Eicosanoid synthesis in duodenal ulcer disease: decrease in leukotriene C4 by colloidal bismuth subcitrate.

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.

Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion.

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<0.05). Endoscopic insertion of a single endoprosthesis will provide good palliation of proximal malignant biliary obstruction caused by unresectable malignancy in 80% of patients. Second stents should be placed only if required. Extensive structuring because of metastatic disease carries a poor prognosis and careful patient selection for treatment is requires.

Needle knife papillotomy: how safe and how effective?

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.

Is duodenal diverticulum a risk factor for sphincterotomy?

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.

Endoscopic therapy of the sump syndrome.

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.

Additional endoscopic procedures instead of urgent surgery for retained common bile duct stones.

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.

Interventional endoscopy in the pancreatobiliary tree.

Since the advent of endoscopic retrograde cholangiopancreatography (ERCP) in 1970 and endoscopic sphincterotomy (EST) in 1974, there has been rapid proliferation of endoscopic techniques for the diagnosis and therapy of benign and malignant biliary and pancreatic disorders. The ability to biopsy under direct vision, reliably obtain a pancreatogram, exclude other upper gastrointestinal disorders, and reexamine with ease, combined with the lack of hepatic puncture, has given the endoscopic route an undeniable advantage over the percutaneous transhepatic route for these interventions. Although some have become routine procedures (EST for postcholecystectomy choledocholithiasis; transpapillary stent insertion for inoperable biliary stenoses), the exact place of many of these interventions remains unclear, and the subject of prospective controlled studies where possible. This review attempts to give an overview of present and developing ERCP- and EST-based diagnostic and interventive techniques and their application to the wide spectrum of pancreatobiliary diseases.

Campylobacter pylori in abattoir workers: is it a zoonosis?

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.

The effect of wavelength, power and treatment pattern on the outcome of laser treatment of port-wine stains.

The argon laser was used to treat 220 patients with port-wine stains with moderate efficacy and few complications although perfect cosmetic results were rarely achieved. Primary failure of the argon laser to produce permanent blanching graded good or excellent was the most important factor limiting the final cosmetic results whilst severe scarring was rare (less than 2%). In order to improve the efficacy of this treatment, a randomized controlled study of different parameters of laser treatment was undertaken in test patches of port-wine stains in 50 patients. A treatment pattern with contiguous or overlapping laser spots was significantly superior to treatment with spots of 1 or 2 mm separation. Increasing the power level to twice the minimum blanching power did not improve efficacy or significantly increase scarring. A randomized study of selective absorption using a neodymium (Nd) YAG laser showed similar efficacy for the different wavelengths although scarring was greater with the Nd-YAG laser. This study has shown that laser treatment can offer a moderately effective treatment for port-wine stains. For best results spot separation needs to be carefully controlled, whilst wavelength and power level appear to be less important than previously reported.

Combination treatment: colloidal bismuth subcitrate with H2-antagonists.

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.

Controlled trial of Nd-YAG laser photocoagulation in bleeding peptic ulcers.

The efficacy of Nd-YAG laser photocoagulation in the endoscopic control of haemorrhage from peptic ulcers was shown in a controlled trial. 527 patients admitted consecutively with acute upper gastrointestinal haemorrhage underwent urgent endoscopy. Peptic ulcers were seen in 260. All 138 ulcer patients with stigmata of recent haemorrhage (SRH) accessible to laser therapy were included in the trial (26 inaccessible, 96 no SRH). Patients were stratified into three groups--those with a visible vessel, those with other SRH, and those with clot that could not be washed off before therapy. Laser and control groups were well matched for other factors known to influence prognosis. Overall, 7/70 laser-treated and 27/68 control ulcers rebled (p less than 0.001). Rebleeding occurred from 6/39 treated and 23/43 control ulcers with a visible vessel (p less than 0.001); 0/17 treated and 1/13 ulcers with other SRH (NS); and 1/13 treated and 2/11 control ulcers with overlying clots (NS). 7/70 treated but 24/68 controls required emergency surgery (p less than 0.005). 1 treated patient but 8 control patients died after an episode of rebleeding (p less than 0.05).

Endoscopic haemostasis of the upper gastrointestinal tract.

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.

Nature of the bleeding vessel in recurrently bleeding gastric ulcers.

