Surgical Management of Early Cervical Cancer: When Is Laparoscopic Appropriate?

PURPOSE OF REVIEW: This paper reviews the recent literature data on minimally invasive surgical approach to early cervical cancer compared to abdominal approach, with the aim of evaluate the oncological outcomes and the appropriateness of current indications. RECENT FINDINGS: A recent multicenter randomized controlled trial and a concurrent large epidemiological study, contrary to the previous retrospective data, showed that minimally invasive surgery is associated with significantly poorer survival than the open approach. Open surgery is to be considered the standard of care for early cervical cancer as implemented in the current guidelines, and the patients must be carefully counseled if minimally invasive surgery is offered. Minimally invasive surgery can be considered safe only for sentinel lymph node mapping in a fertility-sparing setting and could be considered after preoperative conization and for small tumors, adopting preventive surgical maneuvers and in reference centers. However, prospective evidences about the suggested indications are not yet available.

Polyketide synthases of Diaporthe helianthi and involvement of DhPKS1 in virulence on sunflower.

BACKGROUND: The early phases of Diaporthe helianthi pathogenesis on sunflower are characterized by the production of phytotoxins that may play a role in host colonisation. In previous studies, phytotoxins of a polyketidic nature were isolated and purified from culture filtrates of virulent strains of D. helianthi isolated from sunflower. A highly aggressive isolate (7/96) from France contained a gene fragment of a putative nonaketide synthase (lovB) which was conserved in a virulent D. helianthi population. RESULTS: In order to investigate the role of polyketide synthases in D. helianthi 7/96, a draft genome of this isolate was examined. We were able to find and phylogenetically analyse 40 genes putatively coding for polyketide synthases (PKSs). Analysis of their domains revealed that most PKS genes of D. helianthi are reducing PKSs, whereas only eight lacked reducing domains. Most of the identified PKSs have orthologs shown to be virulence factors or genetic determinants for toxin production in other pathogenic fungi. One of the genes (DhPKS1) corresponded to the previously cloned D. helianthi lovB gene fragment and clustered with a nonribosomal peptide synthetase (NRPS) -PKS hybrid/lovastatin nonaketide like A. nidulans LovB. We used DhPKS1 as a case study and carried out its disruption through Agrobacterium-mediated transformation in the isolate 7/96. D. helianthi DhPKS1 deleted mutants were less virulent to sunflower compared to the wild type, indicating a role for this gene in the pathogenesis of the fungus. CONCLUSION: The PKS sequences analysed and reported here constitute a new genomic resource that will be useful for further research on the biology, ecology and evolution of D. helianthi and generally of fungal plant pathogens.

Long-Term Oncologic and Reproductive Outcomes in Young Women With Early Endometrial Cancer Conservatively Treated: A Prospective Study and Literature Update.

OBJECTIVE: This study aimed to analyze the long-term oncologic and reproductive outcomes in endometrial cancer (EC) in young patients conservatively treated by combined hysteroscopic resection (HR) and levonorgestrel intrauterine device (LNG-IUD). METHODS: Twenty-one patients (age ≤ 40 years; Stage IA, G1-2 endometrioid EC), wishing to preserve their fertility, were enrolled into this prospective study. The HR was used to resect (1) the tumor lesion, (2) the endometrium adjacent to the tumor, and (3) the myometrium underlying the tumor. Hormonal therapy consisted of LNG-IUD (52 mg) for at least 6 months. RESULTS: The median follow-up time is 85 months (range, 30-114). After 3 months from the progestin start date, 18 patients (85.7%) showed a complete regression (CR), 2 (9.5%) showed persistent disease, whereas 1 patient (4.8%) presented with progressive disease and underwent definitive surgery (Stage IA, G3 endometrioid). At 6 months, 1 of the 2 persistences underwent definitive surgery (Stage IA, G1 endometrioid), whereas the other was successfully re-treated. Two recurrences (10.5%) were observed, both involving the endometrium and synchronous ovarian cancer (OC) (atypical hyperplasia and Stage IIB G1 endometrioid OC; Stage IA endometrioid G1 EC, and Stage IA G1 endometrioid OC). The median duration of complete response was 85 months (range, 8-117). Sixty-three percent of complete responders attempted to conceive with 92% and 83% pregnancy and live birth rates, respectively. To date, all patients are alive and have no evidence of disease. CONCLUSIONS: After a long follow-up, combined HR and LNG-IUD would seem to improve the efficacy of progestin alone. High pregnancy and live birth rates were observed in women attempting to conceive. This approach is still experimental and should be offered only in the framework of scientific protocols conducted in cancer centers.

