Article pp.117-126 du Vol.3 n°2 (2009)

DOI 10.1007/s11725-009-0152-x

REVUE DE PRESSE /PRESS REVIEW

© Springer-Verlag 2009

Budesonide for maintenance of remission in Crohn

s disease

Benchimol EI, Seow CH, Otley AR, Steinhart AH (2009) Cochrane Database Syst Rev 1:CD002913

Background: Corticosteroids have been shown to be effective for induction, but not maintenance of remission in Crohn’s disease. However, significant concerns exist regarding their risk for adverse events, particularly when used for long treatment courses. Budesonide is a gluco- corticoid with limited systemic bioavailability due to extensive first-pass hepatic metabolism. Budesonide has been shown to be effective for induction of remission in Crohn’s disease.

Objectives: To evaluate the efficacy and safety of oral budesonide for maintenance of remission in Crohn’s disease.

Search strategy: The following electronic databases were searched: Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Refe- rence lists of articles, as well as conference proceedings were manually searched. Study authors, study sponsors and pharmaceutical companies were also contacted.

Selection criteria: Randomized controlled trials compar- ing budesonide to a control treatment, or comparing two doses of budesonide, were included. The study population included patients of any age with Crohn’s disease in remission. The primary outcome was maintenance of remission at various reported follow-up times during the study, up to 12 months following enrollment. Secondary outcomes included: time to relapse, mean change in CDAI, clinical, histological or endoscopic improvement, improve- ment in quality of life, adverse events and study withdrawal.

Data collection and analysis: Two independent investi- gators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad’s criteria. A random or fixed effects model was chosen based on an assessment of heterogeneity, and studies were weighted using the DerSimonian and Laird or the Mantel-Haenszel method accordingly. Meta-analysis was performed using RevMan 4.2.10 software.

Main results: Eleven studies were included in the review:

8 studies compared budesonide with placebo, one compared

budesonide to 5-aminosalicylates, one compared budesonide to traditional systemic corticosteroids, and one compared two doses of budesonide with no control group. Eight studies used a controlled ileal release form of budesonide, while three used a pH-modified release formulation. Budesonide 6 mg daily was no more effective than placebo for maintenance of remission at 3 months (RR: 1.25; 95% CI: [1.00 to 1.58];

P= 0.05), 6 months (RR: 1.15; 95% CI: [0.95 to 1.39];

P= 0.14), or 12 months (RR: 1.13; 95% CI: [0.94 to 1.35];

P= 0.19). Budesonide was not more effective than weaning doses of prednisolone for maintenance of remission at 12 months (RR: 0.79; 95% CI: [0.55 to 1.13];P= 0.20), but was better than mesalamine 3 g per day (RR of remission 2.51; 95% CI: [1.03 to 6.12];P= 0.04). Budesonide 3 mg daily was more effective than placebo at 3 months (RR: 1.31; 95%

CI: [1.03 to 1.67];P= 0.03). This benefit was not sustained at 6 months (RR: 1.10; 95% CI: [0.81 to 1.50];P= 0.53), or 12 months (RR: 1.04; 95% CI: [0.84 to 1.30];P= 0.70).

No differences in efficacy were detected based on the different formulations of budesonide, methods used to induce remission, or budesonide dose. The use of budesonide 6 mg resulted in slight improvements in CDAI scores when assessed at 6 months (WMD:–24.3; 95% CI: [–46.31 to–2.29]; P= 0.03) and 12 months (WMD:–23.49; 95%

CI: [–46.65 to–0.32];P= 0.05) and mean time to relapse of disease (WMD: 59.93 days; 95% CI: [19.02 to 100.84];

P= 0.004). Adverse events were more frequent in patients treated with 6 mg of budesonide compared with placebo (RR: 1.49; 95% CI: [1.01 to 2.19]; P= 0.05), but not in patients using lower doses of budesonide. These events were relatively minor and did not result in increased rates of study withdrawal. Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg daily (RR: 2.88; 95% CI: [1.72 to 4.82]; P < 0.0001) and 3 mg daily (RR: 2.73; 95% CI: [1.34 to 5.57];P= 0.006) compared with placebo.

Authors’ conclusions: Budesonide is not more effective than placebo or weaning prednisolone for maintenance of remission in Crohn’s disease. Some modest benefits are noted in patients receiving budesonide compared with placebo in terms of lower CDAI scores and longer time to relapse of disease. However, these benefits are offset by higher treatment-related adverse event rates and more frequent adrenocorticoid suppression in patients receiving

budesonide. Therefore, budesonide is not recommended for maintenance of remission in Crohn’s disease.

