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The release of immunoreactive prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) from antral and duodenal mucosal biopsy specimens taken from 20 patients with duodenal ulcer disease was measured by radioimmunoassay before and four weeks after treatment with colloidal bismuth subcitrate. Gastroscopic and histological examination showed complete ulcer healing in 15/18 patients and duodenal histology looked normal (n = 15) or improved (n = 3): two patients failed to attend for a second endoscopy. Analysis of the supernatant from incubations of biopsy tissue in vitro showed that unstimulated antral release of PGE2 was significantly more than that from the duodenal mucosa (p less than 0.05), whereas basal release of LTC4 was significantly lower from antral biopsy specimens (p less than 0.05). Subsequent incubation of specimens with calcium ionophore A23187 caused an increase in LTC4 but not in PGE2 generation. The ability of antral and duodenal mucosa to form ionophore mediated LTC4 in patients with duodenal ulcer disease was significantly greater (p less than 0.05; p less than 0.01 respectively) than that of normal gastroduodenal mucosa. After colloidal bismuth subcitrate treatment, basal synthesis of PGE2 was unchanged in duodenal and antral specimens. In contrast, basal duodenal LTC4 was reduced (p less than 0.05), and the capacity for ionophore mediated duodenal LTC4 formation was substantially and significantly reduced after treatment (p less than 0.001). These results indicate that after therapeutic healing of duodenal ulcer (accompanied by clearance of inflammatory cell infiltrate), there is a reduced ability of duodenal mucosa to generate proinflammatory peptidoleukotrienes.

For four years up to December 1987, 190 patients (median age 73 years) with proximal malignant biliary obstruction were treated by endoscopic endoprosthesis insertion. Altogether 101 had cholangiocarcinoma, 21 gall bladder carcinoma, 20 local spread of pancreatic carcinoma, and 48 metastatic malignancy. Fifty eight patients had type I, 54 type II, and 78 type III proximal biliary strictures (Bismuth classification). All patients were either unfit or unsuitable for an attempt at curative surgical resection. A single endoprosthesis was placed initially, with a further stent being placed only if relief of cholestasis was insufficient or sepsis developed in undrained segments. The combined percutaneous-endoscopic technique was used to place the endoprosthesis when appropriate, after failed endoscopic endoprosthesis insertion or for second endoprosthesis placement. Full follow up was available in 97%.Thirteen patients were still alive at the time of review and all but one had been treated within the past six months. Initial endoprosthesis insertion succeeded technically at the first attempt in 127 patients, at the second in 30, and at a combined procedure in a further 13 (cumulative total success rate 89% - type I: 93%; type II: 94%; and type III: 84%). There was adequate biliary drainage after single endoprosthesis insertion in 152 of the 170 successful placements, giving an overall successful drainage rate of 80%. Three patients had a second stent placed by combined procedure because of insufficient drainage, giving an overall successful drainage rate of 82% (155 of 190). The final overall drainage success rates were type I: 91%; type II: 83%; and type III: 73%. The early complication rates were type I: 7%; type II: 14%; and type III: 31%. The principle early complication was clinical cholangitis, which occurred in 13 patients (7%) and required second stent placement in five. The 30 day mortality was 22% overall (type I: 14%; type II: 15%; and type III: 32%) but the direct procedure related mortality was only 3%. Median survival overall for types I, II, and III strictures were 21, 12, and 10 weeks respectively but survival was significantly shorter for metastatic than primary malignancy (p

Between January 1986 and July 1988 needle knife papillotomy was attempted in 103 patients after failure of conventional access for endoscopic sphincterotomy (96 cases) or diagnostic cholangiography (seven cases). Access was obtained at the same session in 36 cases and at a subsequent attempt within 2 to 5 days in a further 43, an overall success rate of 77%. The procedure related morbidity and mortality in the therapeutic group were 5.2% and 2.0% respectively. There were no deaths or complications in the diagnostic group. Needle knife papillotomy is a valuable adjunct to conventional techniques of biliary access.

