Meat intake and the recurrence of colorectal adenomas.

A large multicenter randomized controlled trial was re-assessed to check whether meat intake and a reduction in its consumption are associated with recurrence of adenomatous polyps of the large bowel, which are precursors of most colorectal malignancies. All subjects (n = 1905; 958 interventions and 947 controls) had one or more histologically confirmed colorectal adenomas removed during a colonoscopy within 6 months before randomization. The subjects were followed-up for approximately 4 years after randomization and a colonoscopy for detecting adenomas was conducted at the 1st and 4th year after randomization. Dietary variables were assessed at baseline (T0) and in conjunction with annual visits at the end of the 1st (T1), 2nd (T2), 3rd (T3) and 4th (T4) years. Odds ratios using logistic regression models for meat variables were estimated based on the average intake at T0, T1, T2, T3 and T4 (prior to the T4 colonoscopy) as well as change (T0-T4) in intake. In the intervention group, the total reduction in median intake of red meat from T0 to T4 was observed by the end of 1st year itself (30 and 31% for men and women, respectively). The analysis provide no evidence to suggest that lower intake or reduction in total and in red meat consumption during a period of 4 years reduces the risk of adenoma recurrence (including multiple or advanced adenoma), whereas the data suggest that high intake of fish is associated with lower risk of adenoma recurrence.

Hormone replacement therapy and colorectal adenoma recurrence among women in the Polyp Prevention Trial.

BACKGROUND: Epidemiologic studies have suggested that estrogen may protect against the development of colorectal cancers and adenomatous polyps. We conducted a prospective study to evaluate the association between hormone replacement therapy (HRT) and adenoma recurrence among perimenopausal and postmenopausal women participating in the Polyp Prevention Trial, a randomized dietary intervention study of individuals with colorectal adenomas. METHODS: We used a questionnaire and interviews to collect detailed information, at baseline and at each of four annual study visits, from 620 women regarding hormone use, menopausal status, diet, alcohol consumption, and other risk factors. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 years. Logistic regression models were used to evaluate the association between hormone use and adenoma recurrence after adjusting for intervention group and for age and body mass index at baseline. All statistical tests were two-sided. RESULTS: Adenomas recurred in 200 women. There was no overall association between adenoma recurrence and either overall hormone use (odds ratio [OR] = 1.01; 95% confidence interval [CI] = 0.70 to 1.45), combined estrogen and progestin use (OR = 0.94; 95% CI = 0.57 to 1.56), or unopposed estrogen use (OR = 1.04; 95% CI = 0.68 to 1.59). HRT use was associated with a reduction in risk for recurrence of distal adenomas (OR = 0.56; 95% CI = 0.32 to 1.00) and a statistically nonsignificant increase in risk for recurrence of proximal adenomas (OR = 1.39; 95% CI = 0.85 to 2.26). We observed a statistically significant interaction between the HRT-adenoma recurrence association and age (P =.02). HRT was associated with a 40% reduced risk of adenoma recurrence among women older than 62 years (OR = 0.58; 95% CI = 0.35 to 0.97) but with an increased risk among women younger than 62 years (OR = 1.99; 95% CI = 1.11 to 3.55). CONCLUSIONS: HRT was not associated with a reduced risk for overall adenoma recurrence in this trial cohort, although there was a suggestion of an age interaction. The effect of age on the association needs to be confirmed in other adenoma recurrence trials.

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

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: 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). RESULTS: 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. CONCLUSION: Motivated, free-living individuals, given appropriate support, can make and sustain major dietary changes over a 4-y period.

Outcome of direct percutaneous endoscopic jejunostomy tube placement for nutritional support in critically ill, mechanically ventilated patients.

