- Email: [email protected]
Duodenogastric Reflux and Pyloric Surgery
April 1970
COMMENTS
patients were mISsmg only the brush border lactase (enzyme I). The use of hetero ,B-galactosides as well as lactose as substrates for the assay of ,B-galactosidase activity in biopsy specimens from the human small intestine seems to give additional information concerning the activity of different ,B-galactosidases, although, quite specific methods for the estimation of the three different enzymes without separation are lacking at present. NILS-GEORG Asp, ARNE DAHLQVIST OTAKAR KOLDOVSKY
Research Department oj the Hospital and Department oj Physiological Chemistry, University oj Lund Lasarettet, Lund, Sweden REFERENCES 1. Doell, R. G., and N. Kretchmer. 1962. Studies of small intestine during development. 1. Distribution and activity of fJ-galactosidase . Biochim. Biophys. Acta 62 : 353-362. 2. Dahlqvist, A., B. Bull, and D . L. Thomson . 1965. Rat intestinal 6-bromo-2-naphthyl glycosidase and disaccharidase activities. II. Solubilization and separation of smallintestinal enzymes. Arch. Biochem. Biophys. 109: 159-167. 3. Koldovsky, 0 ., R. Noack, G. Schenk, V. Jirsova, A. Heringova, H. Brana, F. Chytil, and M. Friedrich. 1965. Activity of fJ-galactosidase in homogenates and isolated microvilli fraction of jejunal mucosa from suckling rats . Biochem. J. 96: 492-494 . 4. Asp, N. G., and A. Dahlqvist. 1968. Rat small-intestinal fJ-gala ctosidases. Separation by ion-exchange chromatography and gel filtration. Biochem. J. 106: 841-845.
593
5. Asp, N . G., and A. Dahlqvist. 1968. Rat small-intestinal fJ-galactosidases. Kinetic studies with three separated fractions. Biochem. J. 110: 143-150. 6. Koldovsky, 0., N. G. Asp, and A. D ahlqvist. 1969. A method for the separate assay of "neutral" and "acid" fJ-galactosidase in homogenates of rat small-intestinal mucosa. Anal. Biochem. 27: 409-418. 7. Alpers, D . H. 1969. Separation and isolation of rat and human intestinal fJ-gal actosidases. J. Bioi. Chem. 244: 1238-1246. 8. Alpers, D. H. 1969. On fJ-galactosidase activity. Gastroenterology 56: 985-986. 9. Gray, G. M.,' and N. A. Santiago. 1969. Intestinal fJ-galactosidases. 1. Separation and characterization of three enzymes in normal human intestine . J. Clin. Invest. 48: 716728. 10. Asp. N. G., A. Dahlqvist, and O. KoldovskY. 1969. Human small intestinal fJ-galactosidases. Separation and characte~ization of one lactase and one hetero fJ-galactosidase. Biochem. J.114: 351-359. 11. Semenza, G., S. Auricchio, and A. Rubino. 1965. Multiplicity of human intestinal disaccharidases. 1. Chromatographic separation of maltases and of two lactases. Biochim. Biophys. Acta 96: 487-497. 12. Gray, G. M., N. A. Santiago, E. H . Colver, and M. Gene!. 1969. Intestinal fJ-galactosidases. II. Biochemical alteration in human lactase deficiency. J. Clin ~ Invest. 48: 729735. 13. Cook, G. C., and A. D ahlqvist. 1968. J ejunal hetero-fJ-galactosidase activities in Ugandans with lactase deficiency. Gastroenterology 55: 328--332. 14. Zoppi, G., B. Hadom , R. Gitzelmann, H. Kistler, and A. Prader. il966. Intestinal fJ-galactosidase activities in malabsorption syndromes. Gastro enterology 50: 557-561.