It is uncertain whether ERCP and associated procedures are more difficult when the papilla is inside or adjacent to a duodenal diverticulum. We have therefore reviewed the data from 2458 consecutive, prospectively reported ERCPs between November 1983 and March 1988. Three hundred and eight patients (12.5%) had periampullary diverticula and in 21 the papilla was located deep within the diverticulum of whom 227 had undergone endoscopic sphincterotomy (73.7%). Comparison was made with the 2150 patients without diverticula of whom 1223 (56.9%) had undergone sphincterotomy. The success rate of specific duct cannulation was 94.2% in the diverticulum group and 96.7% in those without diverticula (p less than 0.05). The overall success rate of endoscopic sphincterotomy was 95.2% in the diverticulum group, as compared with 98.0% in those without diverticula (p less than 0.05). The procedure related morbidity and mortality of sphincterotomy were 5.2%/0.9% and 4.0%/0.7% respectively (NS). If only those who had successful cholangiography were included there was no difference in sphincterotomy success between those with and without diverticula. The group of patients with papilla deep within diverticula had a slightly higher failure rate of pure endoscopic sphincterotomy (11.8% v 5.7%: NS) but did not have a higher complication rate. In the subgroup of patients with choledocholithiasis, duct clearance of stones was as successful after sphincterotomy in those with diverticula as in those without. Medium term complications (mean 26 months) occurred in 1.4% of patients with diverticula and in 0.7% of patients without diverticula. We conclude that diagnostic cholangiography is more difficult when the papilla is closely associated with a diverticulum but that if diagnostic cholangiography is obtained, sphincterotomy may be performed as successfully and as safely in those with or without diverticula.

Tissue changes produced in the dog stomach by exposure to a Nd YAG laser varied from mild mucosal oedema to cell vaporisation. Intermediate degrees of damage caused a marked inflammatory response leading to extensive fibrosis in the submucosa and muscularis propria. The true extent of tissue damage was not apparent immediately, and treated mucosa that initially appeared intact sometimes sloughed several days later to leave an ulcer. The extent of damage and the rate of healing depended on the amount of laser energy used. With pulses at optimum laser power (75 w) and exposure time (0.4 sec), however, haemostasis was achieved in induced ulcers with total energy concentrations that did not produce full thickness tissue damage nor alter the healing rate from that observed in untreated ulcers. Thermal contraction was the primary haemostatic mechanism, thrombosis only occurring as a secondary effect.

Laser photocoagulation is one of a number of methods currently under investigation for the endoscopic treatment of gastrointestinal haemorrhage. The Argon ion and Neodymium Yttrium Aluminium Garnet (Nd YAG) lasers are theoretically suitable as the beam from each may be transmitted via a flexible fibre. Argon laser photocoagulation has been shown to be effective and we have elucidated which factors determine its safety and efficacy. Studies on normal canine gastric mucosa showed that the depth of tissue damage depended chiefly on the total incident laser energy on any one spot, and that below 50 J the risk of perforation was extremely low. The energy density was much less important. The haemostatic effect depended more on the laser power. In artificial bleeding gastric ulcers in heparinised dogs the most effective level was 7--9 W, at which 22 out of 23 ulcers (96%) stopped bleeding completely, compared with one out of 12 controls. Photocoagulation was achieved in these cases with energies well within the safe limits. The procedure was effective endoscopically, and these results justify early clinical studies in man.

Seventeen consecutive patients with the sump syndrome were treated at the Middlesex Hospital between November 1983 and December 1987. Fifteen were treated primarily by endoscopic sphincterotomy and two primarily by resective surgery because of coincident severe painful chronic pancreatitis. Endoscopic sump clearance was successful in thirteen out of fifteen cases (87%) with no morbidity or mortality. The two endoscopic failures were managed surgically. Follow-up (mean 18 months; range 2-48 months) has shown complete resolution of symptoms in twelve (71%), with mild or moderate ongoing symptoms in the remaining five. All patients with ongoing symptoms after sump clearance had abnormal retrograde pancreatograms at the time of ERCP. Endoscopic sphincterotomy is the treatment of choice for the sump syndrome, with the possible exception of patients with coincident painful severe chronic pancreatitis, who may require pancreatic resection. Indeed, the sump may be a factor in the development and perpetuation of an obstructive chronic pancreatitis, and a trial of endoscopic clearance may be indicated even in these patients. The sump syndrome should no longer be regarded as a major long-term disadvantage of side-to-side biliary bypass, provided that the condition is considered early in those with compatible symptoms after biliary bypass, and appropriate investigation and treatment is instigated.

