The effect of COVID-19 on the frequency of Pneumocystis jirovecii pneumonia: a monocentric, retrospective, and observational study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The COVID-19 pandemic required rapid action to curb transmission and mitigate its lethiferous impact. Non-pharmaceutical interventions (NPIs) were globally adopted. We hypothesized that these measures reduced the transmission and acquisition of P. jirovecii in both hospital and community settings. METHODS: We conducted a retrospective observational study on 2950 respiratory specimens from patients with suspected pulmonary infection, analyzed at the Laboratory of Parasitology Unit of the Policlinico Tor Vergata of Rome, Italy, from January 2014 to December 2022. RESULTS: We show a significant reduction in the frequency of PCP in the COVID-19 pandemic era compared to the previous period. Among the four sequence types of P. jirovecii identified, genotype 1 was the most prevalent (37%). We observed a non-significant trend of decreasing cases with genotype 1 and increasing cases with genotype 3 over the study period. CONCLUSIONS: The nationwide implementation of NPIs against COVID-19 may have changed the microbiological landscape of exposure, thereby decreasing the exposure to P. jirovecii and consequently reducing the incidence of PCP.

Predictors of Early Thrombotic Events in Adult Patients with Acute Myeloid Leukemia: A Real-World Experience.

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count >50 × 109/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (≥2 points) versus 6.4% in the low-risk group (0−1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p < 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis.

Pneumocystis jirovecii pneumonia in patients with previously untreated acute myeloid leukaemia.

BACKGROUND: Several studies in immunocompromised patients, such as those with HIV infection, undergoing cancer chemotherapy or organ transplant, have led to the development of guidelines on the use of prophylaxis to prevent Pneumocystis jirovecii pneumonia (PJP), in these specific conditions. Instead, since the association between PJP and acute myeloid leukaemia (AML) is not clearly defined, the role of prophylaxis in patients with AML is not yet established. METHODS: We retrospectively analysed 251 consecutive patients with newly diagnosed non-M3-AML, admitted at the Hematology Unit of University Tor Vergata in Rome, during the period 2010-2020. The aim of the study was to evaluate the incidence of PJP among AML patients during their first hospital admission, and to identify subjects at a high risk to develop PJP. RESULTS: Among 251 consecutive patients with non-M3-AML, 67 bronchoalveolar lavages (BAL) were performed. PJP was proven in 11/67 (16.7%) subjects undergoing BAL (11 males, median age 71 years), with an incidence of 4.3%. The most common reason for BAL execution were radiological findings such as ground-glass opacities (6/11, 55%) and atypical patterns like consolidations and nodules (5/11, 45%). One patient died because of PJP after 11 days of trimethoprim/sulfamethoxazole therapy. In multivariate analysis older age and smoking habit were independent factors significantly associated with PJP (p = .021 and 0.017 respectively). CONCLUSION: We conclude that PJP infection is not uncommon among patients with AML. If intensive chemotherapy is planned, physicians should be aware of this risk and prophylaxis should be considered, particularly in older patients.

Impact of fellow participation on colon adenoma detection rates: a multicenter randomized trial.

BACKGROUND AND AIMS: There are limited and conflicting data on the impact of fellow participation in improving the colon adenoma detection rate. We performed a multicenter randomized controlled trial to evaluate whether fellow involvement might have a beneficial effect on adenoma detection rate. METHODS: The trial was conducted at 4 tertiary hospitals between April and December 2019. Eight hundred twelve patients were randomized to undergo colonoscopy performed by a fellow under the supervision of a staff endoscopist or by an attending physician alone. RESULTS: No significant differences in demographic or adenoma risk factors were detected between the 2 groups. The adenoma detection rate in the intervention group was 44.8% versus 37.1% in the control arm (P = .02). The mean number of adenomas per colonoscopy was significantly higher in the intervention group (0.65 ± 0.3 vs 0.53 ± 0.2 in the control arm, P < .001). The polyp detection rate was 69.7% in the intervention group and 62.5% in the control arm (P = .03), whereas rates of advanced and sessile/serrated adenoma detection were not different between the trial arms (P = .50 and .42, respectively). In the subgroup of more experienced fellows, the adenoma detection rate and polyp detection rate were 49.5% and 75.7%, respectively. No difference was observed between less-experienced fellows and attending physicians alone (P = .53 and 0.86, respectively). The level of bowel preparation and fellow involvement were significant predictors of increased adenoma detection rate in a multivariate analysis. CONCLUSIONS: Our multicenter trial represents the first prospective validation of the beneficial role of fellow involvement in colonoscopy procedures. (Clinical trial registration number: NCT03908229.).