An unselected consecutive series of 826 patients admitted for acute upper gastrointestinal bleeding underwent urgent endoscopy. Peptic ulcers were found in 402 (49%). Of the 329 ulcer craters that could be fully examined, visible vessels were identified in 156 (47%), other stigmata of recent hemorrhage in 66, and no stigmata of recent hemorrhage in 107. One hundred twenty-nine patients with stigmata of recent hemorrhage (93 of whom had visible vessels) randomly allocated to no endoscopic treatment were observed for evidence of further bleeding. Fifty-four of the 93 patients (58%) with visible vessels rebled, compared with 2 of 36 (6%) with other stigmata of recent hemorrhage. No patient without stigmata of recent hemorrhage rebled. Twenty-seven patients in whom a visible vessel in a gastric ulcer was identified at endoscopy underwent urgent partial gastrectomy because of recurrent bleeding. The vessel identified at endoscopy was found in 26 of 27 resection specimens (96%). The arterial vessel wall protruded above the surface of the ulcer crater in 10 specimens, and clot in continuity with a breach in the vessel wall protruded in a further 10 specimens. Postoperative angiography, when technically possible, showed that the breached artery ran across the base of the ulcer in all of these specimens. Pathological changes were common in the bleeding artery and included arteritis in 24 of 29 (83%) eroded arteries found in these specimens, with aneurysmal dilatation in 14 of 27 (52%) bleeding points that could be fully examined. The ulcer had penetrated to serosa in 13 specimens (45%). The bleeding artery had a mean external diameter of 0.7 mm with a range of 0.1-1.8 mm. This study provides new information about the nature of the bleeding vessel in gastric ulcers, and some of this information is relevant in planning studies of endoscopic therapy for bleeding peptic ulcers. It validates the endoscopic identification of a visible vessel, and confirms that such identification has a high predictive value for the development of recurrent hemorrhage.

Comparative inhibition of coffee-induced gastric acid secretion employing misoprostol and cimetidine.

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.

Endoscopic laser treatment of vascular anomalies of the upper gastrointestinal tract.

Vascular anomalies of the gastrointestinal tract are an important source of both acute and chronic blood loss. They present difficult management problems as they are often multiple, involving more than one part of the gastrointestinal tract, and may give rise to bleeds of increasing frequency and severity over a period of many years. We present the results of endoscopic argon and Nd YAG laser treatment of 18 patients with documented recurrent, severe haemorrhage from vascular lesions of the upper gastrointestinal tract with follow up of up to five years. Four patients with hereditary haemorrhagic telangiectasia, five with single angiodysplasias and three with multiple angiodysplasias have had their transfusion requirements reduced to minimal levels after one or more courses of laser treatment. Two of these have required no blood for over two years despite previous total requirements of 52 and 129 units of blood. Four patients were submitted to surgery (two in whom the laser failed to control haemorrhage and two who did not have immediate access to laser therapy at the time of severe bleed). Two of these, however, bled again soon afterwards. Two patients are still undergoing courses of laser therapy although have already shown reductions in transfusion requirements. Both lasers were effective. The Nd YAG laser appears to produce better long term results as its greater penetration makes it possible to ablate the main areas of vascular ectasia in the submucosa, although it does have a slightly higher risk of causing haemorrhage in the first few days after treatment.

Which electrode? A comparison of four endoscopic methods of electrocoagulation in experimental bleeding ulcers.

Several inexpensive endoscopic methods of electrocoagulation have been advocated for treatment of gastrointestinal haemorrhage. We compared four types of electrode: dry monopolar - Cameron Miller (M), liquid monopolar - Storz (L), bipolar - Bicap ACMI (B), and heater probe - Seattle (H). The electrical and thermal properties of these probes were studied using computerised monitoring of energy deposition and their efficacy and safety was tested in a randomised study in 140 experimental canine gastric ulcers. At optimal pulse settings 20J (M), 70J (L), 17J (B), 15J (H), effective haemostasis was achieved in all ulcers, the mean number of pulses being M5, L6, H6 and B11, the first three requiring significantly (p less than 0.01) less pulse than B. Relative safety of the electrodes was assessed by comparing the incidence of full thickness damage at histology: B24%, H20%, L58% and M69%; B and H proving significantly (p less than 0.01) safer than L and M. Sticking was assessed as H greater than B greater than M much greater than L. Insensitivity to extreme angulation and force of application was assessed as L greater than B greater than M (H is preset). Of the two safer electrodes the heater probe was more effective than the bipolar probe. Despite its greater tendency to stick than the other devices, the heater probe appeared the most promising of the endoscopic electrodes tested.