Multiple roles and effects of a novel Trichoderma hydrophobin.

Fungi belonging to the genus Trichoderma are among the most active and ecologically successful microbes found in natural environments, because they are able to use a variety of substrates and affect the growth of other microbes and virtually any plant species. We isolated and characterized a novel type II hydrophobin secreted by the biocontrol strain MK1 of Trichoderma longibrachiatum. The corresponding gene (Hytlo1) has a multiple role in the Trichoderma-plant-pathogen three-way interaction, while the purified protein displayed a direct antifungal as well as a microbe-associated molecular pattern and a plant growth promotion (PGP) activity. Leaf infiltration with the hydrophobin systemically increased resistance to pathogens and activated defense-related responses involving reactive oxygen species, superoxide dismutase, oxylipin, phytoalexin, and pathogenesis-related protein formation or activity. The hydrophobin was found to enhance development of a variety of plants when applied at very low doses. It particularly stimulated root formation and growth, as demonstrated also by transient expression of the encoding gene in tobacco and tomato. Targeted knock-out of Hytlo1 significantly reduced both antagonistic and PGP effect of the wild-type strain. We conclude that this protein represents a clear example of a molecular factor developed by Trichoderma spp. to establish a mutually beneficial interaction with the colonized plant.

Genetic variability and evolutionary diversification of membrane ABC transporters in plants.

BACKGROUND: ATP-binding cassette proteins have been recognized as playing a crucial role in the regulation of growth and resistance processes in all kingdoms of life. They have been deeply studied in vertebrates because of their role in drug resistance, but much less is known about ABC superfamily functions in plants. RESULTS: Recently released plant genome sequences allowed us to identify 803 ABC transporters in four vascular plants (Oryza. sativa, Solanum lycopersicum, Solanum tuberosum and Vitis vinifera) and 76 transporters in the green alga Volvox carteri, by comparing them with those reannotated in Arabidopsis thaliana and the yeast Saccharomyces cerevisiae. Retrieved proteins have been phylogenetically analysed to infer orthologous relationships. Most orthologous relationships in the A, D, E and F subfamilies were found, and interesting expansions within the ABCG subfamily were observed and discussed. A high level of purifying selection is acting in the five ABC subfamilies A, B, C, D and E. However, evolutionary rates of recent duplicate genes could influence vascular plant genome diversification. The transcription profiles of ABC genes within tomato organs revealed a broad functional role for some transporters and a more specific activity for others, suggesting the presence of key ABC regulators in tomato. CONCLUSIONS: The findings achieved in this work could contribute to address several biological questions concerning the evolution of the relationship between genomes of different species. Plant ABC protein inventories obtained could be a valuable tool both for basic and applied studies. Indeed, interpolation of the putative role of gene functions can accelerate the discovering of new ABC superfamily members.

Identification and characterization of GEO1, a new class II hydrophobin from Geosmithia spp.

In the present paper we describe a new noncatalytic protein belonging to the hydrophobin family, designated GEO1, purified from the culture filtrate of Geosmithia pallida (Ascomycota: Hypocreales), and the corresponding gene sequence. In the fungal genome, GEO1 was encoded by a single-copy gene with a 450 bp open reading frame interrupted by 2 small introns whose primary translation product was 109 amino acids long and included a 23 amino acids signal peptide. The mature protein had a molecular mass of 8111.75 Da and a theoretical pI of 4.33. The deduced amino acid sequence showed similarity to class II hydrophobins and contained 8 conserved cysteine residues, present in all hydrophobins isolated so far. Biochemical properties, such as foam-forming ability and trapezoid-like shape of a GEO1 drop, also resembled the typical features of the class II hydrophobins. Expression of the geo1 gene was assessed after 2, 4, 7, 9, and 11 days of culture and showed that the geo1 transcript appeared after 7 days and increased up to 11 days.

Phytotoxicity, not nitrogen immobilization, explains plant litter inhibitory effects: evidence from solid-state 13C NMR spectroscopy.

