The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

Background: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy. The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). Methods/Design: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and powe

Familial adenomatous polyposis. Surgery, genetics and experimental models

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease that affects about 1 in 8000 individuals. Patients with FAP typically develop hundreds to thousands of adenomas or adenomatous polyps during their second and third decades of life. Although these benign tumours are not individually life-threatening, their large number virtually guarantees that some will progress to invasive carcinomas. Additionally, FAP patients often carry congenital retinal lesions and later develop other extracolonic manifestations, including osteomas, desmoids tumours, cysts of the skin, brain tumours and some other, rarer neoplastic formations. Throughout our different studies, the purpose was the prevention of colorectal cancer in aptients with FAP. In Part I, we emphasised the importance of including the patients and their families in a national register. The principal aim of a polyposis register is to imrpov the prognosis of FAP through family tracing, and through appropriate information, education and counselling of familu memebers at risk. This has a beneficial effect on the incidence of established colorectal cancer at diagnosis of FAP. Moreover, a register will ensure a regular follow-up of patients after surgery. A secondary aim is to provide a database for research and for national or international collaborative studies. To date, surgery is still the only effective prophylactic treatment of FAP to prevent cancerous degeneration, but the choice of a surgical procedure is controversial. In Part II, we showed that ileal pouch-anal anastomosis (IPAA) with endoanal mucosectomy offers the best prevention by removing all the diseased epithelium. In order to avoid urinary and sexual dysfunction in the often young and healthy patients with FAP, we advocate a dissection close to the rectal wall when performing the protectomy, to avoid injury of the pelvic autonomic nerves. Compared to ileorectal anastomosis (IRA), IPAA is a rather complex, technically demanding surgical procedure; it is safe, and though it carries a significant risk of complications, it offers god to excellent functional results and quality of life. Moreover, we have shown that a secondary protectomy and IPAA after a previous IRA is easy to perform, although it can be impossible in some cases because of the development of desmoids tumour. Therefore, in most of our patients with FAP we have chosen to perform the more definitive operation, namely IPAA, directly without a preliminary stage of IRA. After a review of the genetic features of FAP, Part III was entirely devoted to APC mutation screening in order to propose a presymptomatic diagnosis of FAP for at-risk members of the family. By screening the entire APC coding sequence among 45 unrelated patients with FAP and by combining heteroduplex analysis (HA), single-strand conformation analysis (SCCA) and the protein truncation test (PTT), we were able to identify AA previously unpublished novel mutations. Furthermore, we have established their precise genotype-phenotype correlations and we have underlined their potential usefulness for new diagnostic strategies in FAP. For instance, we were able to find two mutations by direct sequencing of APC regions according to CHRPE status. On the other hand, precise knowledge of phenotype-genotype correlations could influence the surveillance for extracolonic manifestations of FAP, such as desmoid tumours or adrenal tumours, for mutations located at the 3’ end of the APC gene. However, since we offer IPAA as a first-choice operation to almost all our patients with FAP, the mutation location along the APC gene does not guide our surgical management. The purpose of screening on patients with family histories of FAP is to achieve a diagnosis at an early stage and to offer prophylactic treatment against colorectal cancer and thereby reduce morbidity and mortality related to FAP. In order to established a stepwise program for APC mutation screening, we compared the usefulness and limitations of both HA and SSCA. We fond a mutation detectability rate of 35% for HA and 46 for SSCA, with a lesser sensitivity of HA fir single base pair subtitutions and of SSCA when analysing large PCR fragments. The two techniques should complement each other, and they can now even be used in the same gel electropheresis. Based on our recent experience, we propose an integrated stepwise strategy for mutation screening in FAP. As the first step, we use the CHRPE status to perform direct sequencing of the relevant APC region. Next, we follow an exon-by-exon strategy for the remaining exons by using HA and SSCA or more sophisticated and highly sensitive techniques. For the remaining patients, after a search for gross structural rearrangements, linkage analysis may be performed with a high reliability (>99%) by using flanking or intragenic polymorphic markers. Reagrding future prospects, the recent development of a high-throughput and cost-effective analytical method for mutation detection, the DNA chip-based assay, will be critical for FAP because of its ability to scan large genes rapidly and accurately for all possible heterozygous mutations in large numbers of patient samples. Part IV is directed towards the potential polyp and cancer prevention effect of a drug, aspirin (ASA), and/or a dietary component, resistant starch (RS) in FAP-gene carriers. This issue was addressed in an animal model of FAP, and among several available transgenic mice we chose the Apc 1638N strain because its milder phenotype allows a longer life-span. In a first study we confirmed and defined the intestinal phenotypic expression of this transgenic mouse. Heterozygous Apc+/Apc 1638N mice progressively develop five to six adenomas and carcinomas of the small intestine within the first 6 months of life following a histological sequence similar to that observed in human intestinal tumours. We further investigated the genetic events in these tumours. We showed that, although the genetic inactivation of both Apc alleles is involved as the initiating event of human as well as murine intestinal tumourgenesis, tumour growth and progression follow different mutational pathways in these two species. In a second study, we analyser the potential chemopreventive effect of ASA and/or RS on tumour formation in these Apc 1638N mice. Surprisingly, we found an unexpected increase of the tumour number in the duodenum in mice fed RS. This contradicts previous epidemiological and experimental studies. The effect of RS on the small intestine was not previously examined in animals or in humans and will require further investigations. ASA shows a relative protection against this deleterious effect of RS in small intestine tumourgenesis. In a final study, we attempted to analyse the potential effect of ASA and/or RS at a cellular level by studying the DNA damage in the mouse gut epithelium. For this purpose, we applied the single cell gel electrophoresis (SCGE) assay or comet assay (CA) for use on the mouse gut. Again, we found a trend towards an increase of DNA damage in the small intestine with RS given alone and we failed to show any significant effect of ASA given alone. However, we did find some protective effect of ASA against the deleterious effect of RS on DNA damage. We showed that CA allows the study of not only individual epithelial cells but also of whole intestinal crypts. Moreover, apoptotic cells were easily identified. CA is therefore a very promising tool for research in the GI tract and may be useful in many different applications in the futureThèse d'agrégation de l'enseignement supérieur (Faculté de médecine) -- UCL, 199

