KRAS G12C mutation and risk of disease recurrence in stage I surgically resected lung adenocarcinoma.

KRAS G12C mutations are found in about 12-13% of LUAD samples and it is unclear whether they are associated with worse survival outcomes in resected, stage I LUAD. We assessed whether KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours and to KRAS wild-type tumours in a cohort of resected, stage I LUAD (IRE cohort). We then leveraged on publicly available datasets (TCGA-LUAD, MSK-LUAD604) to further test the hypothesis in external cohorts. In the stage I IRE cohort we found a significant association between the KRAS-G12C mutation and worse DFS in multivariable analysis (HR: 2.47). In the TCGA-LUAD stage I cohort we did not find statistically significant associations between the KRAS-G12C mutation and DFS. In the MSK-LUAD604 stage I cohort we found that KRAS-G12C mutated tumours had worse RFS when compared to KRAS-nonG12C mutated tumours in univariable analysis (HR 3.5). In the pooled stage I cohort we found that KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours (HR 2.6), to KRAS wild-type tumours (HR 1.6) and to any other tumours (HR 1.8); in multivariable analysis, the KRAS-G12C mutation was associated with worse DFS (HR 1.61). Our results suggest that patients with resected, stage I LUAD with a KRAS-G12C mutation may have inferior survival outcomes..

Do we really need fine-needle biopsy needle for an ultrasound-guided biopsy of pancreatic adenocarcinoma? A retrospective study.

OBJECTIVE: Endoscopic ultrasound (EUS)-guided FNB was not demonstrated to be better than EUS fine-needle aspiration (FNA) to obtain adequate samples for diagnosis of pancreatic tumors. We report our experience using a 22-gauge needle aspiration to obtain both cytologic and histologic samples. PATIENTS AND METHODS: In a total of 232 patients (51% men), 22-gauge needles (Cook Medical) were used to obtain a cytological sample (between 2008 and 2016, Cohort A) and a cytologic and a histologic sample (between 2016 and 2019, Cohort B) to evaluate the usability of this needle to collect material for cytologic and histologic examination. MOSE was used. RESULTS: Pancreatic adenocarcinoma was diagnosed in 76/113 (68%) patients in Cohort A and in 88/119 (74%) in Cohort B. Non-diagnostic sampling occurred in 30/113 (26%) patients in Cohort A and in 25/119 (21%) in Cohort B. The median number of passages was three in both cohorts. Lesions were in the head/uncinated process 57% vs. 51% and body/tail 43% vs. 49% in Cohorts A and B, respectively; the mean tumor size was 34.5 mm (SD 10.7) in Cohort A and 35.4 mm (SD 14.7) in Cohort B. CONCLUSIONS: FNA needle (22-gauge) with adequate passes, MOSE determination and adequate processing of specimens, provided FNA and FNB specimen collection.

The bacterial quorum sensing molecule, 2-heptyl-3-hydroxy-4-quinolone (PQS), inhibits signal transduction mechanisms in brain tissue and is behaviorally active in mice.

Interkingdom communication between bacteria and host organisms is one of the most interesting research topics in biology. Quorum sensing molecules produced by Gram-negative bacteria, such as acylated homoserine lactones and quinolones, have been shown to interact with host cell receptors, stimulating innate immunity and bacterial clearance. To our knowledge, there is no evidence that these molecules influence CNS function. Here, we have found that low micromolar concentrations of the Pseudomonas aeruginosa quorum sensing autoinducer, 2-heptyl-3-hydroxy-4-quinolone (PQS), inhibited polyphosphoinositide hydrolysis in mouse brain slices, whereas four selected acylated homoserine lactones were inactive. PQS also inhibited forskolin-stimulated cAMP formation in brain slices. We therefore focused on PQS in our study. Biochemical effects of PQS were not mediated by the bitter taste receptors, T2R4 and T2R16. Interestingly, submicromolar concentrations of PQS could be detected in the serum and brain tissue of adult mice under normal conditions. Levels increased in five selected brain regions after single i.p. injection of PQS (10 mg/kg), peaked after 15 min, and returned back to normal between 1 and 4 h. Systemically administered PQS reduced spontaneous locomotor activity, increased the immobility time in the forced swim test, and largely attenuated motor response to the psychostimulant, methamphetamine. These findings offer the first demonstration that a quorum sensing molecule specifically produced by Pseudomonas aeruginosa is centrally active and influences cell signaling and behavior. Quorum sensing autoinducers might represent new interkingdom signaling molecules between ecological communities of commensal, symbiotic, and pathogenic microorganisms and the host CNS.

