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REFERENCES 1. Cooper, H., R. L. Levitan, J . S. Fordtran, and

F. J. Ingelfinger. 1966. A method for studying absorption of water and solute from the human small intestine. Gastroenterology 50: 1- 7. 2. Whalen, G. E., J. A. Harris, J . E. Geenen, and K. H. Soergel. 1966. Sodium and water absorption from the human small intestine. The accuracy of the perfusion method. Gastroenterology 51: 975- 984. 3. Fordtran, J. S. 1966. Marker perfusion techniques

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for measuring intestinal absorption in man. Gastroenterology 51: 1089- 1093. 4. Sladen, G. E ., and A. M . Dawson. 1968. An evaluation of perfusion techniques in the study of water and electrolyte absorption in man; the problem of endogenous secretions. Gut 9: 530-535.

5. Fordtran, J. S., R. Levitan, V. Bikerman, B. A. Burrows, and F. J . Ingelfinger. 1961. The kinetics of water absorption in the human intestine. Trans. Assn . Amer. Phys. 74: 195-205.

BRITISH SOCIETY OF GASTROENTEROLOGY MEETINGS The 29th Annual General Meeting of the British Society of Gastroenterology was held in London, November 7 to 9, 1968, with the President, Mr. N. C. Tanner (London), in the chair. The sessions on November 7 and 8 were held at the Royal College of Physicians, and that on November 9 at the Royal College of Surggeons. The meeting opened with a symposium on carcinoma of the esophagus. Dr. M. J. Langman (Nottingham) discussed the epidemiology of the disease, pointing out the very striking variations in different countries throughout the world. It was unlikely that climatic conditions alone were important, since neighboring countries with very similar climates could display large differences in the esophageal cancer pattern. He also indicated that the variations in the incidence of cancer of the esophagus did not parallel the equally striking variations in carcinoma of the stomach. Available evidence suggested environmental rather than hereditary causes for the majority of esophageal cancers, and there seemed to be some association with both alcohol consumption and tobacco smoking. It was often difficult to separate these two factors one from the other, but as also appears for carcinoma of the bronchus, there was some encouraging evidence that the cessation of smoking might be followed by a reduction in the incidence of esophageal cancer. There was no evidence to incriminate any specific dietary factor or the ingestion of unduly hot liquids. The very marked regional variations in

incidence of carcinoma of the esophagus in East Africa were discussed in detail by Mr. D. Burkitt (East Africa) . The particular areas under study were around the eastern shores of Lake Victoria and on the slopes of Mount Kenya. In some areas the tumor constituted 70% of all malignant disease in males over the age of 30 years. By contrast, in communities 50 to 70 miles away from these high incidence areas, the esophagus was involved in less than 1% of malignancies. At present there is no obvious explanation for these differences. A system of analyzing the clinical presentation of dysphagia was proposed by Dr. D. A. W. Edwards (University College Hospital, London). His basic thesis was that earlier diagnosis of carcinoma of the esophagus was required to make a substantial contribution to the results of surgical treatment. He felt that greater and earlier accuracy in diagnosis could be reached by a more precise evaluation of the clinical history rather than by either X-ray or endoscopic diagnosis. Symptoms in patients with diverse esophageal diseases were analyzed for their value in discriminating among different specific disease states. Discussion arose regarding the basic premise that increased cure rates might be expected from making earlier diagnoses, in view of the evidence from other parts of the gastrointestinal tract that there might be an inverse relationship between the lapse of time between first symptom and treatment, and ultimate survival from treatment. However, this is a slightly dif-

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ferent point from the usefulness of treating both slowly and rapidly growing tumors basically at an earlier stage in their development, and it was generally agreed that there was still every reason to attempt the earliest possible diagnosis. Dr. J. G. Pearson (Edinburgh) reviewed the results of radiation treatment of squamous carcinoma of the esophagus in the radiotherapy center for Southeast Scotland, located in Edinburgh. Over the past 20 years there has been a steady swing from surgical resection to radiotherapy, and this applied to tumors located in the upper, mid, and lower regions of the esophagus. Comparison was made of the 5-year survival rates from both forms of treatment, the surgical ones based on the years 1948 to 1962, and the radiotherapy ones from 1956 to 1962. For tumors in the upper esophagus, the 5-year survival rates from operation were 21 % and from radiotherapy 23%. In the midesophagus the corresponding figures were 9 and 20%, and in the lower third of the gullet 12 and 17%, respectively. In view of these findings, carcinoma, of the esophagus has been almost exclusively treated by irradiation in the last 2 years. Dr. Pearson described the majority of survivors as having few residual symptoms, and in particular stressed the advantages of unimpaired voice production, adequately maintained body weights, and the possession of intact stomachs. A few with posttherapy strictures appeared to be treated satisfactorily by either a single esophageal dilation or repeated dilation with mercury bougies or other instruments. On the other hand, Mr. N. C. Tanner (Charing Cross Hospital, London) preferred surgical excision of those tumors located in either the mid or lower thirds of the esophagus. He described the surgical techniques for resection of these tumors and the alternative means of reconstruction of alimentary continuity. To ensure adequate removal of the tumors, he usually employed a very radical excision, often amounting to virtually complete resection of the esophagus. The right or transverse colon was interposed between upper esoph-

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agus and jejunum when an esophagogastric anastomosis was not possible. He was unimpressed by the palliation from synthetic tubes placed in inoperable carcinomas, and preferred a Roux loop bypass procedure to relieve dysphagia in these cases. Operative mortality for resection of carcinomas of the lower end of the esophagus was now around 18% and still decreasing, and 5-year survival figures in those undergoing resection were between 20 and 30%. In discussing the various merits of radiotherapy and surgical resection for malignant disease of the esophagus, few were able to report such good results from radiotherapy as had been obtained in Edinburgh. Although the exact treatment details were not discussed, it seemed likely that differences in radiotherapy technique might explain in part the differing experience in different centers. After this symposium the following short papers were presented. Drs. J . D. Banwell, S. L. Gorbach, B. Chatterjee, and R. Mitra (The Johns Hopkins University Center, Calcutta) discussed in detail studies of gastrointestinal bacteriology and small bowel absorption in 6 patients with tropical sprue. Control observations were also made on 13 subjects without known gastrointestinal disease. A triple lumen tube was used to sample the contents of the stomach, jejunum, and ileum. Cultures were made under both aerobic and anaerobic conditions. Water and electrolyte absorption in the small intestine was measured by perfusing an isotonic electrolyte solution with Bromsulphthalein as a marker. All 6 sprue patients had abnormal flora in the small intestine and 2 had coliform organisms grown from gastric aspirates. The mean bacteriological counts at all levels from which samples were taken were significantly greater in the sprue patients than in the controls. Malabsorption of vitamin B 12 , xylose, and fat was present in the sprue patients, and 5 had evidence of water and electrolyte secretion into the intestinal lumen. After 48 hr of tetracycline therapy the absorption of vitamin B 12 , folate, and

