DOI 10.1007/s11725-013-0444-z
REVUE DE PRESSE / PRESS REVIEW
Adalimumab for the treatment
of moderate to severe hidradenitis suppurativa:
a parallel randomized trial
Kimball AB, Kerdel F, Adams D, et al. (2012) Ann Intern Med 18: 846–55
Background: Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults.
Objective: To evaluate the efficacy and safety of adali- mumab, an anti-tumor necrosis factor-α antibody, in patients with moderate to severe HS.
Design: Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study (ClinicalTrials.gov:
NCT00918255).
Setting: 26 academic and private practice medical centers in the United States and Europe.
Patients: 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics.
Intervention: Patients were assigned in a 1:1:1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimu- mab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Phy- sician’s Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31.
Measurements: The primary outcome measure (clinical response) was the proportion of patients achieving an HS- PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16.
Results: At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. pla- cebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted dif- ference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo
difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group.
A decrease in response was seen after the switch from weekly to EOW dosing in period 2.
Limitations: Weeks 16 to 52 of the study were open- label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders.
Conclusion: Adalimumab dosed once per week alleviates moderate to severe HS.
Primary funding source: Abbott Laboratories.
Commentaires : L’hidradénite suppurée ou maladie de Verneuil est une affection dont la fréquence est mal connue, certaines estimations avoisinant les 1 % de la population générale. Sa sévérité est variable, cependant chez certains patients la maladie entraîne une importante altération de la qualité de vie. Le traitement de référence est l’excision des territoires cutanés touchés par l’affection. Cependant, le recours à un traitement chirurgical de façon itérative, les sacrifices cutanés importants parfois nécessaires font rechercher une alternative de traitement médicamenteux.
Les antibiotiques sont ainsi fréquemment prescrits, les réti- noïques et les antiandrogènes ont été testés. La multiplicité des traitements proposés souligne que la physiopathologie de l’affection est mal connue sinon mystérieuse. Plus récem- ment ont été proposés des traitements de type biothérapie.
L’essai ici présenté est le second concernant l’adalimu- mab. Le premier, publié en 2011, favorable au traitement, concernait un groupe restreint de patients (21), celui-ci est d’envergure plus importante. Il montre une améliora- tion dose-dépendante des patients traités par adalimumab qui peut paraître limité puisque l’amélioration maximale obtenue concernait moins de 20 % des malades avec une posologie de 40 mg par semaine. La posologie optimale reste sans doute à définir, mais cette voie thérapeutique est intéressante dans un champ où les praticiens sont parfois démunis en matière thérapeutique.
Cotation : ☺☺☺☺
A. Senéjoux
Faecal incontinence in inflammatory bowel disease:
associations and effect on quality of life Norton C, Dibley LB, Bassett P (2012) J Crohns Colitis (sous presse)
King’s College, London & Imperial College Healthcare NHS Trust, London, United Kingdom. Electronic address:
christine.norton2@imperial.nhs.uk
Background and aims: No previous study has reported on faecal incontinence (FI) amongst people with IBD.
We aimed to determine the frequency and severity of FI in people with IBD, its association with known FI risk factors, and the effect on quality of life.
Method: We randomly sampled 10,000 members of a national Crohn’s and Colitis organisation over 18years old.
Demographic information, medical history, FI (ICIQ-B), urinary continence (ICIQ-UI), quality of life (IBD-Q) and free text responses about FI were collected. Current disease activity was reported using the Harvey Bradshaw Index for Crohn’s Disease (CD), and the Walmsley Index for ulcera- tive colitis (UC). Data were managed using Excel, Stata and SPSS 18.
Results: 4827 responses were received: 3264 were com- plete and included (32.6% response). 2178 respondents were female (66.7%); mean age 50.26yrs (range 19-92); CD 1543 (46.98%); UC 1599 (48.97%); other IBD 126 (3.85%);
no diagnosis given 6 (0.18%). 74% (2391) of respondents reported FI (95% CI 72-75). Nine percent (299) reported regular FI. No association was found between FI and diag- nosis. Significant associations were found in multivariable analysis between FI and age (P = 0.005), gender (P < 0.001), anal stretch (P = 0.004), anal fistula surgery (P < 0.001), colo-rectal surgery (P ≤ 0.001), and urinary incontinence (P ≤ 0.001), but not with vaginal delivery. Quality of life was significantly affected by FI (P < 0.001).
