310 research outputs found
UNRESECTABLE HEPATOCELLULAR CARCINOMA:META-ANALYSIS OD ARTERIAL EMBOLIZATION
No full text. Radiology. 2002 Jul;224(1):47-54.
Transarterial chemoembolization for unresectable hepatocellular carcinoma:
meta-analysis of randomized controlled trials.
Cammà C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P,
Craxì A, Cottone M.
National Council of Research, Istituto Metodologie Diagnostiche Avanzate,
Palermo, Italy. [email protected]
Comment in
Radiology. 2003 May;227(2):611-2; author reply 612-3.
Radiology. 2004 Jan;230(1):300-1; author reply 301-2.
PURPOSE: To review the available evidence of chemoembolization for unresectable
hepatocellular carcinoma (HCC).
MATERIALS AND METHODS: Computerized bibliographic searches with MEDLINE and
CANCERLIT databases from 1980 through 2000 were supplemented with manual
searches, with the keywords "hepatocellular carcinoma," "liver cell carcinoma,"
"randomized controlled trial [RCT]," and "chemoembolization." Studies were
included if patients with unresectable HCC were enrolled and if they were RCTs in
which chemoembolization was compared with nonactive treatment (five RCTs) or if
different transarterial modalities of therapy (13 RCTs) were compared. Data were
extracted from each RCT according to the intention-to-treat method. Five of the
RCTs with a nonactive treatment arm were combined by using the random-effects
model, whereas all 18 RCTs were pooled from meta-regression analysis.
RESULTS: Chemoembolization significantly reduced the overall 2-year mortality
rate (odds ratio, 0.54; 95% CI: 0.33, 0.89; P =.015) compared with nonactive
treatment. Analysis of comparative RCTs helped to predict that overall mortality
was significantly lower in patients treated with transarterial embolization (TAE)
than in those treated with transarterial chemotherapy (odds ratio, 0.72; 95% CI:
0.53, 0.98; P =.039) and that there is no evidence that transarterial
chemoembolization is more effective than TAE (odds ratio, 1.007; 95% CI: 0.79,
1.27; P =.95), which suggests that the addition of an anticancer drug did not
improve the therapeutic benefit.
CONCLUSION: In patients with unresectable HCC, chemoembolization significantly
improved the overall 2-year survival compared with nonactive treatment, but the
magnitude of the benefit is relatively small
Incidence of HSV and HPV with azathioprine
No full textIBd
Incidence of HSV and HPV
with azathioprine
Mario Cottone and Sara Renna
severe infections are an established risk of immunosuppressive therapy;
however, the risk of opportunistic infections in patients with IBd who
receive immunosuppressive therapy has so far only been studied
retrospectively. the increased incidence of herpes flares and development
or worsening of viral warts in patients with IBd who receive azathioprine
has now been demonstrated for the first time in a prospective study.
the rate of opportunistic infections
in patients with iBD is dependent on the
patient’s nutritional status, degree of innate
immune system activity, whether the
patient has undergone surgery and their
use of immunosuppressive drugs or biological
therapy.1 severe infections are a
welldocumented
risk in patients who are
treated with immunosuppressive therapy;2
however, use of immunosuppressants
as maintenance therapy in patients with
iBD is becoming increasingly common.
in a 2004–2005 crosssectional
study of
20,000 patients with iBD, conducted in
France, >50% of patients with Crohn’s
disease and approximately 25% of patients
with ulcerative disease had received the
immuno suppressant azathioprine.3
infections with varicellazoster
virus and
herpes simplex virus (Hsv) are common,
nonfatal conditions characterized by a unilateral,
painful, vesicular rash in a dermatomal
distribution. Patients with iBD are
hypothesized to be at increased risk of
these viral infections because of diseaserelated
alterations in immune function
and frequent use of immunosuppressive
medications. Data on infection with human
papillomavirus (HPv) species in patients
with iBD are scarce but seem to show
an increased incidence of this infection
in such patients.4 Different studies have
used various metho dological approaches
to evaluate the risk of these three viral
infections in patients with iBD but no
studies have evaluated the incidence of all
three viruses.