Commentaires :La Cochrane Collaboration a travaillé de façon intensive sur le bénéfice des différentes thérapeu- tiques disponibles dans le maintien en rémission de la maladie de Crohn. La qualité des méta-analyses est excellente, et les questions posées sont pertinentes. Elles semblent aujourd’hui sonner le glas de la place de plusieurs thérapeutiques alternatives aux immunosuppres- seurs dans le maintien en rémission de la maladie de Crohn. Avec le budésonide, les études contrôlées randomi- sées intégrées dans la méta-analyse sont souvent d’excel- lente qualité (score de Jadad), mais la difficulté provient de la variation des doses utilisées (3 à 6 mg par jour) et des médicaments proposés dans les groupes témoins (placebo, mésalazine, stéroïdes classiques). La principale conclusion invite à ne pas recommander l’utilisation du budésonide dans le traitement d’entretien de la maladie de Crohn en rémission. S’il existe un CDAI significativement plus faible et une survenue de rechute plus tardive dans le groupe des malades traités par budésonide à la posologie de 6 mg par jour, le niveau du bénéfice n’est pas cliniquement très pertinent (variation du CDAI de 40 points, rechute différée de deux mois, pas de différence dans la proportion de malades en rémission à 3, 6 et 12 mois). L’absence d’efficacité par rapport au placebo est observée pour les doses de 3 et 6 mg par jour, mais des posologies supérieures (9 mg) n’ont pas été évaluées. Finalement, les effets indésirables sont rapportés plus fréquemment chez les malades ayant une posologie de 6 mg, ce qui va rendre encore plus délicat le challenge d’une évaluation d’effica- cité pour une posologie supérieure.

Cotation :

L. Siproudhis

Omega-3 fatty acids (fish oil) for maintenance of remission in Crohn

s disease

Turner D, Zlotkin SH, Shah PS, Griffiths AM (2009) Cochrane Database Syst Rev 1:CD006320

Background: The anti-inflammatory effects of n-3 (omega-3 fatty acids, fish oil) have been suggested to be beneficial in chronic inflammatory disorders such as inflammatory bowel disease.

Objectives: To systematically review the efficacy and safety of n-3 for maintenance of remission in Crohn’s disease (CD).

Search strategy: The following databases were searched from their inception without language restriction: Cochrane Central Register of Controlled Trials, Medline, Embase, Healthstar, Pubmed, and ACP journal club. Experts were contacted for unpublished data.

Selection criteria: Randomized placebo-controlled trials (RCT) of n-3 for maintenance of remission in CD were included. Studies must have enrolled patients of any age group, who were in remission at the time of recruitment, and were followed for at least six months. The intervention must have been fish oil or n-3 given in predefined dosage. Co- interventions were allowed only if they were balanced between the study groups. The primary outcome was the relapse rate and secondary outcomes included change in disease activity scores, time to first relapse and adverse events.

Data collection and analysis: Two independent investi- gators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad’s criteria. Meta-analyses were performed using RevMan 4.2 software weighted by the Mantel-Haenszel method. Random or fixed effect models were used according to degree of heterogeneity and subgroup analyses were performed in an attempt to explore possible sources of heterogeneity.

Main results: Six studies were eligible for inclusion.

There was a marginal significant benefit of n-3 therapy for maintaining remission (RR: 0.770; 95% CI: [0.61 to 0.98];

P= 0.03). However, the studies were both clinically and statistically heterogeneous (P= 0.03, I [2] = 58%). Two large studies showed negative results. When considering the estimated rather than the observed 1-year relapse rate of these two studies, the benefit was no longer statistically significant (RR: 0.59; 95% CI: [0.34 to 1.03];P= 0.06). A funnel plot suggested publication bias. No serious adverse events were recorded in any of the studies but in pooled analyses there was a significantly higher rate of diarrhoea (RR: 1.36; 95% CI: [1.01 to 1.84]) and symptoms of the upper gastrointestinal tract (RR: 1.98; 95% CI: [1.38 to 2.85]) in the n-3 treatment group.

Authors’ conclusions: Omega-3 fatty acids are safe but probably ineffective for maintenance of remission in CD.

The existing data do not support routine maintenance treatment of Crohn’s disease with omega-3 fatty acids.

Commentaires : Les oméga-3 ont le vent en poupe dans les boutiques bio et au sein de toute la grande famille des compléments alimentaires. Ils ont des vertus anti-inflam- matoires et anti-oxydantes dont le bénéfice est apprécié dans le maintien en rémission de la maladie de Crohn à travers cette méta-analyse. On dispose aujourd’hui de 238 publications dont 17 études contrôlées randomisées, mais finalement l’analyse n’a pu porter que sur six études dont les critères de qualité permettaient de mener un tel travail. Le bénéfice thérapeutique est jugé statistique (RR variant selon les variables et les essais entre 0,6 et 0,8) mais peu pertinent sur le plan clinique : pas de bénéfice dans les travaux numériquement les plus impor- tants, pas de maintien significatif des résultats à un an dans ces études et survenue d’effets secondaires deux fois plus importants (mauvaise haleine, brûlures rétrosternales,

nausées, diarrhées). Il semble aujourd’hui très utile d’attendre des galéniques qui réduisent ces effets secon- daires indésirables avant de proposer ces alternatives.

