REVUE DE PRESSE / PRESS REVIEW
Irritable bowel syndrome and negative
appendectomy: a prospective multivariate analysis Lu CL, Liu CC, Fuh JL, et al. (2007)
Gut 56: 655-60
Objective: To determine in a prospective study whether irritable bowel syndrome (IBS) and other variables–such as psychiatric profile, health-related quality of life (HRQoL) and clinical presentation–correlate with nega- tive appendectomy (NA).
Design:Longitudinal study.
Setting: Inpatient and emergency service in a university-affiliated teaching hospital.
Patients: Four hundred (and) thirty consecutive patients underwent emergency surgery for suspected appendicitis.
Main outcome measures:The Rome-II IBS questionnaire, Hospital Anxiety and Depression Scale, Short-Form 36 Health Survey, and clinical, pathological and CT findings.
Results:The younger, predominantly female NA group (N = 68, 15.8%) had higher Rome-II IBS and anxiety- depression scores yet lower HRQoL scores compared to the positive appendectomy group. The NA patients tended to have atypical presentations (absence of pain migration/fever/muscle guarding), lower white cell counts, including the percentage of polymorphonuclear leukocytes (PMNL) and lower rates of CT scan evaluations than the positive group. After multiple logistic regression, IBS (OR 2.17; 95% CI: 1.14-4.24), degree of anxiety (OR 1.12; 95% CI: 1.02-1.49), absence of pain migration (OR 3.43; 95% CI: 1.90-5.95)-muscle guarding (OR 3.72; 95% CI: 2.07-6.70), lower PMNL percentage (< 75%; OR 3.05; 95% CI: 1.69-5.51) and no CT scan evaluation (OR 2.32; 95% CI: 1.27-4.26) were found to be independent factors in predicting NA.
Conclusion: Both patients (IBS, anxiety, and atypical presentation) and physicians (low CT scan usage) are independent determinants that predict NA. Physicians must exercise caution before performing surgery or referring patients with IBS for appendectomies. CT scans should be considered in patients with suspected appen- dicitis, particularly in those with IBS and atypical clinical presentations.
Commentaire :Il est maintenant clairement e´tabli que les patients ayant un syndrome de l’intestin irritable
(SII) ont un risque plus e´leve´ de subir une intervention chirurgicale non justifie´e, que ce soit une appendicectomie (OR : 1,45), une chole´cystectomie (OR : 2,09), une hyste´- rectomie (OR : 1,70), voire une intervention sur le rachis lombaire (OR : 1,22)1. Non seulement ces interventions ne modifient pas le profil e´volutif du SII, mais elles ont une morbidite´ propre, un couˆt non ne´gligeable, risquent d’induire des complications a` distance et d’engager le patient dans une escalade the´rapeutique totalement injustifie´e. Cette e´tude prospective taı¨wanaise est un plaidoyer en faveur d’une part, de la re´alisation d’un scanner abdominal syste´matique en cas de suspicion d’appendicite aigue¨ qui diminue le risque de re´aliser des gestes inutiles et d’autre part, pour une meilleure diffusion et une meilleure connaissance par les non-spe´cialistes des douleurs fonctionnelles des crite`res diagnostiques du SII, les crite`res de Rome, dont la pre´sence permet de suspecter qu’il s’agit d’une douleur fonctionnelle et non organique.
Il faut espe´rer, a` l’heure de la tarification a` l’activite´, ou`
rendement ou activite´ ope´ratoire de jour comme de nuit risquent de devenir notre mode de pense´e unique sous peine de rendus de moyens, que l’on garde les pieds sur terre pour en revenir a` une bonne analyse se´miologique recueillie lors d’un interrogatoire de´taille´ qui permette de retenir le bon diagnostic pour nos patients.
Cotation :
B. Coffin
Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer
Van Cutsem E, Peeters M, Siena S, et al. (2007) J Clin Oncol 25: 1658-1664
Purpose: Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR). We compared the activity of panitu- mumab plus best supportive care (BSC) to that of BSC alone in patients with metastatic colorectal cancer who had progressed after standard chemotherapy.
Patients and methods: We randomly assigned 463 patients with 1% or more EGFR tumour cell
1Longstreth GF, Yao JF (2004) Irritable bowel syndrome and surgery: a multivariable analysis. Gastroenterology 126: 1665-73.
DOI 10.1007/s11725-007-0044-x
membrane staining, measurable disease, and radiological documentation of disease progression during or within 6 months of their most recent chemotherapy to groups receiving panitumumab 6 mg/kg every 2 weeks plus BSC (N= 231) or BSC alone (N= 232). Tumour assessments by blinded central review were scheduled from week 8 until disease progression. The primary end point was progres- sion-free survival (PFS). Secondary end points included objective response, overall survival (OS), and safety. BSC patients who progressed had the option of receiving panitumumab in a crossover study.
Results: Panitumumab significantly extended PFS (hazard ratio [HR]: 0.54; 95% CI: 0.44-0.66, [P< 0.0001]).
The median PFS time was 8 weeks (95% CI: 7.9-8.4) for panitumumab and 7.3 weeks (95% CI: 7.1-7.7) for BSC. The mean (standard error) PFS time was 13.8 (0.8) weeks for panitumumab and 8.5 (0.5) weeks for BSC.
Objective response rates also favoured panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10% for panitumumab and 0% for BSC (P< 0.0001). No difference was observed in OS (HR, 1.00;
95% CI: 0.82-1.22), which was confounded by the similar activity of panitumumab after 76% of BSC patients entered the crossover study. Panitumumab was well tolerated. Skin toxicity, hypomagnesaemia, and diarrhoea were the most common toxicities observed. No patients had grade 3/4 infusion reactions.
Conclusion:Panitumumab significantly improved PFS in patients with chemorefractory colorectal cancer, with manageable levels of toxicity.