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fat was markedly improved, and the water and electrolyte absorption defects were partially corrected. However, malabsorption persisted even after restoring the bacteriological pattern to within normal limits. It was noteworthy that the patient with the shortest history of symptoms had the most complete return of small bowel function to nonnallevels. The apparently high incidence of psychiatric morbidity in patients with malabsorption syndromes prompted Dr. G. P. Goldberg (Institute of Psychiatry and St. Thomas's Hospital, London) to investigate in detail psychological factors in three groups of patients with malabsorption, 46 with celiac disease, 21 with Crohn's disease, and 11 with alactasia. A carefully standardized psychiatric interview of known reliability was performed on each attendance at the Outpatient Department during 1 survey year. Psychological disturbances were no more frequent in patients with generalized malabsorption or diarrhea than in other patients; this suggested that deficiency or diarrhea was not a cause for these disturbances. The prevalence of psychiatric illness was broadly comparable in each of the three diseases. Patients who manifested psychiatric abnormalities attended the Outpatient Department more frequently during the survey year than those patients in each group without evidence of psychiatric abnormality. The most frequently encountered psychiatric illnesses were minor affective syndromes. The occurrence of steatorrhea in 6 out of 10 consecutive patients with thyrotoxicosis was reported by Drs. W. R. J. Middleton and G. R. Thompson (Royal Postgraduate Medical School, London). This finding led to a study of fat absorption in rats before and after induction of hyperthyroidism by feeding thyroid extract. Within 10 days of starting treatment the animals regularly developed both hyperthyroidism and gross steatorrhea. Studies with 14C_ triolein and 14C-oleic acid showed that these animals malabsorbed both triglyceride and fatty acid, thus indicating that the steatorrhea was not likely to be the

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effect of pancreatic malfunction. The absorption of !4C-linoleic acid infused into the duodenum as a micellar solution or as an ultrasonified emulsion was similar in thyrotoxic and control rats. The ratios of trihydroxy to dihydroxy bile acids were decreased in the hyperthyroid rats as compared with control animals, but the total intestinal concentration of conjugated bile acids was the same in both groups; it thus appeared to be unlikely that the malabsorption would be due to defective micelle fonnation. Finally, the rates of gastric and small intestine transit were estimated by following the passage of !4C-triolein; greatly increased rates of transit through both stomach and small intestine were observed. It was concluded that the enhanced rate of gastrointestinal transit was the most likely cause of the steatorrhea. The possibility that the thyroid extract exerted a local effect in the stomach after ingestion was rendered unlikely by the delay of a few days before the effects on gastrointestinal motility were apparent. Drs. J . J . Bernier, J. C. Rambaud, D. Cattan, and A. Prost (H6pital Saint-Lazare, Paris) discussed the occurrence of diarrhea in 5 patients with medullary carcinoma of the thyroid. They made detailed studies of serum electrolytes, liver function tests, serum proteins, and stool analyses in all 5 patients, and concluded that the principal defect was in absorption of water and electrolytes from the intestinal tract. Steatorrhea when it occurred was mild, and the intestinal absorption of both sugar and vitamin B12 was normal. No histological abnonnality was seen on jejunal biopsy. Since removal of the tumor usually cured the diarrhea, it was likely that there was a humoral agent responsible for the diarrhea. Tumor production of serotonin, bradykinin, and histamine was inconstant, and therefore none of these agents was likely to be the responsible one. The possibility that prostaglandin might play a significant role was raised, but could not be confirmed. Thyrocalcitonin, the principal hormone produced in medullary carcinoma of the thyroid, was not known to