PURPOSE: Gastrointestinal function is adversely affected in critically ill mechanically ventilated patients. The most common abnormality is delayed gastric emptying. Among the options for postpyloric feeds, direct percutaneous endoscopic jejunostomy (PEJ) provides a permanent, reliable, and direct access to the small bowel and can be used for full enteral feedings, thus eliminating the need for parenteral nutrition. PATIENTS AND METHODS: All patients who underwent direct PEJ tube placement while mechanically ventilated in the intensive care unit (ICU) were evaluated. For each patient the following factors were identified: age, indication for ICU admission and PEJ placement, nutritional support before and after PEJ placement, calories received, complications, and outcome. RESULTS: Seventeen patients underwent the procedure. All had successful placement of direct PEJ tube. There was a single complication. Within 24 hours of PEJ placement, 16 of 17 patients tolerated jejunal feedings. All patients progressed to their established nutritional goals. There were no cases of aspiration of enteral feedings. In the 16 patients, total parenteral nutrition (TPN) was not required once PEJ tubes were placed. Thirteen patients were discharged home or to a rehabilitation facility with jejunal feedings. CONCLUSIONS: Direct PEJ placement is a safe and reliable device that can be successfully placed in critically ill, mechanically ventilated patients. With this procedure, all patients can meet their nutritional requirements and eliminate the need for TPN.

Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group.

BACKGROUND: We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers. METHODS: We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization. RESULTS: A total of 1905 of the randomized subjects (91.6 percent) completed the study. Of the 958 subjects in the intervention group and the 947 in the control group who completed the study, 39.7 percent and 39.5 percent, respectively, had at least one recurrent adenoma; the unadjusted risk ratio was 1.00 (95 percent confidence interval, 0.90 to 1.12). Among subjects with recurrent adenomas, the mean (+/-SE) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group. The rate of recurrence of large adenomas (with a maximal diameter of at least 1 cm) and advanced adenomas (defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia, including carcinoma) did not differ significantly between the two groups. CONCLUSIONS: Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas.

Long term tolerance of high dose three-dimensional conformal radiotherapy in patients with localized prostate carcinoma.

BACKGROUND: The current study was undertaken to evaluate the incidence and predictors of late toxicity in patients with localized prostate carcinoma treated with high dose three-dimensional conformal radiotherapy (3D-CRT). METHODS: A total of 743 patients with prostate carcinoma classified as T1c-T3 were treated with 3D-CRT that targeted the prostate and seminal vesicles. A minimum tumor dose of 64.8 gray (Gy) was given to 96 patients (13%), 70.2 Gy to 266 patients (365), 75.6 Gy to 320 patients (43%), and 81.0 Gy to 61 patients (8%). The median follow-up time was 42 months (range, 18-109 months). Late toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale. RESULTS: Late gastrointestinal (GI) and urinary (GU) toxicities were absent or minimal (Grade 0 or 1) in 90% of patients. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GI toxicities was 11% and 0.75%, respectively. A multivariate analysis identified doses > or =75.6 Gy (P<0.001), history of diabetes mellitus (P = 0.01), and the presence of acute GI symptoms during treatment (P = 0.02) as independent predictors of Grade > or =2 late GI toxicity. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GU toxicities was 10% and 3%, respectively. Doses > or =75.6 Gy (P = 0.008) and acute GU symptoms (P<0.001) were independent predictors of Grade > or =2 late GU toxicity. Among 544 patients who were potent before treatment (73% of all patients), 211 (39%) became impotent after 3D-CRT. The 5-year actuarial risk of potency loss was 60%. Doses > or =75.6 Gy (P<0.001) and the use of neoadjuvant androgen deprivation (P = 0.01) were independent predictors of posttreatment erectile dysfunction. CONCLUSIONS: The incidence of severe late complications after high dose 3D-CRT was minimal. Radiation doses > or =75.6 Gy and the presence of acute treatment-related symptoms during 3D-CRT correlated with a higher incidence of Grade > or =2 late GI and GU toxicities. In addition to higher doses, the use of androgen deprivation therapy increased the likelihood of permanent impotence in these patients. Intensity-modulated radiotherapy, which makes it possible to enhance the conformality of the dose distribution, has recently been implemented in an attempt to reduce the incidence of moderate grade toxicities in patients receiving high dose 3D-CRT.

