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The majority of large bowel cancers arise from benign adenomatous polyps. The identification of groups at high risk, the effective investigation and surveillance of these groups, together with a more discerning clinical approach to patients with bowel symptoms provides the best hope of cure.
We reviewed the long-term results of management of 38 patients with carcinoma in colorectal polyps. Of these, 16 patients demonstrated malignant invasion of the lamina propria but not the muscularis mucosa (group I), and 22 patients showed malignant invasion of the muscularis mucosa (group II). Primary therapy for group I patients consisted of polypectomy in 12, local excision in one, and colonic resection in three. One patient had a subsequent abdominal-perineal resection and was found to have no residual disease and no lymph node involvement. Follow-up of the group I patients showed that 11 were alive and well (mean 5.8 years) and five died of unrelated causes (mean 5.2 years). Of group II patients, 12 underwent polypectomy, six local excision, and four colectomy. Of these 22 patients, 11 underwent further operation, including nine major bowel resections and two local re-excisions. None of these 11 patients had either residual tumor or lymph node metastases. One patient died of complications after abdominal-perineal resection. Follow-up showed that 18/22 group II patients were alive and well 5 to 15 years later (mean 7.5 years); four died of unrelated causes (mean 3.2 years). We then reviewed another group of 220 patients who had undergone resection for invasive colon cancer to relate the presence or absence of lymph node metastases to the depth of malignant invasion in the bowel wall. We found that 44% of this entire group had lymph node involvement. Of 36 patients with tumor confined to the bowel wall, nodal metastases occurred in only 22%. Of eight patients with malignancy superficial to the muscularis propria, only one had nodal involvement. We conclude that colon cancer tends to progress in an orderly fashion and the risk of nodal metastases increases with the depth of invasion. Carcinoma in a polyp represents a very early stage of colon cancer. We therefore recommend polypectomy as primary treatment for pedunculated polyps containing carcinoma either superficial to or invading muscularis mucosa. If histologic review demonstrates incomplete excision, lymphatic invasion, or poor differentiation, patients with lesions invading the muscularis mucosa should undergo formal colonic resection.
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From 1980 to 1985, 319 adenomatous colorectal polyps were removed in 297 patients. All patients were entered into a computerized follow-up programme with yearly follow-up. The recommended follow-up was rejected by 58 patients (22.1%). 93 new adenomatous polyps were found in the course of the follow-up in 53 patients (35.8%), five of them histologically invasive carcinomas. The proportion of carcinomas was lowered from 10.6% at first examination to 5.4% in the follow-up period. Size of polyp correlated significantly with carcinomatous change. Size of the adenomas removed at follow-up was markedly smaller than that removed at first examination (69.4% smaller than 1 cm compared with 44.2% at follow-up). In six patients with early invasive carcinoma, further resections were undertaken, while in six others only the polyps were removed. But local recurrences occurred in both groups. Regular follow-up after polypectomy of colorectal adenoma is thus essential.
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New data and approaches bring novel perspectives and possibilities to old problems. The speculation of this chapter attempts to merge the puzzling MS data observed in human tumours (Figs. 3 and 4B) within a multistep tumour progression model. Clearly the current models are gross simplifications and other, more sophisticated models may better account for the distribution of MS alleles found in human tumours. The findings and the data are also limited to MMR deficient tumours, and studies in non-mutator phenotype tumours may be more difficult since fewer polymorphisms will arise during progression. The current model, however, precisely defines proliferation and clearly delineates two very distinct patterns. Further studies using MS loci in MMR deficient tumours will allow fairer tests of alternative pathways (Fig. 4C) to cancer. Evolution proceeding in occult progenitor populations allows mutations to accumulate throughout life and not just in the last decades after polyps appear.
A total of 252 consecutive screening flexible sigmoidoscopies were done by two community-based general internists on asymptomatic patients with stool negative for occult blood. Neoplastic lesions were found in 26 patients (10.3%), including 27 adenomatous polyps, 2 with carcinoma-in-situ and 1 carcinoid tumor. No complications resulted from flexible sigmoidoscopy. Nineteen patients with positive screening sigmoidoscopy underwent colonoscopy, and additional adenomatous polyps were found in six patients (31.6%), but no additional malignancy. Total cost for screening flexible sigmoidoscopy and additional studies was $30,359 ($1,168 per patient with a polyp or malignancy and $10,119 per patient with a malignant lesion). Screening flexible sigmoidoscopy can be safely done by community-based general internists in asymptomatic patients with a diagnostic yield comparable with that reported by subspecialists; total costs are acceptable.
