Metabolomics Reveals a 26-Membered Macrolactone Produced by Endophytic Colletotrichum spp. from Alcatrazes Island, Brazil.

Comparative metabolomics analysis of nonphytotoxic endophytic Colletotrichum spp. isolated from Anthurium alcatrazense endemic to Alcatrazes island (Brazil) and phytopathogenic Colletotrichum spp. isolated from the mainland of Brazil revealed significant differences in chemical composition. Examination of endophytic Colletotrichum spp. from Alcatrazes island led to the discovery of a 26-member macrolactone, colletotrichumolide (1), containing a phosphatidyl choline side chain. Further examination of the phytopathogenic strains from the mainland identified a family of phytopathogenic metabolites not present in the nonpathogenic island-derived strains, suggesting that geographical isolation could influence the secondary metabolism of fungal strains.

Liver-directed therapies for liver metastases from neuroendocrine neoplasms: Can laser ablation play any role?

Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases (LM) from neuroendocrine neoplasms (NEN), and minimally invasive, liver-directed therapies are gaining increasing interest. Catheter-based treatments are used in disseminated disease, whereas ablation techniques are usually indicated when the number of LM is limited. Although radiofrequency ablation (RFA) is by far the most used ablative technique, the goal of this opinion review is to explore the potential role of laser ablation (LA) in the treatment of LM from NEN. LA uses thinner needles than RFA, and this is an advantage when the tumors are in at-risk locations. Moreover, the multi-fiber technique enables the use of one to four laser fibers at once, and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter. Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor, sparing the liver parenchyma more than any other liver-directed therapy, and allowing for repeated treatments with low risk of liver failure. A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA, that can play a useful role in the multimodality approach to LM from NEN.

Percutaneous Laser Ablation of Liver Metastases from Neuroendocrine Neoplasm. A Retrospective Study for Safety and Effectiveness.

PURPOSE: To retrospectively assess safety and efficacy of laser ablation (LA) of multiple liver metastases (LM) from neuroendocrine neoplasms (NEN). METHODS: Twenty-one patients with NEN and at least 3 LM ≤ 4 cm in diameter underwent ultrasonography-guided LA. Up to seven LM were ablated in a single session; if the number of LM exceeded seven, the remaining LM were ablated in further LA sessions with a time interval of 3-4 weeks. LA was performed according to the multifiber technique. The patients underwent contrast-enhanced CT 1 month after LA, and were subsequently monitored every 3 months for the first 2 years and then every 6 months. RESULTS: In total, 189 LM were treated in 21 patients (mean 9 ± 8.2, median 6) in 41 LA sessions (range 1-5). The diameter of LM ranged from 5 to 35 mm (median 19 mm, mean 17.9 ± 6.4 mm). One grade 4 complication occurred (0.53%): a bowel perforation managed by surgery. Technical efficacy was 100%, primary efficacy rate 94.7%, and secondary efficacy rate 100%. Complete relief of hormone-related symptoms was obtained in all the 13 symptomatic patients. Median follow-up was 39 months (range 12-99). 1-, 2-, 3-, and 5-year survival rates were 95%, 86%, 66%, and 40%, respectively. Overall survival resulted higher for patients with Ki-67 expression ≤ 7% than for those with Ki-67 > 7% (p = 0.0347). CONCLUSIONS: LA is a promising and safe technique to treat LM from NEN. A longer follow-up should provide definitive information on the long-term efficacy of this liver-directed therapy. LEVEL OF EVIDENCE: Retrospective study, local non-random sample, level 3.

Role of the antioxidant defense system during the production of lignocellulolytic enzymes by fungi

Fungi are used for the production of several compounds and the efficiency of biotechnological processes is directly related to the metabolic activity of these microorganisms. The reactions catalyzed by lignocellulolytic enzymes are oxidative and generate reactive oxygen species (ROS). Excess of ROS can cause serious damages to cells, including cell death. Thus, the objective of this work was to evaluate the lignocellulolytic enzymes produced by Pleurotus sajor-caju CCB020, Phanerochaete chrysosporium ATCC 28326, Trichoderma reesei RUT-C30, and Aspergillus niger IZ-9 grown in sugarcane bagasse and two yeast extract (YE) concentrations and characterize the antioxidant defense system of fungal cells by the activities of superoxide dismutase (SOD) and catalase (CAT). Pleurotus sajor-caju exhibited the highest activities of laccase and peroxidase in sugarcane bagasse with 2.6 g of YE and an increased activity of manganese peroxidase in sugarcane bagasse with 1.3 g of YE was observed. However, P. chrysosporium showed the highest activities of exoglucanase and endoglucanase in sugarcane bagasse with 1.3 g of YE. Lipid peroxidation and variations in SOD and CAT activities were observed during the production of lignocellulolytic enzymes and depending on the YE concentrations. The antioxidant defense system was induced in response to the oxidative stress caused by imbalances between the production and the detoxification of ROS

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Chemical composition, nutritional value and bioactive compounds in six uvaia accessions.

