Plant-derived health: the effects of turmeric and curcuminoids.

Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.

Plant-derived health - the effects of turmeric and curcuminoids / Efectos saludables de la cúrcuma y de los curcuminoides

Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor κ B (NF-κB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease (AU)

Las plantas contienen un gran número de sustancias de naturaleza polifenólica con capacidad para reducir los procesos inflamatorios y, por lo tanto, incrementar la resistencia a determinadas enfermedades. Ejemplos de algunos polifenoles son los isotiocianatos presentes en la col y el brócoli, epigalocatequinas del té verde, capsaicina de las guindillas, chalonas, rutina y naringenina de las manzanas, resveratrol del vino tinto y de los cacahuetes, y curcumina y curcuminoides de la cúrcuma. La mayoría de las enfermedades tienen un componente discreto pero obvio de inflamación sistémica. Muchos trabajos han sugerido que los efectos de estos tratamientos podrían ser mejorados tras la restricción de la ingesta de moléculas proinflamatorias, como los productos avanzados de la glicación (AGE) y lipoperoxidación (ALE), junto con la suplementación de moléculas antiinflamatorias, como algunos polifenoles obtenidos de las plantas. Concretamente, los efectos de los curcuminoides y de su principal componente, la curcumina, han sido ampliamente documentados. Esta revisión, recopila los datos actuales acerca de las principales moléculas activas derivadas de la cúrcuma, para las cuales se ha demostrado que poseen una potente actividad antioxidante, inhiben la ciclooxigenasa 1 (COX-1), la lipoperoxidasa (LPO), el factor nuclear NF-κB (NF-κB), así como los AGE. La mayoría de los efectos han sido demostrados mediante estudios experimentales; sin embargo, los estudios clínicos en humanos son escasos. Se ha sugerido que la suplementación con curcuminoides podría ser interesante como un complemento para los tratamientos farmacológicos, además de cómo tratamiento prebiótico en condiciones en las que no existe una terapia eficaz, como en el caso de la enfermedad de Crohn, en pacientes ingresados en Unidades de Cuidados Intensivos durante periodos prolongados, y también en patologías tales como el cáncer, la cirrosis hepática, la enfermedad renal crónica, la enfermedad digestiva obstructiva, la diabetes y la enfermedad de Alzheimer. (Full spanish translation in www.nutricionhospitalaria.com) (AU)

The probiotic bacterium Lactobacillus plantarum species 299 reduces intestinal permeability in experimental biliary obstruction.

AIMS: Extrahepatic biliary obstruction is associated with the failure of intestinal barrier function, allowing bacteria and other substances from the intestine to enter the circulation and initiate a systemic inflammatory response, causing impairment of organ function. Probiotic bacteria have been shown to have beneficial effects on intestinal barrier function in other conditions, but their effects have never been studied in biliary obstruction. METHODS AND RESULTS: This study examined the effects of enteral administration of Lactobacillus plantarum species 299 (LP299) in oatmeal fibre compared with sterile oatmeal fibre in water or water alone in an animal model of biliary obstruction. Administration of LP299 was associated with reduced intestinal permeability compared with sterile oatmeal alone (0.262 +/- 0.105%vs 0.537 +/- 0.037%, P=0.019, percentage excretion of (14)Carbon), but there was no evidence of reduced endotoxin exposure or blunting of the systemic inflammatory response. Animals receiving sterile oatmeal fibre alone also failed to develop the hyperpermeability after biliary obstruction seen in animals receiving water only (0.512+/- 0.05%vs 0.788 +/- 0.18%), suggesting that oatmeal itself may have some beneficial effects on intestinal barrier function. CONCLUSION: Enteral administration of the probiotic bacterium LP299 reduces intestinal hyperpermeability associated with experimental biliary obstruction. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides insight to direct further work into the modulation of intestinal barrier function by probiotic bacteria.