Cotation :

L. Siproudhis

Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn

s disease

Background: The therapeutic role of 6-mercaptopurine and azathioprine remains controversial due to their perceived relatively slow-acting effect and adverse effects. A meta- analysis was performed to evaluate the efficacy of these agents for the maintenance of remission of quiescent Crohn’s disease.

Objectives: To assess the efficacy of azathioprine and 6-mercaptopurine for maintenance of remission in quiescent Crohn’s disease.

Search strategy: Pertinent studies were selected using the Medline database (1966-May 1998), the Cochrane Con- trolled Trials Register, the Inflammatory Bowel Disease Register, as well as abstracts from major gastrointestinal research meetings and references from published articles and review. This search strategy was updated (1998-May 2008) using the Medline, Embase and International Pharmaceutical Abstracts databases, the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD group Specialized Trials Register.

Selection criteria: Randomized, double blind, placebo- controlled trials of oral azathioprine or 6-mercaptopurine involving adult patients (> 18 years) with quiescent Crohn’s disease.

Data collection and analysis: Data were extracted by three independent observers (EP, MC, LRS) based on the intention to treat principle. Peto odds ratios (OR) and 95%

confidence intervals for maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined.

Main results: Seven trials of azathioprine therapy and one of 6-mercaptopurine were included in the review.

Azathioprine and 6-mercaptopurine had a positive effect on maintaining remission. The Peto OR for maintenance of remission with azathioprine was 2.32 (95% CI: [1.55 to 3.49]) with a NNT of 6. The Peto OR for maintenance of remission with 6-mercaptopurine was 3.32 (95% CI: [1.40 to 7.87]) with a NNT of 4. Higher doses of azathioprine

improved response. A steroid sparing effect with azathioprine was noted, with a Peto OR of 5.22 (95% CI: [1.06 to 25.68]) and NNT of 3 for quiescent disease. Withdrawals due to adverse events were more common in patients treated with azathioprine (Peto OR: 3.74; 95% CI: [1.48 to 9.45], NNH = 20) than with placebo.

Authors’ conclusions: Azathioprine and 6-mercaptopur- ine are more effective than placebo for maintenance of remission in Crohn’s disease. Higher response rates were obtained with azathioprine than 6-mercaptopurine. However, the one study evaluating 6-mercaptopurine used a relatively low dose of the drug. Future studies should look at the effect of higher doses of 6-mercaptopurine. There is weak evidence for a steroid sparing effect with azathioprine treatment.

Commentaires :Azathioprine et 6-MP sont deux médica- ments efficaces dans le maintien en rémission de la maladie de Crohn. Cette donnée peut apparaître une lapalissade à bon nombre de cliniciens impliqués dans la prise en charge thérapeutique des maladies inflammatoires chroniques de l’intestin. L’immense intérêt de cette méta-analyse est d’en avoir quantifié leurs effets. Ces deux thérapeutiques ont une très nette efficacité dans le maintien en rémission de la maladie de Crohn (avec un NNT moyen de trois) et à réduire nettement le niveau de corticodépendance des malades. Il y a un bénéfice à augmenter les posologies de l’azathioprine (1 à 2,5 mg/kg) pour obtenir un gain d’efficacité, mais cette donnée n’est pas documentée actuellement pour la 6-MP. Les études montrent une petite supériorité d’efficacité de l’azathioprine, mais cela peut être lié aux faibles posologies de la 6-MP utilisées dans les essais contrôlés disponibles. Cette méta-analyse souligne et quantifie la survenue d’événements indésirables préoccu- pants : l’interruption thérapeutique en rapport avec un effet secondaire y est trois fois plus fréquente par rapport au placebo.

Cotation :

L. Siproudhis

Systematic review on the efficacy and

safety of injectable bulking agents for passive fecal incontinence

Luo C, Samaranayake C, Plank LD, Bisset IP (2009) Colorectal Dis (in press)

Objective: The aim of this study was to systematically review all published evidence to determine the efficacy and safety of injectable bulking agents for passive fecal incontinence (FI) in adults.

Methods: Electronic searches were performed for Med- line, Embase, ISI Web of Knowledge and other relevant databases. Hand searching of relevant conference

proceedings was undertaken. Studies were considered if they met the predefined inclusion criteria of more than ten adult patients and receiving an injectable bulking agent for passive fecal incontinence with a validated means of assessing preoperative and postoperative incontinence.

Results: Thirteen case series studies and one randomized placebo-controlled trial (RCT) were included with a total of 420 patients. Two completed RCTs with placebo control were identified but results were unobtainable. Coaptite, Contigen, Durasphere, EVOH and PTQ injections were assessed with 24, 73, 83, 21 and 208 patients respectively.

Most studies reported a statistically significant improvement in incontinence scores and quality of life. No statistically significant difference was found between the treatment and placebo arms in the RCT. No serious adverse events were reported.