DUODENOGASTRIC REFLUX AND PYLORIC SURGERY The findings of increased reflux of bile in gastric ulcer! raises certain questions of surgical interest concerning the effects and incidence of duodeno gastric reflux. Gastritis occurs when the gastric mucosa is exposed to duodenal juices.2 - 4 There is an association between chronic gastritis and the presence of bile in the stomach.5 Clinical studies also show a link between dis-
tressing symptoms and intragastric bile in certain sensitive individuals. 6 Radi6log~ lcal studies indicate failure of anti reflux mechanisms in gastric ulcer and other dyspepsias.7 It is of some importance to the surgeon to know the effect of surgical procedures involving the pylorus in relation to reflux phenomena. Do pyloroplasty and pyloric
594
Vol. 58, No . 4
COMMENTS
excision precipitate, increase, or reduce reflux from duodenum to stomach? The full answer requires further research into local pressure gradients and their correlation with observed movements within the gastroduodenal lumen. Some information may, however, be obtained from present physiological knowledge and also from clinical studies of duodenal motility and gastric emptying. After vagotomy and pyloroplasty, solid material is evacuated more slowly and fluids more quickly than before operation. R. U The mixing ability of the stomach is reduced following surgery involving the py lorus, since gastric retropulsion is impaired. Normally the pylorus closes ahead of th e gastric wave forcing antral contents back into the body of the stomach. This can no lon ger occur efficiently after surgery and such energy becomes directed into gastric evacuation. Gastric mixing is reduced and distal gastric evacuation is improved . The result is seen when marked as dumping. A corollary of this effect must be that any material regurgitated from duod enum to distal stomach is evacuated, rather than mixed, with gastric contents. The subject has become clarified further by personal radiological observation of gastroduodenal movements in 400 patients, in cludin g 30 with pyloroplasty and 15 with pyloric resection (Billroth 1 procedures). Video recordings permitted detailed review of screening procedures and the studies were supplemented by fine duodenal intubation in each case for the introduction of contrast medium. The method used has been described elsewhere. 7 These radiological studies of reflux in, for example, patients with gastric ulcer indicate that the quantity of reflux is to a great extent determined by systolic contraction of the duodenal cap, which may be compared in its pumping action with a chamber of the heart. If the pumping action is destroyed by pyloroplasty or pyloric excision, the ability of the proximal duodemun to produce reflux is reduced considerably. To summarize, widening the gastroduodenal junction produces four effects in relation to reflux: reduction in quantity of
reflux, reduction in force of reflux, less mlxmg of regurgitated material with gastric contents, and more efficient evacuation of regurgitated fluids. Surprisingly, therefore, surgical procedures involving the pylorus, even when combined with vagotomy, may be expected on physiological and clinical grounds to reduce rather than encourage the force, quantity, and effect of reflux from the duodenum . In a patient with normally acting antireflux mechanisms, when reflux is rare or absent, the destruction of pyloric function produces some reflux from the duodenum. Unless the individual is particularly susceptible to the irritant effects of small amounts of intra gastric duodenal juices or gastric emptying excessively delayed significant disability is unlikely. Occasionally however, unpleasant symptoms, usually accompanied by gastritis, require further surgical intervention. For the severe case, a Roux-en-Y diversion is indicated,lO although it may be sufficient simply to increase the efficiency of gastric evacuation by partial gastric resection or widening of the stoma. JOHN O. KILBY, M.B. Department of Gastroenterology South mead Hospital Bristol, England REFERENCES 1. Rhodes, J., D . E. Barnardo, S. F . Phillips, R. A. Rovelstadt, and A. F. Hofmann . 1969. Increased reflux of bile in patients with gastric ulcer. Gastroenterology 57: 241. 2. Lawson, H. S. 1964. Effect of duodenal contents on the gastric mucosa under experimental conditions. Lancet 1: 469. 3. Capper, W. M., T . J. Butler, and K. G. Buckler. 1966. Alkaline areas in gastric mucosa after surgery. Gut 7: 220. 4. Delaney, J. P ., P. Ritchie, and J. Cheng. 1969. Atrophic gastritis, the primary lesion in gastric ulcerogenesis. Gastroent erology 56: 1147. 5. SiuraIa, M., and M . Tawast. 1956. Duodenal regurgitation and the state of the gastric mucosa, with special reference to the occurence of surface lowering factors in the gastric contents of cases with chronic atrophic gastritis. Acta M ed Scand. 153: 451. 6. Toye, D., and J. A. Williams. 1965. Post-gastrectomy bile vomiting. Lancet 2: 524.
