Stig Bengmark

The natural history of primary and secondary malignant tumors of the liver I. The prognosis for patients with hepatic metastases from colonic and rectal carcinoma by laparotomy

In a series of 156 patients operated on for colonic and rectal carcinoma, 38 were shown to have hepatic metastases. Twenty‐four of them died within 6 months, 30 within 12 months, and all except one within 18 months. The survival rate was not influenced by the age of the patient, location of the primary tumor or the type of palliative large bowel operation performed. The patients with elevated alkaline phosphatases at the time of operation had a shorter mean survival than those with normal values.

Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis

Minimal hepatic encephalopathy (MHE) is an important disorder that may seriously impair daily functioning and quality of life in patients with cirrhosis. Treatment with lactulose is of benefit. The possible role of synbiotics (probiotics and fermentable fiber) has not been assessed. We screened 97 consecutive cirrhotic patients without overt hepatic encephalopathy for MHE using the number connection test and measurement of brainstem auditory evoked potentials. MHE, defined by abnormality on at least one test modality, was present in 58 (60%) patients. Fifty‐five of these patients with MHE were randomized to receive a synbiotic preparation (n = 20), fermentable fiber alone (n = 20), or placebo (n = 15) for 30 days. Cirrhotic patients with MHE were found to have substantial derangements in the gut microecology, with significant fecal overgrowth of potentially pathogenic Escherichia coli and Staphylococcal species. Synbiotic treatment significantly increased the fecal content of non‐urease‐producing Lactobacillus species at the expense of these other bacterial species. Such modulation of the gut flora was associated with a significant reduction in blood ammonia levels and reversal of MHE in 50% of patients. Synbiotic treatment was also associated with a significant reduction in endotoxemia. The Child‐Turcotte‐Pugh functional class improved in nearly 50% of cases. Treatment with fermentable fiber alone was also of benefit in a substantial proportion of patients. In conclusion, treatment with synbiotics or fermentable fiber is an alternative to lactulose for the management of MHE in patients with cirrhosis. (HEPATOLOGY 2004;39:1441–1449.)

Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: A controlled trial in liver transplant recipients

Background. Early enteral nutrition with solutions containing prebiotics (fiber) and probiotics (Lactobacillus) is suggested to reduce bacterial translocation and minimize the incidence of infections after liver transplantation. Methods. In a prospective, randomized placebo-controlled trial consisting of 95 patients, we compared the incidence of postoperative infections and other complications after liver transplantation among three different groups, all supplied with early enteral nutrition: (a) standard formula plus selective bowel decontamination (SBD), (b) fiber-containing formula plus living Lactobacillus plantarum 299, and (c) fiber-containing formula plus heat-killed L plantarum 299. Results. The groups were comparable regarding preoperative American Society of Anesthesiologists classification, Child-Pugh classification of cirrhosis, operative data, and degree of immunosuppression. The patients who received living lactobacilli plus fiber developed significantly fewer bacterial infections (13%) than the patients with SBD (48%). The incidence of infections was 34% in the group with inactivated lactobacilli and fiber. Cholangitis and pneumonia were the leading infections and enterococci the most commonly isolated bacteria. In the living Lactobacillus group, the mean duration of antibiotic therapy, the mean total hospital stay, and the stay on the intensive care unit were also shorter than in the groups with inactivated lactobacilli and fiber as well as with SBD. However, these differences did not reach statistical significance. Conclusions. Early enteral nutrition with fiber-containing solutions and living L plantarum 299 was well tolerated. It decreases markedly the rate of postoperative infections both in comparison with inactivated L plantarum 299 and significantly with SBD and a standard enteral nutrition formula. As it is a cheap and feasible alternative to SBD, further studies should evaluate whether this ecoimmunonutrition should be already started while patients are on the waiting list for transplantation.

Curcumin, An Atoxic Antioxidant and Natural NFκB, Cyclooxygenase-2, Lipooxygenase, and Inducible Nitric Oxide Synthase Inhibitor: A Shield Against Acute and Chronic Diseases.