The clinical and radiological findings in four patients with primary sclerosing cholangitis one of whom had coexistent cholangiocarcinoma, are reported. The need for surgical exploration to make the diagnosis was averted by the use of endoscopic retrograde cholangiography in one patient who was managed initially with medical treatment alone. Endoscopic cholangiography may be used to monitor the progress of the sclerosing lesions; but failure to fill the intrahepatic ducts is associated with a poor prognosis due either to the severity of the sclerosing process or the presence of coexistent cholangiocarcinoma.

The tissue changes in canine gastric mucosa caused by exposure to an argon laser beam vary from mild mucosal oedema to complete cell destruction. Intermediate degrees of damage cause an inflammatory cell response with the formation of granulation tissue, particularly in the submucosa. The rate of healing is similar to that after other forms of injury to the gastric mucosa. Cell destruction at the surface of the mucosa starts with energies greater than 8 Joules on any one spot, and occurs at greater depths as the energy is increased but, unless cells are actually destroyed, the extent of histological damage is limited to a zone 1 mm lateral to, or below, the area exposed to the laser beam. Haemostasis is achieved by thermal contraction of bleeding vessels and of the surrounding tissue, thrombosis only occurring as a secondary effect.

One hundred and twenty seven patients were treated by nasobiliary drainage, or stenting, to prevent biliary obstruction after endoscopic failure to clear stones from the common bile duct. At presentation, 91 (72%) patients were jaundiced and 39 (31%) had cholangitis. Placement of either a nasobiliary drain or stent was successful in 124 (98%) patients. One hundred and twenty one (95%) patients were followed up. Clearance was ultimately achieved endoscopically in 52 and surgically in 25 patients after (mean) 2.4 months. Thirty day mortality was 3%. There were no complications of nasobiliary drainage, but two of 39 patients treated by temporary stents developed cholangitis, both successfully managed by endoscopic duct clearance. Forty two patients unfit for surgery or further endoscopic attempts at duct clearance were followed with stents in situ for a mean 15.9 months (range 2.5-37.5). Cholangitis developed in four patients and was successfully managed by stent change. These results indicate that longterm stenting can be useful for poor risk surgical patients and that nasobiliary drainage or temporary stenting permits further elective rather than urgent endoscopic or surgical treatment.

Fifty-one patients with large bowel disease were examined with the Olympus CF-SB fibreoptic colonoscope. With adequate bowel preparation and employing inhalational analgesia administered by a self-demand valve the whole sigmoid colon could be examined in the majority of patients within 30 minutes. In 23% of cases (12/51) the diagnosis was either made or confirmed by this procedure alone. Fibreoptic sigmoidoscopy is especially helpful in patients with either equivocal or failed barium enemas and is indicated in patients with unexplained rectal bleeding, extending the search for polyps and cancer, and studying patients with inflammatory bowel disease. About one quarter of biopsies taken from a flat mucosal surface with the Olympus flexible biopsy forceps may be insufficient for detailed histology due to their small size. For this reason multiple biopsies may be taken. Adequate biopsies were always obtained from projecting lesions and could be very accurately sited. Colour photography employing automatic exposure control is used to supplement the information obtained. It is concluded that fibreoptic sigmoidoscopy is a valuable additional investigation in selected patients with suspected disease of the large bowel and to date has been without complications.

Using a strictly defined grading system to eliminate subjective assessment of mucosal architecture, the jejunal mucosa from cases of extensive psoriasis has been shown to be significantly different from that of normal controls obtained both in life and at postmortem examination. The same changes, however, are shown to occur in patients who are ill and losing weight for reasons other than psoriasis. Diminshed lactose utilization, demonstrated in extensive psoriasis, supports the suggestion of a decreased mucosal surface area in this disease.