595
COMMENTS
April 1970
7. Capper, W . M., G. R. Airth, and J. O. Kilby. 1966. A test for pyloric regurgitation. Lancel 2: 621. 8. Buckler, K. G. 1967. Effects of gastric surgery upon gastric emptying in cases of peptic ulceration. Gut 8: 137. 9. Wastell, C., P. Aylett, and 1. Wise. 1969. Gastric secretion and emptying before and
after vagotomy and pyloroplasty with and without continuous infusion of peptavlon pentagastrin. Amer. J . Dig. Dis. 14: 245. 10. Du Plessus, D. J. 1969. Alkaline reflux gastritis, p. 124-137. In H. N. Harkins and L. M. Nyhus [eds.], Surgery of the stomach and duodenum, Ed. 2. Little, Brown & Company, Boston.
LACTULOSE IN THE TREATMENT OF PORTAL-SYSTEMIC ENCEPHALOPATHY Report of a symposium
Under the chairmanship of U. P. Haemmerli (Zurich), investigators from 12 countries met at Baden near Vienna on September 8, 1969, for a working session on predominantly unpublished experiences with lactulose. Basic Action
H. Haenel (Potsdam) reported that the disaccharide lactulose (a keto analogue of lactose, 1,4-j]-galactosido-fructose) is not hydrolyzed by the small intestinal mucosa of man, rat, rabbit, and cattle. Less than 0.4% is absorbed and excreted in the urine. In the colon lactulose is broken down by lactobacilli, bacterioids, and Escherichia coli, but not by Proteus mirabilis and Streptococcus faecalis. The lactic acid produced by this breakdown of lactulose leads to a lowering of fecal pH and stimulates the growth of lactobacilli with a decrease in that of bacteroids. D. Muting (Homburg/Saar) found that addition of lactulose to cultures of E . coli and Proteus decreased the formation of ammonia and free phenols. A small portion of lactulose is probably hydrolized in the colon into its constituent monosaccharides, galactose and fructose, as evidenced by observation of A. Charbonnier (Paris) that galactosuria still occurred 4 to 8 hI' after lactulose administration. U. P. Haemmerli (Zurich) described the introduction of lactulose into the treatment of chronic hepatic encephalopathy in 1966 and pointed out that lactulose ingestion induced an artificial disaccharide malabsorption syndrome and, when given
in sufficient doses, led to a watery acid diarrhea. The osmotic effect of lactulose breakdown products in the colon was verified radiologically by S. Pertsiounis (Berne), who calculated an average increase in colon volume of about 400 ml 90 min after 20 g of lactulose. In a carefully controlled study, W. R. Ebert (Weesp, Nederland) noticed that the daily dose necessary to achieve about one soft bowel movement per day in constipated subjects varied between 15 and 30 m!. Clinical Evaluation
S. G. Elkington (West Haven, Connecticut ) treated 7 patients with chronic portal system encephalopathy in a double blind study and noted clinical improvement in 5 instances. Simultaneously lowered fecal pH and arterial ammonia values were observed. G. Rorsman (Eksjo) quantitated alterations in the electroencephalograph by plotting wavelength frequency diagrams. In each of 3 patients, significant improvement occurred during lactulose administration, although the frequency curves did not revert completely to a normal shape. One of the most detailed studies was described by R. Zeegen (London). In addition to daily stool frequency and weight, bacteriological examination of the stool, and arterial and venous blood ammonia, they had applied a method for quantitative psychometric testing, which appeared particularly suitable for the serial evaluation of patients with chronic encephalopathy. When analyzed by the cumulative sum technique, they found a