Commentaire : L’arsenal des the´rapies cible´es s’agrandit ! Apre`s le cetuximab, un nouvel anticorps dirige´ contre le re´cepteur de l’EGFR vient de de´montrer son inte´reˆt, par rapport a` un traitement symptomatique seul, en termes d’ame´lioration de la survie sans progres- sion des cancers colorectaux me´tastatiques en progression apre`s chimiothe´rapie. Contrairement au cetuximab, le panitumumab est un anticorps d’origine humaine et donc a priorisans risque de re´action allergique. Son adminis- tration se fait toutes les deux semaines, contre une injection hebdomadaire pour son concurrent. Les toxicite´s observe´es le plus fre´quemment, lie´es au mode d’action de ces mole´cules, sont cutane´es et digestives avec e´galement un risque d’hypomagne´se´mie. Le panitumumab devrait prochainement obtenir son AMM a` la suite de cette e´tude, sa tole´rance et son efficacite´ en association avec les chimiothe´rapies utilise´es dans le traitement des cancers colorectaux sont actuellement en cours d’e´valuation.
Cotation :
E. Mitry
Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin,
and irinotecan (FOLFIRI) as first-line treatment of metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest
Falcone A, Ricci S, Brunetti I, et al. (2007) J Clin Oncol 25: 1670-1676
Purpose: The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2day 1, oxaliplatin 85 mg/m2day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI).
Methods: Selection criteria included unresectable metastatic colorectal cancer, 18 to 75 age range, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR).
Results:A total of 244 patients were randomly assigned.
An increase from grade 2 to 3 peripheral neurotoxicity (0vs19%;P < 0.001) and grade 3 to 4 neutropenia (28vs 50%;P< 0.001) was observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3 vs5%) and grade 3 to 4 diarrhoea (12 vs 20%) was not significantly different.
Responses, as assessed by investigators, were complete in 6 and 8% of the patients receiving FOLFIRI and FOLFOXIRI, respectively, and partial in 35 and 58% (RR, 41 vs 66%;
P = 0.0002). RR confirmed by an external panel was 34 versus 60% (P < 0.0001). The R0 resection rate of secondary metastases was greater in the FOLFOXIRI arm (6vs15%;P= 0.033, among all 244 patients; and 12vs36%;
P = 0.017 among patients with liver metastases only).
Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 vs 9.8 months; hazard ratio [HR]: 0.63;
P = 0.0006; median OS, 16.7 vs 22.6 months; HR: 0.70;
P= 0.032).
Conclusion: The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer and favourable prognostic characteristics.
Further studies of FOLFOXIRI in combination with targeted agents and in neoadjuvant settings are warranted.
Commentaire : Quelle prise en charge optimale pro- poser aux patients pre´sentant un cancer colorectal me´tastatique ? Quelle association permettra de rendre re´se´cables, et donc potentiellement gue´rissables, le plus grand nombre de patients ? Faut-il associer d’emble´e une
chimiothe´rapie et une the´rapie cible´e ou « frapper fort » et utiliser en association l’oxaliplatine et irinote´can qui sont les deux substances majeures dans cette indication ? La re´ponse a` ces interrogations n’est pas connue et il est probable que diffe´rentes strate´gies the´rapeutiques se valent. L’e´tude de Falcone et al. apporte cependant des arguments forts en faveur de la trithe´rapie par FOLFIRI- NOX. Cette e´tude randomise´e de phase III, sans biais me´thodologique apparent, a en effet montre´ une augmen- tation significative du taux de re´ponse et des taux de survie sans progression et globale chez les patients traite´s par FOLFIRINOX par rapport aux patients traite´s par FOLFIRI, au prix d’une tole´rance tout a` fait acceptable.
Surtout, 36 % des patients pre´sentant des me´tastases he´patiques isole´es ont pu be´ne´ficier secondairement d’une exe´re`se a` vise´e curative apre`s FOLFIRINOX contre seulement 12 % (p = 0,017) en cas de traitement par FOLFIRI. En cas de me´tastases he´patiques d’origine colorectale potentiellement re´se´cables, un traitement optimal associe´ a` un important taux de re´ponse s’impose, et dans cette indication la place de l’association FOLFI- RINOX est maintenant de´montre´e.
Cotation :
E. Mitry
Rates of new or missed colorectal cancer after colonoscopy and associated risk factors:
a population-based analysis
Bressler B, Paszat LF, Chen Z, et al. (2007) Gastroenterology 132: 96-102
Background and aims: The rate of new or missed colorectal cancer (CRC) after colonoscopy and the associated risk factors in standard practice are unknown.
Our objective was to evaluate the rate of CRC and its risk factors in a population-based study.
Methods: We analyzed data from the Canadian Institute for Health Information, Ontario Health Insu- rance Program, and Ontario Cancer Registry for all patients (> 20 years of age) newly diagnosed with right- sided, transverse, splenic flexure-descending, rectal or sigmoid CRC in Ontario from 1st April 1997 to 31 March 2002, who received colonoscopies within 3 years prior to their diagnoses. Patients with new or missed cancer underwent their most recent colonoscopy 6 to 36 months before diagnosis. We examined characteristics that might be risk factors for new or missed CRC.
Results: We identified CRC in 3288 (right sided), 777 (transverse), 710 (splenic flexure-descending), and 7712 (rectal or sigmoid) patients. The rates of new or missed cancers were 5.9, 5.5, 2.1 and 2.3%, respectively. Independent risk factors for these cancers in men and women were older age, diverticular disease, right-sided or transverse CRC,
colonoscopy by an internist or family physician, and office colonoscopy.
Conclusions: Because office colonoscopies and certain patient, procedure, and physician characteristics are inde- pendent risk factors for new or missed CRC, physicians must inform patients of the small risk (2 to 6%) of discovering these cancers after colonoscopy. The influence of type of physician and care setting, potentially modifiable risk factors, on the accuracy of colonoscopies warrants further study.
Commentaire :L’Ontario est la province canadienne la plus peuple´e (12 millions d’habitants) et dispose d’un syste`me public de couverture maladie unique et universel, avec une base de donne´e exhaustive de tous les actes pratique´s pour l’ensemble de la population. Il y existe e´galement un registre du cancer comportant plus de 95 % des cancers diagnostique´s pour les re´sidents de la province.