Conclusion: Even if all non-respondents are continent, FI affects 24% of people with IBD. In our sample 74%
reported FI, which can occur without active disease. There is a large currently unmet need for continence care in people with IBD.
Commentaires : Il existe actuellement très peu de don- nées concernant les troubles de la continence anale chez les malades souffrant de maladies inflammatoires intestinales (MICI), hormis chez ceux ayant bénéficié d’une anasto- mose iléoanale ou d’une chirurgie de fistule anale. Cette enquête, menée sur un très large échantillon de patients, met en évidence une prévalence importante des troubles de la continence dans une population souvent jeune : 24 % versus généralement autour de 5 %, selon les séries publiées, dans la population générale. Certains facteurs sont particulièrement péjoratifs chez les malades atteints de MICI
pour la continence avec des risques relatifs en analyse uni- variée respectivement : anastomose iléoanale (RR = 3,15 [1,5–7,36]), dilatation anale (RR = 3,09 [1,54 ; 6,20]) chirurgie de fistule anale (RR = 2,05 [1,35–2]), fissure anale (RR = 2,67 [1,32 ; 5,39]). L’analyse multivariée confirmait le rôle de ces facteurs de risque ainsi que celui de l’âge avancé et du sexe féminin. De façon logique, l’incontinence était plus fréquente chez les malades ayant des selles liquides (évaluation par échelle de Bristol) et constituait un facteur altérant la qualité de vie.
Cotation : ☺☺☺
A.Senéjoux
Randomized double-blind crossover study of alternative stimulator settings in sacral nerve stimulation for faecal incontinence
Duelund-Jakobsen J, Dudding T, Bradshaw E, et al. (2012) Br J Surg 99: 1445–52
Background: Sacral nerve stimulation is an established treatment for faecal incontinence. Nearly half of all patients experience loss of efficacy at some point. Standard repro- gramming restores efficacy for some, but not all, patients.
This study aimed to determine whether alternative stimula- tor settings would increase treatment efficacy.
Methods: Patients with sustained loss of efficacy were recruited from two international specialist centres. A number of alternative stimulation parameters were tested using a double-blind randomized crossover study design. Stimu- lation settings tested were pulse frequencies of 6.9 and 31 Hz, and pulse widths of 90 and 330 µs, compared with one standard setting of 14 Hz/210 µs. Treatment efficacy was evaluated using a disease-specific quality-of-life score (Fecal Incontinence Quality of Life Scale, FIQLS) and a bowel habit diary completed before randomization, during the study period and after 3 months of follow-up with one preferred setting.
Results: Fifteen patients were analysed. With one pre- ferred setting, three of four subdomains in the FIQLS improved significantly. The mean (s.d.) total number of incontinence episodes dropped from 11.7(10.8) to 4.8(4.5) per 3 weeks (P = 0.011) and improvements were maintained after 3 months of follow-up. Optimal pacemaker settings were individual, but a trend towards highest patient satisfac- tion and improved treatment outcome was evident for high- frequency stimulation (31 Hz/210 µs), which was preferred by eight of the 15 patients.
Conclusion: Patients experiencing loss of efficacy can experience improvement If alternative pacemaker settings are tested. High-frequency stimulation (31 Hz/210 µs) was
preferred by more than half of the patients, and improved treatment outcome was sustained at 3 months.
Commentaires : Environ un tiers des malades implantés après un test de neuromodulation ont une perte d’efficacité de la thérapeutique au cours du suivi. Dans ces conditions, des modifications des paramètres de stimulation sont entre- prises pour tenter de restaurer une efficacité. Les auteurs se sont intéressés à deux paramètres de variations qui concernent soit la fréquence de la stimulation, soit la durée de la période des spikes dans le cadre d’un essai contrôlé randomisé en cross-over concernant un petit groupe de patients en perte d’efficacité. La modification des para- mètres permettait d’améliorer globalement la qualité de vie et de diminuer de moitié les accidents d’incontinence.
L’augmentation de la fréquence de la stimulation semblait être une étape plus favorable que celle de l’augmentation de la durée des spikes.
Cotation : ☺☺☺
L. Siproudhis
Transcutaneous electrical tibial nerve stimulation in the treatment of fecal incontinence:
a randomized trial (CONSORT 1a)
Leroi AM, Siproudhis L, Etienney I, et al. (2012) Am J Gastroenterol 107: 1888–96
Objectives: The objective of this study was to show that although transcutaneous electrical tibial nerve stimulation (TENS) is being increasingly used to treat fecal inconti- nence (FI), its efficacy has never been proved using control- led trials.
