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.

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.

Antibiotics Do Not Decrease the Rate of Infection After Endoscopic Ultrasound Fine-Needle Aspiration of Pancreatic Cysts.

BACKGROUND: In spite of the weak evidence, antibiotic prophylaxis prior to endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions is routinely used in the clinical practice. AIMS: To compare a group of patients treated with antibiotics before fine-needle aspiration of pancreatic cystic lesions and a group who did not undergo antimicrobial prophylaxis. METHODS: Out of 335 patients with suspected pancreatic cystic lesions referred to our center between 2006 and 2018, after propensity score matching two groups were compared: 135 subjects who underwent endoscopic ultrasound fine-needle aspiration under antibiotic prophylaxis and 135 treated with no antimicrobial agents. Primary outcome was infection rate; secondary endpoints included other complications or antibiotic-related adverse events. RESULTS: Median age was 64 (interquartile range 61-68) and median cyst size was 24 mm (22-28), with no difference between groups. Overall, 10 adverse events (7.1%) of which 2 serious (1.4%) were observed in the antibiotic group and 8 (5.8%) of which 1 (0.7%) serious in the non-antibiotic group. Cyst infection was observed in 2 patients (1.4%) in the antibiotic group and 3 patients (2.2%) in the other cohort (p = 0.65). CONCLUSIONS: Prophylactic antibiotics do not seem to substantially reduce this risk of infection, and their routine use should be abandoned.

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.

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.

Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation.

BACKGROUND AND AIM: Hepatic iron accumulation is considered to be a cofactor that influences liver injury and hepatocarcinogenesis. Aim of this study is to determine whether serum ferritin (SF) levels relate to overall survival (OS) and time to recurrence (TTR) in hepatocellular carcinoma (HCC) patients treated with percutaneous radiofrequency ablation (RFA). METHODS: We measured SF levels in 103 HCC patients (median age 70, M/F = 82.5%/17.5%) who underwent RFA between 2005 and 2010. Correlation between SF and other prognostic factors at baseline was analyzed. SF levels were entered into a Cox model and their influence on OS and TTR was evaluated in univariate and multivariate analyses. RESULTS: SF did not correlate with α-fetoprotein (rho: -0.12, P = 0.22), neutrophil/lymphocyte ratio (rho: -0.1020, P = 0.30), Model for End-Stage Liver Disease (rho: 0.18, P = 0.06), Child-Pugh score (P = 0.5), or Barcelona Cancer of the Liver Clinic stage (P = 0.16). A log-rank test found the value of 244 ng/mL as the optimal prognostic cut-off point for SF. Median OS was 62 months (54-78) and survival rate was 97%, 65%, and 52% at 1, 4, and 5 years, respectively. Performance status and SF were the only predictors of OS at multivariate analysis. Median TTR was 38 months (34-49) with a recurrence-free survival rate of 82.5%, 26.2%, and 23.3% at 1, 4, and 5 years, respectively, while SF and age were the only predictors of TTR. CONCLUSIONS: SF level, possibly reflecting the degree of hepatic inflammation and fibrosis, is a negative risk factor for survival and recurrence after percutaneous RFA in HCC patients.

TRANS-TACE: Prognostic Role of the Transient Hypertransaminasemia after Conventional Chemoembolization for Hepatocellular Carcinoma.

The aim of the present study was to correlate laboratory data and postprocedural parameters after conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) with the radiological response. The study consisted of a retrospective analysis of prospectively collected data from 70 consecutive patients who underwent cTACE. Laboratory parameters were assessed daily after cTACE and compared to pretreatment values. Post-treatment radiological response was assessed using mRECIST at one month from cTACE, and factors associated with treatment response (complete and objective response) were assessed by logistic regression analysis. The optimal cutoff points in predicting the complete response of target lesions were a 52% ALT and a 46% AST increase after cTACE compared to the pre-treatment values. Using multivariate analyses, >46% AST and >52% ALT increases with respect to the pre-treatment value were significantly correlated with the objective response (p = 0.03 and p = 0.04, respectively) and the complete response (p = 0.02 and p = 0.02, respectively). No patients experienced liver function deterioration after cTACE, and no specific treatment was required. This study showed that post-treatment transient transaminase elevation was predictive of objective response to superselective cTACE in clinical practice, representing a simple tool to guide treatment strategy of HCC patients in a tailored approach.

Sarcopenia represents a negative prognostic factor in pancreatic cancer patients undergoing EUS celiac plexus neurolysis.