KEAP1-driven co-mutations in lung adenocarcinoma unresponsive to immunotherapy despite high tumor mutational burden.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated significant overall survival (OS) benefit in lung adenocarcinoma (LUAD). Nevertheless, a remarkable interpatient heterogeneity characterizes immunotherapy efficacy, regardless of programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). KEAP1 mutations are associated with shorter survival in LUAD patients receiving chemotherapy. We hypothesized that the pattern of KEAP1 co-mutations and mutual exclusivity may identify LUAD patients unresponsive to immunotherapy. PATIENTS AND METHODS: KEAP1 mutational co-occurrences and somatic interactions were studied in the whole MSKCC LUAD dataset. The impact of coexisting alterations on survival outcomes in ICI-treated LUAD patients was verified in the randomized phase II/III POPLAR/OAK trials (blood-based sequencing, bNGS cohort, N = 253). Three tissue-based sequencing studies (Rome, MSKCC and DFCI) were used for independent validation (tNGS cohort, N = 289). Immunogenomic features were analyzed using The Cancer Genome Atlas (TCGA) LUAD study. RESULTS: On the basis of KEAP1 mutational co-occurrences, we identified four genes potentially associated with reduced efficacy of immunotherapy (KEAP1, PBRM1, SMARCA4 and STK11). Independent of the nature of co-occurring alterations, tumors with coexisting mutations (CoMut) had inferior survival as compared with single-mutant (SM) and wild-type (WT) tumors (bNGS cohort: CoMut versus SM log-rank P = 0.048, CoMut versus WT log-rank P < 0.001; tNGS cohort: CoMut versus SM log-rank P = 0.037, CoMut versus WT log-rank P = 0.006). The CoMut subset harbored higher TMB than the WT disease and the adverse significance of coexisting alterations was maintained in LUAD with high TMB. Significant immunogenomic differences were observed between the CoMut and WT groups in terms of core immune signatures, T-cell receptor repertoire, T helper cell signatures and immunomodulatory genes. CONCLUSIONS: This study indicates that coexisting alterations in a limited set of genes characterize a subset of LUAD unresponsive to immunotherapy and with high TMB. An immune-cold microenvironment may account for the clinical course of the disease.

Understanding the biomimetic properties of gallium in Pseudomonas aeruginosa: an XAS and XPS study.

Pyochelin (PCH) is a siderophore (extracellular chelator) produced by the pathogenic bacterium Pseudomonas aeruginosa (PAO). PCH is implicated in iron (Fe3+) transport to PAO, and is crucial for its metabolism and pathogenicity. Due to the chemical similarity with Fe3+, gallium (Ga3+) interferes with vital iron-dependent processes in bacterial cells, thereby opening new perspectives for the design of specific metal-based antibacterial drugs. However, the structural basis for the Fe3+-mimetic properties of Ga3+ complexed with the PCH siderophore is still lacking. A precise knowledge of the coordination chemistry at the metal site is one of the topmost issues in the production of novel biomimetic metal-based drugs. Elucidation of this issue by means of a deep structural spectroscopic investigation could lead to an improved interference with, or a specific inhibition of, relevant biological pathways. For this reason, we applied Synchrotron Radiation induced X-ray Photoelectron Spectroscopy (SR-XPS) and X-ray Absorption Spectroscopy (XAS) to probe the electronic nature and coordination chemistry of Fe3+ and Ga3+ coordinative sites in PCH metal complexes. Combined XAFS and SR-XPS studies allow us to demonstrate that both Fe and Ga have the same valence state in Fe-PCH and Ga-PCH, and have the same octahedral coordination geometry. Moreover, a similar next neighbour distribution for Fe and Ga, resulting from the EXAFS data analysis, strongly supports similar coordination chemistry at the origin of the biomimetic behaviour of Ga.

Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections.

Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying. Powder composition and process conditions were selected after in depth formulation studies aimed at selecting the 5-FC/HA/mannitol formulation with convenient aerosolization properties and drug release profile in simulated lung fluids. The optimized 5-FC/HA/mannitol powder for inhalation (HyaMan_FC#3) was effectively delivered from different breath-activated dry powder inhalers (DPI) already available to CF patients. Nevertheless, the aerodynamic assessment of fine particles suggested that the developed formulation well fit with a low-resistance DPI. HyaMan_FC#3 inhibited the growth of the fungus Candida albicans and the production of the virulence factor pyoverdine by P. aeruginosa at 5-FC concentrations that did not affect the viability of both wild type (16HBE14o-) and CF (CFBE41o-) human bronchial epithelial cells. Finally, pharmacokinetics of HyaMan_FC#3 inhalation powder and 5-FC solution after intratracheal administration in rats were compared. In vivo results clearly demonstrated that, when formulated as dry powder, 5-FC levels in both bronchoalveolar lavage fluid and lung tissue were significantly higher and sustained over time as compared to those obtained with the 5-FC solution. Of note, when the same 5-FC amount was administered intravenously, no significant drug amount was found in the lung at each time point from the injection. To realize a 5-FC lung concentration similar to that obtained by using HyaMan_FC#3, a 6-fold higher dose of 5-FC should be administered intravenously. Taken together, our data demonstrate the feasibility to deliver 5-FC by the pulmonary route likely avoiding/reducing the well-known side effects associated to the high systemic 5-FC doses currently used in humans. Furthermore, our results highlight that an appropriate formulation design can improve the persistence of the drug at lungs, where microorganisms causing severe infections are located.

Tyr1068-phosphorylated epidermal growth factor receptor (EGFR) predicts cancer stem cell targeting by erlotinib in preclinical models of wild-type EGFR lung cancer.

Tyrosine kinase inhibitors (TKIs) have shown strong activity against non-small-cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations. However, a fraction of EGFR wild-type (WT) patients may have an improvement in terms of response rate and progression-free survival when treated with erlotinib, suggesting that factors other than EGFR mutation may lead to TKI sensitivity. However, at present, no sufficiently robust clinical or biological parameters have been defined to identify WT-EGFR patients with greater chances of response. Therapeutics validation has necessarily to focus on lung cancer stem cells (LCSCs) as they are more difficult to eradicate and represent the tumor-maintaining cell population. Here, we investigated erlotinib response of lung CSCs with WT-EGFR and identified EGFR phosphorylation at tyrosine1068 (EGFRtyr1068) as a powerful biomarker associated with erlotinib sensitivity both in vitro and in preclinical CSC-generated xenografts. In contrast to the preferential cytotoxicity of chemotherapy against the more differentiated cells, in EGFRtyr1068 cells, erlotinib was even more active against the LCSCs compared with their differentiated counterpart, acquiring potential value as CSC-directed therapeutics in the context of WT-EGFR lung cancer. Although tumor growth was inhibited to a similar extent during erlotinib or chemotherapy administration to responsive tumors, erlotinib proved superior to chemotherapy in terms of higher tolerability and reduced tumor aggressiveness after treatment suspension, substantiating the possibility of preferential LCSC targeting, both in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) tumors. We conclude that EGFRtyr1068 may represent a potential candidate biomarker predicting erlotinib response at CSC-level in EGFR-WT lung cancer patients. Finally, besides its invariable association with erlotinib sensitivity in EGFR-WT lung CSCs, EGFRtyr1068 was associated with EGFR-sensitizing mutations in cell lines and patient tumors, with relevant diagnostic, clinical and therapeutic implications.

