DOI 10.1007/s11725-009-0174-4
REVUE DE PRESSE /PRESS REVIEW
© Springer-Verlag France 2009
The impact of stapled transanal rectal resection on anorectal function in patients with obstructed defecation syndrome
Reboa G, Gipponi M, Logorio M, et al. (2009) Dis Colon Rectum 52: 1598–604
Purpose: A careful preoperative selection of patients was performed in order to identify those eligible for stapled transanal rectal resection to correct obstructed defecation syndrome. The aim was to assess the consequences of surgery on anorectal function and patient outcomes.
Methods: From January 2004 to June 2007, 33 female patients (median age, 56.3 years; range, 27-77 years) eligi- ble for stapled transanal rectal resection completed standard- ized questionnaires for the assessment of constipation (constipation scoring system), quality of life (Patient Assessment of Constipation-Quality of Life Questionary), and patient satisfaction (visual analogue scale). A complete clinical reassessment including anorectal manometry and defecography was performed after one year.
Results: At a median follow-up of 18 months, significant improvement in constipation scoring system, quality of life, and visual analog scale (P < 0.0001) was observed.
Postoperative defecography confirmed the correction of internal rectal prolapse (P < 0.01) and rectocele (P < 0.0001) with an increase in rectal sensitivity (P< 0.0001). Significant correlations were observed between rectocele correction and rectal sensitivity, as evidenced by a decrease in rectal sensory threshold volumes (P= 0.017; ψ = 0.7), increased rectal sensitivity, and patient’s satisfaction index (P= 0,011;ψ= 0,64).
Conclusions: Stapled transanal rectal resection allowed for the correction of rectocele and intussusceptions. These corrections increased rectal sensitivity, diminished symp- toms of obstructed defecation syndrome, and improved the quality of life of patients.
Commentaires : Encore un travail italien évaluant l’efficacité de la résection rectale transanale agrafée dans la prise en charge thérapeutique des malades souffrant de troubles de l’évacuation ! La méthode est jugée efficace à la fois sur les données de la correction anatomique, de l’amélioration symptomatique et de la qualité de vie après un recul moyen de 18 mois. Ces données sont peu originales, et la richesse de la publication réside finalement ailleurs.
Ce travail souligne la sélection importante des malades
candidats à un tel geste chirurgical : un quart des malades adressés au centre de référence semblent réunir les critères du geste, mais seule la moitié de l’effectif sélectionné est opérée (efficacité des thérapeutiques rééducatives, contre- indications au geste sont des critères de non inclusion). Le deuxième intérêt a été d’utiliser des critères d’évaluation validés autres que le score ODS (créé lors et pour le développement de la technique). Finalement, les bons résultats symptomatiques ne s’accompagnent pas nécessai- rement d’une correction adéquate des anomalies anatomi- ques : il persiste en postopératoire une rectocèle de plus de 3 cm et une procidence interne de haut grade chez la moitié de la population d’étude. Les auteurs font l’hypothèse que l’efficacité de la méthode pourrait finalement résider dans l’amélioration des troubles de la sensibilité (et peut-être de la compliance) induite par cette chirurgie de réduction du réservoir rectal. Une piste physiopathologique à suivre…
Cotation :☺☺☺
L. Siproudhis
Pathophysiology of bowel dysfunction in patients with motor incomplete spinal cord injury: comparison with patients with motor complete spinal cord injury
Vallès M, Mearin F (2009) Dis Colon Rectum 52: 1589–97
Purpose: Bowel dysfunction is a major problem in patients with spinal cord injury. Previous work has provided partial information, particularly about motor incomplete lesions.
The purposes of this study were to evaluate the pathophysio- logic features of neurogenic bowel in patients with motor incomplete spinal cord injury and to compare them with those in patients with motor complete lesions.
Methods: Fifty-four patients (59% men; mean age, 43 years) with chronic spinal cord injury and fecal inconti- nence and/or constipation were evaluated; 32 had motor incomplete lesions, and 22 had motor complete lesions.
Clinical assessment, colonic transit time, and anorectal manometry were performed.
Results: Colonic transit time was delayed similarly in patients with motor complete lesions and those with motor incomplete lesions. Anal squeeze pressure was present in most patients with motor incomplete lesions and absent in all
patients with motor complete lesions. The cough-anal reflex was less frequent in patients with motor complete lesions with a neurologic level above T7 (P < 0.05). Rectal sensitivity was less severely impaired in those with motor incomplete lesions (P< 0.05). Most patients in both groups did not show anal relaxation during defecatory maneuvers.
Rectal contractions and anal sphincter activity during distention of the rectum were detected more often in patients with motor complete lesions (P< 0.05).
Conclusion: Many severe pathophysiologic mechanisms are involved in neurogenic bowel; affecting patients with motor incomplete spinal cord injury similarly to those of patients with motor complete lesions with spinal sacral reflexes. The pathophysiologic mechanisms of constipation are obstructed defecation, weak abdominal muscles, impaired rectal sensation, and delayed colonic transit time;
the mechanisms of fecal incontinence are impaired external anal sphincter contraction, uninhibited rectal contractions, and impaired rectal sensation. However, specific evaluation is required in individual cases.