This study analyzed six uvaia (Eugenia pyriformis Cambess) accessions ('Comum', 'Rugosa', 'Doce de Patos de Minas', 'Pêra', 'Rugosa Doce' and 'Dura') with respect to chemical composition, nutritional value, bioactive compounds and antioxidant capacity. The 'Rugosa Doce' and 'Doce de Patos de Minas' accessions were sweeter (20.18 g 100 g-1 and 18.88 g 100 g-1, respectively), while the 'Rugosa' and 'Pêra' accessions were less acid (0.28 g 100 g-1 and 0.33 g 100 g-1, respectively). Terpenes were the major volatile compounds (46.75%) identified by SPME-GC/MS. The 'Rugosa' accession contained high levels of fibers (43.81 g 100 g-1) and minerals (2235.10  mg 100 g-1). The 'Rugosa Doce' and 'Rugosa' accessions were distinguished by total flavonoids and phenolic compounds. 'Rugosa Doce' and 'Rugosa' may potentially serve as a raw material for food, while 'Doce de Patos de Minas' and 'Pêra' can be used for cosmetic and pharmaceutical industries purposes.

Role of the antioxidant defense system during the production of lignocellulolytic enzymes by fungi.

Fungi are used for the production of several compounds and the efficiency of biotechnological processes is directly related to the metabolic activity of these microorganisms. The reactions catalyzed by lignocellulolytic enzymes are oxidative and generate reactive oxygen species (ROS). Excess of ROS can cause serious damages to cells, including cell death. Thus, the objective of this work was to evaluate the lignocellulolytic enzymes produced by Pleurotus sajor-caju CCB020, Phanerochaete chrysosporium ATCC 28326, Trichoderma reesei RUT-C30, and Aspergillus niger IZ-9 grown in sugarcane bagasse and two yeast extract (YE) concentrations and characterize the antioxidant defense system of fungal cells by the activities of superoxide dismutase (SOD) and catalase (CAT). Pleurotus sajor-caju exhibited the highest activities of laccase and peroxidase in sugarcane bagasse with 2.6 g of YE and an increased activity of manganese peroxidase in sugarcane bagasse with 1.3 g of YE was observed. However, P. chrysosporium showed the highest activities of exoglucanase and endoglucanase in sugarcane bagasse with 1.3 g of YE. Lipid peroxidation and variations in SOD and CAT activities were observed during the production of lignocellulolytic enzymes and depending on the YE concentrations. The antioxidant defense system was induced in response to the oxidative stress caused by imbalances between the production and the detoxification of ROS.

The potential of compounds isolated from Xylaria spp. as antifungal agents against anthracnose

ABSTRACT Anthracnose is a crop disease usually caused by fungi in the genus Colletotrichum or Gloeosporium. These are considered one of the main pathogens, causing significant economic losses, such as in peppers and guarana. The current forms of control include the use of resistant cultivars, sanitary pruning and fungicides. However, even with the use of some methods of controlling these cultures, the crops are not free of anthracnose. Additionally, excessive application of fungicides increases the resistance of pathogens to agrochemicals and cause harm to human health and the environment. In order to find natural antifungal agents against guarana anthracnose, endophytic fungi were isolated from Amazon guarana. The compounds piliformic acid and cytochalasin D were isolated by chromatographic techniques from two Xylaria spp., guided by assays with Colletotrichum gloeosporioides. The isolated compounds were identified by spectrometric techniques, as NMR and mass spectrometry. This is the first report that piliformic acid and cytochalasin D have antifungal activity against C. gloeosporioides with MIC 2.92 and 2.46 µmol mL-1 respectively. Captan and difenoconazole were included as positive controls (MIC 16.63 and 0.02 µmol mL-1, respectively). Thus, Xylaria species presented a biotechnological potential and production of different active compounds which might be promising against anthracnose disease.