Diet and lifestyle in the prevention of colorectal cancer: an overview.

Numerous lifestyle factors have been implicated in colorectal carcinogenesis. These include diet, inadequate physical activity, obesity, alcohol consumption, and smoking. Epidemiologic studies, animal experiments, and randomized clinical trials have shown that dietary factors can influence all stages of colorectal carcinogenesis, from cell proliferation to transformation to cancer. Defining the precise role of diet and other lifestyle factors in colorectal carcinogenesis may require the elucidation of genetic susceptibility and genetic-environmental interactions. Despite the preoccupation with nutrition by the public and the media in the United States, trends in food consumption have not been favorable. The average U.S. diet is still too high in calories and fat and too low in fiber, cereals, fruits, and vegetables. Dietary modifications along with secondary prevention measures may have a major impact on reducing the mortality from colorectal cancer.

Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy? The Polyp Prevention Trial.

BACKGROUND & AIMS: The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas. METHODS: We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial. RESULTS: Four hundred sixty patients (46.9%) had >/=1 distal adenoma that was pathologically advanced (villous component, high-grade dysplasia, or >/=1 cm); 21.5% (211 of 981) had any proximal adenoma; and 4.3% (42 of 981) (95% confidence interval [CI], 3.0-5.5) had an advanced proximal adenoma. A greater percentage of patients with an advanced distal adenoma (5.9%) (95% CI, 3.7-8.0) had an advanced proximal adenoma compared with those with a nonadvanced distal adenoma (2.9%) (95% CI, 1.4-4.3) (OR, 2.1; 95% CI, 1.1-4.3; P = 0.03). Not performing a colonoscopy in patients with a nonadvanced distal adenoma would have missed 36% (15 of 42) of the advanced proximal adenomas. CONCLUSIONS: Patients with an advanced distal adenoma are twice as likely to have an advanced proximal adenoma as patients with a nonadvanced distal adenoma. However, eschewing a colonoscopy in patients with a nonadvanced distal adenoma would result in not detecting a sizeable percentage of the prevalent advanced proximal adenomas. These data support performance of a colonoscopy in patients with a nonadvanced distal adenoma. Confirmation of these results in asymptomatic subjects undergoing screening sigmoidoscopy is advisable.

Direct percutaneous endoscopic jejunostomy.

Jejunal feeding often is preferable to gastric feeding, particularly in the following situations: high risk for aspiration; gastric resection (partial or total); gastric pull-up; gastric outlet obstruction; obstructed or nonfunctioning gastrojejunostomy; and gastric dysmotility. The technique of placing a thin tube through a gastrostomy tube and pulling it endoscopically into the proximal jejunum allows delivery of nutrients into the jejunum. The results of this technique, however, have been poor. The direct percutaneous endoscopic jejunostomy technique allows placement of tubes directly in the jejunum with a success rate of around 85% and a minimal complication rate which is comparable to that of PEGs.

A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy.

OBJECTIVE: The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula (IEF) decreases morbidity, mortality, and length of hospital stay in patients with upper gastrointestinal (GI) cancer. SUMMARY BACKGROUND DATA: Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients. Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited. METHODS: Between March 1994 and August 1996, 195 patients with a preoperative diagnosis of esophageal (n = 23), gastric (n = 75), peripancreatic (n = 86), or bile duct (n = 11) cancer underwent resection and were randomized to IEF via jejunostomy tube or control (CNTL). Tube feedings were supplemented with arginine, RNA, and omega-3 fatty acids, begun on postoperative 1, and advanced to a goal of 25 kcal/kg per day. The CNTL involved intravenous crystalloid solutions. Statistical analysis was by t test, chi square, or logistic regression. RESULTS: Patient demographics, nutritional status, and operative factors were similar between the groups. Caloric intake was 61% and 22% of goal for the IEF and CNTL groups, respectively. The IEF group received significantly more protein, carbohydrate, lipids and immune-enhancing nutrients than did the CNTL group. There were no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring reoperation. Hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups. CONCLUSION: Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies.