Ce travail repose sur l’exploitation de ces bases de donne´es, avec une cohorte de 12 487 patients porteurs de cancer. La proportion de cancers « manque´s » par une coloscopie re´alise´e dans les trois ans e´tait globalement de 3,4 % : 2,3 % pour le rectum et 5,5 % pour le coˆlon droit.
Ces chiffres sont utiles a` notre pratique quotidienne et doivent eˆtre pris en compte dans l’information donne´e au patient avant et apre`s la coloscopie. Certains facteurs de risque de´pendent du patient : aˆge, diverticules, locali- sation... D’autres sont lie´s au me´decin et, au moins en Ontario, la qualite´ de la coloscopie est meilleure lorsqu’elle est re´alise´e en clinique et... par un gastroente´rologue !
Cotation :
P. Bulois
Colonoscopic withdrawal times and adenoma detection during screening colonoscopy Barclay RL, Vicari JJ, Doughty AS, et al. (2006) N Engl J Med 355: 2533-41
Background:Colonoscopy is commonly used to screen for neoplasia. To assess the effectiveness of screening colonoscopy in everyday practice, we conducted a study of the detection rates for adenomas and the amount of time taken to withdraw the colonoscope among endosco- pists in a large community-based practice.
Methods: During a 15-month period, 12 experienced gastroenterologists performed 7882 colonoscopies, of which 2053 were screening examinations in subjects who had not previously undergone colonoscopy. We recorded the numbers, sizes, and histological features of the neoplastic lesions detected during screening as well as the duration of insertion and withdrawal of the colono- scope during the procedure. We compared detection rates for neoplastic lesions among gastroenterologists who had mean colonoscope withdrawal times of less than
6 minutes with the rates of those with mean withdrawal times of 6 minutes or more. According to experts, 6 minutes is the minimum length of time to allow adequate inspection during instrument withdrawal.
Results: Neoplastic lesions (mostly adenomatous polyps) were detected in 23.5% of screened subjects.
There were large differences among gastroenterologists in the detection rates for adenomas (range of the mean number of lesions per subject screened: 0.10 to 1.05;
range of the percentage of subjects with adenomas: 9.4 to 32.7%) and times of colonoscope withdrawal from the caecum to the anus (range: 3.1 to 16.8 minutes for procedures during which no polyps were removed).
Compared with colonoscopists with mean withdrawal times of less than 6 minutes, those with mean withdrawal times of 6 minutes or more had higher rates of detection of all types of neoplasia (28.3 vs 11.8%, P < 0.001), including advanced neoplasia (6.4vs2.6%,P= 0.005).
Conclusions:In this large community-based gastroen- terology practice, we observed higher detection rates for adenoma among colonoscopists who had longer mean times for colonoscope withdrawal. The effect of withdra- wal time variation on lesion detection and the prevention of colorectal cancer in the context of widespread colonoscopic screening is unknown. Our study was preliminary, so general guidelines and implications for clinical practice must be determined by future studies.
Commentaire :La dure´e du retrait est un crite`re de qualite´
de la coloscopie de de´pistage. Un minimum de six minutes est souvent recommande´. Les auteurs ont compare´le nombre et le type de le´sions de´couvertes par 12 ope´rateurs en fonction de leur dure´e moyenne de retrait. Il s’agissait d’endoscopistes expe´rimente´s, avec un taux d’intubation cæcale compris entre 97 et 100%. Le nombre d’ade´nomes de´tecte´s e´tait significati- vement plus important chez les ope´rateurs qui prenaient plus de six minutes pour retirer le coloscope. Cette diffe´rence e´tait e´galement significative pour les le´sions que la classification de Vienne qualifie de « ne´oplasies avance´es ». Cette limite de six minutes est cependant arbitraire, car la relation entre le
nombre d’ade´nomes de´tecte´s et le temps passe´ au retrait du coloscope apparaıˆt line´aire (Fig. 1). L’amplitude de la diffe´rence doit eˆtre note´e : les plus me´ticuleux de´tectaient jusqu’a` dix fois plus d’ade´nomes et de ne´oplasies avance´es que les plus rapides !
Cotation :
P. Bulois
Prevalence of and risk factors for anal cytological abnormalities and human papillomavirus infection in a rural population of HIV-infected males Ciobotaru B, Leiman G, St John T, et al. (2007) Dis Colon Rectum 50, in press
Purpose: This study was designed to determine the prevalence of and risk factors for anal squamous intraepithelial lesions and human papillomavirus infec- tion in a rural population of HIV-infected males.
Methods:A cross-sectional study was performed and risk factors determined. Anal Papanicolaou smears and human papillomavirus screening for oncogenic types were performed.
Results: Of 211 eligible male patients, 149 (70.6%) participated. HIV transmission risk was predominantly associated with males who have sex with males (82%).
The mean duration of HIV infection was 9.9 years.
Ninety (60%) males had abnormal anal cytology, including 40 with atypical cells of unknown significance (26%), 28 with low-grade squamous intraepithelial lesions (19%), and 22 with high-grade squamous intraepithelial lesions (15%). Human papillomavirus was detected in 61% of the participants. The risk factors for abnormal anal cytology, adjusted by binary logistic regression, included: males who have sex with males (P< 0.001), human papillomavirus infection (P< 0.001), history of anogenital warts (P = 0.014), and the mean lowest CD4 count (158 with abnormal cytology (standard deviation: 135), 208 with negative cytology (standard deviation: 180; P = 0.017)). Twenty-two patients with high-grade squamous intraepithelial lesions underwent colorectal surgical examination and anoscopy. Two (10%) were found to have invasive squamous-cell carcinoma and three (15%) had mass lesions with high- grade squamous intraepithelial lesions.
Conclusions: Anal squamous intraepithelial lesions and oncogenic human papillomavirus are highly pre- valent in males infected with HIV and living in rural environments.