Histological ex vivo evaluation of peri-incisional thermal effect created by a new-generation CO2 superpulsed laser.

The purpose of this study is the evaluation of the histological effects of a new-generation superpulsed CO2 laser through an "ex vivo" study. A CO2 ( λ = 10,600 nm) ultra-speed laser (SmartUS20D, DEKA, Florence, Italy) has been used at different parameters from 2 to 4 watt in Continuous Wave (CW) and Pulsed Wave (PW, 50 Hz) to obtain 30 samples from pig cadaver tongues. All the specimens have been subdivided into 6 groups (from A to F) and each group consisted of 5 samples. A final specimen has been taken by scalpel and used as control group. Histological analysis has been performed using an optical microscope (Leica DM 2000) at a magnification of × 40. Results showed that histological readability was optimal in all the samples. The thermal damage has been negligible in all the groups. Furthermore, the average of thermal damage was 0,095 mm in the epithelial, while it was 0.245 mm in the connective tissue. Statistical analysis using Graphpad Prism 5 software showed no significant differences among the groups. CO2 laser demonstrated a good surgical effectiveness provoking little peripheral damage onto the cut edges and allowing a safe histological diagnosis.

Carbapenem resistance and acquired class D beta-lactamases in Acinetobacter baumannii from Croatia 2009-2010.

The molecular epidemiology and the genetic basis of carbapenem resistance was investigated in 185 Acinetobacter baumannii isolates obtained from 13 centers of northern Croatia and Istria during 2009-2010. All isolates were multidrug-resistant, and 35 % (n = 64) were resistant to both imipenem and meropenem. ISAba1-driven overexpression of the intrinsic bla OXA-51-like gene was observed in all carbapenem resistant isolates, and 69 % of these (n = 44) also produced acquired OXA-type carbapenemases. The presence of bla OXA-58-like, bla OXA-24/40-like, and bla OXA-23-like genes was demonstrated in 33 % (n = 21), 27 % (n = 17) and 9 % (n = 6) of carbapenem-resistant isolates, respectively. None of the isolates harbored the bla IMP, bla VIM, bla SIM, bla NDM or bla PER ß-lactamase genes, while bla TEM-1 was detected in five carbapenem- and ampicillin/sulbactam-resistant isolates. Sequence group determination showed a high prevalence (81 %) of isolates belonging to the International clonal lineage (ICL)-I, although the majority (80 %) of isolates carrying acquired carbapenemase genes belonged to the ICL-II. Random amplified polymorphic DNA analysis and multilocus-sequence typing of a subset of carbapenem-resistant isolates revealed a low degree of genetic variability within both ICL-I and ICL-II populations, irrespective of the genetic basis of carbapenem resistance. Overall, an increasing trend toward carbapenem resistance was observed for A. baumannii in Croatia, and the emergence of ICL-II strains producing a variety of acquired carbapenemases.

Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma.

We identified a discrete number of microRNAs differentially expressed in benign or malignant mesothelial tissues. We focused on mir-145 whose levels were significantly downregulated in malignant mesothelial tissues and malignant pleural mesothelioma (MPM) cell lines as compared to benign tissues (pleura, peritoneum or cysts). We show that promoter hyper-methylation caused very low levels in MPM cell lines and specimens. Treatment of MPM cell lines with mir-145 agonists negatively modulated some protumorigenic properties of MPM cells, such as clonogenicity, cell migration and resistance to pemetrexed treatment. The main effector mechanism of the clonogenic death induced by mir-145 was that of accelerated senescence. We found that mir-145 targeted OCT4 via specific binding to its 3'-UTR. Increased intracellular levels of mir-145 decreased the levels of OCT4 and its target gene ZEB1, thereby counteracting the increase of OCT4 induced by pemetrexed treatment which is known to favor the development of chemoresistant cells. In line with this, reintroduction of OCT4 into mimic-145 treated cells counteracted the effects on clonogenicity and replicative senescence. This further supports the relevance of the mir-145-OCT4 interaction for the survival of MPM cells. The potential use of mir-145 expression levels to classify benign vs malignant mesothelial tissues and the differences between pemetrexed-induced senescence and that induced by the re-expression of mir-145 are discussed.