Two-hundred fibreoptic examinations of the duodenal bulb were carried out on 149 patients. The importance of combining the initial examination with a general endoscopic survey of the oesophagus and stomach is stressed. At the present time full examination of the duodenal bulb requires the use of both a side-viewing and forward-viewing endoscope in more than a quarter of cases. The safety and acceptability to the patient of multiple endoscopic examinations carried out as an outpatient procedure has been demonstrated, and the value of the procedure in x-ray negative dyspepsia, in the follow up of ulcer therapy, and in acute upper gastrointestinal haemorrhage has been shown.

Expired radiocarbon dioxide has been collected by a simple autotitration method following the ingestion of lactose-1-(14)C. With this method, which is suitable for clinical use, 12 subjects with alactasia have been readily separated from 24 normals, both groups being defined by strict criteria. This test, which may be used to measure the absorption of other sugars, is especially suitable for population surveys and may be used to investigate the distribution of disaccharidase deficiency.A further advantage is that false low readings resulting from rapid plasma clearance of absorbed sugar do not occur with this method although they may do so in up to one in three lactose tolerance tests, thereby overestimating the prevalence of alactasia.

Six healthy subjects (three men, three women) were studied to compare the effects of misoprostol and cimetidine on coffee-induced gastric secretion. Gastric secretion was measured after a 12-hr fast according to the Hobsley method, employing phenolsulfonphthalein (PSP) as a marker. Each subject was studied on three occasions separated by at least one week: as control, basal gastric secretion was measured followed by sample collection after oral placebo and then coffee; basal gastric secretion was measured followed by sample collection after 200 micrograms of misoprostol and then coffee; basal gastric secretion was measured followed by 300 mg [corrected] of cimetidine and then coffee. The order of treatment was randomized. Basal gastric secretion collection, sample collection, and the administration of coffee were carefully standardized. Titratable acidity; acid output; and sodium, potassium, chloride, and PSP concentrations were measured in each sample to assess hydrogen ion secretion, pyloric losses, and duodenogastric reflux. Mathematical corrections were available for the last. Results confirmed that coffee is associated with a marked rise in titratable acidity, peak acid output (PAO), and volume with a modest fall in mean gastric pH. Both misoprostol and cimetidine lowered titratable acidity, compared with placebo (P = 0.03). Mean PAO was reduced by both misoprostol and cimetidine in a similar manner, and there was a significant difference between the three treatment groups (P = 0.02). These findings document and confirm the antisecretory effect of a single oral dose (200 micrograms) of misoprostol on gastric secretion.

The realm of endoscopy has gone from that of diagnosis to that of diagnosis and therapy. Therapeutic endoscopy is a rapidly advancing frontier in the field of gastroenterology. Its use in securing haemostasis has recently flourished. Considerable progress has been made. Various experimental techniques have been tried and found lacking, while others, such as laser photocoagulation, electrohydrocoagulation and endoscopic sclerotherapy, are proving to be very useful. The mortality for upper gastrointestinal bleeding has remained high for decades, despite recent advances in medicine. This may be related to the shift in the population toward the older age group. Recent advances in endoscopic haemostasis seem to be showing promise in improving survival rates. This is a result of improved recognition of risk factors, including the stigmata of recent haemorrhage, of early surgical intervention in the elderly, and of the ability to reliably secure haemostasis endoscopically. This chapter gives an account of the various techniques of endoscopic haemostasis and explains the numerous controversies through the discussion of selected experimental and clinical trials.

A formal single-blind multicentre study has been set up to investigate the probable benefit of combined therapy of the cytoprotective agent De-Nol (colloidal bismuth subcitrate, CBS) and an acid-suppressing drug (cimetidine) in the treatment of duodenal ulcer. The protocol compares the therapeutic benefit of CBS alone and cimetidine alone with CBS + cimetidine, the treatment period being 28 or 56 days. Patients whose ulcers heal within the therapeutic phase will be followed up until relapse or 12 months, whichever is the longer. The paper presented reports interim results from this trial. Comments and clinical observations on the probable value of this combined treatment and the selection of patients suitable for such treatment are discussed.