Control bioecológico y nutricional de la enfermedad: prebióticos, probióticos y simbióticos / Bioecological and nutritional control of disease: prebiotics probiotics and synbiotics

Un número creciente de pacientes en todo el mundo sufre de enfermedades agudas y crónicas. Evidencias actuales apoyan la asociación de las enfermedades crónicas con los hábitos de vida moderna y la disfunción del sistema inmunológico. La morbilidad y mortalidad de los pacientes afectados de enfermedades crónicas son inaceptablemente elevadas a pesar de los avances en los tratamientos médicos y quirúrgicos. Actualmente, existe un interés elevado en el control bioecológico y nutricional de las enfermedades. El uso de prebióticos, probióticos y simbióticos tales como antioxidantes, emulsiones lipídicas antiinflamatorias de ácidos grasos omega-3, fibras bioactivas, bacterias del ácido láctico (LAB), etc., aparece como una nueva herramienta para el tratamiento de la enfermedad. Los efectos de los antioxidantes y de las emulsiones lipídicas de ácidos grasos omega-3 aún están ampliamente inexplorados, pero se conocen sus efectos moduladores sobre los neutrófilos y la morbilidad. Es muy significativo que estos compuestos se estén utilizando en el tratamiento de pacientes críticos, incluidos los pacientes quirúrgicos. Algunas fibras bioactivas y algunas bacterias probióticas han demostrado una extraordinaria eficacia para restaurar y mantener la inmunidad y prevenir las complicaciones. Las LAB han demostrado su capacidad para reducir o eliminar microorganismos potencialmente patogénicos, así como varias toxinas, mutágenos y carcinógenos; también promueven la apoptosis, sintetizan y liberan numerosos nutrientes, antioxidantes, factores de crecimiento, compuestos implicados en la coagulación y otros compuestos bioactivos, y modulan los mecanismos de defensa inmunológica innata y adaptativa. Estudios más recientes sugieren que las LAB promueven y mantienen la motilidad gastrointestinal (GI) y previenen la parálisis GI y el íleo postoperativo, y tienen la capacidad de inhibir la inflamación. Se necesitan estudios ulteriores para determinar los mecanismos moleculares por los cuales los prebióticos, probióticos y simbióticos influencian la recuperación de los pacientes en una amplia variedad de enfermedades agudas y crónicas (AU)

A growing number of patients worlwide suffer acute and chronic diseases. Evidence supports the association of chronic diseases to modern lifestyle habits and malfunction of the immune system. Morbidity and mortality for patients affected of chronic diseases is unacceptably high despite advanced surgical and medical treatments. Nowadays there is an increasing interest in the bioecological and nutritional control of diseases. The use of prebiotics, probiotics and synbiotics, e.g. antioxidants, antiinflammatory ?-3 lipid emulsions, bioactive fibers, lactic acid bacteria (LAB), etc, appears as a new tool for the treatment of disease. The effects of antioxidants and ?-3 lipid emulsions remain largely unexplored, but significant modulatory effects on neutrophils and morbidity have been observed. It is burning that these compounds are tried in patients including surgically and critically ill patients. Some bioactive fibers and some probiotic bacteria have demonstrated extraordinary efficacy to restore and maintain immunity and prevent complications. Lactic acid bacateria (LAB) have demonstrated ability to reduce or eliminate potential pathogen micro-organisms, as well as various toxins, mutagens and carcinogens; they also promote apoptosis, synthesize and release numerous nutrients, antioxidants, growth-factors, coagulation and other bioactive compounds, and modulate the innate and adaptive immune defence mechanisms and maintain. More recent studies suggest that LAB promote and maintain gastrointestinal (GI) motility and prevent GI paralysis and postoperative ileus and have the ability to inhibit inflammation. Further studies are needed to ascertain the molecular mechanisms by which pre-, pro- and synbiotics influence the outcome in a variety of acute and chronic diseases (AU)

Ecoimmunonutrition: a challenge for the third millennium.