Conclusions: Currently there is little evidence for the effectiveness of injectable bulking agents in managing passive FI. The inability to obtain results from two further RCTs concerned the reviewers and hindered their ability to

make strong recommendations. The identified injectable bulking agents appear to be safe with only minor complications reported.

Commentaires : Les biomatériaux inertes semblent une alternative séduisante à la prise en charge thérapeutique de l’incontinence fécale. Il s’agit en effet d’une approche mini- invasive dont l’objectif serait de compenser l’hypotonie de repos du canal anal ou combler des zones de déformation cicatricielle responsables des troubles de la continence.

Cette revue systématique (n = 420) n’incite pas à pour- suivre des projets thérapeutiques de cette nature chez les malades, alors même qu’elle porte principalement sur des études ouvertes (une seule étude contrôlée randomisée). La plupart des études analysées montrent une amélioration significative des scores symptomatiques et de qualité de vie, mais là encore la pertinence clinique est mince (sauf dans trois études) et de peu d’intérêt en pratique clinique (Tableau 1).

Cotation :

L. Siproudhis

Legend:

PTQ (Case Series) PTQ (RCT) Durasphere (CS)

Coaptite (CS) EVOH (CS) Contigen (CS) Number of participants at longest follow-up

16 33 12 10 7 10 5 22 22 33 16 15 11 24 16 73

0%

10%

20%

30%

40%

50%

60%

70%

80%

Gaj Soerensen

Jorge Lindsey

de la PortillaTjandra ψ

Tjandra Ω Siproudhis

α Siproudhis

β

Altomare Irukulla Davis Aigner Ezio

Farmer Stojkovic α = PTQ arm; β = Pacebo arm (saline) ψ = US guided; Ω = Non-US guided

* = Statistically significant (P<0.05)

*

*

* *

*

* *

*

*

*

*

*

* *

Tableau 1 Rapportant le pourcentage d’amélioration par rapport aux données préthérapeutiques en fonction de la nature des biomatériaux utilisés

Risk of late bleeding following hemorrhoidal banding in patients on antithrombotic prophylaxis

Am J Surg 196:994–999

Background: The risk of bleeding following rubber band ligation of internal hemorrhoids is 1-2%. This risk may be increased in patients taking antithrombotic therapy. The goal of the current study was to find a safer approach to banding without increasing the risk of bleeding.

Methods: This retrospective review identified patients undergoing banding while on antithrombotic therapy.

These medications were held for 7-10 days following the procedure. The number of bands placed while on antithrombotic therapy and their post band complications were recorded.

Results: There were 605 bands placed on 364 patients taking antithrombotic medications. There were 23 compli- cations involving bleeding, a value that was not statistically different from those not taking antithrombotic therapy.

Patients on clopidogrel experienced 50% of the significant bleeding episodes and 18% of the insignificant bleeding episodes.

Conclusions: Holding antithrombotic medication follow- ing banding appears to equalize the risk of bleeding to that of patients not taking antithrombotic medications. Patients taking clopidogrel may be at higher risk for bleeding complications.

Commentaires :Voici une étude assez troublante basée sur un bon sens de pratique de soins mais assez peu pertinente par ses conclusions du fait des faiblesses à la fois pathogéniques et méthodologiques. En effet, les auteurs ont pu proposer aux malades ayant un traitement anticoagulant ou anti-agrégant d’interrompre cette thérapeutique après ligature élastique pendant sept à dix jours. Ils observent finalement un taux de complications hémorragiques suffisamment faibles pour inviter à poursuivre leur pratique dans les mêmes conditions, sauf peut-être avec le clopidogrel (Tableau 2). Cette déduction est certainement hâtive parce qu’il ne s’agit que d’un travail rétrospectif,

que les effectifs par sous-groupe sont très différents, que la nature des anticoagulants et des anti-agrégants est diversifiée, parce que la période d’analyse du risque hémorragique est courte, parce que le risque d’accident ischémique lié à l’arrêt des médicaments anti-agrégants et anticoagulants n’est pas pris en compte. Lecteur, sois donc méfiant et critique de tels travaux même lorsqu’ils sont publiés dans de grandes revues.

Cotation :

L. Siproudhis

Ciprofloxacin or metronidazole for the treatment of perianal fistulas in patients with Crohn

s disease: a randomized, double blind, placebo-controlled pilot study

Thia KT, Mahadevan U, Feagan BC, et al (2009) Inflamm Bowel Dis 15:17-24

Background: Although metronidazole and ciprofloxacin are used to treat perianal Crohn’s disease (CD), no placebo- controlled trials have been performed.

Methods: We performed a placebo-controlled pilot trial to evaluate the efficacy and safety of metronidazole and ciprofloxacin in patients with perianal CD. Twenty-five patients with CD and actively draining perianal fistulas were randomized to receive ciprofloxacin 500 mg, metro- nidazole 500 mg, or placebo twice daily for 10 weeks.