Diagnostic yield of EUS-guided through-the-needle biopsy in pancreatic cysts: a meta-analysis.

BACKGROUND AND AIMS: There is currently limited evidence supporting the use of EUS-guided through-the-needle biopsy for sampling pancreatic cystic lesions. The aim of this meta-analysis was to provide a pooled estimate of the diagnostic performance of through-the-needle biopsy for sampling of pancreatic cysts. METHODS: A bibliographic search on the main databases was performed in September 2019. Pooled effects were calculated using a random-effects model by means of the DerSimonian and Laird test. The primary outcome was sample adequacy. Additional endpoints were diagnostic accuracy, optimal histologic core procurement, mean number of needle passes, pooled specificity, and sensitivity. Adverse event rates were also analyzed. RESULTS: Eleven studies enrolling 490 patients were included. Eight articles compared through-the-needle biopsy with cytology/cystic fluid analysis. Most patients were female, and the body/tail was the most frequent location of cystic lesions. Sample adequacy with through-the-needle biopsy was 85.3% (78.2%-92.5%), and subanalysis performed according to cyst morphology, size, and location confirmed the result. Through-the-needle biopsy clearly outperformed FNA both in terms of sample adequacy (odds ratio, 4.83; 95% confidence interval, 1.63-14.31; P =.004) and diagnostic accuracy (odds ratio, 3.44; 95% confidence interval, 1.32-8.96; P =.01). The pooled diagnostic accuracy rate, sensitivity, and specificity of through-the-needle biopsy were 78.8%, 82.2%, and 96.8%, respectively. A mean of 3.121 (2.98-3.25) passes through the cyst was needed to obtain adequate histologic samples. The incidence rates of mild bleeding and pancreatitis were 4% and 2%, respectively. CONCLUSION: Our meta-analysis speaks in favor of the use of through-the-needle biopsy as a safe and effective tool in EUS-guided tissue acquisition of pancreatic cysts.

Comparison between fine-needle biopsy and fine-needle aspiration for EUS-guided sampling of subepithelial lesions: a meta-analysis.

BACKGROUND AND AIMS: There is limited evidence on the diagnostic performance of EUS-guided fine-needle biopsy (FNB) sampling in patients with subepithelial lesions. The aim of this meta-analysis was to compare EUS-guided FNB sampling performance with FNA in patients with GI subepithelial lesions. METHODS: A computerized bibliographic search on the main databases was performed through May 2019. The primary endpoint was sample adequacy. Secondary outcomes were diagnostic accuracy, histologic core procurement rate, and mean number of needle passes. Summary estimates were expressed in terms of odds ratio (OR) and 95% confidence interval (CI). RESULTS: Ten studies (including 6 randomized trials) with 669 patients were included. Pooled rates of adequate samples for FNB sampling were 94.9% (range, 92.3%-97.5%) and for FNA 80.6% (range, 71.4%-89.7%; OR, 2.54; 95% CI, 1.29-5.01; P = .007). When rapid on-site evaluation was available, no significant difference between the 2 techniques was observed. Optimal histologic core procurement rate was 89.7% (range, 84.5%-94.9%) with FNB sampling and 65% (range, 55.5%-74.6%) with FNA (OR, 3.27; 95% CI, 2.03-5.27; P < .0001). Diagnostic accuracy was significantly superior in patients undergoing FNB sampling (OR, 4.10; 95% CI, 2.48-6.79; P < .0001) with the need of a lower number of passes (mean difference, -.75; 95% CI, -1.20 to -.30; P = .001). Sensitivity analysis confirmed these findings in all subgroups tested. Very few adverse events were observed and did not impact on patient outcomes. CONCLUSIONS: Our results speak clearly in favor of FNB sampling, which was found to outperform FNA in all diagnostic outcomes evaluated.