Bilan pré-opératoire du cancer du rectum

The diagnosis of colorectal cancer must be considered in the presence of suggestive symptoms and must be endoscopy. Assessment of operability, including chest x-ray, is completed by CEA determination and x-rays of the colon, looking for a synchronous lesion. Complementary assessments must answer 3 questions: what operation needs to be performed, is any preoperative adjuvant treatment indicated, do any prognostic factors need to be identified before the operation. The treatment of cancer of the colon is now clearly defined; intraoperative hepatic ultrasonography and histological examination of the resection specimen provide all of the necessary data in the majority of the cases. In the presence of a cancer of the rectum, various therapeutic alternatives are available according to the site and stage of the tumour. The complementary assessment includes biopsy to confirm the malignant nature of the lesion, and measurement of the distance of the lower pole from the anal margin (digital rectal examination, endoscopy). A more precise preoperative staging by ultrasonography, computed axial tomography or magnetic resonance is required when the clinician considers that the invasive nature of the lesion justifies preoperative radiotherapy. This precise staging is fully justified in the presence of a small rectal tumour amenable to local resection. Although infiltration of the rectal wall is now very clearly defined, formal identification of metastatic lymphadenopathy still remains hazardous. Finally, the search for distant metastases by invasive and/or expensive techniques is indicated when looking for contraindications to surgery (high-risk patients, surgery for recurrence and metastases). In other cases, the presence of metastases does not contraindicate a palliative colonic resection and intraoperative exploration allows reliable identification of any liver metastasis

[Preoperative assessment of cancer of the rectum.]

The diagnosis of colorectal cancer must be considered in the presence of suggestive symptoms and must be endoscopy. Assessment of operability, including chest x-ray, is completed by CEA determination and x-rays of the colon, looking far a synchronous lesion. Complementary assessments must answer 3 questions: what operation needs to be performed, is any preoperative adjuvant treatment indicated, do any prognostic factors need to be identified before the operation. The treatment of cancer of the colon is now clearly defined; intraoperative hepatic ultrasonography and histological examination of the resection specimen provide all of the necessary data in the majority of the cases. In the presence of a cancer of the rectum, various therapeutic alternatives are available according to the site and stage of the tumour. The complementary assessment includes biopsy to confirm the malignant nature of the lesion, and measurement of the distance of the lower pole from the anal margin (digital rectal examination, endoscopy). A more precise preoperative staging by ultrasonography, computed axial tomography or magnetic resonance is required when the clinician consideres that the invasive nature of the, lesion Justifies preoperative radiotherapy. This precise staging is fully justified in the presence of a small rectal tumour amenable to local resection. Although infiltration of the rectal wall is now very clearly defined, formal identification of metastatic lymphadenopathy still remains hazardous. Finally, the search for distant metastases by invasive and/or expensive techniques is indicated when looking for contraindications to surgery (high-risk patients, surgery for recurrence and metastases). In other cases, the presence of metastases does not contraindicate a palliative colonic resection and intraoperative exploration allows reliable identification of any liver metastase

Comprendre le vécu des patients stomisés : quels besoins d’aide et d’éducation ?