Sera from 98 abattoir workers were tested for IgG to Campylobacter pylori, C jejuni, and klebsiella. Clerical workers had significantly lower C pylori and C jejuni IgG titres than any of the groups in direct contact with freshly cut animal parts. No difference was found for antibodies to klebsiella. 28 non-clerical workers with high-titre C pylori IgG consented to upper gastrointestinal endoscopy. C pylori associated gastritis was found in all 28, and four weeks of colloidal bismuth subcitrate (240 mg twice daily) was prescribed. On repeat testing at three months all showed a decrease in IgG titres to C pylori but not to C jejuni, whereas 18 untreated non-endoscoped workers showed no change. These findings raise the possibility that C pylori infection is a zoonosis.

coherent fibre glass bundle had any practical application in medicine. During the past ten years when rapid and major advances in fibreoptic technology have been made, the medical requirement of a flexible endoscope for examination of the gastro-intestinal tract has very largely been met by advances in bioengineering. For the upper gastro-intestinal tract the chief medical requirements have been the performance of combined oesophago-gastro-duodenoscopy, tissue diagnosis, and examination of the cardia and fundus of the stomach. These have been made possible by the development of long forward viewing endoscopes, biopsy and cytology facilities, and the ability to perform inversion manoeuvres within the stomach. Because of marked light attenuation with increased fibre bundle length and the loss of light at optical interfaces, the development of the integral fibre bundle coupled with new illumination sources has provided the opportunity for increasing the lengths of endoscopes. The development of more powerful illumination sources, particularly the GEC Marc 300 metal halide lamp and the xenon arc lamp, have provided the possibility of photography and closedcircuit colour television endoscopy. The ability to obtain a tissue diagnosis remains the single most important advance by gastro-intestinal endoscopy. Flexible biopsy forceps pose considerable problems in design and manufacture but these have now largely been overcome so that current biopsy forceps provide flexibility, durability and operate on the principle of opposing biopsy cups with a central spike, providing the ability to spear the lesion under examination in order to hold it firm prior to biopsy. Multiple target biopsy is now possible at all sites where endoscopic vision can be obtained within the bowel. The cytology brush has likewise been developed for brush cytology. This consists of a flexible assembly with a distal nylon brush which can be rotated on the lesion under suspicion and then withdrawn into an outer sleeve in order to retain the trapped cells prior to withdrawal from the operating channel of the instrument. The combination of multiple target biopsy and brush cytology is providing a more accurate diagnosis of cancer than biopsy alone, and when applied to all cases of gastric ulcer may reduce the current very poor mortality statistics for gastric cancer. The ability to perform an inversion manoeuvre in the stomach and [ 243 ]

Considerable discussion still centres around the relative merits of the Argon and Neodymium Yttrium Aluminum Garnet (NdYAG) lasers for the endoscopic treatment of gastrointestinal haemorrhage, although both are undoubtedly effect. We have carried out experiments to elucidate which factors determine the safety and efficacy of NdYAG laser photocoagulation. Histological studies on normal gastric mucosa showed that the depth of tissue damage depended mainly on the total incident laser energy, whereas the effectiveness of photocoagulation of induced gastric ulcers in heparinised animals depended on the laser power and the exposure time used. Optimum haemostasis with minimum tissue damage was obtained using pulses of 300 to 500 ms duration with energies of 25 to 40 J. We consider these parameters safe and effective for use in pilot clinical studies.

Hereditary pancreatitis is a rare form of chronic pancreatitis inherited as an autosomal dominant. Pancreas divisum results from a developmental failure of fusion of the dorsal and ventral parts of the pancreas and is associated with an increased incidence of pancreatitis. Co-existence of the two conditions in one patient is very rare. We report a case.

An isolated ventral pancreas results from failure of fusion of the dorsal and ventral pancreatic ducts. Until the advent of endoscopic retrograde cholangiopancreatography (ERCP), the clinical significance of this abnormality was not known. A series of 11 such patients in 850 consecutive ERCP examinations is described. No other cause for their symptoms was discovered. Secretory studies showed a low volume of pancreatic juice with normal concentration of bicarbonate and trypsin. In 5 cases operative dorsal pancreatography was performed: it was normal in all cases. In 3 cases the pancreatic tail was amputated and found unexpectedly to be the seat of pancreatitis in 2. Isolated ventral pancreas may be associated with pancreatitis, but this is not proved.

