Hepatocellular carcinoma risk in hepatitis C stage-3 fibrosis after sustained virological response with direct-acting antivirals.

BACKGROUND & AIMS: Patients with chronic hepatitis C and stage 3 fibrosis are thought to remain at risk of hepatocellular carcinoma after sustained virological response. We investigated this risk in a large cohort of patients with well-defined stage 3 fibrosis. METHODS: We performed a multicentre, ambispective, observational study of chronic hepatitis C patients with sustained virological response after treatment with direct-acting antivirals started between January and December 2015. Baseline stage 3 was defined in a two-step procedure: we selected patients with transient elastography values of 9.5-14.5 kPa and subsequently excluded those with nodular liver surface, splenomegaly, ascites or collaterals on imaging, thrombopenia or esophago-gastric varices. Patients were screened twice-yearly using ultrasound. RESULTS: The final sample comprised 506 patients (median age, 57.4 years; males, 59.9%; diabetes, 17.2%; overweight, 44.1%; genotype 3, 8.9%; HIV coinfection, 18.4%; altered liver values, 15.2%). Median follow-up was 33.7 (22.1-39.1) months. Five hepatocellular carcinomas and 1 cholangiocarcinoma were detected after a median of 29.4 months (95% CI: 26.8-39.3), with an incidence of 0.47/100 patients/year (95% CI: 0.17-1.01). In the multivariate analysis, only males older than 55 years had a significant higher risk (hazard ratio 7.2 [95% CI: 1.2-41.7; P = .029]) with an incidence of 1.1/100 patients/year (95% CI: 0.3-2.8). CONCLUSIONS: In a large, well-defined cohort of patients with baseline hepatitis C stage-3 fibrosis, the incidence of primary liver tumours was low after sustained virological response and far from the threshold for cost-effectiveness of screening, except in males older than 55 years.

Hematemesis With Gastric Laceration After Tattooing a Polyp With Purified Carbon: A Review of the Literature.

Endoscopic tattooing is a simple and effective technique for marking small lesions, so they can be localized during surgery or in later endoscopies. Various agents can be used such as India ink or a solution of purified carbon particles. The number of complications from tattooing is relatively small, but not rare. The majority of the literature on the subject refers to complications in the colon. We present a case of gastric bleeding secondary to a laceration following tattooing with purified carbon, and a literature review.

Transarterial chemoembolisation in intermediate-stage hepatocellular carcinoma. Survey on clinical practice in hospitals in the Madrid Region.

BACKGROUND: Transarterial chemoembolisation (TACE), having demonstrated survival benefits, is the treatmentof choice in intermediate-stage hepatocellular carcinoma, although there is great heterogeneity in its clinical application. MATERIAL AND METHODS: A survey was sent to the Madrid Regional hospitals to assess applicability, indications and treatment protocols. The assessment was made overall and according to the type of hospital (groups A vs. B and C). RESULTS: Seventeen out of 22 hospitals responded (8/8 group A, 9/ 14 group B-C). All do/indicate transarterial chemoembolisation, 13/17 at their own facilities. Eight of the 17 hospitals have multidisciplinary groups (5/8 A, 3/9 B-C). Nine hospitals perform > 20 procedures/year (7 group A), and 6 from group B-C request/perform < 10/year. It is performed on an "on-demand" basis in 12/17. In 5 hospitals, all the procedures use drug-eluting beads loaded with doxorubicin. The average number of procedures per patient is 2. The mean time from diagnosis of hepatocellular carcinoma to transarterial chemoembolisation is ≤ 2 months in 16 hospitals. In 11/17 hospitals, response is assessed by computed tomography. Radiological response is measured without specific criteria in 12/17 and the other five hospitals (4 group A) assessed using standardised criteria. CONCLUSION: Uniformity among the Madrid Regional hospitals was found in the indication and treatment regimen. The use of DEB-TACE has become the preferred form of TACE in clinical practice. The differentiating factors for the more specialised hospitals are a larger volume of procedures, decision-making by multidisciplinary committees and assessment of radiological response more likely to be standardised.