Remission and response of perianal fistulas were defined as closure of all fistulas and closure of at least 50% of fistulas that were draining at baseline, respectively. The primary endpoint was remission at 10 weeks.

Results: Ten patients were randomized to ciprofloxacin, 7 to metronidazole, and 8 to placebo. Remission at week 10 occurred in 3 patients (30%) treated with ciprofloxacin, no patients (0%) treated with metronidazole, and 1 patient (12.5%) treated with placebo (P= 0.41). Response at week 10 occurred in 4 patients (40%) treated with ciprofloxacin, 1 patient (14.3%) treated with metronidazole, and 1 patient

Tableau 2 Évaluation brute des accidents hémorragiques (faibles et importants) en fonction de la nature de l’anti-agrégant/anticoagulant

Medication No of patients No of bands Insignificant bleeds

per banding

Significant bleeds per banding

Aspirin 81 mg 174 282 7 (2.4%) 3 (1.1%)

Aspirin 325 mg 109 177 5 (2.8%) 0 (0%)

Clopidogrel 75 mg 18 35 3 (8.6%) 3 (8.6%)

NSAIDs 42 74 1 (1.4%) 0 (0%)

Coumadin 21 37 1 (2.7%) 0 (0%)

Totals 364 605 17 (2.8%) 6 (0.9%)

(12.5%) treated with placebo (P= 0.43). Termination of the trial prior to week 10 occurred in 1 patient (10%) treated with ciprofloxacin, 5 patients (71.4%) treated with metro- nidazole, and 1 patient (12.5%) treated with placebo (P= 0.02). No serious adverse events occurred.

Conclusion: Remission and response occurred more frequently in patients treated with ciprofloxacin but the differences were not significant in this pilot study.

Ciprofloxacin was well tolerated.

Commentaires :Ce travail prospectif randomisé reste une étude pilote ayant vraiment un faible effectif. Il avait pour objectif de comparer l’efficacité de deux antibiotiques (métronidazole, ciprofloxacine) pendant dix semaines dans le contrôle des manifestations suppuratives anales de la maladie de Crohn. La méthodologie de l’essai est correcte, mais on comprend assez mal le faible nombre de malades inclus (25 pour 12 centres sollicités) et la justification d’une publication à cette étape si précoce du travail. Malgré l’absence de données significatives (effectif faible), cette étude offre deux champs de réflexion : l’efficacité potentielle des traitements antibiotiques au long cours et la supériorité de la ciprofloxacine sur la métronidazole en termes de réponse et d’événements indésirables. Une affaire à suivre…

Cotation :

L. Siproudhis

Peri-operative adjuvant therapy with infliximab in complicated anal Crohn

s disease

Kraemer M, Kirschmeier A, Marth T (2008) Int J Colorectal Dis 23:965–969

Purpose: Infliximab may represent an adjuvant to surgical therapy in patients with severe anal Crohn’s disease as it has been shown to affect rapid remissions in a proportion of cases.

Patients and methods: Nineteen patients underwent infliximab therapy 5 mg/kg peri-operatively to scheduled anal reconstructive surgery for complicated fistulising anal Crohn’s disease.

Results: One adverse event was recorded (generalized exanthema with subsequent resolution). Eight patients showed complete clinical remission refusing further surgery.

One of the eight relapsed during follow-up and was continued on infliximab. Surgery consisted of advancement flaps. It was successful at first attempt in nine of the remaining 11 patients (82%). Operative fistula closure remained unsuccessful in two patients. Overall, 16 of 19 patients (84%) with advanced anal Crohn’s disease had a favorable outcome.

Conclusion: The use of infliximab as adjuvant to surgery in this series of patients with complicated anal Crohn’s disease was safe. Although the data is uncontrolled a positive effect of

infliximab on the outcome of surgery may be postulated since our results compare favorably with other studies.

Commentaires : Encore un travail tentant de préciser le bénéfice d’une approche thérapeutique combinée alliant l’infliximab et l’approche chirurgicale dans le traitement des suppurations anales de la maladie de Crohn. Ce travail rejoint des données récemment rapportées au Journées francophones d’hépatogastroentérologie et d’oncologie digestive (voir rubrique congrès dans ce même numéro). En dépit de carences méthodologiques fortes et d’un faible effectif, deux éléments méritent une évaluation prospective rigoureuse ultérieure : l’infliximab permet dans ce travail une rémission clinique complète dans 40 % des cas en l’absence même de geste chirurgical. Le lambeau rectal d’avancement chez les autres malades est un succès thérapeutique plus de huit fois sur dix. Il est vraisemblable que ces bons résultats ne supportent pas l’épreuve du temps (suivi médian : huit mois).

Cotation :

L. Siproudhis

Outcomes for patients developing anastomotic leak after ileal pouch-anal anastomosis:

does a hand-sewn vs stapled anastomosis matter?

Lian L, Kiran RP, Remzi FH, et al (2009) Dis Colon Rectum 3:387–393

Purpose: Outcomes for patients developing a leak after ileal pouch-anal anastomosis have not been well investigated.