Thiamine status in patients receiving long-term home parenteral nutrition.

OBJECTIVES: Clinical thiamine deficiency can occur in patients receiving total parenteral nutrition (TPN) without thiamine supplementation. Because considerable breakdown of thiamine may occur in the presence of bisulfite-containing amino acid solutions, subclinical thiamine deficiency may develop with the use of these solutions, even with appropriate thiamine supplementation. The current American Medical Association-Food and Drug Administration approved injectable multivitamin formula contains 3 mg of thiamine. This study was undertaken to determine whether this quantity of thiamine is sufficient to avoid clinical thiamine deficiency in long-term home TPN patients with negligible oral thiamine absorption and in the presence of bisulfite-containing amino acid solutions. METHODS: Twenty-four long-term home TPN patients with oral caloric intakes below the norm were evaluated. Seventeen patients suffered from short bowel syndrome or radiation enteritis, and another three had draining gastrostomies that precluded all intestinal absorption. The duration of TPN therapy ranged between 1 and 164 months. Thiamine status was assessed by assaying thiamine pyrophosphate, transketolase activity, and blood thiamine levels. RESULTS: All thiamine pyrophosphate and erythrocyte transketolase activity levels were within the normal range. CONCLUSIONS: This study demonstrates that the currently recommended 3 mg of thiamine hydrochloride added to TPN solutions is adequate to maintain normal thiamine status. This should prevent the development of thiamine deficiency even in patients with compromised intestinal thiamine absorption, and in the presence of bisulfite-containing amino acid solutions.

Direct percutaneous endoscopic jejunostomies for enteral feeding.

BACKGROUND: Enteral feeding through percutaneous endoscopic gastrostomy (PEG) is increasingly utilized in hospitals, homes, and institutions. However, PEGs have two major limitations: (1) risk for aspiration, which occurs in up to 30% of patients, and (2) it does not allow enteral feeding in patients with gastric outlet obstruction, gastroparesis, or gastric resection. METHODS: A new endoscopic method for placement of direct percutaneous endoscopic jejunostomy (DPEJ) was attempted in 150 patients with or without a history of major abdominal surgery. Patients were followed-up until tube utilization ceased because of death or resumption of oral feeding. RESULTS: There were 129 (86%) successful procedures and 21 (14%) unsuccessful attempts. Procedure-related complications included nine (6%) incisional infections. Bleeding, abscess, and colonic perforation each occurred in one patient (.6%), and all required surgical intervention. On long-term follow-up (n = 97), tube malfunction occurred in 3 patients (3%) and aspiration in 3 (3%). Duration of tube use in this population was 113 +/- 173 days. CONCLUSIONS: DPEJs can be performed successfully with a low complication rate. Enteral feeding through DPEJs drastically reduces aspiration, which commonly occurs with PEG feeding. DPEJs allow feeding and hydration of patients with gastric outlet obstruction due to cancer who are not surgical candidates, eliminate the need for intravenous hydration and feeding, and can cut costs of hospitalization and treatment.

The polyp prevention trial I: rationale, design, recruitment, and baseline participant characteristics.

The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy: age 35 years of more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and 10% are minorities. At study entry, participants averaged 61.4 years of age; 14% of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of participants had two or more adenomas, and 29% had at least one large (> of = 1 cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are comparable across the two study arms. Participants have repeat colonoscopies after 1 (T(1)) and 4 (T(4)) years of follow-up. The primary end point is adenoma recurrence; secondary end points include number, size, location, and histology of adenomas. All resected lesions are reviewed centrally by gastrointestinal pathologists. The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based is 3 years (T(1) to T(4)), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1), given that at least 10-15% of polyps may be missed at baseline. The final (T(4)) colonoscopies are expected to be completed in early 1998.