Cirrhosis Is a Predictor of Adverse Events in Endoscopic Ultrasound Fine-Needle Aspiration: A Propensity-Score Analysis.

BACKGROUND: Cirrhotic patients are at increased risk of adverse events (AEs) after invasive procedures. However, the safety profile of endoscopic ultrasound (EUS) fine-needle aspiration in cirrhotic patients is still unknown. OBJECTIVES: To examine the AEs rate after EUS fine-needle aspiration in cirrhotic patients as compared to a control group of noncirrhotic patients. METHODS: Out of 735 patients with suspected abdominal lesions referred to our center between 2006 and 2018, after propensity-score matching, 2 groups were compared: 95 cirrhotics and 95 controls. Primary variables included rate of overall and serious AEs. Secondary endpoint was incidence of acute-on-chronic liver failure. RESULTS: Median age was 64 years, and pancreatic lesions represented the sampled tissue in 57 patients (60%) in each group (p = 1.0) with mean size of 22 mm in both cohorts (p = 0.3). Overall, 20 AEs (21%) of which 9 serious (9.4%) were observed in cirrhotic patients and 3 (3.1%) mild events were experienced by noncirrhotic subjects. Only liver cirrhosis was confirmed as a significant predictor of AEs in multivariate analysis (OR 8.11, 2.34-28; p = 0.001). Overall rate of infections was 6/95 (6.3%), of which 4 were serious (4.2%) in cirrhotics and 1/95 (1%) in the control group (p = 0.05). All serious infections led to the occurrence of acute-on-chronic liver failure. Minor bleeding events were more frequent in cirrhotic patients (4.2 vs. 0%; p = 0.04). CONCLUSIONS: The rate of AEs after EUS fine-needle aspiration is higher in cirrhotic patients, and acute-on-chronic liver failure may represent a serious complication of this procedure.

Statins decrease the risk of acute pancreatitis after endoscopic ultrasound fine-needle aspiration of pancreatic cysts.

BACKGROUND: Basic and clinical studies suggest that statins may prevent and even ameliorate acute pancreatitis. The present study was to evaluate whether statin decreases the risk of acute pancreatitis in patients undergoing endoscopic ultrasound-guided fine-needle aspiration of pancreatic cysts. METHODS: Out of 456 patients with pancreatic cysts referred to our center between 2006 and 2018, 365 were finally included in analyses: 86 were treated with statins and 279 were not at the time of endoscopic ultrasound fine-needle aspiration. We compared the acute pancreatitis incidence between the two groups, and we also compared other complications such as bleeding and infections. RESULTS: Median age was 64 years [interquartile range (IQR) 62-69] and median cyst size was 24 mm (IQR, 21-29). The most frequent histology was intraductal papillary mucinous neoplasm (45.3% and 42.3% in the two groups, respectively; P = 0.98). All 13 patients experiencing post-endoscopic ultrasound acute pancreatitis were from the control group (4.7%), of which 3 were classified as severe pancreatitis. None of statin users developed post-procedural acute pancreatitis (odds ratio: 0.15; 95% confidence interval: 0.03-0.98; P = 0.03). No difference was registered with regard to severe pancreatitis and other complications. CONCLUSIONS: Statins exert a beneficial role in preventing acute pancreatitis in patients with pancreatic cysts undergoing endoscopic ultrasound-guided fine-needle aspiration. If confirmed in prospective trials, our findings may pave the way to an extensive use of statins as prophylactic agents in pancreatic interventional endoscopy.

Diagnostic yield of Franseen and Fork-Tip biopsy needles for endoscopic ultrasound-guided tissue acquisition: a meta-analysis.

