DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Mammotome: biopsia microistologica mammaria con aspirazione automatica sotto guida ecografica

Abstract. Purpose. Vacuum-assisted breast biopsy is a diagnostic procedure that is clinically performed with the aid of a mammogram or an ultrasound, for the diagnosis of breast carcinoma. The purpose of this study is to evaluate its effectiveness versus other bioptic techniques. Material and mehods. From September 2003 to February 2006, in our Centre we carried out 300 ultrasound plus mammotome, to women between the ages of 19 and 75 years old (average age 47). The decision to permorm this type of procrdure was made excluding the patients at high risk of malignancy according to the classification BIRADS. Results. The results of the histological examination were the following: 153 F.A., 28 typical hiperplasias, 8 ALH, 16 DCI, 3 LCI, 7 CIS and 85 other benign pathologies characterized as typical epitheliosis, focal microscopic papillomatosis, sclerosing adenosis, etc. The patients with atypical lobular hyperplasia, CIS and infiltrating duct or lobular carcinima were submitted to a subsequent surgical extraction. Conclusion. The vacuum-assisted breast biopsy sonographically-guided can be considered a fast and low risk diagnostic method that is well tolerated by patients and therefore is a valid alternative to the other biopsy methods for the diagnosis of breast cancer

Use of Core Needle Biopsy rather than Fine-Needle Aspiration Cytology in the Diagnostic Approach of Breast Cancer

In the following study case, we reviewed breast ultrasound-guided core needle biopsy (CNB), using Mammotome (vacuum-assisted breast biopsy) and Tru-cut, carried out on palpable and nonpalpable uncertain breast lumps or malignant large lesions to be submitted to neoadjuvant chemotherapy. Examinations were conducted during a 4-year period of clinical activity in a highly specialized center, from December 2009 to December 2013, in 712 patients previously subjected to fine-needle aspiration cytology (FNAC). The results demonstrated that among the 712 breast biopsies, in many cases FNAC was not conclusive, and therefore we proceeded with the echo-guided biopsy, through which we were able to collect sufficient material for the histological examination in order to direct patients to surgery or follow-up. CNB is far superior to FNAC, especially in cases of uncertainty, where it is preferable to proceed directly with CNB, which may also determine additional prognostic and predictive markers. Initially FNAC is less expensive, but the actual costs involved tend to be higher for FNAC as it is less accurate and a CNB is often required. In accordance with recent publications, we can confirm the full validity of CNB in the diagnostic approach of breast lesions

Use of Core Needle Biopsy rather than Fine-Needle Aspiration Cytology in the Diagnostic Approach of Breast Cancer

Background and Aims: In the following study case, we reviewed breast ultrasound-guided core needle biopsy (CNB), using Mammotome (vacuum-assisted breast biopsy) and Tru-cut, carried out on palpable and nonpalpable uncertain breast lumps or malignant large lesions to be submitted to neoadjuvant chemotherapy. Material and Methods: Examinations were conducted during a 4-year period of clinical activity in a highly specialized center, from December 2009 to December 2013, in 712 patients previously subjected to fine-needle aspiration cytology (FNAC). Results: The results demonstrated that among the 712 breast biopsies, in many cases FNAC was not conclusive, and therefore we proceeded with the echo-guided biopsy, through which we were able to collect sufficient material for the histological examination in order to direct patients to surgery or follow-up. Conclusions: CNB is far superior to FNAC, especially in cases of uncertainty, where it is preferable to proceed directly with CNB, which may also determine additional prognostic and predictive markers. Initially FNAC is less expensive, but the actual costs involved tend to be higher for FNAC as it is less accurate and a CNB is often required. In accordance with recent publications, we can confirm the full validity of CNB in the diagnostic approach of breast lesions

Valutazione dell'espressione di urochinasi (Upa) nei leucociti e nei tessuti di pazienti affette da patologia mammaria benigna e maligna

