Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment: a prospective cohort study.

AIM: To assess clinical outcome of transarterial chemoembolization (TACE) in a series of patients with early-stage hepatocellular carcinoma (HCC), within Milan criteria, but clinically unfit for liver transplantation (OLT). METHODS: From January 2006 to May 2009, 67 patients (43 males, mean age 70 ± 7.6 years) with very early or early-stage unresectable HCC, within Milan selection criteria but clinically unfit for OLT, underwent TACE. The primary endpoint of the study was overall survival. Secondary endpoints were: safety, liver toxicity, 1-month tumour response according to the amended RECIST criteria, time to local and distant intrahepatic tumour recurrence and time to radiological progression. RESULTS: Two major periprocedural complications occurred (3%), consisting of liver failure. Periprocedural mortality rate was 1.5% (1 patient). A significant increase in ALT and bilirubin levels 24h after treatment was reported, with progressive decrease at discharge. At 1-month follow-up, complete and partial tumour response rates were 67.2% and 29.8%, respectively, with two cases of progressive disease. Mean follow-up was 37.3 ± 15 months. The 1-, 2-, and 3-year overall survival rates were 90.9%, 86.1%, and 80.5%, respectively. Median expected time to local tumour recurrence and intrahepatic tumour recurrence were 7.9 and 13.8 months, respectively. Radiological disease progression was observed in 12 patients (17.9%) with a mean expected time of 26.5 months. CONCLUSION: In patients with early-stage HCC, clinically excluded from OLT and unfit for surgery or percutaneous ablation, TACE is a safe and effective option, with favourable long-term survival.

Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: To compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead (DEB) transarterial chemoembolization in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with unresectable HCC unsuitable for ablative therapies were randomly assigned to undergo conventional or DEB chemoembolization. The primary endpoints of the study were safety, toxicity, and tumor response at 1 month. Secondary endpoints were number of repeated chemoembolization cycles, time to recurrence and local recurrence, time to radiologic progression, and survival. RESULTS: In total, 67 patients (mean age, 70 y ± 7.7) were evaluated. Mean follow-up was 816 days ± 361. Two periprocedural major complications occurred (2.9%) that were treated by medical therapy without the need for other interventions. A significant increase in alanine aminotransferase levels 24 hours after treatment was reported, which was significantly greater after conventional chemoembolization (n = 34) than after DEB chemoembolization (n = 33; preprocedure, 60 IU ± 44 vs 74 IU ± 62, respectively; at 24 h, 216 IU ± 201 vs 101 IU ± 89, respectively; P = 0.007). No other differences were observed in liver toxicity between groups. At 1 month, complete and partial tumor response rates were 70.6% and 29.4%, respectively, in the conventional chemoembolization group and 51.5% and 48.5%, respectively, in the DEB chemoembolization group. No differences were observed between groups in time to recurrence and local recurrence, radiologic progression, and survival. CONCLUSIONS: Conventional chemoembolization and DEB chemoembolization have a limited impact on liver function on short- and long-term follow-up and are associated with favorable clinical outcomes.

Complete response for advanced liver cancer during sorafenib therapy: case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common neoplasia in the world. In the past, treatment of advanced HCC with conventional antineoplastic drugs did not result in satisfactory outcomes: recently, in this patient population the oral multikinase inhibitor sorafenib has been able to induce a statistically significant improvement of overall survival. Similarly to other anti-angiogenic drugs employed in other tumour types, also sorafenib seldom induces the dimensional tumour shrinking usually observed with conventional cytotoxic drugs: data gathered from studies carried out with sorafenib and other competitors under development do not report any complete response in HCV-induced HCC. CASE PRESENTATION: An 84-year old man with a long-lasting history of chronic HCV hepatitis was referred to our Institution for an ultrasonography investigation of a focal hepatic lesion. To better characterize the liver disease and clearly define the diagnosis of the focal hepatic lesion, the patient was hospitalized in our department. Laboratory and instrumental investigations confirmed the clinical picture of HCV-related liver cirrhosis and identified a hepatic lesion of about 6 cm featuring infiltrating HCC with thrombosis of the portal trunk. Due to the advanced stage of the disease, therapy with sorafenib 400 mg bid was started. Right from one month after the treatment was started, a reduction of alpha-fetoprotein level was observed which, by the third month, turned down within the normal limits. In addition the CT scan showed 50% reduction of the neoplastic lesion along with canalization of the portal trunk. At the sixth month the normalization of the alpha-fetoprotein level at the lower limit of normality was confirmed and the MRI showed complete disappearance of the neoplasia. In addition a reduction of a metallo-proteinase serum level was observed. At the twelfth month a further MRI confirmed complete response had been maintained. At present the patient is in a follow-up program to evaluate the duration of the complete response. CONCLUSIONS: This case is worth mentioning since, to the best of our knowledge, it represents the first evidence of complete response to sorafenib in an elderly patient with advanced HCV-related HCC.

Quantitative determination of hepatitis C core antigen in therapy monitoring for chronic hepatitis C.

The correlation and kinetics of hepatitis C virus (HCV) RNA and HCV core antigen levels in chronic hepatitis C patients treated with pegylated interferon + ribavirin were evaluated in order to envision a combined use of the two assays in therapy monitoring. HCV core antigen levels by a chemiluminescent immunoassay (Abbott ARCHITECT) and HCV-RNA levels by branched DNA (bDNA) or real-time PCR have been evaluated on plasma specimens from 32 patients treated for chronic hepatitis C. An early virological response (undetectable levels of HCV-RNA 4 weeks after start of treatment) was found in 10/23 subjects (43.5%) followed up for 5 months or more. The response was linked to the HCV genotype (20% in genotype 1B vs. 61.5% in other genotypes; p < 0.05). HCV RNA and HCV antigen showed a good correlation (r = 0.814); HCV antigen was still detectable in 3 samples with undetectable (<615 IU/ml) RNA by bDNA, while no differences in clinical sensitivity were recorded in comparison with real-time PCR. These findings suggest that HCV-RNA and HCV antigen may be used at different time points in order to tailor therapy monitoring to individual needs.

Endotics system vs colonoscopy for the detection of polyps.

AIM: To compare the endotics system (ES), a set of new medical equipment for diagnostic colonoscopy, with video-colonoscopy in the detection of polyps. METHODS: Patients with clinical or familial risk of colonic polyps/carcinomas were eligible for this study. After a standard colonic cleaning, detection of polyps by the ES and by video-colonoscopy was performed in each patient on the same day. In each single patient, the assessment of the presence of polyps was performed by two independent endoscopists, who were randomly assigned to evaluate, in a blind fashion, the presence of polyps either by ES or by standard colonoscopy. The frequency of successful procedures (i.e. reaching to the cecum), the time for endoscopy, and the need for sedation were recorded. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ES were also calculated. RESULTS: A total of 71 patients (40 men, mean age 51.9 ± 12.0 years) were enrolled. The cecum was reached in 81.6% of ES examinations and in 94.3% of colonoscopies (P = 0.03). The average time of endoscopy was 45.1 ± 18.5 and 23.7 ± 7.2 min for the ES and traditional colonoscopy, respectively (P < 0.0001). No patient required sedation during ES examination, compared with 19.7% of patients undergoing colonoscopy (P < 0.0001). The sensitivity and specificity of ES for detecting polyps were 93.3% (95% CI: 68-98) and 100% (95% CI: 76.8-100), respectively. PPV was 100% (95% CI: 76.8-100) and NPV was 97.7% (95% CI: 88-99.9). CONCLUSION: The ES allows the visualization of the entire colonic mucosa in most patients, with good sensitivity/specificity for the detection of lesions and without requiring sedation.

Entecavir for hepatitis B virus flare treatment in patients with Crohn's disease.

Chronic hepatitis B virus (HBV) infection is a global health problem and has an increased prevalence in patients with Crohn's disease due to their increased requirement for high-risk procedures. A balance between viral replication and host immune response exists and drugs such as the immunosuppressive agents used to treat Crohn's disease may alter this balance. These may result in a hepatic flare, which manifests as high viremia, increased transaminase levels, and hepatic decompensation. The present study describes two cases of hepatic flare thought to be caused by treatment of acute Crohn's disease with systemic corticosteroids and/or azathioprine. Both patients presented with raised transaminase and gamma glutamyl transferase levels and viremia. One patient experienced a decrease in hepatic function, as evidenced by a reduced serum albumin (2.5g/ dL) and jaundice (total bilirubin 5.2 mg/dL), and hepatic decompensation, with ascites. Both patients were treated with the nucleoside analogue entecavir 0.5 mg/day and experienced reductions in HBV-DNA and hepatic enzyme levels within 4-7 days. The patient with decompensation received diuretic therapy and parenteral nutrition to support hepatic function and a clinical improvement was seen. Both patients were discharged 2 weeks after admission and, during follow-up, HBV-DNA levels became negative after 1 and 5 months, respectively. No adverse events were reported in either patient. To the best of our knowledge, this is the first documented report of treatment of HBV flare with entecavir in patients co-affected with Crohn's disease.

Functional evaluation of the endotics system, a new disposable self-propelled robotic colonoscope: in vitro tests and clinical trial.

OBJECTIVE: Currently, the best method for CRC screening is colonoscopy, which ideally (where possible) is performed under partial or deep sedation. This study aims to evaluate the efficacy of the Endotics System, a new robotic device composed of a workstation and a disposable probe, in performing accurate and well-tolerated colonoscopies. This new system could also be considered a precursor of other innovating vectors for atraumatic locomotion through natural orifices such as the bowel. The flexible probe adapts its shape to the complex contours of the colon, thereby exerting low strenuous forces during its movement. These novel characteristics allow for a painless and safe colonoscopy, thus eliminating all major associated risks such as infection, cardiopulmonary complications and colon perforation. METHODS: An experimental study was devised to investigate stress pattern differences between traditional and robotic colonoscopy, in which 40 enrolled patients underwent both robotic and standard colonoscopy within the same day. RESULTS: The stress pattern related to robotic colonoscopy was 90% lower than that of standard colonoscopy. Additionally, the robotic colonoscopy demonstrated a higher diagnostic accuracy, since, due to the lower insufflation rate, it was able to visualize small polyps and angiodysplasias not seen during the standard colonoscopy. All patients rated the robotic colonoscopy as virtually painless compared to the standard colonoscopy, ranking pain and discomfort as 0.9 and 1.1 respectively, on a scale of O to 10, versus 6.9 and 6.8 respectively for the standard device. CONCLUSIONS: The new Endotics System demonstrates efficacy in the diagnosis of colonic pathologies using a procedure nearly completely devoid of pain. Therefore, this system can also be looked upon as the first step toward developing and implementing colonoscopy with atraumatic locomotion through the bowel while maintaining a high level of diagnostic accuracy;

Clinical impact of selective transarterial chemoembolization on hepatocellular carcinoma: a cohort study.

AIM: To prospectively evaluate the short and long term clinical impact of selective transarterial chemoembolization (TACE) on liver function in patients with hepatocellular carcinoma (HCC). To assess side effects in relation to treatments. To analyze the overall survival and HCC progression free survival probability. METHODS: One hundred and seventeen cirrhotic patients with HCC were enrolled. Baseline liver function included Child-Pugh score and serum levels of alanine-aminotransferase (ALT), prothrombin time (PT) and bilirubin. According to Cancer Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer (BCLC) staging systems, 71 patients were eligible for TACE; 32 had previously received treatment for HCC. No significant differences in liver function were observed between previously treated and not treated patients. TACE was performed by selective catheterization of the arteries nourishing the lesions. While hospitalized, patients underwent clinical, hematologic and ultrasonographic assessments. One month after TACE a CT scan was performed to assess tumor response. A second TACE was performed "on demand". Liver function tests were checked in all patients every four months. RESULTS: After first TACE, the mean Child-Pugh score increased from a mean baseline 5.62 +/- 1.12 to 6.11 +/- 1.57 at discharge time (P < 0.0001), decreasing after four months to 5.81 +/- 0.73 (not significant). ALT, PT and bilirubin significantly (P < 0.0001) increased 24 h after TACE and progressively decreased until discharge. After the second TACE, variations in Child-Pugh score, ALT, PT and bilirubin were comparable to that described after the first TACE. No major complications were observed. The mean follow-up was 14.7 +/- 6.3 mo (median: 16 mo). Only one patient died. No other patient experienced important long term worsening of clinical status. The overall survival probability at twenty-four months was 98.18% with a correspondent HCC progression free survival probability of 69%. CONCLUSION: Selective TACE may produce significant, but transitory increases in ALT values, with no major impact on liver function and Child-Pugh score. Preservation of liver function is achievable also in patients previously treated with other therapeutic modalities and in patients undergoing multiple TACE cycles. Liver function can remain stable in the long-term, with optimal medium term survival. This result can be achieved through rigorous patient selection on the basis of tumour characteristics and clinical conditions.

Granulocytapheresis versus methylprednisolone in patients with acute ulcerative colitis: 12-month follow up.

AIM: To evaluate granulocytapheresis (GCAP) in active ulcerative colitis (UC), with particular attention to the long-term effects of such treatment. METHODS: We included 80 patients with UC. Activity of the disease was evaluated by clinical activity index and endoscopic index. Patients were randomly divided in two groups: Group A received a five-session (1 session/week) treatment with GCAP, Group B were treated with i.v. or i.m. methylprednisolone (MP). Concomitant therapy with oral 5-aminosalicylic acid (5-ASA) 2.4 g/day was maintained in both groups. Subjects who achieved a remission were clinically and endoscopically followed for 12 months after the end of GCAP or MP. RESULTS: Remission was observed in 72.5% of those treated with GCAP versus 50% of those treated with MP. After a 12-month follow up, a sustained remission was recorded in 40% of those treated with GCAP and in 25% of those treated with MP. During the GCAP only a transient mild headache was recorded in 10% of patients, whereas side-effects were observed in 50% of those treated with MP (P < 0.05). CONCLUSION: GCAP results were superior to MP for the treatment of UC, even though no statistically significant difference was observed. Side-effects in the GCAP group were significantly lower than in the MP group. This new therapeutic approach seems able to maintain the condition of remission for a longer time after a flare. In fact, the patients who had obtained a remission after a course of CGAP showed fewer relapses during the follow up compared to the patients treated with MP.

The role of video capsule endoscopy for evaluating obscure gastrointestinal bleeding: usefulness of early use.

BACKGROUND: We report our preliminary experience with the use of video capsule endoscopy (VCE) in 64 patients with obscure gastrointestinal bleeding (OGIB) and suspected small intestine disease. METHODS: To be eligible for VCE, patients had to have undergone upper endoscopy, small bowel series, and colonscopy without discovering any source of bleeding. To find the best timing to perform VCE, the patients were retrospectively divided in two groups of 32 cases each: group 1 with patients who had been submitted to VCE within 15 days from OGIB diagnosis, and group 2 with patients who had been submitted to VCE at least 15 days after OGIB diagnosis. RESULTS: Lesions were found by VCE in 29 (91%) in group 1: angioectasia-like lesions of the small bowel in 12, some erosions of the ileum without signs of bleeding in 14, a polyp with erosions in 1, and a bleeding site where the surgery showed a tumor of the ileum in 2 patients. In 2 cases, VCE missed showing two small tumors that were revealed by laparoscopy in 1 case and by push enteroscopy in the other. In group 2, lesions were found by VCE in 11 (34%): angioectasia-like lesions of the small bowel in 6, some erosions in 3, a short segmental stenosis in 1, and two polyps in 1. In 1 case, VCE missed showing a small polyp in the jejunum that was revealed by push enteroscopy. In none of these cases was a bleeding site identified. VCE was well tolerated and able to acquire good images in patients with OGIB. It showed lesions in 91% of the patients in group 1 and 34% of cases in group 2. CONCLUSIONS: Our data suggest that the optimal timing to perform VCE is within a few days after the occurrence of bleeding, possibly within 2 weeks.