Commentaires :Il s’agit d’un très beau travail de référence qui aborde le problème des troubles fonctionnels anorectaux des blessés médullaires non plus sous le seul angle du niveau lésionnel (le niveau lésionnel T7 est le plus souvent déterminant), mais également sur le caractère complet ou incomplet de la lésion médullaire. Le mode d’exploration et le recueil des données symptomatiques sont optimisés mais finalement assez classiques (temps de transit colique, manométrie anorectale et questionnaire symptomatique). Le message simpliste attendu est que les malades ayant des lésions incomplètes ont des anomalies physiologiques plus discrètes que les malades ayant des lésions médullaires complètes (à hauteur lésionnelle comparable). L’intérêt physiopathologique et les implications thérapeutiques sont finalement moindres, lorsque ces données sont mesurées à l’aune de la nature et de la prévalence des plaintes. Celles-ci semblent, dans ce travail, quantitativement et qualitativement comparables entre les malades qui ont des lésions médullaires complètes et ceux pour lesquels elles sont incomplètes.
Cotation :☺
L. Siproudhis
Factors associated with failure of the artificial bowel sphincter: a study of over 50 cases from Cleveland Clinic Florida
Wexner SD, Jin HY, Weiss EG, et al. (2009) Dis Colon Rectum 52: 1550–7
Purpose: This study investigated the risk factors related to artificial bowel sphincter infection, complications, and failure.
Method: Complications may occur at any time after artificial bowel sphincter implantation. Early-stage compli- cation is defined as any complications that occurred before artificial bowel sphincter activation, whereas late-stage complications are defined as any complications that occurred after device activation. Assessment of the outcomes of all artificial bowel sphincter operations included evaluation of factors related to patient demographics, operative procedu- res, and postoperative events.
Result: From January 1998 to May 2007, 51 artificial bowel sphincter implantations were performed in 47 patients (43; 84.3% female) with a mean age of 48.8 ± 12.5 years (range, 19-79) and a mean incontinence score of 18 ± 1.4 (range, 0-20). In 24 patients (54.5%), the etiology of incontinence was secondary to imperforate anus; 15 (24.2%) patients had obstetric injury or anorectal trauma.
Twenty-three (41.2%) artificial bowel sphincter implanta- tions became infected, 18 (35.3%) of which developed early- stage infection, whereas five (5.9%) had late-stage infection.
One patient in the latter group had associated erosion, and two patients had fistula formation. Late-stage complications continued to increase with time. Multivariate analysis revealed that the time between artificial bowel sphincter implantation and first bowel movement and a history of perineal sepsis were independent risk factors for early-stage artificial bowel sphincter infection.
Conclusion: The time from implantation to first bowel movement and history of perineal infection were risk factors for early-stage artificial bowel sphincter infection and failure.
Late-stage failures were more often the result of device malfunction and indicated the need for mechanical refinement.
Commentaires :Une publication concernant une évalua- tion de pratique de plus à laquelle ce groupe nous habitue au gré des numéros de Dis Colon Rectum. Elle concerne les complications liées à l’implantation d’un sphincter anal artificiel. Celles-ci sont dominées par les complications mécaniques et les infections qui font considérer cette option thérapeutique comme une stratégie lourde. L’originalité du travail réside dans la recherche de facteurs associés à l’infection dans le cadre d’une analyse multivariée où la responsabilité de l’acte lui-même joue peu (histoire passée d’infection pelvipérinéale, délai de l’obtention de la première selle postopératoire) de même que les circons- tances ayant conduit à l’indication (imperforation anale pour la moitié de l’effectif). Sa faiblesse réside probablement dans l’incidence particulièrement élevée des complications infectieuses (près d’un malade sur deux) principalement précoces. Ce taux, à lui seul, devrait inviter à remettre en cause les conditions de réalisation du geste chirurgical lui- même…
Cotation :☺
L. Siproudhis
Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH
Jones N, Vogt S, Nielsen M, et al. (2009) Gastroenterology 137: 489–94
Background and aims: MUTYH-associated polyposis (MAP) is an autosomal recessive disorder caused by mutations in theMUTYH gene. Patients with MAP are at extremely high-risk of colorectal cancer, but the risks of colorectal and other cancers in heterozygous carriers of a single MUTYH mutation are uncertain. We performed a retrospective study of cancer incidence and causes of death among obligateMUTYHheterozygote individuals.
Methods: MAP index cases were identified from poly- posis registers in Germany, The Netherlands, and the United Kingdom. Cancer incidence, cancer mortality, and all causes of mortality data were collected from 347 parents of unrelated MAP index cases and the spouses of three index cases who were also found to be heterozygous for single MUTYH mutations. These data were compared with appropriate national sex-, age-, and period-specific popula- tion data to obtain standardized mortality ratios (SMR) and standardized incidence ratios (SIR).
Results: There was a 2-fold increase in the incidence of colorectal cancer among parents of MAP cases, compared with the general population (SIR, 2.12; 95% confidence interval [CI]: [1.30-3.28]). Their colorectal cancer mortality was not increased significantly (SMR, 1.02; 95% CI: [0.41- 2.10]) nor was overall cancer risk (SIR, 0.92; 95% CI: [0.70- 1.18]), cancer mortality (SMR, 1.12; 95% CI: [0.83–1.48]), or overall mortality (SMR, 0.94; 95% CI: [0.80-1.08]).
Conclusions: The risk of colorectal cancer in heterozy- gous carriers of singleMUTYHmutations who are relatives of patients with MAP is comparable with that of first-degree relatives of patients with sporadic colorectal cancer.
Screening measures should be based on this modest increase in risk.