In two patients, treatment of amebic dysentery was followed (despite the disappearance of the infecting organism) by an illness with the clinical, pathological, and radiological characteristics of nonspecific ulcerative colitis. Their case histories indicate that in addition to persistent or recurrent amebic infection, the irritable colon syndrome, and ulcerative postdysenteric colitis, nonspecific ulcerative colitis should be kept in mind in the evaluation and therapy of continuing symptoms in patients with treated amebic dysentery.

There has been growing confidence in the ability of therapeutic endoscopy to control bleeding from the upper gastrointestinal tract. This chapter attempts to review the recently published data on this topic, concentrating on sclerotherapy for variceal bleeding, laser photocoagulation and electrocoagulation for bleeding peptic ulcers, with particular emphasis on the results of published controlled trials which are essential for demonstration of clinical benefit.

A double-blind, placebo-controlled trial of colloidal bismuth (De-Nol) was performed on 20 patients with active duodenal ulceration employing endoscopic selection and follow up after a treatment period of 28 days. By these means it was shown that healing of ulcers was significant in those patients treated with the active compound. In addition a greater number (9/10) of patients treated with colloidal bismuth showed symptomatic improvement than those receiving placebo (6/10) but this difference did not reach statistical significance. The results of endoscopic and symptomatic assessment of the patients receiving colloidal bismuth were in complete agreement although there was a poor correlation between these results in those receiving the placebo. This supports the results from a previous study that endoscopic assessment of duodenal ulcer healing provides a more objective assessment than do clinical methods.

Nine cases of superficial gastric carcinoma have been detected with upper gastrointestinal endoscopy in Bristol in the past two years. This contrasted with only six cases found from postoperative gastrectomy specimens examined in the previous eight years. It is often difficult to distinguish a superficial carcinoma from a benign ulcer, and endoscopic diagnosis is effective only if multiple biopsy specimens are taken. Endoscopy should also be repeated and multiple specimens taken until the lesion has healed; even malignant ulcers may heal, and any healed area that is depressed with interrupted mucosal folds should be suspected of malignancy. The endoscopic and histological appearances, the age of the patients, and the clinical behaviour of the disease resembled descriptions of the disease, principally from Japan. Superficial gastric carcinoma is probably under-diagnosed in Britain.

A prospective study of the endoscopic, radiological, and surgical features of chronic duodenal ulceration has been performed. Double contrast barium meal and upper gastrointestinal endoscopy were both performed within five days of elective surgery for chronic duodenal ulceration on 50 patients. The surgical diagnosis correlated with endoscopy in 88% and radiology in 82%, but if both techniques were employed, an accurate pre-operative diagnosis was achieved in 96% of cases. There was poorer correlation in determining the position of the ulcer within the bulb, with only 41% correlation between all three parameters and complete disagreement in 24%. Surgery correlated with endoscopy in 71% but with radiology in only 41%. The correlation between endoscopy and surgery in the diagnosis of duodenitis was only 42%, suggesting that this should be a histological diagnosis. This study suggests that endoscopy is slightly more precise than radiology in the diagnosis of chronic duodenal ulceration, but with a combination of the two techniques almost 100% accuracy can be achieved.

The drawbacks of monopolar electrocoagulation in the control of gastrointestinal bleeding include tissue adherence, unpredictable energy deposition, and a high incidence of tissue damage. Introduction of a conductive interfacial film of liquid between the monopolar electrode and the bleeding point during electrocoagulation may overcome these drawbacks. A prospective, controlled study was undertaken to evaluate the efficacy and safety of a monopolar electrode in liquid and dry modes when used to coagulate experimental canine bleeding ulcers. All experiments were done in open fashion via a gastrotomy with hand-held electrodes. An analog computer, which could be connected between a standard electrosurgical generator and the electrode, was designed and built to monitor and control the energy delivered to the tissue. Both liquid and dry electrodes were highly effective in stopping bleeding. The liquid electrode was found to be superior to the dry electrode in that tissue adherence was eliminated and energy deposition was more predictable, varying less with angle of incidence. The liquid electrode caused less macroscopic serosal damage and less full-thickness histologic damage if the total energy or number of pulses was limited; however, both caused microscopic full-thickness damage in one-half of the experimental ulcers treated, although no perforations occurred.