Commentaire : Le de´veloppement de techniques d’analyse cytologique dites en couche mince ou en phase liquide autorise pourtant un suivi comparable a` celui qui est propose´ au niveau du col ute´rin. L’analyse cytologique repose sur la classification de Bethesda modifie´e. Dans le travail rapporte´ par une e´quipe de Burlington (E´tats-Unis,
Fig. 1.
Vermont), les pre´valences de frottis anormaux, de dys- plasies de bas grade et de haut grade sont particulie`rement e´leve´es sugge´rant que l’exposition au risque de dysplasie anale n’est pas l’apanage des seuls se´ropositifs citadins...
Ces donne´es sont a` rapprocher des re´sultats d’une analyse cytologique syste´matique effectue´e en consulta- tion chez 205 malades et re´cemment rapporte´e par l’e´quipe des Diaconesses lors des dernie`res Journe´es francophones de pathologie digestive (I. Etienney et al. Gastroenterol Clin Biol 2007; 31: A86) dont 13 % avaient des ante´ce´dents de le´sions condylomateuses anales. Les facteurs associe´s a`
un frottis anormal (LSIL chez quatre malades ou ASCUS chez 40 malades) e´taient l’ante´ce´dent de le´sion condylo- mateuse anale (OR 4,9 [2,1-11,5]), la se´ropositivite´ pour le virus de l’immunode´ficience humaine (OR 4,0 [1,6-9,9]) et le tabac (OR 2,1 [1,1-11,5]).
La sensibilite´ et la spe´cificite´ des techniques de frottis pour l’identification des le´sions de dysplasie varient entre 69 et 93 %, 32 et 59 % respectivement. La re´pe´tition du de´pistage a` deux ans d’intervalle permet d’augmenter de fac¸on tre`s significative les valeurs pre´dictives des tests.
L’impact d’une telle proce´dure de de´pistage n’a pas encore donne´ lieu a` un e´largissement des pratiques et de propositions rationnelles de suivi, et il n’est pas aujour- d’hui de´montre´ qu’une politique de de´pistage des malades infecte´s par le VIH par exemple ame´liore la survie et le pronostic de ceux qui sont victimes d’un cancer du canal anal.
Cotation :
L. Siproudhis
Infrared coagulator ablation of high-grade anal squamous intraepithelial lesions in HIV-negative males who have sex with males
Goldstone SE, Hundert JS, Huyett JW (2007) Dis Colon Rectum 50, in press
Purpose: The incidence of anal squamous carcinoma in males who have sex with males is rising. We previously reported that infrared coagulation of high-grade squamous intraepithelial lesions in HIV-positive males who have sex with males yields a recurrence rate of 65% after the first ablation and 58% after the second ablation. The cure rate of an individual lesion was 72%. We set out to determine whether this technique demonstrates improved results in HIV-negative males who have sex with males.
Methods:We performed a retrospective review of the medical records of HIV-negative males who have sex with males and underwent infrared coagulation ablation of
anal high-grade squamous intraepithelial lesions. Patients had at least six months of follow-up, with cytology, high- resolution anoscopy, and biopsy. Recurrent high-grade squamous intraepithelial lesions were retreated.
Results: Seventy-five patients were enrolled, with a median age of 36, and 113 lesions were treated. Forty patients (53%) developed a recurrence in a median time of 238 days and 35 patients (47%) were disease free for a median of 516 days. When patients were treated a second or third time, recurrence rates dropped to 28% and 0%, respectively. The probability of successfully treating an individual lesion with the first infrared coagulation was 81% and 93% when retreated. HIV-positive patients were twice as likely to have persistent lesions and 1.7 times more likely to develop recurrent high-grade squamous intraepithelial lesions. No patients developed squamous-cell carcinoma or anal stenosis, or serious complications.
Conclusions: Infrared coagulation is a safe and effective office-based procedure for treating anal high- grade squamous intraepithelial lesions. Although recur- rence was high after the first infrared coagulation, repeated treatment led to the resolution of high-grade squamous intraepithelial lesions. Treatment success with infrared coagulation is significantly higher in HIV-negative patients compared with HIV-positive patients.
Commentaire : La prise en charge the´rapeutique du carcinome invasif du canal anal n’est, pour l’instant, pas influence´e par les concepts pathoge´niques le liant a` l’infection virale VHP : l’infection par le VIH ne modifie pas les options propose´es (Abramowitz et al. Gastroenterol Clin Biol 2007; 31: A86). Le carcinome e´pidermoı¨de invasif du canal anal a, comme beaucoup de pathologies tumorales malignes, un pronostic domine´ par le stade anatomique de prise en charge the´rapeutique : le taux de survie a` cinq ans est de 78, 56 et 18 % selon qu’il s’agisse respectivement d’une atteinte anatomique locale, re´gio- nale ou d’un processus d’extension me´tastatique. En revanche, la prise en charge the´rapeutique des le´sions de dysplasie de haut grade ne fait aujourd’hui l’objet d’aucun consensus. Les re´sultats de cette e´tude new-yorkaise soulignent l’incidence particulie`rement e´leve´e des re´cidi- ves apre`s photodestruction des le´sions de dysplasie (plus de la moitie´ des cas), quel que soit le statut VIH des malades traite´s. Ces donne´es ont de´ja` fait l’objet d’une publication2. Le message important du travail pre´sente´ est l’incitation a` renouveler les se´ances de photocoagulation chez les malades se´rone´gatifs afin de diminuer au gre´ des consultations de suivi le risque de re´cidive. Ce message est diffe´rent de celui des malades se´ropositifs pour lequel le
2Goldstone SE, Kawalek AZ, Huyett JW (2005) Infrared coagulator: a useful tool for treating anal squamous intraepithelial lesions.
Dis Colon Rectum. 48: 1042-54.
risque de re´cidive reste e´leve´ en de´pit des retraitements.