BACKGROUND AND OBJECTIVES: Increasing evidence suggests a prognostic role of sarcopenia in pancreatic cancer patients. The aim of this study was to assess the influence of sarcopenia on treatment outcomes after EUS-guided celiac plexus neurolysis (CPN). MATERIALS AND METHODS: Data regarding 215 patients treated with EUS CPN between 2004 and 2019 were reviewed. Determination of body composition was conducted on contrast-enhanced CT scan, and pain response was considered as the primary outcome. Univariate and multivariate logistic regression was performed to identify the independent predictors of pain response. RESULTS: Treatment was successful in 187 patients (86.9%). The median age was 62 (range 39-84) years, and most patients were male (61.8%). Of the whole study population, 139 patients (64.6%) were defined as sarcopenic, of which 116 (83.4%) responded to the treatment and 5 (3.5%) experienced a complete response. Among 76 nonsarcopenic participants, 71 (93.4%) responded to the treatment and 22 (28.9%) obtained a complete response (P = 0.03 and <0.001, respectively). The median duration of pain relief was 8 (2-10) and 15 (8-16) weeks in sarcopenic and nonsarcopenic patients, respectively (P = 0.01). The median overall survival after neurolysis was 4 months (3-5) in sarcopenic participants and 7 months (6-8) in nonsarcopenic participants (P = 0.05). Tumoral stage, interval from the diagnosis to treatment, and sarcopenia resulted as significant prognostic factors for treatment response both in univariate and multivariate regression analyses. No severe treatment-related adverse events were reported in the whole study population, with no difference between the two groups. CONCLUSIONS: Sarcopenia represents a predictor of poorer response to EUS CPN.

Primary and secondary prophylaxis of spontaneous bacterial peritonitis: current state of the art.

Introduction: Spontaneous bacterial peritonitis represents a frequent and severe complication in cirrhotic patients with ascites. In daily practice, the diagnosis of spontaneous bacterial peritonitis might be challenging in the absence of the typical signs and symptoms of infection such as fever or leukocytosis. Areas covered: Aim of this review is to revise the current state of the art on primary and secondary spontaneous bacterial peritonitis. Literature search in Medline/Pubmed was performed. Expert opinion: Historically, gram-negative bacteria were the most frequent etiologic agents of spontaneous bacterial peritonitis, with Escherichia coli and Klebsiella spp. being the most frequently isolated bacteria. However, major changes in this regard occurred over the last few decades with an increasing prevalence of gram-positive, quinolone-resistant, and multidrug-resistant bacteria. In particular, the increasing prevalence of quinolone-resistant bacteria challenged the prominent role of norfloxacin in spontaneous bacterial peritonitis prevention. Given the high mortality rate and the risk of developing the hepatorenal syndrome, prophylaxis of spontaneous bacterial peritonitis is indicated in three high-risk populations: patients with acute gastrointestinal hemorrhage, patients with low total protein content in ascitic fluid and advanced cirrhosis, and patients with a previous history of spontaneous bacterial peritonitis (secondary prophylaxis).

Non-polypoid colorectal neoplasms: Classification, therapy and follow-up.

In the last years, an increasing interest has been raised on non-polypoid colorectal tumors (NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally, called laterally spreading tumors (LST). LSTs and large sessile polyps have a greater frequency of high-grade dysplasia and local invasiveness as compared to pedunculated lesions of the same size and usually represent a technical challenge for the endoscopist in terms of either diagnosis and resection. According to the Paris classification, NPTs are distinguished in slightly elevated (0-IIa, less than 2.5 mm), flat (0-IIb) or slightly depressed (0-IIc). NPTs are usually flat or slightly elevated and tend to spread laterally while in case of depressed lesions, cell proliferation growth progresses in depth in the colonic wall, thus leading to an increased risk of submucosal invasion (SMI) even for smaller neoplasms. NPTs may be frequently missed by inexperienced endoscopists, thus a careful training and precise assessment of all suspected mucosal areas should be performed. Chromoendoscopy or, if possible, narrow-band imaging technique should be considered for the estimation of SMI risk of NPTs, and the characterization of pit pattern and vascular pattern may be useful to predict the risk of SMI and, therefore, to guide the therapeutic decision. Lesions suitable to endoscopic resection are those confined to the mucosa (or superficial layer of submucosa in selected cases) whereas deeper invasion makes endoscopic therapy infeasible. Endoscopic mucosal resection (EMR, piecemeal for LSTs > 20 mm, en bloc for smaller neoplasms) remains the first-line therapy for NPTs, whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory and cannot be achieved by means of EMR. After piecemeal EMR, follow-up colonoscopy should be performed at 3 mo to assess resection completeness. In case of en bloc resection, surveillance colonoscopy should be scheduled at 3 years for adenomatous lesions ≥ 1 cm, or in presence of villous features or high-grade dysplasia patients (regardless of the size), while less intensive surveillance (colonoscopy at 5-10 years) is needed in case of single (or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at histology.