Methods: In this randomized, double-blind, sham-control- led trial, 144 patients aged 30-82 years from nine centers were randomly assigned to receive either active or sham stimula- tions for 3 months. The primary end point was the response to treatment based on the number of incontinence and urgency episodes. Secondary end points were severity scores, qual- ity of life scores, delay to postpone defecation, patient self- assessment of treatment efficacy, physician assessment of TENS efficacy, anorectal manometry, and adverse events.
Results: No statistically significant difference was seen between active and sham TENS in terms of an improve- ment in the median number of FI/urgency episodes per week. Thirty-four patients (47%) who received the active TENS treatment exhibited a > 30% decrease in the FI sever- ity score compared with 19 patients (27%) who received the sham treatment (odds ratio 2.4, 95% confidence inter- val 1.1-5.1, P = 0.02). No differences in delay to postpone defecation, patient self-assessment of treatment efficacy, or anorectal manometry were seen between the two groups.
The evaluating physicians rated the active stimulations as more effective than the sham stimulations (P = 0.01). One minor therapy-related adverse event was observed (1.5%).
Conclusions: We failed to demonstrate any benefit of TENS on our primary end-point.
Randomized controlled trial of percutaneous versus transcutaneous posterior tibial nerve stimulation in faecal incontinence
George AT, Kalmar K, Sala S, et al. (2013) Br J Surg 100: 330–8
Background: Percutaneous, transcutaneous and sham trans- cutaneous posterior tibial nerve stimulation was compared in a prospective blinded randomized placebo-controlled trial.
Methods: Patients who had failed conservative treatment for faecal incontinence were randomized to one of three groups: group 1, percutaneous; group 2, transcutaneous;
group 3, sham transcutaneous. Patients in groups 1 and 2 received 30-min sessions of posterior tibial nerve stimula- tion twice weekly for 6 weeks. In group 3, transcutaneous electrodes were placed in position but no stimulation was delivered. Symptoms were measured at baseline and after 6 weeks using a bowel habit diary and St Mark’s continence score. Response to treatment was defined as a reduction of at least 50 per cent in weekly episodes of faecal inconti- nence compared with baseline.
Results: Thirty patients (28 women) were enrolled. Nine of 11 patients in group 1, five of 11 in group 2 and one of eight in group 3 had a reduction of at least 50 per cent in weekly episodes of faecal incontinence at the end of the 6-week study phase (P = 0.035). Patients undergoing per- cutaneous nerve stimulation had a greater reduction in the number of incontinence episodes and were able to defer defaecation for a longer interval than those undergoing transcutaneous and sham stimulation. These improvements were maintained over a 6-month follow-up period.
Conclusion: Posterior tibial nerve stimulation has short- term benefits in treating faecal incontinence. Percutaneous therapy appears to have superior efficacy to stimulation applied by the transcutaneous route.
Commentaires : Voici deux études contrôlées randomisées publiées à quelques semaines d’intervalle évaluant l’effica- cité de la stimulation tibiale postérieure dans le traitement de l’incontinence fécale. L’une est multicentrique française et teste la stimulation transcutanée non invasive dans des conditions méthodologiques exemplaires et une évaluation aveugle. L’autre est monocentrique et compare deux métho- des de stimulation tibiale, l’une transcutanée l’autre percu- tanée. La méthodologie est médiocre, l’effectif par groupe est faible. L’efficacité de la méthode n’est pas supérieure au
placebo dans le premier essai et très supérieure au placebo dans le second essai alors que le critère de jugement prin- cipal est le même. L’analyse précise des deux essais tend à conclure que cette modalité thérapeutique offre un bénéfice faible sinon insuffisant sur des critères d’efficacité ténus.
Cette méthode ne peut donc pas être recommandée dans le traitement de l’incontinence fécale.
Cotation : ☺☺☺
L. Siproudhis
Fistulotomy with end-to-end primary sphincteroplasty for anal fistula:
results from a prospective study Ratto C, Litta F, Parello A, et al. (2013) Dis Colon Rectum 56: 226–33.
Background: Fistulotomy plus primary sphincteroplasty for complex anal fistulas is regarded with scepticism, mainly because of the risk of postoperative incontinence.