Risk of acquiring tick-borne infections in forestry workers from Lazio, Italy.

The seroprevalence of antibodies to Borrelia burgdorferi and tick-borne encephalitis (TBE) virus was evaluated in a group of forestry rangers in the Lazio region of Italy. One hundred and forty-five forestry rangers and 282 blood donors were examined by two-tiered serological tests for B. burgdorferi and TBE virus. Information on occupation, residence, tick bites, outdoor leisure activities and other risk factors was obtained. The prevalence of IgG/IgM antibodies to B. burgdorferi showed no statistical difference between the two groups, but there was a higher occurrence of IgM antibodies. There were significant differences between indoor and outdoor, urban and rural workplaces among the 145 exposed workers (χ² test: p < 0.001), and a higher risk for outdoor rural than urban tasks was detected among the ten Western blot-tested forestry rangers positive to B. burgdorferi (χ² test: p < 0.1). No seropositivity was observed for the TBE virus. Forestry rangers from the Lazio region did not have a higher risk of Borrelia infection than the blood donors, though an increase in the risk for outdoor tasks in a rural environment was observed.

Pulmonary sarcoidosis in a patient with psoriatic arthritis during infliximab therapy.

The occurrence of sarcoidosis during anti-TNF-alpha therapy has occasionally been published. We report the case of a psoriasis patient who developed pulmonary sarcoidosis during a cycle of therapy with infliximab.

Epidemic multidrug-resistant Acinetobacter baumannii related to European clonal types I and II in Rome (Italy).

The molecular epidemiology and the genetic basis of antibiotic resistance in 88 multidrug-resistant (MDR) Acinetobacter baumannii strains isolated during 18 months from infected patients in seven intensive care units (ICUs) in Rome were investigated. Random amplified polymorphic DNA and macrorestriction analysis identified two predominant clonal types, genetically related to the European epidemic clones I (type 2) and II (type 1), accounting for 98.9% of A. baumannii ICU isolates. Type 1 was isolated from all ICUs under survey. Class 1 integrons of 2.2 and 2.5 kb were detected in type 1 and type 2 isolates, respectively. The integron structures were similar to those previously determined for epidemic A. baumannii strains from various European countries, and suggestive of integron rearrangement/exchange among isolates related to the European epidemic clones I and II. Carbapenem resistance was associated with the presence of the bla(OXA-58) gene in type 1 isolates. The results indicate that the A. baumannii type 1 clone has a high potential of spreading among hospitals.

[Fiberoptic bronchoscopy as diagnostic tool in primitive lung cancer]. / Ruolo diagnostico della fi brobroncoscopia nelle neoplasie polmonari primitive.

OBJECTIVE: The aim of this study was to assess the diagnostic role of fiberoptic bronchoscopy in primitive lung cancers in relation to the sensibility, the specificity and the cost of the examination. MATERIALS AND METHODS: We analysed the diagnostic flow-charts of 473 patients with suspected primitive lung cancer consecutively examined during a period of 4 years (2003-2006). The results were analysed comparing patients observed in the period 2003-2004 with those observed during 2005-2006. The number and type of samples collected and the protocols utilized were considered. RESULTS: In overall patients the reliability of the fiberoptic bronchoscopy was 61.7%, with a significant increase from 47.5% in 2003-2004 to 74.4% in 2005-2006. An important role in improving the diagnostic relevance of the exam was assumed by the more frequent adoption of biopsies and trans-bronchial needle aspiration on parenchyma and mediastinal lymph nodes. CONCLUSIONS: The fiberoptic-bronchoscopy associated to advanced tissue sampling techniques represents the gold standard for the diagnosis of lung cancer, due to high sensitivity and specificity and moderate cost.

