activity of pemetrexed is promising in light of the tumor burden in these patients (all patients were stage IV and 39% had three or more organs involved). Toxicities were remarkably decreased with folic acid supplementation. Combination studies are warranted.

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Morphologic criteria illustrated in WHO guidelines are the most significant prognostic factor in human gliomas, but novel biomarkers are needed to identify patients with a poorer outcome. The present study examined the expression of the oncofetal protein IMP3 in a series of 135 patients affected by high-grade (grade III and IV) gliomas, correlating the results with proliferative activity, molecular parameters, and clinical and follow-up data. Overall, IMP3 expression was higher in glioblastomas (68%) than in grade III tumors (20%, P < 0.0001), and IMP3-positive high-grade gliomas showed a shorter overall and disease-free survival than negative ones (P = 0.0002 and P = 0.006, resp.). IMP3 expression was significantly associated with the absence of mutations of IDH1 gene (P = 0.0001) and with the unmethylated phenotype of MGMT in high-grade gliomas (P = 0.004). High Ki67 levels were correlated with better prognosis in glioblastomas but IMP3 expression was not correlated with the proliferation index. These findings confirm the role of IMP3 as a marker of poor outcome, also in consideration of its association with IDH1 wild-type phenotype and MGMT unmethylated status. The data suggest that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas.