Giuseppe Parisi

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

BackgroundWe 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.MethodsTo 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.ResultsLesions 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.ConclusionsOur data suggest that the optimal timing to perform VCE is within a few days after the occurrence of bleeding, possibly within 2 weeks.

Conventional versus Doxorubicin-eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma

PURPOSEnTo compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead (DEB) transarterial chemoembolization in hepatocellular carcinoma (HCC).nnnMATERIALS AND METHODSnPatients 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnConventional 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.

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

AIMnTo 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).nnnMETHODSnFrom 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.nnnRESULTSnTwo 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.nnnCONCLUSIONnIn 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.

Granulocytapheresis in steroid-dependent and steroid-resistant patients with inflammatory bowel disease: A prospective observational study

BACKGROUNDnDespite the mounting importance of granulocytapheresis (GCAP) for inflammatory bowel disease (IBD) treatment, its effectiveness in steroid-dependent (SD) and steroid-resistant (SR) patients has not been clearly evaluated. This prospective observational study describes the use of GCAP in SD and SR patients with either Ulcerative Colitis (UC) or Crohns Disease (CD).nnnMETHODSn118 patients, 83 affected by UC (55 SD and 28 SR) and 35 by CD (22 SD and 13 SR), were treated with GCAP, using Adacolumn™, for 5 consecutive weeks, 1 session/week. All patients were followed for 12 months after the end of GCAP. Clinical remission was defined as Clinical Activity Index (CAI) ≤6 for UC patients and Crohns Disease Activity Index (CDAI) <150 for CD patients.nnnRESULTSnAll patients completed the study; no major complications were reported. At the end of GCAP 71% of UC and 63% of CD patients showed clinical remission. At 6 months the remission was maintained by 66% and 54% of UC and CD patients respectively, while at 12 months the percentages were 48% and 43%, respectively. No differences between SD and SR subgroups were reported at any timepoint. CAI and CDAI values significantly dropped after GCAP treatment and at 6 and 12 months follow-up (p<0.05 vs baseline for both timepoints). No differences were measured in CAI and CDAI between SD and SR patients.nnnCONCLUSIONnGCAP therapy is safe and effective in inducing and maintaining clinical remission both in SD and in SR patients affected by either UC or CD.

Long-term results of sorafenib in advanced-stage hepatocellular carcinoma: what can we learn from routine clinical practice?

Background and aims: Prospective randomized trials have proven that sorafenib is a valid treatment option for patients with advanced-stage hepatocellular carcinoma (HCC). The aim of the present study is to evaluate the effectiveness and safety of sorafenib in patients encountered in routine clinical practice. Methods: From September 2008 to March 2011, 42 cirrhotic patients (30 male; 12 female; mean age: 70.2 ± 7.6 years; range: 56–85 years) with HCC of Barcelona Clinic Liver Cancer stage B (n = 5) or C (n = 37; mean size: 66.6 ± 42.3 mm; mean number per patient: 3.3 ± 2.8) were treated with sorafenib at either a standard dose of 800 mg/day (n = 29; 69.1%) or at 400 mg/day with subsequent dose escalation (ramp-up strategy; n = 13, 30.9%). Baseline clinical parameters were comparable. Clinical data and side effects, laboratory analyses (in particular, serum α-fetoprotein) and radiological data (tumor response according to amended RECIST criteria) were assessed every 3 months. Survival was calculated by Kaplan–Meier analysis. Results: Mean follow-up was 12.2 ± 9 months (range: 1–32 months). Median overall survival was 26.1 months with overall 6- and 12-month survival rates of 92.1 and 85%, respectively. Median time to radiological progression was 8 months. The progression-free rate was 64.3%. Fatigue, skin disorders and diarrhea were the most frequent grade 3–4 side effects. Treatment discontinuation occurred in 25 patients. The starting dose for the last 13 enrolled patients was 400 mg/day; in the absence of toxicity this dosage was gradually increased to 800 mg/day after 3 weeks (‘ramp-up strategy’). No grade 3/4 adverse events were observed in the ramp-up group. Conclusion: Sorafenib is a valid treatment option for advanced-stage HCC. Starting at a lower dosage may allow prolonged compliance to treatment and might be considered according to patient tolerance.

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

Aim:u2002 To evaluate granulocytapheresis (GCAP) in active ulcerative colitis (UC), with particular attention to the long‐term effects of such treatment.