Korelitz et al.5 reported the incidence of
varicellazoster
infection in patients with
iBD who were treated with 6mercaptopurine
to be 2.2%. However, the researchers
did not provide a comparison with the
incidence of this infection in a control
population, which limits the conclusions
that can be drawn.
a case–control study by toruner et al.1
sought to identify the factors associated
with iBD and infection by comparing 100
consecutive patients with iBD who had
opportunistic infections to patients with
iBD who did not have a history of opportunistic
infection. although the relative
risk of infection was greatest in patients
>50 years of age (compared with those
≤24 years of age) and was independent
of immuno suppressant treatment, use of
cortico steroids, azathioprine and infliximab
was also associated with a significantly
increased risk of opportunistic infection.
the researchers reported a higher incidence
of varicellazoster,
Candida albicans and
Hsv infections in patients who received
immunosuppressant treatment than in
those who did not receive this therapy, but
did not provide values for the risk of any
single infection.
Gupta et al.6 carried out a similar but
larger study, in which the incidence of
varicellazoster
infections in 7,823 patients
with Crohn’s disease and 1,930 patients with
ulcerative colitis was compared with its
Practice points
■ The incidence of opportunistic infections,
for example with varicella-zoster virus
and human papillomavirus species,
are increased in patients with iBD who
receive immunosuppressant therapy
■ Concomitant treatment of the
opportunistic infection or suspension of
immunosuppressive medication are two
possible therapeutic strategies
■ vaccination for human papillomavirus
species is recommended for women
with iBD
© 2009 Macmillan Publishers Limited. All rights reserved
nature reviews | gastroenterology & hepatology volume 6 | auGust 2009 | 445
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incidence in 79,563 individuals without
iBD. Patients with Crohn’s disease or
ulcerative colitis had a higher risk of
varicellazoster
infection than indivi duals
in the control group. in a nested, case–
control study, 185 patients with Crohn’s
disease and varicellazoster
infections
and 266 patients with ulcerative colitis and
varicellazoster
infections were compared
with 1,787 patients with iBD but without
varicellazoster
infection. Patients who
received immuno suppressant medications
had a greater risk of varicellazoster
infection than those who did not receive
such therapy. the unadjusted and adjusted
odds ratios for receipt of a prescription
for azathioprine or 6mercapto
purine and
varicellazoster
infection were both 3.1.
unfortunately, this study did not investigate
the incidence of other opportunistic
infections, such as Hsv.
the studies described above are all
retrospec tive and are, therefore, constrained
by the usual limitations of this study type.
retrospective analyses of safety data cannot
accurately assess the true incidence of
benign infections because they are transient
conditions. such analyses, therefore,
rely on accurate recall of information by the
patient and can result in an underestimation
of incidence of infection. thus, the information
available from case–control studies
is of limited value; no direct way exists to
estimate the incidence or prevalence of
disease, nor the attributable or excess risk
of particular groups of patients.
the study by seksik et al.7 is the first
prospec tive study to investigate the
incidence of opportunistic infection in
patients with iBD who receive azathioprine
therapy. in this study, 230 patients with
iBD received either azathioprine (n = 169)
or nonimmuno suppressive therapy (n = 61).
the patients underwent a comprehensive
skin examination and completed a questionnaire
every 3–6 months, and the number
of opportunistic infections, including ear,
nose, and throat infections, bronchitis and
oral or genital Hsv flares was recorded.
