Pharmacological nutrition in inflammatory bowel diseases.

Inflammatory Bowel Diseases--ulcerative colitis and Crohn's disease--are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted. Total parenteral nutrition has been used to correct and prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with a high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission of disease in adults and promoting growth in children. Recent research has focused on the use of specific nutrients as primary treatment agents. Although some reports have indicated that glutamine, short-chain fatty acids, antioxidants and immunonutrition with omega-3 fatty acids are an important therapeutic alternative in the management of inflammatory bowel diseases, the beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these nutrients still need further evaluation through prospective and randomized trials.

Impact of parenteral n-3 fatty acids on experimental acute colitis.

The present study was undertaken to investigate the effects of parenteral lipid emulsions (LE) enriched with n-3 fatty acids (n-3 FA) in experimental acute colitis. Seventy-four adult male Wistar rats were randomized into six groups, five of which had acetic acid-induced colitis. The animals received a fat-free diet and water ad libitum in individual metabolic cages. By a central venous catheter, saline was infused (0.5 ml/h) into the control groups CS (without colitis) and CC (with colitis), while the test groups received specific LE for 7 days. The n-3/n-6 FA ratio and the lipidic compositions regarding long chain (LCT) and medium chain (MCT) triglycerides were: group L--1:7.7 (LCT, n = 12), M--1:7.0 (MCT and LCT, n = 12), LW-3--1:4.5 (LCT plus n-3 FA, n = 12) and MW-3--1:3.0 (MCT and LCT plus n-3 FA, n = 13). The frequency of diarrhea, oral intake/body weight ratio, intestinal alterations, macrophage cellularity were evaluated and colonic concentrations of leukotrienes (LTB4, LTC4), prostaglandins (PGE2) and thromboxanes (TXB2) were measured. Groups M, MW-3 and LW-3 had less diarrhea than the CC group (P<0.05). Average oral intake/body weight ratio in MW-3 animals was comparable to the CS and better than the CC group. n-3 FA treated rats (LW-3 and MW-3) presented less intestinal inflammatory alterations than CC rats. Mucosal ulcer formation in MW-3 group did not differ from CS rats. M and MW-3 rats had less macrophages in the colon than the CC group. Compared with CC group, lower concentrations of LTB4 in the CS, LW-3 and MW-3 groups; of PGE2 in the CS, M and MW-3 groups; and of TXB2 in the CS and MW-3 groups were found. Mean concentrations of LTC4 did not differ among the groups. Thus, a LCT-containing LE with a low n-3-n-6 ratio does not modify inflammatory colitis manifestations; LE with a high n-3-n-6 ratio reduces diarrhea, preserves oral intake-weight ratio, attenuates morphological consequences and decreases colonic concentrations of inflammatory mediators; MCT/LCT-containing LE with 1:3 n-3-n-6 ratio exerts the most profound beneficial impact on the inflammatory response.

Low rectal cancer: impact of radiation and chemotherapy on surgical treatment.

INTRODUCTION: The aim of this study was to evaluate the impact of combined radiotherapy and chemotherapy (leucovorin and 5-fluorouracil) on the treatment of potentially resectable low rectal cancer using the following end points: 1) toxicity of this combined modality regimen; 2) clinical and pathologic response rate and local control; 3) down-staging of the tumor and its influence on the number of sphincter-saving operations; 4) disease-free interval, patterns of relapse, and overall survival. METHODS: From 1991 to 1996, 118 patients with potentially resectable cases of histologically proven adenocarcinoma and no distant metastases were enrolled into this protocol. All patients were evaluated by clinical and proctologic examination, abdominal computed tomography, transrectal ultrasound, and chest radiography. Therapy consisted of 5,040 cGy (6 weeks) and concurrent leucovorin (20/mg/m2/day) with bolus doses of 5-fluorouracil administered intravenously at 425 mg/m2/day for three consecutive days on the first and last three days of radiation therapy. After two months, all patients underwent repeat evaluation and biopsy of any suspected residual lesions or scar tissue. RESULTS: Median follow-up was 36 months. Toxicity of chemotherapy regimen was minimum. Thirty-six patients (30.5 percent) were classified as being complete responders. In six of these patients, complete response was confirmed by the absence of tumor in the surgical specimens (3 abdominoperineal resections and 3 proctosigmoidectomies with coloanal anastomosis). In the remaining 30 patients, confirmation of a complete response was made by the absence of symptoms, negative findings on physical examination, and biopsy, transrectal ultrasound, and pelvic computed tomographic test results during follow-up. Eighty-two patients (69.4 percent) were considered incomplete responders. Residual lesions had already been identified during the first examination in 74 patients. In the other eight patients, residual tumor was only identified after 3 to 14 months. All patients underwent surgical treatment, except one patient who refused surgery. Eighty-seven patients underwent 90 surgical procedures: local excision, 9; coloanal anastomosis, 36; abdominoperineal resection, 4; Hartmann's procedure, 1. Isolated local recurrences occurred in five patients (4.3 percent) and combined local and distant failure in eight patients (6.7 percent). Ninety patients are alive and disease-free at a median follow-up of 36 months. CONCLUSIONS: Combined up-front chemoradiotherapy was associated with tolerable and acceptable side effects. A significant number of patients had complete disappearance of their tumors (30.5 percent) within a median follow-up of 36 months. This regimen spared 26.2 percent of patients from surgical treatment and allowed sphincter-saving management in 38.1 percent of patients who may have required abdominoperineal resection. Preliminary results of this trial suggests a reduction in the number of local recurrences and reinforces the concept that infiltrative low rectal cancer may be initially treated by chemoradiotherapy.

