Recurrence Of Adenomatous Polyps Research Articles

Does Nonsteroidal Anti-inflammatory Drug Use Modify the Effect of a Low-Fat, High-Fiber Diet on Recurrence of Colorectal Adenomas?

The Polyp Prevention Trial was designed to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), low-fat (20% energy) diet on recurrence of adenomatous polyps. Participants > or =35 years of age, with histologically confirmed colorectal adenoma(s) removed in the prior 6 months, were randomized to the intervention or control group. Demographic, dietary, and clinical information, including use of nonsteroidal anti-inflammatory drugs (NSAID), was collected at baseline and four annual visits. Adenoma recurrence was found in 754 of 1,905 participants and was not significantly different between groups. NSAID use was associated with a significant reduction in recurrence [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.63-0.95]. In this analysis, NSAIDs modified the association between the intervention and recurrence at baseline (P = 0.02) and throughout the trial (P = 0.008). Among participants who did not use NSAIDs, the intervention was in the protective direction but did not achieve statistical significance (OR, 0.87; 95% CI, 0.69-1.09). The intervention was protective among males who did not use NSAIDs at baseline (OR, 0.71; 95% CI, 0.54-0.94), but not among NSAIDs users (OR, 1.09; 95% CI, 0.74-1.62). For females, corresponding OR estimates were 1.28 (95% CI, 0.86-1.90) and 2.30 (95% CI, 1.24-4.27), respectively. The protective association observed for NSAID use was stronger among control (OR, 0.63; 95% CI, 0.47-0.84) than for intervention group participants (OR, 0.97; 95% CI, 0.74-1.28). These results should be interpreted cautiously given that they may have arisen by chance in the course of examining multiple associations and Polyp Prevention Trial study participants were not randomly assigned to both dietary intervention and NSAID use. Nevertheless, our results suggest that adopting a low-fat, high-fiber diet rich in fruits and vegetables may lower the risk of colorectal adenoma recurrence among individuals who do not regularly use NSAIDs.

Joint modelling of recurrence and progression of adenomas: a latent variable approach

In this paper, we treat the number of recurrent adenomatous polyps as a latent variable and then use a mixture distribution to model the number of observed recurrent adenomatous polyps. This approach is equivalent to zero-inflated Poisson regression, which is a method used to analyse count data with excess zeros. In a zero-inflated Poisson model, a count response variable is assumed to be distributed as a mixture of a Poisson distribution and a distribution with point mass of one at zero. In many cancer studies, patients often have variable follow-up. When the disease of interest is subject to late onset, ignoring the length of follow-up will underestimate the recurrence rate. In this paper, we modify zero-inflated Poisson regression through a weight function to incorporate the length of follow-up into analysis. We motivate, develop, and illustrate the methods described here with an example from a colon cancer study.

No Association between Fatty Acid Intake and Adenomatous Polyp Recurrence in the Polyp Prevention Trial

Dietary fat intake and cancer risk have been investigated in detail in many populations, although the results have been inconsistent for colorectal cancer. Several molecular mechanisms have been proposed to explain how specific dietary fatty acids could alter colorectal cancer risk due to their

Analysis of colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp Prevention Trial

Interval colorectal cancer (CRC) occasionally is detected in patients who have recently undergone colonoscopy. Systematic evaluation of CRC detected after colonoscopy could identify ways to improve the quality and the outcome of colonoscopy. This study examined cancer diagnoses in the course of the dietary Polyp Prevention Trial, a randomized study of a dietary intervention on recurrence of adenomatous polyps. An algorithm was developed to classify each cancer into one of 4 etiologies: (1) incomplete removal (cancer at the site of previous adenoma), (2) failed biopsy detection (cancer in an area of suspected neoplasia with negative biopsy specimens), (3) missed cancer (large, advanced stage cancer found at a short interval after colonoscopy), or (4) new cancer (small, early stage cancer after a longer time interval). Of 2079 patients, 13 had cancer detected over 5810 person years of observation (PYO) (2.2 cases/1000 PYO); 7/13 or 53.8% of patients had either a potentially "avoidable" cancer or one detectable at an earlier time interval because of incomplete removal (4/13) or missed cancer (3/13). Interval cancer occurs despite colonoscopy. Improved quality of colonoscopy may have reduced cancer prevalence or resulted in earlier cancer detection in over 50% of prevalent cancers in the dietary Polyp Prevention Trial.