This study explored whether the use of a stapled or hand- sewn anastomosis was associated with different outcomes when an anastomotic leak developed.

Patients and methods: Patients were identified from a prospectively maintained pouch database. Functional out- comes regarding bowel movements, urgency, continence, and seepage were evaluated. The Cleveland Global Quality of Life Score assessed quality of life.

Results: One hundred and seventy-five patients with anastomotic leak (141 stapled and 34 hand-sewn anastomo- sis) were identified. The two groups were similar in gender and diagnosis. Patients with hand-sewn anastomosis were younger (P= 0.04), had less peri-operative steroid use (P= 0.05), more proximal diversion (P= 0.02), and S-pouch creation (P= 0.003). More hand-sewn cases had intraopera- tive transfusion (P= 0.04) and postoperative haemorrhage within the pelvis (P= 0.003). Long-term pouch failure was 35.3% in the hand-sewn group and 12% in the stapled group (P= 0.002), which was confirmed by Kaplan-Meier analysis (log-rank, P= 0.007). On multivariate analysis, leak after hand-sewn anastomosis was independently asso- ciated with pouch failure. Leak after stapled anastomosis carried a lower incontinence rate at 5 years (P= 0.03), while

hand-sewn had higher nocturnal seepage rate at 3, 5, and 10 years, and most recent follow-up. Cleveland Global Quality of Life Score was comparable between the groups during follow-up.

Conclusion: Outcomes including functional results and pouch failure rates for patients developing a leak after stapled anastomosis at ileal pouch-anal anastomosis were significantly better than outcomes for patients who develop a leak after hand-sewn anastomosis.

Commentaires : Cet article entretient la polémique qui est manifestement encore d’actualité du choix délicat de l’anastomose iléoanale manuelle après mucosectomie ou mécanique à l’aide d’une pince agrafeuse circulaire.

L’expérience de l’équipe de la Cleveland Clinic (pour le moins défenseurs de la technique mécanique), ici rapportée, étudie le devenir des patients qui ont fait des complications anastomotiques (fistules) en fonction du type d’anastomose confectionnée. Les résultats font apparaître une différence significative en faveur de la technique agrafée. Le maintien du réservoir est significativement plus probable, et le risque d’incontinence à terme moindre. Il convient cependant de pondérer ces résultats par des populations qui apparaissent finalement et honnêtement assez peu comparables (déjà par l’effectif…). Par ailleurs, il faut aussi reconnaître le

« parti pris » de cette équipe peut-être plus habituée à la technique mécanique que manuelle. Cependant, faute de disposer d’une étude contrôlée (serait-elle vraiment justifiée ?), on peut retenir actuellement que la littérature ne permet pas de dégager une attitude consensuelle pour le choix de telle ou telle approche, le débat reste ouvert, et nous attendons la réponse des défenseurs de la technique manuelle !

Cotation :

G. Meurette

Long-term outcome of sacral nerve stimulation for fecal incontinence

Altomare DF, Ratto C, Ganio E, et al (2009) Dis Colon Rectum 1:11–17

Purpose: Sacral nerve stimulation is a safe and effective procedure for fecal incontinence. We investigated whether its efficacy is maintained long-term.

Patients and methods: Sixty patients with fecal incon- tinence underwent permanent sacral nerve stimulation.

Patients’ data were prospectively recorded in the national registry of the Italian Group of sacral nerve stimulation. The Wexner score evaluated the severity of fecal incontinence, and data were collected in a bowel function diary. Quality of life was evaluated by the Italian version of the Medical Outcomes Survey Short Form (SF-36) questionnaire.

Results: Fifty-two patients were available for long-term follow-up lasting at least 5 years. Compared with baseline, the Wexner score decreased significantly after definitive implantation (from 15 ± 4 to 5 ± 5;P< 0.001). At least 50%

improvement in continence was achieved in 74% of the patients, and at least 70% improvement (median value) was achieved in 50%. The mean number of solid/liquid incontinence episodes decreased significantly from 0.5 (± 0.5) to 0.1 (± 0.3) per day (P= 0.004). Quality of life improved in all domains. The overall mean improvement in SF-36 scores was 39.8%. Both mean resting and squeeze anal pressures increased significantly, and maximum volume tolerated decreased significantly.

Conclusions: Sacral nerve stimulation maintains its efficacy long-term, not only in regard to control of symptoms but also regarding quality of life.

Commentaires : Est-il encore nécessaire de discuter la place de la neurostimulation des racines sacrées dans le traitement de l’incontinence fécale ? Cet article apporte un argument supplémentaire, en rapportant les résultats à long terme (supérieur à cinq ans) de cette technique. Le bénéfice est significatif en termes de fonction et de qualité de vie.

Même si les résultats des articles de cette équipe paraissent parfois un peu optimistes, avec des scores d’incontinence que plusieurs autres auteurs peinent à atteindre, on peut néanmoins retenir globalement que la technique offre des résultats satisfaisants et stables à long terme.