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have any significant effect on gastroin- to the serosal aspect of guinea pig intestinal motility. testine diminished peristalsis, whereas A fine study of the changes in the my- intravenous injections were without effect enteric plexus in pseudo-obstruction was on motility. The rapid clearance of prospresented by Dr. B. Smith (St. Barthol- taglandins by the liver and lungs and the omew's Hospital, London) . The specimens hypotension which results from intravenous were from 2 patients who presented with administration make it unlikely that they long histories of previously unexplained are involved normally in the regulation of incomplete intestinal obstruction with gastrointestinal motility, although the intractable constipation as the major symp- possibility that they might exert such a tom . Gross thickening of the muscle walls, role on local release within the intestinal particularly the inner layer, was noted, but wall cannot be excluded. the principal abnormality lay in changes A detailed study of the pharmacology of in the myenteric plexus indicated by sil- muscle strips from the lower esophageal ver preparations cut in the plane of the sphincter was reported by Drs. J. J. Misieplexus. Striking loss of neurons was dem- wicz, S. Waller, P . P . Anthony, and J. W. onstrated, and in the place of the destroyed P . Gummer (Central Middlesex Hospital, nerve fibers there was marked proliferation London). Muscle strips were taken from of the Schwann cells. It was not known 16 patients operated on for achalasia of what had originally damaged the nerve the cardia, and comparison was made with cells, but in their absence it was believed the responses in 20 muscle strips from 11 that the only residual movements in the patients having esophageal resection for intestinal musculature would be segmen- carcinoma not involving this area, and 1 tation. This in turn probably led to the each with esophageal diverticulum and muscle hypertrophy. Normal peristalsis benign stricture. The numbers of ganglion was required to keep the intestinal bac- cells in the muscle strips from both groups teria in the normal colonic site, and some were assessed histologically so that comproximal proliferation of these bacteria parison might be made between the pharmight well explain the degree of malab- macological responses and the histological sorption noted in these patients. The his- appearances. tological changes were unlike those in By the use of specific a and /3 blocking Hirschsprung's disease. agents, ganglion blockers, and anticholinerConsiderable interest in these striking gic drugs, it was possible to demonstrate pictures was shown in the discussion, and that both a- and /3-adrenergic receptors in reply to questions Dr. Smith claimed were present in both muscle layers of the that the picture was quite unlike that in sphincter. The a receptors mediated conChaga's disease, Ogilvie's syndrome, and traction while the /3 receptors mediated the state of the bowel after prolonged use relaxation. In the normal strips there were of cathartics. It was not known whether /3-adrenergic inhibitor receptors in both any such changes might be apparent muscle layers, and additional cholinergic after vagotomy, but she believed that at contractile activity in the longitudinal least 10 to 12 years would have to elapse layer. In achalasia, neither layer showed before looking for such changes. the /3-adrenergic inhibitory activity. This Drs. B. D. Scholes, K. G. Eley, and A. loss in /3-adrenergic activity correlated well Bennett (King's College Hospital, Lon- with the diminution in number of ganglion don) studied the effect of prostaglandins cells from the cardiac sphincter area in the on intestinal motility in pieces of human achalasia patients; sometimes striking and guinea pig ileum, and in the ileum lymphocytic infiltration was observed in in intact guinea pigs. In both species lon- the area of these ganglia . gitudinal muscle contracted, and circular The use of pneumatic dilation for achamuscle relaxed, in the presence of prosta- lasia of the cardia was advocated by Drs. glandins E\ and E 2 • Prostaglandins applied J . R. Bennett, E. Bargaza, T. R. Hendrix,

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and C. I. Siegel (Johns Hopkins Hospital, Baltimore). Results were presented of treatment of 51 patients over 11 years with forceful dilation of the cardia with a pneumatic dilator under fluoroscopic control. The procedure was performed with only local pharyngeal anesthesia. The instrument had an expansion limited at 3 em, and the technique employed was to site the balloon with the achalasia stricture at its midpoint, and then apply increments of pressure of 3 Ib per sq inch at a time until the stricture was overcome, and no indentation of the stretching balloon was seen on the fluoroscopic screen. A pressure of 12 to 15 Ib per sq inch was usually required. The patients were then allowed only water to drink for the rest of the day, but the following morning were encouraged to eat a normal, large meal. The average period of hospitalization was 3 1/2 days after treatment. Three failures occurred, 2 in patients with carcinoma of the gastroesophageal junction unsuspected before dilation. In the remaining patient the dilator could not be induced to enter the cardia. Three perforations of the esophagus occurred, but only one of these required thoracotomy and repair. All 3 patients recovered. Seven patients developed recurrent dysphagia but 5 had further successful dilations. Two others were regarded as having poor results on account of symptoms of gastroesophageal reflux. Two year follow-up figures showed an over-all relief from symptoms of over 90%. The session on November 8 began with an account of studies on the localization of peptidases in various fractions of small intestinal mucosal cells presented by Dr. T. J. Peters (Royal Postgraduate Medical School, London). Two different techniques for preparing subcellular fractions were compared, namely that of Eicholtz and Crane and that by Hiibscher et al. The cell fractions studied were brush borders, mitochondria, lysosomes, microsomes, and cell sap. The first technique gave a purer brush border preparation than the other, and there were minor quantitative differences in the distribution of various peptidases in the different fractions produced by

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these two techniques. Tripeptidases and dipeptidases were more abundant in the cell sap; only small proportions (between 5 and 20%) of the enzymes were localized in the brush border. A fine demonstration of the surface ultrastructure of small intestinal mucosa using the scanning electron microscope was presented by Drs. M. N. Marsh, J. A. Swift, and E. D. Williams (Royal Postgraduate Medical School, London, and Unilever Research Laboratories). The main advantage of this instrument was that it allowed magnification up to X 10,000, and had a greater depth of field focus than other instruments. Stereo electronmicrography could be obtained by slight alteration in the angle of the table on which the specimen was mounted. Differences in the villi and epithelial cells between control subjects and patients with celiac disease were recorded. Dr. M. A. Hassan and Mr. M. Hobsley (The Middlesex Hospital, London) discussed the importance of radiological checking of the position of a gastric tube in obtaining satisfactory aspirates of gastric secretion for analysis. They compared the recovery of fixed volumes of instilled phenol red solution via tubes positioned with or without X-ray screening. They concluded that X-ray screening was unnecessary and advocated instead a simple test of recovery by injecting a known quantity of liquid down the tube at the onset of a test. They also suggested that there was no "optimal" position for siting of the tube. The controversy well known to gastroenterologists interested in this problem then ensued. Mr. M. C. Mason and Mr. G. R. Giles (Leeds) were concerned with the possibility that patients with different gastric disorders might display differences in the sensitivity to stimulation of gastric acid secretion. Instead of using maximal stimulation, they determined the threshhold of various groups of individuals to stimulation with minute doses of pentagastrin given by continuous intravenous infusion. Doses of pentagastrin ranged from 0.0003 Ilg per kg per hr to 1.2 Ilg per kg per hr, this latter

