Volume 64 - 2001 - Fasc.3 - Symposium
Colorectal cancer : controversies
« Ne soyez ni obstinés dans le maintien de ce qui s'écroule, ni trop pressés dans l'établissement de ce qui semble s'annoncer »
Henri (dit Benjamin) Constant de Rebecque (1767-1830)
The molecular basis of colorectal cancer
Colorectal cancers, whether sporadic or hereditary, are caused by a defined set of molecular events. The genes and pathways involved in the earliest steps of tumorigenesis have crucial functions in the regulation of normal crypt homeostasis. Further insight into these pathways can lead to the development of useful prognostic indicators, and target preventive and therapeutic strategies in the management of colorectal cancer. Mutations in the APC/ 0-catenin/Tef-4 pathway lead to important changes in stem cell dynamics, before clinically identifiable lesions appear. Preventive strategies aimed at reversing these changes or therapeutic interventions targeting cell populations with these alterations should be most efficacious.
Colorectal cancer screening
Colorectal cancer (CCR) is the second cause of cancer death in developed western world. Most colorectal cancers are probably preventable through screening.
Surgeon-related aspects of the treatment and outcome after radical resection for rectal cancer
Aim : To summarise the magnitude and mechanisms of surgeonrelated variability in the outcome after radical resection for rectal cancer and to present a solution and targets. Methods : A review of the literature, consultation of the "Guidelines for the management of colorectal cancer" published by the Association of Coloproctology of Great-Britain and Ireland, and analysis of data from the database of the Belgian Ministry of Health, RIZIV-INAMI, on radical resection for rectal cancer in Belgium during the years 1995-1997. Results : The proportion of abdominoperineal excision of the rectum (APER) varies between 23-58% in specialised centres and 43-57 % general practice. In Belgium the APER rate for rectal cancer located between 4 and 16 cm above the anal verge is 50% with an overall in-hospital mortality of 3.5% ; both APER rate and postoperative mortality are lower in university than in community hospitals. Most studies observe an effect of specialisation, reducing mortality with a factor of 2.5 - 3. The magnitude of surgeonrelated variability in the oncological outcome has been well documented indicating that the impact of the surgeon-factor is considerably larger than that of adjuvant therapy. When comparing subspecialised with general surgeons, relative risk factors of 0.3-0.8 are reported for local recurrence rate, and 0.7-0.8 for disease free survival. Conclusion : Inter-surgeon variability is to be related with surgical skill and adequate implementation of recent diagnostic and therapeutic methods. Guidelines and centralisation are appropriate concepts, but do not guarantee improved quality of care. The targets are an APER rate of < 40 % with an operative risk of < 2 %, a local recurrence rate of < 10% and a disease free survival of > 70%. External audit is essential, but subspecialty training is a prerequisite and the surgeon is not the only factor to be audited.
Adjuvant treatment for colorectal cancer
Colorectal cancer is a leading cause of cancer in Western countries. Surgery remains the only way to cure it. Recent trials led to the general acceptance of adjuvant chemotherapy in Dukes C cancer by identifying bolus 5FU and leucovin during 6 months (5 days monthly) as the current standard. The role of adjuvant chemotherapy remains questionable in Dukes B2 (stage 11) colon cancer, in rectal cancer and after curative resection of liver metastases The development of total mesorectum excision (TME) technique has dramatically resulted in improving local recurrence control and will be the standard in rectal cancer surgery ; pre-operative irradiation is widely used in Europe for stage 11 and III rectal cancer but its definite place and its optimal regimen await further assessment as well as the role of adjuvant chemotherapy in rectal cancer. New chemotherapeutic combinations based on new effective agents in colorectal cancer such as CPT-11 and oxaliplatine have been currently used for downstaging liver metastases initially unresectable. This new approach, combined with the development of local ablative therapies such as cryotherapy and radiofrequency allows curative strategies in a significant number of patients primarily unfit for surgical resection of liver mets. The present paper aims to review the different aspect of (neo)adjuvant therapies in the multimodal curative management Dukes B2 colon cancer of colorectal cancers.
