Quality assessment of studies comparing percutaneous ablative treatments in hepatocellular carcinoma.

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Transarterial chemoembolization: Evidences from the literature and applications in hepatocellular carcinoma patients

Transarterial chemoembolization (TACE) is the current standard of care for patients with large or multinodular hepatocellular carcinoma (HCC), preserved liver function, absence of cancer-related symptoms and no evidence of vascular invasion or extrahepatic spread (i. e., those classified as intermediate stage according to the Barcelona Clinic Liver Cancer staging system). The rationale for TACE is that the intra-arterial injection of a chemotherapeutic drug such as doxorubicin or cisplatin followed by embolization of the blood vessel will result in a strong cytotoxic effect enhanced by ischemia. However, TACE is a very heterogeneous operative technique and varies in terms of chemotherapeutic agents, treatment devices and schedule. In order to overcome the major drawbacks of conventional TACE (cTACE), non-resorbable drug-eluting beads (DEBs) loaded with cytotoxic drugs have been developed. DEBs are able to slowly release the drug upon injection and increase the intensity and duration of ischemia while enhancing the drug delivery to the tumor. Unfortunately, despite the theoretical advantages of this new device and the promising results of the pivotal studies, definitive data in favor of its superiority over cTACE are still lacking. The recommendation for TACE as the standard- of- care for intermediate-stage HCC is based on the demonstration of improved survival compared with best supportive care or suboptimal therapies in a meta- analysis of six randomized controlled trials, but other therapeutic options (namely, surgery and radioembolization) proved competitive in selected subsets of intermediate HCC patients. Other potential fields of application of TACE in hepato-oncology are the pre-transplant setting (as downstaging/bridging treatment) and the early stage (in patients unsuitable to curative therapy). The potential of TACE in selected advanced patients with segmental portal vein thrombosis and preserved liver function deserves further reports

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity

Transarterial radioembolization vs chemoembolization for hepatocarcinoma patients: A systematic review and meta-analysis

To compare the efficacy and safety of yttrium-90 radioembolization (Y90RE) and transarterial chemoembolization (TACE) in hepatocellular carcinoma patients

Local ablative treatments for hepatocellular carcinoma: An updated review

Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are effective as bridging/downstaging therapies before orthotopic liver transplantation. Contraindications based on size, number, and location of nodules are quite variable in literature and strictly dependent on local expertise. Among ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety. Although survival outcomes are similar to percutaneous ethanol injection, the lower local recurrence rate stands for a wider application of RFA in hepato-oncology. Moreover, RFA seems to be even more cost-effective than liver resection for very early HCC (single nodule ≤ 2 cm) and in the presence of two or three nodules ≤ 3 cm. There is increasing evidence that combining RFA to transarterial chemoembolization may increase the therapeutic benefit in larger HCCs without increasing the major complication rate, but more robust prospective data is still needed to validate these pivotal findings. Among other thermal treatments, microwave ablation (MWA) uses high frequency electromagnetic energy to induce tissue death via coagulation necrosis. In comparison to RFA, MWA has several theoretical advantages such as a broader zone of active heating, higher temperatures within the targeted area in a shorter treatment time and the lack of heat-sink effect. The safety concerns raised on the risks of this procedure, due to the broader and less predictable necrosis areas, have been recently overcome. However, whether MWA ability to generate a larger ablation zone will translate into a survival gain remains unknown. Other treatments, such as high-intensity focused ultrasound ablation, laser ablation, and cryoablation, are less investigated but showed promising results in early HCC patients and could be a valuable therapeutic option in the next future

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

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

Echoendoscopic ethanol ablation of tumor combined to celiac plexus neurolysis improved pain control in a patient with pancreatic adenocarcinoma

A 75-year-old man suffering from opioid-refractory due to an advanced pancreatic adenocarcinoma was treated with endoscopic ultrasound (EUS)-guided celiac plexus neurolysis (CPN) combined to EUS-guided tumor ablation. No major complications were recorded during the procedure. In the days following the procedure, mild diarrhea and fever were the only minor complications experienced by the patient. Complete tumor devascularization was assessed by means of computed tomography (CT) 48 h after the procedure. The patient remained pain-free without need of opioid, and was treated only with paracetamol for 20 weeks. Our results were optimal in terms of pain relief and immediate tumor response (assessed by means of CT and tumor marker levels). The present case demonstrates that the combined approach (EUS-guided ethanol ablation and CPN) may be a valuable option in patients with pancreatic cancer. Randomized-controlled trials are needed to confirm this result

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

AIM: To test the correlation between lymphocyte-tomonocyte 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