Background and study aims Although newer needle designs are thought to improve diagnostic outcomes of endoscopic ultrasound-guided fine-needle biopsy, there is limited evidence on their diagnostic performance. The aim of this meta-analysis was to provide a pooled estimate of the diagnostic performance and safety profile of Franseen and Fork-tip fine-needle biopsy needles. Patients and methods Computerized bibliographic search on the main databases was performed through March 2019. The primary endpoint was sample adequacy. Secondary outcomes were diagnostic accuracy, optimal histological core procurement, mean number of needle passes, pooled specificity and sensitivity. Safety data were also analyzed. Results Twenty-four studies with 6641 patients were included and pancreas was the prevalent location of sampled lesions. Overall sample adequacy with the two newer needles was 94.8 % (93.1 % - 96.4 %), with superiority of Franseen needle over Fork-tip (96.1 % versus 92.4 %, P  < 0.001). Sample adequacy in targeting pancreatic masses was 95.6% and both needles produced results superior to fine-needle aspiration (FNA) (odds ratio 4.29, 1.49 - 12.35 and 1.79, 1.01 - 3.19 with Franseen and Fork-tip needle, respectively). The rate of histological core procurement was 92.5%, whereas diagnostic accuracy and sensitivity were 95 % and 92.8 %, again with no difference between the two needles. Number of needle passes was significantly lower in comparison to FNA (mean difference: -0.42 with Franseen and -1.60 with Fork-tip needle). No significant adverse events were registered. Conclusion Our meta-analysis speaks in favor of use of newer biopsy needles as a safe and effective tool in endoscopic ultrasound-guided tissue acquisition.

Response to repeat echoendoscopic celiac plexus neurolysis in pancreatic cancer patients: A machine learning approach.

BACKGROUND: /Objectives: Efficacy of repeat echoendoscopic celiac plexus neurolysis is still unclear. Aim of the study was to assess the efficacy of repeat celiac plexus neurolysis and to build an artificial neural network model able to predict pain response. METHODS: Data regarding 156 patients treated with repeat celiac plexus neurolysis between 2004 and 2019 were reviewed. Artificial neural network and logistic regression models were built to predict pain response after treatment. Performance of the models was expressed in terms of accuracy, positive predictive value, and positive likelihood ratio. RESULTS: Median age was 62 years (range 39-86) and most patients were male (66%) with pre-procedural visual analogue score 7. Fifty-one patients (32.6%) experienced treatment response, of which 6 (3.8%) complete pain suppression. Median duration of pain relief was 6 (2-8) weeks. Tumoral stage, interval from initial to repeat treatment, response to initial neurolysis, and tumor progression between the two treatments resulted as significant predictors of pain response. The performance of the artificial neural network in predicting treatment response was higher than regression model (area under the curve: 0.94, 0.89-0.97 versus 0.85, 0.78-0.89; p < 0.001). Positive predictive value and positive likelihood ratio resulted 90.3% and 19.35, respectively. Classification error rate was 5.7% with the artificial neural network compared to 14.7% of regression model (p < 0.001). These findings were confirmed through ten-fold cross validation. CONCLUSIONS: Pain response following repeat neurolysis is generally less pronounced than after initial treatment. Artificial neural network may help to identify those subjects likely to benefit from repeat neurolysis.

Long-term liver stiffness assessment in hepatitis C virus patients undergoing antiviral therapy: Results from a 5-year cohort study.

BACKGROUND AND AIM: Observational studies showed significant liver stiffness regression after sustained virological response, but long-term effects of antiviral therapy are still unknown. The aim of this study was to assess the magnitude of change in stiffness up to 5 years after therapy in hepatitis C patients undergoing antiviral treatment. METHODS: Data of 153 patients were retrieved. Stiffness was assessed by Fibroscan at baseline, end of treatment, 6 months after treatment, and every year hereafter up to 5 years. RESULTS: Seventy patients were treated with interferon-based regimens and 83 with direct antiviral agents. Baseline cirrhosis was diagnosed in 53 (34.6%) patients. Sustained virological response was achieved in 112 patients, whereas 41 were non-responders. In responders, stiffness decreased from 12.3 kPa (9-17.8) to 6.6 kPa (5.3-7.4) at 5 years. A sharper decline was observed immediately after treatment (-2.5 kPa at the end of treatment and -3.7 kPa at 6 months), while from 1 year onwards, the magnitude of stiffness decrease was progressively lower. In non-responders, stiffness showed a slight decrease at the end of treatment (from 19.2 to 18.1 kPa), then returned to baseline levels at 6 months (19.4 kPa), and finally increased over time up to 23.7 kPa (15-32.5) at 5 years. The proportion of cirrhotic patients decreased by 50% at 6 months and finally fell < 5% at 4 years after treatment. CONCLUSIONS: Stiffness declines significantly after achieving response, and the magnitude of decline is greater in the first year after treatment, while it tends to plateau from 1 year onwards.