Cotation :

G. Meurette

Toilet reading habits in Israeli adults

Although toilet reading (TR) is a common habit, the effect of TR on bowel movements is neglected in the medical literature. Our hypothesis was that TR provides a distraction and acts as an unconscious relaxation technique and allows an easier defecation process. The aim of this study was to assess how common is TR and to map the reading/playing toilet habits in the Israeli adult population. In addition, we aimed to explore a possible connection between TR and the nature of bowel habits in general and constipation and haemorrhoids in particular. Five hundred adults who represent the diverse demographic backgrounds have been asked to fill an anonymous short questionnaire. The subjects were questioned regarding their demographic details, their TR and playing habits, their bowel habits, whether they suffer from haemorrhoids and whether they use some sort of faecal softener. We found that TR is common and involves 52.7% of the population. Males, younger age, secular

population, higher education level and white-collar workers compose the TR profile. Although toilet readers spent significantly more time in the toilets, no differences were noted for the type or frequency of stools. Nevertheless, the TR group considered themselves to be less constipated (8.0 vs 13.7%) and had more haemorrhoids (23.6 vs 18.2%).

These differences, however, were not significant. Toilet reading is a common and benign habit. It is involved with a longer time spent in the toilet. It seems to be more for fun and not necessarily to solve or due to medical problems.

Commentaires :Il a fallu attendre le troisième millénaire pour savoir pourquoi les hommes et les femmes lisaient aux toilettes. Comme le soulignent les auteurs, cette habitude existe probablement depuis l’invention du livre et s’est sans doute largement développée depuis celle de l’imprimerie. Il y eut bien une brève controverse dans le Lancet en 1989, des avis d’expert suggéraient que la lecture aux toilettes favorisait la constipation et l’apparition d’hémorroïdes, alors que d’autres suggéraient le contraire. Le niveau de preuve dans l’EBM était bien faible. Depuis cette date… rien. L’hypothèse de ce travail était que la lecture aux toilettes agissait comme une technique de relaxation et favorisait les efforts défécatoires. Un échantillon de 500 Israéliens adultes, hommes et femmes, représentatif de la population (y compris les origines ethniques et religieuses), a donc répondu à un questionnaire. Le taux de réponse était formidable, 499 questionnaires étant exploitables ! Il en résulte que les hommes lisent plus souvent que les femmes (64,1 vs 41 % ; p < 0,0001), que plus on vieillit moins on lit aux toilettes, que la lecture aux toilettes est plus fréquente chez les sujets ayant un niveau d’éducation élevée et que l’on y lit le plus souvent ce qui tombe sous la main (42 %) ou les journaux (38 %). La lecture aux toilettes n’était associée à aucun trouble défécatoire ni modification du transit. Finalement, dans 84 % des cas, les sujets lisaient aux toilettes pour passer le temps ou avoir un moment de tranquillité ! À noter enfin qu’il existe un facteur familial…

Cotation :

B. Coffin

Impact of complex Crohn

s disease on

the outcome of laparoscopic ileocecal resection:

a comparative clinical study in 124 patients

Purpose: This prospective study assessed the feasibility of laparoscopic ileocolonic resection for complex Crohn’s disease, i.e., recurrence or complication from abscess and/or fistula, and compared postoperative outcomes in patients with and without complex Crohn’s disease.

Methods: Between November 1998 and August 2007, 124 laparoscopic ileocolonic resections were attempted for Crohn’s disease: 54 patients with complex Crohn’s disease (group I) and 70 patients without complex Crohn’s disease (group II). Postoperative mortality and morbidity were compared between group I and group II.

Results: Indications for surgery in group I included fistula (43%), abscess (30%), and recurrent disease after ileocolonic resection (27%). Complex Crohn’s disease was significantly associated with increased mean (standard deviations) operative time (214 [13] vs 191 minutes [53], P< 0.05), increased conversion rate to open procedure (37 vs 14%, P< 0.01), and increased use of temporary stoma (39 vs 9%, P< 0.001). No patients died. Overall postoperative morbidity was similar between both groups [17 vs 17%, P= not significant (NS)], including major surgical postoperative complications (7 vs 6%, P= NS).

Mean (SD) hospital stay was not statistically different between both groups (8 [3] vs 7 days [3],P= NS).

Conclusions: This large comparative study suggested that laparoscopic ileocolonic resection for complex Crohn’s disease was feasible and safe with good postoperative outcomes. In our experience, complex Crohn’s disease does not appear as a contraindication to a laparoscopic approach.

Commentaires : Bien que contre-indiquée en théorie, certaines équipes ont publié les résultats de l’approche laparoscopique dans le traitement chirurgical de la maladie de Crohn iléale (MC) complexe, incluant l’abcès, la fistule et la récidive. Toutefois, les effectifs étaient faibles.