On peut se demander en revanche si le message scientifique et clinique est valide a` l’aune de la courte pe´riode de suivi (un a` deux ans), le caracte`re habituellement multifocal de la dysplasie et la me´thodologie inadapte´e (deux groupes compare´s au lieu d’une stratification d’analyse sur le statut VIH). Enfin, l’outil de traitement propose´
(photoagulation infrarouge) risque, a` court terme, d’eˆtre rendu caduc par la photothe´rapie dynamique dans ces indications.
Cotation :
L. Siproudhis
Is the increasing rate of local excision of stage I rectal cancer in the United States justified?
A nationwide cohort study from the National Cancer Database
You YN, Baxter NN, Stewart A, Nelson H (2007) Ann Surg 245: 726-733
Objective: To determine the rates of local excision (LE) over time and test the hypothesis that LE carries increased oncological risk but reduced perioperative morbidity when compared with standard resection (SR).
Summary background data:Despite the lack of level- I-level-II evidence supporting its oncological appropria- teness, LE is often performed to treat stage I rectal cancer.
Methods:The surgical treatment of 35,179 patients with stage I rectal cancer diagnosed from 1989 to 2003 was examined over time, using the National Cancer Database.
A special study then analyzed perioperative outcomes, local recurrence and survival in 2124 patients diagnosed between 1994 and 1996, including 765 (T1, 601; T2, 164) treated by LE and 1359 (T1, 493; T2, 866) treated by SR.
Results:From 1989 to 2003, the use of LE has increased (T1, 26.6-43.7%; T2, 5.8-16.8%;P= 0.001 both). The special study demonstrated significantly lower 30-day morbidity after LEversusSR (5.6vs14.6%;P= 0.001). After adjusting for patient and tumour characteristics, the 5-year local recurrence rate after LE versus SR was 12.5 versus 6.9%
(P = 0.003; hazard ratio = 0.38; 95% CI: 0.23-0.62) for T1 tumours, and 22.1versus15.1% (P= 0.01; hazard ratio = 0.69;
95% CI: 0.44-1.07) for T2 tumours. The 5-year overall survival (T1, 77.4 vs 81.7%, P = 0.09; T2, 67.6 vs 76.5%, P = 0.01) was influenced by age and comorbidities but not the type of surgery.
Conclusions:This study provides the best evidence of both the increasing use and associated risks of LEversus SR. For each patient, the benefits of LE must be weighed against the heightened risk of local failure.
Commentaire : Combien faudra-t-il d’e´tudes pour reconnaıˆtre qu’une exe´re`se locale d’un « petit » cancer
du rectum classe´e T1 en e´choendoscopie donne un moins bon re´sultat carcinologique qu’une exe´re`se totale du me´sorectum ? Dans cette tre`s large e´tude ame´ricaine, pre`s de 800 patients traite´s localement contre pre`s de 1400 patients traite´s par proctectomie, e´videmment la morbi- dite´ postope´ratoire est plus faible apre`s exe´re`se locale, ce qui est l’argument essentiel de cette technique. Malheu- reusement, ce bon re´sultat ope´ratoire est associe´ a` une augmentation tre`s largement significative du taux de re´cidive locale a` cinq ans (7 % apre`s proctectomie contre 12,5 % apre`s traitement local). Quand on sait que la re´intervention pour re´cidive locale apre`s traitement local donne de mauvais re´sultats carcinologiques, il est clair que proposer aujourd’hui un traitement local a` un cancer T1 du rectum est une « perte de chance » sur le plan carcinologique. Cela ne veut pas dire bien suˆr que ce traitement doit eˆtre abandonne´. Mais, il doit re´ellement eˆtre discute´ au cas par cas. Ainsi, si une exe´re`se locale pouvait eˆtre une bonne alternative a` l’amputation abdominope´rine´ale, est-ce aussi vrai en cas de possibilite´
de conservation sphincte´rienne ? De meˆme, si une tumeur classe´e T1sm1 est probablement une bonne indication, ce n’est suˆrement pas le cas en cas de tumeur T1sm3, voire sm2. Enfin, le de´bat est-il le meˆme entre un patient aˆge´ a`
lourde comorbidite´, et un patient jeune dont on sait que la proctectomie sera associe´e a` une mortalite´ quasi nulle et une morbidite´ certes importante, mais qui doit eˆtre mis en balance avec l’espe´rance de vie, qui apre`s proctectomie pour tumeur T1 est supe´rieure a` 90 %. En conclusion, cette e´tude ne peut qu’inciter a` la prudence avant de proposer un traitement local, ce qui va dans le sens des RPC franc¸aises qui recommandaient ce traitement local uniquement en cas de tumeur T1sm1.
Cotation :
Y. Panis
Results at up to 20 years after ileal pouch-anal anastomosis for chronic ulcerative colitis Hahnloser D, Pemberton JH, Wolff BG, et al. (2007) Br J of Surg 94: 333-340
Background: Ileal pouch-anal anastomosis (IPAA) is performed routinely for chronic ulcerative colitis.
Methods:Using data from a prospective database and annual standardized questionnaires, we assessed func- tional outcome, complications and quality of life (QoL) after IPAA.
Results:About 1885 IPAA procedures were performed for chronic ulcerative colitis over a 20-year period (mean follow-up 11 years). The mean age at the time of IPAA was 34.1 years, increasing from 31.2 years (1981-1985) to 36.3 years (1996-2000). The overall rate of pouch success at 5, 10, 15 and 20 years was 96.3, 93.3, 92.4 and 92.1%, respectively. Mean daytime stool frequency increased
from 5.7 at 1 year to 6.4 at 20 years (P <0.001), and also increased at night (from 1.5 to 2.0; P < 0.001). The incidence of frequent daytime faecal incontinence increa- sed from 5 to 11% during the day (P <0.001) and from 12 to 21% at night (P <0.001). QoL remained unchanged and 92% of patients remained in the same employment.
Seventy-six patients were eventually diagnosed with indeterminate colitis and 47 with Crohn’s disease.