Comparative Efficacy of Colonoscope Distal Attachment Devices in Increasing Rates of Adenoma Detection: A Network Meta-analysis.

BACKGROUND & AIMS: Several add-on devices have been developed to increase rates of colon adenoma detection (ADR). We assessed their overall and comparative efficacy, and estimated absolute magnitude of benefit through a network meta-analysis. METHODS: We searched the PubMed/Medline and Embase database through March 2017 and identified 25 randomized controlled trials (comprising 16,103 patients) that compared the efficacy of add-on devices (cap; Endocuff; Arc Medical Design Ltd, Leeds, UK, and Endorings; Us Endoscopy, Mentor, OH) with each other or with standard colonoscopy. The primary outcome was ADR; secondary outcomes included rate of polyp detection, and rate of and time to cecal intubation. We performed pairwise and network meta-analyses, and appraised quality of evidence using Grading of Recommendations Assessment, Development and Evaluation. We estimated the magnitude of increase in ADR by low-performing endoscopists (baseline ADR, 10%) and high-performing endoscopists (baseline ADR, 40%) with use of these devices. RESULTS: Overall, distal attachment devices increased ADR compared with standard colonoscopy (relative risk [RR], 1.13; 95% CI, 1.03-1.23; low-quality evidence), with potential absolute increases in ADR to 11.3% for low-performing endoscopists and to 45.2% for high-performing endoscopists. In a comparative evaluation, we found low-quality evidence that Endocuff increases ADR compared with standard colonoscopy (RR, 1.21; 95% CI, 1.03-1.41), with anticipated increases in ADR to 12% for low-performing endoscopists and to 48% for high-performing endoscopists. We found very low quality evidence to support the use of Endorings (RR, 1.70; 95% CI, 0.86-3.36) or caps (RR, 1.07; 95% CI, 0.96-1.19) vs standard colonoscopy for increasing ADR. The benefit of one distal attachment device over another was uncertain due to very low quality evidence. CONCLUSIONS: Based on network meta-analysis, we anticipate only modest improvement in ADRs with use of distal attachment devices, especially in low-performing endoscopists.

Full-spectrum versus standard colonoscopy for improving polyp detection rate: A systematic review and meta-analysis.

BACKGROUND AND AIM: Full-spectrum endoscopy represents a new endoscopic platform allowing a panoramic 330 degree view of the colon, but evidence of its superiority over standard colonoscopy is still lacking. Our study is the first meta-analysis comparing the efficacy of full-spectrum endoscopy with standard colonoscopy. METHODS: Through a systematic literature review until May 2017, we identified eight randomized-controlled trials. Primary outcomes were polyp detection rate and adenoma detection rate, while cecal intubation time and total colonoscopy time were secondary outcomes. Direct meta-analysis was performed using a random effects model. RESULTS: No difference in terms of polyp detection rate and adenoma detection rate was found (risk ratio: 1.00, 95% confidence interval 0.89-1.12, P = 0.96, and 1.05, 0.94-1.17, P = 0.40, respectively). Adenoma miss rate resulted significantly in favor of full-spectrum endoscopy (risk ratio: 0.35, 0.25-0.48, P < 0.01), although the difference was not significant for greater (>5 mm) and pedunculated lesions (risk ratio: 0.38, 0.09-1.60, P = 0.19, and risk ratio: 0.15, 0.01-3.00, P = 0.21, respectively). Cecal intubation time was not different between the two techniques (mean standardized difference: 0.22 min, -1.18 to 1.62, P = 0.76), while total colonoscopy time was significantly shorter when adopting full-spectrum endoscopy (mean difference: -2.60, -4.60 to -0.61, P = 0.01). Sensitivity analysis confirmed all the findings. CONCLUSIONS: Full-spectrum endoscopy appears as a promising and reliable technology able to significantly decrease the number of adenomas missed and procedural times, while its superiority over standard colonoscopy in terms of adenoma detection rate results is still unclear.