Commentaires :Une nouvelle publication de cette équipe anglaise qui a beaucoup travaillé sur cette nouvelle forme de polypose. Plusieurs papiers avaient déjà étudié le risque des porteurs monoalléliques de mutations sur MYH. Cette affection étant de transmission récessive, le risque pour les porteurs monoalléliques devrait être théoriquement similaire à celui de la population générale. Les résultats des précédentes études étaient contradictoires et les séries souvent avec de faibles effectifs. Dans cette série inter- nationale avec une large cohorte, le risque de cancer colorectal était multiplié par deux en rapport avec le risque de patients ayant un antécédent de cancer colorectal au premier degré. De surcroît, ces cancers survenaient sans l’existence d’une polypose adénomateuse colique. Les autres
cancers n’étaient pas plus fréquents. La surveillance de ces patients porteurs d’une seule mutation sur MYH doit donc être corrélée à ce risque modéré.
Cotation :☺☺
J.-H. Lefèvre
Capsule endoscopy vs colonoscopy for the detection of polyps and cancer
Van Gossum A, Navas MM, Fernandez-Urien I, et al. (2009) J N Engl J Med 361(3): 264–70
Background: An ingestible capsule consisting of an endo- scopy equipped with a video camera at both ends was designed to explore the colon. This study compared capsule endoscopy with optical colonoscopy for the detection of colorectal polyps and cancer.
Methods: We performed a prospective, multicenter study comparing capsule endoscopy with optical colonoscopy (the standard for comparison) in a cohort of patients with known or suspected colonic disease for the detection of colorectal polyps or cancer. Patients underwent an adapted colon preparation, and colon cleanliness was graded from poor to excellent. We computed the sensitivity and specificity of capsule endoscopy for polyps, advanced adenoma, and cancer.
Results: A total of 328 patients (mean age, 58.6 years) were included in the study. The capsule was excreted within ten hours after ingestion and before the end of the lifetime of the battery in 92.8% of the patients. The sensitivity and specificity of capsule endoscopy for detecting polyps that were 6 mm in size or bigger were 64% (95% confidence interval [CI], 59 to 72) and 84% (95% CI, 81 to 87), respectively, and for detecting advanced adenoma, the sensitivity and specificity were 73% (95% CI, 61 to 83) and 79% (95% CI, 77 to 81), respectively. Of 19 cancers detected by colonoscopy, 14 were detected by capsule endoscopy (sensitivity, 74%; 95% CI, 52 to 88). For all lesions, the sensitivity of capsule endoscopy was higher in patients with good or excellent colon cleanliness than in those with fair or poor colon cleanliness. Mild-to-moderate adverse events were reported in 26 patients (7.9%) and were mostly related to the colon preparation.
Conclusions: The use of capsule endoscopy of the colon allows visualization of the colonic mucosa in most patients, but its sensitivity for detecting colonic lesions is low as compared with the use of optical colonoscopy.
Commentaires : Une belle étude randomisée, multicen- trique en simple insu sur l’efficacité de la capsule pour le dépistage de lésions coliques. Principalement utilisée pour explorer l’intestin grêle, les auteurs ont programmé la capsule pour qu’elle se mette en pause pendant 1 h 45 avant
de reprendre les photographies afin d’explorer principale- ment le côlon. Les malades étaient tous préparés et après élimination de la capsule une coloscopie de contrôle était réalisée. Si la capsule a permis d’explorer la muqueuse colique chez 97 % des patients, elle n’a pas encore la sensitivité et la spécificité suffisante pour devenir un examen de dépistage. Dans cette cohorte de 328 patients à risque de lésions coliques, seuls 60 % des polypes de plus de 1 cm étaient visualisés, et un cancer colorectal sur quatre était manqué par la capsule…Cette nouvelle technologie qui ne permet pas d’éviter la préparation colique n’est donc pas prête encore pour remplacer la colonoscopie…
Cotation :☺☺
J.-H. Lefevre
Laparoscopic vs. open surgery for rectal cancer: long-term oncologic results
Laurent C, Leblanc F, Wütrich P, et al. (2009) Ann Surg 250: 54–61
Objective: The goal was to assess long-term oncologic outcome after laparoscopic vs. open surgery for rectal cancer and to evaluate the impact of conversion.
Summary background data: Laparoscopic resection of rectal cancer is technically feasible, but there are no data to evaluate the long-term outcome between laparoscopic and open approach. Moreover, the long-term impact of conver- sion is not known.
Methods: Between 1994 and 2006, patients treated by open (1994-1999) and laparoscopic (2000-2006) curative resection for rectal cancer were included in a retrospective comparative study. Patients with fixed tumors or metastatic disease were excluded. Those with T3-T4 or N+ disease received long course preoperative radiotherapy. Surgical technique and follow-up were standardized. Survival were analyzed by Kaplan-Meier method and compared with the log-rank test.
Results: Some 471 patients had rectal excision for invasive rectal carcinoma: 238 were treated by laparoscopy and 233 by open procedure. Postoperative mortality (0.8 vs. 2.6%;
P= 0.17), morbidity (22.7 vs. 20.2%;P= 0.51), and quality of surgery (92.0 vs. 94.8% R0 resection; P= 0.22) were similar in the two groups. At five years, there was no difference of local recurrence (3.9 vs. 5.5%;P= 0.371) and cancer-free survival (82 vs. 79%; P= 0.52) between laparoscopic and open surgery. Multivariate analysis con- firmed that type of surgery did not influence cancer outcome.
Conversion (36/238, 15%) had no negative impact on postoperative mortality, local recurrence, and survival.
Conclusions: The efficacy of laparoscopic surgery in a team specialized in rectal excision for cancer (open and
laparoscopic surgery) is suggested with similar long-term local control and cancer-free survival than open surgery.
Moreover, conversion had no negative impact on survival.