COMMENTS
patients were mISsmg only the brush border lactase (enzyme I). The use of hetero ,B-galactosides as well as lactose as substrates for the assay of ,B-galactosidase activity in biopsy specimens from the human small intestine seems to give additional information concerning the activity of different ,B-galactosidases, although, quite specific methods for the estimation of the three different enzymes without separation are lacking at present. NILS-GEORG Asp, ARNE DAHLQVIST OTAKAR KOLDOVSKY
Research Department oj the Hospital and Department oj Physiological Chemistry, University oj Lund Lasarettet, Lund, Sweden REFERENCES 1. Doell, R. G., and N. Kretchmer. 1962. Studies of small intestine during development. 1. Distribution and activity of fJ-galactosidase . Biochim. Biophys. Acta 62 : 353-362. 2. Dahlqvist, A., B. Bull, and D . L. Thomson . 1965. Rat intestinal 6-bromo-2-naphthyl glycosidase and disaccharidase activities. II. Solubilization and separation of smallintestinal enzymes. Arch. Biochem. Biophys. 109: 159-167. 3. Koldovsky, 0 ., R. Noack, G. Schenk, V. Jirsova, A. Heringova, H. Brana, F. Chytil, and M. Friedrich. 1965. Activity of fJ-galactosidase in homogenates and isolated microvilli fraction of jejunal mucosa from suckling rats . Biochem. J. 96: 492-494 . 4. Asp, N. G., and A. Dahlqvist. 1968. Rat small-intestinal fJ-gala ctosidases. Separation by ion-exchange chromatography and gel filtration. Biochem. J. 106: 841-845.
593
5. Asp, N . G., and A. Dahlqvist. 1968. Rat small-intestinal fJ-galactosidases. Kinetic studies with three separated fractions. Biochem. J. 110: 143-150. 6. Koldovsky, 0., N. G. Asp, and A. D ahlqvist. 1969. A method for the separate assay of "neutral" and "acid" fJ-galactosidase in homogenates of rat small-intestinal mucosa. Anal. Biochem. 27: 409-418. 7. Alpers, D . H. 1969. Separation and isolation of rat and human intestinal fJ-gal actosidases. J. Bioi. Chem. 244: 1238-1246. 8. Alpers, D. H. 1969. On fJ-galactosidase activity. Gastroenterology 56: 985-986. 9. Gray, G. M.,' and N. A. Santiago. 1969. Intestinal fJ-galactosidases. 1. Separation and characterization of three enzymes in normal human intestine . J. Clin. Invest. 48: 716728. 10. Asp. N. G., A. Dahlqvist, and O. KoldovskY. 1969. Human small intestinal fJ-galactosidases. Separation and characte~ization of one lactase and one hetero fJ-galactosidase. Biochem. J.114: 351-359. 11. Semenza, G., S. Auricchio, and A. Rubino. 1965. Multiplicity of human intestinal disaccharidases. 1. Chromatographic separation of maltases and of two lactases. Biochim. Biophys. Acta 96: 487-497. 12. Gray, G. M., N. A. Santiago, E. H . Colver, and M. Gene!. 1969. Intestinal fJ-galactosidases. II. Biochemical alteration in human lactase deficiency. J. Clin ~ Invest. 48: 729735. 13. Cook, G. C., and A. D ahlqvist. 1968. J ejunal hetero-fJ-galactosidase activities in Ugandans with lactase deficiency. Gastroenterology 55: 328--332. 14. Zoppi, G., B. Hadom , R. Gitzelmann, H. Kistler, and A. Prader. il966. Intestinal fJ-galactosidase activities in malabsorption syndromes. Gastro enterology 50: 557-561.