Litter decomposition provides nutrients that sustain ecosystem productivity, but litter may also hamper root proliferation. The objectives of this work were to assess the inhibitory effect of litter decomposition on seedling growth and root proliferation; to study the role of nutrient immobilization and phytotoxicity; and to characterize decomposing litter by (13)C NMR spectroscopy. A litter-bag experiment was carried out for 180 d with 16 litter types. Litter inhibitory effects were assessed by two bioassays: seed germination and root proliferation bioassays. Activated carbon (C) and nutrient solutions were used to evaluate the effects of phytotoxic factors and nutrient immobilization. An inhibitory effect was found for all species in the early phase of decomposition, followed by a decrease over time. The addition of activated C to litter removed this inhibition. No evidence of nutrient immobilization was found in the analysis of nitrogen dynamics. NMR revealed consistent chemical changes during decomposition, with a decrease in O-alkyl and an increase in alkyl and methoxyl C. Significant correlations were found among inhibitory effects, the litter decay rate and indices derived from NMR. The results show that it is possible to predict litter inhibitory effects across a range of litter types on the basis of their chemical composition.

Uterine papillary serous, clear cell, and poorly differentiated endometrioid carcinomas: a comparative study.

INTRODUCTION: Uterine papillary serous and clear cell carcinomas (UPSCs/CCs) show a different spreading from that of poorly differentiated endometrioid carcinomas (PDECs) and are usually thought to be prognostically more aggressive than PDECs. On the contrary, it has been recently claimed that UPSC/CC and PDEC have a similar prognosis. In this retrospective study on 2 institutional databases, the surgical-pathological data and survival have been compared in patients with UPSC/CC and PDEC. METHODS: A total of 139 surgically staged consecutive patients, 63 with UPSC/CC (37 UPSC; 26 CC) and 76 with PDEC clinically limited to the uterine corpus, have been compared for nuclear ploidy, myometrial invasion, (occult) cervical extension, peritoneal, and lymph node metastasis. Prognostic factors have been correlated through multivariate analysis with survival (disease-specific [DSS] and disease-free [DFS]). RESULTS: Peritoneal metastases and aneuploidy were found to be the only parameters significantly different in the 2 groups: peritoneal metastases 28.6% in UPSC/CC (extrapelvic 19%) and 7.9% in PDEC (extrapelvic 2.6%) (P = 0.001), aneuploidy 48.6% in UPSC/CC and 30.6% in PDEC (P = 0.05). Five-year DSS was 57.9% versus 75.2% (P = 0.02), and DFS was 52.3% versus 71.4% (P = 0.04) for UPSC/CC and PDEC, respectively. All but cervical and lymph node involvement were significant predictors of survival. After multivariate analysis, histotype (DSS: hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.02-3.86; P = 0.04; DFS: HR, 1.94; 95% CI, 1.04-3.63; P = 0.04), stage (DSS: HR, 2.26; 95% CI, 1.10-4.65; P = 0.03; DFS: HR, 2.21; 95% CI, 1.12-4.38; P = 0.02), and myometrial invasion (DSS: HR, 2.86; 95% CI, 1.22-6.69; P = 0.01; DFS: HR, 3.96; 95% CI, 1.63-9.62; P = 0.002) were independent risk factors for survival. CONCLUSIONS: Uterine papillary serous and clear cell carcinomas spread to abdominal peritoneum more frequently than PDEC; multivariate analysis confirms UPSC/CC as an independent, unfavorable predictor of outcome.

Biochars from olive mill waste have contrasting effects on plants, fungi and phytoparasitic nematodes.

Olive mill waste (OMW), a byproduct from the extraction of olive oil, causes serious environmental problems for its disposal, and extensive efforts have been made to find cost-effective solutions for its management. Biochars produced from OMW were applied as soil amendment and found in many cases to successfully increase plant productivity and suppress diseases. This work aims to characterize biochars obtained by pyrolysis of OMW at 300 °C to 1000 °C using 13C NMR spectroscopy, LC-ESI-Q-TOF-MS and SEM (Scanning Electron Microscopy). Chemical characterization revealed that biochar composition varied according to the increase of pyrolysis temperature (PT). Thermal treated materials showed a progressive reduction of alkyl C fractions coupled to the enrichment in aromatic C products. In addition, numerous compounds present in the organic feedstock (fatty acids, phenolic compounds, triterpene acids) reduced (PT = 300 °C) or completely disappeared (PT ≥ 500 °C) in biochars as compared to untreated OMW. PT also affected surface morphology of biochars by increasing porosity and heterogeneity of pore size. The effects of biochars extracts on the growth of different organisms (two plants, one nematode and four fungal species) were also evaluated. When tested on different living organisms, biochars and OMW showed opposite effects. The root growth of Lepidium sativum and Brassica rapa, as well as the survival of the nematode Meloidogyne incognita, were inhibited by the untreated material or biochar produced at 300 °C, but toxicity decreased at higher PTs. Conversely, growth of Aspergillus, Fusarium, Rhizoctonia and Trichoderma fungi was stimulated by organic feedstock, while being inhibited by thermally treated biochars. Our findings showed a pattern of association between specific biochar chemical traits and its biological effects that, once mechanistically explained and tested in field conditions, may lead to effective applications in agriculture.