Efficacy and safety of ERCP in a low-volume hospital.

BACKGROUND AND AIMS: there is little scientific evidence on the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) performed in low-volume hospitals; however, in our country, it is growing up its implementation. The objectives of our study were to evaluate the efficacy and safety of this technique performed by two endoscopists with basic training in a center of this nature and analyze the learning curve in the first procedures. PATIENTS AND METHODS: single-center retrospective study of the first 200 ERCP performed in our hospital (analyzing the evolution between the first 100 and 100 following procedures), comparing them with the quality standards proposed in the literature. RESULTS: from February 2009 to April 2011, we performed 200 ERCP in 169 patients, and the most common indications were: Choledocholithiasis (77 %), tumors (14.5 %) and other conditions (8.5 %). The cannulation rate rose from 85 % in the first 100 ERCPto 89 % in the next 100 procedures, clinical success from 81 % to 87 %, decreasing the post-ERCP acute pancreatitis rate from 11 % to 4 %, upper gastrointestinal bleeding (UGIB) from 3 % to 2 % and acute cholangitis from 4 % to 1 %. There was a death from a massive UGIB in a cirrhotic patient in the first group of patients and a case of biliary perforation resolved by surgery in the second one. CONCLUSIONS: the results obtained after performing 200 procedures support the ability to practice ERCP in low-volume hospitals obtaining levels of efficacy and safety in accordance with published quality standards.

Serum level of soluble vascular cell adhesion molecule in patients with hepatocellular carcinoma and its association with severity of liver disease.

BACKGROUND: VCAM-1 (soluble vascular cell adhesion molecule-1) plays a role in liver angiogenesis. Hepatocellular carcinoma (HCC) has important angiogenic activity, so expression of VCAM-1 may be pathogenic. AIM: To assess the association between serum VCAM-1 (sVCAM-1) levels and features of tumour and liver disease in patients with and without HCC, and to study the influence of HCC treatment on sVCAM-1 levels. MATERIAL AND METHODS: Concentrations in peripheral (sVCAM-1-P) and hepatic (sVCAM-1-H) veins were analysed using ELISA in 134 consecutive patients with chronic liver disease between May 2004 and February 2006, who underwent a splanchnic haemodynamic study. Of these patients, 58 had HCC. RESULTS: sVCAM-1-P and sVCAM-1-H were well correlated in both groups. No association was found between sVCAM-1-H and tumour features. No differences were observed in sVCAM-1-H between HCC and non-HCC cirrhotic patients. There was a significant linear association between Child-Pugh stage and sVCAM-1-H in HCC-patients (Child-Pugh A [2,485 ± 1,294 ng/mL] vs. Child-Pugh B [3,408 ± 1,338 ng/mL] vs. Child-Pugh C [4,096 ± 862 ng/mL]; p = 0.007). Seven non-cirrhotic HCC patients had a significantly lower sVCAM-1-H than cirrhotic HCC patients. Treatment of HCC leads to an increase in sVCAM-1-H levels although this was not associated with the necrosis response to treatment. CONCLUSIONS: sVCAM-1 levels are more closely associated with the severity of underlying liver disease than with the presence of HCC. sVCAM-1 levels are not associated with tumour features or invasiveness; therefore, sVCAM-1 does not seem to play an important role in the angiogenic processes of HCC.

Efficacy and safety of entecavir and/or tenofovir in hepatitis B compensated and decompensated cirrhotic patients in clinical practice.