Ultrasound-guided percutaneous laser ablation is safe and effective in the treatment of small renal tumors in patients at increased bleeding risk.

PURPOSE: The aim of this retrospective study was to assess the safety and effectiveness of laser ablation (LA) in patients with small renal cell carcinomas (RCC) and increased risk of bleeding. MATERIAL AND METHODS: From 2013 to 2017, nine patients (six males, three females, aged 68.5 ± 12.2 years) at high risk of bleeding underwent ultrasonography-guided LA for an RCC. Patients were considered at increased risk of bleeding because of impairment of coagulation parameters, concomitant antiplatelet therapy, or at-risk location of the tumor (one, five, and three patients, respectively). RCC diameter ranged from 11 to 23 mm. According to tumor size, two or three laser fibers were introduced through 21-gauge needles and 1800 J per fiber were delivered in 6 min with a fixed power of 5 W. Major and minor complications, technical success, and primary and secondary technical effectiveness and tumor recurrence were recorded. RESULTS: Just one Grade 1 complication was observed: a small asymptomatic hematoma that spontaneously resolved. Technical success was 100%, 1 month technical efficacy was 88.9% (8/9 patients). One patient with residual tumor was successfully retreated 1 month later, and secondary efficacy rate was 100%. No local tumor recurrence occurred during a median follow-up of 26 months (range 11-49 months). CONCLUSIONS: LA is safe and effective in the treatment of small RCC and might represent a valid option in patients with increased risk of bleeding.

The potential of compounds isolated from Xylaria spp. as antifungal agents against anthracnose.

Anthracnose is a crop disease usually caused by fungi in the genus Colletotrichum or Gloeosporium. These are considered one of the main pathogens, causing significant economic losses, such as in peppers and guarana. The current forms of control include the use of resistant cultivars, sanitary pruning and fungicides. However, even with the use of some methods of controlling these cultures, the crops are not free of anthracnose. Additionally, excessive application of fungicides increases the resistance of pathogens to agrochemicals and cause harm to human health and the environment. In order to find natural antifungal agents against guarana anthracnose, endophytic fungi were isolated from Amazon guarana. The compounds piliformic acid and cytochalasin D were isolated by chromatographic techniques from two Xylaria spp., guided by assays with Colletotrichum gloeosporioides. The isolated compounds were identified by spectrometric techniques, as NMR and mass spectrometry. This is the first report that piliformic acid and cytochalasin D have antifungal activity against C. gloeosporioides with MIC 2.92 and 2.46µmolmL-1 respectively. Captan and difenoconazole were included as positive controls (MIC 16.63 and 0.02µmolmL-1, respectively). Thus, Xylaria species presented a biotechnological potential and production of different active compounds which might be promising against anthracnose disease.

Treatment of Metastatic, Castration-resistant, Docetaxel-resistant Prostate Cancer: A Systematic Review of Literature With a Network Meta-analysis of Randomized Clinical Trials.

INTRODUCTION: To compare the efficacy of abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 in the treatment of castration-resistant, docetaxel-resistant metastatic prostate cancer. METHODS: An indirect comparison of Overall Survival (OS) and time to PSA progression among abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 was performed with a network metaanalysis. OS in the entire population of patients was the primary endpoint. OS in ECOG 0-1/2, BPISF≤ 4/>4, pretreated with 1 or 2 courses of chemotherapy, age≤65/>65 patients, patients with only bone metastases or bone and visceral metastases, and time to PSA progression were the secondary endpoints. An indirect comparison of the Hazard Ratio and the 95% Confidence Interval was performed, assuming an alpha error of 5% as an index of statistical significance. The among-the-trial heterogeneity was assessed using a qualitative methodological and clinical analysis. RESULTS: Four trials were selected. In three trials, the comparator was placebo, in one trial it was mitoxantrone, the effect of which in improving survival was considered negligible. No significant difference in OS among abiraterone acetate, enzalutamide, cabazitaxel and radium 223 was observed in neither the entire population nor all the subgroups of patients. Enzalutamide resulted significantly better than abiraterone acetate, cabazitaxel or radium-223 in time to PSA progression. CONCLUSION: Since no significant difference in efficacy seems to exist between the four therapeutic options in the treatment of castration-resistant, docetaxel-resistant, metastatic prostate cancer, the safety of the treatment, patient's compliance and costs should represent the criteria to guide clinicians' choice in clinical practice.