The Association of Calcium and Vitamin D with Risk of Colorectal Adenomas

The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel. Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants. We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group, age, gender, nonsteroidal anti-inflammatory drug use, total energy intake, and the interaction of gender and intervention group. Vitamin D models were also adjusted for the location of the clinic site. Dietary variables were adjusted for total energy intake via the residual method. There were no overall significant associations between adenoma recurrence and dietary calcium intake [odds ratio (OR) for the 5th compared with the lowest quintile = 0.91; 95% CI = 0.67-1.23; P-trend = 0.68], total calcium intake (OR = 0.86; 95% CI = 0.62-1.18; P-trend = 0.20), or dietary vitamin D intake (OR = 0.93; 95% CI = 0.69-1.25; P-trend = 0.43) averaged over follow-up. Total vitamin D intake was weakly inversely associated with adenoma recurrence (OR = 0.84; 95% CI = 0.62-1.13; P-trend = 0.03). Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence (OR for any compared with no use = 0.82; 95% CI = 0.68-0.99; and OR = 0.82; 95% CI = 0.68-0.99; for calcium and vitamin D, respectively). Slightly stronger associations were noted for the prevention of multiple recurrences. Our analyses did not suggest a significant effect modification between total calcium and total vitamin D intake (P = 0.14) on risk for adenoma recurrence. This trial cohort provides some evidence that calcium and vitamin D may be inversely associated with adenoma recurrence.

Relationship of Visceral Adipose Tissue to Recurrence of Adenomatous Polyps

Insulin is a growth factor for colorectal cancer. Visceral adipose tissue (VAT) is strongly associated with insulin levels, and insulin and visceral obesity have been associated in cohort studies with colorectal cancer. The aim of this investigation was to determine whether VAT is associated with recurrence of adenomatous polyps, the precursor to colorectal cancer. As an ancillary study to the Polyp Prevention Trial, a randomized clinical trial that evaluated the effect of a low-fat, high-fiber, high vegetable and fruit diet on adenomatous polyp recurrence, subjects at one clinical center underwent measurement of VAT with a single-slice CT scan through the L4-L5 interspace. The scan was performed around the time of the subject's year 4 colonoscopy that determined adenoma recurrence. Of 119 subjects, 44 of 84 men (52%) and 16 of 35 women (46%) had a recurrent adenoma (p= 0.51). Body mass index (BMI) and weight at baseline and at year 4 colonoscopy were unrelated to adenoma recurrence. In a multivariate model including visceral fat quartile, remote history of polyps, gender, age, and randomization group, only remote history of polyps was statistically significantly associated with recurrent adenoma with a relative risk of 4.6 (95% CI 1.7, 12.4, p= 0.001). There was no consistent monotonic trend of increased or decreased risk of recurrence as one ascended quartiles of adipose tissue for visceral, subcutaneous, or total abdominal fat. In this study, no association between visceral adipose tissue and adenomatous polyp recurrence was observed. Further study and exploration of the role of VAT in adenoma progression is required.

Analysis of Colorectal Cancer Occurrence During Surveillance Colonoscopy in the Dietary Polyp Prevention Trial