Conclusion: IPAA is a reliable surgical procedure for patients requiring proctocolectomy for chronic ulcerative colitis and indeterminate colitis. The clinical and functional outcomes are excellent and stable for 20 years after surgery.
Commentaire : Quel est le devenir d’une anastomose ile´o-anale 20 ans apre`s l’intervention ? Quand on sait que dans la tre`s grande majorite´ des cas, l’intervention est propose´e pour une pathologie be´nigne, cette question est plus que le´gitime. La Mayo Clinic, qui a une des deux plus grandes expe´riences de cette intervention (avec la Cleveland Clinic) rapporte donc ici une expe´rience de pre`s de 2000 patients suivis jusqu’a` 20 ans apre`s l’intervention. Les re´sultats sont a` la fois rassurants (qualite´ de vie stable avec le temps, taux d’e´chec assez faible de l’intervention), mais aussi un peu inquie´tant du fait d’une alte´ration certes mode´re´e, mais significative de la fonction, avec augmentation notamment du nombre de selles diurnes et nocturnes, et de l’incontinence diurne et nocturne a` 20 ans. Bien suˆr, ces re´sultats s’expliquent en partie par l’alte´ration physiologique de la fonction sphincte´rienne avec l’aˆge. De plus, il n’existe pas aujourd’hui d’alternative a` l’ile´oanale en cas de rectum malade et de polypose ou de RCH. Mais, ces re´sultats doivent rendrent vigilants en cas de fonction sphincte´- rienne me´diocre, et surtout doivent eˆtre annonce´s au patient avant l’intervention. Enfin, ils soulignent la ne´cessite´ d’une surveillance inde´finie, a` la recherche de petits moyens permettant d’ame´liorer la fonction, notam- ment chez le patient qui avance en aˆge.
Cotation :
Y. Panis
Natalizumab for the treatment of active Crohn’s disease: results of the ENCORE trial
Targan SR, Feagan BG, Fedorak RN, et al. (2007) Gastroenterology 132: 1672-1683
Background and aims:A randomized, placebo-controlled trial evaluated the efficacy of natalizumab induction therapy in patients with Crohn’s disease.
Methods:Patients (N= 509) with moderately to severely active Crohn’s disease and active inflammation chara- cterized by elevated C-reactive protein concentrations
were randomized (1:1) to receive natalizumab 300 mg or placebo intravenously at weeks 0, 4, and 8. The primary end point was induction of response (70-point decrease from the baseline in the Crohn’s Disease Activity Index score at week 8, sustained through week 12). Additional efficacy end points included the proportion of patients with sustained remission (Crohn’s Disease Activity Index score < 150 points) and response or remission over time.
Results: Response at week 8 sustained through week 12 occurred in 48% of natalizumab-treated patients and 32%
of patients receiving placebo (P < 0.001). Sustained remission occurred in 26% of natalizumab-treated patients and 16% of patients receiving placebo (P= 0.002).
Week-4 response rates were 51% for natalizumab and 37%
for placebo (P= 0.001). Responses remained significantly higher at subsequent assessments (P < 0.001) of natalizu- mab-treated patients. Natalizumab-treated patients also had significantly higher remission rates at weeks 4, 8 and 12 (P= 0.009). The frequency and types of adverse events were similar between treatment groups.
Conclusions:Natalizumab-induced response and remis- sion at week 8 was sustained through week 12. The response and remission rates for natalizumab were superior to those for placebo at weeks 4, 8 and 12, demonstrating the early and sustained efficacy of natalizumab in induction therapy in patients with elevated C-reactive protein and active Crohn’s disease. Natalizumab was well-tolerated in this study.
Commentaire : Il s’agit du deuxie`me grand essai fait par la firme ELAN qui a mis au point le natalizumab pour prouver l’efficacite´ de cette mole´cule pour l’induction d’une re´ponse dans la maladie de Crohn active. En effet, le premier essai de cet anticorps monoclonal dirige´ contre l’4 inte´grine e´tait ne´gatif. L’essai ENACT-1 avait inclus 905 patients et avait compare´ trois perfusions de natalizumab 400 mg a` un placebo3. Une re´ponse clinique avait e´te´ enregistre´e dans 56 % des cas dans le groupe natalizumab et 49 % dans le groupe placebo (NS). Une analyse post-hoc en sous-groupes avait cependant note´
une diffe´rence dans le sous-groupe des patients avec PCR e´leve´e (58 vs 45 %, p = 0,007) ce qui a motive´ le sche´ma de l’e´tude publie´e par Targan et al. Les patients devaient avoir une PCR au-dessus de la normale (> 2,87 mg/l dans un laboratoire centralise´) pour pouvoir eˆtre inclus. Les re´sultats d’ENCORE confirment ceux obtenus dans l’analyse en sous-groupes de l’essai ENACT avec 48 vs 32 % de re´ponse soutenue (baisse du CDAI 70 points) de la semaine 8 a` la semaine 12 (p < 0,001). A` la 12esemaine, le pourcentage de patients en re´mission e´tait de 38 vs 25 %. Il s’agit cependant de diffe´rences assez faibles avec un nombre de sujet ne´cessaire de traiter (NNT) de 6 et 7,5 pour l’obtention d’une re´ponse ou de la
3Sandborn WJ, Colombel JF, Enns R, et al. (2005) Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med 353: 1912-25.
re´mission. On sait par ailleurs depuis l’essai ENACT-2 que le natalizumab est efficace pour le maintien en re´mission de la maladie de Crohn avec a` six mois un patient sur deux en re´mission clinique sans corticoı¨des. Un des proble`mes majeurs que pose le natalizumab est constitue´ par la description de trois cas de leucoence´phalopathie multi- focale progressive dans les essais cliniques pre´ce´dents avec une fre´quence de survenue de cette infection opportuniste a` virus JC, habituellement mortelle, de 1 pour 1000 patients traite´s. Si le natalizumab a e´te´ introduit sur le marche´
pour traiter la scle´rose en plaques en raison de son efficacite´ remarquable dans cette maladie et de l’absence d’autre solution the´rapeutique dans les SEP graves rebelles au traitement par interfe´ron, la situation est diffe´rente dans la maladie de Crohn ou` nous avons toujours la possibilite´ du traitement chirurgical meˆme si celui-ci est quelquefois mutilant.Primum non nocereest quelquefois un adage hippocratique bien oublie´, mais il est vrai qu’aucune nouvelle classe de biothe´rapie de MICI n’est disponible depuis les anti-TNF et que certains patients devenus re´fractaires a` ces traitements posent des pro- ble`mes de´licats de strate´gie the´rapeutique.