Objectives: The aim of this study was to evaluate safety and effectiveness of this technique in medium-term fol- low-up and to identify potential predictive factors of suc- cess and postoperative continence impairment.
Design and setting: This was a prospective observational study conducted at a tertiary care university hospital in Italy.
Patients: A total of 72 patients with complex anal fistula of cryptoglandular origin underwent fistulotomy and end- to-end primary sphincteroplasty; patients were followed up at 1 week, 1 and 3 months, 1 year, and were invited to par- ticipate in a recent follow-up session.
Main outcome measures: Success regarding healing of the fistula was assessed with 3-dimensional endoanal ultra- sound and clinical evaluation. Continence status was evalu- ated using the Cleveland Clinic fecal incontinence score and by patient report of post-defecation soiling.
Results: Of the 72 patients, 12 (16.7%) had recurrent fis- tulas and 29 patients (40.3%) had undergone seton drain- age before definitive surgery. At a mean follow-up of 29.4 (SD, 23.7; range, 6–91 months, the success rate of treatment was 95.8% (69 patients). Fistula recurrence was observed in 3 patients at a mean of 17.3 (SD, 10.3; range, 6–26) months of follow-up. Cleveland Clinic fecal incontinence score did not change significantly (P = 0.16). Eight patients (11.6% of those with no baseline incontinence) reported de novo postdefecation soiling. None of the investigated fac- tors was a significant predictor of success. Patients with recurrent fistula after previous fistula surgery had a 5-fold increased probability of having impaired continence (rela- tive risk = 5.00, 95% CI, 1.45-17.27, P = 0.02).
Limitations: The study was limited by potential single- institution bias, lack of anorectal manometry, and lack of quality of life assessment.
Conclusions: Fistulotomy with end-to-end primary sphincteroplasty can be considered to be an effective ther- apeutic option for the treatment of complex anal fistulas, with low morbidity, a high rate of success even at long-term follow-up, and a very low rate of postoperative major fecal incontinence, although minor impairment of continence (postdefecation soiling) may occur. Caution should be used in selecting patients with a history of recurrent fistula and fecal incontinence.
Commentaires : Il s’agit donc ici d’une nouvelle série prospective de patients ayant une fistule anale complexe opérés par fistulotomie et sphinctéroplastie (end-to-end et non-overlapping on précise). Bien que moins médiati- sée récemment que le LIFT (car beaucoup moins nouvelle peut-être, la 1re publication datant de 1985), cette technique chirurgicale n’en a pas moins fait l’objet d’un nombre signi- ficatif d’articles originaux, y compris ces dernières années.
Par rapport aux précédentes études, celle-ci est prospective, a inclus un plus grand nombre de patients que la plupart et exclusivement des fistules complexes, et le suivi était raison- nable à l’échelle de la littérature (même si l’échelle clinique idéale exigerait des suivis beaucoup plus longs que ce qui est fait et raisonnablement faisable, les récidives tardives étant communes). L’évaluation de l’anatomie et de la continence pré- et postopératoire était rigoureuse. Comparativement aux séries précédentes, les résultats sont bons : pour faire simple, 5 % de récidives, 10 % de troubles de la continence et 2 % d’incontinences majeures. Comparativement aux autres techniques chirurgicales possibles dans la même indi- cation, les résultats semblent également recevables même si la comparaison est hasardeuse. Il n’en reste pas moins qu’il ne s’agit « que » d’une série et non d’une étude contrôlée (un tiers des publications originales sur la fistule anale au cours des cinq dernières années sont des essais contrôlés et randomisés), que tous les malades ont été opérés par un seul chirurgien (c’est donc plus une étude d’efficacy que d’ef- fectiveness) et qu’au-delà des limites exposées par l’auteur (absence de manométrie, pas d’évaluation de la qualité de vie), les patients inclus représentent une population hété- rogène et imparfaitement décrite (certains étaient préala- blement drainés, d’autres pas, l’anatomie des trajets était variable, etc.). Cela nous renvoie à l’irréductible diversité des fistules anales et à la grande difficulté pour le commen- tateur de comparer les résultats de publications différentes.
Pour paraphraser un éditorial récent du BMJ, des essais comparatifs avec d’autres techniques chirurgicales sont nécessaires. D’autres séries ouvertes ne le sont pas.
Cotation : ☺☺
J.D. Zeitoun
Identifying important predictors for anastomotic leak after colon and rectal resection.