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dose apparently evoking "maximal" response. Significant increase in acid production over basal levels was noted only in duodenal ulcer patients with a dose of 0.000625 J.Lg per kg per hr; none of the 8 patients with gastric ulcer, 11 normal volunteers, or 16 patients with X-ray negative dyspepsia had a significant acid response until doses 0.005 J.Lg per kg per hr or greater were used. It was postulated that duodenal ulcer subjects might therefore produce an acid response under conditions which would not stimulate acid production in normal subjects. It is possible that this increase in response to threshold doses might simply be a manifestation of the greater capacity of duodenal ulcer patients to secrete acid. The problem of high levels of unconjugated bilirubin in the blood in the absence of hemolytic factors was investigated by Drs. M . Black and B. H . Billing (Royal Free Hospital, London). A new method of estimating the specific enzyme, bilirubinuridine diphosphate glucuronyl transferase activity, was used and adapted for assays of tissue obtained by needle biopsy of the liver. First, a fairly narrow range of enzyme activity was defined in normal subjects, and then observations were made in biopsies from patients with hepatitis, cirrhosis, extrahepatic biliary obstruction, Wilson's disease, and Gilbert's syndrome. Only in the latter syndrome was there regularly found to be a reduction in enzyme activity. In patients with hepatitis and extrahepatic biliary obstruction there was usually an increase in enzyme activity. It was not known whether the bilirubin glucuronyl transferase activity increased in Gilbert's syndrome following the administration of phenobarbitone. The relatively high incidence of granulomata in the liver and other organs of patients with primary biliary cirrhosis might be explained by a chronic delayed hypersensitivity reaction, argued Drs. R. A. Fox, P . J. Scheuer, S. Sherlock, O. Sharma, and D. G. James (Royal Free Hospital and Royal Northern Hospital, London). Patients with primary biliary cirrhosis were found to be relatively aner-

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gic. Fifty-eight per cent of these patients could not be sensitized with dinitrochlorobenzene as compared with 6% of control subjects. Patients with primary biliary cirrhosis gave negative skin tests to purified protein derivative and Candida antigen significantly more often than did controls, and their peripheral lymphocytes showed a reduced response to phytohemagglutinin. The degree of depression of lymphocyte transformation was not related to increased levels of serum alkaline phosphatase or bilirubin . The possibility that anergy may have been a nonspecific response to severe illness (as has been seen in advanced malignant disease) was discussed. Drs. R. N. Melmed and I. A. D. Bouchier (Royal Free Hospital, London) confirmed the generalized pancreatic enlargement in rats fed a diet containing soybean flour . The effect was not noted after heating the soybean flour. Purified trypsin inhibitor administered orally in low concentrations caused a generalized enlargement of the rat pancreas and a parallel increase in the amylase content of the gland. Prior vagotomy did not interfere with the effect of the trypsin inhibitors, and the effect of these inhibitors on pregnant rats was transferable across the placenta to the fetus. It was suggested that the trypsin inhibitors released a "trophic" substance from the intestinal mucosa, which in tum acted upon the pancreatic acinar cells. Intraperitoneal administration of the trypsin inhibitor was without significant effect on stimulating the pancreas. In response to questions, Dr. Melmed stated that the increased gland enlargement was chiefly the result of hyperplasia of the exocrine cells. Dr. M. Baum, Mr. C. T. Howe, Dr. S. B. Osborne, and Dr. N. Strickland (King's College Hospital, London) gave" a somewhat pessimistic account of the use of pancreatic scintiscanning in the detection of pancreatic tumors. In approximately onethird of 43 scans it was impossible to give a useful opinion regarding the state of the pancreas. Three false positives and two false negatives were obtained, and it was particularly regretted that those with the false positive result were submitted to

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laparotomy which might otherwise have proved unnecessary. The main cause of failure was the overlap of the liver scan, or unaccountable failure to demonstrate a definite pancreatic outline . The addition of liver scanning did not appear to improve the over-all diagnostic results. A number of speakers in discussion took a differing view to that presented by Mr. Howe, and commented much more favorably on their diagnostic discrimination using this technique. The second Sir Arthur Hurst Memorial Lecture was given by Dr. Brian Creamer (St. Thomas's Hospital, London) . This was a truly outstanding account of the birth, migration pattern, and death of intestinal mucosal cells, with each stage illustrated in detail both from Dr. Creamer's own considerable experience and from the work of many other investigators. He recounted the evidence for both goblet cells and the principal epithelial cells having the same stem origin. A strictly controlled birth rate of one cell per 100 crypt cells per hour seemed to be maintained in the crypts; after maturation there was movement of the cells up the villi at a rate of one change in cell position per hour. Rate of migration in the human subject was on average longer by 1 to 2 days than in the smaller laboratory animals, in which it was more frequently studied. Special areas were present at the tips of villi for .extrusion of dead cells, and techniques to estimate the rate of discarded cells were described. The possibly important role of the pericryptal sheath of fibroblasts in the migration of cells up the villi was discussed, but this still begged the question of what initiated these movements. Dr. Creamer then went on to describe his beautiful series of experiments oil denuded mucosa leaving only the basement membrane for examination. His thesis was that the intervillous ridges were pathways along which maturing cells were directed from the crypts to the villi, and these enlarged when there was a greater number of cells to be transferred. With increased turnover rate, elongation of the base of the

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villi and corresponding heightening of the intervillous ridges occurred. A flat mucosa represented the grossest degree of proliferation of the ridges, each concealing the openings of several crypts. The mechanisms which maintained the constancy of the small intestinal gland structure were unknown, but there did not appear to be a diurnal rhythm. Interference with autonomic nerve supply and various endocrine disturbances were known to alter structure and function, and there were curious responses to resection of segments of the small intestine. The various effects of nutritional disturbance, pregnancy, and trauma were discussed, and the roles of bacterial and other infestations were stressed. The question of why there should be such a rapid turnover rate of intestinal mucosa cells was raised, and it was argued that it probably took some time for immature cells to become fully efficient at the various acts of absorption. One adult cell, for example, might function fully only for the ingestion of one particular meal. A considerable re-use of the discarded material in the intestine was certain, and all of the fluid and other exchanges appear to be under strict homeostatic control. Finally, the relationships between various disease states and specific functional alterations in intestinal absorption were detailed. Dr. F. Saidi (Iran) related how common volvulus of the small and large intestine was in the adult population of southern Iran. He analyzed 120 cases, 50% of whom had volvulus of the small intestine, 37% of the sigmoid colon and 13% of the cecum. Small intestine volvulus was more common in males, and nearly always the ileal segment was more involved than the upper small bowel. "Primary" volulus was unexplained in 80% of the cases, and the remainder were secondary to adhesions, Meckel's diverticulum, or congenital bands. A disproportionate ratio of bowel length to mesenteric width as compared with control patients suggested a congenital basis for the volvulus rather than

