Medication of Diseases News - Part 80

ASA, NSAIDs, coxibs and colorectal cancer prevention (Part 5)

intake of NSAIDsThis paper sets the stage for longer term prospective studies. Based on the potential revenue coxibs could generate if proven to prevent cancer, their manufacturers may be able to justify the funding of such trials. Subject recruitment may be largely comprised of patients somewhat younger than those examined in this case-control study, but it is easy to imagine that a multicentre collaboration would be able to enroll sufficient numbers to provide adequate statistical power for such a prospective study. Until then, most of us will still view this class of drugs with cautious respect.

ASA, NSAIDs, coxibs and colorectal cancer prevention (Part 4)

An additional observation made in this study is worthy of comment. The likelihood of finding CRA or CRC was smaller for patients with bowel symptoms, other than bleeding, than for asymptomatic patients, who were presumably investigated for screening purposes rather than for diagnosis. This finding supports the emerging opinion of many experts that, for the assessment of symptoms like chronic abdominal pain or constipation, colonoscopy should not be considered essential, and the choice of investigation should be determined by the individual clinical situation.

ASA, NSAIDs, coxibs and colorectal cancer prevention (Part 3)

celecoxibFor CRC prevention, celecoxib was most effective (OR 0.23), followed by rofecoxib (OR 0.53) and standard NSAIDs (OR 0.67). When data for CRA and CRC were combined, the ORs were 0.47, 0.64 and 0.73 for standard NSAIDs, rofecoxib and celecoxib, respectively. For patients with previous colorectal neoplasia, only rofecoxib was protective (OR 0.43). Insufficient numbers of patients took high dosages of ASA or NSAIDs for at least three months to ascertain either a dose or duration effect.

ASA, NSAIDs, coxibs and colorectal cancer prevention (Part 2)

The paper reviewed here outlines the background and rationale for using these drugs in CRC prevention in the general population. Cox-2 expression is vastly greater in neoplastic tissue than in normal colorectal mucosa. Cox-2 inhibition results in CRC prevention and in CRA prevention and regression in animals, as has been previously reviewed in this Journal and elsewhere . Similar effects have been noted in patients with familial adenomatous polyposis, in whom the role of coxibs is chiefly to retard the development and progression of intestinal neoplasms for which surgery may be deemed inappropriate.

ASA, NSAIDs, coxibs and colorectal cancer prevention (Part 1)

colorectal cancer preventionCRC prevention is increasingly prominent as a public health issue and as a reason for referral to gastroenterologists. Because of our awareness of the adenoma-carcinoma sequence and evidence that adenoma detection by screening reduces CRC incidence and mortality, screening has emerged as the pre-eminent modality of CRC prevention. The resources invested in CRC screening are large and increasing, and have been the subject of a great deal of economic analysis.

Predicting residual rectal adenocarcinoma in the surgical specimen: Conclusions

The addition of deep tissue needle biopsy of endosonographically suspicious residual intramural masses, using curvilinear EUS and fine-needle aspiration (FNA) technique, is a possible future solution to this problem, with or without polymerase chain reaction to look for micrometas-tases. However, a negative cytology would still not completely exclude the presence of residual tumour.

One limitation of this study is the poor sensitivity of EUS for N-staging. Nodal re-staging was not a primary endpoint ofthis particular study; we did not expect BT to alter lymph node status because of its limited depth of penetration and its lack of effect on N-staging, as shown in previous studies.

Predicting residual rectal adenocarcinoma in the surgical specimen: Discussion (Part 2)

urgently operatedAlthough higher stage tumours, in theory, could have been more urgently operated on and consequently missed their post-BT EUS, the high prevalence (89%) of stage T3 lesions in our cohort suggests this did not occur. Overstaging by EUS after BT was a significant problem: the inflammation that extends to the serosal edge, producing an irregular margin with small pseudopod-like projections, will likely remain indistinguishable from serosal invasion.

Predicting residual rectal adenocarcinoma in the surgical specimen: Discussion (Part 1)

Also, proportionally, nodal disease was more prevalent in the sterilized group than in the group with residual disease; however, the CI of the difference was wide (Table 2). These negative exploratory analyses lack the statistical power to be definitive. The accurate identification of patients with and without residual tumour after a BT protocol that promises a high tumour sterilization rate in rectal adenocarcinoma would be ideal and could, in theory, lead to less extensive surgical intervention.

Predicting residual rectal adenocarcinoma in the surgical specimen: Results (Part 4)

pathological T-stageIn eight patients (44%; 95% CI 21% to 67%), the pathological T-stage was exactly predicted on the post-BT EUS. Of the remaining 10, seven (70%; 95% CI 42% to 98%) were overstaged, but four of these (40%) were still within one T-stage of the pathological stage. This comparison is summarized in Table 1, with exact matches bolded. Again, the corresponding kappa was poor for agreement beyond chance (0.11). In the post-BT nodal assessments, there were four false negative and two false positive EUS examinations. These correspond to a sensitivity of 50% (95% CI 15% to 85%) and a specificity of 80% (95% CI 55% to 100%).

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