Follow-up after curative surgery for colorectal cancer
Approximately 1 in 3 colorectal patients treated by surgery with curative intent will develop cancer recurrence, and most of them will die from disseminated disease. Post-operative follow-up aims at improving these ominous figures. Any strategy is justified as far as it influences evolution : global survival, disease-free period, quality of life. The value of follow-up for patients remains controversial. The literature review suggests that more intensive followups lead to an increased number of reoperations, a more aggressive oncological approach in non resectable cases, provide data for an efficient quality control and have a major cost impact. Surveillance is appreciated by the patients who are confident in the efficacy of such policies. On the other hand, the benefit on the outcome of the patients is not forirnally established. Outcome might depend on tumoural characteristics rather than on the moment of recurrence detection. Not all schedules are alike, and CEA deterirnination is required. Including all patients in intensive programs is not evidence-based medicine and is highly cost ineffective. Follow-ups must be tailored to individual characteristics. The most intensive ones are dedicated to the patients with the highest risk of treatable recurrence : high risk patients (tumour site and stage), able and willing to undergo reoperation (age, general condition, ...). Research should try to determine curability tumoural factors (genetic tumour factors). In the meantime, and for the other patients, the most effective follow-ups could be programs in which only a few tests are routinely used : referential colonoscopy, history and physical examination, CEA deterniination and a rectoscopy for rectal cancers.
Visceral sensitivity in explaining functional bowel disorders : from concepts to clinical practice
Functional digestive disorders (FDD) consist of several syndromes characterized by the absence of any organic or biochemical abnormality and mainly defined by a cluster of symptoms more or less related to one segment of the gut (1). The most frequent and most studied of them are Non-Ulcer Dyspepsia (NUD) and Irritable Bowel Syndrome (IBS). Abdominal pain is the most f equent complaint of these patients. It may result from organic or functional disorders and may be related to different neurophysiological mechanisms. Classical aetiological theories have implicated psycho-social factors and abnormalities in gastrointestinal motility. Consequently to this hypothesis, most of the prevailing therapeutic approaches to resolve pain in patients with FDD have focused on motility patterns, using antispasmodics, bulk-forming agents and more recently prokinetic compounds. These drugs are mainly acting on the efferent nerve pathways controlling the function of digestive muscle. Over the last decade, a large attention has been paid to the role of visceral sensitivity in the pathophysiology of FDD and especially the Irritable Bowel Syndrome (IBS) (see Rev. Mayer Raybould) (2). These studies have enlightened the role of nerve afferent pathways arising from the gut and processing information to the peripheral and central nervous systems and thereby triggering a number of reflexes. The afferent nerve pathways have thus been recognized as a possible target for new treatments aimed to relief pain in patients with FDD.
Role of GI motor abnormalities in irritable bowel syndrome
There is still no category of gastrointestinal disease that fosters a greater sens@ of frustration in physicians and patients than functional gastrointestinal disorders. This frustration reflects the paucity of effective medications, and is only tempered for the physician by the knowledge the diagnosis is most often correct, and safe, that is, patients do not develop significant complications or die from these disorders. Regrettably, the patients experience impaired quality of life, and utilize health care resources extensively as they seek better "solutions" (including unnecessary repeated investigations or even surgery). From a societal standpoint, there is also a significant economic burden estimated for 1998 at $41 billion for the 8 most industrialized countries ; two thirds of this burden reflects absenteeism from work and the indirect costs.
Therapeutic strategy in irritable bowel syndrome
Functional gastrointestinal disorders are among the most frequent problems encountered not only in specialised gastroenterology consultations, but also in general medical practice (1,2). Irritable bowel syndrome (IBS) is a major component of this group of disorders. This syndrome was first clearly identified and defined by Manning (Table 1) (3). Using his criteria a positive diagnosis can be proposed in the absence of an organic disease. More recently working parties on functional gastrointestinal disorders have developed new definitions and criteria. These are synthesised in the recently published Rome