the incidence of Hsv flares was significantly
greater in the group of patients who
received azathioprine than in patients
who did not do so (1.0 ± 2.6 versus 0.2 ± 0.8
per year, P = 0.04). similarly, significantly
more patients who received azathioprine
treatment experienced newonset
or
worsening viral warts (17.2% versus 3.3%
P = 0.004). these findings are in line with
those from other studies that have reported
an increased incidence of warts in immunosuppressed
patients—an observation that
was initially reported in renal transplant
recipients.8 Contrary to other studies in
the literature,1,5,6,9 however, seksik et al. did
not show an increase in the incidence of
varicellazoster
or cytomegalovirus infection
in patients with iBD who received
immunosuppressant therapy.
what are the implications of seksik et al.’s
findings? a detailed history of herpes infection
should be collected before immunosuppressive
treatment is initiated in
patients with iBD. However, no agreement
exists on what to do when an Hsv or other
infection is diagnosed during immunosuppressive
therapy. viget et al.10 suggest
that immunosuppressant therapy should
be withdrawn as soon as possible after the
identification of an opportunistic infection,
but seksik et al. suggest azathio prine
treatment should be maintained and concomitant
treatment with antiHsv
drugs
should be initiated. no data on the risk
of anogenital cancer related to persistent
HPv infection exist; therefore, in the case
of warts, suspension of immuno suppressive
treatment is advisable.
importantly, the findings from this
study suggest that gynecological examination
and cervical cancer screening should
be planned for women with iBD before
and after immuno suppressant treatment.
HPv vaccination is safe, immunogenic
and highly effective against infection with
specific species of HPv. Predictive data
also indicate that implementation of HPv
vaccination within a national screening
program is likely to be more costeffective
than current clinical practice methods.
the increasing incidence of HPv infection
in young women with iBD also indicates
that, in the future, emphasis may be placed
on the new generation of recombinant
HPv vaccines.
Dipartimento di Medicina, Pneumologia e
Fisiologia della Nutrizione, Università di
Palermo, Palermo, Italy (M. Cottone, S. Renna).
Correspondence: M. Cottone, Dipartimento di
Medicina, Pneumologia e Fisiologia della
Nutrizione, Università di Palermo. Ospedale V.
Cervello, Via Trabucco 180, 90146 Palermo,
Italy
[email protected]
doi:10.1038/nrgastro.2009.110
competing interests
The authors declare no competing interests.
1. Toruner, M. et al. Risk factors for opportunistic
infections in patients with inflammatory bowel
disease. Gastroenterology 134, 929–936
(2008).
2. Lichtenstein, G. R. et al. serious infections and
mortality in association with therapies for
Crohn’s disease: TReAT registry. Clin.
Gastroenterol. Hepatol. 4, 621–630 (2006).
3. Beaugerie, L. et al. The use of
immunomodulators and biologics in
inflammatory bowel diseases (iBD): a crosssectional
French nationwide cohort 2004–
2005 [Abstract]. Gastroenterology
130 (4 suppl. 2), A2 (2006).
4. Kane, s., Khatibi, B. & Reddy, D. Higher
incidence of abnormal Pap smears in women
with inflammatory bowel disease. Am. J.
Gastroenterol. 103, 631–636 (2008).
5. Korelitz, B. i., Fuller, s. R., warman, J. i. &
Goldberg, M. D. shingles during the course of
treatment with 6-mercaptopurine for
inflammatory bowel disease. Am. J.
Gastroenterol. 94, 424–426 (1999).
6. Gupta, G., Lautenbach, e. & Lewis, J. D.
incidence and risk factors for herpes zoster
among patients with inflammatory bowel
disease. Clin. Gastroenterol. Hepatol. 4,
1483–1490 (2006).
7. seksik, P. et al. incidence of benign upper
respiratory tract infections, Hsv and HPv
cutaneous infections in inflammatory bowel
disease patients treated with azathioprine.
Aliment. Pharmacol. Ther. 29, 1106–1113
(2009).
8. spencer, e. s. & Andersen, H. K. viral
infections in renal allograft recipients treated
with long-term immunosuppression. Br. Med. J.
2, 829–830 (1979).