Clinical enteral nutrition solutions, produced by mixing chemicals or defined nutrients, have repeatedly been shown to lack important ingredients; in the formulation of these solutions several key nutrients have simply been overlooked. The aim of this particular issue of the journal is to discuss some of these nutrients that were earlier neglected, but that today have proven to have key functions, especially in stress situations such as disease. The metabolism of the body is a complex system, one can not expect that supplying the body with one or a few chemicals, natural or synthetic, will lead to maximal health and performance. Most often an amalgam of substances is needed. Only natural food has the potential to supply most of the components needed, and thereby provide effective and successful nutrition. In stress situations such as premature life, disease, or aging, or extreme conditions such as exercise, eating normal food might not be enough; in these situations supplements will prove to be of the greatest value.

Pectin-supplemented enteral diet reduces the severity of methotrexate induced enterocolitis in rats.

BACKGROUND: Administration of methotrexate (MTX) to rats fed an elemental diet results in a high mortality from severe enterocolitis. Previous studies have shown that pectin is an important precursor of substrates for intestinal structure and function and may facilitate intestinal recovery after enterocolitis. The aim of this study is to evaluate the effect of pectin on MTX-induced enterocolitis in rats. METHODS: Rats received intragastric infusion of either 1% pectin-supplemented or pectin-free elemental diet from the beginning of the study via a gastrostomy. On the 4th day animals received either MTX, 20 mg/kg intraperitoneally, or saline injection and were killed on the 7th day for sampling. RESULTS: Pectin supplementation significantly decreased body weight loss, organ water content, and intestinal myeloperoxidase levels and increased mucosal protein, DNA, and RNA content in enterocolitis rats. The intestinal permeability was increased by administration of MTX, and pectin supplementation significantly reversed the increased permeability in the distal small bowel and colon. Pectin supplementation also lowered the magnitude of bacterial translocation, decreased plasma endotoxin levels, and restored bowel microecology. CONCLUSIONS: Pectin significantly decreased MTX-induced intestinal injury and improved bowel integrity.

Swedish health care delivery system and its effects on surgical education.

Sweden, with a small, decentralized population, has a similarly decentralized network of hospitals that comprise the national health care system, which is nonetheless highly regulated by the national government. Medical education and graduate training in surgery are likewise regulated. Reforms implemented in 1992 made a 21-month general rotating internship mandatory for all medical graduates, after which they enter specialty training. The training, which lasts a minimum of 5 years, is done under the tutelage of a Board-certified practitioner in the field. During the trainee and program contract for the amount of time spent in clinical and didactic experiences, the trainee is personally responsible for ensuring that much of his or her individual program is accomplished. Rising health care costs have spurred increased rationalization of resources and are expected to constrict training opportunities for future surgeons.

Inhibition of bacterial translocation in obstructive jaundice by muramyl tripeptide phosphatidylethanolamine in the rat.

Obstructive jaundice is frequently associated with septic complications and enteric bacteria have been isolated from both the infectious focus and bile in jaundiced patients. The present study aimed to evaluate bacterial translocation and the influence of a macrophage-stimulant (muramyl tripeptide phosphatidylethanolamine) on bacterial translocation in obstructive jaundice. Male Sprague-Dawley rats were subjected to sham operation (n = 10) or common bile-duct ligation and transection (n = 35). Two weeks later, jaundiced animals received either physiological saline (n = 15), muramyl tripeptide phosphatidylethanolamine liposomes (n = 10) or placebo (empty) liposomes (n = 10) orally, while sham-operated rats received physiological saline, 48 h prior to evaluation of enteric bacterial translocation. Blood, bile and caecal contents were collected and cultured aerobically and anaerobically, as were tissue samples from the liver, spleen and mesenteric lymph nodes. Positive mesenteric lymph node cultures in animals with jaundice + saline (7/15; 47%) and jaundice + placebo liposomes (4/10; 40%) significantly differed (p < 0.05) from sham-operated animals (1/10; 10%) and muramyl tripeptide phosphatidylethanolamine treated animals (0/10). Caecal counts (CFU/g) of Escherichia coli, Lactobacilli and aerobic and microaerobic bacteria did not differ statistically among the groups, although the number of E. coli tended to be higher in jaundiced animals. Thus, liposomal muramyl tripeptide phosphatidylethanolamine inhibits bacterial translocation, probably by activating mucosal macrophages and enhancing reticuloendothelial system function in rats with biliary obstruction.