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The mechanisms that regulate ionic balance, fluid absorption and secretion in the gastrointestinal tract are complex. Disturbance of this homeostatic state by bile acids, bacterial enterotoxins and neoplasm-derived secretagogues, for example, can lead to diarrhea. Determining the causes of chronic diarrhea in individual patients may, therefore, represent a diagnostic challenge. The gastrointestinal tract has finely tuned mechanisms to maintain ionic balance, fluid absorption and secretion. To achieve this homeostasis, various ionic transport proteins/complexes are targeted to the apical, basal or basolateral membranes of epithelial cells. Na, K and Cl ion transport proteins are regulated by endogenous activators (e.g. cAMP, PGE2, Ca), dietary-related factors (e.g. bile acids) and through post-translational modifications (e.g. phosphorylation). In certain pathophysiologic states, this homeostatic ionic/fluid exchange becomes dysfunctional as a result of failure of compensatory pro-absorptive/anti-secretory mechanisms. The excessive secretion of Na and Cl ions followed by the release of a large amount of H2O into the colonic lumen results in diarrhea, which may be acute or chronic, and can be life-threatening if not ameliorated. Diverse infectious organisms (e.g. bacteria, protozoa, viruses) utilize different mechanisms to cause intestinal disease and diarrhea. These pathophysiologic mechanisms include alterations in ion transport, disruption of tight junctions and elicitation of inflammatory responses. Studies of patients infected with certain pathogens, those with ulcerative colitis and those harboring extra-colonic or colonic neoplasms have elucidated some of these pathophysiologic mechanisms of diarrhea. Determining the etiology of chronic diarrhea in specific cases may be a diagnostic challenge for both gastroenterologists and primary care physicians.
Androgen, progesterone and estrogen receptors were analyzed in 12 primary colonic cancers and 16 primary rectal cancers. Androgen and progesterone receptors were positive in some colonic cancers and rectal carcinomas; however, none of the specimens analyzed showed estradiol receptor.
BACKGROUND: The role of dietary factors in the aetiology of human cancer is an area, which has attracted intense interest in recent years. The suggestion that approximately one third of all cancers may be caused by an 'inappropriate' balance of food components has led to the attractive contention that we can significantly decrease cancer incidence through dietary recommendations and a change in dietary habits in populations. Thus, a key issue must be to establish clear criteria, which must be met in order to be able to make 'cancer risk reduction' claims for food components. In this area, the one true marker is the malignant human tumour, which for practical reasons is usually not accessible to claims. In its absence, we must rely on alternative markers--biomarkers/surrogate endpoints. This paper mainly deals with the link of these biomarkers to the endpoint tumour and their usefulness for making claims. Some claims have been made based on epidemiological studies. AIM: Can we identify targets/ biomarkers in the chain of events from initial 'exposure' to overt malignant tumour, whose modification can be used to make 'anticancer' claims for food components? RESULTS: We identified 18 targets/markers in the above chain of events whose modification 'have the potential' to be used for 'reduction of cancer risk' claims for food components. These targets/markers fall under 5 broad headings: tumours and preneoplastic changes; cellular targets/markers; gut luminal markers; angiogenesis and metastasis; carcinogen metabolising enzymes; genetic events. CONCLUSIONS: The strongest markers presently available are precancerous lesions (e. g. polyps or aberrant crypt foci) in humans and precancerous lesions and tumours in animal models. The only marker that presently can be used for a 'reduction of disease risk' claim (type B) for food components is 'polyp recurrence'. Type B claims cannot be made on the basis of results in animal models. All of the other biomarkers examined presently lack validation against the 'true endpoint', the tumour, and thus cannot be used for type B claims. 'Reduction of disease risk' claims in the area of 'diet-related cancer' should be based primarily on human intervention studies using relevant/acceptable endpoints. An important area for future research will be the validation of these surrogate endpoints.
Cancer prevention clinical trials use food frequency questionnaires (FFQs) to assist in eligibility screening. FFQ reliability and validity studies are available, but these studies do not evaluate FFQs as screening tools. The Wheat Bran Fiber Trial of the University of Arizona used a FFQ as an eligibility screen with the goal of screening out subjects whose true daily calcium intake was less than 500 mg per day (for safety) and whose true dietary fiber intake was greater than 30 g per day (for safety and trial efficiency). Subjects ineligible by FFQ were interviewed for final dietary eligibility determinations. A study was undertaken within the Wheat Bran Fiber Trial to evaluate the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of the FFQ used in this context. Four-day food records were collected on 183 potential participants before entry into the study. Using the 4-day averages as the "true" value, sensitivity, specificity, positive predictive value, and NPV were calculated for men and women separately under two screening conditions: using the target calcium and dietary fiber values and using "revised" values identified in interim analysis within the study. NPV was acceptable in all analyses. Sensitivity for low calcium intake was inadequate under the original criteria (0.33 for men and 0.09 for women) but acceptable under the revised criteria (0.80 for men and 0.81 for women). With the revised criteria, specificity declined, resulting in heavy screening burdens deemed worthwhile for the safety considerations. Dietary fiber eligibility screening worked well at target values. These differences were not predicted by reliability/validity studies.