Prospective Study on 616 patients
Trencheva K, Morrissey KP, Wells M, et al. (2013) Ann Surg 257: 108–13
Objective: The purpose of this study was to identify patient, clinical, and surgical factors that may predispose patients to anastomotic leak (AL) after large bowel surgery.
Background: Anastomotic leak is still one of the most devastating complications following colorectal surgery.
Knowledge about factors predisposing patients to AL is vital to its early detection, decision making for surgical time, managing preoperative risk factors, and postoperative complications.
Methods: This was a prospective observational, quality improvement study in a cohort of 616 patients undergoing colorectal resection in a single institution with the main outcome being AL within 30 days postoperatively. Some of the predictor variables were age, sex, Charlson Comor- bidity Index (CCI), radiation and chemotherapy, immu- nomodulator medications, albumin, preoperative diagnoses, surgical procedure(s), surgical technique (laparoscopic vs open), anastomotic technique (staple vs handsewn), number of major arteries ligated at surgery, surgeon’s experience, presence of infectious condition at surgery, intraoperative adverse events, and functional status using 36-Item Short Form General Health Survey.
Results: Of the 616 patients, 53.4% were female.
The median age of the patients was 63 years and the mean body mass index was 25.9 kg/m2. Of them, 80.3% patients had laparoscopic surgery and 19.5% had open surgery.
AL occurred in 5.7% (35) patients. In multivariate analysis, significant independent predictors for leak were anastomoses less than 10 cm from the anal verge, CCI of 3 or more, high inferior mesenteric artery ligation (above left colic artery), intraoperative complications, and being of the male sex.
Conclusions: Multiple risk factors exist that predispose patients to ALs. These risk factors should be considered before and during the surgical care of colorectal patients.
Commentaires : Une étude de plus sur les facteurs de risque de fistule me direz-vous ? Et vous aurez raison…
Néanmoins, cette dernière a un mérite : elle remet sur le tapis quelques critères que certains chirurgiens devraient toujours avoir en tête au moment de décider de ne pas faire de stomie temporaire car « ça sert à rien »… En analyse multivariée, on retrouve en effet comme facteurs de risque indépendants les comorbidités et le sexe masculin (facteur difficile à modifier…) qui est dû aux difficultés rencon- trées dans un pelvis étroit dans la chirurgie rectale. Mais de manière beaucoup plus intéressante, on retrouve aussi une anastomose située à moins de 10 cm de la marge anale.
Donc oui les amis, faire une stomie temporaire à 100 % des exérèses rectales pour cancer ce n’est pas un crime…
Au contraire… On retrouve aussi les difficultés peropératoi- res lors de l’anastomose (saignement, plaie du grêle, diffi- culté à faire l’anastomose : donc oui ce n’est pas non plus un scandale de faire une stomie temporaire si problèmes per- opératoires (même si l’anastomose paraît « jolie »). Enfin, on découvre comme facteur un peu nouveau le fait de faire une ligature haute de l’artère mésentérique inférieure, néces- saire dans le cancer… mais inutile en pathologie en bénigne.
Donc, faisons là uniquement si c’est justifié ! En conclusion, plein de bons conseils à suivre grâce à cette étude.
Cotation : ☺☺☺☺
Y. Panis
Single-port laparoscopic appendectomy versus conventional laparoscopic appendectomy.
A prospective randomized controlled study Lee W, Choi ST, Lee JN, et al. (2013)
Ann Surg 257: 214–8
Objective: To compare surgical outcomes and quality of life between singleport laparoscopic appendectomy (SPLA) and conventional laparoscopic appendectomy (CLA) in patients with acute appendicitis.
Background: A prospective randomized single center study was performed to compare the outcome of SPLA and CLA in patients with acute appendicitis.
Methods: A total of 248 patients were randomized, but because of 18 withdrawals, the outcome of 224 is analyzed, 116 in CLA and 114 in SPLA.
Results: There was no significant difference in the over- all complication rate (P = 0.470). There were no significant differences in infectious complications between the SPLA group and the CLA group (10.2% and 12.4%, respectively).
The wound complication rate between the 2 groups was not significant (5.1% and 10.6%, respectively; P = 0.207).
Cosmetic satisfaction score, 36-item short-form health survey, and postoperative pain scores were not significantly different between 2 groups.
Conclusions: SPLA failed to show any advantages over CLA relative to pain and cosmesis. However, SPLA is as safe as CLA (RCT number 01348464).