Role of topical phospholipids in the prophylaxis of silicone elastomer-associated infection in the abdominal cavity.

The present study evaluated the influence of phospholipids (phosphatidyl choline and phosphatidyl inositol) on the prevention of abdominal biomaterial-associated infection. Phospholipid-impregnated silicone elastomer (SE) fragments were either intraperitoneally implanted in rats or immersed in serum for 0, 4, and 14 days, and 3 x 10(9) cfu of 3H-labeled, live Escherichia coli were added in the peritoneal cavity or in vitro incubation medium. Three hours after incubation, the adherence of bacteria significantly decreased to phospholipid-impregnated SE fragments, which had been immersed/implanted for 0 and 4 days. However, the number of adhering bacteria did not differ between the impregnated and unimpregnated SE fragments after 14 days of immersion/implantation. A significantly lower number of adhering bacteria was noted on all unimpregnated SE fragments when phospholipid was supplemented in the peritoneal cavity or in vivo medium, compared with fragments with no supplement. The rate of bacterial DNA synthesis decreased significantly after incubation with phospholipid 2 h or more. Phospholipids did not further influence peritoneal morphology. Thus topical administration of phospholipids by impregnation to the surface of SE fragments or supplement in the incubation medium prevented bacterial adherence onto the SE fragments. This implies that the use of phospholipids might be a mode of preventing biomaterial-associated infections.

Green banana protection of gastric mucosa against experimentally induced injuries in rats. A multicomponent mechanism?

The protective capacities of fresh green (unripe) sweet bananas and of phosphatidylcholine and pectin (banana ingredients) against acute (ethanol- or indomethacin-induced) and chronic (indomethacin-induced) gastric mucosal lesions were evaluated in rats. Banana pulp was mixed with saline and given by gavage, as a pretreatment in a single dose. The identical protocol was used for pectin and phosphatidylcholine solution, and the dosages were adjusted to equal the amount of ingredients in the banana mixture, but higher concentrations were also given. The banana suspension reduced acute lesions, as did pectin and phosphatidylcholine in higher concentrations, but in concentrations as in fresh fruit no protective effects were observed except by pectin against indomethacin injury. In the model of chronic ulcers the banana suspension provided an incomplete and temporary protective effect. We conclude that the protective capacity of fresh green sweet bananas cannot be confined to only one active component. Pectin and phosphatidylcholine may protect gastric mucosa by strengthening the mucous-phospholipid layer, but the mechanism of protection afforded by bananas has to be further elucidated.

Phospholipid impregnation of abdominal rubber drains: resistance to bacterial adherence but no effect on drain-induced bacterial translocation.

In order to evaluate the effect of surface modification of biomaterials on bacterial adherence and bacterial translocation after intraperitoneal biomaterial implantation, phosphatidylcholine- or phosphatidylinositol-impregnated rubber drain pieces, which had been intraperitoneally implanted in the rat for 2 and 7 days, or unimplanted, were incubated in vitro with 3H-labelled Escherichia coli and Enterobacter cloacae. As compared with unimpregnated pieces, the adherence of bacteria significantly decreased to phosphatidylcholine- and phosphatidylinositol-impregnated rubber drain pieces that were either unimplanted or implanted for 2 days, but not for 7 days. The supplementation of albumin in the medium reduced the adherence of bacteria to the unimplanted, unimpregnated drain pieces, but did not further decrease adherence of bacteria to the unimplanted, phospholipid-impregnated brain pieces. Bacterial growth was inhibited after incubation in nutrient broth supplemented with phospholipids. The incidence of enteric bacterial translocation induced by intraperitoneal drain implantation did not differ between phospholipid-impregnated and unimpregnated drain pieces. Scanning electron microscopy revealed a large amount of biofilm and fibrous deposition on the surface of the implanted, phospholipid-impregnated rubber drain pieces. Thus, phospholipid impregnation of rubber drains reduces bacterial adherence and inhibits bacterial growth, without influencing the incidence of bacterial translocation.

Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis.

There exists no ideal model for experimental ulcerative colitis in common laboratory animals. Therefore, we tried in the present study to establish a reproducible model for inducing colitis in rats by using acetic acid. A blind loop of the colon including the cecum, ascending colon and part of the transverse colon, was brought out through two colostomies. After mechanical washing with warm normal saline, acetic acid was instilled at different doses (4, 6 and 8%) for different exposure times (10, 15, 20, 25 and 30 s). The excluded colon was examined by light microscopy on the 1st, 2nd, 3rd, 4th, 7th and 14th days after operation and acetic acid instillation. We found that 4% acetic acid for 15 s produced a moderate, superficial colitis on the 1st day after operation, whereafter a uniform colitis evolved in all rats on the 4th day after operation. The developed colitis showed morphological similarities with human ulcerative colitis. Signs of healing and regeneration of the mucosa were seen on the 7th day, and the mucosa became almost normal at the 14th day after operation. 6 or 8% acetic acid solution or exposure times exceeding 15 s resulted in severe, deep colitis with a concomitant high mortality rate. In contrast, at exposure times less than 15 s, acetic acid induced only mild superficial colitis. We conclude that by using 4% acetic acid for 15 s in the excluded colon a uniform and reproducible colitis pathologically resembling human ulcerative colitis could be achieved. Furthermore, no mortality was encountered and the general health of the rats was similar to that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitomycin C and lipiodol do not improve the effect of intermittent hepatic artery occlusion on liver tumour growth. An experimental study in the rat.

The effect of Mitomycin C (MMC 2.0 mg/kg bw), lipiodol (0.2 ml/kg bw) and intermittent hepatic artery occlusion on liver tumour growth, as well as their possible interrelation, were studied in 29 rats. An adenocarcinoma was inoculated in the left liver lobe. After one week, the tumour size was measured and the rats then divided into five different groups of treatment. Intermittent hepatic artery occlusion was performed during five days for 1 hour daily alone, of initially in combination with MMC and lipiodol. One group was treated with MMC and lipiodol in combination and one group with lipiodol only. The tumour growth six days later was compared between the groups and with control rats. It was found that intermittent arterial occlusion significantly reduced the tumour growth (P = 0.01). However, the retarding effect of intermittent arterial occlusion on tumour growth was not significantly improved with additional treatment of MMC and lipiodol.

Phosphatidylcholine prevents postoperative peritoneal adhesions: an experimental study in the rat.

Phosphatidylcholine (PC) is the main constituent of the surface-active material coating peritoneal mesothelium. It may prevent postoperative adhesion formation through production of a lubricant film on mesothelial defects. We therefore examined the effect of its soluble form on surgically induced intraabdominal adhesions in rats. The adhesions were induced at laparotomy by any of four different operative models. PC was administered intraperitoneally (20 mg/rat) or intravenously (20 mg/rat or 50 mg/rat) at the end of the operation and on the second and third postoperative day. It was found that the degree of postoperative adhesion formation was significantly reduced by the intraperitoneal injection of PC in all 4 models. In contrast, no effect was achieved by the intravenous injection of PC, not even at a very high dose level. Our results suggest that soluble PC administered intraperitoneally might be a potent adjunct in postoperative adhesion prevention.