Contrast-enhanced ultrasonography of post-interventional hematoma: the bleeding mushroom is growing inside.

Catheter ablation is an effective treatment in patients with symptomatic atrial fibrillation. Complications are infrequent and usually resolve with minimal or no intervention, but active bleeding due to arterial injury during the vascular access can sometimes represent a life-threatening complication. Contrast-enhanced computed tomography is the standard technique to detect active bleeding, but it may not be immediately available. We report a case of iatrogenic hemorrhage after catheter ablation, in which contrast-enhanced ultrasonography played a decisive role in the recognition of active arterial bleeding due to injury to the right common femoral artery.

Antimetabolites in the treatment of advanced pleural mesothelioma: a network meta-analysis of randomized clinical trials.

An indirect comparison of cisplatin-pemetrexed (CP) and cisplatin-raltitrexed (CR) was performed. The Odds Ratios of 10, 15 and 20 month survival rate and response rate were assumed as indexes of efficacy; the Odds Ratio of grade III-IV side effects, and the absolute risk of overall, hematologic and non-hematologic toxicity, were assumed as indexes of safety. The outcomes of 352 patients were analysed. The Odds Ratios and 95% Confidence Interval (95% CI) of 10, 15 and 20 months survival rate and response rate were 1.2 (95% CI 0.65-2.24, p = 0.559), 1.02 (95% CI 0.49-2.12, p = 0.953), 1.13 (95% CI 0.44-2.91, p = 0.805) and 0.56 (95% CI 0.26-1.21, p = 0.141), respectively. An absolute increased risk of grade III-IV side effects was observed for CP: 6% (95% CI 3-9%, p < 0.001), 9% (95% CI 2-16%, p = 0.008) and 3% (95% CI 0-5%, p = 0.035) for overall, hematological and non-hematological toxicity. CP and CR can be considered comparable in terms of efficacy in the treatment of metastatic pleural mesothelioma, with a modest increased risk of grade III-IV side effects for CP.

Unusual tumour ablations: report of difficult and interesting cases.

Image-guided ablations are nowadays applied in the treatment of a wide group of diseases and in different organs and regions, and every day interventional radiologists have to face more difficult and unusual cases of tumour ablation. In the present case review, we report four difficult and unusual cases, reporting some tips and tricks for a successful image-guided treatment.

Laser ablation of liver tumors: An ancillary technique, or an alternative to radiofrequency and microwave?

Radiofrequency ablation (RFA) is currently the most popular and used ablation modality for the treatment of non surgical patients with primary and secondary liver tumors, but in the last years microwave ablation (MWA) is being technically improved and widely rediscovered for clinical use. Laser thermal ablation (LTA) is by far less investigated and used than RFA and MWA, but the available data on its effectiveness and safety are quite good and comparable to those of RFA and MWA. All the three hyperthermia-based ablative techniques, when performed by skilled operators, can successfully treat all liver tumors eligible for thermal ablation, and to date in most centers of interventional oncology or interventional radiology the choice of the technique usually depends on the physician's preference and experience, or technical availability. However, RFA, MWA, and LTA have peculiar advantages and limitations that can make each of them more suitable than the other ones to treat patients and tumors with different characteristics. When all the three thermal ablation techniques are available, the choice among RFA, MWA, and LTA should be guided by their advantages and disadvantages, number, size, and location of the liver nodules, and cost-saving considerations, in order to give patients the best treatment option.

Early Docetaxel and Androgen Deprivation in the Treatment of Metastatic, Hormone-sensitive Prostate Cancer.

BACKGROUND: To assess the role of docetaxel plus androgen deprivation in metastatic, hormone- sensitive prostate cancer. METHODS: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing docetaxel plus androgen deprivation with androgen deprivation alone in patients with metastatic, hormone-sensitive prostate cancer were considered eligible and included into the analysis. RESULTS: Six papers (3 randomized clinical trials, and 3 systematic reviews with meta-analysis) were considered eligible and included into the analysis. A significant improvement in time to progression and OS in the entire population treated with docetaxel plus androgen deprivation was reported in all the trials and meta-analyses, and in two trials and all meta-analyses, respectively. One trial reported improvement of OS only in patients with high volume disease, and the meta-analysis that also analyzed the subgroups of patients with high or low volume disease reported a benefit of docetaxel plus androgen deprivation for either the entire population or the two subgroups of patients. CONCLUSION: The early use of docetaxel combined with androgen deprivation improves the main outcomes in the treatment of metastatic, hormone-sensitive prostate cancer. The available data suggest that docetaxel plus androgen deprivation could be considered the novel standard for fit patients with metastatic, hormone-sensitive prostate cancer.