Commentaires :Félicitations à l’équipe de Bordeaux qui publie leurs résultats à long terme de la chirurgie laparoscopique pour cancer du rectum sous-péritonéal.
Peu de données étaient jusqu’ici disponibles dans la littérature. Même si la comparaison est historique avec le groupe laparotomie, les résultats carcinologiques de la voie laparoscopique sont identiques à la laparotomie que ce soit le taux de résection R0 ou le pourcentage de récidive locale ainsi que la survie sans récidive chez plus de 200 malades dans chaque groupe. L’autre information importante est l’absence d’impact négatif de la conversion sur les résultats opératoires et les résultats carcinologiques. Cette donnée va à l’encontre de ce qui avait été précédemment publié dans une étude randomisée. Ces très bons résultats soulignent l’expertise de cette équipe dans la prise en charge des cancers du rectum sous-péritonéaux.
Cotation :☺☺
A. Alves
Thiopurine therapy is associated with postoperative intra-abdominal septic complications in abdominal surgery for Crohn ’ s disease
Myrelid P, Olaison G, Sjödahl R, et al. (2009) Dis Colon Rectum 52: 1387–94
Purpose: Thiopurines are important as maintenance therapy in Crohn’s disease, but there have been concerns whether thiopurines increase the risk for anastomotic complications.
The present study was performed to assess whether thiopurines alone, or together with other possible risk factors, are associated with postoperative intra-abdominal septic complications after abdominal surgery for Crohn’s disease.
Methods: Prospectively registered data regarding periop- erative factors were collected at a single tertiary referral center from 1989 to 2002. Data from 343 consecutive abdominal operations on patients with Crohn’s disease were entered into a multivariate analysis to evaluate risk factors for intra-abdominal septic complications. All operations either involved anastomoses, stricture plasties or both; no opera- tions, however, involved proximal diversion.
Results: Intra-abdominal septic complications occurred in 26 of 343 operations (8%). Thiopurine therapy was associated with an increased risk of intra-abdominal septic complications (16% with therapy; 6% without therapy;
P= 0.044). Together with established risk factors such as preoperative intra-abdominal sepsis (18% with sepsis;
6% without sepsis;P= 0.024) and colocolonic anastomosis (16% with such anastomosis; 6% with other types of anastomosis;P= 0.031), thiopurine therapy was associated with intra-abdominal septic complications in 24% if any two or all three risk factors were present compared with 13% if any one factor was present, and only 4% in patients if none of these factors were present (P< 0.0001).
Conclusions: Thiopurine therapy is associated with post- operative intra-abdominal septic complications. The risk for intra-abdominal septic complications was related to the number of identified risk factors. This increased risk should be taken into consideration when planning surgery for Crohn’s disease.
Commentaires :Une publication concernant les facteurs de risque de sepsis postopératoire intra-abdominal après résection intestinale dans la maladie de Crohn. Cette étude rapporte l’effet délétère des immunosuppresseurs (azathio- prine et 6-mercaptopurine) administrés pendant plus de trois mois et dans les six semaines précédant la résection intestinale. Les autres facteurs de risque en analyse statistique multivariée sont la présence d’un abcès ou d’une fistule et la réalisation d’une anastomose colocolique.
Le risque de sepsis intra-abdominal est multiplié par trois en présence d’un facteur de risque et multiplié par six en présence de deux ou trois facteurs. Par rapport aux publications précédentes, ni la dénutrition préopératoire ni l’utilisation des corticoïdes ne sont des facteurs de risque en analyse statistique multivariée. Toutefois, la population d’étude n’est pas homogène, puisque les auteurs ont inclus aussi bien des résections iléocoliques, que des stricturo- plasties ou des résections colorectales. L’identification préopératoire de tels facteurs de risque de sepsis intra- abdominal est donc primordiale afin de ne pas rétablir la continuité digestive chez les patients à haut risque.
Cotation :☺
A. Alves
Increased short- and long-term risk of inflammatory bowel disease after Salmonella or Campylobacter gastroenteritis
Gradel KO, Nielsen HL, Schønheyder HC, et al. (2009) Gastroenterology 137: 495–501
Background and aims: Various commensal enteric and potentially pathogenic bacteria may be involved in the pathogenesis of inflammatory bowel diseases (IBD). We compared the risk of IBD between a cohort of patients with documented Salmonella or Campylobacter gastroenteritis and an age- and gender-matched control group from the same population in Denmark.
Methods: We identified 13,324 patients withSalmonella / Campylobacter gastroenteritisfrom laboratory registries in
North Jutland and Aarhus counties, Denmark, from 1991 through 2003, and 26,648 unexposed controls from the same counties. Of these, 176 exposed patients with IBD before the infection, their 352 unexposed controls, and 80 unexposed individuals with IBD before the Salmonella/Campylobacter infection were excluded. The final study cohort of 13,148 exposed and 26,216 unexposed individuals were followed for up to 15 years (mean, 7.5 years).
Results: A first-time diagnosis of IBD was reported in 107 exposed (1.2%) and 73 unexposed individuals (0.5%). By age, gender, and comorbidity adjusted Cox proportional hazards regression analysis, the hazard ratio (95% confi- dence interval) for IBD was 2.9 (2.2-3.9) for the whole period and 1.9 (1.4–2.6) if the first year after the Salmonella/
Campylobacter infection was excluded. The increased risk in exposed subjects was observed throughout the 15-year observation period. The increased risk was similar for Salmonella (n = 6463) and Campylobacter (N= 6,685) and for a first-time diagnosis of Crohn’s disease (N= 47) and ulcerative colitis (N= 133).