Commentaires : Une nouvelle étude randomisée sur la chirurgie colorectale à trocart unique. La troisième seu- lement à notre connaissance. Donc, il faut en parler. Une méthodologie correcte, un nombre de patients suffisant, et donc des conclusions intéressantes… et pas surprenantes pour le rédacteur de ce commentaire. En effet, cette étude confirme la fiabilité de l’approche à trocart unique, sans
augmentation de la morbidité par rapport à la laparoscopie traditionnelle. C’est un résultat rapporté déjà par toutes les autres études. Mais surtout, elle démontre qu’elle n’apporte rien dans l’appendicectomie, ce qui fait très plaisir. Comme dans la cholécystectomie, on ne voit pas vraiment son intérêt pour des interventions « simples » où la pièce opératoire est extraite par un trocart de 1 cm : pourquoi s’embêter dans ce cas à mettre un trocart unique de 2,5 cm de diamètre ? Au contraire, pour des interventions plus importantes comme la colectomie, le trocart unique pourrait trouver son intérêt…
Cotation : ☺☺☺☺
Y. Panis
Nonoperative management of rectal cancer with complete clinical response
after neoadjuvant therapy
Smith JD, Ruby JA, Goodman KA, et al. (2012) Ann Surg 256: 965–72
Introduction: Nonoperative management (NOM) of rectal cancer after a complete clinical response (cCR) to neo- adjuvant therapy is controversial. In this article, we retro- spectively reviewed the outcomes of patients managed with selective NOM after a cCR to neoadjuvant treatment and compared these with patients who underwent standard rec- tal resection with a pathological complete response (pCR).
Methods: Patients completing neoadjuvant chemo- radiotherapy (CRT) for stage I to III rectal cancer between January 2006 and August 2010 were retrospectively reviewed. Median follow-up was calculated in months after completion of CRT.
Results: Thirty-two patients (median follow-up 28 months) were treated by NOM after a cCR. Among 265 treated by CRT and rectal resection, 57 patients (22%) had a pCR and formed the control group (median follow-up 43 months). Factors associated with selective use of NOM included lower pretreatment stage, older age, and distal tumor location (P < 0.05). In the NOM group, 6 recurred locally (median 11 months, range 7–14), 3 of whom also had concurrent distant recurrence. All 6 local failures were controlled by salvage rectal resection with no further local recurrence of disease (median follow-up 17 months).
In the rectal resection/pCR group, there were no local fail- ures. The 2-year distant disease-free survival (88 vs 98%, P = 0.27) and overall survival (96 vs 100%, P = 0.56) were similar for NOM and rectal resection/pCR groups.
Conclusions: Rectal resection was successfully avoided in 81% of patients selected for NOM. When combined with salvage surgery, NOM appears to achieve similar local and distant disease control compared with patients with a pCR
treated by rectal resection. Longer follow-up and prospec- tive trials are warranted to evaluate this promising treat- ment option.
Commentaires : Nouvelle étude sur la surveillance sim- ple après traitement néoadjuvant pour cancer du rectum publiée dans Annals of Surgery… Les auteurs du MSKCC rapportent une série de 32 patients surveillés et la compare aux résultats de 57 patients opérés avec une pièce de résec- tion stérilisée. Les résultats globaux semblent, comme sou- vent, excellents laissant penser que dans quelques années il ne sera plus nécessaire d’opérer les patients. Le diable est dans les détails cependant : la moitié des malades sur- veillés ne pouvaient pas être opérés (refus, comorbidités), 57 % ont reçu une chimiothérapie, un quart des patients avaient une tumeur classée T1-T2N0. Dans cette série, on retrouve un taux de récidive locale de 19 % ayant conduit à une exérèse (amputation, résection antérieure). Cette réci- dive locale s’accompagnait de métastases dans la moitié des cas. La comparaison avec les patients opérés donne à réfléchir : à deux ans, le taux de récidive locale est de 21 % en cas de surveillance et 0 % après résection chirurgicale.
Plus inquiétant, un taux de récidive métastatique quatre fois plus important en cas de surveillance (8 vs 2 %, p = 0,3) et une survie sans récidive moins bonne de 10 % (88 vs 98 %) pour des tumeurs de très bon pronostic. Cette série confirme donc les résultats de la revue récente publiée dans Br J Surg avec un taux de récidive locale aux alentours de 30 %.