[Molecular approach in the treatment of dermatofibrosarcoma protuberans]. / Approccio molecolare nella terapia del dermatofi brosarcomaprotuberans.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous low-grade malignancy with a high recurrence rate that rarely generates distant metastases. In most cases this tumor is associated with a chromosomal translocation involving the COL1A1 gene on chromosome 17 and the platelet-derived-growth-factor B gene on chromosome 22, generating a fusion gene that constitutively activates the PDGF receptor (PDG-FR). In the early stages of disease traditional surgery (wide excision) or Mohs micrographic surgery represent the standard of care. When surgical margins are positive, postoperative radiotherapy is a valuable option. Recently it has been shown that inhibiting PDGFR with imatinib can induce a high response rates in case of unresectable or metastatic disease. This targeted agent now represents the therapy of choice of advanced DFSP and it is the fi rst great therapeutic success in this disease after unsuccessful years using cytotoxic drugs. It is likely that a better knowledge of molecular biology of DFSP could, as it was the case for GISTs, may improve treatment results leading to the development of new targeted agents.

Cryptococcal lymphadenitis as a manifestation of immune reconstitution inflammatory syndrome in an HIV-positive patient: a case report and review of the literature.

Cryptococcus neoformans infections are typically associated with T-cell deficiencies, including acquired immunodeficiency syndrome (AIDS). Although highly active antiretroviral therapy (HAART) has strongly reduced AIDS-related opportunistic infections, the restoration and reactivation of CD4+ cells can induce an immune reconstitution inflammatory syndrome (IRIS), consisting in a deregulated inflammatory response to latent infectious pathogens and/or to their residual antigens. Cryptococcal lymphadenitis has occasionally been documented in IRIS. Here we report a case of histology- and culture-negative cryptococcal lymphadenitis associated with IRIS in an adult AIDS patient with a history of disseminated cryptococcosis, after the start of fully adherent HAART. Appropriate diagnosis was established on nested-PCR and sequence analysis of the interspacer region 2 of C. neoformans ribosomal DNA, and detection of slow-growing blastospores in enrichment cultures of fine-needle lymph node aspirate. Review of recent literature and our case findings suggest that IRIS-associated cryptococcal lymphadenitis is more likely the flare up of a latent infection rather than an immunopathological response to residual antigen of unviable cryptococci.

Nuclear and cytoplasmic cellular distribution of survivin as survival predictor in resected non-small-cell lung cancer.

AIM: Survivin is a member of the inhibitors of apoptosis (IAP) gene family that acts through pathways different from those involving the bcl-2 family. Largely undetectable in normal adult tissues, survivin is deregulated in most human cancers including non-small-cell lung cancer (NSCLC) and may represent a tumor marker with prognostic and therapeutic implications. Aim of our study was to determine the prognostic role of survivin as an apoptosis-related biomarker in a series of resected NSCLC patients. METHODS: A retrospective series of resected NSCLC patients were retrieved from the files of the Regina Elena National Cancer Institute. Survivin was detected by immunohistochemistry (IHC) using a polyclonal antibody. Survivin displayed two kinds of immunoreactivity: (i) a diffuse cytoplasmic staining and (ii) a distinct nuclear staining. A score-scale to distinguish positive (score 1-2) vs. negative (score 0) pattern was applied. Clinical and biological (nuclear and cytoplasmic survivin staining) covariables were screened for a prognostic relationship with overall survival (OS) and disease-free survival (DFS) into the univariate and multivariate analyses. RESULTS: Data referring to 116 NSCLC patients who underwent surgery for stage I-IIIA NSCLC were collected. Multivariate analyses identified tumor size, nodal status and nuclear, but not cytoplasmic, expression of survivin as significant independent predictors of OS, with a hazard ratio of 2.40 (95% CI 1.44, 3.99, p=0.001), 2.03 (95% CI 1.26, 3.26, p=0.003) and 1.83 (95% CI 1.01, 3.30, p=0.044), respectively. Median OS for nuclear survivin positive (score 1-2) and negative (score 0) patients were 23 months (95% CI 15, 31) and 36 months (95% CI 1, 76), respectively (p=0.01); five-year survival for score 1-2 and score 0 patients were 20% and 44.5%, respectively. Conversely, no significant impact on survival is found when patients are stratified according to cytoplasmic survivin expression. CONCLUSIONS: Data presented herein open the issue that prognosis of stage I-IIIA NSCLC can be linked to the cellular pattern of distribution of survivin.