DUODENOGASTRIC REFLUX AND PYLORIC SURGERY The findings of increased reflux of bile in gastric ulcer! raises certain questions of surgical interest concerning the effects and incidence of duodeno gastric reflux. Gastritis occurs when the gastric mucosa is exposed to duodenal juices.2 - 4 There is an association between chronic gastritis and the presence of bile in the stomach.5 Clinical studies also show a link between dis-
tressing symptoms and intragastric bile in certain sensitive individuals. 6 Radi6log~ lcal studies indicate failure of anti reflux mechanisms in gastric ulcer and other dyspepsias.7 It is of some importance to the surgeon to know the effect of surgical procedures involving the pylorus in relation to reflux phenomena. Do pyloroplasty and pyloric
594
Vol. 58, No . 4
COMMENTS
excision precipitate, increase, or reduce reflux from duodenum to stomach? The full answer requires further research into local pressure gradients and their correlation with observed movements within the gastroduodenal lumen. Some information may, however, be obtained from present physiological knowledge and also from clinical studies of duodenal motility and gastric emptying. After vagotomy and pyloroplasty, solid material is evacuated more slowly and fluids more quickly than before operation. R. U The mixing ability of the stomach is reduced following surgery involving the py lorus, since gastric retropulsion is impaired. Normally the pylorus closes ahead of th e gastric wave forcing antral contents back into the body of the stomach. This can no lon ger occur efficiently after surgery and such energy becomes directed into gastric evacuation. Gastric mixing is reduced and distal gastric evacuation is improved . The result is seen when marked as dumping. A corollary of this effect must be that any material regurgitated from duod enum to distal stomach is evacuated, rather than mixed, with gastric contents. The subject has become clarified further by personal radiological observation of gastroduodenal movements in 400 patients, in cludin g 30 with pyloroplasty and 15 with pyloric resection (Billroth 1 procedures). Video recordings permitted detailed review of screening procedures and the studies were supplemented by fine duodenal intubation in each case for the introduction of contrast medium. The method used has been described elsewhere. 7 These radiological studies of reflux in, for example, patients with gastric ulcer indicate that the quantity of reflux is to a great extent determined by systolic contraction of the duodenal cap, which may be compared in its pumping action with a chamber of the heart. If the pumping action is destroyed by pyloroplasty or pyloric excision, the ability of the proximal duodemun to produce reflux is reduced considerably. To summarize, widening the gastroduodenal junction produces four effects in relation to reflux: reduction in quantity of
reflux, reduction in force of reflux, less mlxmg of regurgitated material with gastric contents, and more efficient evacuation of regurgitated fluids. Surprisingly, therefore, surgical procedures involving the pylorus, even when combined with vagotomy, may be expected on physiological and clinical grounds to reduce rather than encourage the force, quantity, and effect of reflux from the duodenum . In a patient with normally acting antireflux mechanisms, when reflux is rare or absent, the destruction of pyloric function produces some reflux from the duodenum. Unless the individual is particularly susceptible to the irritant effects of small amounts of intra gastric duodenal juices or gastric emptying excessively delayed significant disability is unlikely. Occasionally however, unpleasant symptoms, usually accompanied by gastritis, require further surgical intervention. For the severe case, a Roux-en-Y diversion is indicated,lO although it may be sufficient simply to increase the efficiency of gastric evacuation by partial gastric resection or widening of the stoma. JOHN O. KILBY, M.B. Department of Gastroenterology South mead Hospital Bristol, England REFERENCES 1. Rhodes, J., D . E. Barnardo, S. F . Phillips, R. A. Rovelstadt, and A. F. Hofmann . 1969. Increased reflux of bile in patients with gastric ulcer. Gastroenterology 57: 241. 2. Lawson, H. S. 1964. Effect of duodenal contents on the gastric mucosa under experimental conditions. Lancet 1: 469. 3. Capper, W. M., T . J. Butler, and K. G. Buckler. 1966. Alkaline areas in gastric mucosa after surgery. Gut 7: 220. 4. Delaney, J. P ., P. Ritchie, and J. Cheng. 1969. Atrophic gastritis, the primary lesion in gastric ulcerogenesis. Gastroent erology 56: 1147. 5. SiuraIa, M., and M . Tawast. 1956. Duodenal regurgitation and the state of the gastric mucosa, with special reference to the occurence of surface lowering factors in the gastric contents of cases with chronic atrophic gastritis. Acta M ed Scand. 153: 451. 6. Toye, D., and J. A. Williams. 1965. Post-gastrectomy bile vomiting. Lancet 2: 524.