Management of incidental renal masses: Time to consider contrast-enhanced ultrasonography.

Proliferation of imaging studies for different clinical purposes and continuous improvement of imaging technology have led to an increasing number of incidental findings of renal masses. It is estimated that over 50% of patients older than 50 years have at least one renal mass. The majority of incidental renal masses are simple cysts that can be easily diagnosed by conventional ultrasonography. However, some incidental renal masses are not simple cysts, and differentiation between benign and malignant entities requires further imaging modalities. In the past, multiphase contrast-enhanced computed tomography and magnetic resonance imaging were considered the primary imaging modalities used to characterize and stage complex cystic and solid renal lesions. Currently, contrast-enhanced ultrasonography represents a novel alternative to contrast-enhanced computed tomography and magnetic resonance imaging. Contrast-enhanced ultrasonography employs microbubble contrast agents that allow the study of different enhancement phases of the kidney without risk of nephrotoxicity and radiation exposure. The diagnostic accuracy of contrast-enhanced ultrasonography in the characterization of complex renal cysts is comparable to that of computed tomography and magnetic resonance imaging, and several studies have demonstrated its reliability also in identifying solid lesions such as pseudotumors, typical angiomyolipomas, and clear cell renal carcinomas. Considering the high incidence of incidental renal masses and the need for rapid and reliable diagnosis, contrast-enhanced ultrasonography could be proposed as the first step in the diagnostic work-up of renal masses because of its safety and cost effectiveness. In this paper, we propose a diagnostic algorithm for the characterization of cystic and solid renal masses.

Thermal ablation in colorectal liver metastases: Lack of evidence or lack of capability to prove the evidence?

Many studies suggest that combined multimodality treatments including ablative therapies may achieve better outcomes than systemic chemotherapy alone in patients with colorectal liver metastases. Nevertheless, ablative therapies are not yet considered as effective options because their efficacy has never been proved by randomized controlled trials (RCT). However, there are in literature no trials that failed in demonstrating the effectiveness of ablative treatments: what are lacking, are the trials. All the attempts to organize phase III studies on this topic failed as a result of non accrual. Just one prospective RCT comparing radiofrequency ablation combined with systemic chemotherapy vs chemotherapy alone has been published. It was designed as a phase III study, but it was closed early because of slow accrual, and was downscaled to phase II study, with the consequent limits in drawing definite conclusions on the benefit of combined treatment. However, the combination treatment met the primary end point of the study and obtained a significantly higher 3-year progression-free survival than systemic chemotherapy alone. It is very unlikely that ultimate efficacy of ablation treatments will ever be tested again, and the best available evidence points toward a benefit for the combination strategy using ablative treatments and chemotherapy.

Early Palliative Care in Advanced Oncologic and Non-Oncologic Chronic Diseases: A Systematic Review of Literature.

BACKGROUND: To assess the role of early palliative care in patients with advanced oncologic and non-oncologic chronic diseases. METHODS: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing early, simultaneous palliative care and standard care in patients with advanced oncologic and non-oncologic diseases were considered eligible and included into the analysis. The outcomes were classified into 6 classes: quality of life, symptoms control, overall survival, quality of care, patients' and caregivers' satisfaction, and costs of the assistance. RESULTS: Twelve papers reporting the data of 9 trials were considered eligible and included into the analysis. Two nonrandomized trials were also included into the selection because of the methods used by the authors. The early, simultaneous approach was reported to improve quality of life in two out of 7 papers, symptoms control in 1 out of 5 papers, overall survival in 2 out of 3 papers, quality of care in 5 out of 8 papers, patients' or caregivers' satisfaction in 3 out of 4 papers; and to reduce the costs of assistance in 2 out of 3 papers. CONCLUSION: Early palliative care improves the main outcomes of the assistance in patients with advanced oncologic and non-oncologic chronic diseases. The available data are probably enough to consider early palliative cares a novel standard of care in these groups of patients.