Lymphocyte-to-monocyte ratio predicts survival after radiofrequency ablation for colorectal liver metastases.

AIM: To test the correlation between lymphocyte-to-monocyte ratio (LMR) and survival after radiofrequency ablation (RFA) for colorectal liver metastasis (CLMs). METHODS: From July 2003 to Feb 2012, 127 consecutive patients with 193 histologically-proven unresectable CLMs were treated with percutaneous RFA at the University of Foggia. All patients had undergone primary colorectal tumor resection before RFA and received systemic chemotherapy. LMR was calculated by dividing lymphocyte count by monocyte count assessed at baseline. Treatment-related toxicity was defined as any adverse events occurred within 4 wk after the procedure. Overall survival (OS) and time to recurrence (TTR) were estimated from the date of RFA by Kaplan-Meier with plots and median (95%CI). The inferential analysis for time to event data was conducted using the Cox univariate and multivariate regression model to estimate hazard ratios (HR) and 95%CI. Statistically significant variables from the univariate Cox analysis were considered for the multivariate models. RESULTS: Median age was 66 years (range 38-88) and patients were prevalently male (69.2%). Median LMR was 4.38% (0.79-88) whereas median number of nodules was 2 (1-3) with a median maximum diameter of 27 mm (10-45). Median OS was 38 mo (34-53) and survival rate (SR) was 89.4%, 40.4% and 33.3% at 1, 4 and 5 years respectively in the whole cohort. Running log-rank test analysis found 3.96% as the most significant prognostic cut-off point for LMR and stratifying the study population by this LMR value median OS resulted 55 mo (37-69) in patients with LMR > 3.96% and 34 (26-39) mo in patients with LMR ≤ 3.96% (HR = 0.53, 0.34-0.85, P = 0.007). Nodule size and LMR were the only significant predictors for OS in multivariate analysis. Median TTR was 29 mo (22-35) with a recurrence-free survival (RFS) rate of 72.6%, 32.1% and 21.8% at 1, 4 and 5 years, respectively in the whole study group. Nodule size and LMR were confirmed as significant prognostic factors for TTR in multivariate Cox regression. TTR, when stratified by LMR, was 35 mo (28-57) in the group > 3.96% and 25 mo (18-30) in the group ≤ 3.96% (P = 0.02). CONCLUSION: Our study provides support for the use of LMR as a novel predictor of outcome for CLM patients.

Prognostic role of 25-hydroxyvitamin D in patients with liver metastases from colorectal cancer treated with radiofrequency ablation.

BACKGROUND AND AIM: Vitamin D is implicated in the etiology of several neoplastic diseases, but its relationship with colorectal cancer survival is still unclear. Aim of this study was to determine whether vitamin D levels influence survival outcomes in colorectal cancer liver metastases patients treated with percutaneous radiofrequency ablation. METHODS: We measured 25-hydroxyvitamin D levels in 143 patients with 215 colorectal liver metastases who underwent radiofrequency ablation between 1999 and 2011 at our institution. The influence of 25-hydroxyvitamin D levels on overall survival and time to recurrence was evaluated in univariate and multivariate Cox analyses. RESULTS: Median age was 68 years (range 41-85), and median number of nodules was 2 (1-3) with a median maximum diameter of 26 mm (10-48). Median survival was 44 months (36-62), and survival rate was 91.4%, 46.5%, and 42.2% at 1, 4, and 5 years in the whole cohort. Median survival was 65 months (52-74) if 25-hydroxyvitamin D >20 ng/mL and 34 months (24-41) if ≤20 ng/mL (P < 0.001). In the whole cohort, median time to recurrence was 34 months (26-47), 50 months (36-62) in the case of 25-hydroxyvitamin D >20 ng/mL and 24 months (20-32) if ≤20 ng/mL (P < 0.001). Nodule size and 25-hydroxyvitamin D resulted as significant predictors of both overall survival and time to recurrence in multivariate analysis. CONCLUSIONS: Our study provides support for the use of 25-hydroxyvitamin D as a new predictor of outcome for colorectal liver metastases patients.