The polyp prevention trial II: dietary intervention program and participant baseline dietary characteristics.

The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial to evaluate whether a low-fat, high-dietary fiber, high-fruit and -vegetable eating pattern will reduce the recurrence of adenomatous polyps of the large bowel. Men and women who had one or more adenomas removed recently were randomized into either the intervention (n = 1037) or control (n = 1042) arms. Food frequency questionnaire data indicate that PPT participants at the beginning of the trial consumed 36.8% of total energy from fat, 9.7 g of dietary fiber/1000 kcal, and 3.8 daily servings of fruits and vegetables. Baseline dietary characteristics, including intake of fat, fiber, and fruits and vegetables, as well as other macro- and micronutrients, were similar in the two study groups. The intervention participants receive extensive dietary and behavioral counseling to achieve the PPT dietary goals of 20% of total energy from fat, 18 g/1000 kcal of dietary fiber, and 5-8 daily servings (depending on total caloric intake) of fruits and vegetables. Control participants do not receive such counseling and are expected to continue their usual intake. Dietary intake in both groups is mentioned annually using a 4-day food record (also completed at 6 months by intervention participants only) and a food frequency questionnaire, with a 10% random sample of participants completing an annual unscheduled 24-h telephone recall. Blood specimens are drawn and analyzed annually for lipids and carotenoids. This article provides details on the rationale and design of the PPT dietary intervention program and describes the participant baseline dietary intake data characteristics.

Body weight and colon cancer.

In 1994, there were approximately 160,000 new cases of colon cancer in the United States with 58,000 fatalities, making this form of cancer the second most common cause of cancer deaths. Up to 50% of colon cancers may have a strong inherited factor, but in the remaining cases, diet and lifestyle factors are thought to play essential roles in the carcinogenic process. Various epidemiologic studies have examined the relation between obesity and colon cancer. The largest prospective study of 750,000 men showed that mortality from colorectal cancer was significantly elevated in men who were > or = 40% overweight. No such increase was found in women. Subsequent studies reported conflicting results. Overweight is likely a surrogate. Other risk factors include a high-fat, energy-dense diet; inadequate consumption of fruit and vegetables; and lack of physical activity, which have been associated with a high incidence of colon cancer.

Nutrition therapy for the cancer patient.

Malnutrition commonly occurs in cancer and adversely affects the quality of life and survival of patients. It is caused by a variety of factors, including decreased food intake, adverse effects from anticancer treatment, and wasteful metabolic processes. Over the past 2 decades, there have been major advances in methods and techniques of feeding patients with cancer and other disease. Special diets can be helpful in the treatment of a variety of conditions, some of which are outlined in Table 1. Enteral feeding is developing rapidly because endoscopic techniques have made it simpler to place feeding tubes, and a variety of enteral feeding solutions are commercially available. Enteral feeding is an effective way to deliver nutrients when patients are unable to ingest food because of neurologic disorders or structural abnormalities in the upper gastrointestinal tract, including the oropharynx, esophagus, and stomach. The role of enteral feeding as an adjuvant to anticancer therapy has not been fully evaluated. Parenteral nutrition is an effective method of delivering nutrients into the blood stream. It has proved to be life-saving for patients with chronic severe gastrointestinal insufficiency (such as short bowel or radiation enteritis), whose cancer is cured or nonprogressive. Numerous studies have assessed the role of TPN as an adjuvant therapy. To date, a clear benefit from its routine use has been demonstrated only in very limited, specific situations. As an adjuvant to chemotherapy, TPN does not seem to be useful, unless there are prolonged periods of gastrointestinal toxicity (as in the case with bone marrow transplantation) that severely limit oral intake and absorption. Malnourished surgical patients undergoing specific major operations for cancer may benefit from perioperative TPN. TPN as an adjunct therapy in the treatment of the cancer patient has to be individually evaluated and appropriately applied in situations in which it has proven beneficial in randomized studies.