L’originalité de cette étude cas-témoin a été de comparer les résultats opératoires de l’approche laparoscopique dans la MC avec et sans complications. En cas de MC complexe, la laparoscopie était significativement associée à une augmentation de la durée opératoire, du taux de conversion et de la nécessité d’une iléocolostomie temporaire. En revanche, la morbidité postopératoire et la durée d’hospi- talisation étaient comparables entre les deux groupes de malades. Sous réserve de l’expertise du centre, l’approche laparoscopie est faisable dans la prise en charge chirurgicale de la MC complexe.

Cotation :

A. Alves

Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin

Elias D, Lefevre JH, Chevalier J, et al (2009) J Clin Oncol 27:681–685

Purpose: To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in

comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC).

Patients and methods: All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreduc- tive surgery plus HIPEC from 1998 to 2003 were evaluated.

Selecting patients constituted the standard group with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time.

Results: Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospec- tively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81 and 51% for the HIPEC group, respectively, and 65 and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P< 0.05, log-rank test).

Conclusion: Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemothera- pies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.

Commentaires :L’originalité de cette étude, issue d’un centre expert, est de rapporter les résultats de la chirurgie carcinologique associée à la chimiohyperthermie intrapér- itonéale (CHIP) pour carcinose péritonéale d’origine colorectale à l’heure des nouveaux médicaments de chimiothérapie, en particulier l’oxaliplatine. Deux groupes de malades ont été comparés de manière rétrospective ; le premier recevant une chimiothérapie intraveineuse seule à base d’oxaliplatine et/ou d’irinotécan et le second ayant une chirurgie carcinologique associée à une CHIP à base d’oxaliplatine et/ou d’irinotécan. La survie globale était significativement meilleure après réalisation d’une CHIP (survie à cinq ans, 51 vs 13 %, p < 0,05 et survie médiane : 63 vs 24 mois, p < 0,05). Cette étude rapporte donc l’efficacité de la CHIP avec les nouveaux médicaments de chimiothérapie dans la prise en charge thérapeutique de la carcinose péritonéale d’origine colorectale. L’utilisation de l’oxaliplatine et/ou d’irinotécan au cours d’une CHIP améliore significativement la survie des malades par rapport à ceux traités uniquement par voie intraveineuse.

Cotation :

A. Alves

Conversion in laparoscopic surgery:

does intraoperative complication influence outcome?

Yang C, Wexner SD, Safar B, et al (2009) Surg Endosc (in press)

Background: Conversion from laparoscopy to laparotomy can be expected in a variable percentage of surgeries.

Patients who experience conversion to a laparotomy may have a worse outcome than those who have a successfully completed laparoscopic procedure. This study aimed to compare the outcomes of converted cases based on whether the case was a reactive conversion (RC, due to an intraoperative complication such as bleeding or bowel injury) or a pre-emptive conversion (PC, due to a lack of progression or unclear anatomy).

Methods: All laparoscopic colorectal procedures con- verted to a laparotomy were retrospectively reviewed from data prospectively entered into an institutional review board-approved database. Patients who underwent an RC were matched with patients who underwent a PC according to age, gender, body mass index (BMI), and diagnosis. Patients who underwent a laparoscopic color- ectal resection (LCR) were taken as the control group. The incidence and nature of postoperative complications, the time to liquid or regular diet, and the length of hospital stay were recorded.

Results: Of 962 laparoscopic procedures performed between 2000 and 2007, 222 (23.1%) converted to a laparotomy were identified. The 30 patients who had undergone an RC were matched with 60 patients who had undergone a PC and 60 patients who had undergone an LCR. The reasons for RC were bleeding in 14 cases, bowel injury in 6 cases, ureteric damage in 3 cases, splenic injury in 3 cases, and other complications in 4 cases. The patients who had undergone RC were more likely to have experienced a postoperative complication (50 vs 27%; P = 0.028), required longer time to toleration of a regular diet (6 vs 5 days; P= 0.03), and stayed longer in the hospital (8.1 vs 7.1 days;

P = 0.080).

Conclusion: Pre-emptive conversion is associated with a better outcome than reactive conversion. Based on this finding, it appears preferable for the surgeon to have a low threshold for performing PC rather than awaiting the need for an RC.

Commentaires :L’originalité de cette étude cas-témoin, issue d’un centre expert en chirurgie colorectale laparosco- pique, est de préciser le bon moment de la conversion. À partir d’une base de données exhaustive, 30 malades ayant eu une conversion due à une complication peropératoire ont été appariés à 60 malades convertis pour des raisons

techniques et à 60 malades opérés par laparoscopie selon, le sexe, l’âge, l’indice de masse corporelle et la maladie. La conversion pour complication peropératoire augmentait significativement la morbidité postopératoire. Les auteurs soulignent dans cette étude l’intérêt d’une conversion rapide en laparotomie afin de ne pas augmenter la morbidité

postopératoire. En effet, il est inutile de persévérer et d’attendre la complication peropératoire pour convertir en laparotomie.

Cotation :

A. Alves