Conclusions: In our population-based cohort study with complete follow-up, an increased risk of IBD was demon- strated in individuals notified in laboratory registries with an episode ofSalmonella / Campylobacter gastroenteritis.
Commentaires : Cette étude cas-témoin scandinave est remarquable par l’importance de la population suivie grâce aux registres de santé, permettant une recherche épidémio- logique de qualité. Cette étude souligne qu’un épisode d’infection digestive est un facteur de risque de développement ultérieur d’une MICI symptomatique. Le biais principal est qu’on ne peut exclure qu’une partie des cas de MICI préexistaient de façon infraclinique, à l’épisode infectieux.
Cependant, cette étude va dans le sens du concept qu’au cours des MICI il existe une fragilité de l’épithélium intestinal, prompt à générer des réponses inflammatoires non contrôlées, lorsqu’il est agressé. Ce qui est vrai pour Salmonella et Campylobacter, l’est probablement aussi pour d’autres facteurs environnementaux (virus, antigènes alimentaires, bactéries, etc.). La recherche des facteurs de cette « suscepti- bilité » intestinale au cours des MICI reste l’enjeu capital.
Cotation :☺☺
X. Treton
Magnetic resonance for assessment of disease activity and severity in ileocolonic
Crohn ’ s disease
Rimola J, Rodriguez S, García-Bosch O, et al. (2009) Gut 58: 1113–20
Objective: Assessment of disease extension and activity is crucial to guide treatment in Crohn’s disease. The objective
of the current cross-sectional study was to determine the accuracy of MR for this assessment.
Design: Fifty patients with clinically active (N= 35) or inactive (N= 15) Crohn’s disease underwent ileocolonos- copy (reference standard) and MR. T2-weighted and precontrast and postcontrast-enhanced T1-weighted sequen- ces were acquired. Endoscopic activity was evaluated by CDEIS (Crohn’s Disease Endoscopic Index of Severity); in addition endoscopic lesions were classified as absent, mild (inflammation without ulcers) or severe (presence of ulceration).
Results: The comparison of intestinal segments with absent, mild and severe inflammations demonstrated a progressive and significant (P< 0.001) increase in the following MR parameters: wall thickness, postcontrast wall signal intensity, relative contrast enhancement, presence of edemas, ulcers, pseudopolyps and lymph node enlargement.
Independent predictors for CDEIS in a segment were wall thickness (P= 0.007), relative contrast enhancement (P= 0.01), presence of edemas (P = 0.02), and presence of ulcers at MR (P= 0.003). There was a significant correlation (R= 0.82; P< 0.001) between the CDEIS of the segment and the MR index calculated according to the logistic regression analysis coefficients. The MR index had a high accuracy for the detection of disease activity (area under the receiver operating characteristic [ROC] curve: 0.891, sensitivity: 0.81, specificity: 0.89) and for the detection of ulcerative lesions (area under the ROC curve: 0.978, sensitivity: 0.95, specificity: 0.91) in the colon and terminal ileum.
Conclusion: The accuracy of MR for detecting disease activity and assessing severity brings about the possibility of using MR as an alternative to endoscopy in the evaluation of ileocolonic Crohn’s disease.
Commentaires :Cette étude espagnole confirme l’intérêt de l’IRM dans l’évaluation de l’atteinte topographique et de l’activité de la maladie de Crohn colique. La corrélation des lésions décrites en IRM, permettant une discrimination assez fine entre œdèmes muqueux et ulcérations, et les lésions endoscopiques, est excellente. Les auteurs ont également proposé un index en IRM, bien corrélé avec le score endoscopique de référence, le CDEIS. Il reste donc à valider ces résultats sur de plus grandes séries, mais l’intérêt de l’IRM pour développer des protocoles de suivis sous traitement, de moins en moins invasifs, est désormais évident. Il faudra donc établir une classification con- sensuelle des signes radiologiques, élargir l’accès aux machines d’IRM et former les radiologues à l’IRM digestive.
Cotation :☺☺☺
X. Treton
Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn ’ s disease: a randomised, double blind, placebo-controlled, phase 2 study
Valentine JF, Fedorak RN, Feagan B, et al. (2009) Gut 58: 1354–62
Objective: Although treatment with corticosteroids induces remission in Crohn’s disease, prolonged exposure to corticosteroids is undesirable. This randomised clinical trial evaluated the efficacy of recombinant human granulocyte- macrophage colony-stimulating factor (sargramostim), an activator of innate immunity, in corticosteroid-dependent patients with Crohn’s disease.
Design: Patients were randomised in a 2:1 ratio, to sargramostim 6 μg/kg subcutaneously once daily or placebo for up to 22 weeks. The study consisted of (1) an adjunctive phase (weeks: 1-4) in which patients received study drug plus corticosteroid therapy; (2) a forced corticosteroid tapering phase (weeks: 4-14); and (3) an observation phase (four weeks) in which patients received study drug plus prednisone inferior or equal to 7.5 mg. The primary endpoint was corticosteroid-free remission (Crohn’s Disease Activity Index [CDAI] ≤150) four weeks after corticosteroid elimi- nation. Secondary endpoints were corticosteroid-free response (CDAI decreased by ≥100) and induction of remission in patients who reduced the dose of corticosteroid to 2.5-7.5 mg.
Results: Eighty-seven patients were randomised to sargramostim and 42 to placebo. Significantly more sargramostim-treated patients than placebo patients achieved corticosteroid-free remission (18.6 vs. 4.9%; P= 0.03).