9. warman, J. i., Korelitz, B. i., Fleisher, M. R. &
Janardhanam, R. Cumulative experience with
short- and long-term toxicity to
6-mercaptopurine in the treatment of Crohn’s
disease and ulcerative colitis. J. Clin.
Gastroenterol. 37, 220–225 (2003).
10. viget, n., vernier-Massouille, G., salmon-
Ceron, D., Yazdanpanah, Y. & Colombel, J. F.
Opportunistic infections in patients with
inflammatory bowel disease: prevention and
diagnosis. Gut 57, 549–558 (2008).
Credit: CDC images
© 2009 Macmillan Publishers Limited. All rights reserve
Infliximab and ulcerative colitis
No full textExpert Opin Biol Ther. 2006 Apr;6(4):401-8.
Infliximab and ulcerative colitis.
Cottone M, Mocciaro F, Modesto I.
Università di Palermo, Istituto di Medicina Generale e Pneumologia, Via Trabucco
180, Palermo, Italy. [email protected]
Tumour necrosis factor (TNF)-alpha is an inflammatory cytokine that plays a main
role in the inflammatory process underlying inflammatory bowel disease (IBD).
Despite the fact that the cytokine profiles associated with ulcerative colitis
(UC) and Crohn's disease (CD) are classically considered different (a Th2 pattern
in UC and a Th1 pattern in CD), there are several evidences in vitro and in vivo
that TNF-alpha has an important role in UC. For this reason, infliximab, the
chimeric monoclonal antibody to TNF-alpha, has been evaluated in the therapy of
UC. The drug has been evaluated in different clinical settings both in adults and
in children: in moderate-severe steroid-dependent UC, in severe refractory UC as
rescue therapy, in active non-steroid-refractory UC, in resistant pouchitis and
in maintenance of moderate-severe UC responsive to infliximab. On the basis of
the randomised controlled trials (RCTs), it is possible to draw the following
conclusions for adults: infliximab seems active in severe steroid-refractory UC,
allowing colectomy to be spared even if further controlled trials are needed with
a larger sample of patients adopting strict and well-defined inclusion criteria.
The drug seems active in inducing remission after 8 weeks in steroid-refractory
patients, in patients taking steroids (even if it is not clear at which dosage of
steroid dependence the drug is more active) and also in patients failing
aminosalicylates therapy. The long-term response of infliximab in comparison to
placebo in these subgroups of patients is not clinically impressive even if it is
statistically significant. Further trials are warranted in order to establish the
role of infliximab in steroid-dependent UC (defined with clear criteria), in
maintaining remission after severe UC, in non-steroid-dependent moderate-severe
UC and in refractory pouchitis. For children it is not possible to draw the same
conclusions, due to a lack of RCTs, despite the encouraging data coming from open
studies, mainly in steroid-refractory UC.
PMID: 16548766 [PubMed - indexed for MEDLINE
Cytomegalovirus and Inflammmatory bowel disease:is there a link ?
No full text1. World J Gastroenterol. 2006 Aug 14;12(30):4813-8.
Cytomegalovirus and inflammatory bowel disease: is there a link?
Criscuoli V, Rizzuto MR, Cottone M.
Division of Internal Medicine, University of Palermo, V. Cervello Hospital Via
Trabucco 180, Palermo 90100, Italy.
The objective of this report is to give an overall view of the epidemiological,
clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection
in inflammatory bowel disease (IBD). A review of published reports on this topic
was carried out, with particular attention paid to the selection of patients
included in studies and the diagnostic methods employed. CMV is frequently
associated with IBD. In some cases, CMV infection is associated with a poor
outcome but it is not clear which patients are more likely to be affected and in
which stage of the disease. The use of anti-viral therapy in IBD is controversial
and an empirical study with controls is needed. The natural history of CMV
infection related to the development and treatment of IBD has not been clarified
but it is important to take it in consideration because of the possibility of
viral persistence in the immunocompromised host and viral interaction with the
immune system
Postoperative maintenance therapy for inflammatory bowel disease
No full text. Curr Opin Gastroenterol. 2006 Jul;22(4):377-81.