Colonoscopy can reduce mortality and incidence of colorectal cancer (CRC). However, interval CRC is occasionally detected in subjects with recent colonoscopy. Systematic evaluation of the reasons for interval cancer may be helpful in improving the quality of colonoscopy and in developing guidelines for surveillance. Methods: The Polyp Prevention Trial (PPT) was a randomized, controlled study evaluating the effect of a dietary intervention on adenomatous polyp recurrence. Subjects underwent a baseline colonoscopy (T0 exam) for eligibility, and were scheduled to undergo a repeat exam at 1 and 4 years. We examined the circumstances surrounding the diagnosis of CRC in the PPT population including demographic information, T0 colonoscopy findings, time interval to cancer diagnosis, location, size, and staging. An algorithm was developed to analyze and classify each cancer occurrence into one of four etiologies: 1) Incomplete polyp removal (with subsequent cancer at that site), 2) False negative biopsy (where a suspicious area was biopsied but cancer was not detected), 3) Missed cancer (cancer that occurred in a different location from the site of previous polyp removal and was diagnosed in a relatively short time frame from the most recent colonoscopy), and 4) New cancer. Results: Of 2079 patients, 15 cancers developed in 14 subjects (0.67%) over 5810 person years of observation (PYO)(2.4 cases/1000 PYO). 71.4%(10/14) had an advanced adenoma and 50% had ≥2 adenomas detected at the baseline examination. The cancers were found throughout the colon; 53.3% (8/15) were proximal to the splenic flexure and 33.3% (5/15) were in the cecum or at one of the flexures. Based on our analysis, 7/14 or 50% of patients had a potentially “avoidable” cancer, with diagnosis due to incomplete removal of an advanced adenoma with cancer developing at that site subsequently (4/14) or an apparent missed cancer (3/14). The “incomplete removal” category highlights the importance of assuring the complete excision of advanced adenomas. Missed cancers were relatively large and were all located proximal to the hepatic flexure, emphasizing the importance of assuring cecal intubation. Conclusion: Interval cancers occur with some frequency despite colonoscopy. Improved colonoscopy quality and follow up of potential incompletely removed high risk adenomas may have reduced cancer incidence, or resulted in earlier cancer detection in up to 50% of incident cancers in the PPT.

Dietary fibre for the prevention of colorectal adenomas and carcinomas.

Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialized countries. Experimental evidence has supported the hypothesis that dietary fibre may be protective for the development of CRC, although epidemiologic data have been inconclusive. We have conducted a systematic review and meta-analysis to assess the effect of dietary fibre on the incidence or recurrence of colorectal adenomas, the incidence of CRC, and the development of adverse events. We identified randomized controlled trials from Medline, Embase, and the Cochrane Controlled Trials Register up to Oct 2001 Randomized or quasi-randomized controlled trials were assessed. The population included all subjects that had adenomatous polyps but no previous history of colorectal cancer (CRC), a documented "clean colon" at baseline and repeated visualization of the colon/rectum after at least two years of follow-up. Dietary fibre was the intervention. The primary outcomes were the number of subjects with: a) at least one adenoma, b) more than one adenoma, c) at least one adenoma greater than or equal to 1 cm or d) a new diagnosis of CRC. The secondary outcome was the number of adverse events. Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as relative risks (RR) and risk difference (RD) with 95% confidence intervals (CI). If statistical significance was reached, the number need to treat (NNTT) or harm (NNTH) was reported. The study data were combined with the fixed effects model if it was clinically, methodologically, and statistically reasonable. Five studies with 4349 subjects met the inclusion criteria. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. When the data were combined there was no difference between the intervention and control groups for the number of subjects with at least one adenoma [RR 1.04 (95% CI 0.95,1.13); RD 0.01 (95% CI 0.02,0.04)]. As well, the combined results for the number of subjects with more than one adenoma [RR 1.02 (95% CI 0.89,1.17), RD 0.00 (-0.02,0.03)] or at least one adenoma 1 cm or greater [RR 0.94 (95% CI 0.77,1.15), RD -0.01 (-0.02,0.01)] were not statistically significant. Other primary and secondary outcomes and subanalyses by type of fibre intervention were not statistically or clinically significant. There is currently no evidence from RCTs to suggest that increased dietary fibre intake will reduce the incidence or recurrence of adenomatous polyps within a two to four year period.

Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary intervention: results of dietary changes in the Polyp Prevention Trial

The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber (4.30 g/MJ), high-fruit-and-vegetable (0.84 servings/MJ), low-fat (20% of energy from fat) diet on the recurrence of adenomatous polyps in the large bowel. Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention's effect on the intake of other food groups and nutrients. Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were randomly assigned to either the intervention (n = 1037) or the control (n = 1042) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change: food-frequency questionnaires (in 100% of the sample), 4-d food records (in a 20% random cohort), and 24-h dietary recalls (in a 10% random sample). Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments; the control participants' intakes remained essentially the same throughout the trial. The absolute differences between the intervention and control groups over the 4-y period were 9.7% of energy from fat (95% CI: 9.0%, 10.3%), 1.65 g dietary fiber/MJ (95% CI: 1.53, 1.74), and 0.27 servings of fruit and vegetables/MJ (95% CI: 0.25, 0.29). Intervention participants also reported significant changes in the intake of other nutrients and food groups. The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group. Motivated, free-living individuals, given appropriate support, can make and sustain major dietary changes over a 4-y period.