This study aimed to evaluate the efficacy and safety of entecavir and/or tenofovir in compensated (CC) or decompensated (DC) hepatitis B cirrhotic patients in real-life clinical practice. Of the 48 patients, included between April 2007 and March 2010, 12 were DC. The mean age was 55 ± 12.2 years, 85.4% were Caucasians and 8 patients were HBeAg positive. Mean viral load was 5.2 ± 1.9 log(10) UI/mL. HBV-DNA undetectability at 3, 6, 12 and 24 months were 53.3%, 78.3%, 83.7% and 97.1%, respectively, similar in CC and DC. At 6 and 12 months, ≥ 80% of CC achieved ALT normalization, while only 42.9% and 71.4% in DC. After a median follow-up of 27.1 (0.7-45.3) months, 43 patients were Child Pugh Turcotte (CPT) class A (n = 39 at entry). In DC, progressive improvement in the MELD scores was observed: 12.73 (SD 4.5), 10.4 (SD 3.6) and 8.2 (SD 2.6), at baseline, 12 and 24 months, respectively. During follow-up, 7 patients died, 4 received liver transplantation and 5 developed hepatocellular carcinoma. In three out of four DC who died due to hepatic causes, these events occurred between the first 0.7 and 6.7 months, and all were CPT class C. Cumulative survival in CC vs. DC at 12 and 24 months were 94.4% vs. 66.7%, and 88.2% vs. 57.1%, respectively (log rank p = 0.03). No severe adverse events associated with entecavir or tenofovir were reported. In conclusion, in compensated and decompensated cirrhotic patients, entecavir and tenofovir were effective and well tolerated.

Serum angiopoietin-2 level as a predictor of tumor invasiveness in patients with hepatocellular carcinoma.

BACKGROUND: Because hepatocellular carcinoma (HCC) has important angiogenic activity, the expression of angiopoietin-2 (Ang-2) may have a pathogenic role. The information about the influence of serum Ang-2 (sAng-2) in patients with HCC is scarce. AIMS: The aim was to assess the association between sAng-2 levels and characteristics of tumor and liver disease in patients with HCC. METHODS: sAng-2 concentrations in peripheral (sAng-2-P) and hepatic (sAng-2-H) veins were analyzed by ELISA in 33 patients with chronic liver disease who underwent a splanchnic hemodynamic study. Thirty-two patients received treatment for HCC. RESULTS: The median age was 61 years and 79% were male. Hepatitis C infection (70%) was the main etiology. Most patients were Child-Pugh grade A (72.7%). sAng-2-P and sAng-2-H were well correlated (r = 0.95; p < 0.0001). A significant association was found between sAng-2-H and lobar tumor extension, vascular thrombosis, BCLC staging, infiltrating pattern, abnormal alpha-fetoprotein level, fulfillment of the Milan criteria, and performance of nonsystemic treatment. sAng-2-H also showed a significant correlation with the MELD score (r = 0.49; p = 0.007), albumin (r = -0.63; p < 0.001), and HVPG (r = 0.44; p = 0.02). Eleven patients received treatment with radiofrequency ablation and eight with transarterial chemoembolization. HCC treatment did not influence the sAng-2 concentration while the necrosis response to treatment was not influenced by previous sAng-2 levels. CONCLUSIONS: Ang-2 seems to play an important role in the angiogenic processes of HCC and its serum levels are associated with tumor characteristics and invasive behavior. Our results suggest that Ang-2 is not related with treatment response and its level is not modified by treatment.

[Granular cell tumor of the esophagus: description of an infrequent benign tumor]. / Tumor esofágico de células granulares: descripción de un tumor benigno poco frecuente.

Granular cell tumors (GCT) are infrequent tumors first described by Abrikossoff in 1926. Gastrointestinal involvement occurs in about 6% of GCT, the esophagus being the most frequent location. These tumors are usually benign and asymptomatic and are usually found incidentally when an upper gastrointestinal endoscopy is carried out for another reason, showing an isolated polyp or sessile submucosal nodule, covered by intact yellowish mucosa and with firm consistency. Endoscopic ultrasonography has significantly improved the diagnosis of these lesions. Nowadays endoscopic mucosectomy is the treatment of choice of esophageal GCT with a low frequency of complications. Histologic analysis of the surgical specimen shows specific characteristics such as positivity for S-100 protein. We present two new cases of esophageal GCT that were diagnosed recently and discuss the most relevant features of this infrequent disease.

[Descriptive study of hepatocellular carcinoma in noncirrhotic liver]. / Estudio descriptivo de la experiencia sobre carcinoma hepatocelular en hígado no cirrótico.

INTRODUCTION AND OBJECTIVE: Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer. In western countries its impact is steadily growing and most of these tumors arise in cirrhotic liver. The aim of this study was to evaluate the incidence and characteristics of HCC developing in noncirrhotic patients. METHODS: We conducted a retrospective review of 469 patients diagnosed with HCC between January 2003 and December 2007. Patients who met the histological criteria, or a combination of clinical, laboratory, imaging and hemodynamic criteria for the absence of cirrhosis were included. RESULTS: We identified 29 patients with a diagnosis of HCC in non-cirrhotic liver (6.2%). Most (86.2%) were men and the median age was 61.6 (23 - 82) years. The most frequent histology of the liver was mild-moderate liver fibrosis (68.9%) and 62.1% of the patients were asymptomatic at diagnosis. HCC was a solitary nodule in 86.2%, and the median size of the main nodule was 46 (20 - 150) mm. Macroscopic vascular invasion was demonstrated in two patients and bone metastases in a further two patients. Active treatment was provided in 25 patients, consisting of tumoral resection in 15, radiofrequency ablation in six and transarterial chemoembolization in four. The overall cumulative survival at 1, 2 and 3 years was 84.3%, 67.2% and 50.1%, respectively. CONCLUSION: HCC arising in non-cirrhotic liver is uncommon and there is wide tumor extension at diagnosis. Nevertheless, in most patients, treatment with curative intent can be applied, achieving better survival than that expected patients with cirrhosis.

[Colorectal melanoma: review of two distinct forms of presentation]. / Melanoma colorrectal: revisión de dos formas diferentes de presentación.

Malignant melanoma of the colon and rectum is an infrequent disease. Primary anorectal melanoma accounts for 0.1-4.6% of all malignant neoplasms of the anal canal. Melanoma metastatic to the colon is symptomatic only in 4.4% of patients with a primary melanoma at another site and most of these tumors are diagnosed postmortem. We report two cases of colorrectal malignant melanoma. The first case concerned a patient with rectal bleeding who was diagnosed with a rectal lesion compatible with melanoma. Abdominoperineal resection was performed due to positivity of the sentinel lymph node. We discuss the utility of sentinel lymph node detection in this kind of tumor. In the second case, we discovered a polyp compatible with metastatic melanoma in the transverse colon in a patient with a previous diagnosis of melanoma. In both surgical specimens, the diagnosis of melanoma was confirmed by positivity for protein S-100, Melan-A and HMB-45.

[Influence of treatment of hepatocellular carcinoma before liver transplantation on post transplant tumor recurrence and survival]. / Influencia del tratamiento del hepatocarcinoma antes del trasplante hepático en la recurrencia tumoral y supervivencia postrasplante.