Protective effects of glutamine enriched diets on acute actinic enteritis.

Radiotherapy plays an important role in cancer treatment, although it may cause collateral effects and sever complications due to cellular damage of peritumoral tissues. Recently different nutritional resources have been indicated to achieve intestinal protection during cancer irradiation. The aim of this study was to set the role of glutamine in acute actinic enteritis prevention. Sixty-five Wistar male rats (200 g) were maintained in individual metabolic cages, where body weight and food ingestion were carefully monitored daily. The animals were chosen at random in three groups and fed isocaloric and isoproteid diets: 1) CRt (23)-polymeric-casein diet (CD); 2) GRt (22)-polymeric-casein diet supplemented with 2% glutamine (GD), and 3) ERt (20)--elemental diet supplemented with 2% glutamine (ED). After an adaptation period (seven days), all rats received 1500 cGy of abdominal radiation in five equal daily doses of 300 cGy. After three days post radiation the rats were submitted to jejunal perfusion test with polyethylene-glicol 4000. Finally, small bowel and colon were resected for histological evaluation. It was observed that ERt group had greater average daily food intake than CRt and GRt groups during all periods (p < 0.05). All rats had equal weight gain during adaptation period; during irradiation all the animals had weight loss, but ERt group had smaller weight loss than CRt. All rats recovered weight after irradiation, and ERt group presented better results than the others (p < 0.05). Sodium transepithelial transport average values (mEq/min/cm) were negative and not statistically different in all groups. Small bowel histological evaluation in ERt and GRt rats were better than CRt rats, by preserving mucosal cellularity and increasing mitosis number and villi length (p < 0.05). Simultaneously, ERt group had greater number of rats with normal villuscrypt relation than CRt of CRt groups (p < 0.05). Large bowel histological data showed that the average crypt's length in ERt and GRt rats were greater than in CRt ones (p < 0.05). By the present work, an elemental diet enriched with 2% glutamine favored greater food ingestion and lessened weight loss during and after radiotherapy. Glutamine-supplemented polymeric or elemental diets given to rats before, during and after abdominal radiotherapy showed protective effects against radiation injury, by supporting mucosal structure and recovery.

[The role of glutamine in nutrition in clinical practice]. / Importância da glutamina em nutrição na prática clínica.

Nutritional therapy using nutrients with pharmacological properties has been intensively discussed in the recent literature. Among these nutrients, glutamine has gained special attention. Glutamine is the most abundant amino acid in the blood stream of the mammals and, besides it has been considered a non-essential amino acid, glutamine is a non-dispensable nutrient in catabolic states. In this situation, there are alterations in its inter-organic flux, leading to lower plasmatic concentrations. Glutamine is the main fuel to enterocytes and it has an important role in the maintenance of intestinal structure and functions. Moreover, supplementation with glutamine has proved to be beneficial to the immunological system functions, improves nitrogen balance and nutritional parameters in the post-operative period and lessens protein loss in severe catabolic states. For these reasons, glutamine enriched-diets must be considered in the nutritional support of many diseases; new controlled, prospective and randomized studies will help to define what group of patients can really benefit from glutamine supplementation.

[Protective effects of glutamine and elemental diet in acute actinic enterocolitis: histological evaluation]. / Efeitos protetores da glutamina e dieta elementar na enterocolite actínica aguda: avaliação histológica.

Radiotherapy plays nowadays an important role in malignancies treatment. However, collateral effects and severe complications owing to cellular damage of peritumoral tissues may occur. Different nutritional resources have been recently indicated to achieve intestinal protection during cancer irradiation. PURPOSE--The aim of this study was to set the role of glutamine and elemental diets in acute actinic enteritis prevention. METHOD--Sixty-five adult male Wistar rats with average weight of 200g were maintained in individual metabolic cages; daily body weight and food ingestion were carefully monitored. The animals were randomized into three groups and fed isocaloric and isonitrogenous diets: 1) CRt-polymeric-casein diet; 2) GRt-polymeric-casein diet supplemented with 2% glutamine and 3) ERt-elemental diet supplemented with 2% glutamine. After an adaptation period (seven days), all rats received abdominal radiation in five daily doses of 300cGy. Four days after the rats were operated on to resect the small intestine and colon for histological evaluation. RESULTS--Small intestine histological data in ERt and GRt rats were better than CRt rats, by preserving mucosal cellularity and increasing mitosis number and villi length. Simultaneously, ERt group had greater number of rats with normal villus-crypt relation than CRt or GRt groups. Large intestine histological data showed that the average crypts length in ERt and GRt rats were greater than in CRt ones. CONCLUSION--Glutamine-supplemented polymeric or elemental diets given to rats before, during and after abdominal radiotherapy showed protective effects against radiation injury, by supporting mucosal structure and recovery.