[Optimal role of docetaxel in adjuvant chemotherapy for early stage HER2-negative breast cancer]. / Uso ottimale del docetaxel nella chemioterapia adiuvante delle pazienti con carcinoma mammario HER2-negativo.

The fundamental imperative of adjuvant treatment of early breast cancer is to improve long-term survival and minimize toxicity. The inclusion of docetaxel in adjuvant chemotherapy regimens has improved patient survival in comparison to anthracycline-containing regimens, even if the incidence of acute side effects has increased in some studies. However, late or persistent toxic effects are becoming more important due to an increasing proportion of patients remaining disease free after treatment for early breast cancer. Several studies have recently reported that docetaxel-containing regimens without anthracyclines are equally active, and have no apparent cardiotoxicity. At present, docetaxel-based combinations represent an appropriate choice in the adjuvant treatment of HER2-negative breast cancer, and several studies are ongoing aiming at a better evaluation of the efficacy of this agent in order to optimize its role.

HPV genotypes concordance between sex partners.

The HPV genotype concordance in the sexual couples could support the sexual viral transmission of HPV infection. The present study contains a case-report of a stable Italian sex couple harbouring the same five HPV genotypes in their genital samples. The female partner, affected by vulvar condilomatosis, evidenced positivity in her cervicovaginal scraping with high risk HPV DNA Hybrid Capture 2 test and was negative at liquid-based performed Pap Test and at colposcopic examination. The male partner was clinically healthy regarding his external genitalia. In both male and female genital scrapings, the following HPV genotypes were detected by means of a PCR-based assay: 6, 16, 53, 73 and 84. This considerably high genotype concordance does not appear to be casual and supports, in our opinion, the hypothesis that genital HPV types are sexually transmitted agents

Endometrial biopsy by means of the hysteroscopic resectoscope for the evaluation of tumor differentiation in endometrial cancer: a pilot study.

AIMS: To assess the diagnostic accuracy of endometrial biopsy by means of the hysteroscopic resectoscope (EBHR) in evaluating tumor differentiation in patients with endometrial cancer. METHODS: Between January and December 2005, all the women with a diagnosis of endometrioid adenocarcinoma of the uterus, when admitted to hospital, were enrolled for this study. Patients eligible for surgical treatment underwent a preoperative work-up consisting in pelvic magnetic resonance imaging (MRI) and EBHR. In all patients submitted to a hysterectomy, a comparison between pre- and postoperative tumor grade was carried out. RESULTS: 42 women were enrolled in the study. Hysteroscopic biopsy was carried out in 39 patients (mean age 62.5 years, range 33-79; FIGO stage I: 34, stage II-IV: 5). No complication related to hysteroscopy was observed. The preoperative tumor grade by hysteroscopy correlated with the final grade in 97.1% of cases. No patient had positive peritoneal washing and after a median follow-up of ten months no intraperitoneal tumor relapse was observed. CONCLUSION: EBHR is a very accurate diagnostic procedure for assessing the preoperative tumor grade in patients with endometrial cancer.