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The purpose of this study was to test the accuracy of 1.5 Tesla magnetic resonance imaging (1.5T MRI) in the preoperative evaluation of axillary lymph nodes in patients with invasive breast cancer. The authors retrospectively analyzed 26 patients with invasive breast cancer who had undergone sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND). All patients had been submitted to preoperative contrast enhanced breast 1.5T MRI. On the basis of lymph nodes morphological and dynamic characteristics, lymph nodes were classified as "negative" (short axis5 mm), "borderline" (short axis5 mm, absence of a hilum) or "positive" (short axis5 mm, absence of a hilum and also other suspicious features). The authors compared 1.5T MRI results with the outcome of histological analysis performed according to the TNM criteria; sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of 1.5T MRI were evaluated. Considering only the lymph nodes "positive", 1.5 T MRI showed: SE 37.8%, SP 99.3%, FP 0.7%, PPV 92.5%, and NPV 88.1%. However, considering also "borderline", 1.5T MRI achieved: SE 75.7%, SP 99.3%, FP 0.7%, PPV 96.1%, and NPV was 95%. Contrast enhanced breast 1.5T MRI is not yet a valid alternative to histological analysis but it is a valid tool for a preoperative study of the topography of axillary lymph nodes and has the potential to become a routine method for evaluating the metastatic lymph nodes before submission to ALND.

To evaluate accuracy of endorectal ultrasonography (ERUS) both in staging and restaging rectal cancer after neoadjuvant chemoradiotherapy treatment.In a group of 80 patients with rectal cancer, we retrospectively selected 67 patients and divided in two groups: 41 patients affected by a stage I were investigated with a single preoperative endorectal sonography; 26 patients with locally advanced rectal cancer (stage II or more) were restaged after neoadjuvant treatment, which consisted of 5,040 cGy in 28 daily fractions associated with continuous infusion of 5-Fluorouracil. All patients underwent surgery and ERUS findings were subsequently compared with histological findings.Diagnostic accuracy of ERUS in the first group of patients was high: in fact T-staging was accurate in 85% of cases. Results in the second group were significantly less accurate, with a correct T-staging just for 47% of cases. Nodes involvement was correctly evaluated in 86% of cases for the first group and in 63% of cases for the second one.Endorectal sonography is a valid staging modality for early rectal malignancy. Advanced cancer is treated with neoadjuvant preoperative chemoradiotherapy which is associated with better outcome than postoperative treatment. We found endorectal sonography, based on the layer model of rectal wall, often fails restaging and we think we have to develop new criteria for a correct preoperative assessment after neoadjuvant chemoradiation.Endorectal ultrasonography, Neoadjuvant chemoradiotherapy, Rectal cancer, Staging.Valutare l’accuratezza dell’ecografia transrettale (TRUS) sia nella stadiazione del cancro del retto che nella restadiazione in seguito a radiochemioterapia neoadiuvante.In un gruppo di 80 pazienti affetti da cancro del retto, abbiamo retrospettivamente selezionato 67 pazienti e li abbiamo divisi in due gruppi: 41 patients con un cancro al I stadio sono stati studiati con una singola ecografia transrettale preoperatoria; 26 pazienti con cancro del retto localmente avanzato (stadio II o maggiore) sono stati restadiati in seguito a trattamento radiochemioterapico neoadiuvante, che consisteva di 5.040 cGy in 28 frazioni giornaliere associate ad infusione continua di 5-Fluorouracile. Tutti i pazienti sono stati sottoposti ad intervento chirurgico e i risultati della TRUS sono stati comparati con quelli istologici.L’accuratezza diagnostica dell’ERUS nel primo gruppo di pazienti che non ha ricevuto trattamenti neoadiuvanti era alta: infatti, la stadiazione T era accurata nell’85% dei casi. I risultati nel secondo gruppo erano significativamente meno accurati, con una stadiazione T corretta solo nel 47% dei casi. Il coinvolgimento linfonodale è stato valutato correttamente nell’86% dei casi per il primo gruppo e nel 63% dei casi per il secondo.L’ecografia endorettale ha dimostrato di essere una valida metodica per la stadiazione di neoplasie rettali in fase iniziale. Il miglior trattamento per i tumori più avanzati prevede la radio chemioterapia neoadiuvante, poiché è stato dimostrato che è associata con risultati migliori rispetto alle terapie adiuvanti postoperatorie. Abbiamo rilevato che con l’ecografia endorettale basata sul modello a strati della parete sono comuni gli errori di sovrastadiazione e riteniamo che sia necessario sviluppare nuovi criteri per migliorare l’accuratezza della valutazione preoperatoria dopo trattamento neoadiuvante radiochemioterapico.