Cotation :
M.-A. Bigard
Ulcerative colitis: no rise in mortality in a Europe-wide, population-based cohort 10 yearsafter diagnosis
Hoie O, Schouten LJ, Wolters FL, et al. (2007) Gut 56 (4): 497-503
Background: Population-based studies have revealed varying mortality rates for patients with ulcerative colitis, but most have described patients from limited geogra- phical areas who were diagnosed before 1990.
Aims:To assess overall mortality in a European cohort of patients with ulcerative colitis, 10 years after diagnosis, and to investigate national ulcerative colitis-related mortality across Europe.
Methods:Mortality 10 years after diagnosis was recorded in a prospective, Europe-wide, population-based cohort of patients with ulcerative colitis diagnosed from 1991 to 1993 in nine centres in seven European countries. Expected mortality was calculated from the sex, age and country- specific mortality rates listed in the WHO Mortality Database for 1995-1998. Standardised mortality ratios (SMR) and 95% confidence intervals (CI) were calculated.
Results: At follow-up, 661 of 775 patients were alive with a median follow-up time of 123 months (107-144).
A total of 73 deaths (median follow-up time 61 months [1-133]) occurred compared with an expected 67. The overall mortality risk was no higher: SMR 1.09 (95%
CI: 0.86-1.37). Mortality by sex was SMR 0.92 (95%
CI: 0.65-1.26) for males and SMR 1.39 (95% CI: 0.97-1.93)
for females. There was a slightly higher risk in older age groups. For disease-specific mortality, a higher SMR was found only for pulmonary disease. Mortality by Euro- pean region was SMR 1.19 (95% CI: 0.91-1.53) for the North and SMR 0.82 (95% CI: 0.45-1.37) for the South.
Conclusions: Higher mortality was not evident in patients with ulcerative colitis 10 years after disease onset. However, a significant rise in SMR for pulmonary disease and a trend towards an age-related rise in SMR was observed.
Commentaire :Cet article va dans le sens actuel d’une re´vision de nos conceptions sur la rectocolite he´morra- gique dont le pronostic n’est probablement pas aussi mauvais que les grandes se´ries des anne´es 1950 et 1960 l’avaient de´termine´.
Dans ce suivi de cohorte qui avait inclus au de´part 2201 patients dans 12 pays europe´ens, un suivi a` dix ans a e´te´ possible sur 774 patients et aucune surmortalite´ n’a e´te´
trouve´e avec cet intervalle de temps. Il y a une tendance a`
une mortalite´ plus e´leve´e par affection pulmonaire, ce qui est e´tonnant, les patients avec RCH ayant moins souvent un tabagisme.
Ces constatations d’absence de surmortalite´ sont rassurantes pour les patients et sont importantes en termes d’assurance. Les malades atteints de MICI sont souvent assure´s avec de lourdes surprimes, et l’accumu- lation de donne´es actuelles plus optimistes sur le sort des patients doit amener a` une baisse des surprimes.
Cotation :
M.-A. Bigard
Induction and maintenance infliximab therapy or the treatment of moderate-to-severe Crohn’s disease in children
Hyams J, Crandall W, Kugathasan S, et al. (2007) Gastroenterology 132: 863-73
Background and aims: The REACH study evaluated the safety and efficacy of infliximab in children with moderately to severely active Crohn’s disease.
Methods: Patients (N = 112) with a Pediatric Crohn’s Disease Activity Index (PCDAI) score greater than 30 received infliximab 5 mg/kg at weeks 0, 2, and 6. Patients responding to treatment at week 10 were randomized to receive infliximab 5 mg/kg every 8 or 12 weeks through week 46. A concurrent immunomodulator was required. Clinical response (decrease from the baseline in the PCDAI score 15 points; total score30) and clinical remission (PCDAI score10 points) were evaluated at weeks 10, 30, and 54.
Results: At week 10, 99 of 112 (88.4%) patients responded to infliximab (95% confidence interval: [82.5, 94.3%]) and 66 of 112 (58.9%) patients achieved clinical remission (95% confidence interval: [49.8, 68.0%]). At
week 54, 33 of 52 (63.5%) and 29 of 52 (55.8%) patients receiving infliximab every 8 weeks did not require dose adjustment and were in clinical response or clinical remission, respectively, compared with 17 of 51 (33.3%) and 12 of 51 (23.5%) patients receiving treatment every 12 weeks (P= 0.002 andP< 0.001, respectively).
Conclusions: Paediatric patients responding to an induction regimen of infliximab were more likely to be in clinical response or remission at week 54 without dose adjustment when their maintenance therapy was adminis- tered every 8 weeks, rather than every 12 weeks. Allowing for dose intensification in the case of relapse, remission rates, but not response rates, at week 54 were superior with every-8-week dosing compared with every-12-week dosing.
Commentaire : Depuis quelques anne´es, l’azathio- prine repre´sente un traitement tre`s couramment utilise´
en pe´diatrie pour traiter la maladie de Crohn. La corticode´pendance et la corticore´sistance sont en effet fre´quemment rencontre´es chez les enfants, et les corticoı¨- des ont un effet ne´faste sur la croissance. L’infliximab constitue une alternative inte´ressante a` la corticothe´rapie en association avec l’azathioprine. Ce grand essai confirme l’efficacite´ de l’infliximab, mais cet essai n’a pas inclus de comparateur actif type corticoı¨de ou de bras placebo. La supe´riorite´ d’une perfusion toutes les huit semaines plutoˆt que toutes les 12 semaines est de´montre´e.