595
COMMENTS
April 1970
7. Capper, W . M., G. R. Airth, and J. O. Kilby. 1966. A test for pyloric regurgitation. Lancel 2: 621. 8. Buckler, K. G. 1967. Effects of gastric surgery upon gastric emptying in cases of peptic ulceration. Gut 8: 137. 9. Wastell, C., P. Aylett, and 1. Wise. 1969. Gastric secretion and emptying before and
after vagotomy and pyloroplasty with and without continuous infusion of peptavlon pentagastrin. Amer. J . Dig. Dis. 14: 245. 10. Du Plessus, D. J. 1969. Alkaline reflux gastritis, p. 124-137. In H. N. Harkins and L. M. Nyhus [eds.], Surgery of the stomach and duodenum, Ed. 2. Little, Brown & Company, Boston.
LACTULOSE IN THE TREATMENT OF PORTAL-SYSTEMIC ENCEPHALOPATHY Report of a symposium
Under the chairmanship of U. P. Haemmerli (Zurich), investigators from 12 countries met at Baden near Vienna on September 8, 1969, for a working session on predominantly unpublished experiences with lactulose. Basic Action
H. Haenel (Potsdam) reported that the disaccharide lactulose (a keto analogue of lactose, 1,4-j]-galactosido-fructose) is not hydrolyzed by the small intestinal mucosa of man, rat, rabbit, and cattle. Less than 0.4% is absorbed and excreted in the urine. In the colon lactulose is broken down by lactobacilli, bacterioids, and Escherichia coli, but not by Proteus mirabilis and Streptococcus faecalis. The lactic acid produced by this breakdown of lactulose leads to a lowering of fecal pH and stimulates the growth of lactobacilli with a decrease in that of bacteroids. D. Muting (Homburg/Saar) found that addition of lactulose to cultures of E . coli and Proteus decreased the formation of ammonia and free phenols. A small portion of lactulose is probably hydrolized in the colon into its constituent monosaccharides, galactose and fructose, as evidenced by observation of A. Charbonnier (Paris) that galactosuria still occurred 4 to 8 hI' after lactulose administration. U. P. Haemmerli (Zurich) described the introduction of lactulose into the treatment of chronic hepatic encephalopathy in 1966 and pointed out that lactulose ingestion induced an artificial disaccharide malabsorption syndrome and, when given
in sufficient doses, led to a watery acid diarrhea. The osmotic effect of lactulose breakdown products in the colon was verified radiologically by S. Pertsiounis (Berne), who calculated an average increase in colon volume of about 400 ml 90 min after 20 g of lactulose. In a carefully controlled study, W. R. Ebert (Weesp, Nederland) noticed that the daily dose necessary to achieve about one soft bowel movement per day in constipated subjects varied between 15 and 30 m!. Clinical Evaluation
S. G. Elkington (West Haven, Connecticut ) treated 7 patients with chronic portal system encephalopathy in a double blind study and noted clinical improvement in 5 instances. Simultaneously lowered fecal pH and arterial ammonia values were observed. G. Rorsman (Eksjo) quantitated alterations in the electroencephalograph by plotting wavelength frequency diagrams. In each of 3 patients, significant improvement occurred during lactulose administration, although the frequency curves did not revert completely to a normal shape. One of the most detailed studies was described by R. Zeegen (London). In addition to daily stool frequency and weight, bacteriological examination of the stool, and arterial and venous blood ammonia, they had applied a method for quantitative psychometric testing, which appeared particularly suitable for the serial evaluation of patients with chronic encephalopathy. When analyzed by the cumulative sum technique, they found a