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an acquired one. The condition most commonly presented a short time after a bulky meal. Sigmoid colon volvulus was also more common in males, but the mean age was generally higher in the fifth decade. The over-all mortality was 35%, mostly due to gangrenous changes in the gut. There was no obvious explanation for the frequency of this lesion. Most cecal volvulus occurred in patients with unduly loose attachment of the cecum to the posterior abdominal wall. Mesenteric gland~ were often grossly enlarged in patients having volvulus, but the significance of these glands was uncertain. A study of the treatment of 12,494 cases of cancer of the colon and rectum in the Birmingham region of England during the period from 1950 to 1961 was reported by Professor G. Slaney and Drs. J. A. Waterhouse and J. Powell (Birmingham) . The population served by this survey represented approximately one-tenth of the population of Great Britain, and it was felt that it was fairly representative of general experience throughout the country. The over-all 5-year survival rate was approximately 21.1 %; in 22.4% of the patients the lesion was inoperable. Lesions at all sites within the colon had virtually the same 5-year prognosis, apart from those of the splenic flexure which appeared to carry a particularly bad prognosis. The yearly trend from 1950 through to 1961 showed no improvement in survival for either colon or rectum. When "radical" surgery was possible, the 5-year expectancy almost doubled. All other forms of treatment appear to have no influence on survival. As with other tumor surveys there was an inverse relationship between the length of history before treatment and the subsequent 5-year survival figures. This applied both to all cases and the surgically treated cases only. It was concluded that the survival rates were quite unsatisfactory and that " current methods of management of large bowel cancer require urgent re-appraisal. " An explanation for the difference in peripheral blood sugar concentration after

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intrajejunal and intravenous sugar administration was sought by Drs. N . McIntyre, D. Turner, and D. Holdsworth (Royal Free Hospital and St. Bartholomew's Hospital, London) . The lower peripheral blood glucose concentration after intrajejunal sugar administration could not be attributed to a difference in glucose uptake by the liver due to glucose entry via the portal vein; similar peripheral blood glucose levels followed intraportal or intrasystemic venous infusions in dogs. Furthermore, portacaval anastomosis did not abolish the difference between intrajejunal and intravenous glucose infusions. It was postulated that oral glucose released intestinal hormones which in turn resulted in insulin release. Experience with extracorporeal pig liver perfusion in the treatment of 4 patients with terminal hepatic coma was recounted by Mr. G. M. Abouna (Newcastle-uponTyne) . Prolongation of survival of the excised pig's liver could be obtained by preserving the organ in a closed vessel in which it was supported by a soft plastic sheet which was rhythmically activated to simulate diaphragm movement. Satisfactory perfusion was maintained for up to 16 hr. All 4 patients had been in deep hepatic coma for not less than 48 hr prior to treatment, and all subsequently succumbed to the disease. Temporary lightening of consciousness, however, was observed in all patients within a short time of commencing the perfusions, and 1 patient recovered full consciousness. In all there was a marked fall in serum bilirubin, serum ammonia, and alkaline phosphatase, and there were significant increases in both prothrombin and fibrinogen levels after the perfusions. The possibility of using this technique to tide a patient over while awaiting transplantation was discussed. Drs. G. E. Sladen, D. S. Parsons, and J . Dupre (Oxford and St. Bartholomew's Hospital, London) were concerned with the effect of bicarbonate ions in facilitating the absorption of sodium and water from the small intestine. Rat intestine was perfused with Krebs-Ringer solution contain-

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ing a fixed quantity of 500 mg per 100 ml of glucose and either bicarbonate or phosphate. The perfused segment of intestine was bathed in liquid paraffin, and the absorbed fluid collected as a "sweat" on the outer aspect. A significant increase in the absorption of both sodium and water was seen in the jejunum only when bicarbonate was added to the perfusing solution. The effect was pH dependent, a quantitative decrease in absorption being demonstrated as the pH was reduced from 7.4. The increase in water and sodium absorption resulting from the addition of bicarbonate was not noted in the ileum. It was concluded, therefore, that the bicarbonate content of perfusing solution was important in many experimental situations, that this action of bicarbonate might be physiological in the jejunum, and that, since both glucose and bicarbonate appeared to display this facilitating action on water and electrolyte absorption in the upper small bowel, there was further support for giving these solutions enterally in diarrheal states. The relative importance of (1) diminution of conjugated bile salts or (2) increase in free bile acids in the causation of steatorrhea in the blind loop syndrome was investigated by Drs. M. Clark and J. Senior (Philadelphia). Bacteria proliferating in the blind loop deconjugated bile salts. The effect of the two divergent changes in the concentration of conjugated bile salts and of free bile acids were studied separately in everted sacs of rat intestine. It was found that both factors, namely an increase in unconjugated bile salt concentration and separately a decrease in conjugated bile salt concentration reduced the rate of uptake and esterification of 14C_pal_ mitate from a micellar solution. A second group of in vivo experiments, using intraduodenal perfusion of micellar solutions of 14C-palmitate, showed that the addition of deoxycholate did not impair fatty acid absorption into the lymph, or the esterification into triglycerides. Reduction of taurocholate concentration, however, reduced the amount of l4C-palmitate absorbed.

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These results were interpreted as favoring the view that the steatorrhea in the blind loop syndrome is due to a decrease in conjugated bile salts, and the consequent interference with the adequate formation of micelles in the small intestine. Dr. M. A. Eastwood (Edinburgh) made a detailed chromatographic study of lipids in samples taken from the stomach, duodenum, jejunum, and ileum after test meals of varying composition. The study was prompted by the interest in adsorption of fatty acids on to lignin present in the vegetable fibers of many foods. There was no evidence of any preferential adsorption of fatty acids by the vegetable fibres containing lignin. Dr. D. A. W. Edwards (University College Hospital, London) presented the clinical details of 3 patients whose presenting complaint was of a loud rhythmic noise from the abdomen, synchronous with breathing, and occurring in episodes of abrupt onset and termination. Fluoroscopy suggested that the noise was produced by excessive downward movement of the left segment of the diaphragm moving the gas-liquid-stomach interface rapidly enough to produce audible sound. The gas bubble was normal in volume, but the shape appeared distorted in all 3 patients. The rate of gastric emptying was measured in patients before and after vagotomy with drainage by Mr. J. D. George and Drs. A. M. Connell and T. Kennedy (Belfast). The emptying time was measured using a double sampling liquid test meal, with phenol red as the marker substance. The rate was expressed by taking the time required for the initial instilled volume to diminish to 10 ml. Twelve patients had truncal vagotomy with a Finney pyloroplasty, 6 had truncal vagotomy with gastrojejunostomy, and a third group of 6 had a selective vagotomy with pyloroplasty. In all groups gastric emptying was appreciably faster after operation than before, and there was no significant difference between any individual drainage group and another. Also studied were 10