Studies of Calcium in Food Supplements in Humans

Colon cancer is one of the commonest cancers in the Western world. Environmental factors appear to predominate as exemplified by a change in incidence in colon cancer within 20 years when people emigrate from a low- to a high-incidence country. It had been suggested that a diet high in energy, fat, and meat content and low in fiber content is most likely responsible. Epidemiologic observations have pointed to a potential effect of calcium or/and vitamin D in reducing the incidence of colon cancer. Other studies have shown a reduction in preneoplastic colon adenomas with increased calcium or/and vitamin D intake. High fat diets were shown to be accompanied by an increase in fecal fatty acids and bile acids or a change in bile acid composition. Soluble fatty acids and bile acids then could interact with the colonic epithelium inducing cell damage and increased proliferation. A hypothesis was developed suggesting that calcium supplementation and increased calcium in the colonic lumen would precipitate these bile acids and fatty acids. Examination of the effect of supplemental calcium or calcium in dairy foods showed a major reduction in fecal bile acids and fatty acids in solution in volunteers and accompanied by a reduction in cytolytic activity. Studies then were performed in patients at risk for colon cancer seeking a change in proliferative biomarkers of risk from a high-risk to a low-risk pattern with supplemental calcium administration. These studies generally have shown a beneficial effect of the addition of calcium at 1.2-2 gm per day in addition to a regular diet for periods of 2 to 6 months. A recently published study also demonstrated that a diet, in which low-fat dairy foods containing an average of about 825 mg of calcium, significantly improved proliferative biomarkers as well as two differentiation bio-markers of risk for colon cancer from a high- to a low-risk pattern. These observations, together with recent studies showing reduced adenomatous polyp recurrence when supplemental calcium was provided, demonstrate the potential of calcium and perhaps vitamin D as chemopreventive agents for colorectal neoplasia.

Dairy Foods and Prevention of Colon Cancer: Human Studies

Colon cancer is the commonest gastrointestinal cancer and the second leading cause of cancer deaths in the United States. Recent approaches to lowering the incidence of colon cancer have included attempts at dietary prevention and chemoprevention. International and national incidence rates for colon cancer suggest an inverse relationship with dietary calcium and/or vitamin D intake (or sun exposure). Several human intervention studies have suggested that supplemental calcium administration will change proliferative indices of risk for colon cancer from high to lower risk patterns. The principal current hypothesis for the action of calcium implies that calcium may precipitate or bring out of solution fatty acids and bile acids that are potentially toxic to the colorectal epithelium. Both calcium administration and dairy food administration are associated with lowering aqueous fecal concentrations of bile acids and fatty acids accompanied by a highly significant lowering of cytotoxicity in studies in vitro. There is biochemical and biological evidence in cell culture systems that exposure to calcium and/or vitamin D reduces the oncogenic properties of colon cancer cells. A recent blinded study of the administration of low-fat dairy foods demonstrated a significant improvement in several parameters of proliferation as well as in two differentiation markers from a high to a lower risk pattern. Furthermore, administration of calcium also has been shown to reduce the incidence of recurrent adenomatous polyps in individuals at increased risk for colon polyp formation because of the presence of prior colon adenomata. These combined data suggest that administration of supplemental calcium or low-fat dairy foods may have a significant effect upon colonic polyp and perhaps colon cancer incidence.

Chemoprevention of epithelial cancers.