Similar differences were seen for corticosteroid-free response and in patients who tapered corticosteroids to 2.5- 7.5 mg per day. Sargramostim treatment was also associated with significant improvements in health-related quality of life. Patients who received sargramostim were more likely to experience musculoskeletal pain, injection site reactions and dyspnoea.
Conclusions: Sargramostim was more effective than placebo for inducing corticosteroid-free remission in patients with Crohn’s disease with corticosteroid dependence.
Sargramostim may provide significant benefit in this population if these findings are confirmed.
Commentaires :Il s’agit d’une deuxième étude randomi- sée contre placebo de phase II, montrant une efficacité du GM CSF pour la rémission et la réponse clinique dans la maladie de Crohn. La population évaluée dans cette étude est une population de patients difficiles à traiter, corticodé- pendants et actifs à des doses non négligeables de corticoïdes oraux, ce qui peut expliquer les taux de rémission particulièrement bas dans les deux bras. La qualité de vie,
critère important dans les maladies chroniques, a également été étudiée en utilisant les scores usuels et est améliorée significativement sous traitement. Il manque des données à long terme et d’autres études pour confirmer l’efficacité du GM CSF. Même si les résultats ne paraissent pas révolutionnaires, l’avantage de ce traitement par rapport aux nouvelles biothérapies à l’étude est qu’il sera tout de suite disponible pour l’utilisation.
Cotation :☺☺
M. Simon
Adalimumab for the treatment of fistulas in patients with Crohn ’ s disease
Colombel JF, Schwartz DA, Sandborn WJ, et al. (2009) Gut 58: 940–8
Objective: To evaluate the efficacy of adalimumab in the healing of draining fistulas in patients with active Crohn’s disease (CD).
Design: A phase III, multicentre, randomised, double blind, placebo controlled study with an open-label extension was conducted in 92 sites.
Patients: A subgroup of adults with moderate to severely active CD (CD activity index 220-450) for inferior or equal to four months who had draining fistulas at baseline.
Interventions: All patients received initial open-label adalimumab induction therapy (80/40 mg at weeks 0/2). At week 4, all patients were randomly assigned to receive double blind placebo or adalimumab 40 mg every other week or weekly to week 56 (irrespective of fistula status).
Patients completing week 56 of therapy were then eligible to enroll in an open-label extension.
Main outcome measures: Complete fistula healing/closure (assessed at every visit) was defined as no drainage, either spontaneous or with gentle compression.
Results: Of 854 patients enrolled, 117 had draining fistulas at both screening and baseline (70 randomly assigned to adalimumab and 47 to placebo). The mean number of draining fistulas per day was significantly decreased in adalimumab-treated patients compared with placebo-treated patients during the double blind treatment period. Of all patients with healed fistulas at week 56 (both adalimumab and placebo groups), 90% (28/31) maintained healing following 1 year of open-label adalimumab therapy (observed analysis).
Conclusions: In patients with active CD, adalimumab therapy was more effective than placebo for inducing fistula healing. Complete fistula healing was sustained for up to two years by most patients in an open-label extension trial.
Commentaires : L’infliximab est le premier antiTNFα dont l’efficacité a été validée par des études spécifiques dans
les fistules de maladie de Crohn. L’étude CHARM randomisée en double insu contre placebo a montré l’efficacité de l’adalimumab, antiTNFα humanisé dans la maladie de Crohn modérée à sévère avec des résultats favorables pour le sous-groupe de patients ayant des fistules.
Cette étude est entièrement consacrée à l’efficacité de l’adalimumab dans les fistules. Il s’agit d’une analyse séparée des patients de l’étude CHARM ayant des fistules à l’inclusion et ayant poursuivi le traitement en ouvert une année supplémentaire. Elle confirme l’efficacité de l’adali- mumab pour l’induction et le maintien de la cicatrisation des fistules. Les points notables de l’étude sont l’utilisation d’un score original « de nombre moyen de fistules par jour » pour prouver la différence sous traitement contre placebo et les résultats très élevés de maintien de cicatrisation pour une durée de suivi supérieure aux études connues pour l’infliximab.
Cotation :☺☺
M. Simon
Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome
Burn J, Bishop DT, Mecklin JP, et al. (2008) CAPP2 Investigators. N Engl J Med 24: 2567–78
Background: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia;
however, the effects of aspirin in the Lynch syndrome (hereditary non-polyposis colon cancer) are not known.
Resistant starch has been associated with an antineoplastic effect on the colon.
Methods: In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose®), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome.
Results: Among 1,071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups.
Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) [Relative risk, 1.0; 95% confidence interval (CI), 0.7 to 1.4].
There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4 and 9.9%, respectively; P= 0.33). Among the 727 participants receiving resistant starch or placebo,
neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed.
Conclusions: The use of aspirin, resistant starch, or both for up to four years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome.