Postoperative maintenance therapy for inflammatory bowel disease.
Cottone M, Orlando A, Modesto I.
Department of General Medicine, Pneumology and Nutrition Clinic, Palermo
University, Palermo, Italy.
PURPOSE OF REVIEW: This review will highlight the knowledge gained from studies
published in the year 2005 on maintenance treatment after surgery for
inflammatory bowel diseases.
RECENT FINDINGS: In Crohn's disease the role of smoking in increasing the risk of
relapse and recurrence after surgery is confirmed. Ornidazole seems effective in
reducing endoscopic recurrence and clinical relapse after surgery. Probiotics do
not appear to be effective in preventing endoscopic recurrence and clinical
relapse: a controlled placebo trial showed that Lactobacillus johnsonii is not
effective in preventing endoscopic recurrence. A retrospective study suggested
that enteral nutrition after surgery may reduce the clinical relapse.
Pathophysiological studies underlined the value of probiotics in pouchitis.
SUMMARY: In Crohn's disease postoperative maintenance treatment is disappointing.
Giving up smoking is still the only effective measure. Mesalamine remains the
drug that has been widely studied with large trials and meta-analysis.
Encouraging results come from small trials on antibiotics. Azathioprine and
6-mercaptopurine must be evaluated in better designed controlled trials. There is
no evidence in favour of probiotics as an effective therapy to prevent
recurrence. Enteral nutrition after surgery is a candidate new therapy, but
further controlled trials are needed. Pathophysiological studies confirm the
beneficial role of probiotics in pouchitis
Radiofrequency thermal ablation vs percutaneous ethanol injection for small hcc in cirrhosis:metanalysis of randomized controlled trials
No full text1. Am J Gastroenterol. 2009 Feb;104(2):514-24. Epub 2009 Jan 13.
Radiofrequency thermal ablation vs. percutaneous ethanol injection for small
hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled
trials.
Orlando A, Leandro G, Olivo M, Andriulli A, Cottone M.
Department of Medicine, Pneumology and Nutrition Clinic, V. Cervello Hospital,
University of Palermo, Piazza Mameli 1, Palermo, Italy. [email protected]
OBJECTIVES: Radiofrequency thermal ablation (RF) and percutaneous ethanol
injection (PEI) have been employed in the treatment of small hepatocellular
carcinoma (HCC) as curative treatments. The aim of the study was to review the
available evidence comparing RF to PEI for small HCC.
METHODS: Search strategy: Cochrane, MEDLINE, CANCERLIT, and ENBASE databases were
used. Selection criteria: randomized clinical trials evaluating RF vs. PEI. Data
were extracted from each randomized controlled trial (RCT). Primary outcomes were
overall survival and local recurrence. Meta-analysis software was used and risk
differences (RDs) and their 95% confidence intervals and Q-test for heterogeneity
were calculated.
RESULTS: Five RCTs were identified including 701 patients. The overall survival
was significantly higher in patients treated with RF than in those treated with
PEI (RD 0.116, 95% CI 0.173/0.060; heterogeneity not present). Local recurrence
rate is significantly higher in patients treated with PEI than in those treated
with RF. In the RF group the 1, 2, and 3 years cancer-free survival rates were
significantly better than in the PEI-treated patients (respectively: RD 0.098-95%
CI 0.006/0.189; heterogeneity P=0.57; RD 0.187, 95% CI 0.082/0.293; heterogeneity
P=0.98; RD 0.210, 95% CI 0.095/0.325; heterogeneity P = 0.78). A small number of
adverse events were reported in the two treatments.
CONCLUSIONS: RF ablation is superior to PEI in the treatment of small HCC with
respect to overall survival, 1, 2, and 3 years survival rates, 1, 2, and 3
cancer-free survival rates, and tumor response. RF shows a significantly smaller
risk of local recurrence
- …