BACKGROUND The world suffers a tsunami of chronic diseases, and a typhoon of acute illnesses, many of which are associated with the inappropriate or exaggerated activation of genes involved in inflammation. Finding therapeutic agents which can modulate the inflammatory reaction is the highest priority in medical research today. Drugs developed by the pharmaceutical industry have thus far been associated with toxicity and side effects, which is why natural substances are of increasing interest. METHODS A literature search (PubMed) showed almost 1500 papers dealing with curcumin, most from recent years. All available abstracts were read. Approximately 300 full papers were reviewed. RESULTS Curcumin, a component of turmeric, has been shown to be non-toxic, to have antioxidant activity, and to inhibit such mediators of inflammation as NFκB, cyclooxygenase-2 (COX-2), lipooxygenase (LOX), and inducible nitric oxide synthase (iNOS). Significant preventive and/or curative effects have been observed in experimental animal models of a number of diseases, including arteriosclerosis, cancer, diabetes, respiratory, hepatic, pancreatic, intestinal and gastric diseases, neurodegenerative and eye diseases. CONCLUSIONS Turmeric, an approved food additive, or its component curcumin, has shown surprisingly beneficial effects in experimental studies of acute and chronic diseases characterized by an exaggerated inflammatory reaction. There is ample evidence to support its clinical use, both as a prevention and a treatment. Several natural substances have greater antioxidant effects than conventional vitamins, including various polyphenols, flavonoids and curcumenoids. Natural substances are worth further exploration both experimentally and clinically.

Early enteral supply of fiber and Lactobacilli versus conventional nutrition: a controlled trial in patients with major abdominal surgery

OBJECTIVE Early enteral nutrition with fiber-containing solutions plus Lactobacillus may reduce bacterial translocation and minimize the incidence of infections after surgery. METHODS In a prospective, randomized trial in three groups (n = 30/group) of patients after major abdominal surgery, we compared our previous regimen with parenteral nutrition or fiber-free enteral nutrition (group A) with enteral fiber-containing nutrition with living Lactobacillus (group B) and heat-killed Lactobacillus (group C). The main endpoint was the development of bacterial infection. Other analyzed parameters were the durations of antibiotic therapy and hospital stay, non-infectious complications, side effects of the nutrition, and onset of bowel movement. Routine parameters, nutritional parameters, and cellular immune status in the blood were measured preoperatively and on 1, 5, and 10 d postoperatively. RESULTS The incidence of infections was significantly lower (P = 0.01) in groups B and C with enteral nutrition containing fibers (10% each) than in group A (30%). Patients in group B received antibiotics for a significantly shorter time (P = 0.04) than did the patients in groups A and C. The length of hospital stay and the incidence of non-infectious complications did not differ significantly. Fibers and lactobacilli were well tolerated. There were no general benefits of living Lactobacillus as opposed to heat-killed Lactobacillus in the entire study population, but benefits were observed in the patients with gastric and pancreas resections, although no statistical analysis was done due to their small numbers. CONCLUSIONS Early enteral nutrition with fiber-containing solutions reduced the rate of postoperative infections in comparison with parenteral nutrition and fiber-free enteral formula. Addition of living Lactobacillus seemed to increase the benefits in patients with gastric and pancreatic resections.

The Effect of Exogenous Administration of Lactobacillus reuteri R2LC and Oat Fiber on Acetic Acid-Induced Colitis in the Rat

The potential beneficial effect of exogenous administration of Lactobacillus on acetic acid-induced colitis was evaluated in the rat. Colitis was induced by instillation of 4% acetic acid for 15 sec in an exteriorized colonic segment. This produced uniform colitis with a threefold increase in myeloperoxidase (MPO) activity of the colonic tissue (an index of neutrophil infiltration) and a sixfold increase in plasma exudation into the lumen of the colon (mucosal permeability) as evaluated 4 days after acetic acid administration. Intracolonic administration of L. reuteri R2LC immediately after acetic acid administration, at a dose of 5 ml of 7 x 10(7) colony-forming units (CFU)/ml in two forms: either as pure bacterial suspension or as fermented oatmeal soup, prevented the development of colitis. Thus, the morphologic score, MPO activity, and mucosal permeability were almost normalized by Lactobacillus treatment. Initiating the treatment 24 h after acetic acid administration or using lower doses of 1 ml for 3 consecutive days resulted in a smaller protective effect. We conclude that exogenous administration of L. reuteri R2LC prevents the development of acetic acid-induced colitis in the rat.

Effect of Enteral Nutrition and Synbiotics on Bacterial Infection Rates After Pylorus-preserving Pancreatoduodenectomy A Randomized, Double-blind Trial

Objective:Patients undergoing pancreas resection carry several risk factors for nosocomial bacterial infections. Pre- and probiotics (synbiotics) are potentially useful for prevention of these infections. Summary Background Data:First trials in patients following major abdominal surgery including liver transplantation using one Lactobacillus (LAB) and one fiber showed significant reduction of infection rates and reduced length of antibiotic therapy compared with a control group. The present study was designed to analyze whether a combination of different LAB and fibers would further improve outcome. Methods:A prospective randomized monocentric double-blind trial was undertaken in 80 patients following pylorus-preserving pancreatoduodenectomy (PPPD). All patients received enteral nutrition immediately postoperatively. One group (A) received a composition of 4 LAB and 4 fibers, and another group (B) received placebo (fibers only) starting the day before surgery and continuing for 8 days. Thirty-day infection rate, length of hospital stay, duration of antibiotic therapy, noninfectious complications, and side effects were recorded. Results:The incidence of postoperative bacterial infections was significantly lower with LAB and fibers (12.5%) than with fibers only (40%). In addition, the duration of antibiotic therapy was significantly shorter in the latter group. Fibers and LAB were well tolerated. Conclusion:Early enteral nutrition supplemented with a mixture of LAB and fibers reduces bacterial infection rates and antibiotic therapy following PPPD.