The aim of the study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0 Tesla diffusion-weighted imaging (3T DWI) varies with the prognostic factors Ki67 and grading in invasive breast cancer.Seventy-three patients with 75 invasive breast cancer lesions who had undergone 3.0 Tesla magnetic resonance imaging (MRI) for local staging were enrolled. All lesions were confirmed by histologic and immunohistochemical analysis. MRI included both dynamic contrast-enhanced and DWI sequences. ADC value was obtained for each lesion. Histologic tumor grade was established according to the Nottingham Grading System (NGS), while Ki67 expression was evaluated by MM1 clone IgG1 mouse anti-human monoclonal antibody. Patients were divided into the following groups: grade 1 (G1), grade 2 (G2), grade 1 plus grade 2 (G1+G2) and grade 3 (G3), and low Ki67 (or = 14%), intermediate Ki67 (15%-30%), and high Ki67 (or = 30%). ADC values were compared with the G and Ki67 groups. Statistical comparison was carried out using the Mann-Whitney U and the Kruskal-Wallis H test.ADC values were significantly higher in G3 than in G1+G2 tumors; no significant difference was observed when G1, G2, and G3 were compared. There was no statistically significant correlation between ADC values and Ki67 percentage (p0.05).ADC values obtained on 3T DWI correlate with low (G1+G2) and high-grade (G3) invasive breast carcinomas.ADC may be a helpful tool for identifying high-grade invasive breast carcinoma.

The cellular effects of a novel DNA-intercalating agent, the bipyridyl complex of platinum(II) with diphenyl thiourea, [Pt(bipy)(Ph(2)-tu)(2)]Cl(2), has been analyzed in the cisplatin (cDDP)-sensitive human ovarian carcinoma cell line, 2008, and its -resistant variant, C13* cells, in which the highest accumulation and cytotoxicity was found among six related bipyridyl thiourea complexes. We also show here that this complex causes reactive oxygen species to form and inhibits topoisomerase II activity to a greater extent in the sensitive than in the resistant line. The impairment of this enzyme led to DNA damage, as shown by the comet assay. As a consequence, cell cycle distribution has also been greatly perturbed in both lines. Morphological analysis revealed deep cellular derangement with the presence of cellular masses, together with increased membrane permeability and depolarization of the mitochondrial membrane. Some of these effects, sometimes differentially evident between the two cell lines, might also be related to the decrease of total cell magnesium content caused by this thiourea complex both in sensitive and resistant cells, though the basal content of this ion was higher in the cDDP-resistant line. Altogether these results suggest that this compound exerts its cytotoxicity by mechanisms partly mediated by the resistance phenotype. In particular, cDDP-sensitive cells were affected mostly by impairing topoisomerase II activity and by increasing membrane permeability and the formation of reactive oxygen species; conversely, mitochondrial impairment appeared to play the most important role in the action of complex F in resistant cells.

The upregulation of pteridine reductase (PTR1) is a major contributor to antifolate drug resistance in Leishmania spp., as it provides a salvage pathway that bypasses dihydrofolate reductase (DHFR) inhibition. The structure-based optimization of the PTR1 inhibitor methyl-1-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]piperidine-4-carboxylate (1) led to the synthesis of a focused compound library which showed significantly improved selectivity for the parasite's folate-dependent enzyme. When used in combination with pyrimethamine, a DHFR inhibitor, a synergistic effect was observed for compound 5b. This work represents a step forward in the identification of effective antileishmania agents.