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.

Endoscopic submucosal dissection vs endoscopic mucosal resection for early gastric cancer: A meta-analysis.

AIM: To compare endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for early gastric cancer (EGC). METHODS: Computerized bibliographic search was performed on PubMed/Medline, Embase, Google Scholar and Cochrane library databases. Quality of each included study was assessed according to current Cochrane guidelines. Primary endpoints were en bloc resection rate and histologically complete resection rate. Secondary endpoints were length of procedure, post-treatment bleeding, post-procedural perforation and recurrence rate. Comparisons between the two treatment groups across all the included studies were performed by using Mantel-Haenszel test for fixed-effects models (in case of low heterogeneity) or DerSimonian and Laird test for random-effects models (in case of high heterogeneity). RESULTS: Ten retrospective studies (8 full text and 2 abstracts) were included in the meta-analysis. Overall data on 4328 lesions, 1916 in the ESD and 2412 in the EMR group were pooled and analyzed. The mean operation time was longer for ESD than for EMR (standardized mean difference 1.73, 95%CI: 0.52-2.95, P = 0.005) and the "en bloc" and histological complete resection rates were significantly higher in the ESD group [OR = 9.69 (95%CI: 7.74-12.13), P < 0.001 and OR = 5.66, (95%CI: 2.92-10.96), P < 0.001, respectively]. As a consequence of its greater radicality, ESD provided lower recurrence rate [OR = 0.09, (95%CI: 0.05-0.17), P < 0.001]. Among complications, perforation rate was significantly higher after ESD [OR = 4.67, (95%CI, 2.77-7.87), P < 0.001] whereas the bleeding incidences did not differ between the two techniques [OR = 1.49 (0.6-3.71), P = 0.39]. CONCLUSION: In the endoscopic therapy of EGC, ESD showed a superior efficacy but higher complication rate with respect to EMR.

Are hematopoietic stem cells involved in hepatocarcinogenesis?

THE LIVER HAS THREE CELL LINEAGES ABLE TO PROLIFERATE AFTER A HEPATIC INJURY: the mature hepatocyte, the ductular "bipolar" progenitor cell termed "oval cell" and the putative periductular stem cell. Hepatocytes can only produce other hepatocytes whereas ductular progenitor cells are considerate bipolar since they can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential and may be multipotent, being this aspect still under investigation. They originate in the bone marrow since their progeny express genetic markers of donor hematopoietic cells after bone marrow transplantation. Since the liver is the hematopoietic organ of the fetus, it is possible that hematopoietic stem cells may reside in the liver of the adult. This assumption is proved by the finding that oval cells express hematopoietic markers like CD34, CD45, CD 109, Thy-1, c-kit, and others, which are also expressed by bone marrow-derived hematopoietic stem cells (BMSCs). Few and discordant studies have evaluated the role of BMSC in hepatocarcinogenesis so far and further studies in vitro and in vivo are warranted in order to definitively clarify such an issue.

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis.

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.

Post-recurrence survival in hepatocellular carcinoma after percutaneous radiofrequency ablation.

BACKGROUND: Overall survival in hepatocellular carcinoma patients treated with percutaneous radiofrequency ablation is influenced by both recurrence and successive treatments. We investigated post-recurrence survival after radiofrequency ablation. METHODS: Data on 103 early/intermediate patients initially treated with radiofrequency ablation and followed for a median of 78 months (range 68-82) were retrospectively analysed. If intrahepatic disease recurrence occurred within or contiguous to the previously treated area it was defined as local, otherwise as distant; recurrence classified as Barcelona Clinic Liver Cancer stage C was defined by neoplastic portal vein thrombosis or metastases. RESULTS: A total of 103 patients were included (82.5% male; median age 70 years, range 39-86). During follow-up, 64 recurrences were observed. Median overall survival was 62 months (95% confidence interval: 54-78) and survival rates were 97%, 65% and 52% at 1, 4 and 5 years, respectively. Median post-recurrence survival was 22 months (95% confidence interval: 16-35). Child-Pugh score, performance status, sum of tumour diameters at recurrence and recurrence patterns were independent predictors of post-recurrence survival. CONCLUSIONS: In patients with hepatocellular carcinoma after radiofrequency ablation, clinical and tumour parameters assessed at relapse, in particular the type of recurrence pattern, influence post-recurrence survival.