Angiotensin receptor blockers improve survival outcomes after radiofrequency ablation in hepatocarcinoma patients.

BACKGROUND AND AIM: Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. The aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. METHODS: Data on 153 patients were reviewed. The study population was classified into three groups: 73 (47.8%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 49 (32%) patients treated with angiotensin-converting enzyme inhibitors (group 2), and 31 (20.2%) patients treated with sartans (group 3). Survival outcomes were analysed by means of Kaplan-Meier analysis and compared with log-rank test. RESULTS: In the whole study population, 85.6% of patients were in Child-Pugh A class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10-40) and alpha fetoprotein was 25 (1.1-2100) UI/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (95% confidence interval: 31-58) in group 1, 72 months (49-89) in group 2, and 84 months (58-92) in group 3 (P = 0.02). Median time to recurrence was 26 (15-42), 44 (33-72), and 69 (44-74) months in the three groups, respectively (P = 0.02). Sartan therapy was a significant predictor of longer overall survival and delayed time to recurrence on multivariate analysis. CONCLUSION: Sartans significantly improved overall survival and time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients.

Medical Systemic Therapies for Hepatocellular Carcinoma: Clinical Perspectives and Safety Profile.

A multidisciplinary approach based on clinical expertise and knowledge of molecular processes involved in hepatocarcinogenesis is needed for the proper management of hepatocellular carcinoma (HCC) patients. Such information must be considered in the context of pathobiology of the underlying liver disease. New drugs targeting specific molecular steps in pathways involved in HCC growth and development bear the promise to radically modify the pharmacological therapies currently in use in hepatooncology. Sorafenib was the first drug approved in the setting of advanced HCC, but although it produces some improvement in survival, the responses are not durable. In addition, there are significant side effects. Other angiogenesis inhibitors are in development to treat HCC both in the first-line setting and after progression following sorafenib failure; among them, tivantinib, an inhibitor of cMET receptor, showed interesting results in a recent phase-II study. Additional agents currently studied for the treatment of HCC patients are briefly examined in this review. Aim of this paper is to discuss the state of the art in the management of advanced HCC patients, with a particular interest for the description of their side effects.

Polidocanol injection decreases the bleeding rate after colon polypectomy: a propensity score analysis.

BACKGROUND: EMR is the standard of care for the resection of large polyps. OBJECTIVE: To compare the efficacy and safety profile of submucosal polidocanol injection with epinephrine-saline solution injection for colon polypectomy with a diathermic snare. DESIGN: After 1-to-1 propensity score caliper matching, comparison of submucosal epinephrine injection was performed with polidocanol injection. SETTING: Endoscopic suite at the University of Foggia between 2005 and 2014. PATIENTS: Of 711 patients who underwent endoscopic resection of colon sessile polyps 20 mm or larger, 612 were analyzed after matching. INTERVENTIONS: Submucosal epinephrine injection in 306 patients and polidocanol injection in 306 patients. MAIN OUTCOME MEASUREMENTS: Univariate and multivariate logistic regression models aimed at identifying independent predictors of postpolypectomy bleeding (PPB). RESULTS: The 2 groups presented similar baseline clinical parameters and lesion characteristics. All patients had a single polyp 20 mm or larger; the median size was 32 mm (interquartile range [IQR], 25-38) in the polidocanol group and 32 (IQR, 24-38) in the epinephrine group (P=.7). Polidocanol was more effective in preventing both immediate and delayed PPB (P<.001 and P=.003, respectively), and its efficacy was confirmed in almost all of the subgroups, regardless of polyp size and histology. Postprocedure perforation was observed in 2 patients (0.3%), both in the epinephrine group (P=.49). The 2 groups did not differ in the number of snare resections of lesions or the procedure duration (P=.24 and .6, respectively). LIMITATIONS: Absence of randomization. CONCLUSION: The submucosal injection of polidocanol for colon EMR is effective and significantly lowers the PPB rate.

