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.

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.

Virtual CT sonographically guided biopsy of a retroperitoneal mass in a patient with Erdheim-Chester disease.

Image fusion between sonography and CT allows real-time synchronization of CT multiplanar reconstructed images with the corresponding sonographic images. This technique has mainly been used in liver imaging. We report the use of image fusion to target and successfully guide the percutaneous biopsy of a retroperitoneal a mass. This technique represents a promising tool in abdominal imaging, and it should be considered for the biopsy of lesions that are difficult to approach with conventional imaging guidance techniques.

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.

Bevacizumab in the treatment of advanced, non-squamous non-small cell lung cancer: an evidence-based approach.

BACKGROUND: To assess the efficacy and safety of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous non-small cell lung cancer (NSCLC) on the basis of the two registrative trials [ECOG E4599 trial and BO17704 (AVAiL) trial]. METHODS: A pooled analysis of the two trials was performed using a random effect model, and the results were summarized as number-needed-to-treat (NNT) and number-needed-to-harm (NNH). A 2-step analysis was performed. The primary analysis included only the patients treated with bevacizumab 15 mg/kg in the experimental arm, whereas the secondary analysis (with descriptive aim) included the patients treated with bevacizumab 15 mg/kg or those treated with bevacizumab 7.5 mg/kg in the experimental arm. The 1-year survival and 6-month progression-free rates were assumed as indexes of efficacy, and grade III-IV side effects were assumed as index of safety in both analyses. RESULTS: 1,921 patients were potentially eligible for the pooled analysis and were included in the secondary analysis, whereas 1,576 patients were included in the primary analysis. A large heterogeneity was documented for both 6-month progression-free interval (I(2) = 88.164%, p = 0.004) and overall survival (I(2) = 73.541, p = 0.052). The absolute risk reduction of 1-year death and 6-month progression were 3.3% (95% CI = -6.5 to 13.2%, p = 0.507), with a NNT = 30; and 15.2% (95% CI = 0.07-29.6%, p = 0.04), with a NNT = 6 (both in favor of the bevacizumab-containing regimens), respectively. The absolute risk of treatment-related death was 2.4% (95% CI = 0.8-3.9%, p = 0.003), with a NNH = 41 against the bevacizumab-containing regimens; that of bleeding was 3.3% (95% CI = 1.6-4.9%, p < 0.001), with a NNH = 30; that of hypertension was 6.6% (95% CI = 4.6-8.6%, p < 0.001), with a NNH = 15; that of proteinuria was 2.1% (95% CI = 0.3-3.8%, p = 0.024), with a NNH = 47; that of neutropenia was 7.3% (95% CI = 3.2-11.4%, p < 0.001), with a NNH = 13; that of thrombocytopenia was 1.5% (95% CI = 0.2-2.7%, p = 0.021), with a NNH = 66. No significant differences were observed in the efficacy and the safety analysis when all the patients treated with bevacizumab 7.5 mg/kg and 15 mg/kg were included into the pooled analysis. CONCLUSION: Adding bevacizumab to standard chemotherapy in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC seems to favor a modest improvement in the main outcomes, with a significant worsening of the safety profile. These data suggest caution in the generalized use of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC.

The second step of the analgesic ladder and oral tramadol in the treatment of mild to moderate cancer pain: a systematic review.

BACKGROUND: To analyse the evidence supporting the widespread use of modified analgesic ladders or oral tramadol as alternatives to codeine/paracetamol for mild to moderate cancer pain. METHODS: A systematic review of the literature was independently performed by two authors. The level of evidence and risk/benefit ratio were assessed in all the selected trials. A comprehensive analysis of the level of evidence, risk/benefit ratio and strength of the recommendations was carried out. The analysis was performed using the GRADE system. RESULTS: Eighteen papers were included into the analysis. The level of evidence was low or very low for all the trials, and as a result the risk/benefit ratio was uncertain. Likewise, the strength of the final recommendations was considered weak negative for either the use of modified analgesic ladders (by-passing the second step of the World Health Organization (WHO) analgesic ladder) or the use of oral tramadol as an alternative to codeine/paracetamol in the second step of the WHO analgesic ladder. CONCLUSIONS: Data supporting the role of modified two-step analgesic ladders or oral tramadol as an alternative to codeine/paracetamol are insufficient to recommend their routine use in cancer patients with mild to moderate cancer pain.

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.

Transdermal fentanyl as a front-line approach to moderate-severe pain: a meta-analysis of randomized clinical trials.

OBJECTIVE: The safety of transdermal fentanyl (TF) in comparison with slow-release oral morphine (SROM) in moderate-severe pain was assessed. DESIGN: A systematic review of the literature was performed to identify all randomized trials comparing TF and SROM in moderate-severe pain. Overall safety was the primary end point. Trials enrolling both cancer and non-cancer patients were included in the analysis. Heterogeneity was assessed using the Mantel-Haenszel test; a random effects model was used for the pooled analysis. Cumulative and distinctive analyses for cancer and non-cancer pain were performed whenever the outcome was reported in at least two trials. RESULTS: Five trials met the inclusion criteria. A significant advantage of TF was documented for constipation, laxative use, and urinary retention. TF was preferred by cancer and non-cancer patients. A difference in favour of SROM was documented for nausea, diarrhea, and sweating in cancer and non-cancer patients. No differences were observed for the other items considered. CONCLUSIONS: TF and SROM seem to have a different side effects profile, and TF seems to be preferred by patients. The hierarchical approach traditionally recommended by the main scientific societies (oral morphine and then TF) could be replaced by a front-line approach based on patients' characteristics and needs.