Selon les chiffres issus du Cahier SIPES de mars 2009 sur le dépistage du cancer colorectal en Communauté française (Jonckheer, 2009), le cancer colorectal touche plus d’un million de personnes chaque année et en tue près de la moitié. En Belgique, en 2004, ce sont 7 582 nouveaux diagnostics qui ont été enregistrés par la Fondation Registre du Cancer. Les données épidémiologiques indiquent que ce cancer constitue une menace grave pour la santé publique en Communauté française. Il est en effet la troisième cause de cancer chez les hommes, la deuxième chez les femmes et la deuxième cause de décès par cancer, ce qui démontre sa sévérité. Nous nous situons d’ailleurs parmi les pays aux plus hauts taux d’incidence et de mortalité liés à ce cancer dans le monde. Le traitement du cancer colorectal étant avant tout chirurgical, l’ablation engendre la pose d’une stomie définitive ou temporaire. Cette intervention est lourde physiquement et psychologiquement pour le patient qui doit, quotidiennement, gérer les conséquences de l’intervention qu’il a subie, sans compter que, la plupart du temps, il est aussi atteint d’un cancer et doit faire face à la maladie. Ces deux paramètres affectent largement sa qualité de vie. De plus, le patient stomisé rencontre des complications d’ordre physique et sexuel. Il subit une grande modification de son image corporelle, des répercussions dans sa vie sociale, professionnelle, familiale et de couple. Cela demande qu’il s’adapte aux changements et les accepte. Le présent dossier technique tente de définir les éléments ayant un impact sur la qualité de vie du patient stomisé et sa capacité d’adaptation à l’intervention. Cela permettra de déterminer les besoins qui en découlent et la manière dont les auteurs proposent d’y répondre. Les 14 publications retenues et analysées rapportent les résultats de diverses recherches sur le sujet. Les méthodes des recherches présentées consistent, la plupart du temps, en un questionnaire envoyé par la poste ou par mail, comprenant des questions d’ordre socio-démographique, des questions d’ordre médical et des questions touchant au ressenti par rapport à la stomie. Les patients sont alors invités à utiliser diverses échelles permettant de mesurer leur qualité de vie, niveau d’information, etc. Pour cette dernière partie, certains chercheurs ont préféré mener des entretiens semi-dirigés. Les personnes interrogées sont des patients stomisés, sortis de l’hôpital depuis 1 jour à 19 an

Endorectal ultrasonography for staging small rectal tumors: technique and contribution to treatment.

Thirty-one tumors, lying in the lower two-thirds of the rectum and possibly suitable for local excision, were analyzed by endorectal ultrasonography (EUS) using the Aloka scanner SSD 520. There were 18 sessile villous adenomas (group I) and 13 invasive cancers 3 cm or less (group II). Preoperative endosonographic staging (uT, uN stages) was compared with the histologic analysis of the specimens (pT, pN) and the possible contribution to therapy was evaluated. In group I, the depth of tumor infiltration was accurately assessed in 89% of cases. Malignant transformation was suspected in 4 cases (uT2) and confirmed postoperatively in 3 cases. In group II, the extent of the tumor was correctly evaluated in 84% of cases. With regard to the overall differentiation between T1 and T2/T3 tumors on one hand, and between T1/T2 and T3 lesions on the other hand, the positive predictive values were 93.3% and 100%, respectively. The negative predictive values were 93.7% and 92.8%. In group II the search for regional lymph nodes was positive in 4 cases and negative in 9 cases. An accuracy rate of 82% (sensitivity 75%, specificity 85%) was estimated by analysis of the specimens and postoperative follow-up. The exact performance could not be evaluated because a radical resection was not carried out in most cases. EUS was useful for planning the treatment of villous adenomas. A board full-thickness excision was carried out without delay for the four uT2 villous tumors, allowing safe margins to be obtained in all cases. Using EUS the choice of local excision was questioned for six small invasive cancers (uT3 and/or uN+), although radical resection was carried out for only two. As high sensitivity could not be achieved when detecting lymphatic metastasis, the choice of limited surgery based on EUS staging requires strict postoperative follow-up