Antifungal susceptibility profiles of bloodstream yeast isolates by Sensititre YeastOne over nine years at a large Italian teaching hospital.

Sensititre YeastOne (SYO) is an affordable alternative to the Clinical and Laboratory Standards Institute (CLSI) reference method for antifungal susceptibility testing. In this study, the MICs of yeast isolates from 1,214 bloodstream infection episodes, generated by SYO during hospital laboratory activity (January 2005 to December 2013), were reanalyzed using current CLSI clinical breakpoints/epidemiological cutoff values to assign susceptibility (or the wild-type [WT] phenotype) to systemic antifungal agents. Excluding Candida albicans (57.4% of all isolates [n = 1,250]), the most predominant species were Candida parapsilosis complex (20.9%), Candida tropicalis (8.2%), Candida glabrata (6.4%), Candida guilliermondii (1.6%), and Candida krusei (1.3%). Among the non-Candida species (1.9%), 7 were Cryptococcus neoformans and 17 were other species, mainly Rhodotorula species. Over 97% of Candida isolates were susceptible (WT phenotype) to amphotericin B and flucytosine. Rates of susceptibility (WT phenotype) to fluconazole, itraconazole, and voriconazole were 98.7% in C. albicans, 92.3% in the C. parapsilosis complex, 96.1% in C. tropicalis, 92.5% in C. glabrata, 100% in C. guilliermondii, and 100% (excluding fluconazole) in C. krusei. The fluconazole-resistant isolates consisted of 6 C. parapsilosis complex isolates, 3 C. glabrata isolates, 2 C. albicans isolates, 2 C. tropicalis isolates, and 1 Candida lusitaniae isolate. Of the non-Candida isolates, 2 C. neoformans isolates had the non-WT phenotype for susceptibility to fluconazole, whereas Rhodotorula isolates had elevated azole MICs. Overall, 99.7% to 99.8% of Candida isolates were susceptible (WT phenotype) to echinocandins, but 3 isolates were nonsusceptible (either intermediate or resistant) to caspofungin (C. albicans, C. guilliermondii, and C. krusei), anidulafungin (C. albicans and C. guilliermondii), and micafungin (C. albicans). However, when the intrinsically resistant non-Candida isolates were included, the rate of echinocandin nonsusceptibility reached 1.8%. In summary, the SYO method proved to be able to detect yeast species showing antifungal resistance or reduced susceptibility.

Conditional survival analysis of hepatocellular carcinoma patients treated with radiofrequency ablation.

AIM: Survival estimates are commonly reported as survival from the first observation, but future survival probability changes based on the survival time already accumulated after therapy, otherwise known as conditional survival (CS). The aim of the study was to describe CS according to different prognostic variables in hepatocellular carcinoma (HCC) patients treated with radiofrequency ablation (RFA). METHODS: Data on 125 very early/early HCC patients treated with RFA between 1999 and 2007 were analyzed. Actuarial survival estimates were computed by means of Kaplan-Meier method and compared by log-rank test. The 5-year CS was calculated with stratification by several predictors for patients who had already survived up to 5 years from diagnosis. RESULTS: Median overall survival (OS) was 72 months (95% confidence interval [CI], 58-86). Age, Child-Pugh (CP), α-fetoprotein (AFP), Cancer of the Liver Italian Program (CLIP) score and type of recurrence (early vs late) were significant predictors of OS. The 5-year CS rates of the entire study cohort assessed at 1, 2, 3 and 5 years from the treatment were 49%, 48%, 30% and 34%, respectively. Subgroup analysis confirmed age and CP as significant predictors of CS at all time points, while the CS of subgroups stratified by AFP and CLIP did not differ significantly from the 3rd year after RFA onward, as more advanced patients had probably escaped early recurrence. CONCLUSION: CS analysis showed that the impact of different variables influencing OS is not linear over time after RFA. Information derived from the study can improve the current management of HCC patients.