Early biochemical and histological changes in rats exposed to a single injection of thioacetamide.

Liver injury was induced by one subcutaneous administration of thioacetamide (200 mg/kg b.wt.) and studied 24 and 48 hrs later. Levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased after 24 and 48 hrs. The lysosomal enzymes beta-hexosaminidase (beta-NAG) and beta-glucuronidase (beta-GLU) increased significantly after 24 hrs, while the level of beta-GLU returned to normal after 48 hrs, but the activity of beta-NAG remained significantly high even after 48 hrs. Histopathological examination showed necrotic hepatocytes around the central vein with infiltration of macrophages, neutrophils and eosinophils. The plasma zinc level decreased after 24 hrs and returned to normal after 48 hrs. Liver zinc content increased simultaneously at 24 hrs, returning to normal after 48 hrs. No alterations of plasma copper were observed after 24 and 48 hrs. Copper content of the liver increased significantly after 24 and 48 hrs. The present study thus shows that one dose of thioacetamide results in profound liver injury and supplementation of zinc prior to and simultaneously with thioacetamide normalized plasma zinc, increased liver zinc content and reduced the increase of beta-NAG, but did not influence the histological changes.

Alterations in trace element and plasma amino-acid profile in experimental gram-negative septicaemia.

Infection can produce changes in the levels of trace metals such as copper, iron and zinc and several amino acids. These trace metals are involved in many metabolic reactions as well as in the host defence response. In the present study we have induced septicaemia in male Sprague-Dawley rats. The rats were made septic by surgical insertion of a gelatine capsule containing known amounts of E. coli (1.25 x 10(7) bact/ml) and Bacteroides fragiles (2.5 x 10(7) bact/ml) along with sterile rat faeces as an adjuvant (50% vol/vol), and barium sulphate (10% weight/weight) as an irritant into the abdomen. Blood samples were collected at 36, 60 and 72 h to study alterations in the pattern of copper, zinc, calcium and magnesium and plasma amino acids. Liver samples were taken after sacrifice at 72 h for inorganic element analysis. Sepsis produced a significant increase in copper and magnesium and a significant decrease in zinc and calcium levels of plasma. Trace element content of the livers the septic rats did not differ appreciably from control rats. Septic rats also had a lowered concentration of branched chain amino acids. These changes especially those of copper and zinc could be expected to have a role in the progress of the disease. The changes observed in the present study might be caused through the release of Interleukin-I or related substances from the phagocytic cells.

[Background and experience of adjuvant cytostatic therapy in gastrointestinal cancer (author's transl)]. / Hintergründe und Erfahrungen mit der adjuvanten Zytostatiktherapie bei gastrointestinalem Karzinom.

Survival rates for patients with colorectal cancer have remained unchanged during the last 30 years. Every third patient with colon cancer Dukes' C and every fourth patient with rectal cancer Dukes' C survives 5 years. Of the patients who succumb to colorectal cancer, 85% will die within 3 years from diagnosis. There are many studies concerning the mechanisms of adjuvant chemotherapy. Its effectiveness has been proven in animal experiments. Micrometastases have a large growth fraction, few non-proliferative cells, and because of this, increased sensibility to cytostatics. Adjuvant chemotherapy aimed at treating occult metastases. In colorectal cancer the combination of 5-FU and Nitrosurea has been shown to have a better effect than 5-FU alone. Grage et al. have shown patients with colorectal cancer Dukes' C to have a longer tumour-free interval with adjuvant 5-FU, and this treatment gives patients with rectal cancer a prolonged survival time. In an adjuvant study, peroral 5-FU 90 days versus placebo did not show any effect. In another adjuvant study Vincristin, CCNU and 5-FU treated patients had fewer tumour recurrences than control patients. The observation time is, however, rather short. Adjuvant chemotherapy for colorectal cancer has shown promising results and it is hoped that further attempts with other forms of cancer in the gastrointestinal tract will also yield the same results.