A 53-year-old woman presented with symptoms of weight loss, diarrhea, and melena. A barium enema with endoscopy revealed multiple colonic polyps which were shown histologically to be metastatic deposits of poorly differentiated adenocarcinoma. The primary tumor, a poorly differentiated gastric adenocarcinoma, had been resected 11 years earlier. This appears to be only the second published report of polypoid colonic metastases from gastric adenocarcinoma.
Among the conditions which need to be filled when generalizing the mass screening of polyps in view of the secondary prevention of colorectal cancers, three are already present: 1) it is a frequent and serious cancer; 2) there is an affiliation between benign tumours and cancer; 3) an effective non-mutilating treatment of benign tumours is available. On the other hand, two additional conditions remain unfilled and yet lie within the domain of research by methodologically rigorous studies: the setting up of a screening test with a high cost-effectiveness relationship; the epidemiological demonstration of the decreasing incidence of colorectal cancers following screening and treatment of precancerous lesions.
The usefulness, efficacy, safety, and tissue effects of Nd:YAG laser photocoagulation were investigated prospectively in 100 patients. Sixty-seven elderly patients with colorectal adenoma and 21 patients with rectal stump polyps after colectomy and ileorectal anastomosis in familial polyposis were evaluated. We subdivided our patients into those with extensive, intermediate, and small lesions, and we assessed completeness of tumor ablation, recurrence, and complications in all three groups. In the extensive group only 8 patients achieved complete (i.e., gross endoscopic and histologic) tumor ablation, whereas in 18 patients adenomatous tissue persisted or recurred after a tumor-free interval. In the intermediate group complete tumor ablation was achieved in 10 of 22 patients. Small adenomas were completely ablated in 18 of 19 patients. Five instances of carcinoma were detected in each subgroup of nonresponding extensive (18 patients) and intermediate (12 patients) lesions at follow-up. Prior to laser photocoagulation, symptoms such as watery diarrhea, excessive mucous discharge, hypokalemia, dehydration, and hematochezia and iron-deficiency anemia were present in 16 of 26 patients with extensive adenoma and in 13 of 22 patients with intermediate adenoma. Symptoms subsided during the course of treatment in all but 1 patient, even with the absence of complete ablation. Major complications, consisting of bleeding, symptomatic stenosis, or perforation occurred in 11.6% with extensive adenomas, in 9.1% with intermediate adenomas, and in none with small adenomas. Minor complications such as transient asymptomatic stenosis, minor posttreatment hemorrhage, pain, and "serositis" occurred in 30.9% with extensive lesions, in 27.3% with intermediate lesions, and in 10.6% with small lesions. There was no mortality. Treatment of multiple tiny polyps in 21 patients with familial polyposis was easy and efficient, without retraction and scarring, and without complications. We have concluded that laser photocoagulation is safe and uniformly effective in the ablation of small colorectal adenoma and in recurrent polyps in patients with familial polyposis. In patients with intermediate or large adenomas, symptoms are highly responsive to treatment, but complete tumor ablation--as documented upon repeated endoscopy and multiple biopsies--can only be expected in approximately 40%-50% in long-term follow-up. The high incidence of cancers in these two groups (21%) underscores the need for continued surveillance and frequent biopsy. Major and minor complications will occur in 40% in these sizeable lesions, being of clinical importance in only 10%.(ABSTRACT TRUNCATED AT 400 WORDS)
Of 282 patients who underwent rigid proctosigmoidoscopy (PSS) in primary care in the city of Västerås during 1985, 5.7% had polyps or tumours in the rectum. Barium examination of the large bowel was performed on 194 of these 282 patients and showed polyps or tumours in 6.2%. Use of these two methods led to diagnosis of polyps or tumour in the large bowel in 9.6% (27/282). Polyps were found by both methods in only one patient. Of four patients with tumours, two were discovered by barium examination and two by PSS. Barium examination and PSS complement each other in the search for polyps and tumours in the large bowel.