Introduzione: I meccanismi di metastatizzazione che permettono alle cellule neoplastiche di colonizzare organi lontani dal sito di origine prevedono la rottura della membrana basale e della matrice extracellulare. L’urochinasi (uPA) svolge un’azione centrale nella proteolisi della matrice extracellulare convertendo il plasminogeno in plasmina. Materiali e metodi: In questo studio abbiamo analizzato la concentrazione di uPA nelle lesioni mammarie maligne, benigne e nel tessuto mammario sano. Sono state arruolate 30 donne con nodulo mammario successivamente sottoposto a biopsia e 10 donne sane di controllo. I campioni raccolti sono stati divisi in tre gruppi: 14 campioni di donne con carcinoma mammario, 16 campioni di donne con lesione mammaria benigna, 10 campioni da volontarie sane (solo leucociti). Da ogni donna è stato prelevato: 1) tessuto da lesione mammaria 2) tessuto sano adiacente alla lesione 3) sangue venoso per l’estrazione dei leucociti. Per ogni campione (leucociti e tessuti) è stata misurata l’espressione del gene urochinasi tramite REAL TIME PCR. E’ stata eseguita inoltre una PCR di prova sul gene 18S. Età media 58 anni; donne in premenopausa 36%; CDI 93%; recettori positivi 70%; Her2 negativi 70%; Ki67 medio basso 85%. Risultati L’espressione di urochinasi è significativamente maggiore nei noduli mammari maligni rispetto alle lesioni benigne (5,7 volte vs 3,8 volte il controllo; p<0,001). Nelle donne affette da carcinoma il tessuto mammario maligno esprime quantità superiori di uPA rispetto alla controparte sana (5,7 volte vs 4,7 volte; p < 0.01). Non ci sono differenze tra i vari tessuti estratti da donne con lesioni benigne. I linfociti delle volontarie sane mostrano una espressione di uPA nettamente inferiore rispetto agli altri campioni analizzati (p < 0,001). I linfociti delle pazienti affette da carcinoma esprimono quantità superiori di uPA rispetto ai linfociti delle donne con lesioni benigne (4,32 volte vs 2,98 ; p < 0,01). L’espressione di uPA tra noduli e linfociti è simile e non differisce significativamente in relazione ai parametri clinico biologici ( stato menopausale, tipo istologico, Ki67, recettori ormonali, HER2). L’unica eccezione è per i casi triplo negativi nei quali l’espressione di uPA è molto elevata (11,9 volte vs 5,5 volte; p < 0,001). Discussione e conclusione: Il presente studio conferma che uPA è iperespressa nelle lesioni mammarie maligne rispetto ai noduli benigni, evidenziando un’espressione di urochinasi speculare tra nodulo maligno e corrispondenti leucociti, quindi indicando la possibilità di utilizzare l’urochinasi leucocitaria come marcatore di uPA nodulare

Matrix-Producing Carcinoma of the Breast: A Case Report

Matrix-producing breast cancer (MPC) is a subtype of metaplastic carcinoma of the breast. It is a very rare tumor, which constitutes less than 1% of all malignant mammary tumors. The origin of this tumor is still unclear: there are molecular studies that suggest an origin from myoepithelial cells, whereas other studies underline the neoplastic transformation of a multipotent stem cell. Even the differential diagnosis of MPC and other breast neoplasms (phyllodes tumors and real sarcomas of the breast) is not always easy. In the literature, a certain chemoresistance has been demonstrated, and a standard treatment of this tumor does not exist at this time. We report the case of a 44-year-old, premenopausal, female patient with a 6-cm breast lump. Neither imaging nor fine needle aspiration biopsy was crucial in achieving a diagnosis. The patient underwent a simple mastectomy. In consideration of the negative lymph node status, the patient was not subjected to radiotherapy or adjuvant chemotherapy. Moreover, since the receptor status was negative, hormone therapy was not necessary. The patient has been disease free for 4 years now

Quadrantectomia e asportazione del linfonodo sentinella in anestesia locale in day hospital

Negli ultimi anni sono stati fatti grandi passi avanti per quanto riguarda sia la diagnostica sia la terapia del carcinoma della mammella. Ciò consente, nella maggior parte dei casi, di poter praticare una chirurgia conservativa. Con l’introduzione della tecnica del linfonodo sentinella, l’intervento chirurgico è stato notevolmente semplificato, tanto da poter essere eseguito in day surgery in anestesia locale. Scopo di questo lavoro è stato valutare se, dopo un attento studio del cavo ascellare con esame ecografico ed eventuale esame citologico, sia possibile dirimere tra linfonodi negativi e metastatici e valutare la fattibilità dell’intervento eseguito in anestesia locale, e quindi senza ricovero. Dal gennaio 2005 al gennaio 2007 54 pazienti, affette da carcinoma della mammella e che presentavano cavo ascellare negativo, sono state sottoposte a intervento chirurgico di quadrantectomia e asportazione del linfonodo sentinella in anestesia locale più eventuale sedazione. Otto di queste hanno presentato micrometastasi o cellule isolate nel linfonodo sentinella e, quindi, successivamente sono state sottoposte a linfoadenectomia. I nostri dati dimostrano che un attento studio del cavo ascellare consente sia di praticare la tecnica del linfonodo sentinella con buona probabilità di assenza di metastasi, sia di eseguire l’intervento in anestesia locale.Abstract In recent years, breast carcinoma diagnostics and therapy have evolved very considerably, allowing conservative surgery in most cases. These kinds of major operations have been greatly simplified since the introduction of the sentinel lymph node approach, with the possibility of a day surgery operation under local anaesthesia. The aim of this study, after thorough analysis of the axillary lymph nodes with ultrasound and cytological examinations, was to assess whether it would be possible to distinguish between negative and metastatic lymph nodes and whether the operation could be performed under local anaesthesia without hospitalisation. From January 2005 to January 2007, 54 breast carcinoma patients with negative axillary lymph nodes (after ultrasound examination) had a quadrantectomy and sentinel lymph node removal under local anaesthesia together with sedation where appropriate. Eight patients who presented micrometastases or isolated tumour cells in the sentinel lymph node underwent a subsequent lymphadenectomy. Our data show that, thanks to thorough analysis of the axillary cavity, it may be possible to use the sentinel lymph node approach with a good chance of the patient remaining free of distant metastases and of operating under local anaesthesia