Commentaires : Il s’agit d’un impressionnant travail international randomisé et prospectif ayant inclus 1 071 personnes présentant une mutation délétère du syndrome de Lynch (donc syndrome « certifié »), dans 43 centres, évaluant :
dans un groupe 1 : 693 patients étaient randomisés entre aspirine 600 mg/j ou placebo. Le résultat est décevant, puisque 66 adénomes ou cancer (18,9 %) ont été identifiés dans le groupe aspirine sur 29 mois en moyenne vs 65 sous placebo (19 %). Il n’existait pas non plus de différence en termes de développement de néoplasies avancées (7,4 vs 9,9 %). Il n’y avait en revanche pas d’augmentation significative des effets secondaires (en particulier d’ulcères gastriques ou duodénaux) ;
dans le groupe 2 : 727 personnes étaient randomisées entre ingestion de fibres ou placebo, étaient suivies 29 mois en moyenne. Les résultats sont là aussi décevants, puisque 67 adénomes ou cancers colorectaux étaient identifiés dans le groupe fibres (18,7 %) vs 68 dans le groupe placebo (18,4 %). Ce travail est remarquablement mené et répond clairement mais négativement à un espoir physiologiquement logique, celui que les salicylés puissent prévenir le développement des adénomes et/ou des adénomes avancés chez les patients porteurs d’une maladie de Lynch : la réponse à moyen terme (deux ans et demi de suivi moyen) est négative, et de telle façon qu’il est peu probable qu’une réponse à plus long terme soit à espérer.
Cotation :☺☺
J.-C. Saurin
Randomized clinical trial comparing laparoscopic and open surgery in patients with rectal cancer
Lujan J, Valero G, Hernandez Q, et al.(2009) Br J Surg 96: 982–9
Background: The laparoscopic treatment of rectal cancer is controversial. This study compared surgical outcomes after
laparoscopic and open approaches for mid- and low-rectal cancers.
Methods: Some 204 patients with mid- and low-rectal adenocarcinomas were allocated randomly to open (103) or laparoscopic (101) surgery. The surgical team was the same for both procedures. Most patients had stage II or III disease, and received neoadjuvant therapy with oral capecitabine and 50-54 Gy external beam radiotherapy.
Results: Sphincter-preserving surgery was performed in 78.6 and 76.2 percent of patients in the open and laparoscopic groups respectively. Blood loss was significantly greater for open surgery (P< 0.001) and operating time was signifi- cantly greater for laparoscopic surgery (P= 0.020), and return to diet and hospital stay were longer for open surgery.
Complication rates, and involvement of circumferential and radial margins were similar for both procedures, but the number of isolated lymph nodes was greater in the laparoscopic group (mean: 13.63 vs. 11.57; P= 0.026).
There were no differences in local recurrence, disease-free or overall survival.
Conclusion: Laparoscopic surgery for rectal cancer has a similar complication rate to open surgery, with less blood loss, rapid intestinal recovery, shorter hospital stay, and no compromise of oncological outcomes.
Commentaires : Voilà seulement la troisième étude randomisée comparant la laparoscopie à la laparotomie dans le cancer du rectum. Elle est donc importante, car l’approche laparoscopique validée dans le cancer du côlon reste utilisée dans le cancer du rectum encore le plus souvent par un nombre d’équipes limité. Cette étude, portant sur des effectifs certes réduits, confirme les résultats de l’étude CLASICC et ceux observés dans le cancer du côlon. En effet, le bénéfice, certes minime, est en faveur de la laparoscopie avec moins de pertes sanguines peropératoires et une réduction du traumatisme opératoire (réduction de la durée d’hospitalisation, retour plus rapide du transit). Ces bénéfices « fonctionnels » s’associent ici à un résultat carcinologique au moins aussi bon que ceux de la laparotomie (avec même un nombre plus important de ganglions sur la pièce). Bien sûr, le suivi est encore un peu court (moins de trois ans), mais il n’existe aucune différence en termes de survie ou de récidive avec la laparotomie. Cette étude nous rappelle finalement les premières « petites » études randomisées sur le cancer du côlon. Les détracteurs vont dire que ce n’est pas suffisant pour valider la technique. Les défenseurs vont dire (à raison à mon avis) que le train de l’histoire est en marche aussi dans le cancer du rectum et ne s’arrêtera plus…
Cotation :☺☺☺
Y. Panis
Multicentre analysis of oncological and survival outcomes following anastomotic leakage after rectal cancer surgery
Den Dulk M, Marijnen CAM, Collette L, et al. (2009) Br J Surg; 96: 1066–75
Background: The association between diverting stomas and symptomatic anastomotic leakage after rectal cancer surgery was studied, as well as the impact of leakage on local recurrence, distant metastasis, and disease-free, overall and cancer-specific survival.
Methods: Data from the Swedish Rectal Cancer Trial, Dutch TME trial, CAO/ARO/AIO-94 trial, EORTC 22,921 trial and Polish Rectal Cancer Trial were pooled (N =5.187). All eligible patients without distant metastases at the time of low anterior resection were selected (N =2,726); overall survival was studied in patients aged 75 years or less (N =2,480). Multivariable models were used to study the association between diverting stomas and anastomotic leakage, and between leakage and recurrence or survival.
Results: Some 9.7 percent of patients were diagnosed with a symptomatic anastomotic leak; diverting stomas were negatively associated with leakage (11.6 percent without and 7.8 percent with a stoma;P =0.002). Anastomotic leakage was negatively associated with overall survival in the multivariable analysis (hazard ratio [HR] 1.29 [95 percent confidence interval 1.02 to 1.63];P =0.034), but not with cancer-specific survival (HR 1.12 [0.83 to 1.52];P =0.466).
Conclusion: Diverting stomas were associated with less symptomatic anastomotic leakage. Oncological outcome was not significantly influenced by leakage, but overall survival was reduced.