Over the past 2 years, new insights into mutator and stromal epithelial cell interactions have enhanced the understanding of the carcinogenesis process and have identified potential new approaches to chemoprevention in diverse epithelial sites. Data testing the efficacy of chemopreventive agents in genetically mutated animal carcinogenesis models as screening tools for chemopreventive agents remain immature and point to a continued need for chemical carcinogenesis models to screen for the potential efficacy of chemopreventive agents. The Breast Cancer Prevention Trial is a published, risk-reduction trial that demonstrated a tamoxifen-induced reduction of the risk for breast cancer and focused attention on the clinical use of chemopreventive agents in healthy women. This trial highlighted the potential chemopreventive activity of selective estrogen-receptor antagonists as chemopreventives for breast cancer. New data from animal and human models continue to support the development of nonsteroidal anti-inflammatory agents as chemopreventives for colorectal cancer. Micronutrient- and diet-intervention trials for colorectal chemoprevention present a mixed picture. Although calcium and vitamin supplements, including folate, reduce the recurrence of adenomatous polyps in humans, the effect is small. Fiber supplementation does not reduce the incidence of polyps or colorectal cancer. New approaches for the chemoprevention of esophageal adenocarcinomas, hepatomas, and squamous cell skin cancers represent promising new approaches to the chemoprevention of epithelial cancers.

Vitamin and calcium supplement use is associated with decreased adenoma recurrence in patients with a previous history of neoplasia.

Although some have suggested that certain vitamins or calcium supplements may reduce adenoma recurrence, our own prior retrospective study found no such effects. The purpose of this case-control study was to further investigate whether regular vitamin or calcium supplement intake influenced the incidence of recurrent adenomatous polyps in patients with previous neoplasia who were undergoing follow-up colonoscopy. This study enrolled 1,162 patients who underwent colonoscopy by one of three surgeons at Columbia-Presbyterian Medical Center in New York City between March 1993 and February 1997. Of these patients 448 (250 males) had a previous diagnosis of colorectal neoplasia (cancer, adenomas, or dysplasia). Of these, 183 (40.8 percent) had an adenoma at the index colonoscopy. Information was collected on personal and family history of colonic diseases, cigarette smoking, medication, and vitamin and micronutrient supplement usage on a questionnaire that was completed by the patients before the colonoscopy. Odds ratios were obtained by unconditional logistic regression analysis, adjusting for age and gender, and used adenoma recurrence at index colonoscopy as the outcome. The mean interval between colonoscopic examinations was 37 months for the recurrent adenoma group and 38 months for the nonrecurrent group of patients (P = not significant). In this case-control study we found a protective effect for the use of vitamin supplements in general (any vitamin) on the recurrence of adenomas (odds ratio, 0.41; 95 percent confidence interval, 0.27-0.61). Specifically, this protective effect was observed for the use of multivitamins (odds ratio, 0.47; 95 percent confidence interval, 0.31-0.72), vitamin E (odds ratio, 0.62; 95 percent confidence interval, 0.39-0.98), and for calcium supplementation (odds ratio, 0.51; 95 percent confidence interval, 0.27-0.96). Nonsignificant protective effects were noted for carotene/vitamin A, vitamin D, and vitamin C. The use of multivitamins, vitamin E, and calcium supplements were found to be associated with a lower incidence of recurrent adenomas in a population of patients with history of previous colonic neoplasia. Prospective, randomized trials are needed to better assess the impact of these agents and to determine whether the use of these supplements is associated with a protective effect against recurrent adenomas.

Chemo- and dietary prevention of colorectal cancer.

Because of the substantial morbidity and mortality associated with colorectal cancer, and the limitations and costs of treating this disease, prevention remains a desirable (if elusive) goal. In this paper, we discuss both chemo- and dietary prevention strategies for colorectal cancer, recognising the overlap and cross-fertilisation between these two approaches. Chemopreventive compounds are drugs and are developed for clinical use like other pharmaceuticals. A formal sequential multi-phase programme for development of chemopreventive agents has been instituted by the National Cancer Institute, U.S.A. This involves both preclinical efficacy and clinical studies. Such studies increasingly employ preneoplastic intermediate markers (such as proliferation measures) as well as neoplastic adenomas as endpoints. Promising chemopreventive agents include calcium, aspirin and other non-steroidal anti-inflammatory drugs, vitamins (such as vitamin E and folate), 2-dimethylfluorornithine (DFMO), oltipraz and ursodeoxycholic acid. Several lines of evidence implicate diet in colorectal carcinogenesis. Key hypotheses in diet and colorectal cancer (which are amenable to prevention, research and action), in addition to those pertaining to the micronutrient chemopreventives, include dietary fat and fibre, food mutagens, red meat, and overall low-fat, high-fibre, high fruit and vegetable dietary patterns and cuisines. Several adenomatous polyp recurrence studies with fibre supplement, macronutrient or dietary pattern interventions have been undertaken internationally. We review early findings from this new generation of studies, and anticipate the future results from these investigations and the ambitious Women's Health initiative in the U.S.A. Results from these studies may convert the promise of colorectal cancer prevention into reality.