Video capsule endoscopy for evaluating obscure gastrointestinal bleeding and suspected small-bowel pathology

accumulation of p53 protein in tumor cells with the wild-type p53 gene can be easily discriminated from the abnormal accumulation of p53 protein in most of the tumor cells with a missense mutation of the p53 gene. In summary, IHC is a simple and useful approach for screening p53 alterations in clinical materials. Tumors that show abnormal nuclear accumulation in tumor cells by IHC must harbor a mutation of the p53 gene: most of such cases have a point mutation in the core domain of the p53 gene. However, negative IHC for p53 protein does not always reflect the wild-type p53 gene in cancer cells (Fig. 2).

Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives

In the last decade trans-arterial radioembolization has given promising results in the treatment of patients with intermediate or advanced stage hepatocellular carcinoma (HCC), both in terms of disease control and tolerability profile. This technique consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound (usually Yttrium(90)), and exerts its therapeutic effect through the radiation carried by these microspheres. A careful and meticulous selection of patients is crucial before performing the radioembolization to correctly perform the procedure and reduce the incidence of complications. Radioembolization is a technically complex and expensive technique, which has only recently entered clinical practice and is supported by scant results from phase III clinical trials. Nevertheless, it may represent a valid alternative to transarterial chemoembolization (TACE) in the treatment of intermediate-stage HCC patients, as shown by a comparative retrospective assessment that reported a longer time to progression, but not of overall survival, and a more favorable safety profile for radioembolization. In addition, this treatment has reported a higher percentage of tumor shrinkage, if compared to TACE, for pre-transplant downsizing and it represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume who are not immediately eligible for surgery. Radioembolization might also be a suitable companion to sorafenib in advanced HCC or it can be used as a potential alternative to this treatment in patients who are not responding or do not tolerate sorafenib.

Transarterial radioembolization for hepatocellular carcinoma: a review

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is the second cause of death due to malignancy in the world. The treatment of HCC is complex and includes potentially curative and palliative approaches. However, both curative and palliative treatments for HCC are often associated with a not-completely favorable safety/efficacy ratio. Therefore, other treatment options appear necessary in clinical practice. Transarterial radioembolization has shown a promising efficacy in terms of disease control and is associated with a good safety profile. This review discusses the use of transarterial radioembolization in HCC, with a focus on the clinical aspects of this therapeutic strategy.

Chronic Hepatitis C

SummaryIn this paper we describe a study in which 150 patients with chronic hepatitis C virus infection who did not respond to 6 months’ treatment with recombinant interferon-α (rIFNα) 3MU 3 times weekly were randomly allocated to 1 of 5 groups of 30 patients each: group A continued the same dose of rIFNα 3MU 3 times weekly; group B was treated with the same rIFNα but received a double dose (6MU 3 times weekly); group C received lymphoblastoid interferon (L-IFN) 3MU 3 times weekly; group D received natural interferon-a (N-IFNα) 3MU 3 times weekly; and group E stopped interferon-a therapy and did not receive any treatment. The patients were treated for a further 6 months. All patients who achieved normalisation of alanine aminotransferase (ALT) levels were followed up for at least 6 months after withdrawal of interferon therapy. A statistical analysis was carried out at the beginning and at the end of the study. The 5 groups were homogeneous. No patient discontinued therapy because of adverse effects. A biochemical response was defined as a simple normalisation of ALT levels, while a complete response was defined as normalisation of ALT levels with disappearance of serum HCV-RNA. After the additional 6-month treatment period, a biochemical response was seen in 5 (17%) patients in group A, 9 (30%) in group B, 6 (20%) in group C and 7 (23%) in group D (none in group E). A complete response was seen in 2 (7%) patients in group A, 5 (17%) in group B and 3 (10%) each in groups C and D (none in group E). At the end of the treatment-free follow-up period, 8 (7%) of 120 treated patients and 3 (10%) controls had a biochemical response, while 5 (3%) patients, all in the treated groups, also had undetectable serum HCV-RNA, without a statistically significant difference among the 4 treatment groups and between the type of response (biochemical or complete). A higher dose of rIFNα given for a longer period produced the best results, but there was no statisically significant difference between the double-dose rIFNα, N-IFNα, L-IFN and control groups. Therefore it can be concluded that there is no really satisfactory treatment for patients who do not respond to a course of rIFNa therapy, even if in our study a second course of double-dosed rIFNa seemed to be the most advantageous therapeutic protocol.