Commentaires :Plusieurs études récentes, le plus souvent unicentriques et rétrospectives ont suggéré le côté néfaste en termes de résultat carcinologique de la survenue d’une fistule anastomotique après chirurgie du cancer du rectum. Il manquait encore une grande étude multicentrique sur le sujet. Celle-ci a inclus l’ensemble des patients provenant de plusieurs grands essais randomisés ayant porté ces der- nières années sur le cancer du rectum. Une analyse multivariée a été faite sur plus de 2 700 patients. L’étude montre que la réalisation d’une stomie temporaire de dérivation est associée de manière indépendante avec une réduction du taux de fistule anastomotique. Cela devrait finir de convaincre les quelques partisans de la non-réalisation d’une stomie temporaire systématique. De plus, et c’est plus qu’intéressant, cette étude ne montre pas d’effet négatif sur le plan carcinologique de la survenue d’une fistule anastomotique. En conclusion, les messages sont clairs.
Dans la chirurgie du cancer du rectum, il est impératif de faire une stomie de dérivation temporaire. De plus,
la survenue d’une fistule ne péjore pas le résultat carcinologique.
Cotation :☺☺☺
Y. Panis
Family history of pilonidal sinus predisposes to earlier onset of disease and a 50% long-term recurrence rate
Doll D, Matevossian E, Wietelmann K, et al. (2009) Dis Colon Rectum. 52: 1610–5
Purpose: It has long been suspected that a family history of pilonidal sinus disease may predispose to higher disease incidence. The influence of family history on recurrence rate has not been investigated. The purpose of this study was to evaluate the recurrence rate in patients with both a personal and a family history of pilonidal sinus disease.
Methods: A standardized telephone interview was used to retrospectively study 578 patients who underwent primary surgery between 1980 and 1996. Differences concerning the long-term recurrence rate between patients with a positive or negative family history were analyzed using Kaplan-Meier statistics.
Results: Sixty-eight of 578 patients (12%) had a positive family history with first-degree relatives, in which 28 brothers and 25 fathers were similarly involved. The long- term recurrence rate was significantly elevated when family history was positive (35 vs. 22% after 15 years and 52 vs.
28% after 25 years;P= 0.02). The long-term recurrence rate was elevated if surgery was needed at a younger age (P= 0.03). The body mass index measured at time of admission for surgery did not seem to have any negative influence on recurrence rates (P= 0.31). Although a positive family history predisposes a person to earlier onset of disease, recurrences occur within 5.1 ± 6.2 years (mean ± standard deviation) in patients with a positive family history and within 5.3 ± 5.2 years in patients with a negative family history (P= 0.95).
Conclusion: Patients with a positive family history need closer surgical monitoring because primary disease will manifest earlier. A remarkable long-term recurrence rate exceeding 50% after 25 years places a much higher disease burden on patients with a positive family history. All available interventions known to reduce recurrence rate should be applied to this group of patients.
Commentaires : Le mécanisme physiopathologique conduisant à la constitution d’un sinus pilonidal et à sa surinfection n’est pas univoque. Des fossettes de sinus peuvent en effet être présentes au niveau interfessier dès l’enfance, mais leur surinfection semble être favorisée par des facteurs locaux parfois acquis (hyperpilosité, surcharge
pondérale, microtraumatismes locaux répétés, etc.). Le rôle de l’hérédité sur cette pathologie a été peu étudié. Les auteurs ont retrouvé des antécédents familiaux de sinus pilonidal chez 12 % des malades. Leur travail montre que les formes familiales de sinus pilonidal débutent de façon plus précoce. De plus, un début précoce de l’affection favorisait les récidives : après 25 ans, le taux de récidive était de 52 % en cas d’antécédents familiaux vs 28 % pour un cas isolé. Ce travail ne démontre cependant pas qu’il existe des facteurs génétiques favorisants, en effet, une histoire familiale de sinus pilonidal pourrait bien aussi être en rapport avec des facteurs environnementaux communs.
Cotation :☺
A. Senéjoux
Hidradenitis suppurativa and inflammatory bowel disease: are they associated?
Results of a pilot study
Van der Zee HH, van der Woude CJ, Florencia EF, Prens EP (2009) Br J Dermatol. Aug 14
Background: The co-occurrence of hidradenitis suppurativa (HS) and Crohn disease (CD) published in a few case reports resulted in the wide acceptance of an association between these two diseases. However, the combined prevalence of these diseases is currently unknown; furthermore, it is unknown whether this co-occurrence also applies for ulcerative colitis (UC).
Objectives: To estimate the prevalence of HS in patients with inflammatory bowel disease (IBD) living in the Southwest of the Netherlands.
Methods: During an IBD patient information meeting, randomly, 158 patients with IBD were interviewed about recurrent painful boils in the axillae and/or groin and were shown illustrative clinical pictures of the appearance of HS.
Results: Of the 158 patients interviewed, 102 (65%) had CD and 56 (35%) had UC. Twenty-five people (16%) responded that they had had or still experienced painful boils in the axillae and/or groin, of whom 17 were patients with CD (17%) and eight had UC (14%).
Conclusions: This pilot study shows for the first time that HS occurs in patients with CD or UC. More prospective studies are warranted to establish the association between HS and IBD and its underlying pathogenesis.
Commentaires : L’association maladie de Crohn-mala- die de Verneuil est essentiellement rapportée sous forme de cas cliniques, elle est parfois mal connue. Cette enquête pilote montre que la fréquence de la maladie de Verneuil paraît plus importante chez les patients ayant une MICI par rapport à la population générale. Ainsi, en France, la prévalence de l’affection a été estimée à 1 % dans la population générale. Ce travail préliminaire est cependant critiquable, puisqu’il existe d’autres étiologies que la maladie de Verneuil pour expliquer une suppuration axillaire ou inguinale et qu’il ne s’agissait que d’une enquête sans examen physique.
Cotation :☺
A. Senéjoux