La surveillance simple ne semble donc pas la solution, et une exérèse de la cicatrice tumorale devrait permettre de mieux sélectionner les vrais répondeurs qui pourraient éviter une proctectomie sans risque carcinologique au long cours.
Cotation : ☺☺☺☺
J. Lefevre
T-cell non-Hodgkin’s lymphomas reported to the FDA AERS with tumor necrosis factor-alpha (TNF-α) inhibitors:
results of the REFURBISH Study Deepak P, Sifuentes H, Sherid M, et al. (2013) Am J Gastroenterol 108: 99–105
Objectives: The risk of non-Hodgkin’s lymphoma (NHL) with tumor necrosis factor alpha (TNF-α) inhibitors is unclear, whether related to concomitant thiopurines usage or due to the underlying inflammatory disease. We sought to review all cases of T-cell NHL reported to the Food and Drug Administration (FDA) in patients receiving TNF-α inhibitors for all approved indications and examine the risk of T-cell NHL with TNF-α inhibitors in comparison with the use of thiopurines in inflammatory bowel disease (IBD).
Methods: The FDA Adverse Event Reporting System (AERS) was queried for all lymphomas following treatment with the following TNF-α inhibitors: infliximab, adali- mumab, certolizumab, etanercept, and their trade names.
Full reports for T-cell NHL cases were identified using the Freedom of Information Act. In addition, T-cell NHL reported in patients IBD with the use of the thiopurines-azathioprine, 6-mercaptopurine, and their trade names were also collected.
A search of MEDLINE was performed for additional T-cell NHL with TNF-α inhibitors or thiopurines, not reported to the FDA but available in published literature. The histo- logical subtypes of T-cell NHL reported with TNF-α inhibi- tors were compared with reported subtypes in Surveillance Epidemiology and End Results (SEER) -17 registry. Reported risk of T-cell NHL in IBD with TNF-α inhibitors, thio purines, or concomitant use was calculated using Fisher’s exact test using 5-aminosalicylates as control drugs.
Results: A total of 3,130,267 reports were downloaded from the FDA AERS (2003-2010). Ninety-one cases of T-cell NHL with TNF-α inhibitors were identified in the FDA AERS and nine additional cases were identified on MEDLINE search. A total of 38 patients had rheumatoid arthritis, 36 cases had Crohn’s disease, 11 had psoriasis, 9 had ulcerative colitis, and 6 had ankylosing spondylitis.
Sixty-eight of the cases (68%) involved exposure to both a TNF-α inhibitor and an immunomodulator (azathioprine, 6-mercaptopurine, methotrexate, leflunomide, or cyclo- sporine). Hepatosplenic T-cell lymphoma (HSTCL) was the most common reported subtype, whereas mycosis fun- goides/Sezary syndrome and HSTCL were identified as more common with TNF-α-inhibitor exposure compared with SEER-17 registry. Nineteen cases of T-cell NHL with
thiopurines were identified in the FDA AERS and one addi- tional case on MEDLINE. Reported risk of T-cell NHL was higher with TNF-α inhibitor use in combination with thiopurines (95% confidence interval (CI) 4.98-354.09;
P < 0.0001) and thiopurines alone (95% CI 8.32-945.38;
P < 0.0001) but not with TNF-α inhibitor use alone (95% CI 0.13-10.61; P = 1.00).
Conclusions: Risk of T-cell NHL is increased with TNF-α inhibitor use in combination with thiopurines but not with TNF-α inhibitors alone.
Commentaires : Le risque de lymphome sous anti-TNF est incertain et constitue une préoccupation dans la prise en charge des patients atteints de MICI depuis la description de cas de lymphomes hépatospléniques de particulièrement mauvais pronostic. Le risque de lymphome sous thiopurine est mieux connu : dans la cohorte prospective CESAME le risque relatif est multiplié par cinq en cas d’exposition aux thiopurines. Dans cette même cohorte, le risque spécifique de lymphome T a été évalué et semble multiplié par dix en cas de traitement combiné (thiopurine/antiTNF). Cette large étude à partir des données de la FDA concernant les effets secondaires rapportés sous anti-TNF, toutes indications confondues, permet de conclure que le traitement anti-TNF en monothérapie ne constitue pas un risque de lymphome T à l’inverse du traitement en association aux thiopurines ou en monothérapie par thiopurines. Ces données sont ras- surantes quant à la sécurité d’emploi des anti-TNF, mais il s’agit d’une étude rétrospective.
Cotation : ☺☺
M. Simon