[Treatment of Deep Anal Fistulas By Advancement of a Flap of Rectal Wall]

Classic treatment of high anal fistulas by the laying open technique requires total or subtotal section of the sphincter muscles and results in anal incontinence. This study assesses the efficacy of the flap advancement technique in these cases. It entails the resection of the crypt at the origin of the fistula, the area being covered by a mucomuscular flap of the rectal wall. From 1977 to early 1992,18 patients (13 female and 5 male patients; mean age : 40 years) presenting with a deep anal fistula underwent such an operation. There were 16 suprasphincteric and 2 high transsphincteric tracts. Associated IBD was noted in 7 cases (5 Crohn's colitis, 2 UC). Five fistulas were of obstetrical origin. In 8 cases, patients had undergone previous surgical treatments without success. All patients had a flap advancement. In 2 cases, a colostomy had been previously carried out. Two more diverting stomies were performed (combined abdominal procedures). No mortality or morbidity was encountered. Mean postoperative stay was 8 days. Current status could be established in all patients. Three immediate failures were observed (1 case of Crohn's disease, two recurring cases). All the other patients did well with persistent healing of the fistula after a mean follow-up of 61 months (range, 6-150). Three stomies were closed ; one patient delayed the procedure. Functional results were excellent. In the > group, all the evaluable patients (14/15) had normal fecal continence. Two female patients are still complaining of mild flatus incontinence. In the failure group, the preoperative anorectal function was maintained. These good results are confirmed by the literature. The flap advancement technique is an effective operation respecting both anatomy and function in the treatment of the deep anal fistulas

Identifier les moments d’apparition des besoins d’information et d’éducation des patients stomisés : étude qualitative, auprès de 55 patients

Introduction : Une revue de la littérature a permis de déterminer quels étaient les besoins d’accompagnement et d’éducation des patients stomisés mais pas le moment où apparaissaient ces besoins. Méthodes : Afin de déterminer cette période pour chaque besoin, 55 patients stomisés digestifs ont été interviewés par des infirmières stomathérapeutes, à trois moments distincts : avant l’intervention, à la sortie de l’hôpital et à distance de l’intervention. Résultats : Cette étude a été réalisée dans sept centres de Wallonie et Bruxelles. D’une part, l’analyse des résultats a permis d’identifier le moment d’apparition des besoins du patient et permettra l’adéquation de sa prise en charge. D’autre part, elle a révélé des attentes non rencontrées. Cette étude sera suivie d’une recherche quantitative afin de valider les résultats obtenus dans la partie qualitative.Introduction: A literature review allowed to determine specific support and educational needs for ostomate patients, but not the moments of appearance of such needs. Methods: In order to know at which moment of the care process support and educational needs do rise, semi-structured interviews were carried out with 55 ostomy patients, by stomaterapist, at three various moments: before surgery, before discharge, and later at home. This study was carried out in seven french belgian surgical departments. Results: Results allowed the identification of moments at which needs do emerge, making support and educational interventions more appropriate. Besides, it revealed unmet expectations. It was also used as a basis for a quantitative confirmation study. © 2012 EDP Sciences, SETE

The transanal endoscopic microsurgery procedure: standards and extended indications.

Transanal endoscopic microsurgery (TEM) was developed in the early 1980s as a minimally invasive technique allowing the resection of benign rectal adenomas. For this indication, TEM was reported to be safe and effective and even exceeded the results compared to classical local excision. Unsurprisingly, the indication expanded to small rectal cancer. There is still much debate, though, whether it is oncologically safe to perform TEM for rectal cancer. Much has been published about the need for proper patient selection, i.e. patients presenting a low-risk T1 rectal cancer seem to be the most adequate subgroup for this technique. Nevertheless, TEM remains controversial concerning high-risk T1 rectal adenocarcinomas and deeper infiltrating tumors. Several retrospective case series and a small prospective study suggest that radiochemotherapy before local excision reduces recurrence to a level comparable with classic radical surgery (total mesorectal excision). However, these studies are collectively limited, and prospective data from larger multicenter trials are awaited. Reports about functional results after TEM have shown that the procedure has no permanent impact on anorectal function. Even if transient anal resting pressure weakening has been repeatedly described, patients do not suffer from any long-term functional sequelae. Nor do they complain of quality of life impairment