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patients with persistent diarrhea and 21 with episodic diarrhea, 1 year after the vagotomy and drainage procedure. These were compared with 18 postoperative patients without any diarrheal symptoms. All patients had insulin evidence of complete vagotomy. The emptying times in both diarrheal groups were significantly faster than the controls, and although the diarrhea appeared to be of a milder variety after the selective procedure, it was noted that even these patients were not immune to the disorder. In discuss,ion it was commented that pyloroplasty alone appeared to have no effect on gastric emptying measured by other techniques. Drs. D. G. Colin-Jones and R. L. Himsworth (University College Hospital, London) studied the effects of 3-0-methyglucose in the stimulation of gastric acid secretory responses in fasting rats, using the perfusion technique of Ghosh and Schild. The main interest in this compound lay in the fact that it is biochemically inert, but competes with o-glucose for the glucose transfer system into cells. It was thus useful for producing an intracellular hypoglycemia, but permitting at the same time the preservation of a normal blood sugar level. The adrenal medulla was denervated to prevent the release of adrenalin in these animals. The infusion of 3-0-methylglucose over a I -h r period resulted in a marked and sustained increase in acid output, which could be t0tally abolished either by vagotomy or by the administration of a sufficient dose of glucose to displace the 3-0-methylglucose. In a number of experiments the onset of the acid response was correlated with the plasma glucose and 3-0-methylglucose concentrations, and the ratio of the two sugars was constant at the time of onset of acid secretion over the wide range of plasma glucose levels. This finding strongly suggests that the vagally mediated acid response to hypoglycemia depends more upon the availability of metabolizable glucose within the nervous system rather than on a critical blood concentration of glucose itself.

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The significance of "early" and "late" gastric secretory responses to intravenous insulin was discussed by Messrs. J . Spencer, R. A. Payne, G. P. Bums, F. C. Y. Chena, and A. G. Cox (Royal Postgraduate Medical School, London) . It had previously been suggested that in postvagotomy insulin testing the occurrence of an acid response in the 2nd hr, as contrasted with the 1st hr, might indicate a degree of incompleteness of vagal nerve section. Mr. Spencer studied 100 duodenal ulcer patients before operation and found that 40 of these had a late type of insulin response. The interpretation of this type of response in the postoperative phase was challenged. From a detailed analysis of both the insulin and maximally stimulated secretory responses in these 100 patients, it was concluded that the occurrence of a late type of insulin response was random. It was not known, however, whether those patients who displayed the late type of insulin response before operation had a similar response after vagotomy. This information would seem to be required before concluding that a postoperative late insulin response, as distinct from a preoperative one, was random, or had clinical significance. Measurements of change in gall bladder size after insulin hypoglycemia were used by Messrs. J. Tinker, T. R. Lawson, and A. G. Cox (Royal Postgraduate Medical School, London) to assess whether selective vagotomy preserved functioning vagal innervation to this organ. In 10 control subjects with intact vagi insulin hypoglycemia caused a mean reduction in gall bladder size of almost 30%. A standard radiological technique was used, and the gall bladder area was measured by planimetry. The alteration in gall bladder size after insulin was abolished after truncal vagotomy (5 patients) or selective vagotomy (5 patients) . Further evidence for denervation was sought by giving subthreshold doses of the stable choline ester carbachol to determine whether the denervated gall bladder was more sensitive to cholinergic stimulation. In 10 control subjects an injection of 75 J.Lg of car-

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bachol caused no gall bladder contraction. The same dose of carbachol caused shrinkage of the gall bladder shadow in 10 patients after truncal vagotomy, and in 10 after the selective operation. These findings were interpreted as being in accordance with Cannon's law and were proposed as further evidence that the gall bladder was denervated in both operative groups. In response to questions it was stated that there was likewise some evidence that the stomach might be "super-sensitive" to carbachol after vagotomy in that a motility response had been noted on subthreshold doses. However, there was less clear evidence with regard to gastric acid secretion. Mr. W. P . Small, Drs. E. L. Cay, P. Dugard, W. Sircus, Mr. C. W. A. Falconer, Mr. A. N. Smith, Dr. J. P . A. McManus, and Sir J . Bruce (Edinburgh) gave a review of the experiences over several years with regard to the relationship between psychological status and response to treatment of peptic ulcer. First, they could find little evidence to support the view that the outcome of surgical treatment for peptic ulcer in the young, and in those with short total histories of symptoms, was likely to be poor. Neither length of history nor age at operation was shown to influence the result. Second, they assessed the physical outcome in a group of patients who, at initial preoperative assessment, displayed some psychiatric abnormalities. These patients appeared to come to surgical treatment neither sooner nor later than those with comparable ulcer histories, but without psychiatric abnormality. A successful physical outcome was noted in approximately 70% of the patients with psychiatric abnormality and, although some deteriorated after operation, the number of such patients was no greater than those deteriorating on medical treatment. There was no evidence that successful surgery for peptic ulcer was followed by the formation of any new psychiatric symptoms which were not apparent in the preoperative assessments.