OBJECTIVES: To evaluate the effectiveness of treatment of hepatocellular carcinoma (HCC) before liver transplantation (LT) and its influence on survival and tumor recurrence in patients transplanted for HCC. PATIENTS AND METHODS: We included 67 liver transplant patients with a preoperative diagnosis of HCC and pathological confirmation in the native liver between January 2000 and October 2007. Treatment before LT was performed in 46 (68.7%) patients [radiofrequency ablation in 18, transarterial chemoembolization in 31 and percutaneous ethanol injection in two]. RESULTS: The median time between inclusion on the waiting list and LT was 4 months and was similar in treated and untreated patients. The median time between pre-transplantation locoregional therapy and LT was less than 6 months in 65.2% of the patients. Treated patients had better liver function (Child A 52.2 vs 19%; Child B 39.1 vs 33.3%; Child C 8.7 vs. 47.6%; p=0.001) and a higher proportion of total tumor size > 3 cm (59.1% vs 30%; p=0.031). Total tumor necrosis was observed in 26.1% of the patients, with no differences according to treatment modality or tumor size. Tumor recurrence occurred in six patients (9%). The median time between LT and tumor recurrence was 26.5 months with a subsequent median survival of 6.6 months. Overall survival was 83.5%, 69.9% and 59.5%, and tumor recurrence-free survival was 83.5%, 68.3% and 58% at 1, 3 and 5 years, respectively. Previous HCC treatment showed no influence on survival or tumor recurrence. Likewise, the grade of tumor necrosis was unrelated to overall survival or the probability of recurrence. CONCLUSION: Treatment of HCC before LT in patients with a waiting list time of less than 6 months does not appear to influence survival or tumor recurrence.

Portal hypertensive colopathy is associated with portal hypertension severity in cirrhotic patients.

AIM: To assess the prevalence of portal hypertension (PH) related colorectal lesions in liver transplant candidates, and to evaluate its association with the severity of PH. METHODS: Between October 2004 and December 2005, colonoscopy was performed in 92 cirrhotic liver transplant candidates. We described the lesions resulting from colorectal PH and their association with the grade of PH in 77 patients who underwent measurement of hepatic venous pressure gradient (HVPG). RESULTS: Mean age was 55 years and 80.7% of patients were men. The main etiology of cirrhosis was alcoholism (45.5%). Portal hypertensive colopathy (PHC) was found in 23.9%, colonic varices in 7.6% and polyps in 38% of patients (adenomatous type 65.2%). One asymptomatic patient had a well-differentiated adenocarcinoma. The manifestations of colorectal PH were not associated with the etiology of liver disease or with the Child-Pugh grade. Ninety percent of patients with colopathy presented with gastroesophageal varices (GEV), and 27.5% of patients with GEV presented with colopathy (P = 0.12). A relationship between higher values of HVPG and presence of colopathy was observed (19.9 +/- 6.2 mmHg vs 16.8 +/- 5.4 mmHg, P = 0.045), but not with the grade of colopathy (P = 0.13). Preneoplastic polyps and neoplasm (P = 0.02) and spontaneous bacterial peritonitis (P = 0.006) were more prevalent in patients with colopathy. We did not observe any association between previous beta-blocker therapy and the presence of colorectal portal hypertensive vasculopathy. CONCLUSION: PHC is common in cirrhotic liver transplant candidates and is associated with higher portal pressure.

[Spontaneous bacterial peritonitis in cirrhotic patients over 65 years]. / Peritonitis bacteriana espontánea en pacientes con cirrosis mayores de 65 años.

AIMS: Our aim was to study the episodes of spontaneous bacterial peritonitis (SBP) in cirrhotic patients older than 65 years. Their clinical characteristics were compared with a cohort of cirrhotic patients with SBP. METHODS: We conducted a retrospective study on all hospital discharged patients diagnosed with SBP in the period from January 2003 to December 2005, obtaining a total of 158 episodes. Two groups of patients were created: those over 65 (group 1: 73 episodes) and those aged 65 years (group 2: 86 episodes). A descriptive study, an analysis of survival by Kaplan Meier curves (compared with log-rank test) and a Cox regression analysis was conducted comparing the two groups. RESULTS: In Group 1, males were 74%, the average age was 72.4 (SD 4.2) years, and the Child-Pugh distribution was 8.2% (A), 68.5% (B) and 23.3% (C).The most usual etiology of cirrhosis was viral (65.8%). In comparison with group 2, there was a superior frequency of renal impairment at admission, hepatocellular carcinoma and a viral etiology. Yet the bilirubin levels were higher in group 2. In-hospital mortality rate was 23.3%. The survival at 3 and 6 months was of 69.5% and 54.8%, while in group 2 it was 80.3% and 78.4% respectively (p=0001). An age> 65 years, the existence of hepatocellular carcinoma and a Mean Arterial Pressure <75 mm Hg at admission, in the overall cohort, were independent predictors of mortality. CONCLUSION: An age above 65 years is an independent predictor of mortality following the development of an episode of spontaneous bacterial peritonitis in cirrhotic patients.