Saponins from Allium minutiflorum with antifungal activity.

Three saponins, named minutoside A (1), minutoside B (2), minutoside C (3), and two known sapogenins, alliogenin and neoagigenin, were isolated from the bulbs of Allium minutiflorum Regel. Elucidation of their structure was carried out by comprehensive spectroscopic analyses, including 2D NMR spectroscopy and mass spectrometry. The structures of the new compounds were identified as (25R)-furost-2alpha,3beta,6beta,22alpha,26-pentaol 3-O-[beta-D-xylopyranosyl-(1-->3)-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-galactopyranosyl] 26-O-beta-D-glucopyranoside (1), (25S)-spirostan-2alpha,3beta,6beta-triol 3-O-beta-D-xylopyranosyl-(1-->3)-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-galactopyranoside (2), and (25R)-furost-2alpha,3beta,5alpha,6beta,22alpha,26-esaol 3-O-[beta-D-xylopyranosyl-(1-->3)-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-galactopyranosyl] 26-O-beta-D-glucopyranoside (3). The isolated compounds were evaluated for their antimicrobial activity. All the novel saponins showed a significant antifungal activity depending on their concentration and with the following rank: minutoside B>minutoside C>>minutoside A. No appreciable antibacterial activity was recorded. The possible role of these saponins in plant-microbe interactions is discussed.

Litter chemistry explains contrasting feeding preferences of bacteria, fungi, and higher plants.

Litter decomposition provides a continuous flow of organic carbon and nutrients that affects plant development and the structure of decomposer communities. Aim of this study was to distinguish the feeding preferences of microbes and plants in relation to litter chemistry. We characterized 36 litter types by 13C-CPMAS NMR spectroscopy and tested these materials on 6 bacteria, 6 fungi, and 14 target plants. Undecomposed litter acted as a carbon source for most of the saprophytic microbes, although with a large variability across litter types, severely inhibiting root growth. An opposite response was found for aged litter that largely inhibited microbial growth, but had neutral or stimulatory effects on root proliferation. 13C-CPMAS NMR revealed that restricted resonance intervals within the alkyl C, methoxyl C, O-alkyl C and di-O-alkyl C spectral regions are crucial for understanding litter effects. Root growth, in contrast to microbes, was negatively affected by labile C sources but positively associated with signals related to plant tissue lignification. Our study showed that plant litter has specific and contrasting effects on bacteria, fungi and higher plants, highlighting that, in order to understand the effects of plant detritus on ecosystem structure and functionality, different microbial food web components should be simultaneously investigated.

Biochar As Plant Growth Promoter: Better Off Alone or Mixed with Organic Amendments?

Biochar is nowadays largely used as a soil amendment and is commercialized worldwide. However, in temperate agro-ecosystems the beneficial effect of biochar on crop productivity is limited, with several studies reporting negative crop responses. In this work, we studied the effect of 10 biochar and 9 not pyrogenic organic amendments (NPOA), using pure and in all possible combinations on lettuce growth (Lactuca sativa). Organic materials were characterized by 13C-CPMAS NMR spectroscopy and elemental analysis (pH, EC, C, N, C/N and H/C ratios). Pure biochars and NPOAs have variable effects, ranging from inhibition to strong stimulation on lettuce growth. For NPOAs, major inhibitory effects were found with N poor materials characterized by high C/N and H/C ratio. Among pure biochars, instead, those having a low H/C ratio seem to be the best for promoting plant growth. When biochars and organic amendments were mixed, non-additive interactions, either synergistic or antagonistic, were prevalent. However, the mixture effect on plant growth was mainly dependent on the chemical quality of NPOAs, while biochar chemistry played a secondary role. Synergisms were prevalent when N rich and lignin poor materials were mixed with biochar. On the contrary, antagonistic interactions occurred when leaf litter or woody materials were mixed with biochar. Further research is needed to identify the mechanisms behind the observed non-additive effects and to develop biochar-organic amendment combinations that maximize plant productivity in different agricultural systems.