Synbiotics, Prebiotics, Glutamine, or Peptide in Early Enteral Nutrition: A Randomized Study in Trauma Patients

BACKGROUND Since the hepatosplanchnic region plays a central role in development of multiple-organ failure and infections in critically ill trauma patients, this study focuses on the influence of glutamine, peptide, and synbiotics on intestinal permeability and clinical outcome. METHODS One hundred thirteen multiple injured patients were prospectively randomized into 4 groups: group A, glutamine; B, fermentable fiber; C, peptide diet; and D, standard enteral formula with fibers combined with Synbiotic 2000 (Synbiotic 2000 Forte; Medifarm, Sweden), a formula containing live lactobacilli and specific bioactive fibers. Intestinal permeability was evaluated by measuring lactulose-mannitol excretion ratio on days 2, 4, and 7. RESULTS No differences in days of mechanical ventilation, intensive care unit stay, or multiple-organ failure scores were found between the patient groups. A total of 51 infections, including 38 pneumonia, were observed, with only 5 infections and 4 pneumonias in group D, which was significantly less than combined infections (p = .003) and pneumonias (p = .03) in groups A, B, and C. Intestinal permeability decreased only in group D, from 0.148 (0.056-0.240) on day 4 to 0.061 (0.040-0.099) on day 7; (p < .05). In group A, the lactulose-mannitol excretion ratio increased significantly (p < .02) from 0.050 (0.013-0.116) on day 2 to 0.159 (0.088-0.311) on day 7. The total gastric retention volume in 7 days was 1150 (785-2395) mL in group D, which was significantly more than the 410 (382-1062) mL in group A (p < .02), and 620 (337-1190) mL in group C (p < .03). CONCLUSIONS Patients supplemented with synbiotics did better than the others, with lower intestinal permeability and fewer infections.

MAJOR LIVER RESECTION FOR HILAR CHOLANGIOCARCINOMA

Between 1968 and 1984 liver resection with curative attempt was performed in 22 patients with hilar cholangiocarcinoma. Right lobectomy was performed in 4 patients, extended right lobectomy in 7, left lobectomy in 8, and excision of the median segment segment of the left lobe (segment IV) in 3. Bilio-en-teric continuity was restored by hepatocholedochostomy in 17 patients and hepatojejunostomy in 4. (One patient had external transhepatic catheter drainage and no internal bile drainage.) Operative mortality rate was 27% and caused by excessive intraoperative bleeding, sepsis, or liver insufficiency. Postoperative complications occurred in 57% of patients surviving the operation and were due mainly to leakage from the hepatocholedochostomy. Median survival was 6 months, and one third of the patients survived 1 year. Three patients survived 10 years and were among the four patients in whom a tumor-free resection margin was obtained (one of them died in the postoperative phase). It is concluded that resection of hilar cholangiocarcinoma may give long-term survival if a free resection margin is obtained. The importance of a free resection margin indicates that surgery should be aggressive and include liver resection.

Impairment of Bacterial Flora in Human Ulcerative Colitis and Experimental Colitis in the Rat

Changes in the colonic mucosa-associated microflora were determined both in patients with active and inactive ulcerative colitis and in rats with acetic acid-induced colitis. In patients with active ulcerative colitis, significant decreases in the number of anaerobic bacteria (Brain Heart Infusion medium), anaerobic gram-negatives and Lactobacillus were found, whereas no changes were seen in the number of aerobic bacteria and Enterobacteriaceae. In patients with inactive ulcerative colitis, no significant differences in colonic mucosa-associated microflora could be demonstrated. Similar changes were seen in rats with acetic acid-induced colitis. Thus, 4 days after acetic acid administration, at which time the colitis was well developed as evaluated by morphological appearance and myeloperoxidase activity, reduction in the number of anaerobic bacteria and Lactobacillus was seen. The first day after acetic acid administration, when the colitis had not developed, or after 14 days, when the colitis had been overcome, no alterations were seen in the mucosa-associated microflora as compared with control rats. We conclude that a reduction in the number of anaerobic bacteria and Lactobacillus is a common feature in active colitis regardless of the origin of colitis.