[Results of colonoscopic examination in the evaluation of cirrhotic candidates for liver transplantation]. / Resultados de la realización de colonoscopia en la evaluación de pacientes cirróticos candidatos a trasplante hepático.

AIM: To assess the presence of preneoplastic and neoplastic colonic lesions, as well as those related to portal hypertensive vasculopathy, and their association with liver disease in cirrhotic patients who are candidates for orthotopic liver transplantation (LT). METHODS: Between October 2004 and December 2005, colonoscopy was performed in 92 patients who were LT candidates, aged >50 years old or aged <50 years old but with clinical indications. RESULTS: Eighty-eight percent of the patients were > 50 years old, the mean age was 55.3 years (29-69) and 81.5% were males. The main etiology of cirrhosis was alcoholic (46.7%), and 21% were Child-Pugh class A. No abnormalities were detected in 20.7%. Polyps were discovered in 38% (35/92) of patients (adenomatous 65.2%; tubular type 86.7%). Six patients with adenomatous polyps had mild dysplasia, and one asymptomatic patient had a well-differentiated adenocarcinoma. An association was found between polyps and male sex (44% males vs 17.6% females; p=0.044) and Child-Pugh grade (63.2% Child A vs 32.9% Child B/C, p=0.016) but not with serum levels of carcinoembryonic antigen (CEA), age or etiology of liver disease. Portal hypertensive colopathy was found in 23.9%, rectal varices in 7.6% and internal or mixed hemorrhoids in 52.3%. CONCLUSION: The prevalence of preneoplastic and neoplastic colonic lesions may support the use of colonoscopy in LT candidates aged >50 years-old or with a history suggesting lower gastrointestinal bleeding or other abnormalities.

[Prognostic value of a spontaneous bacterial peritonitis episode in cirrhotic patients in clinical practice]. / Valor pronóstico de un episodio de peritonitis bacteriana espontánea en pacientes cirróticos en la práctica clínica.

OBJECTIVES: To assess survival and predictive factors of mortality after an episode of spontaneous bacterial peritonitis (SBP) in cirrhotic patients and to analyze the diagnostic and therapeutic measures used. METHODS: We retrospectively reviewed the medical records of 158 consecutive episodes of SBP treated between January 2003 and December 2005. Survival was studied by Kaplan-Meier curves, compared by the log-rank test. Independent predictive factors of mortality were obtained by a Cox regression model, while independent predictive factors of in-hospital mortality were obtained by logistic regression analysis. RESULTS: A total of 80.4% of the SBP episodes occurred in men and the mean age was 61.23 +/- 12.49 years. The most frequent etiology of cirrhosis was viral (51.3%), followed by alcoholic (39.9%). The distribution of Child-Pugh classification was 5.7% (A), 63.3% (B) and 31% (C). Overall 3-year survival in the sample was 43.3%. Four variables were identified as independent predictive factors of in-hospital and 3-month mortality: renal impairment, hepatic encephalopathy, diagnosis of hepatocellular carcinoma (HCC) and mean arterial pressure (MAP) < 75 mmHg. At the end of the monitoring period, the results of the analysis were as follows: diagnosis of HCC, MAP < 75 mmHg, and age > 65 years. Microbiological detection was achieved in 21% of the episodes. The most frequent microorganisms detected were Escherichia coli in ascitic fluid and Staphylococcus aureus in blood cultures. CONCLUSIONS: SBP has a poor short- and long-term prognosis in cirrhotic patients. Independent predictive factors of short-term survival are renal impairment, hepatic encephalopathy, MAP < 75 mmHg, and the presence of HCC.