Study of the three-way interaction between Trichoderma atroviride, plant and fungal pathogens by using a proteomic approach.

The main molecular factors involved in the complex interactions occurring between plants (bean), two different fungal pathogens (Botrytis cinerea, Rhizoctonia solani) and an antagonistic strain of the genus Trichoderma were investigated. Two-dimensional (2-D) electrophoresis was used to analyze separately collected proteomes from each single, two- or three-partner interaction (i.e., plant, pathogenic and antagonistic fungus alone and in all possible combinations). Differential proteins were subjected to mass spectrometry and in silico analysis to search for homologies with known proteins. In the plant proteome, specific pathogenesis-related proteins and other disease-related factors (i.e., potential resistance genes) seem to be associated with the interaction with either one of the two pathogens and/or T. atroviride. This finding is in agreement with the demonstrated ability of Trichoderma spp. to induce systemic resistance against various microbial pathogens. On the other side, many differential proteins obtained from the T. atroviride interaction proteome showed interesting homologies with a fungal hydrophobin, ABC transporters, etc. Virulence factors, like cyclophilins, were up-regulated in the pathogen proteome during the interaction with the plant alone or with the antagonist too. We isolated and confidently identified a large number of protein factors associated to the multi-player interactions examined.

Draft whole-genome sequence of the Diaporthe helianthi 7/96 strain, causal agent of sunflower stem canker.

Diaporthe helianthi is a fungus pathogenic to sunflower. Virulent strains of this fungus cause stem canker with important yield losses and reduction of oil content. Here we present the first draft whole-genome sequence of the highly virulent isolate D. helianthi strain 7/96, thus providing a useful platform for future research on stem canker of sunflower and fungal genomics. The genome sequence of the D. helianthi isolate 7/96 was deposited at DDBJ/ENA/GenBank under the accession number MAVT00000000 (BioProject PRJNA327798).

Climate, Soil Management, and Cultivar Affect Fusarium Head Blight Incidence and Deoxynivalenol Accumulation in Durum Wheat of Southern Italy.

Fusarium head blight (FHB) is a multifaceted disease caused by some species of Fusarium spp. A huge production of mycotoxins, mostly trichothecenes, often accompanied this disease. Amongst these toxic compounds, deoxynivalenol (DON) and its derivatives represent a major issue for human as well as for animal health and farming. Common and durum wheat are amongst the hosts of trichothecene-producing Fusaria. Differences in susceptibility to fungal infection and toxin accumulation occur in wheat cultivars. Recently, increasing incidence and severity of Fusarium infection and a higher DON accumulation in durum wheat were observed in Italy, especially in Northern regions. In this study, we analyzed wheat yield, technological parameters, the incidence of Fusarium infection and DON content in kernel samples of durum wheat coming from three locations of Southern Italy with different climatic conditions and grown during two seasons, with two methods of cultivation. Four different durum wheat cultivars prevalently cultivated in Southern Italian areas were chosen for this study. Our analysis showed the effects of environment and cultivar types on wheat productivity and key technological parameters for the quality level of the end-product, namely pasta. Notably, although a low rate of mycotoxin contamination in all study sites was assessed, an inverse relation emerged between fungal infection/DON production and durum wheat yield. Further, our study pinpoints the importance of environment conditions on several quality traits of durum wheat grown under Mediterranean climate. The environmental conditions at local level (microscale) and soil management practices may drive FHB outbreak and mycotoxin contamination even in growing area suitable for cropping this wheat species.

Pseudomonas lipodepsipeptides and fungal cell wall-degrading enzymes act synergistically in biological control.

Pseudomonas syringae pv. syringae strain B359 secreted two main lipodepsipeptides (LDPs), syringomycin E (SRE) and syringopeptin 25A (SP25A), together with at least four types of cell wall-degrading enzymes (CWDEs). In antifungal bioassays, the purified toxins SRE and SP25A interacted synergistically with chitinolytic and glucanolytic enzymes purified from the same bacterial strain or from the biocontrol fungus Trichoderma atroviride strain P1. The synergism between LDPs and CWDEs occurred against all seven different fungal species tested and P. syringae itself, with a level dependent on the enzyme used to permeabilize the microbial cell wall. The antifungal activity of SP25A was much more increased by the CWDE action than was that of the smaller SRE, suggesting a stronger antifungal role for SP25A. In vivo biocontrol assays were performed by using P. syringae alone or in combination with T. atroviride, including a Trichoderma endochitinase knock-out mutant in place of the wild type and a chitinase-specific enzyme inhibitor. These experiments clearly indicate that the synergistic interaction LDPs-CWDEs is involved in the antagonistic mechanism of P. syringae, and they support the concept that a more effective disease control is given by the combined action of the two agents.