The scope of nutrition intervention trials with cancer-related endpoints

The National Cancer Institute currently is supporting three full-scale dietary modification trials with cancer-related endpoints. These studies are the dietary component of the Women's Health Initiative, designed to determine whether a low-fat diet will reduce the incidence of breast and colorectal cancer and/or coronary heart disease; the Women's Intervention Nutrition Study, designed to test whether a dietary fat reduction program will decrease breast cancer recurrence and increase patient survival; and the Polyp Prevention Trial, designed to determine whether a low-fat, high-fiber diet will reduce the recurrence of adenomatous polyps. Design issues associated with these full-scale dietary modification outcome trials have been addressed successfully in a series of feasibility studies. The ability to achieve a sustained reduction of 50% in dietary fat intake with maintenance of nutritional adequacy has been demonstrated in randomized trials of postmenopausal populations with resected breast cancer and in populations at increased risk for breast cancer. In these studies comparing dietary fat reduction programs with control lifestyles, a series of associated biologic changes, consistent with the self-reported dietary alterations, have been observed. These changes include body weight reduction, serum and/or plasma estradiol concentration reduction, fasting plasma cholesterol concentration reduction, and alteration in free fatty acid levels. Such results provide a substantial basis for reliably estimating the level of adherence that can be anticipated in trials of dietary change, a prerequisite for appropriate calculation of the sample size needed for multicenter, full-scale outcome studies. As a result, the efficacy of a series of dietary alterations (including fat reduction, fiber addition, and/or increased fruit and vegetable intake) on cancer-related endpoints with potential major public health significance (breast cancer recurrence, breast cancer development, and colonic polyp recurrence) now are being addressed definitively in prospective clinical trials.

Experimental Approaches to Colon Cancer Prevention in Humans

Colorectal cancer is a major illness in the Western world. International and migrant studies suggest that environmental causes, notably a fat- and calorie-dense diet (even if adopted in adulthood), are associated with the disease. Case-control studies have not conclusively identified specific etiologic dietary factors, however. In addition, the emphasis placed on migrant studies has led many to overlook potentially important genetic factors that might help to explain some of the discrepancies in the epidemiologic data. Thus, the cause(s) of colorectal cancer remain unclear and hence effective preventive strategies are not presently available. Numerous tenable hypotheses have been generated as a consequence of observational and analytical epidemiologic studies, as well as rodent experiments. Controlled trials to test these hypotheses using colorectal cancer as an endpoint are not justifiable at present. It is possible, however, that "intermediate markers" (such as epithelial cell proliferation rates and others) that are associated with colorectal cancer in both humans and experimental animal systems might provide the means for hypothesis testing in short-term clinical trials. Despite the fact that this approach has several caveats, consistent results obtained in short-term studies would more readily justify the undertaking of a large-scale, long-term controlled study using colon cancer or adenomatous polyp recurrence as an endpoint.

Results of surgical treatment for familial polyposis coli

Seventy-seven patients with polyposis coli operated on at The Mount Sinai Hospital in the last 40 years were studied. Forty-two patients had a subtotal colectomy. Sixteen were found to have colon cancer at the time of operation, and a second rectal cancer developed in 50 percent of the survivors within 1 to 13 years after subtotal colectomy. Rectal cancer subsequently developed in only 3 of 23 patients without colon cancer. Thirty-five patients had total proctocolectomy or total colectomy with mucosal proctectomy and ileoanal anastomosis. Recurrent adenomatous polyps developed in two patients after mucosal proctectomy. A villous adenoma with carcinoma in situ of the ileum developed in one patient 30 years after total proctocolectomy and ileostomy. Another patient died from a periampullary carcinoma 24 years after subtotal colectomy. It seems that as the life expectancy of patients with polyposis improves, the incidence of small bowel and duodenal cancers may be expected to increase.