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Thus, although the patients with detectable psychological abnormality were not so likely to do well as the psychologically normal group, a sufficiently large proportion of these patients were substantially improved in both physical and psychological health to advise surgical treatment for peptic ulcer where necessary without undue hestitation. The results of a computer-based random trial of pyloroplasty and gastrojejunostomy as the drainage procedures to .accompany vagotomy in the elective treatment of chronic duodenal ulcers were presented by Dr. F. Kennedy, Mr. I. E. Gill~spie, and Professor A. W. Kay (Glasgow). In spite of theoretical considerations, it was not known whether one form of drainage possessed distinct advantages over the other. Two hundred patients were discussed, 100 having pyloroplasty and the other 100 gastrojejunostomy. The two groups were comparable with regard to sex distribution, mean age, mean length of history, previous complications, acid secretion, and numerous other factors. Postoperatively, no clear cut difference emerged in the over-all incidence of early complications or late sequelae. Although there were one or two minor differences in the individual details of postoperative course, there was as yet no significant indication that one form of procedure was significantly superior to the other. The final session was held at the Royal College of Surgeons. The first paper of this session, by Drs. H. C. Whittle, A. A. Blair, G. Neale, N. Thalassinos, and G. R. Thompson (Royal Postgraduate Medical School, London) dealt with the increase in serum phosphate concentration observed after an intravenous injection of vitamin D. First, 5 healthy control subjects showed a variation of less than 25% in the serum phosphate level during the > 5 days following an intravenous injection of 1 mg of vitamin D3 in propylene glycol. Observations were then made on 43 consecutive patients with various malabsorptive disorders. Eleven of these patients showed a greater than 25% increase in serum phosphate during the 5-day period

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after intravenous vitamin D 3 • The group comprised 6 after gastrectomy, 1 with adult celiac disease, 1 after resection of small intestine, 1 with alcoholic cirrhosis, and 2 with diets singularly low in vitamin D content. Mter treatment with vitamin D, the previously abnormally low serum phosphate levels increased to within the normal range. This test was suggested as a suitably sensitive index of vitamin D deficiency for clinical use. An account of the fate of small intestine mucosal cells discarded from the tops of villi was given by Drs. I. J. Pink, D . N. Croft, and B. Creamer (St. Thomas's Hospital, London) . Samples were obtained by washing segments of normal small intestine with physiological saline, those from rats being obtained by direct perfusion, and those from human subjects being obtained by a triple lumen tube. Although only recently shed cells were collected, there was considerable variation in the degree of autolysis in the samples. Since the main interest was to determine the proportion of epithelial cells to those of other origins, an additional technique to clearly identify mucosal epithelial cells was required. It was found useful to look for typical brush border microvilli by electron microscopy since this particular part of the epithelial cell seems more resistant to damage than the remainder. Cells with such brush borders were easily identified in specimens obtained by saline washing, but were not found when a perfusion technique was used .. The proportion of epithelial cells to other types was approximately 9 to 1. Four per cent were identified as polymorphonuclear leucocytes, and about 10% were unidentifiable. Bacteria were only rarely seen in these samples. It was concluded that in the normal small intestine the surface epithelial cells are shed in a relatively intact state, but are thereafter rapidly destroyed. Drs. B. Miller, S. Tabaqchali, and G. Neale (Royal Postgraduate Medical School, London) studied the effect of experimental blind loops on the metabolism of several dietary nitrogenous and vegetable substances. Self-filling blind loops

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of jejunum situated close to the duodenojejunal junction were made in rats, and thereafter these animals grew more slowly than originally matched controls. The urinary excretion of the breakdown products of several amino acids such as tryptophan, ornithine, arginine, lysine, glycine, sarcosine, and creatinine, and hippuric acid, volatile phenol, and phenolic acids were all estimated repeatedly. The blind loop animals regularly excreted greater quantities of most metabolites. The differences between the two groups of animals were abolished by the addition of neomycin or lincomycin to the diet, and the improvement was paralleled by diminution in bacterial counts in the upper small intestine. Dr. J. L. Pace (Malta) described a detailed investigation of the microanatomy of the muscular wall of the human colon, using microdissection techniques on postmortem material. In both the outer longitudinal and inner circular layers the muscle was divided by connective tissue septa which linked together to form expansile meshworks. The fibrous material separated bands of muscle fibers, but not the individual fasciculi. The circular layer bands were continuous beneath the teniae. The teniae presented different structure patterns in the outer and inner layers, the former being predominantly longitudinal. In the inner region a greater mingling of directions was noted. Near the edges of the teniae the muscle fibers were found to change direction quite abruptly, and, interlacing with the more peripheral fibers, they traveled toward, and fused with, the main circular muscle layers. On distension, the circular muscle bands became more widely separated, and in the longitudinal layers of the te~iae the innermost fibers apparently disappeared, as if pulled outward by their attachment to the circular muscle . This structure pattern was felt to be admirably suited to maintenance of mechanical strength during distension of the bowel. A quantitative study of haustral patterns on double contrast barium enema films in different colonic disease groups

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was made by Drs. M. Chapman and J. J. Misiewicz (St. Mark's Hospital, London). Eighty-three patients with intestinal polyps, 103 with left sided diverticulosis, 51 with total diverticulosis, and 69 with the "irritable colon syndrome" were studied. The main aim was to see whether there might be evidence of motility disturbance in the proximal colon in patients with the apparently predominantly left sided conditions of sigmoid diverticulosis and irritable colon. A haustral index was calculated by dividing the total number of haustra observed by the length of the colon. Although there was a considerable overlap in the individual values of each group of patients, the haustral index was significantly higher in the ascending and transverse segments of the colon in those patients with left sided diverticulosis than in the other groups. In those with "irritable colon" there was a significant increase in haustral index only in the transverse colon. There was no correlation between haustral index and age in any of the four groups. Likewise, there was little support for the concept that irritable colon might precede diverticular disease. Drs. J. A. Ritchie, S. C. Truelove, and G. M. Ardran (Oxford) used time-lapse cinefluorography to follow both propulsive and retropulsive movements in the human colon. Each subject was given 100 ml of a barium micropaque suspension by mouth 12 hr before the period of observation, and films were exposed at 1 frame per min for 1 to 2 hr. This technique demonstrated that flow movements, at a rate of 1 to 10 em per min, occurred and could shift the contents of the bowel in either direction over a period of several minutes. One film demonstrated a propulsive movement which took 12 min to traverse 60 em of bowel, and a second demonstrated powerful retropulsion at a similar slow rate. This latter movement was believed to be genuine retroperistalsis since simultaneous intraluminal pressure measurement demonstrated a zone of relaxation preceding the contraction. The results of a retrospective study of