A` un an, un peu plus de la moitie´ des patients sont en re´mission avec le rythme d’une perfusion tous les deux mois. En l’absence de groupe placebo, il n’est pas possible de calculer le nombre de sujet ne´cessaire de traiter (NNT).
Le proble`me de la bithe´rapie est repre´sente´ par la description de lymphomes T he´patosple´niques, au pro- nostic le plus souvent fatal chez des patients recevant cette combinaison the´rapeutique. Cette constatation doit faire rester tre`s prudent pour l’utilisation de cette bithe´rapie, et une monothe´rapie, soit par infliximab, soit par azathioprine est suˆrement pre´fe´rable : on n’a cependant pas d’essai de l’infliximab en monothe´rapie versus placebo. A` noter qu’il y avait tre`s peu d’enfants de moins de dix ans dans cet essai puisque l’aˆge moyen e´tait de 13,3 ans avec un e´cart-type de 2,5 ans.
Cotation :
M.-A. Bigard
Quadrivalent vaccine against human
papillomavirus to prevent anogenital diseases Suzanne M. Garland, et al. (2007)
N Engl J Med 356: 1928-43
Background:A phase III trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in
preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16 and 18.
Methods: In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24, we assigned 2723 women to receiving vaccine and 2732 to receiving placebo at day 1, month 2 and month 6. The co-primary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the occurrence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis was collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose.
Results: The women were followed for an average of 3 years after administration of the first dose. In the per- protocol population, those followed for vulvar, vaginal, or perianal disease included 2261 women (83%) in the vaccine group and 2279 (83%) in the placebo group.
Those followed for cervical disease included 2241 women (82%) in the vaccine group and 2258 (83%) in the placebo group. Vaccine efficacy was 100% for each of the co- primary end points. In an intention-to-treat analysis, which included patients with prevalent infection or disease caused by vaccine-type and non-vaccine-type HPV, vaccination reduced the rate of vulvar or vaginal perianal lesions by 34% (95% confidence interval [CI]:
15-49) and the rate of cervical lesions by 20% (95% CI:
8-31), both regardless of the causal HPV type.
Conclusions: The quadrivalent vaccine significantly reduced the incidence of HPV-associated anogenital diseases in young women.
Commentaire : Il est estime´ que les papillomavirus (HPV) sont implique´s dans la gene`se de 5 a` 10 % de l’ensemble des cancers. HPV 16 et 18 sont les deux se´rotypes oncoge`nes le plus souvent incrimine´s dans la survenue des cancers du col ute´rin et de l’anus, HPV 6 et 11 sont responsables de la majorite´ des papillomes anoge´nitaux. Cette large e´tude testant le vaccin quadri- valent contre HPV 6, 11, 16 et 18 confirme que ce vaccin pre´vient les le´sions anoge´nitales lie´es a` HPV (condylomes ge´nitaux et de la marge anale, ne´oplasies intrae´pithe´lia- les cervicales ou CIN). A` noter qu’un second travail, publie´ dans le meˆme nume´ro du New England Journal of Medicine, confirme l’efficacite´ du vaccin quadrivalent pour pre´venir les CIN de haut grade4. Il n’est malheu- reusement pas possible, a` l’heure actuelle, de transposer les donne´es sur la pre´vention des dysplasies du col a`
l’anus. En effet, on manque d’e´le´ments sur la trans- sudation du vaccin au niveau du canal anal et il n’est pas
4Garlan SM, et al (2007) Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. The future II study group. N Engl J Med 356: 1915-27.
certain que l’efficacite´ au niveau anal soit superposable a` celle de´montre´e au niveau ge´nital.
Cotation :
A. Sene´joux
Proctalgia fugax: demographic and clinical characteristics. What every doctor should know from a prospective study of 54 patients
Vincent de Parades et al. (2007) Dis Colon Rectum 50: in press
Purpose:This prospective study was designed to describe a typical attack of proctalgia fugax.
Methods: Patients were recruited from May 2003 to June 2004. Regardless of the reason for consultation, they were systematically asked the following question:
"Do you ever suffer intermittent and recurring anorectal pain lasting for at least three seconds?" If the response was yes, they were interviewed using a questionnaire and received a proctological examination. The criterion for proctalgia fugax was a positive answer with a negative examination.
Results:The study included 1809 patients. Fifty-four of these patients (3%) had proctalgia fugax, and 83% never sought medical advice for the condition. The mean age was 51 (range, 18-87). Thirty-seven patients were female (69%). The onset of pain was sudden and without trigger
in 85% of the cases. Attacks occurred in the daytime (33%) as well as at night (35%). Seventy-six percent of the patients described the pain as cramping, spasm-like, or stabbing. It did not radiate in 93% of the cases, and there were no concomitant symptoms in 81% of the cases.
Attacks stopped spontaneously 67% of the time. The average duration was 15 minutes (range: 5 seconds to 90 minutes). The average, annual number of attacks was 13 (range: 1-180).
Conclusions: Proctalgia fugax affects twice as many females as males at approximately age 50. Usually, the attacks occur about once a month as a sudden pain with no trigger, as much during the day as at night. On average, the non-radiating cramp, spasm, or stabbing pain, without concomitant symptoms, is most severe after 15 minutes and declines spontaneously.
Commentaire : La proctalgie fugace, qui fait partie des de´sordres fonctionnels anorectaux selon les crite`res de Rome, est une affection fre´quente pourtant mal connue des me´decins peut-eˆtre parce que la litte´rature a` son sujet est pauvre. Ce travail en pre´cise les caracte´ristiques se´miologiques. Il s’agit d’une douleur de survenue brutale affectant deux fois plus souvent les femmes, autour de la cinquantaine. La douleur est aussi souvent diurne que nocturne, ce´dant le plus souvent spontane´ment apre`s une dure´e moyenne de 15 minutes. La physiopathologie de cette affection reste impre´cise.
Cotation :
A. Sene´joux