Interspecific variability of class II hydrophobin GEO1 in the genus Geosmithia.

The genus Geosmithia Pitt (Ascomycota: Hypocreales) comprises cosmopolite fungi living in the galleries built by phloeophagous insects. Following the characterization in Geosmithia species 5 of the class II hydrophobin GEO1 and of the corresponding gene, the presence of the geo1 gene was investigated in 26 strains derived from different host plants and geographic locations and representing the whole phylogenetic diversity of the genus. The geo1 gene was detected in all the species tested where it maintained the general organization shown in Geosmithia species 5, comprising three exons and two introns. Size variations were found in both introns and in the first exon, the latter being due to the presence of an intragenic tandem repeat sequence corresponding to a stretch of glycine residues in the deduced proteins. At the amino acid level the deduced proteins had 44.6 % identity and no major differences in the biochemical parameters (pI, GRAVY index, hydropathy plots) were found. GEO1 release in the fungal culture medium was also assessed by turbidimetric assay and SDS-PAGE, and showed high variability between species. The phylogeny based on the geo1 sequences did not correspond to that generated from a neutral marker (ITS rDNA), suggesting that sequence similarities could be influenced by other factors than phylogenetic relatedness, such as the intimacy of the symbiosis with insect vectors. The hypothesis of a strong selection pressure on the geo1 gene was sustained by the low values (<1) of non synonymous to synonymous nucleotide substitutions ratios (Ka/Ks), which suggest that purifying selection might act on this gene. These results are compatible with either a birth-and-death evolution scenario or horizontal transfer of the gene between Geosmithia species.

Widespread horizontal transfer of the cerato-ulmin gene between Ophiostoma novo-ulmi and Geosmithia species.

Previous work had shown that a sequence homologous to the gene encoding class II hydrophobin cerato-ulmin from the fungus Ophiostoma novo-ulmi, the causal agent of Dutch Elm Disease (DED), was present in a strain of the unrelated species Geosmithia species 5 (Ascomycota: Hypocreales) isolated from Ulmus minor affected by DED. As both fungi occupy the same habitat, even if different ecological niches, the occurrence of horizontal gene transfer was proposed. In the present work we have analysed for the presence of the cerato-ulmin gene 70 Geosmithia strains representing 29 species, isolated from different host plants and geographic locations. The gene was found in 52.1 % of the strains derived from elm trees, while none of those isolated from nonelms possessed it. The expression of the gene in Geosmithia was also assessed by real time PCR in different growth conditions (liquid culture, solid culture, elm sawdust, dual culture with O. novo-ulmi), and was found to be extremely low in all conditions tested. On the basis of these results we propose that the cerato-ulmin gene is not functional in Geosmithia, but can be considered instead a marker of more extensive transfers of genetic material as shown in other fungi.

Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study.

OBJECTIVES: To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours. DESIGN: Observational diagnostic study using prospectively collected clinical and ultrasound data. SETTING: 24 ultrasound centres in 10 countries. PARTICIPANTS: Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients. MAIN OUTCOME MEASURES: Histological classification and surgical staging of the mass. RESULTS: The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate. CONCLUSIONS: The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Antifungal saponins from bulbs of garlic, Allium sativum L. var. Voghiera.

A bioassay-guided phytochemical analysis of the polar extract from the bulbs of garlic, Allium sativum L., var. Voghiera, typical of Voghiera, Ferrara (Italy), allowed the isolation of ten furostanol saponins; voghieroside A1/A2 and voghieroside B1/B2, based on the rare agapanthagenin aglycone; voghieroside C1/C2, based on agigenin aglycone; and voghieroside D1/D2 and E1/E2, based on gitogenin aglycone. In addition, we found two known spirostanol saponins, agigenin 3-O-trisaccharide and gitogenin 3-O-tetrasaccharide. The chemical structures of the isolated compounds were established through a combination of extensive nuclear magnetic resonance, mass spectrometry and chemical analyses. High concentrations of two eugenol diglycosides were also found for the first time in Allium spp. The isolated compounds were evaluated for their antimicrobial activity towards two fungal species, the air-borne pathogen Botrytis cinerea and the antagonistic fungus Trichoderma harzianum.