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the use of corticosteroids in Crohn's disease in 76 patients was presented by Drs. G. M. Roberts and J. M. Naish (Bristol). The patients had been observed between the years 1958 and 1967, and diagnoses had been established on clinical and radiological grounds with histological confirmation in 35, and typical gross laparotomy appearances in a further 14. A large variety of different treatment schedules including the administration of adrenal corticosteroids, made the analyses of various subgroups a little difficult, but the general impression was obtained that those with diffuse involvement of the gastrointestinal tract and little radiological evidence of stricture formation were likely to improve on steroids. Prolonged treatment, however, appeared to be necessary since one-third of these relapsed when corticosteroid treatment was withdrawn. There was also a suggestion that preoperative steroid treatment might diminish the chance of recurrence after surgery. By contrast, steroids used for treatment of relapse after operations was less successful, the majority of these patients requiring still further operative treatment. This paper provoked considerable discussion, and a plea was made for a prospective random trial of corticosteroid treatment in at least selected groups of Crohn's disease patients. Messrs. G. Gillespie, B. S. Bedi, H. T. Debas, and 1. E. Gillespie (Glasgow) described dog experiments to investigate the question of whether fat coming in contact with the upper small intestine inhibited the gastric acid response to gastrin stimulation by interfering with the release of gastrin from the pyloric antrum, or by antagonizing already circulating gastrin. Dogs with vagally innervated antral pouches and denervated Heidenhain-type pouches were used, and matched Heidenhain pouch responses were first obtained to either the endogenous release of gastrin from the antral pouch on irrigation by acetylcholine solution, or alternatively a continuous intravenous infusion of pentagastrin. Identical inhibition of both responses was seen

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on feeding the animals a fixed volume of com oil. No inhibition of matched Heidenhain pouch responses to continuous intravenous histamine was noted. It was concluded, therefore, that the humoral inhibitor agent released by fat coming in contact with the small intestine mucosa inhibited gastrin already in the circulation, and it was therefore unnecessary to postulate an additional inhibitor mechanism acting against the gastrin release. Messrs. B. S. Bedi, G. Gillespie, and 1. E. Gillespie (Glasgow) studied the effects of bile salt solutions on gastrin release from the isolated, vagally innervated antrum of dogs. Weak solutions of sodium taurocholate and glycocholate irrigated through the antral pouch evoked acid responses from a denervated Heidenhain pouch, thus giving good indication of gastrin release from the antrum. Dose-response curves to both the bile salts and to acetylcholine irrigation of the antrum were studied, and then submaximal doses of both antral stimulants were combined. The resulting acid responses from the Heidenhain pouches gave convincing evidence of potentiation between the bile salts and the acetylcholine in the liberation of endogenous gastrin from the antral pouch. These results suggested that bile regurgitation into the antrum might be responsible for a significant degree of gastric acid stimulation. Another influence of bile reflux into the stomach was studied by Drs. J. Rhodes, D. E. Bamardo, S. F. Phillips, R. A. Rovelstad, and A. F. Hofmann (Mayo Clinic, Rochester). Since bile reflux, with consequent damage to gastric mucosa by the bile salts, might be important in the etiology of gastric ulcer, the amount of bile regurgitation into the stomach occurring before and after standard liquid meals labeled with polyethylene glycol was measured in 10 patients with gastric ulcer, 10 with duodenal ulcer, and 10 normal controls, each group being matched for age and sex. The bile salt pool was labeled with 14C-chenodeoxycholic acid. Gastric samples were obtained by a tube,

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the tip of which was located in the proximal antrum under fluoroscopic control. Fifteen-mihute samples were taken for 1 hr before and 3 hr after the standard meal. The radioactivity of all samples was measured; in addition, bile salt concentrations were determined enzymatically in 2 subjects. There was a significantly greater content of bile salts in the gastric aspirates after meals in the gastric ulcer patients than in the normal controls. There was, however, no difference in the bile salt concentration in the fasting contents. Four of the gastric ulcer patients had repeat observations performed several months later, when the ulcer was judged to have healed, and in 3 of these the bile salt concentrations after feeding returned to within the normal range. Dr. C. N . Mallinson (Guy's Hospital, London) compared the efficiency of different carbohydrate contents of liquid meals in the regulation of gastric emptying rates . Previous observations had shown that isocaloric solutions of starch and glucose exerted the same slowing effect on gastric emptying in spite of gross differences in osmolarity. Likewise, lactose was as effective in delaying gastric emptying as isocaloric meals containing a mixture of glucose and galactose. Since intra gastric digestion of starch or lactose did not occur during these experiments, it was believed that hydrolysis of these substances beyond the pylorus would normally be rapidly achieved, so that the constituent simple sugars would stimulate the osmoreceptors and thereby initiate the mechanism delaying gastric emptying. Impairment of the slowing effects of starch on gastric emptying was demonstrated in 4 patients with steatorrhea resulting from pancreatic disease. Three further patients without steatorrhea also showed diminution in the effects of the starch; 3 showed the normal response. In 1 further patient with proven intestinal lactase deficiency, the slowing effect of lactose was absent. Thus deficiency of either amylase or lactase may increase the rate of gastric emptying.

May 1969

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The diagnosis and management of nongangrenous ischemic colitis was discussed by Mr. A. R. Brown (St. James's Hospital, Balham). The clinical details of 14 patients were presented, the main symptoms being lower or left sided abdominal pain, occasional vomiting, diarrhea and rectal bleeding, and usually a relative lack of corresponding clinical signs to go along with this picture. The attacks were usually self-limiting. The characteristic barium enema appearances located usually in the splenic flexure region or descending colon were demonstrated. No resections were performed during the acute

episodes, and 9 patients were managed conservatively for up to 3 years. In 5patients resection was done as an interval procedure, and all resected specimens showed widening of the submucosa, superficial mucosal ulceration, and marked narrowing of the lumen. In those not submitted to surgical treatment, considerable functional and radiological recovery . was sometimes noted. lAIN

E.

GILLESPIE

Department of Surgery Western Infirmary Glasgow, W.l, Scotland