[Screening for colorectal cancer in high-risk and intermediate-risk subject: what's the best tool?]. / Screeening per la prevenzione del cancro del colon nei soggetti ad alto rischio ed in quelli a rischio intermedio. Qual e la migliore opzione?

Although several screening tests are now available, at present none of them has been proven the best one. Colonoscopy is usually used in high-risk subjects (family history of either colorectal cancer [CRC] or adenomas). In intermediate-risk subjects, fecal occult blood test (FOBT) is preferred, and colonoscopy is performed only when FOBT results positive. The aim of this study is to better define the role of colonoscopy in a screening program. Three groups of subjects were retrospectively reviewed. RSP (Regional Screening Program), FDR (First Degree Relatives), and Control-groups included 362, 581, and 300 subjects, respectively. Adenoma or carcinoma were more frequent in RSP-group than in FDR- and Control-group (53%, 23.7%, and 20%, respectively; p < 0.001). CRC rate was 11.6% in RSP-group, 2.2% in FDR-group (p < 0.001), 6% in Control-group (p < 0.05). Adenoma rate was 41.4% in RSP-group, 21.5% in FDR-group (p < 0.05), 14% in Control-group (p < 0.01). Our results showed that colonoscopy probably can not be regarded as a first-line tool for the screening of CRC in FDR of patients with CRC or adenoma. Some stratification or scoring system for the risk of CRC should be adopted. As an alternative, FOBT could be used also in these subjects.

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.

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.

Subcapsular liver tumors treated with percutaneous radiofrequency ablation: a prospective comparison with nonsubcapsular liver tumors for safety and effectiveness.

PURPOSE: To assess the safety and effectiveness of percutaneous radiofrequency (RF) ablation of subcapsular liver tumors. MATERIALS AND METHODS: The study protocol was approved by the institutional review board, and all patients gave written informed consent. One hundred eighty-one patients (79 men, 102 women; age range, 36-85 years) underwent ultrasonographically (US) guided percutaneous RF ablation of 361 primary or secondary (metastatic) liver tumors. Forty-four patients had one or more subcapsular nodules (group 1), and 137 had nonsubcapsular nodules only (group 2). Overall, 80 nodules were subcapsular and 281 were nonsubcapsular. The completeness of the ablation was assessed with contrast material-enhanced computed tomography (CT) 1 month after RF ablation. If residual tumor was documented, RF ablation was repeated. All patients in whom the ablation was complete after the first or second ablation session were monitored with CT or contrast-enhanced US every 3 months. Major complication, complete ablation, and local tumor progression rates were compared by using the chi(2) test or Fisher exact test. RESULTS: Three (7%) major complications (intraperitoneal bleeding, skin burn, and tumor seeding) occurred in group 1, and two (1.5%) cases of tumor seeding occurred in group 2 (P = .093). No RF ablation-related deaths occurred. The complete ablation rate was 98% (43 of 44 patients) in group 1 and 98.5% (135 of 137 patients) in group 2 (P = .756). The local tumor progression rate after a median follow-up of 25 months (range, 13-54 months) was 16% (seven of 43 patients) in group 1 and 9.6% (13 of 135 patients) in group 2 (P = .355). CONCLUSION: The difference in major complication rate between the subcapsular and nonsubcapsular liver tumors was not significant. The safety of RF ablation of subcapsular tumors seems acceptable, and the effectiveness is comparable to that of RF ablation of nonsubcapsular tumors.

Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature.

BACKGROUND: To assess the adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison with slow release oral morphine. METHODS: A systematic review of the literature in the MEDLINE and EMBASE databases from 1966 to June 2007 was independently performed by two authors. All phase 3 randomized trials comparing transdermal opiates and slow-release oral morphine in the treatment of moderate-severe cancer pain were considered eligible and included in the analysis. The primary end point was the overall adverse effects odds ratio (OR); secondary end points were the overall gastrointestinal adverse effects, constipation, nausea, somnolence, patients' preference, and trial withdrawal. Heterogeneity was analyzed using the Mantel-Haenszel test, and outcome analysis was performed using a random effect model; an alpha error lower than 5% was assumed as statistically significant. RESULTS: Four trials met the selection criteria. The safety of transdermal opiates (fentanyl and buprenorphine) and slow-release oral morphine was analyzed in 425 patients. A significant difference in favor of transdermal opiates was observed for constipation (OR=0.38, p<0.001), and patients' preference (OR=0.43, p=0.014, in the three trials investigating transdermal fentanyl). No significant differences were observed for overall adverse effects, overall gastrointestinal adverse effects, overall neurologic adverse effects, nausea, somnolence, hypoventilation, trial withdrawal, and changes in opiate treatments. CONCLUSION: Although no difference in the overall adverse effect profile exists between transdermal opiates and slow release oral morphine, the difference in some adverse effects (mainly constipation) seems to favor transdermal opiates in the preference of patients with moderate-severe cancer pain.

Disseminated intravascular coagulation during treatment with thalidomide. A case report.

The treatment with thalidomide is associated with an increased risk of thromboembolic events, in particular when it is combined with chemotherapy or dexamethasone. However, despite this well-documented prothrombotic effect, to our knowledge disseminated intravascular coagulation has never been reported in hematological or oncological patients treated with thalidomide. We report a case of disseminated intravascular coagulation in a patient treated with thalidomide and dexamethasone for advanced, heavily pretreated hormone-resistant prostate cancer in which a relationship with the treatment appears highly likely.

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.

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.